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121.
Optimal Selection of Sib Pairs from Random Samples for Linkage Analysis of a QTL Using the EDAC Test
Percentages of extremely concordant and extremely discordant sib pairs are calculated that maximize the power to detect a quantitative trait locus (QTL) under a variety of circumstances using the EDAC test. We assume a large fixed number of randomly sampled sib pairs, such as one would hope to find in the large twin registries, and limited resources to genotype a certain number of selected sib pairs. Our aim is to investigate whether optimal selection can be achieved when prior knowledge concerning the QTL gene action, QTL allele frequency, QTL effect size, and background (residual) sib correlation is limited or absent. To this end we calculate the best selection percentages for a large number of models, which differ in QTL gene action allele frequency, background correlation, and QTL effect size. By averaging these percentages over gene action, over allele frequency, over gene action, and over allele frequencies, we arrive at general recommendations concerning selection percentages. The soundness of these recommendations is subsequently in a number of test cases. 相似文献
122.
Abstract: We analyzed the expression of CEA, CA19-9, CA125, CA15-3 (DF3), PCNA and p53 immunohistochemically in 14 tissue specimens of mucosal cancers in adenoma, seven tubulovillous adenoma specimens, and 16 tubular adenoma specimens. The rates of positive staining for mucosal cancer in adenoma, tubulovillous adenoma and tubular adenoma specimens, respectively, were: for CEA: 100%, 85.7% and 75%; for CA19-9: 71.4%, 71.4% and 56.2%; for CA125:0%, 0% and 0%;for CA15-3 (DF3): 64.3 %, 0% and 0 %; for PCNA: 100%, 88.9% and 56.2%; and for p53: 35.7%, 0% and 0% . The results suggest that the expressions of CEA, CA19-9, CA15-3 (DF3), PCNA and p53 are related to colorectal tumorigenesis. None of the specimens studied showed staining for CA125, suggesting that CA125 is not involved in the early stages of colorectal carcinogenesis. There was no significant difference in the rates of positive staining for CEA and CA19-9 among mucosal cancer in adenoma, tubular adenoma and tubulovillous adenoma specimens. However, the rates of positive staining for PCNA and p53 were significantly higher in mucosal cancer in adenoma specimens than for tubular adenoma specimens (p<0.05), and the rate of CA15-3 (DF3) positive staining was significantly higher for mucosal cancer in adenoma than for tubulovillous adenoma (p<0.01) and tubular adenoma (p< 0.001) specimens. Therefore, the CA15-3 (DF3) antigen is an immunohistochemical marker for colorectal carcinomas. The present results suggest that CA15-3 (DF3), PCNA and p53 play important roles in the genesis of colorectal adenomas. 相似文献
123.
Rolf W. Hartmann Martin Frotscher Dorothea Ledergerber Gerald A. Wchter Gertrud L. Grün Tom F. Sergejew 《Archiv der Pharmazie》1996,329(5):251-261
In search of potential drugs for the treatment of estrogen- and androgen-dependent cancer as well as the prophylaxis of metastases, tetralones, tetralins, and dihydronaphthalenes bearing a OCH3 substituent at the benzene nucleus and an imidazol-4-yl, imidazol-1-yl, or 1,2,4-triazol-1-yl substituent in 2-position were synthesized with and without C1-spacer between the rings (compounds 2 – 26 ). The compounds were tested in vitro for inhibition of the three target enzymes P450 arom (human placental microsomes), P450 17 (rat testicular microsomes), and P450 TxA2 (citrated human whole blood). To examine selectivity, some compounds were further tested in vitro for inhibition of P450 18 (bovine adrenal mitochondria), P450 see (bovine adrenal mitochondria) and corticoid formation (aldosterone, corticosterone; ACTH stimulated rat adrenal tissue). In vivo, selected compounds were examined in Sprague Dawley rats regarding P450 TxA2 inhibition, reduction of plasma testosterone concentration, antiuterotrophic activity (inhibition of the uterotrophic activity of androstenedione), reduction of plasma estradiol concentration (pregnant mares' serum gonadotropin-primed rats), and mammary tumor inhibiting activity (dimethylbenzanthracene-induced tumor; pre- and postmenopausal model). In the series of imidazol-4-yl compounds, which represent a novelty in the field of azole inhibitors of steroidogenic P450 enzymes, strong inhibitors of P450 arom and/or P450 17 were found: 7-OCH3-2-(imidazol-4-ylmethylene)-1-tetralone ( 4 ) and 7-OCH3-2-(imidazol-4-ylmethyl)-tetralin ( 12 ) are among the most potent inhibitors of P450 arom in vitro known so far. Compound 4 is a selective inhibitor, whereas 12 shows in addition strong inhibition of P450 17. In contrast to 12 , the 6-OCH3 derivative (compound 11 ) is a selective inhibitor of P450 17, being 50 times more potent than ketoconazole. Some imidazol-1-yl compounds show a marked inhibition of P450 TxA2: 2-(imidazol-1-ylmethyl)-1-tetralone ( 13 ) is a selective inhibitor of P450 TxA2, whereas 7-OCH3-2-(imidazol-1-ylmethyl)-tetralin ( 17 ) as well as 2-(imidazol-1-ylmethyl)-tetralin ( 16 ) and 7-OCH3-2-imidazol-1-yl-3,4-dihydronaphthalene ( 25 ) additionally show strong inhibition of P450 arom and P450 17. Regarding the other steroidogenic P450 enzymes as well as corticosterone formation, the compounds show only little inhibitory activity. Aldosterone formation, however, is inhibited at low concentrations. Nevertheless, 4 and 12 are more selective, i.e. inhibit aldosterone synthesis less than the well known inhibitor of P450 arom fadrozole. The compounds show activity in the aforementioned in vivo tests. 相似文献
124.
