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Biomedical subjects

S K Jain

Publications and source records attributed to S K Jain.

At least 73 records · Page 4Linked to original sources
PubMed2000

Overexpression of N-acetylglucosaminyltransferase III enhances the epidermal growth factor-induced phosphorylation of ERK in HeLaS3 cells by up-regulation of the internalization rate of the receptors.

N-Acetylglucosaminyltransferase III (GnT-III) is a key enzyme that inhibits the extension of N-glycans by introducing a bisecting N-acetylglucosamine residue. In this study we investigated the effect of GnT-III on epidermal growth factor (EGF) signaling in HeLaS3 cells. Although the binding of EGF to the epidermal growth factor receptor (EGFR) was decreased in GnT-III transfectants to a level of about 60% of control cells, the EGF-induced activation of extracellular signal-regulated kinase (ERK) in GnT-III transfectants was enhanced to approximately 1.4-fold that of the control cells. A binding analysis revealed that only low affinity binding of EGF was decreased in the GnT-III transfectants, whereas high affinity binding, which is considered to be responsible for the downstream signaling, was not altered. EGF-induced autophosphorylation and dimerization of the EGFR in the GnT-III transfectants were the same levels as found in the controls. The internalization rate of EGFR was, however, enhanced in the GnT-III transfectants as judged by the uptake of (125)I-EGF and Oregon Green-labeled EGF. When the EGFR internalization was delayed by dansylcadaverine, the up-regulation of ERK phosphorylation in GnT-III transfectants was completely suppressed to the same level as control cells. These results suggest that GnT-III overexpression in HeLaS3 cells resulted in an enhancement of EGF-induced ERK phosphorylation at least in part by the up-regulation of the endocytosis of EGFR.

Endocytosis↗
PubMed2000

Induction of hepatic antioxidants in freshwater catfish (Channa punctatus Bloch) is a biomarker of paper mill effluent exposure.

Enzymatic and non-enzymatic antioxidants serve as an important biological defense against environmental oxidative stress. Information on antioxidant defense in fish is meager despite that fish are constantly exposed to a myriad of environmental stress including the oxidants. This study, therefore, assesses the activities of antioxidant enzymes viz., glutathione peroxidase, catalase and glutathione S-transferase and the non-enzymatic antioxidants viz., glutathione and metallothionein in various tissues of freshwater fish Channa punctatus (Bloch), in response to short-term and long-term exposures to paper mill effluent. The fish were exposed to the effluent at a concentration of 1.0% (v/v) for 15, 30, 60 and 90 days. The exposure caused a time-dependent increase in glutathione level (P < 0.001), activities of glutathione peroxidase (P < 0.05 to P < 0.001), glutathione S-transferase (P < 0.001) and a marginal initial decrease in catalase activity in the liver (P < 0.01 to P < 0.001). Metallothionein was induced in liver after 60 days of exposure. Two isoforms of metallothionein were detected. Catalase activity also increased 60 days afterwards. Antioxidant pattern was different in gill and kidney showing that liver was more resistant to oxidative damage as compared to gills and kidney. Our results demonstrate a pollutant-induced adaptive response in fish. In addition, levels of enzymatic and non-enzymatic tissue antioxidants may serve as surrogate markers of exposure to oxidant pollutants in fish.

Animals↗
PubMed2000

Effect of LDL+VLDL oxidizability and hyperglycemia on blood cholesterol, phospholipid and triglyceride levels in type-I diabetic patients.

