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Biomedical subjects

S Sen

Publications and source records attributed to S Sen.

At least 73 records · Page 4Linked to original sources

Gene therapy and pharmaceutical modulation of apoptosis.

Apoptosis is detectable in cardiovascular disease in various forms. Although the methods to detect apoptosis need improvement, and its magnitude is not known clearly, there is sufficient evidence to postulate that it might be important in progression of disease. Clinicians now have some specific compounds that can be used to modulate apoptosis. The preliminary data suggest that we can modulate apoptosis in animal models and that this is associated with obvious benefits in terms of tissue salvage and possibly improved function. There are no human data as yet. Many questions must be addresses before undertaking human studies. Despite these shortcomings, there is a tremendous potential for apoptotic modulation in preventing or ameliorating cardiovascular disease in the near future.

Animals↗

Sialic acid binding protein of human endometrium: its regulation by steroids.

In the present study, we have observed that sialic acid binding protein (SABP - a 54 kDa glycoprotein which was isolated from human endometrial scrapings taken at various stages of the menstrual cycle from normal cycling females and purified to apparent homogeneity and was earlier reported from this laboratory) was found in sufficiently detectable amount in the endometrium of normal cycling women whereas it was found in lesser amount in tissue from women who have recently entered the postmenopause stage. SABP was observed in both follicular and luteal phase of menstrual cycle which was found by western blot analysis. In the de-novo synthesis experiment, synthesis and secretion of SABP was found to be stimulated by estradiol (E2) whereas progesterone (P4) was found to have no significant stimulatory effect on it which was also confirmed by HEC cell culture. In the HEC cell culture, priming of cells with E2 was found to influence the effect of P4 on SABP when it was added 2 h after E2 administration. This was observed by doing immunoprecipitation followed by SDS-PAGE and autoradiography. Hence this report clearly indicates that E2 regulates the synthesis and secretion of 54 kDa SABP from human endometrium. How E2 priming of endometrium influences the effect of P4 on SABP has been discussed.

Adult↗

The anaesthetic management of a deliberately created bronchoatmospheric fistula in bilateral pulmonary hydatids.

Postoperative empyema and bronchopleural fistula are well known complications after surgery for pulmonary hydatid disease. The pneumonostomy technique of deliberately creating a bronchoatmospheric fistula after removal of the parasite has been used to prevent these complications. This technique, however, is an added anaesthetic challenge, especially if the child presents again for surgery before this fistula has healed. We describe the anaesthetic management of such a case where controlled increase of the resistance to the air leak via the fistula during intermittent positive pressure ventilation helped circumvent these problems.

Anesthesia↗

Mesenchymal chondrosarcoma of the orbit: a clinicopathological study.

Extraskeletal mesenchymal chondrosarcoma of the orbit is a rare tumour and generally presents in young females. We report the clinical presentation and histopathological features of a case of orbital mesenchymal chondrosarcoma in a middle-aged man. The prognosis of this tumour is poor and though rare it should be kept in the differential diagnosis of orbital masses.

Journal Article↗

Maternal knowledge, attitude and practice regarding folic acid intake during the periconceptional period.

OBJECTIVE: To study the knowledge, attitude and practice of pregnant women regarding periconceptional folic acid (FA) intake. DESIGN: Questionnaire-based prospective study. SETTING: Antenatal clinic of a District General Hospital. SUBJECTS: Three-hundred pregnant women in an antenatal clinic. RESULTS: Nearly all (298/300) had heard of FA. A majority (275/300, 91%) knew that FA could prevent neural tube defects, and married women those with higher education those of Social Classes 1-3 and women over 30 years of age were more likely to be thus aware. Knowledge about the correct timing of FA intake was seen in 76% and was more likely in those with higher education married women and women age over 30 years Intake of FA in the periconceptional period was seen in 134/300 (44.6%) women and was most likely in the married, Social Classes 1-3, women with higher education (all P<0.001), non-smokers women with a planned pregnancy and women aged 30 years and over CONCLUSIONS: The knowledge of the correct timing of FA intake was present in only 76%. Less than half (44.6%) had taken FA in the periconceptional period, and this was far more common in the more 'privileged' classes. Low socio-economic status, age less than 30 years, lower educational status and unplanned pregnancy were high risk factors for not taking FA. The challenge to the medical profession for targeting this group cannot be over-emphasised.

Adolescent↗

Research strategies for design and development of NSAIDs: clue to balance potency and toxicity of acetanilide compounds.

