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排序方式: 共有7546条查询结果,搜索用时 31 毫秒
11.
12.
Ladenstein Ruth; Pearce Rachel; Hartmann Olivier; Patte Catherine; Goldstone Tony; Philip Thierry 《Blood》1997,90(8):2921-2930
13.
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
14.
Glutathione S-transferases in human testicular germ cell tumors: changes of expression and activity.
Glutathione S-transferases are involved in the detoxification of carcinogens and xenobiotics and are potentially associated with the development of drug-resistance. Forty-six testicular germ cell tumors and 33 adjacent normal testicular tissue specimens were analyzed at the RNA level for the expression of glutathione S-transferase alpha and pi. Glutathione S-transferase alpha was expressed in 31 of the 33 normal testicular tissues (94%) but in only three of the 46 germ cell tumors (7%). Glutathione S-transferase pi mRNA was detected in all normal and malignant testicular tissue samples. Thirteen testicular germ cell tumors and eight normal testicular tissue samples were analyzed at the protein level. The mean specific activity of total cytosolic glutathione S-transferase in tumor tissue was decreased by about 80% as compared to normal testicular tissue. Protein analysis of the glutathione S-transferase subunits of normal testicular tissue demonstrated the presence of the glutathione S-transferase classes alpha, mu and pi, with a predominance of the mu class. In testicular germ cell tumors the glutathione S-transferase subunit pattern showed a predominance of glutathione S-transferase pi representing 88% +/- 3% of total glutathione S-transferase. Since all three glutathione S-transferase isoenzyme classes contribute to the resistance to antineoplastic drugs, the altered glutathione S-transferase isoenzyme pattern and the decrease of glutathione S-transferase activity may play a role in the high inherent drug sensitivity of human testicular germ cell tumors. 相似文献
15.
M S Marx P Werner J Cohen-Mansfield E E Hartmann 《Investigative ophthalmology & visual science》1990,31(3):593-596
The acuity card procedure has been shown to provide reliable grating acuity estimates in pediatric patients. The current study was conducted to determine the usefulness of this procedure in another group of persons in whom conventional acuity measurements are not possible, ie, nursing home residents who suffer from dementing disorders. Binocular visual acuity estimates were obtained in 13 cognitively impaired nursing home residents. Test sessions took 20-30 min each. Both test-retest agreement and inter-observer agreement of Teller Acuity Card (TAC) acuity estimates were good (within 0.5 octave for all residents), demonstrating that this procedure yields reasonable acuity estimates in noncommunicative nursing home residents. The authors stress the potential of this tool for nursing home administrators as well as for researchers. 相似文献
16.
A 2?year-old boy had the onset of pain and swelling of his penis during the past 3 days. The swelling and pain increased significantly within the past 24 hours. The child's penis is shown in the Figure. DENOUEMENT AND DISCUSSION PARAPHIMOSIS Paraphimosis is an urologic emergency that results when the foreskin is retracted away from the glans penis and cannot be reduced to its former position. The opening in the prepuce, when forcibly retracted beyond the coronal sulcus, becomes a constricting ring that cannot be reduced. The constricting ring created causes a tension greater than the lymphatic pressure and results in edema of the prepuce, the penile shaft, and the glans penis distal to the incarcerated foreskin.1,2As lymphatic drainage is impaired and tissue swelling increases, reduction of the foreskin becomes more difficult. Pain occurs as a result of swelling, and, eventually, as a result of vascular compromise. If. 相似文献
17.
18.
Caroline Hartmann Hervé Récipon Marie-France Jubier Christiane Valon Evelyne Delcher-Besin Yves Henry Jacques De Buyser Bernard Lejeune André Rode 《Current genetics》1994,25(5):456-464
The mitochondrial genome of the selfed progeny of a plant regenerated from long-term somatic tissue culture displays specific structural rearrangements characterized by the appearance of novel restriction fragments. A mitochondrial DNA library was constructed from this selfed progeny in the SalI site of cosmid pHC79 and the novel fragments were subsequently studied. They were shown to arise from reciprocal recombination events involving DNA sequences present in the parental plant. The regions of recombination were sequenced and the nucleotide sequences were aligned with those of the presumptive parental fragments. We characterized an imperfect short repeated DNA sequence, 242 bp long, within which a 7-bb DNA repeat could act as a region of recombination. The use of PCR technology allowed us to show that these fragments were present in both parental plants and tissue cultures as low-abundance sequence arrangements. 相似文献
19.
Rechtsanwalt Professor Dr. iur. Karl Otto Bergmann Rechtsanwältin Dr. iur. Carolin Wever 《MedR Medizinrecht》2007,25(8):475-476
Ohne Zusammenfassung 相似文献
20.
Rechtsanwalt Professor Dr. iur. Karl Otto Bergmann Rechtsanwältin Dr. iur. Carolin Wever 《MedR Medizinrecht》2007,25(11):649-650
Ohne Zusammenfassung 相似文献