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11.
Vankeerberghen A; Wei L; Jaspers M; Cassiman JJ; Nilius B; Cuppens H 《Human molecular genetics》1998,7(11):1761-1769
In order to gain a better insight into the structure and function of the
regulatory domain (RD) of the cystic fibrosis transmembrane conductance
regulator (CFTR) protein, 19 RD missense mutations that had been identified
in patients were functionally characterized. Nine of these (I601F, L610S,
A613T, D614G, I618T, L619S, H620P, G628R and L633P) resulted in aberrant
processing. No or a very small number of functional CFTR proteins will
therefore appear at the cell membrane in cells expressing these mutants.
These mutations were clustered in the N- terminal part of the RD,
suggesting that this subdomain has a folding pattern that is very sensitive
to amino acid changes. Mutations that caused no aberrant processing were
further characterized at the electrophysiological level. First, they were
studied at the whole cell level in Xenopus laevis oocytes. Mutants that
induced a whole cell current that was significantly different from
wild-type CFTR were subsequently analysed at the single channel level in
COS1 cells transiently expressing the different mutant and wild-type
proteins. Three mutant chloride channels, G622D, R792G and E822K CFTR, were
characterized by significantly lower intrinsic chloride channel activities
compared with wild-type CFTR. Two mutations, H620Q and A800G, resulted in
increased intrinsic chloride transport activities. Finally, T665S and E826K
CFTR had single channel properties not significantly different from
wild-type CFTR.
相似文献
12.
13.
Polyetheretherketone--cytotoxicity and mutagenicity in vitro 总被引:4,自引:0,他引:4
The results of the incubation of polyetheretherketone (PEEK) fibre material with seven different genotype variants of salmonella bacterium showed with and without an external metabolic activation system (S9) with no mutagenic or cytotoxic activity of the test material. In the so-called "plate incorporation test" in which the PEEK raw material is finely cut and applied direct to the agar plate without the addition of solvent there was, as expected, no evidence of cytotoxic or mutagenic effects. In the HPRT test there was a significant increase in the number of mutants per dish, both after addition of N-acetylaminofluorene and N-methyl-N'-nitro-N-nitrosoguanidine (with and without an external metabolic activation system = +S9), but not after treatment of the cells with PEEK-DMSO-eluate. This means that the PEEK material under study did not release any substances that cause V79 cells to mutate. The investigation of the toxic reaction on the material under study revealed that the number of surviving colonies per 10(5) surviving cells lay within the range of or below the solvent control even in the presence of high PEEK concentrations (5.0 microg/ml). Therefore, in summary, the study produced no evidence of cell damage caused by PEEK. 相似文献
14.
Zaeem Lone Prithvi B. Murthy JJ Haijing Zhang Kyle J. Ericson Lewis Thomas Abhinav Khanna Georges-Pascal Haber Byron H. Lee 《Urologic oncology》2021,39(5):301.e1-301.e9
PurposeRenal function outcomes following robot-assisted radical cystectomy (RARC) have not been well established. We sought to compare long-term renal function outcomes between open radical cystectomy, RARC with extracorporeal urinary diversion and intracorporeal urinary diversion at a high volume institution.Materials and MethodsWe retrospectively reviewed our institutional bladder cancer database for patients who underwent RC from 2010 to 2019 with pre-operative estimated glomerular filtration rate (eGFR) > 45 ml/min/1.73m2. Changes in renal function were assessed through locally weighted scatter plot smoothing and comparison of median eGFR between surgical groups. Chronic Kidney Disease Stage 3B was defined as eGFR < 45 ml/min/1.73m2. Renal function decline was defined as a ≥10 ml/min/1.73m2 drop in eGFR. Kaplan Meier method with log-rank was used to compare CKD 3B-free survival and renal function decline. Cox Proportional Hazards model was used to identify predictors of CKD 3B.ResultsSix hundred and forty four patients were included with median follow-up of 32 months (IQR 12–56). Preoperative characteristics were similar among the groups with no differences in median pre-operative eGFR (ORC: 74.6, extracorporeal urinary diversion: 74.3, intracorporeal urinary diversion: 71.6 ml/min/1.73m2, P = 0.15). Median postoperative eGFR on follow up was not different between groups (P = 0.56). 33% of patients developed CKD 3B. There were no differences in CKD 3B-free survival by surgical approach (P = 0.23) or urinary diversion (P = 0.09). 64% of patients experienced renal function decline with a median time of 2.4 years (P 0.23). Predictors of CKD were pathologic T3 disease or greater (HR: 1.77, P = 0.01), ureteroenteric anastomotic stricture (HR: 2.80, P < 0.001), preoperative CKD Stage 2 (HR: 1.81, P =0.02), and preoperative CKD Stage 3A (HR: 5.56, P < 0.001).ConclusionRenal function decline is common after RC. Tumor stage, pre-operative eGFR, and ureteral stricture development, not surgical approach, influence renal function decline. 相似文献
15.
