Biomedical subjects

M Mandal

Publications and source records attributed to M Mandal.

At least 55 records · Page 3Linked to original sources

PubMed1997

Bcl-2 deregulation leads to inhibition of sodium butyrate-induced apoptosis in human colorectal carcinoma cells.

Epidemiological studies have linked dietary fiber to the prevention of human colorectal cancer and suggest that short chain fatty acids such as butyric acid, which is produced by fermentation of dietary fiber in the large intestine, may be an important mediator of the protective effects of fiber. We investigated the role of Bcl-2 deregulation on the sensitivity of colorectal carcinoma cells to undergo butyrate-induced apoptosis. Here we report an inverse relationship between the levels of Bcl-2 and the sensitivity of colorectal carcinoma cell lines to undergo apoptosis in response to butyrate. Overexpression of Bcl-2 in colorectal carcinoma DiFi cells resulted in suppression of butyrate-induced apoptosis and enhanced cell survival in response to butyrate. Butyrate-induced apoptosis was accompanied by inhibition of expression of a 30 kDa protein (p30, immunorecognized by anti-Bcl-2 mAb) and this cellular effect of butyrate was inhibited by Bcl-2 overexpression. These findings suggest that deregulation of Bcl-2 in human colorectal carcinoma cells confers resistance to induction of apoptosis by butyrate, a dietary micronutrient.

Apoptosis↗

PubMed1997

Physiological analysis to quantify training load in badminton.

OBJECTIVE: To estimate the training load of specific on court training regimens based on the magnitude of variation of heart rate-lactate response during specific training and to determine the magnitude of variation of biochemical parameters (urea, uric acid, and creatine phosphokinase (CPK)) 12 hours after the specific training programme so as to assess training stress. METHODS: The study was conducted on six national male badminton players. Maximum oxygen consumption (VO2), ventilation (VE), heart rate, and respiratory quotient were measured by a protocol of graded treadmill exercise. Twelve training sessions and 35 singles matches were analysed. Heart rate and blood lactate were monitored during technical training routines and match play. Fasting blood samples collected on two occasions--that is, during off season and 12 hours after specific training--were analysed for serum urea, uric acid, and CPK. RESULTS: Analysis of the on court training regimens showed lactate values of 8-10.5 mmol/l in different phases. The percentage of maximum heart rate ranged from 82% to 100%. Urea, uric acid, and CPK activity showed significant changes from (mean (SD)) 4.93 (0.75) mmol/l to 5.49 (0.84) mmol/l, 0.23 (0.04) to 0.33 (0.06) mmol/l, and 312 (211.8) to 363 (216.4) IU/l respectively. CONCLUSION: Maximum lactate reported in the literature ranges from 3-6 mmol/l. Comparatively high lactate values and high percentage of maximum heart rate found in on court training show a considerable stress on muscular and cardiovascular system. The training load needs appropriate monitoring to avoid over-training. Workouts that are too intensive may interfere with coordination, a factor that is important in sports requiring highly technical skill such as badminton.

Adult↗

PubMed1996

Bcl-2 prevents CD95 (Fas/APO-1)-induced degradation of lamin B and poly(ADP-ribose) polymerase and restores the NF-kappaB signaling pathway.

