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11.
Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP) 总被引:8,自引:0,他引:8
Rowe PS; Oudet CL; Francis F; Sinding C; Pannetier S; Econs MJ; Strom TM; Meitinger T; Garabedian M; David A; Macher MA; Questiaux E; Popowska E; Pronicka E; Read AP; Mokrzycki A; Glorieux FH; Drezner MK; Hanauer A; Lehrach H; Goulding JN; O'Riordan JL 《Human molecular genetics》1997,6(4):539-549
Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with
homologies to endopeptidases, on the X-chromosome), are responsible for
X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family
of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has
raised important questions regarding PEX function at the molecular level.
The aim of this study was to analyse 99 HYP families for PEX gene
mutations, and to correlate predicted changes in the protein structure with
Zn2+ metallopeptidase gene function. Primers flanking 22 characterised
exons were used to amplify DNA by PCR, and SSCP was then used to screen for
mutations. Deletions, insertions, nonsense mutations, stop codons and
splice mutations occurred in 83% of families screened for in all 22 exons,
and 51% of a separate set of families screened in 17 PEX gene exons.
Missense mutations in four regions of the gene were informative regarding
function, with one mutation in the Zn2+-binding site predicted to alter
substrate enzyme interaction and catalysis. Computer analysis of the
remaining mutations predicted changes in secondary structure,
N-glycosylation, protein phosphorylation and catalytic site molecular
structure. The wide range of mutations that align with regions required for
protease activity in NEP suggests that PEX also functions as a protease,
and may act by processing factor(s) involved in bone mineral metabolism.
相似文献
12.
Alvaro P Pinto AP Felipe F B Tuon Luiz Fernando Bleggi Torres Luiz Martins Colla?o 《Diagnostic cytopathology》2002,26(1):15-18
The present study sought possible factors leading to the cytological diagnosis of atypical squamous cells of uncertain significance (ASCUS) in cases of high-grade squamous intraepithelial lesions (HSIL). Based on retrospective histopathological analysis of loop electrical excision procedure (LEEP) products that diagnosed HSIL, two study groups were randomly selected. The first was consisted of cases with two consecutive Papanicolaou (Pap) smears with the diagnosis of ASCUS. The second (control) group was represented by cases diagnosed as HSIL by cytology. From the Pap smears diagnosed as ASCUS, the sampling limitations was different from control group (P < 0.05). The median size of the largest lesion in each case with ASCUS was 2.66 mm (+/- 1.71 mm). In the control group, the median size of the largest lesion was 5.15 mm (+/-2.58 mm) (P < 0.05). The size of the lesion and sample limitations led patients with cervical intraepithelial neoplasms to be diagnosed as ASCUS for two consecutive times, after a 6-mo period. 相似文献
13.
Isaguliants MG Petrakova NV Mokhonov VV Pokrovskaya K Suzdaltzeva YG Krivonos AV Zaberezhny AD Garaev MM Smirnov VD Nordenfelt E 《Immunology letters》2003,88(1):1-13
Nonstructural protein 3 (NS3) of human hepatitis C virus (HCV) is a conserved multi-functional protein essential for replication and translation of viral RNA and polyprotein processing. Early T-cell response against NS3 is capable of restricting viremia. We aimed at characterizing the immunogenicity in gene immunization of the conserved regions of NS3 critical for protein folding and activity. C57BL/6 mice were injected with NS3 gene of Russian HCV 1b isolate 274933RU. Immunization did not exert any overt histological changes and had no long-term effects on the immune status of NS3 gene-recipients. The immune response in NS3 gene-recipients was screened by antibody ELISA, T-cell proliferation test and immune assays for specific cytokine production. T-lymphocytes of NS3 gene-recipients proliferated in response to peptides representing conserved regions of protease and ATPase/helicase. Stimulated T-lymphocytes produced IL-2, and in response to protease-derived peptides, also IFN-gamma. Potent and long-lasting antibody response was raised against conserved NS3 regions including "Greek-key" motif of protease, motifs II, V and polynucleotide-binding domains of ATPase/helicase. Thus, gene immunization effectively targeted conserved regions critical for NS3 protease and helicase function. In type and specificity, immune response of NS3 gene-immunized mice mimicked immunity achieved in the acute self-limiting HCV infection of human and primates and in virus-exposed healthy individuals, indicating promiscuity of NS3 as immunogen. 相似文献
14.
