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Biomedical subjects

S K Roy

Publications and source records attributed to S K Roy.

At least 55 records · Page 3Linked to original sources
PubMed2000

Requirement for follicle-stimulating hormone action in the formation of primordial follicles during perinatal ovarian development in the hamster.

Whereas FSH action is critical for the growth of preantral follicles, its role in the development of primordial follicles is controversial. The objective of the present study was to evaluate whether perinatal (fetal through early postnatal) FSH action is needed for the formation of primordial follicles, which first appear in the hamster ovary on the 7th to 8th day of postnatal life. A single dose of FSH-specific polyclonal antibody was injected into pregnant hamsters on the 12th, 13th, or 14th day of gestation and into newborn hamsters. Some of the antibody-exposed postnatal hamsters were injected with a single dose of equine CG (eCG) to check the reversibility of the antibody action. Ovaries were collected on D8pn or D12pn, and the percentage of primordial, primary, and secondary follicles was quantitated morphometrically. Ovaries of 8-day-old hamsters that were born to mothers treated with a single s.c. dose of the anti-FSH-antibody on day 12 of gestation had significantly reduced numbers of primordial follicles, compared with those treated with preimmune serum or saline (2.4% vs. 25%); however, the antibody inhibition was nearly completely reversed (approximately 18%) by a single injection of eCG on the first day of life. Delaying antibody treatment during late gestation caused a time-dependent block in granulosa cell differentiation, with a consequent proportional increase in the percentage of primordial follicles. This indicates that FSH-induction of primordial follicle development begins at a critical time of ovarian development. On the other hand, shortening the postnatal duration of eCG exposure reduced the degree of reversal, suggesting that prolonged perinatal FSH action is essential for developing the full gamut of primordial follicles. These results provide the first direct evidence that FSH action during fetal ovarian development is critical for the onset of primordial follicle formation.

Aging↗
PubMed2000

Bleomycin-induced chromosome damage in lymphocytes indicates inefficient DNA repair capacity in breast cancer families.

In vitro mutagen susceptibility has been observed as a predictor of cancer risk. To evaluate susceptibility to mutagen, we have studied the response to in vitro bleomycin (BLM) treatment in cultured peripheral blood lymphocytes (PBL) of 9 breast cancer families (BCFs). Eleven breast cancer patients (BCPs) and 36 healthy blood relatives (HBRs) from BCFs were included in the study. Data were compared with 22 healthy control women. The frequencies of chromosomal aberrations were evaluated after exposure to BLM in the last five hours. Mean frequency of BLM-induced chromosomal aberrations per cell (CA) observed among BCPs was significantly higher as compared to their HBRs as well as control subjects. Moreover, mean BLM-induced CA/cell value observed for HBRs was also significantly higher than that of control subjects. In comparison to controls, it was observed that there was four times more cancer risk in BCPs (OR=4.148, 95% CI=5.83-687.46) and 2.5 times more cancer risk in HBRs (OR=2.67, 95% CI=5.31-39.25). Lymphocytes from 90% of BCPs and 69% of HBRs were found to be sensitive to BLM (using a cutoff value = controls group mean + 1 SD). Thus, lymphocytes of BCPs and their HBRs were more sensitive to BLM exposure as compared to controls. Our finding indicated inefficient DNA repair capacity in BCFs. The HBRs in BCFs, having increased BLM-sensitivity, may be at higher risk to develop a similar cancer.

Adult↗
PubMed2000

Plasma and cerebrospinal fluid pharmacokinetics of O6-benzylguanine and analogues in nonhuman primates.

