Non-Epstein-Barr virus-associated T-cell lymphoma following cardiac transplantation for Barth syndrome

Barth syndrome is a metabolic disease characterized by infantile cardiomyopathy, neutropenia and organic aciduria. We report disease evolution in one of the first affected boys to undergo successful cardiac transplantation. CONCLUSION: Although cardiac status stabilized, he developed disabling skeletal myopathy, protracted lymphopenia and--5 y after transplant--fatal Epstein Barr (EBV)-negative T-cell non-Hodgkin's lymphoma.     

Molecular characterization of commercial porcine factor VIII concentrate

Commercial porcine factor VIII concentrate (Hyate:C) is effective in treatment of patients with hemophilia A who have circulating antibodies to factor VIII. The molecular forms of factor VIII in the concentrate were identified and evaluated in light of the known properties of porcine and human factor VIII. The factor VIII in the concentrate was isolated by tandem chromatography on gelatin-Sepharose and monoclonal anti-factor VIII-Sepharose. The factor VIII was 1% of the protein mass of the concentrate when calculated by either quantity of protein recovered or by radioimmunoassay. Both functional assay and Western blotting of the crude concentrate indicated that maximum coagulant function was achieved by proteolytic activation of procofactor forms of factor VIII. The factor VIII can be fractionated by cation-exchange high-performance liquid chromatography (HPLC) into two or three species of heterodimers depending on the lot. The specific activity of the purified porcine factor VIII was 550 U/mg using pooled porcine plasma at 1 U/mL as a standard. From this value, a factor VIII concentration in normal pig plasma of 2 micrograms/mL was calculated. This agreed well with a value of 3 micrograms/mL obtained by radioimmunoassay (RIA) of factor VIII in porcine plasma. In contrast, reported values for human factor VIII average 5800 U/mg, resulting in a calculated concentration in plasma of 0.2 microgram/mL. The finding that porcine plasma contains a significantly higher circulating mass of factor VIII than human plasma appears to explain previous difficulties in comparing porcine and human factor VIII in standard assays.     

Activation and increased expression of adhesion molecules on peripheral blood lymphocytes is a mechanism for the immediate lymphocytopenia after administration of OKT3

We investigated the mechanism by which antihuman CD3 monoclonal antibodies of the isotypes IgG2a (eg, OKT3) and IgA (eg, IXA) can induce the rapid disappearance of virtually all circulating T lymphocytes. We hypothesize that upregulation of adhesion molecules on the lymphocyte membrane contributes to this effect. However, this hypothesis is difficult to test, because of the inherent lymphocytopenia and/or shifts in lymphocyte populations between intra and extra-vascular compartments. Therefore, studies in vitro were performed, as well. Analysis of peripheral blood lymphocytes isolated at several times after addition of OKT3 or IXA to whole blood of healthy individuals showed an immediate increase in the proportion of T cells expressing NKI-L16, an activation epitope on CD11a/CD18. Likewise, an increase in CD11b/CD18 expression occurred. In parallel experiments, a transiently increased adhesion of T cells to endothelial cell monolayers was observed. This adhesion could be completely blocked by anti-CD18 or anti-CD11a monoclonal antibodies and only partly by an anti-CD11b antibody. Our data indicate that upregulation of activation epitopes of CD11a/CD18, as well as increased expression of CD11b/CD18 on T lymphocytes, may result in increased adhesion of these cells to intercellular adhesion molecule-1 (ICAM-1) and ICAM-2 on vascular endothelium. This phenomenon may, at least, partly explain the rapidly occurring peripheral lymphocytopenia observed in vivo.     

