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3. Protein intake and urinary albumin excretion rates in the EURODIAB IDDM Complications Study

Author

Toeller, M, Buyken, A, Heitkamp, G, Brämswig, S, Mann, J, Milne, R, Gries, F. A, Keen, H, Karamanos, B, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Roussipenessi, D, Cignarelli, M, Giorgino, R, Degeco, Ml, Ramunni, I, Ionescutirgoviste, C, Strachinariu, R, Nicolau, A, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, B, Cronin, Cc, Humphreys, M, Klischan, A, Forst, T, Schumacher, W, Rottiers, R, Priem, H, Deschoolmeester, Mj, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Krans, Hmj, Lemkes, Hhpj, Jansen, Jj, Eltedewever, Bm, Nunescorrea, J, Boavida, J, Carvalho, R, Afonso, Mj, Monteiro, M, Mitchell, DAVID ROSS, Jepson, E, Mchardyyoung, S, Fuller, Jh, Betteridge, Dj, Milne, M, Thompson, T, Michel, G, Wirion, R, Paquet, S, Hornick, H, Boulton, Ajm, Ashe, H, Fernando, Djs, Curwell, J, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, F, Marchi, Manuel, Mehnert, H, Nuber, A, Janka, H, Nichting, M, Standl, E, Crepaldi, G, Nosadini, R, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Baclet, N, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Navalesi, R, Penno, G, Miccoli, R, Nannipieri, M, Manfredi, S, Bertolotto, A, Ghirlanda, G, Cotroneo, P, Manto, A, Teodonio, C, Minnella, A, Careddu, G, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Estivi, Sivieri, P., R, Carta, Q, Petraroli, G, Papazoglu, N, Goutzourela, M, Manes, C, Bensoussan, D, Fallas, Mc, Fallas, P, Dhanaeus, C, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Branzi, P, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Strohner, H, Just, M, Walford, S, Wardle, Henio, Ev, S, Cooke, H, Roglic, G, Resman, Z, Metelko, Z, Skrabalo, Z, Vrhovac, V., Toeller, M, Buyken, A, Heitkamp, G, Bramswig, S, Mann, J, Milne, R, Gries, Fa, Keen, H, Karamanos, B, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Roussipenessi, D, Cignarelli, M, Giorgino, R, Degeco, Ml, Ramunni, I, Ionescutirgoviste, C, Strachinariu, R, Nicolau, A, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, B, Cronin, Cc, Humphreys, M, Klischan, A, Forst, T, Schumacher, W, Rottiers, R, Priem, H, Deschoolmeester, Mj, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Krans, Hmj, Lemkes, Hhpj, Jansen, Jj, Eltedewever, Bm, Nunescorrea, J, Boavida, J, Carvalho, R, Afonso, Mj, Monteiro, M, David, R, Jepson, E, Mchardyyoung, S, Fuller, Jh, Betteridge, Dj, Milne, M, Thompson, T, Michel, G, Wirion, R, Paquet, S, Hornick, H, Boulton, Ajm, Ashe, H, Fernando, Dj, Curwell, J, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, F, Marchi, M, Mehnert, H, Nuber, A, Janka, H, Nichting, M, Standl, E, Crepaldi, G, Nosadini, R, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Baclet, N, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Navalesi, R, Penno, G, Miccoli, R, Nannipieri, M, Manfredi, S, Bertolotto, A, Ghirlanda, G, Cotroneo, P, Manto, A, Teodonio, C, Minnella, A, Careddu, G, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Papazoglu, N, Goutzourela, M, Manes, C, Bensoussan, D, Fallas, Mc, Fallas, P, Dhanaeus, C, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Branzi, P, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Strohner, H, Just, M, Walford, S, Wardle, Ev, Henio, S, Cooke, H, Roglic, G, Resman, Z, Metelko, Z, Skrabalo, Z, and Vrhovac, V

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Urinary system, Physiology, Albuminuria, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Diabetic Nephropathies, Dietary Proteins, Europe, Female, Humans, Middle Aged, Nephropathy, Protein intake, urinary albumin, Diabetic nephropathy, Excretion, Diabetes mellitus, Internal medicine, Diabetes Mellitus, Internal Medicine, Medicine, Proteinuria, business.industry, medicine.disease, Endocrinology, Blood pressure, medicine.symptom, business, Type 1, Kidney disease
Abstract

For people with insulin-dependent diabetes mellitus (IDDM) renal disease represents a life-threatening and costly complication. The EURODIAB IDDM Complications Study, a cross-sectional, clinic-based study, was designed to determine the prevalence of renal complications and putative risk factors in stratified samples of European individuals with IDDM. The present study examined the relationship between dietary protein intake and urinary albumin excretion rate (AER). Food intake was assessed centrally by a standardized 3-day dietary record. Urinary AER was determined in a central laboratory from a timed 24-h urine collection. Complete data were available from 2696 persons with IDDM from 30 centres in 16 European countries. In individuals who reported protein consumption less than 20 % of total food energy intake, mean AER was below 20 μg/min. In those in whom protein intake constituted more than 20 %, mean AER increased, a trend particularly pronounced in individuals with hypertension and/or poor metabolic control. Trends reached statistical significance for intakes of total protein (% of energy, p = 0.01) and animal protein (% of energy, p = 0.02), while no association was seen for vegetable protein (p = 0.83). These findings support the current recommendation for people with diabetes not to exceed a protein intake of 20 % of total energy. Monitoring and adjustment of dietary protein appears particularly desirable for individuals with AER exceeding 20 μg/min (approximately 30 mg/24 h), especially when arterial pressure is raised and/or diabetic control is poor. [Diabetologia (1997) 40: 1219–1226]

Published
1997
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4. Repeatability of three-day dietary records in the EURODIAB IDDM Complications Study

Author

Toeller M, Buyken A, Heitkamp G, Milne R, Klischan A, Gries FA, Fuller JH, Keen H, Krans HMJ, Navalesi R, Sjolie AK, Stephenson JM, Viberti GC, Karamanos B, Tountas C, Kofinis A, Petrou K, Katsilambros N, RoussiPenessi D, Cignarelli M, Giorgino R, DeGeco ML, Ramunni I, IonescuTirgoviste C, Strachinariu R, Nicolau A, Tamas G, Kerenyi Z, Ahmed AM, Toth J, Kempler P, Muntoni S, Songini M, Stabilini M, Fossarello M, Pintus S, Ferriss B, Cronin CC, Humphreys M, Forst T, Schumacher W, Wagener W, Venhaus A, Rottiers R, Priem H, Deschoolmeester MJ, Ebeling P, Sinisalo M, Koivisto VA, IdziorWalus B, Solnica B, SzopinskaCiba L, Solnica K, Lemkes HHPJ, Jansen JJ, EltedeWever BM, NunesCorrea J, Boavida J, Carvalho R, Afonso MJ, Monteiro M, David R, Jepson E, McHardyYoung S, Betteridge DJ, Milne M, Thompson T, Michel G, Wirion R, Paquet S, Hornick H, Boulton AJM, Ashe H, Fernando DJS, Curwell J, Pozza G, Slaviero G, Comi G, Fattor B, Marchi M, Mehnert H, Nuber A, Janka H, Nichting M, Standl E, Crepaldi G, Nosadini R, Cathelineau G, Cathelineau BV, Jellal M, Grodner N, Feiss PG, Baclet N, Santeusanio F, Rosi G, Ventura MRM, Cagini C, Marino C, Penno G, Miccoli R, Nannipieri M, Manfredi S, Bertolotto A, Ghirlanda G, Manto A, Cotroneo P, Ward JD, Tesfaye S, Mody C, Rudd C, Papazoglou N, Goutzourela M, Manes C, Molinatti GM, Vitelli F, Porta M, Pagano GF, Estivi P, Sivieri R, Carta Q, Petraroli G, BenSoussan D, Fallas MC, Fallas P, Dhanaeus C, Bourgeois MD, Muggeo M, Cacciatori V, Bellavere F, Galante P, Gemma ML, Branzi P, Irsigler K, Abrahamian H, Gurdet C, Hornlein B, Willinger C, Strohner H, Just M, Walford S, Wardle EV, Henio S, Cooke H, Roglic G, Resman Z, Metelko Z, Skrabalo Z., BANDELLO , FRANCESCO, Toeller, M, Buyken, A, Heitkamp, G, Milne, R, Klischan, A, Gries, Fa, Fuller, Jh, Keen, H, Krans, Hmj, Navalesi, R, Sjolie, Ak, Stephenson, Jm, Viberti, Gc, Karamanos, B, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Roussipenessi, D, Cignarelli, M, Giorgino, R, Degeco, Ml, Ramunni, I, Ionescutirgoviste, C, Strachinariu, R, Nicolau, A, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, B, Cronin, Cc, Humphreys, M, Forst, T, Schumacher, W, Wagener, W, Venhaus, A, Rottiers, R, Priem, H, Deschoolmeester, Mj, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Lemkes, Hhpj, Jansen, Jj, Eltedewever, Bm, Nunescorrea, J, Boavida, J, Carvalho, R, Afonso, Mj, Monteiro, M, David, R, Jepson, E, Mchardyyoung, S, Betteridge, Dj, Milne, M, Thompson, T, Michel, G, Wirion, R, Paquet, S, Hornick, H, Boulton, Ajm, Ashe, H, Fernando, Dj, Curwell, J, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, Francesco, Marchi, M, Mehnert, H, Nuber, A, Janka, H, Nichting, M, Standl, E, Crepaldi, G, Nosadini, R, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Baclet, N, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Penno, G, Miccoli, R, Nannipieri, M, Manfredi, S, Bertolotto, A, Ghirlanda, G, Manto, A, Cotroneo, P, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Papazoglou, N, Goutzourela, M, Manes, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Bensoussan, D, Fallas, Mc, Fallas, P, Dhanaeus, C, Bourgeois, Md, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Branzi, P, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Strohner, H, Just, M, Walford, S, Wardle, Ev, Henio, S, Cooke, H, Roglic, G, Resman, Z, Metelko, Z, and Skrabalo, Z.

