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Biomedical subjects

S Roy

Publications and source records attributed to S Roy.

At least 469 records · Page 26Linked to original sources
PubMed1994

Increased expression of basement membrane collagen in human diabetic retinopathy.

Basement membrane thickening is the most prominent and characteristic feature of early diabetic microangiopathy. Unknown is not only the causative process but also whether the thickening reflects increased synthesis of specific components. Because collagen type IV is uniquely present in basement membranes and represents their predominant structural element, we studied its expression in retinas obtained postmortem from five patients with 8 +/- 3 yr of diabetes and six nondiabetic controls. The collagen IV transcript proved to be rare in adult human retina and undetectable by Northern analysis. We thus identified a set of primers and conditions to detect the transcript by the reverse transcriptase polymerase chain reaction and to measure its level relative to an endogenous internal standard (beta-actin mRNA). In the diabetic patients the levels of collagen IV mRNA were increased twofold over levels in controls, whereas the actin mRNA levels were similar in the two groups. Hence, the collagen IV/actin ratio was 0.53 +/- 0.15 in diabetic samples and 0.24 +/- 0.09 in control samples (P = 0.004). These results indicate that diabetes induces a twofold increase in the expression of collagen IV by the cells that synthesize basement membranes in the adult retina (vascular cells). Insofar as high ambient glucose in vitro elicits the same effect, it may be proposed that basement membrane thickening in diabetes results from enhanced synthesis of specialized component molecules sustained by hyperglycemia.

Actins↗
PubMed1994

Renal Na(+)-phosphate cotransport in murine X-linked hypophosphatemic rickets. Molecular characterization.

The X-linked Hyp mouse is characterized by a specific defect in proximal tubular phosphate (Pi) reabsorption that is associated with a decrease in Vmax of the high affinity Na(+)-Pi cotransport system in the renal brush border membrane. To understand the mechanism for Vmax reduction, we examined the effect of the Hyp mutation on renal expression of Na(+)-Pi cotransporter mRNA and protein. Northern hybridization of renal RNA with a rat, renal-specific Na(+)-Pi cotransporter cDNA probe (NaPi-2) (Magagnin et al. 1993. Proc. Natl. Acad. Sci. USA. 90:5979-5983.) demonstrated a reduction in a 2.6-kb transcript in kidneys of Hyp mice relative to normal littermates (NaPi-2/beta-actin mRNA = 57 +/- 6% of normal in Hyp mice, n = 6, P < 0.01). Na(+)-Pi cotransport, but not Na(+)-sulfate cotransport, was approximately 50% lower in Xenopus oocytes injected with renal mRNA extracted from Hyp mice when compared with that from normal mice. Hybrid depletion experiments documented that the mRNA-dependent expression of Na(+)-Pi cotransport in oocytes was related to NaPi-2. Western analysis demonstrated that NaPi-2 protein is also significantly reduced in brush border membranes of Hyp mice when compared to normals. The present data demonstrate that the specific reduction in renal Na(+)-Pi cotransport in brush border membranes of Hyp mice can be ascribed to a proportionate decrease in the abundance of Na(+)-Pi cotransporter mRNA and protein.

Animals↗
PubMed1994

Increased renal 25-hydroxyvitamin D3-24-hydroxylase messenger ribonucleic acid and immunoreactive protein in phosphate-deprived Hyp mice: a mechanism for accelerated 1,25-dihydroxyvitamin D3 catabolism in X-linked hypophosphatemic rickets.

