Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cerebellum, frontal cortex, hippocampal and parahippocampal regions of 100 patients older than 80 years, most of whom had died of stroke, were examined. Eighteen percent were diagnosed as clinically demented. On the specimens labeled previously with Thioflavin S and Bielschowsky method, immunohistochemical studies were performed with Fab (antigen-binding fragment) of the anti beta-amyloid antibody 4G8. Positive amyloid immunoreactivity was observed in the cerebrum in 71 of 100 cases, Cerebella of 31 subjects of 71 with cerebral amyloidosis also revealed amyloid deposits. They appeared in various morphological forms, such as diffuse plaques and focal subpial deposits, as well as classical and primitive neuritic plaques. Cases with amyloid in the cerebellum alone were not observed. Beta-amyloid deposits in the cerebellum were associated with a significant number of beta-amyloid plaques in the cerebrum, which showed other Alzheimer-type pathology, also in individuals without clinical symptoms of dementia. There was no correlation either between cerebellar amyloid deposits and clinical cerebellar symptoms or between the presence of diabetes mellitus, arterial hypertension, and neuropathological changes. A clear association of microglial cells with amyloid deposits in the cerebellum was demonstrated. In our experience, LN-1 and RCA-1 were not as suitable for formalin-fixed paraffin-embedded tissue, as was anti-ferritin. Negative staining for tau-1 and positive staining for anti-ubiquitin characterized neurites within primitive and classical plaques. No neurofibrillary pathology was detected in the cytoplasm of cerebellar neurons when we used anti tau-1 labeling.
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PMID:beta-Amyloid deposits within the cerebellum of persons older than 80 years of age. 134 Sep 21

The 2.2 A resolution crystal structure of recombinant human manganese superoxide dismutase, a homotetrameric enzyme that protects mitochondria against oxygen-mediated free radical damage, has been determined. Within each subunit, both the N-terminal helical hairpin and C-terminal alpha/beta domains contribute ligands to the catalytic manganese site. Two identical 4-helix bundles, symmetrically assembled from the N-terminal helical hairpins, form novel tetrameric interfaces that stabilize the active sites. Structurally altered polymorphic variants with reduced activity, such as tetrameric interface mutant Ile-58 to Thr, may produce not only an early selective advantage, through enhanced cytotoxicity of tumor necrosis factor for virus-infected cells, but also detrimental effects from increased mitochondrial oxidative damage, contributing to degenerative conditions, including diabetes, aging, and Parkinson's and Alzheimer's diseases.
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PMID:The structure of human mitochondrial manganese superoxide dismutase reveals a novel tetrameric interface of two 4-helix bundles. 139 26

Studies of diseases caused by mitochondrial DNA mutations suggest that a variety of degenerative processes may be associated with defects in oxidative phosphorylation (OXPHOS). Application of this hypothesis has provided new insights into such diverse clinical problems as ischemic heart disease, late-onset diabetes, Parkinson's disease, Alzheimer's disease, and aging.
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PMID:Mitochondrial genetics: a paradigm for aging and degenerative diseases? 153 53

A retrospective analysis was performed on the transient and steady-state pattern electroretinograms recorded from 42 patients with glaucoma, 13 patients with senile dementia of the Alzheimer's type, 58 patients with diabetes mellitus, and 92 control subjects to evaluate the pattern of electroretinographic changes associated with retinal and optic nerve disease. The amplitudes of both the initial positive component (N1 to P1) and the subsequent negative component (P1 to N2) of the transient (4 rps) responses were measured. From these measurements the (P1 to N2)/(N1 to P1) was derived. The N1 to P1 amplitude of the steady-state pattern electroretinogram also was measured. In the glaucoma patients all three amplitude measures, as well as the amplitude ratio of the components of the transient response, were reduced significantly compared with age-matched controls (p less than 0.05). A similar pattern was detected in the patients with Alzheimer's disease, but in this case the only statistically significant amplitude reduction was in the steady-state pattern electroretinogram. A different pattern was observed among the diabetic patients (both with and without retinopathy). Only minor reductions in the amplitude of the transient pattern electroretinogram, which were not statistically significant, were noted. In addition, the ratio of the amplitudes of the components of the transient response did not differ from age-matched controls. The amplitude of the steady-state pattern electroretinogram was reduced in diabetics, but this was significant only for those patients with retinopathy (p less than 0.01). These findings support the suggestion that an analysis of both the positive and negative components of the pattern electroretinogram may be useful for differentiating the contributions of retinal and optic nerve dysfunction to visual impairment. The results also indicate that in both retinal and optic nerve disease the steady-state pattern electroretinogram can be an earlier sign of dysfunction than the transient pattern electroretinogram.
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PMID:The pattern electroretinogram in retinal and optic nerve disease. A quantitative comparison of the pattern of visual dysfunction. 176 Sep 71

The somatostatinergic system has proven to be one of the best models of neuropeptide biology. Originally characterized as a hypothalamic regulator of growth hormone secretion, somatostatin also regulates the secretion of several other pituitary, pancreatic, and gastrointestinal (GI) hormones including thyrotropin-stimulating hormone, insulin, glucagon, and gastrin. Disorders in somatostatin metabolism have been proposed to contribute to the pathogenesis of Alzheimer's disease, epilepsy, GI motility disorders, and diabetes. On a more basic level, studies of somatostatin action have integrated divergent concepts of intracellular signal transduction. Advances in the understanding of somatostatin biosynthesis have had an impact on areas outside the field of endocrinology by providing new concepts of eukaryotic gene regulation. This report focuses on the transcriptional regulation of somatostatin gene expression. Two aspects of somatostatin gene transcription will be considered--regulated expression by second messengers and tissue-specific basal expression.
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PMID:Somatostatin gene regulation: an overview. 197 13