Subjects
Dietary Fiber, medicine.medical_specialty, Alcohol Drinking, European community, Saturated fat, Population, Medicine (miscellaneous), the EURODIAB IDDM Study, Diabetes mellitus, Dietary Carbohydrates, medicine, Humans, education, education.field_of_study, Nutrition and Dietetics, business.industry, Reproducibility of Results, Repeatability, medicine.disease, Dietary Fats, Diet Records, Confidence interval, Surgery, Europe, three-day dietary records, Diabetes Mellitus, Type 1, Nutrition Assessment, Quartile, Cohort, Dietary Proteins, Energy Intake, business, Demography
Abstract

Objectives: Repeatability of a dietary method is important in determining the quality of nutritional data. It should be assessed in the population of interest. This study evaluated the repeatability of nutritional data from standardized three-day dietary records, from the clinic-based, cross-sectional multi-centre EURODIAB IDDM Complications Study. Design and Subjects: 15% of the total EURODIAB cohort was randomly selected to test the repeatability of nutritional intake data. Two three-day records, completed three weeks apart, were available for 216 diabetic patients (7.5%) representative of the total cohort. All records were analysed centrally, for intakes of protein (animal and vegetable), fat (saturated fat and cholesterol), carbohydrate, fibre, alcohol and energy. Repeatability was measured comparing mean intakes, determining the proportion of patients classified into the same/opposite quartile by the two three-day records and assessing mean differences with standard deviations (s.d.d). Results: There were no significant differences in mean energy and nutrient intakes between the first and second records. Classification of individuals into the opposite quartile occurred only in 0–4% of patients and overall about 50% (range 44–74%) of the subjects were classified into the same quartiles of intakes. Only small mean differences were found for energy intake (−156 (1633) kJ; 95% confidence limits −375, 63 kJ) and nutrients with s.d.ds comparable to intra-individual variations in the general population. The differences in energy intake were randomly distributed over the range of intakes. Conclusions: The present study demonstrates that standardized three day dietary records show a high degree of repeatability within a short period of time in a sample of European IDDM patients. The good repeatability strengthens the conclusions drawn from the nutritional data in the EURODIAB IDDM Complications Study. Sponsorship: Nutrition Co-ordinating Centre research funds, Diabetes Research Institute at Heinrich-Heine University, Dusseldorf. The EURODIAB IDDM Complications Study was supported by the European Community.

Published
1997
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5. Fibrinogen and von Willebrand factor in IDDM: relationships to lipid vascular risk factors, blood pressure, glycaemic control and urinary albumin excretion rate: the EURODIAB IDDM Complications Study

Author

Greaves, M, Malia, Rg, Goodfellow, K, Mattock, M, Stevens, Lk, Stephenson, Jm, Fuller, Jh, Karamanos, B, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Giorgino, R, Cignarelli, M, Decicco, Ml, Ramunni, I, Ionescutirgoviste, C, Iosif, Cm, Pitei, D, Buligescu, S, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, Jb, Cronin, Cc, Whyte, Ae, Cleary, Pe, Toeller, M, Klischan, A, Forst, T, Gries, Fa, Rottiers, R, Priem, H, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Krans, Hmj, Lemkes, Hhpj, Jansen, Jj, Brachter, J, Nunescorrea, J, Boavida, J, Michel, G, Wirion, R, Boulton, Ajm, Ashe, H, Fernando, Djs, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, F, Janka, Hu, Nuber, A, Mehnert, H, Bensoussan, D, Fallas, Mc, Fallas, P, Jepson, E, Mchardyyoung, S, Betteridge, Dj, Milne, M, Crepaldi, G, Nosadini, R, Segato, T, Midena, E, Cipollina, Mr, Fedele, D, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Navalesi, R, Penno, G, Miccoli, Roberto, Nannipieri, Monica, Manfredi, S, Ghirlanda, G, Cotroneo, P, Manto, A, Teodonio, C, Minnella, A, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Perin, Pc, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Papazoglou, N, Manes, G, Triantaphyllou, G, Ioannides, A, Skazagar, G, Kontogiannis, I, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Walford, S, Wardle, Ev, Hughes, S, Roglic, G, Resman, Z, Metelko, Z, Skrabalo, Z, Keen, H, Navelesi, R, Sjolie, Ak, Viberti, Gc, Ward, J, Partridge, T, John, Wg, Collins, A, Dredge, A, Sharp, R, Kohner, E, Aldington, S, Cockley, S., Greaves, M, Malia, Rg, Goodfellow, K, Mattock, M, Stevens, Lk, Stephenson, Jm, Fuller, Jh, Karamanos, B, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Giorgino, R, Cignarelli, M, Decicco, Ml, Ramunni, I, Ionescutirgoviste, C, Iosif, Cm, Pitei, D, Buligescu, S, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, Jb, Cronin, Cc, Whyte, Ae, Cleary, Pe, Toeller, M, Klischan, A, Forst, T, Gries, Fa, Rottiers, R, Priem, H, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Krans, Hmj, Lemkes, Hhpj, Jansen, Jj, Brachter, J, Nunescorrea, J, Boavida, J, Michel, G, Wirion, R, Boulton, Ajm, Ashe, H, Fernando, Dj, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, Francesco, Janka, Hu, Nuber, A, Mehnert, H, Bensoussan, D, Fallas, Mc, Fallas, P, Jepson, E, Mchardyyoung, S, Betteridge, Dj, Milne, M, Crepaldi, G, Nosadini, R, Segato, T, Midena, E, Cipollina, Mr, Fedele, D, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Navalesi, R, Penno, G, Miccoli, R, Nannipieri, M, Manfredi, S, Ghirlanda, G, Cotroneo, P, Manto, A, Teodonio, C, Minnella, A, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Perin, Pc, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Papazoglou, N, Manes, G, Triantaphyllou, G, Ioannides, A, Skazagar, G, Kontogiannis, I, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Walford, S, Wardle, Ev, Hughes, S, Roglic, G, Resman, Z, Metelko, Z, Skrabalo, Z, Keen, H, Navelesi, R, Sjolie, Ak, Viberti, Gc, Ward, J, Partridge, T, John, Wg, Collins, A, Dredge, A, Sharp, R, Kohner, E, Aldington, S, and Cockley, S.

Subjects
Blood Glucose, Male, Glycated Hemoglobin A, Endocrinology, Diabetes and Metabolism, Blood lipids, Blood Pressure, Fibrinogen, Body Mass Index, Risk Factors, biology, Smoking, von Willebrand factor, fibrinogen, The EURODIAB IDDM Study, Europe, Cholesterol, Cardiovascular Diseases, Female, medicine.symptom, medicine.drug, Type 1, Adult, medicine.medical_specialty, HDL, LDL, Von Willebrand factor, Internal medicine, Diabetes mellitus, von Willebrand Factor, Internal Medicine, medicine, Diabetes Mellitus, Humans, Albuminuria, Cholesterol, HDL, Cholesterol, LDL, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Diabetic Angiopathies, Triglycerides, Glycated Hemoglobin, business.industry, Vascular disease, medicine.disease, Blood pressure, Endocrinology, biology.protein, Microalbuminuria, business
Abstract

The interrelationships between fibrinogen, von Willebrand factor, a marker of vascular endothelial cell damage, and serum lipids were explored in well-characterised subjects with insulin-dependent diabetes mellitus. The 2091 subjects were enrolled into a cross-sectional, clinic-based study of complications, from 16 European countries: the EURODIAB IDDM Complications study. The anticipated significant relationships between both plasma fibrinogen and plasma von Willebrand factor concentrations and age and glycaemic control, and between fibrinogen and body mass index, were noted. Fibrinogen, adjusted for age and glycated haemoglobin concentration, was also related to smoking habits and was higher in the quartiles with highest systolic and diastolic blood pressures. There was a clustering of vascular risk factors, with a positive relationship between plasma fibrinogen and serum triglyceride concentrations in both genders and between fibrinogen and total cholesterol in males. An inverse relationship between fibrinogen and high density lipoprotein cholesterol was also apparent in males. A prominent feature was a positive relationship between both fibrinogen and von Willebrand factor and albumin excretion rate (p < 0.001 and p < 0.003 respectively) in those with retinopathy but not in these without this complication. In view of previous observations on blood pressure and albuminuria in these subjects the findings are consistent with the hypothesis that microalbuminuria and increased plasma von Willebrand factor are due to endothelial cell perturbation in response to mildly raised blood pressure in subjects with retinopathy. Fibrinogen may also contribute to microvascular disease and its relationships to lipid vascular risk factors suggest a possible pathogenic role in arterial disease in diabetes.

