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71.
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
72.
Processing of tactile stimuli within somatosensory cortices has been shown to be complex and hierarchically organized. However, the precise organization of nociceptive processing within these cortices has remained largely unknown. We used whole-head magnetoencephalography to directly compare cortical responses to stimulation of tactile and nociceptive afferents of the dorsum of the hand in humans. Within the primary somatosensory cortex (SI), nociceptive stimuli activated a single source whereas tactile stimuli activated two sequentially peaking sources. Along the postcentral gyrus, the nociceptive SI source was located 10 mm more medially than the early tactile SI response arising from cytoarchitectonical area 3b and corresponded spatially to the later tactile SI response. Considering a mediolateral location difference between the hand representations of cytoarchitectonical areas 3b and 1, the present results suggest generation of the single nociceptive response in area 1, whereas tactile stimuli activate sequentially peaking sources in areas 3b and 1. Thus nociceptive processing apparently does not share the complex and hierarchical organization of tactile processing subserving elaborated sensory capacities. This difference in the organization of both modalities may reflect that pain perception rather requires reactions to and avoidance of harmful stimuli than sophisticated sensory capacities. 相似文献
73.
Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations 总被引:9,自引:1,他引:9
Meyer J; Sudbeck P; Held M; Wagner T; Schmitz ML; Bricarelli FD; Eggermont E; Friedrich U; Haas OA; Kobelt A; Leroy JG; Van Maldergem L; Michel E; Mitulla B; Pfeiffer RA; Schinzel A; Schmidt H; Scherer G 《Human molecular genetics》1997,6(1):91-98
It has previously been shown that, in the heterozygous state, mutations in
the SOX9 gene cause campomelic dysplasia (CD) and the often associated
autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one
recurrent mutation were characterized in one SOX9 allele each, and in one
case, no mutation was found. Four missense mutations are all located within
the high mobility group (HMG) domain. They either reduce or abolish the
DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense
and three frameshift mutations identified, two leave the C-terminal
transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or
almost completely intact. When tested in cell transfection experiments, the
recurrent nonsense mutation Y440X, found in two patients who survived for
four and more than 9 years, respectively, exhibits some residual
transactivation ability. In contrast, a frameshift mutation extending the
protein by 70 residues at codon 507, found in a patient who died shortly
after birth, showed no transactivation. This is apparently due to
instability of the mutant SOX9 protein as demonstrated by Western blotting.
Amino acid substitutions and nonsense mutations are found in patients with
and without XY sex reversal, indicating that sex reversal in CD is subject
to variable penetrance. Finally, none of 18 female patients with XY gonadal
dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP
assays, providing evidence that SOX9 mutations do not usually result in XY
sex reversal without skeletal malformations.
相似文献
74.
Alternative splicing of exon 14 determines nuclear or cytoplasmic localisation of fmr1 protein isoforms 总被引:6,自引:9,他引:6
Impaired expression of the FMR1 gene is responsible for the fragile X
mental retardation syndrome. The FMR1 gene encodes a cytoplasmic protein
with RNA-binding properties. Its complex alternative splicing leads to
several isoforms, whose abundance and specific functions in the cell are
not known. We have cloned in expression vectors, cDNAs corresponding to
several isoforms. Western blot comparison of the pattern of endogenous FMR1
proteins with these transfected isoforms allowed the tentative
identification of the major endogenous isoform as ISO 7 and of a minor band
as an isoform lacking exon 14 sequences (ISO 6 or ISO 12), while some other
isoforms (ISO 4, ISO 5) were not expressed at detectable levels.
Surprisingly, in immunofluorescence studies, the transfected splice
variants that exclude exon 14 sequences (and have alternate C-terminal
regions) were shown to be nuclear. Such differential localisation was
however not seen in subcellular fractionation studies. Analysis of various
deletion mutants suggests the presence of a cytoplasmic retention domain
encoded in exon 14 and of a nuclear association domain encoded within the
first eight exons that appear however to lack a typical nuclear
localisation signal.
相似文献
75.
