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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the course of studying the role of hsp70 in the differentiation of pancreatic beta cells, transgenic founder mice were generated with the human hsp70 gene fused to the human insulin gene promoter. One resulted in a transgenic line that consistently developed diabetes mellitus, but unexpectedly three other independent transgenic founders developed generalized malignant lymphoma within 10 months after birth. Immunochemical and RT-PCR analyses revealed that the transgene was expressed in the lymphoma cells. Flow cytometric analyses revealed that the tumor was originated from T lymphocytes. Our results provide the first experimental evidence that hsp70 is involved in the tumorigenesis of T cells most likely through the blockage of apoptotic signals.
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PMID:T cell lymphoma in transgenic mice expressing the human Hsp70 gene. 856 99

The structural alterations of endocardial endothelial cells of the heart right atrium and left ventricle were investigated in Golden Syrian hamsters subjected to streptozotocin-induced diabetes and to a combination of diabetes and diet-induced hyperlipidemia. Animals were examined at time intervals ranging from 2 weeks to 6 months. Anionic sites of the endothelial plasmalemma were visualized by in situ perfusion of cationized ferritin. The results indicated that: (a) both atrial and ventricular endocardial endothelium are affected in streptozotocin-induced diabetes: endothelium converts from continuous into a fenestrated type, (b) although the anionic charge of the plasmalemma decreased in advanced diabetes, the newly formed fenestrae highly bound cationized ferritin, (c) combined diabetes and hyperlipidemia induced more severe alterations of endocardial endothelium: new permeable endothelial structures were formed (transendothelial channels, open intercellular junctions, fused plasmalemmal vesicles), and the cells became particularly enriched in cytoskeleton (intermediate filaments and microtubules), (d) the thick subendocardial layer of connective tissue contained, in the combined experimental model, macrophage derived foam cells indicative for the occurrence of alterations of atherosclerotic type.
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PMID:The pathomorphological alterations of endocardial endothelium in experimental diabetes and diabetes associated with hyperlipidemia. 877 84

To determine whether glycogen synthase (GS) activity remains impaired in skeletal muscle of non-insulin-dependent diabetes mellitus (NIDDM) patients or can be normalized after prolonged culture, needle biopsies of vastus lateralis were obtained from 8 healthy nondiabetic control (ND) and 11 NIDDM subjects. After 4-6 wk growth and 4 d fusion in media containing normal physiologic concentrations of insulin (22 pM) and glucose (5.5 mM), both basal (5.21 +/- 0.79 vs 9.01 +/- 1.25%, P < 0.05) and acute insulin-stimulated (9.35 +/- 1.81 vs 16.31 +/- 2.39, P < 0.05) GS fractional velocity were reduced in NIDDM compared to ND cells. Determination of GS kinetic constants from muscle cells of NIDDM revealed an increased basal and insulin-stimulated Km(0.1) for UDP-glucose, a decreased insulin-stimulated Vmax(0.1) and an increased insulin-stimulated activation constant (A(0.5)) for glucose-6-phosphate. GS protein expression, determined by Western blotting, was decreased in NIDDM compared to ND cells (1.57 +/- 0.29 vs 3.30 +/- 0.41 arbitrary U/mg protein, P < 0.05). GS mRNA abundance also tended to be lower, but not significantly so (0.168 +/- 0.017 vs 0.243 +/- 0.035 arbitrary U, P = 0.08), in myotubes of NIDDM subjects. These results indicate that skeletal muscle cells of NIDDM subjects grown and fused in normal culture conditions retain defects of basal and insulin-stimulated GS activity that involve altered kinetic behavior and possibly reduced GS protein expression. We conclude that impaired regulation of skeletal muscle GS in NIDDM patients is not completely reversible in normal culture conditions and involves mechanisms that may be genetic in origin.
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PMID:Glycogen synthase activity is reduced in cultured skeletal muscle cells of non-insulin-dependent diabetes mellitus subjects. Biochemical and molecular mechanisms. 878 86

