A comparative study on the immunological effects of bovine and porcine thymic extracts: induction of lymphoproliferative response and enhancement of interleukin-2, gamma-interferon and tumor necrotic factor production in vitro on cord blood lymphocytes

Forty samples of cord blood lymphocytes were isolated from 40 normal healthy full-term newborns. The initial 20 samples were used to determine the dose-response curve of three different thymic extracts (TP-1, bovine thymic extract; TG-15-I and TG-15-II, both porcine thymic extracts) and one of renal origin (KG-1) as a control of non-lymphoid organ extract, by measuring the E-rosette T cells. Results showed that E-rosette T cells increased significantly when the thymic extract concentration was increased to 12.5 micrograms/ml. However, there was no statistical difference between TP-1, TG-15-I and TG-15-II in the increase of E-rosette-forming cells. The remaining 20 samples were preincubated with 0, 12.5, 25 or 50 micrograms/ml of thymic extracts. It was observed that the lymphoproliferation, interleukin-2 (IL-2), gamma-interferon (IFN-gamma) and tumor necrotic factor (TNF) production were all significantly increased after thymic extract treatment. No statistical difference between these three thymic preparations in the stimulation of lymphoproliferative response was found. However, among the three thymic extracts, TP-1 appears to induce the highest amounts of IL-2, IFN-gamma and TNF. Of the TG-15-I and TG-15-II, the former stimulates higher IL-2 production whereas the latter enhances IFN-gamma and TNF production. The different immunostimulating effects and potencies that these three thymic extracts showed may reflect not only the species difference but also the difference in preparation procedures. Different components in these thymic extracts may be responsible for different biological activities. Results from these comparative studies may provide useful information in future clinical trials for the treatment of the primary immunodeficiency diseases according to their pathogenesis and may also indicate a possible beneficial effect of the combination of chemotherapy and thymic extracts.     

Junctional epidermolysis bullosa keratinocytes in culture display adhesive, structural, and functional abnormalities.

An unusual, elongated, refractile cell morphology was observed in keratinocytes cultured from three patients with non-lethalis forms of junctional epidermolysis bullosa (JEB). To determine whether these changes might be related to altered cell adhesion, keratinocyte strains established from one patient were examined for adhesive, structural, and functional characteristics. JEB keratinocytes expressed keratin tonofilaments, as determined by staining with AE1 monoclonal antibodies and direct observation of tonofilaments by electron microscopy. JEB keratinocytes showed diminished cell-substratum adhesions, judged by interference reflection microscopy. Areas of diminished cell-substratum adhesion corresponded to F-actin-rich cell adhesions (focal adhesions) and not to cellular areas that abundantly express hemidesmosomal antigens. Analysis of cell-substratum adhesion by electron microscopy revealed extensive areas of cell-substratum separation in JEB keratinocytes that were not present in normal keratinocytes maintained in serum-free medium. Normal keratinocytes displayed numerous regions of focal contact between the ventral plasma membrane and the culture substratum, but these structures were not seen in JEB keratinocytes. Bundled actin filaments (stress fibers) were greatly diminished in expected regions of cell-substratum adhesion in JEB keratinocytes and, instead, displayed disorganized individual filaments. The growth rate of JEB keratinocytes was quite slow in culture, with a population doubling time of 2.7 d versus 1.5 d for normal keratinocytes under identical conditions. JEB keratinocytes also displayed a reduced ability to aggregate into colonies upon exposure to medium with increased extracellular calcium. JEB keratinocytes thus display adhesive, structural, and functional abnormalities that suggest this cell type may be central to the pathogenesis of junctional epidermolysis bullosa. Study of affected keratinocytes could be important to characterize associated molecular pathologies.     

Early uptake of 99mTc-C2A in the acute phase of myocardial infarction as a prognostic indicator for follow-up cardiac dysfunction

