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Biomedical subjects

A Basu

Publications and source records attributed to A Basu.

At least 109 records · Page 6Linked to original sources
PubMed1998

Studies on the possible mechanism of the gastric mucosal protection by Calotropis procera--involvement of 5-lipoxygenase pathway.

The role of chloroform fraction of Calotropis procera root extract on different experimental ulcer models in rats was investigated. The extract demonstrated significant anti-ulcer activity against aspirin, indomethacin, ethanol, indomethacin + ethanol, or stress-induced ulcerations. Significant inhibition of gastric secretory volume and total acidity in pylorus ligated rats were observed to occur with the extract. It was also observed that the root extract significantly inhibited arachidonic acid metabolism induced by soyabean lipoxygenase. The results suggest that the anti-ulcer activity of the extract might be attributable to the inhibition of 5-lipoxygenase (5-LO).

Animals↗
PubMed1998

Development and evaluation of a multiplex PCR assay for rapid detection of toxigenic Vibrio cholerae O1 and O139.

A multiplex polymerase chain reaction assay was developed for concurrent detection of rfb sequences specific for the O1 and the O139 serogroups of Vibrio cholerae and for ctxA specific sequences. The multiplex PCR assay was found to be highly specific and sensitive and was capable of detecting 65 cfu and 200 cfu per assay of V. cholerae O1 and O139, respectively. Evaluation of the multiplex PCR assay using 121 stool samples from patients admitted to the Infectious Diseases Hospital, Calcutta, showed the assay to be 100% sensitive and 95.2% specific when the culture method was taken as the standard. In addition to the 38 PCR positive stool samples, an additional four samples which were negative by culture method but positive by PCR assay belonged to the O139 serogroup. All the 38 stool samples positive for either O1 or O139 serogroup by PCR assay were also positive for the ctxA amplicon indicating that the O1 and O139 V. cholerae strains have the genetic potential of producing cholera toxin.

Bacterial Proteins↗
PubMed1998

The involvement of novel protein kinase C isozymes in influencing sensitivity of breast cancer MCF-7 cells to tumor necrosis factor-alpha.

Protein kinase C (PKC) has been implicated in tumor necrosis factor-alpha (TNF) signaling. Structurally and functionally distinct PKC activators and selective inhibitors of PKC were used to investigate the involvement of PKC isozymes in influencing TNF sensitivity in MCF-7 cells. Activators of PKC, such as phorbol-12, 13-dibutyrate (PDBu) (1.0 microM), indolactam V (10 microM), and bryostatin 1 (1.0 microM) decreased the sensitivity of MCF-7 cells to TNF by 5-, 10-, and 1.7-fold, respectively. The PKC-specific inhibitor bisindolylmaleimide II (BIM) (> or = 1 microM) antagonized the effect of PDBu in protecting MCF-7 cells against TNF cytotoxicity. High concentrations of BIM (> or = 10 microM) also significantly enhanced the sensitivity of MCF-7 cells to TNF. In contrast, Gö 6976, a specific inhibitor of cPKCs, did not potentiate TNF sensitivity and failed to reverse the effect of PDBu. In addition, BIM but not Gö 6976 blocked PDBu-mediated down-regulation of TNF receptors. There was no correlation between down-regulation of PKC alpha, -delta, and -epsilon, and protection against TNF cytotoxicity by PKC activators. A 6-hr exposure to 1.0 microM PDBu, 10 microM indolactam V, and 1.0 microM bryostatin 1 caused a 1.8-, 3.5- and 1.2-fold induction, respectively, of nPKC eta in MCF-7 cells. Similar exposure to BIM but not Gö 6976 led to a significant down-regulation of nPKC eta. This novel regulation of PKC eta implicates this isozyme in PDBu-mediated protection of MCF-7 cells against TNF cytotoxicity.

Antineoplastic Agents↗
PubMed1998

Molecular analysis of non-O1, non-O139 Vibrio cholerae associated with an unusual upsurge in the incidence of cholera-like disease in Calcutta, India.