Oxidative modification of low-density lipoproteins has been implicated in impaired lipid metabolism and its deposition in the arterial wall, and atherosclerosis. This study was carried out to determine the relationship between the in vitro oxidizability of low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) and the cholesterol, phospholipid and triglyceride (TG) levels in the blood of Type-I diabetic patients. LDL+VLDL was isolated using a micro-affinity column from serum of diabetic patients (n = 34) and age-matched normal individuals (n = 22). The oxidative susceptibility of LDL+VLDL was determined by treatment with 25 microM CuCl(2) for 1.5 h. The levels of total-, LDL-, and HDL-cholesterol, phospholipids and triglycerides, as well as glycated hemoglobin (HbA(t)), were measured in the blood using standard methods. The diabetics had significantly higher levels of triglycerides and phospholipids, but cholesterol levels were similar between Type-I diabetics and age-matched normals. However, among diabetics, there was a significant correlation between the in vitro oxidation of LDL+VLDL at 1.5 h and total cholesterol (r = 0.49, P<0.002), and LDL cholesterol (r = 0.54, P<0.001) and TG (r = 0.34, P<0.05) levels. The level of in vitro oxidizability of LDL+VLDL did not have any correlation with HDL-cholesterol or phospholipid levels. The level of glycemic control (HbA(1)) did not have any correlation with levels of LDL- or HDL-cholesterol or triglycerides, but was significantly correlated with phospholipid levels (r = 0.48, P<0.005). This study suggests that the levels of LDL-cholesterol and triglycerides in the blood are directly related to the degree of in vitro oxidative susceptibility of low-density lipoproteins in Type-1 diabetic patients.

Adolescent↗
PubMed2000

Lipoic acid decreases lipid peroxidation and protein glycosylation and increases (Na(+) + K(+))- and Ca(++)-ATPase activities in high glucose-treated human erythrocytes.

Lipoic acid supplementation has been found to be beneficial in preventing neurovascular abnormalities in diabetic neuropathy. Insufficient (Na(+) + K(+))-ATPase activity has been suggested as a contributing factor in the development of diabetic neuropathy. This study was undertaken to test the hypothesis that lipoic acid reduces lipid peroxidation and glycosylation and can increase the (Na(+) + K(+))- and Ca(++)-ATPase activities in high glucose-exposed red blood cells (RBC). Washed normal human RBC were treated with normal (6 mM) and high glucose concentrations (45 mM) with 0-0.2 mM lipoic acid (mixture of S and R sterioisomers) in a shaking water bath at 37 degrees C for 24 h. There was a significant stimulation of glucose consumption by RBC in the presence of lipoic acid both in normal and high glucose-treated RBC. Lipoic acid significantly lowered the level of glycated hemoglobin (GHb) and lipid peroxidation in RBC exposed to high glucose concentrations. High glucose treatment significantly lowered the activities of (Na(+) + K(+))- and Ca(++)-ATPases of RBC membranes. Lipoic acid addition significantly blocked the reduction in activities of (Na(+) + K(+))- and Ca(++)-ATPases in high glucose- treated RBC. There were no differences in lipid peroxidation, GHb and (Na(+) + K(+))- and Ca(++)-ATPase activity levels in normal glucose-treated RBC with and without lipoic acid. Thus, lipoic acid can lower lipid peroxidation and protein glycosylation, and increase (Na(+) + K(+))- and Ca(++)-ATPase activities in high-glucose exposed RBC, which provides a potential mechanism by which lipoic acid may delay or inhibit the development of neuropathy in diabetes.

Adenosine Triphosphatases↗
PubMed2000

Evidence for the induction of apoptosis by endosulfan in a human T-cell leukemic line.

