Genetic differences in red cell osmotic fragility: analysis in allophenic mice

Mice of strain DBA/2J were found to produce red cells considerably more resistant to osmotic lysis than cells from C57BL/6J or the F1 hybrid between the two strains. Such strain-specific differences in osmotic fragility could be the result of genetically determined humoral or other systemic differences that indirectly influence red cell properties. Alternatively, this phenotypic variation might be an inherent property of the erythrocyte themselves and be directly controlled by their genotype. Analysis of red cells from allophenic (mosaic) mice of the strain composition C57BL/6J in equilibrium DBA/2J demonstrated that the latter possibility is the case. In such mice, erythrocytes of the DBA/2J genotype are relatively more resistant to osmotic lysis than are those of the C57BL/6J genotype; partial lysis of allophenic blood at intermediate salt concentrations results in marked enrichment for DBA/2J cells among the survivors. Future experiments designed to determine the mechanism underlying this difference can now focus on the properties of the red blood cells per se with the certainty that this property is inherent to the genotype of each cell.     

Functional characterization of platelet-bound factor XIa: retention of factor XIa activity on the platelet surface

Previously we have shown that both factor XI and factor XIa are bound specifically to distinct, high-affinity sites on the surface of activated platelets in the presence of high Mr kininogen. To determine the functional significance of factor XIa binding to platelets, bound factor XIa has now been compared with the unbound enzyme. Platelets incubated with thrombin, high Mr kininogen, and 125I-labeled factor XIa bound 130 to 500 molecules of factor XIa per platelet. Scatchard analysis of binding data give a dissociation constant (Kd) of 822 pmol/L +/- 140 (SEM). Rates of factor IX activation, assayed by release of trichloroacetic acid-soluble 3H-labeled activation peptide from purified [3H]-factor IX, were similar when factor XIa was bound to platelets and when it was free in solution. The platelet-bound factor XIa was isolated by centrifugation through 20% sucrose and was functionally characterized both in a factor XIa coagulation assay and in the factor IX activation peptide release assay in comparison with unbound factor XIa in the presence of treated platelets. The functional activity of platelet-bound factor XIa as a factor IX activator as well as its structural integrity were shown to be fully retained on the platelet surface. Since platelets bind factor XI and promote its proteolytic activation to factor XIa, factor XIa binding to platelets may serve to localize factor IX activation to the hemostatic plug, where factor XIa is protected from inactivation by plasma protease inhibitors and where acceleration of subsequent coagulation reactions can occur.     

Inhibition of maturation of human precursor lymphocytes by coformycin, and inhibitor of the enzyme adenosine deaminase

High concentrations of adenosine are known to be toxic to fibroblasts and lymphocytes under conditions of in vitro culture (1,2). Normally, accumulation of adenosine nucleotides in all mammalian cells is prevented by the presence of adenosine deaminase, an aminohydrolase which converts adenosine to inosine (3). A genetically determined deficiency of adenosine deaminase has been associated with the autosomal recessive form of severe combined immunodeficiency, a syndrome in which precursor lymphocytes fail to mature into T cells and B cells (4-7). Erythrocytes of affected infants convert exogenous adenosine to AMP and ATP at an abnormally increased rate as a consequence of the enzyme defect, and ATP at an abnormally increased rate as a consequence of the enzyme defect, and fail to form inosine from the exogenous adenosine (8). These metabolic disturbances can be mimicked in normal erythrocytes by coformycin (8), a potent competitive inhibitor of adenosine deaminase (9, 10). In this study, the effects of coformycin were examined on the in vitro function of normal lymphocytes.     

CD73 and adenosine generation in the creation of regulatory microenvironments

Extracellular adenosine 5′‐triphosphate (ATP) acts on many immune cells to promote inflammation. Conversely, the ATP metabolite adenosine is mainly an anti‐inflammatory molecule. The ecto‐enzymes CD39 and CD73 can dephosphorylate extracellular ATP to adenosine, thereby controlling this important pathway of immune modulation. Despite their established roles in the immune system, little is known of how CD39 and CD73 are themselves regulated. Recent data have shown that CD73 expression and adenosine generation are up‐regulated by transforming growth factor‐β, depending on the cytokine content of the local microenvironment. We review here these recent findings and discuss their implications in disease.     

Habitus of home and traditional drinking: a qualitative analysis of reported middle‐class alcohol use

There is evidence that alcohol consumption among those in middle‐class occupations consistently exceeds safe levels, yet there has been little research into why this occurs. This article explores the meanings associated with alcohol use among professional, managerial and clerical workers. Qualitative data were collected from five focus groups of male and female employees aged 21–55 (N =49: 32 male, 17 female). Each focus group was conducted on the premises of a medium‐scale or large‐scale employer, four public sector and one private sector, in the north‐east of England. Using Bourdieu's concepts of ‘habitus’, ‘capitals’ and ‘fields’ we found that, among these middle‐class occupational groups, alcohol use was associated with two habitus: a ‘home drinking’ habitus and a ‘traditional drinking’ habitus. Those of the home drinking habitus particularly used wine as a source of cultural capital and a means of distinction, whereas those in the traditional habitus consumed lager, beer and spirits to have fun in social settings. A small minority appeared to belong to a third, omnivorous, habitus where a wide range of alcoholic drinks were consumed in a variety of contexts. Existing public health initiatives to reduce alcohol consumption may require modification to accommodate a range of drinking cultures.     

吡啶丙烯酰氨基酸衍生物的设计、合成及其对离体HeLa-S3细胞的放射增敏作用

本文设计、合成了一类新型的放射增敏剂—吡啶丙烯酰氨基酸衍生物,并测定了对HeLa-Sa细胞的增敏作用和细胞毒性。3-吡啶丙烯酰甲基甘氨酸(3A)和4-吡啶丙烯酰甲基甘氨酸(4A)的主要作用分别为减小细胞存活曲线的肩宽和Do值。这类化合物,尤其是3A和4A,或其结构类似物,如果体内实验证明有明显增敏作用,将有重要的潜在临床应用价值。     

Bronchobiliary fistula: complete percutaneous treatment with biliary drainage and stricture dilation

Percutaneous transhepatic cholangiography was performed on an 18-year-old man who presented with jaundice and cholangitis 19 months after right hepatic lobe resection. The cholangiogram demonstrated a bronchobiliary fistula and a stricture of the common hepatic duct. Percutaneous therapy consisting of biliary drainage and balloon dilation cholangioplasty was successful in eradicating the fistula and reestablishing normal bile flow.