FGF-10 is a chemotactic factor for distal epithelial buds during lung development

BACKGROUND: We investigated the ability of a variety of growth factors to regulate the differentiation of prostatic fibroblasts into smooth muscle cells. METHODS: Smooth muscle actin levels were monitored by immunoblot analysis and immunocytochemistry. Proliferation was measured in clonal growth assays and by cell counts. RESULTS: We determined that TGFbeta inhibited proliferation and induced smooth muscle differentiation of stromal cells derived from prostatic adenocarcinomas, as we previously reported for cells derived from the normal peripheral zone. Basic FGF, EGF, TGFalpha, and PDGF, but not IGF, retinoic acid, 1,25-dihydroxyvitamin D3, or androgen, attenuated induction of differentiation by TGFbeta, by a mechanism apparently unrelated to proliferation. CONCLUSIONS: Regulation of growth and differentiation occurs equivalently in prostatic stromal cells derived from adenocarcinomas and normal peripheral zone. TGFbeta is a potent inducer of the smooth muscle phenotype. Basic FGF, EGF and/or TGFalpha, and PDGF attenuate TGFbeta's activity, and promote a fibroblastic phenotype. Our studies provide an in vitro model system in which fibroblastic or smooth muscle cells can be promoted, maintained, and investigated in a defined manner. The results suggest that the ratio of fibroblasts to smooth muscle cells in the stroma reflects the relative levels of growth factors, which may be altered in diseased states.     

Development of GM-CSF antagonist peptides

Granulocyte/macrophage colony stimulating factor (GM-CSF) is both a hematopoietic growth factor and a cytokine implicated in inflammatory disease. The development of GM-CSF antagonist peptides corresponding to the GM-CSF native sequence should allow their modification into higher affinity analogs, but this is hampered by the low affinity of linear peptides. To adequately evaluate such low affinity peptides, the use of several independent assays should allow specific versus nonspecific inhibitors to be distinguished. In this study, inhibition of GM-CSF-dependent cell growth, inhibition of GM-CSF binding and immunologic cross-reactivity between GM-CSF-derived peptides and native protein by neutralizing antibodies have been used to evaluate peptide analogs with potential bioactivity. The GM-CSF sequence was divided into 6 peptides ranging in size from 15-24 amino acids. Antisera were raised to these peptides in mice and assayed for immunologic cross-reactivity. 4/6 anti-peptide antisera bound GM-CSF on ELISA and 3/6 on immunoprecipitation. Antisera to two of the peptides (corresponding to residues 17-31 and 96-112) inhibited GM-CSF-dependent cellular proliferation in two cell lines, with one peptide derived from residues 17-31 demonstrating inhibition of GM-CSF binding and direct biological inhibitory activity. A peptide that did not elicit native GM-CSF reactive antibodies, corresponding to residues 54-78, was recognized by two neutralizing monoclonal antibodies. It exhibited inhibition of GM-CSF binding and direct biological antagonist activity. These studies implicate two sites in mediating GM-CSF biological activity, and indicate that biological antagonists can be developed based on these sites.     

Mesenteric vascular problems. A 26-year experience

Mesenteric vascular problems are infrequent, but may be catastrophic. During a 26-year period, 55 private patients were treated for the following disorders: (1) 12 patients with visceral artery aneurysms, (2) 8 with celiac compression syndrome, (3) 13 with chronic mesenteric ischemia, (4) 12 with acute mesenteric ischemia, and (5) 10 with mesenteric ischemia associated with aortic reconstructions. Splenic artery aneurysms were managed by excision and splenectomy, while celiac and hepatic had excision with graft replacement. Patients with celiac compression syndrome underwent lysis of the celiac artery. Two patients had compression of both celiac and superior mesenteric artery (SMA). One patient required vascular reconstruction of both arteries for residual stenoses. Patients having chronic mesenteric ischemia were treated with bypass grafts, with one death (7.7% mortality) and good long-term results. Those with acute mesenteric ischemia were treated by SMA embolectomy, bowel resection, or both, with a mortality of 67%. When associated with aortic reconstructions, mesenteric ischemia carried a mortality of 100% if bowel infarction occurred after operation, but when prophylactic mesenteric revascularization was performed at the time of aortic surgery, prognosis was greatly improved, with only one death among six patients. An aggressive approach including prompt arteriography with early diagnosis and surgical therapy is advocated for these catastrophic acute mesenteric problems.     

