Enhancement of NF-kappaB activity by resveratrol in cytokine-exposed mesangial cells

Resveratrol, a natural polyphenolic phytoalexin, has been considered as a potential anti-inflammatory agent because of its suppressive effect on nuclear factor-kappaB (NF-kappaB). However, we recently found that treatment of glomerular mesangial cells with resveratrol significantly and dose-dependently enhanced NF-kappaB activation triggered by proinflammatory cytokines. This finding was evidenced by different reporter assays as well as by expression of an endogenous NF-kappaB-dependent gene, intercellular adhesion molecule-1. The NF-kappaB promoting effect of resveratrol was also observed in renal tubular LLCPK1 cells, but not in HepG2 hepatoma cells. In all cell types tested, treatment with resveratrol alone did not affect NF-kappaB activity. The enhanced activation of NF-kappaB by resveratrol progressed for at least 24 h and was accompanied by sustained down-regulation of an endogenous NF-kappaB inhibitor, IkappaBbeta, but not IkappaBalpha. Although expression of inducible nitric oxide synthase was suppressed by resveratrol, nitric oxide, a negative regulator of NF-kappaB, was not involved in the regulation of NF-kappaB by resveratrol. These data elucidated, for the first time, that resveratrol may enhance activation of NF-kappaB under certain circumstances.     

Characterization of Hprt mutations in cDNA and genomic DNA of T-cell mutants from control and 1,3-butadiene-exposed male B6C3F1 mice and F344 rats

A multiplex PCR procedure for analysis of genomic DNA mutations in the mouse hypoxanthine-guanine phosphoribosyltransferase (Hprt) gene was developed and then used with other established methods for the coincident identification of large- and small-scale genetic alterations in the Hprt gene of mutant T-cell isolates propagated from sham- and 1,3-butadiene (BD)-exposed mice and rats. The spectra data for RT-PCR/cDNA analysis and multiplex PCR of genomic DNA from Hprt mutants were combined, and statistical analyses of the mutant fractions for the classes of mutations identified in control versus exposed animals were conducted. Under the assumption that the mutant fractions are distributed as Poisson variates, BD exposure of mice significantly increased the frequencies of (1) nearly all types of base substitutions; (2) single-base deletions and insertions; and (3) all subcategories of deletions. Significantly elevated fractions of G:C-->C:G and A:T-->T:A transversions in the Hprt gene of BD-exposed mice were consistent with the occurrence of these substitutions as the predominant ras gene mutations in multiple tumor types increased in incidence in carcinogenicity studies of BD in mice. BD exposure of rats produced significant increases in (1) base substitutions only at A:T base pairs; (2) single-base insertions; (3) complex mutations; and (4) deletions (mainly 5' partial and complete gene deletions). Future coincident analyses of large- and small-scale mutations in rodents exposed to specific BD metabolites should help identify species differences in the sources of deletion mutations and other types of mutations induced by BD exposures in mice versus rats.     

Emergency department visits for asthma: the role of frequent symptoms and delay in care.

BACKGROUND: Use of the emergency department (ED) for asthma care is a costly form of health care that is largely preventable. However, little is known about how to reduce the number of people using the ED for asthma care. OBJECTIVE: To identify modifiable factors related to ED visits for asthma among a diverse nonelderly adult population. METHODS: This study used cross-sectional data from the 2001 California Health Interview Survey. A total of 4,359 adult respondents ages 18 to 64 years who reported being diagnosed as having asthma and experiencing symptoms in the past year were included. Any ED visits due to asthma in the previous 12 months among all nonelderly respondents with asthma, with stratification by those with daily or weekly symptoms and with less frequent symptoms, were examined. RESULTS: Adults with daily or weekly asthma symptoms, with fair or poor health status, and who delayed care for asthma because of cost or insurance issues were more likely to visit the ED for asthma. Stratification of the study population into those with daily or weekly symptoms and those with less frequent symptoms revealed that delay in care due to cost or insurance issues and fair or poor health status remained significant for both groups. Latinos and women were more likely to visit the ED in the severe asthma group, whereas Asian, African American, and uninsured adults were more likely to visit the ED in the group with less severe asthma. CONCLUSIONS: Results suggest that to prevent ED visits for asthma, it is important to control asthma symptoms. However, it is equally if not more important to reduce delays in receiving asthma care.     

川崎病休克综合征合并心力衰竭1例临床病例分析及文献复习

目的 探讨川崎病休克综合征 (Kawasaki Disease Shock Syndrome,KDSS) 合并心力衰竭的临床特征。方法 分析 1例KDSS合并心力衰竭患儿的临床资料,并复习相关文献。结果 KDSS在川崎病中不常见,但表现严重,在急性期可以导致循环衰竭,表现为心动过速、毛细血管充盈时间延长、四肢末端发凉、脉搏细弱、尿量减少或意识障碍等而发生全身循环衰竭,早期识别,及时给予人免疫球蛋白和激素等综合治疗可明显改善患者休克的状况。结论 KDSS是川崎病中少见但较为严重的临床并发症,早期识别及综合的临床治疗方法是减少KDSS的有效措施。     

Distinct roles of type I bone morphogenetic protein receptors in the formation and differentiation of cartilage

The bone morphogenetic proteins (BMPs), TGFβ superfamily members, play diverse roles in embryogenesis, but how the BMPs exert their action is unclear and how different BMP receptors (BMPRs) contribute to this process is not known. Here we demonstrate that the two type I BMPRs, BMPR-IA and BMPR-IB, regulate distinct processes during chick limb development. BmpR-IB expression in the embryonic limb prefigures the future cartilage primordium, and its activity is necessary for the initial steps of chondrogenesis. During later chondrogenesis, BmpR-IA is specifically expressed in prehypertrophic chondrocytes. BMPR-IA regulates chondrocyte differentiation, serving as a downstream mediator of Indian Hedgehog (IHH) function in both a local signaling loop and a longer-range relay system to PTHrP. BMPR-IB also regulates apoptosis: Expression of activated BMPR-IB results in increased cell death, and we showed previously that dominant-negative BMPR-IB inhibits apoptosis. Our studies indicate that in TGFβ signaling systems, different type I receptor isoforms are dedicated to specific functions during embryogenesis.     

