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Biomedical subjects

S Kumar

Publications and source records attributed to S Kumar.

At least 325 records · Page 18Linked to original sources

Pediatric celiac disease in India is associated with multiple DR3-DQ2 haplotypes.

The role of human leukocyte antigen (HLA) DQ2 heterodimer (DQA1*0501-DQB1*0201) in presenting gluten peptides to effector T cells in celiac disease (CD) has been well documented. Because HLA-DQ2 is carried on DR3 haplotypes due to linkage disequilibrium, such haplotypes are encountered more frequently in patients with autoimmune disease. This study analyzed 35 North Indian children below 15 years of age and diagnosed to have CD as per the ESPGAN criteria, which included histopathologic alterations in duodenal biopsies, clinical response to gluten withdrawal, and presence of antiendomysial antibodies. The HLA class I and class II alleles were determined by polymerase chain reaction-sequence-specific primers, sequence-specific oligonucleotide probe, and reverse line strip molecular techniques. A statistically significant positive association of the disease with HLA-DRB1*03 (94.2% versus 22.1% in controls, chi(2) = 73.4, p = 7.54E-11), and a negative association with DRB1*15 (chi(2) = 7.4, p = 6.5E-03) and DRB1*13 alleles was observed. The HLA-DQB1*0201 was observed in all the 35 patients (100%), whereas the DQ2 heterodimer alpha(0)beta(0) occurred in 97.1% of CD patients (31.4% in double dose, 65.7% in single dose) and revealed significant deviation from healthy controls (chi(2) = 102.08, p = 7.56E-11). Further analysis revealed involvement of multiple DR3+ve haplotypes with CD in Indians, of which A26-B8-DR3 was the most common DR3 haplotype among patients (34.28%, chi(2) = 40.57, p = 2.65E-10) followed by Ax-B21-DR3 (11.4%) (chi(2) = 13.8, p = 2E-04) and the classical Caucasian haplotype A1-B8-DR3 (5.7%). The former two haplotypes are characteristic of Asian Indians and are involved in the development of CD. We conclude that the high risk DR3 haplotypes that play a crucial role in the development of CD are unique in Asian Indians. Detailed analysis of these haplotypes in Indian patients with autoimmune diseases may help understand the influence of other intervening genes within the major histocompatibility complex.

Adolescent↗

The in vitro antimutagenic activity of Triphala--an Indian herbal drug.

A study to evaluate an antimutagenic potential of water, chloroform and acetone extracts of Triphala has been made in an Ames histidine reversion assay using TA98 and TA100 tester strains of Salmonella typhimurium against the direct-acting mutagens, 4-nitro-o-phenylenediamine (NPD) and sodium azide, and the indirect-acting promutagen, 2-aminofluorene (2AF), in the presence of phenobarbitone-induced rat hepatic S9. A combination drug 'Triphala' - a composite mixture of Terminalia bellerica, T. chebula and Emblica officinalis, has been used in traditional system of medicine for the treatment of many malaises, such as heart ailments and hepatic diseases. The drug was sequentially extracted with water, acetone and chloroform at room temperature. The study revealed that water extract was ineffective in reducing the revertants induced by the mutagens. The results with chloroform and acetone extracts showed inhibition of mutagenicity induced by both direct and S9-dependent mutagens. A significant inhibition of 98.7% was observed with acetone extract against the revertants induced by S9-dependent mutagen, 2AF, in co-incubation mode of treatment. Various spectroscopic techniques, namely 1H-NMR, normal 13C-NMR, distortionless enhancement by polarization transfer (DEPT-90 and DEPT-135), UV and IR, are under way to identify the polyphenolic compounds from an acetone extract.

Acetone↗

Antimutagenic activities of acetone and methanol fractions of Terminalia arjuna.

The antimutagenic effect of benzene, chloroform, acetone and methanol fractions from Terminalia arjuna, a well-known medicinal plant, was determined against Acid Black dye, 2-aminofluorene (2AF) and 4-nitro-o-phenylenediamine (NPD) in TA98 Frameshift mutagen tester strain of Salmonella typhimurium. Among the different fractions, the antimutagenic effect of acetone and methanol fractions was more than that observed with other fractions. Co-incubation and pre-incubation modes of experimentation did not show much difference in the antimutagenic activity of the extracts. Moreover, these fractions inhibited the S9-dependent mutagens, 2AF and Acid Black dye more effectively than the direct-acting mutagens. Studies are under way to isolate and elucidate the nature of the antimutagenic factor in acetone and methanol fractions.