Published
1997

6. Nutritional intake of 2868 IDDM patients from 30 centres in Europe

Author

Toeller, M, Klischan, A, Heitkamp, G, Schumacher, W, Milne, R, Buyken, A, Karamanos, B, Gries, Fa, Fuller, Jh, Keen, H, Krans, Hmj, Navalesi, R, Sjolie, Ak, Stephenson, Jm, Viberti, Gc, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Roussipenessi, D, Cignarelli, M, Giorgino, R, Degeco, Ml, Ramunni, I, Ionescutirgoviste, C, Strachinariu, R, Nicolau, A, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, B, Cronin, Cc, Humphreys, M, Forst, T, Wagener, W, Venhaus, A, Rottiers, R, Priem, H, Deschoolmeester, Mj, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Lemkes, Hhpj, Janse, Jj, Eltedewever, Bm, Nunescorrea, J, Boavida, J, Carvalho, R, Alfonso, Mj, Monteiro, M, David, R, Jepson, E, Mchardyyoung, S, Betteridge, Dj, Milne, M, Michel, G, Wirion, R, Paquet, S, Hornick, H, Boulton, Ajm, Ashe, H, Fernando, Djs, Curwell, J, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, F, Marchi, M, Mehnert, H, Nuber, A, Janka, H, Nichting, M, Crepaldi, G, Nosadini, R, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Baclet, N, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Penno, G, Miccoli, Roberto, Nannipieri, Monica, Manfredi, S, Bertolotto, A, Ghirlanda, G, Cotroneo, P, Manto, A, Teodonio, C, Minnella, A, Careddu, G, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Papazoglou, N, Goutzourela, M, Manes, C, Bensoussan, D, Fallas, Mc, Fallas, P, Dhanaeus, C, Bourgeois, Md, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Branzi, P, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Strohner, H, Just, M, Walford, S, Wardle, Ev, Henio, S, Cooke, H, Roglic, G, Resman, Z, Metelko, Z, Skrabalo, Z., Toeller, M, Klischan, A, Heitkamp, G, Schumacher, W, Milne, R, Buyken, A, Karamanos, B, Gries, Fa, Fuller, Jh, Keen, H, Krans, Hmj, Navalesi, R, Sjolie, Ak, Stephenson, Jm, Viberti, Gc, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Roussipenessi, D, Cignarelli, M, Giorgino, R, Degeco, Ml, Ramunni, I, Ionescutirgoviste, C, Strachinariu, R, Nicolau, A, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, B, Cronin, Cc, Humphreys, M, Forst, T, Wagener, W, Venhaus, A, Rottiers, R, Priem, H, Deschoolmeester, Mj, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Lemkes, Hhpj, Janse, Jj, Eltedewever, Bm, Nunescorrea, J, Boavida, J, Carvalho, R, Alfonso, Mj, Monteiro, M, David, R, Jepson, E, Mchardyyoung, S, Betteridge, Dj, Milne, M, Michel, G, Wirion, R, Paquet, S, Hornick, H, Boulton, Ajm, Ashe, H, Fernando, Dj, Curwell, J, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, Francesco, Marchi, M, Mehnert, H, Nuber, A, Janka, H, Nichting, M, Crepaldi, G, Nosadini, R, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Baclet, N, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Penno, G, Miccoli, R, Nannipieri, M, Manfredi, S, Bertolotto, A, Ghirlanda, G, Cotroneo, P, Manto, A, Teodonio, C, Minnella, A, Careddu, G, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Papazoglou, N, Goutzourela, M, Manes, C, Bensoussan, D, Fallas, Mc, Fallas, P, Dhanaeus, C, Bourgeois, Md, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Branzi, P, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Strohner, H, Just, M, Walford, S, Wardle, Ev, Henio, S, Cooke, H, Roglic, G, Resman, Z, Metelko, Z, and Skrabalo, Z.

Subjects
medicine.medical_specialty, education.field_of_study, Cross-sectional study, business.industry, Endocrinology, Diabetes and Metabolism, Saturated fat, Population, Nutritional intake, IDDM patients, medicine.disease, Diet Records, Endocrinology, Internal medicine, Diabetes mellitus, Cohort, Internal Medicine, medicine, Population study, education, business, Cohort study
Abstract

The EURODIAB IDDM Complications Study, a cross-sectional, clinic-based study, was designed to measure the prevalence of diabetic complications in stratified samples of European insulin-dependent diabetic (IDDM) patients. As diet may be related to diabetic complications, nutritional intake was analysed in the study population. The aims of this first nutritional paper are to describe the nutrient intake in 2868 IDDM patients from 30 centres in 16 countries throughout Europe, to investigate the degree of regional differences in nutrient intake and to compare current intakes with recommended levels. Nutritional intake from 1458 male and 1410 female IDDM patients was assessed by a validated 3-day record (two weekdays, Sunday) and centrally analysed. Mean energy intake for all patients was 2390 +/- 707 kcal/day. Mean protein intake was 1.5 +/- 0.5 g/kg body weight. Carbohydrate intake was 43% and fibre intake 18 g/day. Alcohol intake for the total cohort was 2% of energy. Total fat contributed 38% of energy, with 14% from saturated fat. The Italian centres reported lower total and saturated fat intakes compared with other centres. Recommendations from the Diabetes and Nutrition Study Group of the EASD for total fat, saturated fatty acids and carbohydrate were only achieved by 14%, 14% and 15% of patients, respectively. The data of the present study clearly indicate current problems in the nutritional intake of European IDDM patients. These findings contribute to the definition of future targets in the nutritional management of IDDM patients, to be achieved as part of the initiatives taken by the St. Vincent Declaration action programme.

Published
1996

7. Cardiovascular disease and its risk factors in IDDM in Europe

Author

Koivisto VA, Stevens LK, Mattock M, Ebeling P, Muggeo M, Stephenson J, IdziorWalus B, Karamanos B, Tountas C, Kofinis A, Petrou K, Katsilambros N, Cignarelli M, Giorgino R, DeGeco ML, Ramunni I, IonescuTirgoviste C, Iosif CM, Pitei C, Buligescu S, Tamas G, Kerenyi Z, Ahmed AM, Toth J, Kempler P, Muntoni S, Songini M, Stabilini M, Fossarello M, Pintus S, Ferris B, Cronin CC, Toeller M, Klischan A, Forst T, Gries FA, Wagener W, Rottiers R, Priem H, Sinisalo M, Solnica B, SzopinskaCiba L, Solnica K, Krans M, Lemkes HHPJ, Jansen JJ, NunesCorrea J, Rogado C, Boavida JM, Correia LG, Michel G, Wirion R, Boulton AJM, Ashe H, Fernando DJS, Pozza G, Slaviero G, Comi B, Fattor F, Janka HU, Nuber A, Mehnert H, BenSoussan D, Fallas MC, Fallas P, Jepson E, McHardyYoung S, Fuller JH, Betteridge DJ, Milne M, Crepaldi C, Nosadini R, Cathelineau G, Cathelineau BV, Jellal M, Grodner N, Feiss PG, Santeusanio F, Rosi G, Cagini C, Marino C, Navalesi R, Penno G, Miccoli R, Nannipieri M, Stefano M, Ghirlanda G, Controneo P, Manto A, Teodonio C, Minnella A, Ward JD, Tesfaye S, Mody C, Rudd C, Molinatti GM, Vitelli F, Porta M, Pagano GF, Estivi P, Sivieri R, Carta Q, Petraroli G, Papazoglou N, Manes G, Triantaphyllou G, Ioannides A, Cacciatori V, Bellavere F, Galante P, Gemma ML, Irsigler K, Abrahamian H, Gurdet C, Hornlein B, Willinger C, Walford S, Wardle EV, Roglic G, Resman Z, Metelko Z, Skrabalo Z, Keen H, Sjolie AK, Viberti GC, Ward J, John G, Collins A, Sharp R., BANDELLO , FRANCESCO, Koivisto, Va, Stevens, Lk, Mattock, M, Ebeling, P, Muggeo, M, Stephenson, J, Idziorwalus, B, Karamanos, B, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Cignarelli, M, Giorgino, R, Degeco, Ml, Ramunni, I, Ionescutirgoviste, C, Iosif, Cm, Pitei, C, Buligescu, S, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferris, B, Cronin, Cc, Toeller, M, Klischan, A, Forst, T, Gries, Fa, Wagener, W, Rottiers, R, Priem, H, Sinisalo, M, Solnica, B, Szopinskaciba, L, Solnica, K, Krans, M, Lemkes, Hhpj, Jansen, Jj, Nunescorrea, J, Rogado, C, Boavida, Jm, Correia, Lg, Michel, G, Wirion, R, Boulton, Ajm, Ashe, H, Fernando, Dj, Pozza, G, Slaviero, G, Comi, B, Fattor, F, Bandello, Francesco, Janka, Hu, Nuber, A, Mehnert, H, Bensoussan, D, Fallas, Mc, Fallas, P, Jepson, E, Mchardyyoung, S, Fuller, Jh, Betteridge, Dj, Milne, M, Crepaldi, C, Nosadini, R, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Santeusanio, F, Rosi, G, Cagini, C, Marino, C, Navalesi, R, Penno, G, Miccoli, R, Nannipieri, M, Stefano, M, Ghirlanda, G, Controneo, P, Manto, A, Teodonio, C, Minnella, A, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Papazoglou, N, Manes, G, Triantaphyllou, G, Ioannides, A, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Walford, S, Wardle, Ev, Roglic, G, Resman, Z, Metelko, Z, Skrabalo, Z, Keen, H, Sjolie, Ak, Viberti, Gc, Ward, J, John, G, Collins, A, and Sharp, R.