In a subset of patients with non-insulin-dependent diabetes mellitus an 8-base pair (bp) repeat was found from -322 to -315 in the 5'-flanking region of the insulin gene. This 8-bp repeat is inserted into a sequence that is highly homologous to a sequence motif, called PISCES (pancreatic islet cell-specific enhancer sequences), found within cell-specific enhancer elements of the rat insulin I (Ins-E1, from -332 to -285), rat glucagon (Glu-G3) and rat somatostatin (SMS-UE) genes. The PISCES motif confers pancreatic islet-specific activity and is recognized by an islet-specific transcription factor (PISCES-BP). The consequences on functional activity and on protein binding of the 8-bp repeat sequence in the human insulin promoter was investigated. When fused to a reporter gene and transiently transfected into an insulin-producing islet cell line, the 8-bp repeat decreased basal transcriptional activity of the human insulin promoter (from -366 to +42) whereas the induction of promoter activity by cAMP was unaffected. The isolated rat Ins-E1 element was sufficient to confer basal transcriptional activity to a minimal promoter; the corresponding fragments of the normal and variant human insulin genes (from -329 to -288), however, were not. Using nuclear extracts in an electrophoretic mobility shift assay, it was found that PISCES-BP recognizes rat Ins-E1, but PISCES-BP binding to the corresponding normal and variant human insulin promoter fragments was not detectable and weak, respectively. However, a nuclear protein was found that binds to the variant but not normal human sequence. These data suggest that the 8-bp repeat in the variant human insulin promoter found in patients with non-insulin-dependent diabetes mellitus allows the binding of a nuclear protein that interferes with promoter function.
Exp Clin Endocrinol Diabetes 1996
PMID:Nuclear protein binding and functional activity of a variant insulin gene found in non-insulin-dependent diabetes mellitus. 881 39

Holoprosencephaly is a rare cerebral malformation resulting from failure or incomplete cleavage of the forebrain. The sonographic diagnosis consists of monoventricle, fused thalami and absent cavum septum pellucidi. Chromosomal anomalies, diabetes mellitus, alcohol, autosomal recessive inheritance and toxins have been implicated. We describe seven cases of holoprosencephaly diagnosed in the antenatal and postnatal periods. The chromosomal anomalies included trisomy 13, triploidy, trisomy 13 with an unbalanced 13; 14 translocation and isochromosome of the long arm of 18. The clinicopathological findings and chromosomal anomalies are correlated.
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PMID:Holoprosencephaly and chromosomal anomalies. 899 41

The D variant of the encephalomyocarditis (EMC-D) virus is diabetogenic in mice by infecting and destroying pancreatic beta cells, but the EMC-B and EMC-DV viruses are not diabetogenic. We have presumed that the nondiabetogenicity of EMC-B and EMC-DV is mainly caused by release of some viral inhibitory factors from lymphocytes or phagocytic cells. Mice were infected with EMC-B and their splenocytes were fused with myeloma cells. The splenocyte hybridoma 12D8 releases the viral inhibitory substance (VIS) which is neither immunoglobulin nor interferon. VIS has inhibitory effects against EMC-D in several kinds of cell lines, and against EMC-D, EMC-B, coxsackie B4, reovirus and the vesicular stomatitis virus in the L cell. VIS has a strong preventive effect (100%) against EMC-D induced diabetes in SJL/J mice and DBN/2N mice. In both pre- and post-treatment studies, VIS remarkably decreased the incidence of both illness and death in SJL/J mice infected with the EMC-D virus. VIS, culture supernate itself of hybridoma, had viral inhibitory activities equivalent to 10(6)-10(7) IU/ml of interferon. VIS was very labile to heat (75% loss of activities at 37 degrees C for 18 h), stable only at pH 5-9, and precipitated at 50% (NH4)2SO4 solution. VIS activities existed in supernatant and pellet prepared from ultracentrifugation, but the properties of their activities could be differentiated quantitatively and qualitatively. It is speculated that VIS may be composed of at least two factors even though interferon may partially participate in one component of supernatant. The prevention and treatment effect of VIS on EMC-D infection in SJL/J mice might be due to the inhibition of the virus replication by VIS.
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PMID:Characterization of viral inhibitory substance released from fused splenocyte. 916 27

