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Biomedical subjects

S Gray

Publications and source records attributed to S Gray.

At least 109 records · Page 6Linked to original sources
PubMed1996

Antigenic diversity of meningococcal outer membrane protein PorA has implications for epidemiological analysis and vaccine design.

The currently used serological subtyping scheme for the pathogen Neisseria meningitidis is not comprehensive, a proportion of isolates are reported as not subtypeable (NST), and few isolates are fully characterized with two subtypes for each strain. To establish the reasons for this and to assess the effectiveness of DNA-based subtyping schemes, dot blot hybridization and nucleotide sequence analyses were used to characterize the genes encoding antigenic variants of the meningococcal subtyping antigen, the PorA protein. A total of 233 strains, including 174 serologically NST and 59 partially or completely subtyped meningococcal strains, were surveyed. The NST isolates were chosen to be temporally and geographically representative of NST strains, isolated in England and Wales, and submitted to the Meningococcal Reference Unit in the period 1989 to 1991. The DNA-based analyses demonstrated that all of the strains examined possessed a porA gene. Some of these strains were serologically NST because of a lack of monoclonal antibodies against certain PorA epitopes; in other cases, strains expressed minor variants of known PorA epitopes that did not react with monoclonal antibodies in serological assays. Lack of expression remained a possible explanation for serological typing failure in some cases. These findings have important implications for epidemiological analysis and vaccine design and demonstrate the need for genetic characterization, rather than phenotypic characterization using monoclonal antibodies, for the identification of meningococcal strains.

Amino Acid Sequence↗
PubMed1996

Cellular distribution of androgen receptors in the liver.

In order to determine the cellular distribution of androgen receptors (AR) in normal liver and to examine whether phenotypic changes occur in a variety of non-neoplastic liver diseases, cryostat sections of explanted livers removed from 52 consecutive patients undergoing orthotopic transplantation were immunostained using an anti-androgen receptor monoclonal antibody. In histologically normal liver, AR was immunolocalised to the nuclei of hepatocytes. The proportion of positive hepatocytes varied from about 50% to greater than 90%. Staining, of variable intensity, was restricted to parenchymal cells with no evidence of zonal heterogeneity with respect to labelling intensity. In tissue from patients with biliary cirrhoses and in some cases of alcoholic cirrhosis, labelling for AR was observed in areas of ductular metaplasia but not in areas of "typical" ductular reaction (ductular proliferation). Otherwise, no consistent abnormalities in immunolabelling were seen in any of the diseased livers.

Adult↗
PubMed1995

Transcriptional repression in the Drosophila embryo.

Transcriptional repression is essential for the conversion of crude maternal gradients into sharp territories of tissue differentiation in the Drosophila embryo. Evidence will be presented suggesting that some of the embryonic repressors function through a short-range 'quenching' mechanism, whereby a repressor works over short distances (ca. 50 b.p.) to block neighbouring activators within a target enhancer. This type of repression can explain how different enhancers work autonomously within complex modular promoters. However, at least one of the repressors operating in the early embryo works through a long-range, or silencing, mechanism. The binding of a silencer to a given enhancer leads to the inactivation of all enhancers within a complex promoter. The analysis of chromatin boundary elements suggest that silencers and enhancers might work through distinct mechanisms. We speculate that silencers constrain the evolution of complex promoters.

Animals↗
PubMed1995

Tumour suppression by the human von Hippel-Lindau gene product.

A partial cDNA sequence for the gene linked to the von Hippel-Lindau (VHL) syndrome was reported in 1993. Mutation or loss of both VHL alleles has been documented in sporadic renal cell carcinomas and in the neoplasms that arise in von Hippel-Lindau kindreds. We have determined that the protein product of the VHL gene is an approximately 30 kilodalton cytoplasmic protein. The renal carcinoma cell line 786-O is known to harbour a VHL mutation and, as shown here, fails to produce a wild-type VHL protein. Reintroduction of wild-type, but not mutant, VHL into these cells had no demonstrable effect on their growth in vitro but inhibited their ability to form tumours in nude mice.

Amino Acid Sequence↗
PubMed1995

The hospital admissions study in England: are there alternatives to emergency hospital admission?

STUDY OBJECTIVE: To assess the potential for substituting alternative forms of care for admission to an acute hospital in particular groups of patients. DESIGN: A screening tool, the intensity-severity-discharge review system with adult criteria (ISD-A), developed for hospital utilisation review in the USA, was used in a cohort of hospital admissions to identify a group of patients who could potentially have been treated outside the acute hospital. These patients were further assessed by a panel of general practitioners (GPs) to determine the most appropriate alternative form of care. A cost analysis was performed on the results obtained. SETTING: General medicine and geriatric specialties in one acute hospital in the south western region. PATIENTS: Patients comprised a sample of 701 admitted to general medical and geriatric specialties. MAIN RESULTS: The screening tool identified 19.7% of admissions for whom there was potential for treatment outside the acute hospital. Assessment by the GP panel reduced this potential to between 9.8% and 15.0% of emergency admissions. The alternatives most frequently identified as "most appropriate" were the community hospital/GP bed and the urgent outpatient assessment (within either 24 or 48 hours). Potential resource savings based on the average cost were relatively small. This potential seemed to be greater for the alternative of the urgent outpatient assessment. CONCLUSIONS: Potential exists for treating a proportion of patients in lower intensity alternatives to the acute hospital. If this potential were exploited few resource savings would occur.