基于知识的CAx集成的系统框架研究

在分析国内外CAx集成技术、PDM产品、PKM研究现状的基础上，提出了基于知识的CAD／CAE／CAPP／CAQ集成技术，基于知识的CAx集成理论；产品数据管理、产品知识管理与协同产品商务的融合技术，构建了协同产品知识管理框架，以此为平台，有效地实现了基于知识的CAD／CAE／CAPP／CAQ的集成。     

The Charles Bonnet syndrome: a review

OBJECTIVES: To discuss the advantages of different methods of determining the effectiveness of healthcare interventions, to evaluate the basis for the assumption that right heart catheterization is effective, and to consider how right heart catheterization may fail to improve outcomes in some circumstances. DATA SOURCE: Published English language literature on right heart catheterization and patient outcomes. DISCUSSION: We recently reported an association between the use of right heart catheterization in the initial care of critically ill patients and increased risk of death. This finding is troubling and warrants future study. In this article I address the role of randomized controlled trials and observational studies in the evaluation of the effectiveness of healthcare interventions. I discuss the basis in the published literature for assuming that right heart catheterization improves outcomes. Finally I present a variety of problems with right heart catheterization which might allow this procedure, which logically should help patients, to fail to achieve a beneficial effect for some patients. CONCLUSION: We must do appropriate prospective studies to determine who benefits from right heart catheterization and who does not. We owe our patients nothing less.     

AT1 angiotensin II receptor inhibition in pacing-induced heart failure: effects on left ventricular performance and regional blood flow patterns

5'-O-Myristoyl analogue derivatives of 3'-azido-2',3'-dideoxythymidine (AZT), designed as potential double-barrelled prodrugs to AZT and the myristic acid analogues, were synthesized. Their ability to protect CEM cells against human immunodeficiency virus (HIV)-induced cytopathogenicity was determined and structure-activity paradigms were developed. 3'-Azido-2',3'-dideoxy-5'-O-(4-oxatetradecanoyl)thymidine (EC50 = 1.4 nM) and 3'-azido-2',3'-deoxy-5'-O-(12-bromododecanoyl)thymidine (EC50 = 3.2 nM) were the most effective anti-HIV-1 agents, relative to AZT (EC50 = 10 nM). These myristoyl analogue derivatives were more lipophilic (calculated log P = 4.5-8.1 range) than the parent compound AZT (log P = 0.06), and a linear correlation between their log P and HPLC log retention times was observed. The ester cleavage half-lives (t1/2) for esters upon in vitro incubation with porcine liver esterase, rat plasma or rat brain homogenate was dependent on the steric bulk, and electronegative inductive effect of the alpha-substituent (H, Br, F), of the 5'-O-myristoyl analogue moiety. 3'-Azido-2',3'-dideoxy-5'-O-(11-(4-iodophenoxy) undecanoyl)-thymidine exhibited t1/2 values of 80.4, 3.7 and 150.0 min upon incubation with porcine liver esterase, rat plasma and rat brain homogenate, respectively.     

Assessing same/different judgments in individuals with severe intellectual disabilities: a status report

This report summarizes state-of-the-art approaches for assessing visual stimulus same/different judgments in individuals with severe intellectual disabilities. Methods are described that permit one to conduct assessments on a population-wide basis, excluding few if any participants due to failure to acquire necessary baseline performances. Methodological investigations summarized here indicate that one can obtain reliable same/different judgments with a variety of stimuli in virtually anyone for whom a basal score on the Peabody Picture Vocabulary Test can be obtained. This approach includes judgments involving not only familiar, readily nameable stimuli, but also abstract two-dimensional forms of the type commonly used to minimize extraexperimental influences on performance. Taken together, recent findings lead to the conclusion that past studies have significantly under-estimated the capacity of participants with low MA scores to make same/different judgments. They also suggest a more general methodological approach that can potentially lead to more sensitive assessment of other behavioral capacities in this difficult-to-test population.