Vu Thuy Khanh Le-Trilling Jana-Fabienne Ebel Franziska Baier Kerstin Wohlgemuth Kai Robin Pfeifer Aart Mookhoek Philippe Krebs Madita Determann Benjamin Katschinski Alexandra Adamczyk Erik Lange Robert Klopfleisch Christian M. Lange Viktoriya Sokolova Mirko Trilling Astrid M. Westendorf 《European journal of immunology》2023,53(2):2249940
Primary and recurrent cytomegalovirus (CMV) infections frequently cause CMV colitis in immunocompromised as well as inflammatory bowel disease (IBD) patients. Additionally, colitis occasionally occurs upon primary CMV infection in patients who are apparently immunocompetent. In both cases, the underlying pathophysiologic mechanisms are largely elusive - in part due to the lack of adequate access to specimens. We employed the mouse cytomegalovirus (MCMV) model to assess the association between CMV and colitis. During acute primary MCMV infection of immunocompetent mice, the gut microbial composition was affected as manifested by an altered ratio of the Firmicutes to Bacteroidetes phyla. Interestingly, these microbial changes coincided with high-titer MCMV replication in the colon, crypt hyperplasia, increased colonic pro-inflammatory cytokine levels, and a transient increase in the expression of the antimicrobial protein Regenerating islet-derived protein 3 gamma (Reg3γ). Further analyses revealed that murine and human intestinal epithelial cell lines, as well as primary intestinal crypt cells and organoids represent direct targets of CMV infection causing increased cell death. Accordingly, in vivo MCMV infection disrupted the intestinal epithelial barrier and increased apoptosis of intestinal epithelial cells. In summary, our data show that CMV transiently induces colitis in immunocompetent hosts by altering the intestinal homeostasis. 相似文献
16.
1 病例报告 女 ,45岁 ,因吞咽困难 16 mo伴发热 15 d,于1999- 0 7- 12入院 .于 16 mo前与人争吵后出现吞咽困难 ,以进食馒头、面条为著 ,剑突下有时出现梗噎感 ,随即呕吐 ,呕出所进食物及粘液 ,情绪波动可诱发症状加重 ,伴食欲减退、返酸 .15 d前无诱因出现不规则发热 ,T38~ 39℃ ,上腹痛加重 ,全身酸困不适 ,乏力、头晕、消瘦 .追问病史 ,患者 5 a前双手、足疼痛麻木 ,尤以受凉、精神刺激后明显 ,手指初发白 ,继而发紫 ,变红 ,且麻木疼痛加重 ,手足小关节渐僵硬、畸形 .曾到多家医院就诊 ,诊断 :“雷诺病、类风湿性关节炎”.2 a前出现… 相似文献
17.
J VALENTINE E ROSSI P O'LEARY TS PARRY JJ KURINCZUK P SLY 《Journal of paediatrics and child health》1997,33(2):117-120
To determine the prevalence of thyroid hormone abnormalities and generalized resistance to thyroid hormone in a population of children with attention deficit hyperactivity disorder (ADHD) as compared to reference ranges determined from a control population and hence to determine if routine thyroid hormone screening in children with non-familial ADHD is indicated.
Children attending the State Child Development Centre in Perth, Western Australia with ADHD, as defined by the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) provided the study population. The control population consisted of 353 normal children with a history of allergy in whom radioallergosorbent (RAST) testing was being performed.
The prevalence of thyroid hormone abnormalities in the study population was 2.3% (95% CI 0.6%, 5.7%). There were no cases of generalized resistance to thyroid hormone. The prevalence of thyroid hormone abnormalities in the general population of children and adolescents has been reported to vary between 1 and 3.7%.
