HLA antigens in East African black patients with Burkitt's lymphoma or nasopharyngeal carcinoma and in controls: A pilot study

A pilot study is reported of HLA-A, B, and C antigens in 141 East African Blacks comprising patients with Burkitt's lymphoma or nasopharyngeal carcinoma, either with active disease or in long-term remission, together with comparable controls. This study forms part of a wider program investigating host factors in these diseases. A protocol was selected for optimal testing of cells processed and cryopreserved between 1972 and 1976, largely under field conditions, which employed a two-color fluorochromasia typing procedure. Antigen distribution and computed haplotype frequencies in the total unrelated population are given. New findings include an approximately equal frequency of Aw23 and Aw24, a high (18%) incidence of Bw21, and the gametic associations of Aw36 with Bw44, and Aw30 with Bw45. Of the major group of B15-related antigens reported earlier, SV is the most common, and there are strong linkages of SV with Cw2 and Bw with Cw3. The possible presence of further variants at the A- and B-loci is reported. The proportion of B-locus antigen “blanks” in this study is 5.9%. Relationships have been sought between the HLA antigens and diseases studied: the antigen A29, possibly in linkage with Bw42, shows a correlation with disease susceptibility, and associations are suggested between Bw44 (in possible combination with Aw36) and resistance to both BL and NPC, and between Bw45 and long-term remission in NPC.     

Molecular Manipulations of Extracellular Superoxide Dismutase: Functional Importance for Learning

Extracellular superoxide dismutase (EC-SOD) controls the availability of extracellular superoxide (O ₂ ^- ), which is important for a variety of physiological pathways, including the primary means of inactivating nitric oxide (NO). The role of EC-SOD in neurobehavioral function has been until now unexplored. In the current studies, the phenotypic expression of genotypic alterations of EC-SOD production in mice were characterized for spatial learning and memory. Dramatic impairments in spatial learning in the win-shift 8-arm radial maze were seen in both EC-SOD knockout mice and EC-SOD overexpressing mice. The EC-SOD overexpressing mice were further characterized as having significant deficits in a repeated acquisition task in the radial-arm maze, which permitted the dissociation of long and short-term learning. Long-term learning was significantly impaired by EC-SOD overexpression, whereas short-term learning was not significantly affected by EC-SOD overexpression. NO systems have been shown to be importantly involved in learning and memory. This may be important in the current studies because EC-SOD has primary control over the inactivation of NO. We found that EC-SOD overexpressing mice were resistant to the cognitive effects of L-NAME (N^G-nitro-L-arginine methyl ester hydrochloride), an NO synthase inhibitor. Decreased NO catabolism in these mice may have served to counter the effects of NOS inhibition by L-NAME. The current finding that EC-SOD levels that were either higher or lower than controls impaired learning demonstrates that the proper control of brain extracellular (O ₂ ^- ) may be more vital than merely reduction of brain extracelluar (O ₂ ^- ) in maintaining adequate learning function.     

SKALP/elafin gene polymorphisms are not associated with pustular forms of psoriasis

Psoriasis is a multifactorial skin disease characterised by epidermal abnormalities and infiltration by lymphocytes and polymorphonuclear leukocytes (PMN). Skin-derived antileukoproteinase (SKALP), also known as elafin, is a potent inhibitor of human leukocyte elastase and proteinase 3, two PMN-derived proteinases implicated in tissue destruction and leukocyte migration. We have shown that, at least at the protein level, SKALP is significantly decreased in lesional skin of patients with pustular psoriasis compared with plaque-type psoriasis. This finding raised the possibility that SKALP could be one of the candidate genes for pustular forms of psoriasis. We therefore performed single strand conformation polymorphism (SSCP) analysis on the SKALP gene to screen for mutations/polymorphisms in the exons of 30 patients with plaque-type psoriasis, 15 patients with pustular psoriasis and 48 healthy controls. In exon 1 a polymorphism was detected at position + 43 relative to the translation start site, resulting in a substitution of threonine for alanine in the signal peptide. In the promoter region a dinucleotide repeat polymorphism was identified. Both polymorphisms were not associated with pustular psoriasis, or psoriasis in general. Our data indicate that the decrease in SKALP activity in pustular psoriasis is not caused by mutations in the coding region of the gene, and that there is no allelic association between pustular psoriasis and SKALP gene polymorphisms.     

