Search PubMed⌕ Search

Biomedical subjects

S Chatterjee

Publications and source records attributed to S Chatterjee.

At least 271 records · Page 15Linked to original sources

Growth-phase-dependent response to DNA damage in poly(ADP-ribose) polymerase deficient cell lines: basis for a new hypothesis describing the role of poly(ADP-ribose) polymerase in DNA replication and repair.

We have studied the role of poly(ADP-ribose) polymerase in the repair of DNA damage induced by x-ray and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) by using V79 chinese hamster cells, and two derivative mutant cell lines, ADPRT54 and ADPRT351, that are deficient in poly(ADP-ribose) polymerase activity. Under exponentially growing conditions these mutant cell lines are hypersensitive to x-irradiation and MNNG compared to their parental V79 cells which could be interpreted to suggest that poly(ADP-ribose) polymerase is involved in the repair of DNA damage. However, the level of DNA strand breaks induced by x-irradiation and MNNG and their rates of repair are similar in all the cell lines, thus suggesting that it may not be the difference in strand break formation or in its rate of repair that is contributing to the enhanced cell killing in exponentially growing poly(ADP-ribose) polymerase deficient cell lines. In contrast, under growth-arrested conditions, all three cell lines become similarly sensitive to both x-irradiation and MNNG, thus suggesting that poly(ADP-ribose) polymerase may not be involved in the repair of DNA damage in growth-arrested cells. These paradoxical results could be interpreted to suggest that poly(ADP-ribose) polymerase is involved in DNA repair in a cell-cycle-dependent fashion, however, it is functionally active throughout the cell cycle. To resolve this dilemma and explain these results and those obtained by many others, we propose that the normal function of poly(ADP-ribose) polymerase is to prevent DNA recombination processes and facilitate DNA ligation.

Animals↗

A rapid protein A binding radioimmunoassay for the evaluation of antiviral agents.

A simple, rapid and quantitative protein A binding radioimmunoassay (RIA) was developed to screen and evaluate antiviral drugs against human cytomegalovirus (HCMV) replication. It was found that (S)-1-[(3-hydroxy-2-phosphonylmethoxy)propyl]cytosine (HPMPC) and human gamma-interferon (IFN) were more effective than 9-[(1-3-dihydroxy-2-propoxy)methyl]guanine (DHPG) and other IFNs against HCMV replication in human fibroblast cells. The block in virus replication was not due to toxic effect of these compounds on human fibroblast cells. The results were in good agreement with those of other workers. The results indicate that protein A binding RIA can be useful for rapid and quantitative screening of compounds effective against HCMV replication.

Antiviral Agents↗

Growth and development of cellular slime mould Dictyostelium discoideum treated with DDT.

The effects of dichlorodiphenyl trichloroethane (DDT) on the growth, phagocytic activity, ultrastructure and developmental stages of a well known species of the cellular slime mould, Dictyostelium discoideum were studied. DDT, at doses of 60 ppm and above, inhibited growth of the vegetative cells and this was also evident from the colony blots which were smaller in size. A dose-dependent inhibition occurred in the phagocytic activity and macromolecular syntheses of DDT-treated cells. The cytomorphology of growing Dictyostelium cells, as revealed under light and electron microscopes, was profoundly affected by DDT treatment. Further, a considerable delay occurred in the various morphogenetic events in the slime mould cells exposed to DDT.

Journal Article↗

Study on the activities of testes and accessory sex glands after losulazine treatment in rats.

Losulazine hydrochloride, an antihypertensive agent, was administered intraperitoneally to adult male Wistar rats in doses of 1, 2 and 5 mg/kg/day for 1 seminiferous epithelium cycle to determine its effects on testicular steroidogenesis, spermatogenesis and accessory sex gland function. Administration of low doses of losulazine (1 and 2 mg/kg) resulted in a significant elevation of the steriodogenic key enzymes activity along with significant depletion of cholesterol content in testicular tissue. In addition, a significant rise in acid phosphatase activity in testes and prostate, and fructose content in accessory sex glands was also observed after low doses of losulazine. However, treatment with a higher dose of losulazine (5 mg/kg) significantly reduced the activities of testicular steroidogenic enzymes and acid phosphatase, and the content of fructose in accessory sex glands. Quantitative evaluation of the different varieties of germ cells at stage VII of the seminiferous epithelium cycle and epididymal sperm count in all losulazine-treated rats revealed a persistant prominent detrimental change in spermatogenesis. The results of our present experiment demonstrate an adverse action of losulazine treatment on functional activities of testes and accessory sex glands in adult rats.

