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.
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The rescue of vesicular stomatitis virus (VSV) from interferon-induced resistance in rabbit (RK-13) and mouse (L) cell cultures superinfected with vaccinia requires early (up to 2 hr) vaccinia DNA-dependent RNA synthesis. The inability of hydroxyurea to inhibit rescue of VSV in interferon-treated RK-13 and L cells, whether the drug is added at the time of or after infection, suggests that vaccinia DNA synthesis is not required for the rescue of VSV in cells superinfected with vaccinia.In both RK-13 and L cells pretreated with homologous interferon and then doubly infected with vaccinia and VSV, there was a significant increase (up to 8 hr) in the lag period before infective VSV progeny appeared. It appears that a product of vaccinia synthesis must accumulate before VSV replication can begin in cells pretreated with interferon. This product could be vaccinia-directed early RNA or a translation product of this RNA.In RK-13 cells pretreated with interferon, the ability of vaccinia to rescue VSV is much more resistant to UV-irradiation than the infectivity of the virus; in L cells there is a close correspondence in the inactivation rates of infectivity and the ability of vaccinia to rescue VSV. These results suggest a difference in the efficiency of uncoating of UV-irradiated vaccinia in RK-13 and L cells. In L cells it is possible that UV-irradiated vaccinia is not uncoated efficiently and the early vaccinia RNA product required for rescue of VSV is not synthesized. 相似文献
Coinfection with vaccinia virus increases the growth of vesicular stomatitis virus (VSV) in mouse L cells by 10- to 20-fold. Although vaccinia has no significant effect on RNA synthesis by VSV, VSV protein synthesis is dramatically stimulated by double infection. The enhancement of VSV growth is correlated with the ability of vaccinia to inhibit the VSV-mediated damage to the host translational machinery. Coinfection with vaccinia fails to stimulate the growth of a VSV mutant which is deficient in its ability to shut off protein synthesis during infection. 相似文献
Y chromosome deletions encompassing the AZFc region have been reported in
13% of azoospermic men and 7% of severely oligozoospermic men. We examined
the impact of these Y deletions on the severity of testicular defects in 51
azoospermic men undergoing intracytoplasmic sperm injection (ICSI) after
testicular sperm extraction (TESE) and 30 men with severe oligozoospermia
undergoing ICSI after ejaculation of spermatozoa. In addition, five
azoospermic patients shown previously to have Y chromosome deletions
underwent histological evaluation of their previously obtained testis
biopsy specimens. A further 27 azoospermic men underwent TESE-ICSI, but not
Y chromosome DNA testing. Ten of 51 azoospermic men (20%) who underwent
TESE-ICSI and Y-DNA testing were found to be deleted for portions of the Y
chromosome AZFc region. Of these 10, five had spermatozoa retrievable from
the testis, and in two cases the wives became pregnant. Of the 41
azoospermic men with no Y chromosome deletion, 22 (54%) had spermatozoa
retrievable from the testis, and in 12 cases (29%) the wives became
pregnant. Four of 30 (13%) severely oligozoospermic patients were found to
be deleted for AZFc and in three (75%) of these pregnancy was achieved. The
other 26 severely oligozoospermic couples who had no AZFc deletions
underwent ICSI, and 12 (46%) have an ongoing or delivered pregnancy. The
embryo implantation rate was not significantly different for azoospermic
(22%), oligozoospermic (16%), Y-deleted (14%) or Y-intact (18%) men. Of the
total of 19 infertile men who had Y chromosome deletions, 14 had deletions
within Y chromosome intervals 6D-6F, in the AZFc region. Twelve of those 14
had some spermatozoa (however few in number) in the ejaculate or testis.
Five of the Y-deleted men had deletions that extended more proximally on
the Y chromosome, and in none of these could any spermatozoa be observed in
either ejaculate or testis. These results support the concept that, in
azoospermic or oligozoospermic men with Y chromosome deletions limited to
intervals 6D-6F (AZFc), there are generally very small numbers of
testicular or ejaculated spermatozoa. Larger Y deletions, including and
extending beyond the AZFc region and encompassing more Y genes, tend to be
associated with a total absence of testicular spermatozoa. In those cases
where spermatozoa were retrieved, the presence of Y deletions had no
obvious impact on fertilization or pregnancy rate.