Despite the fact that many modern drug therapies are based on the concept of enzyme inhibition, inhibition of several enzymes leads to pathological disorders. Clinically used nonsteroidal anti-inflammatory drugs (NSAIDs) bind to the active site of the membrane protein, cyclooxygenase (COX) and inhibit the synthesis of prostaglandins, the mediators for causing inflammation. At the same time, inhibition of hepatic cysteine proteases by some NSAID metabolites like NAPQI is implicated in the pathogenesis of hepatotoxicity. As a part of our efforts to develop new effective NSAIDs, a comprehensive investigation starting from synthesis to the study of the final metabolism of acetanilide group of compound has been envisaged with appropriate feedback from kinetic studies to enhance our knowledge and technical competency to feed the know-how to the medicinal chemist to screen out and design new acetanilide derivatives of high potency and low toxicity. Structure-function relationship based on the interaction of acetanilide with its cognate enzyme, cyclooxygenase has been studied critically with adequate comparison with several other available crystal structures of COX-NSAID complexes. Furthermore, to make the receptor based drug design strategy a novel and comprehensive one, both the mechanism of metabolism of acetanilide and structural basis of inhibition of cysteine proteases by the reactive metabolite (NAPQI) formed by cytochrome P450 oxidation of acetanilide have been incorporated in the study. It is hoped that this synergistic approach and the results obtained from such consorted structural investigation at atomic level may guide to dictate synthetic modification with judicious balance between cyclooxygenase inhibition and hepatic cysteine protease inhibition to enhance the potential of such molecular medicine to relieve inflammation on one hand and low hepatic toxicity on the other.

Acetanilides↗

A statistical framework for quantitative trait mapping.

We describe a general statistical framework for the genetic analysis of quantitative trait data in inbred line crosses. Our main result is based on the observation that, by conditioning on the unobserved QTL genotypes, the problem can be split into two statistically independent and manageable parts. The first part involves only the relationship between the QTL and the phenotype. The second part involves only the location of the QTL in the genome. We developed a simple Monte Carlo algorithm to implement Bayesian QTL analysis. This algorithm simulates multiple versions of complete genotype information on a genomewide grid of locations using information in the marker genotype data. Weights are assigned to the simulated genotypes to capture information in the phenotype data. The weighted complete genotypes are used to approximate quantities needed for statistical inference of QTL locations and effect sizes. One advantage of this approach is that only the weights are recomputed as the analyst considers different candidate models. This device allows the analyst to focus on modeling and model comparisons. The proposed framework can accommodate multiple interacting QTL, nonnormal and multivariate phenotypes, covariates, missing genotype data, and genotyping errors in any type of inbred line cross. A software tool implementing this procedure is available. We demonstrate our approach to QTL analysis using data from a mouse backcross population that is segregating multiple interacting QTL associated with salt-induced hypertension.

Algorithms↗

P53 protein expression in eccrine poroma and porocarcinoma.

The role of p53 mutation has been shown in different human malignancies, including various skin cancers. In this study, we examined p53 protein expression in 25 eccrine poromas and 11 porocarcinomas by immunohistochemistry. P53 expression was observed in 88% (22 of 25) of eccrine poromas and 73% (8 of 11) of porocarcinomas. In eccrine poromas, percentage of cells reactive for p53 was less than 5% (low expresser) in 6 cases, 5 to 50% (moderate expresser) in 14 and greater than 50% (high expresser) in 2 cases. In terms of intensity, 13 cases showed weak staining, 8 moderate, and 1 case showed strong reactivity. On the other hand, 2 cases of porocarcinoma were low expresser, 2 were moderate and 4 were high expresser. All of the high expressers had also strong staining. This study has demonstrated that eccrine poromas showed significant p53 expression as much as porocarcinomas and, therefore, p53 positivity cannot be accepted as a valuable parameter for malignancy. P53 gene may involve in the carcinogenetic pathway of porocarcinoma but it is likely that other oncogenes may also have a role.

Acrospiroma↗

Effect of adenosine on cerebral blood flow velocity.

BACKGROUND AND PURPOSE: Evidence suggests that adenosine (ADN) is a potent vasodilator of cerebral vessels. However, the feasibility of manipulating human cerebral vascular resistance with ADN has not been assessed by means of TCD. The purpose of this study was to quantitatively estimate the change in middle cerebral artery cerebral blood flow velocity (CBFV) in response to intravenous ADN infusion in humans. METHODS: Eleven patients with subacute cerebrovascular events (ischemic stroke, transient ischemic attack, or hemorrhage) undergoing adenosine-thallium stress testing were studied before, during, and after ADN infusion to evaluate the effect of ADN on cerebral blood flow velocity. Continuous blood pressure (BP), heart rate (HR), respiration rate (RR), end-tidal CO2 (ET-CO2), and transcranial Doppler ultrasonography monitoring of CBFV and pulsatility index (PI) in both middle cerebral arteries were performed. RESULTS: The mean CBFVs were 65.4 +/- 19.2 cm/s before, 55.4 +/- 18.1 cm/s during, and 64.1 +/- 22.5 cm/s after ADN infusion, which represents a statistically significant decrease during ADN test compared with both baseline (P = .007) and posttest levels (P = .017). The PI was increased during the test (0.91 +/- 0.2) when compared with baseline (0.71 +/- 0.1) (P = .007). During ADN injection, mean HR increased (P = .004) and mean ET-CO2 levels decreased significantly (P = .003). Mean BP and RR did not change significantly. CONCLUSIONS: The authors hypothesize that any direct vasodilatory effect of ADN on the distal cerebral peripheral vasculature may be negated by an effect of ADN on depth of respiration resulting in hypocapnia and secondary distal vasoconstriction.

