Search

Your search keyword '"Antinozzi, P"' showing total 86 results
Start Over Author "Antinozzi, P"
86 results on '"Antinozzi, P"'

2. Forecast cosmological constraints from the number counts of Gravitational Waves events

Author

Antinozzi, Giovanni, Martinelli, Matteo, and Maoli, Roberto

Subjects
Astrophysics - Cosmology and Nongalactic Astrophysics, General Relativity and Quantum Cosmology
Abstract

We present a forecast for the upcoming Einstein Telescope (ET) interferometer with two new methods to infer cosmological parameters. We consider the emission of Gravitational Waves (GWs) from compact binary coalescences, whose electromagnetic counterpart is missing, namely Dark Sirens events. Most of the methods used to infer cosmological information from GW observations rely on the availability of a redshift measurement, usually obtained with the help of external data, such as galaxy catalogues used to identify the most likely galaxy to host the emission of the observed GWs. Instead, our approach is based only on the GW survey itself and exploits the information on the distance of the GW rather than on its redshift. Since a large dataset spanning the whole distance interval is expected to fully represent the distribution, we applied our methods to the expected ET's far-reaching measuring capabilities. We simulate a dataset of observations with ET using the package $\texttt{darksirens}$, assuming an underlying $\Lambda$CDM cosmology, and including the possibility to choose between three possible Star Formation Rate density (SFR) models, also accounting for possible population III stars (PopIII). We test two independent statistical methods: one based on a likelihood approach on the theoretical expectation of observed events, and another applying the $\textit{cut-and-count method}$, a simpler method to compare the observed number of events with the predicted counts. Both methods are consistent in their final results, and also show the potential to distinguish an incorrect SFR model from the data, but not the presence of a possible PopIII. Concerning the cosmological parameters, we find instead that ET observations by themselves would suffer from strong degeneracies, but have the potential to significantly contribute to parameter estimation if used in synergy with other surveys., Comment: 29 pages, 11 figures

Published
2023
Full Text
View/download PDF

3. Low-Dose Anti-Thymocyte Globulin Preserves C-Peptide, Reduces HbA1c, and Increases Regulatory to Conventional T-Cell Ratios in New-Onset Type 1 Diabetes: Two-Year Clinical Trial Data

Author

Haller, Michael J, Long, S Alice, Blanchfield, J Lori, Schatz, Desmond A, Skyler, Jay S, Krischer, Jeffrey P, Bundy, Brian N, Geyer, Susan M, Warnock, Megan V, Miller, Jessica L, Atkinson, Mark A, Becker, Dorothy J, Baidal, David A, DiMeglio, Linda A, Gitelman, Stephen E, Goland, Robin, Gottlieb, Peter A, Herold, Kevan C, Marks, Jennifer B, Moran, Antoinette, Rodriguez, Henry, Russell, William E, Wilson, Darrell M, Greenbaum, Carla J, Battaglia, Manuela, Becker, Dorothy, Bingley, Penelope, Bosi, Emanuele, Buckner, Jane, Clements, Mark, Colman, Peter G, DiMeglio, Linda, Evans-Molina, Carmella, Gottlieb, Peter, Herold, Kevan, Knip, Mikael, Lernmark, Ake, Moore, Wayne, Muir, Andrew, Palmer, Jerry, Peakman, Mark, Philipson, Louis, Raskin, Philip, Redondo, Maria, Russell, William, Sosenko, Jay M, Spain, Lisa, Wentworth, John, Wherrett, Diane, Winter, William, Ziegler, Anette, Anderson, Mark, Antinozzi, Peter, Insel, Richard, Kay, Thomas, Pugliese, Alberto, Roep, Bart, Toppari, Jorma, Leschek, Ellen, Bourcier, Katarzyna, Ridge, John, Rafkin, Lisa, Santiago, Irene, Bundy, Brian, Abbondondolo, Michael, Adams, Timothy, Asif, Ilma, Bjellquist, Jenna, Boonstra, Matthew, Burroughs, Cristina, Cleves, Mario, Cuthbertson, David, DeSalvatore, Meagan, Eberhard, Christopher, Fiske, Steve, Ford, Julie, Garmeson, Jennifer, Geyer, Susan, and Hays, Brian

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Immunology, Clinical Trials and Supportive Activities, Clinical Research, Diabetes, 6.1 Pharmaceuticals, Metabolic and endocrine, Adolescent, Adult, Antilymphocyte Serum, C-Peptide, CD4-CD8 Ratio, Child, Diabetes Mellitus, Type 1, Double-Blind Method, Female, Flow Cytometry, Glycated Hemoglobin, Granulocyte Colony-Stimulating Factor, Humans, Immunologic Factors, Male, T-Lymphocytes, Regulatory, Young Adult, Type 1 Diabetes TrialNet ATG-GCSF Study Group, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract

A three-arm, randomized, double-masked, placebo-controlled phase 2b trial performed by the Type 1 Diabetes TrialNet Study Group previously demonstrated that low-dose anti-thymocyte globulin (ATG) (2.5 mg/kg) preserved β-cell function and reduced HbA1c for 1 year in new-onset type 1 diabetes. Subjects (N = 89) were randomized to 1) ATG and pegylated granulocyte colony-stimulating factor (GCSF), 2) ATG alone, or 3) placebo. Herein, we report 2-year area under the curve (AUC) C-peptide and HbA1c, prespecified secondary end points, and potential immunologic correlates. The 2-year mean mixed-meal tolerance test-stimulated AUC C-peptide, analyzed by ANCOVA adjusting for baseline C-peptide, age, and sex (n = 82) with significance defined as one-sided P < 0.025, was significantly higher in subjects treated with ATG versus placebo (P = 0.00005) but not ATG/GCSF versus placebo (P = 0.032). HbA1c was significantly reduced at 2 years in subjects treated with ATG (P = 0.011) and ATG/GCSF (P = 0.022) versus placebo. Flow cytometry analyses demonstrated reduced circulating CD4:CD8 ratio, increased regulatory T-cell:conventional CD4 T-cell ratios, and increased PD-1+CD4+ T cells following low-dose ATG and ATG/GCSF. Low-dose ATG partially preserved β-cell function and reduced HbA1c 2 years after therapy in new-onset type 1 diabetes. Future studies should determine whether low-dose ATG might prevent or delay the onset of type 1 diabetes.

Published
2019

5. Transcription Factor 7-Like 2 (TCF7L2) Gene Polymorphism and Progression From Single to Multiple Autoantibody Positivity in Individuals at Risk for Type 1 Diabetes

Author

Redondo, Maria J, Steck, Andrea K, Sosenko, Jay, Anderson, Mark, Antinozzi, Peter, Michels, Aaron, Wentworth, John M, Atkinson, Mark A, Pugliese, Alberto, Geyer, Susan, and Group, the Type 1 Diabetes TrialNet Study

Subjects
Biomedical and Clinical Sciences, Health Sciences, Prevention, Genetics, Autoimmune Disease, Nutrition, Diabetes, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Adolescent, Adult, Antibody Specificity, Autoantibodies, Autoimmunity, Child, Child, Preschool, Cohort Studies, Diabetes Mellitus, Type 1, Disease Progression, Female, Gene Frequency, Genetic Predisposition to Disease, Humans, Infant, Male, Middle Aged, Obesity, Overweight, Polymorphism, Single Nucleotide, Risk Factors, Transcription Factor 7-Like 2 Protein, Young Adult, Type 1 Diabetes TrialNet Study Group, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences, Health sciences
Abstract

ObjectiveThe type 2 diabetes-associated alleles at the TCF7L2 locus mark a type 1 diabetes phenotype characterized by single islet autoantibody positivity as well as lower glucose and higher C-peptide measures. Here, we studied whether the TCF7L2 locus influences progression of islet autoimmunity, from single to multiple (≥2) autoantibody positivity, in relatives of patients with type 1 diabetes.Research design and methodsWe evaluated 244 participants in the Type 1 Diabetes TrialNet Pathway to Prevention study with confirmed single autoantibody positivity at screening and Immunochip single nucleotide polymorphism data (47.5% male; median age 12.8 years, range 1.2-45.9; 90.2% white). We analyzed risk allele frequency at TCF7L2 rs4506565 (in linkage disequilibrium with rs7903146). Altogether, 62.6% participants carried ≥1 risk allele. Univariate and multivariable Cox proportional hazards models and Kaplan-Meier statistical methods were used.ResultsDuring follow-up (median 5.2 years, range 0.2-12.6), 62% of the single autoantibody-positive participants developed multiple autoantibody positivity. In the overall cohort, the TCF7L2 locus did not significantly predict progression to multiple autoantibody positivity. However, among single GAD65 autoantibody-positive participants (n = 158), those who carried ≥1 risk allele had a lower rate of progression to multiple autoantibody positivity (hazard ratio [HR] 0.65, P = 0.033) than those who did not, after adjustment for HLA risk haplotypes and age. Among subjects who were either IA-2 or insulin autoantibody positive only, carrying ≥1 TCF7L2 risk allele was not a significant factor overall, but in overweight or obese participants, it increased the risk of progression to multiple autoantibody positivity (HR 3.02, P = 0.016) even with adjustment for age.ConclusionsThe type 2 diabetes-associated TCF7L2 locus influences progression of islet autoimmunity, with differential effects by autoantibody specificity and interaction by obesity/overweight.

Published
2018

6. Low-Dose Anti-Thymocyte Globulin (ATG) Preserves β-Cell Function and Improves HbA1c in New-Onset Type 1 Diabetes

Author

Haller, Michael J, Schatz, Desmond A, Skyler, Jay S, Krischer, Jeffrey P, Bundy, Brian N, Miller, Jessica L, Atkinson, Mark A, Becker, Dorothy J, Baidal, David, DiMeglio, Linda A, Gitelman, Stephen E, Goland, Robin, Gottlieb, Peter A, Herold, Kevan C, Marks, Jennifer B, Moran, Antoinette, Rodriguez, Henry, Russell, William, Wilson, Darrell M, Greenbaum, Carla J, Greenbaum, C, Atkinson, M, Baidal, D, Battaglia, M, Becker, D, Bingley, P, Bosi, E, Buckner, J, Clements, M, Colman, P, DiMeglio, L, Evans-Molina, C, Gitelman, S, Goland, R, Gottlieb, P, Herold, K, Knip, M, Krischer, J, Lernmark, A, Moore, W, Moran, A, Muir, A, Palmer, J, Peakman, M, Philipson, L, Raskin, P, Redondo, M, Rodriguez, H, Russell, W, Spain, L, Schatz, DA, Sosenko, J, Wherrett, D, Wilson, D, Winter, W, Ziegler, A, Anderson, M, Antinozzi, P, Benoist, C, Blum, J, Bourcier, K, Chase, P, Clare-Salzler, M, Clynes, R, Cowie, C, Eisenbarth, G, Fathman, CG, Grave, G, Harrison, L, Hering, B, Insel, R, Jordan, S, Kaufman, F, Kay, T, Kenyon, N, Klines, R, Lachin, J, Leschek, E, Mahon, J, Marks, JB, Monzavi, R, Nanto-Salonen, K, Nepom, G, Orban, T, Parkman, R, Pescovitz, M, Peyman, J, Pugliese, A, Ridge, J, Roep, B, Roncarolo, M, Savage, P, Simell, O, Sherwin, R, Siegelman, M, Skyler, JS, Steck, A, Thomas, J, Trucco, M, and Wagner, J

Subjects
Pediatric, Diabetes, Clinical Trials and Supportive Activities, Clinical Research, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Metabolic and endocrine, Adolescent, Adult, Antilymphocyte Serum, C-Peptide, Child, Cytoprotection, Diabetes Mellitus, Type 1, Dose-Response Relationship, Drug, Double-Blind Method, Drug Therapy, Combination, Female, Glycated Hemoglobin, Granulocyte Colony-Stimulating Factor, Humans, Insulin-Secreting Cells, Male, Pilot Projects, Polyethylene Glycols, Recombinant Proteins, Young Adult, Type 1 Diabetes TrialNet ATG-GCSF Study Group
Abstract

ObjectiveA pilot study suggested that combination therapy with low-dose anti-thymocyte globulin (ATG) and pegylated granulocyte colony-stimulating factor (GCSF) preserves C-peptide in established type 1 diabetes (T1D) (duration 4 months to 2 years). We hypothesized that 1) low-dose ATG/GCSF or 2) low-dose ATG alone would slow the decline of β-cell function in patients with new-onset T1D (duration

Published
2018

7. TCF7L2 Genetic Variants Contribute to Phenotypic Heterogeneity of Type 1 Diabetes

Author

Redondo, Maria J, Geyer, Susan, Steck, Andrea K, Sosenko, Jay, Anderson, Mark, Antinozzi, Peter, Michels, Aaron, Wentworth, John, Xu, Ping, and Pugliese, Alberto

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Diabetes, Prevention, Autoimmune Disease, Clinical Research, Nutrition, Genetics, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Adolescent, Adult, Alleles, Child, Child, Preschool, Cohort Studies, Diabetes Mellitus, Type 1, Female, Genetic Heterogeneity, Genetic Predisposition to Disease, Humans, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Transcription Factor 7-Like 2 Protein, Young Adult, Type 1 Diabetes TrialNet Study Group, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences, Health sciences
Abstract

ObjectiveThe phenotypic diversity of type 1 diabetes suggests heterogeneous etiopathogenesis. We investigated the relationship of type 2 diabetes-associated transcription factor 7 like 2 (TCF7L2) single nucleotide polymorphisms (SNPs) with immunologic and metabolic characteristics at type 1 diabetes diagnosis.Research design and methodsWe studied TrialNet participants with newly diagnosed autoimmune type 1 diabetes with available TCF7L2 rs4506565 and rs7901695 SNP data (n = 810; median age 13.6 years; range 3.3-58.6). We modeled the influence of carrying a TCF7L2 variant (i.e., having 1 or 2 minor alleles) on the number of islet autoantibodies and oral glucose tolerance test (OGTT)-stimulated C-peptide and glucose measures at diabetes diagnosis. All analyses were adjusted for known confounders.ResultsThe rs4506565 variant was a significant independent factor of expressing a single autoantibody, instead of multiple autoantibodies, at diagnosis (odds ratio [OR] 1.66 [95% CI 1.07, 2.57], P = 0.024). Interaction analysis demonstrated that this association was only significant in participants ≥12 years old (n = 504; OR 2.12 [1.29, 3.47], P = 0.003) but not younger ones (n = 306, P = 0.73). The rs4506565 variant was independently associated with higher C-peptide area under the curve (AUC) (P = 0.008) and lower mean glucose AUC (P = 0.0127). The results were similar for the rs7901695 SNP.ConclusionsIn this cohort of individuals with new-onset type 1 diabetes, type 2 diabetes-linked TCF7L2 variants were associated with single autoantibody (among those ≥12 years old), higher C-peptide AUC, and lower glucose AUC levels during an OGTT. Thus, carriers of the TCF7L2 variant had a milder immunologic and metabolic phenotype at type 1 diabetes diagnosis, which could be partly driven by type 2 diabetes-like pathogenic mechanisms.

Published
2018

12. Clinically relevant radioresistant rhabdomyosarcoma cell lines: functional, molecular and immune-related characterization

Author

Petragnano, Francesco, Pietrantoni, Ilaria, Camero, Simona, Codenotti, Silvia, Milazzo, Luisa, Vulcano, Francesca, Macioce, Giampiero, Giordani, Ilenia, Tini, Paolo, Cheleschi, Sara, Gravina, Giovanni Luca, Festuccia, Claudio, Rossetti, Alessandra, Delle Monache, Simona, Ordinelli, Alessandra, Ciccarelli, Carmela, Mauro, Annunziata, Barbara, Barboni, Antinozzi, Cristina, Schiavetti, Amalia, Maggio, Roberto, Di Luigi, Luigi, Polimeni, Antonella, Marchese, Cinzia, Tombolini, Vincenzo, Fanzani, Alessandro, Bernabò, Nicola, Megiorni, Francesca, and Marampon, Francesco

Published
2020
Full Text
View/download PDF

13. Testosterone-mediated activation of androgenic signalling sustains in vitro the transformed and radioresistant phenotype of rhabdomyosarcoma cell lines

Author

Giannattasio, S., Megiorni, F., Di Nisio, V., Del Fattore, A., Fontanella, R., Camero, S., Antinozzi, C., Festuccia, C., Gravina, G. L., Cecconi, S., Dominici, C., Di Luigi, L., Ciccarelli, C., De Cesaris, P., Riccioli, A., Zani, B. M., Lenzi, A., Pestell, R. G., Filippini, A., Crescioli, C., Tombolini, V., and Marampon, F.

Published
2019
Full Text
View/download PDF

22. Das Rüsten der anderen.

Author

Antinozzi, Isabella

Subjects
MILITARY spending, RUSSIAN invasion of Ukraine, 2022-
Abstract

The article discusses the increased defense spending by European nations in response to Russia's invasion of Ukraine but points out the lack of collaborative effort in the defense sector, resulting in a fragmented European defense industry dominated by national markets.

