血管细胞粘附分子调控造血的研究进展

本文简述了血管细胞粘附分子 (Vascularcelladhesionmolecule 1,VCAM 1)的结构和生物学功能 ,总结了VCAM 1在恶性血液病骨髓基质中的表达和意义 ,探讨了VCAM 1在造血干细胞动员和归巢中的作用 ,指出VCAM 1作用机制的深入研究将对恶性血液病的治疗提供更为有效的方法。     

Action of piracetam and clonidine on different mitochondrial populations from hippocampus

The maximum rate (Vmax) of some mitochondrial enzymatic activities related to energy transduction (citrate synthase, malate dehydrogenase, NADH-cytochrome c reductase (as total activity), cytochrome oxidase) and amino acid metabolism (glutamate dehydrogenase) were evaluated in non-synaptic (free) and synaptic mitochondria from rat brain hippocampus. Three types of mitochondria were isolated from rats subjected to single i.p. treatments with piracetam (300 mg.kg-1) or with clonidine (750 micrograms.kg-1). With respect to the enzymatic pattern of three types of non-synaptic and synaptic mitochondria, in hippocampus a different maximum rate of both NADH-cytochrome c reductase and cytochrome oxidase was observed, these activities in particular being lowest in the "synaptic heavy" mitochondrial subfraction than in the "synaptic light" one; in addition, other enzyme activities are different in the "free" as compared to both the "light" and "heavy" mitochondria. This confirms that in various types of brain mitochondria a different metabolic machinery exists. Acute treatment with piracetam decreased citrate synthase, glutamate dehydrogenase, NADH-cytochrome c reductase and cytochrome oxidase activities only in the "heavy" mitochondria obtained from synaptosomes. Acute treatment with clonidine decreased the citrate synthase, NADH-cytochrome c reductase and cytochrome oxidase activities only in the same type of mitochondria, i.e. synaptic "heavy" mitochondria. However, this drug increased the same enzymatic activities in "free" mitochondria, some of them being increased or decreased in "light" intrasynaptic ones. Therefore in vivo administration of piracetam mainly affects some specific enzyme activities (suggesting a specific molecular trigger mode of action) of the intrasynaptic mitochondria (suggesting a specific subcellular trigger site of action), the effect on enzyme activities by clonidine being more complex.     

Glycoproteins present in human follicular fluid that inhibit the zona- binding capacity of spermatozoa

Previous studies have suggested that human follicular fluid contains factors that reduce the zona-binding capacity of spermatozoa. The present study provides further evidence of the existence of such factors. Using the hemizona binding assay (HZA), we have shown that the inhibitory effect of human follicular fluid on the zona-binding capacity of spermatozoa is concentration-dependent, an inhibitory effect being detected when the concentration of human follicular fluid was > or = 10%. A 1% concentration of human follicular fluid did not possess this inhibitory activity. Heating human follicular fluid at 56 degrees C for 30 min did not affect its inhibitory properties; treatment with proteinase-K abolished such inhibition. Human follicular fluid was fractionated sequentially by concanavalin-A affinity chromatography, Mono Q ion-exchange chromatography and Superose-12 gel filtration. The zona binding inhibitory activity resided in the fraction which bound to the lectin and Mono Q column and contained molecules with native molecular weights of 32 and 192 kDa. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis suggested that the 192 kDa glycoprotein was a tetramer, while the 32 kDa glycoprotein remained as a single molecular species under denaturing conditions. We conclude that two glycoproteins were responsible for the zona binding inhibitory activity of human follicular fluid. The physiological role of these factors remains unclear.      

Response from lieberman and colleagues

Respond on comments on Lieberman's article: Cyclosiloxanes Produce Fatal Liver and Lung Damage in Mice. Environ Health Perspect 107:161-165     

Different normalizations for body size and population attributable risk of left ventricular hypertrophy: the MAVI study

