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161.
162.
Optimization of 2-phenylaminoimidazo[4,5-h]isoquinolin-9-ones: orally active inhibitors of lck kinase 总被引:2,自引:0,他引:2
Goldberg DR Butz T Cardozo MG Eckner RJ Hammach A Huang J Jakes S Kapadia S Kashem M Lukas S Morwick TM Panzenbeck M Patel U Pav S Peet GW Peterson JD Prokopowicz AS Snow RJ Sellati R Takahashi H Tan J Tschantz MA Wang XJ Wang Y Wolak J Xiong P Moss N 《Journal of medicinal chemistry》2003,46(8):1337-1349
The tyrosine kinase p56lck (lck) is essential for T cell activation; thus, inhibitors of lck have potential utility as autoimmune agents. Our initial disclosure of a new class of lck inhibitors based on the phenylaminoimidazoisoquinolin-9-one showed reasonable cellular activity but did not work in vivo upon oral administration. Our current work highlights the further use of rational drug design and molecular modeling to produce a series of lck inhibitors that demonstrate cellular activity below 100 nM and are as efficacious as cyclosporin A in an in vivo mouse model of anti-CD3-induced IL-2 production. 相似文献
163.
Cadmium-induced antioxidant defense mechanism in freshwater teleost Oreochromis mossambicus (Tilapia) 总被引:11,自引:0,他引:11
Antioxidant defenses consisting of catalase, superoxide dismutase (SOD), xanthine oxidase (XOD), glutathione peroxidase (GPX), and glutathione S-transferase were estimated in liver and kidney of freshwater fish subjected to a sublethal concentration of cadmium chloride (Cd2+), i.e., 5 ppm. The aim of the study was to evaluate the role of antioxidant defenses during cadmium-induced oxidative stress. Significant elevations in liver and kidney of all of the above detoxification enzymes were evident from the 7th day onward, were maintained until the 15th day, and then decreased slightly on the 30th day of exposure to cadmium stress. Between the two tissues studied, liver recorded higher activity for all enzymes except GPX, which was elevated significantly in kidney (82.85%). Both liver and kidney recorded more or less similar increases of SOD (86.61% and 86.32%, respectively), and XOD (86.41% and 84.19%, respectively). The findings indicate that tissue glutathione-dependent enzymes as well as other antioxidant enzymes function in protection against Cd2+ toxicity and that these antioxidants provide a first line of defense against Cd2+ before the induction of any metallothionein synthesis occurs. 相似文献
164.
Danforth DN Cowan K Altemus R Merino M Chow C Berman A Chaudhry U Shriver C Steinberg SM Zujewski J 《Annals of surgical oncology》2003,10(6):635-644
Background: Preoperative chemotherapy for stage II breast cancer may reduce locoregional tumors and provides initial treatment for systemic micrometastases. We conducted a prospective, randomized trial to evaluate the ability of intensive preoperative chemotherapy to enhance the outcome of this approach.Methods: Patients with clinical stage II breast cancer (T2N0, T1N1, and T2N1) were prospectively randomized to receive either preoperative or postoperative chemotherapy with five 21-day cycles of fluorouracil, leucovorin calcium, doxorubicin, and cyclophosphamide (FLAC)/granulocyte-colony-stimulating factor. Local therapy consisted of modified radical mastectomy or segmentectomy/axillary dissection/breast radiotherapy, according to patient preference.Results: Fifty-three women were randomized (26 preoperative chemotherapy and 27 postoperative chemotherapy). The objective clinical response rate of the primary tumor to preoperative chemotherapy was 80%, and the pathologic complete response rate was 20%. Preoperative chemotherapy reduced the overall incidence and number of axillary lymph node metastases. There was no difference in the use of breast-conserving local therapy between the two treatment arms. There were 20 local/regional or distant recurrences (9 preoperative and 11 postoperative). There was no difference in the overall or disease-free survival between the preoperative and postoperative chemotherapy arms.Conclusions: Preoperative FLAC/granulocyte-colony-stimulating factor chemotherapy was effective against local/regional tumors in stage II breast cancer but was otherwise comparable to postoperative chemotherapy. 相似文献
165.
