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41.
Thrombin causes subsecond changes in protein phosphorylation of platelets   总被引:1,自引:0,他引:1  
Carty  DJ; Spielberg  F; Gear  AR 《Blood》1986,67(6):1738-1743
We have developed a general quenched-flow approach to study platelet function as early as 0.3 seconds after stimulation. Phosphorylation of 20- and 40-kd proteins has been analyzed during the first five seconds of platelet response to thrombin from 0.1 to 5.0 U/mL and compared with the progress of aggregation and serotonin secretion. The onset time for aggregation and phosphorylation of both proteins was less than one second, although with lowest (less than 0.5 U/mL) thrombin levels, a lag of up to 0.6 seconds occurred before 40K phosphorylation increased. The thrombin sensitivity of aggregation and 20K phosphorylation was approximately twice that of 40K phosphorylation, with Ka values of 0.51 and 0.53 v 1.10 U/mL, respectively. External calcium was necessary for maximal 20K phosphorylation, since EDTA inhibited this by 30%. The 40K phosphorylation was not affected by EDTA. Platelet activation by thrombin thus induced biochemical changes well before one second. The quenched-flow approach may help to reveal relationships between phospholipase activation, calcium fluxes, and protein phosphorylation during these early periods of platelet function.  相似文献   
42.
Thompson  AR; Chen  SH; Smith  KJ 《Blood》1988,72(5):1633-1638
In hemophilia B, assays based on a monoclonal antifactor IX specific for the Thr-148 variant of an exonic polymorphism have diagnosed carriers in selected families by either establishing linkage or by indicating the presence or absence of a given normal factor IX. The sensitivity of the immunoassays for detecting heterozygous women was explored by comparing results from immunoassays with solid-phase polyclonal v the monoclonal antifactor IXs. Factor IX with the normal Ala-148 variant gave a flat dilution curve, qualitatively distinct from factor IX with the Thr-148 variant in the monoclonal assay. The two were indistinguishable in the polyclonal assay. Mixtures of equal amounts of the two types gave an intermediate result, about half as reactive in the monoclonal as compared with the polyclonal assay system. Whereas mixtures with 10% Ala-148 and 90% Thr-148 factor IXs could not readily be distinguished from Thr-148 factor IX plasma, as little as 1% of the Thr-148 protein was detected in Ala-148 factor IX plasma. The frequency of the Ala-148 variant varied in individuals with different ethnic backgrounds; it was found in 29% of white, 12% of black, and none of Asian blood donors' factor IX genes in Seattle. Only 4% of samples from South African black men were nonreactive (ie, Ala- 148). The Thr/Ala-148 dimorphism is in strong linkage disequilibrium with Taql restriction fragment length polymorphisms (RFLPs). Three recombinations were noted in normal white genes and one in a normal black factor IX gene (less than 2% of those examined). In 34 white families with at least one woman being a possible carrier, genetically, the immunoassay results were informative in 18. RFLP analyses were informative in eight of the 15 families tested. In five families each, assignment of carrier status was made to a woman by only DNA or only immunoassay results, whereas the other approach was noninformative. The immunoassays provide a rapid, inexpensive screening test and complement DNA analysis in white women who are potential carriers of hemophilia B.  相似文献   
43.

Background

This study aimed to evaluate fetal echocardiographic measurements at the time of the first fetal echocardiogram as predictors of neonatal outcome for tetralogy of Fallot (TOF).

Methods

The study reviewed all infants with a prenatal diagnosis of TOF from January 2004 to June 2011. Aortic valve (AoV), pulmonary valve (PV), main pulmonary artery (MPA), left and right pulmonary artery diameters, and ductus arteriosus flow were evaluated on fetal echocardiograms, and associations between the fetal echocardiogram and the neonatal echocardiogram measurements and outcomes were assessed.