O6-Benzylguanine (BG) is a potent, specific inactivator of the DNA repair protein, O6-alkylguanine-DNA alkyltransferase, that enhances the sensitivity of tumor cell lines and tumor xenografts to chloroethylnitrosoureas. To search for BG analogues with greater penetration into the cerebrospinal fluid (CSF), we evaluated plasma and CSF pharmacokinetics of BG, 8-aza-O6-benzylguanine (8-azaBG), O6-benzyl-8-bromoguanine (8-BrBG), O6-benzyl-8-oxoguanine (8-oxoBG), O6-benzyl-8-trifluoromethylguanine (8-tfmBG), and O6-benzyl-2'-deoxyguanosine (B2dG) after i.v. administration of 200 mg/m2 of drug through an indwelling Ommaya reservoir in a nonhuman primate model. BG and its analogues were quantified in plasma and CSF using reverse-phase high-performance liquid chromatography assays. The plasma clearances of the four 8-substituted BG analogues were similar (0.04-0.06 l/h/kg), but half-lives ranged from <2 to >24 h. BG was converted to 8-oxoBG, an equally potent O6-alkylguanine-DNA alkyltransferase inactivator, and the elimination of 8-oxoBG was much slower than that of BG. As a result, the plasma area under the curve of 8-oxoBG was 3.5-fold greater than that of BG. B2dG was metabolized to BG and 8-oxoBG, but this pathway accounted for only 20% of B2dG elimination. The CSF penetration percentages (based on the ratio of AUC(CSF): AUCplasma) for BG, 8-azaBG, 8-oxoBG, 8-tfmBG, 8-BrBG, and B2dG were 3.2, 0.18, 4.1, 1.4, <0.3, and 2.0%, respectively. The CSF penetration of BG and its active metabolite 8-oxoBG is greater than the penetration of 8-azaBG, 8-BrBG, 8-tfmBG, and B2dG.

Animals↗
PubMed2000

Unusual presentation of schwannoma.

Schwannomas are slow growing benign tumours arising from the nerve sheath. Two cases of schwannoma arising from the vagus nerve are presented here. One case was found in a 6-year-old boy and another one in a 30-year-old man. In the first case the tumour was detected on the left side of the neck just below the angle of the mandible, and in the second case it was found on the lower part of the right side of the neck. Histopathology confirmed the diagnosis as first one to be of Antoni-A type and the second one to be of Antoni-B type. Both the tumours were excised and on follow-up the patients were doing well.

Adult↗
PubMed2000

Incidence of malignancy in microscopic haematuria: a study of 100 cases.

During June, 1998 to April, 2000, one hundred cases of microscopic haematuria were evaluated. All were symptomatic patient with age ranging from 24-68 years. 70 (70%) cases were male and 30 (30%) cases were female. Commonest presentation was dysurea 70 (70%). Urinary stone disease was the commonest cause found to be present in 25 (25%) cases. Malignant lesion was found in 16 (16%) cases of which bladder tumour was found in 10 (10%) cases.

Adult↗
PubMed1999

Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators' Collaborative Group.

OBJECTIVES: This study assessed the effects of zinc supplementation in the prevention of diarrhea and pneumonia with the use of a pooled analysis of randomized controlled trials in children in developing countries. STUDY DESIGN: Trials included were those that provided oral supplements containing at least one half of the United States Recommended Daily Allowance (RDA) of zinc in children <5 years old and evaluated the prevention of serious infectious morbidity through household visits. Analysis included 7 "continuous" trials providing 1 to 2 RDA of elemental zinc 5 to 7 times per week throughout the period of morbidity surveillance and 3 "short-course" trials providing 2 to 4 RDA daily for 2 weeks followed by 2 to 3 months of morbidity surveillance. The effects on diarrhea and pneumonia were analyzed overall and in subgroups defined by age, baseline plasma zinc concentration, nutritional status, and sex. The analysis used random effects hierarchical models to calculate odds ratios (OR) and 95% CIs. RESULTS: For the zinc-supplemented children compared with the control group in the continuous trials, the pooled ORs for diarrheal incidence and prevalence were 0.82 (95% CI 0.72 to 0.93) and 0.75 (95% CI 0.63 to 0.88), respectively. Zinc-supplemented children had an OR of 0.59 (95% CI 0.41 to 0.83) for pneumonia. No significant differences were seen in the effects of the zinc supplement between the subgroups examined for either diarrhea or pneumonia. In the short-course trials the OR for the effects of zinc on diarrheal incidence (OR 0.89, 95% CI 0.62 to 1.28) and prevalence (OR 0.66, 95% CI 0.52 to 0.83) and pneumonia incidence (OR 0.74, 95% CI 0.40 to 1.37) were similar to those in the continuous trials. CONCLUSIONS: Zinc supplementation in children in developing countries is associated with substantial reductions in the rates of diarrhea and pneumonia, the 2 leading causes of death in these settings.

