Atherosclerosis in APOE*3-Leiden transgenic mice: from proliferative to atheromatous stage

BACKGROUND: This study documents (1) the progression of atherosclerosis along the entire arterial tree in APOE*3-Leiden mice after 1, 4, 6, 9, and 12 months of a high-fat/high-cholesterol (HFC) diet and (2) the amount and phenotype of DNA-synthesizing and apoptotic cells in different lesion types after 6 months of HFC diet. METHODS AND RESULTS: Diet duration was correlated with a craniocaudal progression of lesion development and with an increase in severity of the lesion. Typically, the lesions contained smooth muscle cells, macrophages, and T lymphocytes and were covered by an intact endothelium. Whereas DNA synthesis (BrdU uptake) was usually elevated in type II lesions (8.6+/-0.8% versus 1.0+/-0.2% in the nondiseased arterial wall; P<0.05), apoptosis was found primarily in advanced lesions (type IV, 1.3+/-0.1% and type V, 1.2+/-0.2% versus 0.04+/-0.04% in the nondiseased arterial wall [P<0.05]). Cell phenotyping revealed that the majority of DNA synthesis and apoptosis was confined to the macrophage-derived foam cell (68.6+/-3. 0% and 82.2+/-4.6%, respectively). CONCLUSIONS: This study shows that in APOE*3-Leiden mice, duration of an HFC diet is associated with (1) a craniocaudal progression of lesion development and (2) an increased complexity of atherosclerotic lesions. Furthermore, DNA synthesis is predominant in early lesions, whereas apoptosis is present mainly in more advanced lesions. Both parameters of cell turnover are confined primarily to the macrophage-derived foam cell.     

The site of the breakpoint within the bcr is a prognostic factor in Philadelphia-positive CML patients [see comments]

The Philadelphia (Ph1) chromosome, characteristic of chronic myelogenous leukemia (CML), arises from a reciprocal translocation between chromosomes 9 and 22. The site of the breakpoint on chromosome 22 is within a small region called the breakpoint cluster region (bcr). We have mapped the breakpoint within the bcr in peripheral blood leukocyte DNA from 22 Ph1-positive CML patients. No correlation between the site of the breakpoint and the clinical phase of the disease was found. However, a striking correlation between the site of the breakpoint and the length of time between presentation and onset of acute phase was observed: on average, patients with a 5' break-point had a fourfold longer chronic phase (median, 203 weeks) than those with a 3' breakpoint (median, 52 weeks).     

Erythropoietin production by the fetal liver in an adult environment

To gain insight into the mammalian liver to kidney erythropoietin (Ep) switch, we heterotopically transplanted livers from preswitch, switched, and postswitch fetal and newborn lambs into normal adult sheep. Recipients' serum Ep and circulating reticulocyte levels were serially determined until rejection of the graft and compared with identical samples from sham-operated control adult ewes. Transplantation of preswitch and switched fetal livers caused an impressive rise in recipients' serum Ep activity and provoked a corresponding increase in reticulocytosis. In contrast, Ep activity and reticulocyte counts did not change from preoperative levels in adult ewes transplanted with postswitch livers or in the sham-operated controls. The production of Ep by the preswitch fetal liver in the adult environment was not dependent on the presence or absence of host kidneys and was stimulated by anemic hypoxia. These results suggest that the fetal liver is capable of producing relatively large amounts of Ep activity, and the production of Ep can be maintained in the adult environment in the presence of functional adult kidneys. This argues against suppression of liver Ep production by renal Ep, or some other factor in the postnatal environment, and suggests that the liver to kidney switch of Ep production during ontogeny may represent a genetically determined event.     

A supervised land cover classification of a western Kenya lowland endemic for human malaria: associations of land cover with larval Anopheles habitats

Background  

A supervised land cover classification was developed from very high resolution IKONOS satellite data and extensive ground truth sampling of a ca. 10 sq km malaria-endemic lowland in western Kenya. The classification was then applied to an investigation of distribution of larval Anopheles habitats. The hypothesis was that the distribution and abundance of aquatic habitats of larvae of various species of mosquitoes in the genus Anopheles is associated with identifiable landscape features.     

垂体催乳素瘤的诊断和治疗指南

首次测定确立高催乳血症必需避免过度的静脉穿刺压力,理想的情况是醒后或饭后致少1h来测试.     

茶碱对有呼吸窘迫综合征的极早产儿患血管运动性肾病的预防作用研究：一项随机双盲安慰剂对照试验

背景:血管运动性肾病是早产儿常见的肾功能障碍性疾患。目的:确定茶碱是否可以预防有呼吸窘迫综合征的极早产儿罹患血管运动性肾病。方法:随机双盲安慰剂对照试验,50例胎龄≤32周须辅助通气的早产儿。婴儿接受3d茶碱(1m g/kg)或安慰剂静脉注射。每天测定其24h尿量。在第2、第5及第11天,收集血样及12h尿并进行电解质、肌酐、尿素分析。结果:茶碱组患儿的第1天排尿量的组别x(s)为2.4(0.9)m l/(kg·h),显著高于安慰剂组[1.6(1.0)m l/(kg·h);P=0.023]。茶碱组少尿或无尿的发生率(5%)显著低于安慰剂组(33%)。在第一次给予茶碱/安慰剂后24h,茶碱…     

Permeability of porcine blood brain barrier to somatostatin analogues

1. Transport of a fluorescent somatostatin analogue (NBD-octreotide) across freshly isolated functionally intact capillaries from porcine brain was visualized by confocal microscopy and quantitated by image analysis. 2. Luminal accumulation of NBD-octreotide showed all characteristics of specific and energy-dependent transport. Steady-state luminal fluorescence averaged 2 - 3 times cellular fluorescence and was reduced to cellular levels when metabolism was inhibited by NaCN. 3. The accumulation of NBD-octreotide in capillary lumens was inhibited in a concentration-dependent manner by unlabelled octreotide, by verapamil, PSC-833 and cyclosporin A, potent inhibitors of p-glycoprotein, and by leucotriene C(4), a strong modulator of Mrp2. Conversely, unlabelled octreotide reduced luminal accumulation of fluorescent BODIPY-verapamil on p-glycoprotein and of fluorescein-methotrexate, on Mrp2. None of the inhibitors used significantly reduced cellular accumulation of the fluorescent substrates. 4. Together, the data are consistent with octreotide being transported across the luminal membrane of porcine brain capillaries by both P-gp and Mrp2, providing further evidence that both transporters contribute substantially to the active barrier function of this endothelium.