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101.
The role of the RGDX putative receptor-recognition sites, which are present on the alpha chains of fibrin, in promoting platelet adhesion has been examined in flowing whole blood using the rectangular perfusion chamber at wall shear rates of 340 and 1,600/s. Platelets adhered to a comparable extent to surfaces coated with native fibrin and surfaces coated with fragment X-fibrin, a product of limited fibrinolysis that lacks the RGDS sites normally present at positions 572 to 575 of the alpha chains. The strengths of these adhesive interactions were comparable based on the concentrations of the antiadhesive peptide D-RGDW required to block platelet deposition to native and fragment X-fibrin at both low and high wall shear rate. Blocking either or both RGDX sequences with peptide-specific monoclonal antibodies did not inhibit platelet deposition in perfusion experiments performed with normal blood at 340/s, indicating that neither RGD motif is required for adhesion. However, adhesion was partly inhibited by anti-RGDX antibodies when perfusions were performed with blood from an afibrinogenemic patient, suggesting the RGDX sequences may play a limited role in platelet deposition. Exposure of fibrin surfaces to plasminogen/tissue-type plasminogen activator did cause a time- dependent loss of adhesiveness, but this effect was only weakly correlated with proteolysis of the fibrin alpha chains. These observations provide evidence that neither RGDX sequence is required for platelets to adhere avidly to fibrin in flowing blood. These results further suggest that incomplete fibrinolysis yields a highly thrombogenic surface. 相似文献
102.
A variant of von Willebrand's disease with abnormal expression of factor VIII procoagulant activity 总被引:2,自引:1,他引:2
Reports on variants of von Willebrand's disease are numerous, but many of these are based on tests that will show marked fluctuations with time and tests that might not be similar in affected family members. This report describes 8 patients with a new variant of von Willebrand';s disease in which there is a normal APTT, slightly reduced one-stage factor VIII:C assay (VIII:C-1), and a drastically reduced two- stage factor VIII:C assay (VIII:C-2). The VIII:C in this variant is more readily adsorbed to AI(OH)3. This variability in VIII:C assays and excessive adsorption to AI(OH)3 are corrected by the addition of either hemophilic plasma or hemophilic factor-VIII-related antigen. This variant is stable with restudy on multiple occasions and is inherited in a stable fashion in three generations of one family. The multimeric structure of the VIIIR:Ag appears normal, although the concentration is moderately reduced. The differences in functional activity, the adsorption to AI(OH)3, and the differences between functional and antigenic (VIII:C Ag) assays of VIII:C support that this is a functional abnormality of type I von Willebrand's disease. 相似文献
103.
Localization of surface vWF on resting and stimulated platelets 总被引:1,自引:0,他引:1
We used immunoelectron microscopic localization techniques to investigate whether platelets stimulated by ADP or ristocetin in the plasma milieu bind von Willebrand factor (vWF) to their surfaces. We found by both peroxidase- and ferritin-based methods that unstimulated platelets lack vWF on their surfaces, whereas platelets that are stimulated with ADP or ristocetin have vWF associated with their surfaces. The specificity of the findings was confirmed by absorption studies using severe von Willebrand disease (vWD) and hemophilic plasmas. The anti-vWF antibodies were blocked by incubation with hemophilic plasma but not by incubation with severe vWD plasma. Thus, in the plasma environment, in the presence of fibrinogen, vWF becomes associated with the platelet surface subsequent to stimulation with ADP or ristocetin. 相似文献
104.
LE Almaguer‐Mederos NS Falcón YR Almira YG Zaldivar DC Almarales EM Góngora MP Herrera KE Batallán RR Armiñán MV Manresa GS Cruz J Laffita‐Mesa TM Cyuz V Chang G Auburger S Gispert LV Pérez 《Clinical genetics》2010,78(2):169-174
Almaguer‐Mederosa LE, Falcón NS, Almira YR, Zaldivar YG, Almarales DC, Góngora EM, Herrera MP, Batallán KE, Armiñán RR, Manresa MV, Cruz GS, Laffita‐Mesa J, Cyuz TM, Chang V, Auburger G, Gispert S, Pérez LV. Estimation of the age at onset in spinocerebellar ataxia type 2 Cuban patients by survival analysis. Previous studies have investigated the close association that exists between CAG repeat number and the age at onset in SCA2 = spinocerebellar ataxia type 2. These studies have focused on affected individuals. To further characterize this association and estimate the risk of a carrier developing SCA2 at a particular age as a function of a specific CAG repeat size, we have analyzed a large group of 924 individuals, including 394 presymptomatic and 530 affected individuals with a CAG repeat length of 32–79 units. Using a Kaplan–Meier survival analysis, we obtained cumulative probability curves for disease manifestation at a particular age for each CAG repeat length in the 34–45 range. These curves were significantly different (p < 0.001) and showed small overlap. All these information may be very valuable in predictive‐testing programs, in the planning of studies for the identification of other genetic and environmental factors as modifiers of age at onset, and in the design of clinical trials for people at enlarged risk for SCA2. 相似文献
105.
