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41.
Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes 总被引:17,自引:8,他引:17
Campuzano V; Montermini L; Lutz Y; Cova L; Hindelang C; Jiralerspong S; Trottier Y; Kish SJ; Faucheux B; Trouillas P; Authier FJ; Durr A; Mandel JL; Vescovi A; Pandolfo M; Koenig M 《Human molecular genetics》1997,6(11):1771-1780
Friedreich ataxia is a progressive neurodegenerative disorder caused by
loss of function mutations in the frataxin gene. In order to unravel
frataxin function we developed monoclonal antibodies raised against
different regions of the protein. These antibodies detect a processed 18
kDa protein in various human and mouse tissues and cell lines that is
severely reduced in Friedreich ataxia patients. By immunocytofluorescence
and immunocytoelectron microscopy we show that frataxin is located in
mitochondria, associated with the mitochondrial membranes and crests.
Analysis of cellular localization of various truncated forms of frataxin
expressed in cultured cells and evidence of removal of an N-terminal
epitope during protein maturation demonstrated that the mitochondrial
targetting sequence is encoded by the first 20 amino acids. Given the
shared clinical features between Friedreich ataxia, vitamin E deficiency
and some mitochondriopathies, our data suggest that a reduction in frataxin
results in oxidative damage.
相似文献
42.
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
43.
Early transvaginal ultrasound following an accurately dated pregnancy: the importance of finding a yolk sac or fetal heart motion 总被引:1,自引:2,他引:1
Deaton JL; Honore GM; Huffman CS; Bauguess P 《Human reproduction (Oxford, England)》1997,12(12):2820-2823
Our goals were to determine the prognostic value of a yolk sac or fetal
heart motion seen during an early accurately dated transvaginal ultrasound
(TVU). We reviewed 225 consecutive pregnancies for fetal heart motion data.
Furthermore, 63 pregnancies following in-vitro fertilization were reviewed
for yolk sac information. The TVU was performed between 5 and 6 weeks
following presumed conception (heart motion data) and between 22 and 32
days following in-vitro fertilization (yolk sac data). Pregnancies were
followed until an ongoing pregnancy or spontaneous abortion was documented.
The presence of a yolk sac between 22 and 32 days from fertilization was
associated with the development of fetal heart motion in 94% of cases. The
absence of the yolk sac by 32 days after fertilization was always
associated with a poor outcome. In women < 36 years of age, the presence
of fetal heart motion was associated with a spontaneous abortion in only
4.5% of the cases. However, the incidence of spontaneous abortion following
fetal heart motion increased to 10% in women 36-39 years and 29% in women
> or = 40 years of age. The presence of heart motion should not be
considered a reassuring sign in the older woman. These data have
implications regarding early embryology and the counselling of infertility
patients.
相似文献
44.
Dongari-Bagtzoglou AI; Warren WD; Berton MT; Ebersole JL 《International immunology》1997,9(9):1233-1241
CD40, a member of the tumor necrosis factor-alpha receptor family, is
constitutively expressed by cells of hematopoietic and non- hematopoietic
origin, including fibroblasts. Signaling through this receptor molecule
regulates inflammatory cytokine secretion by many cell types. Based on the
recently described cytokine secretory heterogeneity of fibroblast cell
subsets, we hypothesized that secretion of inflammatory cytokines by
gingival fibroblast cultures may be dictated by the existence of
differential proportions of cytokine- secreting subpopulations which
express high levels of CD40. After examining a large number of gingival
fibroblast (GF) cultures we find that the frequency of IL-6- and
IL-8-secreting cells mirrors the frequency of cells expressing high levels
of CD40 in these cultures. In addition, we demonstrate a direct functional
relationship between CD40 expression and IL-6 or IL-8 secretion by showing
that ligation of this molecule on GF, and CD40+ fibroblast subsets in
particular, up- regulates secretion of these cytokines in vitro.
相似文献
45.
Berge-Lefranc JL; Jay P; Massacrier A; Cau P; Mattei MG; Bauer S; Marsollier C; Berta P; Fontes M 《Human molecular genetics》1996,5(10):1637-1641
While constructing a cDNA library of human embryos, we have isolated a
clone homologous to jumonji, a mouse gene required for neural tube
formation. We have determined the complete coding sequence of the human
homologue (JMJ) and deduced the amino acid sequence of the putative
protein. We show here that human and mouse jumonji putative proteins are
homologous and present 90% identity. During human embryogenesis, JMJ mRNAs
are predominantly expressed in neurons and particularly in dorsal root
ganglion cells. They are also expressed in neurons of human adult cerebral
cortex. In view of these observations, we propose JMJ as a candidate gene
for developmental defects of the central nervous system in the human. The
human JMJ gene maps at position 6p24-6p23.
