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S Kumar

Publications and source records attributed to S Kumar.

At least 1,207 records · Page 67Linked to original sources
PubMed1995

Inhibition of apoptosis by the expression of antisense Nedd2.

Nedd2 belongs to a family of mammalian cysteine proteases which share similarity with the Caenorhabditis elegans cell death protein, Ced-3. Overexpression of Nedd2 has been shown to induce apoptosis in mammalian cells but in the absence of a specific known inhibitor, it remains to be seen whether this represents cytotoxic effects of the Nedd2 protease or the specific activation of an apoptotic pathway. The present work shows that the factor-dependent cell line FDC-P1 expressing mouse antisense Nedd2 mRNA, exhibits significant inhibition of cell death upon removal of the cytokines, thus providing evidence for a direct role of Nedd2 in mediating apoptosis.

Animals↗
PubMed1995

Human thioredoxin reductase directly reduces lipid hydroperoxides by NADPH and selenocystine strongly stimulates the reaction via catalytically generated selenols.

Human placenta thioredoxin reductase (HP-TR) in the presence of NADPH-catalyzed reduction of (15S)-hydroperoxy-(5Z),(8Z),11(Z),13(E)-eicosatetraenoic acid ((15S)-HPETE) into the corresponding alcohol ((15S)-HETE). Incubation of 50 nM HP-TR and 0.5 mM NADPH with 300 microM 15-HPETE for 5 min resulted in formation of 16.5 microM 15-HETE. After 60 min, 74.7 microM 15-HPETE was reduced. The rate of the reduction of 15-HPETE by the HP-TR/NADPH peroxidase system was increased 8-fold by the presence of 2.5 microM selenocystine, a diselenide amino acid. In this case, 15-HPETE was catalytically reduced by the selenol amino acid, selenocysteine, generated from the diselenide by the HP-TR/NADPH system. To a smaller extent, selenodiglutathione or human thioredoxin also potentiated the reduction of 15-HPETE by HP-TR. Hydrogen peroxide and 15-HPETE were reduced at approximately the same rate by HP-TR, thioredoxin, and selenocystine. In contrast, t-butyl hydroperoxide was reduced at a 10-fold lower rate. Our data suggest two novel pathways for the reduction and detoxification of lipid hydroperoxides, hydrogen peroxide, and organic hydroperoxides, i.e. the human thioredoxin reductase-dependent pathway and a coupled reduction in the presence of selenols or selenide resulting from the reduction of selenocystine or selenodiglutathione.

Catalysis↗
PubMed1995

Molecular attributes of bovine aortic endothelial cell heparan sulfate.

Heparan sulfate (HS) secreted into the medium of bovine aortic endothelial cell (BAEC) cultures was subjected to chemical and enzymatic degradation followed by analysis using gel-filtration and ion-exchange chromatography. Treatment with HNO2 showed that 41% of the disaccharides were N-sulfated. Degradation by Heparin lyases I (Hep I) showed that 8-9% of the disaccharides contained IdoA(2S) residues. Heparin lyase III (Hep III) degradation produced mainly disaccharides with 67% of the molecules glycosidic linkages susceptible to cleavage. Further degradation of Hep III-resistant fragments with Hep I showed that IdoA(2S) residues were predominantly positioned centrally within the repeating GlcNSO3(+/- 6S)alpha 1-4IdoA containing domains. Digestion with a mixture of Heparin lyases I, II and III degraded the molecule almost entirely to disaccharides, with small amounts of tetrasaccharides containing resistant linkages, suggesting the presence of 3-O sulfated GlcNSO3. Further analysis of the disaccharide products by ion-exchange chromatography and comparison with the data from single enzymatic digestion, allowed an estimate of the disaccharide composition to be made. The results suggest an ordered arrangement of structural domains; however, variations in the structure of these domains results in a heterogeneous population of HS chains. It is suggested that biosynthetic differences in HS structure may act as a regulator of bFGF induced cellular responses.

Animals↗
PubMed1995

Iodine-123 metaiodobenzylguanidine scintigraphic assessment of the transplanted human heart: evidence for late reinnervation.