Satheesh Kumar Bhandary B. Usha Ranganna 《Indian journal of otolaryngology and head and neck surgery》2008,60(4):373-375
Lupus vulgaris is the commonest form of cutaneous tuberculosis which commonly involve trunk and buttocks. Lupus vulgaris affecting
nose and face, are rarely reported in India. This study reports an unusual case of lupus vulgaris involving the external nose
that showed dramatic outcome after six months of anti- tubercular treatment. 相似文献
166.
PURPOSE: To explore the sensitivity of children with specific language impairment (SLI) to amplitude-modulated and durational cues that are important for perceiving suprasegmental speech rhythm and stress patterns. METHOD: Sixty-three children between 7 and 11 years of age were tested, 21 of whom had a diagnosis of SLI, 21 of whom were matched for chronological age to the SLI sample, and 21 of whom were matched for language age to the SLI sample. All children received a battery of nonspeech auditory processing tasks along with standardized measures of phonology and language. RESULTS: As many as 70%-80% of children diagnosed with SLI were found to perform below the 5th percentile of age-matched controls in auditory processing tasks measuring sensitivity to amplitude envelope rise time and sound duration. Furthermore, individual differences in sensitivity to these cues predicted unique variance in language and literacy attainment, even when age, nonverbal IQ, and task-related (attentional) factors were controlled. CONCLUSION: Many children with SLI have auditory processing difficulties, but for most children, these are not specific to brief, rapidly successive acoustic cues. Instead, sensitivity to durational and amplitude envelope cues appear to predict language and literacy outcomes more strongly. This finding now requires replication and exploration in languages other than English. 相似文献
167.
Aims: To establish a correct method of evaluation and management of contracted sockets Results: Anopthalmic socket were frequently seen in orbit and Oculoplasty clinic of Aravind Eye Hospital, Madurai, South India. Prospective evaluation of Anophthalmic Sockets was done in this study. Anophthalmic Socket which can not support prosthetic eye is called contracted socket.4,5,14. These sockets were graded as congenital and acquired, which were managed using single, combined and multiple procedures. Surgical outcome of each case were analyzed. Key words: Anophthalmos, contracted sockets, prosthesis, conformer, volume deficit. 相似文献
168.
Freund's complete adjuvant (FCA) treated group of mice when challenged with lethal Plasmodium berghei showed increased survival value; survival period (SP) and median survival day (MSD) compared to their respective control groups. K values were affected and mean parasitaemia during infection period was lower than that of control. In general survival rate after 35 days of infection was 10.5% in FCA recipients. The survival rate in a particular group of animals which received 0.2 ml FCA 3 days before challenge was 22.7%. FCA was found to contribute to increased survival of the host against P. berghei infection. The study indicates that adjuvants, like FCA induce protective immunity and future studies should include non-specific immunization against human malaria. 相似文献
169.
A 13-year-old male child had gradually progressive, bilaterall, symmetrical, erythematous hyperkeratotic plaques over knees, elbows, natal cleft, dorsa of hands and feet with palmoplantar keratoderma. High arched palate, fissured tongue and sternal depression (pectus-excavatum) were unusual associations. 相似文献
170.
Abortion was induced by extraovular placement of rubber catheter -- the abortifacient efficacy of which was augmented by serial intramusclar administration of a small dose of 15 methyl analogue of prostaglandin F2 alpha -- among 75 consecutive physically healthy gravidas over a 3-month period beginning in March 1978. 96% of the patients aborted successfully within 40 hours by the effect of the combined treatment with extraovular catheter and intramuscular 15 methyl analogue of prostalandin F2 alpha. The mean induction-abortion interval was 24.15 hours, with a range of 5-39 hours. The procedure was found to be comparatively safe with no untoward complications such as hemorrhage or uterine rupture. Cervical injuries occurring in 2 nulliparous women of 16-20 weeks' gestational age were the only complications. There was no excessive blood loss in these patients, and the cervical tears were sutured promptly. There was no difficulty in inserting the catheter in the patients who were 13-15 weeks pregnant. The mean abortion time for the 18 nulliparous women did not differ significant from the mean abortion time for the 57 parous women. 50% of the parous women aborted within 24 hours, but only 41% of the nulliparous women did so within that period. It is demonstrated that utilization of the catheter method combined with intramuscular administration of a small dose of 15 methyl analogue of prostaglandin F2 alpha every 3 hours is promising. 相似文献