相似文献
46.
Screening for proteins with polyglutamine expansions in autosomal dominant cerebellar ataxias 总被引:2,自引:8,他引:2
Stevanin G; Trottier Y; Cancel G; Durr A; David G; Didierjean O; Burk K; Imbert G; Saudou F; Abada-Bendib M; Gourfinkel-An I; Benomar A; Abbas N; Klockgether T; Grid D; Agid Y; Mandel JL; Brice A 《Human molecular genetics》1996,5(12):1887-1892
Expansion of trinucleotide CAG repeats coding for polyglutamine has been
implicated in five neurodegenerative disorders, including spinocerebellar
ataxia (SCA) 1 and SCA3 or Machado-Joseph disease (SCA3/MJD), two forms of
type I autosomal dominant cerebellar ataxias (ADCA). Using the 1C2 antibody
which specifically recognizes large polyglutamine tracts, particularly
those that are expanded, we recently reported the detection of proteins
with pathological glutamine expansions in lymphoblasts from another form of
ADCA type I, SCA2, as well as from patients presenting with the distinct
phenotype of ADCA type II. We now have screened a large series of patients
with ADCA or isolated cases with cerebellar ataxia, for the presence of
proteins with polyglutamine expansions. A 150 kDa SCA2 protein was detected
in 16 out of 40 families with ADCA type I. This corresponds to 24% of all
ADCA type I families, which is much more frequent than SCA1 in this series
of patients (13%). The signal intensity of the SCA2 protein was negatively
correlated to age at onset, as expected for an expanded and unstable
trinucleotide repeat mutation. The disease segregated with markers closely
linked to the SCA2 locus in all identified SCA2 families. In addition, a
specific 130 kDa protein, which segregated with the disease, was detected
in lymphoblasts of patients from nine families with ADCA type II. It was
also visualized in the cerebral cortex of one of the patients,
demonstrating its translation in the nervous system. Finally, no new
disease-related proteins containing expanded polyglutamine tracts could be
detected in lymphoblasts from the remaining patients with ADCA or isolated
cases with cerebellar ataxia.
相似文献
47.
Ramesh JL. Kandimalla Prabhakar S Binukumar BK Willayat Yousuf Wani Deep Raj Sharma V.K. Grover Neerja Bhardwaj Kajal Jain Kiran Dip Gill 《Neuroscience letters》2011
Alzheimer's disease (AD) is the most common form of dementia, and is characterized by the degeneration of neurons and their synapses, and a higher number of amyloid plaques and neurofibrillary tangles (NFTs) compared with that found in non-demented individuals. Amyloid-β-peptides (Aβ) are major components of amyloid plaques in AD brain whereas NFTs are composed of Tau and associated with ubiquitin. The aim of the present study was to analyze the levels of Aβ42, hTau (total Tau) and ubiquitin in CSF of North Indian population. CSF Aβ42, Tau and ubiquitin were measured in CSF of AD patients as well as controls using ELISA assays. Here we report low Aβ42 levels in AD patients (324.24 ± 76.38 pg/ml) as compared to those in non-AD (NAD) (668.34 ± 43.13 pg/ml), neurological controls (NCs) (727.28 ± 46.49 pg/ml) and healthy controls (HCs) (976.47 ± 124.46 pg/ml). In contrast, hTau and ubiquitin levels were significantly high (568.65 ± 48.89 pg/ml and 36.82 ± 4.34 ng/ml, respectively) in AD patients compared to those in NAD, NC and HC. The hTau levels were 267.37 ± 36.64 pg/ml, 167.34 ± 44.27 pg/ml and 107.62 ± 24.27 pg/ml in NAD, NC and HC, respectively. Similarly, ubiquitin levels were 23.57 ± 2.32 ng/ml, 19.76 ± 3.64 ng/ml and 13.24 ± 4.56 ng/ml in NAD, NC and HC, respectively. In conclusion, low Aβ42 and high Tau–ubiquitin levels were found in North Indian AD patients. 相似文献
48.