In the study presented here, we investigated the possible interactions between CD95 (Fas/APO-1) and Bcl-2 by studying the effects of Bcl-2 on the modulation of cellular pathways activated by CD95 using HeLa cells as a model system. We report that stable expression of Bcl-2 in HeLa cells is associated with multiple phenotypic changes. Treatment of HeLa cells with anti-CD95 monoclonal antibody (mAb) resulted in preferential degradation of lamin B compared with lamins A and C. Significant lamin B degradation was detected as early as 1 h after anti-CD95 mAb treatment. In contrast, lamins A and C as well as actin remained unchanged until 4 h after treatment with anti-CD95 mAb, a time point that correlated with the period of DNA fragmentation. These results indicate that selective degradation of lamin B is an early cellular event in response to activation of the CD95 pathway and that it precedes DNA fragmentation. Overexpression of Bcl-2 resulted in prevention of lamin B degradation and DNA fragmentation into oligonucleosome fragments in response to the apoptotic signal by anti-CD95 mAb. In addition, in Bcl-2-overexpressing cells that were protected against apoptosis, anti-CD95 mAb-induced cleavage of poly(ADP-ribose) polymerase was completely blocked. Overexpression of Bcl-2 also resulted in restoration of the CD95-mediated signaling pathway involving activation of the transcription factor NF-kappaB (p50/RelA). These findings suggest that Bcl-2 prevents apoptosis in part by preventing the degradation of major nuclear polypeptides such as lamin B and poly(ADP-ribose) polymerase. In addition, our results demonstrate that CD95-mediated signaling involves activation of NF-kappaB (p50/RelA).

Apoptosis↗

PubMed1996

Cell cycle-dependent modulation of telomerase activity in tumor cells.

Telomerase is a ribonucleoprotein complex that is thought to add telomeric repeats onto the ends of chromosomes during the replicative phase of the cell cycle. We tested this hypothesis by arresting human tumor cell lines at different stages of the cell cycle. Induction of quiescence by serum deprivation did not affect telomerase activity. Cells arrested at the G1/S phase of the cell cycle showed similar levels of telomerase to asynchronous cultures; progression through the S phase was associated with increased telomerase activity. The highest level of telomerase activity was detected in S-phase cells. In contrast, cells arrested at G2/M phase of the cell cycle were almost devoid of telomerase activity. Diverse cell cycle blockers, including transforming growth factor beta1 and cytotoxic agents, also caused inhibition of telomerase activity. These results establish a direct link between telomerase activity and progression through the cell cycle.

Antineoplastic Agents↗

PubMed1996

NDF induces expression of a novel 46 kD protein in estrogen receptor positive breast cancer cells.

Most human breast tumors start as estrogen-dependent, but during the course of the disease become refractory to hormone therapy. The transition of breast tumors from estrogen dependent to independent behavior may be regulated by autocrine and/or paracrine growth factor(s) that are independent of the estrogen receptor (ER). We have investigated the role(s) of NDF (neu-differentiation factor) in the biology of estrogen positive breast cancer cells by using MCF-7 cells as a model system. Treatment of MCF-7 cells with human recombinant NDF-beta 2 (NDF) inhibited the ER expression by 70% and this was associated with growth stimulation in an estrogen-independent manner. To explore the mechanism(s) of action of NDF in MCF-7 cells, we examined the expression of NDF-inducible gene products. We report here that NDF stimulated the levels of expression of a 46 kD protein (p46) (in addition to few minor proteins) in ER positive breast cancer cells including MCF-7, T-47-D, and ZR-75-R cells but not in ER negative breast cancer cells including MDA-231, SK-BR-3, and MDA-468 cells. This effect of NDF was due to induction in the rate of synthesis of new p46. The observed NDF-mediated induction of p46 expression was specific as there was no such effect by epidermal growth factor or 17-beta-estradiol, and inclusion of actinomycin D partially inhibited the p46 induction elicited by NDF. NDF-inducible stimulation of p46 expression was an early event (2-6 h) which preceded the period of down-regulation of ER expression by NDF. These results support the existence of NDF-responsive specific cellular pathway(s) that may regulate ER, and these interactions could play a role(s) in hormone-independence of ER positive breast cancer cells.

Gene Expression Regulation, Neoplastic↗

PubMed1996

A study of physiological responses during match play in Indian national kabaddi players.