Subjects
medicine.medical_specialty, Cross-sectional study, Endocrinology, Diabetes and Metabolism, Population, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Cardiovascular disease, EURODIAB IDDM study, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Internal medicine, Diabetes mellitus, Internal Medicine, Medicine, Risk factor, education, Advanced and Specialized Nursing, education.field_of_study, business.industry, medicine.disease, 3. Good health, Endocrinology, Blood pressure, Albuminuria, Metabolic syndrome, medicine.symptom, business
Abstract

OBJECTIVE To study the prevalence of cardiovascular disease (CVD), its risk factors, and their associations in IDDM patients in different European countries. RESEARCH DESIGN AND METHODS The prevalence of CVD (a past history or electrocardiogram abnormalities) and its risk factors were examined in a cross-sectional study in 3,250 IDDM patients from 16 European countries (EURODIAB IDDM Complications Study). The patients were examined in 31 centers and were stratified between centers for age, sex, and duration of diabetes. The mean ± SD duration of diabetes was 14.7 ± 9.3 years. RESULTS The prevalence of CVD was 9% in men and 10% in women. The prevalence increased with age (from 6% in patients 15–29 years old to 25% in patients 45–59 years old) and with duration of diabetes. The between-center variation for the whole population was from 3 to 19%. In both sexes, fasting triglyceride concentration was higher and HDL cholesterol lower in those patients with CVD than in those without. In men, duration of diabetes was longer, waist-to-hip ratio greater, and hypertension more common in patients with CVD. In women, a greater BMI was associated with increased prevalence of CVD. There was no association between insulin dose, HbA1c level, age-adjusted rate of albumin excretion, or smoking status and CVD. Waist-to-hip ratio, particularly in men, was positively associated with age, age-adjusted HbA1c, prevalence of smoking, daily insulin dose, albumin excretion rate, and fasting triglyceride concentrations. CONCLUSIONS The overall prevalence of CVD in these IDDM patients was ∼ 10%, increasing with age and duration of diabetes and with a sixfold variation between different European centers. CVD prevalence was most strongly associated with elevated triglyceride and decreased HDL cholesterol concentrations. CVD was also associated with albuminuria, but when adjusted by age, this association vanished. Increasing waist-to-hip ratio was associated with a number of adverse characteristics, particularly in IDDM men, reflecting the metabolic syndrome previously described in other populations.

Published
1996

9. BLOOD-PRESSURE, RETINOPATHY AND URINARY ALBUMIN EXCRETION IN IDDM - THE EURODIAB IDDM COMPLICATIONS STUDY

Author

Stephenson, Jm, Fuller, Jh, Viberti, Gc, Sjolie, Ak, Navalesi, R, Karamanos, B, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Giorgino, R, Cignarelli, M, Decicco, M, Ramunni, I, Ionescutirgoviste, C, Iosif, Cm, Pitei, D, Buligescu, S, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, Jb, Cronin, Cc, Whyte, Ae, Cleary, Pe, Toeller, M, Klischan, A, Forst, T, Gries, Fa, Wagener, W, Rottiers, R, Priem, H, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Krans, Hmj, Lemkes, Hhpj, Jansen, Jj, Brachter, J, Nunescorrea, J, Boavida, J, Michel, G, Wirion, R, Boulton, Ajm, Ashe, H, Fernando, Djs, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, F, Mehnert, H, Nuber, A, Janka, H, Bensoussan, D, Fallas, Mc, Fallas, P, Jepson, E, Mchardyyoung, S, Betteridge, Dj, Milne, M, Crepaldi, G, Nosadini, R, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Penno, G, Miccoli, Roberto, Nannipieri, Monica, Manfredi, S, Ghirlanda, G, Cotroneo, P, Manto, A, Teodonio, C, Minnella, A, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Perin, Pc, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Papazoglou, N, Manes, G, Triantaphyllou, G, Ioannides, A, Skazagar, G, Kontogiannis, I, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Walford, S, Wardle, Ev, Hughes, S, Roglic, G, Resman, Z, Metelko, Z, and Skrabalo, Z.

Subjects
Adult, Male, medicine.medical_specialty, THE EURODIAB IDDM COMPLICATIONS STUDY, Endocrinology, Diabetes and Metabolism, Urology, Blood Pressure, Nephropathy, Diabetic nephropathy, Diastole, Reference Values, Risk Factors, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Confidence Intervals, Prevalence, Albuminuria, Humans, Age of Onset, Proteinuria, Diabetic Retinopathy, business.industry, Diabetic retinopathy, medicine.disease, Europe, Endocrinology, Blood pressure, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Female, medicine.symptom, business, Retinopathy
Abstract

Several studies have shown an association between blood pressure and nephropathy, but few have been large enough to examine whether, or how, this relation is influenced by retinopathy. We have therefore examined the independent relations of blood pressure to urinary albumin excretion and retinopathy in a cross-sectional observational study of over 3000 insulin-dependent diabetic patients (the EURODIAB IDDM Complications Study). The relation of blood pressure to urinary albumin excretion differed strikingly between patients with (46%) and without (54%) retinopathy. In those with retinopathy, mean urinary albumin excretion rate was normal (20 micrograms/min) below median diastolic pressure (75 mmHg) and increased steeply (p0.001) with blood pressure above this level. However, in patients without retinopathy, mean albumin excretion rate was normal across the range of diastolic pressure. This finding could not be explained by differences in glycaemic control or duration of diabetes between patients with and without retinopathy. These data identify a subgroup of patients whose high risk of nephropathy may reflect abnormal renal vulnerability to mildly raised blood pressure. Retinopathy is a close correlate of this vulnerability. Detection of even mild retinopathy, together with raised blood pressure, may be important in assessing nephropathy risk.

Published
1995

10. The relationship between smoking and microvascular complications in the EURODIAB IDDM Complications Study

Author

Chaturvedi, N, Stephenson, Jm, Fuller, Jh, Karamanos, B, Tountas, C, Kofinis, A, Petrou, K, Katsilambros, N, Giorgino, R, Cignarelli, M, Decicco, Ml, Ramunni, I, Ionescutirgoviste, C, Iosif, Cm, Pitei, D, Buligescu, S, Tamas, G, Kerenyi, Z, Ahmed, Am, Toth, J, Kempler, P, Muntoni, S, Songini, M, Stabilini, M, Fossarello, M, Pintus, S, Ferriss, Jb, Cronin, Cc, Whyte, Ae, Cleary, Pe, Toeller, M, Klischan, A, Forst, T, Gries, Fa, Wagener, W, Rottiers, Rr, Priem, H, Ebeling, P, Sinisalo, M, Koivisto, Va, Idziorwalus, B, Solnica, B, Szopinskaciba, L, Solnica, K, Krans, Hmj, Lemkes, Hhpj, Jansen, Jj, Brachter, J, Nunescorrea, J, Boavida, J, Michel, G, Wirion, R, Boulton, Ajm, Ashe, H, Fernando, Djs, Pozza, G, Slaviero, G, Comi, G, Fattor, B, Bandello, Fb, Janka, Hu, Nuber, A, Mehnert, Hm, Bensoussan, D, Fallas, Mc, Fallas, P, Jepson, E, Mchardyyoung, S, Betteridge, Dj, Milne, M, Crepaldi, G, Nosadini, R, Cathelineau, G, Cathelineau, Bv, Jellal, M, Grodner, N, Feiss, Pg, Santeusanio, F, Rosi, G, Ventura, Mrm, Cagini, C, Marino, C, Navalesi, R, Penno, G, Miccoli, Roberto, Nannipieri, Monica, Manfredi, S, Ghirlanda, G, Cotroneo, P, Manto, A, Teodonio, C, Minnella, A, Ward, Jd, Tesfaye, S, Mody, C, Rudd, C, Molinatti, Gm, Vitelli, F, Porta, M, Pagano, Gf, Perin, Pc, Estivi, P, Sivieri, R, Carta, Q, Petraroli, G, Papazoglou, N, Manes, G, Triantaphyllou, G, Ioannides, A, Skazagar, G, Kontogiannis, I, Muggeo, M, Cacciatori, V, Bellavere, F, Galante, P, Gemma, Ml, Irsigler, K, Abrahamian, H, Gurdet, C, Hornlein, B, Willinger, C, Walford, S, Wardle, Ev, Hughes, S, Roglic, G, Resman, Z, Metelko, Z, and Skrabalo, Z.

Subjects
Adult, Blood Glucose, Male, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Sex Factors, Risk Factors, Internal medicine, Diabetes mellitus, Surveys and Questionnaires, Internal Medicine, medicine, Odds Ratio, Prevalence, Albuminuria, Humans, Risk factor, Glycemic, Demography, Advanced and Specialized Nursing, Glycated Hemoglobin, Sex Characteristics, Diabetic Retinopathy, business.industry, Incidence (epidemiology), Smoking, Odds ratio, Diabetic retinopathy, Middle Aged, medicine.disease, EURODIAB IDDM COMPLICATIONS STUDY, Hypoglycemia, Surgery, SMOKING AND MICROVASCULAR COMPLICATIONS, Diabetes Mellitus, Type 1, Smoking cessation, Microalbuminuria, Female, Smoking Cessation, business, Diabetic Angiopathies
Abstract

OBJECTIVE To examine the relationship between smoking and both glycemic control and microvascular complications in patients with insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS This was a prevalence survey of 3,250 men and women aged 15–60 years with IDDM from 31 diabetes centers in 16 European countries. Participants completed a questionnaire, had retinal photographs taken, and performed a 24-h urine collection. HbA1c, frequency of hypoglycemic and ketoacidotic episodes, urinary albumin excretion rates, and retinopathy were compared by smoking category. RESULTS The prevalence of smoking was 35% in men and 29% in women. Current smokers had poorer glycemic control and, among men, were more likely to have had a ketoacidotic episode than were those who never smoked. Ex-smokers had equivalent glycemic control and marginally more hypoglycemic episodes did than those who never smoked. Current smokers had a higher prevalence of microalbuminuria and total retinopathy than did those who never smoked. Ex-smokers had a higher prevalence of macroalbuminuria and proliferative retinopathy than did those who never smoked, but both had a similar prevalence of microalbuminuria. Adjustment for either current or long-term glycemic control could not fully account for these differences. CONCLUSIONS Smoking is associated with poorer glycemic control and an increased prevalence of microvascular complications compared with not smoking. Ex-smokers can achieve glycemic control equivalent to and have a prevalence of early complications similar to that of those who never smoked. We suggest that poorer glycemic control can account for some of the increased risk of complications in smokers, and that quitting smoking would be effective in reducing the incidence of complications. Urgent action is required to reduce the high smoking rates in people with IDDM.