49.
P Valenzuela MS Saiz Puente JL Valero R Azorín R Ortega R Guijarro 《BJOG : an international journal of obstetrics and gynaecology》2009,116(3):436-441
Objective To evaluate the repair techniques of continuous and interrupted methods for episiotomy or perineal tears.
Design A randomised controlled trial.
Setting The Hospital Universitario Principe de Asturias, a state hospital belonging to the community of Madrid.
Sample Four hundred forty-five women who had undergone vaginal deliveries with episiotomies or second-grade tearing of the perineum between September 2005 and July 2007.
Methods One group was repaired with continuous, nonlocking sutures involving the vagina, perineum, and subcutaneous tissues. The other group had continuous, locking sutures of the vagina, interrupted sutures in the perineal muscles, and interrupted transcutaneous sutures. The threads used for stitching were identical in both groups.
Main outcome measures The participants were questioned regarding the sensation of pain and the use of painkillers on the second and the tenth days, and 3 months postpartum.
Results When comparing the group with continuous suture to the group with interrupted sutures, the differences included less repair time (1 minute; P = 0.017) and less suture material used (relative risk [RR], 3.2, 95% CI: 2.6–4.0). The comparison of pain on the second and tenth days, and 3 months postpartum were not statistically different between the two techniques (RR, 1.08, 95% CI: 0.74–1.57; RR, 0.96, 95% CI: 0.59–1.55; and RR, 0.68, 95% CI: 0.19–2.46, respectively).
Conclusions Although we did not demonstrate that one technique was better than the other in the incidence of pain in the short or long term, we showed that episiotomy and perineal tear repairs with continuous suturing were quicker and used less suture material without an increase in complication than interrupted suturing. 相似文献
Design A randomised controlled trial.
Setting The Hospital Universitario Principe de Asturias, a state hospital belonging to the community of Madrid.
Sample Four hundred forty-five women who had undergone vaginal deliveries with episiotomies or second-grade tearing of the perineum between September 2005 and July 2007.
Methods One group was repaired with continuous, nonlocking sutures involving the vagina, perineum, and subcutaneous tissues. The other group had continuous, locking sutures of the vagina, interrupted sutures in the perineal muscles, and interrupted transcutaneous sutures. The threads used for stitching were identical in both groups.
Main outcome measures The participants were questioned regarding the sensation of pain and the use of painkillers on the second and the tenth days, and 3 months postpartum.
Results When comparing the group with continuous suture to the group with interrupted sutures, the differences included less repair time (1 minute; P = 0.017) and less suture material used (relative risk [RR], 3.2, 95% CI: 2.6–4.0). The comparison of pain on the second and tenth days, and 3 months postpartum were not statistically different between the two techniques (RR, 1.08, 95% CI: 0.74–1.57; RR, 0.96, 95% CI: 0.59–1.55; and RR, 0.68, 95% CI: 0.19–2.46, respectively).
Conclusions Although we did not demonstrate that one technique was better than the other in the incidence of pain in the short or long term, we showed that episiotomy and perineal tear repairs with continuous suturing were quicker and used less suture material without an increase in complication than interrupted suturing. 相似文献
50.
北京市社区妇女人乳头瘤病毒感染率及其对HPV和疫苗认知情况的调查分析 总被引:2,自引:0,他引:2
[目的]评估北京市社区妇女人乳头瘤病毒(HPV)的感染率;调查社区人群对HPV的认知情况以及对HPV疫苗接种的态度。[方法]采用横断面调查方法,对北京市展览路社区15 ̄54岁女性进行HPV认知和流行病学问卷调查,并留取了宫颈脱落细胞或会阴部标本进行HPV DNA检测。[结果]1013名女性接受了问卷调查,832例HPV DNA检测结果纳入了统计学分析。HPV总检出率为15.38%,高、低危型HPV感染率分别为13.34%和3.25%,同时感染高、低危型HPV的检出率为1.20%。1013名调查对象中有30.7%听说过HPV,其中51.78%知道HPV感染与宫颈癌有关;HPV的知晓率与年龄和教育程度有关(P〈0.05);经过简单宣教后,75.91%愿意接种HPV疫苗。[结论]北京市社区妇女HPV现患率较高,对HPV的知晓率也较高。开展公众健康教育,提高人群的认识水平是疫苗计划获得成功的关键因素。 相似文献