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Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 631 records · Page 35Linked to original sources
PubMed2000

Medicinal plants from nepal: evaluation as inhibitors of leukotriene biosynthesis.

The methanolic extracts of 25 different Nepalese medicinal plants were tested for their activity to inhibit the biosynthesis of leukotriene B(4) in bovine polymorphonuclear leukocytes. The selected indigenous plants are used in traditional herb remedies to treat inflammatory diseases such as asthma, bronchitis, rheumatism, and skin disorders presumed to be mediated by leukotrienes. The leaves of Zanthoxylum nepalensis were shown to be the most potent inhibitor with an IC(50) value of 11 microgram/ml. The extracts obtained from Astercantha longifolia and Hedychium ellipticum also exhibited potent inhibitory action with IC(50) values of 20 and 22 microgram/ml, respectively.

Humans↗
PubMed2000

Metabolism of benzo(a)pyrene by duck liver microsomes.

The metabolism of benzo(a)pyrene [BP], a model carcinogenic PAH, by hepatic microsomes of two duck species, mallard (Anas platyrhynchos) and common merganser (Mergus merganser americanus) collected from chemically-contaminated and relatively non-contaminated areas was investigated. The rate of metabolism of BP by liver microsomes of common merganser and mallard collected from polluted areas (2,650 +/- 310 and 2,200 +/- 310 pmol/min per mg microsomal protein, respectively) was significantly higher than that obtained with liver microsomes of the two species collected from non-polluted areas (334 +/- 33 and 231 +/- 30 pmol/min per mg microsomal protein, respectively). The level of cytochrome P-450 1A1 was significantly higher in the liver microsomes of both duck species from the polluted areas as compared to the ducks from the non-polluted areas. The major BP metabolites, including BP-9, 10-diol, BP-4, 5-diol, BP-7, 8-diol, BP-1, 6-dione, BP-3, 6-dione, BP-6, 12-dione, 9-hydroxy-BP and 3-hydroxy-BP, formed by liver microsomes of both duck species from polluted and non-polluted areas, were qualitatively similar. However, the patterns of these metabolites were considerably different from each other. Liver microsomes of ducks from the polluted areas produced a higher proportion of benzo-ring dihydrodiols than the liver microsomes of ducks from the non-polluted areas, which converted a greater proportion of BP to BP-phenols. The predominant enantiomer of BP-7,8-diol formed by hepatic microsomes of the two duck species had an (-)R,R absolute stereochemistry. The data suggest that duck and rat liver microsomal enzymes have different regioselectivity but similar stereoselectivity in the metabolism of BP.

Animals↗
PubMed2000

The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome.

Although there is a binding site on the proteasome for the polyubiquitin chains attached to degradation substrates by the ubiquitination machinery, it is currently unclear whether in vivo the activities of the ubiquitination machinery and the proteasome are coupled. Here we show that two human homologs of the yeast ubiquitin-like Dsk2 protein, hPLIC-1 and hPLIC-2, physically associate with both proteasomes and ubiquitin ligases in large complexes. Overexpression of hPLIC proteins interferes with the in vivo degradation of two unrelated ubiquitin-dependent proteasome substrates, p53 and IkappaBalpha, but not a ubiquitin-independent substrate. Our findings raise the possibility that the hPLIC proteins, and possibly related ubiquitin-like family members, may functionally link the ubiquitination machinery to the proteasome to affect in vivo protein degradation.

Adaptor Proteins, Signal Transducing↗
PubMed2000

Paramagnetic resonance and visible spectroscopic properties of binuclear Cu-Cu and Cu-Zn imidazolate-bridged complexes: effective model for active site of superoxide dismutase.

Syntheses of the imidazolate-bridged heterometallic binuclear copper-zinc complex [(glyala)Cu-im Zn(g-lyala)]Na, where H2glyala = glycylalanine, and im = imidazolate ion, has been achieved. X-band e.p.r and visible absorption spectra of the complex [(glyala)Cu-im-Zn(glyala)]Na at different pH values in frozen solution (50% aqueous DMSO, 77K) show that the imidazolate-bridged complex is stable in the pH range 7.15-10.50.

Copper↗
PubMed2000

Free and esterified fatty acid and cholesterol synthesis in adult males and its effect on the doubly-labelled water method.