OBJECTIVES: This study attempted to determine whether cardiac sympathetic reinnervation occurs late after orthotopic heart transplantation. BACKGROUND: Metaiodobenzylguanidine (MIBG) is taken up by myocardial sympathetic nerves. Iodine-123 (I-123) MIBG cardiac uptake reflects intact myocardial sympathetic innervation of the heart. Cardiac transplant recipients do not demonstrate I-123 MIBG cardiac uptake when studied < 6 months from transplantation. However, physiologic and biochemical studies suggest that sympathetic reinnervation of the heart can occur > 1 year after transplantation. METHODS: We performed serial cardiac I-123 MIBG imaging in 23 cardiac transplant recipients early (< or = 1 year) and late (> 1 year) after operation. In 16 subjects transmyocardial norepinephrine release was measured late after transplantation. RESULTS: No subject had visible I-123 MIBG uptake on imaging < 1 year after transplantation. However, 11 (48%) of 23 subjects developed visible cardiac I-123 MIBG uptake 1 to 2 years after transplantation. Only 3 (25%) of 12 subjects with a pretransplantation diagnosis of idiopathic cardiomyopathy demonstrated I-123 MIBG uptake compared with 8 (73%) of 11 with a pretransplantation diagnosis of ischemic or rheumatic heart disease (p = 0.04). All 10 subjects with a net myocardial release of norepinephrine had cardiac I-123 MIBG uptake; all 6 subjects without a net release of norepinephrine had no cardiac I-123 MIBG uptake. CONCLUSIONS: Sympathetic reinnervation of the transplanted human heart can occur > 1 year after operation, as assessed by I-123 MIBG imaging and the transmyocardial release of norepinephrine. Reinnervation is less likely to occur in patients with a pretransplantation diagnosis of idiopathic cardiomyopathy than in those with other etiologies of congestive heart failure.

3-Iodobenzylguanidine↗
PubMed1995

The role of hyaluronan in tumour neovascularization (review).

Tumour growth and metastasis are totally dependant upon neovascularization. The target cell for tumour neovascularization is the blood-vessel endothelial cell, and specific angiogenic molecules produced or induced by the tumour are believed to initiate the process. In this report, we review one of these angiogenic molecules, the glycosaminoglycan hyaluronan (HA), which appears to have differing roles in neovascularization depending on its molecular mass. High-molecular-mass HA is anti-angiogenic whereas oligosaccharides of HA, of specific size, actively stimulate endothelial-cell proliferation and migration, 2 of the key events associated with neovascularization, and induce angiogenesis in vivo. We provide details of the action of HA oligosaccharides on endothelial cells, from binding to cell-surface receptors, through activation of signal transduction pathways and gene expression to protein synthesis, cell proliferation and cell migration. We also suggest a model to account for HA of differing molecular mass being present, at different locations, within a single tumour and how this HA aids both general tumour growth and tumour metastasis.

Cell Division↗
PubMed1995

Nucleotide sequence and peptide motifs of mouse uromodulin (Tamm-Horsfall protein)--the most abundant protein in mammalian urine.

The mouse uromodulin cDNA sequence was sequenced. The predicted peptide sequence is 642 amino acids long and contains several modular components including four epidermal growth factor like repeats, one betaglycan-like domain (ZP domain), and a consensus sequence for attachment of a glycosyl-phosphatidyl-inositol anchor. An arginine-glycine-aspartate tripeptide reported for rat and human sequence is absent in the mouse. There are several potential sites for post-translational modification.

Amino Acid Sequence↗
PubMed1995

Human trunk strength profile in flexion and extension.

STUDY DESIGN: Isometric and isokinetic trunk flexion-extension strengths were studied among 73 subjects (41 males and 32 females) and 10 patients (9 males and 1 female). The isometric strengths were measured in four postures of trunk flexion. The isokinetic trunk strengths were measured through the range of these postures. OBJECTIVES: The study had two objectives: to develop a database for isometric flexion-extension strength at different levels of trunk flexion and isokinetic strength at corresponding angles and to determine the decrement in strength characteristics among patients of idiopathic low back pain. SUMMARY OF BACKGROUND DATA: Though flexion-extension strength among normal subjects and patients has been studied, its variation due to standardized postural change has not been reported extensively. The influence of postural deviation on flexion-extension ratios are also largely unknown. METHODS: To achieve the objectives of the study, a device flexion-extension-lateral flexion tester (FELT) was designed and fabricated. The male and female subjects performed isometric flexion and extension at 0 degree, 20 degrees, 40 degrees and 60 degrees of trunk flexion; and isokinetic flexion starting at neutral posture, and isokinetic extension starting at 60 degrees of trunk flexion. The patients performed isometric flexion and extension in neutral posture only; and isokinetic flexion-extension similar to normal sample. RESULTS: The average strength in each activity was between 70 and 80% of the corresponding peak strength. The isokinetic activity strengths ranged between 60 and 70% of the corresponding isometric activities in each group. The strength of females ranged between 60 and 70% of males. The ANOVA revealed that posture had a significant effect on strength. The multiple regression explained 73% of variance in isometric and 34% in isokinetic modes. CONCLUSIONS: A patient's strength profile should be determined in a posture that simulates activities of daily living to determine impairment and plan rehabilitation.

