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Biomedical subjects

P Sethi

Publications and source records attributed to P Sethi.

At least 19 recordsLinked to original sources
PubMed2006

Ubiquitin E3 ligase WWP1 as an oncogenic factor in human prostate cancer.

The gene for E3 ubiquitin ligase WWP1 is located at 8q21, a region frequently amplified in human cancers, including prostate cancer. Recent studies have shown that WWP1 negatively regulates the TGFbeta tumor suppressor pathway by inactivating its molecular components, including Smad2, Smad4 and TbetaR1. These findings suggest an oncogenic role of WWP1 in carcinogenesis, but direct supporting evidence has been lacking. In this study, we examined WWP1 for gene dosage, mRNA expression, mutation and functions in a number of human prostate cancer samples. We found that the WWP1 gene had copy number gain in 15 of 34 (44%) xenografts and cell lines from prostate cancer and 15 of 49 (31%) clinical prostate cancer samples. Consistently, WWP1 was overexpressed in 60% of xenografts and cell lines from prostate cancer. Mutation of WWP1 occurred infrequently in prostate cancer. Functionally, WWP1 overexpression promoted colony formation in the 22Rv1 prostate cancer cell line. In PC-3 prostate cancer cells, WWP1 knockdown significantly suppressed cell proliferation and enhanced TGFbeta-mediated growth inhibition. These findings suggest that WWP1 is an oncogene that undergoes genomic amplification at 8q21 in human prostate cancer, and WWP1 overexpression is a common mechanism involved in the inactivation of TGFbeta function in human cancer.

Animals↗
PubMed1996

Safe use of hepatic allografts from donors older than 70 years.

Between March 1991 and August 1995, 36 livers from donors >/=70 years old were transplanted. In donors, we recorded the following risk factors: alanine aminotransferase > 120 and rising, dopamine dose > 15 microg/kg/min, hypotension (systolic blood pressure <80) >1 hr, stay in the intensive care unit >5 days and body mass index >/=27. In 35 recipients, we recorded pretransplant United Network for Organ Sharing (UNOS) status, cold/warm ischemia time, intraoperative blood loss, and occurrence of poor early graft function or primary nonfunction. Mean recipient age was 55 years (range, 25-75 years). Four recipients were UNOS status 1, 19 were UNOS 2, and 12 were UNOS 3. Two livers were used as second grafts for primary graft nonfunction. Mean donor age was 73 years (range, 70-84 years). Intracranial bleeding was the cause of death in the majority of donors. The 36 donors had 40 risk factors; 10 donors had >1 risk factor. Mean cold and warm ischemia times were 9:08 +/- 2:57 hr and 51 +/- 9 min. Mean total operative time was 7.5 hr. Posttransplant mean peak alanine aminotransferase and aspartate aminotransferase levels were 937.3 +/- 703.1 IU/L and 923.3 +/- 708.5 IU/L, respectively. Mean prothrombin time on postoperative day 2 was 14.9 +/- 1.6 sec. Average total bilirubin on postoperative day 5 was 4.9 mg/dl. Median length of stay in the intensive care unit was 4 days. One recipient had poor early graft function; two recipients had primary nonfunction. Mean follow-up was 503 days (range, 110-1714 days). Three-month actual graft and patient survival rates were 85% and 91%, respectively. One-year actuarial graft and patient survival rates were also 85% and 91%, respectively. We conclude that older livers can be used safely. Advanced donor age should not be a contraindication to liver procurement.

Adult↗
PubMed1991

Urinary incontinence: prevalence, need for treatment, and effectiveness of intervention by nurse.

OBJECTIVE: To measure the unmet need of patients with regular urinary incontinence (incontinence twice or more a month) treatable by a nurse. DESIGN: Self completed postal questionnaire and randomised controlled trial of assessment and intervention by a nurse. SETTING: One urban and one rural general practice in Somerset. SUBJECTS: 7300 adults randomly selected from 10,300 aged 35 and over on the combined practice lists. 515 women and 185 men with regular incontinence were offered assessment and treatment, of whom 134 women and 49 men had no intervention for three months (historical controls). They then joined the assessment and treatment programme. INTERVENTION: Four sessions of pelvic floor exercises and bladder retraining supervised by non-specialist nurse who had taken a three week course on assessing and treating uncomplicated incontinence. MAIN OUTCOME MEASURES: Number of patients desiring treatment; self reported cure, improvement, or deterioration in continence after three months. RESULTS: The questionnaire achieved a 79% response. Validated responses showed a prevalence of 4.4% in men and 16.4% in women aged 35-64. 315 (45%) of the 700 patients offered assessment refused it and seven had moved away or died, 64 men and 41 women were referred to their general practitioner. 197 of 292 treated women (68%) reported cure or improvement compared with seven (5%) of controls. 22 of the 86 men desiring treatment were suitable for intervention by the nurse. Seventeen were cured or improved compared with none of the men in the control group. CONCLUSIONS: About half the people with regular urinary incontinence took up the offer of treatment (9.2% of women and 3.4% of men in the study population). This condition can be effectively managed by a nurse with limited training.

Adult↗
PubMed1987

Gastritis and gastric campylobacter-like organisms in patients without peptic ulcer.