Published
2022

23. Identical and Nonidentical Twins: Risk and Factors Involved in Development of Islet Autoimmunity and Type 1 Diabetes

Author

Triolo, T.M., Fouts, A., Pyle, L., Yu, L., Gottlieb, P.A., Steck, A.K., Greenbaum, C.J., Atkinson, M., Baidal, D., Battaglia, M., Becker, D., Bingley, P., Bosi, E., Buckner, J., Clements, M., Colman, P., DiMeglio, L., Gitelman, S., Goland, R., Gottlieb, P., Herold, K., Knip, M., Krischer, J., Lernmark, A., Moore, W., Moran, A., Muir, A., Palmer, J., Peakman, M., Philipson, L., Raskin, P., Redondo, M., Rodriguez, H., Russell, W., Spain, L., Schatz, D.A., Sosenko, J., Wentworth, J., Wherrett, D., Wilson, D., Winter, W., Ziegler, A., Anderson, M., Antinozzi, P., Benoist, C., Blum, J., Bourcier, K., Chase, P., Clare-Salzler, M., Clynes, R., Eisenbarth, G., Fathman, C.G., Grave, G., Hering, B., Insel, R., Kaufman, F., Kay, T., Leschek, E., Mahon, J., Marks, J.B., Nanto-Salonen, K., Nepom, G., Orban, T., Parkman, R., Pescovitz, M., Peyman, J., Pugliese, A., Roep, B., Roncarolo, M., Savage, P., Simell, O., Sherwin, R., Siegelman, M., Skyler, J.S., Steck, A., Thomas, J., Trucco, M., Wagner, J., Krischer, J.P., Rafkin, L., Cowie, C., Foulkes, M., Krause-Steinrauf, H., Lachin, J.M., Malozowski, S., Ridge, J., Zafonte, S.J., Sosenko, J.M., Kenyon, N.S., Santiago, I., Bundy, B., Abbondondolo, M., Adams, T., Amado, D., Asif, I., Boonstra, M., Burroughs, C., Cuthbertson, D., Deemer, M., Eberhard, C., Fiske, S., Ford, J., Garmeson, J., Guillette, H., Geyer, S., Hays, B., Henderson, C., Henry, M., Heyman, K., Hsiao, B., Karges, C., Keaton, N., Kinderman, A., Law, P., Leinbach, A., Liu, S., Lloyd, J., Malloy, J., Maddox, K., Martin, J., Miller, J., Milliot, E., Moore, M., Muller, S., Nguyen, T., O'Donnell, R., Roberts, A., Sadler, K., Stavros, T., Tamura, R., Wood, K., Xu, P., Young, K., Alies, P., Badias, F., Baker, A., Bassi, M., Beam, C., Boulware, D., Bounmananh, L., Bream, S., Freeman, D., Gough, J., Ginem, J., Granger, M., Kieffer, M.H.M., Lane, P., Linton, C., Nallamshetty, L., Oduah, V., Parrimon, Y., Paulus, K., Pilger, J., Ramiro, J., Ritzie, A.L., Sharma, A., Shor, A., Song, X., Terry, A., Weinberger, J., Wootten, M., Harding, P., McDonough, S., Mcgee, P.F., Hess, K.O., Phoebus, D., Quinlan, S., Raiden, E., Batts, E., Buddy, C., Kirpatrick, K., Ramey, M., Shultz, A., Webb, C., Romesco, M., Fradkin, J., Aas, S., Blumberg, E., Beck, G., Brillon, D., Gubitosi-Klug, R., Laffel, L., Vigersky, R., Wallace, D., Braun, J., B. lo, Mitchell, H., Naji, A., Nerup, J., Orchard, T., Steffes, M., Tsiatis, A., Veatch, R., Zinman, B., Loechelt, B., Baden, L., Green, M., Weinberg, A., Marcovina, S., Palmer, J.P., Babu, S., Eisenbarth, G.S., Marks, J., Matheson, D., Gomez, D., McDonald, A., Pena, S., Pietropaolo, M., Shippy, K., Brown, T., Dove, A., Hammond, M., Hefty, D., Klein, J., Kuhns, K., Letlau, M., Lord, S., McCulloch-Olson, M., Miller, L., Odegard, J., Sachter, E., St Marie, M., Stickney, K., VanBuecken, D., Vellek, B., Webber, C., Allen, L., Bollyk, J., Hilderman, N., Ismail, H., Lamola, S., Sanda, S., Vendettuoli, H., Tridgell, D., Monzavi, R., Bock, M., Fisher, L., Halvorson, M., Jeandron, D., Kim, M., Wood, J., Geffner, M., Salazar, C., Cook, S., Freeby, M., Gallagher, M.P., Gandica, R., Greenberg, E., Kurland, A., Pollak, S., Wolk, A., Chan, M., Koplimae, L., Levine, E., Smith, K., Trast, J., Evans-Molina, C., Hufferd, R., Jagielo, B., Kruse, C., Patrick, V., Rigby, M., Spall, M., Swinney, K., Terrell, J., Christner, L., Ford, L., Lynch, S., Menendez, M., Merrill, P., and Pesc

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Concordance, Twins, Autoimmunity, 030209 endocrinology & metabolism, Type 2 diabetes, Environment, medicine.disease_cause, Islets of Langerhans, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Seroepidemiologic Studies, Diabetes mellitus, Internal medicine, Diseases in Twins, Twins, Dizygotic, Internal Medicine, medicine, Genetic predisposition, Humans, Insulin, Mass Screening, Genetic Predisposition to Disease, 030212 general & internal medicine, Child, Mass screening, Autoantibodies, Advanced and Specialized Nursing, Type 1 diabetes, Glutamate Decarboxylase, business.industry, Siblings, Autoantibody, Twins, Monozygotic, Predicting Diabetes Using Genetic Risk Scores, medicine.disease, Diabetes Mellitus, Type 1, Endocrinology, Child, Preschool, Disease Progression, Female, business
Abstract

OBJECTIVE There are variable reports of risk of concordance for progression to islet autoantibodies and type 1 diabetes in identical twins after one twin is diagnosed. We examined development of positive autoantibodies and type 1 diabetes and the effects of genetic factors and common environment on autoantibody positivity in identical twins, nonidentical twins, and full siblings. RESEARCH DESIGN AND METHODS Subjects from the TrialNet Pathway to Prevention Study (N = 48,026) were screened from 2004 to 2015 for islet autoantibodies (GAD antibody [GADA], insulinoma-associated antigen 2 [IA-2A], and autoantibodies against insulin [IAA]). Of these subjects, 17,226 (157 identical twins, 283 nonidentical twins, and 16,786 full siblings) were followed for autoantibody positivity or type 1 diabetes for a median of 2.1 years. RESULTS At screening, identical twins were more likely to have positive GADA, IA-2A, and IAA than nonidentical twins or full siblings (all P < 0.0001). Younger age, male sex, and genetic factors were significant factors for expression of IA-2A, IAA, one or more positive autoantibodies, and two or more positive autoantibodies (all P ≤ 0.03). Initially autoantibody-positive identical twins had a 69% risk of diabetes by 3 years compared with 1.5% for initially autoantibody-negative identical twins. In nonidentical twins, type 1 diabetes risk by 3 years was 72% for initially multiple autoantibody–positive, 13% for single autoantibody–positive, and 0% for initially autoantibody-negative nonidentical twins. Full siblings had a 3-year type 1 diabetes risk of 47% for multiple autoantibody–positive, 12% for single autoantibody–positive, and 0.5% for initially autoantibody-negative subjects. CONCLUSIONS Risk of type 1 diabetes at 3 years is high for initially multiple and single autoantibody–positive identical twins and multiple autoantibody–positive nonidentical twins. Genetic predisposition, age, and male sex are significant risk factors for development of positive autoantibodies in twins.

Published
2019
Full Text
View/download PDF

25. Effect of Oral Insulin on Prevention of Diabetes in Relatives of Patients With Type 1 Diabetes A Randomized Clinical Trial

Author

Greenbaum, C., Atkinson, M., Baidal, D., Battaglia, M., Bingley, P., Bosi, E., Buckner, J., Clements, M., Colman, P., DiMeglio, L., Evans-Molina, C., Gitelman, S., Goland, R., Gottlieb, P., Herold, K., Knip, M., Krischer, J., Lernmark, A., Moore, W., Moran, A., Muir, A., Palmer, J., Peakman, M., Philipson, L., Raskin, P., Redondo, M., Rodriguez, H., Russell, W., Spain, L., Schatz, D.A., Sosenko, J., Wherrett, D., Wilson, D., Winter, W., Ziegler, A., Anderson, M., Antinozzi, P., Benoist, C., Blum, J., Bourcier, K., Chase, P., Clare-Salzler, M., Clynes, R., Cowie, C., Eisenbarth, G., Fathman, C.G., Grave, G., Harrison, L., Hering, B., Insel, R., Jordan, S., Kaufman, F., Kay, T., Kenyon, N., Klines, R., Lachin, J., Leschek, E., Mahon, J., Marks, J.B., Monzavi, R., Nanto-Salonen, K., Nepom, G., Orban, T., Parkman, R., Pescovitz, M., Peyman, J., Pugliese, A., Ridge, J., Roep, B., Roncarolo, M., Savage, P., Simell, O., Sherwin, R., Siegelman, M., Skyler, J.S., Thomas, J., Trucco, M., Wagner, J., Greenbaum, C.J., Krischer, J.P., Rafkin, L., Foulkes, M., Krause-Steinrauf, H., Lachin, J.M., Malozowski, S., Zafonte, S.J., Kenyon, N.S., Santiago, I., Bundy, B., Abbondondolo, M., Adams, T., Asif, D.A.I., Boonstra, M., Boulware, D., Burroughs, C., Cuthbertson, D., Eberhard, C., Fiske, S., Ford, J., Garmeson, J., Guillette, H., Geyer, S., Hays, B., Henderson, C., Henry, M., Heyman, K., Hsiao, B., Karges, C., Kinderman, A., Lane, L., Leinbach, A., Liu, S., Lloyd, J., Malloy, J., Maddox, K., Martin, J., Miller, J., Moore, M., Muller, S., Nguyen, T., O'Donnell, R., Parker, M., Pereyra, M.J., Reed, N., Roberts, A., Sadler, K., Stavros, T., Tamura, R., Wood, K., Xu, P., Young, K., Alies, P., Badias, F., Baker, A., Bassi, M., Beam, C., Bounmananh, L., Bream, S., Deemer, M., Freeman, D., Gough, J., Ginem, J., Granger, M., Holloway, M., Kieffer, M., Lane, P., Law, P., Linton, C., Nallamshetty, L., Oduah, V., Parrimon, Y., Paulus, K., Pilger, J., Ramiro, J., Ritzie, A.Q.L., Sharma, A., Shor, A., Song, X.H., Terry, A., Weinberger, J., Wootten, M., Harding, M.F.P., McDonough, S., Mcgee, P.F., Hess, K.O., Phoebus, D., Quinlan, S., Raiden, E., Fradkin, J., Beck, G., Blumberg, E., Gubitosi-Klug, R., Laffel, L., Veatch, R., Wallace, D., Braun, J., Brillon, D., B. lo, Mitchell, H., Naji, A., Nerup, J., Orchard, T., Steffes, M., Tsiatis, A., Zinman, B., Loechelt, B., Baden, L., Green, M., Weinberg, A., Marcovina, S., Palmer, J.P., Yu, L.P., Shultz, A., Batts, E., Fitzpatrick, K., Ramey, M., Guerra, R., Webb, C., Caffey, F., Carr, L., Ergun-Longmire, B., Fenton, C., Giebner, D., Johnson, J., Maglionico, D., Marinelli, M., Martin, K., Minnozzi, E., Riley, W., Wilson, M., Gougeon, C., Ho, J., Huang, C., Pacaud, D., Virtanen, H., Craig, C., Ghatak, A., Henderson, T., Leyland, H., Padmore, K., Paul, P., Brickman, W., Halsey-Lyda, M., Petrie, P., Rizzo, D., Steuer, R., Suchyta, K., Torchen, L., Zimmerman, D., Bode, B., Dial, M., Gazaway, K., Hosey, R., Alkanani, A., Barker, J., Barr, M., Blau, A., Burdick, P., Burke, B., Chase, H., Drye, M., Escobar, E., Fitzgerald-Miller, L., Fouts, A., Gage, V., Gall, E., Goettle, H., Harris, S., Ketchum, K., King, M., Klingensmith, G., Lehr, D., Lehr, J., Lewis, L., Logsden-Sackett, N., Lykens, J., Maahs, D., Michels, A., Pelletier, S., Rihanek, M., Rodriguez, P., Schauwecker, A., Simmons, K., Smith, J., Steck, A., Tran, B., Tran, T., Wadwa, P., Wagner, R., Wright, H., Betancourt, J., Bui, V., DeSalvo, D., Gomez, D., Jake, K., Lynds, J., McCartney, T., McDonald, A., Pena, S., Pietropaolo, M., Greenbaum, C., Atkinson, M., Baidal, D., Battaglia, M., Becker, D., Bingley, P., Bosi, E., Buckner, J., Clements, M., Colman, P., Dimeglio, L., Evans-Molina, C., Gitelman, S., Goland, R., Gottlieb, P., Herold, K., Knip, M., Krischer, J., Lernmark, A., Moore, W., Moran, A., Muir, A., Palmer, J., Peakman, M., Philipson, L., Raskin, P., Redondo, M., Rodriguez, H., Russell, W., Spain, L., Schatz, D. A., Sosenko, J., Wherrett, D., Wilson, D., Winter, W., and Ziegler, A.

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Administration, Oral, 030209 endocrinology & metabolism, Placebo, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Interquartile range, law, Internal medicine, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, Insulin, Family, Treatment Failure, Child, Original Investigation, Autoantibodies, Type 1 diabetes, Glucose tolerance test, medicine.diagnostic_test, business.industry, General Medicine, ta3121, Glucose Tolerance Test, medicine.disease, 030104 developmental biology, Diabetes Mellitus, Type 1, Child, Preschool, Cohort, Female, business, Follow-Up Studies
Abstract

Importance Type 1 diabetes requires major lifestyle changes and carries increased morbidity and mortality. Prevention or delay of diabetes would have major clinical effect. Objective To determine whether oral insulin delays onset of type 1 diabetes in autoantibody-positive relatives of patients with type 1 diabetes. Design, Setting, and Participants Between March 2, 2007, and December 21, 2015, relatives with at least 2 autoantibodies, including insulin autoantibodies and normal glucose tolerance, were enrolled in Canada, the United States, Australia, New Zealand, the United Kingdom, Italy, Sweden, Finland, and Germany. The main study group (n = 389) had first-phase insulin release on an intravenous glucose tolerance test that was higher than the threshold. The 55 patients in the secondary stratum 1 had an identical antibody profile as the main study group except they had first-phase insulin release that was lower than the threshold. Secondary strata 2 (n = 114) and strata 3 (n = 3) had different autoantibody profiles and first-phase insulin release threshold combinations. Follow-up continued through December 31, 2016. Interventions Randomization to receive 7.5 mg/d of oral insulin (n = 283) or placebo (n = 277), including participants in the main study group who received oral insulin (n = 203) or placebo (n = 186). Main Outcome and Measures The primary outcome was time to diabetes in the main study group. Significance was based on a 1-sided threshold of .05, and 1-sided 95% CIs are reported. Results Of a total of 560 randomized participants (median enrollment age, 8.2 years; interquartile range [IQR], 5.7-12.1 years; 170 boys [60%]; 90.7% white non-Hispanic; 57.6% with a sibling with type 1 diabetes), 550 completed the trial including 389 participants (median age, 8.4 years; 245 boys [63%]), 382 (96%) in the main study group. During a median follow-up of 2.7 years (IQR, 1.5-4.6 years) in the main study group, diabetes was diagnosed in 58 participants (28.5%) in the oral insulin group and 62 (33%) in the placebo group. Time to diabetes was not significantly different between the 2 groups (hazard ratio [HR], 0.87; 95% CI, 0-1.2;P = .21). In secondary stratum 1 (n = 55), diabetes was diagnosed in 13 participants (48.1%) in the oral insulin group and in 19 participants (70.3%) in the placebo group. The time to diabetes was significantly longer with oral insulin (HR, 0.45; 95% CI, 0-0.82;P = .006). The HR for time to diabetes for the between-group comparisons for the 116 participants in the other secondary stratum was 1.03 (95% CI, 0-2.11;P = .53) and for the entire cohort of 560 participants was 0.83 (95% CI, 0-1.07;P = .11), which were not significantly different. The most common adverse event was infection (n = 254), with 134 events in the oral insulin group and 120 events in the placebo group, but no significant study-related adverse events occurred. Conclusions and Relevance Among autoantibody-positive relatives of patients with type 1 diabetes, oral insulin at a dose of 7.5 mg/d, compared with placebo, did not delay or prevent the development of type 1 diabetes over 2.7 years. These findings do not support oral insulin as used in this study for diabetes prevention. Trial Registration clinicaltrials.gov Identifier:NCT00419562

Published
2017

26. A Type 1 Diabetes Genetic Risk Score Predicts Progression of Islet Autoimmunity and Development of Type 1 Diabetes in Individuals at Risk

Author

Redondo, MJ, Geyer, S, Steck, AK, Sharp, S, Wentworth, JM, Weedon, MN, Antinozzi, P, Sosenko, J, Atkinson, M, Pugliese, A, Oram, RA, Redondo, MJ, Geyer, S, Steck, AK, Sharp, S, Wentworth, JM, Weedon, MN, Antinozzi, P, Sosenko, J, Atkinson, M, Pugliese, A, and Oram, RA

Abstract

OBJECTIVE: We tested the ability of a type 1 diabetes (T1D) genetic risk score (GRS) to predict progression of islet autoimmunity and T1D in at-risk individuals. RESEARCH DESIGN AND METHODS: We studied the 1,244 TrialNet Pathway to Prevention study participants (T1D patients' relatives without diabetes and with one or more positive autoantibodies) who were genotyped with Illumina ImmunoChip (median [range] age at initial autoantibody determination 11.1 years [1.2-51.8], 48% male, 80.5% non-Hispanic white, median follow-up 5.4 years). Of 291 participants with a single positive autoantibody at screening, 157 converted to multiple autoantibody positivity and 55 developed diabetes. Of 953 participants with multiple positive autoantibodies at screening, 419 developed diabetes. We calculated the T1D GRS from 30 T1D-associated single nucleotide polymorphisms. We used multivariable Cox regression models, time-dependent receiver operating characteristic curves, and area under the curve (AUC) measures to evaluate prognostic utility of T1D GRS, age, sex, Diabetes Prevention Trial-Type 1 (DPT-1) Risk Score, positive autoantibody number or type, HLA DR3/DR4-DQ8 status, and race/ethnicity. We used recursive partitioning analyses to identify cut points in continuous variables. RESULTS: Higher T1D GRS significantly increased the rate of progression to T1D adjusting for DPT-1 Risk Score, age, number of positive autoantibodies, sex, and ethnicity (hazard ratio [HR] 1.29 for a 0.05 increase, 95% CI 1.06-1.6; P = 0.011). Progression to T1D was best predicted by a combined model with GRS, number of positive autoantibodies, DPT-1 Risk Score, and age (7-year time-integrated AUC = 0.79, 5-year AUC = 0.73). Higher GRS was significantly associated with increased progression rate from single to multiple positive autoantibodies after adjusting for age, autoantibody type, ethnicity, and sex (HR 2.27 for GRS >0.295, 95% CI 1.47-3.51; P = 0.0002). CONCLUSIONS: The T1D GRS independently predicts p

Published
2018

27. TCF7L2 Genetic Variants Contribute to Phenotypic Heterogeneity of Type 1 Diabetes

Author

Redondo, MJ, Geyer, S, Steck, AK, Sosenko, J, Anderson, M, Antinozzi, P, Michels, A, Wentworth, J, Xu, P, Pugliese, A, Redondo, MJ, Geyer, S, Steck, AK, Sosenko, J, Anderson, M, Antinozzi, P, Michels, A, Wentworth, J, Xu, P, and Pugliese, A

Abstract

OBJECTIVE: The phenotypic diversity of type 1 diabetes suggests heterogeneous etiopathogenesis. We investigated the relationship of type 2 diabetes-associated transcription factor 7 like 2 (TCF7L2) single nucleotide polymorphisms (SNPs) with immunologic and metabolic characteristics at type 1 diabetes diagnosis. RESEARCH DESIGN AND METHODS: We studied TrialNet participants with newly diagnosed autoimmune type 1 diabetes with available TCF7L2 rs4506565 and rs7901695 SNP data (n = 810; median age 13.6 years; range 3.3-58.6). We modeled the influence of carrying a TCF7L2 variant (i.e., having 1 or 2 minor alleles) on the number of islet autoantibodies and oral glucose tolerance test (OGTT)-stimulated C-peptide and glucose measures at diabetes diagnosis. All analyses were adjusted for known confounders. RESULTS: The rs4506565 variant was a significant independent factor of expressing a single autoantibody, instead of multiple autoantibodies, at diagnosis (odds ratio [OR] 1.66 [95% CI 1.07, 2.57], P = 0.024). Interaction analysis demonstrated that this association was only significant in participants ≥12 years old (n = 504; OR 2.12 [1.29, 3.47], P = 0.003) but not younger ones (n = 306, P = 0.73). The rs4506565 variant was independently associated with higher C-peptide area under the curve (AUC) (P = 0.008) and lower mean glucose AUC (P = 0.0127). The results were similar for the rs7901695 SNP. CONCLUSIONS: In this cohort of individuals with new-onset type 1 diabetes, type 2 diabetes-linked TCF7L2 variants were associated with single autoantibody (among those ≥12 years old), higher C-peptide AUC, and lower glucose AUC levels during an OGTT. Thus, carriers of the TCF7L2 variant had a milder immunologic and metabolic phenotype at type 1 diabetes diagnosis, which could be partly driven by type 2 diabetes-like pathogenic mechanisms.

Published
2018

28. Sulodexide counteracts endothelial dysfunction induced by metabolic or non-metabolic stresses through activation of the autophagic program.

Author

DE FELICE, F., MEGIORNI, F., PIETRANTONIO, I., TINI, P., LESSIANI, G., MASTROIACOVO, D., MATTANA, P., ANTINOZZI, C., DI LUIGI, L., DELLE MONACHE, S., ANGELUCCI, A., FESTUCCIA, C., FANZANI, A., MAGGIO, R., TOMBOLINI, V., GRAVINA, G. L., and MARAMPON, F.