Results

The study identified 67 TOF patients who had an initial fetal echocardiogram at a mean gestational age of 25.0 ± 5.2 weeks. Patients with absent PV syndrome or major aortopulmonary collaterals were excluded from the study, as were those without anterograde pulmonary blood flow at the first fetal echocardiogram. Of the remaining 44 patients, 10 were ductal dependent and required neonatal surgery. Infants who were ductal dependent had lower fetal PV (?5.38 ± 2.95 vs. ?3.51 ± 1.66; p < 0.05) and MPA (?3.94 ± 1.66 vs. ?2.87 ± 1.04; p < 0.05) z-scores. A fetal PV z-score of ?5 predicted ductal dependence with 78 % sensitivity and 87 % specificity, and a PV z-score of ?3 showed 100 % sensitivity and 34 % specificity (p < 0.001). Fetuses with a reversed left-to-right flow across the ductus arteriosus (DA) were more likely to be ductal dependent (odds ratio, 25; p < 0.001) than those who had normal ductal flow.

Conclusions

In TOF, fetal PV and MPA z-scores and direction of the DA blood flow predict neonatal ductal dependence. Patients with fetal PV z-scores lower than ?3 or any left-to-right flow at the level of the DA should be admitted to a center where prostaglandin is available.  相似文献   
44.
目的数值模拟抗血管生成因子Angiostatin和Endostatin对肿瘤血管生成的影响。方法建立肿瘤内外血管生成的二维离散数学模型。模型耦合两种抗血管生成因子Angiostatin和Endostatin的抑制效应,数值模拟在促血管生成因子诱导下肿瘤微血管网生成,讨论血管生成抑制因子的影响。结果抗血管生成因子Angiostatin对肿瘤内外血管网络生成的速度和成熟度有抑制作用。抗血管生成因子Angiostatin和Endostatin耦合作用时,在肿瘤血管生成的早期有明显的抑制效应;在肿瘤血管生成的中后期,它们可以降低肿瘤血管化程度。结论本文模型能够较好的模拟抗血管生成因子Angiostatin和Endostatin对内皮细胞迁移和增殖的抑制作用。  相似文献   
45.
The aim of this study was to investigate the effect of pre-irradiation with microwaves on the induction of radioadaptive response. In the 1st phase of the study, 110 male mice were divided into 8 groups. The animals in these groups were exposed/sham-exposed to microwave, low dose rate gamma or both for 5 days. On day six, the animals were exposed to a lethal dose (LD). In the 2nd phase, 30 male rats were divided into 2 groups of 15 animals. The 1st group received microwave exposure. The 2nd group (controls) received the same LD but there was no treatment before the LD. On day 5, all animals were whole-body irradiated with the LD. Statistically significant differences between the survival rate of the mice only exposed to lethal dose of gamma radiation before irradiation with a lethal dose of gamma radiation with those of the animals pre-exposed to either microwave (p=0.02), low dose rate gamma (p=0.001) or both of these physical adapting doses (p=0.003) were observed. Likewise, a statistically significant difference between survival rates of the rats in control and test groups was observed. Altogether, these experiments showed that exposure to microwave radiation may induce a significant survival adaptive response.  相似文献   
46.
Background Pityriasis rubra pilaris (PRP) is a rare inflammatory dermatosis with frequent clinical presentation as erythroderma. Conventional systemic treatment is often unsatisfactory and limited by long‐term toxicity. The use of tumour necrosis factor (TNF) antagonists has been reported previously in single cases, but lacking long‐term follow‐up or comparison between different biological agents. Objectives To assess the long‐term efficacy and safety of TNF‐alpha antagonist, infliximab and etanercept, either in monotherapy or in combination therapy of severe, refractory adult‐onset PRP. Methods Seven patients of adult‐onset PRP, six newly diagnosed type‐I and 1 type‐II, which were resistant or ineligible to conventional systemic treatment, received a single course of infliximab or etanercept therapy, alone or in combination with low‐dose acitretin (>0.25 mg/kg/daily). After complete remission and treatment discontinuation, a follow‐up period of 12 months was evaluated for relapses. Results Six patients obtained complete remission after a single course of anti‐TNF‐alpha therapy: mean therapy duration was 19.3 weeks (range 6–48 weeks). All patients obtained significant clearing (>75% of body surface area) of skin lesions at week 12. Two patients with marked keratoderma developed localized disease recurrence during treatment. During follow‐up, only a single patient, affected by type II PRP, had disease relapse. Conclusions Both TNF‐alpha antagonists proved successful for the treatment of refractory, adult‐onset PRP, yielding complete and persistent clinical responses in type‐I PRP. Infliximab was associated with a more rapid onset of action, while treatment duration was comparable with etanercept. PRP type II warranted long‐term therapy and showed relapse after drug discontinuation.  相似文献   