BACKGROUND: Different methods of normalizing left ventricular (LV) mass for body size identify generally similar relative risks of adverse cardiovascular outcome but with variable prevalences of LV hypertrophy (H). Preliminary results from a population with high prevalence of obesity suggest that the population attributable-risk percent (PAR%) of LVH is substantially higher when LV mass is normalized for allometric power of height. METHODS: We calculated the PAR% of LVH by different definitions in the cohort of the MAssa Ventricolare sinistra nell' Ipertensione (MAVI) study (n = 1019, 62% women), a population with low prevalence of obesity (22%, with only 3% and 0.1% in class II and class III obesity, respectively). Composite fatal and nonfatal cardiovascular events occurred in 53 participants (5.2%). RESULTS: Prevalence of LVH was between 28% and 56%, with slight greater values for height-based normalization. Age- and sex-adjusted hazard ratios were comprised between 1.37 and 1.44 for different measures of LV mass index. The PAR% was not meaningfully different among the different methods of normalization (between 47% and 56%), and height-based methods showed in general a performance similar to body surface area-based normalizations. CONCLUSIONS: In a large clinical population of hypertensive subjects with low prevalence of obesity, population risk attributable to LV hypertrophy was not meaningfully different in relation to the type of normalization of LV mass for body size. Height-based methods perform as well as body surface area-based ones. We suggest that the prevalence of obesity in hypertensive populations might substantially influence differences in population risk attributable to LVH identified by different methods of normalizing LV mass.     

Modulation of in vitro eosinophil progenitors by hydrocortisone: role of accessory cells and interleukins

The growth of human eosinophil progenitors (CFU-Eo) and the modulation of growth by hydrocortisone were studied as functions of the presence of lymphocytes and monocytes in marrow cells under study; and the source of colony-stimulating factors, specifically, media conditioned by macrophage-like cell line, GCT; phytohemagglutinin-stimulated mononuclear cells (PHA-LCM); or the T cell line, MO. CFU-Eo growth was greatest in marrow containing accessory cells as compared to marrow depleted of accessory cells; and in marrow treated with phytohemagglutinin-stimulated leukocyte conditioned media (PHA-LCM) or MO (T cell line)-conditioned medium (MO-CM) as compared with GCT cell- conditioned medium (GCT-CM). Hydrocortisone reproducibly inhibited eosinophil progenitor growth in unfractionated marrow stimulated by GCT- CM. This effect was abrogated by admixing irradiated mononuclear cells or T lymphocytes with the target marrow or by adding interleukin 1 or interleukin 2 (IL-1, IL-2). Inhibition by hydrocortisone did not occur when monocyte and T lymphocyte depleted marrow was studied. Unlike GCT- CM, MO-CM and PHA-LCM stimulated equal proportions of eosinophil progenitors in nondepleted and accessory cell-depleted marrow and demonstrated less hydrocortisone inhibition. However, both GCT-CM and PHA-LCM produced in the presence of hydrocortisone stimulated significantly fewer CFU-Eos in both unfractionated and accessory cell- depleted marrow target populations. These results indicate that the growth of CFU-Eo and inhibition of growth by hydrocortisone is a direct function of a monocyte-T cell interaction and probably is mediated through effects on the production/release of eosinophil colony stimulating factor (Eo-CSF).     

Substrate for endothelial prostacyclin production in the presence of platelets exposed to collagen is derived from the platelets rather than the endothelium

Interactions between vascular endothelial cells and blood platelets have been investigated using a model microcirculation consisting of microcarrier beads colonized with human umbilical vein endothelial cells (HUVECs) and perfused with washed platelet suspensions. To simulate the effects of endothelial desquamation and exposure of subendothelium, fibrillar collagen in suspension was coinjected with the platelets. In this model, neither the passage of platelets alone nor collagen alone stimulated prostacyclin (PGI2) production by the HUVECs. Platelets activated by coinjection with collagen released thromboxane A2 (TXA2), and this was associated with the simultaneous production of PGI2 by the HUVECs. By means of double-isotope experiments with [3H]arachidonic acid (AA) incorporated into platelets and [14C]-AA into HUVECs, it was shown that all the PGI2 generated was derived from platelet AA and/or endoperoxides. This interpretation was strengthened by the finding that PGI2 production was not prevented by treatment of HUVECs with indomethacin followed by perfusion with collagen-stimulated platelets. AA metabolites in double-isotope label experiments were further characterized by reverse-phase chromatography, and it was shown that both cyclooxygenase and lipoxygenase products of the HUVECs were derived from platelet membrane lipid. Thrombin regularly produced transient PGI2 release, but showed rapid tachyphylaxis. Platelet-derived compounds including ADP, ATP, and platelet-activating factor (PAF) did not produce PGI2 release by HUVECs in this system. Thus, the transfer of AA and metabolites from collagen- stimulated platelets is likely to be the mechanism for PGI2 production in the context of minor degrees of endothelial desquamation.