Acetone↗

Aluminium-induced changes in the rat brain serotonin system.

Aluminium exposure, apart from producing cholinotoxicity, can include changes in other neurotransmitter levels since neurotransmitter levels are closely interrelated. Reports of aluminium (Al) effects on brain neurotransmitters are limited. To investigate the effect of Al on the rat brain serotonergic system, the present study was conducted to explore brain region-specific changes and duration-specific changes. Male Wistar albino rats were exposed orally to Al chloride (AlCl(3).6H(2)O; 320 mg/kg body weight) daily for up to 60 days and changes in the 5-hydroxytrytamine (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA) levels were observed after 4, 14 and 60 days of exposure in olfactory lobe (OLB), cerebellum (CBL), pons (PON), medulla oblongata (MOB), spinal cord (SPI), hypothalamus (HYP), hippocampus (HIP), striatum (STR), midbrain (MBR) and cortex (COR) brain regions. Significantly increased 5-HT levels observed in brain regions OLB (60 days), HIP (4,14 days), STR (14 days), HYP (14, 60 days), MBR (4 and 14 days), PON (4 days), MOB (4 days) and SPI (4, 14 and 60 days) following Al exposure may be due to Al deactivating 5-HT system by decreased release and subsequent breakdown of 5-HT. Decreased 5-HT levels observed in cerebral COR, HIP (60 days) and in CBL after 4 and 60 days of exposure suggest an inhibitory effect of Al on the 5-HT system due to withdrawal of cholinergic input in these brain regions. 5-HIAA level changes correlate with 5-HT level changes in many brain regions studied. The results reveal that the neurochemical changes due to Al were dependent on the duration of exposure and are brain-region-specific. The observed changes may be related to the cholinergic toxicity of Al.

Aluminum↗

Emission of nitrous oxide from rice-wheat systems of Indo-Gangetic plains of India.

Nitrous oxide (N2O) accounts for 5% of the total enhanced greenhouse effect and responsible for the destruction of the stratospheric ozone. The rice-wheat cropping system occupying 26 million ha of productive land in Asia could be a major source of N2O as most of the fertilizer N in this region is consumed by this system. Emission of N2O as influenced by application of urea, urea plus farm yard manure (FYM), and urea plus dicyandiamide (DCD), a nitrification inhibitor, was studied in rice-wheat systems of Indo-Gangetic plains of India. Total emission of N2O-N from the rice-wheat systems varied between 654 g ha(-1) in unfertilized plots and 1,570 g ha(-1) in urea fertilized plots. Application of FYM and DCD reduced emission of N2O-N in rice. The magnitude of reduction was higher with DCD. In wheat also N2O-N emission was reduced by DCD. FYM applied in rice had no residual effect on N2O-N emission in wheat. In rice intermittent wetting and drying condition of soil resulted in higher N2O-N emission than that of saturated soil condition. Treatments with 5 irrigations gave higher emissions in wheat than those with 3 irrigations. In rice-wheat system, typical of a farmer's field in Indo-Gangetic plains, where 240 kg N is generally applied through urea, N2O-N emission is 1,570 g ha(-1) (0.38% of applied N) and application of FYM and DCD reduced it to 1,415 and 1,096 g ha(-1), respectively.

Air Pollutants↗

Omission of day +11 methotrexate after allogeneic bone marrow transplantation is associated with increased risk of severe acute graft-versus-host disease.