Child↗
PubMed1999

Chromosomal aberrations in young cancer patients.

Spontaneous level of chromosomal aberrations (CA) is considered to be indicative of inherent cancer predisposition, which plays a major role in total cancer incidence. We have studied spontaneous CA levels in in vitro cultured peripheral blood lymphocytes of pediatric cancer patients (n = 77). Results were compared with those of control subjects (n = 72), including: age-matched controls; elder controls (minimum age 60 years); and healthy first-degree relatives (FDR) of pediatric cancer patients. Pediatric cancer patients showed the highest mean CA/cell value, which was statistically significant as compared to their age-matched counterparts, elder controls, and the FDRs. As compared to 7% of all the three control groups collectively, 32.4% of pediatric cancer patients showed > 0.1 mean CA/cell value. One of the FDRs with a very high frequency of CA developed cancer within three years. The results suggest that spontaneous levels of chromosomal aberrations may be used as one of the biomarkers for cancer predisposition study.

Adolescent↗
PubMed1999

Impact of zinc supplementation on subsequent growth and morbidity in Bangladeshi children with acute diarrhoea.

OBJECTIVE: To assess the impact of zinc supplementation during acute diarrhoea on subsequent growth and morbidity in malnourished young children. DESIGN: Double blind randomized controlled clinical trial SETTING: International Centre for Diarrhoeal Disease Research, Bangladesh. SUBJECTS: Sixty-five children aged 3-24 months with acute diarrhoea for less than 3 d. INTERVENTION: Either elemental zinc (20 mg/d) in a multivitamin syrup or multivitamin syrup alone divided in three divided daily doses for a period of two weeks. Children were followed up weekly at home to assess subsequent growth and morbidity for a period of eight weeks. MAIN OUTCOME MEASURES: Gain in length and body weight and reduction in diarrhoea and respiratory tract infection. RESULTS: During the follow-up, zinc supplemented children showed significantly greater cumulative length gain (18.9 mm vs 14.5 mm, P <0.03) and comparable body weight gain than the children of the control group. Subsequent length gain was not correlated with initial height in the zinc-supplemented group (r=-0.13), P = 0.5), but was significantly correlated in the control group (r = -0.6, P < 0.0007). Zinc-supplemented and stunted children (< or = 90% length for age n = 18) experienced significantly fewer episodes of diarrhoea (0.07 vs 0.6, P < 0.05) and respiratory illness (1.0 vs 2.4, P < 0.01) compared to the control group. The underweight children (< or = 71% weight/age n = 38) receiving zinc-supplementation also had fewer episodes of diarrhoea (0.4 vs 1.0, P<0.04) and shorter duration of diarrhoeal episodes (1.0 vs 3.0d, P<0.04) compared to their counterparts in the control group. CONCLUSION: These results suggest that a short course of zinc supplementation to malnourished children during acute diarrhoea reduces growth-faltering and diarrhoeal and respiratory morbidity during subsequent two months.

Acute Disease↗
PubMed1999

Purification and characterization of the 16-kDa heat-shock-responsive protein from the thermophilic cyanobacterium Synechococcus vulcanus, which is an alpha-crystallin-related, small heat shock protein.

A 16-kDa protein, one of the major proteins that accumulates upon heat-shock treatment in the thermophilic cyanobacterium Synechococcus vulcanus, was purified to apparent homogeneity. The N-terminal and internal amino acid sequences of the protein exhibited a homology to the alpha-crystallin-related, small heat shock proteins from other organisms. The protein was designated HspA. Size-exclusion chromatography and nondenaturing gel electrophoresis demonstrated that HspA formed a large homo-oligomer consisting of 24 subunits. It prevented the aggregation of porcine malic dehydrogenase at 45 degrees C and 50 degrees C and citrate synthase at 50 degrees C. The activity of the malic dehydrogenase, however, was not protected under these heat-shock conditions or reactivated after a shift in temperature from 45 or 50 degrees C to 21 degrees C. HspA was able to enhance the refolding of chemically denatured rabbit muscle lactate dehydrogenase in an ATP-independent manner. A homologue to the 16-kDa protein was also found to be induced upon heat-shock treatment in the mesophilic cyanobacterium Synechocystis sp. PCC 6803.

