Synergistic effects of Nell-1 and BMP-2 on the osteogenic differentiation of myoblasts.

Osteogenesis is synergistically enhanced by the combined effect of complimentary factors. This study showed that Nell-1 and BMP-2 synergistically enhanced osteogenic differentiation of myoblasts and phosphorylated the JNK MAPK pathway. The findings are important because of the osteochondral specificity of Nell-1 signaling and the potential therapeutic effects of coordinated BMP-2 and Nell-1 delivery. INTRODUCTION: BMPs play an important role in the migration and proliferation of mesenchymal cells and have a unique ability to alter the differentiation of mesenchymal cells toward chondrogenic and osteogenic lineages. Signaling upstream of Cbfa1/Runx2, BMPs effects are not limited to cells of the osteoblast lineage. Thus, additional osteoblast-specific factors that could synergize with BMP-2 would be advantageous for bone regeneration procedures. NELL-1 (NEL-like molecule-1; NEL [a protein strongly expressed in neural tissue encoding epidermal growth factor like domain]) is a novel growth factor believed to preferentially target cells committed to the osteochondral lineage. MATERIALS AND METHODS: C2C12 myoblasts were transduced with AdLacZ, AdNell-1, AdBMP-2, or AdNell-1+AdBMP-2 overexpression viruses. Effects were studied by cell morphology, alkaline phosphatase activity, osteopontin production, and MAPK signaling. Additionally, in a nude mouse model, viruses were injected into leg muscles, and new bone formation was examined after 2 and 8 wk. RESULTS: C2C12 myoblasts co-transduced with AdNell-1+AdBMP-2 showed a synergistic effect on osteogenic differentiation as detected by alkaline phosphatase activity and osteopontin production. Nell-1 stimulation on AdNell-1 + AdBMP-2 preconditioned C2C12 cells revealed significant activation of the non-BMP-2 associated c-Jun N-terminal kinase (JNK) MAPK signaling pathway, but not the p38 or extracellular signal-regulated kinase (ERK1/2) MAPK pathways. Importantly Nell-1 alone did not induce osteogenic differentiation of myoblasts. In a nude mouse model, injection of AdNell-1 alone stimulated no bone formation within muscle; however, injection of AdNell-1+AdBMP-2 stimulated a synergistic increase in bone formation compared with AdBMP-2 alone. CONCLUSIONS: These findings are important because of the confirmed osteochondral specificity of Nell-1 signaling and the potential therapeutic effects of enhanced BMP-2 action with coordinated Nell-1 delivery.     

Expression of CD68 CD45RO CD20 and proliferating cell nuclear antigen in nasal polyps]

OBJECTIVE: To study the cellular expression of CD45RO, CD20, CD68 and proliferating cell nuclear antigen (PCNA) in nasal polyps. METHODS: Nasal polyp tissues from 50 patients were evaluated for cellular expression of CD45RO, CD20, CD68 and PCNA using immunohistochemistry SP by counting the average number in 5 chosen high-power fields, Histopathological observations were combined with HE. Analyses were performed on SPSS10.0. RESULTS: CD68+ cells were expressed more in nasal polyps dominated by eosinophils than by neutrophils(P < 0.05). There was no difference between CD45RO and CD20, but both of them had negative correlation(P = 0.05). Significant correlation was found between CD68+ cells and eosinophils or PCNA positive cells on epithelium. PCNA positive cells on epithelium had significant correlation on fibroblast (P < 0.05). CONCLUSION: Inflammatory cell infiltration (eosinophilia CD45RO, CD20, CD68) and cell proliferating in epithelium cells, glandular cell and fibroblast are strongly correlated with formation of nasal polyps. The nasal polyps are not only characteristic of eosinophilia but also by lymphocytes dominated by CD45RO and CD68 positive cells. CD68 may be stem cell of nasal polyp.     