There was an inexplicable upsurge in the incidence of non-O1, non-O139 Vibrio cholerae among hospitalized patients admitted to the Infectious Diseases Hospital, Calcutta, India, between February and March 1996. Of the 18 strains of V. cholerae isolated during this period, 15 belonged to the non-O1, non-O139 serogroups (4 belonged to O144, 3 belonged to O11, 1 each belonged to O6, O8, O12, O19, O39, and O58, and 2 strains could not be typed), 2 belonged to the O139 serogroup, and 1 belonged to the O1 serogroup. Cell-free culture supernatants of 13 representative non-O1, non-O139 V. cholerae strains evoked a distinct cytotoxic effect on CHO and HeLa cells, and the strains examined produced the nonmembrane-damaging cytotoxin. By several PCR assays, it was determined that none of the non-O1, non-O139 strains were positive for the ctxA, zot, ace, and tcpA genes and for the genes representing the heat-labile toxin, heat-stable toxin, and verotoxin of Escherichia coli and the various variants of these genes. Studies on the clonality of non-O1, non-O139 V. cholerae strains by restriction fragment length polymorphism (RFLP) analysis of rRNA genes and of other genes (hlyA, hlyU, hlx, toxR, and attRS1) and by pulsed-field gel electrophoresis (PFGE) collectively indicate that the upsurge which occurred in February and March 1996 was caused by strains belonging to different clones. Overall, there was an excellent correlation between the results of ribotyping, RFLP analysis of various genes, and PFGE, with strains belonging to a particular serogroup showing nearly identical restriction patterns and PFGE profiles. It is clear from this study that some serogroups of V. cholerae can cause diarrhea by a mechanism quite different from that of toxigenic V. cholerae O1 and O139, and we have proposed the nomenclature of enteropathogenic V. cholerae to include these serogroups.

Bacterial Typing Techniques↗
PubMed1998

Molecular epidemiology of reemergent Vibrio cholerae O139 Bengal in India.

We report the prevalence of the O139 serogroup in Calcutta, India, after its reemergence in August 1996 and the spread of the reemerged clone to other parts of the country by using previously established molecular markers. Phenotypically, the reemerged Vibrio cholerae O139 displayed a difference compared to those that appeared in late 1992 and 1993 in that the current O139 strains are sensitive to co-trimoxazole. Ribotyping with the enzyme BglI produced two rRNA restriction patterns in the O139 strains isolated after August 1996, and these patterns were identical to those exhibited by strains of O139 isolated in 1992. Three clones of V. cholerae O139 are currently prevailing in the country, with strains exhibiting three bands after HindIII digestion and hybridization with a ctxA probe being dominant. The reemergence of V. cholerae O139 in Calcutta after a 32-month quiescent period reestablishes the O139 serogroup as an entity which is likely to play a crucial role in the temporal antigenic variations among the serogroups of V. cholerae causing cholera.

Bacterial Typing Techniques↗
PubMed1998

Microtubule-damaging drugs triggered bcl2 phosphorylation-requirement of phosphorylation on both serine-70 and serine-87 residues of bcl2 protein.

Specifically anti-microtubule agents such as taxol, vincristine, vinblastine and dolastatin can trigger Bcl2 phosphorylation at G2-M phase of the cell cycle in malignant cells derived from a variety of human cancers. In this study, the status of Bcl2 phosphorylation was investigated in response to more antimicrotubule agents such as colchicine, colcemid or podophyllotoxin. Although these agents are not currently used for cancer therapy, they were able to trigger Bcl2 phosphorylation with simultaneous apoptosis in cancer cells. Previously, by using extensive site-directed mutagenesis studies we determined that mutation of serine-70 to alanine could not completely abrogate taxol induced Bcl2 phosphorylation. Studies reported here clearly indicate that serine-87 residue along with serine-70 of Bcl2 protein are necessary for microtubule damaging drug induced phosphorylation.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Projection of HIV infection in Calcutta.

