The roles of CD8 in cytotoxic T lymphocyte function

The CD8 glycoprotein of cytotoxic T cells is both an adhesion protein and a cosignalling receptor. These functions are regulated by signals from the T-cell antigen receptor complex (TCR-CD3), and CD8 acts to couple TCR occupancy to second messenger pathways. Here Anne O'Rourke and Matthew Mescher examine the roles of CD8 in activating the adhesion and signalling cascade initiated by antigen binding.     

Heat transfer between fish and ambient water

A theoretical model is developed to predict pressure changes and velocity profiles within the foetal lung during its sporadic bursts of activity. Because of the small volume flow rates and relatively high frequencies, the linearised, unidirectional Navier-Stokes equations are used to calculate these values. About 70% of the pressure drop occurs in the first four generations and is an order of magnitude higher than the equivalent Poiseuille pressure drop. Velocity profiles, pressure falls within each generation together with the total pressure drop at different times during the cycle are illustrated.     

Ferromanganese Production with Oxygen Enrichment

Tests with oxygen enrichment of the blast of ferromanganese furnaces to 26.5 pet have shown a production increase of 29 pet and a reduction in the coke rate of 11 pet. Indications are that at higher levels of oxygen enrichment, additional improvements are possible.     

Mental status and fragile X expression in relation to FMR-1 gene mutation

The fragile X mental retardation syndrome is caused by unstable expansion of a CGG repeat in the FMR-1 gene. Clinical expression is associated with a large expansion of the CGG repeat. The mutation in the FMR-1 gene and the cytogenetic expression of the fragile site at Xq27.3 have been studied in 52 fragile X male patients. The percentage of the cytogenetic expression of the fragile site at Xq27.3 positively correlates with the mean size of the full mutation in the FMR-1 gene (p < 0.0001) irrespective of the presence of additional premutation alleles. We noted a less frequent occurrence of additional premutation alleles in adult patients compared with juveniles, suggesting a continued mitotic instability in life. Additionally, the level of mental retardation has been ascertained in 35 patients using the Stanford-Binet or Terman-Merrill test of general intelligence. The presence of a full mutation in the FMR-1 gene seemed decisive for the occurrence of mental impairment in the patient. No correlation is observed between the degree of mental retardation and the size of the full mutation. The degree of mental retardation seemed not to be influenced by the presence of premutation alleles in part of the cells in addition to a full mutation. One patient is described with the 'Prader-Willi-like' subphenotype of the fragile X syndrome, showing a deletion in the FMR-1 gene in a part of his cells in addition to a full mutation.     

Hematopoietic cell transplantation in the twitcher mouse. The effects of pretransplant conditioning with graded doses of busulfan

The effects of congenic hematopoietic cell transplantation (HCT; transplantation of bone marrow and spleen cells) after graded doses of busulfan (BU), a myeloablative but nonimmunosuppressive alkylating agent, were evaluated in the twitcher mouse model of human galactosylceramidase deficiency, a demyelinating sphingolipid storage disease. C57BL/6 twitcher mice (immunophenotype Ly-5.1) were given 10 to 50 mg/kg of BU or total-body irradiation (9.0 Gy) at age nine days and HCT from congenic Ly-5.2 donors 24 hr later. The 30-day post-HCT survival, an indicator of tolerance of the preparative regimen, was at least 83% in twitcher mice given 45 mg/kg or less of BU, was 50% in recipients of 50 mg/kg BU and 75% in TBI-conditioned twitchers. The lifespan of twitcher mice given HCT after 10 or 20 mg/kg of BU was similar to that of untreated twitchers (median survival, 42 days; range, 30-47). In contrast, mice transplanted after 35 to 50 mg/kg of BU had significantly prolonged survival (median, 82 days; range, 56-208) and stabilization of hindlimb paralysis, similar to TBI-conditioned recipients. Post-HCT repopulation by donor Ly-5.2 cells was determined by flow cytometry. Thirty days after HCT, only 11-15% of lymphohematopoietic cells in blood, bone marrow, and spleens were of Ly-5.2 donor origin in twitcher mice transplanted after 10 mg/kg of BU but 60-80% were of Ly-5.2 donor origin in mice transplanted after higher doses of BU. These levels further increased to 70-90% by 90 days after HCT, comparable to that seen after TBI. Levels of galactosylceramidase in livers, spleens, and brains of twitchers transplanted after 35-50 mg/kg of BU or after TBI increased to 30-116% of normal control values by 90 days after HCT. Conditioning for HCT with as little as 35 mg/kg of BU provides minimal peritransplant mortality, rapid and sustained establishment of donor lymphohematopoiesis, replacement of lysosomal hydrolase, and prolonged survival in this murine model of human sphingolipidosis.