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Biomedical subjects

G Bhattacharya

Publications and source records attributed to G Bhattacharya.

At least 19 recordsLinked to original sources

The role of insulin dependent NO synthesis in the impaired production of maspin in human breast cancer.

PURPOSE: The synthesis of maspin, a protein with various anti-breast cancer properties has been reported to be produced in normal breast tissue but not in breast cancer cells. We investigated the role of insulin receptors and their upregulation by prostaglandin E(1) in vitro for the stimulation of NO synthesis by the hormone, and its consequence on maspin production in normal neutrophils and malignant cells in breast cancer. METHODS: Maspin and NO were determined by ELISA and methemoglobin method, respectively. RESULTS: The treatment of neutrophils and malignant breast cancer cells with prostaglandin E(1) resulted in partial restoration of the impaired receptor numbers, and resulted in partial normalization of NO and maspin production in these cells compared to normal counterparts. It was not feasible to stimulate NO synthesis to normal ranges by the upregulation of receptor number due to intrinsic decrease of insulin receptors in breast cancer cells. However, aspirin, which was found to stimulate NO synthesis to normal ranges, normalized maspin production in these cells in breast cancer. CONCLUSION: The impaired maspin production was found to be the consequence of impaired insulin induced NO production in breast cancer due to the decrease of insulin receptor binding. Restoration of NO production by aspirin can be useful for the restoration of maspin production in breast cancer.

Aged↗

Restoration by aspirin of impaired plasma maspin level in human breast cancer.

Maspin, an anti breast cancer protein, is produced in the normal mammary cells but not in malignant cells in breast cancer. We investigated the effect of aspirin induced increase of plasma nitric oxide (NO) on plasma maspin production in breast cancer patients. Fifteen breast cancer patients (35-65 years), who had not yet undergone any cancer therapy, and an equal number of age matched normal female volunteers participated in the study. They were asked not to take any medication for two weeks. All participants then ingested 150 mg of aspirin. Plasma NO and maspin levels were determined before and at 60 min after the ingestion of aspirin. It was found that the maspin level in plasma increased to 4.63+/-0.02 nM from the basal 0.95+/-0.012 nM (p<0.001) with increase of plasma NO from 0.60+/-0.03 microM to 2.08+/-0.030 microM (p<0.001) in breast cancer patients. In normal volunteers the basal maspin increased from 4.76+/-0.041 to 9.36+/-0.036 nM (p<0.001) with increase of NO from 2.15+/-0.08 to 3.36+/-0.04 microM (p<0.001) at the same period. These results indicated that the ingestion of aspirin might be beneficial for breast cancer through increased maspin production.

Aged↗

Synthesis and autoxidation of new tetracyclic 9H,10H-indolizino[1,2-b]indole-1-ones.

The new tetracyclic 9H,10H-indolizino[1,2-b]indole-1-one derivatives (7a-d, 7ea, 7eb) have been synthesized by modified Fischer indole synthesis from the enol ether of 2,5-dihydroxy-7-methyl-6-cyano-indolizine (3) and arylhydrazines (4a-g). Attempted N-methylation of 7a-d produced a series of autoxidized products including 10-hydroperoxy-1-methoxyindolizino[1,2-b]indole (9a-d) as the major product accompanied with methylperoxides (10a-d and 11a-d) and 2-formyl-3-(pyridine-2-yl)indole (12a, 12c) derivatives as the minor products. A plausible mechanism of the autoxidation is postulated based on the isolation of some intermediates. The reaction is thought to proceed through azaenolate/enamine intermediates following a novel type of autoxidation.

Indicators and Reagents↗

Knowledge about HIV/AIDS, the perceived risks of infection and sources of information of Asian-Indian adolescents born in the USA.

This study examined the extent and specificity of knowledge about HIV/AIDS, the most used sources of information and the usefulness of these sources among Asian-Indian adolescents who were born in the USA and whose parents emigrated from India. Although 86% knew that having unsafe sex with a person infected with HIV could transmit HIV, 47% did not know that sharing a razor with an HIV-positive person could do so, and a significant proportion believed that donating blood (27%) and taking blood tests (14%) could transmit HIV. Television was the most used source of information, but school programmes on HIV/AIDS were considered the most useful source. The results indicated that to be effective, HIV/AIDS prevention programmes must assess the gap in scientific knowledge and beliefs, and clarify misconceptions, reinforce school programmes to present clear messages about the transmission of HIV/AIDS and utilize television to reach adolescents.

Acquired Immunodeficiency Syndrome↗

The school adjustment of South Asian immigrant children in the United States.

This study examined the school adjustment process among South Asian children who had immigrated to the United States with their parents, and who had below-average grades. Both risk and protective factors for dropping out of school were explored in the context of the traditions, familial values, and social norms of South Asians. Data were collected from 75 parents and 75 children in separate semistructured interviews. Content analysis revealed three major themes: congruence of the parents' and school's views on the value of education, congruence of the parents' and children's beliefs that education is the tool to achieve goals, and determination of the children to achieve goals. The low level of proficiency in English was found to be a critical factor in low achievement and school failure. It was concluded that parental encouragement to succeed, in conjunction with teachers' efforts, can be used to facilitate children's school adjustment. Strategies for assisting immigrant children are discussed.