Uremia is a chemical, toxic, potentially fatal condition. In a variable pattern, uremia ultimately kills almost every cell in the body. Uremia is produced by hundreds of diseases, both kidney and systemic (e.g., diabetes). These kinds of uremic conditions range from the acute and catastrophic to the slowly and moderately progressive. Humans and medicine have struggled at least since Hippocrates to understand, prevent and treat uremia and thereby prolong the useful lives of the young and the aging. Accelerated by the spectacle of premature uremic deaths from crush syndrome, shock, and forms of nephritis during major wars and disasters, medicine fused clinical and basic science with industrial technology and came up with two effective treatments. Dialysis in several modes and kidney transplantation became feasible but proved complex and expensive. How people, struggling to survive, were able to use a representative form of government to treat all kidney patients, forms a human story: A "people" story. Since it culminated within a single medical generation, it is possible to tell the story as a participant and eye-witness. This is how the medical, social and national organization of substitution therapy for uremia evolved. Since it is legislatively called end-stage renal disease, we titled the entitlement, "How ESRD-Medicare Developed."
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PMID:How end-stage renal disease (ESRD)-Medicare developed. 916 44

Human skeletal muscle cultures (HSMCs) from type II diabetic subjects were used to determine whether metabolic abnormalities such as hyperglycemia or hyperinsulinemia contribute to the defective muscle glycogen synthase (GS) activity present in this disorder. Following approximately 6 weeks of growth, diabetic cultures were fused for 4 days in normal, hyperglycemia, or hyperinsulinemia medium. Fusion of diabetic HSMCs in hyperglycemia medium (20 mmol/l vs. 5.5 mmol/l) had no effect on GS fractional velocity (FV) or mRNA levels, but impaired acute insulin-stimulation of glycogen synthesis and GS activity at 0.1 mmol/l glucose-6-phosphate, and reduced GS protein content by approximately 15% (P < 0.05). Fusion of diabetic muscle cultures in hyperinsulinemia medium (30 micromol/l vs. 22 pmol/l) improved basal GS activity, increasing the reduced GS FV by approximately 50% (P < 0.05), and decreasing the elevated Km(0.1) (half-maximal substrate concentration) by approximately 47% (P < 0.05). Hyperinsulinemia also significantly increased (P < 0.05) the reduced GS mRNA and protein levels of diabetic muscle to levels similar to that in nondiabetic subjects. In contrast to the improvements in the basal state, hyperinsulinemia completely abolished acute insulin responsiveness of GS activity and glycogen synthesis in muscle of type II diabetic subjects. The combination of hyperinsulinemia and hyperglycemia produced effects on both basal and insulin-responsive GS FV and mRNA similar to hyperinsulinemia alone, but hyperinsulinemia prevented hyperglycemia's effect of lowering GS protein and glycogen synthesis. We concluded that, in diabetic muscle, hyperinsulinemia may serve to partially compensate for the impaired basal GS activity and for the adverse effects of hyperglycemia on GS protein content, activity, and glycogen formation by both pre- and posttranslational mechanisms. Despite these beneficial effects, hyperinsulinemia also induces severe impairment of insulin-stimulated GS activity and glycogen formation, which may contribute to acquired muscle insulin resistance of type II diabetes.
Diabetes 1997 Jun
PMID:Regulation of glycogen synthase activity in cultured skeletal muscle cells from subjects with type II diabetes: role of chronic hyperinsulinemia and hyperglycemia. 916 74

