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Biomedical subjects

M Basu

Publications and source records attributed to M Basu.

At least 19 recordsLinked to original sources
PubMed2005

Dosimetry parameters of BARC OcuProsta I-125 seed source.

A new model of 125I seed source, named OcuProsta seed, was designed and fabricated by Radiopharmaceuticals Division of Bhabha Atomic Research Centre for ophthalmic and interstitial applications. AAPM TG 43 recommended dosimetry parameters for this seed source were determined experimentally using TLD as well as by Monte Carlo (MC) simulation. Measured and MC calculated values of the dose rate constant (DRC) are 0.95 +/- 0.065 cGyh(-1)U(-1) and 0.972 +/- 0.005 cGyh(-1)U(-1), respectively. The mean of measured and calculated DRC (lambda = 0.96 cGyh(-1)U(-1)) was recommended for the clinical dosimetry of OcuProsta seed. Measured and MC calculated radial dose function, g(r), anisotropy function, F(r,theta), anisotropy factor and anisotropy constants are also found to be in good agreement to each other. Dosimetry parameters of OcuProsta seed were compared with the published values of similar in-design 125I seed sources. The DRC of BARC OcuProsta seed is very close to Amersham 6711 seed and is also comparable to the DRC of Best model 2301, Syncor PharmaSeed and Isotron selectSeed within the uncertainty of measurement/calculation. The g(r) of OcuProsta seed shows a difference of up to 10% in comparison to the g(r) values of the similar in-design seed sources. The values of anisotropy function of OcuProsta are 7-13% different from the anisotropy function of Amersham 6711 and Syncor PharmaSeed. The anisotropy constant of OcuProsta is close to Amersham 6711 seed while it is about 9% smaller than the anisotropy constant of Best model 2301 and Synchor PharmaSeed.

Algorithms↗
PubMed2003

Bony fragments in the uterus: an association with secondary subfertility.

Bone within the uterine cavity is an unusual finding in women with secondary subfertility, and is usually associated with a past history of termination of pregnancy. The etiology is unknown, but theories include retained fetal bone and osseous metaplasia of endometrial tissue. We describe the cases of three subfertility patients, all with a history of surgical termination of pregnancy. Each patient underwent a hysteroscopy after highly echogenic foci were seen in the uterus on transvaginal ultrasound examination. During hysteroscopy, several coral-like bony fragments were seen and removed by sharp curettage. On histological examination, these fragments were found to be mature, necrotic bone. This case report confirms the importance of routine baseline evaluation of the endometrium in subfertile women with a history of termination of pregnancy.

Abortion, Induced↗
PubMed2002

A new method of colorimetric assay of beta-lactamase suitable for estimation of beta-lactamase inhibition in crude microbial culture filtrates.

A simple procedure is described for the rapid assay of beta-lactamases suitable for use in the quantitation of beta-lactamase inhibition in crude culture filtrates of soil microbes. The proposed method is based on measuring the blue reaction product (lambda max 750 nm) formed during reduction of phosphomolybdic acid with reducing products generated from beta-lactam hydrolysis and is not influenced significantly by the metabolites of microbial culture filtrates which often interfere with conventional beta-lactamase assay techniques.

Actinobacteria↗
PubMed2002

Glucocorticoids as prophylaxis against acute mountain sickness.

