心房颤动的电生理重构

心房颤动 (atrial fibrillation,AF)是临床上最常见的一种持续性心律失常 ,其发病率随年龄而增加 ,40岁以下人群发病率约为 0 .2 %～ 0 .3% ,6 0～ 90岁年龄组发病率增至5 %～ 9% [1 ] 。新近 Framingham的研究表明 AF可以成为一种独立的因素使患者病死率增加 [2 ] 。 AF的发病机制尚未完全清楚 ,可能为非单一机制 ,普遍认为持续性 AF是由于心房内的多子波折返 ,每 1个折返环本身都在不停地改变其大小及传导方向。近年来 ,在 AF的基础及临床研究中 ,两个方面的进展具有十分重要的意义 :一是发现部分 AF起源于心房内某些部位如肺静脉口…     

Full-length but not truncated CD34 inhibits hematopoietic cell differentiation of M1 cells

CD34 is expressed on human and murine hematopoietic stem and progenitor cells and its clinical usefulness for isolation of stem/progenitor cells has been well established. Although expression of CD34 is regulated in a developmental stage-specific manner, the function of CD34 is not known. Recently we have shown that both a full-length and truncated form of CD34 protein is expressed by hematopoietic cells (Blood 84:691, 1994). To test whether failure to suppress either form of CD34 could affect terminal myeloid differentiation, we constitutively expressed these CD34 proteins in murine M1 myeloid leukemia cells, which can be terminally differentiated to macrophages by treatment with interleukin-6 of leukemia inhibitory factor. Surprisingly our results show that forced expression of the full-length but not the truncated form of CD34 impedes terminal differentiation by these agents. Because the difference between the two forms of CD34 protein resides in the length of their respective cytoplasmic tail domains, our findings strongly suggest that the cytoplasmic domain region of full-length CD34 is responsible for the observed maturation arrest phenotype. These findings suggest a potential negative regulatory role for full-length CD34 in hematopoietic cell differentiation and may explain, at least in part, the block in maturation observed in CD34+ acute myeloid leukemia.     

Isolation of intestinal spirochaetes from homosexuals

Spirochaetes were isolated from rectal swabs of two homosexuals and the faeces of a third, using simple isolation techniques not previously applied to specimens of this type. The ease of culture of these organisms will enable their distribution and pathogenicity to be studied, particularly in relation to their significance in homosexuals.     

Role of p21 RAS in p210 bcr-abl transformation of murine myeloid cells

The p21 RAS product has been implicated as part of the downstream signaling of certain nonreceptor tyrosine kinase oncogenes and several growth factor receptor-ligand interactions. We have reported that the chronic myelogenous leukemia oncogene p210 bcr-abl transforms a growth- factor-dependent myeloid cell line NFS/N1.H7 to interleukin-3 (IL-3) independence. In these p210 bcr-abl-transformed cells (H7 bcr-abl.A54) and in two other murine myeloid cell lines transformed to IL-3 independence by p210 bcr-abl, endogenous p21 RAS is activated as determined by an elevated ratio of associated guanosine triphosphate (GTP)/guanosine diphosphate (GDP), assayed by thin-layer chromatography of the nucleotides eluted from p21 RAS after immunoprecipitation with the Y13-259 antibody. Treatment of p210 bcr-abl-transformed cells with a specific tyrosine kinase inhibitor herbimycin A resulted in diminished tyrosine phosphorylation of p210 bcr-abl and associated proteins, without major reduction in expression of the p210 bcr-abl protein itself. Inhibition of p210 bcr-abl-dependent tyrosine phosphorylation resulted in a reduction of active p21RAS-GTP complexes in the transformed cells, in diminished expression of the nuclear early response genes c-jun and c-fos, and in lower cellular proliferation rate. To further implicate p21 RAS in these functional events downstream of p210 bcr-abl tyrosine phosphorylation, we targeted G- protein function directly by limiting the availability of GTP with the inosine monophosphate dehydrogenase inhibitor, tiazofurin (TR). In p210 bcr-abl-transformed cells treated for 4 hours with TR, in which the levels of GTP were reduced by 50%, but GDP, guanosine monophosphate, and adenosine triphosphate (ATP) were unaffected, p210 bcr-abl tyrosine phosphorylation was at control levels. However, expression of c-fos and c-jun nuclear proto-oncogenes were strongly inhibited and p21 RAS activity was downregulated. These findings show that p210 bcr-abl transduces proliferative signals, in part, through downstream activation of p21 RAS. Furthermore, p21 RAS activity is linked to pathways that regulate c-jun and c-fos expression.     

