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41.
The P-selectin gene is highly polymorphic: reduced frequency of the Pro715 allele carriers in patients with myocardial infarction 总被引:10,自引:3,他引:10
Herrmann SM; Ricard S; Nicaud V; Mallet C; Evans A; Ruidavets JB; Arveiler D; Luc G; Cambien F 《Human molecular genetics》1998,7(8):1277-1284
P-selectin is an adhesion molecule, expressed at the surface of activated
cells, that mediates the interaction of activated endothelial cells or
platelets with leukocytes. P-selectin expression is increased in
atherosclerotic plaques, and high plasma levels of this molecule have been
observed in patients with unstable angina. We investigated the P-selectin
gene as a possible candidate for myocardial infarction (MI). The P-selectin
gene is situated on chromosome 1q21-q24, spans >50 kb and contains 17
exons. The sequences of the 5'-flanking region and exons of 40 alleles from
patients with MI were screened for polymorphisms using polymerase chain
reaction/single-strand conformation polymorphism (PCR-SSCP) and sequencing.
Thirteen polymorphisms were identified: five in the 5'-flanking and eight
in the exonic sequences. Four polymorphisms (Ser290Asn, Asn562Asp,
Leu599Val and Thr715Pro) predicted a change in the amino acid sequence of
the P- selectin protein. All P-selectin polymorphisms as well as a common
E- selectin polymorphism, Ser128Arg which has been reported as being
associated with an increased risk of premature coronary heart disease
(CHD), and is in tight linkage disequilibrium with several P-selectin
polymorphisms, were investigated in 647 patients with MI and 758 control
subjects from four regions of France and Northern Ireland (the ECTIM
study). The entire set of P-selectin polymorphisms provided a
heterozygosity of 91%. The polymorphisms were tightly associated with one
another and displayed patterns of linkage disequilibrium suggesting the
existence of highly conserved ancestral haplotypes. The five polymorphisms
in the 5'-flanking region of the gene were unrelated to MI or any relevant
phenotype measured in the ECTIM study. We inferred that the four missense
variants identified in the coding region predicted eight common forms of
the P-selectin protein. The Pro715 allele which characterizes one of these
forms was less frequent in France than in Northern Ireland ( P < 0.002)
and in cases than in controls ( P < 0.002; P < 0.02 after correction
for the number of tests). We conclude that the P-selectin gene is highly
polymorphic and hypothesize that the Pro715 variant may be protective for
MI. Whether this variant affects the properties of the P-selectin protein
in a way which is compatible with this hypothesis needs to be checked
experimentally.
相似文献
42.
Glycoproteins present in human follicular fluid that inhibit the zona- binding capacity of spermatozoa 总被引:1,自引:0,他引:1
Previous studies have suggested that human follicular fluid contains
factors that reduce the zona-binding capacity of spermatozoa. The present
study provides further evidence of the existence of such factors. Using the
hemizona binding assay (HZA), we have shown that the inhibitory effect of
human follicular fluid on the zona-binding capacity of spermatozoa is
concentration-dependent, an inhibitory effect being detected when the
concentration of human follicular fluid was > or = 10%. A 1%
concentration of human follicular fluid did not possess this inhibitory
activity. Heating human follicular fluid at 56 degrees C for 30 min did not
affect its inhibitory properties; treatment with proteinase-K abolished
such inhibition. Human follicular fluid was fractionated sequentially by
concanavalin-A affinity chromatography, Mono Q ion-exchange chromatography
and Superose-12 gel filtration. The zona binding inhibitory activity
resided in the fraction which bound to the lectin and Mono Q column and
contained molecules with native molecular weights of 32 and 192 kDa. Sodium
dodecyl sulphate-polyacrylamide gel electrophoresis analysis suggested that
the 192 kDa glycoprotein was a tetramer, while the 32 kDa glycoprotein
remained as a single molecular species under denaturing conditions. We
conclude that two glycoproteins were responsible for the zona binding
inhibitory activity of human follicular fluid. The physiological role of
these factors remains unclear.
相似文献
43.
Fifty women with polycystic ovaries took part in a prospective randomized
study. All women required treatment by in-vitro fertilization (IVF) for
reasons other than anovulation. They had all previously undergone ovarian
stimulation with gonadotrophin therapy which had failed to result in
pregnancy or had been abandoned due to high risk of developing ovarian
hyperstimulation syndrome (OHSS). Twenty-five women were treated by
long-term pituitary desensitization followed by gonadotrophin therapy,
oocyte retrieval and embryo transfer (group 1). Twenty-five women underwent
laparoscopic ovarian electrocautery after pituitary desensitization
followed by gonadotrophin therapy, oocyte retrieval and embryo transfer
(group 2). A significantly higher number of women in group 1 had to have
the treatment cycle abandoned due to impending or actual OHSS, determined
by endocrine and clinical findings. In addition, the development of
moderate or severe OHSS in completed cycles was higher in group 1. The
pregnancy rate and miscarriage rates in the two treatment groups were
similar. The authors propose that laparoscopic ovarian electrocautery is a
potentially useful treatment for women who have previously had an IVF
treatment cycle cancelled due to risk of OHSS or who have suffered OHSS in
a previous treatment cycle.