OBJECTIVE: Acute mountain sickness (AMS) characterized by presence of symptoms including headache, nausea, excessive fatigue, loss of appetite, irritability and insomnia is a major impediment to work performance in human subjects who are rapidly inducted to high altitude (HA) during the initial phase of induction. The present study aims at to evaluate the efficacy of prophylactic administration of low dose glucocorticoids in prevention of AMS in normal healthy men who are inducted to HA by air. DESIGN: Fifty healthy men were randomly divided into five groups of 10 each. Group I received prednisolone (Pred) 10 mg, Group II Pred 20 mg, Group III Pred 40 mg, Group IV dexamethasone 0.5 mg, Group V received placebo once a day in the morning for 2 days at sea level (SL) and for 3 days on arrival at an altitude of 3450 m by air. MEASUREMENTS: The severity of AMS was assessed using Lake Louise AMS scoring system. Physiological parameters like blood pressure, respiratory rate, peripheral blood O2 saturation and heart rate were measured at sea level and on arrival at HA. Circulatory levels of cortisol and adrenocorticotropic hormone (ACTH) were measured by radioimmunoassay (RIA) and immunoradiometreic assay (IRMA), respectively. RESULTS: In the placebo group, significant AMS could be detected at 12 h of arrival at HA, peaked by day 1 or 2 of stay and started declining thereafter. As compared to the placebo group, the steroid treated groups showed a significant (P < 0.01) reduction in daily AMS score. When compared with prednisolone 10 mg, 40 mg and dexamethasone groups, the prednisolone 20 mg group showed an optimal response in reduction of AMS symptoms. The O2 saturation showed a significant decline (P < 0.001) on arrival at HA, but the pattern of O2 saturation in placebo and glucocorticoid groups was identical. Similarly, the rise in heart rate and blood pressure and on day 3 of stay at HA was similar in placebo and glucocorticoid-treated groups. An increase in plasma cortisol in placebo group was observed on day 3 of stay at HA and continued to rise till day 8 of observations. The cortisol levels in Pred 10 mg and Pred 20 mg groups on day 1 and 3 of arrival at HA were not significantly different than the SL post-treatment values but were found to be significantly higher on day 8 of stay. Plasma cortisol in Pred 40 mg and dexamethasone groups was significantly lower (P < 0.01) on day 1 and 3 of stay but showed an increase by day 8 of stay. The ACTH levels were increased at HA in placebo group but did not show any significant change till day 3 of stay in steroid treated subjects and were found to be higher in all groups on day 8 of observations. CONCLUSION: These observations suggest that administration of low-dose glucocorticoids can curtail acute mountain sickness significantly without influencing the normal adreno cortical response to hypoxia.

Acute Disease↗
PubMed2002

Hypothalamic-pituitary-adrenal axis following glucocorticoid prophylaxis against acute mountain sickness.

The pituitary-adrenocortical and adrenomedullary response to high altitude (HA) stress was studied following daily single dose administration of prednisolone as a prophylaxis against altitude-induced acute mountain sickness (AMS). Forty healthy men, randomly divided into two groups of twenty, received placebo or prednisolone 20 mg once a day at 08.00 h for two days prior to induction to HA and during an initial three days stay at an altitude of 3450 m. The AMS score and circulatory levels of ACTH, cortisol, epinephrine and norepinephrine were measured at sea level (SL) and during residency at HA. The sensitivity of the hypothalamic-pituitary-adrenal axis in subjects receiving prednisolone therapy was evaluated at SL and on day four of stay at HA. Administration of prednisolone significantly (p < 0.01) decreased the severity of AMS in all the subjects. The steroid dose used did not inhibit endogenous secretion of ACTH, cortisol, epinephrine or norepinephrine, as HA response to adrenocortical and adrenomedullary hormones was identical in placebo and prednisolone treated subjects. The integrity of the hypothalamic-pituitary-adrenal axis was maintained well in subjects receiving low dose prednisolone therapy. These observations suggest that short-term administration of prednisolone is able to curtail AMS without causing suppression of the hypothalamic-pituitary-adrenal axis.

Adrenal Glands↗
PubMed2001

Mechanisms of hormonal carcinogenesis in the p53+/- hemizygous knockout mouse: studies with diethylstilbestrol.

