135 results on '"D. Lann"'
Search Results
2. Apolipoprotein E deficiency abrogates insulin resistance in a mouse model of type 2 diabetes mellitus
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D. Lann, Yuki Kawashima, Roger J. Hajjar, Shoshana Yakar, Hui Sun, Derek LeRoith, and J. Chen
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Blood Glucose ,Male ,Apolipoprotein E ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Mice, Inbred Strains ,Type 2 diabetes ,Fatty Acids, Nonesterified ,Biology ,Article ,Apolipoproteins E ,Cholesterol, Dietary ,Mice ,Insulin resistance ,Internal medicine ,Internal Medicine ,medicine ,Animals ,Insulin ,Triglycerides ,Body Weight ,Type 2 Diabetes Mellitus ,Lipid metabolism ,Atherosclerosis ,Lipid Metabolism ,medicine.disease ,Mice, Mutant Strains ,Disease Models, Animal ,Endocrinology ,Adipose Tissue ,Diabetes Mellitus, Type 2 ,Liver ,Body Composition ,Female ,lipids (amino acids, peptides, and proteins) ,Insulin Resistance ,Diabetic Angiopathies ,Lipoprotein - Abstract
Although it is known that lipid metabolism plays a role in insulin resistance in type 2 diabetes and in obesity, the mechanism is still largely unknown. Apolipoprotein E (ApoE) regulates plasma lipid levels and also plays a role in the uptake of lipids into various tissues. To investigate whether the suppression of whole-particle lipoprotein uptake into tissues affects insulin responsiveness and the diabetic condition, we examined the effect of an ApoE (also known as Apoe) gene deletion in MKR mice, a mouse model of type 2 diabetes.ApoE ( -/- ), MKR, ApoE ( -/- )/MKR and control mice were placed on a high-fat, high-cholesterol diet for 16 weeks. Glucose tolerance, serum insulin, blood glucose, insulin tolerance, tissue triacylglycerol content and atherosclerotic lesions were assessed.ApoE ( -/- )/MKR and ApoE ( -/- ) mice showed significantly improved blood glucose, glucose tolerance and insulin sensitivity. Reduced triacylglycerol content in liver and reduced fat accumulation in liver and adipose tissue were found in ApoE ( -/- )/MKR and ApoE ( -/- ) mice compared with control and MKR mice. ApoE ( -/- ) and ApoE ( -/- )/MKR mice demonstrated similarly large atherosclerotic lesions, whereas MKR and control mice had small atherosclerotic lesions.We demonstrated that ApoE deficiency abrogates insulin resistance in a mouse model of type 2 diabetes, suggesting that lipid accumulation in tissue is a major cause of insulin resistance in this mouse model.
- Published
- 2009
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3. The Role of Endocrine Insulin-Like Growth Factor-I and Insulin in Breast Cancer
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Derek LeRoith and D. Lann
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Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Breast Neoplasms ,Endocrine System ,Type 2 diabetes ,Insulin-like growth factor ,Breast cancer ,Insulin resistance ,Risk Factors ,Diabetes mellitus ,Internal medicine ,medicine ,Hyperinsulinemia ,Humans ,Insulin ,Insulin-Like Growth Factor I ,skin and connective tissue diseases ,business.industry ,Cancer ,medicine.disease ,business ,Signal Transduction - Abstract
Epidemiologic studies demonstrate that breast cancer is the most common type of cancer diagnosed in women and is a significant cause of morbidity and mortality. While there are many risk factors known to be associated with increased breast cancer risk, this review will focus specifically on circulating IGF-I, hyperinsulinemia, and type 2 diabetes. Their effects on promoting breast cancer development, progression, and adverse outcomes have been demonstrated in both animal and human studies, suggesting that the IGF system is a potential target for breast cancer therapy. In addition, in the clinical setting, emphasizing metabolic risk modifications to patients including weight loss, dietary changes, and diabetes control may also play an important role in breast cancer risk reduction.
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- 2008
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4. Insulin-mediated acceleration of breast cancer development and progression in a non-obese model of type 2 diabetes
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Joan M. Carboni, Ruslan Novosyadlyy, Yvonne Fierz, Archana Vijayakumar, D. Lann, Wilson Mejia, Teresa L. Wood, Alfredo A. Molinolo, Derek LeRoith, Anne M. Rowzee, Marco M. Gottardis, Deborah A. Lazzarino, N Kurshan, Shoshana Yakar, Patricia Pennisi, and Stefania Santopietro
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Cancer Research ,medicine.medical_specialty ,CIENCIAS MÉDICAS Y DE LA SALUD ,Pyridones ,medicine.medical_treatment ,education ,Mice, Transgenic ,Medicina Clínica ,medicine.disease_cause ,Article ,Diabetes Mellitus, Experimental ,Receptor, IGF Type 1 ,Mice ,Phosphatidylinositol 3-Kinases ,Breast cancer ,Mammary Glands, Animal ,Internal medicine ,Endocrinología y Metabolismo ,Hyperinsulinism ,medicine ,Animals ,Insulin ,Phosphorylation ,Protein kinase B ,biology ,business.industry ,Cancer ,Mammary Neoplasms, Experimental ,medicine.disease ,Receptor, Insulin ,Type 2 Diabetes ,Oncogene Protein v-akt ,Insulin receptor ,Disease Models, Animal ,Endocrinology ,Oncology ,Diabetes Mellitus, Type 2 ,Tumor progression ,biology.protein ,IGF-1 ,Benzimidazoles ,Female ,Breast disease ,business ,Carcinogenesis - Abstract
Epidemiologic studies suggest that type 2 diabetes (T2D) increases breast cancer risk and mortality, but there is limited experimental evidence supporting this association. Moreover, there has not been any definition of a pathophysiological pathway that diabetes may use to promote tumorigenesis. In the present study, we used the MKR mouse model of T2D to investigate molecular mechanisms that link T2D to breast cancer development and progression. MKR mice harbor a transgene encoding a dominant-negative, kinase-dead human insulin-like growth factor-I receptor (IGF-IR) that is expressed exclusively in skeletal muscle, where it acts to inactivate endogenous insulin receptor (IR) and IGF-IR. Although lean female MKR mice are insulin resistant and glucose intolerant, displaying accelerated mammary gland development and enhanced phosphorylation of IR/IGF-IR and Akt in mammary tissue, in the context of three different mouse models of breast cancer, these metabolic abnormalities were found to accelerate the development of hyperplastic precancerous lesions. Normal or malignant mammary tissue isolated from these mice exhibited increased phosphorylation of IR/IGF-IR and Akt, whereas extracellular signal-regulated kinase 1/2 phosphorylation was largely unaffected. Tumor-promoting effects of T2D in the models were reversed by pharmacological blockade of IR/IGF-IR signaling by the small-molecule tyrosine kinase inhibitor BMS-536924. Our findings offer compelling experimental evidence that T2D accelerates mammary gland development and carcinogenesis,and that the IR and/or the IGF-IR are major mediators of these effects. Fil: Novosyadlyy, Ruslan. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Lann, Danielle E.. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Vijayakumar, Archana. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Rowzee, Anne. Rutgers University; Estados Unidos Fil: Lazzarino, Deborah A.. Rutgers University; Estados Unidos Fil: Fierz, Yvonne. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Carboni, Joan M.. Bristol Myers Squibb Research Institute; Estados Unidos Fil: Gottardis, Marco M.. Bristol Myers Squibb Research Institute; Estados Unidos Fil: Pennisi, Patricia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Gobierno de la Ciudad de Buenos Aires. Centro de Investigaciones Endocrinológicas "Dr. César Bergada". Fundación de Endocrinología Infantil. Centro de Investigaciones Endocrinológicas "Dr. César Bergada"; Argentina Fil: Molinolo, Alfredo A.. National Institute of Dental and Craniofacial Research; Estados Unidos Fil: Kurshan, Naamit. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Mejia, Wilson. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Santopietro, Stefania. No especifíca; Fil: Yakar, Shoshana. Icahn School of Medicine at Mount Sinai; Estados Unidos Fil: Wood, Teresa L.. Rutgers University; Estados Unidos Fil: LeRoith, Derek. Icahn School of Medicine at Mount Sinai; Estados Unidos
