Microarray studies of gene expression in circulating leukocytes in kidney diseases

The molecular characterization of changes in mRNA expression in renal tissue during disease is hampered by the acquisition of sufficient mRNA to do genomewide expression profiling. In many renal diseases, such as systemic lupus erythematosus, IgA nephropathy, antineutrophil cytoplasmic autoantibody (ANCA) associated glomerulonephritis, and small-vessel vasculitis (ANCA disease), circulating leukocytes play a role in onset, progression, and severity of the condition. Circulating leukocytes are readily isolated and supply sufficient mRNA for analysis, allowing molecular investigation into their involvement in the disease process. Our laboratory has undertaken a systematic study of the genomewide expression profiles of the circulating leukocytes from patients with a variety of renal diseases (ANCA disease, IgA nephropathy, lupus nephritis, focal segmental glomerulosclerosis), using the Affymetrix high-density gene chip array technology. Analysis of the data showed clustering of expressed genes unique for each individual disease group. These results imply that significant gene expression changes occur in leukocytes that are circulating in patients with renal diseases. In addition, gene expression has been studied in leukocytes activated in vitro by mechanisms that mimic pathogenic events in vivo. The expression levels of genes identified in in vitro studies were compared with the patient leukocyte gene expression to determine whether similar pathological events were occurring in vivo.     

称重法和化学分析法评估人群膳食矿物质摄入量的比较

目的探讨称重法和化学分析法评估人群矿物质摄入量的差异和相关性。方法同时使用称重法和化学分析法对89名上海市居民进行膳食调查,并对两种调查方法测得的钙、镁、铁、锌、铜、锰摄入量进行比较分析。结果称重法调查的6种矿物质元素的摄入量高于化学分析法(P<0.05),称重法调查的平均每天钙、镁、铁、锌、铜、锰摄入量比化学分析法分别高20.9%、67.4%、19.5%、84.4%、46.7%和33.3%;称重法与化学分析法测得的钙、镁、铁、锌、铜、锰摄入量均呈显著正相关(P<0.01),相关系数分别为0.571、0.672、0.521、0.524、0.538和0.691。结论称重法测得的人群膳食矿物质摄入量高于化学分析法。     

腹腔镜在小儿离断性肾盂成形术中的应用与随访

目的 探讨腹腔镜下离断性肾盂成形术的效果及适应证.方法 总结21例经腹腔途径行腹腔镜离断性肾盂成形术治疗肾盂输尿管连接部狭窄(UPJO)所致肾积水的经验,对比同期开放手术治疗的35例患儿术后影像学.结果 第一例腹腔镜肾盂成形术历时4 h 50 min,随后的20例为1 h 40 min～2 h 30 min,术中出血量5～10 ml.20例术后3～5 d出院,恢复好.1例术后7 d因患儿外伤性肾盂内出血,血块堵塞双J管,致肾盂漏尿、形成尿腹,遂行开放探查术;术中见吻合口良好,清除肾盂内血块,冲洗双J管,放置.肾造瘘管,7 d后拔除肾造瘘管出院.21例患儿术后4～6周拔除双J管.2组患儿均分别在术后1个月、3个月、6个月行B超或CTU检查.腔镜组吻合口通畅率为95.2%(20/21),开放组为100%(35/35),二者差异无显著性意义.结论 熟练掌握腹腔镜缝合技术,是圆满完成经腹腔镜离断性肾盂成形术的基础.腹腔镜下手术创伤轻微,手术效果与传统的开放手术无差别;在应用腹腔镜肾盂成形术的初期,宜选择中度以下肾盂扩张的病例,待熟练后,逐步应用于重度积水病例,确保手术效果.     

Growth Hormone: A Promising Treatment for the Failing Heart?

Many pathologic processes that accelerate the progression of heart failure, such as cardiac remodeling and impaired contractility, may be modulated by administration of recombinant growth hormone. The agent improves structural and functional aspects of the failing heart both in the short term and after several months of therapy. However, conflicting clinical results cast doubt on whether it has a clear benefit in all of these patients. In addition, growth hormone therapy may be associated with cardiac and noncardiac adverse effects. Many questions must be addressed before its place in heart failure therapy is established. Optimal patient population, dosing regimen, duration of therapy, and effect on patient survival are unknown. Until larger, blinded studies are completed, growth hormone therapy remains an investigational approach to managing refractory heart failure.     

Components of intrinsic drug resistance in the rat hepatoma.