Abstract

OBJECTIVE: Endothelial dysfunction (ED) predisposes to venous thrombosis (VT) and post-thrombotic syndrome (PTS), a long-term VT-related complication. Sulodexide (SDX) is a highly purified glycosaminoglycan with antithrombotic, pro-fibrinolytic and anti- inflammatory activity used in the treatment of chronic venous disease (CVD), including patients with PTS. SDX has recently obtained clinical evidence in the "extension therapy" after initial-standard anticoagulant treatment for the secondary prevention of recurrent deep vein thrombosis (DVT). Herein, we investigated how SDX counteracts ED. MATERIALS AND METHODS: Human umbilical vein endothelial cells (HUVEC) were used. Metabolic and non metabolic-induced ED was induced by treating with methylglyoxal (MGO) or irradiation (IR), respectively. Bafilomycin A1 was used to inhibit autophagy. The production of reactive oxygen species (ROS), tetrazolium bromide (MTT) assay for cell viability, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay for cell apoptosis, Real-time PCR and Western blot analysis for gene and protein expression were used. RESULTS: SDX protected HUVEC from MGOor IR-induced apoptosis by counteracting the activation of the intrinsic and extrinsic caspase cascades. The cytoprotective effects of SDX resulted from a reduction in a) ROS production, b) neo-synthesis and release of pro-inflammatory cytokines (TNFα, IL1, IL6, IL8), c) DNA damage induced by MGO or IR. These effects were reduced when autophagy was inhibited. CONCLUSIONS: Data herein collected indicate the ability of SDX to counteract ED induced by metabolic or non-metabolic stresses by involving the intracellular autophagy pathway. Our experience significantly increases the knowledge of the mechanisms of action of SDX against ED and supports the use of SDX in the treatment of CVD, PTS and in the secondary prevention of recurrent DVT. [ABSTRACT FROM AUTHOR]

Published
2019

29. Success!

Author

James, James J., Satyamitra, Merriline, Hu, Tom, and Antinozzi, Peter

Published
2024
Full Text
View/download PDF

30. The Beta secretase BACE1 drives fibroblasts activation in Systemic Sclerosis through the APP/β-catenin/Notch signalling axis

Author

Wasson, Christopher W., De Lorenzis, Enrico, Clavane, Eva M., Ross, Rebecca L., Walker, Kieran A., Caballero-Ruiz, Begoña, Antinozzi, Cristina, Wells, Rebecca, Migneco, Gemma, Brown, Jane M.Y., Turvey, Samuel J., Simmons, Katie J., Riobo-Del Galdo, Natalia A., Di Luigi, Luigi, McKimmie, Clive S., Del Galdo, Francesco, and Meakin, Paul J.

Abstract

The beta-amyloid precursor protein cleaving enzyme 1 (BACE1) is well known for its role in the development of Alzheimer’s disease. Recent publications, including our own, have demonstrated a role for this enzyme in other chronic diseases. The aim of this study was to investigate the role of BACE1 in the autoimmune disease systemic sclerosis (SSc). BACE1 protein levels were elevated in SSc patient skin. Inhibition of BACE1 with small molecule inhibitors or siRNA blocked SSc and fibrotic stimuli mediated fibroblast activation. Furthermore, we show that BACE1 regulation of dermal fibroblast activation is dependent on β-catenin and Notch signalling. The Neurotropic factor BDNF negatively regulates BACE1 expression and activity in dermal fibroblasts. Finally, sera from SSc patients show higher Aβ and lower BDNF levels compared to healthy controls. The ability of BACE1 to regulate SSc fibroblast activation reveals a therapeutic target in SSc. Several BACE1 inhibitors have been shown to be safe in clinical trials for Alzheimer’s disease and could be repurposed to ameliorate fibrosis progression.

Published
2024
Full Text
View/download PDF

38. RISREAC Study: Assessment of Cutaneous Radiation Injury Through Clinical Documentation

Author

Ghaffar, Aqsa, Xie, Yunna, Antinozzi, Peter, and Ryan Wolf, Julie

Abstract

AbstractObjective:Radiation dermatitis (RD) occurs in 95% of patients receiving radiation therapy (RT) for cancer treatment, affecting 800 million patients annually. We aimed to demonstrate the feasibility of developing a historical RD cohort, Radiation Induced Skin Reactions (RISREAC) cohort.Methods:This retrospective study evaluated RD-related clinical documentation for 245 breast cancer patients who received RT at the University of Rochester Medical Center, to understand the RD progression, scoring, and management. All statistical analyses were performed at 0.05 level of significance.Results:Clinician-documented RD severity was observed for 169 (69%) patients with a mean severity of 1.57 [1.46, 1.68]. The mean descriptor-based severity score of 2.31 [2.18, 2.45] moderately correlated (r = 0.532, P< 0.0001) with documented RD grade. Most patients (91.8%) received skin care treatment during RT, with 66.7% receiving more than 2 modalities.Conclusions:The RISREAC cohort is the first retrospective cohort established from clinical documentation of radiation-induced skin changes for the study of RD and cutaneous radiation injury (CRI). RD symptom descriptors were more reliably documented and suitable for all skin types compared to Radiation Therapy Oncology Group (RTOG) or Common Toxicity Criteria for Adverse Events (CTCAE) grades. A new descriptor-based scoring tool would be useful for RD and CRI.

Published
2023
Full Text
View/download PDF

39. Profile of Children Under the Age of 13 in Georgia's Juvenile Justice System.

Author

Houchins, David E., Herk, Monica, Shippen, Margaret E., Antinozzi, Jennifer, Haberlen, Sabina, Heffelfinger, Priscilla, and Norman, English

Subjects
JUVENILE courts, AMERICAN children, STATISTICS, MENTAL health, JUVENILE justice administration
Abstract

A significant number of children under the age of 13 come before the juvenile courts in the United States. However, minimal data are available about the characteristics of this population or the appropriate interventions for them. This article provides descriptive and statistical data about a sample of this population in Georgia, information that can be used to guide future research and interventions. Extant records of 84 children under the age of 13 in Georgia who were either detained by or committed to the Georgia Department of Juvenile Justice (DJJ) were examined. Descriptive variables include (a) race, gender, and age; (b) types of charges; (c) juvenile justice placements; (d) educational histories; (e) family histories; (f) mental health; (g) sexual offenses and abuse; and (h) history of involvement with state agencies. Statistical analysis was limited to correlations between age and IQ, age and the number of contacts with the DJJ, and the number of contacts with the DJJ and mental health diagnoses. A discussion about the potential implications of the data is provided along with policy recommendations. [ABSTRACT FROM AUTHOR]

Published
2006

40. Glycerol-stimulated proinsulin biosynthesis in isolated pancreatic rat islets via adenoviral-induced expression of glycerol kinase is mediated via mitochondrial metabolism.

Author

Skelly, Robert H., Wicksteed, Barton, Antinozzi, Peter A., Rhodes, Christopher J., Skelly, R H, Wicksteed, B, Antinozzi, P A, and Rhodes, C J

Subjects
GLYCERYL ethers, PROINSULIN, ISLANDS of Langerhans
Abstract

In this study, we examined whether adenoviral-mediated glycerol kinase (AdV-CMV-GlyK) expression in isolated rat pancreatic islets could introduce glycerol-induced proinsulin biosynthesis. In AdV-CMV-GlyK-infected islets, specific glycerol-induced proinsulin biosynthesis translation and insulin secretion were observed in parallel from the same islets. The threshold concentration of glycerol required to stimulate proinsulin biosynthesis was lower (0.25-0.5 mmol/l) than that for insulin secretion (1.0-1.5 mmol/l), reminiscent of threshold differences for glucose-stimulated proinsulin biosynthesis versus insulin secretion. The dose-dependent glycerol-induced proinsulin biosynthesis correlated with the rate of glycerol oxidation in AdV-CMV-GlyK-infected islets, indicating that glycerol metabolism was required for the response. However, glycerol did not significantly increase lactate output from AdV-CMV-GlyK-infected islets, but the dihydroxyacetone phosphate (DHAP) to alpha-glycerophosphate (alpha-GP) ratio significantly increased in AdV-CMV-GlyK-infected islets incubated at 2 mmol/l glycerol compared with that at a basal level of 2.8 mmol/l glucose (P < or = 0.05). The DHAP:alpha-GP ratio was unaffected in AdV-CMV-GlyK-infected islets incubated at 2 mmol/l glycerol in the added presence of alpha-cyanohydroxycinnaminic acid (alpha-CHC), an inhibitor of the plasma membrane and mitochondrial lactate/pyruvate transporter. However, alpha-CHC inhibited glycerol-induced proinsulin biosynthesis and insulin secretion in AdV-CMV-GlyK-infected islets (>75%; P = 0.05), similarly to glucose-induced proinsulin biosynthesis and insulin secretion in AdV-CMV-GlyK-infected and control islets. These data indicated that in AdV-CMV-GlyK-infected islets, the importance of mitochondrial metabolism of glycerol was required to generate stimulus-response coupling signals to induce proinsulin biosynthesis and insulin secretion. [ABSTRACT FROM AUTHOR]

Published
2001
Full Text
View/download PDF

41. Adenovirus-mediated overexpression of liver carnitine palmitoyltransferase I in INS1E cells: effects on cell metabolism and insulin secretion

Author

RUBÍ, Blanca, ANTINOZZI, Peter A., HERRERO, Laura, ISHIHARA, Hisamitsu, ASINS, Guillermina, SERRA, Dolors, WOLLHEIM, Claes B., MAECHLER, Pierre, and HEGARDT, Fausto G.

Abstract

Lipid metabolism in the β-cell is critical for the regulation of insulin secretion. Pancreatic β-cells chronically exposed to fatty acids show higher carnitine palmitoyltransferase I (CPT I) protein levels, higher palmitate oxidation rates and an altered insulin response to glucose. We examined the effect of increasing CPT I levels on insulin secretion in cultured β-cells. We prepared a recombinant adenovirus containing the cDNA for the rat liver isoform of CPT I. The overexpression of CPT I in INS1E cells caused a more than a 5-fold increase in the levels of CPT I protein (detected by Western blotting), a 6-fold increase in the CPT activity, and an increase in fatty acid oxidation at 2.5mM glucose (1.7-fold) and 15mM glucose (3.1-fold). Insulin secretion was stimulated in control cells by 15mM glucose or 30mM KCl. INS1E cells overexpressing CPT I showed lower insulin secretion on stimulation with 15mM glucose (−40%; P<0.05). This decrease depended on CPT I activity, since the presence of etomoxir, a specific inhibitor of CPT I, in the preincubation medium normalized the CPT I activity, the fatty-acid oxidation rate and the insulin secretion in response to glucose. Exogenous palmitate (0.25mM) rescued glucose-stimulated insulin secretion (GSIS) in CPT I-overexpressing cells, indicating that the mechanism of impaired GSIS was through the depletion of a critical lipid. Depolarizing the cells with KCl or intermediary glucose concentrations (7.5mM) elicited similar insulin secretion in control cells and cells overexpressing CPT I. Glucose-induced ATP increase, glucose metabolism and the triacylglycerol content remained unchanged. These results provide further evidence that CPT I activity regulates insulin secretion in the β-cell. They also indicate that up-regulation of CPT I contributes to the loss of response to high glucose in β-cells exposed to fatty acids.

Published
2002
Full Text
View/download PDF

42. Mitochondrial Metabolism Sets the Maximal Limit of Fuel-stimulated Insulin Secretion in a Model Pancreatic Beta Cell

Author

Antinozzi, Peter A., Ishihara, Hisamitsu, Newgard, Christopher B., and Wollheim, Claes B.

Abstract

The precise metabolic steps that couple glucose catabolism to insulin secretion in the pancreatic beta cell are incompletely understood. ATP generated from glycolytic metabolism in the cytosol, from mitochondrial metabolism, and/or from the hydrogen shuttles operating between cytosolic and mitochondrial compartments has been implicated as an important coupling factor. To identify the importance of each of these metabolic pathways, we have compared the fates of four fuel secretagogues (glucose, pyruvate, dihydroxyacetone, and glycerol) in the INS1-E beta cell line. Two of these fuels, dihydroxyacetone and glycerol, are normally ineffective as secretagogues but are enabled by adenovirus-mediated expression of glycerol kinase. Comparison of these two particular fuels allows the effect of redox state on insulin secretion to be evaluated since the phosphorylated products dihydroxyacetone phosphate and glycerol phosphate lie on opposite sides of the NADH-consuming glycerophosphate dehydrogenase reaction. Based upon measurements of glycolytic metabolites, mitochondrial oxidation, mitochondrial matrix calcium, and mitochondrial membrane potential, we find that insulin secretion most tightly correlates with mitochondrial metabolism for each of the four fuels. In the case of glucose stimulation, the high control strength of glucose phosphorylation sets the pace of glucose metabolism and thus the rate of insulin secretion. However, bypassing this reaction with pyruvate, dihydroxyacetone, or glycerol uncovers constraints imposed by mitochondrial metabolism, each of which attains a similar maximal limit of insulin secretion. More specifically, we found that the hyperpolarization of the mitochondrial membrane, related to the proton export from the mitochondrial matrix, correlates well with insulin secretion. Based on these findings, we propose that fuel-stimulated secretion is in fact limited by the inherent thermodynamic constraints of proton gradient formation.

Published
2002
Full Text
View/download PDF

43. Circadian rhythm of ANP, aldosterone and PRA in normotensive IUGR

Author

Maggioni, Cristina, Lucini, Daniela, Antinozzi, Roberto, and Pagani, Massimo

Abstract

Atrial natriuretic peptide (ANP) increases are reported during normal pregnancy, but the relation to arterial pressure and the renin-angiotensin system is debatable. We assessed whether normotensive pregnancies with intrauterine growth retardation (IUGR) present an alteration of maternal ANP levels.

Published
2001

44. Overexpression of a Modified Human Malonyl-CoA Decarboxylase Blocks the Glucose-induced Increase in Malonyl-CoA Level but Has No Impact on Insulin Secretion in INS-1-derived (832/13) β-Cells*

Author

Mulder, Hindrik, Lu, Danhong, Finley, John, An, Jie, Cohen, Jonathan, Antinozzi, Peter A., McGarry, J. Denis, and Newgard, Christopher B.

Abstract

The long-chain acyl-CoA (LC-CoA) model of glucose-stimulated insulin secretion (GSIS) holds that secretion is linked to a glucose-induced increase in malonyl-CoA level and accumulation of LC-CoA in the cytosol. We have previously tested the validity of this proposal by overexpressing goose malonyl-CoA decarboxylase (MCD) in INS-1 cells, but these studies have been criticized due to: 1) the small insulin secretion response (2–4−fold) of the INS-1 cells used; 2) unknown contribution of the ATP-sensitive K+(KATP) channel-independent pathway of GSIS in INS-1 cells, which has been implicated as the site at which lipids regulate insulin granule exocytosis; and 3) deletion of the N-terminal mitochondrial targeting sequence, but not the C-terminal peroxisomal targeting sequence in the goose MCD construct, raising the possibility that a significant fraction of the overexpressed enzyme was localized to peroxisomes. To address these outstanding concerns, INS-1-derived 832/13 cells, which exhibit robustKATPchannel-dependent and -independent pathways of GSIS, were treated with a new adenovirus encoding human MCD lacking both its mitochondrial and peroxisomal targeting sequences (AdCMV-MCDΔ5), resulting in large increases in cytosolic MCD activity. Treatment of 832/13 cells with AdCMV-MCDΔ5 completely blocked the glucose-induced rise in malonyl-CoA and attenuated the inhibitory effect of glucose on fatty acid oxidation. However, MCD overexpression had no effect onKATPchannel-dependent or -independent GSIS in 832/13 cells. Furthermore, combined treatment of 832/13 cells with AdCMV-MCDΔ5 and triacsin C, an inhibitor of long chain acyl-CoA synthetase that reduces LC-CoA levels, did not impair GSIS. These findings extend our previous observations and are not consistent with the LC-CoA hypothesis as originally set forth.

Published
2001
Full Text
View/download PDF

45. Hepatocyte Nuclear Factor 4α Regulates the Expression of Pancreatic β-Cell Genes Implicated in Glucose Metabolism and Nutrient-induced Insulin Secretion*

Author

Wang, Haiyan, Maechler, Pierre, Antinozzi, Peter A., Hagenfeldt, Kerstin A., and Wollheim, Claes B.

Abstract

Mutations in the HNF4αgene are associated with the subtype 1 of maturity-onset diabetes of the young (MODY1), which is characterized by impaired insulin secretory response to glucose in pancreatic β-cells. Hepatocyte nuclear factor 4α (HNF4α) is a transcription factor critical for liver development and hepatocyte-specific gene expression. However, the role of HNF4α in the regulation of pancreatic β-cell gene expression and its correlation with metabolism secretion coupling have not been previously investigated. The tetracycline-inducible system was employed to achieve tightly controlled expression of both wild type (WT) and dominant-negative mutant (DN) of HNF4α in INS-1 cells. The induction of WT-HNF4α resulted in a left shift in glucose-stimulated insulin secretion, whereas DN-HNF4α selectively impaired nutrient-stimulated insulin release. Induction of DN-HNF4α also caused defective mitochondrial function substantiated by reduced [14C]pyruvate oxidation, attenuated substrate-evoked mitochondrial membrane hyperpolarization, and blunted nutrient-generated cellular ATP production. Quantitative evaluation of HNF4α-regulated pancreatic β-cell gene expression revealed altered mRNA levels of insulin, glucose transporter-2, L-pyruvate kinase, aldolase B, 2-oxoglutarate dehydrogenase E1 subunit, and mitochondrial uncoupling protein-2. The patterns of HNF4α-regulated gene expression are strikingly similar to that of its downstream transcription factor HNF1α. Indeed, HNF4α changed the HNF1α mRNA levels and HNF1α promoter luciferase activity through altered HNF4α binding. These results demonstrate the importance of HNF4α in β-cell metabolism-secretion coupling.

