ADAM28: A potential oncogene involved in asbestos‐related lung adenocarcinomas

Asbestos‐related lung cancer accounts for 4–12% of all lung cancers worldwide. Since putative mechanisms of carcinogenesis differ between asbestos and tobacco induced lung cancers, tumors induced by the two agents may be genetically distinct. To identify gene expression biomarkers associated with asbestos‐related lung tumorigenicity we performed gene expression array analysis on tumors of 36 patients with primary lung adenocarcinoma, comparing 12 patients with lung asbestos body counts above levels associated with urban dwelling (ARLC‐AC: asbestos‐related lung cancer‐adenocarcinoma) with 24 patients with no asbestos bodies (NARLC‐AC: non‐asbestos related lung cancer‐adenocarcinoma). Genes differentially expressed between ARLC‐AC and NARLC‐AC were identified on fold change and P value, and then prioritized using gene ontology. Candidates included ZNRF3, ADAM28, PPP1CA, IRF6, RAB3D, and PRDX1. Expression of these six genes was technically and biologically replicated by qRT‐PCR in the training set and biologically validated in three independent test sets. ADAM28, encoding a disintegrin and metalloproteinase domain protein that interacts with integrins, was consistently upregulated in ARLC across all four datasets. Further studies are being designed to investigate the possible role of this gene in asbestos lung tumorigenicity, its potential utility as a marker of asbestos related lung cancer for purposes of causal attribution, and its potential as a treatment target for lung cancers arising in asbestos exposed persons. © 2010 Wiley‐Liss, Inc.     

Rare detection of hepatitis B and hepatitis C virus genomes by polymerase chain reaction in seronegative donors with elevated alanine aminotransferase

BACKGROUND: Since screening for antibody to hepatitis C virus (HCV) was introduced in 1990, posttransfusion hepatitis has been reduced to nearly background levels. This has led to reconsideration of the value of testing donated blood for elevated alanine aminotransferase (ALT). The contribution of ALT testing in detecting seronegative infection was evaluated by the performance of polymerase chain reaction (PCR) for hepatitis B virus (HBV) or HCV in plasma from ALT-elevated blood units. STUDY DESIGN AND METHODS: Testing was performed on 375 units of plasma, derived from an equivalent of 47,500 blood donations, with a highly sensitive hemi-nested PCR procedure. Using a triplet of primers directed at the conserved regions of HBV DNA and 5'-noncoding regions of HCV RNA, the hemi-nested PCR assay can reliably amplify 10 viral molecules to levels detectable in ethidium bromide-stained agarose gels. Pools of plasma from groups of four donors were screened with hemi-nested PCR. For any reactive pools, the plasma from individual donors was retested twice on different aliquots. RESULTS: Two of 375 units, both with midrange ALT elevation, were repeatedly reactive in hemi-nested PCR (one each for HBV DNA and HCV RNA). However, samples from the two suspect donors tested 9 and 5 months later revealed no seroconversion, elevated ALT, or viral genomes in hemi-nested PCR. CONCLUSION: The lack of confirmed HBV or HCV infection in this study representing an estimated 47,500 voluntary blood donations suggests that routine ALT testing for further prevention of posttransfusion hepatitis after exclusion of HBV- and/or HCV-seropositive blood may be superfluous.     

