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排序方式: 共有1288条查询结果,搜索用时 250 毫秒
31.
Nagarathnam D Miao SW Lagu B Chiu G Fang J Murali Dhar TG Zhang J Tyagarajan S Marzabadi MR Zhang F Wong WC Sun W Tian D Wetzel JM Forray C Chang RS Broten TP Ransom RW Schorn TW Chen TB O'Malley S Kling P Schneck K Bendesky R Harrell CM 《Journal of medicinal chemistry》1999,42(23):4764-4777
Dihydropyrimidinones such as compound 12 exhibited high binding affinity and subtype selectivity for the cloned human alpha(1a) receptor. Systematic modifications of 12 led to identification of highly potent and subtype-selective compounds such as (+)-30 and (+)-103, with high binding affinity (K(i) = 0.2 nM) for alpha(1a) receptor and greater than 1500-fold selectivity over alpha(1b) and alpha(1d) adrenoceptors. The compounds were found to be functional antagonists in human, rat, and dog prostate tissues. Compound (+)-103 exhibited excellent selectively to inhibit intraurethral pressure (IUP) as compared to lowering diastolic blood pressure (DBP) in mongrel dogs (K(b)(DBP)/K(b)(IUP) = 40) suggesting uroselectivity for alpha(1a)-selective compounds. 相似文献
32.
Harley B Messinger Egilius LH Spierings Arnaud JP Vincent John Lebbink 《Cephalalgia : an international journal of headache》1991,11(1):13-18
In two headache questionnaire surveys we inquired about the occurrence of headache in the mothers, fathers, siblings and children of the respondents. In total, 633 people completed valid questionnaires, 260 in the first survey and 373 in the second. The hypothesis was that familial headache occurrence would be positively associated with headache frequency. In each survey, the regression of headache frequency on the number of parents having headache was highly significant. Neither sex nor the sibling and children variables were significant predictors. In the cross-tabulations of the parental occurrence of headache with headache frequency we saw a clear "break-point" between the "no headache" and the headache frequency categories studied. For the final analyses the dichotomy "headache/no headache" was related in fourfold tables to headache occurrence in the father and the mother separately, and to the number of headache parents. The positive associations were not simply due to the large number of migraine cases since they remained after removing the migraineurs. 相似文献
33.
The present analysis comprises 3 studies on the interrater reliability of the Positive and Negative Syndrome Scale for Schizophrenia (PANSS; German version). To our knowledge this is the first empirical report on interrater reliability and on results of rater training of the German version of the PANSS despite the widespread use of the scale. In a total of 47 training participants with different clinical experience standardized PANSS rater training was carried out and subsequently evaluated. Therefore, concordance rates with an expert standard (C) and weighted coefficients kappa (kappa W) were calculated. As a main outcome of the studies, at least 3 training sessions were necessary but also sufficient to reach acceptable interrater reliability of the PANSS (C > 80%, kw > 0.60). In training participants with low psychiatric experience the level of interrater reliability of schizophrenic negative symptoms did not reach the results of positive symptoms after the training. Despite some conceptual limitations with respect to negative symptoms, the German version of the PANSS seems highly suitable to assess a broad spectrum of schizophrenic psychopathology in a reliable and economic manner. The present results also underline the practicability of our recommendations for conducting PANSS rater training in the clinical and scientific field as part of quality control and quality assurance in psychopathological assessment. 相似文献
34.
35.
Early stage nasopharyngeal carcinoma: radiotherapy dose and time factors in tumor control 总被引:1,自引:0,他引:1
Chang JT; See LC; Liao CT; Chen LH; Leung WM; Chen SW; Chen WC 《Japanese journal of clinical oncology》1998,28(3):207-213
OBJECTIVE: To evaluate radiotherapy dose and length of treatment in the
control of early stage nasopharyngeal carcinoma (NPC) treated with a
combination of external radiotherapy and brachytherapy, MATERIALS &
METHODS: We reviewed the records of 133 patients with early stage
nasopharyngeal carcinoma (stage I or II, AJC/UICC staging system) who
received definitive radiotherapy in Chang Gung Memorial Hospital from 1979
to 1991. The median follow-up time was 7.1 years with a minimum of 2 years.
All patients were treated with megavoltage external radiotherapy to the
nasopharynx area (63-72 Gy) followed by high dose rate intracavitary
brachytherapy (5-16.5 Gy in one to three fractions, spaced 1-2 weeks
apart). The median total dose and time of irradiation was 75 Gy (69.8-81.4
Gy) and 11.6 weeks (7.8-20 weeks) respectively. Survival analysis was used
to examine the effect of several variables on prognosis. RESULTS: The
5-year rates were 86.4% for local control, 84.7% for disease free survival,
88.5% for actuarial survival and 84.2% for overall survival. The treatment
group (combination of time and dose of irradiation) was the most important
prognostic factor according to Cox's proportional hazard model. Patients
receiving radiation at a total dose of < or = 75 Gy completed in < 12
weeks showed the best prognosis. CONCLUSION: Treatment time and total
treatment dose are both important factors in treating early stage NPC.
Decreasing the total radiation time to < 12 weeks and not exceeding a
radiation dose of 75 Gy gave the best results.
相似文献
36.
