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Biomedical subjects

S Mehta

Publications and source records attributed to S Mehta.

At least 73 records · Page 4Linked to original sources
PubMed2001

Thyroid hormone profile in obese subjects--a clinical study.

Fifty obese subjects with body weight above 120% of the ideal weight for that height or body mass index greater than 27.8 kg/m2 in men or 27.3 kg/m2 in women were studied for thyroid hormone profile. Nearly three-fourths obese subjects had body mass index of 30-40 kg/m2. Eighty-six per cent subjects were clinically and biochemically euthyroid. Fourteen per cent of the subjects had hypothyroidism; out of them, 8% were clinically and biochemically hypothyroid while 6% were only biochemically hypothyroid. None of the hypothyroid subjects had morbid obesity (greater than 40 kg/m2 body mass index). Duration of obesity in hypothyroid subjects was less than 10 years in nearly three-fourths of cases.

Adult↗
PubMed2001

Arsenite activation of P13K/AKT cell survival pathway is mediated by p38 in cultured human keratinocytes.

BACKGROUND: Arsenic has been considered as a carcinogen. Recently the issue of arsenic in drinking water raised an unprecedented social concern on human health, and yet the molecular mechanisms through which arsenic induces cancer remain unknown. Activation of cell survival pathway leading to the activation of eNOS has been associated with various types of cancer. The objective of this study was to investigate the pathway leading to the activation of eNOS in response to arsenite using human keratinocytes. MATERIALS AND METHODS: Cultured keratinocytes (HaCat cells) were exposed to arsenite with or without pretreatment of various inhibitors. Western blot analysis was performed to determine the activation of p38, AKT, eNOS. EGFR tyrosine phosphorylation was detected by immunoprecipitation and Western blot analysis. pNPP assay was used to measure phosphatase activity in cell lysate. FACS analysis was performed for the determination of generation of reactive oxygen species. RESULTS: Arsenite induced the activation of AKT at both Ser473 and Thr308, and its downstream effector eNOS in cultured human keratinocytes. Arsenite also induced phosphorylation of p38. PI-3-kinase inhibitors, Wortmannin and LY294002 inhibited arsenite-induced phosphorylation of AKT and eNOS but had no effect on phosphorylation of p38. Interestingly, however, SB203580, a known p38 inhibitor, completely inhibited arsenite-induced phosphorylation of AKT and eNOS. Arsenite induced generation of reactive oxygen species and inactivated phosphatase activity, but did not activate EGF receptor tyrosine phosphorylation. CONCLUSIONS: Collectively, our data indicate that arsenite induces activation of AKT and eNOS, via PI-3-kinase and p38 pathway, likely bypassing the activation of EGF receptor in cultured human keratinocytes.

Arsenites↗
PubMed2000

The complete genomic sequence of a BLV strain from a Holstein cow from Argentina.

DNA was extracted from the peripheral blood of a seropositive, PCR-positive, BLV-infected Holstein cow (No. 38) from Argentina. The DNA was amplified via PCR with a series of overlapping primers encompassing the entire BLV proviral DNA. The amplified BLV ARG 38 DNA was cloned, sequenced, and compared phylogenetically to three other full-length BLV sequences. Characterization of its deduced proteins and its relationship to other members of the PTLV/BLV genus of retroviruses are discussed.

Amino Acid Sequence↗
PubMed2000

Differential requirement for classic and novel PKC isoforms in respiratory burst and phagocytosis in RAW 264.7 cells.

The binding of Ab (IgG)-opsonized particles by FcgammaRs on macrophages results in phagocytosis of the particles and generation of a respiratory burst. Both IgG-stimulated phagocytosis and respiratory burst involve activation of protein kinase C (PKC). However, the specific PKC isoforms required for these responses have yet to be identified. We have studied the involvement of PKC isoforms in IgG-mediated phagocytosis and respiratory burst in the mouse macrophage-like cell line, RAW 264.7. Like primary monocyte/macrophages, their IgG-mediated phagocytosis was calcium independent and diacylglycerol sensitive, consistent with novel PKC activation. Respiratory burst in these cells was Ca2+ dependent and inhibited by staurosporine and calphostin C as well as by the classic PKC-selective inhibitors Gö 6976 and CGP 41251, suggesting that classic PKC is required. In contrast, phagocytosis was blocked by general PKC inhibitors but not by the classic PKC-specific drugs. RAW 264.7 cells expressed PKCs alpha, betaI, delta, epsilon, and zeta. Subcellular fractionation demonstrated that PKCs alpha, delta, and epsilon translocate to membranes during phagocytosis. In Ca2+-depleted cells, only novel PKCs delta and epsilon increased in membranes, and the time course of their translocation was consistent with phagosome formation. Confocal microscopy of cells transfected with green fluorescent protein-conjugated PKC alpha or epsilon confirmed that these isoforms translocated to the forming phagosome in Ca-replete cells, but only PKC epsilon colocalized with phagosomes in Ca2+-depleted cells. Taken together, these results suggest that the classic PKC alpha mediates IgG-stimulated respiratory burst in macrophages, whereas the novel PKCs delta and/or epsilon are necessary for phagocytosis.

