Resistin is elevated in cystic fibrosis sputum and correlates negatively with lung function

Background

Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.

高能聚焦超声刀联合氟脲嘧啶、四氢叶酸治疗晚期胰腺癌临床疗效观察

目的探讨高能聚焦超声刀加氟脲嘧啶、四氢叶酸治疗晚期胰腺癌临床疗效及毒副作用。方法30例经病理学或细胞学确诊的晚期胰腺癌病人先用高能聚焦超声刀(HIFU)治疗，再予氟脲嘧啶、四氢叶酸联合化疗。氟脲嘧啶500mg／m^2加入5％GNS500ml静滴持续6小时以每天1次连用5天，CF(四氢叶酸)100mg／m^2加入生理盐水250ml静滴每天1次连用5天，28天为1周期，至少治疗2个周期。结果CR1例；PR9例；MR9例；NC5例；PD6例。总有效率63％。毒副作用主要消化道反应，其他副作用轻微。结论应用HIFU局部治疗胰腺癌同时合用四氢叶酸加氟脲嘧啶全身化疗近期疗效提高明显，止痛明显达75％，副反应小，值得应用。     

等离子接枝处理的CF/PAA复合材料层间剪切强度及其形貌研究

采用等离子技术对碳纤维(CF)进行接枝芳基乙炔(PAA)处理，研究了影响CF／PAA复合材料层间剪切强度(ILSS)的因素。结果表明，经等离子接枝PAA处理后，复合材料的ILSS有了很大提高。SEM显示经接枝处理后CF和PAA树脂之间的界面结合紧密，改善了复合材料的界面结合性能。     

Sputum induction as a research tool for the study of human respiratory mucus

The study objectives were to compare in vitro transportability and physical properties of respiratory mucus, obtained invasively by direct collection (DC) right after endotracheal intubation and non-invasively by sputum induction with 3% hypertonic saline solution inhalation (SI) 24 h before the anesthesia. Twenty-two patients with no pulmonary disease scheduled for elective abdominal surgical procedures were studied. The parameters analyzed and the main results are as follows. (1) Transportability by cilia (MCT), SI was higher than DC (0.94+/-0.25 and 0.62+/-0.25; P<0.001). There was a significant correlation between the two methods and DC could be estimated by: DC=0.21+(0.44 SI) (r=0.44; P<0.001). (2) Transportability by cough (CC), SI was higher than DC (68.23+/-32.1 and 33.58+/-19.04 mm; P=0.002). (3) Contact angle (CA), SI was lower than DC (10+/-3 degrees and 22+/-14 degrees ; P=0.025). (4) Rheological properties (no significant difference obtained between SI and DC). These results indicated that SI changes mucus physical properties and transportability in non-expectorators.     

DHPLC screening of cystic fibrosis gene mutations

Denaturing high performance liquid chromatography (DHPLC) using ion-pairing reverse phase chromatography (IPRPC) columns is a technique for the screening of gene mutations. In order to evaluate the potential utility of this assay method in a clinical laboratory setting, we subjected the PCR products of 73 CF patients known to bear CFTR mutations to this analytic technique. We used thermal denaturation profile parameters specified by the MELT program tool, made available by Stanford University. Using this strategy, we determined an initial analytic sensitivity of 90.4% for any of 73 known CFTR mutations. Most of the mutations not detected by DHPLC under these conditions are alpha-substitutions. This information may eventually help to improve the MELT algorithm. Increasing column denaturation temperatures for one or two degrees above those recommended by the MELT program allowed 100% detection of CFTR mutations tested. By comparing DHPLC methodology used in this study with the recently reported study based on Wavemaker 3.4.4 software (Transgenomic, Omaha, NE) [Le Marechal et al., 2001) and with previous SSCP analysis of CFTR mutations [Ravnik-Glavac et al., 1994] we emphasized differences and similarities in order to refine the DHPLC system and discuss the relationship to the alternative approaches. We conclude that the DHPLC method, under optimized conditions, is highly accurate, rapid, and efficient in detecting mutations in the CFTR gene and may find high utility in screening individuals for CFTR mutations. Hum Mutat 19:374-383, 2002. Published 2002 Wiley-Liss, Inc.     

The cystic fibrosis transmembrane conductance regulator attenuates the endogenous Ca2+ activated Cl– conductance of Xenopus oocytes

