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Biomedical subjects

S Chatterjee

Publications and source records attributed to S Chatterjee.

At least 253 records · Page 14Linked to original sources
PubMed1995

A novel point mutation in the 3' flanking region of the DNA-binding domain of topoisomerase II alpha associated with acquired resistance to topoisomerase II active agents.

V511 and V513 are Chinese hamster cell lines with acquired resistance to topoisomerase II (topo II) directed agents. These cell lines were obtained by mutagenizing Chinese hamster V79 cells with N-methyl-N'-nitro-N-nitrosoguanidine and subsequently selecting in etoposide (VP-16). We have previously shown that this resistance is not associated with alterations in drug uptake. To elucidate whether any alterations in the functionally important domains of topo II alpha were associated with VP-16 resistance, we used reverse transcriptase-polymerase chain reaction, single-strand conformational polymorphism analysis, and subsequent sequencing of topo II alpha from V79, V511, and V513 to search for mutations in five major functional domains including the regions of the consensus ATP binding sequences (Motif A and Motif B/dinucleotide binding site), the DNA binding domain, and the 5' and 3' flanking regions of the DNA binding position. The V511 cells showed no mutational changes in these regions. However, the topo II alpha gene from V513 showed a point mutation at nucleotide 2552 that resulted in a glycine-to-aspartate mutation at amino acid position 851 in the 3' flanking region of the DNA binding site. This mutation at amino acid position 851 in V513 cells is associated with reduced VP-16-induced cleavable complex formation demonstrated by potassium-sodium dodecyl sulfate assay and band-depletion analysis. Our results suggest that the mutation at amino acid position 851 may play a role in drug resistance, presumably by interfering with enzyme-DNA binding.

Amino Acid Sequence↗
PubMed1995

Effect of tobacco consumption on the function of male accessory sex glands.

The function of accessory sex glands in 29 tobacco smokers, 25 tobacco chewers and 30 non-users of tobacco was investigated by determining the ejaculate contents of various glandular markers: N-acetyl amino sugar and total phosphate (seminal vesicles) zinc and acid phosphatase (prostate gland), and alpha-1,4-glucosidase (epididymis). Both vesicular and prostatic parameters were reduced significantly in smokers compared with non-users of tobacco, whereas these parameters were unchanged in tobacco chewers. This difference may be due either to the difference in constitution of xenobiotics emitted as a result of burning tobacco, or to differences in the pharmacokinetics of the two forms of tobacco consumption. The activity of alpha-1,4-glucosidase was significantly lowered in both types of tobacco users. It is concluded that use of tobacco, especially by smoking, impairs the secretory function of accessory sex glands in man.

Acid Phosphatase↗
PubMed1995

Drastic reduction of topoisomerase II alpha associated with major acquired resistance to topoisomerase II active agents but minor perturbations of cell growth.

V511 and V513 cell lines, derived from Chinese hamster V79 cells following alkylating agent mutagenesis and subsequent selection with VP-16, showed resistance to cytotoxicity and DNA strand breaks induced by topoisomerase (topo) II inhibitors and were resistant to VP-16-induced sister chromatid exchanges. They showed no amplification of the multidrug-resistant p-glycoprotein. In a kinetoplast-DNA decatenation assay, V511 and V513 showed 51% and 49% topo II activity relative to parental V79 cells, respectively. By western-blot analysis all three logarithmically growing cell lines showed similar levels of topo II beta (M(r) 180,000), which increased as cells progressed to quiescence. In contrast, immunoreactive levels of topo II alpha (M(r) 170,000) were 6.8% in V511 and 62.4% in V513 relative to V79. V511 showed drastically decreased topo II alpha in both log growth and quiescence. In a second approach, immunoreactive topo II was analyzed in different phases of the cell cycle in logarithmically growing cells fractionated by fluorescence-activated cell sorting. All cell lines demonstrated relatively stable topo II beta throughout the cell cycle. Topo II alpha showed little cell cycle variation in V79 or V513. However, in V511, it was only detectable at low levels in G2/M phase. When cell growth parameters were measured, V511 and V513 showed a 17% increase in cell doubling time relative to V79. These studies indicate that cells with a drastic reduction in topo II alpha (V511) or mutant topo II alpha (V513) but with normal levels of topo II beta show only minor perturbations of cell growth.

Alkylating Agents↗
PubMed1995

Significance of exercise induced increase in diastolic pressure as an indicator of severe coronary artery disease.

A total of 100 patients were studied for the diastolic blood pressure response to treadmill exercise testing. No change in the diastolic pressure or lowering of the pressure was considered normal response. Seventy four patients had normal and 26 patients had abnormal diastolic blood pressure response. Out of these, 40 patients underwent coronary angiography. Fifty five percent of the patients with normal diastolic pressure response had normal coronaries compared to 20% with abnormal response (p < 0.03). Fifteen percent with normal response had triple vessel disease or left main coronary artery disease whereas forty percent with an abnormal response had significant disease (p < 0.03). Exercise induced ST segment depression was almost equal in both groups. Hence we can conclude that abnormal diastolic pressure response to treadmill exercise testing is a fairly good indicator of coronary artery disease irrespective of ST segment changes.

