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141.
T. Hansson C. von Bahr M. Marklund J.-O. Svensson M. Ingelman-Sundberg J. Lundstrm 《Basic & clinical pharmacology & toxicology》1992,71(6):416-419
Abstract: Incubation of the tricyclic antidepressant desmethylimpramine (DMI) with rat liver or brain microsomes in the presence of NADPH or t-butyl-hydroperoxide (TBH) revealed different regiospecificities in the hydroxylation reactions between the tissues. In brain preparations 10-OH-DMI was formed in reactions supported by NADPH or TBH, whereas in the latter case also an unidentified metabolite could be detected. Inclusion of exogenous NADPH-cytochrome P450 reductase in the brain preparations caused a 10-fold higher rate of 10-hydroxylation but no 2-OH-DMI could be detected. By contrast, liver microsomal preparations in the presence of NADPH catalyzed formation of both 2- and 10-OH-DMI, whereas only 10-OH-DMI was formed in TBH-supported reactions. The results indicate that antidepressant drugs can be metabolized in brain with different stereospecificity as compared to liver. 相似文献
142.
D M Geiser M L Arnold W E Timberlake 《Proceedings of the National Academy of Sciences of the United States of America》1994,91(6):2349-2352
Aspergillus nidulans is a holomorphic fungus, capable of producing both meiotically and mitotically derived spores. Meiosis may be an evolutionary relic in this species because it is potentially capable of mitotic recombination and because most Aspergilli lack the ability to produce meiotic spores. We tested the null hypothesis that meiosis has been a major factor in the origin of strains of A. nidulans from Great Britain by estimating linkage disequilibrium among restriction fragment length polymorphisms. These strains belong to different heterokaryon compatibility groups and are thus incapable of undergoing mitotic recombination with one another, so any recombination evidenced by linkage equilibrium is assumed to be the result of meiosis. Eleven cosmid clones of known chromosomal origin were used to generate multilocus genotypes based on restriction-pattern differences for each heterokaryon compatibility group. Low levels of genetic variation and little linkage disequilibrium were found, indicating that the heterokaryon compatibility groups represent recently diverged lineages that arose via meiotic recombination. The null hypothesis that loci are independent could not be rejected. Additionally, low levels of electrophoretic karyotype variation were indicative of meiosis. We conclude that although A. nidulans probably propagates in a primarily clonal fashion, recombination events are frequent enough to disrupt the stable maintenance of clonal genotypes. We further conclude that the British heterokaryon compatibility groups arose via recombination and not through novel mutation. 相似文献
143.
R K Lamb S A Qureshi J L Wilkinson R Arnold C R West D I Hamilton 《The Journal of thoracic and cardiovascular surgery》1988,96(3):368-375
Between 1968 and 1985, 80 children underwent correction of total anomalous pulmonary venous drainage. There were 47 boys and 33 girls whose ages ranged from 3 days to 16 years (median 2 months, interquartile range 5 years). Seventy (87.5%) were less than 1 year of age at operation. Fifty-eight (72.5%) weighed less than 5 kg, the range being 1.6 to 42 kg (median 3.7 kg, interquartile range 2.4 kg). Forty-five (56%) patients had supracardiac, 14 (17.5%) cardiac, 15 (19%) infracardiac, and 6 (7.5%) had mixed total anomalous pulmonary venous drainage. Follow-up was complete in 78 (97.5%) and ranged from 6 to 189 months (median 58 months, interquartile range 59 months). There were 14 (17.5%) early and six (7.5%) late deaths. Analysis by various factors revealed year of operation as the only factor to affect survival at the 5% level of significance. Early mortality was 29% between 1968-1977 and 11% between 1978-1985 (p = 0.04). Postoperative pulmonary venous obstruction occurred in five (6%) patients between 6 weeks and 3 months after operation. All 5 died, three after reoperation. Five (6%) other children had reoperations, four for residual shunts and one for superior vena caval obstruction. 相似文献
144.
Kari T Kivist? Olaf Grisk Ute Hofmann Konrad Meissner Klaus-Uwe M?ritz Christoph Ritter Katja A Arnold Dieter Lutj?ohann Klaus von Bergmann Ingrid Kl?ting Michel Eichelbaum Heyo K Kroemer 《Drug metabolism and disposition》2005,33(11):1593-1596
The aim of this study was to characterize the role of the efflux transporter Mrp2 (Abcc2) in the pharmacokinetics of orally and intravenously administered pravastatin in rats. Eight Mrp2-deficient TR- rats and eight wild-type rats were given an oral dose of 20 mg/kg pravastatin. Four TR- animals and four wild-type animals were studied after intravenous administration of pravastatin (5 mg/kg). The TR(-) rats showed a 6.1-fold higher mean area under the plasma concentration-time curve (AUC) of pravastatin (p < 0.001) after oral administration and a 4.7-fold higher AUC (p < 0.01) after intravenous administration of pravastatin as compared with the wild-type animals. The mean systemic (total) clearance of pravastatin was 4.6-fold higher (39.2 versus 8.50 l/h/kg, p < 0.001) and the mean V 4.3-fold higher (14.1 versus 3.29 l/kg, p < 0.01) in the wild-type rats. The mean renal clearance of pravastatin in the TR(-) rats was 16.5-fold increased as compared with the wild-type animals (0.695 versus 0.042 l/h/kg, p < 0.05). The increased systemic exposure to oral pravastatin in the TR- rats was associated with a greater inhibitory effect on 3-hydroxy-3-methylglutaryl CoA reductase, as shown by smaller lathosterol to cholesterol concentration ratios. These results suggest that the reduced biliary pravastatin excretion in the Mrp2-deficient TR- rats is partly compensated for by increased urinary excretion of pravastatin. Furthermore, intestinal Mrp2 does not appear to play a major role in the oral absorption of pravastatin in normal rats. 相似文献
145.
