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.     

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.     

Energy available from corn oil is not different than that from beef tallow in high- or low-fiber diets fed to humans

The impact of the source of dietary fat and the level of dietary fiber on digestibility and energy metabolism were studied in human (six male, six female) volunteers. Subjects were divided into two diet treatment groups, high fiber [29.0 g total dietary fiber (TDF)/d] and low fiber (18.6 g TDF/d), for the duration of the study. Each participated in three, 2-wk controlled feeding periods. Either beef tallow (BT), corn oil (CO) or carbohydrate (CHO) was added (25% of diet energy) to a base diet in a three-way crossover study. Energy expenditure, substrate oxidation and digestibility determinations were conducted at the end of each period. The protein, fat and CHO digestibility of the base diet was significantly different between the fiber levels. The digestibility (high-fiber/low-fiber) averaged 82%, 90% for protein, 96% and 98% for fat. After adjusting for TDF, the CHO digestibility averaged 96% and was not different between fiber levels. The digestibility of the added CO and BT was 99.6 and 99.8% respectively, and was not significantly different between the fiber levels. No significant differences in 24-h energy expenditure existed nor the thermic effect of food due either to fiber level or between the CHO, BT or CO. Fat oxidation in subjects consuming the low-fiber diet was 14% higher (P < 0.03) with the BT treatment than with the CO treatment but not different in those that consumed the high-fiber diet. The energy value of the two fat sources was not different but their utilization by individuals near energy balance may lead to differences in long-term weight maintenance.     

精馏塔理论板数的计算方法

本文介绍了用Maple和MathCAD计算精馏过程所需理论塔板数的方法。这两种方法使用简单,易于掌握,应用范围广泛,又能有效地提高计算准确性,对精馏塔的设计和操作调节具有指导作用。