Blood Pressure↗
PubMed1995

Do we need to do comprehensive surgical staging in all cases of clinical early ovarian cancer?

Meticulous staging of ovarian cancer has so far been a prerequisite for treatment planning. However, more than 80% of patients operated by non-oncologists all over the world do not under go a complete staging. Recently there have been reports questioning the need for extensive staging from the point of cervical benefit. We have analysed our data of 64 stage ovarian cancer patients to see if clinical staging was adequate or relaparotomy with restaging is necessary. We conclude that though pathological staging is important for proper reporting of results and evaluation of treatment modalities, in the existing circumstances, a judicious use of clinical methods and taking available pathological factors into account, we can still produce comparable results with restricted use of relaparotomy.

Female↗
PubMed1995

Mutagenic activity of topoisomerase I inhibitors

Topoisomerase I-directed agents are now in Phase I and II clinical trials and show great promise as potentially important agents for cancer chemotherapy. Because of their mechanism of action they may also be potential mutagens; however, their mutagenicity and oncogenicity still remain to be elucidated. We have previously shown that VP-16, a topoisomerase II-directed agent, induces sister chromatid exchanges and gene deletions and/or rearrangements in vitro. These observations may account for both the cytotoxic effects of topoisomerase II-directed agents as well as their recently reported leukemonogenic potential. To evaluate the potential mutagenicity of topoisomerase I-directed drugs, we measured mutant frequencies at the hypoxanthine phosphoribosyl transferase locus of the V79 Chinese hamster fibroblast cell line treated with the topoisomerase I-directed drugs camptothecin and topotecan, and compared these results with mutant frequency obtained with the topoisomerase II-directed drug VP-16 and an alkylating agent, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). All of these drugs showed a dose-dependent increase in mutant frequency at the hypoxanthine phosphoribosyl transferase locus. At a dose producing approximately 30% survival, VP-16, camptothecin, and topotecan induced mutant frequencies of 11.3 x 10(-6), 4.9 x 10(-6), and 2.7 x 10(-6), respectively, whereas the spontaneous mutant frequency at this locus was 0.3 x 10(-6). In contrast, the alkylating agent MNNG produced a mutant frequency of 562 x 10(-6) at 26% survival dose. The molar mutagenic potencies, expressed as mutant frequency/mol-h exposure, for VP-16, camptothecin, topotecan, and MNNG at approximately 30% survival dose were 0.9, 8.2, 2.3, and 56.8, respectively. On Southern blot analysis after EcoRI, PstI, or HindIII digestion, 6 of 12 independent thioguanine-resistant mutants induced by topotecan showed gene deletions or rearrangements. In contrast, five of five independent spontaneous mutants and six of six independent mutants induced by MNNG demonstrated the same restriction pattern as the parental V79 cells. These results indicate that the mutant frequency and the mutagenic potential of topoisomerase I and II active agents are quantitatively similar. The results further demonstrate that topoisomerase I and II active agents introduce mutations characterized by gene deletions and rearrangements, whereas spontaneous mutations and those induced by alkylating agents appeared to be more characteristically associated with point mutations. Thus, clinical use of the topoisomerase I and II active agents is expected to cause similar mutagenic effects that could potentially lead to secondary malignancies.

Journal Article↗
PubMed1994

Health Behavior of International Travelers to Calcutta: Identifying the Need for a Travelers' Clinic.

With the growing rates of travel and, potentially therefore, of travel-related illness in India, this study was conducted to establish both the need of a travelers' clinic in Calcutta and a profile of the group or groups at risk of illness best served by such facilities. A total of 452 visitors, half business and package holiday travelers (group A) and half younger, low-budget tourists with less pretravel advice (group B), were compared. Through a questionnaire, their health, pretravel advice and prophylaxis, use of first aid, safe water use, posttravel treatment, and opinion concerning the need for a travelers' clinic were determined. Group A travelers stayed in deluxe hotels with more pretravel advice (90% compared to 72% in group B), were taking antimalarial agents (82% compared to 61% in group B), remained healthy (72% compared to 58% in group B), consumed safe water (87% compared to 47% in group B), and were more likely to seek posttravel treatment (75% compared to 60% in group B). The group B travelers, consequently, felt an increasing need for a travelers' clinic (92% compared to 82% in group A). Given the complexities of travel in India, there is a palpable need for appropriate medical attention to travelers, especially among the young, budget tourists, which is best provided at a travelers' clinic.

Journal Article↗
PubMed1994

Induction of M(r) 78,000 glucose-regulated stress protein in poly(adenosine diphosphate-ribose) polymerase- and nicotinamide adenine dinucleotide-deficient V79 cell lines and its relation to resistance to the topoisomerase II inhibitor etoposide.