17-Hydroxysteroid Dehydrogenases↗

Recent developments in the assessment of chromosomal damage.

Ionizing radiation and restriction endonucleases are very efficient in inducing chromosomal aberrations (CAs). These aberrations are mainly consequences of misrepair of DNA double-strand breaks (DSBs). The fast repairing component of DSBs induced by ionizing radiation seems to be responsible for exchange aberration. Use of premature chromosome condensation technique in combination with DNA repair inhibitors such as ara A has given valuable information on the assessment of the frequencies of initial chromosome breaks and the kinetics of their repair following low LET radiation. The recently developed 'chromosome painting' technique using chromosome-specific libraries has also increased considerably the resolution of identifying and scoring of CAs. After low LET radiation, stable chromosome exchanges (translocations) are induced more frequently than unstable chromosome exchanges (dicentrics). Fluorescence in situ hybridization employing telomeric probe has made it possible to score efficiently exchange aberrations involving the acrocentric chromosomes of mouse. Chinese hamster cells have several intercalary telomeric sequences present in most of the chromosomes. These telomeric blocks have been found to be associated with chromosomal aberrations induced by restriction endonucleases and short wave UV and evidence has been obtained for apparent amplification of telomeric sequences at the break points.

Aneuploidy↗

Rapid diagnosis of early ectopic pregnancy in an emergency gynaecology service--are measurements of progesterone, intact and free beta human chorionic gonadotrophin helpful?

The clinical usefulness of measuring serum concentrations of progesterone, human chorionic gonadotrophin (HCG) and the free beta-subunit of HCG in distinguishing between early viable and non-viable pregnancy, before an accurate ultrasound diagnosis is possible, was evaluated in a prospective study of patients presenting to our emergency gynaecology service with a clinical suspicion of ectopic pregnancy. Patients were selected on the basis of initial HCG concentrations; samples with HCG 25-10,000 IU/l were later analysed for progesterone and free beta HCG. Of the 181 patients studied, 38 (21%) had an ectopic pregnancy, 108 (60%) had a spontaneous abortion and 35 (19%) had a viable intra-uterine pregnancy. Concentrations of HCG and free beta HCG in the group with viable pregnancies were significantly higher than in the group with ectopic pregnancy (P < 0.001) and than those destined to miscarry (P < 0.01). Progesterone concentrations were also significantly higher in the viable versus the ectopic and the spontaneous abortion groups (P < 0.001 in each case). Despite these highly significant differences there was a degree of overlap such that it was impossible to devise a cut-off level for any hormone analysed, either singly or in combination, which would offer a clinically useful predictor of outcome.

Chorionic Gonadotropin↗

Identification of staphylococcal enterotoxin B sequences important for induction of lymphocyte proliferation by using synthetic peptide fragments of the toxin.

A series of 13 synthetic peptides, approximately 30 amino acids each, which spanned the entire sequence of staphylococcal enterotoxin B (SEB) were tested to evaluate their effects on T-cell proliferation in a culture system containing elutriated human peripheral blood lymphocytes incubated with a specific ratio of mononuclear cells. Four peptide regions were found to inhibit SEB-induced proliferation; they included sequences 1 to 30 (previously thought to be involved in major histocompatibility complex class II binding), 61 to 92 (sequences which relate to the T-cell receptor site), 93 to 112 (a linear sequence corresponding to the cysteine loop), and 130 to 160 (containing a highly conserved sequence, KKKVTAQEL). Antisera raised to this last peptide were capable of neutralizing SEB-induced proliferation. Antisera raised against the peptides which overlapped this sequence also were somewhat inhibitory. Neutralizing antisera were not produced from any other peptide sequence tested. To determine if any of these effects were nonspecific with regard to SEB-induced proliferation, the peptides were tested for inhibition of phorbol dibutyryl ester-induced proliferation, and only the sequence 93 to 112 (corresponding to the cysteinyl loop region) was consistently inhibitory (40%). Of the regions which displayed inhibition of SEB-induced proliferation, the peptide 130 to 160 inhibited binding of 125I-SEB to lymphocytes. These data suggest that the residues containing and surrounding the sequence KKKVTAQEL may be critical in the SEB-induced proliferation and may be useful for developing neutralizing antisera to SEB.

