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.     

Molecular analysis of the recF gene of Escherichia coli.

We analyzed the nucleotide sequence of a 1.325-kilobase region of wild-type Escherichia coli containing a functional recF gene and six Tn3 mutations that inactivate recF. The analysis shows a potentially translatable reading frame of 1071 nucleotides, which is interrupted by all six insertions. A protein of 40.5 kilodaltons would result from translation of the open reading frame, and a radioactive band of protein of an apparent molecular weight of approximately 40 kilodaltons was seen by the maxicell method using a recF+ plasmid. Putative truncated peptides were seen when two recF::Tn3 mutant plasmids were used. Differential expression of dnaN and recF from a common promoter was noted. recF332::Tn3 was transferred to the chromosome where, in hemizygous condition, it produced UV sensitivity indistinguishable from that produced by two presumed recF point mutations.     

Anti-Xa activity after subcutaneous administration of dalteparin in ICU patients with and without subcutaneous oedema: a pilot study

Introduction  

Intensive care unit (ICU) patients often suffer from subcutaneous oedema, due to administration of large fluid volumes and the underlying pathophysiological condition. It is unknown whether the presence of subcutaneous oedema impairs the absorption of dalteparin, a low molecular weight heparin, when it is given by subcutaneous administration for venous thromboembolism prophylaxis. The objective of this study is to compare the anti-Xa activity of dalteparin after subcutaneous administration in ICU patients with and without subcutaneous oedema.     

Administration of pegylated recombinant human megakaryocyte growth and development factor to humans stimulates the production of functional platelets that show no evidence of in vivo activation

This report describes the effect of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) on platelet production and platelet function in humans. Subjects with advanced solid tumors received PEG-rHuMGDF daily for up to 10 days. There was no increase in circulating platelet count at doses of 0.03 or 0.1 microgram/kg/d by day 12 of study. At doses of 0.3 and 1.0 microgram/kg/d there was a threefold median increase (maximum 10-fold) in platelet count by day 16. The platelets produced in vivo in response to PEG-rHuMGDF showed unchanged aggregation and adenosine triphosphate (ATP)-release responses in in vitro assays. Tests included aggregation and release of ATP in response to adenosine diphosphate (ADP) (10, 5, 2.5, and 1.25 mumol/L), collagen (2 micrograms/mL), thrombin-receptor agonist peptide (TRAP, 10 mumol/L) and ristocetin (1.5 mg/mL). Administration of aspirin to an individual with platelet count of 1,771 x 10(3)/L resulted in the typical aspirin-induced ablation of the normal aggregation and ATP-release response to stimulation with arachidonic acid (0.5 mg/mL), collagen, and ADP (2.5 and 1.25 mumol/L). There was no change in the expression of the platelet-surface activation marker CD62P (P-selectin) nor induction of the fibrinogen binding site on glycoprotein IIb/IIIa as reported by the monoclonal antibody, D3GP3. An elevation of reticulated platelets was evident after 3 days of treatment with PEG-rHuMGDF and preceded the increase in circulating platelet count by 5 to 8 days; this reflected the production of new platelets in response to PEG-rHuMGDF. At later time points, the mean platelet volume (MPV) decreased in a manner inversely proportional to the platelet count. Levels of plasma glycocalicin, a measure of platelet turnover, rose 3 days after the initial increase in the peripheral platelet count. The level of plasma glycocalicin was proportional to the total platelet mass, suggesting that platelets generated in response to PEG-rHuMGDF were not more actively destroyed. Thus, the administration of PEG-rHuMGDF, to humans, increased the circulating platelet count and resulted in fully functional platelets, which showed no detectable increase in reactivity nor alteration in activation status.     

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.