The combination of CYA and short-course MTX is commonly used for GVHD prophylaxis after allogeneic BMT. Severe mucositis and organ dysfunction early after transplantation often lead to omission of the day +11 dose of MTX. To examine whether this omission increases the risk of acute or chronic GVHD, we reviewed 135 allogeneic BMTs performed at our institution in which CYA and short-course MTX prophylaxis were used. Patients receiving less than three doses of MTX and those who died before day +11 were excluded. Of the 123 eligible patients, 84 received all four doses and 39 received three doses, with the fourth dose withheld because of severe mucositis (n = 27) or hepatic or renal dysfunction (n = 12). Acute GVHD of any grade developed in 23 patients (59%) in the three-dose group compared with 57 patients (68%) in the four-dose group (P = 0.33). Chronic GVHD developed in 15 patients (38%) in the three-dose group compared with 31 patients (37%) in the four-dose group (P = 0.87). There was no difference in the overall rate of acute or chronic GVHD between the groups. However, the three-dose group was more likely to develop grade III or IV acute GVHD (12 of 39 (31%) ) compared with the four-dose group (12 of 84 (14%); P = 0.03). Relapse-free survival was similar for the two groups. We conclude that omitting day +11 MTX appears to increase the risk of severe acute GVHD.

Acute Disease↗

Caspase-2 is not required for thymocyte or neuronal apoptosis even though cleavage of caspase-2 is dependent on both Apaf-1 and caspase-9.

We have generated rat monoclonal antibodies that specifically recognise caspase-2 from many species, including mouse, rat and humans. Using these antibodies, we have investigated caspase-2 expression, subcellular localisation and processing. We demonstrate that caspase-2 is expressed in most tissues and cell types. Cell fractionation and immunohistochemistry experiments show that caspase-2 is found in the nuclear and cytosolic fractions, including a significant portion present in the Golgi complex. We found that caspase-2 is processed in response to many apoptotic stimuli but experiments with caspase-2 deficient mice demonstrated that it is not required for apoptosis of thymocytes or dorsal root ganglia (DRG) neurons in response to a variety of cytotoxic stimuli. Caspase-2 processing does not occur in thymocytes lacking Apaf-1 or caspase-9, suggesting that in this cell type, activation of caspase-2 occurs downstream of apoptosome formation.

Animals↗

Early lymphocyte recovery is a predictive factor for prolonged survival after autologous hematopoietic stem cell transplantation for acute myelogenous leukemia.

Absolute lymphocyte count (ALC) recovery correlates with survival after autologous hematopoietic stem cell transplantation (AHSCT) for patients with multiple myeloma, non-Hodgkin's lymphoma, and metastatic breast cancer. The role of ALC recovery in relationship to clinical outcome after AHSCT in patients with acute myelogenous leukemia is unknown. We analyzed 45 patients who underwent AHSCT at Mayo Clinic, Rochester, Minnesota between 1990 and 2000. The ALC threshold was selected at 500 cells/microl on day 15 post-AHSCT based on our previous studies. Thirty-two females and 13 males were included in the study with a median age of 45 years (range 12-75). The median follow-up was 14 months with a maximum of 129 months. The median overall and leukemia-free survival were significantly better for the 23 patients with ALC at day 15 > or =500 cells/microl compared with 22 patients with ALC <500 cells/microl (not yet reached vs 10 months, P < 0.0009; 105 vs 9 months, P < 0.0008, respectively). In conclusion, ALC > or =500 cells/microl on day 15 post-AHSCT is associated with better survival in acute myelogenous leukemia and requires further studies.

Adolescent↗

A set of cattle microsatellite DNA markers for genome analysis of riverine buffalo (Bubalus bubalis).

One hundred and eight microsatellite primer pairs, originally identified from cattle, were evaluated for their applicability in buffalo. Eighty-one primer pairs (75%) amplified discrete products, and of these, 61 pairs (56%) gave polymorphic band patterns on a panel of 25 buffaloes. The mean number of alleles per polymorphic marker was 4.50 +/- 0.20, and the mean heterozygosity per polymorphic marker was 0.66 +/- 0.02. Successful genotyping of buffaloes using cattle specific primers suggests that the latter can be a valuable resource for genome analysis in bubaline species.

Animals↗

Chronic pain after laparoscopic and open mesh repair of groin hernia.

