Search PubMedSearch

Biomedical subjects

R K Bansal

Publications and source records attributed to R K Bansal.

At least 19 recordsLinked to original sources

G1 cell cycle arrest and apoptosis induction by nuclear Smad4/Dpc4: phenotypes reversed by a tumorigenic mutation.

The tumor suppressor Smad4/Dpc4 is a transcription activator that binds specific DNA sequences and whose nuclear localization is induced after exposure to type beta transforming growth factor-like cytokines. We explored an inducible system in which Smad4 protein is activated by translocation to the nucleus when cell lines that stably express wild-type or mutant Smad4 proteins fused to a murine estrogen receptor domain are treated with 4-hydroxytamoxifen. This induced Smad4-mediated transcriptional activation and a decrease in growth rate, attributable to a cell cycle arrest at the G1 phase and an induction of apoptosis. A tumor-derived mutation (Arg-100 --> Thr) affecting a residue critical for DNA-binding demonstrated an "oncogenic" phenotype, having decreases in both the G1 fraction and apoptosis and, consequently, an augmentation of population growth. This model should be useful in the exploration and control of components that lie further downstream in the Smad4 tumor-suppressor pathway.

Amino Acid Substitution

Transforming growth factor-beta responsiveness in DPC4/SMAD4-null cancer cells.

DPC4/SMAD4 is a candidate tumor suppressor gene with a strikingly high frequency of gene alterations in pancreatic cancer that suggests a discrete role for DPC4 in these tumors. DPC4 tumor-suppressive function has been implicated to mediate the transforming growth factor-beta (TGFbeta)-suppressive pathway; however, in a DPC4-null pancreatic cancer cell line, TGFbeta growth-inhibitory and transcriptional responses were found to be DPC4-independent. This was observed within native cells having a natural homozygous deletion and in clones engineered for stable expression of wild-type DPC4 integrated into the genome. This observation contrasted with the absolute DPC4 dependence of TGFbeta responses in a breast cancer cell line studied in parallel. This growth-inhibitory response to TGFbeta in DPC4-null cells relied on an intact ras effector pathway. These data further suggest a major categorization of TGFbeta responses into DPC4-dependent and -independent signaling pathways and specifically suggest that disruption of the TGFbeta-independent signal might be a basis of selection for the emergence of DPC4 alterations during tumorigenesis in the pancreas and other sites.

Alleles

Germline and somatic mutations of the STK11/LKB1 Peutz-Jeghers gene in pancreatic and biliary cancers.

Peutz-Jeghers syndrome (PJS) is an autosomal-dominant disorder characterized by hamartomatous polyps in the gastrointestinal tract and by pigmented macules of the lips, buccal mucosa, and digits. Less appreciated is the fact that PJS also predisposes patients to an increased risk of gastrointestinal cancer, and pancreatic cancer has been reported in many PJS patients. It was recently shown that germline mutations of the STK11/LKB1 gene are responsible for PJS. We investigated the role of STK11/LKB1 in the development of pancreatic and biliary cancer in patients with and without the PJS. In a PJS patient having a germline splice site mutation in the STK11/LKB1 gene, sequencing analysis of an intestinal polyp and pancreatic cancer from this patient revealed loss of the wild-type allele of the STK11/LKB1 gene in the cancer. Inactivation of STK11/LKB1, by homozygous deletions or somatic sequence mutations coupled with loss of heterozygosity, was also demonstrated in 4-6% of 127 sporadic pancreatic and biliary adenocarcinomas. Our results demonstrate that germline and somatic genetic alterations of the STK11/LKB1 gene may play a causal role in carcinogenesis and that the same gene contributes to the development of both sporadic and familial forms of cancer.

AMP-Activated Protein Kinase Kinases

Research skills acquisition by interns: a case study.

This study shows the impact of a holistic structured training programme on the acquisition of research skills by a batch of 13 interns of Pramukhswami Medical College, Gujarat, India, commensurate with their envisaged roles according to the concept of "Essential National Health Research" (ENHR). There was a significant improvement in the knowledge scores of the participants, subsequent to the training programme, as evidenced by an improvement over their mean pretest score of 16.4 +/- 11.0 to a posttest score of 87.1 +/- 19.9. The study also discussions the suggestions and feedback of the participants about the programme.

Clinical Competence

Truck crew and risk of contraction of STDS, including HIV: encouraging the use of condoms by the method of applying theories.

Studies from India conclude that the long distance truck crew are at a high risk of contracting and transmitting STDs and HIV on account of their high risk sexual behaviours. These studies indicate the necessity of changing the behaviour of the truck crew in favour of safer sexual practices. This article addresses this important issue of developing an intervention to decrease the risk of contraction of STDs, including HIV, by encouraging the use of condoms by the method of applying psycho-social theories, which aim at changing behaviours of the target group.