Adult↗
PubMed1995

Human trunk strength profile in lateral flexion and axial rotation.

STUDY DESIGN: To determine the functional capability in asymmetric trunk motion, isometric and isokinetic lateral flexion and axial rotation strengths of a normal and patient samples were measured. Seventy-three normal asymptomatic subjects (41 males and 32 females) and ten patients (9 males and 1 female) were tested. OBJECTIVES: The dual objectives of the study were to develop a database for isometric and isokinetic lateral flexion and axial rotation strength capabilities of a normal sample and to determine the functional impairment of a sample of patients. SUMMARY OF BACKGROUND DATA: More than 60% of low back injuries are associated with trunk twisting. Asymmetric motions are important risk factors. However, strength capability data for axial rotation are sparse and those for lateral flexion nonexistent. METHODS: To achieve the objectives of the study, two devices were designed and fabricated. Isometric lateral flexion was tested bilaterally in neutral posture and at 10 degrees, 20 degrees, and 30 degrees of lateral bending. Isometric axial rotation was tested bilaterally in neutral posture and at 5 degrees, 10 degrees, 15 degrees, and 20 degrees of axial rotation. Isokinetic lateral flexion and axial rotation strengths were tested bilaterally starting from the neutral posture. RESULTS: The strength invariably declined progressively for all groups with increasing postural asymmetry. The strength in isokinetic activities ranged between 60% to 70% of the strength measured in isometric activities. All groups were significantly stronger in lateral flexion compared with axial rotation. The female sample ranged between 60% to 70% values of males for all activities studied. The patient group was weakest, ranging between 45% to 55% for isometric and 52% to 58% for isokinetic activities of their control group.

Adult↗
PubMed1995

Allele frequency distribution for the variable number of tandem repeat locus D10S28 in Tamil Nadu (south India) population.

Allele frequencies were determined in unrelated individuals of Tamil speaking population from the Madras City (Tamil Nadu, South India) area for the polymorphic DNA locus D10S28 using the probe TBQ7. Membranes hybridized with the probe YNH24 were subjected to deprobing and were subsequently hybridized with random priming - labeled, purified inserts of TBQ7. The sizes of the fragments were grouped to 100 bp as well as to arbitrary fixed bins (Federal Bureau of Investigation / Royal Canadian Mounted Police). There were 14 bins in the latter with the most common bin being 11 (1789-1924 bp) with a frequency of 9.8%. We observed a heterozygosity of 92% comparable to Caucasian populations. The data presented here can be used as the basis for utilizing this variable number of tandem repeats (TNTR) DNA marker for paternity determinations and forensic investigations.

Alleles↗
PubMed1995

Induction of tissue inhibitor and matrix metalloproteinase by serum in human heart-derived fibroblast and endomyocardial endothelial cells.

To understand the regulatory mechanisms of extracellular matrix (ECM) turnover and proteinase expression in human cardiovascular tissue, we have isolated and characterized human heart fibroblast (HHF) and human heart endothelial (HHE) cells from endomyocardial biopsy specimens. HHE cell in culture exhibited the typical cobblestone growth pattern and positive immunofluorescent staining for factor VIII related antigen. HHF demonstrated the typical spindle shape during culture and were positive for vimentin. Both cell types were negative for alpha-actin, indicating that these cells were of nonmuscle origin. Cell growth studies revealed significant growth when maintained in limiting serum concentration, suggesting mitogenic activity of these cells, and demonstrated growth inhibitory activity when grown in serum-free medium. Serum-dependent matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) expression was measured by zymography, immunoblot, and Northern blot analysis. Results indicated that serum induces both the MMP and TIMP expression at the mRNA and protein levels in a dose-dependent manner. This induction was inhibited by actinomycin D and cycloheximide, suggesting transcriptional and translational regulation of MMP and TIMP. Indirect immunofluorescence labeling indicated expression of MMP and TIMP in HHF and HHE cells. These results suggested that the serum induces proliferation as well as expression of MMP and TIMP in HHE and HHF cells. The growth inhibitory activity of these cell cultures will enable us to explore further the nature of this response and compare this phenomenon with other growth inhibitors and growth promoters identified in other normal and transformed cells.