X-Linked Hyp mice exhibit rachitic bone disease, hypophosphatemia, impaired renal phosphate reabsorption, and abnormal regulation of renal 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] metabolism. We demonstrated that phosphate deprivation of Hyp mice, but not normal littermates, elicits a dramatic fall in serum 1,25-(OH)2D levels and an increase in renal 1,25-(OH)2D3 catabolism that can be ascribed to an increase in the activity of renal mitochondrial 25-hydroxyvitamin D3-24-hydroxylase (24-hydroxylase), the first enzyme in the C-24 oxidation pathway. The present study was undertaken to elucidate the mechanism for the increase in renal 24-hydroxylase activity in phosphate-deprived Hyp mice. Phosphate deprivation of Hyp mice resulted in a 3-fold increase in the maximum velocity for 24-hydroxylase (n = 5; P < 0.001) accompanied by an increase in 24-hydroxylase immunoreactive protein relative to the level of ornithine aminotransferase. Phosphate deprivation of Hyp mice also elicited a 3-fold increase in renal 24-hydroxylase mRNA abundance relative to that of beta-actin mRNA (n = 7; P < 0.001). The increase in 24-hydroxylase mRNA was specific to the kidney and was evident as early as 1 day of the low phosphate diet. Phosphate deprivation had no effect on renal 24-hydroxylase immunoreactive protein or mRNA in normal littermates. In contrast to the abnormal 24-hydroxylase response to dietary phosphate, Hyp mice exhibited an appropriate increase in renal 24-hydroxylase mRNA and catalytic activity in response to increasing doses of 1,25-(OH)2D3. The present results demonstrate that elevated renal 24-hydroxylase activity in phosphate-deprived Hyp mice can be ascribed to an increase in the abundance of 24-hydroxylase mRNA and protein and suggest that inappropriate regulation of 1,25-(OH)2D3 catabolism in Hyp mice occurs at the pretranslational level.

Animals↗
PubMed1994

Defects in carbohydrate metabolism in oral contraceptive users without apparent metabolic risk factors.

We performed oral glucose tolerance tests and frequently sampled iv glucose tolerance tests in a cross-sectional sample of women taking monophasic norgestrel containing oral contraceptives (OC). The goal of the study was to quantify the individual factors that determine glucose tolerance to assess responsibility for the reduced glucose tolerance associated with the use of OCs. Subjects were selected using stringent criteria to exclude confounding effects of ethnicity, adiposity, or conditions that may predispose subjects to metabolic disorders. Users of the low dose OC (Lo/Ovral and Nordette) and high dose OC (Ovral) were compared to controls, who were required to never have used OCs or to have discontinued OC use for at least 24 months. Oral glucose tolerance tests results confirmed the development of impaired glucose tolerance in both pill groups. Frequently sampled iv glucose tolerance test data were analyzed using the minimal model method to estimate parameters of insulin sensitivity, glucose effectiveness (SG), and beta-cell function. Lo/Ovral users had lower insulin sensitivity and SG compared to controls and inappropriately low beta-cell function in relation to the insulin resistance. Ovral users had metabolic parameters that were not different from controls. Based upon comparisons between normal and impaired glucose tolerant subjects combined with stepwise regression analysis, we conclude that Lo/Ovral use results in insulin and glucose resistance, which is not compensated by increased beta-cell function. The reduced glucose tolerance is due primarily to the defect in SG, and these OC users may place themselves at higher risk for the development of diabetes or cardiovascular disease. The reduced tolerance in Ovral users cannot be explained by the parameters measured in this study. We speculate that these latter subjects represent a special self-selected population in which tolerance is regulated by other factors. Ovral appears to be well tolerated by these women.

Adolescent↗
PubMed1994

Antigenicity and antigenic relatedness of the outer membrane proteins of Shigella species.

SDS-PAGE analysis of the outer membrane proteins (OMP) of Shigella dysenteriae, S. flexneri, S. boydii and S. sonnei showed similar profiles after isolation from Shigella species grown at 30, 37 and 42 degrees C. In S. dysenteriae there was a 25 and a 17 kD polypeptide at 37 degrees C only, compared with the other two temperatures. In all four Shigella spp the major protein band was around 34-38 kD. Antibodies raised in mice against formalinized bacteria gave a strong OMP specific response in both IgM and IgG classes, with IgG1 being the dominant subclass in all the species. Western blotting showed the major OMP to be the predominant antigen which was present in all the three temperatures tested. Cross-reactivity studies of the antigenic OMP of Shigella revealed that the major protein around 38 kD was related in the four species. Biochemical analysis of the partially purified major OMP indicated it to be porin.

Animals↗
PubMed1994

A quantitative microbiological study of bacterial vaginosis.

A quantitative microbial study of vaginal secretions from 100 women with bacterial vaginosis (BV) and 50 healthy women matched for age, was undertaken. This was aimed at comparing the bacterial flora colonising the vagina of sexually active asymptomatic women with those with BV and correlating bacterial counts with presence of symptoms. Of the total 475 bacteria isolated anaerobes were predominant among controls and among patients aerobes and anaerobes had equal prevalences. The increased viable counts of all anaerobes (> 10(7) cfu/g) were related with symptoms. Mobiluncus mulieris could be isolated from one patient and Chlamydia trachomatis antigen was absent in all samples tested. Bacteroides, G. vaginalis and Ureaplasma urealyticum were found to be the most commonly occurring group in women with BV. Lactobacillus, and probably Coryneforms have a protective role in health, preventing disease.