WBG Macdonald AP Patrikeos RI Thompson BD Adler AA Van Der Schaaf 《Journal of Medical Imaging and Radiation Oncology》2005,49(1):32-38
The present study compared the accuracy of ventilation perfusion scintigraphy (VQS) and CT pulmonary angiography (CTPA) for the diagnosis of pulmonary embolism. This was a prospective observational study of 112 patients with suspected pulmonary embolism (PE) who could be studied with both investigations within 24 h. Results were compared to final diagnosis at completion of 6-month follow up, using receiver operating characteristic (ROC) analysis. Pulmonary embolism was diagnosed in 27 referred patients (24%). The sensitivity and specificity of VQS and CTPA were similar to that reported from the literature. A normal VQ scan had the highest negative predictive value (100%), while a high-probability VQ scan had the highest positive predictive value (92%). There was no overall difference (area under the ROC curve (AUC)) between VQS (AUC (95% CI) = 0.82 (0.75,0.89)) and CTPA (AUC = 0.88 (0.81,0.94)) for the diagnosis of PE. Among patients with abnormal chest X-rays, CTPA (AUC 0.90 (0.83,0.97)) appeared somewhat better than VQS (AUC 0.78 (0.68,0.88)) but this difference did not reach statistical significance. In this instance, CTPA is at least as accurate as VQS and may provide an opportunity to make alternative diagnoses. 相似文献
15.
de Jesus Lopes Filho G Matone J Arasaki CH Kim SB Mansur NS 《International surgery》2000,85(4):339-343
Psoas abscess (PA) is an infrequent clinical entity and presents diagnostic and therapeutic challenges. Six cases are reported concerning diagnostic and therapeutic considerations. Clinical diagnosis is difficult because of non-specific symptoms. The primary psoas abscess has no definite etiology and is spread by hematogeneous route from a distant occult site. The PA can also be secondary to gastrointestinal pathology through direct infection of adjacent structures. The most common causes are Crohn's disease, appendicitis, diverticulitis and carcinoma. Routine laboratory evaluation is seldom useful for localizing the disease process. Conventional radiological techniques are often unhelpful. Modern imaging diagnosis techniques such as ultrasound and computerized tomography have allowed for a refinement in both the etiologic diagnosis and the treatment by means of CT-guided or ultrasound-guided percutaneous drainage of the abscess, thus avoiding surgical drainage in many cases. Immediately on diagnosis of PA prompt treatment is necessary. Percutaneous drainage should be performed whenever possible and in case of failure, surgical drainage should be practiced as well as intestinal resection, whenever indicated. 相似文献
16.
An enzyme-linked immunosorbent assay has been developed for the quantitation of activated Hageman factor-C1 inactivator (HF-C1 INH) complexes. Addition of increasing quantities of either of the major forms of activated Hageman factor (HFa or HFf) to normal plasma or to Hageman factor-deficient plasma leads to a dose-dependent increase in activated HF-C1 INH complexes. As little as 0.5 micrograms/mL of activated HF added to plasma can be detected, corresponding to activation of approximately 2% of plasma HF. The sensitivity of the assay is increased at least tenfold when complexes are formed in HF- deficient plasma, indicating competition between unactivated HF and activated HF-C1 INH complexes for binding to the antibody. Specificity is demonstrated in that addition of activated HF to hereditary angioedema plasma yields less than 1% of the activated HF-C1 INH complex formation obtained with normal plasma. Kaolin activation of HF- deficient plasma yields no detectable complex formation. Kaolin activation of prekallikrein-deficient plasma demonstrates a time- dependent increase in formation of activated HF-C1 INH complex consistent with the ability of HF in this plasma to autoactivate as the time of incubation with the surface is increased. Kaolin treatment of high-molecular weight (HMW) kininogen-deficient plasma yields an even more profound abnormality in the rate of formation of activated HF-C1 INH complexes reflecting the complex role of HMW kininogen in the initiation of contact activation. Although addition of corn inhibitor to plasma prevents activated HF-C1 INH complex formation, it does not inhibit activated HF sufficiently fast to prevent prekallikrein activation. 相似文献
17.
