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Biomedical subjects

S Sen

Publications and source records attributed to S Sen.

At least 181 records · Page 10Linked to original sources

Sexually-transmitted disease (STD) markers in multitransfused children in relation to human immunodeficiency virus type-1 (HIV-1) infection: impact of STD markers in blood donors.

Association of serological markers for various sexually transmitted diseases (STDs) with Human Immunodeficiency Virus type 1 (HIV-1) infection among heterosexually promiscuous blood donors is well recognized. However, possibility of similar association among children receiving transfusion from these donors has not been adequately explored. Study on the association of some STD markers with HIV-1 infection in multitransfused (MT) children showed that both HIV-1 positive and HIV-1 negative groups of children had significantly higher prevalence of hepatitis B virus (HBV) markers, i.e. HBsAg (23 and 30 per cent), anti-HBs (46 and 57 per cent), anti-HBc (18 and 23 per cent), antibodies to cytomegalovirus of IgM class (36 and 37 per cent) and IgG class (72.7 and 70 per cent), IgG antibodies to Herpes Simplex Virus type-2 (23 and 23 per cent) compared to control group. However, seropositivity for HIV-1 infection could not be attributed as a risk factor for any of these markers in the group of MT children. On the contrary, significant association of anti HBc, anti HCV, CMV IgG and antitreponemal antibody with HIV-1 infection could be recorded in the group of blood donors. It appeared that due to low prevalence of HIV-1 infection among blood donors in India, both HIV-1 positive and HIV-1 negative groups of MT children received transfusion from HIV negative donors predominantly resulting in a comparable prevalence of STD markers in both the groups of MT children due to cumulative effect of transfusion from HIV-1 negative donors.

Biomarkers↗

Low energy transvenous cardioversion of short duration atrial tachyarrhythmias in humans using a single lead system.

The purpose of this study was to investigate the efficacy and safety of atrial cardioversion using an endocardial single lead system presently used for ventricular defibrillation. The study population consisted of 26 recipients of an ICD in combination with a conventional endocardial single lead system with the proximal spring electrode as anode in the SVC and the distal as cathode in the apex of the RV. Atrial tachyarrhythmias were induced by right atrial burst pacing. If the arrhythmia sustained > 1 minute, biphasic shocks synchronized with the R wave were delivered using the implanted device, beginning with an energy of 4 J. If 4 J failed to terminate the arrhythmia, energy was increased stepwise, if the first shock was successful, a step-down testing was performed after reinduction of atrial tachyarrhythmias. The mean atrial defibrillation threshold was 2.3 +/- 1.2 J (range, 0.5-5 J). A total of 154 shocks were delivered and no adverse effects were observed. The mean defibrillation threshold for atrial flutter was somewhat lower than that for AF (1.8 +/- 1 J vs 2.7 +/- 1.4 J, P = 0.08). There was no correlation between the atrial defibrillation threshold and a history of previously occurring atrial tachyarrhythmias, the kind of the underlying heart disease, a prescription of antiarrhythmic drugs, the dimension of the LA, the LVEF, or the ventricular DFT. Internal atrial cardioversion of short duration atrial tachyarrhythmias using a transvenous single lead system designed for ventricular defibrillation is feasible and safe at low energies, and may have important clinical applications.

Adult↗

Angiotensin II and myocyte growth: role of fibroblasts.

Angiotensin II (Ang II) has been implicated in stimulating myocyte growth in vitro, but the mechanism for such stimulation is still an open question. To understand the role of Ang II, we studied its effect on protein synthesis in rat neonatal and adult myocytes. Ang II (10(-8) mol/L) stimulated protein synthesis in neonatal myocytes by 43+/-3.5% over control. To prevent the proliferation of fibroblasts, bromodeoxyuridine was added, and protein synthesis in neonatal myocytes was reduced to 21+/-2.2% over control. In adult myocytes (cultured without bromodeoxyuridine), Ang II stimulated [3H]leucine incorporation by 24+/-2.3% over control; with bromodeoxyuridine, that stimulation was reduced significantly (13+/-0.93% over control). These data suggest that the presence of fibroblasts in the cultures may control myocyte growth. When supernatant from pure fibroblast culture was added to myocyte preparations, a significant increase (49.8+/-3.5% over control) in protein synthesis occurred. Pretreatment of these fibroblasts with Ang II (10(-3) mol/L) further stimulated protein synthesis, suggesting that Ang II directly stimulates the production of a factor from fibroblasts. The stimulatory effect of Ang II on the release of the factor can be completely blocked by pretreatment with losartan, an Ang II receptor (AT1) blocker. Our data are the first to demonstrate a paracrine effect of a fibroblast-derived factor that modulates myocyte growth. Fibroblast-derived factor loses its biological activity by (1) tryptic digestion, (2) exposure to pH below 4.0 and above 9.0, and (3) heating to 95 degrees C. The molecular weight of the factor is approximately 65 kD. The antibodies against fibroblast growth factor (both acidic and basic) could not inhibit this factor's stimulatory effect. Furthermore, this factor is heart specific and is produced at least up to the 16th passage of neonatal rat heart fibroblasts. Skin fibroblasts, aortic endothelial cells, and aortic smooth muscle cells do not produce this protein. Our data suggest that the observed myocyte growth by Ang II comes about via fibroblast-derived factor, which is increased by Ang II. Cross talk between fibroblasts and myocytes is an important factor in stimulating myocyte growth by Ang II.