Cell lines deficient in poly(ADP-ribose) synthesis due to enzyme deficiency (ADPRT54 and ADPRT351) or substrate deficiency (N2, N3, and N4) are resistant to topoisomerase II-directed agents, including etoposide (VP-16), N-[4-(9-acridinylamino)-3-methoxyphenyl]methanesulfonamide, and Adriamycin, relative to the effect of these agents on parental V79 Chinese hamster cells. Resistance is stable in the ADPRT54 and ADPRT351 cell lines, whereas resistance in the N2, N3, and N4 cell lines occurs when the cells are grown in nicotinamide-deficient medium to produce a state of NAD deficiency. However, sensitivity to VP-16 reverts to normal when cellular NAD levels return to control levels during growth in nicotinamide-containing complete medium. Poly(ADP-ribose) polymerase-deficient cell lines show constitutively increased levels of a protein at M(r) 78,000 on Coomassie blue-stained, sodium dodecyl sulfate-polyacrylamide gels that was subsequently confirmed with monoclonal antibodies to be M(r) 78,000 glucose-regulated stress protein (GRP78). Similarly, N2, N3, and N4 cells show induction of GRP78 under nicotinamide-deficient conditions. Induction of GRP78 is associated with elevated levels of GRP78 mRNA and appears to be regulated at the transcriptional level. When N3 cells with deficiency of poly(ADP-ribose) synthesis due to NAD deficiency are shifted to complete, nicotinamide-containing medium, they restore their NAD content, undergo a decrease in GRP78 levels, and regain sensitivity to VP-16. When V79 cells are shifted to nicotinamide-deficient medium they undergo a reduction in NAD content, followed by a progressive elevation in GRP78 levels, and they subsequently become increasingly resistant to VP-16. These studies demonstrate a clear association between deficiency of the NAD-poly(ADP-ribose) synthesis system, induction of GRP78 synthesis, and resistance to VP-16.

Animals↗
PubMed1994

Free radical bombing of spermatozoa in spermatic granuloma: an attempt to prevent autoimmune switch-on.

Even though vasectomy-associated reactions in subjects are established, the biochemical attributes of the granuloma cells enabling them to potently dispose of the accumulating spermatozoa remain unelucidated. This study demonstrates a careful "free-radical bombing" within the granuloma interior to efficiently disintegrate all the structural elements of the sperm cells, especially the proteins. A free radical triggered and instantaneous protein-disposal could be important in avoiding early post-vasectomy autoimmune triggering.

Animals↗
PubMed1994

Neutral sphingomyelinase action stimulates signal transduction of tumor necrosis factor-alpha in the synthesis of cholesteryl esters in human fibroblasts.

We have investigated biochemical mechanisms of tumor necrosis factor (TNF)-alpha signaling in cultured human skin fibroblasts. We found that TNF-alpha signaling may involve activation of a cell membrane neutral sphingomyelinase (N-SMase) in that within 2.5-5 min of treatment of cells with TNF-alpha there was a 2-fold increase in the activity of N-SMase compared to control. This reaction led to the hydrolysis of sphingomyelin as evidenced by a decrease in sphingomyelin mass and in the radioactivity associated with [14C]choline-labeled sphingomyelin. This was accompanied by a 4-fold increase in the formation of cholesteryl [14C]oleate within 2.5 min of incubation with TNF-alpha. This reaction also stimulated the mobilization of cell surface-associated [3H]cholesterol and its utilization in the synthesis of [3H]cholesteryl esters via acyl coenzyme-A cholesterol acyltransferase (ACAT). Gas chromatographic analysis revealed that the cellular level of cholesteryl esters increased about 2.5-3-fold following treatment with TNF-alpha compared to control. Cholesteryl ester synthesis was compromised upon incubation of cells with antibody against N-SMase and remained unaltered with TNF-beta and fibroblast growth factor. Furthermore, TNF-alpha-mediated stimulation of cholesteryl ester synthesis was compromised by incubation of cells with an inhibitor of ACAT. These findings suggest a possible biological role of N-SMase in the signal transduction of TNF-alpha in the synthesis of cholesteryl esters in human fibroblasts.

Cells, Cultured↗
PubMed1994

Pinocytic stimulation in Dictyostelium discoideum by gamma-benzene hexachloride.

Pinocytic activity is greatly stimulated in gamma-BHC (gamma isomer of benzene hexachloride) treated, vegetative cells of Dictyostelium discoideum as measured by 14C sucrose or FITC-dextran uptake. Transmission electron microscopic studies also reveal the presence of a greater number of pinosomal vesicles in the pesticide-treated Dictyostelium amoebae. The enhanced pinocytic activity has been discussed in relation to lipophilic interactions of gamma-BHC with the hydrophobic cell surface and the observed changes in the cytoskeletal proteins of the treated cells.

Animals↗