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Biomedical subjects

A White

Publications and source records attributed to A White.

At least 181 records · Page 10Linked to original sources

Early ontogeny of immune cells and their functions in the fetal pig.

The origin of immune cells and their products have been studied in the prenatal period in miniature pigs. Macrophages were first detected on day 25, and myelocytes and lymphoid cells by day 28. Membrane antigens SLA-DR and CD45 were found by day 22, membrane molecules MG-7, 8/1, CD1, CD2 and 74-22 by day 28, Gamma/delta T cells were found initially in extrathymic sites (in the liver). The first gamma/delta T cells were detected as early as 40 days of gestation. The expression of fibronectin, Thy-1 and its message, Ig isotypes and the first induction of IFN alpha were described.

Animals↗

Tuberculosis case finding in remote mountainous areas--are microscopy camps of any value? Experience from Nepal.

SETTING: In the remote hills of North-East Nepal tuberculosis case-finding is believed to be low. The Britain-Nepal Medical Trust (BNMT), a well funded non-governmental organisation supporting Tuberculosis Control Programmes in this area, has a stable structure and sufficiently high case-holding to explore ways to increase case-finding. OBJECTIVES: To increase case-finding without decreasing case-holding, by expanding outreach services into remote areas away from existing health services. DESIGN: Between 1990 and 1993, 45 temporary outreach tuberculosis diagnostic "microscopy camps' were run in the eight districts covered by the BNMT (population 1330000). Camp-diagnosed patients were followed up by cohort. RESULTS: The camps did not appreciably increase the low rate of case-finding. However, the percentage of women who attended the camps was significantly higher than at existing services, as was the number diagnosed with smear-positive tuberculosis. The cured treatment completion rate of this camp-diagnosed cohort was 76%. Cost analysis revealed a low overall additional cost to the programme; however, it would be prohibitively expensive for an under-funded government health service. CONCLUSIONS: The implications of these camps go beyond tuberculosis control in their ability to reach those who would otherwise not utilise health care facilities.

Adult↗

Crystallographic observation of a covalent catalytic intermediate in a beta-glycosidase.

The three-dimensional structure of a catalytically competent glycosyl-enzyme intermediate of a retaining beta-1,4-glycanase has been determined at a resolution of 1.8 A by X-ray diffraction. A fluorinated slow substrate forms an alpha-D-glycopyranosyl linkage to one of the two invariant carboxylates, Glu 233, as supported in solution by 19F-NMR studies. The resulting ester linkage is coplanar with the cyclic oxygen of the proximal saccharide and is inferred to form a strong hydrogen bond with the 2-hydroxyl of that saccharide unit in natural substrates. The active-site architecture of this covalent intermediate gives insights into both the classical double-displacement catalytic mechanism and the basis for the enzyme's specificity.

Binding Sites↗

A theoretical framework created from a repertory grid analysis of graduate nurses in relation to the feelings they experience in clinical practice.

This paper outlines a theoretical framework that was created as a result of an investigation into the feelings graduate nurses have towards clinical practice. The framework offers an explanation of the complexity of emotions which need to be considered when considering why it is that people react in the way they do to their environment. The study from which this framework emerged was a repertory grid analysis of six graduates from an English university in their first year of practice. From the elicited constructs six themes emerged: feelings related to connectedness; feelings related to job satisfaction; feelings related to effectiveness; feelings related to ability; feelings related to threat to self; and feelings related to pressure of work.

Burnout, Professional↗

Alteration of cell cycle kinase complexes in human papillomavirus E6- and E7-expressing fibroblasts precedes neoplastic transformation.

Expression of viral oncoproteins results in the loss of cell cycle checkpoint control and the accumulation of chromosomal abnormalities. Expression of both human papillomavirus type 16 oncoproteins, E6 and E7, in normal human fibroblasts completely dissociates p21 and proliferating cell nuclear antigen from the quarternary cyclin-cyclin-dependent kinase (CDK) complexes present in normal cells, causes disruption of the cyclin D-CDK4 complex and replacement with a CDK4-p16 complex, and leaves binary complexes of cyclin B1-CDC2 and cyclin A-CDK2 intact. These results are identical to those observed in fully transformed cells. The expression of the individual oncoproteins dramatically affects the association of proliferating cell nuclear antigen into the complexes while leaving the total cellular levels unaltered. Expression of low-risk human papillomavirus has no effect on cyclin complexes. These findings provide evidence for the gross alteration of cyclin-CDK complexes in preneoplastic cells and links this alteration to the loss of genomic stability.