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- 2010
5. Elevated circulating IGF-I promotes mammary gland development and proliferation
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Shoshana Yakar, Sebastien Elis, Dara Cannata, Deborah A. Lazzarino, D. Lann, Teresa L. Wood, Hui Sun, Yingjie Wu, Derek LeRoith, Icahn School of Medicine at Mount Sinai [New York] (MSSM), University of Medecine and Dentistry of New Jersey, Partenaires INRAE, NICHD, and National Institutes of Health GCO 00-0123ME DK60612-06 CA128799-01A1
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Aging ,medicine.medical_specialty ,[SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT] ,Transgene ,Mammary gland ,Mice, Transgenic ,Biology ,Weight Gain ,Article ,Mice ,03 medical and health sciences ,Mammary Glands, Animal ,0302 clinical medicine ,Endocrinology ,Internal medicine ,medicine ,Animals ,Endocrine system ,Insulin-Like Growth Factor I ,Phosphorylation ,Cell Proliferation ,030304 developmental biology ,Mice, Knockout ,Regulation of gene expression ,0303 health sciences ,Cell growth ,Myoepithelial cell ,Gene Expression Regulation, Developmental ,Epithelial Cells ,Organ Size ,Rats ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Immunohistochemistry ,Female ,Animal studies - Abstract
International audience; Animal studies have shown that IGF-I is essential for mammary gland development. Previous studies have suggested that local IGF-I rather than circulating IGF-I is the major mediator of mammary gland development. In the present study we used the hepatic IGF-I transgenic (HIT) and IGF-I knockout/HIT (KO-HIT) mouse models to examine the effects of enhanced circulating IGF-I on mammary development in the presence and absence of local IGF-I. HIT mice express the rat IGF-I transgene under the transthyretin promoter in the liver and have elevated circulating IGF-I and normal tissue IGF-I levels. The KO-HIT mice have no tissue IGF-I and increased circulating IGF-I. Analysis of mammary gland development reveals a greater degree of complexity in HIT mice as compared to control and KO-HIT mice, which demonstrate similar degrees of mammary gland complexity. Immunohistochemical evaluation of glands of HIT mice also suggests an enhanced degree of proliferation of the mammary gland, whereas KO-HIT mice exhibit mammary gland proliferation similar to control mice. In addition, HIT mice have a higher percentage of proliferating myoepithelial and luminal cells than control mice, whereas KO-HIT mice have an equivalent percentage of proliferating myoepithelial and luminal cells as control mice. Thus, our findings show that elevated circulating IGF-I levels are sufficient to promote normal pubertal mammary epithelial development. However, HIT mice demonstrate more pronounced mammary gland development when compared to control and KO-HIT mice. This suggests that both local and endocrine IGF-I play roles in mammary gland development and that elevated circulating IGF-I accelerates mammary epithelial proliferation.
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- 2010
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6. Physical and functional interaction between polyoma virus middle T antigen and insulin and IGF-I receptors is required for oncogene activation and tumour initiation
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N Kurshan, Ruslan Novosyadlyy, D. Lann, Derek LeRoith, Archana Vijayakumar, and Yvonne Fierz
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Cancer Research ,medicine.medical_specialty ,MAP Kinase Signaling System ,oncogenes ,viruses ,medicine.medical_treatment ,Antigens, Polyomavirus Transforming ,Mammary Neoplasms, Animal ,Mice, Inbred Strains ,Mice, Transgenic ,Biology ,medicine.disease_cause ,Article ,Receptor, IGF Type 1 ,crosstalk ,03 medical and health sciences ,Mice ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,Antigen ,Internal medicine ,Cell Line, Tumor ,Genetics ,medicine ,Animals ,Insulin ,Phosphorylation ,insulin receptor ,Receptor ,neoplasms ,Molecular Biology ,Pancreatic hormone ,030304 developmental biology ,0303 health sciences ,Receptor, Insulin ,3. Good health ,polyoma virus middle T oncogene ,Insulin receptor ,Endocrinology ,030220 oncology & carcinogenesis ,Gene Knockdown Techniques ,Cancer research ,biology.protein ,Viral disease ,Carcinogenesis ,IGF-I receptor - Abstract
Polyoma virus middle T antigen (PyVmT) is a powerful viral oncogene; however, the mechanisms of PyVmT activation are poorly understood. The insulin-like growth factor I receptor (IGF-IR) and the insulin receptor (IR) are known to be implicated in the development of many cancers. Furthermore, PyVmT-overexpressing mouse mammary carcinoma Met-1 cells are highly responsive to IGF-I and insulin. Herein, we demonstrate that PyVmT physically interacts with IGF-IR and IR in Met-1 cells. Insulin and IGF-I increase association of the IR and IGF-IR with PyVmT, enhance tyrosine phosphorylation of PyVmT and augment the recruitment of Src and PLCgamma(1) to PyVmT. This is accompanied by robust and sustained phosphorylation of Akt and ERK1/2, which are implicated in both PyVmT and IGF-IR/IR signalling. Both ligands significantly increase proliferation, survival, migration and invasion of Met-1 cells. Furthermore, orthotopic inoculation of Met-1 cells with shRNAmir-mediated knockdown of IR or IGF-IR fails to initiate tumour growth in recipient mice. In conclusion, our data indicate that the physical and functional interaction between PyVmT and cellular receptor tyrosine kinases, including IR and IGF-IR, is critical for PyVmT activation and tumour initiation. These results also provide a novel mechanism for oncogene activation in the host cell.
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- 2009
7. Obesity and type 2 diabetes are associated with an increased risk of developing cancer and a worse prognosis; epidemiological and mechanistic evidence
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Derek LeRoith, Ruslan Novosyadlyy, D. Lann, Emily J. Gallagher, Archana Vijayakumar, and Shoshana Yakar
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Oncology ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Type 2 diabetes ,Models, Biological ,Proinflammatory cytokine ,Endocrinology ,Insulin resistance ,Risk Factors ,Internal medicine ,Diabetes mellitus ,Neoplasms ,Internal Medicine ,medicine ,Hyperinsulinemia ,Animals ,Humans ,Obesity ,Risk factor ,business.industry ,nutritional and metabolic diseases ,Cancer ,General Medicine ,medicine.disease ,Prognosis ,Disease Models, Animal ,Diabetes Mellitus, Type 2 ,business ,Signal Transduction - Abstract
Both obesity and Type 2 diabetes are independently associated with an increased risk of developing cancer and an increased mortality. The etiology is yet to be determined but insulin resistance and hyperinsulinemia maybe important factors. Hyperglycemia, hyperlipidemia and inflammatory cytokines in addition to the insulin-like growth factors are also possible factors involved in the process.
- Published
- 2008
8. Insulin resistance and the metabolic syndrome
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D, Lann, E, Gallagher, and D, Leroith
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Inflammation ,Metabolic Syndrome ,Glucose Transporter Type 4 ,Fatty Acids, Nonesterified ,Glucose ,Insulin-Secreting Cells ,Hypertension ,Insulin Secretion ,Cytokines ,Humans ,Insulin ,Obesity ,Insulin Resistance ,Dyslipidemias - Abstract
The metabolic syndrome is a constellation of risk factors including glucose dysregulation, central obesity, dyslipidemia, and hypertension. There are multiple definitions that have been described by various health organizations. However, we do know that insulin resistance plays a major role as the underlying cause for the development and potentiation of the metabolic syndrome. At present, it is unclear if the diagnosis of metabolic syndrome is greater than the sum of its parts. However, the presence of more than one of the associated risk factors should indicate that a patient is at increased risk for developing diabetes, cardiovascular disease and death. Thus, the primary care physician should aggressively treat the metabolic risk factors in their patients to prevent the onset and progression to more severe disease.
