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Biomedical subjects

J Williams

Publications and source records attributed to J Williams.

At least 577 records · Page 32Linked to original sources

Constructing chimeric type 12/type 5 adenovirus E1A genes and using them to identify an oncogenic determinant of adenovirus type 12.

The E1A gene of highly oncogenic type 12 adenovirus (Ad12) possesses a segment unique to this serotype and comprising 60 base pairs contiguous with and separating conserved regions 2 and 3 in the gene. A similar but slightly longer segment is also present in the E1A gene of highly oncogenic simian adenovirus type 7 (D. Kimelman, J. S. Miller, D. Porter, and B. E. Roberts, J. Virol. 53:399-409, 1985). This segment is missing entirely from the E1A gene of type 5 adenovirus, which is nononcogenic. To test the hypothesis that this unique separating or "spacer" region influences the oncogenicity of Ad12, we constructed ClaI and SmaI restriction sites on either side of it, which allowed reciprocal exchange between this and the equivalent cassette from type 5 adenovirus E1A, bounded by the same restriction sites intrinsic to that gene. The resultant Ad12-based chimeric viruses, ch702 and ch704, in which the spacer region is replaced with (in-frame) type 5 sequence, grow normally on human A549 cells and display wild-type transformation frequencies on baby rat and mouse kidney cells. In contrast, the oncogenic capacity of these chimeric viruses, as measured by tumor induction following virus inoculation in Hooded Lister rats, is greatly reduced. Likewise, cells transformed by ch702 and ch704 display reduced tumorigenicity compared with wild-type transformants in syngeneic rats. These results, coupled with recent preliminary tests using a mutant with a point mutation in this region, support the view that the unique spacer region of type 12 is an oncogenic determinant of this virus.

Adenovirus E1A Proteins↗

Confirmation of association between the e4 allele of apolipoprotein E and Alzheimer's disease.

The Apo E genotype of 86 patients with Alzheimer's disease (AD) and 77 age matched controls was determined by digestion of Apo E PCR products with the restriction enzyme CfoI. The frequency of the e4 allele was significantly increased in the patient group (0.33) as compared with controls (0.12). This effect was seen in patients with a family history and in sporadic cases. The odds ratio in homozygotes for the e4 allele was 11.24 (95% confidence interval 2.45-51.50). There was no relationship between age of onset and Apo E genotype. There was no linkage disequilibrium between the apolipoprotein E locus and a TaqI polymorphism at the Apo CII locus, and no allelic association between Apo CII and AD.

Age of Onset↗

Relation of pulmonary lymphangio-leiomyomatosis to use of the oral contraceptive pill and fertility in the UK: a national case control study.

BACKGROUND: Pulmonary lymphangioleiomyomatosis is a rare progressive disease of unknown aetiology affecting premenopausal women. Since the oral contraceptive pill has been implicated in its pathogenesis, a case control study was carried out to determine whether women with the disease were more likely to have taken the oral contraceptive pill, and whether the disease was associated with other conditions related to sex hormones including pregnancy, parity, and fibroids. METHODS: All chest physicians in the UK were asked for details of all live patients with pulmonary lymphangioleiomyomatosis; the patient's family doctor was then asked for four age and sex matched control subjects from their patient register. Details of lifetime use of the oral contraceptive pill, pregnancy, parity, history of fibroids, and smoking were obtained from cases and controls. Relative odds of exposure to potential risk factors were estimated by conditional logistic regression. RESULTS: Medical details were obtained from all 23 cases of lymphangioleiomyomatosis identified; questionnaires were completed by 21 cases (one by proxy) and by 46 matched controls of mean (SD) age 43 (10) and 44 (11) years, respectively. The patients had a mean age of 34 (9) years at onset of symptoms and a median (range) time of 2 (0-29) years from onset of symptoms to diagnosis. Compared with control subjects, cases did not differ in the use of the oral contraceptive pill (odds ratio (OR) 0.39, 95% CI 0.09 to 1.68), diagnosis of fibroids (OR 3.12; 95% CI 0.52 to 18.7), age of menarche, menstrual history, or lifetime smoking. They were, however, less likely to have been pregnant (OR 0.14, 95% CI 0.03 to 0.71) or to have had children (OR 0.13, 95% CI 0.03 to 0.67). More pregnancies had ended in spontaneous abortion (28% v 8%) but the proportion of women undergoing spontaneous abortion was similar in cases and controls (OR 2.13, 95% CI 0.47 to 9.3). CONCLUSIONS: This study does not support the hypothesis that use of the oral contraceptive pill is causally associated with the development of pulmonary lymphangioleiomyomatosis. Sex hormones may be involved, however, since patients were less likely to have been pregnant or to have had children, and tended to have had more spontaneous abortions and an increased incidence of fibroids.

