Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase.
TL;DR: The pancreatic islet β-cell autoantigen of relative molecular mass 64,000 (64K), which is a major target of autoantibodies associated with the development of insulin-dependent diabetes mel-litus (IDDM), has been identified as glutamic acid decarboxylase, the biosynthesizing enzyme of the inhibitory neurotransmitter GABA.
Abstract: The pancreatic islet β-cell autoantigen of relative molecular mass 64,000 (64K), which is a major target of autoantibodies associated with the development of insulin-dependent diabetes mel-litus (IDDM) has been identified as glutamic acid decarboxylase, the biosynthesizing enzyme of the inhibitory neurotransmitter GABA (γ-aminobutyric acid). Pancreatic β cells and a subpopulation of central nervous system neurons express high levels of this enzyme. Autoantibodies against glutamic acid decarboxylase with a higher titre and increased epitope recognition compared with those usually associated with IDDM are found in stiff-man syndrome, a rare neurological disorder characterized by a high coincidence with IDDM.
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TL;DR: Flavonoids are plant pigments that are synthesised from phenylalanine, generally display marvelous colors known from flower petals, mostly emit brilliant fluorescence when they are excited by UV light, and are ubiquitous to green plant cells.
2,424 citations
TL;DR: Anti-GAD is a valuable early predictive marker and is associated with a very high risk for development of IDDM, and was measured in prediabetic sera from 151 women aged 20-39 years with newly diagnosed diabetes mellitus who had been identified through a nationwide diabetes register.
1,703 citations
TL;DR: New guidelines for laboratory testing for patients with diabetes mellitus provide specific recommendations that are based on published data or derived from expert consensus, and several analytes have minimal clinical value at present and are not recommended.
Abstract: Background: Multiple laboratory tests are used in the diagnosis and management of patients with diabetes mellitus The quality of the scientific evidence supporting the use of these assays varies substantially
Approach: An expert committee drafted evidence-based recommendations for the use of laboratory analysis in patients with diabetes An external panel of experts reviewed a draft of the guidelines, which were modified in response to the reviewers’ suggestions A revised draft was posted on the Internet and was presented at the AACC Annual Meeting in July, 2000 The recommendations were modified again in response to oral and written comments The guidelines were reviewed by the Professional Practice Committee of the American Diabetes Association
Content: Measurement of plasma glucose remains the sole diagnostic criterion for diabetes Monitoring of glycemic control is performed by the patients, who measure their own plasma or blood glucose with meters, and by laboratory analysis of glycated hemoglobin The potential roles of noninvasive glucose monitoring, genetic testing, autoantibodies, microalbumin, proinsulin, C-peptide, and other analytes are addressed
Summary: The guidelines provide specific recommendations based on published data or derived from expert consensus Several analytes are of minimal clinical value at the present time, and measurement of them is not recommended
1,481 citations
TL;DR: The double-edged sword roles of PARP in DNA damage signaling and cell death are reviewed and the underlying mechanisms of the anti-inflammatory effects ofPARP inhibitors are summarized.
Abstract: Poly(ADP-ribose) polymerase-1 (PARP-1) is a member of the PARP enzyme family consisting of PARP-1 and several recently identified novel poly(ADP-ribosylating) enzymes. PARP-1 is an abundant nuclear protein functioning as a DNA nick-sensor enzyme. Upon binding to DNA breaks, activated PARP cleaves NAD(+) into nicotinamide and ADP-ribose and polymerizes the latter onto nuclear acceptor proteins including histones, transcription factors, and PARP itself. Poly(ADP-ribosylation) contributes to DNA repair and to the maintenance of genomic stability. On the other hand, oxidative stress-induced overactivation of PARP consumes NAD(+) and consequently ATP, culminating in cell dysfunction or necrosis. This cellular suicide mechanism has been implicated in the pathomechanism of stroke, myocardial ischemia, diabetes, diabetes-associated cardiovascular dysfunction, shock, traumatic central nervous system injury, arthritis, colitis, allergic encephalomyelitis, and various other forms of inflammation. PARP has also been shown to associate with and regulate the function of several transcription factors. Of special interest is the enhancement by PARP of nuclear factor kappa B-mediated transcription, which plays a central role in the expression of inflammatory cytokines, chemokines, adhesion molecules, and inflammatory mediators. Herein we review the double-edged sword roles of PARP in DNA damage signaling and cell death and summarize the underlying mechanisms of the anti-inflammatory effects of PARP inhibitors. Moreover, we discuss the potential use of PARP inhibitors as anticancer agents, radiosensitizers, and antiviral agents.
