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

We have previously used rat hepatic messenger ribonucleic acid (mRNA) activity profiles to categorize various pathophysiologic states. To test the hypothesis that similar techniques can be used to categorize disease states in humans, we examined the mRNA activity profiles by using in vitro translational assays of Ficoll-Hypaque-separated mononuclear cells obtained from six normal volunteers, six patients with type I diabetes, and five patients with type II diabetes as example of different disease states. Translated proteins were labeled with sulfur 35-labeled methionine, separated by two-dimensional gel electrophoresis, and quantitated by videodensitometry of autoradiographs derived from the two-dimensional gels. Of approximately 160 quantitated mRNAs, the levels of 12 were found to be altered in one of the diabetic states. The values of nine were changed in patients with type I diabetes and the values of 11 were altered in patients with type II diabetes. Although the values of most mRNAs increased, significant decreases were also observed. Moreover, four spots showed significant differences in response between the two diabetic states. Discriminant analysis allowed the separation of all three states. Finally, several mRNAs also displayed an age-related correlation. We have demonstrated that unstimulated mononuclear cell mRNAs can be used to study the effects of pathophysiologic states on gene expression in humans. Furthermore, our results support the potential use of this issue to study the effect of a wide variety of disease states on gene expression.
 ...
PMID:Human lymphocyte messenger RNA activity profiles in type I and type II diabetes: a tool for classification of metabolic disease. 318 94

Mononuclear leukocytes (MNL) were isolated from human blood by Ficoll-Hypaque. These cells were further separated into lymphocyte (L) and monocyte (M) enriched fractions. L contained 99% lymphocytes and M contained 74% monocytes, a threefold enrichment over MNL. Specific binding to somatostatin, glucagon, and insulin was measured in the three fractions. Binding of all three hormones in the M fraction was increased by a factor of 3 compared with MNL and was linear with cell number. Binding of glucagon and insulin to the L fraction was very low while, in contrast, somatostatin binding was substantial and linear with lymphocyte number. Autoradiography confirmed the binding of glucagon to monocytes and of somatostatin to both monocytes and lymphocytes. Somatostatin is the first of the peptide hormones shown to bind to both types of circulating mononuclear cells, perhaps complicating quantification of somatostatin binding in disease states in which differential alteration of binding of lymphocytes or monocytes might occur.
Diabetes 1981 Feb
PMID:Identification of human mononuclear leukocytes bearing receptors for somatostatin and glucagon. 611 May 96

Contrast agents used for cardiac angiography are different in regard to ionicity, osmolality and physiologic effects. The nonionic contrast media have been shown to have less toxic effects and a better safety profile than do higher osmolar agents. To better assess this risk, clinically stable patients undergoing cardiac angiography were stratified according to the presence of diabetes mellitus, and level of serum creatinine, and then randomized to receive either iohexol (Omnipaque 350) or sodium meglumine diatrizoate (Renografin 76). All adverse events that occurred during and immediately after angiography were tabulated. A multivariate model was used to identify patients at increased risk for adverse outcome. The 1,390 patients were randomized to iohexol (n = 696) or diatrizoate (n = 694). Significant differences were found in the number of patients with contrast media-related adverse (iohexol vs diatrizoate: 10.2 vs 31.6%; p < 0.001) and cardiac adverse (7.2 vs 24.5%; p < 0.001) events. Severe reactions and the need for treatment were more frequent with diatrizoate than with iohexol, but there was no difference in the incidence of death. The presence of New York Heart Association classification 3 or 4 and serum creatinine > or = 1.5 mg/dl predicted a higher incidence of adverse events as a result of contrast media alone. Use of iohexol is associated with a lower incidence of all types of adverse events during cardiac angiography than is diatrizoate.
 ...
PMID:Multicenter trial of ionic versus nonionic contrast media for cardiac angiography. The Iohexol Cooperative Study. 821 8