The purpose of the present study was to estimate whole-body fatty acid and cholesterol synthesis in weight-stable adults and to determine the likely effect on the doubly-labelled water (DLW) method for measuring energy expenditure. Synthesis was measured by 2H incorporation over 14 d in six adult males in approximate energy balance following noradrenaline infusion to maximize mobilization of free fatty acid from adipose tissue. The inter-individual variation in synthesis rates was large and in one subject the proportion of free fatty acid synthesized was ten times that of the mean of the rest of the group; the fasting concentration of esterified fatty acid in this subject was five times that of the rest of the group indicating likely violation of the assumptions underlying the calculation of whole-body synthesis. After 14 d of labelling in the other five subjects, 0.9 (SEM 0.3)% of the circulating free fatty acid, 9.3 (SEM 3.0)% of the esterified fatty acid, 14.6 (SEM 2.4)% of the free cholesterol and 28.3 (SEM 3.7)% of esterified cholesterol had been synthesized de novo. A high rate of synthesis correlated with a low pre-dose 2H abundance both within and between lipid classes suggesting that natural 2H abundance variations in some lipid classes may be used to determine their metabolic origin. Whole-body synthetic rates were 8 g/d for fatty acid and 0.3-0.5 g/d for cholesterol. These values correspond to very small errors on DLW-derived estimates of CO2 production; -2.5 litres/d for fatty acid and -0.1 to -0.2 litres/d for cholesterol. These results, obtained in subjects typically consuming a diet with a lower fat and cholesterol content that the typical Western diet, suggest that the DLW method is unlikely to be affected by fatty acid and cholesterol synthesis in subjects in energy balance consuming a typical Western diet.

Adipose Tissue↗
PubMed2000

Use of three different marker systems to estimate genetic diversity of Indian elite rice varieties.

Genetic diversity among 42 Indian elite rice varieties, which is important for selection of parents for conventional breeding and hybrid program, was evaluated using three different types of DNA markers and parentage analysis. Random amplified polymorphic DNA (RAPD), inter-simple sequence repeat (ISSR) and sequence tagged microsatellite site (STMS) markers resulted in mean heterozygosity values of 0.429, 0.675 and 0.882 over all loci, respectively, and marker index values of 2.21, 4.05 and 5.49, respectively. The three molecular marker systems together provide wider genome coverage and, therefore, would be a better indicator of the genetic relationships among the 42 elite rice cultivars than those revealed using individual molecular markers. A total of 153 bands (91%) were polymorphic out of 168 bands amplified, considering all the markers together. The average genetic similarity coefficient across all the 861 cultivar pairs was 0.70 while the average coefficient of parentage was 0.10. Cluster analysis revealed that there was a very poor correlation (correlation coefficient <0.1) between dendrograms generated using coefficients of parentage and molecular marker generated genetic similarities, which can be attributed to selection pressure, genetic drift, sampling of loci and unknown relationships among supposedly unrelated ancestors.

DNA, Plant↗
PubMed2000

LMNA, encoding lamin A/C, is mutated in partial lipodystrophy.

The lipodystrophies are a group of disorders characterized by the absence or reduction of subcutaneous adipose tissue. Partial lipodystrophy (PLD; MIM 151660) is an inherited condition in which a regional (trunk and limbs) loss of fat occurs during the peri-pubertal phase. Additionally, variable degrees of resistance to insulin action, together with a hyperlipidaemic state, may occur and simulate the metabolic features commonly associated with predisposition to atherosclerotic disease. The PLD locus has been mapped to chromosome 1q with no evidence of genetic heterogeneity. We, and others, have refined the location to a 5.3-cM interval between markers D1S305 and D1S1600 (refs 5, 6). Through a positional cloning approach we have identified five different missense mutations in LMNA among ten kindreds and three individuals with PLD. The protein product of LMNA is lamin A/C, which is a component of the nuclear envelope. Heterozygous mutations in LMNA have recently been identified in kindreds with the variant form of muscular dystrophy (MD) known as autosomal dominant Emery-Dreifuss MD (EDMD-AD; ref. 7) and dilated cardiomyopathy and conduction-system disease (CMD1A). As LMNA is ubiquitously expressed, the finding of site-specific amino acid substitutions in PLD, EDMD-AD and CMD1A reveals distinct functional domains of the lamin A/C protein required for the maintenance and integrity of different cell types.