OBJECTIVE: To determine the physical and physiological profile of kabaddi players and the physiological demands of playing a kabaddi match. METHODS: Maximum aerobic capacity (VO2max), maximum ventilation (VEmax), O2 pulse, respiratory equivalent (RE), maximum heart rate, and O2 debt were assessed on 16 players. The somatotype of the players was calculated by the Health and Carter method. Heart rate was monitored during a selection trial match on eight players who represented India in the Asian Games, 1994. From the playing heart rate, oxygen consumption (VO2) was computed through a heart rate v VO2 regression equation. Maximum lactate was evaluated from the blood samples collected at the end of the match. RESULTS: The average heart rate and oxygen consumption during the match were 146.5 (SD 9.25) beats min-1 and 2.25(0.59) litre min-1 respectively. During raiding the maximum heart rate attained varied from 162.4(11.3) to 177.4(4.2) beats min-1. Out of 40 min of match play a raider raided on average on 8.13(2.03) occasions. The average time per raid was 20.8(6.26) s. The match heart rate and oxygen consumption was 72.3-83.3% of the maximum heart rate, and 43.5-70.5% of VO2max respectively. Maximum lactate at the end of the match was 6.13(2.53) mmol litre-1. Kabaddi players had the somatotype of 2.68-4.71-1.83, with absolute back strength of 175.0 kg. VO2max and O2 debt were 3.59(0.36) litre min-1 [47.82(3.68) ml kg-1 min-1] and 5.3(1.85) litres (70 ml kg-1) respectively. CONCLUSIONS: Kabaddi is an intermittent sport. The rest pause during the game is sufficient for recovery. During raiding the main source of energy is anaerobic.

Adult↗

PubMed1996

Bcl-2 expression regulates sodium butyrate-induced apoptosis in human MCF-7 breast cancer cells.

Sodium butyrate (butyrate) is a potent growth inhibitor and differentiating agent for many cell types, including breast cancer cells. Programmed cell death, or apoptosis, is a physiological mechanism of cell death that is dependent on both preexisting proteins and de novo protein synthesis. In the studies presented here, we investigated the role of apoptosis in the growth regulation of human MCF-7 breast cancer cells by sodium butyrate. We report that butyrate treatment of breast cancer MCF-7 cells causes a nonreversible growth inhibition by inducing apoptosis in a time- and dose-dependent manner. Treatment of MCF-7 cells for as little as 12 h with butyrate caused a 5.6-fold induction in apoptotic cell death, which continued to increase up to 27-fold by 48 h treatment. The butyrate-induced apoptosis in MCF-7 cells was closely linked with the down-regulation of expression of Bcl-2 mRNA and Bcl-2 protein, a gene product known to be involved in the regulation of apoptosis in mammalian cells. The observed relationship between the down-regulation of Bcl-2 and induction of apoptosis was not causal because stable overexpression of Bcl-2 resulted in protection of MCF-7 cells from the cytotoxic morphological changes and growth-inhibitory effects of butyrate (15% growth inhibition compared to 60% growth inhibition in the parental cells). In addition, Bcl-2-overexpressing MCF-7 cells exhibited a significant suppression in butyrate-induced stimulation of apoptosis (5-fold increase in apoptosis compared to 27-fold in parental MCF-7 cells). These findings demonstrate that the levels of Bcl-2 expression regulate the butyrate-induced apoptosis in breast cancer cells and that butyrate may potentially be useful in sensitizing the breast cancer cells to chemotherapy-induced apoptosis.

Apoptosis↗

PubMed1996

Overexpression of HER2 modulates bcl-2, bcl-XL, and tamoxifen-induced apoptosis in human MCF-7 breast cancer cells.

Overexpression of HER2 in estrogen receptor (ER)-positive human breast tumors has been associated with resistance to endocrine therapy. Here we investigated the effects of HER2 on expression of apoptotic pathways and modulation of tamoxifen-induced apoptosis in ER-positive MCF-7 breast cancer cells. We report that HER2 overexpression in MCF-7 cells is accompanied by up-regulation of antiapoptotic Bcl-2 and Bcl-XL proteins and suppression of tamoxifen-induced apoptosis. In addition, human tumor cell lines that are both ER positive and overexpress HER2 also express enhanced levels of Bcl-2 compared to cells that are either ER positive or overexpress HER2 alone. Our findings suggest that possible deregulation of antiapoptotic Bcl-2 and Bcl-XL may be associated with the enhanced survival of HER2-overexpressing and ER-positive breast cancer cells treated with antiestrogens.