Published
2000
Full Text
View/download PDF

46. 35th Annual Meeting of the European Association for the Study of Diabetes

Author

Melander, A., Olsson, J., Lindberg, G., Salzman, A., Howard, T., Stang, P., Lydick, E., Emslie-Smith, A., Boyle, D. I. R., Evans, J. M. M., Macdonald, T. M., Bain, J., Sullivan, F., Juhl, C., Pørksen, N., Sturis, J., Hollingdal, M., Pincus, S., Veldhuis, J., Dejgaard, A., Schmitz, O., Kristensen, J. S., Frandsen, K. B., Bayer, Th., Müller, P., Dunning, B. E., Paladini, S., Gutierrez, C., Deacon, R., Valentin, M., Grunberger, G., Weston, W. M., Patwardhan, R., Rappaport, E. B., Sargeant, L. A., Wareham, N. J., Khaw, K. T., Zethelius, Björn, Lithell, Hans, Hales, C. Nicholas, Berne, Christian, Lakka, H.-M., Oksanen, L., Tuomainen, T.-P., Kontula, K., Salonen, J. T., Dekker, J. M., de Boks, P., de Vegt, F., Stehouwer, C. D. A., Nijpels, G., Bouter, L. M., Heine, R. J., Bruno, G., Cavallo-Perin, P., Bargero, G., D’Errico, N., Borra, M., Macchia, G., Pagano, G., Newton, R. W., Ruta, D. A., New, J. P., Wallace, C., Roxburgh, M. A., Young, R. J., Vaughan, N. J. A., Elliott, P., Brennan, G., Devers, M., MacAlpine, R., Steinke, D., Lawson, D. H., Decallonne, B., Casteels, K., Gysemans, C., Bouillon, R., Mathieu, C., Linn, Thomas, Strate, Christine, Schneider, Kerstin, Funda, D. P., Jirsa, M., Kozáková, H., Kaas, A., Kofronová, O., Tlaskalová-Hogenová, H., Buschard, K., Wanka, H., Hartmann, A., Kuttler, B., Rasmussen, S. B., Sørensen, T. S., Markholst, H., Petersen, J. S., Karounos, D., Dyrberg, T., Mabley, J. G., Haskó, G., Szabó, C., Seissler, J., Nguyen, T. B. T., Steinbrenner, H., Scherbaum, W. A., Cipriani, R., Gabriele, A., Sensi, M., Guidobaldi, L., Pantellini, F., Cerrito, M. G., Scarpa, S., Di Mario, U., Morano, S., Ceolotto, G., Iori, E., Baritono, E., Del Prato, S., Semplicini, A., Trevisan, R., Zerbini, G., Meregalli, G., Asnaghi, V., Tentori, F., Maestroni, A., Mangili, R., Marescotti, C., Vedovato, M., Tiengo, A., Tadjieva, J., Mankovsky, B. N., Van Aken, S., Raes, A., Vande Walle, J., Matthys, D., Craen, M., Hansen, H. P., Lund, S. S., Rossing, P., Jensen, T., Parving, H.-H., Andersen, S., Tarnow, L., Hansen, B. V., Trautner, C., Haastert, B., Ennenbach, N., Willich, S., Tabák, Á. Gy., Orchard, T. J., Spranger, J., Preissner, K. T., Schatz, H., Pfeiffer, A., Cantón, A., Burgos, R., Hernández, C., Lecube, A., Mesa, J., Segura, R. M., Mateo, C., Simó, R., Fathallah, L., Greene, D. A., Obrosova, I., Gilbert, R. E., Kelly, D. J., Cox, A. J., Berka-Wilkinson, J. L., Taylor, H. R., Panagiotopoulos, S., Lee, V., Jerums, G., Cooper, M. E., Hitman, G. A., Aganna, E., Ogunkolade, W. B., Rema, M., Deepa, R., Shanthi-Rani, C. S., Barakat, K., Kumarajeewa, T. R., Cassell, P. G., McDermott, M. F., Mohan, V., Ways, K., Bursell, S., Devries, T., Woodworth, J., Alatorre, C., King, G., Aiello, L. P., Karisen, A. E., Pavlovic, D., Nielsen, K., Jensen, J., Andersen, H. U., Pociot, F., Mandrup-Poulsen, T., Eizirik, D. L., Nerup, J., Lortz, S., Tiedge, M., Lenzen, S., Lally, F. J., Bone, A. J., Darville, M. I., Ho, Y.-S., Sternesjö, J., Sandler, S., Chen, M.-C., Schuit, F., Pipeleers, D. G., Merezak, S., Hardikar, A., Hoet, J. J., Remacle, C., Reusens, B., Bréant, B., Garofano, A., Czernichow, P., Kubota, N., Terauchi, Y., Miki, H., Tamemoto, H., Yamauchi, T., Nakano, R., Komeda, K., Eto, K., Tobe, K., Kimura, S., Kadowaki, T., Ide, T., Murakami, K., Tsunoda, M., Mochizuki, T., Ozanne, S. E., Nave, B. T., Wang, C. L., Dorling, M. W., Petry, C. J., Koopmans, S. J., van der Bent, C., Que, I., Radder, J. K., Sebokova, E., Sana, A. K., Klimes, I., Ruderman, N., Morviducci, L., Pastore, L., Morelli, S., Sagratella, E., Zorretta, D., Buongiomo, A., Tamburrano, G., Giaccari, A., Martinenghi, Sabina, De Angelis, Gabriella Cusella, Ravasi, Flavio, Bifari, Francesco, Bordignon, Claudio, Falqui, Luca, Kessler, A., Dransfeld, O., Sasson, S., Tomas, E., Zorzano, A., Eckel, J., Thorsby, P., Rosenfalck, A. M., Kjems, L., Hanssen, K. F., Madsbad, S., Birkeland, K. I., Hamilton-Wessler, M., Markussen, J., Bergman, R. N., Melki, V., Hanaire-Broutin, H., Bessières-Lacombe, S., Tauber, J.-P., Home, P. D., Lindholm, A., Riis, A., Rosenstock, J., Schwartz, S., Clark, C., Edwards, M., Donley, D., Swift, P., Mortensen, H. B., Lynggaard, H., Hougaard, P., Cull, C. A., Neil, H. A. W., Frighi, V., Manley, S. E., Holman, R. R., Turner, R. C., Steiner, G., Davis, W. A., Weeraratna, T., Bruce, D. G., Davis, T. M. E., Vergès, B., Duvillard, L., Pont, F., Florentin, E., Gambert, Ph., Benko, B., Ljubić, S., Turk, Z., Granić, M., März, W., Wollschläger, H., Klein, G., Neiss, A., Wehling, M., Huxtable, S. J., Saker, P. J., Walker, M., Frayling, T. M., Levy, J. C., O’Rahilly, S., Hattersley, A. T., McCarthy, M. I., Orecchio, A., Giacchini, A., Dominici, R., Canettieri, G., Trinti, B., Zani, M., Andreoli, M., Sciacchitano, S., de Silva, A. M., Whitecross, K., Pasco, J., Kotowicz, M., Nicholson, G., Zimmet, P., Boyko, E. J., Collier, G. R., Frittitta, L., Pizzuti, A., Argiolas, A., Graci, S., Goldfine, I. D., Bozzali, M., Ercolino, T., Costanzo, B., Iacoviello, L., Tassi, V., Trischitta, V., Wauters, M., Rankinen, T., Mertens, I., Chagnon, M., Bouchard, C., Van Gaal, L., Sivenius, K., Valve, R., Hakkarainen, V., Niskanen, L., Laakso, M., Uusitupa, M., Beridze, N., Japaridze, M., Kurashvili, R., Dundua, M., Kebuladze, G., Kazakhashvili, N., Offley-Shore, B., Thomas, B., Ghebremeskel, K., Crawford, M., Lowy, C., Eriksson, Ulf J., Martin Simán, C., Wisse, Bert, Gittenberger-de Groot, Adriana C., Wentzel, P., Eriksson, U. J., Wender-Ożegowska, E., Drews, K., Biczysko, R., Bronisz, A., Rość, D., Graczykowska-Koczorowska, A., Kotschy, M., Sokup, A., Kohnert, K. D., Besch, W., Strese, J., Frick, U., Zander, E., Kemer, W., Škrha, J., Kvasnička, J., Kalvodová, B., Hilgertová, J., Schatteman, K., Goossens, F., Scharpé, S., De Leeuw, I., Hendriks, D., Legakis, I. N., Panayiotou, D., Mountokalakis, Th. D., Enderle, M. D., Beckmann, P., Balletshofer, B., Rittig, K., Maerker, E., Volk, A., Meisner, C., Jacob, S., Matthaei, S., Häring, H. U., Rett, K., Ueda, K., Nakagawa, T., Shimajiri, Y., Kokawa, M., Matsumoto, E., Sasaki, H., Sanke, T., Nanjo, K., McKinnon, Caroline M., Macfarlane, Wendy M., Docherty, Kevin, Furukawa, N., Shirotani, T., Kishikawa, H., Kaneko, K., Araki, E., Shichiri, M., Prentki, M., Roduit, R., Susini, S., Buteau, J., Ejrnæs, A. M., Andersen, N. Aa., Osterhoff, M., Möhlig, M., Ortmann, J., Bikashaghi, F., Mayer, C., Bikashagi, F., Ackermans, M. T., Pereira Arias, A. M., Bisschop, P. H. L. T., Endert, E., Sauerwein, H. P., Romijn, J. A., Gastaldelli, A., Baldi, S., Pettiti, M., Natali, A., Frascerra, S., Camastra, S., Toschi, E., Ferrannini, E., Stingl, H., Krssak, M., Bischof, M. G., Krebs, M., Fürnsinn, C., Nowotny, P., Waldhäusl, W., Roden, M., Neeft, M., Meijer, A. J., Båvenholm, P., Pigon, J., Efendic, S., Kästenbauer, T., Sauseng, S., Sokol, G., Auinger, M., Irsigler, K., Abbott, C. A., Carrington, A. L., Faragher, B., Kulkarni, J., Van Ross, E. R. E., Boulton, A. J. M., Armstrong, D. G., Hadi, S., Nguyen, H. C., Harkless, L. B., Jirkovská, A., Kasalicky, P., Hosová, J., Skibova, J., Uccioli, L., Caselli, A., Giacomozzi, C., Macellari, V., Giurato, L., Lardieri, L., Menzinger, G., Pham, H. T., Rosenblum, B. I., Lyons, T. E., Giurini, J. M., Smakowski, P., Chrzan, J. S., Habershaw, G. M., Veves, A., Foster, A. M., Bates, M., Doxford, M., Edmonds, M. E., Kecha, O., Winkler, R., Martens, H., Collette, J., Lefèbvre, P. J., Greiner, D., Geenen, V., Atlan-Gepner, C., Naspetti, M., Valéro, R., Barad, M., Lepault, F., Vialettes, B., Naquet, P., de Galan, B., Netea, M. G., Hancu, N., Smits, P., Van der Meer, J. W. M., Osterbye, T., Jørgensen, K. H., Tranum-Jensen, J., Fredman, P., Høy, M., Bokvist, K., Olsen, H. L., Horn, T., Gromada, J., Laub, R., Lohmann, T., Hahn, H. J., Adler, T., Emmrich, F., Rabuazzo, A. M., Lupi, R., Dotta, F., Patanè, G., Marselli, L., Realacci, M., Piro, S., Del Guerra, S., Santangelo, C., Navalesi, R., Purrello, F., Marchetti, P., de Vos, P., Visser, L., de Haan, B. J., Klok, P., van Schilfgaarde, R., Poppema, S., Juang, J.-H., Kuo, C.-H., Hsu, B. R.-S., Nacher, V., Pérez, M., Biarnés, M., Raurell, M., Soler, J., Montanya, E., Ritzel, R., Maubach, J., Büsing, M., Becker, T., Klempnauer, J., Hücking, K., Schmiegel, W. H., Nauck, M. A., Bouček, P., Saudek, F., Adamec, M., Kožitarová, R., Jedináková, T., Vlasáková, Z., Skibová, J., Bartoš, V., Maffi, P., Bertuzzi, F., Aldrighetti, L., Taglietti, M. V., Castelnuovo, A., Pozza, G., Di Carlo, V., Secchi, A., Renier, G., Mamputu, J.-C., Gillespie, J. S., McMaster, D., Mercer, C., Trimble, E. R., Lecomte, M., Véricel, E., Paget, C., Ruggiero, D., Lagarde, M., Wiernsperger, N., Pricci, F., Leto, G., Amadio, L., Cordone, S., Iacobini, C., Catalano, S., Violi, F., Rotella, C. M., Pugliese, G., Zicari, A., Gradini, R., Sale, P., Pala, L., Cresci, B., Giannini, S., Manuelli, C., Dahlfors, G., Arnqvist, H. J., Gonelle-Gispert, C., Halnan, P. A., Sadoul, K., Wolter, S., Lang, J., Niwa, T., Yu, W., Hidaka, H., Senda, T., Niki, I., Fukasawa, T., Renstrom, E., Barg, S., Seward, E., Rorsman, P., Rutter, G. A., Molinete, M., Lilla, V., Ravazzola, M., Halban, P. A., Efanov, A. M., Bertorello, A. M., Zaitsev, S. V., Zwiller, J., Berggren, P.-O., MŞengül, A., Salman, F., Sargrn, M., Özer, E., Karşidaǧ, K., Salman, S., Gedik, S., Satman, İ., Dinççaǧ, N., Yılmaz, M. T., Lloyd, A., Hopkinson, P. K., Testa, M. A., Blonde, L., Turner, R. R., Hayes, J., Simonson, D. C., van der Ven, N. C. W., Lubach, C. H. C., Snoek, F. J., Mollema, E. D., van der Ploeg, H. M., Danne, T., Hoey, H., McGee, H., Fitzgerald, H., Lernmark, B., Thernlund, G., Fredin, K., Hägglöf, B., Lugari, R., Dell’Anna, C., Ugolotti, D., Dei Cas, A., Barilli, A. L., Sard, L., Marani, B., Iotti, M., Zandomeneghi, R., Gnudi, A., Kjems, L. L., Volund, Aa., Toft-Nielsen, M., Damholt, M. B., Hilsted, L., Hughes, T. E., Krarup, T., Holst, J. J., Young, A., Gottlieb, A., Fineman, M., Kolterman, O., Cancelas, J., García-Martínez, J. A., Villanueva-Peñacarrillo, M. L., Valverde, I., Malaisse, W. J., Filipsson, K., Ahrén, B., Balkan, B., Kwasnik, L., Battle, B., Li, X., Egan, J. M., Clocquet, A. R., Elahi, D., Petrella, E., Pricket, K., Petersen, K. F., Sullivan, J. T., Amatruda, J. M., Livingston, J. N., Shulman, G. I., Freyse, E.-J., Knospe, S., Glund, K., Demuth, H.-U., Walker, D., Malik, R. A., Reljanovic, M., Barada, A., Milicevic, Z., Tack, Cees J., Goldstein, David S., Van Huysen, C., Stevens, M. J., Cao, X., Sundkvist, G., Dahlin, L.-B., Eriksson, K.-F., Rosén, I., Lattimer, S. A., Sima, A. A. F., Sullivan, K., Shaw, J. E., de Courten, M. P., Zimmet, P. Z., Gourdy, P., Ruidavets, J. B., Arveiler, D., Amouyel, Ph., Bingham, A., Tauber, J. P., Lam, K. S. L., Wat, N. M. S., Lam, T. H., Janus, E. D., de Pablos, P., Rodriguez, F., Martínez, J., Sánchez, V., Santana, C., García, I., Macías, A., Levin, K., Hother-Nielsen, O., Henriksen, J. E., Beck-Nielsen, H., Brechtel, K., Machann, J., Koch, M., Nielsen, M., Löblein, K., Becker, R., Denignger, M., Renn, W., Machicao, F., Claussen, C. D., Schick, F., Diraison, F., Moulin, P., Beylot, M., Thams, P., Capito, K., Eliasson, Lena, Barg, Sebastian, Göpel, Sven, Kanno, Takahiro, Renström, Erik, Meda, P., Charollais, A., Gjnovci, A., Calabrese, A., Wonkam, A., Caton, D., Wisznievski, L., Serre, V., Cogne, F., Bauquis, J., Bosco, D., Huarte, J., Herrera, P., Gotfredsen, C. F., Vessby, B., Manuel y Keenoy, B., Engelen, W., Vertommen, J., Schrans, S., Louheranta, A., Lindström, J., Tuomilehto, J., Segal, K. R., Heymsfield, S., Hauptman, J., Boldrin, M., Lucas, C., Pandolfi, A., Cetrullo, D., Polishchuck, R., Alberta, M., Pellegrini, G., Calafiore, A., Vitacolonna, E., Capani, F., Consoli, A., Halleux, C. M., Gillot, E. F., Brichard, S. M., Van der Planken, M., Corthouts, B., Peiffer, F., Scholten, D., Walke, M., Assert, R., Pirags, V., Pedula, K. L., Hillier, T. A., Brown, J. B., Santini, S. A., Marra, G., Cotroneo, P., Manto, A., Di Leo, M. A. S., Di Gregorio, S., Tordi, A., Pitocco, D., Ruotolo, V., Ghirlanda, G., Temelkova-Kurktschiev, T., Schaper, F., Koehler, C., Henkel, E., Hanefeld, M., Mancini, L., Citterio, F., Cotroneo, A., Ceroone, S., Castagneto, M., Rajbhandari, S. M., Dent, M. T., Plater, M. E., Harris, N. D., Tesfaye, S., Ward, J. D., Dupuy, O., Mayaudon, H., Lecoules, S., Bauduceau, B., Palou, M., Farret, O., Molinié, C., Antonelli-Incalzi, R., Fuso, L., Giordano, A., Calcagni, M. L., Todaro, L., Basso, S., Tramaglino, L. M., Troncone, L., Pistelli, R., Guillot, R., Bringuier, A., Porokhov, B., Guillausseau, P. J., Feldmann, G., Zivanic, S., Cizmic, M., Dragojevic, R., Vanovic, M., Borghouts, L. B., van Kranenburg, G. P. J., Schaart, G., Keizer, H. A., Niess, A. M., Dickuth, H. H., Lutz, O., Barbe, P., Calazel-Fournier, C., Hernandez, G., Saint-Martin, F., Galitzky, J., Gonçalves, A. A., da Silva, E. C., Brito, I. J. L., da Silva, C. A., Lawrence, N. J., Kousta, E., Mulnier, H., Penny, A., Millauer, B., Johnston, D. G., Robinson, S., Perriello, G., Pimenta, W., Pampanelli, S., Lucidi, P., Lepore, M., Porcellati, F., Cordoni, M. C., De Feo, P., Bolli, G. B., Sjöstrand, M., Holmäng, A., Lönnroth, P., Hauer, B., Grauer, P., Artzner, S., Lang, R., Stumvoll, M., Monti, L. D., Piatti, P. M., Gemone, F., Valsecchi, G., Magni, M., Barbieri, E., Setola, E., Sandoli, E. P., Galli-Kienle, M., Pontiroli, A. E., Nichols, Gregory A., Brown, Jonathan B., Salzsieder, E., Boltz, H., Ramirez, J. C., Rutscher, A., Fischer, U., Koenig, Ch., Friske, M., Schramm, W., Landgraf, R., Bachmann, W., Bangemann, M., Groeneveld, G., Edvell, Anders, Lindström, Per, Tsiotra, P., Koukourava, A., Raptis, S. A., Tsigos, C., Boutou, E., Triandaffilopoulou, A., Egido, E. M., Rodríguez-Gallardo, J., Gutiérrez, E., García, P., Silvestre, R. A., Marco, J., Khan, Akhtar, Ling, Zong-Chao, Ahren, Bo, Efendic, Suad, Bünting, C., Du, X., Zhi Sui, G., Rösen, P., Koschinsky, T., Kearney, T. M., Sharp, P. S., Lapolla, A., Fedele, D., Martano, L., Garbeglio, M., Seraglia, R., Favretto, D., Traldi, P., Meerwaldt, R., Smit, A. J., Links, Th. P., v. Roon, A. M., Graaf, R., Gans, R. O. B., Deynelİ, O., Ersöz, H. Ö., Gogas, D., Fak, A. S., Akalin, S., Veglio, M., Sivieri, R., Chinaglia, A., Scaglione, L., Le, T., Wong, N., Detrano, R., Charles, M. A., Colhoun, H. M., Francis, D. P., Rubens, M., Underwood, S. R., Fuller, J. H., Knudsen, E., Sato, A., Nielsen, F. S., Bonora, E., Kiechl, S., Willeit, J., Oberhollenzer, F., Egger, G., Bonadonna, R., Muggeo, M., Festa, A., D’Agostino, R., Howard, G., Mykkänen, L., Tracy, R. P., Haffner, S. M., Poulsen, P., Vach, K., Ijzerman, R. G., Bakker, S. J. L., Truster, J., Crowther, N. J., Cameron, N., Gray, I. P., Chaillous, L., Carel, J. C., Thivolet, C., Boitard, C., Charbonnel, B., Saï, P., Decochez, K., Keymeulen, B., Somers, G., Dorchy, H., Rottiers, R., Winnock, F., ver Elst, K., Weets, I., Pipeleers, D., Gorus, F., Seebaum, S., Schumm-Draeger, P.