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91.
92.
Expression of c-fos mRNA was studied in the adult rat brain following cochlear ablations by using in situ hybridization. In normal animals, expression was produced by acoustic stimulation and was found to be tonotopically distributed in many auditory nuclei. Following unilateral cochlear ablation, acoustically driven expression was eliminated or decreased in areas normally activated by the ablated ear, e.g., the ipsilateral dorsal and ventral cochlear nuclei, dorsal periolivary nuclei, and lateral nucleus of the trapezoid body and the contralateral medial and ventral nuclei of the trapezoid body, lateral lemniscal nuclei, and inferior colliculus. These deficits did not recover, even after long survivals up to 6 months. Results also indicated that neurons in the dorsal cochlear nucleus could be activated by contralateral stimulation in the absence of ipsilateral cochlear input and that the influence of the contralateral ear was tonotopically organized. Results also indicated that c-fos expression rose rapidly and persisted for up to 6 months in neurons in the rostral part of the contralateral medial nucleus of the trapezoid body following a cochlear ablation, even in the absence of acoustic stimulation. This response may reflect a release of constitutive excitatory inputs normally suppressed by missing afferent input or changes in homeostatic gene expression related to sensory deprivation. Instances of transient, surgery-dependent increases in c-fos mRNA expression in the absence of acoustic stimulation were observed in the superficial dorsal cochlear nucleus and the cochlear nerve root on the ablated side. 相似文献
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The steady-state kinetics of the ThTP hydrolysis by thiamine triphosphatase (EC 3.6.1.28) from bovine brain testified to the presence of two kinetically significant conformational states of the protein, their equilibrium being determined by the substrate concentration. The ThTPase isomeric forms had different activities, affinities for ThTP and activation energies. The form with high affinity for the substrate was characterized by the Km and Vmax values of 43 microM and 9.9 mumol.s-1.mg-1 whereas for the form with lower affinity these values were equal to 298 microM and 19.3 mumol.s-1.mg-1, respectively. The activation energies of the ThTP hydrolysis reactions were 85.3 and 47.1 kJ.mol-1. Several mechanisms of the enzyme activity regulation in the cell are suggested. One of the mechanisms is related to the allosteric ThTP effect inducing reversible transition of the protein to a more active conformational state, while the others include the inhibition activity by ATP and the activation of ThTP-ase by Mg2+ free ions. 相似文献
95.
GK Abruzzo AM Flattery CJ Gill L Kong JG Smith VB Pikounis JM Balkovec AF Bouffard JF Dropinski H Rosen H Kropp K Bartizal 《Canadian Metallurgical Quarterly》1997,41(11):2333-2338
The in vivo activity of the Merck antifungal echinocandin drug candidate MK-0991 (L-743,872) was evaluated in mouse models of disseminated candidiasis, aspergillosis, and cryptococcosis. The echinocandins are potent inhibitors of 1,3-beta-D-glucan synthase. Two models of disseminated candidiasis were used. In a Candida albicans mouse survival model with both DBA/2N and CD-1 mice, estimates of the 50% effective doses (ED50s) of MK-0991 were 0.04 and 0.10 mg/kg of body weight/dose at 21 days after challenge, respectively. In a C. albicans target organ assay (TOA) with DBA/2N mice, MK-0991 at levels of > or =0.09 mg/kg/dose significantly reduced the numbers of C. albicans CFU/g of kidneys compared to the numbers in the kidneys of control mice from 1 to 28 days after challenge. Even when given as a single intraperitoneal dose either 30 min or 24 h after challenge, MK-0991 was effective and significantly reduced the numbers of C. albicans CFU/g of kidney compared to those in the controls. MK-0991 was >300-fold less active when it was administered orally than when it was administered parenterally. MK-0991 was efficacious in mouse TOAs against other C. albicans strains and Candida species including Candida tropicalis, Candida (Torulopsis) glabrata, Candida lusitaniae, Candida parapsilosis, and Candida krusei. MK-0991 was ineffective against disseminated Cryptococcus neoformans infections. In the model of disseminated aspergillosis in mice, MK-0991 at doses of > or =0.02 mg/kg/dose significantly prolonged the survival of DBA/2N mice, with estimates of the ED50 and ED90 of MK-0991 being 0.03 and 0.12 mg/kg/dose, respectively, at 28 days after challenge. MK-0991 is a potent, parenterally administered therapeutic agent against disseminated candidiasis and aspergillosis that warrants further investigation in human clinical trials. 相似文献
96.
