Ligands that activate protein kinase-C differ in their ability to regulate basic fibroblast growth factor and insulin-like growth factor-I messenger ribonucleic acid levels

In this study, rat dermal fibroblasts were used as a model system to examine the ability of ligands that are known to activate protein kinase-C to regulate the levels of the mRNAs encoding basic fibroblast growth factor (bFGF) and insulin-like growth factor-I (IGF-I), two growth factors that are thought to be important in processes such as tissue repair and regeneration and wound healing. Treatment of fibroblasts with the phorbol ester phorbol 12-myristate 13-acetate (PMA), thrombin, bradykinin, serotonin, angiotensin-II, or bombesin increased protein kinase-C activity to a similar degree. Treatment of fibroblasts with 1 microM serotonin transiently increased bFGF mRNA levels about 3-fold compared to the level in control cells maintained in serum-free medium with 0.25% BSA and decreased IGF-I mRNA levels by approximately 50% compared to the level in control cells. This is similar to the previously described changes induced by bradykinin in these cells, but different from the more marked and sustained changes induced by thrombin and PMA. In contrast, angiotensin-II and bombesin had no effect on bFGF or IGF-I mRNA levels. The effects of serotonin, bradykinin, and PMA on bFGF and IGF-I mRNA levels were abrogated by preincubation of cells in 250 nM PMA to down-regulate protein kinase-C. In contrast, the effect of thrombin on bFGF mRNA levels was only partially inhibited by down-regulation of protein kinase-C, while its effect on IGF-I mRNA levels was unaffected. The activation of signaling pathways by the different ligands was further investigated to begin to determine the mechanism for the differences in the effects of thrombin vs. serotonin and bradykinin and in the effects of these three ligands vs. angiotensin-II and bombesin. All of the ligands activated phospholipase-D to a similar degree, suggesting that activation of this enzyme was not responsible for the differential effects of the ligands. In contrast, thrombin, serotonin, and bradykinin had marked effects on the hydrolysis of phosphatidylcholine and phosphatidylinositol, whereas bombesin and angiotensin-II had a small effect on phosphatidylcholine hydrolysis and no effect on phosphatidylinositol hydrolysis.(ABSTRACT TRUNCATED AT 400 WORDS)     

Isolation and characterization of three Dictyostelium myosin-I isozymes

Using ion exchange chromatography and an ATP-dependent actin precipitation step, we have isolated three myosin-I isozymes that, together, account for most of the K+EDTA-ATPase activity recovered from extracts of Dictyostelium. The two major myosin-I isozymes, present in approximately equal amounts, had apparent molecular masses of 125 kDa on SDS gels and have been identified by amino acid sequence analysis as the products of the Dictyostelium myosin-IB (DMIB) and myosin-ID (DMID) genes. DMIB, with a specific K+EDTA-ATPase activity 10-fold higher than DMID, was responsible for most of the activity in cell extracts. The third isozyme, present in low amounts, had an apparent molecular mass of 137 kDa on SDS gels and is too large to be the product of any of the known myosin-I genes. DMIB eluted from DE53 cellulose columns as two distinct peaks (II and III). Addition of the phosphatase inhibitor okadaic acid to the extraction buffer increased the fraction of DMIB recovered from growth phase cells in peak III from 35 to 70%. DMIB isolated from peak III, but not from peak II, displayed a significant level of actin-activated MgATPase activity. These results indicate that peak III represents a phosphorylated, actin-activatable form of DMIB.     

Swenson's operation for neonatal Hirschsprung's disease

OBJECTIVE: To describe our experience with Swenson's operation for Hirschsprung's disease done during the neonatal period. DESIGN: Retrospective study. SETTING: University department of paediatric surgery. SUBJECTS: 10 Neonates with Hirschsprung's disease. INTERVENTIONS: Rectosigmoidectomy and pull through (Swenson's operation), with covering transverse colostomy. MAIN OUTCOME MEASURES: Mortality, morbidity, and continence. RESULTS: The median age at definitive operation was 25 days (range 15-35). There was one late death three weeks after discharge from hospital of respiratory and cardiac failure. Two patients presented with caecal perforation and two with intestinal obstruction; in all four Hirschsprung's disease was diagnosed on frozen section, a transverse colostomy was done, and the Swenson's operation was done electively. The other six were diagnosed by barium enema examination and biopsy, and underwent total bowel irrigation followed by Swenson's operation and transverse colostomy. The colostomies were closed three to four weeks later. There were no postoperative complications. All nine surviving patients were continent (3-4 stools/day), at a mean (SD) follow up of 21 (5) months. CONCLUSION: With the current high standards of anaesthesia and neonatal intensive care, and an experienced surgeon, Swenson's operation for neonatal Hirschsprung's disease is safe and the procedure of choice for this condition.     