Amino Acid Sequence↗
PubMed2000

Myogenin is a specific marker for rhabdomyosarcoma: an immunohistochemical study in paraffin-embedded tissues.

Myogenin belongs to a group of myogenic regulatory proteins whose expression determines commitment and differentiation of primitive mesenchymal cells into skeletal muscle. The expression of myogenin has been demonstrated to be extremely specific for rhabdomyoblastic differentiation, which makes it a useful marker in the differential diagnosis of rhabdomyosarcomas (RMS) from other malignant small round cell tumors of childhood. Commercially available antibodies capable of detecting myogenin in routinely processed formalin-fixed paraffin-embedded (FFPE) tissue are now available. In this study, we evaluated myogenin expression using the monoclonal myf-4 antibody (Novocastra Labs) on FFPE in a large number of pediatric tumors in order to define the clinical utility of this marker. A total of 119 tumors were studied. These included 48 alveolar RMS (ARMS), 20 embryonal RMS (ERMS), one spindle cell RMS, 16 Ewing's sarcomas (ES), six nephroblastomas, two ectomesenchymomas, seven precursor hematopoietic neoplasms, five olfactory neuroblastomas, three neuroblastomas, six desmoplastic small round cell tumors, and five rhabdoid tumors. Distinct nuclear staining for myogenin was noted in all 69 RMS. Notably, the number of positive tumor cells differed between the ARMS and ERMS. In ARMS, the majority of tumor cells (75 to 100%) were positive, in contrast to ERMS, in which the positivity ranged from rare + to 25% in all but three tumors. Additionally, myogenin positivity was seen in two of two ectomesenchymomas and in two nephroblastomas with myogenous differentiation. All other tumors were clearly negative. Our results indicate that staining for myogenin is an extremely reliable and specific marker for rhabdomyoblastic differentiation. It gives consistent and easily interpretable results in routinely fixed tissues.

Biomarkers, Tumor↗
PubMed2000

Subcellular localization and CARD-dependent oligomerization of the death adaptor RAIDD.

RAIDD, a caspase recruitment domain (CARD) containing molecule, interacts with procaspase-2 in a CARD-dependent manner. This interaction has been suggested to mediate the recruitment of caspase-2 to the tumour necrosis factor receptor 1 (TNFR1). In this paper we have studied the subcellular localization of RAIDD and its interaction with caspase-2. We demonstrate that endogenous RAIDD is mostly localized in the cytoplasm and to some extent in the nucleus. RAIDD localization is not affected by TNF-treatment of HeLa cells, but in cells ectopically expressing caspase-2, a fraction of RAIDD is recruited to the nucleus. In transfected cells, coexpression of RAIDD and caspase-2 leads to CARD-dependent colocalization of the two proteins to discrete subcellular structures. We further show that overexpression of the RAIDD-CARD results in the formation of filamentous structures due to CARD-mediated oligomerization. These structures were similar to death effector filaments (DEFs) formed by FADD and FLICE death effector domains (DEDs), and partially colocalized with DEFs. Our results suggest that similar to the DED, the RAIDD-CARD has the ability to form higher order complexes, believed to be important in apoptotic execution. We also present evidence that RAIDD-CARD oligomerization may be regulated by intramolecular folding of the RAIDD molecule.

Apoptosis↗
PubMed2000

The fly caspases.

Caspases, a group of cysteine proteases, constitute the effector arm of the cell death machinery. There are seven caspases known in Drosophila, three of which contain long amino-terminal prodomains. Although, compared to mammalian caspases, much less is known about the biology of Drosophila caspases, many studies have shown that caspases are essential for programmed cell death in the fly and are likely to be regulated in ways similar to their mammalian counterparts. Studies on fly caspases have revealed some new insights on cell death regulation. For example, the transcript for the fly caspase DRONC is regulated by the hormone ecdysone during programmed cell death in specific tissues. Recent data on DRONC also suggest that some fly caspases may have unique substrate specificities not ascribed to mammalian caspases. The presence of multiple caspases in Drosophila indicates that apoptotic pathways in insects are likely to be as complex as in vertebrates.