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- 2008
9. Insulin-like growth factor-I protects cells from ER stress-induced apoptosis via enhancement of the adaptive capacity of endoplasmic reticulum
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Derek LeRoith, D. Lann, N Kurshan, Ruslan Novosyadlyy, Shoshana Yakar, and Archana Vijayakumar
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p38 mitogen-activated protein kinases ,Apoptosis ,Biology ,Endoplasmic Reticulum ,Wortmannin ,chemistry.chemical_compound ,Mice ,Cell Line, Tumor ,medicine ,Staurosporine ,Animals ,Humans ,Cycloheximide ,Enzyme Inhibitors ,Insulin-Like Growth Factor I ,STAT3 ,Molecular Biology ,Endoplasmic Reticulum Chaperone BiP ,Protein Kinase Inhibitors ,PI3K/AKT/mTOR pathway ,Protein Synthesis Inhibitors ,Endoplasmic reticulum ,Cell Biology ,Recombinant Proteins ,Cell biology ,chemistry ,Unfolded protein response ,biology.protein ,NIH 3T3 Cells ,Thapsigargin ,Signal transduction ,medicine.drug ,Signal Transduction - Abstract
Disruption of endoplasmic reticulum (ER) homeostasis causes accumulation of unfolded and misfolded proteins in the ER, triggering the ER stress response, which can eventually lead to apoptosis when ER dysfunction is severe or prolonged. Here we demonstrate that human MCF-7 breast cancer cells, as well as murine NIH/3T3 fibroblasts, are rescued from ER stress-initiated apoptosis by insulin-like growth factor-I (IGF-I). IGF-I significantly augments the adaptive capacity of the ER by enhancing compensatory mechanisms such as the IRE1 alpha-, PERK- and ATF6-mediated arms of ER stress signalling. During ER stress, IGF-I stimulates translational recovery and induces expression of the key molecular chaperone protein Grp78/BiP, thereby enhancing the folding capacity of the ER and promoting recovery from ER stress. We also demonstrate that the antiapoptotic activity of IGF-I during ER stress may be mediated by a novel, as yet unidentified, signalling pathway(s). Application of signal transduction inhibitors of MEK (U1026), PI3K (LY294002 and wortmannin), JNK (SP600125), p38 (SB203580), protein kinases A and C (H-89 and staurosporine) and STAT3 (Stattic) does not prevent IGF-I-mediated protection from ER stress-induced apoptosis. Taken together, these data demonstrate that IGF-I protects against ER stress-induced apoptosis by increasing adaptive mechanisms through enhancement of ER stress-signalling pathways, thereby restoring ER homeostasis and preventing apoptosis.
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- 2008
10. Insulin resistance as the underlying cause for the metabolic syndrome
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Derek LeRoith and D. Lann
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Blood Glucose ,medicine.medical_specialty ,Proinflammatory cytokine ,Impaired glucose tolerance ,Insulin resistance ,Risk Factors ,Internal medicine ,Insulin Secretion ,medicine ,Humans ,Insulin ,Metabolic Syndrome ,biology ,business.industry ,General Medicine ,medicine.disease ,Prognosis ,Pathophysiology ,Insulin receptor ,Endocrinology ,Lipotoxicity ,biology.protein ,Metabolic syndrome ,Insulin Resistance ,business ,Dyslipidemia - Abstract
Classically, the metabolic syndrome is characterized as group of pathologies including visceral obesity, hypertension, dyslipidemia, and impaired glucose tolerance. It is now realized that insulin resistance plays a principal role in initiating and perpetuating the pathologic manifestations of the metabolic syndrome. A more in-depth understanding of the basic pathophysiologic mechanisms underlying insulin resistance may aid clinicians in treating and possibly delaying or even preventing the onset of the metabolic syndrome and its complications. This article outlines how abnormal insulin signaling and secretion, impaired glucose disposal, lipotoxicity, and proinflammatory cytokines exacerbate insulin resistance and result in the perturbations of the metabolic syndrome.
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- 2007
11. Comparative effectiveness of fluphenazine decanoate injections every 2 weeks versus every 6 weeks
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Helen D. Lann, Brian Kirkpatrick, Ann Summerfelt, William T. Carpenter, Robert W. Buchanan, and Alan Breier
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Fluphenazine ,Adult ,Male ,Side effect ,medicine.medical_treatment ,Schizoaffective disorder ,Injections, Intramuscular ,Drug Administration Schedule ,law.invention ,Randomized controlled trial ,Double-Blind Method ,law ,medicine ,Secondary Prevention ,Fluphenazine Decanoate ,Humans ,Antipsychotic ,business.industry ,medicine.disease ,Psychiatry and Mental health ,Regimen ,Treatment Outcome ,Psychotic Disorders ,Schizophrenia ,Patient Satisfaction ,Anesthesia ,Delayed-Action Preparations ,Patient Compliance ,Female ,Schizophrenic Psychology ,business ,medicine.drug - Abstract
Objective: Dose reduction strategies for the maintenance treatment of schizophrenia are designed to maintain the benefits of antipsychotic drug therapy while reducing risks. Previous strategies with decanoate preparations have been based on the use of lower doses per injection to achieve dose reduction; these strategies have achieved dose reduction but have resulted in some increase in symptoms. The authors tested a new dose reduction approach: increasing the interval between injections during intramuscular decanoate antipsychotic treatment. Method: Fifty outpatients with schizophrenia or schizoaffective disorder were randomly assigned to receive 25 mg of fluphenazine decanoate intramuscularly either every 2 weeks or every 6 weeks for 54 weeks in a double-blind design. Results: The two dose regimens did not differ significantly in relapse, symptom, or side effect measures. The every-6-weeks regimen was associated with a significant reduction in total antipsychotic exposure. Conclusions: The use of injections every 6 weeks instead of every 2 weeks may increase compliance and improve patients’ comfort as well as decrease cumulative antipsychotic exposure, without increasing relapse rates or symptoms. (Am J Psychiatry 1999; 156:412‐418)
- Published
- 1999
12. HIV infection in Maryland public psychiatric facilities: results of an informal survey
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C G, Lyketsos, D D, Storch, H D, Lann, R, Finn, R, Haber, and R, Meng
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Male ,Health Services Needs and Demand ,Baltimore ,Prevalence ,Humans ,Female ,HIV Infections ,Community Mental Health Services - Abstract
The Maryland Psychiatric Society (MPS) Public Psychiatry Committee, concerned with the preparedness of Baltimore mental health facilities to deal with the accelerating human immunodeficiency virus (HIV) epidemic, surveyed public sector mental health facilities. The survey results indicated that the number of HIV-infected patients is greatly underestimated. Care providers acknowledged awareness of the problem and wanted more education.
- Published
- 1993
13. OR8,44 Increased levels of circulating IGF-I normalizes mammary gland development in mice deficient of local IGF-1
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D. Lann, Derek LeRoith, D.H. Cannata, Hui Sun, Yingjie Wu, Shoshana Yakar, Teresa L. Wood, and D. Lazzarino
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chemistry.chemical_classification ,medicine.medical_specialty ,Phage display ,Endocrinology, Diabetes and Metabolism ,Peptide ,Ligand (biochemistry) ,Mammary gland development ,Cell biology ,Endocrinology ,chemistry ,Ectodomain ,Internal medicine ,medicine ,Receptor - Abstract
Surprisingly, these findings provide structural insights into the mode of binding of (i) a peptide family of IGF-1R/IR agonists and antagonists originally derived from phage display technology, and (ii) a family of affibodies selected to target IGF-1R. The mode of binding of these molecules is now seen to involve mimicry, not only of the ligand, but also of the aCT segment of the receptor itself . These findings provide new opportunities for the design of smallmolecule antagonists that target the IGF-1R ectodomain.
