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  • 1
    ISSN: 1365-2303
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Introduction
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Anti-CD4 monoclonal antibodies are potential therapeutic agents for the prevention of autoimmune disease and treatment of rejection after organ transplantation and are capable of both restoring tolerance to self-antigens and inducing tolerance to antigens introduced under the cover of the antibody therapy in vivo. Tolerance to donor alloantigens can be induced in vivo by administering donor alloantigen in combination with either depleting (YTA 3.1) or nondepleting (YTS 177) anti-CD4, 28 days before heart transplantation in the mouse. The effect of anti-CD4 on proximal T-cell receptor (TCR) signalling pathways and proliferation was investigated in vitro and in vivo in the presence and absence of YTA 3.1 or YTS 177. Anti-CD4 was found to perturb proximal signalling events upon TCR/CD3 ligation, resulting in reduced tyrosine phosphorylation of Zap-70 and LAT (linker for activation of T cells) and reduced association of tyrosine-phosphorylated LAT with lck. This ultimately resulted in severely reduced proliferation of the responding CD4+ T cells. The signalling profile of the anti-CD4-treated cells resembled that of anergic T cells. This could be a result of a common mechanism involving perturbation in the formation of the central supramolecular activation cluster of the immunological synapse by impaired recruitment of CD4 and CD28, thereby resulting in severely reduced lck activation.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Key words Rat ; pancreatic islet ; transplantation ; diabetes mellitus ; nephropathy.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies of intraportal islet autotransplantation in large animals have reported graft failure after months or years. In the rat it has been reported that intraportal islet isografts eventually failed whilst islets transplanted to the renal subcapsule functioned up to a year. We made Dark Agouti (DA) rats severely diabetic with streptozotocin, then 1000 or 3000 DA islets were transplanted beneath the renal capsule or into the liver. One set of transplanted rats and untreated diabetic and normal non-diabetic littermates were monitored lifelong by measurement of plasma glucose, others were killed at 6, 12 and 18 months for measurement of haemoglobin A1c, intravenous glucose tolerance test, pancreas insulin content and histology of the kidney. Renal glomerular basement membrane thickness was measured by the orthogonal intercept method. The results showed that intraportal isografts reversed hyperglycaemia significantly faster than renal subcapsular isografts. In the renal subcapsular site, consistent reversal of diabetes was achieved with 3000 islets but not with 1000 islets. Furthermore, intraportal islet grafts with 3000 islets led to lower, normal random glucose level than renal subcapsular grafts for the first 13 months. Normoglycaemia was maintained lifelong in all rats that achieved early normoglycaemia after transplantation of 3000 islets, irrespective of the site of islet transplantation. The fasting glucose, haemoglobin A1c levels, K value and glomerular basement membrane thickness of the recipients of 3000 islets to either the intraportal and subcapsular site were not significantly different from each other and the normal controls up to 18 months. We conclude that, in streptozotocin diabetic DA rats, normoglycaemia following transplantation of an adequate mass of pancreatic islet tissue (3000 islets) to the liver or beneath the renal capsule is lifelong and the development of glomerular basement membrane thickening is prevented. [Diabetologia (1995) 38: 1014–1024]
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0428
    Keywords: Keywords Insulin-dependent diabetes mellitus; polymerase chain reaction ; diabetic nephropathy ; angiotensinogen ; angiotensin converting enzyme ; gene polymorphism.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Premature cardiovascular disease is common in insulin-dependent diabetic (IDDM) patients who develop diabetic nephropathy. Genetic polymorphism within the renin-angiotensin system has been implicated in the aetiology of a number of cardiovascular disorders; these loci are therefore candidate genes for susceptibility to diabetic renal disease. We have examined the angiotensin converting enzyme insertion/deletion polymorphism and angiotensinogen methionine 235 threonine polymorphism in a large cohort of Caucasian patients with IDDM and diabetic nephropathy. Patients were classified as having nephropathy by the presence of persistent dipstick positive proteinuria (in the absence of other causes), retinopathy and hypertension (n = 242). Three groups were examined for comparison: ethnically matched non-diabetic subjects (n = 187); a geographically defined cohort of newly diagnosed diabetic patients (n = 341); and IDDM patients with long duration of disease ( 〉 15 years) and no evidence of overt nephropathy (n = 166). No significant difference was seen in distribution of angiotensin converting enzyme or angiotensinogen genotypes between IDDM patients with nephropathy and recently diagnosed diabetic subjects (p = 0.282 and 0.584, respectively), nor the long-duration non-nephropathy diabetic subjects (p = 0.701 and 0.190, respectively). We conclude that these genetic loci are unlikely to influence susceptibility to diabetic nephropathy in IDDM in the United Kingdom. [Diabetologia (1996) 39: 1108–1114]