1,410 citations
TL;DR: Anti-α/β T cell receptor monoclonal antibody provides an efficient therapy for autoimmune diabetes in nonobese diabetic (NOD) mice and prediabetic NOD mice are protected from disease when treated with antibodies that interfere with antigen recognition.
1,270 citations
Cites background from "Identification of the 64K autoantig..."
...The recent discovery that the two proven to be a reliable predictive marker for progression tryptic fragments are derived from the putative tyrosine to overt diabetes (Baekkeskov et al., 1990; Hagopian phosphatase IA-2 should aid in assessing T cell reactivet al., 1993)....
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TL;DR: A method has been devised for the electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets that results in quantitative transfer of ribosomal proteins from gels containing urea.
Abstract: A method has been devised for the electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets. The method results in quantitative transfer of ribosomal proteins from gels containing urea. For sodium dodecyl sulfate gels, the original band pattern was obtained with no loss of resolution, but the transfer was not quantitative. The method allows detection of proteins by autoradiography and is simpler than conventional procedures. The immobilized proteins were detectable by immunological procedures. All additional binding capacity on the nitrocellulose was blocked with excess protein; then a specific antibody was bound and, finally, a second antibody directed against the first antibody. The second antibody was either radioactively labeled or conjugated to fluorescein or to peroxidase. The specific protein was then detected by either autoradiography, under UV light, or by the peroxidase reaction product, respectively. In the latter case, as little as 100 pg of protein was clearly detectable. It is anticipated that the procedure will be applicable to analysis of a wide variety of proteins with specific reactions or ligands.
53,030 citations
TL;DR: This technique provides a method for estimation of the number of proteins made by any biological system and can resolve proteins differing in a single charge and consequently can be used in the analysis of in vivo modifications resulting in a change in charge.
18,633 citations
3,329 citations
TL;DR: The partition of proteins during phase separation in solutions of Triton X-114 is investigated and integral membrane proteins with an amphiphilic nature are recovered in the detergent phase.
3,150 citations
TL;DR: Quantitative study of insular tissue has revealed that the number of B cells is greatly diminished in Patients with acute juvenile diabetes from the time of clinical onset of the disease, and may be assumed that during the preclinical phase of juvenile diabetes, an extrapancreatic factor has exerted a strong stimulant action on theinsular tissue.
Abstract: 1. Quantitative study of insular tissue has revealed that the number of B cells is greatly diminished in Patients with acute juvenile diabetes from the time of clinical onset of the disease. The number of these cells is as a rule less than 10 per cent of normal. Such B cells as are still present show the cytological signs of marked activity. 2. The normal or supranormal insular activity that is usually found in juvenile diabetics in this stage of the disease cannot therefore be due to the presence of a normal insular tissue, but is produced by a small number of hyperactive B cells. 3. On the basis of histological findings (presence of islets of large size, signs of new islet formation), it may be assumed that during the preclinical phase of juvenile diabetes, an extrapancreatic factor has exerted a strong stimulant action on the insular tissue. In the long run this must lead to exhaustion of the islet-forming capacity on the pancreatic parenchyma and to a decrease in the number of the B cells. By the time the disease becomes clinically manifest only the latter stage of this process can be observed and the majority of islets consist of A cells or of atrophic tissue devoid of B cells. 4. Peri- and intra-insular inflaminatory infiltrates have been found in 68 per cent of those patients with juvenile diabetes who died soon after the clinical onset of their disease. In other words, and contrary to the generally held view, this lesion is not uncommon. It is specific for diabetes and has never been observed in the chronic cases 5. In patients with chronic juvenile diabetes, the B cells are completely absent, except in occasional cases. The islets consist of small, atrophic cells. 6. A valid assessment of the functional capacity of insular tissue can only be achieved if as much use as pos sible is made of quantitative technics and of cytological examination
1,309 citations