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- 2010
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14. OR12,3 Insulin-like growth factor I protects cells from ER stress-induced apoptosis via enhancement of the adaptive capacity of endoplasmic reticulum
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N Kurshan, D. Lann, Archana Vijayakumar, Shoshana Yakar, Ruslan Novosyadlyy, and Derek LeRoith
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Insulin-like growth factor ,Endocrinology ,Apoptosis ,Chemistry ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Endoplasmic reticulum ,medicine ,Unfolded protein response ,Cell biology - Published
- 2008
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15. Authors' reply
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L. Meyer, J. Bouyer, E. Papiernik, D Lann, L. Moukengue, and J. Dreyfus
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Obstetrics and Gynecology - Published
- 1989
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16. The 2020 Election in Myanmar: The NLD Supporters and Facebook.
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Khin Nway Nway Hlaing
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ELECTIONS ,SOCIAL media & politics - Published
- 2024
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17. Diabetic Mastopathy: A Review of a Breast Carcinoma Mimic.
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Salati, Sajad Ahmad and AlSulaim, Lamees
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BREAST tumor diagnosis ,DIABETES complications ,BREAST tumor treatment ,BREAST diseases ,DIFFERENTIAL diagnosis ,COMPUTED tomography ,AXILLARY lymph node dissection ,MAGNETIC resonance imaging ,ULTRASONIC imaging ,FIBROCYSTIC breast disease ,NEEDLE biopsy ,MAMMOGRAMS ,MASTITIS ,DIABETES - Abstract
Diabetic mastopathy is a rare fibro-inflammatory breast disease that closely mimics breast carcinoma. The disease predominantly affects insulin-dependent diabetics, and the etiology is still unclear. A proper physical examination, imaging, and core-needle biopsy usually lead to a diagnosis. Management is conservative and revolves around counseling the patient to allay fears and regular follow-up. In this review, we highlight the recent information on diabetic mastopathy with emphasis on historical background, epidemiology, etiopathogenesis, diagnostic approaches, and treatment choices. [ABSTRACT FROM AUTHOR]
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- 2024
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18. Lactobacillus rhamnosus GG administration partially prevents diet-induced insulin resistance in rats: a comparison with its heat-inactivated parabiotic.
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Arellano-García, L., Macarulla, M. T., Cuevas-Sierra, A., Martínez, J. A., Portillo, M. P., and Milton-Laskibar, I.
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- 2023
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19. Idiopathic Granulomatous Mastitis: Six years of experience and the current evidence in literature.
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Al Awfi, Mahmood M. and Al Rahbi, Salim K.
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MASTITIS ,PATIENT preferences ,TERTIARY care - Abstract
Objectives: This study aimed to retrospectively describe the clinicopathological pattern and management experience of idiopathic granulomatous mastitis in women receiving care at the Royal Hospital, a tertiary care centre in Oman. The study then compared the researchers' experience with the current literature trends. Methods: The data of patients from January 2012 to December 2017 were reviewed retrospectively, after receiving ethical approval from the Centre of Studies and Research. Results: This retrospective study included 64 patients were confirmed to have idiopathic granulomatous mastitis. All patients were in the premenopausal phase, with only one being nulliparous. Mastitis was the most common clinical diagnosis; furthermore, half of the patients had a palpable mass. Most patients had received antibiotics during the span of their treatment. Drainage procedure was done in 73% of the patients, whereas excisional procedure was done for 38.7%. Only 52.4% of patients were able to achieve complete clinical resolution within six months of follow-up. Conclusion: There is no standardised management algorithm due to the paucity of high-level evidence comparing different modalities. However, steroids, methotrexate and surgery are all considered to be effective and acceptable treatments. Moreover, current literature tends towards multimodality treatments planned tailored case-to-case based on the clinical context and patients' preference. [ABSTRACT FROM AUTHOR]
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- 2023
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20. Contributions to Automatic Continuity of -Derivations on Banach Algebras.
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Hosseini, A.
- Abstract
The main purpose of this paper is to investigate the automatic continuity of )-derivations on Banach algebras and to present several results in this regard. For instance, we prove the following theorem: Let and be two Banach algebras such that has the Cohen's factorization property and , and let be two linear mappings. Let be a generalized -derivation associated with a -derivation . If for any there exists an element such that , then is continuous if and only if is continuous. [ABSTRACT FROM AUTHOR]
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- 2023
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21. The Insulin-like Growth Factor Signaling Pathway in Breast Cancer: An Elusive Therapeutic Target.
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Lee, Ji-Sun, Tocheny, Claire E., and Shaw, Leslie M.
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SOMATOMEDIN ,CELLULAR signal transduction ,BREAST cancer ,MAMMARY glands ,GLUCOSE metabolism - Abstract
In this review, we provide an overview of the role of the insulin-like growth factor (IGF) signaling pathway in breast cancer and discuss its potential as a therapeutic target. The IGF pathway ligands, IGF-1 and IGF-2, and their receptors, primarily IGF-1R, are important for normal mammary gland biology, and dysregulation of their expression and function drives breast cancer risk and progression through activation of downstream signaling effectors, often in a subtype-dependent manner. The IGF signaling pathway has also been implicated in resistance to current therapeutic strategies, including ER and HER2 targeting drugs. Unfortunately, efforts to target IGF signaling for the treatment of breast cancer have been unsuccessful, due to a number of factors, most significantly the adverse effects of disrupting IGF signaling on normal glucose metabolism. We highlight here the recent discoveries that provide enthusiasm for continuing efforts to target IGF signaling for the treatment of breast cancer patients. [ABSTRACT FROM AUTHOR]
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- 2022
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22. Polyphenols and Lactation: Molecular Evidence to Support the Use of Botanical Galactagogues.
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Kelleher SL, Burkinshaw S, and Kuyooro SE
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- Female, Humans, Animals, Dietary Supplements, Mammary Glands, Animal drug effects, Signal Transduction drug effects, Mammary Glands, Human drug effects, Mammary Glands, Human metabolism, Lactation drug effects, Polyphenols pharmacology, Galactogogues pharmacology
- Abstract
Botanicals and herbal supplements contain a diverse array of polyphenols that may affect mammary gland function and promote galactagogue activity. This scoping review is conducted to identify scientific literature elucidating how polyphenols affect mammary gland biology and cellular mechanisms critical for lactation. A literature search of PubMed and Medline reviews relevant studies in dairy animals, rodent models, and cultured mammary epithelial cells that are published from January 2010 until July 2023, to ascertain effects of polyphenols on mechanisms regulating milk production and composition. The PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Review) strategy is applied and 80 studies on polyphenols and their implications on milk production and composition are included in this review. Limited information delineating effects of polyphenols on the molecular pathways that affect lactation are found, although available information suggests modulation of Stat5 signaling/differentiation, Stat3 signaling/remodeling, mTOR and insulin signaling/energy production, and nuclear factor kappa beta (NFκβ) signaling/oxidative stress and inflammation may play roles. A profound lack of mechanistic information underscores the critical need for further research to understand the impact of botanical supplements and polyphenols on milk production and composition in humans to establish maternal nutritional guidelines to support lactation and breastfeeding goals., (© 2024 The Authors. Molecular Nutrition & Food Research published by Wiley‐VCH GmbH.)
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- 2024
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23. A variant associated to IGF-1 mRNA and protein expression in sheep.
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Flores-Encinas, Luis A., Rodríguez-Almeida, Felipe A., Felix-Portillo, Monserrath, Jahuey-Martínez, Francisco J., and Martínez-Quintana, José A.