Cohort Studies↗
PubMed1995

Diagnostic yield of routine ileoscopy.

Intubation of the ileum during colonoscopy, although well described, is not routinely performed. It can establish the completeness of colonoscopic examinations and is useful in the diagnosis of inflammatory bowel disease. However, the diagnostic utility of routine ileoscopy during all colonoscopic procedures has not been well studied. We prospectively evaluated ileal intubations in 138 patients undergoing colonoscopy. The incidence of a positive diagnosis from ileoscopy was 2.7% in asymptomatic patients undergoing surveillance colonoscopy, and 29% of patients complained of diarrhea (18% in non-HIV patients, 67% in HIV-positive patients). We feel ileal intubation is an important adjunct to colonoscopy, especially in patients with diarrhea.

Colonoscopy↗
PubMed1995

Primary care management of acute herpes zoster: systematic review of evidence from randomized controlled trials.

Although a number of randomized controlled trials of treatment for herpes zoster have been performed, there is no consensus on how it should be managed in general practice. A systematic review of existing trials, including meta-analysis, was performed to determine the efficacy of available therapies in reducing the incidence of postherpetic neuralgia. The treatments studied included antiviral agents, corticosteroids and other drugs which had been studied in randomized trials. Trials were included if the subjects were immunocompetent adults and the intervention was feasible in general practice. The main outcome measure was prevalence of pain at one, three and six months after onset of the acute herpetic rash. Data for each time point were not available for all trials. The quality of studies was also assessed. Pooled analyses of trials with acyclovir failed to detect a significant reduction of pain in the treatment group at one or six months, but found a 35% reduction at three months. Confidence limits were wide, and a modest benefit of treatment cannot be ruled out at one and six months. Pooled analyses were not possible for other treatments, either because too few trials had been performed, or because completed trials demonstrated significant heterogeneity. Many clinical trials in this area have been too small to give reliable results. Variations in the definition and reporting of postherpetic neuralgia create difficulties in combining data from different studies. Firm recommendations for clinical practice are not possible because existing evidence neither confirms nor refutes the hypothesis that treatment during the acute phase of herpes zoster reduces pain later.

Acute Disease↗
PubMed1995

Attitudes and behaviors of African-American and Mexican-American women delivering newborns in inner-city Los Angeles.

To study some of the factors relating to the care of mothers and newborns in an inner-city hospital, three sources of information were reviewed: an obstetric database including information on prenatal care and perinatal mortality, a database of all admissions to the hospital neonatal intensive care unit over the past 5 years, and a detailed questionnaire concerning attitudes and behaviors of recently delivered women. While analyses from these hospital-based data are not conclusive, the results add evidence for the following propositions: 1) Optimal prenatal care is infrequently obtained by mothers delivering at inner-city hospitals. Lack of prenatal care is clearly associated with increased perinatal mortality. While the need for prenatal care is appreciated by 98% of the mothers in this sample, the most frequent reasons why prenatal care is not obtained earlier or more frequently involve knowledge about and access to prenatal care. 2) Inner-city mothers, in general, manifest attitudes and behaviors that promote the welfare of their pregnancies and newborns. These attitudes and behaviors are in stark contrast to those that are frequently attributed to inner-city women by the media. 3) Acute perinatal medical and nursing care are perceived by many postpartum women as suboptimal, particularly in terms of the lack of respect shown to patients by nurses and doctors. 4) Improved acute obstetric and neonatal care improves perinatal morbidity and mortality of infants delivered at inner-city hospitals.

Adult↗
PubMed1994

Short-range repression permits multiple enhancers to function autonomously within a complex promoter.

Transcriptional repressors play a key role in establishing localized patterns of gene expression in the early Drosophila embryo. Several different modes of repression have been implicated in previous studies, including competition and direct interference with the transcription complex. Here, we present evidence for "quenching," whereby activators and repressors co-occupy neighboring sites in a target promoter, but the repressor blocks the ability of the activator to contact the transcription complex. This study centers on a zinc finger repressor, snail (sna), which represses the expression of neuroectodermal regulatory genes in the presumptive mesoderm. We show that sna can mediate efficient repression when bound 50-100 bp from upstream activator sites. Repression does not depend on proximity of sna-binding sites to the transcription initiation site. sna is not a dedicated repressor but, instead, appears to block disparate activators. We discuss the importance of quenching as a means of permitting separate enhancers to function autonomously within a complex promoter.

Animals↗
PubMed1994

Effectiveness of training health professionals to provide smoking cessation interventions: systematic review of randomised controlled trials.