应用Heath-Carter体型法分析辽西地区城市汉族儿童青少年1263名体型特征

目的:分析辽西地区城市汉族儿童青少年的体型发育规律和特点,为体质人类学补充必要的数据。方法:按整群分层抽样法,抽取2001-07/2003-09辽西地区城市7所中小学7～19岁经学校正常体质检查证明身体健康的汉族学生,按性别分两大组,每大组按年龄分12小组,7～18岁每岁为1个年龄组,18～19岁为1个年龄组,每小组45～86名,共分24组,搜集完整资料1263名(男657名,女606名)。采用Heath-Carter体型法,每项指标测量2次,取平均值,10项指标由专人负责,测试数据按年龄和性别在微机中建立数据库,依次计算出各年龄组的内因子、中因子和外因子,体型图上的X,Y坐标值,身高/体质量1/3,样本中平均体型点到所有体型点空间距离的均数,三维空间中两个体型点间的差异,体脂含量和各类体型分布频数。结果:参加调查1263名,均进入结果分析。①7～17岁儿童青少年身高、体质量随年龄的增加而增长。平均身高、体质量男生大于女生。身高/体质量1/3指数除14,16和17岁外,各年龄组女生>男生,平均值女生>男生。体脂含量11岁以前男生>女生,12岁以后女生>男生。②辽西地区城市汉族男生的平均体型值为3.9-3.5-3.4,属中间型,女生平均体型值为4.3-2.9-3.6,属偏外胚层的内胚层体型。体型频数的变化提示辽西城市汉族男生体型分布较散,女生分布较集中,主要在内胚层体型。③内因子男生在3.18～4.81,女生在3.05～5.33,11岁以前男生>女生,12岁以后女生>男生;中因子男生在3.02～4.23,女生在2.54～3.42,除16岁男女相差不多外,其他年龄组男生>女生,外因子男生在2.64～4.22,女生在2.92～4.14,13岁以前女生>男生,14岁以后男生>女生。因此,男生较女生骨骼粗壮,肌肉发达,随着年龄的增长,女生的皮下脂肪更发达,体态丰满,男生的身体相对瘦高程度增长,身材修长。男女各年龄组间体型比较,7～,8～,9～,10～,11～,12～,13～,14～,15～,16～,17～,18～19岁三维空间中两个体型点间的差异值分别为0.95,0.85,1.10,1.06,1.37,0.43,0.87,1.44,1.42,1.12,1.11,1.33,7～,8～,12～,14～,17～,18～19年龄组男女间体型差异有显著性(t=2.07,4.09,3.12,3.86,3.39,3.99,P<0.05)。④与国内汉族及其他少数民族相比,辽西汉族男生体脂最多,骨骼肌肉不发达,身体相对矮小;辽西地区汉族女生体脂较多,骨骼肌肉不发达,体型修长。结论:辽西地区城市男生较女生骨骼粗壮,肌肉发达,随着年龄的增长,女生的皮下脂肪更发达,体态丰满,男生的身体相对瘦高程度增长,身材修长。与国内汉族及其他少数民族相比,辽西地区城市汉族儿童青少年体脂发育较好,骨骼肌肉欠发达,青春期是形成健壮体型的关键时期,辽西地区城市儿童青少年应注意合理饮食和加强体育锻炼。     

神经生长因子对局灶性脑缺血神经干细胞巢蛋白表达及细胞类型的影响

目的:实验于2006-02/07在锦州医学院科学实验中心完成。将72只健康SD大鼠按随机数字表法分为假手术组、模型组、神经生长因子治疗组,每组24只。采用Logna等改良法复制大脑中动脉血栓模型,动物清醒2h后进行功能评价,动物神经功能达到2级的纳入实验。假手术组除不进行大脑中动脉线栓外,其余同模型组。神经生长因子治疗组于缺血后立即腹腔注射神经生长因子1000μg/kg,1次/d。于缺血后1,3,7,14d处死动物,运用免疫组化和免疫荧光双标的方法观察神经生长因子对脑缺血后神经干细胞巢蛋白的表达及其细胞类型的影响。结果:72只大鼠均进入结果分析。①神经生长因子治疗组和模型组大脑皮质均可见巢蛋白阳性细胞,细胞呈圆形或椭圆形。与模型组相比,除缺血后1d外,神经生长因子治疗组其他时间点的巢蛋白阳性细胞数均明显高于模型组,两组缺血后各时间点的巢蛋白阳性细胞数均高于假手术组[模型组:(3.47±0.51),(5.13±1.14),(13.95±3.56),(8.97±2.08)个;神经生长因子治疗组:(3.81±0.66),(9.88±2.08),(19.87±3.86),(26.17±2.90)个,假手术组:0,P<0.05,P<0.01]。②模型组和神经生长因子治疗组3d时缺血皮质巢蛋白阳性突起主要与胶质纤维酸性蛋白共存,14d时巢蛋白与神经元特异性烯醇化酶共存明显增多。结论:神经生长因子能增加局灶性脑缺血后巢蛋白的阳性细胞的数目,并促进其分化为神经元和神经胶质细胞。     

Disseminated coxsackievirus B fulminant myocarditis in an immunocompetent adult: A case report: Case of disseminated coxsackievirus myocarditis

Coxsackieviral myocarditis is associated with systemic involvement in neonates; however, fulminant coxsackieviral myocarditis is rare in adults, and its dissemination with fatal myocarditis involving kidneys, liver, and adrenal is further rarely reported. We report a case of fulminant myocarditis along with dissemination of coxsackievirus, which was clinically unrecognized.     