K. E. Anderson A. M. Dart E. A. Woodcock 《Clinical and experimental pharmacology & physiology》1994,21(2):141-144
1. Global myocariial ischaemia (MI) for periods greater tan 5 min caused an inhibition of phosphatidylinositol specific phospholipase C (PtdIns-PLC) activity. 2. Two min reperfusion following a 20 min MI period, a time point associated with reperfusion-induced arrhythmias, resulted in an activation of PtdIns-PLC activity, dependent on endogenous noradrenaline and mediated via al-adrenoceptors. 3. This 2 min reperfusion response, in contrast to healthy myocardium, resulted in: (i) enhanced PtdIns-PLC activity; (ii) increased sensitivity to endogenous noradrenaline; (iii) rapid increases in inositol(1,4,5)trisphosphate (Ins(1,4,5)P3); and (iv) PLC hydrolysis primarily of PtdIns(4,5)P2, such that the majority of InsP isomers derive from Ins(1,4,5)P3. 4. Together, these data suggest a functional role for Ins(1,4,5)P3 under postischaemic reperfusion conditions, and provide a possible link between al-adrenoceptor stimulation of the PtdIns turnover pathway and reperfusion injury. 相似文献
125.
126.
Jack C. Kim 《Archives of pharmacal research》1994,17(3):204-206
A regioselective preparation of 10-methoxy-11-hydroxyaporphine (“Apocodeine,1b”) from (R,S)-10, 11-dihydroxyaporphine(apomorphine,1a) is described. The isopropylidene ketal ring of 10,11-(isopropylidenyldioxy) aporphine (2) obtained by the isopropylidenation of apomorphine, was regioselectively opened by the ten equivalent of trimethylaluminum
to give 10-hydroxy-11-t-butyloxyaporphine (3). The free 10-hydroxyl position of 3 was methylated with methyl p-toluenesulfonate/NaH, and afforded 10-methoxy-11-t-butyloxyaporphine
(4) in high yield. Selective debutylation gave the desired 10-methoxy-11-hydroxyaporphine (“apocodeine”,1b) in good yield. 相似文献
127.
Dongrun Tang Guoxiang Song Shimin Cui Lingen Chen Qingbin LiDepartment of Ophthalmology the Second Affiliated Hospital Tianjin Medical UniversityTianjin ChinaDepartment of Neurosurgery Tianjin Huan Hu Hospital 《眼科学报》1994,(3)
By digital subtraction angiography(DSA), the authors made observations on 108 normal ophthalmic arteries in 80 patients with regard to the origins, courses, branching, morphology and anastomoses of the vessels. The merits and demerits of DSA in observing the ophthalmic artery were discussed. Eye Science 1994; 10: 157- 162. 相似文献
128.
We studied the effects of Wallerian degeneration in the cerebral peduncle shown by magnetic resonance imaging (MRI) following a supratentorial vascular lesion, to identify the somatotopic localisation of the descending cortical tracts. Patients with a lesion involving a large area of a cerebral hemisphere had an area of abnormal signal intensity in the whole cerebral peduncle, suggesting Wallerian degeneration of all the whole descending cortical tracts. With a small lesion confined to the precentral gyrus, corona radiata, or posterior limb of the internal capsule there was an abnormal signal at the centre of the peduncle, suggesting degeneration of the precentrospinal tract. Those with a small lesion confined to the paracentral gyrus had an abnormal area slightly lateral to the centre of the peduncle, suggesting degeneration of the parietospinal tract. Patients with a lesion of the parietal or temporal lobes, not including the paracentral or precentral gyri, corona radiata, or the posterior limb of the internal capsule, had an abnormal area laterally in the peduncle, suggesting degeneration of the parietopontine or temporopontine tract. 相似文献
129.
130.
视网膜脱离手术复位后ERG的恢复 总被引:5,自引:0,他引:5
为探讨视网膜脱离手术复位后ERG的改变,对35例(35眼)患者进行手术前后ERG检测,结果表明;(1)视网膜脱离术前ERGa、b波幅明显低于有视网膜格子样变性而无脱离者。(2)手术复位后ERGa、b波幅随时间延长逐渐回升。(3)视网膜脱离范围二个象限以内者ERGa、b波幅回升高于二象限以上者。(4)手术范围一个象限以内者与超过一个象限者相比前者ERG恢复优于后者。(5)视网膜脱离时间2月以内与超过2月相比,ERG恢复前者明显优于后者。结果证实视网膜脱离术后ERG恢复与手术后时间、脱离范围、病程及手术范围密切相关。 相似文献