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High blood alcohol levels in women. The role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism 总被引:35,自引:0,他引:35
M Frezza C di Padova G Pozzato M Terpin E Baraona C S Lieber 《The New England journal of medicine》1990,322(2):95-99
After consuming comparable amounts of ethanol, women have higher blood ethanol concentrations than men, even with allowance for differences in size, and are more susceptible to alcoholic liver disease. Recently, we documented significant "first-pass metabolism" of ethanol due to its oxidation by gastric tissue. We report a study of the possible contribution of this metabolism to the sex-related difference in blood alcohol concentrations in 20 men and 23 women. Six in each group were alcoholics. The first-pass metabolism was determined on the basis of the difference in areas under the curves of blood alcohol concentrations after intravenous and oral administration of ethanol (0.3 g per kilogram of body weight). Alcohol dehydrogenase activity was also measured in endoscopic gastric biopsies. In nonalcoholic subjects, the first-pass metabolism and gastric alcohol dehydrogenase activity of the women were 23 and 59 percent, respectively, of those in the men, and there was a significant correlation (rs = 0.659) between first-pass metabolism and gastric mucosal alcohol dehydrogenase activity. In the alcoholic men, the first-pass metabolism and gastric alcohol dehydrogenase activity were about half those in the nonalcoholic men; in the alcoholic women, the gastric mucosal alcohol dehydrogenase activity was even lower than in the alcoholic men, and first-pass metabolism was virtually abolished. We conclude that the increased bioavailability of ethanol resulting from decreased gastric oxidation of ethanol may contribute to the enhanced vulnerability of women to acute and chronic complications of alcoholism. 相似文献
14.
Preimplantation genetic diagnosis principles and ethics 总被引:4,自引:0,他引:4
15.
Life expectancy in British Marfan syndrome populations 总被引:2,自引:0,他引:2
JR Gray AB Bridges RR West L. McLeish AG Stuart JCS Dean MEM Porteous M. Boxer SJ Davies 《Clinical genetics》1998,54(2):124-128
A total of 206 patients with Marfan syndrome were ascertained throughout genetic clinics in Wales and Scotland during the period 1970–1990. There were 45 deaths representing 22% of the cohort. Mean age at death was 45.3 ± 16.5 years. 50% median cumulative survival in the total cohort (n = 206) was 53 years for males and 72 years for females. Multivariate analysis confirmed severity as the best independent indicator of survival. These findings and survival curves will assist in the counselling of British families and individuals with Marfan syndrome. 相似文献
16.
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
17.
Recessively inherited L-DOPA-responsive parkinsonism in infancy caused by a point mutation (L205P) in the tyrosine hydroxylase gene 总被引:4,自引:0,他引:4
18.
19.
Quantitative analysis of muscle fibre type and myosin heavy chain Distribution in the frog hindlimb: implications for locomotory design 总被引:2,自引:0,他引:2
Lutz Gordon J. Bremner Shannon Lajevardi Nahal Lieber Richard L. Rome Lawrence C. 《Journal of muscle research and cell motility》1998,19(7):717-731
To investigate the design of the frog muscular system for jumping, fibre type distribution and myosin heavy chain (MHC) isoform composition were quantified in the hindlimb muscles of Rana pipiens. Muscles were divided into two groups: five large extensor muscles which were predicted to shorten and produce mechanical power during jumping (JP), and four much smaller muscles commonly used in muscle physiology studies, but that do not shorten or produce power during jumping (NJP). Fibres were classified as one of four different types (type 1, 2, 3 or tonic) or an intermediate type (type 1–2) based ontheir relative myosin-ATPase reactivity and MHC immunoreactivity in muscle cross-sections according to previous nomenclature established for amphibian skeletal muscle. Type 1 fibres correspond to the fastest and most powerful of the twitch fibres, and type 3 fibres are the slowest and least powerful. Myosin-ATPase histochemistry revealed that the JP muscles were co mposed primarily of type 1 fibres (89%) with a small percentage of type 2 (7%) and intermediate type 1–2 fibres (4%). The fibre type composition of NJP muscles was more evenly distributed between type 1 (29%), type 2 (46%) and type 1–2 (24%) fibres. Tonic fibres comprised less than 2% of the muscle cross-section in both JP and NJP groups. Similarly, MHC composition determined by quantitative SDS–PAGE revealed that JP muscles were composed predominantly of type 1 MHC (86%), with a balance of type 2 MHC (14%). The opposite pattern was found for MHC composition in the NJP muscles: type 1 (28%), type 2 (66%) and type 3 (6%). These results demonstrate that the large extensor muscles that produce the power required for jumping have a fibre type distribution that enables them to generate high levels of mechanical power, with the type 1 isoform accounting for 85–90% of the total M HC content. 相似文献
20.
Y chromosome deletions in azoospermic and severely oligozoospermic men undergoing intracytoplasmic sperm injection after testicular sperm extraction 总被引:11,自引:16,他引:11
Silber SJ; Alagappan R; Brown LG; Page DC 《Human reproduction (Oxford, England)》1998,13(12):3332-3337
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.
相似文献