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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Scandinavian journal of immunology 55 (2002), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The HLA class II molecule, DQ6, confers strong natural protection against the development of type 1 diabetes. The mechanism of disease protection is unknown, but is likely to be related to the function of the molecule in antigen presentation. In order to investigate this function, we have created an in vitro model which expresses DQ6 in isolation by introducing the relevant DQ alleles into an Epstein–Barr virus (EBV)-transformed, human leucocyte antigen (HLA) class II-deficient B cell line, bare lymphocyte syndrome (BLS)-1. A recent report suggested that the expression of transferred genes in human EBV-transformed B cells might be limited in duration. We present a plasmid-based transfection method that allows long-term stable expression of the DQ molecule. The DQA1*0102 and DQB1*0602 alleles were cloned into the pCIneo expression vector and the constructs were introduced into BLS-1 by electroporation. Stable transfectants were selected using magnetic sorting and cloned by limiting dilution. Two clones were shown to express functionally active DQ6 molecules even after 14 months of continuous culture. These clones will be used in functional studies to investigate the antigen binding and T-cell activation properties of the DQ6 molecule.
    Type of Medium: Electronic Resource
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  • 2
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    Oxford : Periodicals Archive Online (PAO)
    Economic Inquiry. 33:3 (1995:July) 506 
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Journal of regulatory economics 13 (1998), S. 245-254 
    ISSN: 1573-0468
    Source: Springer Online Journal Archives 1860-2000
    Topics: Economics
    Notes: Abstract The goal of universal service has dominated the telecommunications policy landscape for at least the past half century. This policy objective has been promoted with cross subsidies from long-distance telecommunications services to subscribers to local telecommunications service. The economic rationale for these cross subsidies is network externalities. In this paper, we show that: (1) the presence of network externalities, even if substantial in overall magnitude, does not generally justify a subscribership subsidy, even a well-designed one; and (2) the empirical realities of telecommunications markets make it unlikely that subscribership subsidies of any kind will increase social welfare.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The polymorphic HLA-DQ A1 and -DQB1 genes encode polypeptides that fold together to form a receptor that specifies T-lymphocyte recognition of self and foreign peptides8"13. DNA sequence analysis of DQ and DR genes from Caucasian patients with IDDM indicates that susceptibility to the disease ...
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0428
    Keywords: Chlorpropamide-alcohol flush ; retinopathy ; glucose tolerance test ; serum insulin ; serum triglycerides ; blood metabolites ; Type 2 diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Serum insulin and blood metabolite responses to oral glucose with and without intravenous naloxone were measured in 24 chlorpropamide-alcohol flush positive and negative Type 2 (non-insulin dependent) diabetic patients with and without retinopathy. In the chlorpropamide-alcohol flush positive patients with retinopathy, fasting blood glucose was increased 〉40% and the serum triglycerides were increased over twofold compared with each of the other three groups. Following oral glucose (50 g), the chlorpropamide-alcohol flush positive diabetic patients with complications had a lower serum insulin and higher blood glycerol than the other three groups. Thus, chlorpropamide-alcohol flush positive subjects with retinopathy showed distinct metabolic differences from the other three groups. There was no evidence that opiate-receptors influenced the metabolic response to oral glucose in the Type 2 diabetic patients since the infusion of intravenous naloxone produced no effect on the serum insulin or blood metabolites.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0428
    Keywords: Type 1 (insulin-dependent) diabetes ; Punjabi Asians ; HLA-DR typing ; DQβ-gene probing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Type 1 (insulin-dependent) diabetes is less common in Asian Indians than in white Caucasoids. Forty-five Punjabi Asians with Type 1 diabetes and 96 racially matched control subjects were HLA-DR typed. DR3 was increased in diabetic patients vs control subjects (82% vs 38%, p〈10−5) with relative risk 7.7 and etiological fraction 0.72. DR4 was increased in diabetic patients vs control subjects (31% vs 7%, p〈0.003) with relative risk 5.7 and etiological fraction 0.26. DR2 showed a negative association (relative risk 0.19, etiological fraction −0.28), as did DR7 (relative risk 0.21, etiological fraction −0.33). HLA-DQβ-chain gene probing using restriction enzyme BamHI in 43 diabetic patients and 90 control subjects showed that the DR1-associated 6.2 and 3.2kb fragments were less common in diabetic patients than in the control subjects (12% vs 36%, p〈0.02). A 12kb fragment was associated with DR4 in both diabetic patients and control subjects. DR3 is the major susceptibility factor for Type 1 diabetes in Punjabi Asians and DR4 is a second marker. Gene probing indicates that the same DR4 subset is associated with the condition as in white Caucasoids. DR1 and its associated DQβ restriction fragments are reduced in Asian Type 1 diabetic patients making it unlikely that DR1 haplotypes carry a predisposing factor in this racial group. We conclude that the genetic component of Type 1 diabetes in Punjabis shows differences from that of the white Caucasoid population and that the lower frequency of DR4 in this population may contribute to the lower prevalence of Type 1 diabetes.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0428
