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Biomedical subjects

A Basu

Publications and source records attributed to A Basu.

At least 19 recordsLinked to original sources
PubMed1999

Regulation of caspase activation and cis-diamminedichloroplatinum(II)-induced cell death by protein kinase C.

Activation of caspases is critical for the induction of apoptosis. We have shown previously that cell death mediated by the anticancer agent cis-diamminedichloroplatinum(II) (cDDP) is influenced by the protein kinase C (PKC) signal transduction pathway. In the present study, we have examined whether regulation of cDDP sensitivity by PKC involves caspase activation. cDDP caused a time- and concentration-dependent increase in the generation of the catalytic fragment (CF) of novel (n) PKCdelta, nPKCepsilon, and atypical (a) PKCzeta but had little effect on conventional (c) PKCalpha. Cleavage of PKC isozymes was associated with the activation of caspase-3 and -7 but not of caspase-2. PKC activators enhanced cDDP-induced cleavage of these isozymes and activation of caspase-3. Rottlerin, an inhibitor of nPKCdelta, blocked caspase-3 activation and proteolytic cleavage of nPKCdelta by cDDP. Bryostatin 1, which elicits a biphasic concentration-response in potentiating cell death by cDDP, exhibited a similar biphasic effect on cDDP-induced activation of caspase-3 and caspase-7 and the cleavage of poly(ADP-ribose) polymerase; while 1 nM bryostatin 1 induced maximum activation of these caspases, 1 microM bryostatin 1 had little effect. z-DEVD-fmk, an inhibitor of caspase-3-like proteases, prevented cDDP-induced cell death. Bryostatin 1 also induced a similar biphasic down-regulation of nPKCdelta but not of cPKCalpha or nPKCepsilon. These results suggest that nPKCdelta not only acts downstream of caspases but also regulates the activation of caspases and that the biphasic concentration response of bryostatin 1 on cDDP-induced cell death could be explained by its distinct effect on nPKCdelta down-regulation and caspase activation.

Acetophenones↗
PubMed1999

Lithium-induced alterations in the testis of the male roseringed parakeet (Psittacula krameri) : evidence for significant structural changes and disruption in the spermatogenetic activity.

In this report, we have examined the effects of lithium on testicular morphology in a male subtropical wild avian species, the roseringed parakeet (Psittacula krameri). Adult male birds were collected during the months of February-March, a time when the testicular gametogenic activity in these seasonally breeding birds is at its peak. They were injected, intramuscularly, twice daily (07:00 and 19:00 h) with lithium chloride (Sigma Chemical Company) at a dosage of 0.5 mEq/Kg body weight either for 5 or 10 days. A significant decrease in both the absolute and relative testicular weights was evident in the lithium-treated birds as compared to those of the saline-injected control animals. Light microscopic studies of the testis in the lithium-treated animals showed a wide range of degenerative changes. These included a) a significant reduction in the diameter of seminiferous tubules; b) necrosis and exfoliation of most of the germ cells in the seminiferous tubular lumen with the exception of the spermatogonia; and c) a significant reduction in the number of mature spermatozoa in the tubular lumen. These degenerative changes were dependent on the duration of lithium treatment and were evident when the plasma lithium concentrations were well below the human therapeutic range. Leydig cell morphology was not affected by lithium however. Our results provide the first experimental evidence of lithium's adverse reproductive function in an avian species. These data provide further support to the view that lithium adversely affects the male reproductive system and that these effects extend beyond mammalian species.

Animals↗
PubMed1999

Indolylquinoline derivatives are cytotoxic to Leishmania donovani promastigotes and amastigotes in vitro and are effective in treating murine visceral leishmaniasis.

