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排序方式: 共有527条查询结果,搜索用时 93 毫秒
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2.
Piet Borgdorff Geert Jan Tangelder Walter J Paulus 《Journal of the American College of Cardiology》2006,48(4):817-823
OBJECTIVES: We aimed to investigate the effect of parecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on in vivo shear stress-induced platelet aggregation in a rat model of arterial bypass with focal narrowing. BACKGROUND: Long-term use of COX-2 inhibitors is associated with increased incidence of adverse cardiovascular events, especially in patients with a history of cardiovascular disease. These patients are at risk for thrombotic occlusion of arterial stenoses initiated by shear stress-induced platelet aggregation. METHODS: To mimic the combination of a tight arterial stenosis and high shear stress in rats, an extracorporeal shunt from carotid to femoral artery was compressed by the rollers of a pump. Platelet aggregation was continuously measured by a photometric detector in the shunt. RESULTS: Pretreatment with parecoxib (20 mg/kg) almost doubled shear stress-induced platelet aggregation (188% vs. 100% in control subjects, p = 0.0003). This was accompanied by a fall in plasma 6-keto-prostaglandin F(1alpha) from 100 +/- 25 pg/ml to 36 +/- 11 pg/ml (p < 0.0001). Enhanced platelet aggregation was also observed with high-dose aspirin (150 mg/kg) (146%; p = 0.02) but not with low-dose aspirin (25 mg/kg), which reduced aggregation (68%; p = 0.01). The effect of parecoxib was neutralized by low-dose (1 mg/kg) clopidogrel (from 188% to 92%; p = 0.0001), but not by low-dose aspirin (from 188% to 177%; p = NS). CONCLUSIONS: In the presence of an arterial stenosis, COX-2 inhibitors enhance shear stress-induced platelet aggregation. This enhancement was prevented by low-dose clopidogrel but not by low-dose aspirin. Clopidogrel might therefore allow COX-2 inhibitors to be used without raising risk of thrombotic occlusion. 相似文献
3.
S den Boon N W White S W P van Lill M W Borgdorff S Verver C J Lombard E D Bateman E Irusen D A Enarson N Beyers 《The international journal of tuberculosis and lung disease》2006,10(8):876-882
SETTING: A tuberculosis (TB) prevalence survey was performed in 2002 in two urban communities in Cape Town, South Africa. The population was 36,334 in 2001, and the TB notification rate was 341 per 100,000 population for new smear-positive TB in 2002. OBJECTIVE: To evaluate the relative contributions of symptom and chest radiographic (CXR) screening in the detection of subjects with smear- and/or culture-positive TB in prevalence surveys. DESIGN: Information on symptoms, CXR abnormalities, sputum smear and culture was gathered from a random cluster sample of 1170 adults (aged > or = 15 years). Smear and/or culture-positive TB was used as the gold standard. RESULTS: Of 1170 adults, 29 had bacteriologically positive TB (smear- and/or culture-positive). The presence of any abnormalities on CXR had the highest sensitivity for detecting subjects with bacteriologically positive TB (0.97, 95%CI 0.90-1.00). Specificity for any abnormalities on CXR was 0.67 (95%CI 0.64-0.70). The specificity of any of five TB-related symptoms was 0.68 (95%CI 0.65-0.71). Individual symptoms had low sensitivities, ranging from 0.10 for fever to 0.54 for cough of > or = 2 weeks. CONCLUSION: In this TB prevalence survey, CXR screening, but not symptom screening, was a sensitive alternative to sputum examination of all participants. 相似文献
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Human ovarian granulosa cells and follicular fluid indices: the relationship to oocyte maturity and fertilization in vitro 总被引:1,自引:0,他引:1
The study investigates the correlation between oocyte maturity and
fertilization and a variety of hormonal parameters in follicular fluid and
ovarian granulosa cells. A methodology for purification of granulosa cells
from contaminating blood cells is also established. A total of 63
follicular aspirates were collected at oocyte retrieval from 30 women
superovulated using the long luteinizing hormone- releasing hormone (LHRH
analogue)/human menopausal gonadotrophin regimen. Oestradiol, progesterone,
testosterone and human chorionic gonadotrophin (HCG) were quantified in
follicular fluid and granulosa cells were immunostained for human chorionic
gonadotrophin. Immunopurification of granulosa cells from contaminating
blood cells was performed. HCG in follicular fluid was significantly high
in follicles yielding immature (grade 3) oocytes (P=0.002); there was no
correlation with fertilization. Aspirates from follicles containing mature
(grade 1) oocytes and oocytes that subsequently fertilized had
significantly more granulosa cells immunobound to HCG (P < 0.001,
P=0.02). Moreover, the immunomagnetic purification technique provided
>98% pure population of granulosa cells. The data demonstrate that HCG
in follicular fluid and on granulosa cells may help to predict oocyte
maturity and fertilization. Furthermore, immunomagnetic beads provide a
reliable procedure for the purification of ovarian granulosa cells.
相似文献
7.