- Subjects
GENE expression ,PROTEIN expression ,LAMBS ,SINGLE nucleotide polymorphisms ,SHEEP ,GENETIC variation ,ANIMAL feeds ,SHEEP farming - Abstract
The insulin-like growth factor-1 (IGF-1), a key hormone in muscle development was investigated for single-nucleotide polymorphisms (SNPs) upstream of the IGF-1 gene and their effects upon its cognate mRNA and hormone levels in sheep. A 70 d feeding trial was conducted with 22 F1 (Dorper × Pelibuey) lambs, individually allocated and fed a diet with a forage-to-concentrate ratio of 36:64 and 17% crude protein. Sequence analyses of 265 bp upstream the IGF-1 gene revealed the variant NC_040254.1:g.[184028491G > C;184028493G > A]. These SNPs generate alleles A and B, with frequencies of 0.66 and 0.34 in F1 lambs and of 0.73 and 0.27 in 81 pure Dorper lambs, respectively. Females were grouped by genotype AA, AB and BB (n = 3). IGF-1 hormone concentrations at 14, 42 and 70 d were higher (p < 0.05) in AA lambs compared to AB + BB lambs. The IGF-1 mRNA level was 2.6-fold higher in AA animals (n = 5, p < 0.05) than in AB + BB lambs (n = 7). A DNA binding site for the Inhibitor of Growth family member 4 (ING4) was found in allele B but not in allele A, which could explain the lower mRNA and hormone expression levels for AB + BB animals. The variant reported here appears to function as an eQTL with a negative effect on the level of IGF-1. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
24. What Can Be Expected from the Image of σ-Derivations on Banach Algebras?
- Author
-
Hosseini, A.
- Abstract
The main purpose of this paper is to obtain some results on the image of -derivations on Banach algebras. One of the main results of this paper is to prove that if is a commutative Banach algebra and is a continuous -derivation such that is a continuous homomorphism, and , then , where denotes the Jacobson radical of . Moreover, we obtain Sinclair's theorem for -derivations without assuming continuity. Indeed, under certain conditions, we prove that if is a -derivation on a Banach algebra , then for every primitive ideal of . Some other related results are also discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
25. Effects of red raspberry polyphenols and metabolites on the biomarkers of inflammation and insulin resistance in type 2 diabetes: a pilot study.
- Author
-
Moreno Uclés, Reynaldo, González-Sarrías, Antonio, Espín, Juan Carlos, Tomás-Barberán, Francisco A., Janes, Marlene, Cheng, Henrique, Finley, John, Greenway, Frank, and Losso, Jack N
- Published
- 2022
- Full Text
- View/download PDF
26. Genetic Polymorphisms of IGF1 and IGF1R Genes and Their Effects on Growth Traits in Hulun Buir Sheep.
- Author
-
Ding, Ning, Tian, Dehong, Li, Xue, Zhang, Zhichao, Tian, Fei, Liu, Sijia, Han, Buying, Liu, Dehui, and Zhao, Kai
- Subjects
HAPLOTYPES ,GENETIC polymorphisms ,SINGLE nucleotide polymorphisms ,SHEEP ,SHEEP breeds ,GENETIC variation - Abstract
The identification of candidate genes and genetic variations associated with growth traits is important for sheep breeding. Insulin like growth factor 1 (IGF1) and insulin like growth factor 1 receptor (IGF1R) are well-accepted candidate genes that affect animal growth and development. The current study attempted to assess the association between IGF1 and IGF1R genetic polymorphisms and growth traits in Hulun Buir sheep. To achieve this goal, we first identified three and ten single nucleotide polymorphisms (SNPs) in exons of IGF1 and IGF1R in Hulun Buir sheep and then constructed six haplotypes of IGF1R based on linkage disequilibrium, respectively. Association studies were performed between SNPs and haplotypes of IGF1 and IGF1R with twelve growth traits in a population encompassing 229 Hulun Buir sheep using a general linear model. Our result indicated three SNPs in IGF1 were significantly associated with four growth traits (p < 0.05). In IGF1R, three SNPs and two haplotype blocks were significantly associated with twelve growth traits (p < 0.05). The combined haplotype H5H5 and H5H6 in IGF1R showed the strong association with 12 superior growth traits in Hulun Buir sheep (p < 0.05). In conclusion, we identified SNPs and haplotype combinations associated with the growth traits, which provided genetic resources for marker-assisted selection (MAS) in Hulun Buir sheep breeding. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
27. Enrichment of Trace Metals (V, Cu, Co, Ni, and Mo) in Arctic Sediments--From Siberian Arctic Shelves to the Basin.
- Author
-
Li Li, Xiaojing Wang, Yijun Ren, Huaqiang Su, Limin Hu, Gang Yang, Zhongqiao Li, Bosin, Aleksandr A., Astakhov, Anatolii S., Jianfang Chen, Yanguang Liu, and Xuefa Shi
- Subjects
TRACE metals ,HEAVY metal content of marine sediments ,SEDIMENTATION & deposition ,OCEANOGRAPHY - Abstract
With 50% of the Arctic Ocean is consisted of continental shelves, extensive shelf-basin exchange processes exist here and plays a key role in regulating the biogeochemical recycling process of trace metals in the Arctic region. In this study, short sediment cores were collected along three transects from Siberian-Chukchi shelves to adjacent slope/basin areas. An increasing trend was found for the bulk concentrations of several metals (V, Cu, Co, Ni, and Mo) from shelf to slope/basin cores with increasing water depth. Sequential extraction experiments indicated that the Fe/Mn oxide fractions increased significantly from shelf (9%~21%) to basin cores (24%~76%) for Cu, Co, Ni, and V, while the organic/sulfide phase remained significant (~40%) for Mo. In addition, the observed dissolved metal concentrations in porewater indicated the remobilization of Fe, Mn, and Mo from shelf sediment, while V was always removed from water to the sediment, both on the shelf or in the slope/basin. Overall, in combination with the statistical analysis, we proposed that metals are transported from shelves to the central Arctic and are scavenged mainly by Mn oxides from the water column, which results in the enrichment of metals in slope/basin sediment. With the climate change, such transport and accumulation mechanism may be intensified over time, slowly leading the Arctic sediment to be a more and more important sink for those metals. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
28. Correlation between Critical Behavior and Magnetocaloric Effect near Paramagnetic to Ferromagnetic Phase Transition of Co2TiAl0.75Si0.25 Heusler Alloy.
- Author
-
Datta, Subhadeep, Guha, Shampa, Panda, Shantanu Kumar, and Kar, Manoranjan
- Subjects
MAGNETOCALORIC effects ,HEUSLER alloys ,PHASE transitions ,MEAN field theory ,MAGNETIC cooling ,HEISENBERG model - Abstract
Heusler alloys have drawn considerable interest, due to their tunable properties, for technological applications. The literature review reveals that the critical exponents and magnetocaloric effect (MCE) of Co2TiAl0.75Si0.25 quaternary Heusler alloy need to be established. Hence, Co2TiAl0.75Si0.25 alloy is prepared by the arc melting method. Critical exponents of the alloy are obtained by analyzing magnetic isotherms with various techniques, such as Arrot plots, Kouvel–Fisher plots, critical isotherm analysis, and magnetocaloric analysis near the transition temperature. The paramagnetic to ferromagnetic transition temperature is found to be ≈235 ±2.5 K. The nature of the Arrot plots and the universal curve of the MCE confirm this as a second‐order phase transition. Despite the moderate magnetocaloric values, the large working temperature (≈75 K at 3 T) makes this alloy a potential candidate for a multistage magnetic refrigeration application. The critical exponents obtained from different techniques fall in between the theoretical prediction from the mean field theory, which indicates long‐range ferromagnetic exchange interaction, and the 3D Heisenberg model, implying short‐range interaction. The range of interaction (σ = 1.727) also confirms this. This complex magnetic interaction may arise from the competition between localized and itinerant electron present in the system. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