Since hyperglycaemia is known to affect normal pulmonary physiology and biochemistry and few structure-function correlations have been reported, we designed experiments on hamsters subjected to streptozotocin-induced diabetes or diabetes associated with hyperlipidaemia, and investigated the impact of these conditions on the lung structure. At time intervals ranging 2-24 weeks from the inception of disease (without correcting blood glucose with insulin), the animals were sacrificed, and plasma glucose and cholesterol assayed. The lung was processed for electron microscopy, and the structural changes of the capillary and venular endothelium, of epithelial cells, and interstitium were examined. In diabetic animals, especially after 6 weeks of disease, a gradual narrowing of approximately 35% of the capillaries and approximately 30% of the alveoli, and hyperplasia of the extracellular matrix, rich in collagen bundles, were observed. Frequently, capillaries contained adherent intravascular macrophages suggestive of an inflammatory process. The capillary endothelium was characterized by numerous plasmalemmal vesicles, often fused, well-developed synthesizing apparatus (endoplasmic reticulum and Golgi complex) and cytoskeleton, and an uneven distribution of the anionic sites on the luminal plasmalemma. The venular endothelium was particularly rich in Weibel-Palade bodies. The alveolar epithelium was often collapsed, compressing surfactant within the airspace. The lung interstitium was apparently enlarged, and the fibroblasts and contractile interstitial cells frequently contained lipid droplets. These alterations were more pronounced and occurred at a faster rate (4 weeks) in diabetes associated with hyperlipidaemia. The structural modifications reported in this study support the functional disturbances observed in association with hyperglycaemia, sustaining the conclusion that the lung is an organ affected by diabetes.
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PMID:Alterations of lung structure in experimental diabetes, and diabetes associated with hyperlipidaemia in hamsters. 927 30

Thirty-seven ankles in twenty-four patients were treated at our institution between July 1, 1974, and December 31, 1996, for atraumatic osteonecrosis of the talus. This group represents 2 per cent of the 1056 patients who were managed for osteonecrosis during this period. There were twenty-one women and three men, and their mean age was forty years (range, twenty-six to sixty-two years) at the time of the diagnosis. Thirteen (54 per cent) of the twenty-four patients had bilateral involvement. Sixteen patients (67 per cent) had a disease that affects the immune system, including systemic lupus erythematosus (thirteen patients), scleroderma (one), insulin-dependent diabetes mellitus (one), and multiple sclerosis (one). Four patients had a history of regular alcohol use, and four patients had a history of moderate smoking. One patient had a protein-S deficiency, one patient had had a renal transplant, and one patient had a history of asthma. Two patients had no identifiable risk factors for osteonecrosis [corrected]. Fifteen patients (63 per cent) had involvement of other large joints. The mean duration of symptoms before the patients were seen was 5.4 months (range, two months to two years). The mean ankle score at the time of presentation was 34 points (range, 2 to 75 points), according to the system of Mazur et al. A radiographic review revealed that, according to the system of Ficat and Arlet, eight ankles had stage-III or IV disease of the talus at presentation. The remaining twenty-nine ankles had stage-II disease. The osteonecrosis was seen in the posterolateral aspect of the talar dome (zones III and IV on the sagittal images and zones II, III, and IV on the coronal images) in twenty-two of the twenty-three ankles for which magnetic resonance images were available. The osteonecrosis was seen in the anteromedial aspect of the talar dome (zones I and II on the sagittal images and zone I on the coronal images) in the remaining ankle. Bone scans, which were available for eleven ankles, revealed increased uptake in the talus. All patients were initially managed non-operatively with restricted weight-bearing, an ankle-foot orthosis, and use of analgesics; two ankles responded to this regimen. Thirty-two ankles that remained severely symptomatic were treated with core decompression, which was useful in the treatment of precollapse (stage-II) disease. Twenty-nine of these ankles had a fair-to-excellent clinical outcome a mean of seven years (range, two to fifteen years) postoperatively; the remaining three ankles had an arthrodesis after the core decompression failed. Three ankles were treated initially with an arthrodesis for postcollapse (stage-III or IV) disease. All six of the ankles that had an arthrodesis fused, at a mean of seven months (range, five to nine months) postoperatively. When patients who have a history of osteonecrosis are seen because of pain in the ankle, the diagnosis of osteonecrosis of the talus should be considered. Early detection may allow the ankle to be treated non-operatively or with core decompression and thus reduce the need for arthrodesis. We also believe that when a patient has osteonecrosis of the talus, the hips should be screened with use of standard radiography or magnetic resonance imaging, or both.
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PMID:Atraumatic osteonecrosis of the talus. 956 82


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