The 2-year rodent bioassay has long had a central role in determining whether a compound is carcinogenic. It has recently been suggested that the use of 6-month studies in transgenic mice could reduce costs and animal numbers, without impairing the validity of cancer risk assessment. The p53+/- hemizygous knockout mouse model is phenotypically stable and develops tumors during the 6-month study period only in response to chemical and physical stimuli, showing a high concordance with genotoxic rodent carcinogens. We treated p53+/- mice and wild-type parent strain (C57BL/6J) animals with diethylstilbestrol (DES). 500 micromol/kg i.p. for 4 days. Following sacrifice, DNA was extracted from various tissues and adducts measured by a modified monophosphate version of the 32P-postlabelling assay. Major DES adducts were detected in the liver DNA of DES-treated wild-type mice at a level of 118.7+/-17.0 (mean +/- SD relative adduct level [RAL]/10(10) nucleotides) compared with 207.7+/-36.4 in p53+/- mice. No such adducts were detected in vehicle-treated animals. Total adduct levels, including endogenous I-compound adducts, in wild-type mice were 192.4+/-17.5 and 311.5+/-58.6 in p53+/- animals. These data support the hypothesis that deficient p53-dependent global genomic repair of DES adducts in p53+/- mice may result in the persistence of exogenous and endogenous DNA adducts that could contribute to earlier carcinogenicity in this model. We also prepared hepatic microsomes from male and female p53+/- and wild-type mice exposed to DES or vehicle. Western blot analysis demonstrated modestly higher basal levels of various cytochrome P450 (CYP) enzymes in the untreated p53+/- mice compared to the wild-type mice. Furthermore, P450 levels were higher in female DES-treated p53+/- mice compared to treated wild-type mice. For the p53+/- knockout mice to be used with contidence in drug safety studies, a further understanding of the metabolic capacity of these animals is needed.

Animal Testing Alternatives↗
PubMed2001

Effect of selenomethionine on N-methylnitronitrosoguanidine-induced colonic aberrant crypt foci in rats.

An association between low selenium intake and the incidence or prevalence of cancers is well known. Selenium in the form of selenomethionine supplemented in drinking water has been found to be highly effective in reducing tumour incidence and preneoplastic foci during the development of hepatocarcinogenesis in rats in our previous studies. Here, an attempt has been made to investigate whether the dose and form of selenium found to be effective during hepatocarcinogenesis is equally effective in N-methylnitronitrosoguanidine-induced colorectal carcinogenesis in terms of antioxidant defence enzyme systems, DNA chain breaks and incidences of aberrant crypt foci. Treatment with selenomethionine either on initiation or on selection/promotion, or during the entire experiment showed that selenomethionine was most effective in regulating the cellular antioxidant defence systems, DNA chain break control and reducing aberrant crypt foci in the colorectal tissues of rats. Our results also confirm that selenium is particularly effective in limiting the action of the carcinogen during the initiation phase of this colorectal carcinogenesis, just as we found with hepatocarcinogenesis in our previous studies.

Animals↗
PubMed2000

Combined supplementation of vanadium and 1alpha,25-dihydroxyvitamin D(3) inhibit diethylnitrosamine-induced rat liver carcinogenesis.

A combination of a differentiation-inducing agent like 1alpha, 25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] with a compound that blocks entry of calcium into cells like vanadium (V) may offer a new approach to differentiation therapy and address the problem of hypercalcemia. Initiation of hepatocarcinogenesis was performed by a single intraperitoneal injection of diethylnitrosamine (DEN) (200 mg/kg b.wt.) in male Sprague-Dawley rats. Supplementation of V, 1, 25(OH)(2)D(3), or both V and 1,25(OH)(2)D(3) were started 4 weeks prior to DEN injection and continued thereafter till 20th week. It was observed that supplementation of V (0.5 ppm) in drinking water ad libitum or 1,25(OH)(2)D(3) (3 microg/ml propylene glycol) per os twice weekly for the entire period of the experiment significantly reduces the number and size of hyperplastic nodules while the combination treatment offered an additive effect in reducing it to 37.5% from 83.3%. V-1,25(OH)(2)D(3) combination was also effective in elevating the level of hepatic microsomal cytochrome P-450 (Cyt. P-450) (P<0.001). Moreover, A significant reduced level of cytosolic glutathione (GSH) (P<0.001) and glutathione S-transferase (GST) (P<0.001) activity as well as reduction in the appearance of gamma-glutamyltranspeptidase (GGT)-positive foci (P<0.001) as compared to carcinogen control were observed in V plus 1, 25(OH)(2)D(3) treated group. These results suggest that V may be useful in combination with 1,25(OH)(2)D(3) in the inhibition of experimental rat hepatocarcinogenesis.

