Interactions of retinoic acid and androgens in human prostatic tissue.

The effect of retinoic acid (RA) on testosterone metabolic pathway was investigated in hyperplastic and neoplastic human prostatic tissues, and also the effects of steroids on RA binding to its receptor. Steroids only had a minimal effect on the binding of RA by its receptor. The conversion of testosterone to DHT by 5 alpha-reductase was reduced in the presence of retinoic acid. The inhibition was probably due to competition with NADPH for enzyme binding sites. The degree of inhibition found with retinoic acid at a concentration of 10(-4)M was greater for hyperplastic (41%) than that for neoplastic tissue (24%). The inhibition of 5 alpha-reductase by retinoic acid was dose-dependent. The activity of 5 alpha-reductase is significantly less in neoplastic compared with hyperplastic tissue.     

A model of waveform reliability in facial nerve electroneurography

This study identifies four factors that should be considered when evaluating the reliability of new testing methods in facial nerve electroneurography (ENOG): (1) waveform peak-to-peak amplitude; (2) response variability; (3) statistical significance of day-to-day test/retest differences; and (4) waveform morphology. These factors were applied to data gathered on seven normal subjects who had three trials of facial-nerve ENOG on three separate test days in order to determine an optimal recording electrode montage. Both bipolar and monopolar recording-electrode montages were used on the nasal alae and on the nasolabial crease. Resultant peak-to-peak amplitudes of combined motor action potentials were recorded and measured using a clinical evoked-potential instrument. A biphasic waveform shape with optimal peak-to-peak point rather than the nasolabial crease. The contribution to the assessment of response reliability of each of the four factors is discussed.     

Lipophosphoglycan expression and virulence in Ricin-resistant variants of Leishmania major

Lipophosphoglycan (LPG) of Leishmania is a polymorphic molecule comprising an alkylglycerol anchor, a conserved oligosaccharide core and a species-specific polymer of oligosaccharide repeats joined by phosphodiester bonds. This molecule, together with the membrane polypeptide gp63, has been implicated as a parasite receptor for host macrophages. To examine the role of LPG in parasite infectivity glycosylation variants of Leishmania major were generated by chemical mutagenesis of a virulent cloned line V121 and variants with modified LPG selected using the galactose-specific lectin Ricinus communis II (RCA II). Twenty RCA II-resistant primary clones were generated. Analysis of LPG profile by immunoblotting using LPG-specific monoclonal and polyclonal antibodies revealed that some of the clones were LPG-deficient. Three clones that did not bind any LPG-specific antibodies but expressed normal levels of the M_r 63 000 glycoprotein (gp63), a second parasite receptor for host, were chosen for detailed studies.All three clones expressed, at least to some extent, a surface molecule which could be labeled by mild periodate oxidation and sodium borotritide and behaved like LPG by hydrophobic interaction chromatography. All clones also bound a well-characterized monoclonal antibody L157 directed to the core oligosaccharide of LPG, but did not bind another monoclonal antibody, CA7AE, to an epitope on a repeating unit shared by Leishmania donovani and L. major LPG. A third monoclonal antibody, 5E6, recognizing LPG on the surface of wild-type V121 promastigotes bound only to RCA II-resistant clone 3A2-C3 and was restricted to an internal structure. The LPG molecule that this clone expressed was a form of LPG by its chromatographic behavior and by its monosaccharide and alkylglycerol composition. Clone 3A2-C3 was the only one to infect mice in vivo and survive in macrophages in vitro, albeit at a much reduced rate compared to wild-type V121 promastigotes. The data suggest that some form of LPG may be necessary to ensure parasite infectivity.     

The effect of zinc and vitamin C supplementation on the immune status of patients with Crohn's disease

The immune status of 29 patients with Crohn's disease given oral supplements of Vitamin C, zinc or placebo for three-week periods was studied. Collectively, the patients showed T-cell hyporesponsiveness, as assessed by phytohaemagglutinin stimulation, which was significantly improved by Vitamin C. Both monocyte function, as assessed by latex phagocytosis, and pan T-Cell number were significantly reduced and were not influenced by supplementation. Humoral immunity, assessed by pokeweed mitogen-induced immunoglobulin synthesis, was normal and remained unchanged. Vitamin C supplements improved T-cell function in Crohn's disease, whereas neither Vitamin C nor zinc had a measurable effect on humoral immunity.     

The contacts which families and children with learning disabilities have with health and social services

This study summarises all the documented service inputs which families who had a child classed as having learning disabilities, received from one community Health and Social Services Trust in Northern Ireland during the 12 month period April 1996 to March 1997.

Using data obtained from three computer-based recording systems used in Northern Ireland - Child Health Record (Module V); L-CID and Soscare - this paper documents the extent and type of service provision for this population. In all, eleven different health professionals were involved while social services offered a further five service inputs. However the services provided varied across different age groupings of children and severity of the disability. Similarities and differences are noted between the Trust's services and those reported in a national U.K. survey of parents with disabled children.

Four key issues are discussed in the light of the Children (N.I.) Order: the development of a common database for this population; the criteria used to determine which children receive a service and those who do not; the co-ordination of service inputs; and the failure of present computer systems to record the outcomes of service inputs.