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Biomedical subjects

N S Kumar

Publications and source records attributed to N S Kumar.

At least 19 recordsLinked to original sources
PubMed2001

New methods of resolution and purification of racemic and diastereomeric amino alcohol derivatives using boric acid and chiral 1,1'-bi-2-naphthol.

Resolution of the racemic amino alcohol derivatives 1-6 is readily achieved to obtain enantiomerically enriched compounds using chiral 1,1'-bi-2-naphthol and boric acid in solvents such as CH(3)CN, THF, and MeOH. Purification of the diastereomeric mixture 7 has also been carried out following this method. The corresponding intermediate ammonium borate complexes were also characterized by X-ray diffraction methods.

Journal Article↗
PubMed2001

Molecular tools to reestablish progestin control of endometrial cancer cell proliferation.

OBJECTIVE: Endometrial cancers often arise in a setting of estrogen stimulation unopposed by the differentiating effects of progesterone. Our laboratory and others have previously shown that progesterone receptor down-regulation or perturbation of progesterone receptor isoform A or B expression is associated with the development of poorly differentiated endometrial cancers that are not growth inhibited by progestins. The purpose of these studies was to reestablish high progesterone receptor isoform A and B gene expressions in such endometrial cancer cells and to examine the effects of progestin treatment on cell growth and metastatic potential after this transformation. STUDY DESIGN: To induce high levels of expression of the progesterone receptor isoforms in KLE and Hec50 endometrial cancer cells, adenoviral vectors encoding the genes for progesterone receptor isoforms A and B were created. The characteristic ability of cancer cells to grow independently of anchorage to the surrounding solid matrix was measured by counting colony formation on soft agar for 8 to 14 days. Cell proliferation in response to a time course of progestin treatment was tested with flow cytometry. RESULTS: After treatment with a control vector without a progesterone receptor--encoding insert, no effect of progestin treatment on cell proliferation was found; after treatment with vectors encoding progesterone receptor isoform A or B, however, progestin treatment resulted in significant inhibition of cell growth. The anchorage-independent cell growth on soft agar assay showed that by 8 to 14 days the number of cell colonies was reduced by 50% relative to control preparations in the presence of progesterone receptor isoform A plus progestin (P <.0001, both Hec50 and KLE cell lines) and by 90% in the presence of progesterone receptor isoform B plus progestin (P <.0001, both Hec50 and KLE cell lines). Progestin treatment also resulted in a time-dependent reduction in cell proliferation as measured by flow cytometry. Although transfection with both progesterone receptor isoforms A and B reduced cell proliferation according to our assays, progesterone receptor isoform B caused a much more dramatic decrease in cell growth (P =.001, Hec50 cells; P <.0001, KLE cells). CONCLUSION: In poorly differentiated endometrial cancer cells that are resistant to progestin therapy, adenovirus-induced expressions of progesterone receptors A and B reestablish progestin control of endometrial cancer cell proliferation.

Blotting, Western↗
PubMed2001

Non-diabetic renal disease in patients with type 2 diabetes mellitus.