29. The Multi-Faced Role of PAPP-A in Post-Partum Breast Cancer: IGF-Signaling is Only the Beginning.
- Author
-
Jenkins, Edmund Charles, Brown, Samantha O., and Germain, Doris
- Subjects
BREAST cancer ,SOMATOMEDIN ,EWING'S sarcoma ,BLOOD proteins ,CARRIER proteins - Abstract
Insulin-like growth factor (IGF) signaling and control of local bioavailability of free IGF by the IGF binding proteins (IGFBP) are important regulators of both mammary development and breast cancer. A recent genome-wide association study (GWAS) identified small nucleotide polymorphisms that reduce the expression of IGFBP-5 as a risk factor of developing breast cancer. This observation suggests that genetic alterations leading to a decreased level of IGFBP-5 may also contribute to breast cancer. In the current review, we focus on Pregnancy-Associated Plasma Protein A (PAPP-A), a protease involved in the degradation of IGFBP-5. PAPP-A is overexpressed in the majority of breast cancers but its role in cancer has only begun to be explored. More specifically, this review aims at highlighting the role of post-partum involution in the oncogenic function of PAPP-A. Notably, we summarize recent studies indicating that PAPP-A plays a role not only in the degradation of IGFBP-5 but also in the deposition of collagen and activation of the collagen receptor discoidin 2 (DDR2) during post-partum involution. Finally, considering the immunosuppressive microenvironment of post-partum involution, we also discuss the unexpected finding made in Ewing Sarcoma that PAPP-A plays a role in immune evasion. While the immunosuppressive role of PAPP-A in breast cancer remains to be determined, collectively these studies highlight the multifaced role of PAPP-A in cancer that extends well beyond its effect on IGF-signaling. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
30. An integrated approach for remanufacturing job shop scheduling with routing alternatives.
- Author
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Lingling Li, Congbo Li, Li Li, Ying Tang, and Qingshan Yang
- Published
- 2019
- Full Text
- View/download PDF
31. Further results on several types of generalized inverses.
- Author
-
Zhu, Huihui
- Subjects
INVERSE relationships (Mathematics) ,ASSOCIATIVE rings ,VON Neumann algebras ,SEMIGROUP rings ,RING theory - Abstract
Let
R be an associative ring with unity 1 and leta ,b ,c ∈R . In this paper, several characterizations for hybrid (b ,c )-inverses ofa are given. Also, the hybrid (b ,c )-inverse ofa is characterized by the group inverse ofab , under certain hypothesis. In particular, existence criteria for the the inverse along an element are obtained. Finally, we get the double commutant property and the reverse order law of annihilator (b ,c )-inverses. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
32. New insights into antidiabetic drugs: Possible applications in cancer treatment.
- Author
-
Shafiei‐Irannejad, Vahid, Samadi, Nasser, Salehi, Roya, Yousefi, Bahman, and Zarghami, Nosratollah
- Subjects
PHYSIOLOGICAL effects of hypoglycemic agents ,DRUG efficacy ,TREATMENT of diabetes ,CANCER treatment ,DISEASE management - Abstract
Globally at 2014, it was estimated that there was 347 million people with diabetes in which 90 percent of them were diagnosed with type 2 diabetes mellitus (T2 DM). Although the association between diabetes mellitus and cancer risk was found about 100 years ago, the issue is not still clear. Many studies especially cohort and case-control studies have suggested a higher risk of cancer in patients with diabetes mainly in those with type 2 diabetes. Insulin concentration is high in these patients, and due to its mitogenic effects, it may be a possible hypotheses for higher risk of cancer in diabetic patients. Therefore, antidiabetic drugs, which are involved in insulin secretion and sensitivity, may have beneficial effects in cancer treatment. Several groups of drugs with different mechanisms of action, mostly prescribed orally, are used for the treatment of type 2 diabetes mellitus including, insulin sensitizers (thiazolidinediones), insulin secretagogues (sulfonylureas), and biguanides. In this review, the possible effects of antidiabetic drugs (biguanides, thiazolidinediones, and sulfonylureas) and some of their mechanisms for overcoming cancer will be discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
33. People with Serious Mental Illness.
- Author
-
McKinnon, Karen, Elkington, Katherine S., Cournos, Francine, Pinho, Veronica, Guimaraes, Mark D. C., and Wainberg, Milton L.
- Published
- 2016
- Full Text
- View/download PDF
34. Fetal Alcohol Exposure and Mammary Tumorigenesis in Offspring: Role of the Estrogen and Insulin-Like Growth Factor Systems.
- Author
-
Cohick, Wendie S., Crismale-Gann, Catina, Stires, Hillary, and Katz, Tiffany A.
- Published
- 2015
- Full Text
- View/download PDF
35. Alternative Description of Three Dimensional Complex Diassociative Algebras with Some Constraints.
- Author
-
Rikhsiboev, Ikrom M. and Venkatesan, Yuvendra Rao
- Subjects
DIMENSIONAL analysis ,MATHEMATICAL complex analysis ,STATISTICAL association ,LIE algebras ,DIMENSIONS - Abstract
Considering significant of classification problems in modern algebra, especially in the algebras which related to Lie algebras, current research pursue investigation on structure theory of low dimensional diassociative algebras. Note that the classification of complex diassociative algebras in low dimensions have been presented in our recent studies, however this paper deals to provide description of such algebras with some constrains in dimension three, applying notion of annihilator. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
36. Two cases of diabetic mastopathy: MR imaging and pathological correlation.
- Author
-
Nasu, Hatsuko, Ikeda, Akiko, Ogura, Hiroyuki, Teruya, Chikako, Koizumi, Kei, Kinoshita, Mana, Tsuchida, Takashi, Baba, Satoshi, Miura, Katsutoshi, Takehara, Yasuo, and Sakahara, Harumi
- Abstract
Diabetic mastopathy is a rare benign condition associated with long-standing diabetes mellitus and presents with breast lumps. This report describes two cases in which diffusion-weighted images (DWI) on magnetic resonance imaging were quite different from each other. In case 1, there were hyperintense lesions on DWI, and surgically removed specimens revealed ductitis with marked lymphocytic infiltration. In case 2, no abnormal intensity was depicted on DWI, and biopsy specimens showed dense stromal fibrosis with mild perivascular lymphocytic infiltration that corresponded to previous reports. Although it is reported that diabetic mastopathy is composed of dense fibrous tissue with low cellularity that results in no hyperintense lesion on DWI, in cases with marked lymphocytic infiltration, strong hyperintensity can be seen on DWI mimicking malignant breast tumors. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
37. Hyperglycemic tumor microenvironment induces perineural invasion in pancreatic cancer.
- Author
-
Li, Junhui, Ma, Jiguang, Han, Liang, Xu, Qinhong, Lei, Jianjun, Duan, Wanxing, Li, Wei, Wang, Fengfei, Wu, Erxi, Ma, Qingyong, and Huo, Xiongwei
- Published
- 2015
- Full Text
- View/download PDF
38. A color petri net based scheduling model for remanufacturing system with stochastic process routing.
- Author
-
Li, Lingling, Li, Congbo, and Tang, Ying
- Published
- 2014
- Full Text
- View/download PDF
39. Uncertainty management in remanufacturing: A review.
- Author
-
Tang, Ying and Li, Congbo
- Abstract
Remanufacturing is practice of importance due to the increasing environmental and economic pressure. The process exhibits high levels of uncertainty, making its planning and control more complex than in traditional manufacturing. This paper reviews recent methods for modeling, analyzing and managing such uncertainty in remanufacturing. The purpose is to survey state-of-the-art of this emerging area to supply important insights for future study. [ABSTRACT FROM PUBLISHER]
