Cystic fibrosis: An update for clinicians. Part 2: Hepatobiliary and pancreatic manifestations

This paper, the second in the series, will build on the first and explore the importance of liver and pancreatic manifestations of cystic fibrosis (CF) and the effect on morbidity and mortality of this multifaceted genetic condition. It will also further develop the critical role of the gastroenterologist as part of the multidisciplinary group of clinicians and allied health staff in the effective management of patients with CF.     

Functional reconstitution of the phagocyte NADPH oxidase by transfection of its multiple components in a heterologous system

The phagocyte NADPH oxidase system, as previously defined by cell-free reconstitution, is comprised of five essential components, three of which are produced during late phagocytic differentiation--namely, two cytosolic proteins, p47- and p67-phox--and the large subunit of cytochrome b558, gp91-phox. To confirm that these are the only phagocyte-specific components necessary for oxidase activity in whole cells, the recombinant NADPH oxidase was reconstituted in a heterologous cell line. An undifferentiated multipotent leukemic cell line, K562, which expresses endogenous Rac and the small subunit of the flavocytochrome b558 (p22-phox), was cotransfected with episomal expression vectors containing cDNAs for the three other oxidase components. After 4 days of selection, the complete oxidase system was functionally reconstituted in transfected cells stimulated with phorbol myristate acetate or calcium ionophore. These easily transfected cells provide an ideal model system in which several oxidase components can be genetically manipulated and readily expressed. This system can be used to test the effects of mutations associated with any of the genes affected in chronic granulomatous disease and will facilitate studies on structure-function relationships within several oxidase components. This system will also aid in delineation of upstream regulators functioning through various signaling pathways.     

经桡动脉冠状动脉介入治疗中5F与6F导引导管的对比研究

目的比较5French(5F)及6French(6F)导引导管在经桡动脉冠状动脉介入治疗(TRI)患者中的安全性及有效性。方法共纳入2009年2月至2010年3月患者,收集相关资料录入数据库,包括患者基线临床资料、导引导管的尺寸、靶血管、靶病变的特点、手术的成功率、手术失败原因、经桡动脉冠状动脉介入治疗手术的成功率及失败原因、患者住院期间主要不良心血管事件率及术后桡动脉闭塞率。结果连续纳入患者共185例,接受195次经桡动脉冠状动脉介入治疗术,平均年龄(57±11)岁(33～81岁);其中54例患者纳入6F导引导管组,共进行56次手术,治疗89处病变;138例患者纳入5F导引导管组,共行146次手术,治疗231处病变。AHA B2/C型病变比例在两组间差异无统计学意义(5F组43.7%/29.0%比6F组46.1%/34.6%,P>0.05),但慢性闭塞性病变、分叉病变、钙化病变5F组显著少于6F组(5.6%比14.6%,P=0.005;23.4%比37.1%,P=0.012;9.5%比47.2%,P<0.001);组间的手术时间[(45±21)min比(46±19)min)]、手术X线曝光时间[(15±12)min比(16±13)min]、使用造影剂量[(140±45)ml比(156±56)ml]差异均无显著统计学意义(P>0.05),但是5F组造影剂用量有减少的趋势(P=0.066);组间住院时间[(1.40±1.26)d比(1.29±0.69)d]和手术成功率(95.2%比94.6%)也差异无统计学意义(P>0.05);5F组1例患者术后桡动脉闭塞,6F组无患者术后桡动脉闭塞(P=1.0),5F组1例发生卒中。结论经桡动脉冠状动脉介入治疗,即使是复杂及高危冠脉病变,5F导引导管有效、安全,手术成功率不低于常规使用的6F导引导管;换用5F导引导管进行冠状动脉介入治疗是一种有吸引力的选择。     

Relationship between skin fold thickness and insulin resistance in the essential hypertensive patients in Vietnam

Background Previous studies reported a close relationship between obesity and insulin resistance in the essential hypertensive patients. Objective In this study, we examined the relationship between the skin fold thickness and insulin resistance then developed a formula to estimate the insulin resistance index according to the skin fold thickness in the essential hypertensive patients. Subjects and Methods Medical records of 80 patients (37 males, 43 females) were reviewed and the data were tabulated. Anthropometric indexes (including height, weight, waist circumference, hip circumference, and skins fold thickness at 5 fatty difference points on the Erdheim diagram), fasting plasma glucose and insulin concentration were recorded. The mean age was 57.0 ?9.2 years. The insulin resistance index was calculated following the Homeostasis Model Assessment (HOMA) formula. Results Compared with the group with BMI < 23 kg/m2, the group with BMI≥23 kg/m2 had higher fasting insulin concentration (8.85±4.97 pmol/L vs 15.60±8.70 pmol/L, P<0.001 ) and higher insulin resistance index in ( 2.15±1,24 vs 3.76±2.22, P<0.001). No significant difference in fasting plasma insulin concentration, insulin resistance index between male and female was observed (P > 0.05). There was a positive correlation between skin fold thickness and the fasting insulin concentration and insulin resistance index. The skin fold thickness at point A8 had the best coefficient correlated with fasting plasma insulin(r=0.79, P < 0.001) and insulin resistance index (r= 0.79, P < 0.001). A formula to estimate the insulin resistance index by skin fold thickness at point A8 as: Insulin resistance index = 0.12×[skin fold thickness at A8 point (mm)] - 1. Conclusion: In the essential hypertensive patients, the formula to estimate insulin resistance index as 0.12×[skin fold thickness at A8 point (mm)]-1 may predict accurately the level of insulin resistance. (J Geriatr Cardiol 2005; 2(4):228-232 )     