Adenosine↗

Role of myocytes in myocardial collagen production.

Excessive collagen deposition may cause abnormal stiffness of the heart during hypertrophy and heart failure. The potent vasoconstrictor angiotensin II seems, via an unknown mechanism, to stimulate collagen production. This study describes the in vitro and ex vivo effects of [Sar(1)]Ang II on collagen production by fibroblasts in culture and in beating, nonworking heart preparations. The effects of [Sar(1)]Ang II on isolated rat hearts or rat heart fibroblasts were determined by quantifying transcript levels of collagen phenotypes I and III through videodensitometry after Northern blot analysis with specific cDNA probes (collagen [P alpha( 2)r(2)] rat alpha( 2)[I] probe for type I and human skin fibroblast alpha(1)[III] probe for type III). When [Sar(1)]Ang II was added in vitro to neonatal or adult 28-week-old Wistar-Kyoto rat heart fibroblasts, questionable stimulation in the mRNAs of types I and III occurred. In contrast, when 10(-8) mol/L [Sar(1)]Ang II was added to beating, nonworking Wistar-Kyoto rat heart preparation ex vivo, a 1.5- to 2.5-fold stimulation of collagen mRNAs of phenotypes I and III was observed. When neonatal fibroblasts were cocultured with neonatal myocytes in vitro, with 10(-10) mol/L [Sar(1)]Ang II added, there was no stimulation of either phenotype. However, significant stimulation of both collagen transcripts was recorded when 10(-10) mol/L [Sar(1)]Ang II was added to adult fibroblasts cocultured with either neonatal or adult myocytes. Our data suggest that factors produced by myocytes are necessary for upregulation of collagen genes in vitro and demonstrate that fibroblast-myocyte cross-talk is required for Ang II-induced collagen upregulation.

Angiotensin II↗

Survey of Theileria parasite infection in cattle in Cambodia and Vietnam using piroplasm surface protein gene-specific polymerase chain reaction.

A survey of Theileria parasite infection in cattle in Cambodia and Vietnam was carried out by using allele-specific polymerase chain reaction. A total of 137 blood samples from draught animals in Cambodia and 40 blood samples from dairy cattle in Vietnam were analyzed. In Cambodia, 69 out of 137(50.4%) samples were PCR-positive containing mainly the Thai and the C type parasites. In Vietnam, 11 (27.5%) samples were positive and all were of the Thai type parasite.

Alleles↗

An update on coeliac disease.

This review article provides an overview of coeliac disease but also highlights its protean manifestations. These can often lead to a delay in diagnosis of this easily treatable condition.

Adult↗

Quantitative trait loci for femoral and lumbar vertebral bone mineral density in C57BL/6J and C3H/HeJ inbred strains of mice.