BACKGROUND: The aim of this study was to compare the incidence of chronic pain or discomfort after laparoscopic totally extraperitoneal (TEP) repair and open mesh repair of groin hernia, and to assess the impact of such pain on patients' physical activity. METHODS: A postal questionnaire was sent to patients who had TEP or open mesh repair of groin hernia between January 1998 and December 1999. The patients were asked about any persistent pain or discomfort in relation to the groin hernia repair and whether this pain or discomfort restricted their ability to undertake physical or sporting activity. RESULTS: Of the 560 available patients 454 (81.1 per cent) replied. Laparoscopic TEP repair was performed in 240 patients (52.9 per cent) and open mesh repair in 214 (47.1 per cent). Of the 454 patients, 136 (30.0 per cent) reported chronic groin pain or discomfort, which was significantly more common after open repair than after laparoscopic repair (38.3 versus 22.5 per cent; P < 0.01). Chronic groin pain or discomfort restricted daily physical or sporting activity in 18.1 per cent of the patients. The patients who had open repair complained of significantly more restriction of daily physical activity than patients who underwent laparoscopic repair (walking, P < 0.05; lifting a bag of groceries, P < 0.01). CONCLUSION: Chronic pain or discomfort was reported by 30.0 per cent of patients after groin hernia repair and was significantly more common after open mesh repair than after laparoscopic TEP repair. It restricted physical or sporting activities in 18.1 per cent of the patients and significantly more so after open mesh repair.

Adult↗

Carbon fibres and plasma-preserved tendon allografts for gap repair of flexor tendon in bovines: gross, microscopic and scanning electron microscopic observations.

The efficacy of carbon fibres and plasma-preserved tendon allografts for gap repair in the superficial digital flexor tendon in the mid-metatarsal region was evaluated in 12 crossbred calves. Experimental tenectomies were performed, followed by implantation of carbon fibres in group I (12 legs) and plasma-preserved tendon allografts in group II (12 legs). Gross observations in group I showed filling of the defect with granulation tissue with more vascularity on day 7, which was less prominent at day 14. On day 30, the neotendon formed was slightly thicker and comparable to normal tendon in appearance and texture. On day 90, it exhibited all the characteristics of a fully developed tendon. Whereas, in group II increased vascularity at the site and encapsulation of the graft with connective tissue in early periods was observed. The gap between graft and host was filled with fibrous connective tissue. Peritendinous adhesions were maximum on day 7 which were gradually reduced in both groups. Microscopically, an acute inflammatory reaction in the periphery of carbon fibres was observed on day 7. Immature fibroblasts were arranged in a haphazard pattern at this stage. By day 14, numerous newly formed capillaries and comparatively more mature fibroblasts were present in between and around the carbon fibres which were aligning parallel to the longitudinal axis of the tendon. By day 30 the healing tissue exhibited longitudinal orientation of collagen fibres and was at a more advance stage of maturation. By day 90, the neotendon formed simulated the picture of normal tendon. In the grafted tendon group, there was normal healing tissue at the functional sites between host and grafted tendon. The fibroblastic activity appeared to be both extrinsic and intrinsic in origin. The connective tissue had invaded the graft to a variable distance and there was resorption of graft which was replaced by newly formed connective tissue on day 90. Scanning electron microscopic observation revealed formation of neotendon between carbon fibre strands, resulting in thickening of the implant. In later stages parallel collagen fibres resembling normal tendon were observed in both groups.

Animals↗

Serum homocysteine concentration is related to diabetes mellitus, but not to coronary heart disease, in Saudi Arabians.

INTRODUCTION: Plasma homocysteine (HCYS) concentration is believed to be an independent risk factor for atherosclerosis. METHODS: HCYS was measured in a cohort of 584 Saudi Arabians participating in a national screening study of coronary heart disease (CHD) risk factors. A total of 173 subjects (114 men and 59 women) had clinical CHD, of whom 82 (47.4%) had type 2 diabetes mellitus (56 men and 26 women). A further 127 subjects (60 men and 67 women) also had type 2 diabetes mellitus but no CHD. A total of 284 individuals (120 men and 164 women) were recruited as healthy controls, and had no previous history of CHD or diabetes. Serum HCYS was measured by high-performance liquid chromatography (HPLC) with electrochemical detection. RESULTS: Univariate analysis showed HCYS concentrations were significantly lower in those with diabetes mellitus (DM) than in controls, for both men [8.7 (4.2-18.6) vs. 10.5 (4.5-20.5) mmol/l, median (5th-95th percentiles, p = 0.009] and women [6.3 (3.3-24.0) vs. 8.1 (4.0-17.9) mmol/l, p = 0.049]. Stepwise multivariate regression analysis indicated a relationship between HCYS concentration and age, sex and the presence of DM, but not with CHD. CONCLUSIONS: In the Saudi Arabian population, serum HCYS is not a risk factor for CHD, but is lower in patients with DM.