Several organochlorinated pesticides including DDT, PCBs and dieldrin have been reported to cause immune suppression and increase susceptibility to infection in animals. Often this manifestation is accompanied by atrophy of major lymphoid organs. It has been suggested that increased apoptotic cell death leading to altered T-B cell ratios, and loss of regulatory cells in critical numbers leads to perturbations in immune function. The major objective of our study was to define the mechanism by which endosulfan, an organochlorinated pesticide, induces human T-cell death using Jurkat, a human T-cell leukemic cell line, as an in vitro model. We exposed Jurkat cells to varying concentrations of endosulfan for 0-48 h and analyzed biochemical and molecular features characteristic of T-cell apoptosis. Endosulfan lowered cell viability and inhibited cell growth in a dose- and time-dependent manner. DAPI staining was used to enumerate apoptotic cells and we observed that endosulfan at 10-200 microM induced a significant percentage of cells to undergo apoptotic cell death. At 48 h, more than 90% cells were apoptotic with 50 microM of endosulfan. We confirmed these observations using both DNA fragmentation and annexin-V binding assays. It is now widely being accepted that mitochondria undergo major changes early during the apoptotic process. We examined mitochondrial transmembrane potential (deltapsim) in endosulfan treated cells to understand the role of the mitochondria in T-cell apoptosis. Within 30 min of chemical exposure, a significant percentage of cells exhibited a decreased incorporation of DiOC6(3), a cationic lipophilic dye into mitochondria indicating the disruption of deltapsim. This drop in deltapsim was both dose- and time-dependent and correlated well with other parameters of apoptosis. We also examined whether this occurred by the down regulation of bcl-2 protein expression that is likely to increase the susceptibility of Jurkat cells to endosulfan toxicity. Paradoxically, the intracellular expression of bcl-2 protein was elevated in a dose dependent manner suggesting endosulfan-induced apoptosis occurred by a non-bcl-2 pathway. Based on these data, as well as those reported elsewhere, we propose the following sequence of events to account for T-cell apoptosis induced by endosulfan: uncoupling of oxidative phosphorylation --> excess ROS production --> GSH depletion --> oxidative stress --> disruption of deltapsim --> release of cytochrome C and other apoptosis related proteins to cytosol --> apoptosis. This study reports for the first time that endosulfan can induce apoptosis in a human T-cell leukemic cell line which may have direct relevance to loss of T cells and thymocytes in vivo. Furthermore, our data strongly support a role of mitochondrial dysfunction and oxidative stress in endosulfan toxicity.

Annexin A5↗
PubMed2000

Inactivation of wild-type BCR/ABL tyrosine kinase in hematopoietic cells by mild hyperthermia.

Temperature-sensitive mutants of BCR/ABL tyrosine kinase have been extensively used to study the mechanisms of cell transformation and signal transduction. However, little is known about the effect of temperature on the activity of wild-type BCR/ABL gene product. In this study, we demonstrate that in vivo tyrosine kinase activity of p210, p190 BCR/ABL and v-abl are temperature-sensitive when expressed in hematopoietic cells and decline when temperature is raised 2 degrees C above normal range. In vitro tyrosine kinase activities of purified recombinant Abl and immunoprecipitated p210 BCR/ABL were also sensitive to increased temperature. Tyrosine phosphorylation of cellular proteins was markedly reduced in BCR/ABL transformed cells after 16 h at 39 degrees C, whereas the expression of BCR/ABL was unchanged. Temperature-induced downregulation of BCR/ABL kinase activity was reversible when cells were shifted back to 37 degrees C. The downregulation of Abl tyrosine kinase activity was not influenced by mutation or deletion of SH2 or SH3 domains or mutation of the GRB2 binding site. No increase in functional activity or expression of protein-tyrosine phosphatases, PTP-1B, SH-PTP1 or SH-PTP2 was detected in cells grown at 39 degrees C. Temperature-induced downregulation in tyrosine kinase activity correlated with decline in phosphotyrosine-associated PI 3-kinase whereas there was no change in growth factor independence of transformed hematopoietic cells. In conclusion, Abl tyrosine kinase has intrinsic sensitivity to temperature and BCR/ABL expressed in hematopoietic cells is downregulated by increasing temperature 2 degrees C. These observations provide a unique opportunity to identify cellular factor(s) which regulate BCR/ABL kinase in vivo and suggests possible novel treatment of CML by a mild hyperthermia.

3T3 Cells↗
PubMed2000

Pharmacokinetics and urinary excretion of sulphadimidine in buffalo calves.

Pharmacokinetics and urinary excretion of sulphadimidine (SDI) were determined in buffalo calves following single oral administration (150 mg/kg). The plasma levels of free sulphadimidine were above minimum effective therapeutic concentration (> 40 micrograms/ml) between 4 and 12 h and the N4-acetylated form of the drug was in the range of 7.2-19.3%. Kinetic evaluation of plasma levels was performed using a two-compartment open model. The absorption and elimination half-lives of SDI were 3.01 and 11.94 h, respectively. Based on this study, an optimal dosage regimen of sulphadimidine in buffalo calves would be 100 mg/kg, followed by 50 mg/kg at 12 h intervals. Sulphadimidine was mainly excreted in the urine as free amine. The percentage of N4-acetyl sulphadimidine in urine was comparatively higher than in plasma.