OBJECTIVES: A wide spectrum of non-diabetic renal diseases (NDRD) are reported to occur in patients with type 2 diabetes mellitus. However, the prevalence and nature of NDRD in type 2 diabetics is not widely documented in our country. Therefore, the objectives of this study were to analyse prevalence and spectrum of non-diabetic renal disease in type 2 diabetic patients. METHODS: Two hundred sixty type 2 diabetic with clinical renal diseases were screened for evidence of NDRD, between April 1997 to March 1999. Renal disease other than diabetic nephropathy was found in 32 (12.3%) patients. Their (male 23; female 9) age ranged between 35-72 (mean 54.15+/-10.3) years. The duration of diabetes was < 5 years in 14 (43.7%), between 5-9 years in 8 (25%) and > 10 years in 10 (31.2%) patients. RESULTS: The presenting clinical syndromes were : chronic renal failure 15 (47%), acute nephritic syndrome 6 (18.7%), nephrotic syndrome 5 (15.6%), acute renal failure 4 (12.5%) and rapidly progressive glomerulonephritis (RPGN) in 2 (6.2%) cases. Overall, incidence of glomerular (46.8%) and tubulo-interstitial lesions (53.2%) were almost equal in type 2 diabetes patients. The spectrum of non-diabetic renal diseases includes : primary isolated glomerulopathy 12 (37.5%); mesangioproliferative GN superimposed on diabetic glomerulosclerosis (DGS) in 3 (9.3%); acute tubulo-interstitial nephropathy (TIN) 4 (12.5%); chronic TIN 10 (31.25%) and three patients had chronic pyelonephritis. Diabetic retinopathy was absent in 22 (69%) cases where 10 (31%) patients had background diabetic retinopathy. None of the patients with non-diabetic glomerular disease had diabetic retinopathy, except two who had DGS in addition to mesangioproliferative GN on renal biopsy. The background diabetic retinopathy was seen in 47% of patients with TIN without clinical evidence of diabetic nephropathy. The recovery of renal function or clinical improvement was observed in 47% of patients with NDRD with institution of appropriate treatment. CONCLUSION: The prevalence of NDRD was 12.3% in our type 2 diabetic patients. Both non-diabetic glomerulopathy (47%) and tubulo-interstitial nephropathy (53%) can occur with nearly equal frequency in such patients. It is also gratifying to diagnose and treat NDRD in type 2 diabetics in selected cases.

Adult↗
PubMed2001

Acute renal failure complicating rifampicin therapy.

BACKGROUND: Since 1971, 55 case-reports of rifampicin-induced acute renal failure (ARF) have been published. Covic et al described 60 consecutive cases of rifampicin-induced ARF during a period of eight years (1987-1995) from Iasi Dialysis Centre, Romania. The systenic data on this condition are not available, in view of the anecdotal nature of the observation from our country. OBJECTIVE: The aims of study were to analyze clinical features, course and outcome of ARF complicating rifampicin therapy at our centre. METHODS: We retrospectively studied prevalence, clinical presentations and renal histology and outcome of 11 cases (eight males, three females, aged 42-72 years) who were referred to Nephrology Unit of University Hospital, Varanasi for acute renal failure following retreatment with rifampicin between period of 1994-1999. RESULTS: The gastrointestinal symptoms (abdominal pain, nausea and vomiting) and 'flu like' (fever, weakness and body ache) syndrome were the most frequent presenting features. The clinical signs of intravascular hemolysis were observed in four cases. The commonest laboratory findings included: Anaemia (7), leukocytosis (5), thrombocytopenia (3) and toxic hepatitis in (2) patients. Toxic hepatitis, hemolysis and ARF was seen in one patient in combination. The typical clinical features of allergic interstitial nephritis and acute tubular necrosis were seen in six and two patients respectively. Renal biopsy in three cases revealed; crescentic GN (1) and ATN in (2) patients. Acute renal failure complicating rifampicin accounted for 1.8% (11/607) of all ARF cases hospitalized in our centre during the study period. Renal function returned to normal in nine cases and one patient died on account of hepatic failure (toxic hepatitis). The patients with crescentic GN remained anuric and became dialysis dependent. Thus, clinical course of rifampicin induced ARF was favourable; with only one mortality, compared to a 18% mortality rate among all ARF patients. CONCLUSION: Acute renal failure complicating rifampicin therapy is not an uncommon condition, and typically occurs after reintroduction of rifampicin. The renal prognosis is usually favourable. Intermittent or interrupted therapy appears to be a significant risk factor for the development of acute renal failure.

Acute Kidney Injury↗
PubMed2001

Generation of monoclonal antibody CIBCgp185 against C-erbB-2 oncoprotein and its clinical evaluation.

