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31.
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
32.
33.
Previous studies demonstrated that the formamidine pesticide chlordimeform (CDM) reversibly inhibited prostaglandin biosynthesis and prevented the late (PG-mediated) phase of carrageenin-induced hind paw edema. This study emphasizes antagonism by CDM of the early (5HT and histamine-mediated) phase of carrageenin edema. CDM and cyproheptadine both antagonized paw edema induced by albumin (5HT and histamine-mediated) and by the direct injection of 5HT and histamine, whereas aspirin and the PG antagonist, SC-19220, were ineffective. As expected, cyproheptadine selectively reduced the early phase, whereas aspirin and SC-19220 selectively reduced the late phase of carrageenin-induced edema. These results are thus consistent with earlier studies demonstrating PG mediation of the late phase of carrageenin edema, and 5HT and histamine mediation of albumin edema and the early phase of carrageenin edema. In addition, they indicate that CDM possesses multiple acute anti-inflammatory, actions not exhibited by aspirin, by SC-19220 or by cyproheptadine alone. 相似文献
34.
Cloning and expression of the gene involved in Sanfilippo B syndrome (mucopolysaccharidosis III B) 总被引:4,自引:1,他引:4
Sanfilippo B syndrome is caused by a deficiency of alpha-N-
acetylglucosaminidase, a lysosomal enzyme involved in the degradation of
heparan sulphate. Accumulation of the substrate in lysosomes results in
degeneration of the central nervous system with progressive dementia often
combined with hyperactivity and aggressive behaviour. In order to clone the
deficient gene, we purified the enzyme from human placenta and obtained
amino acid sequence information. Alignment of one of the CNBr generated
internal peptides to sequence from the database revealed the chromosomal
location of the gene in the 5' upstream flanking region of the gene for
17-beta-hydroxysteroid-dehydrogenase at 17q21.1. The available DNA sequence
was used to clone the cDNA coding for alpha-N- acetylglucosaminidase and
analyse its gene structure. The gene is fully contained in the 5' upstream
flanking region of the gene for 17-beta- hydroxysteroid-dehydrogenase and
interrupted by five introns. The cDNA clone has a length of 2575 bp and
encodes a protein of 743 amino acids. Chinese hamster ovary cells
transfected with the cDNA construct show alpha-N-acetylglucosaminidase
activity about 17-fold over background. This will allow correction studies
with NAG deficient Sanfilippo B cell lines and facilitate the development
of enzyme replacement therapy for these patients.
相似文献
35.
We describe the use of suicide vectors to generate site-specific mutations in group B streptococcus. This is accomplished by cloning gene-specific sequences into a temperature sensitive plasmid and selecting for clones which have undergone homologous recombination. The recombinan clones can be easily isolated by selecting for clones which have retained the antibiotic resistance markers that are present on the vector or cloned into the gene-specific sequences. To confirm the fidelity of the recombination events, PCR analysis is performed on chromosomal DNA isolated from the recombinant clones. Using this strategy, we have generated site- specific insertions in several capsule genes and have found that these insertions occurred as expected and that the mutations result in loss of capsule expression. In this report, we specifically detail the construction of cpsB mutants by single and double cross-over recombination and demonstrate that the resulting strains are acapsular. 相似文献
36.
Mi-Ju Kim Kun-Pyo Kim Eunhye Choi June-Hyuck Yim Chunpil Choi Hyun-Sun Yun Hee-Yoon Ahn Ji-Young Oh Yunhi Cho 《Nutrients》2021,13(4)
Lactobacillus plantarum CJLP55 has anti-pathogenic bacterial and anti-inflammatory activities in vitro. We investigated the dietary effect of CJLP55 supplement in patients with acne vulgaris, a prevalent inflammatory skin condition. Subjects ingested CJLP55 or placebo (n = 14 per group) supplements for 12 weeks in this double-blind, placebo-controlled randomized study. Acne lesion count and grade, skin sebum, hydration, pH and surface lipids were assessed. Metagenomic DNA analysis was performed on urine extracellular vesicles (EV), which indirectly reflect systemic bacterial flora. Compared to the placebo supplement, CJLP55 supplement improved acne lesion count and grade, decreased sebum triglycerides (TG), and increased hydration and ceramide 2, the major ceramide species that maintains the epidermal lipid barrier for hydration. In addition, CJLP55 supplement decreased the prevalence of Proteobacteria and increased Firmicutes, which were correlated with decreased TG, the major skin surface lipid of sebum origin. CJLP55 supplement further decreased the Bacteroidetes:Firmicutes ratio, a relevant marker of bacterial dysbiosis. No differences in skin pH, other skin surface lipids or urine bacterial EV phylum were noted between CJLP55 and placebo supplements. Dietary Lactobacillus plantarum CJLP55 was beneficial to clinical state, skin sebum, and hydration and urine bacterial EV phylum flora in patients with acne vulgaris. 相似文献
37.
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
38.
下消化道出血221例分析 总被引:4,自引:2,他引:2
0 引言 下消化道出血是消化科的常见病 ,是指十二指肠空肠移行部 ,屈氏韧带以下的小肠和大肠疾病引起的肠道出血 .有人认为一般不包括痔和肛裂出血 [1 ] .临床最常见为慢性出血 ,但有时出血量大危及生命 ,需要做紧急处理 ,现将我院1992 - 0 1/ 1999- 0 8门诊及病房收治的 2 2 1例下消化道出血进行分析 ,报告如下 :1 临床资料 男 12 0例 ,女 10 1例 ,年龄 14~ 72 (平均 42 )岁 ,病程 16 h~ 10 a.患者分别以脓血便、暗红色血便、鲜血便或果酱色血便为主诉前来就诊 ,其中有休克症状的大出血者6例 .血 Hb<110 g·L- 1 40例 ,<80 g·L- 1… 相似文献
39.
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
40.
The1H-NMR signals of 2-cephems and 3-cephems have been assigned and the Nuclear Overhauser Effect (NOE) study of these compounds
was undertaken. 相似文献