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Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 1,297 records · Page 72Linked to original sources

Study of oestrogen and progesterone receptors in meningiomas by a technique utilizing the binding hormones in a polymerized state.

Forty six cases of meningiomas were studied by utilizing oestrogen and progesterone hormone bound to fluroscent-iso-thiocynate (FITC) for the presence of oestrogen and progesterone receptors. Oestrogen receptors were present in 33% cases and only one fourth of these showed strong positivity. Progesterone receptors were positive in 41% cases, and more than half of these showed strong positivity. Thus this study revealed higher positivity rate for progesterone receptors than oestrogen receptors.

Adolescent↗

Serum beta 2-microglobulin as a tumour marker in space occupying lesions of central nervous system.

We prospectively evaluated serum concentrations of beta 2-microglobulin in twenty healthy controls and fifty cases of CT scan proven and operated intracranial tumours. The later group comprised of twenty subjects of benign and thirty cases of malignant tumours respectively. Mean serum beta 2-microglobulin in healthy subjects was 1.80 +/- 0.5 mg/ litre, none had value of more than 3.0 mg/ltr. On the contrary 75% of benign and 63.3% of malignant tumour cases had statistically significant rise in the beta 2-microglobulin. Elevated serum level of beta 2-microglobulin may prove to be a reliable tumour marker.

Adult↗

Comparison of the immune responses in children vaccinated with three strains of BCG vaccine.

The present study was conducted to evaluate and compare the specific cellular responses of children vaccinated with three different strains of BCG. The study comprised of normal children with normal weight and normal general responses (PHA) to in vitro leukocyte migration inhibition test (LMIT). The three strains of BCG under study were Japan-BCG, Glaxo-BCG and Madras-BCG. One hundred children were selected at random from each group. The mean ages of these infants were 9.9 +/- 9.5, 9.8 +/- 7.6 and 9.8 +/- 8.3 weeks, respectively. Six weeks after vaccination, the diameter (in mm) of induration at the vaccination site was measured. Three months after vaccination, in vitro LMIT was performed against PPD tuberculin antigen. This test was done again after 3 months in all the children who tested negative. The mean value of the diameter of the Glaxo-BCG group (10.0 +/- 13.5 mm) was significantly higher (p < 0.05) than the mean values of Japan-BCG (9.10 +/- 3.9 mm) and Madras-BCG (8.38 +/- 4.1 mm). The mean LMI values were similar in all the three groups. There was no correlation between the in vitro and in vivo parameters. The number of children positive to LMI (PPD) were 59, 58 and 63, for the Madras, Japan and Glaxo-BCG groups, respectively. A total number of 91, 91 and 95 were positive to LMIT at the end of 6 months after BCG in the Madras, Japan and Glaxo-BCG groups, respectively. The observations suggested that there were no major differences between the three strains of BCG in their capacity to induce cellular responses.

Analysis of Variance↗

Identification and purification of a chicken brain neuroglia-associated protein.

The identification, purification, and biochemical characterization of specific markers for neuroglial cells in the central nervous system is an essential step toward a better understanding of the function of glial cells. This manuscript reports the identification and purification of a neuroglia-associated protein (NAP-185) with an apparent molecular mass of 185 kDa. While its expression is not restricted to the brain, it was first identified in a specific subpopulation of glial cells when chick brain stem sections were analyzed with an affinity-purified rabbit antiserum raised against the catalytic domain of the T-cell protein tyrosine phosphatase. This 185-kDa antigen was purified to apparent homogeneity and confirmed to be responsible for the neuroglial staining observed. In spite of its immunological relation to T-cell protein tyrosine phosphatase, purified NAP-185 failed to display tyrosine phosphatase activity. The primary sequence of five NAP-185-derived peptides shows that this protein has not yet been characterized and that it is possibly related to AP180, a clathrin-associated protein.

Amino Acid Sequence↗

Quadriceps femoris activation changes in genu varum: a possible biomechanical factor in the pathogenesis of osteoarthrosis.