The C-erbB-2 proto-oncogene encodes the production of a cell surface receptor protein, with tyrosine kinase activity. Over expression of this gene either due to gene amplification and/or increased transcription has been observed and has been correlated with poor prognosis in patients with Breast (10-33%) and ovarian (20-33%) cancers. The very low levels of expression of C-erbB-2 by normal tissues makes this receptor a potential target for diagnosis and therapy with Monoclonal antibodies raised against its extracellular domain. One such monoclonal antibody designated as CIBCgp185 of IgG2a isotype has been generated in our laboratory using BT474 breast carcinoma cell line as immunogen. This monoclonal antibody immunoprecipitated a 185 KD glycoprotein. The specificity of this antibody was confirmed by the formation of a single discrete band and positive reaction with BT474 antigen in Western blot and Dot blot respectively. Flowcytometric analysis performed using various cancer cell lines revealed that this Monoclonal antibody exhibited high binding affinity with BT474 and SKBR3 cells whichoverexpresses C-erbB-2. By immunoperoxidase test, this antibody stained specifically the tumor cell membrane in frozen tissue sections of breast and ovarian tumors indicating overexpression of the C-erbB-2 product. All these results well correlated with those obtained using a control antibody ICR12, an anti-C-erbB-2 antibody. These studies clearly indicate that Monoclonal antibody CIBCgp185 might prove useful to identify tumors with over expression of C-erbB-2 which are often associated with poor prognosis and early recurrence.

Animals↗
PubMed2000

Identification and purification of the 69-kDa intracellular protease involved in the proteolytic processing of the crystal delta-endotoxin of Bacillus thuringiensis subsp. tenebrionis.

The dynamics of appearance of intracellular proteases in relation to the synthesis of crystal delta-endotoxin was studied to identify the native intracellular protease(s) involved in the proteolytic processing of the 73-kDa protoxin of Bacillus thuringiensis subsp. tenebrionis. In vitro proteolytic activation of the 73-kDa protoxin indicated the possible role of 69-kDa protease in the proteolytic processing of 73-kDa protoxin. The purified 69-kDa protease was able to cause the proteolytic activation of the 73-kDa protoxin to 68-kDa toxin and this conversion was inhibited by ethylenediamine tetraacetic acid and 1,10-phenanthroline.

Bacillus thuringiensis↗
PubMed2000

Anemia and nutritional status of pre-school children in Kerala.

A study on the pattern of anemia and its relation to nutritional status and dietary habits was conducted among 3633 pre-school children of 108 selected anganwadi centers in rural areas of Kerala State during the period 1996 to 1998. Children were invited with their parent or guardian. Capillary blood was collected from each child and hemoglobin was estimated by cyanomethemoglobin method. Weight and height of children were taken for assessing their nutritional status. The information regarding their age, sex, clinical condition and dietary habits was collected in a performa through an interview. Chi-square test was used to assess the relationship of anemia to sex, dietary habits, and nutritional status. For multivariate analysis logistic regression model was employed. The prevalence of anemia was 11.4%. The percentage of anemic children among male and female children was 10.25 and 12.55 respectively and statistical analysis showed that female children were more susceptible to anemia. Normal nutritional status was seen among 46.7% of the children. When 187 (11.78%) of the mild undernourished children were anemic, the percentage anemic among the moderate undernourished children was 57 (16.37%). Moderate under nutrition and anemia showed a significant association. Anemia was reported among both vegetarians and non-vegetarians. Among 927 vegetarians, 86 (9.27%) were anemic and among 2,706 non-vegetarians, 328 (12.1%) were anemic. Dietary survey revealed that, consumption of iron sources, whether haem or non-haem, was below the recommended level. Undernutrition can be attributed as the major reason for nutritional anemia. Changes in eating behaviour could have potentially affected the iron bio-availability.

Anemia↗
PubMed2000

Influence of host plant on growth and reproduction of Aphis nerii and feeding and prey utilization of its predator Menochilus sexmaculatus.