Animals↗
PubMed2000

Preparation of 1,5-disubstituted pyrrolidin-2-ones.

1,5-Disubstituted pyrrolidin-2-ones 18a-g, 19a-h, and 20a-f were synthesized in good to excellent yields via the nucleophilic substitution of 5-(benzotriazol-1-yl)-1-substituted-pyrrolidin-2-ones 9 with allylsilanes, organozinc reagents, and phosphorus compounds. Compounds 9 and 5-(benzotriazol-2-yl)-1-substituted-pyrrolidin-2-one isomers 10 are readily prepared in total 70-84% yields from 2, 5-dimethoxy-2,5-dihydrofuran (7), primary amines 8, and benzotriazole; 9 and 10 react identically with nucleophiles.

Drug Design↗
PubMed2000

Ready access to sialylated oligosaccharide donors.

[formula: see text] Numerous glycoconjugates contain the disaccharide Neu5Ac alpha (2-->3)DGalp. An efficient way to incorporate this disaccharide into synthetic glycoconjugates is to develop a disaccharide building block. This communication reports a chemoenzymatic route to such a building block which requires as few as four steps. Some examples using more chemical steps are also presented, which increase the flexibility. These disaccharide donors were used to prepare synthetic trisaccharides.

Carbohydrate Conformation↗
PubMed2000

Pulmonary microvascular changes during sepsis: evaluation using intravital videomicroscopy.

A variety of pulmonary microvascular changes occur during sepsis. These include abnormal vascular reactivity, leukocyte sequestration, and leakage of protein into the alveoli. Based on intravital videomicroscopy we have developed a method to directly assess in vivo the changes that occur in the pulmonary microcirculation in a rat model of sepsis. Male Sprague-Dawley rats were assigned to control or sepsis groups. Sepsis was induced by cecal ligation and perforation. Twenty four hours later, rats were anesthetized, mechanically ventilated, and their lung prepared for intravital videomicroscopy. A specially designed transparent thoracic window was inserted into the chest wall. The dependent surface of the lung was superfused with saline solution and visualized with an inverted microscope. Vascular contractility, to phenylephrine, (PE) and hypoxia of small (15-25 microm in diameter) and medium (40-50 microm) arterioles was examined. Leukocyte traffic in the pulmonary microcirculation was studied after in vivo labeling of leukocytes with Rhodamine and visualized with fluorescence microscopy. Leak of albumin into the alveolar space was measured with FITC-labeled albumin and fluorescence microscopy. Both small and medium sized pulmonary arterioles in septic animals exhibited attenuated vascular contractility to phenylephrine, but only medium-sized arterioles displayed hypocontractility to hypoxia. Further, in septic animals there was an increase in both the number of stationary leukocytes in the pulmonary microcirculation and an increase in alveolar capillary protein leak. We conclude: (1) direct visualization of the pulmonary microvascular pressor response to hypoxia and PE in the rat is possible using this technique, (2) similar to previous in vitro studies with larger vessels, pulmonary arterioles have an attenuated contractile response to PE and hypoxia in sepsis, and (3) there is an increase in both the number of stationary leukocytes and protein leak into the alveolus in the lungs of septic animals.

Animals↗
PubMed2000

Combined cytotoxic action of paclitaxel and ceramide against the human Tu138 head and neck squamous carcinoma cell line.

PURPOSE: Paclitaxel, a chemotherapeutic agent used in the treatment of recalcitrant ovarian and breast as well as other neoplasms, is being investigated for the treatment of squamous cell carcinoma of the head and neck. Our previous studies have demonstrated that exogenously added ceramide enhances apoptosis in paclitaxel-exposed human leukemic cells. In this study, we showed that exogenous ceramide augmented paclitaxel-induced apoptosis in Tu138 cells in vitro when added simultaneously in combination with the paclitaxel. METHODS: The combined cytotoxic effects of paclitaxel and ceramide exposure against Tu138 cells were assessed by an MTT dye assay, cell cycle analysis, TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay, and isobologram analysis for synergistic activity. RESULTS: The MTT dye assay results indicated augmentation of time- and concentration-dependent paclitaxel-mediated cell cytotoxicity by simultaneous ceramide treatment. Paclitaxel treatment of Tu138 cells also resulted in an accumulation of cells in the G2-M phase of the cell cycle. This paclitaxel-mediated G2-M phase accumulation decreased significantly with the addition of ceramide, indicating that combined paclitaxel/ceramide treatment resulted in the elimination of Tu138 cells from the S and/or G2-M phases of the cell cycle. Furthermore, ceramide enhancement of paclitaxel-mediated apoptosis was also detected by the TUNEL assay. CONCLUSION: Our results suggest that paclitaxel/ceramide combination therapy may be an attractive alternative to conventional methods of chemotherapy for head and neck cancer, and should be further explored.

Carcinoma, Squamous Cell↗
PubMed2000

Steroid hormone contraception and bone mineral density: a cross-sectional study in an international population. The WHO Study of Hormonal Contraception and Bone Health.