Published
1995

14. Retinopathy and Vision Loss in Insulin-dependent Diabetes in Europe

Author

Sjølie, Anne Katrin, primary, Stephenson, Judith, additional, Aldington, Steve, additional, Kohner, Eva, additional, Janka, Hans, additional, Stevens, Lynda, additional, Fuller, John, additional, Karamanos, B., additional, Tountas, C., additional, Kofinis, A., additional, Petrou, K., additional, Katsilambros, N., additional, Cignarelli, M., additional, Giorgino, R., additional, De Geco, M.L., additional, Ramunni, I., additional, Ionescu-Tirgoviste, C., additional, Iosif, C.M., additional, Pitei, C., additional, Buligescu, S., additional, Tamas, G., additional, Kerenyi, Z., additional, Ahmed, A.M., additional, Toth, J., additional, Kempler, P., additional, Muntoni, S., additional, Songini, M., additional, Stabilini, M., additional, Fossarello, M., additional, Pintus, S., additional, Ferriss, B., additional, Cronin, C.C., additional, Toeller, M., additional, Klischan, A., additional, Forst, T., additional, Gries, F.A., additional, Rottiers, R., additional, Priem, H., additional, Ebeling, P., additional, Sinisalo, M., additional, Koivisto, V.A., additional, Idzior-Walus, B., additional, Solnica, B., additional, Szopinska-Ciba, L., additional, Solnica, K., additional, Krans, H.M.J., additional, Lemkes, H.H.P.J., additional, Jansen, J.J., additional, Nunes-Cornea, J., additional, Boavida, J., additional, Michel, G., additional, Wirion, R., additional, Boulton, A.J.M., additional, Ashe, H., additional, Fernando, D.J.S., additional, Pozza, G., additional, Slaviero, G., additional, Comi, G., additional, Fattor, B., additional, Bandello, F., additional, Mehnert, H., additional, Nuber, A., additional, Janka, H., additional, Ben Soussan, D., additional, Fallas, M.C., additional, Fallas, P., additional, Jepson, E., additional, McHardy-Young, S., additional, Fuller, J.H., additional, Betteridge, D.J., additional, Milne, M., additional, Crepaldi, G., additional, Nosadini, R., additional, Cathelineau, G., additional, Villatte Cathelineau, B., additional, Jellal, M., additional, Grodner, N., additional, Gervais Feiss, P., additional, Santeusanio, F., additional, Rosi, G., additional, Ventura, M.R.M., additional, Cagini, C., additional, Marino, C., additional, Navalesi, R., additional, Penno, G., additional, Miccoli, R., additional, Nannipieri, M., additional, Manfredi, S., additional, Ghirlanda, G., additional, Cotroneo, P., additional, Manto, A., additional, Teodonio, C., additional, Minnella, A., additional, Ward, J.D., additional, Tesfaye, S., additional, Mody, C., additional, Rudd, C., additional, Molinatti, G.M., additional, Vitelli, F., additional, Porta, M., additional, Pagano, G.F., additional, Cavallo Perin, P., additional, Estivi, P., additional, Sivieri, R., additional, Carta, Q., additional, Petraroli, G., additional, Papazoglou, N., additional, Manes, G., additional, Triantaphyllou, G., additional, Ioannides, A., additional, Muggeo, M., additional, Cacciatori, V., additional, Bellavere, F., additional, Galante, P., additional, Gemma, M.L., additional, Irsigler, K., additional, Abrahamian, H., additional, Gurdet, C., additional, Hornlein, B., additional, Willinger, C., additional, Walford, S., additional, Wardle, E.V., additional, Roglic, G., additional, Resman, Z., additional, Metelko, Z., additional, and Skrabalo, Z., additional

Published
1997
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16. Brinker is a sequence-specific transcriptional repressor in the Drosophila embryo.

Author

Zhang, H, Levine, M, and Ashe, H L

Abstract

A Dpp activity gradient specifies multiple thresholds of gene expression in the dorsal ectoderm of the early embryo. Some of these thresholds depend on a putative repressor, Brinker, which is expressed in the neurogenic ectoderm in response to the maternal Dorsal gradient and Dpp signaling. Here we show that Brinker is a sequence-specific transcriptional repressor. It binds the consensus sequence, TGGCGc/tc/t, and interacts with the Groucho corepressor through a conserved sequence motif, FKPY. An optimal Brinker binding site is contained within an 800-bp enhancer from the tolloid gene, which has been identified as a genetic target of the Brinker repressor. A tolloid-lacZ transgene containing point mutations in this site exhibits an expanded pattern of expression, suggesting that Brinker directly represses tolloid transcription. We discuss other examples of transcriptional repressors constraining the activities of signaling pathways.

Published
2001
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17. Dpp signaling thresholds in the dorsal ectoderm of the Drosophila embryo.

Author

Ashe, H L, Mannervik, M, and Levine, M

Abstract

The dorsal ectoderm of the Drosophila embryo is subdivided into different cell types by an activity gradient of two TGF(β) signaling molecules, Decapentaplegic (Dpp) and Screw (Scw). Patterning responses to this gradient depend on a secreted inhibitor, Short gastrulation (Sog) and a newly identified transcriptional repressor, Brinker (Brk), which are expressed in neurogenic regions that abut the dorsal ectoderm. Here we examine the expression of a number of Dpp target genes in transgenic embryos that contain ectopic stripes of Dpp, Sog and Brk expression. These studies suggest that the Dpp/Scw activity gradient directly specifies at least three distinct thresholds of gene expression in the dorsal ectoderm of gastrulating embryos. Brk was found to repress two target genes, tailup and pannier, that exhibit different limits of expression within the dorsal ectoderm. These results suggest that the Sog inhibitor and Brk repressor work in concert to establish sharp dorsolateral limits of gene expression. We also present evidence that the activation of Dpp/Scw target genes depends on the Drosophila homolog of the CBP histone acetyltransferase.

Published
2000

18. New approach to antifolate treatment of certain cancers as demonstrated in tissue culture.

Author

Halpern, R M, Halpern, B C, Clark, B R, Ashe, H, Hardy, D N, Jenkinson, P Y, Chou, S C, and Smith, R A

Abstract

The selective toxicity of antifolates for a variety of cancers can be improved, as illustrated by the combined administration of N5-methyltetrahydrofolate and methotrexate in tissue culture. When a variety of neoplastic cell types characterized by a deficiency of vitamin B12-dependent N5-methyltetrahydrofolate methyltransferase (5-methyltetrahydropteroyl-L-glutamate:L-homocysteine S-methyltransferase, EC 2.1.1.13) and normal adult cells are grown in media containing methotrexate and either N5-methyltetrahydrofolate or N5-formyltetrahydrofolate, not only is the selective toxicity of methotrexate demonstrated, but the advantage of using N5-methyltetrahydrofolate in place of N5-formyltetrahydrofolate is also revealed. The implications and applications of this particular combination in the treatment of human cancer are discussed.

Published
1975
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19. Intergenic transcription and transinduction of the human beta-globin locus.

Author

Ashe, H L, Monks, J, Wijgerde, M, Fraser, P, and Proudfoot, N J

Abstract

We have identified novel nuclear transcripts in the human beta-globin locus using nuclear run-on analysis in erythroid cell lines and in situ hybridization analysis of erythroid tissue. These transcripts extend across the LCR and intergenic regions but are undetectable in nonerythroid cells. Surprisingly, transient transfection of a beta-globin gene (epsilon, gamma, or beta) induces transcription of the LCR and intergenic regions from the chromosomal beta-globin locus in nonerythroid cell lines. The beta-globin genes themselves, however, remain transcriptionally silent. Induction is dependent on transcription of the globin gene in the transfected plasmid but does not require protein expression. Using in situ hybridization analysis, we show that the plasmid colocalizes with the endogenous beta-globin locus providing insight into the mechanism of transinduction.

Published
1997

20. A Monumental Study—Reconstruction of a 1920 Granite Shed

Author

Ayer, H. E., Dement, J. M., Busch, K. A., Ashe, H. B., Levadie, B. T. H., Burgess, W. A., and DiBERARDINIS, L.

Abstract

A small granite shed in Barre, Vermont was operated for one week without any ventilation, protecting the granite cutters by means of respirators. “Respirable” dust concentrations up to 49 mg/m3 and “respirable” free silica concentrations up to 4.4 mg/m3 were observed. Average respirable dust concentrations were 10 to 20 mg/m3 of which 15% was free silica. Under the conditions of the study, it appeared that 10 mppcf of granite dust was equivalent to about 0.2 mg/m3 of “respirable” free silica. Implications for the quartz TLV are discussed.