肱骨髁间骨折的手术治疗及疗效评价

目的 探讨肱骨髁间骨折的手术方式并评价疗效。方法 1998年1月～2004年12月共手术治疗肱骨髁间骨折28例，进行随访分析。结果 28例中26例获随访，时间6个月～4年7个月，其中22例获2年以上随访。疗效评价参照casse‰。评分系统，优良率为65％。结论 骨折类型及手术方式直接影响预后。关节良好的复位和牢固的固定，以及术后早期积极的功能锻炼是得到良好疗效的保证。     

腹茧症的影像诊断

目的探讨腹茧症的影像特点，提高术前诊断水平。方法回顾性分析经手术病理证实的腹茧症6例，术前均进行立位腹部X线平片和腹部CT检查，4例同时行胃肠道钡剂造影，复习其影像表现。结果6例立位腹部X线平片中3例诊断为肠梗阻。4例胃肠道钡剂造影，均可见小肠交错盘绕成团，呈“菜花”状或“手风琴”状表现。6例CT检查，均可见小肠聚集成团，其周围可见膜样的囊状物将其包裹。结论对患者进行胃肠道造影时观察到“菜花”状征象，或CT检查时观察到小肠聚集成团被一层膜样物包裹，应考虑到腹茧症的可能。     

Neural network forecasts of the tropical Pacific sea surface temperatures.

A nonlinear forecast system for the sea surface temperature (SST) anomalies over the whole tropical Pacific has been developed using a multi-layer perceptron neural network approach, where sea level pressure and SST anomalies were used as predictors to predict the five leading SST principal components at lead times from 3 to 15 months. Relative to the linear regression (LR) models, the nonlinear (NL) models showed higher correlation skills and lower root mean square errors over most areas of the domain, especially over the far western Pacific (west of 155 degrees E) and the eastern equatorial Pacific off Peru at lead times longer than 3 months, with correlation skills enhanced by 0.10-0.14. Seasonal and decadal changes in the prediction skills in the NL and LR models were also studied.     

Association of the GNAS1 gene variant with hypertension is dependent on alcohol consumption.

The beta-adrenoceptor (beta-AR)-stimulatory guanine nucleotide-binding (Gs) protein system has been shown to play important roles in the cardiovascular system. The gene encoding the alpha-subunit of Gs proteins (GNAS1) is a candidate genetic determinant for hypertension. Because alcohol consumption is known to affect blood pressure partly through the beta-AR-Gs protein system, we examined the possible interaction between GNAS1 T393C polymorphism and drinking status in the association with hypertension in the present study. As a result, a non-significant but reasonable trend supporting the presence of an interaction was shown (p = 0.076). In line with this trend, the T393C polymorphism significantly interacted with drinking status in the association with systolic blood pressure (p = 0.028). Moreover, supporting the presence of an interaction, T allele carriers consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than CC homozygotes in non-drinkers and light drinkers. In contrast, CC homozygotes consistently had a higher probability of hypertension, higher systolic blood pressure, and higher diastolic blood pressure than T allele carriers in moderate to heavy drinkers. The present study also showed a significant interaction between the T393C polymorphism and drinking status in the association with pulse pressure (p = 0.026), reflected by a significant association between the T393C polymorphism and pulse pressure in moderate to heavy drinkers (p = 0.026). These findings may be helpful in conducting further molecular and biological studies on the relationship among the effects of alcohol, the beta-AR-Gs protein system, and hypertension.     

Proposal of a modified Child-Turcotte-Pugh scoring system and comparison with the model for end-stage liver disease for outcome prediction in patients with cirrhosis.

The model for end-stage liver disease (MELD) has a better predictive accuracy for survival than the Child-Turcotte-Pugh (CTP) system and has been the primary reference for organ allocation in liver transplantation. The CTP system, with a score range of 5-15, has a ceiling effect that may compromise its predictive power. In this study, we proposed a refined CTP scoring method and investigated its predictive ability. An additional point was given to patients with serum albumin < 2.3 g/dL, bilirubin > 8 mg/dL or prothrombin time prolongation > 11 seconds. The modified CTP system, containing class D, was compared to the MELD and original CTP system in 436 patients. There was a significant correlation between the MELD and modified CTP score (rho = 0.59, P< 0.001). Using mortality as the endpoint, the area under receiver operating characteristic curve for modified CTP system was 0.895 compared with 0.872 for MELD (P = 0.450) and 0.809 for original CTP system (P < 0.001) at 3 months; the area was 0.890, 0.837 and 0.756, respectively (P = 0.051 and < 0.001, respectively) at 6 months. The risk ratio per unit increase for the modified CTP score was 2.7 and 3.08 at 3 and 6 months respectively (P < 0.001). In conclusion, the modified CTP system can be proposed as an alternative prognostic model for cirrhotic patients. By extending the score range according to the influence of the laboratory-derived variables, the modified CTP system has a better performance than the original system and is as efficient as the MELD for outcome prediction.     