Nateglinide and glibenclamide metabolic effects in naïve type 2 diabetic patients treated with metformin

Background and objective: Most antidiabetic agents target only one of several underlying causes of diabetes. The complementary actions of the glinides and the biguanides may give optimal glycemic control in patients with type 2 diabetes mellitus. The aim of the present study was to compare the effects of nateglinide plus metformin with glibenclamide plus metformin on glucose and lipid metabolism, and haemodynamic parameters in patients with type 2 diabetes mellitus. Methods: We enrolled 248 type 2 diabetic patients. Patients were randomly assigned to receive nateglinide (n = 124) or glibenclamide (n = 124), after 6 months of run‐in, in which we titrated nateglinide (starting dose 180 mg/day), glibenclamide (starting dose 7·5 mg/day), and metformin (starting dose 1500 mg/day). The final doses were (mean ± standard deviation), 300 ± 60, 12·5 ± 2·5, and 2500 ± 500 mg/day, respectively. We followed these patients for 1 year after titration. We assessed body mass index (BMI), fasting (FPG) and post‐prandial (PPG) plasma glucose, glycosylated haemoglobin (HbA_1c), fasting (FPI) and post‐prandial (PPI) plasma insulin, homeostasis model assessment (HOMA) index, and lipid profile [total cholesterol (TC), low density lipoprotein‐cholesterol (LDL‐C), high density lipoprotein‐cholesterol (HDL‐C), triglycerides (Tg), apolipoprotein A‐I (Apo A‐I), and apolipoprotein B (Apo B)], systolic blood pressure (SBP), and diastolic blood pressure (DBP). All variables were evaluated at baseline and after 3 and 6 months in the run‐in period, and at baseline, and after 3, 6, 9 and 12 months for both treatment groups. Results and discussion: Body mass index did not show any significant change during the study. We observed a significant improvement from baseline to 1 year on HbA_1c (P < 0·01 vs. baseline and vs. glibenclamide group, respectively), FPG (P < 0·01 vs. baseline), PPG (P < 0·01 vs. baseline), and on HOMA index (P < 0·05 vs. baseline) in the nateglinide group. In the glibenclamide group, we found significant changes in HbA_1c (P < 0·05 vs. baseline), FPG (P < 0·01 vs. baseline), PPG (P < 0·05 vs. baseline), and HOMA index (P < 0·05 vs. baseline). No significant change was observed in TC, LDL‐C, HDL‐C, Tg, Apo A‐I, Apo B, SBP, DBP and HR in either group after 3, 6, 9 and 12 months. These effects of nateglinide and glibenclamide on insulin‐resistance parameters are in agreement with previous reports. Contrarily to previous reports, we did not observe any significant BP change in patients treated with glibenclamide. Although both nateglinide and glibenclamide attenuated PPG and HOMA index, they did not have significant effects on lipid metabolism, as already shown in subjects with type 2 diabetes and good glycemic control. Conclusion: Nateglinide improved glycemic control better than glibenclamide in combination with metformin.     

The immunogenicity and safety of a reduced PRP-content DTPw-HBV/Hib vaccine when administered according to the accelerated EPI schedule

Background  

Combination vaccines improve coverage, compliance and effectively introduce new antigens to mass vaccination programmes. This was a phase III, observer-blind, randomized study of GSK Biologicals diphtheria-tetanus-whole cell pertussis vaccine combined with hepatitis B and Haemophilus influenzae type b vaccines, containing a reduced amount of polyribosyl-ribitol-phosphate (PRP) and a DTPw component manufactured at a different site (DTPw-HBV/Hib_2.5 [Kft]). The primary aim of this study was to demonstrate that DTPw-HBV/Hib_2.5 [Kft] was not inferior to the licensed DTPw-HBV/Hib (Tritanrix(tm)-HepB/Hiberix(tm)) vaccine or the DTPw-HBV/Hib_2.5 vaccine, also containing a reduced amount of PRP, with respect to the immune response to the PRP antigen, when administered to healthy infants, according to the Expanded Programme for Immunization (EPI) schedule at 6, 10 and 14 weeks of age.     

Cytogenetic and histologic correlations in malignant lymphoma

Although a number of studies have indicated correlations between histologic subtypes of tumors and certain nonrandom chromosome changes, cytogenetic studies of lymphoma are in an early stage compared to those of leukemia. No comprehensive analysis of available data has so far been attempted in the literature either. Here we present an analysis of chromosome changes and their correlation with subtypes of lymphoma studied by conventional histology and cell surface markers, as observed in two sets of data: a group of 65 karyotypically abnormal tumors sequentially ascertained and studied by us during the period January 1, 1984 to April 30, 1985, and a larger data set derived by combining our data with those from two published series from the University of Minnesota that are comparable to our data. These combined data, which comprise the largest data set on the cytogenetics of lymphomas assembled so far, enabled a comprehensive analysis of correlation between chromosome change and tumor histology and the patterns of chromosome instability in these tumors. We found several significant associations, some previously described and others now recognized, between nonrandom chromosome gains, breaks, translocations, and deletions and histologic subtypes of tumors that characterize lymphomas. The data indicate that finding of chromosome breaks at certain sites (eg, 8q24, 14q32, 18q21) is of diagnostic value in dealing with cases of unusual lymphoma. Furthermore, nonrandom chromosome breakage exhibited three distinct patterns that reflected three levels of etiologically relevant genetic change.