Animals↗
PubMed2000

Pigtail stents: an alternative in the treatment of difficult bile duct stones.

BACKGROUND: When bile duct stones cannot be removed after sphincterotomy by balloon or basket extraction, stent placement can serve as a bridge to additional procedures. Biliary stents may also fragment large stones, allowing them to pass spontaneously or making them easier to extract at a later time. METHODS: Twenty patients with difficult to extract bile duct stones were prospectively studied. The patients underwent ERCP and placement of a 7F double-pigtail stent in the bile duct for 6 months. RESULTS: In seven patients (35%), repeat ERCP revealed no stones in the duct. Four patients (20%) had small stone fragments that were easily extracted with a balloon. Six patients (30%) continued to have large stones at repeat ERCP; two of these patients eventually underwent surgery, the duct was cleared in three with mechanical lithotripsy, and one had long-term stenting. Three patients (15%) did not undergo repeat ERCP and were therefore treated with long-term stent placement. CONCLUSIONS: This study suggests that placement of a pigtail biliary stent is a safe and effective alternative in the management of bile duct stones that resist extraction if lithotripsy is not available. After 6 months of stent placement, stones may pass or become easier to remove in a significant proportion of patients.

Adult↗
PubMed2000

Self-assembled carbohydrate-stabilized ceramic nanoparticles for the parenteral delivery of insulin.

The insulin-bearing aquasomes were fabricated by first preparing the nanosize calcium phosphate dihydrate core. The calcium phosphate dihydrate core was prepared by colloidal precipitation and sonication of disodium hydrogen phosphate solution and calcium chloride solution at low temperature. This core was coated with cellobiose, pyridoxal-5-phosphate, or trehalose under sonication and was further loaded with the drug at low temperature by a partial adsorption mechanism. The prepared systems were characterized for size, shape, size distribution, drug loading efficiency, and in vivo performance. The in vivo performance of the formulated aquasome was compared with standard porcine insulin solution, and better results were observed compared to insulin solution.

Animals↗
PubMed2000

Vitamin E supplementation restores glutathione and malondialdehyde to normal concentrations in erythrocytes of type 1 diabetic children.

OBJECTIVE: This study examined the relationship between cellular glutathione and vitamin E concentrations and the effect of vitamin E (alpha-tocopherol) supplementation on glutathione and lipid peroxidation product concentrations in the erythrocytes of type 1 diabetic patients. RESEARCH DESIGN AND METHODS: We obtained written informed consent to participate in this study from diabetic patients (n = 29) and their age-matched nondiabetic siblings (n = 21) according to the guidelines of the Institutional Review Board on Human Experimentation. Diabetic patients were supplemented with a DL-alpha-tocopherol (vitamin E) capsule (100 IU/orally) or placebo for 3 months in a double-blind clinical trial. Fasting blood samples were collected from each diabetic patient before the start of and after the 3 months of vitamin E or placebo supplementation. Glutathione, malondialdehyde (which is a product of lipid peroxidation), and alpha-tocopherol were determined using high-performance liquid chromatography A total of 5 diabetic patients were excluded after randomization from the data analyses. Data were analyzed statistically using a paired Students t test to compare 12 diabetic patients taking vitamin E with 12 diabetic patients receiving placebo supplementation and to compare diabetic patients with healthy nondiabetic subjects. RESULTS: Erythrocytes of diabetic patients had 21% higher (P<0.001) malondialdehyde and 15% lower (P<0.05) glutathione concentrations than healthy subjects. Vitamin E in erythrocytes had a significant correlation with the glutathione concentrations in the erythrocytes (r = 0.46, P<0.02). Vitamin E supplementation increased glutathione concentrations by 9% (P<0.01) and lowered concentrations of malondialdehyde by 23% (P<0.001) and of HbA1c by 16% (P<0.02) in erythrocytes of diabetic patients. No differences were evident in these parameters before versus after placebo supplementation. CONCLUSIONS: Glutathione level is significantly related to vitamin E level, and supplementation with vitamin E (100 IU/day) significantly increases glutathione and lowers lipid peroxidation and HbA1c concentrations in the erythrocytes of type 1 diabetic patients.