A wide variety of biologically active compounds contain indole and quinoline nuclei. Some novel indolylquinoline derivatives were synthesized from indole by Friedel-Crafts acylation reaction. Out of the four derivatives tested, 2-(2''-acetamidobenzyl)-3-(3'-indolylquinoline) (C) had no effect on the promastigotes or amastigotes of Leishmania donovani in vitro. The remaining three analogues, 2-(2''-dichloroacetamidobenzyl)-3-(3'-indolylquinoline) (A), 2-(2''-chloroacetamidobenzyl)-3-(3'-indolylquinoline) (B), and 2-(2''-aminobenzyl)-3-(3'-indolylquinoline) (D), inhibited the growth of L. donovani promastigotes in vitro and were cytotoxic to both the promastigote and amastigote forms of the parasite. These three derivatives were also effective in eliminating L. donovani amastigotes from BALB/c mouse peritoneal macrophages in vitro. One indolylquinoline derivative [A] was used to treat established visceral leishmaniasis in BALB/c mice. This compound was significantly more effective than sodium antimony gluconate (SAG) in reducing the splenic parasite load at a much lower concentration (5% of SAG). Our results suggest that indolylquinoline derivatives may be exploited as antileishmanial agents.

Animals↗
PubMed1999

Identification of the A-band localization domain of myosin binding proteins C and H (MyBP-C, MyBP-H) in skeletal muscle.

Although major constituents of the thick filaments of vertebrate striated muscles, the myosin binding proteins (MyBP-C and MyBP-H) are still of uncertain function. Distributed in the cross-bridge bearing zone of the A-bands of myofibrils, in a series of transverse 43 nm stripes, the proteins are constructed of a tandem series of small globular domains, each composed of approximately 90-100 amino acids, which have sequence similarities to either the C2-set of immunoglobulins (IgC2) and the fibronectin type III (FnIII) motifs. MyBP-C is composed of ten globular domains ( approximately 130 kDa) whereas MyBP-H is smaller ( approximately 58 kDa) and consists of a unique N-terminal segment followed by four globular domains, the order of which is identical to that of MyBP-C (FnIII-IgC2-FnIII-IgC2). To improve our understanding of this protein family we have characterized the domains in each of these two proteins which are required for targeting the proteins to their native site(s) in the sarcomere during myogenesis. Cultures of skeletal muscle myoblasts were transfected with expression plasmids encoding mutant constructs of the MyBPs bearing an N-terminal myc epitope, and their localization to the A-band examined by immunofluorescence microscopy. Based on the clarity and intensity of the myc A-band signals we concluded that constructs encoding the four C-terminal motifs of MyBP-C and MyBP-H ( approximately 360 amino acids) were all that was necessary to efficiently localize each of these peptides to the A-band. Truncation mutants lacking one of these 4 domains were less efficiently targeted to the C-zone of the sarcomere. Deletion of the last C-terminal motif of MyBP-H, its myosin binding domain, abolished all localization to the A-band. A chimeric construct, HU-3C10, in which the C-terminal motif of MyBP-H was replaced by the myosin binding domain of MyBP-C, efficiently localized to the A-band. Taken together, these observations indicate that MyBP-C and MyBP-H are localized to the A-band by the same C-terminal domain, composed of two IgC2 and two FnIII motifs. A model has been proposed for the interaction and positioning of the MyBPs in the thick filament through a ternary complex of the four C-terminal motifs with the myosin rods and titin.

Animals↗
PubMed1998

Variations in the subunit content and catalytic activity of the cytochrome c oxidase complex from different tissues and different cardiac compartments.

The composition and activity of cytochrome c oxidase (COX) was studied in mitochondria from rat liver, brain, kidney and heart and also in different compartments of the bovine heart to see whether any correlation exists between known oxidative capacity and COX activity. Immunoblot analysis showed that the levels of ubiquitously expressed subunits IV and Vb are about 8-12-fold lower in liver mitochondria as compared to the heart, kidney and brain. The heart enzyme with higher abundance of COX IV and Vb showed lower turnover number (495) while the liver enzyme with lower abundance of these subunits exhibited higher turnover number of 750. In support of the immunoblot results, immunohistochemical analysis of heart and kidney tissue sections showed an intense staining with the COX Vb antibody as compared to the liver sections. COX Vb antibody stained certain tubular regions of the kidney more intensely than the other regions suggesting region specific variation in the subunit level. Bovine heart compartments showed variation in subunit levels and also differed in the kinetic parameters of COX. The right atrium contained relatively more Vb protein, while the left ventricle contained higher level of subunit VIa. COX from both the ventricles showed high Km for cytochrome c (23-37 microM) as compared to the atrial COX (Km 8-15 microM). These results suggest a correlation between tissue specific oxidative capacity/work load and changes in subunit composition and associated changes in the activity of COX complex. More important, our results suggest variations based on the oxidative load of cell types within a tissue.