Condoms

A decline in myometrial nitric oxide synthase expression is associated with labor and delivery.

The mechanisms that maintain relative uterine quiescence during pregnancy remain largely unknown. A possible role for nitric oxide has recently emerged, however, the expression of nitric oxide synthase within human myometrium at midgestation, a time when the uterus is normally quiescent, has not been investigated. The purpose of this study was to identify cell types in human myometrium that contain inducible nitric oxide synthase (iNOS), and to examine changes in its expression during pregnancy and labor. We found that iNOS is expressed in smooth muscle cells of pregnant myometrium. Expression of iNOS was highest in myometrium of preterm not-in-labor patients. At term, iNOS expression fell by 75%, and was barely detectable in preterm in-labor or term in-labor specimens. There was no staining in the myocytes of nonpregnant myometrium. Western blotting also revealed a similar pattern of changes in iNOS expression. In summary, iNOS expression in the myocytes of human myometrium is increased greatly during pregnancy, and declines towards term or with labor. Significantly, preterm inlabor patients also had a large decline in iNOS expression. These data suggest that changes in myometrial iNOS expression may participate in the regulation of uterine activity during human pregnancy.

Adult

Is there a benefit to episiotomy at operative vaginal delivery? Observations over ten years in a stable population.

OBJECTIVE: Our purpose was to examine the association between maternal vaginal and perineal morbidity and episiotomy performed at operative vaginal delivery. STUDY DESIGN: We obtained data from 2041 consecutive operative vaginal deliveries and compared yearly rates of episiotomy, lacerations, and potential confounders with linear regression and stratified analyses. RESULTS: Between 1984 and 1994 the use of episiotomy for operative vaginal deliveries fell significantly (93.4% to 35.7%, R2 = 0.85, p = 0.0001). This change was associated with a rise in the rate of vaginal lacerations (16.1% to 40.0%, R2 = 0.80, p = 0.0002), a decrease in the rate of fourth-degree lacerations (12.2% to 5.4%, R2 = 0.62, p = 0.004), but no significant change in the rate of third-degree lacerations. These associations held in separate analyses stratified by parity and type of instrument used for delivery. The prevalence of other previously reported risks for perineal morbidity did not change during the study period. CONCLUSION: At our institution a statistically and clinically significant reduction in the use of episiotomy for operative vaginal deliveries was not associated with a change in the rate of third-degree lacerations but was associated with an increase in the rate of vaginal lacerations and a decrease in the rate of fourth-degree lacerations.

Confounding Factors, Epidemiologic

Evaluation of provision and availability of health care services in Iran: a human rights approach.

In this review article, we have attempted to illustrate the provision and availability of health care services in Iran using a human rights approach. First and foremost, we should emphasize that we have not come across any text which endeavours to address holistically the aforesaid issue in the context of Iran. It appears to us to be a very complex issue and in order to satisfactorily address this issue, we have argued some of its various associated aspects. Basically, we believe that the right to health care should be a human right, but whether this right should be to basic care or comprehensive care, whether legally enforceable or not, are issues which are political and must echo the socio-political climate and resources of a particular country. However, this deliberation may be of vital importance in the development and nurturing of the health care services sector of a country; in determining the attitudes associated with the dynamics of the various sub-system/sub-process components, and finally the actual access and availability of health care to its citizens. Our own views are given in this text when appropriate.

Evaluation Studies as Topic

Influence of talc on the properties of polycarboxylate cement.

Zinc oxide, the inorganic component of polycarboxylate cement, was mixed with talc in various proportions from 10% to 50%. These powder mixtures were spatulated with poly(acrylic acid) in three powder to liquid (P/L) ratios of 1:1, 1.5:1 and 2:1 (w/w). Properties such as setting time and compressive and diametral tensile strengths of the resultant cements were determined. It was observed that the setting time of the resultant cements increased with increasing talc content. The compressive and diametral tensile strengths also increased by approximately 54% with a 10% concentration of talc.

Acrylic Resins

Increased expression of nitric oxide synthase in the myometrium of the pregnant rat uterus.

Nitric oxide (NO) relaxes uterine smooth muscle and is produced by the pregnant uterus. Our previous studies revealed an increase in rat uterine NO synthase (NOS) activity in pregnancy and a decline at term. In the present study, we have examined the distribution of NOS isoform expression to determine whether their regulation is consistent with a role in the inhibition of uterine contractions before term. At day 17-18 of pregnancy, NOS immunohistochemistry revealed expression of two isoforms: endothelial constitutive form of NOS (ecNOS) in vascular endothelium and inducible form of NOS (iNOS) in myometrial and vascular smooth muscle and in decidual epithelium. Immunoblotting revealed that expression of iNOS declined nearly fivefold, whereas ecNOS declined twofold in laboring rats at term. We conclude that iNOS is expressed in myometrium of pregnant rat uterus but not the virgin rat and that iNOS expression declines at term when labor is present. The pattern of changes in myometrial iNOS expression with advancing gestation suggests that NO could act in an autocrine and/or paracrine manner to inhibit uterine contractions before term.