Starting with the base year of 1991, the HIV infection projection for 1992-99 for the total, as well as various high-risk sub-populations of Calcutta, the first of its kind is provided. These projections are based on statistical methodology developed in this paper. Our methodology for spread of HIV infection takes into account various social interactions and practices and also uses available data. Rates of these interactions and practices and estimates of demographic parameters used in making projections were obtained primarily from surveys and census data. Since one of these estimated rates, that of HIV transmission rate through heterosexual encounters between an infected and an uninfected had a large range, we have provided two sets of projections based on the largest of these rates (worst-case scenario) and another that is consistent with the available data. The total projection of the number of HIV infected cases in Calcutta for 1999 is between 49,000 and 1,26,000. Separate projections are also provided for high-risk sub-groups. Among these, the sex workers expectedly will continue to manifest the highest numbers of newly infected cases. The temporal rate of increase in prevalence is projected to be alarmingly higher in the general population than even among sex workers, although the actual prevalence will continue to be the lowest in the general population compared to all other sub-groups of the population.

Female↗
PubMed1998

SPARC deficiency leads to early-onset cataractogenesis.

PURPOSE: To determine the role of SPARC (secreted protein, acidic, and rich in cysteine) in cataractogenesis by examining mice deficient in a matricellular protein SPARC. METHODS: Mice were rendered SPARC-deficient by a targeted disruption of the gene. Slit-lamp microscopy and histology were used to examine the eyes of SPARC-null and wild-type mice from birth to 14 months of age. RESULTS: SPARC-null mice developed opacities in the posterior cortex of the eye as early as 1.5 months after birth. The diffuse cataracts appeared to progress toward the anterior cortex and reached maturity in many animals by 3.5 months of age. Early stages of cataractogenesis in SPARC-null mice included inhibition of normal lens fiber cell differentiation, degeneration of fiber cells, vacuole formation at the equator, and liquefaction of the cortex. No cataracts were detected in wild-type mice up to the age of 8 months. CONCLUSIONS: The early onset of cataracts in SPARC-null mice establishes that the gene is essential to the maintenance of lens transparency.

Animals↗
PubMed1997

Identification of an intronic enhancer that nullifies upstream repression of SPARC gene expression.

The SPARC gene 5'flanking sequence has been shown to contain enhancer elements, but also negative control elements immediately upstream of the enhancer elements. Although these 5'enhancer elements are active in F9 and PYS-2 cells, their activities are nullified by the 5'repressor activity. In the present study we have identified within intron 1 between nucleotides (nt) +5000 and +5150 of the SPARC gene an enhancer element that bound to two transcription factors of 48 and 52 kDa and between nt +5000 and +5523 a DNase I hypersensitive site. Furthermore, a region containing the 3'intron 1 enhancer element, together with the 5'enhancer elements, neutralized the 5'repressor activity and stimulated efficient transcription. The resulting SPARC promoter activity is about equal in F9, differentiated F9 and PYS-2 cells. We consistently found that the rate of SPARC transcription is nearly the same in F9 and PYS-2 cells. Association of the 3'enhancer element in intron 1 with the DNase I hypersensitive site suggests that both play a role in regulating SPARC expression in vivo .

Base Sequence↗
PubMed1997

Transgenic elite indica rice plants expressing CryIAc delta-endotoxin of Bacillus thuringiensis are resistant against yellow stem borer (Scirpophaga incertulas).

Generation of insect-resistant, transgenic crop plants by expression of the insecticidal crystal protein (ICP) gene of Bacillus thuringiensis (Bt) is a standard crop improvement approach. In such cases, adequate expression of the most appropriate ICP against the target insect pest of the crop species is desirable. It is also considered advantageous to generate Bt-transgenics with multiple toxin systems to control rapid development of pest resistance to the ICP. Larvae of yellow stem borer (YSB), Scirpophaga incertulas, a major lepidopteran insect pest of rice, cause massive losses of rice yield. Studies on insect feeding and on the binding properties of ICP to brush border membrane receptors in the midgut of YSB larvae revealed that cryIAb and cryIAc are two individually suitable candidate genes for developing YSB-resistant rice. Programs were undertaken to develop Bt-transgenic rice with these ICP genes independently in a single cultivar. A cryIAc gene was reconstructed and placed under control of the maize ubiquitin 1 promoter, along with the first intron of the maize ubiquitin 1 gene, and the nos terminator. The gene construct was delivered to embryogenic calli of IR64, an elite indica rice cultivar, using the particle bombardment method. Six highly expressive independent transgenic ICP lines were identified. Molecular analyses and insect-feeding assays of two such lines revealed that the transferred synthetic cryIAc gene was expressed stably in the T2 generation of these lines and that the transgenic rice plants were highly toxic to YSB larvae and lessened the damage caused by their feeding.