Aging↗

Interrelationship of dietary lipids and ascorbic acid with hepatic enzymes of cholesterol metabolic pathway.

Effect of unsaturated and saturated fats on cholesterol metabolism was studied in ascorbate sufficient and deficient guineapigs. Experimental animals were made chronic ascorbic acid deficient by allowing oral intake of 0.5 mg ascorbic acid/day/animal. Elevation in serum and liver cholesterol and triglyceride along with depression in cholesterol oxidation and 7 alpha-hydroxylation in liver was observed in unsaturated fat fed guineapigs with ascorbate deficiency. Liver microsomal cytochrome P-450 level was found to be low in ascorbate deficient animals. Polyunsaturated fat intake could not lower the serum cholesterol level in ascorbate deficiency. Today polyunsaturated fat in the diet is encouraged all over the world for its hypocholesterolemic effect. This study indicates that polyunsaturated fat intake with ascorbic acid deficiency may produce hypercholesterolemia.

Animals↗

Phenethyl isothiocyanate modulates clastogenicity of mitomycin C and cyclophosphamide in vivo.

Phenethyl isothiocyanate (PEITC), a constituent of many cruciferous vegetables, is an effective chemopreventive agent against N-nitrosamine-induced carcinogenesis. We have investigated the extent to which PEITC modulates the clastogenicity of standard genotoxicants, mitomycin C and cyclophosphamide, using bone marrow cells of Swiss albino mice. PEITC, 1 mumol/kg body weight in corn oil was administered by gavage for 7 consecutive days to prime the animals. 24 h later, mice received a single dose of cyclophosphamide (10 or 20 mg/kg body weight) or mitomycin C (1 or 2 mg/kg body weight) intraperitoneally. Clastogenicity of the chemicals was compared using PEITC-primed and non-primed animals 24 h after clastogen treatment. As a single agent, PEITC is not clastogenic even after 7 days of priming. Oral priming with PEITC decreased the aberrations per cell values by 22-67% in all cases. PEITC could only alleviate the clastogenicity of 1 mg/kg body weight mitomycin C to near-control values (p < or = 0.05). Although PEITC is reported to be effective against N-nitrosamine-induced tumorigenesis by preventing metabolic activation and by blocking the reactive species formed, it is virtually ineffective against the clastogenicity of cyclophosphamide. The results of inhibition by PEITC of the clastogenicity of mitomycin C suggest that the modulation of mitomycin C bio-activation contributes to, but may not be sufficient for, PEITC chemoprevention of clastogenicity by mitomycin C.

Animals↗

DNA polymerases from a parasitic protozoa Leishmania donovani UR6: evidence of presence of a novel kind of DNA polymerase.

DNA polymerases of Leishmania donovani have been isolated and purified. The cell extract has been chromatographed on a phosphocellulose column that separated into three peaks. The activity peak 1 was further purified to homogeneity. The DNA polymerase is a 64 KDa polypeptide, resistant to N-ethylmaleimide and aphidicolin. It requires MnCl2 and a high concentration of KCl (0.5 M) for maximal activity. It has both 3' to 5' and 5' to 3' exonuclease activities that reside in the same polypeptide.

Animals↗

A synthetic model for triple-helical domains in self-splicing group I introns studied by ultraviolet and circular dichroism spectroscopy.