Nathan DM美 Buse JB美 Davidson MB美 Ferrannini E意大利 Holman RR英 Sherwin R美 Zinman B加拿大 钱荣立 《中华糖尿病杂志》2009,17(1):75-77
在不到一年时间由同一批专家代表ADA和EASD先后起草和发布了两次关于“2型糖尿病高血糖处理的共识声明”同时发表在2008年1月和12月的《DiabetesCare》和《Diabetologia》上。第一次共识声明内容主要围绕TZDs药物的安全性,本刊作了摘译转载(参阅《中国糖尿病杂志22008年第7期)。第二次修订的共识声明,关注点为降糖药的新分级,论据及观点比较清晰,故仍摘译供读者参考。 相似文献
106.
Ozkan B Wilkins K Muralee S Tampi RR 《American journal of Alzheimer's disease and other dementias》2008,23(4):344-354
The aim of this study is to systematically review the published literature on pharmacotherapy for inappropriate sexual behaviors in dementia. Literature search of the 5 databases (PubMed, MEDLINE, EMBASE, PsychINFO, and COCHRANE collaboration) and the analysis of the data available for the pharmacotherapeutic treatments of inappropriate sexual behaviors in dementia were carried out. There are no published randomized controlled trials of pharmacotherapy for inappropriate sexual behaviors in dementia, but available data form uncontrolled trials, case series, and individual case reports suggest efficacy for antidepressants, antipsychotics, mood stabilizers, hormonal agents, cimetidine, and pindolol for the treatment of these behaviors. Although there are no controlled data for the treatment of inappropriate sexual behaviors in dementia, available data suggest efficacy for some commonly used pharmacotherapeutic agents. 相似文献
107.
M-J Castro AH Stam C Lemos B de Vries KRJ Vanmolkot J Barros GM Terwindt RR Frants J Sequeiros MD Ferrari JM Pereira-Monteiro & AMJM van den Maagdenberg 《Cephalalgia : an international journal of headache》2009,29(3):308-313
Almost all mutations in the SCN1A gene, encoding the α1 subunit of neuronal voltage-gated NaV 1.1 sodium channels, are associated with severe childhood epilepsy. Recently, two mutations were identified in patients with pure familial hemiplegic migraine (FHM). Here, we identified a novel SCN1A L263V mutation in a Portuguese family with partly co-segregating hemiplegic migraine and epilepsy. The L263V mutation segregated in five FHM patients, three of whom also had epileptic attacks, occurring independently from their hemiplegic migraine attacks. L263V is the first SCN1A mutation associated with FHM and co-occurring epilepsy in multiple mutation carriers, and is the clearest molecular link between migraine and epilepsy thus far. The results extend the clinical spectrum associated with SCN1A mutations and further strengthen the molecular evidence that FHM and epilepsy share, at least in part, similar molecular pathways. 相似文献
108.
109.
In the West, in countries where many serious infectious diseases
have been eliminated or brought under control, cardiovascular disease
has become the most frequent cause of death among adults(I). Illness
from heart failure causes an enormous loss of time and money, so that
the economic aspects of heart djsease loom la.rge(2). Its prevention is,
therefore, a most important problem of public health, taking rank next
after tuberculosis (3) Realization of this need is growing rapidly, as is
shown by the formation of national associations with the principal pur-
pose of attacking the.problem. State public health, administrations have
hardly entered the field as yet, but they must soon do so. . 相似文献
110.
Characterization of four N-3-thymidine adducts formed in vitro by the reaction of thymidine and butadiene monoxide 总被引:1,自引:0,他引:1
Four products were characterized from the reaction of thymidine with
butadiene monoxide (BM), a known human mutagen and possible human
carcinogen. These products were purified by HPLC and characterized as
diastereomeric pairs of N-3-(1-hydroxy-3-buten-2-yl)thymidine and N-3-
(2-hydroxy-3-buten-1-yl)thymidine based upon their UV spectra, 1H NMR and
fast atom bombardment mass spectra. Incubation of thymidine with an excess
of BM at pH 7.4 and 37 degrees C allowed calculation of the
pseudo-first-order kinetic rate constants for the adduct formation, but
when these rate constants were compared with the rates we previously
determined with guanosine, adenosine and deoxycytidine, the results
suggested a lower reactivity with thymidine in comparison with the other
nucleosides. When incubations were carried out at lower BM concentrations,
the formation of adducts appeared to be linearly dependent on BM
concentration. The four thymidine adducts were completely stable for 1 week
when incubated at 37 degrees C in pH 7.4 phosphate buffer. These results
suggest that the interactions of BM with thymidine may play a role in the
molecular mechanisms of mutagenesis and carcinogenesis of BM.
相似文献