H. R. van Doorn P. E. W. de Haas K. Kremer C. M. J. E. Vandenbroucke-Grauls M. W. Borgdorff D. van Soolingen 《Clinical microbiology and infection》2006,12(8):769-775
A previous limited study demonstrated that Mycobacterium tuberculosis isolates with a mutation at amino-acid position 315 of katG (Delta315) exhibited high-level resistance to isoniazid and were more frequently resistant to streptomycin. In the present study, isoniazid-resistant M. tuberculosis isolates from 8,332 patients in The Netherlands (1993-2002) were screened for the Delta315 mutation. Isoniazid resistance was found in 592 (7%) isolates, of which 323 (55%) carried Delta315. IS6110 restriction fragment length polymorphism analysis showed that Delta315 isolates occurred in clusters, suggesting recent transmission, at the same frequency as isoniazid-susceptible isolates. In contrast, other isoniazid-resistant isolates clustered significantly less frequently. Delta315 isolates were high-level isoniazid-resistant, streptomycin-resistant and multidrug-resistant significantly more often, and may have a greater impact on public health, than other isoniazid-resistant isolates. 相似文献
8.
Burwinkel B; Maichele AJ; Aagenaes O; Bakker HD; Lerner A; Shin YS; Strachan JA; Kilimann MW 《Human molecular genetics》1997,6(7):1109-1115
Glycogen storage disease due to phosphorylase kinase deficiency occurs in
several variants that differ in mode of inheritance and tissue-
specificity. This heterogeneity is suspected to be largely due to mutations
affecting different subunits and isoforms of phosphorylase kinase. The gene
of the ubiquitously expressed beta subunit, PHKB, was a candidate for
involvement in autosomally transmitted phosphorylase kinase deficiency of
liver and muscle. To identify such mutations, the complete PHKB coding
sequence was amplified by RT-PCR of RNA isolated from blood samples of
patients and analyzed by direct sequencing of PCR products. The
characterization of mutations was complemented by PCR of genomic DNA. In
one female and four male patients, we identified five independent nonsense
mutations (Y418ter; R428ter; Y974H+E975ter; Q656ter in two cases), one
single-base insertion in codon N421, one splice-site mutation affecting
exon 31, and a large deletion involving the loss of exon 8. Although these
severe translation-disrupting mutations occur in constitutively expressed
sequences of the only known beta subunit gene of phosphorylase kinase,
PHKB, they are associated with a surprisingly mild clinical phenotype,
affecting virtually only the liver, and relatively high residual enzyme
activity of approximately 10%.
相似文献
9.
Delivery of a hammerhead ribozyme specifically down-regulates the production of fibrillin-1 by cultured dermal fibroblasts 总被引:4,自引:1,他引:4
Kilpatrick MW; Phylactou LA; Godfrey M; Wu CH; Wu GY; Tsipouras P 《Human molecular genetics》1996,5(12):1939-1944
The hammerhead ribozyme is a small catalytic RNA molecule. Potential
hammerhead ribozymes that possess a catalytic domain and flanking sequence
complementary to a target mRNA can cleave in trans at a putative cleavage
site within the target molecule. We have investigated the potential of
hammerhead ribozymes to down-regulate the product of the fibrillin-1 gene
(FBN1). Fibrillin is a 347 kDa glycoprotein that is a major constituent of
the elastin-associated microfibrils. Mutations in the FBN1 gene are
responsible for Marfan syndrome (MFS), a common systemic disorder of the
connective tissue. Many FBN1 mutations responsible for MFS appear to act in
a dominant-negative fashion, raising the possibility that reduction of the
amount of product from the mutant FBN1 allele might be a valid therapeutic
approach for MFS. A trans-acting hammerhead ribozyme (FBN1-RZ1) targeted to
the 5' end of the human FBN1 mRNA has been designed and synthesized, and
shown to cleave its target efficiently in vitro. FBN1-RZ1 cleavage is
magnesium dependent and efficient at both 37 and 50 degrees C. Delivery of
the FBN1-RZ1 ribozyme into cultured dermal fibroblasts, by receptor-
mediated endocytosis of a ribozyme-transferrin-polylysine complex,
specifically reduces both cellular FBN1 mRNA and the deposition of
fibrillin in the extracellular matrix. These results suggest that the use
of hammerhead ribozymes is a valid approach to the study of fibrillin gene
expression and possibly to the development of a therapeutic approach to
MFS.
相似文献
10.
Protective cytotoxic T lymphocyte responses against paramyxoviruses induced by epitope-based DNA vaccines: involvement of IFN-gamma 总被引:1,自引:0,他引:1
Hsu SC; Obeid OE; Collins M; Iqbal M; Chargelegue D; Steward MW 《International immunology》1998,10(10):1441-1447
Plasmid DNA vectors have been constructed with minigenes encoding a single
cytotoxic T lymphocyte (CTL) epitope from either the M2 protein of
respiratory syncytial virus (RSV) or from the nucleoprotein of measles
virus (MV) with or without a signal sequence (also called secretory or
leader sequence). Following intradermal immunization, plasmids in which the
CTL epitopes were expressed in-frame with the signal sequence were more
effective at inducing peptide- and virus- specific CTL responses than
plasmids expressing CTL epitopes without the signal sequence. This
immunization resulted in protection against MV-induced encephalitis and a
significant reduction in viral load following RSV challenge. The reduction
of viral load following RSV challenge was abrogated by prior injection with
anti-IFN-gamma antibodies. These results highlight the ability of
epitope-based DNA immunization to induce protective immune responses to
well-defined epitopes and indicate the potential of this approach for the
development of vaccines against infectious diseases.
相似文献