Amino Acid Sequence↗

Efficient gene transfer into nondividing cells by adeno-associated virus-based vectors.

Gene transfer vectors based on adeno-associated virus (AAV) are emerging as highly promising for use in human gene therapy by virtue of their characteristics of wide host range, high transduction efficiencies, and lack of cytopathogenicity. To better define the biology of AAV-mediated gene transfer, we tested the ability of an AAV vector to efficiently introduce transgenes into nonproliferating cell populations. Cells were induced into a nonproliferative state by treatment with the DNA synthesis inhibitors fluorodeoxyuridine and aphidicolin or by contact inhibition induced by confluence and serum starvation. Cells in logarithmic growth or DNA synthesis arrest were transduced with vCWR:beta gal, an AAV-based vector encoding beta-galactosidase under Rous sarcoma virus long terminal repeat promoter control. Under each condition tested, vCWR:beta Gal expression in nondividing cells was at least equivalent to that in actively proliferating cells, suggesting that mechanisms for virus attachment, nuclear transport, virion uncoating, and perhaps some limited second-strand synthesis of AAV vectors were present in nondividing cells. Southern hybridization analysis of vector sequences from cells transduced while in DNA synthetic arrest and expanded after release of the block confirmed ultimate integration of the vector genome into cellular chromosomal DNA. These findings may provide the basis for the use of AAV-based vectors for gene transfer into quiescent cell populations such as totipotent hematopoietic stem cells.

Aphidicolin↗

Aerobic capacity of the brick-field workers in eastern India.

Forty two male brick-field workers of two age groups, viz. 20-29 and 30-39 yrs were studied with a view to determine their aerobic capacity (VO2 max). The average values of VO2 max in l.min-1 showed only small change between the young and the aged groups, but the values of the VO2 max in ml.kg.-1min-1 showed significant difference between the groups due to body weight increase in the aged group. The aerobic capacity of the workers engaged in heavy manual work such as puddlers and load carriers were found to be comparatively higher and a positive significant relationship has been established between the aerobic capacity and different occupations in the brick-field workers.

Adult↗

Balhimycin, a new glycopeptide antibiotic produced by Amycolatopsis sp. Y-86,21022. Taxonomy, production, isolation and biological activity.

A new glycopeptide antibiotic, balhimycin, has been isolated from the fermentation broth of a Amycolatopsis sp. Y-86,21022. Balhimycin belongs to the vancomycin class of glycopeptides and contains a dehydrovancosamine sugar. The biological activity of balhimycin has been compared extensively with that of vancomycin against methicillin resistant staphylococci and also against anaerobes. Balhimycin is marginally superior to vancomycin in its in vitro activity against anaerobes and in its bactericidal properties.

Actinobacteria↗

Ribozyme-mediated in vitro cleavage of transcripts arising from the major transforming genes of human papillomavirus type 16.

Human papillomaviruses (HPV) have been strongly implicated as important cofactors in the development of several human malignancies, particularly anogenital carcinomas. Products arising from the E6 and E7 open reading frames (ORFs) from HPV-16, a type commonly associated with human cervical carcinoma, are essential for viral transformation. Unfortunately, a highly effective treatment for this infection is not available. To develop a novel treatment for this disease, ribozymes were designed to cleave all transcripts encoding HPV-16 E6 and E7 ORFs in proximity to their translational start sites ("AUG"). Cleavage sites for Rz110 and Rz558 occur immediately 3' to nucleotides 110 and 558 of the viral genomic DNA, respectively. Oligonucleotides corresponding to these ribozymes were synthesized and inserted into a eucaryotic viral vector derived from the nonpathogenic parvovirus, adeno-associated virus. Ribozyme transcription from this vector, termed CWRT7:SVN, is under control of both the highly active Rous sarcoma virus long terminal repeat and bacteriophage T7 promoters. T7 transcripts of the E6 and E7 ribozymes efficiently cleaved their cognate targets in vitro under a variety of conditions, including physiological temperature. These results may provide the basis for the development of a ribozyme-based, gene therapeutic treatment for HPV-associated diseases.

Avian Sarcoma Viruses↗

Schedule-dependent cytotoxicity of topotecan alone and in combination chemotherapy regimens.