- Published
- 2012
- Full Text
- View/download PDF
40. Stromal matrix metalloproteinase-11 is involved in the mammary gland postnatal development.
- Author
-
Tan, J, Buache, E, Alpy, F, Daguenet, E, Tomasetto, C-L, Ren, G-S, and Rio, M-C
- Subjects
MATRIX metalloproteinases ,DEVELOPMENT of mammary glands ,BREAST cancer prognosis ,CANCER invasiveness ,IMMUNOHISTOCHEMISTRY ,LABORATORY mice - Abstract
MMP-11 is a bad prognosis paracrine factor in invasive breast cancers. However, its mammary physiological function remains largely unknown. In the present study we have investigated MMP-11 function during postnatal mammary gland development and function using MMP-11-deficient (MMP-11−/−) mice. Histological and immunohistochemical analyses as well as whole-mount mammary gland staining show alteration of the mammary gland in the absence of MMP-11, where ductal tree, alveolar structures and milk production are reduced. Moreover, a series of transplantation experiments allowed us to demonstrate that MMP-11 exerts an essential local paracrine function that favors mammary gland branching and epithelial cell outgrowth and invasion through adjacent connective tissues. Indeed, MMP-11−/− cleared fat pads are not permissive for wild-type epithelium development, whereas MMP-11−/− epithelium transplants grow normally when implanted in wild-type cleared fat pads. In addition, using primary mammary epithelial organoids, we show in vitro that this MMP-11 pro-branching effect is not direct, suggesting that MMP-11 acts via production/release of stroma-associated soluble factor(s). Finally, the lack of MMP-11 leads to decreased periductal collagen content, suggesting that MMP-11 has a role in collagen homeostasis. Thus, local stromal MMP-11 might also regulate mammary epithelial cell behavior mechanically by promoting extracellular matrix stiffness. Collectively, the present data indicate that MMP-11 is a paracrine factor involved during postnatal mammary gland morphogenesis, and support the concept that the stroma strongly impact epithelial cell behavior. Interestingly, stromal MMP-11 has previously been reported to favor malignant epithelial cell survival and promote cancer aggressiveness. Thus, MMP-11 has a paracrine function during mammary gland development that might be harnessed to promote tumor progression, exposing a new link between development and malignancy. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
41. STED super-resolution microscopy reveals an array of MINOS clusters along human mitochondria.
- Author
-
Jans, Daniel C., Wurm, Christian A., Riedel, Dietmar, Wenzel, Dirk, Stagge, Franziska, Deckers, Markus, Rehling, Peter, and Jakobs, Stefan
- Subjects
MITOCHONDRIAL membranes ,MITOCHONDRIAL proteins ,ELECTRON microscopy ,ORGANELLES ,BIOMOLECULES spectra ,BIOLOGICAL membranes - Abstract
The mitochondrial inner membrane organizing system (MINOS) is a conserved large hetero-oligomeric protein complex in the mitochondrial inner membrane, crucial for the maintenance of cristae morphology. MINOS has been suggested to represent the core of an extended protein network that controls mitochondrial function and structure, and has been linked to several human diseases. The spatial arrangement of MINOS within mitochondria is ill-defined, however. Using super-resolution stimulated emission depletion (STED) microscopy and immunogold electron microscopy, we determined the distribution of three known human MINOS subunits (mitofilin, MINOS1, and CHCHD3) in mammalian cells. Super-resolution microscopy revealed that all three subunits form similar clusters within mitochondria, and that MINOS is more abundant in mitochondria around the nucleus than in peripheral mitochondria. At the submitochondrial level, mitofilin, a core MINOS subunit, is preferentially localized at cristae junctions. In primary human fibroblasts, mitofilin labeling uncovered a regularly spaced pattern of clusters arranged in parallel to the cell growth surfaces. We suggest that this array of MINOS complexes might explain the observed phenomenon of largely horizontally arranged cristae junctions that connect the inner boundary membrane to lamellar cristae. The super-resolution images demonstrate an unexpectedly high level of regularity in the nanoscale distribution of the MINOS complex in human mitochondria, supporting an integrating role of MINOS in the structural organization of the organelle. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
42. Sclerosing lymphocytic lobulitis in a male patient with asthma.
- Author
-
Batrani, Meenakshi, Bhardwaj, Minakshi, and Biswal, U.C.
- Subjects
DIABETES ,DERMATOFIBROMA ,LYMPHOCYTIC leukemia ,AUTOIMMUNE diseases ,OBSTRUCTIVE lung diseases ,ASTHMA - Abstract
Sclerosing lymphocytic lobulitis is commonly but not exclusively associated with type I diabetes mellitus. Association with other autoimmune diseases is known and also disease is infrequently seen in males. We herein report a rare case of sclerosing lymphocytic lobulitis in a male patient with asthma. Recognition of this entity in the absence of diabetes and awareness of its existence in males is important to avoid unwarranted surgical procedures because it may mimic carcinoma both clinically and radiologically. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
43. Inhibiting PI3K reduces mammary tumor growth and induces hyperglycemia in a mouse model of insulin resistance and hyperinsulinemia.
- Author
-
Gallagher, E J, Fierz, Y, Vijayakumar, A, Haddad, N, Yakar, S, and LeRoith, D
- Subjects
BREAST cancer treatment ,TYPE 2 diabetes ,HYPERINSULINISM ,INSULIN resistance ,HYPERGLYCEMIA ,PHOSPHATIDYLINOSITOL 3-kinases ,LABORATORY mice - Abstract
Women with type 2 diabetes mellitus (T2DM) are at a greater risk of developing and dying from breast cancer than women without T2DM. Insulin resistance and hyperinsulinemia underlie the pathogenesis of T2DM. In the MKR mouse model of insulin resistance, we have previously shown increased activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway in association with accelerated mammary tumor growth. In this study, we demonstrate that inhibiting PI3K with the oral pan-class I PI3K inhibitor, NVP-BKM120 reduced the growth of Met-1 and MCNeuA mammary tumor orthografts in the MKR mouse. NVP-BKM120 treatment decreased phosphorylation of Akt and S6 ribosomal protein (S6rp); no change in Erk1/2 phosphorylation was seen. Hyperglycemia, hypertriglyceridemia and greater hyperinsulinemia developed in the MKR mice treated with NVP-BKM120. We previously reported reduced tumor growth using intraperitoneal rapamycin in the MKR mouse, with the development of hyperglycemia and hypertriglyceridemia. Therefore, we examined whether the oral PI3K/mTOR inhibitor NVP-BEZ235 augmented the tumor suppressing effects of PI3K inhibition. We also investigated the effect of targeted PI3K/mTOR inhibition on PI3K/Akt/mTOR and Erk1/2 signaling, and the potential effects on glycemia. NVP-BEZ235 suppressed the growth of Met-1 and MCNeuA tumor orthografts, and decreased Akt and S6rp phosphorylation, despite increased Erk1/2 phosphorylation in Met-1 orthografts of MKR mice. Less marked hyperglycemia and hyperinsulinemia developed with NVP-BEZ235 than NVP-BKM120. Overall, the results of this study demonstrated that inhibiting PI3K/Akt/mTOR signaling with the oral agents NVP-BKM120 and NVP-BEZ235 decreased mammary tumor growth in the hyperinsulinemic MKR mouse. Inhibiting PI3K alone led to more severe metabolic derangement than inhibiting both PI3K and mTOR. Therefore, PI3K may be an important target for the treatment of breast cancer in women with insulin resistance. Monitoring for hyperglycemia and dyslipidemia should be considered when using these agents in humans, given the metabolic changes detected in this study. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
44. Mammary gland development.
- Author
-
Macias, Hector and Hinck, Lindsay
- Published
- 2012
- Full Text
- View/download PDF
45. Idiopathic granulomatous lobular mastitis.
- Author
-
Pereira, Frederick A., Mudgil, Adarsh V., Macias, Edgar S., and Karsif, Karen
- Subjects
MASTITIS ,BREAST diseases ,CORYNEBACTERIACEAE ,ADRENOCORTICAL hormones ,METHOTREXATE ,ANTIBIOTICS - Abstract
Idiopathic granulomatous lobular mastitis (IGLM) is a rare breast condition with prominent skin findings. It is typically seen in young parous women. Painful breast masses, draining sinuses, scarring, and breast atrophy are the main clinical manifestations. IGLM can resemble a variety of other inflammatory and neoplastic processes of the breast. It is thought to result from obstruction and rupture of breast lobules. Extravasated breast secretions then induce an inflammatory reaction. Corynebacteria have also been implicated in the pathogenesis. Treatment is surgical, but systemic corticosteroids, methotrexate, and antibiotics also play a role. [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
46. Targeted Loss of GHR Signaling in Mouse Skeletal Muscle Protects Against High-Fat Diet--Induced Metabolic Deterioration.