-M., Petzoldt, R., Federlin, K., Bonnevie-Nielsen, V., Martensen, P. M., Justesen, J., Worsaa, A., Karlsson, Maria, Sederholm, Sofia, Ludvigsson, Johnny, Bélicar, P., Dale, C., Vague, Ph., Alessis, C., Lassmann-Vague, V., Bode, B. W., Gross, T. M., Ghegan, M., Steed, R. D., Davidson, P. C., Ordoñez, A., Rubio, J. L., Sulleiro, J. M., Buendía, J. P., Zamora, J., Castillo, M., Schaupp, L., Ellmerer, M., Brunner, G. A., Sendlhofer, G., Schlack, Ch., Skrabal, F., Wach, P., Pieber, T. R., Heinemann, L., Krämer, U., Klötzer, H. M., Hermann, M., Cosgrove, K. E., Chapman, J. C., Shepherd, R. M., McIntyre, S., Butler, P. C., Dunne, M. J., Brekardin, E., Dörschner, H., Schwanstecher, C., Schwanstecher, M., Uhde, I., Emmanouilidou, E., Teschemacher, A. G., Pouli, A. E., Gylfe, E., Tengholm, A., Hellman, B., Perfetti, R., Aggarwal, S., Müller, Günter, Welte, Stefan, Wied, Susanne, Valverde, A. M., Mur, C., Kahn, C. R., Benito, M., Rondinone, C. M., Peterson, T., Laviola, L., Belsanti, G., Logoluso, F., Napoli, R., Davalli, A. M., Weir, G. C., Giorgino, R., Giorgino, F., Flesch, S., Hompesch, B., Rave, K., Susanto, F., Kühn-Velten, W. N., Heise, T., Rendell, M., Dole, J., Esper, R. J., Stein, E., Lemme, L., Rubinstein, A., Maritz, F. J., Soule, S., Market, A., Chajek-Shaul, T., Maislos, M., Tal, S., Stolero, D., Josefsen, K., Beckmann, H., Petersen, C., Ekman, R., Efanova, I., Zaitsev, S., Berggren, P. O., Birkenbach, M., Holl, R. W., Rosenbauer, J., Grabert, M., Icks, A., Schwab, O., Reile, K., Janssen, M. M. J., de Jongh, R. T., Casteleijn, S., Masurel, N., Hoogma, R. P. L. M., Santeusanio, F., Brunetti, P., Fanelli, C. G., Laureti, S., Bartocci, L., Maran, A., Crepaldi, C., Trupiani, S., Macdonald, I. A., Avogaro, A., Bouman, S. D., Keitz, M., Bruggink, J. E., Scheurink, A. J. W., Strubbe, J. H., Steffens, A. B., Ferguson, S. C., McCrimmon, R. J., Perros, P., Best, J. J. K., Deary, I. J., Frier, B. M., Robinson, R. T. C. E., Ireland, N. H., Bedford, C., Fairclough, E., Hudson, S., Heller, S. R., Borch-Johnsen, K., Berger, M., Overmann, H., Bender, R., Blank, M., Sawicki, P., Jörgens, V., Mühlhauser, I., Nosadini, R., Sailer, A., Dalla Vestra, M., Brocco, E., Piarulli, F., Frigato, F., Sambataro, M., Velussi, M., Baggio, B., Fioretto, P., Jager, A., van Hinsbergh, V. W. M., Kostense, P. J., Nrjpels, G., Gæde, P., Pedersen, O., Andrysiak-Mamos, E., Majkowska, L., Krzyżanowska, B., Pilarska, K., Czekalski, S., Mazzon, C., Brocco, S., Field, L. L., Nejentsev, S., Gombos, Z., Veijola, R., Knip, M., Simell, O., Vaarala, O., Åkerblom, H. K., Ilonen, J., Krokowski, M., Bodalski, J., Andrzejewski, W., Ławnik, M., Teodorczyk, A., Heinrich, A., Caillat-Zucman, S., Buzzetti, R., Petrone, A., Mesturino, C., Giorgi, G., Fiori, R., Nisticò, L., Di Genova, G., Cascino, I., Klöting, I., Kovacs, P., McKinney, P. A., Okasha, M., Parslow, R. C., Law, G. R., Gurney, K. A., Williams, R., Bodansky, H. J., Herzig, P., Giani, G., Vervoort, G., Lutterman, J. A., Berden, J. H. M., Wetzels, J. F. M., Paniagua, O., Shaw, L., Austin, C., Heagerty, A. M., Seppälä-Lindroos, A., Vehkavaara, S., Yki-Järvinen, H., Caballero, A. E., Lim, S. C., LoGerfo, F. W., Horton, E. S., Zembowicz, A., Fragasso, G., Caumo, A., Phan, V. C., Costa, S., Conti, M., Chierchia, S. L., Vigili de Kreutzenberg, S., Marchetto, S., Calò, L., Wascher, T. C., Wölkart, G., Brunner, F., Tripathy, Devjit, Carlsson, Martin, Isomaa, Bo, Tuomi, Tiinamaija, Groop, Leif, Stoffers, D. A., Muller, D. C., Wideman, L., Chin, G. A., Clarke, W. L., Hanks, J. B., Habener, J. F., Guazzarotti, L., Toffolo, G., Clementi, L., Vespasiani, G., Cobelli, C., Clauin, S., Bellanné-Chantelot, C., Bartolotta, E., Gautier, J.-F., Wilson, C., Weyer, C., Mort, D., Knowler, W. C., Polonsky, K., Bogardus, C., Pratley, R. E., Porksen, N., Veldhuis, J. D., Polonsky, K. S., Byrne, M. M., Brandt, A., Arnold, R., Katschinski, M., Göke, B., Hardt, E., Fritsche, A., Stefan, N., Schützenauer, S., Lüddeke, H. J., Renner, R., Hepp, K. D., Shnawa, N., Krugluger, W., Hopmeier, P., Schernthaner, G., Kautzky-Willer, A., Prager, R., Fallucca, F., Sabbatini, A., Sciullo, E., Torresi, P., Mazziotti, F., Maroccia, E., Napoli, A., Buongiorno, A., Deberg, M., Dozio, N., Castiglioni, M. T., Sodoyez-Goffaux, F., Carvalheiro, M., Fagulha, I., Fagulha, A., Gomes, L., Paiva, S., Marta, E., Sobral, E., Leitão, F., Pinto, L., Ruas, M., Buchanan, T., Di Cianni, G., Volpe, L., Casadidio, I., Bottone, P., Teti, G., Boldrini, A., Benzi, L., Rasera, T., Becciu, V., Beretta, A., Almirante, G., Castiglioni, M., Kerényi, Zs., Stella, P., Nádasdi, Á., Baranyi, É., Csákány, M. Gy., Tamás, Gy., Mehta, Z. M., Manley, S., Zimmett, P., Bottazzo, G. F., Hoey, Hilary, Mollensen, Henrik, Hougaard, Philip, McGee, Hanna, Vidal, J., Fernández, M., Sesmilo, G., Casamitjana, R., Gomis, R., Conget, I., Rathmann, W., Curran, S., Mitchell, J., Hennings, S., Katsaros, T., Saflianis, I., Gigiakou, E., Kasi, E., Polychroniades, V., Dzien, A., Dzien-Bischinger, Ch., Hadjidakis, D., Apostolopoulou, N., Sfakianakis, M., Raptis, A. E., Ryysy, L., Häkkinen, A.-M., Goto, T., Westerbacka, J., Halavaara, J., Libman, I., Pietropaolo, M., LaPorte, R., Pietropaolo, S., Becker, D., Pirie, F. J., York, D. F., Motala, A. A., Omar, M. A. K., Tzaneva, V., Iotova, V., Jaeger, C., Hatziagelaki, E., Stroedter, A., Becker, F., Bretzel, R. G., Strebelow, M., Schlosser, M., Ziegler, B., Ziegler, M., Wassmuth, R., Ostrauskas, R., Žalinkevičius, R., Norkus, A., Jarosz-Chobot, P., Otto-Buczkowska, E., Koehler, B., Maklakiewicz, E., Green, A., Ionescu-Tirgoviste, C., Serban, V., Guja, C., Mota, M., Creteanu, G., Calin, A., Morosanu, M., Ferariu, I., Halmagy, I., Cristescu, I., Strugariu, M., Minescu, A., Barbul, R., Visalli, N., Sabastiani, L., Adorisio, E., Cassone Faldetta, M. R., Multari, G., Casu, A., Songini, M., Pozzilli, P., Muntoni, Sa., Wäänänen, S., Law, G., Muntoni, S., Shubnikov, E., Choubnikova, J., Mikulecký, M., Michalková, D., Hlava, P., Teuscher, A. U., Reinli, K., Teuscher, A., Zhao, H. X., Stenhouse, E., Moyeed, R., Demaine, A. G., Millward, B. A., Feltbower, R. G., Holland, P., Campbell, F., Fear, N. T., Wasmuth, H. E., Elliott, R. B., McLachlan, C., Erhardt, G., Kolb, H., Guaita, G., Pelligra, I., Motzo, C., Obinu, M., Cossu, E., Cirillo, R., Kinalski, M., Krętowski, A., Bingley, P., Kinalska, I., Douek, I. F., Bingley, P. J., Gale, E. A. M., Imagawa, A., Hanafusa, T., Miyagawa, J., Matsuzawa, Y., Todd, J. A., Welsh, K., Marshall, S., Nolsøe, R., Kristiansen, O. P., Larsen, Z., Johannesen, J., Jahromi, M. M., Larsen, Z. M., Kyvik, K. O., Jeanclos, E., Schork, N. J., Aviv, A., Sieradzki, J., Małecki, M. T., Klupa, T., Hanna, L., Sieradzka, J., Frey, J., Królewski, A. S., Calvo, B., Bilbao, J. R., Perez de Nanclares, G., Castaño, L., Santos, J. L., Pérez-Bravo, F., Piquer, S., Puig-Domingo, M., Carrasco, E., Calvillán, M., De Leiva, A., Albala, C., Cavallo, M. G., Manca Bitti, M. L., Suraci, C., Crinò, A., Giordano, C., Cervoni, M., Sbriglia, M. S., Bizzarri, C., Marietti, G., Füchtenbusch, M., Bonifacio, E., Kredel, K., Schnell, O., Ziegler, A. G., Assaad-Khalil, S. H., Michelsen, B. K., El-Azzouni, O., Abou-Seif, M., Kamel, F., Fouad, K., Abdel-Aty, T., El-Sheikh, S., Zamani, Mahdi, Pociot, Hemming, Nerup, Jorn, Cassiman, Jean-Jacques, Olivares, E., Ladrière, L., Laghmich, A., Sener, A., Scott, F. W., Ivanova, O., Poltorack, V., Gorbenko, N., Gladkich, A., Nikitchenko, I., Dunger, A., Augstein, P., Berg, S., Williams, A. J. K., Norcross, A. J., Gillmor, H. A., Lampasona, V., Bernasconi, L., Hermite, L., Martin-Moutot, N., Boucraut, J., Seagar, M., Couraud, F., Scirpoli, M., Maioli, M., Tonolo, G., Bekris, L., Schranz, D., Ciccarese, M., Lernmark, A., Lee, H. C., Nam, J. H., Ahn, C. W., Song, Y. D., Lim, S. K., Kim, K. R., Huh, K. B., Fajardo, C., Carmona, E., Sanchez-Cuenca, J. M., Campos, V., Carles, C., Brazales, A., Merino, F., Piñón, F., Mašek, Z., Perušičová, J., Bárová, H., Šterzl, I., Hejduková, H., Schneiderka, P., Hink, S., Muzyka, B., Streit, G., Kopp, H. P., Kroiss, A., Tankova, T., Dakovska, L., Kirilov, G., Koev, D., Abrams, P., De Block, C., Rooman, R., Du Caju, M., Eibl, N. L., Wolf, H., Eibl, M. M., Di Cesare, E., Previti, M., Lombardo, F., Di Benedetto, A., Romano, G., De Luca, F., Cucinotta, D., Brunelle, R. L., Huang, J., Fineberg, S. E., Anderson, J. H., List, C., Lamesch, P., Kohlhaw, K., Schwarz, C., Wenzke, M., Richter, O., Hauss, J., Zeng, S. F., Xu, X. S., Zheng, S. X., Shii, K., Baba, S., Bonfanti, R., Bazzigaluppi, E., Meschi, F., Bognetti, E., Bosi, E., Chiumello, G., Cinapri, V., Quilici, S., Forotti, G., Giampietro, O., Matteucci, E., Luppi, P., Zanone, M. M., Rudert, W., Haluszczak, C., Alexander, A., Bertera, S., Gottlieb, P., Trucco, M., Irnstetter, A., Jäger, G., Schenker, M., Ziegler, M. A. G., Myśliwiec, J., Szelachowska, M., Monetini, L., Valente, L., Coppolino, G., Stefanini, L., Corbi, S., Spera, S., Matteoli, M. C., Ferrazzoli, F., Cantagallo, A., De Mattia, G. C., Walker, B., Sonnet, E., Gibassier, J., Derrien, C., Massart, C., Allannic, H., Maugendre, D., Leech, N. J., Elsegood, K. A., Narendran, P., Hubbard, A., Dayan, C. M., Mianowska, B., Bodalska-Lipińska, J., Chrul, S., Wyka, K., Geissler, A., Schneider, M. L., Bochow, B., Koop, I., Zhang, T. M., Zhang, Y., Han, C. H., Jin, S. X., Dervogormiyacıyan, H., Araslı, M., Aydemir, D., Yıllar, G., Deniz, G., Gürol, A. O., Aktaş, E., Tütüncü, Y., Pertyñska, M. P., Banasik, M., Zeman, K., Cypryk, K., Wilczyñski, J., Tchórzewski, H., Müser, E. S., Baier, J. E., Bergbauer, M., Schmutz, G., Figge, A., Reiser, M., Schmiegel, W., Burkart, V., Kim, Y.-E., Kauer, M., Utsugi, T., Kanda, T., Kobayashi, I., Uchiyama, T., Ito, H., Ohyama, Y., Tomono, S., Kawazu, S., Nagai, R., Hehmke, B., Heinke, P., Kelemen, K., Wegmann, D., Hutton, J. C., Wachlin, G., Schröder, D., Schmidt, S., Schloot, N. C., Hanifi-Moghaddam, P., Goebel, C., Rothe, H., Hausmann, A., Laureys, J., Depovere, J., Waer, M., Karsten, V., Tritschler, S., Belcourt, A., Pinget, M., Kessler, L., Gregori, S., Sala, L., Smiroldo, S., Davalli, A., Adorini, L., Bo, S., Repetti, E., Gentile, L., Fornengo, P., Bruno, A., Ferrero, L., Kanoun, F., Harzallah, F., Ftouhi, B., Mekaouar, A., Bellaaj, R., Fekih, M., Mebazaa, A., Zouari, B., Ben Khalifa, F., Spijkerman, A. M. W., Ruige, J. B., Colagiuri, S., Colagiuri, R., Palu, T., Na’ati, E., Muimui-heata, S., Samiu, O., deBlieck, C., Ta’ai, A., Foliaki, S., Hussain, Z., McLennan, M., Hansen, C. N., Ibsen, H., Dogadin, S. A., Nozdratchev, K. G., Lidfeldt, J., Nerbrand, C., Lindholm, L. H., Samsioe, G., Scherstén, B., Agardh, C.-D., Wójcikowski, Cz., Grzeszczak, W., Łopatyński, J., Bandurska-Stankiewicz, E., Mardarowicz, G., Król, H., Matej, A., Czupryniak, L., Kropiwnicka, A., Drzewoski, J., Viljoen, E., Costa, A., Martinez, S., Carmona, F., Levy, I., Baruffaldi, L., Solerte, B., Mantovani, E., Boullu, S., Jeandidier, N., Legaludec, V., Costa, B., Franch, J., Martín, F., Morató, J., Donado, A., Basora, J., Daniel, J., Sayeed, M. A., Mahtab, H., Kibriya, M. G., Khanam, P. A., Azad Khan, A. K., de Courten, M., Chitson, P., Cox, H., King, R., Dachtler, J., Johnston, D., Ito, C., Kataoka, M., Lakhdar, A. A., Myers, M. A., Fuecker, K., Echwald, S. M., Hansen, T., Ekstrøm, C. T., Urhammer, S. A., Eiberg, H., Roberts, S., Barrow, B. A., Hainsworth, J., Schousboe, K., Henriksenog, J. E., Sørensen, T. I. A., Herlihy, O. M., Timmer, B., Grant, P. J., Bennett, S. M. A., Ghunaim, S. A., Stewart, M. W., Baroni, M. G., Sentinelli, F., Lovari, S., Vitali, M., Capici, F., Barbetti, F., Weng, J. P., Lehto, M., Li, H., Forsblom, C., Groop, L., Blanche, H., Morel, V., Hansen, L., Stanojevic, V., Petersen, H. V., Urioste, S., Stoffers, D., Møller, A. M., Serup, P., Ek, J., Durviaux, S., Clausen, J. O., Rousseau, G. G., Lemaigre, F. P., Bjørkhaug, L., Njølstad, P. R., Lindner, T., Cockburn, B. N., Molven, A., Søvik, O., Lindner, T. H., Horikawa, Y., Sovik, O., Frederiksen, S. K., Almind, K., Van Obberghen, E., Kovács, P., van den Brandt, J., Fenger, M., Vaag, A., Haist, K., Weisser, M., Rettig, A., Zhang, M., Chung, S. S. M., Pihlajamäki, J., Karjalainen, L., Karhapää, P., Vauhkonen, I., Cassell, P., Uwakwe, N., Kopelman, P., Ramachandran, A., Snehalatha, C., Rasmussen, S. K., Lautier, C., Grigorescu, F., Smith, R. J., Frayling, T., Turner, R., Hitman, G., Subba Rao, P., Bennett, A. J., Jones, E., Lathrop, G. M., Menzel, S., Wahid, F., Cooper, L., Scott, J., Aitman, T. J., Galli, J., Fakhrai-Rad, H., Kamel, A., Marcus, C., Norgren, S., Luthman, H., Wallis, R. H., Collins, S. C., Kaisaki, P. J., Ktorza, A., Lathrop, M., Gauguier, D., Huxtable, S., McCarthy, M., Shimomura, H., Hanabusa, T., Tsunoda, K., Lazdins, M., Dalgaard, L. T., Jensen, N. M., Jensen, J. N., Lynn, S., Turnbull, D. M., Pérez de Nanclares, G., Gaztambide, S., Vázquez, J. A., Groves, C. J., Izmajlowicz, M. L., Horton, V. A., Owen, R. J., Stratton, I. R., Green, F. R., Groves, C., Horton, V., Owen, R., Stratton, I., Clark, L. A., Voigt, A., Rochlitz, H., Rau, H., Braun, J., Schmidt, K., Plock, K., Donner, H., Schöneberger, A., Usadel, K. H., Badenhoop, K., Bendlová, B., Mazura, I., Včelák, J., Vondra, K., Palyzová, D., Svatoš, J., Mikšová, P., Russo, G., Couture, P., Wilson, P. W. F., Cupples, L. A., Otvos, J. D., Schaefer, E. J., Ordovas, J. M., Malecki, M. T., Ji, L., Curtis, S., Rich, S. S., Warram, J. H., Krolewski, A. S., Gudayol, M., Usac, E. F., van Essen, E. H. R., Roep, B. O., ’t Hart, L. M., Janssen, J. J., van den Ouweland, J. M. W., Lemkes, H. H. P. J., Maassen, A. J., Nakano, S., Fukuda, M., Maejima, K., Imaizumi, N., Kitazawa, M., Nishizawa, M., Kigoshi, T., Uchida, K., Le Gall, J. Y., David, V., Baltrusch, S., Richter, T., da Silva Xavier, G., Dickens, M., Belin, V. D., Green, I. C., Burns, C. J., Squires, P. E., Howell, S. L., Persaud, S. J., Ban, N., Yamada, Y., Someya, Y., Ihara, Y., Tsuda, K., Seino, Y., Alcazar, O., Tyrberg, B., Carlsson, C., Andersson, A., Mukai, E., Ishida, H., Fujimoto, S., Kajikawa, M., Fujita, J., Tsuura, Y., Malaisse-Lagae, F., Picton, S., Tamarit-Rodriguez, J., Mukala-Nsengu-Tshibangu, A., Fernández, S., Giné, E., Ortsäter, H., Liss, P., Åkerman, K. E. O., Bergsten, P., Hu, S., Wang, S., Roos, E. S., Gounarides, J. S., Shapiro, M. J., de Souza, C. J., Papas, K. K., Nishimura, M., Kadiata, M. M., Louchami, K., Jijakli, H., Rajan, A. S., Kuang, S., Iyer, D., Waddell, I. D., Holloway, B. R., Ishihara, H., Wang, H., Wollheim, C. B., Ayvaz, G., Mercan, D., Rasschaert, J., Giroix, M.-H., Scruel, O., Portha, B., Broca, C., Fernandez-Alvarez, J., Manteghetti, M., Gross, R., Sauvaire, Y., Petit, P., Ribes, G., McClenaghan, N. H., Ball, A. J., Flatt, P. R., Rustenbeck, I., Dickel, C., Winkler, M., Grimmsmann, T., Meyer, U., Gross, I., Barnes, P. D., O’Brien, R. E., Abdel-Wahab, Y. H. A., Hashmi, M. N., Giesberts, A. N., White, S. J., Cooper, E. J., Hudson, A. L., Eglen, R. M., Dillon, M. P., Chan, S. L. F., Morgan, N. G., Parini, A., Gotfredsen, C., Ullrich, S., Su, J., Rösier, M., Hescheler, J., Greger, R., Wardt, R., Arredouani, A., Gailly, P., Henquin, J. C., Gilon, P., Macfarlane, W. N., Docherty, K., Jonkers, F. C., Schöfl, C., Börger, J., von zur Mühlen, A., Brabant, G., Grapengiesser, E., Harris, T. E., Buchan, A. M. J., Jones, P. M., Jaikaran, E. T. A. S., Marcon, G., St George-Hyslop, P. H., Fraser, P. E., Clark, A., Lebrun, P., Antoine, M.-H., Nguyen, Q.-A., Rorsman, Patrik, Wasmeier, C., Antinozzi, P., Maechler, P., Schwartz, E., Wollheim, C., Roderigo, H. M., Matsumoto, K., Ebihara, K., Yamamoto, H., Tabuchi, H., Fukunaga, K., Yasunami, M., Ohkubo, H., Miyamoto, E., Horn, P. A., García-Barrado, M. J., Sancho, C., Martín, M., Moratinos, J., Westerlund, J., Lin, J. M., Brown, R., Björklund, A., Grill, V., Detimary, P., Guiot, Y., Rahier, J., Elmi, A., Sehlin, J., Hauge-Evans, A. C., Cybal, M., Druzyńska, J., Wierzchowska, J., Krippeit-Drews, P., Drews, G., Krämer, C., Jornot, L., Düfer, M., Nöda, M., Yamashita, S., Takahashi, N., Tsubamoto, Y., Kasai, H., Sharp, G. W. G., Lembert, N., Joos, H. C., Ammon, H. P. T., Wahl, M. A., Ainscow, E. K., Zhao, C., Fabregat, M. E., Fernández-Álvarez, J., Franco, C., Novelli, M., Fernàndez-Alvarez, J., Masiello, P., Lajoix, A., Beffy, P., Roux, S., Chardès, T., Roye, M., Lajoix, A. D., Reggio, H., Peraldi-Roux, S., Henningsson, R., Salehi, A., Lundquist, I., Stickings, P., Mistry, S., Ratcliff, H., Morris, S. M., Cunningham, J. M., Ekelund, M., Ermakova, N. V., Paulssen, R. H., Florholmen, J., Carmellini, M., Mosca, F., Patané, G., Longo, D., Squatrito, S., Clement, L., Magnan, C., Vincent, M., Penicaud, L., Assimacopoulos-Jeannet, F., Vigneri, R., Rolfsen, S. E. D., Gregersen, S., Hermansen, K., Blondeau, B., Rojas, I., Novials, A., Femández-Usac, E., Cristóbal, P., Higham, C. E., Lawrie, L., Sherman, K. I. J., Birch, N., Tito, P., Robinson, C. V., de Koning, E. J. P., Verbeek, J. S., Esapa, C., Laube, B., Powell, D. S., Maksoud, H., Chargé, S. B. P., Matthews, D. R., Stratton, I. M., Karlsson, S., Myrsén-Axcrona, U., Östlund, B., Sundler, F., Bertrand, G., Puech, R., Bockaert, J., Persson-Sjögren, S., Täljedal, I.