Animals↗
PubMed1998

Serine-70 is one of the critical sites for drug-induced Bcl2 phosphorylation in cancer cells.

Taxoids and other microtubule-damaging drugs are known to induce Bcl2 phosphorylation at the G2-M phase of the cell cycle, with concomitant apoptosis in malignant cells derived from a variety of human malignancies, including leukemia, lymphoma, and breast and prostate cancer. We have investigated the ability of another antineoplastic drug, dolastatin 10, in inducing Bcl2 phosphorylation and apoptosis. We also investigated the effects of a phosphatase inhibitor okadaic acid in the regulation of Bcl2 phosphorylation, cell cycle arrest, and programmed cell death. Moreover, site-directed mutagenesis studies were performed to determine the specific serine residue(s) responsible for drug-induced Bcl2 phosphorylation. Our results indicate that these antimicrotubule agents or okadaic acid can induce posttranslational modification (phosphorylation) of Bcl2 protein at multiple serine residues. Interestingly, mutation of a serine residue at position 70 to alanine can significantly decrease drug-induced posttranslational modification (phosphorylation) of Bcl2 protein. Apparently, Ser70 seems to be a critical site for drug-induced posttranslational modification (phosphorylation) of the Bcl2 protein.

Alanine↗
PubMed1998

Heterogeneity in the organization of the CTX genetic element in strains of Vibrio cholerae O139 Bengal isolated from Calcutta, India and Dhaka, Bangladesh and its possible link to the dissimilar incidence of O139 cholera in the two locales.

After a lapse of 33 months, Vibrio cholerae O139, the new serogroup associated with cholera, has re-emerged in Calcutta, India and has become the dominant serogroup causing cholera from September 1996. In neighbouring Bangladesh, V. cholerae O1 biotype El Tor continues to be the dominant cause of cholera with the O139 serogroup accounting for only a small proportion of cases. Comparison of the phenotypic traits of representative O139 strains from Calcutta and Dhaka isolated between December 1996 and April 1997 showed similar phenotypic traits with the exception that Dhaka O139 strains were susceptible to streptomycin whilst Calcutta O139 strains were resistant. The Dhaka and Calcutta O139 strains displayed identical ribotypes but showed remarkable differences in the structure and organization of the CTX genetic element. In the Dhaka O139 strains, two copies of the CTX element were arranged in tandem and this resembled the pattern displayed by the 1992 epidemic strains of O139. The Calcutta O139 strains, in contrast, carried three copies of the CTX genetic element arranged in tandem with the loss of a conserved BglII restriction site in the RS1 element and the appearance of a new HindIII site in the same region. While there may be other factors, it appears that the reorganization of the CTX genetic element in the Calcutta O139 strains may have contributed to the resurgence of this serogroup in Calcutta.

Anti-Bacterial Agents↗
PubMed1998

Failure of nocturnal changes in growth hormone to alter carbohydrate tolerance the following morning.

To determine whether the increases in growth hormone that occur during sleep alter carbohydrate tolerance the following morning, two groups of volunteers were studied on two occasions. In one group saline alone was injected and infused (i.e. no octreotide) on one occasion and on the other octreotide was injected at 23.00 hours to inhibit endogenous growth hormone secretion followed by saline infusion to create a state of relative nocturnal growth hormone deficiency. In the other group the octreotide injection was followed on one occasion by a constant growth hormone infusion designed to maintain growth hormone concentrations at "basal" levels throughout the night whereas on the other it was followed by a constant infusion plus two supplemental growth hormone infusions given at midnight and 02.30 hours to mimic the normal nocturnal rise in growth hormone. The next morning, subjects were fed a radiolabelled mixed meal. The differences in the nocturnal growth hormone concentrations had no effect on the glucose, insulin, C-peptide and glucagon concentrations following breakfast ingestion nor did they alter postprandial rates of glucose production, disappearance or substrate oxidation. Thus, the normal nocturnal rise in growth hormone does not appear to be an important regulator of carbohydrate tolerance the following morning.