相似文献
44.
45.
46.
SM Ismail 《Journal of clinical pathology》1993,46(11):1067-1068
47.
Abnormal expression of the cell cycle regulators P16 and CDK4 in Alzheimer's disease. 总被引:13,自引:6,他引:13
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A. McShea P. L. Harris K. R. Webster A. F. Wahl M. A. Smith 《The American journal of pathology》1997,150(6):1933-1939
In this study, we demonstrate that two important regulators of the cell cycle, cyclin-dependent kinase-4 and its inhibitor p16, are increased in the brains of cases of Alzheimer's disease patients compared with age-matched controls. Both proteins are increased in the pyramidal neurons of the hippocampus, including those neurons containing neurofibrillary tangles and granulovacuolar degeneration. As p16 is not normally found in terminally differentiated neurons, it seems paradoxical that it is increased in Alzheimer's disease unless it is responding to increases in cyclin-dependent kinase-4 or other cell cycle regulators. Induction of the latter, a protein that signals re-entry and progression through the cell cycle, may itself be the consequence of alpha response to a growth stimulus. Re-entry into the cell cycle is likely deleterious in terminally differentiated neurons and may contribute to the biochemical abnormalities, such as oxidative stress and hyperphosphorylated tau protein, as well as the neuronal degeneration characteristic of the pathology of Alzheimer's disease. 相似文献
48.
Multiple IgE-mediated sensitizations to enzymes after occupational exposure: evaluation by skin prick test, RAST, and immunoblot 总被引:1,自引:0,他引:1
We investigated 10 sensitized and 10 nonsensitized workers from a pharmaceutic factory who had been exposed to powdered trypsin, chymotrypsin, bromclain, papain, amylase, and lipase. Ten nonallergic subjects served as a control group. Titrated skin prick tests (SPT), RAST, and immunoblot studies were performed with all six enzymes. SPT reactivity revealed multiple sensitizations to proteolytic enzymes, i.e., papain (specifically sensitized/total number of sensitizations: 9/10), trypsin (8/10), chymotrypsin (8/10), and bromelain (7/10) and appeared to be more frequent and more pronounced than sensitizations to amylase (3/10) or lipase (3/10). The low molecular weight of proteolytic enzymes (20–30 kDa) and their biologic activity might facilitate mucosal penetration more easily and thus - compared to amylase and lipase - permit an immune response and induction of allergic hypersensitivity. Immunoblot studies demonstrated IgG-binding bands in both SPT-positive and -negative workers, indicating exposure to the enzymes, but not in 10 unexposed control subjects. IgE-binding bands of the enzymes were detected only in workers with a positive SPT reaction and/or a positive RAST result. IgG bands were more frequent and the IgG/IgE ratio was increased in workers without allergic complaints compared to symptomatic workers. This might indicate that high levels of specific IgG antibodies to enzymes arc associated with an immune response lacking allergic manifestations in spite of IgE-mediated sensitizations to the enzymes. Atopic subjects were at greater risk of developing IgE-mediated sensitization (7/10) and allergic symptoms to enzymes (5/7). However, even without risk of atopy, IgE-mediated hypersensitivity occurred in a few subjects (3/13) exposed to enzymes by inhalation for prolonged periods of time. 相似文献
49.
F Bruder Stapleton Patricia W Wahl Tom E Norris Paul G Ramsey 《Academic medicine》2006,81(10):897-901
Widespread interest in global health issues is a common characteristic of students and faculty in schools of public health and schools of medicine. Building on strong university-based and community-based programs in global health, the University of Washington has created a unique Department of Global Health that is housed jointly in its School of Public Health and Community Medicine and its School of Medicine. The creation of this department has generated significant enthusiasm throughout the university and the Seattle community as a new paradigm for addressing global health education, research, and service. Placing the new Department of Global Health in two university schools and finding the appropriate niche for the department among the university's many global health initiatives presented challenges, as well as opportunities. This article describes the goals of the department, the process by which it was created, and what it expects to accomplish. 相似文献
50.
Application of capillary electrophoresis in clinical chemistry: the clinical value of urinary modified nucleosides 总被引:3,自引:0,他引:3
Liebich HM Lehmann R Xu G Wahl HG Häring HU 《Journal of chromatography. B, Biomedical sciences and applications》2000,745(1):189-196
Urinary modified nucleosides were determined by capillary electrophoresis using a 300 mM SDS-25 mM sodium tetraborate-50 mM sodium dihydrogenphosphate buffer. The nucleosides were extracted from urine by phenylboronate affinity gel chromatography. In cancer patients the levels of the modified nucleosides are generally elevated. By an artificial neural network method breast cancer patients were differentiated from normal individuals, which indicates that the modified nucleosides could be of clinical value as tumor markers. 相似文献