-B., Mooney, M. H., O’Harte, F. P. M., Simonsson, E., Abdel-Halim, Samy M., Efendić, Suad, Ahrén, Bo, Yanagida, K., Arima, T., Yada, T., Egéa, J. C., Hirtz, C., Deville de Périère, D., Meoni, C., Falqui, L., Arcelloni, C., Paroni, R., Folli, F., Barry, R., Turner, N. C., Tadayyon, M., Arch, J. R., Sutti, F., Perego, L., Baglioni, S., Otte, A., Socci, C., Raffaele, H. S., Stumpf, E., Aalto, Y., Otonkoski, T., Knuutila, S., Andersson, L. C., Berra, C., Furlan, R., Coppelli, A., Tellini, C., Bordignon, C., Rouiller, D. G., Lister, C. A., Moore, G. B. T., Piercy, V., Newman, M., Chapman, H., Smith, S. A., Anastasi, E., Bulotta, A., Tiberti, C., Ponte, E., Liddi, R., Taruscio, D., Falchi, M., Annerén, C., Welsh, M., Bernard, C., Ilic, C., Guilbert, V., Palgi, J., Korbutt, G. S., Rayat, G. R., Rajotte, R. V., Kieffer, T. J., Karlsson, Ella, Sandler, Stellan, Boujendar, S., Huotari, M.-A., Miettinen, P. J., Keski-Oja, J., Breda, E., Pacini, G., Vilsbøll, T., Toft-Nielsen, M.-B., Dinesen, B., Corssmit, E. P. M., Qvigstad, E., Mostad, I. L., Bjerve, K., Ann, C. W., Kume, M., Hiramatsu, M., Taniguchi, J., Saito, Y., Kawasaki, Y., Kanazawa, M., Notoya, Y., Hayashi, T., Djemli, A., Gallice, P., Coste, T., Jannot, M. F., Dufayet, D., Raccah, D., Vague, P., Sattar, S., Basak, R. C., Hasan, Z., Ali, L., Nikulina, M. A., Karlsen, A. E., Hong, T. P., Andersen, N. A., Puren, A. J., Fantuzzi, G., Dinarello, C. A., Gysemans, C. A., Sparre, T., Fey, S., Larsen, P. M., Andersson, A. K., John, N. E., Fey, S. J., Mose Larsen, P., Frigerio, S., Ghayur, T., Holländer, G. A., Zumsteg, U., Pinach, S., Monge, L., Grassi, G., Pasquero, P., Ruiu, G., Dall’Omo, A., Carta, Q., Hadjivassiliou, V., Dunger, A. M., Green, M. H. L., Rasilainen, S., Roivainen, M., Ylipaasto, P., Bouwens, L., Hovi, T., Sekine, N., Takahashi, K., Ishikawa, T., Okazaki, T., Fujita, T., Elliott, J., Scarpello, J. H. B., Conroy, S., Byrne, P., Newsholme, P., Harrison, M., Greenl, I. C., Kaya, F., Süsleyici, B., Öztürk, M., Eisner, M., Guldbakke, B., Karpenko, N., Brizgalova, G., Alesina, M., Røder, M. E., Schwartz, R. S., Prigeon, R., Kahn, S. E., Kendereški, A., Micić, D., Šumarac, M., Macut, Dj., Zonć, S., Čolić, M., Cvijović, G., Gligorović, P., Courtney, C. H., Atkinson, A. B., Ennis, C., Sheridan, B., Bell, P. M., Jolly, M., Amin, R., Godsland, I., Horvoka, R., Anyaoku, V., Lawrence, N., Krasova, N., Sergienko, L., Mingrone, G., Plat, L., Balasse, E. O., Zykova, T., Jenssen, T., Strelkova, A., Zykova, S., Tipisova, E., Féry, F., Wijenaike, A. N., Watt, P. W., Jung, R. T., Bolton-Smith, C., Rennie, M. J., Ludvik, B., Aigmueller, Th., Waldhaeusl, W., Courtois, P., Bource, F., Guenat, E., Philippe, J., Jéquier, E., Tappy, L., Benny, Santosa, Grönemeyer, Dietrich, Aygen, Sitke, Scholz, Nicole, Busch, Martin, Tauveron, I., Rochon, C., Dejax, C., Benoit, P., Capitan, P., Bayle, G., Prugnaud, J., Fabricio, A., Champredon, C., Thieblot, P., Grizard, J., Nielsen, M. F., Nyholm, B., Chandramouli, V., Schumann, W. C., Landau, B. R., Rizza, R. A., Mitrakou, A., Meyer, C., Tolias, A., Platanisiotis, D., Vlachos, L., Gerich, J., Wajngot, A., Sprangers, F., Jellema, W. T., Lopuhaä, C. E., van Lieshout, J. J., van der Zee, J. S., Mithieux, G., Croset, M., Zitoun, C., Hurot, J. M., Rajas, F., Montano, S., Willem, R., Verbruggen, I., Grue-Sørensen, G., Björkling, F., Watson, N. D., Burns, S. P., Murphy, H. C., Iles, R. A., Cohen, R. D., Rooney, K., Swan, V., Phuyal, J., Millar, J., Bryson, J., Denyer, G., Caterson, I., Thompson, C., Gaster, M., Handberg, Aa., Schrøder, H. D., Alzaid, A., Sobki, S., Thye-Rønn, P., Alford, F., Christopher, M., Gras, F., Brunmair, B., Neschen, S., Py, G., Lambert, K., Raynaud, E., Mercier, J., Tsuchihashi, K., Sumida, Y., Fujimoto, H., Nakamura, M., Miyata, E., Furuta, M., Katsuki, A., Ito, K., Sasaki, R., Hori, Y., Yano, Y., Adachi, Y., Lauritz, J., Eriksson, J. W., Burén, J., Zhao, L. J., Li, Z.-C., Kullin, M., Karlsson, F. A., Redondo, A., Puente, J., Clemente, F., González, N., Moberg, E., Amer, P., Hagström-Toft, E., Bolinder, J., Björnholm, M., Krook, A., Galuska, D., Myers, M., Zierath, J. R., Wallberg-Henriksson, H., Niklasson, M., Strindberg, L., Sternberg, F., Hebeda, S., Kratzer, W., Salgado, M. I., Hoss, U., Kalatz, B., Lohmann, S., Fussgänger, R., Khomazjuk, A. I., Ncscheret, A. P., Gonchar, I. V., Quinones-Galvan, A., Sironi, A. M., Cominacini, L., Nagai, Y., Yamashita, H., Takamura, T., Kobayashi, K., Szanto, I., Peth, J. A., Kinnick, T. R., Youngblood, E. B., Tritschler, H. J., Henriksen, E. J., Gašperíková, D., Rufo, C., Teran-Garcia, M., Nakamura, M. T., Clarke, S. D., Pye, S., Zhang, Z., Radziuk, J., Guignot, L., Bell, K. S., Lim-Fraser, M., Cooney, G., Kraegen, E. W., Takayama, S., Legare, D. J., Macedo, M. P., Lautt, W. W., Bradley, B., Barron, P., Davies, J., Ader, M., Richey, J. M., Ait El Mkadem, S., Macari, F., Renard, E., Méchaly, I., Brun, J. F., Cros, G., Bringer, J., del Aguila, L. F., Krishnan, R. K., Farrell, P. A., Ulbrecht, J., Correll, P. H., Kirwan, J. P., Mei, J., Rahn-Landström, T., Brindley, D., Manganiello, V., Degerman, E., Ziv, E., Shafrir, E., Kaiman, R., Galer, S., Bar-On, H., Gerő, L., Földes, K., Janssen, J., Járay, J., Perner, F., Haap, M., Houdali, B., Schmit, M. B., Dietze, G. J., Perrini, S., Natalicchio, A., Montrone, C., de Robertis, O., De Pergola, G., Strack, V., Kellerer, M., Kausch, C., Condorelli, G., Beguinot, F., Häring, H.-U., Song, X. M., Chibalin, A. V., Ryder, J. W., Jiang, X. J., Alessi, D. R., Hennige, A. M., Metzinger, E., Seipke, G., Trüb, T., Hey, A., Sørensen, A. R., Schäffer, L., Drejer, K., Kurtzhals, P., Hansen, B. F., Matozaki, T., Noguchi, T., Yamao, T., Takada, T., Ochi, F., Takeda, H., Inagaki, K., Hosoka, T., Kasuga, M., Schürt, M., Meier, M., Drenckhan, M., Meyer, M., Aries, S. P., Klein, H. H., Telting, D., van der Zon, G. C. M., Dorrestijn, J., Maassen, J. A., Clapham, J. C., Holder, J. C., Tomlinson, K. M., Pickavance, L., Buckingham, R., Wilding, J., Jacinto, S. M., Harrold, J., Ljung, B., Kjellstedt, A., Thalén, P., Widdowson, P., Williams, G., Oakes, N., Aoki, K., Saito, T., Satoh, S., Mukasa, K., Kaneshiro, M., Kawasaki, S., Hoshino, K., Okamura, A., Sekihara, H., Smith, U., Johansson, A., Nilsson, E., Olausson, T., Nakazawa, T., Suzuki, M., Martinez, J., Murado, P., Azal, Ö., Yönem, A., Çakır, B., Polat, Z., Kutlu, M., Çorakçı, A., Bayraktar, M., Gürlek, A., Koray, Z., Damian, M. S., Linn, T., Laube, H., Arzner, S., Meißner, H.-P., Giunti, S., Comune, M., Cassader, M., Conte, M. R., Sacchi, C., Musso, G., Mecca, F., Depetris, N., Gambino, R., Perin, P. Cavallo, Kawakami, S., Sandqvist, M., Jansson, P.-A., Šindelka, G., Widimský, J., Haas, T., Prázný, M., Mari, A., Nolan, J. J., Uusitupa, M. I. J., Karşıdağ, K., Hacıhanefioğlu, B., Dinççağ, N., Drivsholm, T., Palacios, R. T., Vølund, A., Pedersen, Oluf B., Letiexhe, M. R., Scheen, A. J., Quiñones Galvan, A., Simeoni, M., Basu, A., Uosukainen, A., Mäkimattila, S., Schlenzka, A., Adler, A. I., Levy, J., Stevens, R., Matthews, D., Holman, R., Boland, B. J., Jeanjean, M., Hermans, M. P., Maudoigt, C., Tonglet, R., Robert, A., Quiñones-Galvan, A., Cini, G., Galetta, F., Sanna, G., Gernone, F., Janssen, M. J., Gonera, R. K., Wolffenbuttel, B. H. R., de Leeuw, P. W., Schaper, N. C., Molęda, P., Kuczerowski, R., Czech, A., Tatoń, J., Taddei, S., Patiag, D., Qu, X., Wilkes, M., Gray, S., Seale, J. P., Donnelly, R., Campión, J., Maestro, B., Dávila, N., Carranza, M. C., Calle, C., Hales, C. N., Fernández-Real, J. M., Grasa, M., Pugeat, M., Barret, C., Ricart, W., Lindmark, S., Olsson, T., Tufvesson, M., Loeblein, K., Mehnert, B., Haering, H. U., Rave, Klaus, Heise, Tim, Clauson, Per, Hirschberger, Sabine, Heinemann, Lutz, Claret, M., Nadal, B., Truc, A., Rossi, L., Hildebrand, P., Ketterer, S., Beglinger, C., Keller, U., Gyr, K., Parvin, S., Overkamp, D., Vayreda, M., González-Huix, F., G-Huix, F., Zavaroni, I., Gasparini, P., Massironi, P., Zuccarelli, A., Delsignore, R., Reaven, G. M., Sheu, W. H. H., Lee, W. J., Chen, Y.-T., Iraklianou, S., Tournis, S., Volonakis, I., Spylopoulou, M., Bilianou, E., Melidonis, A., Foussas, S., Güler, Serdar, çakir, Bekir, Demi̇rbaş, Berrin, Gürsoy, Gül, Serter, Rüştü, Aral, Yalçin, Morton, G., Lee, S., Fahey, R., de Silva, A., Cai, X. J., Buckingham, R. E., Arch, J. R. S., Wilson, S., Clausen, J. T., Kristensen, P., Nielsen, P. F., Wulff, B. S., Thim, L., Holness, M. J., Sugden, M. C., Fryer, L. G. D., Munns, M. J., Mannucci, E., Ognibene, A., Cremasco, F., Bardini, G., Mencucci, A., Ciani, S., Pierazzuoli, E., Tsuchihashil, K., Rigalleau, V., Delafaye, C., Baillet, L., Vergnot, V., Brunou, P., Gatta, B., Gin, H., Felber, J. P., Munger, R., Assimacopoulos, F., Bobbioni, E., Golay, A., Wilken, M., Larsen, F. S., Buckley, D., Molina, L. M., Marquez, L., Arbeo, A., Hernandez, C., Kofod, H., Damholt, A. B., Buchan, A., Márquez, L., Luque, M. A., Sarti, L., Sutton, P. J., Behle, K., Heimesaat, M. M., Hüfner, M., Gravholt, Claus Højbjerg, Mølier, Niels, Christiansen, Jens Sandahl, Schmitz, Ole, Deacon, C. F., Brock, B., Knudsen, L. B., Agersø, H., Huusfeldt, P. O., Kelly, C. M. N., Brunn, C., Schioos, J., Sewing, S., Lemansky, P., Wawro, S., Mest, H. J., Taguchi, T., Motoshima, H., Yoshizato, K., Guenifi, Amel, Henriksson, M., Johansson, J., Shafqat, J., Tally, M., Wahren, J., Jömvall, H., Ekberg, K., Rigler, R., Pramanik, A., Kratz, G., Johansson, B.-L., Uhlén, M., Jörnvall, H., Forst, T., Dufayet De La Tour, D., Kunt, T., Pfützner, A., Goitom, K., Pohlmann, T., Schneider, S., Johansson, B. L., Löbig, M., Engelbach, M., Beyer, J., Ekman, Bertil, Nyström, Fredrik, Arnqvist, Hans J., Halvatsiotis, P. G., Meek, S., Bigelow, M., Nair, K. S., Maghsoudi, S., Fisker, S., Vølund, A. A., Jörgensen, J. O. L., Christiansen, J. S., Hilsted, J., Mazerkina, N. A., Tiulpakov, A. N., Gorelyshev, S. K., Peterkova, V. A., Macut, D. J., Dieguez, C., Casanueva, F. F., Catalina, P. F., Mallo, F., Andrade, A., García-Mayor, R. V. G., Popova, V. V., ter Maaten, J. C., Popp-Snijders, C., Madsen, L., Ukropec, J., Bergene, E., Rnstan, A. C., Berge, R., Arner, P., Wahl, G., Häring, H., Bryson, J. M., Curtis, S. E., Caterson, I. D., Winzell, M. Sörhede, Svensson, H., Ahnén, B., Holm, C., Phillips, C., Madigan, C., Owens, D., Collins, P., Johnson, A., Tomkin, G. H., Cabezas, M. Castro, van Oostrom, A. J. H. H. M., Erkelens, D. W., Summers, L. K. M., Fielding, B. A., Ilic, V., Clark, M. L., Frayn, K. N., Pietzsch, J., Julius, U., Nitzsche, S., Fischer, S., Lindgren, C., Amrot-Fors, L., Hoffmann, M. M., Luft, D., Schmülling, R.-M., D’Adamo, M., Leonetti, F., Paoloni, A., Ribaudo, M. C., Basso, M. S., Elmore, U., Restuccia, A., Sbraccia, P., Emilsson, V., O’Dowd, J., Heyman, R., Cawthorne, M. A., Pelikánová, T., Kazdová, L., Žák, A., Chvojková, Š., Özer, E. M., Kadıoğlu, P., Korugan, Ü., Hatemi, H., Rivellese, A. A., Dullaart, R. P. F., Riemens, S. C., Sluiter, W. J., van Tol, A., Farnier, M., Megnien, S., Turpin, G., Stulp, B. K., Brambilla, P., Brunelli, A., Riva, M. C., Manzoni, P., de Poli, S., Riboni, S., Stolk, R. P., Meijer, R., Wink, O., Zelissen, P. M. J., van Gils, A. P. G., Grobbee, D. E., Vilarrasa, N., Gimenez, O., Lopez, L., Insa, R., Fdez Castañer, M., Cabrera-Rode, E., Perich, P., Diaz-Horta, O., Molina, G., Fernández Castañer, M., López, L., Jiménez, O., Boltaña, A., Ampudia-Blasco, F. J., Martínez, I., Civera, M., Ascaso, J. F., Carmena, R., Ahmed, K., Luzio, S., Furmaniak, V., Owens, D. R., Dionadji, Mbainguinam, Mbaissouroum, Mouanodji, Anderson, J., Garg, S., MacKenzie, T., Shephard, M., Peery, B., Chase, H., Holstein, A., Thießen, E., Kaufmann, N., Egberts, E.-H., Lutgers, H. L., Hullegie, L. M., Hoogenberg, K., Wientjes, K. J., Schoonen, A. J., Wientjes, K. J. C., Schoonen, A. J. M., Weitgasser, R., Gappmayer, B., Pichler, M., Sapin, R., Friess, P., Eskes, S. A., de Vries, J. H., Pouwer, F., van Ballegooie, E., Spijker, A. J., Jeng, L., Winsett, J., Tubiana-Rufi, N., Munz-Licha, G., Polak, M., Sheehan, J., Ulchaker, M., Toeller, M., Üstün, A., Yilmaz, M. T., Aparicio, M., Peyron, E., Rizkalla, S. W., Taverna, M., Guerre-Millo, M., Chevalier, A., Pacher, N., Slama, G., Gorshunska, M., Buyken, A. E., Heitkamp, G., Kabir, M., Oppert, J. M., Wursch, P., Bruzzo, F., Rahman, M. H., Fatima, K., Ahmed, S., Mondal, H. N., Yilmaz, M., Öztok, U., Karakoç, A., Çakır, N., Düzgün, E., Yetkin, İ., Arslan, M., Şardaş, S., Wilding, John, Géloën, A., Baret, G., Dalmaz, Y., Peyronnet, J., Clémenceau, B., Martignat, L., Lalain, S., Gouin, E., Kenda-Ropson, N., Miller, A. O. A., You, S., Aguilera, E., Recasens, M., Flores, L., Ricart, M. J., Fernández-Cruz, L., Esmatjes, E., Crenier, L., Noël, C., Le Moine, A., Mahy, M., Danguy, A., Kiss, R., Goldman, M., Bracci, C., De Haan, B., Nilsson, K., Deschamps, J. Y., Glagoličová, A., Smrčková, I., Dieterle, C., Illner, W. D., Land, W., Feldmeier, H., Scheuer, R., Lalli, C., Di Loreto, C., Ellringmann, U., Balks, H. J., v. zur Mühlen, A., Dengler, R., Weissenborn, K., Rasmussen, B. M., Ørskov, L., Watson, J., Owen, G., Barrett, G., Ingleby, J., Weiss, M., Deary, I., Cavan, D., Kerr, D., Bruneiii, A., Cuce’, A., Elsing, H. G., Kühne, D., Quinn, N. D., Warner, D. P., Buysschaert, M., Jamal, R., O’Brien, T., Latare, P., Mullen, J., Rein, A., Wargo, M., Parkes, J. L., Ginsberg, B., Sotiropoulos, A., Peppas, Th. A., Kotsini, V., Apostolou, O., Bousboulas, S., Michailidis, E., Sawala, M., Pappas, S., Nilsson, P. M., Nilsson, J. Å., Berglund, G., Molins, T., Esteban, J. I., Genescà, J., Paris, I., Haufroid, V., Selvais, Ph., Petit, J. M., Duong, M., Grappin, M., Guiguet, M., Rudoni, S., Portier, H., Brun, J. M., Bagg, W., Plank, L., Drury, P. L., Sharpe, N., Braatvedt, G. D., Carrascosa, J. M., Molero, J. C., Fermίn, Y., Andrés, A., Satrústegui, J., Rietzsch, H., Patzak, A., Schwanebeck, U., Simpson, H., Robertson-Mackay, F., Montegriffo, E., Fox, C., Chiasson, J.-L., Josse, R. G., Dorman, J. M., Gerstein, H. C., Lau, D., Leiter, L. A., Maheux, P., Meneilly, G. S., Murphy, L., Rodger, N. W., Ross, S. A., Ryan, E., Yale, J.-F., Wolever, T. M. S., Haller, T., Elias, I., Segal, P., Standi, E., Rybka, J., Sencer, E., Satman, I., Schlcnzka, A., Vakkilainen, J., Tsaglis, H., Ioannidis, I., Giakoumaki, A., Amantou, A., Komitopoulos, N., Georgiou, S., Varsamis, E., Katsilambros, N., El Gayar, M., Shereba, N., Botros, R., Fikry, R., Jackson, D., Balme, M., Silva-Nunes, J., Alves, J., Bogalho, P., Gardete-Correia, L., Nunes-Corrêa, J., Kot’átková, A., Němcová, D., Vrbíková, J., Zamrazil, V., Meyer, L., Delbachian, I., Lehert, P., Cugnardey, N., Drouin, P., Guerci, B., Wagner, O. F., Jones, N. P., Vallance, S. E., Thompson, K. A., Miller, A. K., Inglis, A. M. L., Patterson, S., Jorkasky, D., Freed, M. I., Mathisen, A. L., Schneider, R., Rubin, C., Houser, V., Beebe, K. L., Kortboyer, J. M., Eckland, D. J. A., Cranmer, H., Mori, Y., Kurokawa, N., Komiya, H., Horikoshi, H., Yokoyama, J., Tajima, N., Ikeda, Y., Bakst, A., Hemyari, P., Lönnqvist, F., Owen, S., Vikramadithyan, R. K., Chakrabarti, R., Misra, P., Prem Kumar, M., Sunil Kumar, K. B., Ghosh, A., Rajagopalan, R., Goldstein, B., Katoh, S., Tsuruoka, N., Hata, S., Matsushima, M., Ikemoto, S., Inoue, Y., Edwards, G., Fonseca, V., Biswas, N., Bakris, G., Viberti, G., Rebuck, A. S., Weill, S., Abel, M. G., Klappoth, W., Brodesser, A., Linkeschowa, R., Pushparaj, P., Tan, C. H., Tan, B. K. H., Bahner, A., Parker, J., Waite, G., Lipson, V., Nahar, N., Rokeya, B., Parveen, S., Nur-e-Alam, M., Mosihuzzaman, M., Hansen, A. Kornerup, Lepore°, M., Kurzhals, R., Pampanelli°, S., Fanelli°, C. G., Bolli°, G. B., Ratner, R. E., Hirsch, I. B., Mecca, T. E., Wilson, C. A., Mohideen, P., Mudaliar, S., Deutsch, R., Ciaraldi, T., Armstrong, D., Kim, B., Morrill, B., Sha, X., Henry, R., Meyer, B. H., Scholtz, H. E., van Niekerk, N., Rosenkranz, B., Schoenle, E., Witthaus, Elke, Bradley, Clare, Stewart, John, Barbeau, M., Myers, S., Flora, D., DiMarchi, R., Chance, R., Plum, A., Larsen, P. S., Larsen, U. D., Kristensen, J. B., Jansen, J. A., Olsen, B., Mortensen, H., Hylleberg, B., Jacobsen, L. V., Gall, M.