Animals↗
PubMed1997

Regulation of murine cytochrome oxidase Vb gene expression in different tissues and during myogenesis. Role of a YY-1 factor-binding negative enhancer.

The mouse cytochrome oxidase (COX) Vb promoter contains three sequence motifs with partial or full consensus for YY-1 and GTG factor binding and a CArG box, located between positions -480 and -390. Individually, all three motifs stimulated transcription of the TKCAT promoter, and bound distinctly different proteins from the liver and differentiated C2C12 nuclear extracts. Collectively, these motifs, together with the downstream flanking sequence, -378 to -320, suppressed the transcription activity of heterologous promoters, thymidine kinase-chloramphenicol acetyltransferase (TKCAT) and COXIV/CAT. The transcription activities of both TKCAT and COXIV/CAT constructs were induced 3-4-fold during induced myogenesis of C2C12 cells. The downstream CArG-like motif binds transcription factor YY-1, while the upstream YY-1-like motif binds to a yet unidentified factor. Co-expression with intact YY-1, but not that lacking the DNA binding domain suppressed the transcriptional activity. Mutations targeted to the CArG-like motif abolished the suppressive effect of the negative enhancer and the inducibility of the promoter during myogenic differentiation. Our results suggest that the activity of the negative enhancer may determine the level of expression of the COX Vb gene in different tissues.

Animals↗
PubMed1997

Bcl2 is the guardian of microtubule integrity.

We have investigated the ability of several drugs commonly used in the treatment of human cancer to induce bcl2 phosphorylation and cell death in human cell lines derived from acute leukemia, lymphoma, breast cancer, and prostate cancer. The results of this analysis indicate that drugs affecting the integrity of microtubules induce bc12 phosphorylation, whereas anticancer drugs damaging DNA do not. Comparison of the effects of taxol and its analogue, taxotere, indicates that taxotere is capable of inducing bcl2 phosphorylation and apoptotic cell death at 100-fold lower concentrations than taxol. Induction of cancer cell death through phosphorylation of bcl2 thus provides an opportunity not only for more refined targeting of therapeutic drugs but for understanding of an important pathway leading to apoptosis. Phosphorylation of bcl2 in drug-treated cancer cells occurs in G2-M, the phase of the cell cycle in which this class of drugs is active. No induction of bcl2 phosphorylation occurs in chronic lymphocytic leukemia cells that overexpress bcl2 but are blocked at G0-G1. Thus, prevention of polymerization or depolymerization of cellular microtubules by this class of cancer therapeutic drugs causes phosphorylation of bcl2, abrogating the normal antiapoptotic function of bcl2 and initiating the apoptotic program in the cycling cancer cells; these results are consistent with a normal physiological role of bcl2 as "guardian of microtubule integrity."

Antineoplastic Agents↗
PubMed1997

A quantitative description of dynamic left ventricular geometry in anaesthetized rats using magnetic resonance imaging.