Amino Acid Sequence↗
PubMed1999

Activities of glucose metabolic enzymes in human preantral follicles: in vitro modulation by follicle-stimulating hormone, luteinizing hormone, epidermal growth factor, insulin-like growth factor I, and transforming growth factor beta1.

Modulation of glucose metabolic capacity of human preantral follicles in vitro by gonadotropins and intraovarian growth factors was evaluated by monitoring the activities of phosphofructokinase (PFK) and pyruvate kinase (PK), two regulatory enzymes of the glycolytic pathway, and malate dehydrogenase (MDH), a key mitochondrial enzyme of the Krebs cycle. Preantral follicles in classes 1 and 2 from premenopausal women were cultured separately in vitro in the absence or presence of FSH, LH, epidermal growth factor (EGF), insulin-like growth factor (IGF-I), or transforming growth factor beta1 (TGFbeta1) for 24 h. Mitochondrial fraction was separated from the cytosolic fraction, and both fractions were used for enzyme assays. FSH and LH significantly stimulated PFK and PK activities in class 1 and 2 follicles; however, a 170-fold increase in MDH activity was noted for class 2 follicles that were exposed to FSH. Although both EGF and TGFbeta1 stimulated glycolytic and Krebs cycle enzymes for class 1 preantral follicles, TGFbeta1 consistently stimulated the activities of both glycolytic enzymes more than that of EGF. IGF-I induced PK and MDH activities in class 1 follicles but negatively influenced PFK activity for class 1 follicles. In general, only gonadotropins consistently stimulated both glycolytic and Krebs cycle enzyme activities several-fold in class 2 follicles. These results suggest that gonadotropins and ovarian growth factors differentially influence follicular energy-producing capacity from glucose. Moreover, gonadotropins may either directly influence glucose metabolism in class 2 preantral follicles or do so indirectly through factors other than the well-known intraovarian growth factors. Because growth factors modulate granulosa cell mitosis and functionality, their role on energy production may be related to specific cellular activities.

Adult↗
PubMed1999

Development of primordial and prenatal follicles from undifferentiated somatic cells and oocytes in the hamster prenatal ovary in vitro: effect of insulin.

Fetal hamster ovaries were cultured for up to 16 days in the presence or absence of various dosages of insulin to evaluate the induction of folliculogenesis in vitro. In the absence of insulin, a few primordial follicle-like structures appeared by the 4th day, and distinct primary follicles (stage 1) appeared by the 12th day of culture. The organelles in the oocytes and adjacent granulosa cells developed along with follicular growth. Moreover, gap junctions between the oocyte and somatic cell plasma membrane also developed as early as 8 days in culture. In the presence of 0.2 microg/ml insulin, primary follicles developed after 8 days, and approximately 4% secondary follicles with 2-3 layers of granulosa cells appeared after 16 days of culture. However, higher dosages (> 0.2 microg/ml) of insulin retarded primary follicle formation and induced the formation of primordial follicles with larger oocytes. An increased number of larger oocytes with a few granulosa cells accumulated at the periphery of the ovary. The results indicate that although primordial and primary follicles can develop after 12 days in vitro in the absence of exogenous insulin, the latter is required for timely progression of follicular development through primary and secondary stages.

Animals↗
PubMed1998

Mitomycin C induced chromosomal aberrations in young cancer patients.

Mitomycin-C (MMC) induced Chromosomal aberration (CA) frequencies were studied in 48 h peripheral blood lymphocyte (PBL) cultures of untreated cancer patients of young age (maximum age 12 years, n=77). Control population (n=71) consisted of age-matched group (maximum age 12 years, n=21); elder controls (minimum age 60 years, n=19) and healthy first degree relatives, i.e., parents or siblings of the pediatric cancer patients (mean age 24.3 years, n=31) as they share their genome and environment. Induced CA levels were found to be significantly higher among pediatric cancer patients as compared to control groups. The age-matched and elder control groups showed comparable CA levels. The first degree relatives controls showed higher induced CA levels as compared to pediatric and elder control groups. The present results indicate that there are different degrees of mutagen sensitivity prevailing in normal population. This may be responsible for differential cancer proneness. High degree of mutagen sensitivity in cancer patients may also be playing a major role in cancer onset at an early age.