-A., Søgaard, B., Ewing, F. M., Ireland, R. H., Hoogwerf, B., Raskin, P., Jovanovic, L., Leiter, L., Boss, A. H., Bott, U., Ebrahim, S., Hirschberger, S., Leukel, P., Sieber, H. J., McGill, J., Kilo, C., Kamp, N. M., Wutte, A., Le Thai, F., Balarac, N., Allicar, M. P., Cazeneuve, B., Augendre, B., Wise, S. D., Seah, E. S., Koivisto, V., Torlone, E., Del Sindaco, P., Ciofetta, M., Hedman, C., Orre Pettersson, A.-C., Lindström, T., Cernigoi, A. M., Kong, N., Kitchen, M. M., Ryder, R. E. J., Petkova, M., Angelova-Gateva, P., Malone, J., Arora, V., Bue-Valleskey, J., Pein, M., Diebler, F., Roach, P., Gudat, U., Dreyer, M., Hanusch, U., Ristic, S., McLeod, J., Hirschberg, Y., Garreffa, S., Keilson, L., Mather, S., Gagen, K., Chen, W., Dragonas, N., Chuang, L. M., Juang, J. H., Wu, H. P., Chiang, Y. D., Li, K. L., Jorgensen, L. N., Tai, T. Y., Cheatham, W. W., Kennedy, F., Woo, V., Jain, R., Boss, A., Moses, R., Clauson, P., Fischer, T., Björk, S., Østergaard, A., Langendorf, K. W., Hatorp, V., Hasslacher, C., Farrar, N. S., Chambers, N. J., Denyer, G. S., Johnston, G. A. R., Hashiguchi, S., Jönsson, A., Hallengren, B., Rydberg, T., Herbaut, C., Turc, A., Mourand, I., Chevassus, H., Molinier, N., Christensen, A.-B. L., Mathiesen, E. R., Stage, E., Damm, P., Boivin, S., Gross, P., Pennington, M., Harder, T., Kohlhoff, R., Dörner, G., Rohde, W., Plagemann, A., Ferdeghini, M., Murru, S., Maffei, M., Cecchetti, P., Dunne, F., Brydon, P., Smith, T., Proffitt, M., Holder, R., Gee, H., Goulis, D. G., Teoh, T. G., Asatiani, N., Elphick, A., Natsvlishvili, M., Chanturia, T., Shelestova, E., Ramazashvili, M., Hod, M., Cederberg, J., Casi, A. Leunda, Pampfer, S., De Hertogh, R., Hinck, L., Aly, S., Bertie, J., Botta, R. M., Imbergamo, M. P., Impiccichè, M. G., Todaro, B., Greco, D., Ekbom, P., Clausen, P., Feldt-Rasmussen, U., Feldt-Rasmussen, B., Mølsted Pedersen, L., Nørgaard, K., Svenningsen, A., Nielsen, L., Zmudzińska, M., Ziętek, I., Min, Y., Crawford, M. A., Bozzoni, F., Corubolo, C., Borrello, E., Di Biase, N., Spagnolo, S., Hawthorne, G., Sen, D., Bagust, A., Maier, W., Currie, C. J., Sailesh, S., Patel, V., Hayes, D., Cockrill, B., Gatling, W., Budd, S., Mullee, M. A., Savill, A. W., Smithers, M. G., Davies, R. R., Sandford, A., Stutz, L., Vadstrup, S., Simonsen, V., Musaeus, L., Molsing, B., Lyholm, B., Turner, B. C., Jenkins, E., Hejlesen, O. J., Andreassen, S., Hovorka, R., Cavan, D. A., Klinge, A., Strauss, K. W., Guthrie, R., Testa, M., Zimmerman, R., Sandberg, M., Steinfatt, H., Hardenberg, R., Gottsmann, M., König, A., Schmauß, S., Hierl, F. X., Renders, C. M., Valk, G. D., van Eijk, J. Th. M., van der Wal, G., Jermendy, G., Hídvégi, T., Müller, U. A., Junghänel, J., Köhler, S., Köhler, C., Schumann, M., Use, G., de Valk, H. W., Blankestijn, J. G., de Bruin, H. J., Bottomley, J., Gillam, S., Holmes, J., Murphy, M., Madani, S. F., Müller, R., Hunger Dathe, W., Grüßer, M., Roien, D., Hussain, M., Vibe-Petersen, J., Braun, A., Schiel, R., Höfer, A., Leppert, K., Trento, M., Passera, P., Tomalino, M., Bajardi, M., Vaccari, P., Pagnozzi, F., Pomero, F., Molinatti, G. M., Porta, M., Blaauwwiekel, E. E., Hania, M., Scholten-Jaegers, S. M. H. J., Links, T. P., Perciun, R., Dumitrescu, C., Skeie, S., Thue, G., Sandberg, S., Nordfeldt, S., Ludvigsson, J., García, Rosario, Suárez, Rolando, Henry, J. L., Kangas, M., Wilson, P. H., Pibernik, M., Szabo, S., Metelko, Ž., González-Clemente, J. M., Galdon, G., De Pedro, B., Fontanals, Ll., Miñarro, A., Topsever, P., Azık, A., Karşıdaǧ, K., Dündar, Y., Şengül, A., Vileikyte, L., Apostolou, T., Tomenson, B., Bundy, C. H., Gokal, R., Gormley, D. A., Baksi, A. K., Hrachovinová, T., Csémy, L., Bartášková, D., Krch, F. D., Gåfvels, M. C., Lithner, F., Branchtein, L., Matos, M. C. G., Gaio, D., Yamashita, T., Pousada, J. M. D. C., Duncan, B. B., Schmidt, M. I., Buchanan, T. A., Xiang, A. H., Tan, S., Peters, R. K., Trigo, E., Kjos, S. L., Lee, W. P., Azen, S., Ilic, S., Mezic, J., Pettitt, D. J., Bastyr, E. J., Camps, I., Salcedo, M. D., Rius, F., Rubio, M., Baptista, C., Martins, T., Ruas, M. M. A., Acosta, D., Cerrillos, L., Soto, A., Quijada, D., Morales, F., Silva, H., García-Hernandez, N., Villamil, F., Astorga, R., Selby, P. L., Jude, E. B., Biggs, A. M., Al-Sabbagh, S., Kumar, S., Rowbotham, J., McKenzie, W. E., Dodson, P. M., Barnett, A. H., Maresh, M., Alevizaki, M., Anastasiou, E., Grigorakis, S. I., Philippou, G., Michalopoulou, G., Souvatzoglou, A., Corcoy, R., Pau, E., Pascual, E., García-Patterson, A., Albareda, M. L., Ccrmeño, J., Altirriba, O., Adelantado, J. M., Ubeda, J., Endocrinologia, S., Reichelt, A. J., Nucci, L., Teixeira, M. M., Costa-e-Forti, A., Ciampalini, P., Giannone, G., Benedetti, S., Borrelli, P., Czerniawska, M., Manowska, B., Rami, B., Schober, E., Hueppe, A., Granditsch, G., Huber, W., Bittmann, B., Jaeger, A., Saukkonen, T., Väisänen, S., Savilahti, E., Šumník, Z., Kotalová, R., Loudová, M., Cinek, O., Šnajderová, M., Kolousková, S., Vavřinec, J., Barbato, M., Viola, T., Formisano, M., Hovind, P., Adler, I. A., Makita, Z., Takeuchi, M., Kamada, Y., Koike, T., Courrèges, J. P., Pradier, P., Bacha, J., Aboud, E., André, L., Lamarca, R., Janeczko-Sosnowska, E., Lewandowski, Z., Janeczko, D., Kopczyñski, J., Nakagami, T., Tomonaga, O., Babazono, T., Iwamoto, Y., Nakanishi, K., Higa, M., Kosugi, E., Elving, L. D., Szadkowska, A., Mirecka, M. W., Czerniawska, E., Weekers, L., Hadjadj, S., Belloum, R., Gallois, Y., Bouhanick, B., Marre, M., Saucha, W., Skwarna, B., Zychma, M., Żukowska-Szczechowska, E., Zychma, M. J., Zukowska-Szczechowska, E., Nazim, J., Dziatkowiak, H., Sanak, M., Cieślik, G., Nannipieri, M., Viberti, G. C., De Cosmo, S., Piras, G., Errannini, E., Uchigata, Y., Miura, J., Okada, T., Gong, J.-S., Zhang, J., Tanaka, M., Wamoto, Y., Zucaro, L., Bacci, S., Miscio, G., Thomas, M., Piras, G. P., Cavallo Perin, P., Mauer, M., Barzon, I., Bortoloso, E., Saller, A., Crepaldi, G., Latif, Z. A., Christensen, P. K., v. Larsen, S., Olsen, S., Bombonato, G., Sacerdoti, D., Chiesura-Corona, M., Marangon, A., Rudberg, S., Rasmussen, L., Bangstad, H.-J., Ösrterby, R., Sivous, G. I., Kasatkina, E. P., Demurov, L. M., Nosikov, V. V., Kotova, A. K., Kuraeva, T. L., Mishina, I. I., Gorashko, N. M., Nosicov, V. V., Petercova, V. A., Berrut, G., Alhenc-Gelas, F., Tsimaratos, M., Gerbi, A., Barone, R., Ollerton, R. L., Playle, R. A., Luzio, S. D., Evans, W. D., Burch, A., Siebenhofer, A., Meinitzer, A., Brandmaier, H., Brunner, G., Plank, J., West, P., Tindall, H., McKenna, K., Smith, D., Tormey, W., Kesson, C. M., Thompson, C. J., Penno, G., Anichini, R., Bandinelli, S., Boldrini, E., Giannarelli, R., Piazza, F., Pucci, L., Karunakaran, S., Morris, R. J., Nádas, J., Farkas, K., Daróczy, A., Péterfai, É., Svensson, M., Weigert, C., Facchin, S., Gambaro, G., Brodbeck, K., Schleicher, E., Tada, H., Nomura, K., Kuboki, K., Tsukamoto, M., Inokuchi, T., Menè, P., Pugliese, F., Iino, K., Yoshinari, M., Iwase, M., Asano, T., Sonoki, K., Wakisaka, M., Takata, Y., Ujishima, M., Del Prete, D., Anglani, F., Antonucci, F., Mauri, J. M., Vallés, M., Gutiérrez, C., Vendrell, J., Shinada, M., Akdeniz, A., Panagiotopoulos, P., Bach, L. A., Law, V. A., Lecomte, P. P., Yokota, C., Okuda, Y., Odawara, M., Yamashita, K., Yamada, N., Kawai, K., Açbay, Ö., Mazlum, A., Kural, E., Gündoğdu, S., Jensen, C., Körner, A., Eklöf, A.-Ch, Jaremko, G., Lal, M., DiBona, G., Aperia, A., Yavuz, D. G., Tuncer, M., Sargon, M., Küçükkaya, B., Ahıskalı, R., Akalın, Sema, Nohara, E., Oates, P. J., Ellery, C. A., Yonem, A., Azal, O., Cakýr, B., Erdogan, M. F., Corakcý, A., Ozdemir, I. C., Stevens, R. J., Yudkin, J. S., Webber, J., Wheeler, D. C., Taylor, K. G., Jones, S. L., Srivatsa, A., Anderson, S. G., Cruikshank, J. K., Florkowski, C. M., Scott, R. S., Graham, P. J., Moir, C. L., Flores, C., Ruggenenti, P., Dodesini, A. R., Vasile, B., Gaspari, F., Arnoldi, F., Ferrari, S., Ciocca, I., Spalluzzi, A., Remuzzi, G., Delvigne, C., Ballaux, D., Bosman, D. R., Winkler, A. S., Marsden, J., Watkins, P. J., Strutton, D., Erbey, J. R., Jacobsen, P., Rossing, K., Jensen, J. S., Mansfield, M. W., Kowalska, I., Telejko, B., Bachórzewska-Gajewska, A., Prokop, J., Kochman, W., Musiał, W., Naskręt, D., Oleksa, R., Zozulińska, D., Sowiński, J., Wierusz-Wysocka, B., Klamann, A., Jonas, M., Müller-Lung, U., Heuser, L., Launhardt, V., Valensi, P., Pariès, J., Torremocha, F., Brulport, V., Sachs, R. N., Vanzetto, G., Levy, M., Lormeau, B., Halimi, S., Perfornis, A., Boumal, D., Zimmermann, C., Bernard, Y., Sabbah, A., Meneveau, N., Gautier, S., Bassand, J. P., Anděl, M., Kraml, P., Potočková, J., Dvořáková, H., Trešlová, L., Nuttall, S. L., Martin, U., Kendall, M. J., Schiaffini, R., Pantaleo, A., Battocletti, T., Vaccari, V., Brufani, C., Martuscelli, E., Gargiulo, P., Nieszner, E., Posa, I., Kocsis, E., Préda, I., Pogatsa, G., Koltai, M. Z. S., Stefanidis, A., Manoussakis, S., Handanis, S., Zairis, M., Vitalis, D., Dadiotis, L., Fiorina, P., La Rocca, E., Astorri, E., Rossetti, C., Lucignani, G., Giudici, D., Castoldi, R., Mazarakis, N., Giagiakou, E., Karavidas, A., Agellou, A., Karamani, O., Matsakas, E., Caviezel, F., Morricone, L., Ranucci, M., Denti, S., Cazzaniga, A., Enrini, R., Isgrò, G., González de Molina, F. J., Sala, J., Masià, R., Marrugat, J., Kruszewski, P., Wolnik, B., Bieniaszewski, L., Świerblewska, E., Semetkowska-Jurkiewicz, E., Krupa-Wojciechowska, B., Vasilikos, P. G., Alaveras, A. E. G., Anastasopoulos, N. G., Chala, E., Sidira, M., Christakopoulos, P. D., Poulsen, P. L., Hansen, K. W., Ebbehøj, E., Knudsen, S. T., Mogensen, C. E., Ramu, Y., Vidyullatha, Y., Strojek, K., Gorska, J., Morawin, E., Ritz, E., Ciavarella, A., Malini, P. L., Strocchi, E., Fiumi, N., Ambrosioni, E., Idzior-Waluś, B., Stevens, L., McEneny, J., O’Kane, M. J., Moles, K. W., McMaster, C., Young, I. S., Leonhardt, W., Konstadelou, E., Gürlek, Alper, Soedamah-Muthu, S., Taskinen, M. R., Ehnholm, C., Wägner, A., Bayen, Laia, Rigla, M., Ortega, E., Caixàs, A., Mestrón, A., Ordóñez, J., Pérez, A., Sotiropoulou, G., Servais, P. L., Bertolotto, A., Pilo, M., Suchánková, G., Andratschke, S., Tschöp, M., Strasburger, C.-J., Rizzo, L., Aerts, P., Vinckx, M., Ansquer, J. C., Ryan, M., Buter, H., Navis, G. J., de Jong, P. E., de Zeeuw, D., Carreras, G., Giménez, G., Pou, J. M., Howorka, K., Gabriel, M., Pumprla, J., Köves, A., Bhowmik, N. B., Haque, A., Rahman, A., Paleari, F., Gamba, P., Mauri, G., Rovaris, G., Giannattasio, C., Piatti, M. L., Zincone, A., Cavaletti, G., Mancia, G., Lan, S., Arezzo, J., Gerber, R. A., Klioze, S. S., Saponara, C., Tartaglione, T., Cercone, S., Caputo, S., Meloni, T., Brunetti, D., Di Lazzaro, V., Xu, G., Jiang, H. Y., Shy, M. E., Sugimoto, K., Zhang, W.-X., Kuchmerovskaya, T., Donchenko, G., Shymansky, I., Kuchmerovsky, N., Pakyrbaeva, L., Cameron, N. E., Keegan, A., Cotter, M. A., Mirrlees, D., Smale, S. E., Biessels, G. J., Duis, S. E. J., Kamal, A., Gispen, W. H., Carrington, A., Carman, S., Smiarowski, H., Lavoie, D., Sawicki, D., Sabetta, A., Litchfield, J., Van Zandt, M., Sredy, J., Smirnova, V., Strokov, I., Ivanova, L., Ichunina, A., Nakamura, J., Nakayama, M., Hamada, Y., Chaya, S., Kato, K., Kasuya, Y., Mizubayashi, R., Miwa, K., Yasuda, Y., Kamiya, H., Hotta, N., Bíró, K., Kukorelli, T., Szilágyi, N., Kürthy, M., Komáromy, A., Mogyorosi, T., Nagy, K., Çakir, M., Baskal, N., Güllü, S., Elhan, A. H., Erdogan, G., Ziegler, D., Piolot, R., Neubauer, J., Senesi, B., Bonetti, R., Napolitano, A., Canepa, F., Ottonello, P., Schabmann, A., Giménez-Pérez, G., Arroyo, J. A., López, T., Ponz, E., Mauricio, D., Diem, P., Zanchin, L., Suter, S. L., Lefrandt, J. D., Smit, A., van Roon, A. M., Dullaart, R., Voita, D., Mackevics, V., Vitols, A., Lengyel, Cs., Farkas, Gy., Török, T., Légrády, P., Várkonyi, T. T., Kardos, A., Gingl, Z., Kempler, P., Rudas, L., Lonovics, J., Marchand, M., Stevens, L. K., Tarnás, Gy., Estrella, F., Christensen, N. J., Keresztes, K., Barna, I., Hermányi, Zs., Vargha, P., Bonnevie, L., Chanudet, X., Larroque, P., Tutuncu, N. Bascil, Deger, A., Batur, M. K., Yildirir, A., Onalan, O., Aksöyek, S., Kabakçι, G., Erbaş, T., Galicka-Latała, D., Surdacki, A., Gerritsen, J., TenVoorde, B. J., Heethaar, R. M., Tagawa, T. S., Kodama, M., Yoshioka, R., Yamasaki, Y., Didangelos, T., Athyros, V., Kontopoulos, A., Papageorgiou, A., Karamitsos, D., Lacigová, S., Rušavý, Z., Kárová, R., Perrild, H., Kay, L., Jørgensen, T., Bień, A. I., Witek, P., Geraldes, Elizabete, Rodrigues, D., Pereira, L., Doménech, A., Leitão, P., Anagnostopoulos, D., Foster, A. V. M., Nag, S., Barsoum, M., Lewis, G., Dunlop, N., Connolly, V., Bilous, R., Kelly, W., Chantelau, E., Gede, A., Sharman, D., O’Halloran, D., Best, C., Abbas, Z. G., Lutale, J., Gill, G. V., Jarvis, W. R., Archibald, L. K., Corcoran, S., Mansell, J., Pibworth, L., Terada, H., Shiba, T., Utugi, N., Utugi, T., Blum, M., Strobel, J., Höffken, K., Razvi, F. M., Kritzinger, E. E., Taylor, K., Jones, S., Illahi, W., Grüβer, M., Hartmann, P., Hoffstadt, K., van Leiden, H. A., Moll, A. C., Polak, B. C. P., Pietragalla, G. B., Maurino, M., Montanaro, M., Karadeniz, Ş., Tommasini, P., Quadrini, C., Demiraj, V., Rispoli, E., Ota, A., Takama, H., Saito, N., Hemández, C., Lepore, D., Antico, L., Giardina, B., Franconi, F., Michoud, E., Chamot, S., Riva, Ch., Hammes, H.-P., Renner, O., Breier, G., Lin, J., Alt, A., Betzholtz, C., Bretzel, R. G., Manti, R., Gallo, M., Molinar Hin, A., Brignardello, E., Boccuzzi, G., Li, Shanfang, Xiang, Kunsan, Zhang, Rugeng, Shangguan, Xinhong, Wu, Jianrong, Donnan, P. T., Broomhall, J., Hunter, K., Morris, A. D., Ioannidis, G., Peppa, M., Rontogianni, E., Kallifronas, M., Lekatsas, I., Chrysanthopoulou, G., Anthopoulos, L., Kesse, M., Thalassinos, N., Neves, C., Medina, J. L., Lopes, F., Yılmaz, M., Güvener, N., Güvener, M., Kocagöz, T., Böke, E., Paşaoglu, I., Bascil Tutuncu, N., Oto, A., Karvonen, M. K., Koulu, M., Pesonen, U., Mercuri, M., Rauramaa, R., Rutter, M. K., Kestevan, P., McComb, J. M., Marshall, S. M., Sobieska, M., Wiktorowicz, K., Kanters, S. D. J. M., Banga, J. D., Algra, A., Frijns, C. J. M., Beutler, J. J., Fijnheer, R., Nicoloff, G., Baydanoff, S., Stanimirova, N., Petrova, Ch., Lario, S., Campistol, J. M., Cases, A., Clària, J., Iñigo, P., Esmatjcs, E., Sármán, B., Tóth, M., Kocsis, I., Somogyi, A., Bumbure, A., Jachimowicz, K., Samson, J., Tomasiak, M., Sobol, A., Stańczyk, L., Watala, C., Stradina, P., Wiśniewska-Jarosińska, M., Marciniak, D., Więcławska, B., Watała, C., Golański, J., Zinnat, R., Mahmud, I., Büyükasik, Yahya, Demiroğlu, H., Szczepanik, A., Skowroński, M., Murawska, A., Meeking, D. R., Allard, S., Munday, J., Chowienczyk, P., Shaw, K. M., Cummings, M. H., Šimková, R., Jirsa, M., Hadoke, P. W. F., McIntyre, C. A., Jones, G. C., Williams, B. C., Elliott, A. I., McKnight, J. A., Pernow, J., Bombonato, G. C., Finucci, G. F., Zotta, L., Senses, V., Ozyazgan, S., Ince, E., Tunçdemir, M., Oztürk, M., Sultuybek, G., Akkan, A. G., Özyazgan, S., Unlücerci, Y., Bekpınar, S., Meyer, M. F., Lee, B. C., Shore, A. C., Humphreys, J. M., Tooke, J. E., Dell’Omo, G., Giovannitti, G., Caricato, F., Mariani, M., Pedrinelli, R., Kiviet-Boehm, C., Schwelling, V., Matthäei, S., Pfohl, M., McInerney, D., Itoh, H., Ohno, T., Katoh, N., Baumgartner-Parzer, S., Artwohl, M., Graier, W., Ludwig, C., Tachi, Y., Bannai, C., Shinohara, M., Shimpuku, H., Ohura, K., Bertacca, A., Sasvári, M., Szaleczki, E., Pusztai, P., Boes, U., Klaus, E., Dittrich, P., Wagner, Z., Wittmann, I., Pótó, L., Wagner, L., Mazák, I., Nagy, J., Feletto, F., Taboga, C., Tonutti, L., Lizzio, S., Russo, A., Selmo, V., Ceriello, A., Lekakis, J., Papamichael, C. M., Stamatelopoulos, K., Stamatelopoulos, S., Yillar, D. O., Gay, M., Lillaz, E., Passaro, A., Vanini, A., Calzoni, F., D’Elia, K., Carantoni, M., Zuliani, G., Fellin, R., Solini, A., Chwatko, G., Bald, E., Dramais, A.-S., Wallemacq, P. E., Vandeleene, B., Ciaria, M. V., Ariano, M., Strom, R., Gibney, J., Weiss, U., Turner, B., O’Gorman, P., Watts, G., Powrie, J., Crook, M., Shaw, K., and Cummings, M.