Factor XIIIa immunoreactivity in primary and secondary tumours of the meninges

Occasionally variants of meningeal hemangiopericytomas (HPC) may be confused with primary and secondary tumours of the meninges by virtue of their features and patterns of growth. Until now, a specific immunohistochemical marker for HPC could not be identified. HPC are reported to express factor XIIIa (F XIIIa) in the cytoplasm of the tumour cells. In an effort to assess the diagnostic value of F XIIIa for meningeal HPC, we investigated 38 primary meningeal tumours (6 HPC, 28 meningiomas of various subtypes, 4 meningeal sarcomas) and 23 secondary meningeal tumors (8 metastatic carcinomas, 6 gliosarcomas, 9 anaplastic gliomas) with anti-F XIIIa antibody. All HPC revealed 5%-20% of F-XIIIa-positive neoplastic cells. Malignant fibrous histiocytomas and gliosarcomas with MFH-like structures also exhibited multiple F-XIIIa-positive cells. Most of the F-XIIIa-positive cells in meningiomas were identified as macrophages. Furthermore, there was a population of small dark cells of uncertain histogenesis. Cells with positive immunoreactivity for F-XIIIa in metastatic carcinomas and gliomas apparently were of macrophage lineage. Though, in some cases, it would have been difficult to distinguish reactive from neoplastic cells without simultaneous immunohistochemical investigation with antibodies for macrophages, cytokeratin, EMA and GFAP. Because of these uncertainties, wo believe that the potential of F XIIIa-antibody in obtaining precise differential diagnostic information is limited.     

The femur-tibia control system of stick insects--a model system for the study of the neural basis of joint control

In a form of top-down analysis, the femur-tibia control system of stick insects is investigated. Open-loop experiments show that it is mainly velocity-sensitive with an extremely low velocity-threshold, that it possesses a very high gain and that it has only a very small phase reserve and thus works close to instability. The closed-loop system generates catalepsy. The system consists of a single sense organ with approximately 80 sense cells with known characteristics, a small number of interneurones (mainly non-spiking ones) and a small number of motor neurones. The characteristics of the whole system can quantitatively be attributed to the characteristics of its elements. The gain of the loop is state-dependent and the system is 'switched off' during active movements and replaced by a control system with different attributes. It is discussed that most of the characteristics of this system are, at least qualitatively, similar to joint control systems in other animals. Because the described system can be more easily investigated than other systems (especially in vertebrates) it can serve as a model against which more complicated joint control loops may be compared.     

The neu-oncogene product in serum and tissue of patients with breast carcinoma

Patients with non-cardiac chest pain (NCCP) (n = 387) and cardiac chest pain (CCP) (n = 93) were compared with community controls (n = 81), using a symptom questionnaire that assessed the presence of irritable bowel syndrome (IBS), functional dyspepsia, and oesophageal dysfunction and chest pain characteristics. A significantly (p < 0.05) increased prevalence of symptoms compatible with IBS occurred in NCCP patients when compared with those with CCP and with controls. Dysphagia was more frequent in both those with non-cardiac and cardiac chest pain than in controls; this was not apparent, however, when patients with concomitant IBS were excluded. The presence of oesophageal or gastrointestinal symptoms did not enable discrimination with regard to the chest pain characteristics. We conclude that unselected referred patients with documented NCCP are more likely to have IBS and that the presence of oesophageal symptoms such as dysphagia may merely reflect the spectrum of the 'irritable gut'.     

Nontuberculous mycobacteriosis as a complication of the Swyer-James syndrome

The chest radiograph of a 35-year-old man with fatigue, exertional dyspnoea and haemoptyses revealed a cavity in the left upper lobe and a shrunken left lung with radiolucency greater than that on the right. Acid-fast rods in sputum were identified as Mycobacterium kansasii on culture. Scintigraphy showed a 9% residual perfusion on the left and abnormal ventilation, compatible with Swyer-James syndrome. This had favoured the development of a mycobacterial infection. There was also a decrease in ciliary function (rate of 4-7 Hz, normal: 10-11). Treatment, begun when tuberculosis had been suspected, was after sensitivity tests changed to a combination of rifampicin (600 mg), ethambutol (1600 mg) and protionamide (500 mg) daily. There was marked regression of the findings within 4 weeks, but treatment was prematurely stopped after 11 months. Two years later there was a recurrence which again responded well to the same drug regimen with additional sulphamethoxazole (1600 mg/d).     

Judgments of social justice: Compromises between equality and efficiency.

Political economists agree that a trade-off exists between equality and efficiency. Using a hypothetical society paradigm, the mean income (representing efficiency) and income variability (representing equality) of distributions of wealth and the correlation between wealth and effort within a society were manipulated. Ss made all pairwise comparisons of distributions within societies of differing meritocracy. A "maximin" principle best described trade-off resolution strategies when effort and outcome were weakly linked: People maximized the minimum standard of living within a society. A compromise principle best described preferences when income was tightly linked to effort: People rejected distributions in which some citizens fell below the "poverty line" but maximized efficiency above this constraint. Ideological polarization was pronounced under moderate meritocracy; here liberals could focus on the role of chance and conservatives on the role of effort and ability. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

基于供应链管理的供应商选择问题初探

首先讨论了供应链环境下选择供应商的意义，然后建立了供应商选择的评价指标体系，重点讨论了应用TOPSIS 方法对供应商选择的模型及算法，最后用一个简单的案例进行了说明。