B lymphoblastoid cell lines with normal and defective O-glycosylation established from an individual with blood group Tn

Individuals with the Tn blood group contain terminal serine/threonine- linked N-acetylgalactosamine residues in their blood cells. This is due to lack of UDP-D-galactose: D-N-acetyl galactosamine beta-D-galactosyl transferase from part of their red cells and probably from their leukocytes. We have established B lymphoblastoid cell lines from such an individual by in vitro infection of his lymphocytes with Epstein- Barr virus. The original line contained a mixture of cells reactive and nonreactive with Helix pomatia lectin (Hp). These cells were subcloned after staining with fluorescent Hp by a fluorescence-activated cell sorter (FACS) into homogeneous, phenotypically stable lines of Hp- positive (Hp+) and Hp-negative (Hp-) cells. The molecular differences between the membrane glycoproteins were characterized by carbohydrate- specific surface labeling techniques, Hp affinity chromatography, polyacrylamide slab gel electrophoresis and glycopeptide/oligosaccharide analysis. The major O-glycosidic membrane glycoprotein (GP105) was retained on Hp-Sepharose columns only from Hp+ cells, whereas the common leukocyte antigen (GP160-200) was partially retained on Hp columns from both lines. These proteins were isolated by immune precipitation with monoclonal antibodies and characterized. The results show that the GP105 glycoprotein from Hp+ cells contains terminal N-acetylgalactosamine residues but also more complex oligosaccharides. The common leukocyte antigen showed different electrophoretic mobilities in Hp+ and Hp- cells. UDP-galactose D-N- acetyl galactosamine beta-galactosyl transferase was almost absent in the Hp+ cells. These cell lines are useful for studies on the functional role and regulation of the biosynthesis of O-glycosidic carbohydrates.     

The prevalence of peanut sensitization and the association to pollen sensitization in a cohort of unselected adolescents – The Odense Adolescence Cohort Study on Atopic Diseases and Dermatitis (TOACS)

In the last decade an increased occurrence of peanut hypersensitivity and severe anaphylactic reactions to peanut have been reported. However, few prevalence studies have been performed in unselected populations. This study evaluated the point prevalence of peanut hypersensitivity in Danish adolescents. The point prevalence of peanut allergy confirmed by oral challenge was estimated to 0.5%. The number of adolescents sensitized to peanut by specific immunoglobulin E (IgE) (CAP FEIA) and skin prick test (SPT) were higher (5.8% resp. 3.4%). In adolescents without clinically relevant peanut sensitization most cases were sensitized to grass pollen and the IgE class for grass was higher than for peanut. A correlation between peanut and pollen (grass) sensitization is therefore plausible. Before a positive SPT or specific IgE measurement to peanut is considered clinically relevant in a patient, the case history should be evaluated together with examination for pollen sensitization.     

新抗胆碱药[3H]三环哌酯对人脑M受体的作用

用放射配体受体结合试验法,研究了新化合物三环哌酯与人大脑皮质M受体的结合特性,并与QNB作了比较。饱和实验结果显示,[³H]三环哌酯的结合参数与[³H]QNB相近,两种配体的作用均符合单位点模型。竞争性抑制实验结果表明二者作用强度相当。[³H]三环哌酯的结合和解离速率常数均较[³H]QNB大,且其与皮质M受体的解离受季铵酚的变构调节,结果提示,两种配体与M受体有一些不同的结合特性,在M受体研究中,[³H]三环哌酯可以作为[³H]QNB的补充工具。     

Growth of the uterus

BACKGROUND: The pattern of growth of the uterus was examined by ultrasound examinations of 358 girls who attended a paediatric endocrine outpatient department but were shown not to have any endocrine defect. METHOD: The uterus was measured in length and width at the cervix and at the fundus (cm). Endometrial thickness was measured (mm). Scans were divided by Tanner breast stage and the dimensions compared by one way analysis of variance (ANOVA, with the Student Newman Keuls post hoc test). RESULTS: There was an increase in uterine length, diameter of the fundus, and endometrial thickness at each breast stage from 1 to 5 (ANOVA, p < 0.05), and in the diameter of the cervix with each breast stage from 1 to 4 (ANOVA, p < 0.05). The ratio of the fundus to the cervix increased from 0.95 to 1.29 between breast stages 1 and 4. CONCLUSION: The onset of puberty is marked by an increase in the dimensions of the uterus and in endometrial thickness, but also by a change in the shape of the uterus from a tubular to a pear shaped organ.