The CD11b promoter directs high-level expression of reporter genes in macrophages in transgenic mice [published erratum appears in Blood 1995 Apr 1;85(7):1983]

CD11b is the alpha chain of the Mac-1 integrin and is preferentially expressed in myeloid cells (neutrophils, monocytes, and macrophages). We have previously shown that the CD11b promoter directs cell-type- specific expression in myeloid lines using transient transfection assays. To confirm that these promoter sequences contain the proper regulatory elements for correct myeloid expression of CD11b in vivo, we have used the -1.7-kb human CD11b promoter to direct reporter gene expression in transgenic mice. Stable founder lines were generated with two different reporter genes, a Thy 1.1 surface marker and the Escherichia coli lacZ (beta-galactosidase) gene. Analysis of founders generated with each reporter demonstrated that the CD11b promoter was capable of driving high levels of transgene expression in murine macrophages for the lifetime of the animals. Similar to the endogenous gene, transgene expression was preferentially found in mature monocytes, macrophages, and neutrophils and not in myeloid precursors. These experiments indicate that the -1.7 CD11b promoter contains the regulatory elements sufficient for high-level macrophage expression. This promoter should be useful for targeting heterologous gene expression to mature myeloid cells.     

Characterization of the p67phox gene: genomic organization and restriction fragment length polymorphism analysis for prenatal diagnosis in chronic granulomatous disease

The genetic defect in the p67phox-deficient form of chronic granulomatous disease (CGD) follows an autosomal recessive pattern of inheritance. When genomic DNA from normal individuals is digested with HindIII and probed with p67phox cDNA an allelic restriction fragment length polymorphism (RFLP) of 4.0 kb or 2.3 kb is detected. We cloned and characterized the p67phox gene using the cDNA and sequenced the exon/intron boundaries, mapping 16 exons on the 40-kb gene. The polymorphic region was then sequenced to identify the inheritance pattern of amniocentesis-derived fetal cells by genomic amplification. The proband, a 9-year-old female patient with p67phox-deficient CGD, and her phenotypically normal mother are homozygous for the RFLP marker, whereas the father and two brothers are heterozygous. The fetus was shown to be heterozygous as well, showing it had inherited at least one normal p67phox gene from the father and that it was predicted to have a normal phenotype. Cord blood samples at birth showed normal oxidative function. Amplification allows rapid detection of the inheritance pattern for fetal diagnosis in informative families. We report the genomic structure of p67phox and an amplification-based method for detection of the marker on chromosome 1q25, used here for prenatal diagnosis of CGD.     

BACCATIN—Ⅲ的氢谱和碳谱及结构研究

Ｂａｃａｔｉｎ－Ⅲ在紫杉醇化学研究中占有重要位置,其结构主要由波谱解析法推导和鉴定的。但文献中Ｂａｃａｔｉｎ－Ⅲ的氢谱和碳谱的各峰归属上存在不少矛盾,给紫杉醇化学研究带来问题。为此,我们测定了ｂａｃｃａｔｉｎ－Ⅲ的高分辨１Ｈ－ＮＭＲ,１３Ｃ－ＮＭＲ,ＤＥＰＴ,１Ｈ－１ＨＤＱＣＯＳＹ,１Ｈ－１３ＣＨＥＴＣＯＲ和ＨＭＢＣＮＭＲ各谱,并据此对ｂａｃａｔｉｎ－Ⅲ的１Ｈ－ＮＭＲ和１３Ｃ－ＮＭＲ的各信号峰作了归属。     

Digital and conventional chest images: observer performance with Film Digital Radiography System

The Film Digital Radiography System (FilmDRS) is a device with a laser optical film digitizer, 2,000 X 2,000 X 12-bit memory, and a 1,000-line video display. To evaluate the adequacy of this device for general radiography of the chest, four readers independently analyzed both radiographs and the corresponding video display of the digitized chest images of 150 patients, consisting of 100 images of abnormalities and 50 normal images. The overall results indicate equal sensitivity for the two systems. The FilmDRS, with interactive windowing, proved superior in the detection of hilar and mediastinal disease. X-ray film was superior in allowing detection of hyperlucent states. There was equivalent sensitivity for other disease categories. Superior specificity was achieved with conventional radiographs.     

Assessment of testicular metabolic integrity with P-31 MR spectroscopy

To evaluate the reliability of phosphorus-31 magnetic resonance (MR) spectroscopy in the assessment of acute testicular ischemia, vascular integrity, and spermatogenesis, the authors studied in vivo canine and primate testicles grouped as follows: group 1 testes (n = 8), in situ canine controls; group 2 (n = 11), canine testes subjected to warm ischemia; group 3, canine (n = 4) and primate (n = 4) testicles from hormone-treated animals. Group 1 control testicles showed high monophosphoester (MP) levels; low levels of inorganic phosphate (Pi), phosphodiester (PD), and phosphocreatine; and high levels of adenosine triphosphate (ATP). Group 2 testes revealed a time-dependent decay of MP/Pi ratios (from 2.1 to 0.70). Regeneration of ATP was noted in the acute reperfusion period. After 6 weeks of pituitary gonadotropin suppression, group 3 testes showed a significant decrease (P less than .05) in MP/PD ratios from a control level of 2.6 +/- 0.3 and a decrease in the MP/beta-ATP ratio from 2.4 +/- 0.1 to 1.8 +/- 0.3. P-31 MR spectroscopy appears to be a potential method for noninvasively assessing testicular ischemic injury and the metabolic integrity of spermatogenesis.