This study was designed to determine whether the presence of an alignment deformity of the lower leg, known as genu varum, causes abnormalities in individual- or group-activation of the surrounding knee extensors, a situation which might accelerate knee deterioration. Nine healthy women with normal tibial alignment were compared with nine age-matched healthy women with genu varum. The outcome measure of maximal quadriceps femoris activity was recorded during successive maximal concentric isometric and isokinetic contractions of the knee extensors performed on a dynamometer using surface electromyography. The results showed that, taken as a whole, the percentage utilization of quadriceps motor units was higher for those subjects with genu varum (p < 0.01). These findings demonstrate that the extensors surrounding a varus knee might function less efficiently than those surrounding a normally aligned knee. As such they suggest that pathological force generation across a varus knee might be caused, in part, by associated alterations in quadriceps tension generating capacity.

Adult↗

Induction of apoptosis by the mouse Nedd2 gene, which encodes a protein similar to the product of the Caenorhabditis elegans cell death gene ced-3 and the mammalian IL-1 beta-converting enzyme.

By subtraction cloning we previously identified a set of mouse genes (named Nedd1 through Nedd10) with developmentally down-regulated expression in brain. We now show that one such gene, Nedd2, encodes a protein similar to the mammalian interleukin-1 beta-converting enzyme (ICE) and the product of the Caenorhabditis elegans cell death gene ced-3 (CED-3). Both ICE and CED-3 are known to encode putative cysteine proteases and induce apoptosis when overexpressed in cultured cells. Overexpression of Nedd2 in cultured fibroblast and neuroblastoma cells also resulted in cell death by apoptosis, which was suppressed by the expression of the human bcl-2 gene, indicating that Nedd2 is functionally similar to the ced-3 gene in C. elegans. We also show that during embryonic development, Nedd2 is highly expressed in several types of mouse tissue undergoing high rates of programmed cell death such as central nervous system and kidney. Our data suggest that Nedd2 is an important component of the mammalian programmed cell death machinery.

Amino Acid Sequence↗

Nuclear localization of tumor necrosis factor-alpha in human osteoblast-like cells.

We have studied the internalization and subsequent nuclear localization of [125I]-rTNF-alpha in a human osteoblast-like cell line, HOS TE85. TNF-alpha is rapidly internalized and optimum cellular levels are achieved in approximately 20 minutes at 37 degrees C. A portion of the internalized cytokine is translocated to the nucleus as judged by its presence in highly purified nuclei as a 17-kDa form.

Amino Acid Sequence↗

Milk composition and lactation of beta-casein-deficient mice.

beta-Casein is a major protein component of milk and, in conjunction with the other caseins, it is assembled into micelles. The casein micelles determine many of the physical characteristics of milk, which are important for stability during storage and for milk-processing properties. There is evidence that suggests that beta-casein may also possess other, nonnutritional functions. To address the function of beta-casein, the mouse beta-casein gene was disrupted by gene targeting in embryonic stem cells. Homozygous beta-casein mutant mice are viable and fertile; females can lactate and successfully rear young. beta-Casein was expressed at a reduced level in heterozygotes and was completely absent from the milk of homozygous mutant mice. Despite the deficiency of beta-casein, casein micelles were assembled in heterozygous and homozygous mutants, albeit with reduced diameters. The absence of beta-casein expression was reflected in a reduced total protein concentration in milk, although this was partially compensated for by an increased concentration of other proteins. The growth of pups feeding on the milk of homozygous mutants was reduced relative to those feeding on the milk of wild-type mice. Various genetic manipulations of caseins have been proposed for the qualitative improvement of cow's milk composition. The results presented here demonstrate that beta-casein has no essential function and that the casein micelle is remarkably tolerant of changes in composition.

Animals↗

Quantitation of endothelial cell specific protein E-9 employing a single monoclonal antibody in an indirect sandwich ELISA.