OBJECTIVE: To evaluate relationships between bone mineral density and use of steroid hormonal contraceptives. METHODS: This was a multicenter cross-sectional study in seven centers in three regions of the developing world from April 1994 to June 1997. Women 30-34 years old attending family planning clinics, with at least 24 months of lifetime use of combined oral contraceptives (OC), depot-medroxyprogesterone acetate (DMPA), or levonorgestrel implants, or no or only short-term (less than 6 months) use of steroid hormonal contraceptives, had bone mineral density (BMD) measured at the distal radius and the midshaft of the ulna using single-photon x-ray absorptiometry. RESULTS: In the study, 2474 women were examined. For OC use, adjusted mean BMD was significantly higher in short-term, current users compared with women who never used hormonal contraceptives. For DMPA and levonorgestrel implants, adjusted mean BMD was statistically significantly lower in short-term current users compared with those who never used hormonal contraceptives. For all three hormonal methods, there were no significant differences in BMD between past users of hormonal contraceptives and never users, even among those who had used the methods for 4 or more years. The magnitude of changes in BMD was small and less than one standard deviation (SD) from the mean of those who never used steroid contraceptives. CONCLUSION: This study suggests that hormonal contraceptive use by young adult women is associated with small changes in BMD that occur early after initiation of use and are reversible.

Adult↗
PubMed2000

Differential markers for regionalization.

OBJECTIVE: To examine the site of delivery for very low birth weight (VLBW) infants and infants with major congenital malformations (MCM) within an established system of perinatal regionalization. STUDY DESIGN: A retrospective study of site of delivery for VLBW infants and infants born with MCM (tracheoesophageal fistula/esophageal atresia, diaphragmatic hernia, or gastroschisis/omphalocele) from 1990 through 1995 in Ohio. RESULTS: A total of 59.8% of VLBW infants and 36.1% of MCM infants were born in a level III hospital. There was a significant trend toward a decrease in VLBW infants (p < 0.01) and an increase in MCM infants (p < 0.05) born in a level III hospital between 1990 and 1995. There were significant regional variations among the six perinatal regions in Ohio in the proportion of both VLBW and MCM infants born in a tertiary center. CONCLUSION: Using the traditional marker of VLBW to assess regionalization in one state, we found significant variation in site of delivery among the perinatal regions and over the time course of the study. The delivery of infants with MCM at level III centers may be an alternative measure of regionalization.

Congenital Abnormalities↗
PubMed2000

Prolonged cyclooxygenase-2 induction in neurons and glia following traumatic brain injury in the rat.

Cyclooxygenase-2 (COX2) is a primary inflammatory mediator that converts arachidonic acid into precursors of vasoactive prostaglandins, producing reactive oxygen species in the process. Under normal conditions COX2 is not detectable, except at low abundance in the brain. This study demonstrates a distinctive pattern of COX2 increases in the brain over time following traumatic brain injury (TBI). Quantitative lysate ribonuclease protection assays indicate acute and sustained increases in COX2 mRNA in two rat models of TBI. In the lateral fluid percussion model, COX2 mRNA is significantly elevated (>twofold, p < 0.05, Dunnett) at 1 day postinjury in the injured cortex and bilaterally in the hippocampus, compared to sham-injured controls. In the lateral cortical impact model (LCI), COX2 mRNA peaks around 6 h postinjury in the ipsilateral cerebral cortex (fivefold induction, p < 0.05, Dunnett) and in the ipsilateral and contralateral hippocampus (two- and six-fold induction, respectively, p < 0.05, Dunnett). Increases are sustained out to 3 days postinjury in the injured cortex in both models. Further analyses use the LCI model to evaluate COX2 induction. Immunoblot analyses confirm increased levels of COX2 protein in the cortex and hippocampus. Profound increases in COX2 protein are observed in the cortex at 1-3 days, that return to sham levels by 7 days postinjury (p < 0.05, Dunnett). The cellular pattern of COX2 induction following TBI has been characterized using immunohistochemistry. COX2-immunoreactivity (-ir) rises acutely (cell numbers and intensity) and remains elevated for several days following TBI. Increases in COX2-ir colocalize with neurons (MAP2-ir) and glia (GFAP-ir). Increases in COX2-ir are observed in cerebral cortex and hippocampus, ipsilateral and contralateral to injury as early as 2 h postinjury. Neurons in the ipsilateral parietal, perirhinal and piriform cortex become intensely COX2-ir from 2 h to at least 3 days postinjury. In agreement with the mRNA and immunoblot results, COX2-ir appears greatest in the contralateral hippocampus. Hippocampal COX2-ir progresses from the pyramidal cell layer of the CA1 and CA2 region at 2 h, to the CA3 pyramidal cells and dentate polymorphic and granule cell layers by 24 h postinjury. These increases are distinct from those observed following inflammatory challenge, and correspond to brain areas previously identified with the neurological and cognitive deficits associated with TBI. While COX2 induction following TBI may result in selective beneficial responses, chronic COX2 production may contribute to free radical mediated cellular damage, vascular dysfunction, and alterations in cellular metabolism. These may cause secondary injuries to the brain that promote neuropathology and worsen behavioral outcome.

Animals↗