A carcinogen-transformed rat hepatoma cell line (Reuber H-35) was utilized as a model system for investigation of the biochemical factors which may limit the effectiveness of chemotherapy in intrinsically resistant tumors such as hepatocellular carcinoma. Northern blotting demonstrated expression of mRNA coding for the P-170 membrane-glycoprotein associated with the multi-drug resistance phenotype, while Western blotting identified the P-170 glycoprotein in the hepatoma cell membrane. Consistent with these observations, tumor cell sensitivity to the vinca alkaloids, vincristine and vinblastine, to the anthracycline antibiotics, Adriamycin and daunorubicin, and to the demethylepipodophyllotoxin derivative, VM-26, was enhanced by continuous incubation in the presence of the calcium channel antagonist, verapamil. Verapamil produced a minimal change in cell sensitivity to the demethylepipodophyllotoxin derivative, VP-16, and to the aminoacridine, m-AMSA. Relatively high detoxification potential via the glutathione metabolic pathway was also observed in the hepatoma cell. The capacity of topoisomerase II in nuclear extracts from the hepatoma cell to mediate cleavable complex formation stimulated by VM-26, VP-16 and m-AMSA appeared to be at least comparable to, if not greater than that from drug-sensitive HL-60 cells, suggesting that drug resistance may not occur at the level of this enzyme. Consistent with findings in a number of tumor cell lines resistant to antineoplastic drugs, the antiproliferative activity of the topoisomerase II inhibitors VM-26, VP-16 and m-AMSA appeared to be dissociable from the induction of DNA strand breaks, suggesting that such lesions in DNA may fail to fully account for the antiproliferative activity of these agents in the hepatoma cell.     

Human myeloid alpha 3-fucosyltransferase is involved in the expression of the sialyl-Lewis(x) determinant, a ligand for E- and P-selectin

The sialyl-Lex determinant (NeuAc alpha 2-->3Gal beta 1-->4[Fuc alpha- 1-->3]GlcNAc) has been identified as a major ligand in the selectin- mediated adhesion of neutrophils and monocytes to activated endothelium or platelets. This carbohydrate epitope is formed by the sequential action of alpha 3-sialyltransferase and alpha 3-fucosyltransferase on N- acetyllactosamine (Gal beta 1-->4GlcNAc) disaccharide termini of glycoconjugates. We have addressed the role of the human myeloid alpha 3-fucosyltransferase in the expression of this epitope at the leucocyte surface by determining its activity in human-mouse leukemic cell hybrids (WEGLI), normal human granulocytes and chronic myeloid leukemia (CML) cells using sialylated and desialylated glycoproteins and oligosaccharides as acceptor substrates. In contrast to what has been reported for the myeloid-type enzyme, we found that the alpha 3- fucosyltransferase of the cells studied can use sialylated acceptors be it that the activity is several times lower than with asialo- substrates. Characterization of the product obtained with a sialylated oligosaccharide indicated that the enzyme can catalyze the formation of the sialyl-Le(x) structure. Flow cytometry of the WEGLI cells using a sialyl-Le(x)-specific monoclonal antibody (MoAb) showed that these cells indeed express sialyl-Lex at their surface, provided that they contain human chromosome 11. Earlier the presence of this chromosome had been correlated with the expression of alpha 3-fucosyltransferase activity. In addition to sialyl-Le(x), WEGLI cells containing chromosome 11 showed high-expression levels of related structures recognized by antibodies VIM-2 and VIM-8, suggesting that fucose addition can occur at both distal and proximal GlcNAc residues in poly- N-acetyl-lactosaminoglycan sequences. Based on the human chromosome contents it could be ruled out that the alpha 3-fucosyltransferase of WEGLI cells is a Lewis-type alpha 3/4- or plasma-type alpha 3- fucosyltransferase, the genes of which have been mapped to chromosome 19. It is concluded that the enzyme studied is of the myeloid-type and indeed is involved in the synthesis of sialyl-Le(x) (and also VIM-2 and VIM-8 structures) in leukocytes provided that its expression is at a sufficiently high level.     

Reduction of sound levels with antinoise in MR imaging

A combination of active and passive techniques was used to reduce the sound levels in magnetic resonance imagers. These techniques were integrated into an existing audio system. Measurements of sound reduction varied with the protocol being used and averaged 9.9 dB with coaxial cabling and 14.2 dB with fiberoptic conduction of the feedback signal to a controller. Patient comfort and communication were improved.