Pachygyriclike changes: topographic appearance at MR imaging and CT and correlation with neurologic status

Studies of 23 pediatric patients with pachygyriclike changes (PLCs) examined with computed tomography (CT) and magnetic resonance (MR) imaging were reviewed to determine topographic patterns and correlate them with various clinical syndromes and degrees of neurologic impairment. Three types of topographic distributions were identified: unilateral, diffuse, and bilateral nondiffuse (of which eight of 10 showed frontotemporal predominance). PLCs were an isolated finding in seven patients, were associated with various congenital syndromes in nine patients, and were associated with congenital infection in seven patients, six of whom showed marked white matter abnormalities. Although most patients had severe developmental delay, three with nondiffuse PLCs had less severe impairment, permitting less required care.     

≥50岁人群多效复方固定制剂的随机交叉试验

2000年Wald等[1]首先介绍了预防心血管疾病的复方制剂,称之为多效复方固定制剂(Polypill).有4项平行组设计的研究显示[2-5],Polypill明显降低胆固醇和血压水平,但疗效不确定.另外,由于治疗组依从性不高或对照组不定期治疗,这4项研究可能低估了Polypill的疗效.     

Central regulation of intestinal basal and stimulated water and ion transport by endogenous opiates in dogs

The influence of intracerebroventricular (ICV) vs intravenous (IV) administration of (D-Ala2, Met5) enkephalinamide (Dalamide) on normal and stimulated (cholera toxin) jejunal fluxes of water, Na+, and K+ were investigated in dogs prepared with a Thiry-Vella (TV) loop. Intestinal transport in the TV loop and concomitant transit time were measured during an infusion (2 ml/min) of an isotonic electrolyte solution alone, or containing 0.4 micrograms/ml of cholera toxin (CT). Basal net water absorption was slightly, but significantly (P less than 0.05), increased during an ICV infusion of Dalamide at 0.5 ng/kg/min, while the secretory effects of cholera toxin were markedly reduced by nearly 75%. Similar effects were observed for Na+ and K+ movement. In contrast, Dalamide infused intravenously at a five times higher dose, ie, 2.5 ng/kg/min did not affect the control and CT-stimulated water and electrolyte movements. The jejunal loop transit times were halved during CT infusion. Similar values were observed under Dalamide ICV administration as well as during a five times higher dose of Dalamide administered intravenously. It was concluded that (1) Dalamide administered into the CNS, but not peripherally, increased the absorption of water, Na+, and K+, causing a net reduction in their secretion induced by cholera toxin; and (2) these effects did not result from changes in transit time. These results also suggest that Met-enkephalin can act in the brain to affect the intestinal transport of water and electrolytes in dogs.     

Biosynthesis and secretion of factor VII, protein C, protein S, and the Protein C inhibitor from a human hepatoma cell line

Using specific radioimmunoassays, 8 day cultures of Hep G2 cells were shown to contain in their supernatants 16, 74, and 828 ng/mL and in their cell lysates, 8, 55, and 48 ng/2 X 10(8) cells of factor VII, protein C, and protein S, respectively. These proteins and the protein C inhibitor were functionally active, and each of these activities was neutralized by their respective polyclonal antibodies. Although vitamin K had a modest effect, warfarin decreased the activity of secreted factor VII, protein C, and protein S by 50% to 90%. Protein C and protein S antigens were reduced three- to fourfold by warfarin. The protein C inhibitor antigen and activity were unaffected by vitamin K or warfarin treatment. Intrinsic labeling and immunoprecipitation indicated that factor VII, protein S, and the protein C inhibitor were secreted as 52,000, 77,000, and 58,000 molecular weight (mol wt) proteins, respectively. Protein C was secreted as a single-chain protein of about 65,000 mol wt, indicating that all of the vitamin K- dependent proteins are translated and secreted as single-chain molecules. Each of the four proteins studied represented their plasma protein counterparts structurally, functionally, and immunochemically. Thus, all of the known soluble components of the protein C pathway are produced by liver parenchymal cells.