Molecular epidemiology of macrolide-resistant Streptococcus pneumoniae isolates in Europe 总被引:3,自引:0,他引:3
Reinert RR Ringelstein A van der Linden M Cil MY Al-Lahham A Schmitz FJ 《Journal of clinical microbiology》2005,43(3):1294-1300
In many European countries, the level of pneumococcal resistance to macrolides has now passed the level of resistance to penicillin G. A total of 82 erythromycin A-resistant isolates of Streptococcus pneumoniae were collected by 11 laboratories in seven European countries. All of the isolates were tested for antimicrobial susceptibility, analyzed for clonal relatedness by multilocus sequence typing, and characterized for macrolide resistance genotypes. The prevalence of the macrolide resistance genotypes varied substantially between countries. In France (87.5% of all strains), Spain (77.3%), Switzerland (80%), and Poland (100%), strains were predominantly erm(B) positive, whereas higher levels of mef(A)-positive strains were reported from Greece (100%) and Germany (33.3%). Macrolide resistance was caused by the oligoclonal spread of some multilocus sequence types, but significant differences in clonal distribution were noted between France and Spain, countries from which high levels of macrolide resistance have been reported. Overall, sequence type 81 (Spain23F-1 clone) was by far the most widespread. The mainly erm(B)-positive serotype 14 clone (sequence type 143), first reported in Poland in the mid-1990s, is now widespread in France. 相似文献
76.
The murine Flavivirus Modoc replicates well in Vero cells and appears to be as equally sensitive as both yellow fever and dengue fever virus to a selection of antiviral agents. Infection of SCID mice, by either the intracerebral, intraperitoneal, or intranasal route, results in 100% mortality. Immunocompetent mice and hamsters proved to be susceptible to the virus only when inoculated via the intranasal or intracerebral route. Animals ultimately die of (histologically proven) encephalitis with features similar to Flavivirus encephalitis in man. Viral RNA was detected in the brain, spleen, and salivary glands of infected SCID mice and the brain, lung, kidney, and salivary glands of infected hamsters. In SCID mice, the interferon inducer poly IC protected against Modoc virus-induced morbidity and mortality and this protection was associated with a reduction in infectious virus content and viral RNA load. Infected hamsters shed the virus in the urine. This allows daily monitoring of (inhibition of) viral replication, by means of a noninvasive method and in the same animal. The Modoc virus model appears attractive for the study of chemoprophylactic or chemotherapeutic strategies against Flavivirus infections. 相似文献
77.
A randomised controlled trial of joint consultations with general practitioners and cardiologists in primary care. 下载免费PDF全文
J F Vlek W P M Vierhout J A Knottnerus J J Schmitz J Winter A M K Wesselingh-Megens H F Crebolder 《The British journal of general practice》2003,53(487):108-112
BACKGROUND: Joint consultation sessions of a small group of general practitioners (GPs) and a specialist in orthopaedics proved to be an effective way of decreasing the referral rate of orthopaedic patients. Cardiac complaints comprise an important category of health problems with high referral rates. AIMS: To study the effects of joint consultation on the quality of care and referrals for patients with cardiac complaints. DESIGN OF STUDY: Randomised controlled trial. SETTING: Forty-nine GPs participated in 16 consultation groups, each with one of 13 cardiologists, in monthly joint consultations over a period of about 18 months. METHOD: The GPs selected patients about whom they were uncertain, and those needing urgent referral were excluded. Patients were randomly assigned to joint consultation or to usual care. After a follow-up period all patients had a joint consultation for outcome assessment. Referral data were provided by two regional health insurance companies and questionnaires were given to the patients, GPs, and cardiologists to gauge their opinion of the trial. RESULTS: One hundred and forty-eight patients in the intervention group and 158 patients in the control group fulfilled the whole protocol. The quality of care was similar in both groups. In the intervention group, 34% of the patients were referred, compared with 55% in the control group (P = 0.001), and fewer patients underwent further diagnostic procedures (7% compared with 16%, P = 0.013). Referrals to cardiology as a proportion of all referrals decreased in the practices of the participating GPs, compared with their reference districts (P = 0.024). CONCLUSION: Joint consultation is an effective method that provides a quality of care that at least equals usual care and that contributes to a better selection of patients who need specialist care. 相似文献
78.