Animals↗
PubMed2000

Factors on the third chromosome affect the level of cyp6a2 and cyp6a8 expression in Drosophila melanogaster.

The expression of two second chromosome-linked cytochrome P450 genes, Cyp6a2 and Cyp6a8, of Drosophila melanogaster was measured in various strains. Six different strains, including ry(506) and 91-C, showed low or undetectable levels of CYP6A2 and CYP6A8 mRNAs, suggesting that low expression is the wild-type phenotype of Cyp6a2 and Cyp6a8 genes. In the 91-R and MHIII-D23 strains, however, both these genes are overexpressed. In order to examine the genetic basis of Cyp6a2 and Cyp6a8 expression, CYP6A2 and CYP6A8 RNA levels were measured in the F1 hybrids of overproducer (91-R and MHIII-D23) and underproducer (ry(506) and 91-C) strains. Results showed that the total amounts of CYP6A2 and CYP6A8 mRNAs in the F1 hybrids were lower than half the amounts of these RNAs found in the overproducer parental strains. This suggested that the underproducer strains carry loci which downregulate Cyp6a2 and Cyp6a8 gene expression. To determine the chromosome linkage of these loci, several stocks homozygous for the second chromosome of overproducer 91-R strain and, therefore, homozygous for the Cyp6a2-91R and Cyp6a8-91R alleles were synthesized. The third chromosomes in all these stocks were from the underproducer ry(506) strain. The levels of expression of both Cyp6a2-91R and Cyp6a8-91R genes in these three stocks were significantly lower than that observed in the 91-R strain. One of these stocks, named iso-2, showing reduced expression, was used to synthesize two new isogenic stocks by resubstituting the third chromosome of ry(506) origin with third chromosomes of the 91-R strain. Expression of both Cyp6a2-91R and Cyp6a8-91R alleles was found to be much higher in these two resubstituted isogenic stocks than in the progenitor iso-2 stock. Taken together, these results suggest that the second chromosome-linked Cyp6a2 and Cypa8 genes are regulated by loci present on the third chromosome, and the wild-type function of these loci is to repress these two Cyp genes. The data also suggest that Cyp6a2 and Cyp6a8 overexpression in the 91-R and MHIII-D23 strains is more likely due to mutation in the repressor locus (or loci) rather than in the cis-regulatory sequences of the Cyp6a2 and Cyp6a8 genes.

Alleles↗
PubMed2000

Beta-carotene prolongs survival, decreases lipid peroxidation and enhances glutathione status in transplantable murine lymphoma.

Carotenoids of dietary origin have recently been the subject of renewed research interest because of epidemiological evidence indicating an inverse relationship between intake of carotenoids-rich plant substances and risk of certain cancers. This study was attempted to understand the biological actions of dietary beta-carotene (BC) on Dalton's lymphoma (DL), a rapidly proliferating transplantable tumor, in effecting the survival of the lymphoma-bearing mice. The glutathione (GSH) level and the extent of lipid peroxidation in the liver, kidney and brain were monitored in BC-treated (100 mg/kg food) mice transplanted with DL. These markers showed substantial alterations during the whole length of tumor progression in lymphoma-bearing mice without BC supplementation. When treated with BC, both malondialdehyde contents (evidence of lipid peroxidation) and the GSH levels in different organs were found to be closer to normal values in the initial period of tumor progression. BC-mediated protection against lipid peroxidation was maximally found to be in hepatic tissue throughout the study following DL transplantation. This was fairly reflected in the higher BC concentration in hepatic tissue of BC-treated lymphoma group compared to untreated lymphoma control. Significantly higher survival time (51-55 days) was observed in BC-treated animals in comparison to their untreated DL counterparts (35-38 days). The prolonged survival observed in the BC-supplemented animals may be attributed to the higher resistance offered by animals receiving BC towards lipid peroxidation-related tissue injury.