The present review focuses on the vascular basement membrane (VBM) and its relationship to the lesions of Alzheimer's disease (AD). Examination of the fine structure of the microvasculature reveals AD-associated VBM alterations, which include both thickening and vacuolization. Immunocytochemistry confirms that all three intrinsic VBM components [collagen type IV, laminin, and heparan sulfate proteoglycan (HSPG)] outline the capillary bed, which is pathologically altered in AD patients (microangiopathy). Ultrastructural analyses of AD tissue samples demonstrate that HSPG's normal staining pattern is disrupted on the endothelial surface of the VBM in brain regions affected by Alzheimer lesions. Similarly altered VBM is reported to occur in the kidney of patients with diabetes mellitus, where it is associated with a leakage of protein. All three VBM components immunolabel capillaries, amyloid and plaque-associated glial processes, suggesting a link between microangiopathy and senile plaque formation. In addition, the consistent colocalization of HSPG with several forms of amyloid implies an involvement in amyloidogenesis. Finally, the neurotrophic effects of beta-amyloid, combined with neurite-promoting effects of laminin and HSPG, could create a strong focus for an aberrant sprouting response. Such a response is postulated to result in plaque-associated degenerating neurites. Thus, VBM components could serve as a nidus for plaque formation, playing a role in the development of neuritic as well as amyloidotic elements.
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PMID:Microangiopathy, the vascular basement membrane and Alzheimer's disease: a review. 219 75

The development of age pathology has been studied in relation to changes occurring in the activity of various genes and in the synthesis of various proteins as well as in relation to the topography of those changes. The relationship between age-related changes in the activity of various genes and the onset of atherosclerosis, cancer, diabetes, Parkinson's disease and Alzheimer's disease has been studied. The appearance of gene regulatory age-related changes in cells of the nervous, endocrine and immune systems determines their involvement in the age pathology development. The prospects of gene regulatory therapy aimed at selective activation and suppression of various gene groups are outlined.
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PMID:[Genoregulatory mechanisms of aging as a basis for the development of age-related pathology]. 227 89

We have prospectively followed over a 5-year period 434 volunteers who were at intake ambulatory, functional, presumably nondemented, and between 75 and 85 years of age. Fifty-six (an incidence of 3.53 per 100 person-years at risk) developed a progressive dementia: 32 met diagnostic criteria for Alzheimer's disease (AD) (an incidence of 2.0 per 100 person-years at risk), 15 had vascular or mixed dementia, and 9 had other disorders or remain undiagnosed. New cases of dementia were as common as myocardial infarction and twice as common as stroke. Risk factors for both dementia and AD were age (over 80) and gender (female); other reported risk factors such as family history, prior head injury, thyroid disease, maternal age, and smoking were not risk factors for AD in this elderly cohort. Prior stroke was the major risk factor for vascular or mixed dementia; diabetes and left ventricular hypertrophy but not a history of hypertension per se were also risk factors for vascular dementia. The major predictor of the development of AD was the mental status score on entry. The 58.5% of the cohort who made zero to two errors on a 33-item mental status test had a less than 0.6% per year chance of developing AD, whereas the 16% of the cohort with five to eight errors on this test developed AD at a rate of over 12% per year. Thus, it is possible to identify a large cohort of 80-year-olds who are at low risk for AD and a smaller cohort at very high risk.
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PMID:Development of dementing illnesses in an 80-year-old volunteer cohort. 271 31

The self-reported physical and mental health of 315 persons caring for a spouse who had been diagnosed with Alzheimer's disease or a related disorder was compared with general population norms for existing data bases controlling for age and gender. Results suggest that across all indicators of mental health, spouse caregivers are more depressed, express higher levels of negative affect, are more likely to use psychotropic drugs, and have more symptoms of psychological distress than the general population. In terms of physical health, caregivers report higher than expected rates of diabetes, arthritis, ulcers, and anemia, yet they use medical services at rates which are similar or lower than those reported by the general population. Since no simultaneous control group was studied, these results suggest, but do not prove, the presence of differences between caregivers and non-caregivers.
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PMID:Caregiving spouses. Physical and mental health in perspective. 275 54

Leuko-araiosis was found in 49 of 140 demented patients compared with 12 out of 110 control subjects. Thirty-one of 95 patients with dementia of the Alzheimer's type had leuko-araiosis. A history of stroke was four times more frequent in patients with leuko-araiosis than in those without leuko-araiosis (17.4% and 4.4%, respectively). It occurred in 25% of controls with leuko-araiosis compared with only 2% of those without leuko-araiosis. Mean systolic blood pressure was associated with leuko-araiosis. No association was found for diastolic blood pressure, myocardial infarction, angina, diabetes, or carotid bruits. On logistic regression analysis, the strong association between dementia and leuko-araiosis was mainly explained by a history of stroke. There are common factors in leuko-araiosis and stroke, but stroke alone does not account for leuko-araiosis.
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PMID:Vascular risk factors and leuko-araiosis. 380 Jul 21


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