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Biomedical subjects

S Sen

Publications and source records attributed to S Sen.

At least 55 records · Page 3Linked to original sources
PubMed1990

Increase in topoisomerase-II-mediated DNA breaks and cytotoxicity of VP16 in human U937 lymphoma cells pretreated with low doses of methotrexate.

Pre-treatment with low, non-toxic concentrations (0.04 microM) of methotrexate (MTX) for 16 hr increased etoposide (VP16)-induced growth inhibition and cytotoxicity in the U937 human histiocytic lymphoma cell line. VP16 cytotoxicity was significantly potentiated when the drug was given for 2 hr immediately after MTX pre-treatment or between 2 and 4 hr or 4 and 6 hr after recovery from MTX pre-treatment. By 24 hr after recovery from MTX, no potentiation was evident. The increased cytotoxicity of VP16 was associated with an increase in drug-induced DNA breaks as assessed by the alkaline elution method after proteinase K digestion. The amount of DNA single-strand breaks (DNA SSB) increased when the drug was given 0, 2, and 4 hr after MTX pre-treatment. DNA SSBs induced by the drug between 6 and 24 hr after MTX pre-treatment were similar to those seen in cells without pretreatment. The amount of DNA double-strand breaks (DNA DSB) caused by VP16 increased significantly when the drug was given 4 hr after recovery from MTX pre-treatment. VP16-induced DNA DSBs were still higher 6 hr after MTX pre-treatment, but by 24 hr they were similar to those observed in MTX-untreated cells. Flow cytometric analysis showed that MTX pre-treatment was causing an accumulation of U937 cells at the G1-S boundary of the cell cycle. When MTX was removed, a wave of synchronization followed. Using Western blot electrophoresis and polyclonal antibodies to antitopoisomerase II, we found that MTX pre-treatment raised the cellular topoisomerase II content. Our findings suggest that the potentiation of VP16 cytotoxicity on U937 cells by low, non-toxic MTX pre-treatment is due to a larger fraction of S-phase cells containing a higher concentration of topoisomerase II, which is the putative target of VP16 action.

Blotting, Western↗
PubMed1990

Transfer of transposon Tn916 from Bacillus subtilis to Thermus aquaticus.

Broad host range conjugating transposon Tn916 has been introduced into the extreme thermophile Thermus by transposon transformation and transposition into the Bacillus subtilis chromosome followed by broth mating with Thermus aquaticus ATCC27634. Tetracycline resistant Thermus transconjugants were obtained at a frequency of 1.4 X 10(-7) per donor and 1.2 X 10(-7) per recipient. Transposon transfer from Thermus to Bacillus subtilis was also demonstrated in similar broth matings. Transfer characteristics were consistent with the conjugation mechanism described for Tn916 in mesophiles.

Bacillus subtilis↗
PubMed1990

Synchronisation of cancer cell lines of human origin using methotrexate.

U937 human histiocytic lymphoma cell line and SW626 ovarian carcinoma line of human origin were synchronised using very low, nontoxic concentrations (0.04-0.08 microM for 16-24 h) of methotrexate (MTX) under standard culture conditions. Satisfactory synchrony was achieved to study S phase events. Various kinetic behaviours and biological properties of the synchronised cells are considered for characterisation of the system. MTX-synchronisation was compared with that induced by aphidicolin (APC) alone and by serum deprivation and APC. In some cancer cell lines MTX appears to be the best choice for obtaining highly synchronised cell populations without cytotoxicity or physiological perturbations.

Carcinoma↗
PubMed1990

Pulmonary hypertension in lambs with congenital diaphragmatic hernia: vasodilator prostaglandins, isoprenaline, and tolazoline.

After antenatal induction of diaphragmatic hernias in fetal lambs, prostaglandins D2, E1, and I2 were compared to tolazoline, or isoprenaline, for the treatment of pulmonary hypertension. When rendered hypoxic, these, and normal lambs, showed an increase in pulmonary artery pressure, a decrease in systemic pressure, and a decrease in pulmonary blood flow. All of the drugs altered that response, but to different degrees. None of the drugs tested was consistently successful in reversing the adverse affects of hypoxia, but prostaglandin D2 came closest to the ideal vasodilator, decreasing the pulmonary artery pressure in all seven hypoxic lambs having a diaphragmatic hernia. There was a concomitant increase in pulmonary blood flow in six; in the remaining lamb the decrease in blood flow induced by the hypoxia was arrested. At the same time, there was an increase in systemic artery pressure in three, the decrease was arrested in two, but the decrease continued in the other two. Isoprenaline was a more effective drug than tolazoline, producing an increase in pulmonary blood flow in five of the seven lambs, with minor decreases in systemic pressure in five. Tolazoline improved blood flow in three of six lambs (not all lambs survived the full study), with a marked decrease in systemic pressure in four of them. Prostaglandin D2 seems to be a useful drug for the treatment of patients having diaphragmatic hernias and pulmonary hypertension, and warrants further study. Isoprenaline was the most effective of the readily available drugs tested in this animal model.

