Oguchi disease: suggestion of linkage to markers on chromosome 2q.

Oguchi disease is a rare autosomal recessive form of congenital stationary night blindness. The condition is associated with fundus discolouration and abnormally slow dark adaptation. Earlier studies suggested that the 48 kD protein S antigen may be involved in the recovery phase of light transduction. Previous cytogenetic and linkage studies have localised the S antigen gene (SAG) to chromosome 2q37.1. In the present study markers which map to distal chromosome 2q were typed in an inbred Oguchi pedigree. The segregation data obtained suggested that the affected subjects are homozygous by descent for a region between D2S172 and D2S345. An intragenic SAG polymorphism was homozygous in all affected people and a recombination event suggested that SAG maps proximal to D2S345. Collectively, these findings support the hypothesis that a defect in S antigen may be responsible for Oguchi disease.     

Sudden total deafness in sickle cell disease

Sickle cell disease is a world-wide problem which has been noted to cause high tone sensorineural hearing loss. We report a case with sudden onset bilateral hearing loss which progressed to total sensorineural deafness. To our knowledge there has been no report of such a case occurring previously.     

Sexual attitudes and practices of selected groups in Northern Ireland since the emergence of AIDS.

One hundred and seventeen heterosexual males and females attending a sexually transmitted disease clinic and 57 homosexual males from a local "gay" club were asked to complete a questionnaire regarding their attitudes and sexual practices since the emergence of AIDS. The results show a trend towards increasing partner change rate among heterosexual males. There has been an increase in the practice of insertive anal intercourse by homosexual men with Northern Ireland contacts but no corresponding increase with contacts outside Northern Ireland. The practice of receptive anal intercourse has remained constant. Significant differences in attitudes between homosexual and heterosexual males were expressed with regard to testing of 'at risk groups' (p less than 0.001), in the uptake of testing (p less than 0.01), and in attitudes to sexual practices if they themselves became HIV positive. There was a low level of anxiety amongst heterosexuals regarding risk of HIV infection in the future. Less than 50% of the heterosexual patients attending this clinic use condoms, though more claim to intend to use them in future.     

Knowledge of HIV infection and AIDS, and attitudes to testing and counselling among general practitioners in Northern Ireland.

All 922 general practitioners in Northern Ireland were sent a questionnaire on human immunodeficiency virus (HIV) infection and the acquired immune deficiency syndrome (AIDS). Five hundred and ninety four general practitioners (64.4%) returned the questionnaire. Thirty eight respondents (6.4%) knew of an HIV positive patient in their practice and 93.3% felt they should be informed if one of their patients was found to be HIV positive at a genitourinary medicine clinic, even without the patient's consent. Of the respondents, 76.8% were willing to be involved in the management of AIDS patients in their practice in cooperation with hospital colleagues but only 37.5% felt confident to provide AIDS counselling and advice. Of the 368 general practitioners who did not feel confident to provide AIDS counselling and advice, 41.3% felt that they had insufficient knowledge and 79.6% felt uncertain of their counselling skills. The information gathered on the administration of injections, taking blood samples and disposal of needles indicated that further education for general practitioners is required to ensure safety at work.     

Roles of tumour necrosis factor-alpha (TNF-alpha), transforming growth factor-beta (TGF-beta), and IL-10 in the modulation of intercellular adhesion molecule-1 (ICAM-1) expression by macrophages during mycobacterial infection

