Homozygosity mapping of achromatopsia to chromosome 2 using DNA pooling

Achromatopsia is an autosomal recessive disease of the retina, characterized clinically by an inability to distinguish colors, impaired visual acuity, nystagmus and photophobia. A genome-wide search for linkage was performed using an inbred Jewish kindred from Iran. To facilitate the genome-wide search, we utilized a DNA pooling strategy which takes advantage of the likelihood that the disease in this inbred kindred is inherited by all affected individuals from a common founder. Equal molar amounts of DNA from all affected individuals were pooled and used as the PCR template for short tandem repeat polymorphic markers (STRPs). Pooled DNA from unaffected members of the kindred was used as a control. A reduction in the number of alleles in the affected versus control pool was observed at several loci. Upon genotyping of individual family members, significant linkage was established between the disease phenotype and markers localized on chromosome 2. The highest LOD score observed was 5.4 (theta = 0). When four additional small unrelated families were genotyped, the combined peak LOD score was 8.2. Analysis of recombinant chromosomes revealed that the disease gene lies within a 30 cM interval which spans the centromere. Additional fine-mapping studies identified a region of homozygosity in all affected individuals, narrowing the region to 14 cM. A candidate gene for achromatopsia was excluded from this disease interval by radiation hybrid mapping. Linkage of achromatopsia to chromosome 2 is an essential first step in the identification of the disease-causing gene.      

Anti-Thy-1-mediated T cell activation. Role of soluble factors and expression of interleukin 2 receptors on T cells

Rabbit anti-Thy-1 antibody bound to T cells induces the appearance of T cell growth factor (interleukin 2, IL 2) receptors and the production of IL 2. IL2 receptors induction by this means occurs within a short time span, and independent of any demonstrable accessory cell. A source of exogenous or endogenous IL 2 is apparently the only requirement for proliferation after these receptors are expressed. IL 2 production, on the other hand, is accessory cell-dependent, and this help is mediated via Fc receptors on the accessory cell. IL 2 production in this model is demonstrable at 4–6 h, or earlier, and is proliferation-independent. X-irradiation actually augments apparent IL 2 production. The data are consistent with the hypothesis that a differentiated subset of T cells in any mixed population is responsible for IL 2 production.     

Polydrug use at raves by a Western Australian sample

This study aimed to quantify the patterns of drug use among a group of participants in the rave scene in Perth, Western Australia. Interviews were conducted with 83 people who had recently been to a 'rave'. The study incorporated a semi-structured qualitative interview and a structured quantitative questionnaire. This paper reports on the quantitative data collected concerning patterns of drug use in association with the last rave attended. Use of 'dance drugs' (ecstasy, amphetamines or LSD) was reported by 86.8% of the 76 respondents who had used at least one drug in association with their last rave. Nearly 80% of these had also used at least one other drug on this occasion (mean number used = 2.4). Cannabis and inhalants were the drugs most commonly combined with the 'dance drugs', several respondents used more than one 'dance drug' concurrently and 16.7% had used alcohol. It seems that a significant proportion of those using 'dance drugs' in association with raves and dance parties are mixing these drugs with other substances despite harm reduction advice to the contrary. The need for more research in this area is discussed.     

In vivo expression of the B7 costimulatory molecule by subsets of antigen-presenting cells and the malignant cells of Hodgkin's disease

The B-lymphocyte/accessory-cell activation antigen B7 (BB1) has been shown in vitro to stimulate T-lymphocyte proliferation and cytokine production via CD28 present on the latter cells. In this study, benign lymphoid tissues, lymphomas, and extralymphoid inflammatory sites were examined immunohistochemically using anti-B7 and other relevant monoclonal antibodies. B7 was expressed by benign transformed germinal center B cells, as it was by B cells of follicular lymphomas. B7 was also expressed by a subpopulation (a mean of 31% to 65%) of macrophages and dendritic cells in a variety of lymphoid tissues. It was present in abundance on all macrophages constituting sarcoid granulomas in lymph nodes. In extralymphoid inflammation, 17% to 35% of macrophages expressed B7 only weakly. Cases of Hodgkin's disease showed expression of B7 by the majority of Reed-Sternberg cells or malignant mononuclear variants, a phenomenon that potentially contributes to the lymphocytic accumulation that is a feature of this condition. CD28+ T cells were seen in all areas where T cells were present. B7+ and CD28+ cells colocalized in, for example, lymphoid follicles, lymph node paracortex, sarcoid granulomas, and Hodgkin's disease tissue, indicating a potential for cellular interaction via these molecules at these sites.