Analysis of Variance

Longitudinal epidemiological study of coronary heart disease in a rural population of Kheda district, Gujarat, India.

The present study was undertaken to determine the incidence and related risk factors for coronary heart diseases and hypertension in the rural population of Kheda district, Gujarat (India). The observations from the first five years of this ongoing project (May 1987-May 1992) are described in this paper. Out of an initial sample of 750 individuals in the age group 30-62 years, who were selected by stratified random sampling, 714 persons (males = 429; females = 285) were actually studied, after excluding those suffering from coronary heart diseases (CHD). Initially, all the included subjects were examined clinically and appropriate laboratory investigations were done. A detailed socio-economic history was also obtained. Subsequently all of them were followed up and biannual clinical and laboratory investigations were performed. Cases of CHD were diagnosed according to the recommendations of the New York Heart Association. The overall five-year incidence of CHD was 25.17 per thousand persons. The incidence in males was 3 times higher than in females. More males suffered from myocardial infarction (MI), while in the females the incidence of sudden death was higher (33.3%). The average yearly mortality rate due to CHD was 2.46 per thousand persons. CHD was significantly associated with increased blood pressure (both diastolic and systolic), smoking, and family history of heart disease, and was weakly associated with body weight (p = 0.06).

Adult

Is there a benefit to episiotomy at spontaneous vaginal delivery? A natural experiment.

OBJECTIVE: Our purpose was to examine the association between maternal vaginal and perineal morbidity and episiotomy performed at spontaneous vaginal delivery. STUDY DESIGN: We obtained data from 17,483 consecutive spontaneous vaginal deliveries and compared the yearly rates of episiotomy, lacerations, and potential confounders with linear regression and stratified analyses. RESULTS: Between 1976 and 1994 the use of episiotomy fell significantly (86.8% to 10.4%, R2 = 0.92, p = 0.0001). This change was associated with a fall in the rate of third- and fourth-degree lacerations (9.0% to 4.2%, R2 = 0.59, p = 0.0001) and a rise in the rate of intact perinea (10.3% to 26.5%, R2 = 0.68, p = 0.0001) and vaginal lacerations (5.4% to 19.3%, R2 = 0.77, p = 0.0001). These associations held in separate analyses stratified by parity and birth weight, except for the subgroup of nulliparous women with macrosomic infants. CONCLUSION: At our institution a large reduction in the use of episiotomy in spontaneous vaginal deliveries was associated with a significant reduction in perineal trauma in all groups of women except for nulliparous women with macrosomic infants.

Episiotomy

Please use the health services--more and more.

A project in Kheda district, Gujarat, India, has been designed to improve the utilization of health services through an educational drive at the grass-roots level, in which a key role is played by women recruited from the local population and trained to serve as village family welfare workers. Substantial progress has been made although much longer than the project's planned duration of three and a half years would probably be required for the gains made to be consolidated and the full potential realized.

Community Health Services

Research stimulating programme for interns.

The present study shows that acquisition of research skills and competence is lacking in the usual training which is imparted to under graduate medical students. It also shows that the acquisition of these skills can be facilitated by suitable structured training programmes during their internship period. Funds for such activities are often available from various agencies, provided that the individual research study areas chosen are of interest to them.

Humans

Influence of cryolite on the properties of polycarboxylate cement.

Zinc oxide, the inorganic component of polycarboxylate cement, was mixed with the filler cryolite (Na3A1F6) in various proportions that ranged from 10% to 50%. These powder combinations were mixed with polyacrylic acid in three powder-to-liquid ratios of 1:1, 1.5:1, and 2:1 (w/w). The physical properties of the resulting cements such as setting time and compressive and diametral tensile strengths were determined. It was observed that the setting time increased with an increase in cryolite content. The compressive and diametral tensile strengths also increased by twofold with a concentration of 20% cryolite.

Acrylic Resins

Modified polyalkenoate (glass-ionomer) cement--a study.

Conventional glass-ionomer cements with varying amounts (5-15%) of borax (Na2B4O7.10H2O) as modifier were prepared. These mixtures were spatulated with an aqueous solution of polyacrylic acid with a powder to liquid (P/L) ratio of 1.5:1. Properties such as working time, setting time, compressive strength, diametral tensile strength, solubility and fluoride release of these cements were determined. It was observed that the working time and setting time of the resultant cements shortened with the addition of borax. Certain physical properties such as compressive and diametral tensile strength, solubility and disintegration of these glass-ionomer cements deteriorated with borax addition but fluoride release from them was unaffected.

Acrylic Resins