Adult↗
PubMed1998

Rapid spread of the new clone of Vibrio cholerae O1 biotype El Tor in cholera endemic areas in India.

Using molecular techniques, we investigated whether the clone of Vibrio cholerae O1 biotype El Tor which appeared in Calcutta, India, in 1994 has spread to other cholera endemic areas in the country. The ribotype of 31 of the 33 strains isolated from different parts of India during 1996 and 1997 was identical to the ribotype displayed by the new clone of V. cholerae O1 which emerged in Calcutta in 1994. Likewise, 12 of the 15 strains examined by pulsed-field gel electrophoresis (PFGE) showed identical profile to that exhibited by the new clone of O1. The restriction fragment length polymorphism (RFLP) of CTX genetic element of these strains also matched with the new clone of O1 which emerged after the outbreak of V. cholerae 0139 in Calcutta. However, two strains (AH042 and AH046) isolated from an outbreak in Ahmedabad (western India) showed different CTX RFLP but had the same ribotype and PFGE profile as the new clone, whereas one strain from Goa (G2) showed distinct ribotype and PFGE profile and the CTX RFLP was identical to the O1 strains which prevailed before the genesis of 0139 in Calcutta. The drug resistance pattern of most of the O1 strains examined in this study, except strain G2, was similar to that of the new clone of V. cholerae O1. None of the strains in this study carried plasmids. Molecular studies clearly show that the new expanded drug resistant clone of V. cholerae O1 has spread to all cholera endemic areas in India and also provide evidence for the evolution of new clones of the O1 serogroup.

Cholera↗
PubMed1998

The relationship between BcI2, Bax and p53: consequences for cell cycle progression and cell death.

Each cell is under constant surveillance to maintain the integrity of its genome. Genomic lesions in a cell must be repaired before the onset of DNA replication and cell division. In the scenario that the genomic lesion is not repairable, the damaged cells are disposed in an orderly manner known as programmed cell death or apoptosis. Apoptosis and cell cycle progression are two intimately linked phenomena. Uncontrollable cell proliferation perturbs the cellular homeostasis and this can lead to malignancies, as well as organ dysfunction and developmental abnormalities. The biological pathway controlling cell fate is sequentially organized at the molecular level. Recent studies have made important contributions in advancing our knowledge of the mechanisms of cell cycle control and apoptosis regulation. A oncogene-derived protein, Bcl2, confers negative control in the pathway of cellular suicide machinery. A Bcl2-homologous protein, Bax, promotes cell death by competing with Bcl2. While Bax-Bax homodimers act as apoptosis inducers, Bcl2-Bax heterodimer formation evokes a survival signal for the cells. Both Bcl2 and Bax are transcriptional targets for the tumour suppressor protein, p53, which induces cell cycle arrest or apoptosis in response to DNA damage. In all, the coordinate performance of these molecules is crucial for controlling life and death of a cell.

Animals↗
PubMed1998

A PC-based Braille library system for the sightless.

This paper presents a novel multiclient braille reading system developed around a single low cost personal computer. The system primarily addresses the needs of the Braille libraries, where different texts are needed to be read by different users simultaneously. Moreover, the system can simultaneously cater to different texts written in different languages. This feature makes it specially suitable for use by multilingual nationalities. The major advantage of this system is its low cost, compared to the other systems available and is specially attractive for the developing or underdeveloped countries. The paper describes the system, first from the user point of view and then presents the hardware and software design details. The system performance has been evaluated by the sightless users and has shown encouraging results.

Blindness↗
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↗