Mistletoe preparations standardised to the content of mistletoe lectin are supposed to improve quality of life (QoL) in patients with cancer. To obtain a validated and sensitive research instrument, the Life Quality Lectin-53 (LQL-53) Questionnaire was developed in three phases: item generation via interviews with 42 patients, item selection by means of a study with 109 cancer patients, and psychometric testing. The LQL-53 includes 46 items assigned to the subscales 'General well-being', 'Emotional well-being', 'Vitality' 'Hope', 'Locus of control', Social relationships', and 'Physical complaints', plus seven items dealing with possible adverse effects of mistletoe treatment. Psychometric testing was carried out in a study with 112 patients with solid tumours who were treated with a mistletoe preparation standardised to mistletoe lectins for 12 weeks. Internal consistency (Cronbach's alpha) was between 0.72 and 0.94. Test-retest reliability was > or = r of 0.72. Subscales correlated highly with external criteria. Construct validity, as determined by Multitrait Scaling Analysis, resulted in an optimal assignment of items to subscales (scaling success) for four of the subscales. During the course of the therapy, significant improvement in QoL was found in all subscales. In two of the subscales, effect size was high (>0.80), and in five other subscales it varied between 0.53 and 0.78. 相似文献
37.
38.
Ion Anghelescu Sabine Germeyer Matthias J. Müller Christoph Klawe Peter Singer Norbert Dahmen Hermann Wetzel Hubertus Himmerich Armin Szegedi 《Alcoholism, clinical and experimental research》2001,25(6):805-809
BACKGROUND: The presence of the A1 allele of the dopamine D2 receptor TaqI restriction fragment length polymorphism has been reported to be associated with an earlier age of onset of alcohol dependence as a marker for severity. METHODS: We tested this hypothesis with special regard to the definition of the age of onset of alcoholism in 243 patients with alcohol dependence, according to DSM-IV criteria assessed by the standardized interview Münchner Composite International Diagnostic Interview (M-CIDI), consecutively admitted for detoxification. Additionally, the Addiction Severity Index (ASI) was performed. The TaqIA polymorphism was amplified by polymerase chain reaction (PCR), and the PCR product was digested by the restriction enzyme TaqI. Patients were subsequently divided into an A1 (presence of at least one A1 allele, n = 88) and an A2 group (absence of an A1 allele, n = 155). The following criteria for different definitions of age of onset were used: (1) age of onset of the first occurring symptom necessary for the diagnosis of alcohol dependence according to M-CIDI; (2) age of onset of the last symptom of alcohol dependence according to M-CIDI; (3) age of onset of more than 3 drinking days per week on a regular basis according to ASI; (4) age of onset of more than 3 drinking days-of more than five drinks per drinking day-or at least one binge drinking episode per week on a regular basis according to ASI. RESULTS: The frequency of the A1 allele in our patient sample was 0.208. No statistically significant association between the A1 allele and the age of onset of alcoholism was found. The mean age of onset according to criterion 1 was 30.4 +/- 10.8 years for the A1 group and 30.2 +/- 10.2 years for the A2 group (p = 0.89); for criterion 2, it was 33.3 +/- 10.0 years for the A1 group and 33.9 +/- 10.2 years for the A2 group (p = 0.77); for criterion 3, it was 18.0 +/- 7.5 years for the A1 group and 18.1 +/- 6.1 years for the A2 group (p = 0.92); and for criterion 4, it was 22.3 +/- 9.7 years for the A1 group and 21.8 +/- 8.5 years for the A2 group (p = 0.76). CONCLUSIONS: No association was found between the A1 polymorphism and age at onset of alcohol dependence according to different specified criteria. 相似文献
39.
40.
Liu SC; Palek J; Yi SJ; Nichols PE; Derick LH; Chiou SS; Amato D; Corbett JD; Cho MR; Golan DE 《Blood》1995,86(1):349-358
Southeast Asian ovalocytosis (SAO) is an asymptomatic trait characterized by rigid, poorly deformable red cells that resist invasion by several strains of malaria parasites. The underlying molecular genetic defect involves simple heterozygous state for a mutant band 3 protein, which contains a deletion of amino acids 400 through 408, linked with a Lys 56-to-Glu substitution (band 3-Memphis polymorphism). To elucidate the contribution of the mutant SAO band 3 protein to increased SAO red blood cell (RBC) rigidity, we examined the participation of the mutant SAO band 3 protein in increased band 3 attachment to the skeleton and band 3 oligomerization. We found first that SAO RBC skeletons retained more band 3 than normal cells and that this increased retention preferentially involved the mutant SAO band 3 protein. Second, SAO RBCs contained a higher percentage of band 3 oligomer-ankyrin complexes than normal cells, and these oligomers were preferentially enriched by the mutant SAO protein. At the ultrastructural level, the increased oligomer formation of SAO RBCs was reflected by stacking of band 3-containing intramembrane particles (IMP) into longitudinal strands. The IMP stacking was not reversed by treating SAO RBCs in alkaline pH (pH 11), which is known to weaken ankyrin-band 3 interactions, or by removing the cytoplasmic domain of band 3 from SAO membranes with trypsin. Finally, we found that band 3 protein in intact SAO RBCs exhibited a markedly decreased rotational mobility, presumably reflecting the increased oligomerization and the membrane skeletal association of the SAO band 3 protein. We propose that the mutant SAO band 3 has an increased propensity to form oligomers, which appear as longitudinal strands of IMP and exhibit increased association with membrane skeleton. This band 3 oligomerization underlies the increase in membrane rigidity by precluding membrane skeletal extension, which is necessary for membrane deformation. 相似文献