Warkentin TE; Hayward CP; Boshkov LK; Santos AV; Sheppard JA; Bode AP; Kelton JG 《Blood》1994,84(11):3691-3699
Heparin-induced thrombocytopenia is characterized by moderate thrombocytopenia and thrombotic complications, whereas quinine/quinidine-induced thrombocytopenia usually presents with severe thrombocytopenia and bleeding. Using flow cytometry and assays of procoagulant activity, we investigated whether sera from patients with these immune drug reactions could stimulate normal platelets to generate platelet-derived microparticles with procoagulant activity. Sera or purified IgG from patients with heparin-induced thrombocytopenia stimulated the formation of platelet-derived microparticles in a heparin-dependent fashion. Further studies showed that heparin-induced thrombocytopenia sera also produced a marked increase in procoagulant activity. In contrast, sera from patients with quinine- or quinidine-induced thrombocytopenia did not generate platelet-derived microparticles nor generate increased procoagulant activity. However, quinine/quinidine-induced thrombocytopenia sera produced a significant increase in the binding of IgG to platelets in a drug-dependent fashion, whereas sera from patients with heparin-induced thrombocytopenia demonstrated no drug-dependent binding of IgG to platelets. We also observed increased levels of circulating microparticles in patients with acute heparin-induced thrombocytopenia compared with control patients. Our observations indicate that the generation of procoagulant platelet-derived microparticles in vivo is a plausible explanation for the thrombotic complications observed in some patients with heparin-induced thrombocytopenia. 相似文献
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20.
Gumurdulu Y Serin E Ozer B Kayaselcuk F Ozsahin K Cosar AM Gursoy M Gur G Yilmaz U Boyacioglu S 《World journal of gastroenterology : WJG》2004,10(5):668-671
AIM:The eradication rate of Helicobacter pylori (H pylon) shows variation among countries and regimens of treatment.We aimed to study the eradication rates of different regimens in our region and some factors affecting the rate of eradication.METHODS:One hundred and sixty-four Hpylori positivepatients (68 males, 96 females; mean age:48±12 years)with duodenal or gastric ulcer without a smoking history were included in the study. The patients were divided into three groups according to the treatment regimens. Omeprazole 20mg, clarithromycin 500mg, amoxicillin 1g were given twice daily for 1 week (Group I) and 2 weeks (Group Ⅱ).Patients in Group Ⅲ received bismuth subsitrate 300mg,tetracyline 500 mg and metronidazole 500mg four times daily in addition to Omeprazole 20mg twice daily.Two biopsies each before and after treatment were obtained from antrum and corpus, and histopathologically evaluated.Eradication was assumed to be successful if no Hpylorus was detected from four biopsy specimens taken after treatment. The effects of factors like age, sex, Hpyloridensity on antrum and corpus before treatment, the total Hpylori density, and the inflammation scores on the rate of Hpylori eradication were evaluated.RESULTS:The overall eradication rate was 42%. The rates in groups Ⅱ and Ⅲ were statistically higher than that in group I (P<0.05). The rates of eradication were 24.5%,40.7% and 61.5% in groups Ⅰ, Ⅱ and Ⅲ, respectively. The eradication rate was negatively related to either corpus Hpylori density or total Hpyloridensity (P<0.05).The median age was older in the group in which the eradication failed in comparison to that with successful eradication (55yr vs 39yr, P<0.001). No correlation between sex and Hpylori eradication was found.CONCLUSION: Our rates of eradication were significantly lower when compared to those reported in literature.We believe that advanced age and high Hpyloridensity are negative predictive factors for the rate of Hpylorieradication. 相似文献