Structural studies were performed on synthetic oligonucleotides with sequences corresponding to the P4/P6 and J3/4, J6/7 regions of the self-splicing group I intron of the bacteriophage T4 nrdB pre-mRNA, which correspond to the proposed triple-helical domain in the Tetrahymena thermophila intron. A 23-mer RNA was synthesized as a mixed ribo-deoxyribo oligonucleotide, modeling an expected base-paired region of P4 along with the J3/4 and P6 (5'-end bases of P6) regions. strand modeling the 3'-end bases of P6 and J6/7 regions, with which a triple helix may form, was synthesized as a pure oligoribonucleotide (7-mer RNA). The interactions of these oligonucleotides have been characterized by UV and circular dichroism (CD) spectroscopy. The results show that the 23-mer RNA forms a stable hairpin modeling the P4 base-paired region. Triple helix association between the 23-mer RNA hairpin and the 7-mer RNA single strand was detected by CD in the presence of Mg2+ (>5mM) but not in presence of a monovalent cation like Na+ (up to 500 mM). Studies on selected variants of both 7-mer and 23-mer RNAs were carried out. The results show that for the association of the two partner strands not only the formation of P6 helix but also triplet interactions between two strands are required. The association of the two strands in general follow a pattern predicted by comparative sequence analysis. Parallel studies on pure oligoribonucleotides having base sequence corresponding to those of the oligoribonucleotides showed no evidence of association under similar conditions, which could indicate that the 2'-hydroxyl groups of the riboses might play an important role in hydrogen bonding to form the required nucleoside triples. Molecular modeling studies on the proposed "plaited triple helix" formed by the association of the 23-mer RNA hairpin and 7-mer RNA single strand showed that the structure is sterically and energetically feasible.

Animals↗

Cardiac myotrophin exhibits rel/NF-kappa B interacting activity in vitro.

Myotrophin is a soluble-12 kilodalton protein isolated from hypertrophied spontaneously hypertensive rat and dilated cardiomyopathic human hearts. We have recently cloned the gene coding for myotrophin and expressed it in Escherichia coli. In the present study, the expression of myotrophin gene was analyzed, and at least seven transcripts have been detected in rat heart and in other tissues. We have further analyzed the primary structure of myotrophin protein and identified significant new structural and functional domains. Our analysis revealed that one of the ankyrin repeats of myotrophin is highly homologous specifically to those of myotrophin is highly homologous specifically to those of I kappa B alpha/rel ankyrin repeats. In addition, putative consensus phosphorylation sites for protein kinase C and casein kinase II, which were observed in I kappa B alpha proteins, were identified in myotrophin. To verify the significance of these homologies, kappa B gel shift assays were performed with Jurkat T cell nuclear extract proteins and the recombinant myotrophin. Results of these assays indicate that the recombinant myotrophin has the ability to interact with NF-kappa B/rel proteins as revealed by the formation of ternary protein-DNA complexes. While myotrophin-specific antibodies inhibited the formation of these complexes, rel-specific p50 and p65 antibodies supershifted these complexes. Thus, these results clearly indicate that the myotrophin protein to be a unique rel/NF-kappa B interacting protein.

Amino Acid Sequence↗

Development of a genus specific primer set for detection of Leishmania parasites by polymerase chain reaction.

We have compared the sequences of a major class of kinetoplast DNA (kDNA) minicircle (pLURkE3) of Leishmania strain UR6 with other minicircle sequences from different Leishmania species. Alignment of these sequences allowed the selection of a pair of oligonucleotides suitable as primers in polymerase chain reaction (PCR) which is specific for Leishmania parasites. PCR with this genus-specific primer set is capable of detecting 1 femtogram of kDNA. These primers have been tested with kDNAs from both old world and new world Leishmania species. The results indicate that the primers may be suitable for detection of any kind of leishmaniasis.

Animals↗

Effect of extracorporeal shock wave lithotripsy on glomerular and tubular functions.

To evaluate the early and late effects of extracorporeal shock wave lithotripsy on renal function, we prospectively designed a controlled study using a Direx lithotriptor. Twenty-five patients with renal stones and 16 healthy volunteers as the control group were included in the study. Blood and urine samples were collected before and after 24 hours, seven days and 8 months in the patient group. White blood cell count, serum levels of haemoglobin, urea, creatinine, SGOT, SGPT, AP, and LDH were determined. 24-hour urine specimens were collected to be tested for volume, excretion of creatinine, albumin, N-acetyl-beta-glucosaminidase, gamma-glutamyltransferase and beta-2-microglobulin. There were statistically significant increments in the secretion of urinary enzymes and albumin in the early period after ESWL, no longer lasting 8 months after the procedure. At 8 months one patient was hypertensive as judged by the diastolic pressure above 95 mm Hg. The results of this study showed that, although there was a transient glomerular and tubular damage after extracorporeal shock wave lithotripsy, the procedure seems safe and causes no permanent deterioration in renal function.