Animals↗
PubMed2000

Vanadium chemoprevention of 7,12-dimethylbenz(a)anthracene-induced rat mammary carcinogenesis: probable involvement of representative hepatic phase I and II xenobiotic metabolizing enzymes.

Vanadium, a non-platinum group metal and dietary micronutrient, is now proving to act as a promising antitumor agent. The present study was conducted to ascertain its antineoplastic potential against an experimental mammary carcinogenesis. Female Sprague-Dawley rats, at 50 days of age, were treated with 7,12-dimethylbenz(a)anthracene (DMBA) (0.5 mg/100 g body weight) by a single tail vein injection in an oil emulsion. Vanadium (ammonium monovanadate) at the concentration of 0.5 ppm was supplemented in drinking water and given ad libitum to the experimental group immediately after the carcinogen treatment and it continued until the termination of the study (24 weeks for histological and biochemical observations and 35 weeks for morphological findings). It was found that vanadium treatment brought about a substantial protection against DMBA-induced mammary carcinogenesis. This was evident from histological findings that showed no sign of hyperplasia or abnormality after vanadium treatment. There was a significant reduction in incidence (P < 0.05), total number, multiplicity (P < 0.01) and size of palpable mammary tumors and delay in mean latency period of tumor appearance (P < 0.001) following vanadium supplementation compared to DMBA control. From the cumulative results of various hepatic biochemical indices namely, lipid peroxidation, reduced glutathione level, superoxide dismutase activity, cytochrome P450 content and glutathione S-transferase activity, the anticarcinogenic potential of vanadium was well reflected through stabilization of these parameters. Results of the study indicate that the anticarcinogenic activity of vanadium during DMBA-initiated mammary carcinogenesis is mediated through alteration of hepatic antioxidant status as well as modulation of phase I and II drug metabolizing enzymes. On the basis of the observed results, vanadium can be considered as a readily available, promising and novel cancer chemopreventive agent.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2000

Functional mapping of protective domains and epitopes in the rotavirus VP6 protein.

The purpose of this study was to determine which regions of the VP6 protein of the murine rotavirus strain EDIM are able to elicit protection against rotavirus shedding in the adult mouse model following intranasal (i.n.) immunization with fragments of VP6 and a subsequent oral EDIM challenge. In the initial experiment, the first (fragment AB), middle (BC), or last (CD) part of VP6 that was genetically fused to maltose-binding protein (MBP) and expressed in Escherichia coli was examined. Mice (BALB/c) immunized with two 9-microg doses of each of the chimeras and 10 microg of the mucosal adjuvant LT(R192G) were found to be protected against EDIM shedding (80, 92, and nearly 100% reduction, respectively; P </= 0.01) following challenge. Because CD produced almost complete protection, we prepared four E. coli-expressed, MBP-fused chimeras containing overlapping fragments of the CD region (i.e., CD1, CD2, CD3, and CD4) whose lengths ranged from 61 to 67 amino acid residues. Following i.n. immunization, CD1, CD2, and CD4 induced significant (P </= 0.004) protection (88, 84, and 92% reduction, respectively). In addition, 11 peptides (18 to 30 residues) of the CD region with between 0 and 13 overlapping amino acids were synthesized. Two 50-microg doses of each peptide with LT(R192G) were administered i.n. to BALB/c mice. Five peptides were found to elicit significant (P </= 0.02) protection. Moreover, a 14-amino-acid region within peptide 6 containing a putative CD4(+) T-cell epitope was found to confer nearly complete protection, suggesting a protective role for CD4(+) T cells. Mice that were protected by fragments BC and CD1 and four of the five protective synthetic peptides did not develop measurable rotavirus antibodies in serum or stool, implying that protection induced by these domains was not dependent on antibody. Together, these observations suggest that multiple regions of VP6 can stimulate protection, a region of VP6 as small as 14 amino acids containing a CD4(+) T-cell epitope can stimulate nearly complete protection, and protection mediated by a subset of epitopes in the VP6 protein does not require antibodies in BALB/c mice.