Cell Division↗
PubMed1995

Modification of in situ gelling behavior of carbopol solutions by hydroxypropyl methylcellulose.

Aqueous solutions of Carbopol [polyacrylic acid (PAA)] are low viscosity acidic solutions that transform into gels upon an increase in the pH and, therefore, may be used as in situ gelling ophthalmic drug delivery systems. However, the amount of PAA required in the solution to form stiff gels upon installation in the eye is not easily neutralized by the buffering action of tear fluid. A reduction in the PAA concentration without comprising the in situ gelling properties as well as the overall rheological behavior of the system can be achieved by adding a suitable viscosity-enhancing polymer. The rheological properties of aqueous solutions containing PAA and hydroxypropyl methylcellulose (HPMC), a viscosity-enhancing polymer, evaluated as a function of temperature and pH, were similar to those of pure PAA solutions; that is, both form low viscosity liquids at pH 4.0 and transform into stiff gels with plastic rheological behavior and comparable viscosities upon increasing the pH to 7.4. In addition, HPMC-PAA gels show slow in vitro release of incorporated timolol maleate. Thus, the HPMC-PAA combination demonstrates properties suitable for formulation as a liquid ophthalmic delivery systems, which upon instillation into the cul-de-sac of the eye can undergo in situ phase transition to form gels capable of sustained drug release.

Acrylic Resins↗
PubMed1995

Broadband SQUID NMR with room-temperature samples.

Superconducting quantum interference devices (SQUIDs) are the most sensitive detectors of magnetic fields. We have used an untuned broadband SQUID detector to detect transverse nuclear magnetic-resonance signals from samples of mineral oil, salt water, and animal tissue at room temperature. Proton NMR signals have been detected from about 20 to 450 kHz. We have also detected fluorine, sodium, and possibly phosphorus NMR signals. SQUID NMR shows promise in NMR imaging, since the SQUID's sensitivity and broad bandwidth make it ideal for low-field imaging. SQUID NMR may also be useful for low-field spectroscopy in biology, chemistry, and materials science.

Animals↗
PubMed1995

Metabolism of 2-acetylaminofluorene by hepatocytes isolated from rainbow trout.

The metabolism of 2-acetyl-[9-14C]aminofluorene (AAF) by hepatocytes isolated from rainbow trout (Oncorhynchus mykiss), Shasta strain, was investigated in order to assess the competing activation and detoxification pathways which may explain the resistance of this species and strain to the initiation of carcinogenesis by this model carcinogenic aromatic amide. Freshly isolated hepatocytes (per milliliter: 1.0 mg dry wt; 1.5 (10(6)) hepatocytes) incubated with 65 microM AAF for 4 hr converted 15.4 nmol AAF to metabolites, including 7.8 nmol of water-soluble compounds. AAF-derived radioactivity extracted from the incubation mixtures, before and after hydrolysis by beta-glucuronidase and arylsulfatase, was analyzed by reversed-phase HPLC. The metabolite profile following incubation of hepatocytes with 6.5 microM AAF for 4 hr included (as percentage of total metabolites); 7-OH-AAF, 5-/8-/9-OH-AAF and 2-aminofluorene (AF) (17, 2.4, and 2.7%, respectively); conjugates of these respective primary metabolites (39, 9, and 4%, respectively). Glucuronides amounted to 49% of the total metabolites. N-OH-AAF and its conjugates always amounted to < 1% of total metabolites. The relative amount of (unconjugated) AF increased considerably (to 26%) following incubation of hepatocytes with 65 microM AAF, with a corresponding decrease in the total amount of glucuronides formed. Following incubation with 65 microM AAF, 1.6% of AAF metabolites was covalently bound to macromolecules, giving a ratio of covalently bound derivatives to detoxification products of 0.028. These data are consistent with the hypothesis that rainbow trout are resistant to AAF-induced hepatocarcinogenesis, in part, because trout liver efficiently detoxifies AAF and forms only relatively small amounts of active intermediates capable of binding to macromolecules, including DNA.

2-Acetylaminofluorene↗
PubMed1995

Incorporation of diaphyseal sequestra in chronic haematogenous osteomyelitis.

Seventeen patients with haematogenous osteomyelitis and long diaphyseal sequestra are reported. Treatment was incision and drainage with antibiotics for at least 6 to 8 weeks, the limb being protected in plaster for a long time. The sequestra became incorporated in every case. Sequestrectomy should only be undertaken when successive radiographs show no reduction in size of the sequestrum and an increase in the amount of the involucrum.

Adolescent↗