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991.
Inbal A; Englender T; Kornbrot N; Randi AM; Castaman G; Mannucci PM; Sadler JE 《Blood》1993,82(3):830-836
Type IIA von Willebrand disease (vWD), the most common type II vWD variant, is characterized by decreased binding of von Willebrand factor (vWF) to platelet glycoprotein Ib (Gplb) and by a decrease in large and intermediate vWF multimers. Mutations reported to cause vWD type IIA are clustered within the A2 domain of vWF, which is encoded by exon 28. Genomic DNA from affected members of 12 unrelated families with type IIA vWD were screened for these mutations by a rapid, nonradioactive, allele-specific oligonucleotide (ASO) hybridization method. Oligonucleotides containing each of eight mutations were cross-linked onto a nylon membrane by UV irradiation. A fragment of vWF exon 28 was amplified from peripheral blood leukocyte DNA using biotinylated primers and hybridized to the immobilized oligonucleotides. Positive signals were detected with an avidin-alkaline phosphatase conjugate and chemiluminescent substrate. Thus, in a single hybridization reaction, a patient sample could be analyzed for a large number of mutations simultaneously. Polymerase chain reaction (PCR) products from four patients did not contain any of the tested mutations and therefore were sequenced. Three additional candidate missense mutations, two of them novel, were identified: Arg(834)-->Gln in one patient, Gly(846)-->Arg in one patient, and Val(902)-->Glu in three ostensibly unrelated patients. By ASO hybridization, the mutations were confirmed in the affected patients and excluded in unaffected relatives and 50 normal controls. In one family, the Val(902)-->Glu mutation was shown to be a de novo mutation. This rapid screening method is applicable to other subtypes of vWD for which mutations have been identified. 相似文献
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995.
AM Low N. Kotecha TO Neild CY Kwan EE Daniel 《Clinical and experimental pharmacology & physiology》1996,23(4):310-316
1. These studies describe the functional effects of modulation of the sarcoplasmic reticulum (SR) Ca2+ stores at three levels of the vasculature: (i) large arteries (rat and guinea-pig aorta); (ii) small resistance arteries (rat tail artery, rabbit mesenteric artery, dog mesenteric artery); and (iii) arterioles (guinea-pig submucosal arterioles of the small intestine). 2. All tissues responded to phenylephrine (PE; 10 μmol/L) with a transient contraction in Ca2+-free Krebs', reflecting Ca2+ release from PE-sensitive Ca2+ stores. After pretreatment with cyclopiazonic acid (CPA; 30 μmol/L) or thapsigargin (TSG; 1 μmol/L), putative SR Ca2+ pump inhibitors, the PE-induced contraction in a Ca2+-free medium was significantly inhibited in arterial tissues at all levels of the vasculature. Similarly, ryanodine (RYA; 30 μmol/L), an agonist that enhances Ca2+ release from the SR, also reduced the PE contraction in a Ca2+-free solution. 3. CPA or TSG alone in the presence of extracellular Ca2+, caused marked and sustained contraction in the rat and guinea-pig aorta and marked but transient or no contraction in the resistance arteries. In the rat and guinea-pig aorta, RYA caused a slowly developing tension. Little increase in basal tension was produced by RYA in resistance arteries and arterioles. 4. The findings show that an agonist-releasable Ca2+ pool is present at all levels of the vasculature that is independent of the size of the vessels and suggest that under normal physiological conditions there is an intimate balance between the roles of the plasma membrane and of the SR in the maintenance of vascular contractility. It appears that the role of the SR diminishes as the arteries become smaller, while Ca2+ fluxes across the plasma membrane predominates. 相似文献
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Cumulative pregnancy rates and selective drop-out of patients in in- vitro fertilization treatment 总被引:5,自引:5,他引:0
Roest J; van Heusden AM; Zeilmaker GH; Verhoeff A 《Human reproduction (Oxford, England)》1998,13(2):339-341
The validity of the cumulative pregnancy rate (CPR) calculated by life-
table approach, obtained in a transport in-vitro fertilization (IVF)
programme, was tested by the determination of possible influence of
selective drop-out of patients with a poor treatment prognosis. A cohort of
1211 patients who had a first IVF cycle was followed, and the CPR after
three IVF cycles was assessed. First cycles of patients who discontinued
treatment after failed IVF, and of those who did not achieve a pregnancy
but proceeded to a subsequent cycle, were compared for fertilization rate
and for occurrence of prognosticators of poor treatment outcome: oocyte
yield < or =2, and replacement of <2 embryos. The CPR after three
cycles was 54.9%. No differences were found in the first and second cycles
of patients who continued treatment and those who dropped out. Selective
drop-out of patients with a poor treatment prognosis was not found.
Therefore, although calculations of CPR using life-table analysis generally
overestimate the real probability of pregnancy after successive IVF cycles,
the calculated CPR after three IVF cycles gives a reliable indication of
the chance of occurrence of a pregnancy for the population studied.
相似文献
998.
Lactating adenoma: US features and literature review 总被引:2,自引:0,他引:2
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