In spite of a reduced rate of new occurrence, gastric cancer is still one of the most common causes of cancer related mortality. Crucial to the value of systemic therapy are the 50% of patients who already have metastasizing or locally advanced stages at first diagnosis which are not surgically curable. In comparison to merely supportive therapy, controlled studies have shown the unmistakable value of chemotherapy. Recently, cisplatin and infused 5-fluorouracil (5-FU) based combination treatments have become the therapeutic standard. The internationally best studied scheme is the “ECF” combination. The taxane and irinotecan group has limited value as monotherapy and is used in combination studies, as are oral fluoropyrimidine and oxaliplatin, with other substances. With the introduction of numerous, new, effective cytostatics, a whole series of combinations are being tested. The main aims of these studies are, on the one hand, lowered toxicity or ease of use with equivalent effectiveness, and on the other hand, higher effectiveness without significantly increased toxicity. 相似文献
146.
Elisabeth Fernell Christopher Gillberg Lennart von Wendt 《Developmental medicine and child neurology》1991,33(5):388-395
The occurrence of behavioural problems in a population-based series of children with infantile hydrocephalus (non-spina bifida) was analysed, using parent questionnaires. Children with both infantile hydrocephalus and mental retardation had significantly more behavioural problems compared with those with no mental retardation and controls. Inattentiveness and hyperactivity were particularly typical. No differences were found between children with infantile hydrocephalus and no mental retardation and the control group. 相似文献
147.
W F?rster H Kasprzak G von Bally H Busse 《Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft》1992,89(6):531-534
Displacement of the surface of the cornea of bovine eyes after disruption of intact structures was investigated by means of holographic interferometry. Double-T-incisions of different depths were made with a diamond knife. Starting at about 80% of the incision depth there is a change in the central holographic interference fringe pattern. These effects can be clearly demonstrated by means of double-exposure holographic interferometry and real-time holographic interferometry. The stability of an existing corneal scar was analyzed by double-exposure holographic interferometry. The region of the scar showed a higher density of holographic interference fringes compared with the non-affected corneal areas, indicating a higher degree of elasticity. All eyes were investigated at an intraocular pressure of 1340 Pa (about 10 mmHg) and an intraocular pressure change of 10 Pa and 20 Pa. Further potential ophthalmic applications of holographic interferometry are discussed. 相似文献
148.
C von Kalle J Wolf A Becker A Sckaer M Munck A Engert U Kapp C Fonatsch D Komitowski W Feaux de Lacroix 《International journal of cancer. Journal international du cancer》1992,52(6):887-891
No animal model exists for the in vivo growth of Hodgkin's-lymphoma-derived cells. Neither unmanipulated Hodgkin's-disease(HD)-derived cell lines nor primary biopsy tissue could be grown in nude mice. Since the severe combined immunodeficient (SCID) mouse has been reported to be a better recipient for transplanted human lymphatic tissue than the nude mouse, we tested whether SCID mice provide suitable conditions for the in vivo growth of HD cell lines. Tumorigenicity of HD cells was tested in untreated and pre-treated SCID mice and in another combined immunodeficient mouse strain, beige/nude/X-linked immunodeficient (BNX) mouse. SCID mice supported in vivo growth of the 6 HD cell lines tested (L428, L540, L591, DEV, HD-LM2, KM-H2). Only one of the 6 lines (DEV) was tumorigenic in BNX mice. No HD cell line proliferated in T-cell-deficient nude mice. Thus, in vivo growth of HD cell lines appeared to be related to the degree of host immunodeficiency. Additional growth supportive treatments such as fibrosarcoma co-transplantation, intraperitoneal mineral oil injection or immunosuppressive pre-treatment (anti-asialo-GMI-antibody injection) permitted growth of 3 additional HD cell lines in BNX mice. The immunophenotype and karyotype of explanted graft cells were identical to the original cell lines. Our experiments describe an effective and reproducible xenograft model for growth of Hodgkin's-disease-derived cell lines. This may be of value for elucidating the growth characteristics of Hodgkin's-lymphoma-derived cells as well as for testing new therapeutic regimens. 相似文献
149.
Four patients with mycotic aneurysm of the extracranial carotid artery, the innominate artery, the ascending aorta, and the infrarenal aorta were treated with local implantation of antibiotic-releasing carriers after resection of the aneurysm, excision of all infected tissue, and in situ reconstruction by prosthetic graft replacement in two patients and patch plasty in two patients. The patient with a mycotic aneurysm of the ascending aorta was operated on again 1 month after the first operation because of a second mycotic aneurysm located on the aortic arch. No early or late signs of recurrent infection were seen on clinical and laboratory postoperative follow-up done between 9 and 16 months or on duplex scan or computed tomography done at these times. Implantation of antibiotic-releasing carriers after débridement of all infected tissue and in situ reconstruction for treatment of mycotic aneurysm was performed successfully in four patients with this life-threatening condition. 相似文献
150.