    Keywords: Genetics ; diabetes mellitus ; mitochondria ; maternal ; deafness
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Non-insulin-dependent diabetes mellitus (NIDDM) has a strong genetic component and maternal factors have recently been implicated in disease inheritance. The mitochondrial myopathies are a group of diseases which often show maternal inheritance as a result of mtDNA defects; some patients have impaired glucose tolerance. Occasional families with maternally inherited diabetes and deafness associated with a deletion or point mutation of mtDNA have been reported. To assess the importance of mitochondrial gene defects in NIDDM, 150 unrelated diabetic subjects from Wales, UK and 68 unrelated patients with diabetes and at least one affected sibling from England, UK were studied. Southern blot analysis did not show any large mtDNA deletions or duplications. One patient had a mutation in the mitochondrial tRNAleu(UUR) gene at bp 3243. This mutation is commonly associated with the syndrome of mitochondrial encephalomyopathy, lactic acidosis and stroke like episodes (MELAS). Study of this patient and his siblings showed a distinct form of late-onset diabetes associated with nerve deafness but no clinical features of the MELAS syndrome. No diabetic subject was shown to have the mtDNA mutation at position 8344 (tRNAlys) which has previously been described in the syndrome of mitochondrial encephalomyopathy and red-ragged fibres (MERRF). The role of other mitochondrial gene defects in diabetes and the pathophysiological basis of glucose intolerance in patients with the MELAS mutation requires further elucidation.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0428
    Keywords: Keywords Type I diabetes ; diabetic nephropathy ; human leucocyte antigen ; insulin gene.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Aims/hypothesis. Diabetic nephropathy seems to have a strong genetic component. Genes involved in the genetic susceptibility to Type I (insulin-dependent) diabetes have been suggested to have a role in the development of diabetic nephropathy. This study aimed to examine the role of human leucocyte antigen and insulin genes in susceptibility to nephropathy in patients with Type I diabetes. Methods. We carried out a genetic association study examining insulin gene polymorphisms using three large cohorts of patients with Type I diabetes: nephropathy (n = 258), long duration non-nephropathy (n = 153) and a recently diagnosed (sporadic) diabetic cohort (n = 264). Human leucocyte antigen typing results were obtained in a smaller number due to assay failures (n = 182, 126 and 200 respectively). Results. No significant difference was seen in the distribution of human leucocyte antigen A, B, C, DR, DQA1 and DQB1 haplotypes and alleles between the three diabetic cohorts. No significant difference was seen in insulin ’ + ' and ’–' genotypes and alleles between the three diabetic cohorts. Conclusion/interpretation. Human leucocyte antigen and insulin gene loci are unlikely to have a major role in the susceptibility to nephropathy in Caucasian patients with Type I diabetes in the United Kingdom. [Diabetologia (1999) 42: 1017–1020]
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 20 (1981), S. 87-93 
    ISSN: 1432-0428
    Keywords: Identical twins ; concordance ; discordance ; insulin dependent diabetes ; non-insulin dependent diabetes ; genetics ; aetiology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 18 (1980), S. 365-368 
    ISSN: 1432-0428
    Keywords: Premature labour ; diabetes ; B-sympathomimetic infusion ; salbutamol ; ritodrine hydrochloride ; dexamethasone ; insulin infusion ; potassium ; maternal and foetal wellbeing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The practical management of premature labour is described, illustrated by ten cases. All the patients were treated with β-sympathomimetic infusion, either salbutamol (0.4–1.6 mg/h) or ritodrine hydrochloride (2–6 mg/h), to stop uterine contractions, and with intramuscular dexamethasone 4 mg eight hourly to accelerate foetal lung maturity. Satisfactory control of blood glucose was achieved (range 2–10 mmol/l) by using high rates of insulin infusion (range 8–32 units per hour). Delivery was postponed in eight cases and seven healthy babies were born. There were three foetal deaths from multiple congenital abnormalities. β-sympathomimetic infusion caused few maternal side-effects and there were no foetal problems. Maternal plasma potassium decreased in all cases studied, the mean fall being from 4.5 mmol/l to 2.7 mmol/l.
    Type of Medium: Electronic Resource
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