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11.
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
12.
Dithiothreitol prevents age-associated decrease in oocyte/conceptus viability in vitro 总被引:2,自引:0,他引:2
The present study was designed to ascertain whether the negative effects on
reproductive potential of post-ovulatory ageing in vitro of oocytes can be
prevented by antioxidant therapy. Mouse metaphase II (MII) oocytes were
aged in vitro for 12 h prior to insemination in the presence of varying
concentrations of L-ascorbic acid, 6-methoxy-
2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox), L-cystine
dihydrochloride, ethylenediaminetetraacetic acid (EDTA), beta-
mercaptoethanol and DL-dithiothreitol (DTT). In-vitro ageing of oocytes was
associated with lower fertilization rate, higher proportion of concepti
exhibiting cellular fragmentation at 24 h post-insemination and lower
percentage of concepti reaching the blastocyst stage. Ascorbic acid, Trolox
and EDTA had no effect on cellular fragmentation or potential of oocytes
for development. However, the probability of an oocyte reaching the
blastocyst stage was decreased (P < or = or = 0.05) in oocytes incubated
in the presence of L-cystine (50 and 500 microM) and beta-mercaptoethanol
(5, 50 and 500 microM) when compared to control aged oocytes.
Age-associated cellular fragmentation at 24 h post-insemination was
partially prevented (P < or = 0.05) by incubating oocytes in the
presence of beta-mercaptoethanol (500 microM). DTT (50 and 500 microM)
increased (P < or = 0.05) fertilization rate and number of cells at 81 h
post-insemination to levels similar to those exhibited by control oocytes.
Furthermore, both age-associated fragmentation at 24 h post-insemination (P
< or = 0.05) and decreased potential of oocytes for development to the
blastocyst stage (P < or = 0.05) were prevented, at least in part, by
culturing oocytes in the presence of DTT (50 microM). Although the
mechanism by which DTT exerts its beneficial effects on aged oocytes
remains to be elucidated, it may protect oocytes by preventing oxidation of
free thiol groups and/or altering a redox-independent signalling pathway
that mediates cellular fragmentation and death.
相似文献
13.
Montero R Serrano L Dávila V Segura Y Arrieta A Fuentes R Abad I Valencia L Sierra P Camacho R 《Environmental and molecular mutagenesis》2003,42(3):216-222
Micronuclei and other biomarkers were evaluated in oral cells from 11- to 16-year-old girls living in a foster home in the central area of México City. Variables analyzed for possible association with these biomarkers include smoking habits, body mass index, metabolic polymorphisms for NAT1 and GSTM1 and whether the cells were obtained from the cheek or pharynx. The results indicated that individuals having the NAT1*10 homozygous genotype showed a significant increase in chromatin buds and binucleated cells. When the damage in the cheek was compared with damage in the pharynx, a significant increase in micronuclei and binucleated cells was found for the latter tissue in all the individuals analyzed. 相似文献
14.
15.
Y chromosome microdeletions, in azoospermic or near-azoospermic subjects, are located in the AZFc (DAZ) subregion 总被引:9,自引:2,他引:9
Submicroscopic deletions of the Y chromosome and polymorphisms of the
androgen receptor (AR) gene in the X chromosome have been observed in men
with defective spermatogenesis. To further define the subregions/genes in
the Y chromosome causing male infertility and its relationship to
polymorphisms of the AR polyglutamine tract, we screened the genomic DNA of
202 subfertile males and 101 healthy fertile controls of predominantly
Chinese ethnic origin. Y microdeletions were examined with 16
sequence-tagged site (STS) probes, including the RBM and DAZ genes,
spanning the AZFb and AZFc subregions of Yq11, and related to the size of
trinucleotide repeat encoding the AR polyglutamine tract. Y microdeletions
were detected and confirmed in three out of 44 (6.8%) of azoospermic and
three out of 86 (3.5%) severely oligozoospermic patients. No deletions were
detected in any of the patients with sperm counts of >0.5 x 10(6)/ml,
nor in any of the 101 fertile controls. All six affected patients had
almost contiguous Y microdeletions spanning the entire AZFc region
including the DAZ gene. The AZFb region, containing the RBM1 gene, was
intact in five of the six subjects. Y deletions were not found in those
with long AR polyglutamine tracts. Our study, the first in a Chinese
population, suggest a cause and effect relationship between Y
microdeletions in the AZFc region (possibly DAZ), and azoospermia or
near-azoospermia. Y microdeletions and long AR polyglutamine tracts appear
to be independent contributors to male infertility.
相似文献
16.