Profiles of ICAM-1 expression on cultured murine peritoneal macrophages infected with Mycobacterium avium complex (MAC) were examined, with special reference to modulating roles of TNF-alpha, TGF-beta, and IL-10. When macrophages were infected with MAC, ICAM-1 expression, measured by microscopic counting of ICAM-1+ macrophages stained with anti-ICAM-1 antibody, ELISA, and flow cytometric analysis, was rapidly increased, peaking at day 3 (early-phase up-regulation) due to endogenous TNF-alpha, and thereafter gradually declined to the normal level within 1 week or more (late-phase down-regulation). The late-phase ICAM-1 down-regulation was also seen in macrophages phagocytosing heat-killed MAC and those stimulated with lipopolysaccharide but not in macrophages phagocytosing latex beads. ICAM-1 mRNA expression was augmented markedly at day 1 after MAC infection and thereafter decreased. While TNF-alpha and IL-10 production by MAC-infected macrophages was observed during the first 3 days, TGF-beta production was initiated from day 3 and continued until day 14. Exogenously added TGF-beta strongly inhibited the early-phase increase in ICAM-1 expression by infected macrophages, and the blockade of endogenous TGF-beta with anti-TGF-beta antibody markedly inhibited late-phase ICAM-1 down-regulation. Moderate blocking effect was also observed for anti-IL-10 antibody. On the other hand, late-phase ICAM-1 down-regulation was not prevented by the addition of exogenous TNF-alpha. Therefore, TGF-beta and IL-10, especially the former, appear to play active roles in the late-phase down-regulation of ICAM-1 in MAC-infected macrophages during long-term cultivation.     

Human leukocyte antigen matching and fetal loss: results of a 10 year prospective study

The role that maternal and fetal human leukocyte antigen (HLA) genes play in pregnancy is unknown, but it has been suggested that fetuses whose HLA alleles do not differ from maternal alleles (i.e. histocompatible fetuses) are more likely to be aborted than fetuses with HLA alleles that differ from maternal alleles (i.e. histoincompatible fetuses). To elucidate the role of HLA compatibility in pregnancy, we tested the hypothesis that couples who match for HLA alleles or haplotypes would have reduced fertility because only these couples could produce histocompatible fetuses. We conducted a 10 year prospective study of HLA matching and pregnancy outcome in 111 Hutterite couples, providing information on 251 pregnancies. A logistic regression analysis was performed to determine the effects of HLA matching at HLA regions and loci on pregnancy outcome (fetal loss versus delivery). Significantly increased fetal loss rates were observed among couples matching for the entire 16-locus haplotype (P = 0.002). Among the individual loci, loss rates were increased among couples matching for HLA-B (P = 0.019), HLA-C (P = 0.033) and the complement component, C4 (P = 0.043). We interpret these results as evidence that matching for the entire 16-locus haplotype and/or alleles at an HLA-B-linked locus confers significant risk for fetal loss.      

Cervical epithelial abnormalities are significantly associated with non-HPV lower genital tract infection in female contacts of warts*

Objectives

• 1 To assess the prevalence of cervical epithelial abnormalities in female sexual partners of men with anogenital warts.
• 2 To examine the possible association between non-HPV lower genital tract infection, and cervical epithelial abnormalities.

Design Retrospective review of the medical records of all female sexual partners of men with anogenital warts attending the GUM clinic in 1990. Setting and patients The department of Genito-Urinary Medicine (GUM), Royal Victoria Hospital, Belfast. Sixty-two female sexual partners of men with anogenital warts. Methods Cervical cytology and colposcopy was performed on all patients. Biopsies were taken of colposcopically identified cervical epithelial abnormalities, Non-HPV lower genital tract infection was detected by routine genito-urinary screening. Demographic data and sexual history were obtained by questionnaire. Outcome measured Overall prevalence of cervical epithelial abnormalities and correlation to the presence of non-HPV lower genital tract infection in the female. Results The overall prevalence of cervical epithelial abnormalities detected with colposcopy and biopsy was 46.8%. The prevalence of koilocytosis and cervical intraepithelial neoplasia (CIN) was 69.6% when non-HPV lower genital tract infection was detected by routine genito-urinary screening. When no infection was detected the prevalence was 33.3% (P < 0.05).     

Marrow regeneration after mechanical depletion

The origin of marrow regeneration after mechanical depletion was reinvestigated in mouse chimeras. The results were compatible with the local origin of stem cells from remnants of incompletely removed marrow, but not with their origin from a common precursor of both bone and hemopoietic cell lines. In transplanted femurs depleted by a modified technique of in vivo evacuation of marrow, hemopoietic regeneration failed to occur. The presence of hemopoietic stem cells in the Haversian canals was thus excluded. The demonstration of ample hemopoiesis with minimal bone formation in nondepleted controls in which bone marrow initially became necrotic provided new evidence that osteogenesis was not a prerequisite of hemopoietic regeneration.