 Oocytes from Xenopus laevis activate a Ca²⁺ dependent Cl^– conductance when exposed to the Ca²⁺ ionophore ionomycin. This Ca²⁺ activated Cl^– conductance (CaCC) is strongly outwardly rectifying and has a halide conductivity ratio (G_I– / G_Cl–) of about 4.4. This is in contrast to the cystic fibrosis transmembrane conductance regulator (CFTR)-Cl^– conductance, which produces more linear I/V curves with a G_I– / G_Cl– ratio of about 0.52. Ionomycin enhanced CaCC (ΔG) in water injected and CFTR expressing ooyctes in the absence of 3-isobutyl-1-methylxanthine (IBMX, 1 mmol/l) by (μS) 23 ± 1.9 (n=9) and 23.6 ± 2.3 (n=11). Stimulation by IBMX did not change CaCC in water injected oocytes. CaCC was inhibited in CFTR-expressing ooyctes after stimulation with IBMX or a membrane permeable form of cAMP and was only 5.1 ± 0.48 μS (n=18) and 6.9 ± 0.6 (n=3), respectively. Inhibition of CaCC was correlated to the amount of CFTR-current activated by IBMX. ΔF508-CFTR which demonstrates only a small residual function in activating a cAMP dependent Cl^– channel in oocytes inhibited CaCC to a lesser degree (ΔG=12.1 ± 1.1 μS; n=7). Changes of CFTR and CaCC-Cl^– whole cell conductances were also measured when extracellular Cl^– was replaced by I^–. The results confirmed the reduced activation of CaCC in the presence of activated CFTR. No evidence was found for inhibition of CFTR-currents by increase of intracellular Ca²⁺. Moreover, intracellular cAMP was not changed by ionomycin and stimulation by IBMX did not change the ionomycin induced Ca²⁺ increase in Xenopus oocytes. Taken together, these results suggest that activation of CFTR-Cl^– currents is paralleled by an inhibition of Ca²⁺ activated Cl^– currents in ooyctes of Xenopus laevis. These results provide another example for CFTR-dependent regulation of membrane conductances other than cAMP-dependent Cl^– conductance. They might explain previous findings in epithelial tissues of CF-knockout mice. Received: 17 June 1997 / Received after revision: 4 September 1997 / Accepted: 5 September 1997     

Differential cytokine profile in children with cystic fibrosis

The previously observed occurrence of antineutrophil cytoplasmic autoantibodies (ANCA) in patients who have cystic fibrosis (CF), together with the reported decrease in IgG2, a Th1-controlled isotype, suggests a potential for Th1/Th2 imbalance in CF patients with a possible Th2 predominance. 48 CF patients and 16 controls had levels of IFNgamma, IL-4, and IL-10 measured in supernatants of whole blood cell cultures stimulated by lipopolysaccharide (LPS) and phytohemaglutinine (PHA). The patients were divided into 2 groups: "low responders", having negligible secretion of cytokines (IFNgamma: 10.0-200.0 pg/ml, IL-4: 0.0-0.3 pg/ml) and "high responders", producing high levels of both IFNgamma (500.0-2000.0 pg/ml) and IL-4 (1.0-200.0 pg/ml). There was a statistically significant (P < 0.01) deterioration of lung function measured by an FEV(1) decline by 11.2% over 3 years in the "low responder" group. 10 of 16 "low responders" had chronic lung infections with P. aeruginosa while such infection was less prevalent in the "high responder" group where only 13 of 32 CF patients had positive cultures. A shift towards Th2 response was observed in the "high responder" group as children chronically infected with P. aeruginosa had greater IL-4 production than non-infected CF patients within the same cohort. ANCA autoantibodies were found only in the "high responder" group. Th2 immune response predominance in a subset of CF patients is associated with chronic P. aeruginosa infection.     

Effects of Cystic Fibrosis Serum and Fibroblast Culture Medium on Ion Distribution in Rat Submandibular Gland

The effects of cystic fibrosis (CF) serum and culture medium from CF fibroblasts on ion distribution in rat submandibular gland cells were investigated by X-ray microanalysis. These effects were compared to the effects of normal serum and culture medium from normal fibroblasts, of cholinergic and adrenergic agonists, and of the uncoupler 2,4-dinitrophenol.

Incubation of gland tissue with CF serum or normal serum caused a significant decrease in potassium and calcium concentrations and an increase in sodium in mucous acinar and serous granular duct cells. CF serum gave a significantly larger decrease of the potassium level than normal serum.

Culture medium from CF fibroblasts altered the cellular ion content in a way similar to CF serum. Exposure to medium from cultured normal fibroblasts did not affect the elemental composition of the gland cells significantly, compared to incubation with fresh medium or buffer. Hence, fibroblast culture medium is more suitable than serum to test specific effects of CF-associated factors.

The changes in elemental composition of gland eelIs caused by CF serum or CF fibroblast culture medium mimic some of the effects of the agonist car-bachol. They could, however, also in part result from nonspecific changes in membrane permeability.     

奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗晚期大肠癌

目的：研究奥沙利铂、氟尿嘧啶、亚叶酸钙联合治疗晚期大肠癌的疗效和毒性反应，并将该方案和氟尿嘧啶与亚叶酸钙联合治疗方案相比较。方法：经病理确诊的晚期大肠癌83例分为以下两组：治疗组行奥沙利铂(oxalipatin)130mg／m^2静脉滴注，第1天给药：氟尿嘧啶(5-FU)425mg／m^2静脉滴注，第1-5天给药；亚叶酸钙(CF)100mg／m^2静脉滴注，第1～5天给药；每3周重复。对照组行氟尿嘧啶(5-FU)42h5mg／m^2静脉滴注,第1～5天给药；亚叶酸钙(CF)100mg／m^2。静脉滴注，第1-5天给药；每3周重复。每例患者至少完成两个周期。结果：治疗组有效率为46．5％，常见的毒性反应为神经毒性；对照组有效率为17．5％，与治疗组差别有统计学意义，未见神经毒性，其他毒性与治疗组无统计学差异。结论：奥沙利铂联合氟尿嘧啶和亚叶酸钙治疗晚期大肠癌,患者对其耐受良好，毒副反应较轻，疗效高于氟尿嘧啶加亚叶酸钙方案。