Induced expression of c-fms in normal hematopoietic cells shows evidence for both conservation and lineage restriction of signal transduction in response to macrophage colony-stimulating factor

Retrovirus-mediated gene transfer was used to obtain expression of the macrophage colony-stimulating factor (MCSF) receptor, c-fms, on hematopoietic lineages that normally do not express this receptor. Cultures of murine fetal liver cells infected with the c-fms retrovirus developed erythroid colonies in cultures stimulated with M-CSF. However, these colonies were fewer and less hemoglobinized than colonies in parallel cultures stimulated by erythropoietin. Culture of isolated clones demonstrated a direct action of M-CSF on erythroid clones. Culture of c-fms retrovirus-infected adult murine bone marrow cells showed megakaryocyte and novel macrophage-megakaryocyte clones when stimulated by M-CSF. Culture of isolated clones again confirmed a direct action of M-CSF on megakaryocyte clones. In contrast, M-CSF stimulation of c-fms-infected granulocytes and granulocyte progenitor cells did not elicit proliferation, enhanced survival, or functional stimulation of granulocytes. These findings provide evidence for both conservation and lineage restriction of signal transduction in normal hematopoietic cells.     

Platelets express a membrane protein complex immunologically related to the fibroblast fibronectin receptor and distinct from GPIIb/IIIa

We have previously identified and characterized a membrane glycoprotein complex (GP150/135) that functions as fibronectin receptor (FN-R) in fibroblast adhesion. Here we report that an immunologically related protein complex is expressed at the surface of human platelets. Antibodies monospecific for the smaller subunit (GP135) of the fibroblast FN-R in fact specifically stained the platelet surface, as determined by FACS analysis, and reacted with a component of molecular weight (mol wt) 138,000 as shown in western blots of platelet membranes. Moreover, the same antibodies precipitated the 138,000 component together with a 160,000 protein, suggesting that the two molecules are associated in a supramolecular complex. A comparative analysis indicated that this protein complex is distinct from the GPIIb/IIIa complex, known to function as a receptor of wide specificity for fibrinogen, fibronectin, and von Willebrand factor. Differential extraction experiments revealed that the platelet 138,000 component is an integral membrane protein.     

缺血性脑卒中的A-S-C-O(表型)分类

背景和目的:国际5国脑血管病专家提出一种新的腩卒中亚型分类法,旨在介绍完整的"脑卒中表型"分类的新观念,该分类是包括脑卒中的病因和存在的所有病因相关的疾病,并将病因疾病按严重程度分成3级.     

Training Australian pharmacists for participation in a collaborative, home-based post-discharge warfarin management service

Objective To describe the development, implementation and outcomes of an anticoagulation education program for pharmacists participating in a community-based post-discharge warfarin management service. Setting Australian community pharmacy practice. Method Three education modules were developed in collaboration with medical experts and delivered electronically and via hands-on training sessions to pharmacists in three Australian states. Educational outcomes were assessed via a short answer assignment and evaluation of their warfarin dosing recommendations for five hypothetical scenarios. Consumer and pharmacist perceptions of the adequacy of the training were surveyed using a structured postal questionnaire. Main outcome measure Pharmacists’ score in the short answer assignment and evaluation of their responses to the hypothetical warfarin dosing scenarios. Results Sixty-two pharmacists successfully completed the training program with a mean score for the short answer assignment of 14.3 out of 15 (95.3%; 95% CI 13.8–14.7). The pharmacists’ warfarin management recommendations were very similar to those of two experienced medical specialists. Pharmacists and consumers expressed confidence in the adequacy of the training program. Conclusion This education program successfully up-skilled a cohort of pharmacists for involvement in a post-discharge warfarin management service. These findings support formalisation and further development of the program to facilitate widespread implementation of home-based post-discharge warfarin care.     

高血压治疗的现代途径(MATH)

标　　题　硝苯地平胃肠治疗系统对老年患者的抗高血压治疗作用作　　者　ＢｒａｖｏＥＬ,ＫｒａｋｏｆｆＬＲ,ＴｕｃｋＭＬ,ｅｔａｌ.　　参考文献　ＡｍＪＨｙｐｅｒｔｅｎｓ,1990,3:326Ｓ目　　的　评估硝苯地平的新剂型胃肠治疗系统ＧＩＴＳ治疗高血压的疗效和安全性。研究疾病　高血压病。设　　计　多中心、开放性临床研究。病人资料　1155例ＤＢＰ在95～110ｍｍＨｇ的高血压患者。随　　访　至目标血压达到后12周。治疗方案　硝苯地平控释片30ｍｇ/ｄ,在6周内剂量逐渐增至最大量180ｍｇ/ｄ,每次增量为30ｍｇ,目标血压为舒张压降至90…     

Spectrum and origin of phenylketonuria mutations in Spain

In order to characterize the molecular heterogeneity of phenylalanine hydroxylase deficiencies in the Spanish population, 37 PKU patients were initially screened for 16 known European mutations. For the remaining unidentified alleles, we used a combined strategy based on single strand conformation polymorphism analysis and DNA sequencing. Overall, a total of 15 different mutations were found in our sample, which account for 62% of the total mutant alleles. We also investigated the association between the mutations, haplotypes and variable number of tandem repeats described on the phenylalanine hydroxylase gene. In addition, we analyzed the geographical distribution in Spain of the two most prevalent mutations in our population: IVS10 and I65T.     

Accuracy and clinical usefulness of the near-patient testing CoaguChek S international normalised ratio monitor in rural medical practice

OBJECTIVE: To compare the accuracy and clinical usefulness of the near-patient testing CoaguChek S INR monitor in rural medical practice. DESIGN, SETTING AND MAIN OUTCOME MEASURES: General practices were identified through Australian university departments of rural health. Study investigators trained general practitioners and/or practice nurses in the use of the CoaguChek S INR monitor. General practices obtained a fingerprick sample for testing with the INR monitor to compare with conventional pathology testing for accuracy. An evaluation questionnaire was administered to users of the machine to assess ease of use and clinical usefulness. RESULTS: A total of 169 patients from 15 general practice sites provided 401 paired (CoaguChek S and laboratory) INR results. The CoaguChek S was found to be accurate when compared to laboratory INR (r = 0.89), despite complicating variables such as multiple users of the monitor and multiple laboratories used for comparison with the CoaguChek S INR. Overall, 88% of dual INR measurements were within 0.5 INR units of each other. For laboratory INR /= 3.6, 97%, 90% and 57% of readings were within 0.5 INR units, respectively. Clinical agreement occurred 93% and 90% of the time against published expanded and narrow criteria, respectively. CONCLUSIONS: The routine use of near-patient testing, with appropriate training and quality assurance programs, has the potential to increase the safety and efficacy of warfarin therapy in rural and remote communities.     

Evidence for B cell participation in the in vitro and in vivo maintenance of in vivo staphylococcal enterotoxin B-induced T cell anergy

The mechanisms involved in the maintenance of staphylococcal enterotoxin B (SEB)-induced T cell anergy are poorly understood. Here, we demonstrate that CD4+ T cell anergy induced by SEB treatment is under partial B cell control. This effect is not mediated by anti-SEB antibodies or any in vitro B cell-produced suppresser factor. At day 13 after SEB immunization, T cells from B cell-deficient mice proliferate upon in vitro stimulation with SEB. These results suggest that SEB- induced T cell anergy is reversible and that B cells have an important function in anergy maintenance in CD4+ T cells, both in vivo and in vitro.