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81.
82.
Reingold JS McGavock JM Kaka S Tillery T Victor RG Szczepaniak LS 《American journal of physiology. Endocrinology and metabolism》2005,289(5):E935-E939
The primary aim of this investigation was to determine the reliability and sensitivity of 1H magnetic resonance spectroscopy (1H-MRS) as a method for quantifying myocardial triglyceride (TG) content in humans over time and in response to metabolic perturbations. Three separate experiments were designed to quantify myocardial TG content 1) over a 90-day period, 2) after a high-fat meal, and 3) after a 48-h fast. Proton spectra were collected from a 10 x 20 x 30-mm3 voxel placed within the intraventricular septum, with measurements acquired at end-systole and end-expiration, using cardiac triggering and respiratory gating. Minimal variation was observed between myocardial TG content determined 90 days apart (r = 0.98, CV = 5%), whereas TG values were unaffected by a high-fat meal despite a significant twofold increase (P < 0.05) in serum TG. In contrast, myocardial TG content increased threefold (P < 0.05) after a 48-h fast despite a 25% reduction in serum TG. Body mass index was significantly related to myocardial TG (r = 0.58, P < 0.05) and the change in myocardial TG after a 48-h fast (r2 = 0.60). 1H-MRS is a reliable method for the determination of myocardial TG in humans and is relatively unaffected by the consumption of one high-fat meal but sensitive to changes following a prolonged fast. 相似文献
83.
Phenotypic hypersusceptibility to multiple protease inhibitors and low replicative capacity in patients who are chronically infected with human immunodeficiency virus type 1 下载免费PDF全文
Martinez-Picado J Wrin T Frost SD Clotet B Ruiz L Brown AJ Petropoulos CJ Parkin NT 《Journal of virology》2005,79(10):5907-5913
Increased susceptibility to the protease inhibitors saquinavir and amprenavir has been observed in human immunodeficiency virus type 1 (HIV-1) with specific mutations in protease (V82T and N88S). Increased susceptibility to ritonavir has also been described in some viruses from antiretroviral agent-naive patients with primary HIV-1 infection in association with combinations of amino acid changes at polymorphic sites in the protease. Many of the viruses displaying increased susceptibility to protease inhibitors also had low replication capacity. In this retrospective study, we analyze the drug susceptibility phenotype and the replication capacity of virus isolates obtained at the peaks of viremia during five consecutive structured treatment interruptions in 12 chronically HIV-1-infected patients. Ten out of 12 patients had at least one sample with protease inhibitor hypersusceptibility (change =0.4-fold) to one or more protease inhibitor. Hypersusceptibility to different protease inhibitors was observed at variable frequency, ranging from 38% to amprenavir to 11% to nelfinavir. Pairwise comparisons between susceptibilities for the protease inhibitors showed a consistent correlation among all pairs. There was also a significant relationship between susceptibility to protease inhibitors and replication capacity in all patients. Replication capacity remained stable over the course of repetitive cycles of structured treatment interruptions. We could find no association between in vitro replication capacity and in vivo plasma viral load doubling time and CD4(+) and CD8(+) T-cell counts at each treatment interruption. Several mutations were associated with hypersusceptibility to each protease inhibitor in a univariate analysis. This study extends the association between hypersusceptibility to protease inhibitors and low replication capacity to virus isolated from chronically infected patients and highlights the complexity of determining the genetic basis of this phenomenon. The potential clinical relevance of protease inhibitor hypersusceptibility and low replication capacity to virologic response to protease inhibitor-based therapies deserves to be investigated further. 相似文献
84.