烧伤诊疗信息管理系统的开发

系统主要以烧伤科病房管理为主，包括病人的诊治和用药管理。通过计算机对病人的用药及诊治进行分析、统计和查询。     

Measurement of human cytomegalovirus loads by quantitative real-time PCR for monitoring clinical intervention in transplant recipients

Quantitative monitoring of human cytomegalovirus (HCMV) infection is helpful in determining appropriate antiviral management of transplant recipients. Quantitative PCR technologies have demonstrated accuracy in measuring systemic HCMV loads. A total of 298 consecutive whole-blood specimens submitted to the Clinical Virology Laboratory at Vanderbilt University Medical Center from 15 February to 31 October 1999 were included in the study. In addition to a qualitative colorimetric microtiter plate PCR assay (MTP-PCR) and a semiquantitative pp65 antigenemia assay, each specimen was measured for HCMV loads by a quantitative PCR assay performed on an ABI PRISM 7700 Sequence Detection System (TaqMan). Compared to results of the MTP-PCR, the sensitivity, specificity, positive predictive value, and negative predictive value were 70.5, 97.5, 87.8, and 92.8% for the antigenemia assay and were 96.7, 92.0, 75.6, and 99.1% for the TaqMan assay, respectively. There was a high correlation between antigenemia values and HCMV loads as determined by the TaqMan (r = 0.989; P < 0.001). Antigenemia values of 0, 1 to 10, 11 to 100, 101 to 1,000, and over 1,000 positive cells per 2 x 10(5) leukocytes corresponded to median HCMV loads measured by TaqMan of 125, 1,593, 5,713, 16,825, and 5,425,000 copies/ml, respectively. Corresponding to antigenemia values of 1 to 2, 10, and 50 positive cells per 2 x 10(5) leukocytes, HCMV viral loads of 1,000, 4,000, and 10,000 copies/ml are proposed as cutoff points for initiating antiviral therapy in patient groups with high, intermediate, and low risk of CMV diseases.     

APAAP免疫印迹技术对抗副流感病毒1，3型单克隆抗体识别抗原表位的研究

副流感病毒１，３型（ＰａｒａｉｎｆｌｕｅｎｚａＶｉｒｕｓｔｙｐｅ１，３：ＰＩＶ＿１．３）单克隆抗体（ＭｃＡｂ）应用免疫印迹技术（Ｗｅｓｔｅｒｎｂｌｏｔｔｉｎｇ）识别抗原表位特性。结果表明：ＰＩＶ＿１．３抗原经还原剂处理后，ＳＤＳ－ＰＡＧＥ５％～１５％梯度胶电泳，能分辨二十多条清晰的蛋白带。转印后采用碱性磷酸酶抗碱性磷酸酶复合物（ＡＰＡＡＰ）染色，本底浅，呈玫瑰红色带，优于ＨＲＰ染色结果。ＰＩＶ＿１的５株ＭｃＡｂ：ＩＣ＿５、ＩＨ＿６、ＩＨ＿２、ＩＣ＿１０、３Ｄ＿５分别与６８ｋＤ～５０ｋＤ、６８ｋＤ、５８ｋＤ～２７ｋＤ、５５ｋＤ～５０ｋＤ、５０ｋＤ对应ＰＩＶ＿１的蛋白质抗原表位起反应。ＰＩＶ＿３的６株ＭｃＡｂ：２Ａ＿１０、５Ｇ＿３、２Ｄ＿１１、２Ｅ＿１０、２Ｂ＿１２、４Ｆ＿１２与７０ｋＤ、６８ｋＤ、６０ｋＤ～５０ｋＤ、５５ｋｐ～４０ｋＤ、５５ｋＤ、４０ｋＤ对应的蛋白质抗原表位特异结合，说明ＰＩＶ＿１．３的１１株ＭｃＡｂ同对应抗原表位点的结合分布较广，有利于对ＰＩＶ＿１．３抗原的快速、敏感、特异检测。     

天然角蛋白自身反应性B细胞亚群及功能的分析

目的:明确天然角蛋白反应性B细胞的亚群及解剖定位,初步分析其分泌天然抗角蛋白自身抗体(anti-keratinautoantibody,AKautoAb)的能力。方法:取SPF级C57BL/6小鼠的脾细胞和腹腔细胞,荧光抗体染色后用流式细胞仪分析角蛋白反应性B细胞亚群。将脾脏和腹腔淋巴细胞体外培养后,用ELISA分析AKautoAb的滴度,用ELISPOT法分析分泌AKautoAb的B细胞数。结果:腹腔中几乎所有结合角蛋白的B细胞均为B-1a细胞,脾脏中结合角蛋白的B细胞以边缘带B细胞为主。腹腔细胞中分泌AKautoAb的细胞数显著多于脾细胞,其培养上清中AKautoAb的滴度显著高于脾细胞。结论:角蛋白反应性B细胞存在于3个成熟B细胞亚群:B-1细胞、滤泡B细胞和边缘带B细胞,其中CD5 的B-1a细胞具有活跃的分泌AKautoAb的能力。