Published
1973
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26. Retinopathy and Vision Loss in Insulin-dependent Diabetes in Europe: The EURODIAB IDDM Complications Study

Author

Karamanos, B., Tountas, C., Kofinis, A., Petrou, K., Katsilambros, N., Cignarelli, M., Giorgino, R., De Geco, M.L., Ramunni, I., Ionescu-Tirgoviste, C., Iosif, C.M., Pitei, C., Buligescu, S., Tamas, G., Kerenyi, Z., Ahmed, A.M., Toth, J., Kempler, P., Muntoni, S., Songini, M., Stabilini, M., Fossarello, M., Pintus, S., Ferriss, B., Cronin, C.C., Toeller, M., Klischan, A., Forst, T., Gries, F.A., Rottiers, R., Priem, H., Ebeling, P., Sinisalo, M., Koivisto, V.A., Idzior-Walus, B., Solnica, B., Szopinska-Ciba, L., Solnica, K., Krans, H.M.J., Lemkes, H.H.P.J., Jansen, J.J., Nunes-Cornea, J., Boavida, J., Michel, G., Wirion, R., Boulton, A.J.M., Ashe, H., Fernando, D.J.S., Pozza, G., Slaviero, G., Comi, G., Fattor, B., Bandello, F., Mehnert, H., Nuber, A., Janka, H., Ben Soussan, D., Fallas, M.C., Fallas, P., Jepson, E., McHardy-Young, S., Fuller, J.H., Betteridge, D.J., Milne, M., Crepaldi, G., Nosadini, R., Cathelineau, G., Villatte Cathelineau, B., Jellal, M., Grodner, N., Gervais Feiss, P., Santeusanio, F., Rosi, G., Ventura, M.R.M., Cagini, C., Marino, C., Navalesi, R., Penno, G., Miccoli, R., Nannipieri, M., Manfredi, S., Ghirlanda, G., Cotroneo, P., Manto, A., Teodonio, C., Minnella, A., Ward, J.D., Tesfaye, S., Mody, C., Rudd, C., Molinatti, G.M., Vitelli, F., Porta, M., Pagano, G.F., Cavallo Perin, P., Estivi, P., Sivieri, R., Carta, Q., Petraroli, G., Papazoglou, N., Manes, G., Triantaphyllou, G., Ioannides, A., Muggeo, M., Cacciatori, V., Bellavere, F., Galante, P., Gemma, M.L., Irsigler, K., Abrahamian, H., Gurdet, C., Hornlein, B., Willinger, C., Walford, S., Wardle, E.V., Roglic, G., Resman, Z., Metelko, Z., Skrabalo, Z., Sjølie, Anne Katrin, Stephenson, Judith, Aldington, Steve, Kohner, Eva, Janka, Hans, Stevens, Lynda, and Fuller, John

Published
1997
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27. FRACTURE OF THE GREATER CORNU OF THE HYOID BONE RESULTING FROM MUSCULAR ACTION

Author

Ashe, H. P.

Abstract

Fractures of the hyoid bone due to muscular action are very rare. Stimson1 mentions only two such cases out of forty-five hyoid fractures collected by Malgaigne, Hamilton, Gibb, Gurlt and himself.The following case of fracture of the left greater cornu of the hyoid bone, having resulted from muscular action, will consequently be of interest:Miss E. H., aged 29, domestic by occupation, called on me, Feb. 18, 1916, complaining of pain and swelling in the neck, and particularly of change of voice, the occasional absence of which so alarmed her as to be the incentive toward seeking medical aid.The week previously, February 11, while engaged in the task of arranging portières, she inclined her head forcibly backward, and at the time felt and heard, as she expressed it, "something break in the neck." Swelling of the neck anteriorly, localized pain in the neck produced by motions of the

Published
1916
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28. "LARREY, THE ORIGINATOR OF THE RAPID EVACUATION OF THE WOUNDED"

Author

Ashe, H. P.

Abstract

TO THE EDITOR: —Anent the interesting historical account of Larrey, the famous surgeon and patriot, by Dr. King of New Orleans, published in The Journal, September 29, and your editorial eulogizing the same surgeon, I would like to quote the following from "La Campagne de Russie, Mémoires du Général Comte de Ségur, Aide-de-Camp de Napoléon," an eye witness and participant in the ill-fated invasion of and retreat from Russia. "In the furious engagement at Borodine, 20,000 wounded were picked up and carried about two leagues to the rear to the great abbey of Kolotshoc." Then the historian continues:"Le chirurgien en chef Larrey venait de prendre des aides dans tous les régiments. Les ambulances avaient rejoint; mais tout fut insuffisant. Il s'est plaint depuis, dans une relation imprimée, qu'aucune troupe ne liu eut été laissée pour requérir les choses de première nécessité dans les villages environnants.""The chief surgeon, Larrey,

Published
1917
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29. On the genetic basis of tail-loss evolution in humans and apes.

Author

Xia B, Zhang W, Zhao G, Zhang X, Bai J, Brosh R, Wudzinska A, Huang E, Ashe H, Ellis G, Pour M, Zhao Y, Coelho C, Zhu Y, Miller A, Dasen JS, Maurano MT, Kim SY, Boeke JD, and Yanai I

Subjects
Animals, Humans, Mice, Alu Elements genetics, Disease Models, Animal, Genome genetics, Introns genetics, Neural Tube Defects genetics, Neural Tube Defects metabolism, Phenotype, Protein Isoforms deficiency, Protein Isoforms genetics, Protein Isoforms metabolism, Exons genetics, Alternative Splicing genetics, Evolution, Molecular, Hominidae anatomy & histology, Hominidae genetics, T-Box Domain Proteins deficiency, T-Box Domain Proteins genetics, T-Box Domain Proteins metabolism, Tail anatomy & histology, Tail embryology
Abstract

The loss of the tail is among the most notable anatomical changes to have occurred along the evolutionary lineage leading to humans and to the 'anthropomorphous apes' 1-3 , with a proposed role in contributing to human bipedalism 4-6 . Yet, the genetic mechanism that facilitated tail-loss evolution in hominoids remains unknown. Here we present evidence that an individual insertion of an Alu element in the genome of the hominoid ancestor may have contributed to tail-loss evolution. We demonstrate that this Alu element-inserted into an intron of the TBXT gene 7-9 -pairs with a neighbouring ancestral Alu element encoded in the reverse genomic orientation and leads to a hominoid-specific alternative splicing event. To study the effect of this splicing event, we generated multiple mouse models that express both full-length and exon-skipped isoforms of Tbxt, mimicking the expression pattern of its hominoid orthologue TBXT. Mice expressing both Tbxt isoforms exhibit a complete absence of the tail or a shortened tail depending on the relative abundance of Tbxt isoforms expressed at the embryonic tail bud. These results support the notion that the exon-skipped transcript is sufficient to induce a tail-loss phenotype. Moreover, mice expressing the exon-skipped Tbxt isoform develop neural tube defects, a condition that affects approximately 1 in 1,000 neonates in humans 10 . Thus, tail-loss evolution may have been associated with an adaptive cost of the potential for neural tube defects, which continue to affect human health today., (© 2024. The Author(s).)

Published
2024
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30. A conditional counterselectable Piga knockout in mouse embryonic stem cells for advanced genome writing applications.

Author

Zhang W, Brosh R, McCulloch LH, Zhu Y, Ashe H, Ellis G, Camellato BR, Kim SY, Maurano MT, and Boeke JD

Abstract

Overwriting counterselectable markers is an efficient strategy for removing wild-type DNA or replacing it with payload DNA of interest. Currently, one bottleneck of efficient genome engineering in mammals is the shortage of counterselectable (negative selection) markers that work robustly without affecting organismal developmental potential. Here, we report a conditional Piga knockout strategy that enables efficient proaerolysin-based counterselection in mouse embryonic stem cells. The conditional Piga knockout cells show similar proaerolysin resistance as full (non-conditional) Piga deletion cells, which enables the use of a PIGA transgene as a counterselectable marker for genome engineering purposes. Native Piga function is readily restored in conditional Piga knockout cells to facilitate subsequent mouse development. We also demonstrate the generality of our strategy by engineering a conditional knockout of endogenous Hprt . Taken together, our work provides a new tool for advanced mouse genome writing and mouse model establishment., Competing Interests: Jef Boeke is a Founder and Director of CDI Labs, Inc., a Founder of and consultant to Neochromosome, Inc, a Founder, SAB member of and consultant to Re-Open Diagnostics, LLC and serves or served on the Scientific Advisory Board of the following: Sangamo, Inc., Modern Meadow, Inc., Rome Therapeutics, Inc., Sample6, Inc., Tessera Therapeutics, Inc., and the Wyss Institute., (© 2022 The Authors.)

Published
2022
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31. Role of the runt-related transcription factor (RUNX) family in prostate cancer.