Determination of the parent of origin in nine cases of prenatally detected chromosome aberrations found after intracytoplasmic sperm injection 总被引:1,自引:17,他引:1
Van Opstal D; Los FJ; Ramlakhan S; Van Hemel JO; Van Den Ouweland AM; Brandenburg H; Pieters MH; Verhoeff A; Vermeer MC; Dhont M; In't Veld PA 《Human reproduction (Oxford, England)》1997,12(4):682-686
Prenatal cytogenetic analysis of 71 fetuses conceived by intracytoplasmic
sperm injection (ICSI) resulted in the detection of nine (12.7%) chromosome
aberrations including two cases of 47,XXY, four cases involving a 45,X cell
line and three autosomal trisomies. Molecular analysis of the parental
origin of the deleted or supernumerary chromosome was performed by using
polymorphic microsatellite markers. Six cases involving a sex chromosome
abnormality were found to be of paternal origin while the two trisomic
cases that could be analysed were of maternal origin. Two cases involved
the same infertile couple who had two consecutive ICSI pregnancies
terminated because of a chromosome abnormality. The replaced embryos in
both cases originated from a single batch of ICSI fertilized oocytes of
which part was used to initiate the first pregnancy and part was
cryopreserved and used to initiate the second pregnancy.
相似文献
17.
Billette J; Janse MJ; van Capelle FJ; Anderson RH; Touboul P; Durrer D 《The American journal of physiology》1976,231(4):1129-1139
18.
Vasoactive intestinal peptide in the immune system: potential therapeutic role in inflammatory and autoimmune diseases 总被引:9,自引:0,他引:9
Delgado M Abad C Martinez C Juarranz MG Arranz A Gomariz RP Leceta J 《Journal of molecular medicine (Berlin, Germany)》2002,80(1):16-24
Vasoactive intestinal peptide (VIP), a neuropeptide that is produced by lymphoid as well as neural cells, exerts a wide spectrum of immunological functions, controlling the homeostasis of the immune system through different receptors expressed in various immunocompetent cells. In the last decade, VIP has been clearly identified as a potent anti-inflammatory factor, which acts by regulating the production of both anti- and pro-inflammatory mediators. In this sense, VIP has been described to prevent death by septic shock, an acute inflammatory disease with a high mortality. In addition, VIP regulates the expression of co-stimulatory molecules, this being an action that may be related to modulating the shift toward Th1 and Th2 differentiation. We have recently reported that VIP prevents the deleterious effects of an experimental model of rheumatoid arthritis, by downregulating both inflammatory and autoimmune components of the disease. Therefore, VIP has been proposed as a promising candidate alternative treatment for acute and chronic inflammatory and autoimmune diseases such as septic shock, arthritis, multiple sclerosis, Crohn disease, or autoimmune diabetes. 相似文献
19.
P. Gayarre Abril J. Subirá Ríos L. Muñiz Suárez C. Murillo Pérez M. Ramírez Fabián J.I. Hijazo Conejos P. Medrano Llorente J. García-Magariño Alonso F.X. Elizalde Benito G. Aleson Hornos L. Pérez Abad J. Rioja Zuazu C. García Artal B. Blasco Beltrán P. Carrera Lasfuentes C. Marín Zaldivar 《Actas urologicas espa?olas》2021,45(4):247-256
20.
Juergen Messner Harpreet Chhina Sophia Davidson Jero Abad Anthony Cooper 《Journal of children's orthopaedics》2021,15(2):114
PurposeComparison of two hexapod frame systems in paediatric tibial deformity correction; the Taylor Spatial Frame (TSF) and Orthex Hexapod System.MethodsPaediatric patients with congenital and acquired tibial deformities treated with either TSF (between 2014 and 2016) or Orthex (between 2017 and 2019) frames were included in a retrospective comparative study. Outcome measures were healing index, pin infection rate, regenerate quality and density, software residual rate, deformity correction accuracy, strut exchanges and quality of life (QoL).ResultsThe TSF group had 17 patients (18 frames) and the Orthex group had 21 patients (25 frames). The most common indications for tibial deformity correction were fibular hemimelia (14) and septic or traumatic growth arrest (8). The median time in frame was 230 days (TSF) versus 203 days (Orthex) (p= 0.06). The mean lengthening achieved was 54 mm (TSF) and 51 mm (Orthex) (p = 0.41). The healing index was 41 days/cm (TSF) versus 43 days/cm (Orthex) (p = 0.70). Pin site infections occurred more in the TSF cohort (40%) than in the Orthex cohort (18%) (p < 0.001). The regenerate in the Orthex group showed higher density at three months (p = 0.029) and was more homogenous (p = 0.023) at six months after frame application. Strut exchanges were less frequent with the Orthex system (p < 0.0001). QoL measures were similar in both cohorts (p = 0.92).ConclusionsThis is the first study to compare two hexapod designs in paediatric orthopaedics. The Orthex system showed superiority in regenerate quality and a significant reduction in pin site infection rates. Both systems delivered predictable and accurate limb deformity correction.Level of evidenceIII 相似文献