Routine thyroid hormone screening is not indicated in children with non-familial ADHD. 相似文献
Method:
Children attending the State Child Development Centre in Perth, Western Australia with ADHD, as defined by the Diagnostic and Statistical Manual of Mental Disorders (fourth edition) provided the study population. The control population consisted of 353 normal children with a history of allergy in whom radioallergosorbent (RAST) testing was being performed.
Results:
The prevalence of thyroid hormone abnormalities in the study population was 2.3% (95% CI 0.6%, 5.7%). There were no cases of generalized resistance to thyroid hormone. The prevalence of thyroid hormone abnormalities in the general population of children and adolescents has been reported to vary between 1 and 3.7%.
Conclusion:
Routine thyroid hormone screening is not indicated in children with non-familial ADHD. 相似文献
18.
Auricular infections caused by high ear piercing in adolescents 总被引:1,自引:0,他引:1
19.
High-density lipoprotein subclasses and esterification rate of cholesterol in children: effect of gender and age 总被引:1,自引:0,他引:1
M. Dobi ov Z. Urbanov H. Rauchov M. am nek JJ Frohlich 《Acta paediatrica (Oslo, Norway : 1992)》1998,87(9):918-923
Since the development of coronary heart disease (CAD) is affected by a specific pattern of plasma high density lipoprotein (HDL) effects it may be useful to know whether this occurs already in childhood. In this study we evaluated particle size distribution of HDL by gradient gel electrophoresis and the determination of cholesterol esterification rate (FERHDL) in plasma depleted of apo B lipoproteins in 221 children (108 boys and 113 girls) aged 4 months to 20 years. Total plasma- (TC), low-density lipoprotein- (LDL-C) and HDL- (HDL-C) cholesterol, HDL unesterified cholesterol (HDL-UC) and plasma triglycerides (TG) were also measured. There were no significant gender and age differences with respect to the plasma TC, LDL-TC and TG but concentration of HDL-TC increased with age. Post-pubertal girls had significantly higher relative concentrations of HDL2b compared to boys (30.4% vs 17.2%), while HDL3b,c was lower in post-pubertal girls (8.7% vs. 16.5 %). FERHDL correlated inversely with HDL2b and positively with HDL3b,c particles and was significantly higher in boys of the post-pubertal group compared to girls (16.9%/h vs 12.5%/h). While in girls there was a positive correlation between age and HDL-C, HDL-UC and the relative concentration of HDL2b no significant correlation were observed in boys. In girls the increase in TC showed a significant correlation with a simultaneous increase in HDL-C, HDL-UC and HDL2b. In boys TC correlated significantly with changes in TG only. When HDL2b and HDL3b,c cholesterol levels are calculated from HDL-C concentration and per cent distribution the differences between males and females are further emphasized. These data indicate that HDL particle size distribution is age- and gender-dependent. 相似文献
20.
P de Lonlay-Debeney JC Fournet D Martin F Poggi C Dionisi Vicci M Spada G Touati J Rahier F Brunelle C Junien JJ Robert C Nihoul-Fékété JM Saudubray 《Archives de pédiatrie》1998,5(12):1347-1352
Persistent hyperinsulinemic hypoglycaemia of infancy (PHHI) is the most frequent cause of hypoglycaemia in infancy. Clinical presentation is heterogeneous, with variable onset of hypoglycaemia and response to diazoxide, and presence of sporadic or familial forms. Underlying histopathological lesions can be focal or diffuse. Focal lesions are characterised by focal hyperplasia of pancreatic islet-like cells, whereas diffuse lesions implicate the whole pancreas. The distinction between the two forms is important because surgical treatment and genetic counselling are radically different. Focal lesions correspond to somatic defects which are totally cured by limited pancreatic resection, whereas diffuse lesions require a subtotal pancreatectomy exposing to high risk of diabetes mellitus. Diffuse lesions are due to functional abnormalities involving several genes and different transmission forms. Recessively inherited PHHI have been attributed to homozygote mutations for the beta-cell sulfonylurea receptor (SUR1) or the inward-rectifying potassium-channel (Kir6.2) genes. Dominantly inherited PHHI can implicate the glucokinase gene, particularly when PHHI is associated with diabetes, the glutamate dehydrogenase gene when hyperammonaemia is associated, or another locus. 相似文献