Author

Ashe H, Krakowiak P, Hasterok S, Sleppy R, Roller DG, and Gioeli D

Subjects
Androgen Antagonists therapeutic use, Humans, Male, Prostatic Neoplasms drug therapy, Prostatic Neoplasms, Castration-Resistant drug therapy, Receptors, Androgen metabolism, Core Binding Factor alpha Subunits metabolism, Prostatic Neoplasms metabolism, Prostatic Neoplasms, Castration-Resistant metabolism, Transcription Factors metabolism
Abstract

Prostate cancer (PCa) is a very complex disease that is a major cause of death in men worldwide. Currently, PCa dependence on the androgen receptor (AR) has resulted in use of AR antagonists and antiandrogen therapies that reduce endogenous steroid hormone production. However, within two to three years of receiving first-line androgen deprivation therapy, the majority of patients diagnosed with PCa progress to castration-resistant prostate cancer (CRPC). There is an urgent need for therapies that are more durable than antagonism of the AR axis. Studies of runt-related transcription factors (RUNX) and their heterodimerization partner, core-binding factor subunit b (CBFβ), are revealing that the RUNX family are drivers of CRPC. In this review, we describe what is presently understood about RUNX members in PCa, including what regulates and is regulated by RUNX proteins, and the role of RUNX proteins in the tumor microenvironment and AR signaling. We discuss the implications for therapeutically targeting RUNX, the potential for RUNX as PCa biomarkers, and the current pressing questions in the field., (© 2021 Federation of European Biochemical Societies.)

Published
2021
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32. Characterization of the differential efficacy of austenitic vs martensitic NiTi rotary files in non-surgical root canal retreatment: a micro-CT analysis.

Author

Alsofi L, Rajkhan W, Al-Habib M, Ashe H, Alnowailaty Y, and Balto K

Subjects
Dental Pulp Cavity diagnostic imaging, Humans, Root Canal Preparation, X-Ray Microtomography, Gutta-Percha, Root Canal Filling Materials
Abstract

Aim : Our study aims to characterize the differential efficacy of martensitic and austenitic files in root canal retreatment regarding defiling ability, debris management and morphometric features. Materials and methods : A total of 10 human premolar teeth with two separate fully formed roots were selected, prepared with BioRace system (BR) up to a size BR2 (0.04/25). Root canals were filled and then divided according to the file type into two groups (n = 10). Two geometrically identical files have been used with the only difference between them is heat treatment; One Curve (OC) martensitic and One Shape (OS) austenitic. Preoperative and postoperative Micro-CT scans were done for all the samples, and the percent volume of residual filling materials was calculated. Canals reshaping and remaining debris in the canals were assessed by calculating the volume of the canals before and after retreatment using Micro-CT software. Results : The percentages of removed filling materials were similar between both groups (97.2% OC vs 97.8% OS). OS was significantly faster than OC ( P < 0.05). Retreatment procedure did not significantly change volume, structure model index, surface area, and canal curvature. OS group transported the canals more than OC at the apical third ( P < 0.05). There were no significant differences between both groups concerning un-instrumented surface area and accumulated hard tissue debris (AHTD) ( P > 0.05). Conclusion : Under the circumstances of this study, neither file systems could completely remove the filling materials. However, OC resulted in less transportation than OS in the apical one third ( P < 0.05). Also, OC resulted less AHTD than OS but with no statistical difference., (© 2021 The Author(s). Published by BRI.)

Published
2021
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33. Glyceollin I enantiomers distinctly regulate ER-mediated gene expression.

Author

Payton-Stewart F, Khupse RS, Boué SM, Elliott S, Zimmermann MC, Skripnikova EV, Ashe H, Tilghman SL, Beckman BS, Cleveland TE, McLachlan JA, Bhatnagar D, Wiese TE, Erhardt P, and Burow ME

Subjects
Cell Line, Tumor, Estrogen Receptor alpha chemistry, Estrogen Receptor beta chemistry, HEK293 Cells, Humans, Models, Molecular, Protein Conformation, Pterocarpans metabolism, Response Elements genetics, Stereoisomerism, Substrate Specificity, Transcriptional Activation drug effects, Estrogen Receptor alpha metabolism, Estrogen Receptor beta metabolism, Gene Expression Regulation drug effects, Pterocarpans chemistry, Pterocarpans pharmacology
Abstract

Glyceollins are pterocarpan phytoalexins elicited in high concentrations when soybeans are stressed. We have previously reported that the three glyceollin isomers (GLY I-III) exhibit antiestrogenic properties, which may have significant biological effects upon human exposure. Of the three isomers, we have recently shown that glyceollin I is the most potent antiestrogen. Natural (-)-glyceollin I recently was synthesized along with its racemate and unnatural (+) enantiomer. In this study, we compared the glyceollin I enantiomers' ER binding affinity, ability to inhibit estrogen responsive element transcriptional (ERE) activity and endogenous gene expression in MCF-7 cells. The results demonstrated similar binding affinities for both ERalpha and ERbeta. Reporter gene assays in MCF-7 cells revealed that while (+)-glyceollin I slightly stimulated ERE transcriptional activity, (-)-glyceollin I decreased activity induced by estrogen. Co-transfection reporter assays performed in HEK 293 cells demonstrated that (+)-glyceollin I increased ERE transcriptional activity of ERalpha and ERbeta with and without estrogen with no antiestrogenic activity observed. Conversely, (-)-glyceollin I decreased the activity of both ER subtypes stimulated by estradiol demonstrating potent antiestrogenic properties. Additionally, each Gly I enantiomer induced unique gene expression profiles in a PCR array panel of genes commonly altered in breast cancer., (Copyright 2010 Elsevier Inc. All rights reserved.)

Published
2010
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34. Glyceollin I, a novel antiestrogenic phytoalexin isolated from activated soy.

Author

Zimmermann MC, Tilghman SL, Boué SM, Salvo VA, Elliott S, Williams KY, Skripnikova EV, Ashe H, Payton-Stewart F, Vanhoy-Rhodes L, Fonseca JP, Corbitt C, Collins-Burow BM, Howell MH, Lacey M, Shih BY, Carter-Wientjes C, Cleveland TE, McLachlan JA, Wiese TE, Beckman BS, and Burow ME

Subjects
Animals, Anticarcinogenic Agents chemistry, Anticarcinogenic Agents isolation & purification, Anticarcinogenic Agents therapeutic use, Binding Sites, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Estrogen Receptor Modulators chemistry, Estrogen Receptor Modulators isolation & purification, Estrogen Receptor Modulators therapeutic use, Estrogen Receptor alpha antagonists & inhibitors, Estrogen Receptor alpha biosynthesis, Estrogen Receptor alpha genetics, Female, Humans, Mice, Mice, Nude, Molecular Structure, Neoplasm Transplantation, Pterocarpans chemistry, Pterocarpans isolation & purification, Pterocarpans therapeutic use, Sesquiterpenes, Stereoisomerism, Tamoxifen pharmacology, Terpenes chemistry, Terpenes isolation & purification, Terpenes therapeutic use, Transcription, Genetic drug effects, Xenograft Model Antitumor Assays, Phytoalexins, Anticarcinogenic Agents pharmacology, Estrogen Receptor Modulators pharmacology, Pterocarpans pharmacology, Glycine max chemistry, Terpenes pharmacology
Abstract

Glyceollins, a group of novel phytoalexins isolated from activated soy, have recently been demonstrated to be novel antiestrogens that bind to the estrogen receptor (ER) and inhibit estrogen-induced tumor progression. Our previous publications have focused specifically on inhibition of tumor formation and growth by the glyceollin mixture, which contains three glyceollin isomers (I, II, and III). Here, we show the glyceollin mixture is also effective as a potential antiestrogenic, therapeutic agent that prevents estrogen-stimulated tumorigenesis and displays a differential pattern of gene expression from tamoxifen. By isolating the individual glyceollin isomers (I, II, and III), we have identified the active antiestrogenic component by using competition binding assays with human ERalpha and in an estrogen-responsive element-based luciferase reporter assay. We identified glyceollin I as the active component of the combined glyceollin mixture. Ligand-receptor modeling (docking) of glyceollin I, II, and III within the ERalpha ligand binding cavity demonstrates a unique type II antiestrogenic confirmation adopted by glyceollin I but not isomers II and III. We further compared the effects of glyceollin I to the antiestrogens, 4-hydroxytamoxifen and ICI 182,780 (fulvestrant), in MCF-7 breast cancer cells and BG-1 ovarian cancer cells on 17beta-estradiol-stimulated expression of progesterone receptor and stromal derived factor-1alpha. Our results establish a novel inhibition of ER-mediated gene expression and cell proliferation/survival. Glyceollin I may represent an important component of a phytoalexin-enriched food (activated) diet in terms of chemoprevention as well as a novel therapeutic agent for hormone-dependent tumors.

Published
2010
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35. Robustness of the BMP morphogen gradient in Drosophila embryonic patterning.

Author

Eldar A, Dorfman R, Weiss D, Ashe H, Shilo BZ, and Barkai N

Subjects
Animals, Bone Morphogenetic Proteins antagonists & inhibitors, Bone Morphogenetic Proteins genetics, Diffusion, Drosophila Proteins genetics, Drosophila Proteins metabolism, Drosophila melanogaster genetics, Gene Dosage, Genotype, Ligands, Macromolecular Substances, Phenotype, Tolloid-Like Metalloproteinases, Transforming Growth Factor beta genetics, Transforming Growth Factor beta metabolism, Body Patterning, Bone Morphogenetic Proteins metabolism, Drosophila melanogaster embryology, Drosophila melanogaster metabolism, Embryo, Nonmammalian embryology, Embryo, Nonmammalian metabolism, Models, Biological
Abstract

Developmental patterning relies on morphogen gradients, which generally involve feedback loops to buffer against perturbations caused by fluctuations in gene dosage and expression. Although many gene components involved in such feedback loops have been identified, how they work together to generate a robust pattern remains unclear. Here we study the network of extracellular proteins that patterns the dorsal region of the Drosophila embryo by establishing a graded activation of the bone morphogenic protein (BMP) pathway. We find that the BMP activation gradient itself is robust to changes in gene dosage. Computational search for networks that support robustness shows that transport of the BMP class ligands (Scw and Dpp) into the dorsal midline by the BMP inhibitor Sog is the key event in this patterning process. The mechanism underlying robustness relies on the ability to store an excess of signalling molecules in a restricted spatial domain where Sog is largely absent. It requires extensive diffusion of the BMP-Sog complexes, coupled with restricted diffusion of the free ligands. We show experimentally that Dpp is widely diffusible in the presence of Sog but tightly localized in its absence, thus validating a central prediction of our theoretical study.