Adolescent↗

The regulation of HSL and LPL expression by DHT and flutamide in human subcutaneous adipose tissue.

Clinical observations suggest a role for testosterone in the accumulation of central adiposity and with an associated increased risk of disease. To date, no human study has analysed the role of dihydrotestosterone (DHT) on adipose tissue mass regulation in vitro. This study investigated the role of DHT and androgen receptors (AR) in the regulation of lipolysis and lipogenesis by examining the key enzymes hormone sensitive lipase (HSL) and lipoprotein lipase (LPL) respectively. Isolated abdominal subcutaneous adipocytes (Scad) (n = 15) were treated with either DHT (10(-7)-10(-9) m), an antiandrogen, flutamide (FLT: 10(-7)-10(-9) m) or a combination of DHT (10(-7)-10(-9) m) with FLT (10(-8) m). Relative protein expression of HSL, LPL and AR was determined. In Scad, DHT inhibited HSL expression maximally at 10(-9) m (0.7 +/- 0.4**; p < 0.01**) compared with control (control: 1.0 +/- (s.e.m.) 0.0), whereas LPL protein expression was stimulated at DHT10(-9) m (2.22 +/- 0.48*; p < 0.05*). Glycerol release assay results correlated with HSL expression data. LPL expression was reduced at all doses with combinations of DHT + FLT compared with DHT alone. Androgen receptor expression studies showed an inverse correlation with DHT, whereas DHT + FLT reduced AR expression. These studies indicate that DHT may alter HSL and LPL expression, whereas only LPL expression appears mediated by AR. These findings suggest a physiological role for DHT in the control of adipose tissue mass in women, and indicate that androgens may also play an important role in regulating lipid metabolism.

Adipocytes↗

ED(27) trophoblast-like cells isolated from first-trimester chorionic villi are genetically identical to HeLa cells yet exhibit a distinct phenotype.

ED(27) trophoblast-like cells were prepared from human chorionic villus samples obtained at 9 weeks gestation and have been grown continuously in vitro without phenotypic drift for nearly a decade. These cells express many trophoblast markers, including cytokeratin, placental alkaline phosphatase (PLAP), secretion of 17beta-estradiol, and a microvillous apical surface. The ED(27) cell line is a useful model system for studies of placental cell biology and has been distributed to laboratories world-wide. However, experiments to investigate their relationship to primary villous cytotrophoblast have shown that these cells do not secrete detectable amounts of human chorionic gonadotropin in culture and, when digested with trypsin, disperse into individual cells. Furthermore, immunocytochemical studies demonstrated that, unlike villous cytotrophoblasts, ED(27) cells were immunoreactive with monoclonal antibodies recognizing some HLA Class I antigens. This was not HLA-G, however, as would be expected if these cells originated from extravillous cytotrophoblasts, but rather classical HLA-A, B which is thought not to be expressed by any trophoblast subpopulations. These inconsistencies prompted us to question the authenticity of the continuous cell line as it now exists. Genetic haplotype analysis using the polymerase chain reaction (PCR) revealed that ED(27) was genetically identically to the HeLa cell line. Inasmuch as HeLa cells have never been grown in the laboratory (DAK), the only possible origin of HeLa cell contamination of ED(27) cells was the WISH cell line, and further PCR analysis revealed that this cell line was also genetically identical to HeLa. Like ED(27) cells, HeLa cells and WISH cells synthesized small amounts of estrogen and were found to express PLAP and antigens recognized by the monoclonal antibodies ED822, directed against the syncytiotrophoblast, and J1B5 directed against villous cytotrophoblast. These results point out the need for adherence to rigorous and consistent quality control measures to assure the authenticity of cell lines used as in vitro model systems.

Adult↗

Suprasellar cystic meningioma: unusual presentation and review of the literature.

We report on a case of suprasellar cystic meningioma. The magnetic resonance imaging of this tumor resembled that of a craniopharyngioma. The definitive diagnosis of meningioma was made only after histopathological confirmation. We conclude that preoperative studies are often equivocal. The possibility of meningioma should be considered in the diagnosis of any intracranial neoplasms with radiological and surgical evidence of a cystic lesion.

Central Nervous System Cysts↗