Cystic fibrosis, an autosomal recessive disease affecting exocrine glands, is associated in many cases with a severe undernutritional state, growth retardation and glucose intolerance. To obtain a better definition of the possible defects of insulin and insulin-like growth factor I (IGF-I) receptors, we investigated 125I-insulin and 125I-IGF-I binding to erythrocytes from patients with cystic fibrosis (n = 23) and controls (n = 13). Erythrocytes were isolated by Ficoll-Hypaque gradient centrifugation, and hormone binding was performed in cell suspensions of 3 x 10(9) cells/ml. Cystic fibrosis patients displayed a statistically significant 33% and 40% (p < 0.05) decrease of insulin and IGF-I binding, respectively, compared to controls. These alterations were due to an almost 50% reduction in the binding capacity of the high-affinity receptor compartment. Affinity constants were modified to a lesser extent, except for a two-fold decrease in K1 of the high-affinity compartment of insulin receptors. Interestingly, the decrease in insulin binding was proportional to the degree of growth failure. The statistical significance of hormone binding alterations was assessed in terms of the graphic distribution of individual affinity constants and binding capacity values. Although variable, 50 to 60% of cystic fibrosis patients displayed alterations in stoichiometric binding parameters located outside the area described by the 95% tolerance interval of controls. A major reduction in insulin and IGF-I binding in conditions of low and normal insulin and IGF-I plasma levels, respectively, as well as the correlation with the degree of growth failure in patients with cystic fibrosis, may contribute to an understanding of the pathogenesis of insulin resistance and glucose abnormalities in undernutritional states.
Diabetes Metab 1997 Dec
PMID:Decrease in insulin and insulin-like growth factor I (IGF-I) binding to erythrocytes from patients with cystic fibrosis. 949 57

Dogs fed a diet containing 30% galactose develop diabetes-like retinal capillary changes. As retinal capillary occlusion is commonly observed in diabetic retinopathy, neutrophil apoptosis and the interaction of neutrophils with retinal capillary endothelial cells were investigated. Neutrophils were isolated with Ficoll-Hypaque centrifugation from dogs fed a 30% galactose diet and dogs fed a normal, control diet containing 30% non-nutrient filler. Apoptosis of neutrophils was microscopically examined after incubation at 37 degrees C for 3 hours with either 100 U/mL tumor necrosis factor alpha (TNF-alpha), 2 microg/mL cycloheximide or 50 ng/mL phorbol 12-myristate 13-acetate (PMA). Neutrophil adhesion to dog retinal capillary endothelial cells was examined by counting the cells attached to the surface of endothelial cells after the incubation in the presence of either 100 U/mL TNF-alpha or 5 microg/mL lipopolysaccharides (LPS) at 37 degrees C for 3 hours. With all three stimulants TNF-alpha, cycloheximide and PMA, the rate of apoptosis was significantly lower for neutrophils isolated from galactose-fed dogs compared to control dogs fed a normal diet. Preincubation of neutrophils from control dogs in medium containing 30% galactose for 3 hours did not affect the rate of apoptosis. Neutrophil adhesion to retinal capillary endothelial cells induced by incubation in the presence of either 100 U/mL TNF-alpha or 5 microg/ml LPS was significantly higher with neutrophils isolated from galactose-fed dogs than those from control dogs. The data indicate that long-term galactose feeding is essential with development of various neutrophil dysfunctions. These neutrophil changes may contribute to the development of retinal microangiopathy associated with diabetes and galactosemia.
J Diabetes Complications
PMID:Neutrophils in galactose-fed dogs: suppressed apoptosis and increased adhesion to retinal capillary endothelial cells. 1050 75

Fractal dimension of pericellular membrane of monocytes was evaluated in diabetic patients and in control subjects. Monocytes were collected from normal healthy volunteers (n = 6) and from diabetic (type 1 and type 2) patients (n = 9). Monocytes from healthy volunteers were also stimulated in vitro with the ionophore A23187 or with the oligopeptide FMLP. Monocytes, obtained by Ficoll-Hypaque, were examined with a Philips 300 transmission electron microscope. The cell contour was extracted, resized to a standard dimension and converted to a single pixel outline. Box-counting method was then applied to determine the fractal dimension. Fractal dimensions of monocytes appeared statistically increased in diabetic patients (type 1 and type 2), compared with sex- and age-matched controls (p < 0.01, p < 0.01). The mechanism underlying the observed increased complexity of pericellular membrane may be explained by the in vivo activation of the circulating monocyte in diabetes. In effect, fractal analysis of stimulated in vitro monocytes showed a significant increase of complexity of pericellular membrane, compared with their controls (p < 0.001). Our approach was able to assess and quantitatively evaluate in diabetic patients morphological modifications of the monocyte linked to its activation, offering new parameters useful to follow the effects of therapeutical procedures.
 ...
PMID:Fractal analysis of monocytes in diabetes. 1689 41