Published
2002
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36. Local inhibition and long-range enhancement of Dpp signal transduction by Sog.

Author

Ashe HL and Levine M

Subjects
Animals, Body Patterning genetics, Body Patterning physiology, Carrier Proteins, Drosophila, Enhancer Elements, Genetic, Female, GTP-Binding Proteins genetics, Homeodomain Proteins genetics, Male, Proteins metabolism, Tolloid-Like Metalloproteinases, Transforming Growth Factor beta metabolism, Xenopus, Bacterial Proteins, Drosophila Proteins, Embryonic Induction, Insect Proteins antagonists & inhibitors, Insect Proteins physiology, Signal Transduction, Transcription Factors, rac GTP-Binding Proteins
Abstract

Extracellular gradients of signalling molecules can specify different thresholds of gene activity in development. A gradient of Decapentaplegic (Dpp) activity subdivides the dorsal ectoderm of the Drosophila embryo into amnioserosa and dorsal epidermis. The proteins Short gastrulation (Sog) and Tolloid (Tld) are required to shape this gradient. Sog has been proposed to form an inhibitory complex with either Dpp or the related ligand Screw, and is subsequently processed by the protease Tld. Paradoxically, Sog appears to be required for amnioserosa formation, which is specified by peak Dpp signalling activity. Here we show that the misexpression of sog using the even-skipped stripe-2 enhancer redistributes Dpp signalling in a mutant background in which dpp is expressed throughout the embryo. Dpp activity is diminished near the Sog stripe and peak Dpp signalling is detected far from this stripe. However, a tethered form of Sog suppresses local Dpp activity without augmenting Dpp activity at a distance, indicating that diffusion of Sog may be required for enhanced Dpp activity and consequent amnioserosa formation. The long-distance stimulation of Dpp activity by Sog requires Tld, whereas Sog-mediated inhibition of Dpp does not. The heterologous Dpp inhibitor Noggin inhibits Dpp signalling but fails to augment Dpp activity. These results suggest an unusual strategy for generating a gradient threshold of growth-factor activity, whereby Sog and its protease specify peak Dpp signalling far from a localized source of Sog.

Published
1999
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37. The prevalence of foot ulceration and its correlates in type 2 diabetic patients: a population-based study.

Author

Kumar S, Ashe HA, Parnell LN, Fernando DJ, Tsigos C, Young RJ, Ward JD, and Boulton AJ

Subjects
Adult, Age Distribution, Aged, Aged, 80 and over, Diabetic Angiopathies epidemiology, Diabetic Foot etiology, Diabetic Neuropathies epidemiology, Female, Humans, Male, Middle Aged, Prevalence, United Kingdom epidemiology, Diabetes Mellitus, Type 2 complications, Diabetic Foot epidemiology
Abstract

The prevalence of peripheral neuropathy, peripheral vascular disease, and foot ulceration in Type 2 diabetic patients in the community were determined in a community-based study. Eight hundred and eleven subjects (404 male, 407 female, mean age 65.4 (range 34-90) years, diabetes duration 7.4 (0-50) years) from 37 general practices in three UK cities were studied. Neuropathy was diagnosed clinically using modified neuropathy disability scores which were ascertained using structured interviews and clinical examinations by one observer in each city. Peripheral vascular disease was diagnosed if a history of revascularization was present or > or = 2 foot pulses were absent. History of current or previous foot ulceration was recorded. The prevalence of neuropathy was 41.6% (95% confidence limits 38.3-44.9%) and the prevalence of PVD, 11% (9.1-13.7%). Forty-eight percent of neuropathic patients reported significant neuropathic symptoms. Forty-three patients (5.3% (3.8-6.8%)) had current or past foot ulcers; 20 of these were pure neuropathic ulcers, 13 neuroischaemic, 5 pure vascular, and 5 were unclassified. Multiple logistic regression showed history of amputation, neuropathy disability score, and peripheral vascular disease to be significantly associated with foot ulceration after adjusting for age and diabetes duration. A substantial proportion of Type 2 diabetic patients, often elderly patients who do not attend hospitals, suffered from peripheral neuropathy and peripheral vascular disease. These patients are at risk of foot ulceration and may benefit from preventive footcare.

Published
1994
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39. Repair of replace.

Author

Ashe HJ

Subjects
Economics, Dental, Equipment and Supplies
Published
1974

40. Evaluation of RA 27-3 rubella vaccine.

Author

Schiff GM, Linnemann CC Jr, Shea L, Grundy B, and Ashe HS

Subjects
Adolescent, Child, Child, Preschool, Female, Fever etiology, Humans, Injections, Subcutaneous, Joint Diseases etiology, Male, Measles immunology, Measles prevention & control, Measles Vaccine administration & dosage, Measles Vaccine adverse effects, Pain etiology, Rubella immunology, Rubella prevention & control, Rubella Vaccine administration & dosage, Rubella Vaccine adverse effects
Published
1974
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43. Effect of methionine replacement by homocystine in cultures containing both malignant rat breast carcinosarcoma (Walker-256) cells and normal adult rat liver fibroblasts.

Author

Halpern BC, Ezzell R, Hardy DN, Clark BR, Ashe H, Halpern RM, and Smith RA

Subjects
Animals, Carcinoma 256, Walker pathology, Cells, Cultured, Culture Techniques, Fibroblasts, Folic Acid metabolism, Injections, Subcutaneous, Mammary Neoplasms, Experimental pathology, Neoplasm Seeding, Rats, Vitamin B 12 metabolism, Culture Media, Homocystine metabolism, Liver metabolism, Methionine metabolism
Abstract

When malignant W-256 rat breast carcinosarcoma cells are mixed with an equal number of normal adult rat liver fibroblasts and allowed to grow in a medium containing sufficient L-methionine and an excess of vitamin B12 and of folic acid, the malignant cells outgrow the normal cells, and within 2 weeks the tissue culture flasks contain only neoplastic cells. However, when ample DL-homocystine or homocysteine replaces methionine in the medium containing the same amount of vitamin B12 and folic acid, and seeded with the same type and number of malignant and normal cells, the malignant cells die and the normal cells thrive. Substantiating this conclusion are the results of injections into rats of comparable numbers of cells from each group after 3 weeks of growth in tissue culture. Fatal malignancies are produced by the homocystein-cultivated cells.

Published
1975
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44. Rubella and measles serosurvey among a nonurban pediatric population.

Author

Schiff GM, Linnemann CC Jr, Shea L, Rotte T, Grundy B, and Ashe HS

Subjects
Adolescent, Age Factors, Child, Child, Preschool, Female, Hemagglutination Inhibition Tests, Humans, Indians, North American, Male, Rural Health, Sex Factors, Socioeconomic Factors, Wisconsin, Antibodies, Viral analysis, Measles immunology, Rubella immunology
Abstract

A serologic survey for rubella and measles immunity was conducted to determine the immunity levels among a nonurban, relatively isolated pediatric population. Among 1,273 students in grades kindergarten through 9, the overall susceptibility rate was 24.3% for rubella and 16.3% for measles. There was significant variation in susceptibility rates among the various grades and schools involved. The susceptibility rates were similar to those found for urban populations. The results indicated that vaccination efforts for the population have been partially successful, but additional effort was needed.

Published
1975
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46. Reye's syndrome and post-influenza-B hepatotoxicity.

Author

Ashe HS

Subjects
Adolescent, Complement Fixation Tests, Humans, Liver Function Tests, Male, Reye Syndrome etiology, Brain Diseases complications, Influenza, Human complications, Reye Syndrome complications
Published
1975

48. N5-methyltetrahydrofolate: homocysteine methyltransferase activity in extracts from normal, malignant and embryonic tissue culture cells.

Author

Ashe H, Clark BR, Chu F, Hardy DN, Halpern BC, Halpern RM, and Smith RA

Subjects
Amnion, Animals, Carbon Radioisotopes, Carcinosarcoma, Cells, Cultured, Chromatography, Ion Exchange, Culture Techniques, Fibroblasts, Homocysteine, Homocystine, Humans, Leukemia L1210 enzymology, Leukemia, Myeloid enzymology, Liver, Methionine, Mice, Rats, Tetrahydrofolates, Thymus Gland, Methyltransferases metabolism
Published
1974
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50. Rubella surveillance and immunization. Susceptibility in nonurban adolescents.

Author

Schiff GM, Linnemann CC Jr, Rotte T, and Ashe HS

Subjects
Adolescent, Age Factors, Antibodies, Viral analysis, Disease Outbreaks prevention & control, Female, Follow-Up Studies, Health Surveys, Humans, Immunization, Male, Pregnancy, Rubella immunology, Rubella Vaccine therapeutic use, Rubella virus immunology, Rural Population, Sex Factors, Wisconsin, Rubella prevention & control
Published
1973

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