PM Hartigan JC Giacomini ED Folland AF Parisi 《Canadian Metallurgical Quarterly》1998,82(12):1445-1450
Despite increasing use of percutaneous transluminal coronary angioplasty (PTCA) to treat stenotic coronary artery disease, there are relatively few prospective studies evaluating its long-term effectiveness. We prospectively randomized 212 stable patients with provocable myocardial ischemia and single-vessel subocclusive coronary disease to receive primary therapy with either PTCA or medical therapy. This report presents the clinical follow-up of these patients at a mean, after randomization, of 2.4 years for interview and 3.0 years for exercise testing. Of the 212 patients originally randomized, 175 received an extended follow-up interview, and 132 underwent exercise testing; 62% of patients in the PTCA group were angina free compared with 47% of patients in the medical group (p <0.05). Furthermore, exercise duration as measured by treadmill testing was prolonged by 1.33 minutes over baseline in the PTCA group, whereas it decreased by 0.28 minutes in the medical group (p <0.04). Although the angina-free time on the treadmill was not different (p=0.50), fewer patients in the medical group developed angina on the treadmill at 3 years than those in the PTCA group (p=0.04). By 36 months, excluding the initial randomized PTCA, use of PTCA and use of coronary artery bypass surgery were not different in the 2 treatment groups. These data indicate that some of the early benefits derived from PTCA in patients with single-vessel coronary artery disease are sustained, making it an attractive therapeutic option for these patients. 相似文献
97.
F Syed B Bingham M Johnson AF Markham JF Morrison 《Canadian Metallurgical Quarterly》1998,91(8):567-572
Phytohaemagglutinin (PHA)-induced T-cell proliferation is suppressed completely in steroid-sensitive asthma (SSA) by fluticasone propionate (FP). By contrast, in patients with steroid-resistant asthma (SRA), this proliferative response is only partially attenuated by steroids, which suggests that the T lymphocyte may harbour a key molecular defect in these patients. Both CD4+ and CD8+ T cells may be involved in orchestrating the inflammation underlying asthma. We examined whether CD4+ or CD8+ T cells isolated from SRA and SSA patients are equally susceptible to steroid suppression of PHA-induced proliferation. Complete suppression of CD4+ T-lymphocyte proliferation was seen in both SSA and control subjects at concentrations of 10(-9) M FP. In contrast, proliferation of CD4+ T cells from SRA patients was only partially inhibited, even at 10(-6) M FP. CD8+ responses from SRA, SSA and controls were all similar, with only a partial suppression of proliferation at 10(-6) M FP. Differential suppression by FP of CD4+ T cells has thus been demonstrated between SRA and SSA patients. 相似文献
98.
99.
Distribution of T-bands on mitotic chromosomes of Bos taurus was studied. Association of T-bands with telomeres and enrichment of T-bands with genes, with a known localization is described. After THA-banding on the chromosomes of cattle, telomeric and pericentromeric regions of all autosomes showed bright fluorescence. The exception was for chromosome 7, which did not have telomeric T-bands. Interstitial T-bands were detected only on chromosomes 7, 16, and Y (7q13, 7q15, 7q22, 7q24, 16q21, and Yp12). A total proportion of centromeric, telomeric, and interstitial T-bands was 11.19, 9.97, and 2.02% of the length of the haploid chromosome set, respectively. By means of fluorescent in situ hybridization (FISH), the presence of the telomeric repeat (TTAGGG)n was shown not only in telomeric regions of all autosome, but also in all pericentromeric regions. The obtained data are indicative of the specificity of T-banding on the chromosomes of Bos taurus. 相似文献
100.