47.
48.
Tuberous sclerosis is an inherited neurocutaneous disorder characterized by seizures, mental retardation, cutaneous lesions and visceral hamartomas. We describe a 17-year-old boy in whom polycystic kidneys of the adult type were fortuitously detected on routine check-up. The patient enjoyed good health and had no evidence of renal dysfunction. Closer scrutiny of his past history and his physical and laboratory findings disclosed that he had tuberous sclerosis. Our case adds to the scant reported experience with the association of tuberous sclerosis and adult-type polycystic kidneys, and suggests that a search of additional manifestations of tuberous sclerosis is warranted in children in whom adult-type polycystic renal disease is detected.  相似文献   
49.
Our research seeks to identify serum profiles, or serotypes, that reflect substantial changes in food intake in both male and female rats. This report validates previously defined subsets of redox-active low-molecular-weight metabolites using independent cohorts of ad libitum consumption (AL) and energy or dietary restricted (DR) 6-mo-old male and female rats. In the male study, both hierarchical cluster analysis (HCA) and principal component analysis (PCA) distinguished the dietary groups of origin in the second male cohort with >85% accuracy using 56 analytically and biologically valid metabolites. Further analysis revealed that 29 metabolites (nine previously unidentified metabolites + 20 chosen from the 56 metabolites) enabled HCA to distinguish dietary groups at 100% efficacy. In the female study, the 63 previously identified serum metabolites were sufficiently robust to enable classification of the dietary intake of two female cohorts (cohorts 2 and 3) that were independent of the cohort on which these markers were initially identified (cohort 1). Classification accuracy was 94 and 100% using HCA and PCA, respectively, in the female cohort 2. HCA and PCA revealed that the 63-metabolite profile distinguished AL and DR samples at 91 and 100% accuracy in the female cohort 3, establishing the 63-metabolite dataset as our baseline profile. These studies used independent cohorts to validate and potentially improve upon previously defined metabolic serotype in male and female rats and set the stage for pattern recognition-based approaches to establish metabolome-based categorical separations.  相似文献   
50.
This population-based, case-control study in King County,Washington examined associations of energy, fat, vitamin D, and calcium with risk of prostate cancer in 605 incident cases (ages 40-64 years) identified from the Seattle-Puget Sound Surveillance Epidemiology and End Results registry and 592 controls recruited from the same underlying population using random-digit telephone sampling. Self-administered food frequency questionnaires were used to assess diet over the 3-5-year period before diagnosis or interview date. Total energy was associated with increased risk for both local and regional/distant stage disease. The adjusted odds ratios [95% confidence intervals (CIs)] contrasting highest to lowest quintile of energy intake were 2.15 (95% CI, 1.35-3.43) for local and 1.96 (95% CI, 1.08-3.56) for regional/distant disease. Fat was associated with regional/distant disease only. Adjusted odds ratios comparing the highest to lowest quintiles of percentage energy from total, saturated, and monounsaturated fats were 2.01 (1.03-3.92), 1.82 (0.93-3.56), and 2.00 (1.03-3.87), respectively. For calcium, adjusted odds ratios contrasting the highest to lowest quartiles were 1.07 (0.63-1.84) for local and 2.12 (1.02-4.38) for regional/distant disease. There were no associations of vitamin D, total polyunsaturated fatty acids, or the highly unsaturated, long-chain eicosapentainoic and docosahexaenoic fatty acids with prostate cancer risk. These results suggest that high energy intake is a risk factor for both localized and nonlocalized prostate cancer, whereas dietary fat and calcium increase the risk of regional/distant disease only. These results are consistent with general dietary guidelines to moderate consumption of total energy and fat, and they motivate further research to consider the potential benefits and risks of high calcium intake.  相似文献   
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