Apoptosis↗

PubMed1995

Purification and characterization of a pregnancy-associated protein: TJ6s.

PROBLEM: Characterization of the soluble form of a novel protein, TJ6 (TJ6s) with immune suppressive activity from murine fetoplacental units. METHOD: Preferential ammonium sulfate precipitation, gel filtration and ion-exchange chromatography were employed to purify the protein TJ6s from murine fetoplacental units using an anti-peptide antibody as a detection tool. Biological activity of the purified protein was studied in lymphocyte proliferation assays. RESULTS: Purified TJ6s has a M(r) of approximately 18 kDa as evidenced by SDS-PAGE in both reducing and non reducing conditions. It exerted a strong anti-proliferative activity in both anti-CD3 and Con A proliferation lymphocyte proliferation assays but not in a PHA assay, suggesting that the anti-proliferative effects on T cells are exerted only on cells specifically activated directly through T cell receptor complex. CONCLUSION: The results indicate that TJ6s is a novel anti-proliferative protein that has many of the characteristics that are considered necessary for survival of the fetal allograft.

Amino Acid Sequence↗

PubMed1993

Neutralization of pathophysiological manifestations of Russell's viper envenoming by antivenom raised against gamma-irradiated toxoid.

Rabbits were immunized against gamma-irradiated (100 krads) Russell's viper venom toxoid adsorbed to aluminium phosphate gel. The antivenom (0.1 ml) neutralized 5 LD50, 8 minimum hemorrhagic doses (MHD) and 14 minimum necrotic doses (MND) of venom. The coagulant and protease activities of the viper venom were neutralized more effectively than phospholipase A activity, by the toxoid antivenom.

Animals↗

PubMed1992

Neutralization potency of Russell's viper venom toxoid antivenom, as compared with standard antivenom.

Rabbits were immunized with gamma (gamma) irradiated Russell's viper venom toxoid, adsorbed to aluminium phosphate adjuvant. Antibody (raised against toxoid inoculation) titer was compared to a commercial antivenom on the basis of its ability to neutralize hemorrhagic, necrotic and lethal effects of viper venom. Toxoid immunization (on day 0, 15 and 30) produced antivenom which showed approximately one-third antilethal, half antihemorrhagic and antinecrotic titers as compared to those of the commercial hyperimmunized, concentrated horse antivenom.

Animals↗

PubMed1992

Epidemiology of snake bite in the district of Burdwan, West Bengal.

An epidemiological field survey on snake bite was conducted on 26 randomly selected villages with a population of 18,892 in the district of Burdwan, West Bengal to assess the magnitude of the problem in a decade (1980-1989). Total number of snake bite, number of presumably poisonous snake bite and deaths due to snake bite poisoning were 307, 48 and 31 respectively. The death rate among snake bite victims was 10.09%. Males (54.72%) were bitten more than females (45.23%) and highest incidence of snake bite was found in the age group of 21-30 years and during the months of July and August. Majority of the snake bites (53%) were encountered in the lower extremities. Among the snake bite patients 201 (65.47% went to the traditional healers (ozhas) and 68 (22.14%) persons received hospital treatment, while 12 (3.09%) people neither went to the ozhas nor to hospital and 26 (8.46%) persons went to hospital after consulting the ozhas. If the present data are extrapolated for the total population of the district, average number of snake bite and death per year would be 7,857 (0.16%) and 793 (0.016%) respectively. Deaths due to snake bite per 100,000 population varied from 5.28 to 31.75 (average 16.4) over 10 years.

Adolescent↗

PubMed1991