Functional Analysis of B-L (Ia-Like) Antigen-Bearing Chicken Peripheral Blood Cells

The functional of B-L (Ia-equivalent)-positive (B-L+) adn -negative (B-L-) chicken peripheral blood lymphocytes (PBL) was studied in vitro and in vivo. The PBL were first stained in direct immunofluorescence tests with a fluorescein isothiocyanate-labelled anti-B-L alloantiserum and then separated by means of a fluorescence-activated cell sorter. In agreement with our previous findings, B-L- cells showed functional properties of T lymphocytes, responding to concanavalin A and phytohaemagglutinin-P in vitro and inducing a graft-versus-host (GVH) reaction when injected into allogeneic embryos. Sorted B-L+ gave no responses in any of these assays. Neither B-L+ nor B-L- cells, when tested alone, responded significantly to pokeweed mitogen, but mixtures of the two restored the responsiveness to that of the original unsorted suspension. Of the B-L+ PBL, 10% were T cells, which may account for the low GVH reactivity given by this population.     

Scanning electron microscopy of teeth in dominant osteogenesis imperfecta: Support for genetic heterogeneity

Scanning electron microscopic studies were performed on 25 deciduous and permanent teeth from members of 7 kindreds with dominant nonlethal osteogenesis imperfects (OI). Two families had normal teeth on clinical and radiological examination; five familes had blue or brown opalescent teeth with specific radiologic findings. Enamel surfaces and prism organization were normal on all teeth. On fractured surfaces, the dentin tubules of normal teeth from patients with OI were evenly distributed and coursed regularly to the dentin-enamel junction. Opalescent teeth had few tubules and those present were short, narrow, and tortuous. Dentin calcification fronts of normal teeth were composed of many nodules with regularly spaced openings on their surfaces. Calcification fronts of opalescent teeth were composed of irregularly spaced, small nodules, which varied greatly in size and the nodules lacked tubule openings on their surfaces. The results of this study support the concept that at least two dominant forms of OI exist – one in which all individuals with IO have normal teeth, and the other in which all with OI have blue or brown opalescent teeth with characteristic changes on SEM.     

bcl-2 transgene expression promotes survival and reduces proliferation of CD3-CD4-CD8- T cell progenitors

Proliferative expansion and apoptotic cell death play prominent roles in T cell development. The molecular control of cell cycle progression and apoptosis appear to be inter-connected since the Bcl-2 protein can inhibit apoptosis and slow cell cycle progression in cortical thymocytes and mature T cells, particularly during the transition from the quiescent state into the cell cycle. Here the impact of bcl-2 transgene expression on CD3-CD4-CD8- T cell progenitors was assessed. Bcl-2 enhanced the survival of these progenitors at all of the four major differentiation stages, CD25- CD44+ (pro-T1), CD25 + CD44+ (pro- T2), CD25 + CD44- (pro-T3) and CD25-CD44- (pro-T4). However, it reduced cell cycling and slowed turnover only in the pro-T4 subset. From an analysis of bcl-2 transgenic mice expressing a TCR transgene or bearing a mutation in the scid or rag-1 gene we conclude that Bcl-2 inhibits proliferation only of T cell progenitors that are activated via the pre- TCR, not those stimulated via c-Kit and the IL-7 receptor.      

Viral Persistence in Neurons Alters Synaptic Plasticity and Cognitive Functions without Destruction of Brain Cells

Neurons have a restricted expression of MHC heavy chain molecules which prevents presentation of antigens of infecting viruses. As a result, such infected cells escape immune surveillance and allow the establishment of noncytolytic persistent infection. Here we show that a chronic noncytolytic viral infection bothin vitroandin vivoselectively perturbed the expression of GAP-43, a protein that plays a central role in neuronal plasticity processes accompanying learning and memory. GAP-43 expression was greatly decreased in the hippocampus, an area of heightened viral replication, while synaptic density was preserved. Concurrently, the ability to learn tasks was significantly impaired in these persistently infected mice. Yet, infected neurons remained free from structural injury.