- Author
-
Vijayakumar, Archana, YingJie Wu, Hui Sun, Xiaosong Li, Jeddy, Zuha, Chengyu Liu, Schwartz, Gary J., Yakar, Shoshana, and LeRoith, Derek
- Subjects
LABORATORY mice ,HIGH-fat diet ,METABOLIC disorders ,SOMATOTROPIN ,MUSCLE physiology - Abstract
Growth hormone (GH) exerts diverse tissue-specific metabolic effects that are not revealed by global alteration of GH action. To study the direct metabolic effects of GH in the muscle, we specifically inactivated the growth hormone receptor (ghr) gene in postnatal mouse skeletal muscle using the Cre/loxP system (mGHRKO model). The metabolic state of the mGHRKO mice was characterized under lean and obese states. High-fat diet feeding in the mGHRKO mice was associated with reduced adiposity, improved insulin sensitivity, lower systemic inflammation, decreased muscle and hepatic triglyceride content, and greater energy expenditure compared with control mice. The obese mGHRKO mice also had an increased respiratory exchange ratio, suggesting increased carbohydrate utilization. GH-regulated suppressor of cytokine signaling-2 (socs2) expression was decreased in obese mGHRKO mice. Interestingly, muscles of both lean and obese mGHRKO mice demonstrated a higher interleukin-15 and lower myostatin expression relative to controls, indicating a possible mechanism whereby GHR signaling in muscle could affect liver and adipose tissue function. Thus, our study implicates skeletal muscle GHR signaling in mediating insulin resistance in obesity and, more importantly, reveals a novel role of muscle GHR signaling in facilitating cross-talk between muscle and other metabolic tissues. Diabetes 61:94--103, 2012 [ABSTRACT FROM AUTHOR]
- Published
- 2012
- Full Text
- View/download PDF
47. Rosai-Dorfman Disease Presenting as a Breast Mass and Enlarged Axillary Lymph Node Mimicking Malignancy: A Case Report and Review of the Literature.
- Author
-
Tenny, Steven O., McGinness, Marilee, Zhang, Da, Damjanov, Ivan, and Fan, Fang
- Subjects
NON-langerhans-cell histiocytosis ,BREAST ,HISTIOCYTOSIS - Abstract
Rosai-Dorfman disease (also called sinus histiocytosis with massive lymphadenopathy) involves lymph nodes or lymph nodes with extranodal sites. We present a unique case of a patient presenting with a breast mass and axillary lymphadenopathy, mimicking malignancy clinically and radiographically. Core needle biopsies of the breast and axillary lymph node showed histologic features concerning the lymphoma. However, excisional biopsy specimen demonstrated characteristic features of Rosai-Dorfman disease. The disease recurred locally 6 months later in the same breast, 1 month later in the contralateral breast, and 11 month later in the subcutaneous tissue of left flank. A review of the literature of Rosai-Dorfman disease involving the breast is also presented. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
48. Alcohol Exposure In Utero Leads to Enhanced Prepubertal Mammary Development and Alterations in Mammary IGF and Estradiol Systems.
- Author
-
Polanco, Tiffany, Crismale-Gann, Catina, and Cohick, Wendie
- Abstract
Exposure to alcohol during fetal development increases susceptibility to mammary cancer in adult rats. This study determined if early changes in mammary morphology and the insulin-like growth factor (IGF)/estradiol axis are involved in the mechanisms that underlie this increased susceptibility. Pregnant Sprague-Dawley rats were fed a liquid diet containing 6.7% ethanol (alcohol), an isocaloric liquid diet (pair-fed), or rat chow ad libitum from days 11 to 21 of gestation. At birth, female pups were cross-fostered to ad libitum-fed control dams. Offspring were euthanized at postnatal days (PND) 20, 40, or 80. Animals were injected with BrdU before euthanasia, then mammary glands, serum, and livers were collected. Mammary glands from animals exposed to alcohol in utero displayed increased epithelial cell proliferation and aromatase expression at PND 20 and 40. Mammary IGF-I mRNA was higher in alcohol-exposed animals relative to controls at PND 20, while mammary IGFBP-5 mRNA was lower in this group at PND 40. Hepatic IGF-I mRNA expression was increased at all time points in alcohol-exposed animals, however, circulating IGF-I levels were not altered. These data indicate that alcohol exposure in utero may advance mammary development via the IGF and estradiol systems, which could contribute to increased susceptibility to mammary cancer later in life. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
49. Development of Laguerre Neural-Network-Based Intelligent Sensors for Wireless Sensor Networks.
- Author
-
Patra, Jagdish Chandra, Meher, Pramod Kumar, and Chakraborty, Goutam
- Subjects
ARTIFICIAL neural networks ,INTELLIGENT agents ,DETECTORS ,WIRELESS sensor networks ,ROBOTS ,TEMPERATURE ,LAGUERRE polynomials - Abstract
The node of a wireless sensor network (WSN), which contains a sensor module with one or more physical sensors, may be exposed to widely varying environmental conditions, e.g., temperature, pressure, humidity, etc. Most of the sensor response characteristics are nonlinear, and in addition to that, other environmental parameters influence the sensor output nonlinearly. Therefore, to obtain accurate information from the sensors, it is important to linearize the sensor response and compensate for the undesirable environmental influences. In this paper, we present an intelligent technique using a novel computationally efficient Laguerre neural network (LaNN) to compensate for the inherent sensor nonlinearity and the environmental influences. Using the example of a capacitive pressure sensor, we have shown through extensive computer simulations that the proposed LaNN-based sensor can provide highly linearized output, such that the maximum full-scale error remains within \pm1.0% over a wide temperature range from -50 ^\circ\C to 200 ^ \circ\C for three different types of nonlinear dependences. We have carried out its performance comparison with a multilayer-perceptron-based sensor model. We have also proposed a reduced-complexity run-time implementation scheme for the LaNN-based sensor model, which can save about 50% of the hardware and reduce the execution time by four times, thus making it suitable for the energy-constrained WSN applications. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
50. A moderate elevation of circulating levels of IGF-I does not alter ErbB2 induced mammary tumorigenesis.
- Subjects
BREAST cancer ,SOMATOMEDIN ,MAMMARY gland tumors ,CARCINOGENESIS ,LABORATORY mice ,TUMOR growth ,GROWTH factors - Abstract
The article offers information on a research that examines the role of moderately increased circulating insulin-like growth factor-1 (IGF-1) in promoting mammary tumorigenesis and enhancing ErbB2 mediated mammary tumor growth. It is mentioned that IGF-1 is associated with high risk of breast cancer and the study was conducted on virgin female mice. It is observed that moderately high levels of circulating IGF-1 are not associated with the development of breast cancer.
- Published
- 2011
- Full Text
- View/download PDF
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