Influence of different physiological stages (young, mature and senescent) of Calotropis gigantea leaves on growth and reproductive ability of A. nerii and feeding, prey utilization, fecundity and lipid content of its predator M. sexmaculatus were investigated. Increased reproductive period, total life span and reproduction of nymphs per female of A. nerii were observed when reared on mature leaves. This relative preference of A. nerii and maximum utilization of mature leaves as compared to other physiological aged leaves are mainly due to changes in the chemical composition such as protein, carbohydrate, lipid, amino acid, nitrogen and phenolic of C. gigantea. Further, aphids reared on mature leaves influenced its predator's (M. sexmaculatus) growth, prey utilization and reproductive performances. Fecundity and longevity were high, while developmental time of predator was shorter on mature leaves fed aphid. Maximum prey utilization and increased efficiency of ingested and digested food of predator was observed on mature leaves reared aphid. The results are interpreted and discussed in relation to plant aphid and predator interaction (tritrophic).

Animals↗
PubMed2000

Monoclonal antibody CIBCHTB1 defining an epitope on carcinoembryonic antigen (CEA).

Carcinoembryonic antigen (CEA) is an oncofoetal protein first identified by Gold and Freedman (1965) in colorectal cancer. It is a cell surface tumor marker which has been characterised as a heterogenous group of glycoproteins. It is also present in a variety of benign and non-neoplastic diseases like ulcerative colitis, Adenomatous polyp, Liver cirrhosis and other cancers like GI tract tumors, Cancer of the breast, lung, ovary, pancreas, prostate, hepatoma etc. Elevated CEA levels serve as clinical tool in the diagnosis, monitoring, detecting early any recurrence or metastasis and in prognostication for confirmed colorectal cancers. In order to develop an Enzyme Immuno Assay and immunocytochemical assay for CEA, an MAb designated as CIBCHTB1 has been generated using CEA isolated from a cell line HT115, human adenocarcinoma of the colon, as immunogen by the conventional Hybridoma technology. This MAb of IgG1 isotope was selected by screening of culture supernatents by ELISA and then by its high binding affinity with HT115 cells as revealed by flowcytometric analysis. By ABC method of immunocytochemical assay, this Ab exhibited strong staining of cells in frozen tissue sections of normal colon and malignant colorectal lesions and various other types of human cancers. This MAb has useful application to study the expression of CEA in human cancers. Serum CEA levels of patients with colorectal cancers and other CEA producing cancers and controls determined by EIA using this MAb were in good correlation with the results obtained using commercial kit. The diagnostic potential of this Mab in the management of colorectal cancers is discussed.

Adenocarcinoma↗
PubMed1999

Identification of the putative mannose 6-phosphate receptor protein (MPR 300) in the invertebrate unio.

In mammals, Mannose 6-phosphate receptor proteins (MPR 300 and MPR46) mediate transport of lysosomal enzymes to lysosomes. Both receptors have been found in non-mammalian vertebrates including fish. To investigate the presence of MPRs in invertebrates, MPR 300 protein was isolated from the mollusc unio by affinity chromatography. It was shown to exhibit biochemical and immunological properties similar to mammalian MPR 300.

Animals↗
PubMed1999

Endocrine cancer risks for women during the perimenopause and beyond.

Cancer and its link to reproductive hormones is an area of intense concern for our patients and has been the subject of much speculation. But if estrogen causes breast cancer, for example, most women would eventually develop the disease. We know this is not the case! Actually, estrogen and progesterone have been linked to a decrease as well as an increase in cancer, depending upon the type of tumor under investigation. The purpose of this manuscript is to review the data supporting those relationships.

Adult↗
PubMed1999

Nutrient absorption.