Acculturation↗

A study of lupus anticoagulant in unexplained fetal wastage.

Lupus Anticoagulant, first discovered in patients of SLE, is now known to be associated with a wide spectrum of diseases. The presence of LA is associated with adverse fetal outcome in an obstetric population. In the present series the incidence of LA was found to be 16.6% and 80% of LA positive subgroup had an unsuccessful outcome.

Abortion, Habitual↗

Peer networks, parental attributes, and drug use among Asian-Indian adolescents born in the United States.

This study examined the interrelationships among peer networks, parental attributes, and drug use among Asian-Indian adolescents born in the United States whose parents emigrated from India. The sample consisted of 200 Asian-Indian adolescents, 116 males and 84 females, aged 13 to 18, who were born in the United States and resided in the greater New York metropolitan area. The subjects were interviewed using a semistructured instrument adapted from relevant validated scales and items from other researchers. Adolescent-reported data were analyzed using descriptive and univariable techniques. Of the 200 subjects, 32.5% had tried some form of tobacco, alcohol, or other drug, and 67.5% did not report drug use of any kind. The adolescents stated whether they had ever (at least one time) smoked cigarettes (16.5%), drank beer (18%), drank wine (20.5%), or smoked marijuana (2.5%). The parents' communication of the harmful consequences of drug use and approval of the adolescents' peer networks correlated (p < .05) independently with less drug use by the adolescents. The parents' concern for education was positively correlated (p < .05) with the adolescents' academic performance. The prevalence of drug use among Asian-Indian adolescents is low. Parents' awareness of their children's school performance, peer networks, and concerns related to the consequences of drug use can be used as an effective mechanism to communicate the prevention of drug use among adolescents.

Journal Article↗

Drug use among Asian-Indian adolescents: identifying protective/risk factors.

The problem of meeting the normative demands of two cultures (host country and country of origin) has been linked to adolescent substance use as a way to cope with conflicts with parents. This paper examines intergenerational conflict as a precursor to alcohol, tobacco, and other drug use among second-generation Asian-Indian adolescents (Asian Americans whose parents emigrated from India). Based on systems theory, a structural model depicting the linkage and temporal sequelae of mediating factors is presented. Risk and protective factors unique to Asian-Indian adolescents--sociodemographic, family relationship, peer bonding, psychological, cultural, and ecological--are identified. Further, the impact of gender differences on family relationships is examined. Implications of the findings for drug use prevention policies, with special emphasis on developing comprehensive primary prevention strategies, are discussed.

Adolescent↗

In vitro and in vivo induction of heat shock (stress) protein (Hsp) gene expression by selected pesticides.

The chloroacetamide insecticide alachlor, polyhalogenated cyclic hydrocarbons endrin and chlordane and the organophosphate pesticides chlorpyrifos and fenthion induce oxidative tissue damaging effects including lipid peroxidation and nuclear DNA-single strand breaks. The mechanism involved in the induction of oxidative stress by these xenobiotics is unknown. No information is available regarding whether these pesticides can induce the expression of heat shock (stress) protein (Hsp) genes as a common protective mechanism against tissue damage. The pesticides were administered p.o. individually to female Sprague-Dawley rats in two 0.25 LD50 doses at 0 h and 21 h. The animals were killed at 24 h, and liver, brain, heart and lung tissues were removed to examine the induction of Hsps by Western and Northern blot analysis. In a separate series of experiments, cultured neuroactive PC-12 cells were treated 24 h with 50, 100 or 200 nM concentrations of these pesticides. Alachlor, endrin, chlorpyrifos and fenthion induced Hsp89 alpha and Hsp89 beta in hepatic and brain tissues, as well as in cultured PC-12 cells. Chlordane induced some expression of Hsp89 alpha but not Hsp89 beta in the hepatic and brain tissues of treated rats. Some expression of Hsp89 beta was observed in lung tissues of endrin and alachlor treated animals. These findings were substantiated by Western blot analysis using Hsp90 antibody. Except chlordane all these pesticides induced enhanced synthesis of Hsp90 in cultured PC-12 cells. The results indicate striking tissue differences in the patterns of the Hsps induced by the pesticides which were used, and demonstrate that these pesticides can induce the expression of Hsp89 alpha and Hsp89 beta genes in various target organs of rats. The results support the hypothesis that these genes may be mechanistically involved in protecting tissues against oxidative stress induced by structurally diverse pesticides.

Acetamides↗

Production of reactive oxygen species by gastric cells in association with Helicobacter pylori.