Adult↗
PubMed1998

Differences in in vivo acceptor specificity of two galactosyltransferases, the gmh3+ and gma12+ gene products from Schizosaccharomyces pombe.

In the fission yeast Schizosaccharomyces pombe, gmh1+, gmh2+ and gmh3+ genes encode alpha-1,2-galactosyltransferase homologues. In an in vitro galactosyltransferase assay, the gmh3+ gene product showed galactose transfer activity toward a-methyl-D-mannoside as an acceptor. The disruption of gma12+, the major galactosyltransferase gene [Chappell, T. G., Hajibagheri, M. A. N., Ayscough, K., Pierce, M. & Warren, G. (1994) Mol. Biol. Cell 5, 519-528], and of gmh3+ in S. pombe caused decreases in the total remaining galactosyltransferase activity and cell surface galactose content. Disruption of gma12+ and gmh3+ also caused an increase in electrophoretic mobility of acid phosphatase, indicating their involvement in the galactosylation of cell surface glycoproteins. The gmh3delta gma12delta double mutant cells had more severe galactose-less phenotypes than single gene mutant cells. HPLC analysis of O-linked mannoprotein oligosaccharides from wild-type and disrupted strains revealed that the gma12+ gene product is responsible for the galactosylation of O-linked oligosaccharide, whereas gmh3+ has no involvement in the process. In contrast, both the gmh3+ and gma12+ gene products are involved in the galactosylation of the N-linked core oligosaccharide Man9GlcNAc2. From these results, it is evident that there are some functional differences between the enzymes in the process of galactosylation. It appears that the gmh3+ gene product transfers galactose to N-linked oligosaccharide, while the gma12+ gene product transfers galactose to both N-linked and O-linked oligosaccharides.

Base Sequence↗
PubMed1998

O6-alkylguanine-DNA alkyltransferase inactivation by ester prodrugs of O6-benzylguanine derivatives and their rate of hydrolysis by cellular esterases.

To modulate the bioavailability and perhaps improve the tumor cell selectivity of O6-alkylguanine-DNA alkyltransferase (AGT) inactivators, pivaloyloxymethyl ester derivatives of O6-benzylguanine (BG) were synthesized and tested as AGT inactivators and as substrates for cellular esterases. The potential prodrugs examined were the 7- and 9-pivaloyloxymethyl derivatives of O6-benzylguanine (7- and 9-esterBG), and of 8-aza-O6-benzylguanine (8-aza-7-esterBG and 8-aza-9-esterBG) and the 9-pivaloyloxymethyl derivative of 8-bromo-O6-benzylguanine (8-bromo-9-esterBG). The benzylated purines were all potent inactivators of the pure AGT and of the AGT activity in HT29 cells and cell extracts. Each ester was at least 75 times less potent than the corresponding benzylated purine against the pure human AGT. In contrast, the activities of esters and their respective benzylated purine were similar in crude cell extracts and in intact cells. The increase in potency of esters in cellular extracts could be explained by a conversion of the respective prodrug to the more potent benzylated purine in the presence of cellular esterases. The apparent catalytic activity (Vmax/Km) of liver microsomal esterase for 8-azaBG ester prodrugs was 70-130 times greater than for BG prodrugs and 10-20 times greater than for 8-bromo-9-esterBG. Tumor cell hydrolysis of the esters varied considerably as a function of cell type and prodrug structure. These data suggest that these or related prodrugs may be advantageous for selective AGT inactivation in certain tumor types.

Animals↗
PubMed1998

Genetic predisposition to the metabolism of irinotecan (CPT-11). Role of uridine diphosphate glucuronosyltransferase isoform 1A1 in the glucuronidation of its active metabolite (SN-38) in human liver microsomes.