Abortion, Spontaneous↗

External quality assessment of techniques for the detection of drugs of abuse in urine.

Five chromatographic and six immunoassay techniques were compared using data reported by 131 participants in the UK National External Quality Assessment Scheme for Drugs of Abuse in Urine. Twenty five samples were studied containing none or one of three concentrations of amphetamine, barbiturates, benzodiazepines, benzoylecgonine, methadone and morphine. Technique sensitivity and specificity achieved with realistic clinical samples of 25 mL vol were assessed as the percentage of true positive and true negative tests, respectively. Thin-layer chromatography was inadequate for the detection of several analytes, the sensitivity for 0.5 mg/L of benzoylecgonine being < 30%, and for 1.5 mg/L of amphetamine < 86%. Gas chromatography with mass spectrometry was significantly less sensitive than other techniques for the detection of 0.5 mg/L of benzoylecgonine (71%) and 1.5 mg/L of morphine (88%). High-performance liquid chromatography was the most sensitive for amphetamine. Immunoassays performed well when operating above their specified cut-off concentrations but, because they are directed to quinalbarbitone showed reduced cross-reactivity with amylobarbitone, the barbiturate more commonly prescribed in the UK.

Chromatography↗

An evaluation of legal outcome following pretrial forensic assessment.

This paper constitutes the first stage of data analysis in a larger controlled study designed to assess the effect of a forensic psychiatric assessment on legal disposition defined in three ways: 1. the number of days spent in custody prior to trial; 2. the number of sentenced days of incarceration; and 3. the conviction rate. A historical cohort design was used to follow two cohorts of individuals remanded, pretrial, to Southern Alberta Provincial Correctional Centres between 1988 and 1989. The study cohort consisted of all offenders detained who received a forensic psychiatric assessment. The comparison cohort consisted of a random sample of persons detained who did not undergo a forensic assessment. Because of small numbers, individuals below the age of 18 and women were excluded from study. This paper compares socio-legal characteristics of study and comparison subjects in order to better understand forensic psychiatric referral patterns and identify potentially confounding factors that would need to be controlled in subsequent analyses of legal outcomes. No differences were noted with respect to educational level but forensic subjects were found to be slightly older (average of 31 years compared to 29 years). Aboriginal peoples (Native Indian, Inuit and Metis) were three times more common among non-forensic offenders. Forensic patients were more likely to have had a prior forensic assessment but less likely to have a prior criminal detention. In addition, forensic patients were three times more likely to be charged with a crime against a person and counted more offenses in the target episode than comparison subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Prone oblique positioning for computed tomographic arthrography of the shoulder.

Computed tomographic arthrography (CTA) of the shoulder is currently the best investigation of the unstable shoulder. 47 patients had CTA in the prone oblique position to assess its ability to demonstrate both anterior and posterior capsular mechanisms simultaneously. The first five patients were also scanned supine oblique to allow direct comparison with the prone oblique position. All studies were reviewed retrospectively by three musculoskeletal radiologists with regard to how well the relevant structures were demonstrated. In the prone oblique position, the anterior capsule was well shown in 98%, anterior labrum 98%, posterior capsule 91%, posterior labrum 89%, subscapularis tendon 98%, biceps tendon 100% and biceps tendon proximal insertion 78%. In 86% of cases both anterior and posterior structures were well seen simultaneously. In the five cases that also had supine imaging the prone oblique images were superior. The cause of poor demonstration of structures was invariably insufficient intraarticular air. It is concluded that the prone oblique is an excellent technique for CTA of the shoulder and should become the standard position for assessing shoulder instability.

Adolescent↗

Scintigraphic and ultrasonographic diagnosis of soft tissue injury in a thoroughbred horse.

A 2.5-year-old female Thoroughbred horse was referred to the veterinary teaching hospital for right front limb lameness of 1 year duration. Physical examination and diagnostic nerve blocks failed to localize the origin of the lameness. Scintigraphy with 99mTc-MDP suggested increased radionuclide uptake in the palmar metacarpal soft tissues of the right front limb. Ultrasonographic examination revealed hypoechoic lesions in the superficial digital flexor tendon and the suspensory ligament, suggesting tendinitis and desmitis. Combined imaging modalities improved detection and characterization of the cause of a long-standing obscure lameness.

Animals↗

Integration of one's religion and homosexuality: a weapon against internalized homophobia?

Internalized homophobia as a psychological phenomenon has attracted little systematic research despite its destructive impact on the mental health of the gay community. This study looks at the relationship between internalized homophobia and the process of integrating one's religious faith and homosexuality by comparing levels of internalized homophobia among male participants of Dignity, an organization of Catholic gay men and lesbians, with a community sample of gay men with Catholic backgrounds. While many gay men believe they must abandon their religious faith (nearly 50% of this community sample no longer endorse a "formal religion") in order to accept their sexuality, Dignity members are actively integrating their religion and homosexuality--a process which we hypothesized would result in the Dignity participants being less homophobic than the community sample. While results showed no significant differences between the groups with regard to level of internalized homophobia, there are suggestions that involvement in Dignity does foster positive attitudes towards one's homosexuality by helping to overcome a delay in the development of a gay orientation. We also examined how other variables such as HIV status, psychological distress, conservative versus liberal ideology, and integration into the gay community would be associated with internalized homophobia.