Adult↗

Selective or universal neonatal BCG immunization: what policy for a district with a high incidence of tuberculosis?

In the United Kingdom, BCG immunization of neonates provides good protection against military and meningeal disease, and probably against other forms of tuberculosis, in all ethnic groups. Serious adverse reactions to BCG immunization are rare. Cost-effectiveness studies of BCG immunization in neonates have not been reported and "universal' BCG immunization is not recommended in the United Kingdom. The Department of Health does recommend immunization for children and infants of immigrants from countries with a high prevalence of tuberculosis. There are problems associated with such a "selective' policy, as determining what is "high' prevalence and thus defining "at risk' groups is difficult, and there may be political and practical difficulties in its implementation. This may result in low coverage in eligible groups. A "universal' policy of BCG immunization for all neonates may be politically more acceptable and easier to implement in districts with high tuberculosis notification rates. Although there is no cost-effectiveness data to determine at what tuberculosis notification rate a universal policy should be adopted, an universal policy has been suggested for districts with overall notification rate of greater than 40 per 100,000. Within districts there may be large variations in tuberculosis notification rates between different areas. This is becoming more common with the amalgamation and merger of smaller districts into new larger purchasing organizations. New River Health Authority is such a district formed by the amalgamation of the former districts of Haringey with a high tuberculosis notification rate, and Enfield with a lower TB notification rate. In order to maximize coverage in the "at risk' neonates, a different neonatal BCG policy has been adopted in the two areas. This has been possible because of the flexibility of the mechanisms for contracting with different provider units. Although the overall notification rate was not thought to be sufficiently high to justify a "universal' neonatal policy throughout the district, a "universal' policy has been instituted in the main provider unit in the former district Haringey. A "selective' policy, subject to ongoing evaluation to ensure high coverage, continues to be operated by the main provider unit in the former district of Enfield.

BCG Vaccine↗

Role of membrane folate-binding protein in the cytotoxicity of 5,10-dideazatetrahydrofolic acid in human ovarian carcinoma cell lines in vitro.

Lometrexol (5,10-dideazatetrahydrofolic acid; DDATHF), is a specific inhibitor of glycinamideribonucleosyl (GAR) transformylase with anti-tumour activity in murine and human carcinomas. The cytotoxicity activity of DDATHF was evaluated in vitro in NIH/3T3 cells transfected with human alpha-folate-binding protein (FBP) complementary DNA to examine the role of the receptor. In FBP-transfected NIH/3T3 (FBP-tNIH/3T3) cells, which internalised about three times more 5-methyltetrahydrofolic acid than the mock-transfected cells, the cytotoxtic potential of DDATHF showed a clear increase. Subsequently, we analysed four ovarian carcinoma cell lines (OVCAR3, IGROV1, SKOV3, and SW626) expressing different amounts of FBP. Cells were conditioned to grow in medium depleted of folic acid then tested by MOv18 and folic acid binding. Only SKOV3 and SW626 cells grown in folic acid-depleted medium showed increased FBP expression, about 3- and 8-fold respectively. The cytotoxic potential of DDATHF was evaluated by a standard clonogenic assay. In a medium containing 2.27 microM folic acid the DDATHF IC50 values were 50 nm on OVCAR3, 500 nM on SW626 and 1000 nM on IGROV1. In folic acid-free medium IC50 values were 2 nM on OVCAR3 and Sw626 and 40 nM on IGROV1. Only on SKOV3 cells was DDATHF cytotoxicity the same regardless of the amount of folic acid in the medium (IC50 8 nM). Thus, DDATHF did not inhibit the growth of IGROV1 cells depleted of folic acid after stripping FBP with phosphatidylinositol-phospholipase C, even at a dose toxic for cells constitutively expressing FBP. Although FBP expression is certainly one of the parameters affecting drug toxicity, taken alone it is not a sufficiently reliable predictor of cancer cell sensitivity to DDATHF.

3T3 Cells↗