Significant differences in vertebral (9%) and femoral (50%) adult bone mineral density (BMD) between the C57BL/6J (B6) and C3H/HeJ (C3H) inbred strains of mice have been subjected to genetic analyses for quantitative trait loci (QTL). Nine hundred eighty-six B6C3F2 females were analyzed to gain insight into the number of genes that regulate peak BMD and their locations. Femurs and lumbar vertebrae were isolated from 4-month-old B6C3F2 females at skeletal maturity and then BMD was determined by peripheral quantitative computed tomography (pQCT). Estimates of BMD heritability were 83% for femurs and 72% for vertebrae. Genomic DNA from F2 progeny was screened for 107 polymerase chain reaction (PCR)-based markers discriminating B6 and C3H alleles on all 19 autosomes. The regression analyses of markers on BMD revealed ten chromosomes (1, 2, 4, 6, 11, 12, 13, 14, 16, and 18) carrying QTLs for femurs and seven chromosomes (1, 4, 7, 9, 11, 14, and 18) carrying QTLs for vertebrae, each with log10 of the odds ratio (LOD) scores of 2.8 or better. The QTLs on chromosomes (Chrs) 2, 6, 12, 13, and 16 were unique to femurs, whereas the QTLs on Chrs 7 and 9 were unique to vertebrae. When the two bone sites had a QTL on the same chromosome, the same marker had the highest, although different, LOD score. A pairwise comparison by analysis of variance (ANOVA) did not reveal significant gene x gene interactions between QTLs for either bone site. BMD variance accounted for by individual QTLs ranged from 1% to 10%. Collectively, the BMD QTLs for femurs accounted for 35.1% and for vertebrae accounted for 23.7 % of the F2 population variances in these bones. When mice were homozygous c3/c3 in the QTL region, 8 of the 10 QTLs increased, while the remaining two QTLs on Chrs 6 and 12 decreased, femoral BMD. Similarly, when mice were homozygous c3/c3 in the QTL region for the vertebrae, five of the seven QTLs increased, while two QTLs on Chrs 7 and 9 decreased, BMD. These findings show the genetic complexity of BMD with multiple genes participating in its regulation. Although 5 of the 12 QTLs are considered to be skeleton-wide loci and commonly affect both femurs and vertebrae, each of the bone sites also exhibited unique QTLs. Thus, the BMD phenotype can be partitioned into its genetic components and the effects of these loci on normal bone biology can be determined. Importantly, the BMD QTLs that we have identified are in regions of the mouse genome that have known human homology, and the QTLs will become useful experimental tools for mechanistic and therapeutic analyses of bone regulatory genes.

Alleles↗

Elevation of hepatic transaminases after enoxaparin use: case report and review of unfractionated and low-molecular-weight heparin-induced hepatotoxicity.

Enoxaparin, a low-molecular-weight heparin (LMWH), is widely used for the treatment and prophylaxis of thromboembolic disorders, such as deep vein thrombosis. Low-molecular-weight heparin products have smaller and more uniform molecular weights than unfractionated heparin, allowing them to exhibit a much greater affinity for factor Xa than factor IIa. Compared with traditional unfractionated heparin, LMWHs have proved to be equally efficacious and may be safer. The distinctive characteristics of LMWHs have resulted in decreased rates of bleeding and equivalent rates of thrombocytopenia compared with unfractionated heparin. This favorable safety profile has been identified in several studies and may have led clinicians to believe that LMWHs have lower frequencies of all common side effects. A 66-year-old woman developed increased hepatic transaminases during treatment with enoxaparin for a deep vein thrombosis; they returned to normal after enoxaparin discontinuation. A causal relationship between unfractionated heparin and asymptomatic, transient increases in hepatic transaminase levels has been documented; these increased levels also appear to be an underrecognized, adverse effect of LMWH therapy.

Aged↗

Drug-induced acute interstitial nephritis and vasculitis or vasculary rejection in renal allografts.

We describe a patient who sought treatment for acute renal allograft dysfunction 2 weeks after renal transplantation. Renal allograft biopsy (RAB) showed intimal arteritis, severe interstitial infiltration with a few eosinophils, and severe tubulitis. Pathologic diagnosis was acute rejection (grade 2b- Banff 93); however, another clinical diagnosis, drug-induced acute interstitial nephritis (AIN), was not excluded. Before the RAB, his trimethaprim-sulfamethoxazole (TMP-SMZ) treatment was discontinued. Renal function began to improve on biopsy day without antirejection therapy. Recovery of renal function without antirejection treatment and discontinuation of TMP-SMZ shows that renal pathology might be related to drug-induced dysfunction and drug-induced AIN and vasculitis. After 5 years, the patient and his renal allograft function are both well.

Adult↗

Genotypic diversity in species of Scilla.

Two cytotypes of Scilla indica and three other species, namely S. nervosa, S. siberica and S. vindobonensis were investigated. The estimation of nuclear DNA content was utilized as a measure of genetic diversity at inter- and intraspecific levels and as an index of the trends of evolution. S. siberica with a very high DNA value was regarded as indicative of a primitive state. The heavy intraspecific difference in DNA content in S. indica has been attributed to amplification of the DNA.

Analysis of Variance↗

Possible antineoplastic agents, part 15: synthesis, biological activity and quantitative structure activity relationship of substituted-2-(4'-methoxybenzenesulphonamido) glutaric acid analogs against Ehrlich ascites carcinoma.

Some substituted-2-(4'-methoxybenzenesulphonamido) glutaric acid analogs (5a-m, 7a-d) have been synthesized and tested for their possible antineoplastic activity against Ehrlich ascites carcinoma (EAC) in Swiss albino mice using tumour (ascitic fluid) weight as activity parameter. Some of these compounds possess encouraging antitumour activity. A QSAR study, performed by the classical Hansch method, explains the significance of hydrophobic binding and electronic influence in the mechanism of antineoplastic action in this group of compounds.

Algorithms↗