Reactive oxygen species (ROS) and Helicobacter pylori have been identified as pathogenic factors in several gastrointestinal disorders. Since little information is available regarding the mechanistic pathways of H. pylori-induced gastric injury, the potential role of ROS was investigated. The induction of ROS in gastric cells (GC) by H. pylori was assessed using chemiluminescence, cytochrome c reduction, nitrobluetetrazolium (NBT) reduction and lactate dehydrogenase (LDH) leakage. The dose-dependent protective abilities of selected ROS scavengers on LDH leakage were determined. Following incubation of GC with three strains of H. pylori (1:1), approximately 5.7-8.0 and 3.8-4.3 fold increases were observed in cytochrome c and NBT reduction, respectively, demonstrating production of ROS. Enhanced chemiluminescence responses of 2.1- and 3.7-fold were observed following incubation of GC with H. pylori (ATCC 43504) at ratios of 1:1 and 1:10, respectively. Approximately 2.2- and 3.5-fold increases in LDH leakage were observed at GC:H. pylori (ATCC 43504) ratios of 1:1 and 1:10, respectively. Substantial inhibition of LDH leakage from GC in the presence of H. pylori was observed following co-incubations with selected ROS scavengers with cimetidine serving as the best chemoprotectant. The antioxidants and H2-receptor antagonists had no effect on growth of H. pylori cells. This study demonstrates that H. pylori induces enhanced production of ROS in GC, and enhances membrane damage.

Antioxidants↗

Purification of the adenomatous polyposis coli (APC) gene product.

Mutation of the adenomatous polyposis coli (APC) gene is responsible for familial adenomatous polyposis and is an etiologic factor for digestive tract malignancies. Although the APC gene product (APC) is believed to play a role in growth suppression of colonocytes, the underlying mechanism is not clear. However, recent evidence does suggest that APC is a microtubule-associated protein (MAP), and like other MAPs, it can be phosphorylated, as we have shown. To facilitate studies of APC function, we purified the APC protein. To purify the full-length APC protein, HCT116 human colon cancer cells were lysed and the particulate fraction from the lysate was extracted with ammonium sulfate followed by Sepharose 4B and DEAE-Sephacel column fractionation and then by sucrose zonal density gradient centrifugation. The final purified APC fraction was determined to be about 1000-fold enriched in APC. The availability of purified APC will be valuable in investigating possible growth-suppressing mechanisms of APC including specific sites of APC phosphorylation and APC's interaction with other cellular proteins.

Adenomatous Polyposis Coli Protein↗

Phosphorylation of the adenomatous polyposis coli protein and its possible regulatory effects in cells.

The adenomatous polyposis coli (APC) gene is etiologically associated with familial adenomatous polyposis and gastrointestinal malignancies, but its cellular function and role in tumorigenesis are unclear. Recent reports indicate that wild-type, but not mutant, APC gene product (APC) is associated with and promotes the assembly of cytoskeletal microtubules in vitro, suggesting that this mechanism has importance in tumor development. Because other microtubule-associated proteins (MAPs) undergo phosphorylation in their normal functioning, we postulated that APC is a phosphoprotein. HCT116 cells, containing full-length APC protein, were [32P]-prelabeled, and a 300-kDa band corresponding to phosphorylated APC was immunoprecipitated using each of three different anti-APC antibodies. High voltage electrophoresis of [32P]-labeled APC showed the presence of phospho-serine and phospho-threonine residues. Further immunoprecipitation analyses showed phosphorylation of i) full-length APC in human lymphoblastoid cells and ii) carboxyl-truncated APC in SW480 and DiFi colon carcinoma cells. Thus, APC is probably a phosphoprotein in normal and malignant tissues. We hypothesize a mechanism whereby phosphorylation of APC may play a regulatory role in its interaction with microtubules. This may involve phosphorylation of (Ser/Thr)-Pro amino acid motifs in APC's basic domain. We propose that deletion of this domain disrupts APC binding to microtubules, explaining how APC mutations are linked to cancer development.

Adenomatous Polyposis Coli Protein↗

Radioimmunoassay of the APC gene product using antibodies against its middle and carboxyl regions.

A radioimmunoassay (RIA) has been developed for the adenomatous polyposis coli protein (APC). High-avidity rabbit polyclonal antibodies were produced against synthetic peptides corresponding to amino acids 1865-1881 (APC-1) and to amino acids 1336-1350 (APC-2) in APC's 2844 amino acid sequence. Both antibodies were utilized in RIA to evaluate full-length APC that is present in the insoluble particulate fraction of cell lysates. High salt extraction, often employed for coiled-coil type protein preparations, was found to be useful for extraction of APC from lysates of normal colonic epithelium. Proteolytic digestion of high salt extracts increased antibody reactivity toward both epitopes, suggesting that APC-1 and APC-2 antigenic sites are partially concealed due to APC's involvement in multiprotein complexes. Thus, RIA using our antibodies will provide a valuable tool for APC protein purification and in studies for elucidating APC's biologic function.

Adenomatous Polyposis Coli Protein↗