Adolescent↗
PubMed1994

Ventricular late potentials after thrombolysis.

High frequency low amplitude signals that prolong the terminal portion of the QRS complex in the electrocardiogram are termed late potentials (LPs). It has been established for quite some time that the presence of LPs after acute myocardial infarction (AMI) is associated with an increased risk of ventricular tachyarrythmias and sudden cardiac death (SCD), and vice versa. It is also known that thrombolytic therapy after AMI significantly decreased the incidence of ventricular tachyarrythmias and SCD. The object of this study was to find out whether thrombolysis in AMI decreased the incidence of LPs. Fifty two male patients of the age group 41-46 years with first anterior wall AMI were studied. Thirty of them presented within 6 hours of chest pain and were given intravenous streptokinase (IVSK) in addition to conventional therapy. The remaining 22 received conventional therapy but no thrombolysis. There was no significant difference in these two groups regarding age, CKMB, hypertension, diabetes, smoking, prior use of beta blockers, and ejection fraction. Eight out of the 30 patients receiving IVSK were positive for LPs as against 13 out of the 22 in the control group. This difference was statistically significant (p > 0.02 < 0.01). Thus thrombolysis in the early hours of anterior AMI diminishes the incidence of LPs.

Adult↗
PubMed1994

Evaluation of laboratory tests for diagnosis of chlamydial infections in conjunctival specimens.

We evaluated the chlamydial direct diagnostic tests and McCoy cell culture methods for detection of Chlamydia trachomatis in 234 conjunctival scrapings from 127 patients. Direct (rapid) diagnostic methods of Giemsa stain cytology, fluorescent antibody test (FAT) and immunoperoxidase (IPO) stain and McCoy cell culture isolation method using IPO staining and FAT for detection of C. trachomatis antigen were carried out. McCoy cell culture isolation using FAT antigen detection method was considered as the gold standard. The specificity of all the direct diagnostic tests were above 90 per cent but sensitivity of Giemsa cytology, FAT and IPO stain were 36, 54 and 53 per cent respectively showing that as direct diagnostic tests Giemsa stain cytology was inefficient and FAT and IPO were useful. Specificity and sensitivity of McCoy cell culture using IPO stain for detection C. trachomatis antigen were above 90 per cent and it is suggested that this test can be used as a routine diagnostic method.

Antigens, Bacterial↗
PubMed1994

Sepsis-induced release of interleukin-6 may activate the immediate-early gene program through a hypothalamic-hypophyseal mechanism.

BACKGROUND: The immediate-early gene c-fos has been implicated in transcriptional regulation after sepsis. We test the hypothesis that sepsis-induced central nervous system release of interleukin (IL)-6 regulates hepatic c-fos gene expression. METHODS: Using a stereotaxically placed intracerebral-ventricular (ICV) catheter in rats with and without hypophysectomy, we measured hepatic c-fos protein accumulation after treatment with either IL-6 or vehicle control. Using a rat cecal ligation and puncture (CLP) model, we studied the following groups: (1) sham-CLP, (2) CLP, (3) hypophysectomized sham-CLP, and (4) hypophysectomized CLP and measured hepatic c-fos mRNA. RESULTS: ICV IL-6 treatment increased hepatic c-fos protein in the IL-6-treated group compared with the vehicle-treated group, and hypophysectomy inhibited the ICV IL-6-mediated increase in c-fos protein. After peritoneal sepsis, CLP increased hepatic c-fos messenger RNA compared to either the sham-CLP or the hypophysectomized sham-CLP group, and hypophysectomy before CLP inhibited hepatic c-fos mRNA compared with the CLP group. CONCLUSIONS: ICV IL-6 results in an increase in hepatic fos protein that is mediated through a hypothalamic-hypophyseal mechanism. Peritoneal sepsis results in an increase in hepatic c-fos gene expression that may be, in part, mediated by central nervous system release of IL-6 through a hypothalamic-hypophyseal mechanism.

Animals↗