Child↗
PubMed2000

Patterns of prescriptions and drug use in two tertiary hospitals in Delhi.

The study was carried out to assess prescribing trends in outpatients at Dr. R.P. Centre for Ophthalmic Sciences (RPC) and other OPD's of All India Institute of Medical Sciences (AIIMS) and Safdarjung hospitals, two premier hospitals in Delhi. Prescriptions of 500 patients were audited and analysed under heads of average number of drugs per patient, percentages of drugs prescribed by generic name, antibiotics, injections, drugs from WHO recommended essential drug list, availability of drugs etc. using WHO basic drug indicators. Prescription analysis showed that 75 to 95% drugs were prescribed from essential drug list. The average number of drugs per prescription was 1.42 to 4.07. Percentage of antibiotics prescribed varied from 14.39% to 22.28%. The use of injections was from nil to 4.4%. Availability of drugs was however, not satisfactory. Though maximum drugs were prescribed from essential drug list, the results indicate that there is a considerable scope for improving prescribing habits according to rational drug use and to provide a feed back to hospital authority for making maximum number of drugs available to the patients.

Cost-Benefit Analysis↗
PubMed1999

Role of PI 3-kinase in angiopoietin-1-mediated migration and attachment-dependent survival of endothelial cells.

Angiopoietin-1 is a unique growth factor which induces Tie2 receptor autophosphorylation and interaction with signal transduction molecules, GRB2 and p85 subunit of PI 3-kinase, but no detectable mitogenic response. Here we show that PI 3-kinase-dependent activation of Akt and attachment to extracellular matrix are required for angiopoietin-1-mediated endothelial cell survival. Apoptosis of growth factor-deprived cells grown in monolayer was decreased by angiopoietin-1 and correlated with Akt activation. In contrast, angiopoietin-1, bFGF or VEGF failed to protect cells in suspension culture. Ceramide, an intermediate of several apoptotic pathways, interferes with growth factor-mediated Akt activation. Ceramide induced endothelial cell death and abolished angiopoietin-1-mediated activation of Akt and the effect on cell survival. In addition, we found that PI 3-kinase activity is necessary for migration of endothelial cells in response to Angiopoietin-1. A transient activation of MAPK/ERKs was also detected within 10 min after stimulation with angiopoietin-1. In contrast to VEGF-mediated biological effects, inhibition of MAPK/ERKs by PD98059 in endothelial cells did not affect angiopoietin-1 mediated survival or migration. These findings indicate significant differences in intracellular signaling between VEGF and angiopoietin-1 and that PI 3-kinase lipid products are key mediators of the biological effects of angiopoietin-1.

Angiopoietin-1↗
PubMed1999

Photo-oxidative stress down-modulates the activity of nuclear factor-kappaB via involvement of caspase-1, leading to apoptosis of photoreceptor cells.

The mechanisms of photoreceptor cell death via apoptosis, in retinal dystrophies, are largely not understood. In the present report we show that visible light exposure of mouse cultured 661W photoreceptor cells at 4.5 milliwatt/cm2 caused a significant increase in oxidative damage of 661W cells, leading to apoptosis of these cells. These cells show constitutive expression of nuclear factor-kappaB (NF-kappaB), and light exposure of photoreceptor cells results in lowering of NF-kappaB levels in both the nuclear and cytosolic fractions in a time-dependent manner. Immunoblot analysis of IkappaBalpha and p50, and p65 (RelA) subunits of NF-kappaB, suggested that photo-oxidative stress results in their depletion. Immunocytochemical studies using antibody to RelA subunit of NF-kappaB further revealed the presence of this subunit constitutively both in the nucleus and cytoplasm of the 661W cells. Upon exposure to photo-oxidative stress, a depletion of the cytoplasmic and nuclear RelA subunit was observed. The depletion of NF-kappaB appears to be mediated through involvement of caspase-1. Furthermore, transfection of these cells with a dominant negative mutant IkappaBalpha greatly enhanced the kinetics of down modulation of NF-kappaB, resulting in a faster photo-oxidative stress-induced apoptosis. Taken together, these studies show that the presence of NF-kappaB RelA subunit in the nucleus is essential for protection of photoreceptor cells against apoptosis mediated by an oxidative pathway.