Carrier Proteins↗

Impaired processing of proopiomelanocortin in corticotroph macroadenomas.

The regulation and secretion of the ACTH precursors POMC and pro-ACTH were assessed directly using a 2-site immunoradiometric assay in six patients with pituitary macroadenomas (> or = 1.2 cm in diameter) and 27 patients with Cushing's disease due to a microadenoma. ACTH precursor levels were elevated in patients with macroadenomas (150-3690 pmol/L; normal range, < 5-40 pmol/L) and significantly higher than those in microadenoma patients (median, 29 pmol/L; range, 9-104 pmol/L; P < 0.001). Patients with macroadenomas also had increased ACTH precursor/ACTH ratios (15-181:1) compared with microadenoma patients (median, 5:1, range, 0.7-18.5:1; P < 0.001). ACTH precursors were unresponsive to high dose dexamethasone in patients with macroadenomas, whereas ACTH and cortisol responses varied. After CRH administration, ACTH precursors were unchanged, whereas cortisol increased significantly, suggesting the release of biologically active ACTH. This study clearly demonstrates reduced processing of POMC to ACTH in large pituitary tumors, a characteristic usually associated with tumors causing the ectopic ACTH syndrome, and provides evidence for differential regulation of ACTH precursors and ACTH by glucocorticoid and CRH. Variation in the clinical symptoms of patients with corticotroph macroadenomas may be attributable to differences in biological potency between the ACTH precursors and ACTH.

Adenoma↗

Reduced insulin-like growth factor binding protein-1 (IGFBP-1) levels correlate with increased cardiovascular risk in non-insulin dependent diabetes mellitus (NIDDM).

IGF-I and -II levels are altered in patients with atherogenic lipid profiles and may contribute to the development of macrovascular disease in NIDDM. We examined cardiovascular risk factors, IGF-I, IGF-II and IGFBP-1 in 74 NIDDM patients analysed as a whole group and according to treatment type. IGF-I was not significantly associated with cardiovascular risk factors but IGF-II levels correlated positively with total and LDL cholesterol most markedly in the diet treated group (0.72, p < 0.01 and 0.76, p < 0.01 respectively). In the whole group reduced IGFBP-1 levels were significantly associated with factors known to increase cardiovascular risk: i.e. low HDL cholesterol (0.31, p < 0.01) and elevated blood pressure (-0.35, p < 0.01), BMI (-0.37, p < 0.01), insulin (-0.29, p < 0.01) and proinsulin (-0.24, p < 0.01). In the treatment groups IGFBP-1 was lower in patients on diet alone (n = 11, 42.6 +/- 11.6 mu g/l) and sulphonylurea +/- insulin (n = 39, 53.2 +/- 7.6 mu g/l) relative to insulin treatment (n = 24, 103.0 +/- 19, 7 mu g/l, p < 0.05). The lower levels of IGFBP-1 were not due to a significant change in phosphorylation status from the highly phosphorylated circulating form since lesser and non-phosphorylated variants were undetectable in 53/74 patients. Multiple regression analysis revealed the best predictors of IGFBP-1 were BMI and MAP (R2 = 0.2. p < 0.001) and for blood pressure, IGFBP-1 and age (R2 = 0.47, p < 0.001). These findings indicate that in NIDDM patients low IGFBP-1 levels are associated with multiple factors predisposing to atherogenesis.

Blood Pressure↗

What is the psychiatrist's role in drugs and alcohol?

OBJECTIVE: This article describes a consensus view of the role of psychiatrists in respect of alcohol and other drug (AOD) problems, in response to the view expressed by Wodak [1]. METHOD: The data were selected on the basis of the knowledge and experience of the authors. RESULTS: Psychiatrists have made major contributions in the primary, secondary and tertiary prevention of AOD problems over many years in Australia and New Zealand. In recent years there has been an explosion of new knowledge in the AOD area and a shift from mental health to primary and public health care for these patients. Substance use disorders (SUD) are highly prevalent in all areas of psychiatric practice, requiring treatment in their own right as well as complicating the treatment of coexisting psychiatric illness. CONCLUSION: It is argued that psychiatrists have important roles in harm reduction, prevention and policy development; brief and early intervention in SUD in liaison and child psychiatry; and systematic treatment for those with dependence and other psychiatric comorbidity. A research and collaborative approach to AOD services and patients should be encouraged, rather than engaging in divisive debate over "ownership' of this area of clinical practice.