Gastric biopsy specimens were obtained from 83 patients without peptic ulcer disease and analysed histologically. Culture and serological studies were done on the last 64 patients. The patients were divided into two age groups (young and old groups.) In 34 patients with chronic superficial gastritis, gastric campylobacter-like organisms (GLCO) were identified histologically in 91% and grown on culture in 88%: antibody to GCLO was detected in 81%. No age-related difference in the prevalence of the organism was demonstrated. In the 23 patients with atrophic gastritis (all elderly), presence of the organisms appeared to be related to the presence of an inflammatory cell infiltrate into the gastric mucosa. These figures for the prevalence of the organism in this selected group of patients are similar to those reported in previous studies of unselected patients which included those with peptic ulcer. This suggests that GCLO is unlikely to be causally related to peptic ulcer.

Adult↗
PubMed1986

Antibody to the gastric campylobacter-like organism ("Campylobacter pyloridis")--clinical correlations and distribution in the normal population.

Different cellular proteins of the gastric campylobacter-like organism (GCLO) were shown to be immunogenic for man. Antibodies to GCLO were detected in sera by both complement fixation and enzyme-linked immunoabsorbent assay. Antibody was found in 133 (52%) of 254 patients attending for gastroscopy. There was a high correlation between presence of antibody and a positive GCLO culture from the gastric mucus. Patients with normal endoscopic appearances, duodenal ulcer, duodenitis and oesophagitis had similar prevalences (c. 50%) of antibody. Only patients with endoscopically visible gastritis or gastric ulcer had a higher frequency (c. 80%) of antibody. In a normal population, antibody was uncommon in individuals less than 20 years old, but the prevalence of antibody increased (to c. 50%) with age. There was little evidence to support an important pathological role for GCLO in disorders of the upper gastrointestinal tract, although the possibility that it may be a co-factor in the pathogenesis of gastric ulcer cannot be excluded.

Adolescent↗
PubMed1984

Theiler's virus antigen detected in mouse spinal cord 2 1/2 years after infection.

Spinal cord sections from mice injected with Theiler's murine encephalomyelitis virus (TMEV) and surviving for 1 year and longer after infection were stained for virus antigen by two immunohistochemical techniques. Virus antigen was detected from 1 to 2 1/2 years after infection, a time when no virus was recovered at an assay sensitivity of 50 plaque-forming units per gram of tissue. The implication this has regarding the detection of a virus in MS is discussed.

Animals↗
PubMed1983

Characterization of Vilyuisk virus as a picornavirus.

The V-1 strain of Vilyuisk virus, isolated from the cerebrospinal fluid of a chronic case of encephalomyelitis in Siberia and subsequently passaged 41 times in mice, was examined to determine its serological relationship to Theiler's murine encephalomyelitis virus (TMEV) and encephalomyocarditis (EMC) virus and some physicochemical characteristics of the virion. On the basis of virion size (28 nm), icosahedral symmetry, buoyant density (1.33 g/ml), sedimentation coefficient (150S), and capsid polypeptide profile, Vilyuisk virus appears to belong to the family Picornaviridae. Acute phase mouse antisera were used to study the antigenic relatedness of Vilyuisk, GDVII (the prototypic strain TMEV), and EMC viruses by enzyme-linked immunosorbent assay (ELISA). The results indicate that Vilyuisk and GDVII viruses are similar but distant subtypes, and that Vilyuisk and EMC viruses are unrelated.

Animals↗
PubMed1983

Location and distribution of virus antigen in the central nervous system of mice persistently infected with Theiler's virus.

The present study has shown that virus can be readily detected by immunofluorescent staining in the central nervous system (CNS) of SJL mice persistently infected with Theiler's murine encephalomyelitis virus (TMEV). Considering the low CNS virus content, large amounts of virus antigen were found in the white matter, the site of demyelinating lesions. Virus antigen was detected in all animals killed after post-infection (PI) Day 21, a time which can be considered as the beginning of the persistent phase of this infection, and the appearance of virus antigen in white matter corresponded closely in time with the onset of demyelination. The pathogensis of this persistent infection can now be reasonably well reconstructed from the temporal observations made in this study. It would appear that between the second and third week PI, virus replication largely shifts from neurons in spinal cord gray matter to other cell types located in white matter. While a lower-grade persistent infection (in terms of the relative number of cells containing virus antigen) is established and maintained in cells in the gray matter and inflammatory and leptomeningeal infiltrates, cells in white matter appear to be mainly responsible for perpetuating the infection. Why these cells should supplant neurons as the most susceptible host cell during the chronic phase of the infection is discussed.

Animals↗
PubMed1981

The growth of four human and animal enteroviruses in the central nervous systems of mice.

The pattern of CNS infection of our enteroviruses, Coxsackievirus A14, encephalomyocarditis (EMC) virus, GDVII virus, and Vilyuisk virus, was investigated. The regional sites of virus replication were correlated with pathological changes. These viruses were found to replicate and produce similar lesions in selected sites in the mouse CNS during acute infection. Virus antigen and histological lesions were essentially confined to the gray matter, with additional but less direct support for this being provided by virus assay of CNS regions. Virus antigen only could be confidently identified in neurons, and, histologically, neurons were observed in various stages of degeneration. The distribution of the involvement varied in the different infections. For example, EMC virus infection primarily affected the cerebral hemispheres and thalamus, while Coxsackievirus a14 infection predominantly involved the brainstem and spinal cord. GDVII and Vilyuisk virus infections more uniformly involved the entire neuraxis. There was no evidence of virus replication in the olfactory bulbs, leptomeninges, ependyma, choroid plexus, and vascular endothelium. The cerebellum was generally spared, with the cerebellar hemispheres affected only in Coxsackievirus A14 infection. It therefore appears that enteroviruses selectively infect different populations of nerve cells.

Animals↗