Amino Acid Sequence↗
PubMed1999

Ceramide glycanase activities in human cancer cells.

Ceramide glycanase (CGase) activities have been detected in different human tumor cells (colon, carcinoma Colo-205; neuroblastoma, IMR-32; breast cancer lines, SKBr3 and MCF7). However, the level of enzymatic activity is lower in these cells compared to that present in other mammalian tissues reported before (Basu, M., Kelly, P., Girzadas, M. A., Li, Z., and Basu, S. Methods Enzymol. (in press)). The majority of CGase activity was found in the 100,000 g soluble supernatant fraction isolated from all these cell lines and tissues. Using the soluble enzyme, the requirement for optimum CGase activity was found to be consistent with previous observations found for rat and rabbit tissues (Basu, M., Dastgheib, S., Girzadas, M. A., O'Donnell, P. H., Westervelt, C. W., Li, Z., Inokuchi, J. I., and Basu, S. (1998) Acta Pol. Biochim. 42:327). The CGase activities from both Colo-205 and IMR-32 cells are optimum at a protein to detergent ratio of one. All the mammalian CGases, including human cancer cells, show an optimum pH between 5.5 and 5.8 in sodium acetate buffer. The CGase activities from cancer cells are found to be cation-independent; however, mercury, zinc, and copper ions seem to inhibit the enzyme activity substantially in both tumor cells lines. The mercury ion inhibition of CGase activities from all different sources indicates a possible structural homology in the CGase proteins. Radiolabeled substrates, labeled at the sphingosine double bond or at the 3-position of sphingosine without modifying double bond of sphingosine were used in this investigation. Both were active substrates with all enzyme preparations isolated from different cancer cells (apparent Km, 500 microM for nLcOse5[3H-DT]Cer and 350 microM for GgOse4[sph-3-3H]Cer with Colo-205 enzyme). Structural analogues of ceramide and sphingosine (L-PPMP. L-PDMP, alkylamines, and Tamoxifen) inhibited cancer cell CGase activities in vitro.

Antineoplastic Agents↗
PubMed1999

Antibody-independent protection against rotavirus infection of mice stimulated by intranasal immunization with chimeric VP4 or VP6 protein.

This study was to determine whether individual rotavirus capsid proteins could stimulate protection against rotavirus shedding in an adult mouse model. BALB/c mice were intranasally or intramuscularly administered purified Escherichia coli-expressed murine rotavirus strain EDIM VP4, VP6, or truncated VP7 (TrVP7) protein fused to the 42.7-kDa maltose-binding protein (MBP). One month after the last immunization, mice were challenged with EDIM and shedding of rotavirus antigen was measured. When three 9-microg doses of one of the three rotavirus proteins fused to MBP were administered intramuscularly with the saponin adjuvant QS-21, serum rotavirus immunoglobulin G (IgG) was induced by each protein. Following EDIM challenge, shedding was significantly (P = 0.02) reduced (i.e., 38%) in MBP::VP6-immunized mice only. Three 9-micrograms doses of chimeric MBP::VP6 or MBP::TrVP7 administered intranasally with attenuated E. coli heat-labile toxin LT(R192G) also induced serum rotavirus IgG, but MBP::VP4 immunization stimulated no detectable rotavirus antibody. No protection against EDIM shedding was observed in the MBP::TrVP7-immunized mice. However, shedding was reduced 93 to 100% following MBP::VP6 inoculation and 56% following MBP::VP4 immunization relative to that of controls (P = <0.001). Substitution of cholera toxin for LT(R192G) as the adjuvant, reduction of the number of doses to 1, and challenge of the mice 3 months after the last immunization did not reduce the level of protection stimulated by intranasal administration of MBP::VP6. When MBP::VP6 was administered intranasally to B-cell-deficient microMt mice that made no rotavirus antibody, shedding was still reduced to <1% of that of controls. These results show that mice can be protected against rotavirus shedding by intranasal administration of individual rotavirus proteins and that this protection can occur independently of rotavirus antibody.

ATP-Binding Cassette Transporters↗