Published
1999
Full Text
View/download PDF

47. Transrectal ultrasound in abacterial chronic prostatitis: Identification of a possible reference pattern

Author

Conti, G., Gianneo, E., Fumagalli, L., Sala, E., Antinozzi, R., and Comeri, G.C.

Abstract

Chronic prostatitis caused by sexually transmitted pathogens (Chlamydia Trachomatis, Ureaplasma Urealyticum, Mycoplasma Hominis) is a quite frequent disease in the mean age of life (20–50 years). Diagnostic difficulties are encountered because of poor symptomatology and inadequacy of common laboratory microbiologic essay. So this disease requires a rather elaborate diagnostic procedure like specific determination of microrganisms in seminal fluid, prostatic and urethral secretion. From the echographic point of view no patognomonic patterns can be referred to at present. The authors identified in a group of 48 patients with proven infection by sexually transmitted pathogens, some echographic findings perhaps indicative of this prostatic disease (more evidence of cranial periurethral prostatic hypoechogenicity in all infected patients, and quite complete resolution in a high percentage of patients after microrganism eradication). If confirmed by a higher number of observations, this data may become a useful diagnostic instrument in the approach to sexually transmitted prostatic disease in order to support and confirm the diagnosis and therapy.

Published
1992
Full Text
View/download PDF

48. Molecular or pharmacologic perturbation of the link between glucose and lipid metabolism is without effect on glucose-stimulated insulin secretion. A re-evaluation of the long-chain acyl-CoA hypothesis.

Author

Antinozzi, P A, Segall, L, Prentki, M, McGarry, J D, and Newgard, C B

Abstract

The mechanism by which glucose stimulates insulin secretion from the pancreatic islets of Langerhans is incompletely understood. It has been suggested that malonyl-CoA plays a regulatory role by inhibiting fatty acid oxidation and promoting accumulation of cytosolic long-chain acyl-CoA (LC-CoA). In the current study, we have re-evaluated this "long-chain acyl-CoA hypothesis" by using molecular and pharmacologic methods to perturb lipid metabolism in INS-1 insulinoma cells or rat islets during glucose stimulation. First, we constructed a recombinant adenovirus containing the cDNA encoding malonyl-CoA decarboxylase (AdCMV-MCD), an enzyme that decarboxylates malonyl-CoA to acetyl-CoA. INS-1 cells treated with AdCMV-MCD had dramatically lowered intracellular malonyl CoA levels compared with AdCMV-betaGal-treated cells at both 3 and 20 mM glucose. Further, at 20 mM glucose, AdCMV-MCD-treated cells were less effective at suppressing [1-14C]palmitate oxidation and incorporated 43% less labeled palmitate and 50% less labeled glucose into cellular lipids than either AdCMV-betaGAL-treated or untreated INS-1 cells. Despite the large metabolic changes caused by expression of MCD, insulin secretion in response to glucose was unaltered relative to controls. The alternative, pharmacologic approach for perturbing lipid metabolism was to use triacsin C to inhibit long-chain acyl-CoA synthetase. This agent caused potent attenuation of palmitate oxidation and glucose or palmitate incorporation into cellular lipids and also caused a 47% decrease in total LC-CoA. Despite this, the drug had no effect on glucose-stimulated insulin secretion in islets or INS-1 cells. We conclude that significant disruption of the link between glucose and lipid metabolism does not impair glucose-stimulated insulin secretion in pancreatic islets or INS-1 cells.

Published
1998

49. Multicenter Evaluation of the COBAS AMPLICOR HCV Assay, an Integrated PCR System for Rapid Detection of Hepatitis C Virus RNA in the Diagnostic Laboratory

Author

Albadalejo, J., Alonso, R., Antinozzi, R., Bogard, M., Bourgault, A.-M., Colucci, G., Fenner, T., Petersen, H., Sala, E., Vincelette, J., and Young, C.

Abstract

ABSTRACTThe benefits shown by the recent introduction of PCR for the in vitro diagnosis of hepatitis C virus (HCV) infection has prompted the development of standardized, ready-to-use assays that can be implemented in routine clinical laboratories. We have evaluated the clinical performance of COBAS AMPLICOR HCV (COBAS), the first instrument system that allows the automation of HCV RNA amplification and detection, to determine its performance in the routine laboratory setting. More than 2,000 specimens collected at five centers were analyzed in parallel by the COBAS and the manual AMPLICOR HCV (AMPLICOR) tests, and the results were compared with the results for biochemical and serological markers of HCV. In this study the two PCR systems showed the same accuracy, with a concordance rate of 99.8%. As expected, the correlation between serology and PCR was not absolute because the presence of anti-HCV antibodies may be associated with a latent or past infection. On the other hand, if the presence of confirmed anti-HCV antibodies and elevated alanine aminotransferase levels are taken as the “gold standard,” indicating an active, ongoing infection, the COBAS and AMPLICOR tests show high and comparable sensitivities (100%) and specificities (98%), with positive and negative predictive values of 100 and 97%, respectively. During the study no false-positive reactions were detected. The use of an internal control allowed the identification of inhibitory substances that prevented amplification for 0.3 and 0.4% of samples tested by the COBAS and AMPLICOR tests, respectively. Compared to the manual system, the COBAS system allowed a significant reduction of hands-on time and could improve the overall laboratory work flow. In conclusion, these results support the use of the COBAS and AMPLICOR tests for the molecular diagnosis of active HCV infections.

Published
1998
Full Text
View/download PDF

50. Engineering of Glycerol-stimulated Insulin Secretion in Islet Beta Cells

Author

Noel, Richard J., Antinozzi, Peter A., McGarry, J. Denis, and Newgard, Christopher B.

Abstract

Insulin secretion from beta cells in the islets of Langerhans can be stimulated by a number of metabolic fuels, including glucose and glyceraldehyde, and is thought to be mediated by metabolism of the secretagogues and an attendant increase in the ATP:ADP ratio. Curiously, glycerol fails to stimulate insulin secretion, even though it has been reported that islets contain abundant glycerol kinase activity and oxidize glycerol efficiently. We have reinvestigated this point and find that rat islets and the well differentiated insulinoma cell line INS-1 contain negligible glycerol kinase activity. A recombinant adenovirus containing the bacterial glycerol kinase gene (AdCMV-GlpK) was constructed and used to express the enzyme in islets and INS-1 cells, resulting in insulin secretion in response to glycerol. In AdCMV-GlpK-treated INS-1 cells a greater proportion of glycerol is converted to lactate and a lesser proportion is oxidized compared with glucose. The two fuels are equally potent as insulin secretagogues, despite the fact that oxidation of glycerol at its maximally effective dose (2–5 mm) occurs at a rate that is similar to the rate of glucose oxidation at its basal, nonstimulatory concentration (3 mm). We also investigated the possibility that glycerol may signal via expansion of the glycerol phosphate pool to allow enhanced fatty acid esterification and formation of complex lipids. Addition of Triacsin-C, an inhibitor of long-chain acyl-CoA synthetase, to AdCMV-GlpK-treated INS-1 cells did not inhibit glycerol-stimulated insulin secretion despite the fact that it blocked glycerol incorporation into cellular lipids. We conclude from these studies that glycerol kinase expression is sufficient to activate glycerol signaling in beta cells, showing that the failure of normal islets to respond to this substrate is due to a lack of this enzyme activity. Further, our studies show that glycerol signaling is not linked to esterification or oxidation of the substrate, but is likely mediated by its metabolism in the glycerol phosphate shuttle and/or the distal portion of the glycolytic pathway, either of which can lead to production of ATP and an increased ATP:ADP ratio.

Published
1997
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results