Cimetidine for anastomotic ulcers after partial gastrectomy. A randomized controlled trial. 总被引:3,自引:0,他引:3
R Gugler H Lindstaedt S Miederer W M?ckel H G Rohner H Schmitz T Székessy 《The New England journal of medicine》1979,301(20):1077-1080
In a randomized double-blind multicenter trial, 15 outpatients with endoscopically proved anastomotic ulceration after Billroth I or Billroth II partial gastrectomy received cimetidine, 1 g daily over eight weeks, or a placebo. All patients also received antiacid. The ulcer healed completely in all seven cimetidine-treated patients and in one of the eight placebo-treated patients (P less than 0.01). Ulcers not healed during the double-blind phase of the trial were all subsequently healed on open cimetidine treatment. There was a trend toward improvement of daytime symptoms in favor of cimetidine (P = 0.06), and nighttime symptoms were significantly relieved during the initial four weeks of cimetidine treatment P = 0.02). We conclude that cimetidine, 1 g daily, promotes healing of anastomotic ulcers after partial gastrectomy. 相似文献
79.
G. Hunsmann J. Schneider H. Bayer R. Kurth A. Werner H. D. Brede V. Erfle W. Mellert H. R. Brodt L. Bergmann I. Helm I. Scharrer W. Kreuz H. Berthold P. Wernet E. M. Schneider K. Schimpf U. Egli U. Bienzle H. Schmitz P. Kern G. Krüger H. Rasokat E. Lechler E. Seifried P. Hellstern W. Schneider E. Holzer F. -D. Goebel R. Hehlmann 《Journal of molecular medicine (Berlin, Germany)》1985,63(5):233-235
Summary In 1984 10,281 sera were collected in the FRG and examined for antibodies to HTLV-III (LAV) with an enzyme-linked immunosorbent assay and confirmative tests. Of the German AIDS patients 81% have antibodies. Individuals belonging to AIDS risk groups, homosexuals, haemophiliacs and i.v. drug abusers, have antibody frequencies between 25%–72%. The detection of HTLV-III antibodies in blood donours indicates that the virus is being transmitted by blood transfusions.Abbreviations AIDS
acquired immunodeficiency syndrome
- LAS
lymphadenopathy syndrome
- ARC
AIDS related complex
- LAV
lymphadenopathy associated virus
- HTLV-III
human T-lymphotropic virus type III
- HBV
hepatitis B virus 相似文献
80.
ObjectivesNon-traditional materials are used for mask construction to address personal protective equipment shortages during the coronavirus disease 2019 (COVID-19) pandemic. Reusable masks made from surgical sterilization wrap represent such an innovative approach with social media frequently referring to them as “N95 alternatives.” This material was tested for particle filtration efficiency and breathability to clarify what role they might have in infection prevention and control.MethodsA heavyweight, double layer sterilization wrap was tested when new and after 2, 4, 6, and 10 autoclave sterilizing cycles and compared with an approved N95 respirator and a surgical mask via testing procedures using a sodium chloride aerosol for N95 efficiency testing similar to 42 CFR 84.181. Pressure testing to indicate breathability was also conducted.ResultsThe particle filtration efficiency for the sterilization wrap ranged between 58% to 66%, with similar performance when new and after sterilizing cycles. The N95 respirator and surgical mask performed at 95% and 68% respectively. Pressure drops for the sterilization wrap, N95 and surgical mask were 10.4 mmH2O, 5.9 mmH2O, and 5.1 mmH2O, respectively, well below the National Institute for Occupational Safety and Health limits of 35 mmH2O during initial inhalation and 25 mmH2O during initial exhalation.ConclusionsThe sterilization wrap’s particle filtration efficiency is much lower than a N95 respirator, but falls within the range of a surgical mask, with acceptable breathability. Performance testing of non-traditional mask materials is crucial to determine potential protection efficacy and for correcting misinterpretation propagated through popular media. 相似文献