Interleukin-18 Affects Local Cytokine Expression But Does Not Impact on the Development of Kidney Allograft Rejection

Interleukin-18 is predominantly a macrophage-derived cytokine with a key role in inflammation and cell-mediated immunity. Having previously demonstrated IL-18 upregulation in a rat model of kidney rejection, here we examined IL-18 in a fully MHC-mismatched murine model of acute kidney rejection using IL-18-deficient recipients (IL-18-/-) and animals administered neutralizing IL-18 binding protein (IL-18BP). Gene expression of IL-18 and its receptor were significantly upregulated in allografts compared to isografts, as was the cellular infiltrate (T cells and macrophages) (p < 0.001). Allografts developed kidney dysfunction (p < 0.05) and tubulitis (p < 0.01) not observed in controls. There was a significant reduction in gene expression of IL-18 downstream pro-inflammatory molecules (iNOS, TNFalpha and IFNgamma) in IL-18-/- recipients (p < 0.01), and IL-18BP-treated animals. The CD4+ infiltrate and IL-4 mRNA expression was greater in the IL-18-/- recipients than wild-type (WT) allografts and IL-18BP-treated animals (p < 0.05), suggesting a Th2-bias which was supported by IFNgamma and IL-4 ELISPOT data and an increased eosinophil accumulation (p < 0.001). Neither IL-18 deficiency nor neutralization prevented renal dysfunction or tubulitis. This study demonstrates increased production of IL-18 in murine kidney allograft rejection and provides evidence that IL-18-induced pathways of inflammation are active. However, neither IL-18 deficiency nor neutralization was protective against the development of allograft rejection.     

食管癌三维适形后程加速超分割放射治疗的疗效分析

目的评价三维适形后程加速超分割放射治疗食管癌的疗效及放疗反应、并发症。方法2002年2月至2004年5月,71例食管鳞癌随机分成两组,三维适形后程加速超分割组36例,食管病变上下外约4cm,前后、左右外约0.5~1cm作为PTV1,每次2GY,每周5次,DT40GY后,病变上下外约2cm,前后、左右外约0.5~1cm作为PTV2,每日2次,每次1.5GY,间隔4~6小时,总疗程6周,总剂量67GY/38次。非三维适形后程加速超分割组35例,时间、剂量、分割方式同适形组。所有病例均采用8MV-X外照射。结果1、2、3年的生存率和原发肿瘤的局控率,与非适形后程加速超分割比较,适形组明显提高,分别为88.9%、75%、63.9%比68.6%、51.4%、40%和86.1%、72.2%、58.3%比65.7%、48.5%、34.3%。适形组的急性放射反应明显低于非适形后程加速超分割组,两组有显著差别。结论本研究的初步结果表明食管癌适形后程加速超分割放射治疗的疗效优于非适形后程加速超分割组。     

Cigarette smoke toxicants alter growth and survival of cultured mammalian cells.

Our purpose was to determine the effects of six cigarette toxicants (pyridine, nicotine, 2-ethylpyridine, 3-ethylpyridine, p-cresol, and pyrazine) on three types of cultured mammalian cells (human umbilical vein endothelial cells [HUVECs], human microvascular endothelial cells [HMVECs], and NIH 3T3 cells) using a cell proliferation/survival assay. Synchronized cells were cultured in proliferation or survival medium containing various doses (10(-18)M-10(-2)M) of the tested chemicals. After 48 h, cells were counted using a hemacytometer. The no observable adverse effect level (NOAEL), lowest observable adverse effect level (LOAEL), and the efficacy were determined for each compound in the cell proliferation and survival assays. Pyridine and p-cresol did not show significant effects with any cell types, except at high doses. Derivitization of the pyridine ring altered its potency, especially when an ethyl group or nitrogen was added. In survival medium, nicotine stimulated proliferation of all three cell types at doses found in smoker's serum (10(-8)M-10(-7)M). For HUVEC and HMVEC, 2-ethylpyridine, 3-ethylpyridine, and pyrazine inhibited proliferation in proliferation medium and induced cell death in survival medium at attomolar and femtomolar doses. All chemicals, except pyridine and pyrazine, stimulated NIH 3T3 cell proliferation at low doses and induced cell death at high doses. LOAELs and efficacies revealed that endothelial cells from a developing organ (umbilical cord) were more sensitive to these chemicals than endothelial cells from an adult organ (lung). 3-Ethylpyridine and pyrazine, which induced cell death at low doses, are added to consumer products and should be subjected to further toxicological testing.