Animals↗
PubMed1990

Stimulation of proteolysis on calmodulin.

The proteolysis of calmodulin by fungal protease (type XIX) was greatly enhanced in the presence of dGTP and MS2 RNA. Whereas, only moderate proteolytic activation on bacterial proteases (type XXVI) was observed in the presence of MS2 RNA. No appreciable proteolysis of calmodulin by bacterial protease (type IX) was observed. Proteolytic fragments of calmodulin cleaved by fungal protease exhibited unusual low mobility during SDS-polyacrylamide gel electrophoresis. Similar decreased electrophoretic mobility was also noted in the proteolytic fragments of other Ca2(+)-binding proteins including S-100A protein and parvalbumin.

Animals↗
PubMed1990

Flow cytometric study of hybridoma cell culture: correlation between cell surface fluorescence and IgG production rate.

Flow cytometry was applied to measure the fluorescence of IgG molecules on hybridoma cell surface stained with FITC-conjugated anti-mouse IgG F(ab')2. Using light scattering to exclude the dead cell population from the analysis, the surface fluorescence intensity allows for the differentiation between producing and nonproducing cells. A linear correlation has been found between the intensity of mean surface fluorescence of the cell population and the specific antibody production rate.

Animals↗
PubMed1990

Electrophysiological effects of nicainoprol in patients with paroxysmal supraventricular tachycardias.

The electrophysiological effects of nicainoprol, a new class I antiarrhythmic drug, were evaluated in 29 patients with supraventricular reentrant tachycardias, due to accessory pathways in 15 and dual atrioventricular nodal pathways in 14 patients. Nicainoprol was administered intravenously as a bolus followed by continuous infusion of 1.5 mg/kg in two and of 2 mg/kg in 27 patients over one hour. Nicainoprol was given as a bolus of 1.5-2 mg/kg during sinus rhythm in 11 patients or during induced supraventricular tachycardia in 18. The drug successfully terminated the tachycardia in 17 patients due to block in the retrograde tachycardia limb in 15 and the antegrade limb in 2 patients. Prolongation of the cycle length preceded the termination in each case. In one case, the termination could not be achieved despite the administration of 3 mg/kg. The sinus cycle length, heart rate corrected QT interval as well as right atrial and right ventricular effective refractory periods remained unchanged. In contrast, the intranodal and infranodal conduction times, as well as QRS duration, were prolonged significantly. In patients with dual atrioventricular nodal pathways, there was a significant (P less than 0.05) increase of the effective refractory periods of the anterograde slow pathways. The changes of the anterograde fast pathways, however, did not reach significance level. More pronounced effects were found on effective refractory periods of the retrograde pathways, which were blocked in 4 patients and significantly (P less than 0.05) prolonged in the remainder. Similarly, in patients with accessory pathways the effect on the retrograde conduction was more marked with complete block in 5 patients and significant prolongation of effective refractory periods and shortest paced cycle lengths in the remainder.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Collagen phenotypes during development and regression of myocardial hypertrophy in spontaneously hypertensive rats.

The myocardium contains collagen matrix that is a major determinant of its architecture, structural integrity, and mechanical properties. This fibrillar matrix consists primarily of type I and type III collagens having epimysial, perimysial, and endomysial components. The present study shows the alteration of collagen phenotypes during the evolution of hypertensive hypertrophy. Therapy with captopril, an angiotensin-converting enzyme inhibitor that regresses cardiac hypertrophy, not only reduces the total amount of collagen but reverses the altered distribution of type I and type III collagen. In normotensive rats, captopril did not significantly reduce collagen content or alter the ratio of type I to type III collagen.

Age Factors↗
PubMed1990

Paralytic poliomyelitis 1976-1988: report from a Sentinel Centre.

Kalawati Saran Children's Hospital, New Delhi, is the Sentinel Centre for poliomyelitis in the Northern region and 52-76% of cases of acute poliomyelitis from the Union Territory of Delhi are registered here. In this paper, data from this hospital for the last 13 years is presented. A detailed analysis of 1874 cases seen during the year 1987 is also presented. Inspite of large scale vaccination being carried out, the total number of cases have not shown a corresponding decline. The incidence of acute polio in Delhi has not declined over the years: it was 14.7/100,000 population in 1976 and 15.25 100,000 in 1988. There has been no change in the epidemiology of the disease over the years, except that the disease among the fully vaccinated children has increased from 1.3% in 1979 to 13.9% in 1988. Inspite of a decade of use of the oral polio vaccine there has been no significant reduction in the incidence of the disease, and urgent alternative strategies are needed.

Child, Preschool↗
PubMed1990

Cronkhite-Canada syndrome with hypothyroidism.

An elderly man with non-familial gastrointestinal polyposis, malabsorption and progressive hypoproteinemia is reported. Associated alopecia, cutaneous hyperpigmentation and nail dystrophy with loss of nails were consistent with the diagnosis of Cronkhite-Canada syndrome. Hypothyroidism was present in this patient and the rare association of these two conditions is discussed.

