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51.
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
52.
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
53.
Leal Filho MB Morandin RC de Almeida AR Cambiucci EC Borges G Gontijo JA Metze K 《Neuroscience letters》2005,373(2):165-170
There are reports describing both provocation and inhibition of neurogenic pulmonary edema by anesthetic drugs. Therefore, we compared the effect of two types of anesthesia on the formation of neurogenic pulmonary edema in rats with balloon-induced acute spinal cord injury. Animals with sham procedure (group 1) were anesthesized by intraperitoneal sodium pentobarbital. In the experimental groups, rats were submitted to acute spinal cord lesion by insufflations of a balloon in the epidural space at T8 for 1 min (group 3 under i.p. sodium pentobarbital and group 2 under i.p. xylazine-ketamine anesthesia). In rats with pentobarbital anesthesia, systolic blood pressure doubled the baseline value during compression, whereas this effect was less pronounced in the ketamine-xylazine group. The pulmonary index (100 x wet lung weight/body weight) was 0.395 (+/-0.018) in sham-operated rats, rose to 0.499 (+/-0.060) in group 2, and was maximum under pentobarbital anesthesia (0.639+/-0.14; p=0.0018). Histologic examination of the spinal cord showed parenchymal ruptures and acute hemorrhage. Comparison of the pulmonary index with histologic slides of lung parenchyma revealed that relevant intra-alveolar edema occurred only for index values above 0.55. On electron microscopy, endothelial alterations, and damage of the alveolar lining cells were found. Our study indicates that neurogenic pulmonary edema caused by spinal cord injury is less pronounced in rats under xylazine-ketamine anesthesia, when compared with pentobarbital. 相似文献
54.
Tania C. Araújo-Jorge Maria de Nazareth Leal de Meirelles Lourdes Isaac 《Parasitology research》1990,76(7):545-552
We report that alpha-2-macroglobulin (A2M), the physiologically important plasma protease inhibitor and suspected immunomodulator, alters the functional ability of murine resident peritoneal macrophages (RM) to ingest and kill the infective trypomastigote stage ofTrypanosoma cruzi, the aetiological agent of Chagas' disease. Treatment of RM with 500 g/ml A2M for 30 min enhanced the uptake of trypomastigotes, epimastigotes, and amastigotes by 125%, 46%, and 300%, respectively. The same treatment also increased the phagocytosis of sheep erythrocytes opsonized with complement and IgG as well as of galactosylated asialoerythrocytes. After 60–90 min parasite-cell interaction, epi-and amastigotes were killed by the RM, whereas the infection with trypomastigotes was controlled only after 24 h. Other protease inhibitors, bovine serum albumin, and LPS showed no such effect. The production of hydrogen peroxide was not affected by A2M treatment, but the ultrastructural aspects showed trypomastigote damage and enhancement of macrophage membrane ruffling, indicative of macrophage activation. These results suggest that A2M has the ability to modulate, at least functionally, certain receptor-mediated endocytic pathways that, in concert with an activation of possibly oxygen-independent microbicidal mechanisms, could contribute to resistance against the parasite.Abbreviations A2M
alpha-2-macroglobulin
- F-A2M
fast A2M
- S-A2M
slow A2M
- RM
resident macrophages
- BT
bloodstream trypomastigotes
- EPI
epimastigotes
- AMA
amastigotes
- DMEM
Dulbecco's Modified Eagle Medium
- PBS
phosphate-buffered saline
- BSA
bovine serum albumin
- LPS
bacto lipopolysaccharide
- STI
sovoean trypsin inhibitor
- PPA
pepstatin A
- LPT
leupeptin
- PNT
1, 10-phenanthroline
- TLCK
N--tosy-L-lysine-chloromethylketone
- E
sheep erythrocyte
- aE
asialoerythrocyte
- Gal R
receptors for galactosylated particles 相似文献
55.
56.
Leal GF Roberts E Silva EO Costa SM Hampshire DJ Woods CG 《Journal of medical genetics》2003,40(7):540-542
57.
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
58.
How to use Chlamydia antibody testing in subfertility patients 总被引:1,自引:9,他引:1
Screening for tubal factor subfertility by means of Chlamydia antibody
testing (CAT) was introduced into the initial work-up of subfertile couples
several years ago. The results reported, however, are heterogeneous, and no
uniformity exists in cut-off levels of titres, or in definitions of tubal
factor subfertility. We performed a prospective cohort study to evaluate
the implications of varying the definitions of tubal pathology and of
modifying the cut-off levels on the clinical impact of CAT in predicting
tubal factor subfertility. In 227 consecutive patients who attended our
fertility clinic, the Chlamydia IgG antibody titre was determined and
related to tuboperitoneal abnormalities at laparoscopy as a reference
standard. According to received operating characteristic (ROC) curve
analysis, a titre of 16 is the optimum cut-off level. Increasing the
cut-off level improves specificity and positive likelihood ratio (LR+), at
the expense of sensitivity and negative LR (LR-). Changing the definition
of tubal factor subfertility from unspecified tuboperitoneal abnormalities
into extensive adhesions and/or bilateral distal tubal occlusion improves
LR+, LR- and kappa significantly. We conclude that CAT is more accurate in
predicting severe distal tubal pathology than unspecified tuboperitoneal
abnormalities. Although from a statistical point of view a titre of 16 is
the optimum cut-off level, from a clinical point of view 32 or 64 may be
preferable, depending on the aim of screening and the inception cohort.
相似文献
59.
Pal L; Leykin L; Schifren JL; Isaacson KB; Chang YC; Nikruil N; Chen Z; Toth TL 《Human reproduction (Oxford, England)》1998,13(7):1837-1840
A case series of eight cycles of in-vitro fertilization (IVF) in five women
diagnosed with malignant disorders is presented. These patients chose to
defer definitive treatment for a chance for preservation of potential
fertility. The response of these patients to ovarian stimulation, and the
outcome, was compared with 17 IVF cycles in 12 age- matched patients with
isolated tubal infertility. An apparent adverse influence of malignant
disease on the quality and behaviour of oocytes was observed. Despite a
comparable total number of oocytes per cycle in the two groups, a
significantly reduced percentage of mature oocytes was retrieved per cycle
from patients with malignant diseases. The oocytes from patients with
malignant disorders were of a poorer quality and exhibited a significantly
impaired fertilization rate compared to the controls. We propose that
neoplastic processes, irrespective of the site or cell of origin, may have
a detrimental impact on the biology of oocytes, an effect akin to that seen
on spermatozoa in men with certain malignancies.
相似文献
60.