Amino Acid Motifs↗
PubMed2000

Gender differences in the regulation of P450 aromatase expression and activity in human adipose tissue.

OBJECTIVE: To investigate the hormonal regulation of P450 aromatase activity (responsible for the conversion of C19 androgens to C18 oestrogens) in human adipose tissue from men and pre- and post-menopausal women. SUBJECTS: Subcutaneous abdominal adipose tissue was obtained from 19 subjects: six pre-menopausal females (mean age 41.8+/-(s.e.m.) 2.5; mean weight 76.01+/-5.6 kg), eight post-menopausal females (mean age 59.9+/-2.0; mean weight 63.5+/-2.6 kg), and five males (mean age 35.8+/-8.8; mean weight 78.5+/-7.8 kg) undergoing elective or cosmetic surgery. MEASUREMENTS: Cell viability and cell size were determined using staining techniques. RT-PCR was used to confirm the presence of aromatase. The regulation of aromatase activity was characterized using androstenedione as a substrate in a tritiated water release assay. Aromatase activity was analysed in abdominal subcutaneous stromal cells (ASC) and mature adipocytes (AD) cultured in serum-free medium with cortisol (10-6-10-7 M), insulin (500 nM) or a combination of both. RESULTS: In ASC aromatase activity increased in females from 14.5+/-1.7 to 29. 3+/-2.6 pmol/mg/h (n=14, P<0.05) and to 25.2+/-2.1 pmol/mg/h with cortisol (10-7 M) and insulin, respectively (P<0.05). In males ASC basal aromatase activity (20.5+/-4.2 pmol/mg/h; n=5) was inhibited by cortisol (10-7 M) alone (12.3+/-1.8 pmol/mg/h) and in combination with insulin (6.6+/-1.2 pmol/mg/h; men vs women, P<0.005). Aromatase activity in mature adipocytes was stimulated by cortisol plus insulin (P<0.05) with no gender-specific differences. Treatment of ASC from both pre- and post-menopausal females with cortisol alone (10-6 M; 10-7 M) or in combination with insulin demonstrated significantly different aromatase regulation compared with male aromatase stromal cell regulation (P<0.05); however there were no differences in aromatase regulation between pre- and post-menopausal females either in stromal cells or adipocytes. CONCLUSION: This study shows intrinsic gender differences in the regulation of aromatase, suggesting that differential enzyme regulation may affect sex steroid metabolism to alter the pattern of fat distribution between the sexes.

Adipocytes↗
PubMed2000

The ultrastructure of the subcommissural organ ependyma of the goat.

The cells of pseudostratified columnar ciliated ependyma of the subcommissural organ in the goat were classified into two types on the basis of the distribution of chromatin material and nuclear clefts. Amongst the cell organelles the endoplasmic reticulum was highly developed and formed three types of Nebenkerne systems. The type-I Nebenkerne had spiral concentric lamellae and was associated with round lipid droplets. The type-II Nebenkerne, with widely spaced coils, was expanded towards its central and peripheral parts. The type-III Nebenkerne, composed of a meshwork of lamellae, was modified into a vacuolated form. The concentration of mitochondria was greatly increased towards the basal processes of the ependymal cells. The inclusion bodies included small electron-dense bodies, osmiophilic asteroid droplets, large round to spherical bodies and large round osmiophilic bodies with inner structures.

Animals↗
PubMed2000

Some in vitro invasion inhibition of red cells by in vivo nonprotective anti-LDH antibodies of Plasmodium berghei.

In Plasmodium berghei, sephadex G-200 purified lactate dehydrogenase (LDH) fraction immunized mice did not exhibit protection when challenged with 1 x 10(6) P. berghei-parasitized erythrocytes. However, LDH immunized mice seroconverted and showed an antibody titre of 1:2048 by indirect haemagglutination (IHA) and 1:160 by indirect fluorescent antibody (IFA) assays. Fluorescence was distributed evenly on P. berghei-parasitized red cells showing no specific location of parasite LDH. Anti-LDH antibodies supplemented in 19 h in vitro culture of P. berghei exhibited 9.2% invasion inhibition into the fresh red cells.

Animals↗