Animals↗
PubMed1999

Effect of vitamin E and N-acetylcysteine on phosphatidylserine externalization and induction of coagulation by high-glucose-treated human erythrocytes.

This study examines the effect of high glucose levels on the markers of oxidative stress, phosphatidylserine (PS) externalization, and induction of coagulation by high-glucose-treated red blood cells (RBCs). Washed normal RBCs were suspended to 15% hematocrit in phosphate-buffered saline and incubated with different concentrations of glucose for 24 hours in a shaking water bath at 37 degrees C. This treatment caused depletion of vitamin E and accumulation of vitamin E-quinone and malondialdehyde ([MDA] an end product of lipid peroxidation), externalization of PS in the membrane bilayer, and induction of coagulation by RBCs. Pretreatment of RBCs with N-acetylcysteine (NAC) and vitamin E reduced membrane lipid peroxidation, PS externalization, and the tendency of high-glucose-treated RBCs to clot plasma. This study provides further evidence for the increased oxidative stress in RBCs exposed to high glucose levels. In addition, it suggests a role for membrane lipid peroxidation in the PS externalization in the membrane bilayer and in the induction of clotting by RBCs exposed to hyperglycemia. It also suggests that certain antioxidants can decrease cellular damage and restore certain cellular functions in diabetes.

Acetylcysteine↗
PubMed1999

Protective role of zeolite on short- and long-term lead toxicity in the teleost fish Heteropneustes fossilis.

The high ion-exchange capacity of zeolite (sodium aluminium silicate) enhances the removal of lead from water, thus decreasing its availability to fish. Zeolites are very important in the field of environmental preservation due to the low cost and ecological compatibility. Zeolites can adsorb metallic ions by cation exchange reactions. Continuous exposure of the teleost fish Heteropneustes fossilis to sublethal concentrations of lead nitrate in water solution for short (35 days) and long (120 days) periods decreased both the soluble protein, RNA and glycogen contents in the liver and the body weight, but increased the cholesterol content. The presence of zeolite in the exposure solution decreased all of the adverse effects. In fish exposed to zeolite as feed additive, all the parameters improved in comparison to control fish, indicating that zeolites can be used safely in biological systems.

Adsorption↗
PubMed1999

Pleuro pulmonary infection with Salmonella group E.

A patient was admitted with a history of cough, shortness of breath and fever. After investigations, he was found to have a left-sided pneumonia with pleural effusion. Culture of the patient's sputum, pleural fluid and blood revealed Salmonella senftenberg. The patient was started on antibiotics according to the sensitivity report and responded to therapy. The past history revealed attempt at suicide by the intake of corrosive acid, which caused an esophageal stricture. The leak of gastric contents into the mediastinum lead to the infection of the pleural cavity and pneumonia.

Adult↗
PubMed1999

Protein and lipid oxidation of banked human erythrocytes: role of glutathione.

In banked human erythrocytes (RBCs), biochemical and functional changes are accompanied with vesiculation and reduced in vivo survival. We hypothesized that some of these changes might have resulted from oxidative modification of membrane lipids, proteins, or both as a result of atrophy of the antioxidant defense system(s). In banked RBCs, we observed a time-dependent increase in protein clustering, especially band 3; carbonyl modification of band 4.1; and malondialdehyde, a lipid peroxidation product. Examination of the antioxidative defense system showed a time-dependent decline in glutathione (GSH) concentration and glutathione-peroxidase (GSH-PX) activity, with a concomitant increase in extracellular GSH, cysteine, and homocysteine, and unchanged catalase activity. When subjected to acute oxidant stress by exposure to ferric/ascorbic acid or tert-butylhydroperoxide (tert-BHT), catalase activity showed a steeper decline compared with GSH-PX. The results demonstrate that GSH and GSH-PX appear to provide the primary antioxidant defense in stored RBCs, and their decline, concurrent with an increase in oxidative modifications of membrane lipids and proteins, may destabilize the membrane skeleton, thereby compromising RBC survival.

Antioxidants↗