Aged↗
PubMed1989

Model for the formation of double minutes from prematurely condensed chromosomes of replicating micronuclei in drug-treated Chinese hamster ovary cells undergoing DNA amplification.

Double minutes (DM) have been associated with gene amplification in drug-resistant cells and tumor cells. However, the mechanisms by which DM are formed have not been elucidated. We present here a model to describe a possible mechanism of DM formation based on the observations made in two independent early drug-selected multidrug-resistant cell lines and from in vitro somatic cell fusion experiments between synchronized S- and M-phase cells. The multidrug-resistant cell lines contain both DM and amplified mdr (P-glycoprotein) gene. Cytogenetic analyses of cells at early stages of selection revealed the presence of a number of micronuclei in a subpopulation of these cells. These micronuclei were often asynchronous in their progression through the cell cycle. As a result, premature condensation of micronuclear chromatin was often observed in metaphase plates. The pulverized chromatin pattern seen in certain instances of S-phase prematurely condensed chromosomes displays a striking resemblance to DM structures. These DM-like structures are linked by replicating DNA as revealed by DNA labeling experiments. Somatic cell hybrids between S- and M-phase cells when grown in vitro demonstrated that S-phase prematurely condensed chromatin indeed gives rise to extra chromosomal structures in the successive cell generations. It is hypothesized that distinct DM-like structures may arise from the partially replicated and prematurely condensed S-phase chromosomes following their liberation as extra chromosomal entities after replication and/or recombination in the succeeding division cycle(s). The enrichment for DM containing specific genes in drug-resistant cells may result from the subsequent drug selections.

Animals↗
PubMed1989

Multiple amylase genes in two strains of Bacillus stearothermophilus.

Plasmid DNA fragments from Bacillus stearothermophilus ATCC29609 (BR135) and chromosomal DNA fragments from B. stearothermophilus ATCC31195 (BR132) were cloned into pBR322 and transformed into Escherichia coli strain HB101. Clones were selected which demonstrate extracellular expression of thermostable amylase. The DNA inserts from both strains showed similar restriction maps. Examination of the parental strains revealed plasmids of approx. 100 kb and 35 kb for BR135 and no discernible plasmids for BR132. Hybridization experiments showed that the amylase gene is contained within a 3.2-kb HindIII fragment on both plasmids, and to be present in multiple copies in the BR135 chromosome. Multiple chromosomal copies of the amylase gene were also observed for BR132. Purification of the alpha-amylase produced by the cloned plasmid amy gene yielded a homogeneous 58-kDa protein with thermostable amylase activity.

Blotting, Southern↗
PubMed1989

Betel cytotoxicity.

An attempt to summarise the phytochemical composition of the betel quid, formation of N-nitrosation products during chewing, results of carcinogenicity and mutagenicity studies and the relationship between betel chewing and submucous fibrosis have been made from presently available literature. The present review provides a better understanding of the capacity of the quid ingredients in inducing preneoplastic changes for evaluation of the risk involved with its chewing.

Animals↗
PubMed1989

Chromosomal alterations and DNA content in rats during ageing.

Chromosome analysis of bone marrow cells from 96 sex-matched Rattus norvegicus of 12 different age groups showed a significant increase in hypodiploid cells with ageing. However, in meiotic preparations from gonadal cells of male rats the frequency of hypodiploid or hyperdiploid cells did not change significantly. In situ DNA estimation of bone marrow nuclei, following Feulgen cytophotometry, also did not show any significant difference with gradual age changes.

Aging↗
PubMed1989

Lactate dehydrogenase isozymes in xenotropic virus producing mice.

Lactate dehydrogenase (LDH; E.C. 1.1.1.27) isozymes were compared in three inbred strains of mice, and two strains of wild mice, as well as the F1 hybrids and other genetic crosses involving two of the inbred strains. The strains examined were NZB/B1NJ, 129/J and C57BL/6J, Mus musculus molossinus and M. musculus castaneus. Genetic crosses were made between the xenotropic virus-producing NZB and the non-virus producing 129/J mice. Tissue specificity of LDH in these strains was studied using homogenates of kidney, liver, spleen and thymus. Polymorphism of the enzyme was studied by agarose gel electrophoresis. Enzyme polymorphism in the tissues of NZB and 129/J has not been previously reported. The liver and spleen tissues of 129/J showed the absence of LDH-1 and LDH-2 isozymes. Thymic homogenates of NZB showed a lack of expression of LDH-1, LDH-2 and LDH-3 isozymes. The F1, F2 and the backcross progeny from genetic crosses involving NZB, and 129/J mice showed an isozyme pattern more similar to the non-virus-producing 129/J strain than the virus-producing NZB. Evidence of genetic regulation at the LDH-B subunit appears to be the reason for the differential expression of the isozymes in NZB and 129/J strains. The other inbred strain of mice, C57BL/6J, also showed a greater similarity to the 129/J strain than NZB. The two strains of wild mice were similar in their expression of LDH-isozymes between each other and to the 129/J strain, with respect to the liver and spleen tissues.

Animals↗