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 38 (1995), S. 1496-1496 
    ISSN: 1432-0428
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Rat ; pancreatic islet ; transplantation ; diabetes mellitus ; nephropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Previous studies of intraportal islet autotransplantation in large animals have reported graft failure after months or years. In the rat it has been reported that intraportal islet isografts eventually failed whilst islets transplanted to the renal subcapsule functioned up to a year. We made Dark Agouti (DA) rats severely diabetic with streptozotocin, then 1000 or 3000 DA islets were transplanted beneath the renal capsule or into the liver. One set of transplanted rats and untreated diabetic and normal non-diabetic littermates were monitored lifelong by measurement of plasma glucose, others were killed at 6, 12 and 18 months for measurement of haemoglobin A1c, intravenous glucose tolerance test, pancreas insulin content and histology of the kidney. Renal glomerular basement membrane thickness was measured by the orthogonal intercept method. The results showed that intraportal isografts reversed hyperglycaemia significantly faster than renal subcapsular isografts. In the renal subcapsular site, consistent reversal of diabetes was achieved with 3000 islets but not with 1000 islets. Furthermore, intraportal islet grafts with 3000 islets led to lower, normal random glucose level than renal subcapsular grafts for the first 13 months. Normoglycaemia was maintained life-long in all rats that achieved early normoglycaemia after transplantation of 3000 islets, irrespective of the site of islet transplantation. The fasting glucose, haemoglobin A1c levels, K value and glomerular basement membrane thickness of the recipients of 3000 islets to either the intraportal and subcapsular site were not significantly different from each other and the normal controls up to 18 months. We conclude that, in streptozotocin diabetic DA rats, normoglycaemia following transplantation of an adequate mass of pancreatic islet tissue (3000 islets) to the liver or beneath the renal capsule is lifelong and the development of glomerular basement membrane thickening is prevented.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Insulin-dependent diabetes mellitus ; polymerase chain reaction ; diabetic nephropathy ; angiotensinogen ; angiotensin converting enzyme ; gene polymorphism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Premature cardiovascular disease is common in insulin-dependent diabetic (IDDM) patients who develop diabetic nephropathy. Genetic polymorphism within the renin-angiotensin system has been implicated in the aetiology of a number of cardiovascular disorders; these loci are therefore candidate genes for susceptibility to diabetic renal disease. We have examined the angiotensin converting enzyme insertion/deletion polymorphism and angiotensinogen methionine 235 threonine polymorphism in a large cohort of Caucasian patients with IDDM and diabetic nephropathy. Patients were classified as having nephropathy by the presence of persistent dipstick positive proteinuria (in the absence of other causes), retinopathy and hypertension (n=242). Three groups were examined for comparison: ethnically matched non-diabetic subjects (n=187); a geographically defined cohort of newly diagnosed diabetic patients (n=341); and IDDM patients with long duration of disease (〉15 years) and no evidence of overt nephropathy (n=166). No significant difference was seen in distribution of angiotensin converting enzyme or angiotensinogen genotypes between IDDM patients with nephropathy and recently diagnosed diabetic subjects (p=0.282 and 0.584, respectively), nor the long-duration non-nephropathy diabetic subjects (p=0.701 and 0.190, respectively). We conclude that these genetic loci are unlikely to influence susceptibility to diabetic nephropathy in IDDM in the United Kingdom.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-2277
    Keywords: Donor age, renal function ; Kidney function, donor age ; Age donor, renal function
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The quality of renal allograft function was assessed by prospective measurement of creatinine clearance at 1 year (n=197) and at 3 years (n=115) after cadaveric renal transplantation in a cohort of 268 patients treated with triple therapy immunosuppression. Donor age (P〈0.0012) and recipient age (P〈0.01) were independently associated with creatinine clearance both at 1 and at 3 years. In patients with donor age above 50 years and recipient age above 45 years, the mean creatinine clearance was 32.7 (SD 10.4) ml/min (n=27). When the donor age was below 30 years and recipient age below 45 years, the mean creatinine clearance was 55.6 (SD 14.4) ml/min (n=47, P〈0.001). However, in these patients there was no significant association between graft function and many of the factors known to influence graft survival, such as HLA matching, sensitisation of the recipient, and the occurrence of rejection. In conclusion, the quality of renal allograft function declined with increasing donor and recipient age in our patients, whilst immunological factors were not significantly associated with function in surviving grafts.
    Type of Medium: Electronic Resource
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