Interesting advances occurred recently in nutrient absorption. Kinetics of triacylglycerol appearance in endoplasmic reticulum, Golgi apparatus, and lymph support the hypothesis that endoplasmic reticulum-to-Golgi transport is rate-limiting for lipid absorption. Apolipoprotein B does not appear necessary for initial formation of chylomicron-sized lipid particles in the endoplasmic reticulum, but rather for their movement out of the endoplasmic reticulum and to the Golgi. If peptides are protected from luminal proteolysis by fatty acylation, or if a nonpeptide drug, acyclovir, is esterified with valine to enhance bioavailability, the peptides nevertheless are absorbed by peptide transporters. Experimental conditions needed to use human ileal mucosa for in vitro absorption studies are described. Intestinal mucosa contains leptin receptors, and leptin inhibits galactose absorption, suggesting a new site for leptin's modulation of body mass. The enhancer element for the apoB gene is located much farther from its structural gene in the intestine than in the liver.

Absorption↗
PubMed1999

Prechylomicron transport vesicle: isolation and partial characterization.

The intestine is able to regulate its output rate of chylomicrons, the major intestinal triacylglycerol (TG) transport vehicle. We have proposed that a vesicle, transporting the developing chylomicron from the endoplasmic reticulum (ER) to the Golgi, is the rate-limiting step in the process of TG transit through the enterocyte [Am. J. Physiol. 273 (Gastrointest. Liver Physiol. 36): G18-G30, 1997]. We wished to isolate and characterize this vesicle. The apical portion of rat intestinal cells were avulsed, and the mucosa was stirred in buffer. The supernatant was centrifuged in two different sucrose gradients, and the top 2.5 ml of the last gradient were collected and concentrated. Electron microscopy showed a 200-nm vesicle. The vesicle contained immunoidentifiable apolipoprotein (apo) B48 and apo A-IV but very little apo A-I, although apo A-I was present in the ER and Golgi. [3H]TG-loaded vesicles delivered [3H]TG to the Golgi but not the ER. Marker enzyme assays also indicate that the isolated fraction is different from the ER and Golgi fractions. We conclude that we have isolated a vesicle that is post-ER but pre-Golgi that vectorially transports TG to the Golgi.

Animals↗
PubMed1998

Selective down-regulation of progesterone receptor isoform B in poorly differentiated human endometrial cancer cells: implications for unopposed estrogen action.

The uterine endometrium responds to unopposed estrogen stimulation with rapid cell proliferation. Progesterone protects the endometrium against the hyperplastic effects of estradiol (E2) through progesterone receptors (PRs), of which two isoforms are expressed: human (h) PRA and PRB. hPRB has a longer NH2 terminus and may function differently from hPRA. Thus, the relative expression of hPRA:hPRB is likely to be important for the action of progesterone. We hypothesized that the hPRA:hPRB ratios may be abnormal in endometrial cancer, leading to a lack of normal progesterone protection against the growth-promoting effects of E2. To test this hypothesis, well-differentiated Ishikawa endometrial cancer cells were compared to poorly differentiated Hec50 and KLE cells. Reverse transcription-PCR was chosen as a sensitive method to detect transcripts for the two forms of PR. The relative expression of PR isoforms under hormonal stimulation was determined by Western blotting. Transient transfections of hPRA and hPRB into endometrial cells allowed the evaluation of the transcriptional activity of each isoform independently on reporter gene transcription under the control of a simple progesterone response element-containing promoter. The effect of coexpressing the estrogen receptor on PR expression was also studied. Ishikawa cells (well-differentiated) express both hPRA and hPRB. Both isoforms, but predominantly hPRB, are up-regulated by E2 and not by tamoxifen or the pure antiestrogen ICI 182,780. Hec50 and KLE cells (poorly differentiated) express only hPRA. No hPRB is present in the poorly differentiated cells, and it is not induced by estrogen receptor expression and/or estrogen treatment. In all cells, hPRB expression, whether endogenous or produced as a result of transfection, acts as a stronger transcription factor than hPRA on a simple progesterone-dependent promoter. We speculate that down-regulation of hPRB may predict for poorly differentiated endometrial cancers that do not respond to progestin therapy.