Irinotecan (CPT-11) is a promising antitumor agent, recently approved for use in patients with metastatic colorectal cancer. Its active metabolite, SN-38, is glucuronidated by hepatic uridine diphosphate glucuronosyltransferases (UGTs). The major dose-limiting toxicity of irinotecan therapy is diarrhea, which is believed to be secondary to the biliary excretion of SN-38, the extent of which is determined by SN-38 glucuronidation. The purpose of this study was to identify the specific isoform of UGT involved in SN-38 glucuronidation. In vitro glucuronidation of SN-38 was screened in hepatic microsomes from normal rats (n = 4), normal humans (n = 25), Gunn rats (n = 3), and patients (n = 4) with Crigler-Najjar type I (CN-I) syndrome. A wide intersubject variability in in vitro SN-38 glucuronide formation rates was found in humans. Gunn rats and CN-I patients lacked SN-38 glucuronidating activity, indicating the role of UGT1 isoform in SN-38 glucuronidation. A significant correlation was observed between SN-38 and bilirubin glucuronidation (r = 0.89; P = 0.001), whereas there was a poor relationship between para-nitrophenol and SN-38 glucuronidation (r = 0.08; P = 0.703). Intact SN-38 glucuronidation was observed only in HK293 cells transfected with the UGT1A1 isozyme. These results demonstrate that UGT1A1 is the isoform responsible for SN-38 glucuronidation. These findings indicate a genetic predisposition to the metabolism of irinotecan, suggesting that patients with low UGT1A1 activity, such as those with Gilbert's syndrome, may be at an increased risk for irinotecan toxicity.

Animals↗
PubMed1998

Functional evidence for UDP-galactose transporter in Saccharomyces cerevisiae through the in vivo galactosylation and in vitro transport assay.

The oligosaccharide profiles in glycoproteins are determined by a series of processing reactions catalyzed by Golgi glycosyltransferases and glycosidases. Recently in vivo galactose incorporation in Saccharomyces cerevisiae has been demonstrated through the expression of human beta-1,4-galactosyltransferase in an alg1 mutant, suggesting the presence of a UDP-galactose transporter in S. cerevisiae (Schwientek, T., Narimatsu, H., and Ernst, J. F. (1996) J. Biol. Chem. 271, 3398-3405). However, this is quite unexpected, because S. cerevisiae does not have galactose residues in its glycoproteins. To address this question we have constructed S. cerevisiae mnn1 mutant strains expressing Schizosaccharomyces pombe alpha-1,2-galactosyltransferase. The mnn1 mutant of S. cerevisiae provides endogenous acceptors for galactose transfer by the expressed alpha-1,2-galactosyltransferase. We present here three lines of evidences for the existence of UDP-galactose transporter in S. cerevisiae. (i) About 15-20% of the total transformed mnn1 cells grown in a galactose medium were stained with fluorescein isothiocyanate-conjugated alpha-galactose-specific lectin, indicating the presence of alpha-galactose residues on the cell surface. (ii) Galactomannan proteins can be precipitated with agarose-immobilized alpha-galactose-specific lectin from a whole cell lysate prepared from transformed mnn1 cells grown in a galactose medium. (iii) The presence of UDP-galactose transporter was demonstrated by direct transport assay. This transport in S. cerevisiae is dependent on time, temperature, and protein concentration and is inhibited by nucleotide monophosphate and Triton X-100. The overall UDP-galactose transport in S. cerevisiae is comparable with that in S. pombe, indicating a more or less similar reaction velocity, while the rate of GDP-mannose transport is higher in S. pombe than in S. cerevisiae.

Biological Transport↗
PubMed1998

Cytogenetic evaluation of 20 sporadic breast cancer patients and their first degree relatives.

Many genetic abnormalities disclosed even in somatic cells like peripheral blood lymphocytes may mark footprint(s) of malignancy(ies). The present cytogenetic study on peripheral blood lymphocytes of sporadic breast cancer patients (n = 20) and their first degree relatives (n = 39) reports abnormalities of chromosomes 16, 5, 12, and 17 respectively in 17.59%, 8.33%, 6.48%, and 5.57% cells of patients and 15.83%, 8.33%, 7.5%, and 5% cells of their first degree relatives. These common chromosomal abnormalities pave the way to assume why first degree relatives of sporadic breast cancer patients are at increased risk of developing the same or other malignancies.

Breast Neoplasms↗