OBJECTIVE: The C2A domain of Synaptotagmin I is a molecular probe for the specific imaging of cell death. Here we test the hypothesis that the uptake of 99mTc-C2A in the acute phase of an infarction is associated with cardiac dysfunction in follow-ups. METHODS: The left coronary artery was occluded in Sprague-Dawley rats for 0, 10, 20, and 30 min. 99mTc-C2A was injected intravenously at 2 h of reperfusion. Anterior planar images were acquired with one million counts on a gamma camera 3 h after injection. 99mTc-C2A uptake was calculated as the total counts in the left ventricle region minus blood pool signal. The in-vivo signal detected was correlated with wall motion score index at 1 and 3 weeks follow-ups measured by echocardiography. RESULTS: 99mTc-C2A uptake was higher with increased ischemic time (2244+/-852, 4054+/-1223, and 6178+/-1451 for 10, 20, and 30 min ischemia, analysis of variance P<0.001). A significant correlation was found between 99mTc-C2A uptake and wall motion score index at 1 week (R=0.800, P=0.0006) and 3 weeks (R=0.810, P=0.0008). CONCLUSION: In this ischemia/reperfusion model, 99mTc-C2A uptake in the acute phase was associated with functional abnormality at 1 and 3 weeks. This demonstrates the potential diagnostic and prognostic value of 99mTc-C2A as a novel imaging agent.     

Keratinocyte conditioned medium abrogates the modulatory effects of IGF-1 and TGF-β1 on collagenase expression in dermal fibroblasts

Overexpression of wound healing-promoting factors such as transforming growth factor-1 (TGF-beta1) and insulin-like growth factor-1 (IGF-1) during the healing process has been implicated in the development of dermal fibrosis in patients following thermal injury, surgical incision, and deep trauma. However, the mechanism through which the expression of these two fibrogenic factors is slowed down and/or abrogated in the late stages of the healing process is not known. Here, we hypothesize that keratinocyte-releasable factors counteract the fibrogenic role of both IGF-1 and TGF-beta1 in fibroblasts. To test this hypothesis, the levels of collagenase (MMP-1), as an index for extracellular matrix degradation, in dermal fibroblasts in response to either keratinocyte-conditioned medium (KCM) or our recently identified keratinocyte-releasable stratifin in the presence and absence of either IGF-1, TGF-beta1, or both were evaluated. The results of Northern analysis showed a significant increase in collagenase mRNA expression in cells treated with KCM in the presence of both IGF-1 and TGF-beta1. The effect was, at least in part, due to keratinocyte-derived stratifin that was present in KCM. This was ascertained as the levels of MMP-1 mRNA were markedly reduced when cells were treated with stratifin-immuno-depleted KCM. The results of Western blot analysis showed an increase in the level of MMP-1 protein in stratifin-treated fibroblasts and this was consistent with the level of MMP-1 mRNA expression detected by Northern analysis. However, in contrast to KCM, whose efficacy on MMP-1 expression was modestly reduced by either IGF-1 and TGF-beta1, or a combination of both, these factors abrogated the MMP-1 stimulatory effect of stratifin in fibroblasts. In summary, the results of this study revealed that both stratifin and KCM stimulate the expression of MMP-1-in fibroblasts and this effect can be abrogated by either IGF-1, TGF-beta1, or a combination of both.     

阴茎勃起神经再生模型和机制的研究

探明神经性勃起功能障碍(NED)的分子生物学机制以期对该类疾病进行神经调控干预,是男科学研究的当务之急。本文回顾了急性神经损伤、前列腺癌、糖尿病和帕金森病所致的NED的研究进展。通过利用大鼠阴茎勃起神经的盆腔大神经节(MPG),在体外构建一个三维培养体系来研究各种生长因子和细胞信号通路对神经再生的影响。体外结果表明脑源性神经生长因子(BDNF)通过JAK/STAT信号通路可显著促进NED的恢复,并在体内证实了该效应。因此,通过调控JAK/STAT信号通路来达到神经调控干预措施预防治疗神经性勃起功能障碍成为可能。     

Development of a risk-adjusted capitation model based on principal inpatient diagnoses in Taiwan.