OBJECTIVE: To assess the effectiveness of interventions that train healthcare professionals in methods for improving the quality of care delivered to patients who smoke. DESIGN: Systematic literature review. SETTING: Primary care medical and dental practices in the United States and Canada. Patients were recruited opportunistically. SUBJECTS: 878 healthcare professionals and 11,228 patients who smoked and were identified in eight randomised controlled trials. In each of these trials healthcare professionals received formal training in smoking cessation, and their performance was compared with that of a control group. MAIN MEASURES: Point prevalence rates of abstinence from smoking at six or 12 months in patients who were smokers at baseline. Rates of performance of tasks of smoking cessation by healthcare professionals, including offering counselling, setting dates to stop smoking, giving follow up appointments, distributing self help materials, and recommending nicotine gum. METHODS: Trials were identified by multiple methods. Data were abstracted according to predetermined criteria by two observers. When possible, meta-analysis was performed using a fixed effects model and the results were subjected to sensitivity analysis. RESULTS: Healthcare professionals who had received training were significantly more likely to perform tasks of smoking cessation than untrained controls. There was a modest increase in the odds of stopping smoking for smokers attending health professionals who had received training compared with patients attending control practitioners (odds ratio 1.35 (95% confidence interval 1.09 to 1.68)). This result was not robust to sensitivity analysis. The effects of training were increased if prompts and reminders were used. There was no definite benefit found for more intensive forms of counselling compared with minimal contact strategies. CONCLUSIONS: Training health professionals to provide smoking cessation interventions had a measurable impact on professional performance. A modest, but non-robust, effect on patient outcome was also found, suggesting that training alone is unlikely to be an effective strategy for improving quality of care, unless organisational and other factors are also considered.

Behavior Therapy↗
PubMed1993

Inner-city pharmacies: can they meet the OBRA '90 mandates?

Visits were made to 21 pharmacies in two poor Chicago neighborhoods as one component of the University of Illinois at Chicago's commitment to help improve health care delivery, ensure that pharmacy services are not overlooked in local health reform efforts, and understand the implications of the Omnibus Budget Reconciliation Act of 1990 (OBRA '90). Pharmacists report that Medicaid reimbursement policies result in: (1) prescribing patterns that have no consistent therapeutic or economic rationale; (2) dispensing of expensive drugs, some of which are then sold on the street or to other pharmacies; and (3) dispensing of unnecessary and often expensive legend drugs when other legend drugs and generics or over-the-counter products would perform just as well. On the positive side, 76% of the pharmacies possess computerized patient-profile systems, and 72% maintain background information on their prescribers. These results suggest that OBRA '90's mandates should contribute toward improving the Medicaid program, but that implementation is likely to be difficult and uneven.

Chicago↗
PubMed1993

The problems of tracing a geographically widespread outbreak of salmonellosis from a commonly eaten food: Salmonella typhimurium DT193 in north west England and north Wales in 1991.

Geographically widespread outbreaks involving commonly isolated organisms and where the vehicles of infection are commonly eaten foodstuffs pose particular difficulties at a technical and organizational level. An outbreak of Salmonella typhimurium infection, affecting 39 people, spread over a wide area in North West England and North Wales in April and May 1991, was detected thanks to the practice of sending specimens to the national reference laboratory where phage typing and characterizing of antibiotic resistance patterns enabled the identification of a cluster of distinctive isolates (S. typhimurium DT193 resistant to sulphonamides, trimethoprim and furazolidone). An investigation, involving twenty environmental health departments in addition to health authorities and the Public Health Laboratory Service, showed an association between the illness and eating loose sliced cooked ham (P = 0.004). Detailed tracing of the chain of supply of the ham showed this to be particularly cooked ham originating from a single small local producer (P = 0.00003). Further investigation of that producer revealed that a batch of ham distributed on one day in early April was undercooked due to a malfunction in cooking equipment.

Adolescent↗
PubMed1993

Mast cell density and PGP 9.5-immunostained nerves in angioleiomyoma: their relationship to painful symptoms.

Angioleiomyoma is frequently painful and the cause of the pain is unknown. The purpose of this study was to compare the mast cell population and innervation of painful and painless angioleiomyomas. Twenty-four cases of angioleiomyoma were examined; 16 painful and 8 painless cases. Pinacyanol erythrosinate and antibodies to protein gene product (PGP) 9.5 were used to demonstrate mast cells and nerves respectively. PGP 9.5-immunoreactive nerve fibres were found in most of the painful (13/16 cases) and painless lesions (5/8). Mast cells were not seen in half of the painful lesions but were seen in most of the painless lesions (7/8). The median mast cell density was 1.1 cells/mm2 for the painful lesions and 21.9 cells/mm2 for the painless lesions (P = 0.048, Mann-Whitney test). The lower mast cell density in the painful lesions may reflect increased mast cell degranulation. It is proposed that neural and vascular events, similar to those occurring in the triple response to mild cutaneous injury, may produce pain in angioleiomyoma and other painful skin tumours.

Carbocyanines↗