Adaptation, Psychological↗

Polymorphisms of the gene coding for the cholesteryl ester transfer protein and plasma lipid levels in Italian and Greek migrants to Australia.

The relation between TaqI restriction fragment length polymorphisms (RFLPs) of the cholesteryl ester transfer protein (CETP) gene and plasma lipid and lipoprotein phenotypes was investigated in a sample of Italian and Greek migrants of both sexes, age 40-69 years. Italians display significantly higher mean triglyceride and lower mean high-density lipoprotein (HDL) cholesterol levels than Greeks. Greek females have significantly higher HDL cholesterol than Greek males, and Italian females have significantly higher low-density lipoprotein (LDL), HDL, and total cholesterol than Italian males. The differences in RFLP allele frequencies between the two ethnic groups and sexes are insignificant. Multivariate analyses show that in the Greek sample the TaqI B RFLP of the CETP gene has a highly significant effect on HDL cholesterol levels regardless of sex and that the TaqI A polymorphism has a significant effect on HDL levels in females but modulates LDL cholesterol concentrations in males. Among Italians, with the sexes considered separately or combined, no such effects of the CETP TaqI polymorphisms are detected. Kruskal-Wallis tests detected associations between the TaqI B polymorphism in all Greek samples but not in the Italian samples. Genotype CETP*B2 exhibits significantly higher HDL cholesterol concentrations than either of the other two TaqI B genotypes, but there is no evidence of a dosage effect of the *B2 allele. These data suggest that associations between the CETP gene and lipid phenotypes can be population specific. Further, they suggest that such associations are mediated in some way by gender.

Adult↗

[Action of growth factors on the ovary in the domestic chicken (Gallus domesticus)].

An original method for the culture of granulosa and thecal cells of the domestic hen was developed and used to investigate the effects of serum, of EGF and of IGFI on the multiplication of these cell types and on their secretion of steroid hormones. The growth of the cultures (measured by the accumulation of DNA in the culture wells) over a 72 hour period was judged to be satisfactory although slower without serum. Both growth factors stimulated cell growth and EGF inhibited steroidogenesis in both cell types. IGFI inhibits the secretion of oestrogens by thecal cells but it stimulates the secretion of progesterone by granulosa cells towards the end of the period of culture.

Animals↗

DNA polymorphisms at the lipoprotein lipase gene and their association with quantitative variation in plasma high-density lipoproteins and triacylglycerides.

Lipoprotein lipase (LPL) plays a critical role in the metabolism of lipoproteins because this enzyme hydrolyzes the triacylglycerides in chylomicrons and very low density lipoproteins. This process influences the production of high-density lipoprotein (HDL), which takes up tissue cholesterol for transport to the liver for excretion. Accordingly, LPL qualifies as a candidate gene for understanding lipid metabolic disorders and atherosclerosis. Studies on the relationship between genetic variation at the LPL locus and lipid phenotypes have produced equivocal results to date. To help clarify this issue, we investigated 144 outwardly healthy male Mediterranean migrants (from Italy and Greece), age between 40 and 70 years and resident in Australia, for associations between two common LPL restriction site polymorphisms and the following lipid and lipoprotein phenotypes: total plasma cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triacylglycerides. A series of analysis of variance tests, controlling for age, body mass index, and ethnicity, showed that the HindIII polymorphism at the LPL locus is significantly associated with both triacylglyceride and HDL cholesterol concentrations in this sample. The PvUII polymorphism, however, showed no association with any lipid. Kruskal-Wallis tests confirmed the significance of the associations between the HindIII RFLP and both HDL (p = 0.008) and triacylglycerides (p = 0.03). When the sample was subdivided into subjects who exhibited primary hypertriacylglyceridemia and normolipidemics, a significant difference was observed in the frequency of HindIII (p < 0.05) but not PvuII genotypes. HindIII heterozygotes (H1,H2) were least and H2,H2 individuals were most at risk for triacylglyceridemia. Examination of the normolipidemic sample revealed some evidence for an independent effect of the PvuII polymorphism on both LDL cholesterol and total cholesterol levels.

Adult↗

The Human Genome Project: implications for nursing.

The United States has set as a national objective the mapping and sequencing of the entire human genome. Nurses must stay informed about discoveries generated by the Human Genome Project so they can apply this knowledge in nursing practice.

Chromosome Mapping↗