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Biomedical subjects

M Cherian

Publications and source records attributed to M Cherian.

13 recordsLinked to original sources

Diabetes affects alpha-crystallin chaperone function.

In vitro glycation was previously shown to influence alpha-crystallin chaperone function. In the present study we show that this function is compromised in diabetes. The alpha H, alpha L and the total alpha fractions were isolated by gel permeation chromatography from the water-soluble protein of streptozotocin-diabetic as well as age-matched normal rats. Based on the beta L-crystallin thermal denaturation assay the chaperone function was significantly decreased in the diabetic rats.

Animals

Decreased molecular chaperone property of alpha-crystallins due to posttranslational modifications.

We studied the effect of oxidation, mixed disulfide formation and glycation of alpha-crystallins on their molecular chaperone property. The ability of alpha-crystallins to protect heat-induced denaturation and aggregation of beta L-crystallin was significantly diminished by these modifications. alpha-Crystallin from senile human lenses also showed significant loss of chaperone-like property. Age-dependent increase in posttranslationally modified alpha-crystallins is the likely cause for this change.

Adolescent

Effect of germanium-132 on galactose cataracts and glycation in rats.

Germanium compounds have been shown to be effective in preventing the formation of advanced glycation end-products and for reversible solubilization of glycated proteins. As protein glycation has been proposed to play a role in lens opacification, we initiated studies to evaluate the effects of 2-carboxyethyl germanium sesquioxide (germanium compound 132 or Ge-132) on galactose-induced cataractogenesis. For this study young Sprague-Dawley rats were fed a 50% galactose diet. One group of rats received topical saline and another group was administered Ge-132 in saline four times a day. The lenses were periodically examined with an ophthalmoscope and at desired intervals processed for light and scanning electron microscopy. Our observations, beginning at 3 days and continuing to 21 days of galactose feeding, exhibited the characteristic galactose-induced morphological alterations, which include the formation of vacuoles, cysts, membrane disruption and swelling of fibers and epithelial cells as well as disorganization of the bow in lenses of rats in both groups. However, in the majority of rats administered Ge-132 these alterations were delayed as compared to the lenses of rats administered saline. Our findings show that, although the initiation, progression and pattern of lens opacification in rats receiving saline and Ge-132 were similar, in the majority of lenses the progression and establishment of mature cataracts in the Ge-132 group of rats were delayed. Analysis of the water-soluble and water-insoluble lens-protein fractions for glycated proteins showed increased levels of the Amadori products and advanced glycation related fluorescent products in galactosemic rats treated with saline eye drops. In rats receiving the topical Ge-132 treatment the levels of these glycation products were substantially reduced to levels lower than control values. Prevention of glycation seems to be a mechanism by which cataract progression is delayed.

Animals

Comparison between endocardial and great vessel endothelial cells: morphology, growth, and prostaglandin release.

The release of vasoactive mediators by vascular (VEC) and endocardial endothelial cells (EEC) has not been directly compared. In this study, in vitro morphological and cell growth characteristics and the rate of prostanoid release were compared in cultured sheep endothelial cells from great vessels (VEC; pulmonary artery and aorta) and endocardium (EEC; right and left ventricles) harvested from the same animals. Morphologically, in flasks, VEC demonstrated the classic cobblestone pattern, whereas EEC developed numerous cytoplasmic interdigitations and overlaps. Rate of cell proliferation was greater for EEC than for VEC (P < 0.05): doubling time was shorter for EEC (34 +/- 3 h) than for VEC (45 +/- 5 h). Under static (no-flow) conditions, in response to arachidonic acid and calcium ionophore A-23187, the rate of prostacyclin (PGI2) and prostaglandin E2 release by VEC and EEC was not different. In contrast, in response to flow and acute hypoxia (O2 tension = 35 Torr), the rate of PGI2 release was greater in EEC than in VEC (P < 0.0001). After 2 h of perfusion, the rate of PGI2 release was 19-fold greater for EEC than for VEC during normoxia and 34-fold greater during hypoxia. Thus our study showed anatomic site of origin-dependent heterogeneity in prostanoid release between VEC and EEC. Endocardial endothelium is a greater source of PGI2 than great vessel endothelium; in vivo, endocardial endothelial PGI2 may inhibit local platelet aggregation and modulate downstream vascular tone.

Analysis of Variance

Site selectivity in the glycation of alpha A- and alpha B-crystallins by glucose.

We determined the site selectivity of glycation by glucose (glucosylation) in alpha A- and alpha B-crystallins using two independent approaches. HPLC purified 14C-glucose labeled chymotryptic peptides and affinity chromatography/HPLC purified fully glycated peptides were identified by FAB-MS. Lys 11 and 78 of alpha A-crystallin and Lys 90 and/or 92 of alpha B-crystallin were the fast reacting sites of glucosylation.

Animals

Lens epithelial cell density and histomorphological study in cataractous lenses.

Human epithelial cell density was determined from flat preparation of 195 cataractous lenses from 108 males and 87 females between 30 and 80 years of age. The mature cataracts had significantly lower cell counts than the other cataracts. Cell density was significantly higher in the females than in the males. Morphohistological study of the epithelia was focused on the following cataract types: (1) nuclear, (2) posterior subcapsular, (3) mature, (4) mixed, (5) hypermature, and (6) black. The major cataractous changes in all types involved vacuolization of the cytoplasm. The mature types of cataractous epithelia showed 56% superimposed cells; the epithelia in nuclear, posterior subcapsular, and black cataracts showed between 6% and 16%. In the hypermature cataracts, four of five tissues analyzed showed superimposed cells. The superimposed areas are probably the source of increased and altered cell activity. We propose that the metaplastic processes leading to posterior capsular opacification originate from these areas. The majority of nuclear and black cataracts were almost similar to the normal human lens epithelium with more or less uniform distribution of cells. Nucleus shrinkage (5 microns) was more evident in nuclear cataracts; in subcapsular cataracts most of the nuclei were large (average 9 microns diameter). Variation in morphological changes like vacuolization of cytoplasm and nuclei, pyknotic nuclei, and superimposed cells was more evident in the mixed type of cataracts.

Adult

Glutathione and glutathione-related enzymes in busulfan treated rat lens.

Glutathione (GSH) and GSH-related enzymes, glutathione reductase (GR), gamma-glutamyl cysteine synthetase (gamma-GCS), gamma-glutamyl transpeptidase (gamma-GTP), glutathione S-transferase (GST) and adenosine triphosphatase (ATPase) enzymes were analysed to study the effect of busulfan on the defence mechanisms of the lens. All these enzymes were found to increase significantly except GSH which showed only 7.9% increase as compared to controls in precataractous stage. These results affirm that busulfan is capable of evoking a response from the enzymes involved in the various pathways of GSH enabling the lens to prolong its clarity. The cataractous lenses showed significant decrease in all these parameters. Here, the impairment of the defense mechanism (GST, GR) and the total ATPase may be attributed to the cumulative action of the drug which can react with -SH groups of these enzymes, ultimately causing opacification.

Animals

Endoscopic diagnosis of small flat carcinoma of the colon. Report of three cases.

Most small carcinomas arise from polyps. Small lesions with cellular features of malignancy and early invasion, but with no histologic evidence of residual adenoma, are rare. Diagnosed by endoscopy, three such lesions are described. They were recognized as mucosal plaques, measuring between 6 and 8 mm in diameter. In each case, there was either synchronous or metachronous carcinoma elsewhere in the colon, as well as benign adenomatous polyps. Colonoscopic identification of such lesions allows inclusion of that bowel segment in any planned resection.

Adenocarcinoma

Cephalgic seizure.

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Adolescent