Blotting, Western↗
PubMed1998

Endogenous protease-activated 66-kDa toxin from Bacillus thuringiensis subsp. kurstaki active against Spodoptera littoralis.

The anti-lepidopteran toxin from sporulated Bacillus thuringiensis subsp. kurstaki cells, generated by the proteolytic action of endogenous protease(s) on the protoxin, was purified and studied to identify the effect of such proteolysis on the biochemical nature of the toxin. The active toxin was purified employing anion-exchange chromatography to absolute homogeneity, as indicated by SDS-PAGE and Western blotting. Antisera to the purified toxin (66 kDa) crossreacted with the protoxin (132 kDa) confirming its origin from protoxin. The purified toxin with a pI of 7.95 was derived from the N-terminal region of the protoxin (pI 7.6). Circular dichroism data revealed that the toxin has significant secondary structure and it undergoes pH dependent conformational change. Unlike the toxin generated by exogenous proteases such as trypsin, etc., the endogenous protease(s) activated toxin is highly lethal to a tolerant insect variety of the lepidopteran order, Spodoptera littoralis.

Amino Acids↗
PubMed1998

Effect of mometasone furoate on early and late phase inflammation in patients with seasonal allergic rhinitis.

BACKGROUND: Mometasone furoate is a potent glucocorticoid that can markedly inhibit proinflammatory Th2 cytokines in vitro. An aqueous nasal spray formulation has been shown to be clinically active in reducing the symptoms of perennial and seasonal allergic rhinitis. OBJECTIVE: To determine whether pretreatment with mometasone furoate 200 microg once daily decreases specific indices of early and late phase nasal inflammation compared with placebo. METHODS: A randomized, double-blind, placebo-controlled crossover study was conducted using nasal provocation with ragweed antigen in 21 patients with ragweed-induced allergic rhinitis out of the ragweed season; the treatment period was 2 weeks. Symptom scores, rhinoprobe cytology, and nasal lavage fluid were collected during early and late phase periods for nasal cytokines (interleukin, 1, 4, 5, 6, and 8) and leukotriene B4 determinations using ELISA and RIA. RESULTS: Mean nasal symptom scores and sneezing frequency were consistently lower with mometasone furoate compared with placebo. Treatment was associated with a statistically significant early phase (30-minute time point) reduction in nasal lavage histamine levels compared with placebo (14.3 versus 20.2 ng/mL, P = .02). Within-treatment comparisons suggested that mometasone furoate reduced the antigen-induced late-phase response for IL-6, IL-8, and eosinophils compared with pretreatment. There were similar, but smaller, changes seen in the placebo group for these measurements. There were no statistically significant changes following antigen challenge in IL-1, IL-4, IL-5, LTB4, or in other nasal cytology parameters. CONCLUSION: These results suggest that the clinical activity of mometasone furoate nasal spray in seasonal allergic rhinitis is likely due, in part, to a reduction in the levels of histamine in nasal secretions related to the early phase response, and reductions in IL-6, IL-8, and eosinophils during the late phase response.

Adult↗
PubMed1998

Analysis of 66 kDa toxin from Bacillus thuringiensis subsp. kurstaki reveals differential amino terminal processing of protoxin by endogenous protease(s).

The endogenous protease(s) activated crystal toxin from Bacillus thuringiensis subsp. kurstaki was purified and examined. The purified toxin was homogenous, as demonstrated by two-dimensional polyacrylamide gel electrophoresis and contained 1.38 mumoles neutral sugar and 9 nmoles sialic acid per mg protein amino terminal amino acid sequence data revealed that the toxin is a cleavage product of 132 kDa protoxin with glutamic acid-30 of the deduced amino acid sequence of the crystal protein (Schnepf, H.E., Wong, H.C. and Whiteley, H.R. (1985) J. Biol. Chem. 260: 6264-6272) at the amino terminus.

Amino Acid Sequence↗