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The aim of this study was to compare the efficacy of pure follicle
stimulating hormone (FSH) with that of FSH/human menopausal gonadotrophin
(HMG) combination in downregulated cycles. A total of 357 patients was
evaluated retrospectively. Sixty percent of patients in the FSH group and
55% in the FSH/HMG group were new; the others were repeat patients.
Ovulation was suppressed with leuprolide acetate in all patients, followed
by either FSH (n = 218) or FSH/HMG (n = 119). There was no difference in
patients' age, infertility factors, number of ampoules used, length of
stimulation, oestradiol levels on day of human chorionic gonadotrophin
(HCG) administration, number of oocytes recovered or the number of embryos
transferred. Also, nuclear maturity at aspiration and fertilization rates
were not different between the two groups. FSH stimulation resulted in a
significantly higher percentage of mature oocytes that showed the typical
'mature' morphological characteristics (P < 0.0001). The clinical
pregnancy rates per transfer were 40 and 28% in patients stimulated with
pure FSH and FSH/HMG respectively (P < 0.05). The significantly higher
number of immature oocytes matured in vitro in the FSH/HMG group (P =
0.001) suggests a possible effect on in-vitro maturation, due to
luteinizing hormone present in HMG. The difference in mature oocyte quality
may be an important determinant in the higher pregnancy rates for the FSH-
stimulated patients.
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Objective: To evaluate the incidence and severity of apnoea and bradycardia in hospitalized preterm infants following immunization at 2 months of age, and identify risk factors. Methodology: A prospective study of 98 preterm infants, of gestational age 24–31 weeks, immunized at approximately 2 months post natal age with diphtheria-tetanus-whole cell pertussis vaccine (DTPw) in the neonatal intensive care unit (NICU) at King George V Hospital Sydney. Half the infants also received Haemophilus influenzae type b conjugate vaccine (Hib) simultaneously. All infants were monitored for apnoea and bradycardia in the 24 h periods pre- and post immunization. Results: Only one infant had apnoea and/or bradycardia pre-immunization compared with 17 post immunization. For 12 infants these events were brief, self-limiting and not associated with desaturations (oxygen saturation <90%). However, for five infants (30%) these events were associated with oxygen desaturation and two of these infants required supplemental oxygen. The group that had apnoea and/or bradycardia and the group that did not were not significantly different in terms of gestational age, birth weight and other variables. Infants who received Hib together with DTPw were less likely to have apnoea and/or bradycardia than those given DTPw alone. Conclusion: When considering immunization for preterm infants, the benefits of early immunization must be balanced against the risk of apnoea and bradycardia. We recommend that the cardio-respiratory function of hospitalized infants born at less than 31 weeks gestation be monitored for 48 h post immunization. 相似文献
The Authors for the Live Organ Donor Consensus Group
JAMA. 2000;284:2919-2926.
Objective To recommend practice guidelines for transplantphysicians, primary care providers, health care planners, andall those who are concerned about the well-being of the liveorgan donor.
Participants An executive group representing the NationalKidney Foundation, and the American Societies of Transplantation,Transplant Surgeons, and Nephrology formed a steering committeeof 12 members to evaluate current practices of living donortransplantation of the kidney, pancreas, liver, intestine, andlung. The steering committee subsequently assembled more than100 representatives of the transplant community (physicians,nurses, ethicists, psychologists, lawyers, scientists, socialworkers, transplant recipients, and living donors) at a nationalconference held June 1-2, 2000, in Kansas City, Mo.
Consensus Process Attendees participated in 7 assignedwork groups. Three were organ specific (lung, liver, and kidney)and 4 were focused on social and ethical concerns (informedconsent, donor source, psychosocial issues, and live organ donorregistry). Work groups' deliberations were structured by a seriesof questions developed by the steering committee. Each workgroup presented its deliberations to an open plenary sessionof all attendees. This information was stored and shaped intoa statement circulated electronically to all attendees for theircomments, and finally approved by the steering committee forpublication. The term consensus is not meant to convey universalagreement of the participants. The statement identifies issuesof controversy; however, the wording of the entire statementis a consensus by approval of all attendees.
Conclusion The person who gives consent to be a live organdonor should be competent, willing to donate, free from coercion,medically and psychosocially suitable, fully informed of therisks and benefits as a donor, and fully informed of the risks,benefits, and alternative treatment available to the recipient.The benefits to both donor and recipient must outweigh the risksassociated with the donation and transplantation of the livingdonor organ.