The schedule-dependent cytotoxic effects of topotecan were evaluated in tissue culture experiments with Chinese hamster V79 cells. One hour exposure to topotecan resulted in a typical phase-specific cell killing curve in which increasing concentrations kill progressively more cells and then reach a plateau when all susceptible cells are killed. In contrast, exposure for 24 h results in a steep concentration-response curve with no plateau. Other S-phase agents such as hydroxyurea or aphidicolin antagonized cytotoxicity when administered by simultaneous exposure with topotecan. Combinations of melphalan, BCNU (1,3 bis(2-chloroethyl)-1-nitrosourea), or cisplatinum with topotecan were most effective when cells were exposed to the alkylating agent or platinating agent during the first hour of a 24-h topotecan exposure. Combinations of topotecan with etoposide or adriamycin produce more cytotoxicity when topotecan is administered by prolonged exposure; however, there is no significant difference depending on whether the topoisomerase II inhibitor is added at the beginning or end of the topotecan exposure. These studies show the importance of appropriate dose scheduling to obtain optimal interaction of chemotherapeutic agents given in combination with topotecan.

Alkylating Agents↗

Physical growth pattern for boys (9-18 yr) from rural west Bengal.

A cross-sectional anthropometric survey on 629 healthy boys (9-18 yr) of the lower and middle class families of Hooghly district of rural West Bengal was undertaken to study the growth pattern of boys of this population. Maximum gain in height and weight of boys was attained at 13-15 yr of age, as has been reported earlier for boys of Calcutta; other anthropometric measurements followed almost similar pattern. The boys of the present study were superior in physique to south Indian boys, boys of rural Udaipur, Lucknow and of those reported by ICMR. They are also found to be taller than the boys of West Bengal studied (longitudinal) between 1952-1966. The Bengalee girls of the same area of West Bengal showed an accelerated growth up to the age of 13 or 14 (for height and weight respectively) than the boys of comparable age but the reverse was observed at the age of 14 or 15. Boys of the present study were shorter and lighter than well-to-do Indian, American and British counterparts.

Adolescent↗

Development of cellular slime mould, Dictyostelium discoideum treated with a carbamate pesticide.

Dictyostelium cells when treated with 100 ppm carbaryl or placed on 20 ppm carbaryl agar showed profound changes in the developmental stages. The treated cells showed larger aggregate formations, inhibition of cAMP-chemotaxis and cAMP dependent extracellular phosphodiesterase activity. The fruiting body formations were also scarce. The developing Dictyostelium cells when placed on carbaryl agar showed aberrant morphogenesis with larger aggregates, abnormal slugs and large fruiting bodies. In all cases the development of the treated cells showed considerable delay when compared with controls.

Animals↗

Factors determining the long-term outcome of surgery for acromegaly.

Seventy-nine patients with acromegaly were investigated before and after transsphenoidal adenomectomy, to determine the immediate and late outcome, the pre-operative features associated with a good result, and the accuracy of post-operative testing in predicting outcome. Pre-operative evaluation included basal growth hormone (GH), GH response to oral glucose tolerance test (OGTT), GH response to thyrotrophin-releasing hormone (TRH), tests of pituitary reserve, and pituitary scanning to assess tumour size. A few weeks after surgery, these tests were repeated. The patients were recalled for late assessment 1-13 years (median 86 months) after the operation. At the immediate postoperative testing, minimum GH after oral glucose was < or = 2 mU/l in 48.7%, < 5 mU/l in 76.3% and < 10 mU/l in 84.2%. Only 12 patients had GH > 10 mU/l. Basal GH was < or = 2 mU/l in 21%, < 5 in 59.2%, < 10 in 73.6% and < 20 in 90.8%. A minimum GH of < or = 2 mU/l during an OGTT was achieved in 67.4% of patients with intrasellar tumours, compared with 27.3% with extrasellar tumours. Basal GH and post-glucose GH correlated with the late outcome. GH response to TRH showed no correlation with outcome. IGF-1, which could not be assessed in detail, correlated with GH but was not a reliable indicator of outcome. Transsphenoidal adenomectomy is thus a very satisfactory treatment for acromegaly. Postoperative levels of basal growth hormone < 5 mU/l and post-glucose GH < or = 2 mU/l can be regarded as a biochemical cure. Postoperative radiotherapy is not required in patients who achieve a good result. The preoperative factors which significantly influenced the final outcome were basal GH, post-glucose minimum GH, tumour size and impaired pituitary reserve.

Acromegaly↗