We report a functional application of magnetic resonance imaging (MRI) for the quantitative description of left ventricular geometry through systole and diastole in normal anaesthetized Wistar rats that might be applicable for the analysis of chronic changes resulting from pathological conditions. Images of cardiac anatomy were acquired through planes both parallel and perpendicular to the principal cardiac axis at times that were synchronized to the R wave of the electrocardiogram. The images of the transverse sections were assembled into three-dimensional representations of left ventricular geometry at consecutive time points through the cardiac cycle. This confirmed the geometrical coherence of the data sets, that each slice showed circular symmetry, and that the images were correctly aligned with the appropriate anatomical axes. Different models for the three-dimensional geometry of the left ventricle were then tested against the epi- and endocardial surfaces reconstructed from images of the transverse sections of the left ventricle in both systole and diastole using least-squares minimizations in three dimensions. In agreement with previous reports in the human heart, an elliptical figure of revolution offered an optimal fit to the epicardial and endocardial geometry for the rat heart in diastole. This was in preference to models that used spherical, quartic or parabolic geometries. However, in contrast to contraction in the human heart, all these geometrical representations broke down during systolic ejection in the rat heart. We therefore introduced a more general hybrid model which described left ventricular geometry in terms of the variation of the radii r(z), independently determined for each slice, with its position z along the principal cardiac axis. The resulting function r(z) could then be described by a simple ellipsoid of revolution not only during diastole, but also throughout ventricular ejection. The findings also ruled out alternative geometrical representations. It was then possible additionally to reconstruct the luminal and total left ventricular volumes, wall thicknesses and ejection fractions through the cardiac cycle and to confirm that the predicted total ventricular wall volume was conserved throughout the cardiac cycle. Our hybrid model of cardiac geometry may thus be useful for non-invasive serial studies of chronic pathological changes that use the rat as a model experimental system.

Animals↗
PubMed1997

Unique organization of the CTX genetic element in Vibrio cholerae O139 strains which reemerged in Calcutta, India, in September 1996.

We studied the restriction fragment length polymorphism of the rRNA gene and CTX genetic element in Vibrio cholerae O139 Bengal, which resurged in Calcutta in September 1996 after a gap of 32 months. While the strains from this resurgence were indistinguishable from the earlier strains by ribotyping, the structure of the CTX genetic element present in the current O139 strains was found to be unconventional.

Cholera↗
PubMed1997

The intracisternal A-particle proximal enhancer-binding protein activates transcription and is identical to the RNA- and DNA-binding protein p54nrb/NonO.

The long terminal repeats of murine intracisternal A particles (IAPs) contain an IAP proximal enhancer (IPE) element that is inactive in murine F9 embryonal carcinoma cells and active in the parietal endoderm cell line PYS-2. The element binds efficiently to a 60-kDa IPE-binding protein (IPEB) present in PYS-2 cells but poorly to F9 proteins, suggesting a role for IPEB in regulating IAP expression. We have purified calf thymus IPEB, which binds to the IPE and transactivates a reporter gene in HeLa cell extracts. Based on the peptide sequence of the purified calf IPEB, we have cloned a 420-bp cDNA and showed that the encoded protein is the homolog of human p54nrb and mouse NonO, which are characterized by the presence of two RNA recognition motifs. We show that p54nrb is an IPE-binding transcription activator with its DNA-binding and activation domains in the N- and C-terminal halves, respectively. The activation domain of p54nrb is active in HeLa, PYS-2, and F9 cells, whereas p54nrb as a whole molecule is active in HeLa and PYS-2 cells but not in F9 cells. Thus, the lack of activity of p54nrb in F9 cells is due to an ineffective DNA-binding domain. We demonstrate that p54nrb also binds to a pre-mRNA. Based on the close sequence relatedness of this protein to PSF, which is required for pre-mRNA splicing in vitro, we discuss the possibility that p54nrb has dual roles in transcription and splicing.

Animals↗
PubMed1997

Assessment of hepatic sensitivity to glucagon in NIDDM: use as a tool to estimate the contribution of the indirect pathway to nocturnal glycogen synthesis.