BACKGROUND AND PURPOSE: Taiwan's National Health Insurance (NHI) program has considered the use of capitation payments to health care providers as a method for control of the rising costs of the system. The establishment of capitation payments usually requires the performance of risk adjustment. The purposes of this study were to develop a diagnosis-based risk adjustment model for the NHI and to evaluate its predictability. METHODS: Using a 2% random sample of 371,620 NHI enrollees, the authors developed a Taiwan version of the Principal Inpatient Diagnosis Cost Groups (TPIPDCGs) from 1996 claim records to predict an individual's expenditure in 1997. Weighted least squares regression models were built in an estimation sample (two-thirds of the study sample), and were cross-validated in a validation sample (the remaining one-third of the study sample). Predictive R2 and predictive ratios were used to evaluate the model's predictability. RESULTS: Only 7.88% of the study sample could be classified into 1 of the 16 TPIPDCGs. Combined with demographic variables, which alone could explain 3.7% of the variation in an individual's future expenditure, the risk adjustment model based on TPIPDCGs could explain 12.2% of expenditure variation. In addition, the finding that the predictive ratios of the TPIPDCG model approximated unity better than those of the demographic model in all subgroups indicates that the capitation payment as predicted by the TPIPDCG model for each subgroup would better correlate to the actual spending. CONCLUSION: Taiwan's risk-adjusted capitation model based on principal inpatient diagnoses has higher predictability on individual's future expenditure than its counterpart in the USA. This finding provides insight into not only the development of Taiwan's diagnosis-based risk adjustment models but also the necessity of modification when applying foreign-developed risk adjustment models to the NHI.     

Histamine and tryptase modulate asthmatic airway smooth muscle GM-CSF and RANTES release.

Degranulating mast cells are increased in the airway smooth muscle (ASM) of asthmatics, where they may influence ASM function. The aim of the present study was to determine whether histamine and tryptase modulate ASM cell granulocyte-macrophage colony-stimulating factor (GM-CSF) and RANTES (regulated on activation, normal T-cell expressed and secreted) release and also to examine which receptors are involved in this release. Confluent, quiescent ASM cells from asthmatic and nonasthmatic donors were treated with histamine (1 microM-100 microM) with and without histamine receptor antagonist pre-treatment, or the protease-activated receptor (PAR)-2 agonists tryptase (0.5-5 nM) and SLIGKV (100 and 400 microM). The cells were then stimulated with interleukin (IL)-1beta and/or tumour necrosis factor (TNF)-alpha (10 ng.mL(-1)) or left unstimulated for 24 h. Release of GM-CSF and RANTES was determined by ELISA and prostaglandin (PG)E(2) measured by enzyme immunoassay. Neither histamine nor tryptase induced ASM GM-CSF or RANTES secretion. However, histamine increased IL-1beta-induced GM-CSF release and markedly reduced TNF-alpha-induced RANTES release by both asthmatic and nonasthmatic cells to a similar extent, but did not modulate PGE(2) release. All changes involved activation of the histamine H1 receptor as they were partially or fully blocked by chlorpheniramine, but not ranitidine. Tryptase, via its proteolytic activity, also potentiated GM-CSF, but not RANTES, release from asthmatic and nonasthmatic ASM cells induced by both cytokines. PAR-2 involvement in the tryptase potentiation was unlikely because SLIGKV had no effect. In conclusion, mast cells, through histamine and tryptase, may locally modulate airway smooth muscle-induced inflammation in asthma.     

如何强化医院医德医风建设

深圳市第二人民医院在不断完善、加大力度、加强医德医风建设方面制订出一系列纠风长效机制，采取有力措施：认真解决“红包”、回扣问题；进一步推动和规范药品集中招标采购工作；加强对中标药品价格和管理；切实加强医德医风建设，规范医疗服务行为；进一步规范药品生产流通秩序，加大源头治理力度；加强监管，严肃查处医药购销和医疗服务中的违纪违法行为。使医德医风常抓不懈，为医院在医疗服务行业、深化改革竞争中赢得了一席之地，也使医院在社会效益和经济效益能在全社会中取得了较高威信奠定了坚实的基础。     

高血压病患者动态脉压与左心室肥厚的关系

OBJECTIVE: To evaluate the relationship between the left ventricular hypertrophy (LVH) and the ambulatory pulse pressure and aortic root dimension (AOD) in essential hypertensive patients. METHODS: We monitored the 24-hour ambulatory blood pressure and applied echocardiography in 107 essential hypertensive patients. Using the left ventricular mass index (LVMI) as an index in evaluating LVH, the patients were divided into 2 groups: 29 cases in the LVH group and 78 in the non-LVH group. RESULTS: The average levels of 24-hour pulse pressure, daytime pulse pressure, nighttime pulse pressure and AOD were significantly different between patients with LVH and without LVH (P < 0.05). Multiple stepwise regression analysis showed that the changes in nighttime pulse pressure and AOD were closely related to LVMI (P < 0.001). CONCLUSION: The pulse pressure and AOD are important factors leading to LVH in patients with essential hypertension.