An indirect enzyme-linked immunosorbent assay is described for the quantitation of protein E-9 which is specifically expressed on human vascular endothelial cells. The assay capitalizes on the dimeric structure of the E-9 protein by utilizing a single monoclonal antibody as both the capture and detection reagent. Detection is achieved by conjugating the Mab with biotin and is followed by the addition of streptavidin peroxidase to provide high sensitivity. Bound activity is measured by enhanced chemiluminescence utilizing standard Amerlite chemistry. The optimised assay is reproducible and is highly sensitive. Using this assay it was possible to detect the presence of E-9 protein in tissue culture media of endothelial cells and in serum samples--in one case even at 1/100 dilution. In vitro, X irradiation resulted in a greater than two-fold increase (P < or = 0.005) in the level of E-9 protein in culture supernatants of human umbilical vein endothelial cells (HUVEC). There are potential applications for measurements of E-9 protein in body fluids and tissue extracts from patients with a vast variety of diseases characterised by vascular endothelial damage and/or activation.

Animals↗

Suppression of non-esterified fatty acids to treat type A insulin resistance syndrome.

A patient with type A insulin-resistance syndrome resistance presented with severe hypertriglyceridaemia and diabetes. Fasting insulin and non-esterified fatty acids (NEFA) were very high (41 mU/L and 3.3 mmol/L). A low-fat diet failed to correct hyperlipidaemia and diabetes. Sustained suppression of NEFA with slow-release acipimox for 8 weeks resulted in substantial reduction of serum fasting NEFA (0.31 mmol/L). Glucose tolerance became normal and insulin sensitivity increased from 7% to 32%. The glucose fatty-acid cycle may operate in patients with severe insulin resistance and hyperlipidaemia: high serum NEFA aggravates insulin resistance and hyperglycaemia by inhibiting glucose uptake and utilisation.

Acanthosis Nigricans↗

Uromodulin (Tamm-Horsfall protein) is a leukocyte adhesion molecule.

Uromodulin (Tamm-Horsfall protein), the most abundant constituent of human urine, is synthesized exclusively in the kidney tubular epithelium and its amino acid sequence suggests a capacity for cell adhesion. We investigated adhesion between human uromodulin and neutrophils by allowing uromodulin, immobilized on microtiter plates, to interact with neutrophils. It was found that neutrophils attached to uromodulin in a saturable manner. The binding was inhibited by uromodulin in solution. It required metabolically active cells, was calcium sensitive and could be inhibited by arginine-glycine- aspartate-containing peptides in solution. These data suggest that uromodoulin can act as a specific ligand for neutrophils. This interaction is potentially important in leukocyte trafficking in the kidney and in the pathogenesis of interstitial nephritis.

Amino Acid Sequence↗

Molecular cloning and biological activity of a novel developmentally regulated gene encoding a protein with beta-transducin-like structure.

In the developing mammalian central nervous system, neural precursor cells show a tightly regulated inverse relationship between cell proliferation and differentiation. The molecular mechanisms which control the inter-relationship between these two events are poorly understood. To approach this problem, we previously identified several novel genes which are most prominently expressed in the early embryonic brain. Further cloning and sequencing of one such gene, Nedd1, revealed that it can encode a protein with a M(r) of 71,000, the amino-terminal half of which shares significant structural similarity with the beta-subunit of heterotrimeric GTP-binding proteins. Nedd1 mRNA is strongly expressed in early embryonic brain, but it can be detected at low levels in a number of adult tissues as well as cell lines and is up-regulated in an embryonal carcinoma cell line upon retinoic acid-induced differentiation. Ectopic expression of Nedd1 gene by means of eukaryotic vectors in various cell lines resulted in varying degrees of growth suppression. The strongest effects were evident in differentiation-competent neuroblastoma-derived cell lines. Our results suggest that the Nedd1 gene may play a role in the differentiation-coupled growth arrest in neuronal cells.

Amino Acid Sequence↗