NIDDM is associated with excessive rates of endogenous glucose production in both the postabsorptive and postprandial states. To determine whether this is due to an intrinsic increase in hepatic sensitivity to glucagon, 9 NIDDM and 10 nondiabetic subjects were studied on three occasions. On each occasion, glycogen was labeled the evening before the study with subjects ingesting meals containing [6-3H]galactose. Beginning at 6:00 A.M. on the following morning, somatostatin was infused to inhibit endogenous hormone secretion. Insulin concentrations were maintained constant at basal levels (defined as that necessary to keep glucose at approximately 5 mmol/l) in each individual. On one occasion, glucagon was infused at a rate of 0.65 ng x kg(-1) x min(-1) throughout the experiment, resulting in glucagon concentrations of approximately 130 pg/ml and a slow but comparable fall in endogenous glucose production with time in both groups. On the other two occasions, the glucagon infusion was increased at 10:00 A.M. to either 1.5 or 3.0 ng x kg(-1) x min(-1), resulting in an increase in glucagon concentrations to approximately 180 and 310 pg/ml, respectively. The increment in endogenous glucose production (i.e., area above basal) did not differ in diabetic and nondiabetic subjects during either the 1.5 ng x kg(-1) x min(-1) (0.75 +/- 0.055 vs. 0.78 +/- 0.048 mmol/kg) or 3.0 ng x kg(-1) x min(-1) (1.06 +/- 0.066 vs. 1.10 +/- 0.073 mmol/kg) glucagon infusions. In contrast, the amount of [6-3H]glucose released from glycogen was lower (P < 0.05) in the diabetic than nondiabetic subjects during both glucagon infusions. The specific activity of glycogen, calculated as the integrated release of [6-3H]glucose divided by the integrated release of unlabeled glucose, was lower (P < 0.05) in diabetic subjects than in nondiabetic subjects during both the 1.5 ng x kg(-1) x min(-1) (19.0 +/- 3.9 vs. 41.4 +/- 5.7 dpm/micromol) and 3.0 ng x kg(-1) x min(-1) (19.1 +/- 3.1 vs. 36.5 +/- 7.2 dpm/micromol) glucagon infusions, implying that a greater portion of the glucose released from glycogen was derived from the indirect pathway. We concluded that although NIDDM is not associated with an intrinsic alteration in hepatic sensitivity to glucagon, it does alter the relative contributions of the direct and indirect pathways to nocturnal glycogen synthesis.

Blood Glucose↗
PubMed1997

Impaired basal glucose effectiveness in NIDDM: contribution of defects in glucose disappearance and production, measured using an optimized minimal model independent protocol.

People with NIDDM are resistant to insulin. The present studies sought to determine whether the ability of glucose to regulate its own metabolism in the presence of basal insulin concentrations is impaired. To address this question, basal insulin concentrations were maintained constant with an exogenous insulin infusion, while endogenous hormone secretion was inhibited by somatostatin. The integrated glycemic response above baseline during identical prandial glucose infusions was greater (1,411 +/- 94 vs. 938 +/- 45 mmol/l per 5 h; P < 0.01) in the diabetic subjects than in the nondiabetic subjects, indicating a decrease in net glucose effectiveness. [6-3H]glucose also was infused to determine whether the decrease in net glucose effectiveness was due to a decrease in the ability of glucose to stimulate its own uptake and/or to suppress its own production. Despite identical rates of tracer infusion, the increment in plasma concentration of [6-3H]glucose was higher (4.50 +/- 0.29 vs. 3.16 +/- 0.21 x 10(5) dpm/ml per 5 h; P < 0.05) in the diabetic subjects than in the nondiabetic subjects. This was due to both a decrease (P < 0.05) in the ability of glucose to stimulate its own disappearance via mass action and to a greater (P < 0.01) inhibitory effect of glucose on its own clearance. The increase in glucose concentration resulted in prompt and comparable suppression of endogenous glucose production in both groups. Under these optimized conditions, indexes of glucose effectiveness calculated with both the "cold" and "hot" minimal models also were lower (P < 0.05) in the diabetic subjects than in the nondiabetic subjects and were highly correlated (r = 0.94-0.99; P < 0.001) with the indexes of glucose effectiveness calculated from the increments above baseline of glucose and [6-3H]glucose concentration. We conclude that the ability of glucose to regulate its own metabolism in the presence of basal insulin concentrations is abnormal in people with NIDDM.

Blood Glucose↗