Adolescent↗

The value of skin testing in patients with chronic rhinitis.

The value of skin prick testing in the management of patients with chronic rhinitis has still to be established. The aim of the study was to determine how accurately atopic status could be predicted from the clinical history of allergy. We carried out a prospective audit of 103 patients undergoing skin tests in three ORL departments over a three-month period. Of 73 patients with a history of allergy or an atopic family history, 44 (60%) had a positive skin test. Twenty-one out of 30 (70%) with no history had a negative skin test. In subjects where a negative atopic history to inhaled allergens is combined with a negative family history, the incidence of negative skin test results was 79%. Skin prick testing is of questionable clinical value in the absence of positive atopic feature in the personal or family history of the patient.

Chronic Disease↗

Clinical experience with atovaquone on a treatment investigational new drug protocol for Pneumocystis carinii pneumonia.

The clinical experience of human immunodeficiency virus (HIV) + patients treated with oral atovaquone for acute Pneumocytstis carinii pneumonia (PCP) under a Treatment Investigational New Drug (IND) protocol (mild or moderate PCP) and an Open-Label Study protocol (severe PCP) was evaluated. A total of 940 patients intolerant of or unresponsive to trimethoprimsulfamethoxazole were enrolled from private practices, clinics, and institutional HIV treatment centers in the United States. Demographics data and the history and severity of PCP were collected at enrollment. The number of therapy days, adverse experiences, clinical response to therapy, and mortality were collected at day 21. Reporting of serious, unexpected adverse experiences attributable to therapy was required. Of the 760 (96%) patients with mild to moderate disease for whom follow-up observation was complete, 591 (78%) responded clinically to treatment, 177 patients (23%) discontinued treatment prematurely, and 50 patients (7%) died. Of the 140 patients (95%) with severe PCP with follow-up data, 79 (56%) responded to treatment, 45 (32%) discontinued treatment early, and 53 patients (38%) died. Adverse events that resulted in temporary or permanent discontinuation of therapy included diarrhea, vomiting, elevated liver enzyme levels, nausea, and fever. No serious unexpected adverse events attributable to the drug were reported. The treatment IND mechanism enabled a large number of patients with acute PCP to be treated with this experimental therapy while the drug was under regulatory view.

AIDS-Related Opportunistic Infections↗

The in vitro pharmacological characterization of naloxone benzoylhydrazone.

On the basis of its in vivo activity and binding affinity, naloxone benzoylhydrazone has been characterized as a kappa 3-opioid receptor agonist and a mu-opioid receptor antagonist. This paper continues its pharmacological characterization with the help of isolated tissue preparations. Naloxone benzoylhydrazone was found to have partial agonist activity in the guinea pig ileum longitudinal muscle/myenteric plexus preparation. As an antagonist, naloxone benzoylhydrazone is similar to naloxone, with pA2 values of 8.8, 7.8, and 7.8 for mu-, delta-, and kappa 1-opioid receptors, respectively. Its agonist activity in the guinea pig ileum preparation was not influenced by beta-funaltrexamine treatment but was reversed by the selective kappa-opioid receptor antagonist nor-binaltorphimine and by the irreversible kappa 1-opioid receptor blocker UPHIT (1S,2S)-trans-2-isothiocyanato-4,5-dichloro-N-methyl-N-[2-(1- pyrrolidinyl)-cyclohexyl] benzeneacetamide. The presence of kappa 3-opioid receptors could not be demonstrated by [3H]naloxone benzoylhydrazone binding in the guinea pig ileum longitudinal muscle/myenteric plexus preparation. From these studies it is concluded that the partial agonist activity of naloxone benzoylhydrazone in this bioassay is probably due to the activation of the kappa 1-opioid receptors.

Animals↗

An adoption study comparing the prevalence of psychiatric illness in women who have adoptive and natural children compared with women who have adoptive children only.

The current study compares the current and lifetime prevalence of affective disorder in women who have adopted and have natural children (n = 110) with women who only have adopted children (n = 176). There was no difference in lifetime prevalence of psychiatric disorder between the two groups and a nonsignificant trend for women who had born children to have had a major depressive episode during their lifetime 48 (44%) cf 62 (35%). The increased prevalence of psychiatric illness in married women with children cannot be explained by the biological fact of bearing children. None of the social variables related to child-rearing which were examined influenced the lifetime prevalence of psychiatric disorder.

Adoption↗