Surgery, radioactive iodine, and suppressive doses of Lthyroxine are commonly used in the treatment of benign nodular thyroid disease, with the best results achieved with surgery. However, recent advances in cytological diagnostic methods enable patients to choose alternative therapies if there are some contraindications or there is no agreement for surgery. Over past 14 years percutaneous ethanol injections (PEI), used in the past as a therapy for liver, kidney, parathyroid and adrenal cortical tumors, have been developed as an alternative method in the management of thyroid nodules. This paper reviews the investigations of a number aspects of PEI in the treatment of thyroid nodules reported in the literature. The evidence demonstrate that PEI is effective in the case of both solid non-toxic and autonomously functioning toxic nodules as well as cystic nodules. In majority of cases restore normal serum fT4, fT3 and TSH concentrations and shrink the tumor volume. The method seems to be safe and generally well tolerated by the patients. However, the current research base on the efficacy and PEI-associated risks is still inadequate to determine definitively its role as a standard treatment of benign nodular thyroid disease. For example, there is no detailed data comparing the results of treatment with PEI to standard treatment with radioactive iodine and L-thyroxine. Despite it, we conclude that PEI is a valuable method that earned recognition among other methods of the thyroid nodules treatment. 相似文献
85.
Westers H Braun PG Westers L Antelmann H Hecker M Jongbloed JD Yoshikawa H Tanaka T van Dijl JM Quax WJ 《Applied and environmental microbiology》2005,71(4):1899-1908
Small lipases of Bacillus species, such as LipA from Bacillus subtilis, have a high potential for industrial applications. Recent studies showed that deletion of six AT-rich islands from the B. subtilis genome results in reduced amounts of extracellular LipA. Here we demonstrate that the reduced LipA levels are due to the absence of four genes, skfABCD, located in the prophage 1 region. Intact skfABCD genes are required not only for LipA production at wild-type levels by B. subtilis 168 but also under conditions of LipA overproduction. Notably, SkfA has bactericidal activity and, probably, requires the SkfB to SkfD proteins for its production. The present results show that LipA is more prone to proteolytic degradation in the absence of SkfA and that high-level LipA production can be improved significantly by employing multiple protease-deficient B. subtilis strains. In conclusion, our findings imply that SkfA protects LipA, directly or indirectly, against proteolytic degradation. Conceivably, SkfA could act as a modulator in LipA folding or as a protease inhibitor. 相似文献
86.
Tegako LI 《Journal of PHYSIOLOGICAL ANTHROPOLOGY and Applied Human Science》2005,24(4):463-464
Anthropological research on children from Minsk was carried out within the framework of medical ecological monitoring. Besides the wide anthropometrical program, a study of the ecological conditions in the areas where the children examined reside and train was carried out. Comparison of the basic parameters of physical development in various age groups and the analysis of annual increases shows intensification of growth among modern children despite some decrease in the rates of acceleration. Some increase in body length and decrease of body weight as well as the reduction of chest circumference is common. Regional studies, particularly in the radiation control zones, show the dependence of physical development on the ecological situation. 相似文献
87.
Lidia?FeliuEmail author Marta?Planas 《International journal of peptide research and therapeutics》2005,11(1):53-97
This review describes the isolation, activities and synthetic approaches of the naturally occurring cyclic peptides containing biaryl and/or biaryl ether linkages. These compounds range from monocyclic, to bicyclic, to the polycyclic glycopeptide antibiotics, and most of them exhibit significant biological properties such as cytotoxic or antimicrobial activities. Interestingly, vancomycin is used clinically as the antibiotic of last resort for the treatment of methicillin-resistant Staphylococcus aureus. The medicinal significance and the structural complexity of these macrocycles have challenged chemists towards the total synthesis of these compounds and in designing synthetic analogues. Non-natural macrocycles reported from 1999 to 2004 are also covered. 相似文献
88.
NF-kappaB and not the MAPK signaling pathway regulates GADD45beta expression during acute inflammation 总被引:2,自引:0,他引:2
Zhang N Ahsan MH Zhu L Sambucetti LC Purchio AF West DB 《The Journal of biological chemistry》2005,280(22):21400-21408
The GADD45 (growth arrest and DNA damage-inducible) family of genes is involved in the regulation of cell cycle progression and apoptosis. To study signaling pathways affecting GADD45beta expression and to examine systematically in vivo the GADD45beta expression in tissues following various toxic stresses, we created a transgenic mouse by fusing the GADD45beta promoter to firefly luciferase (Gadd45beta-luc). In vivo GADD45beta expression was assessed by measuring the luciferase activity in the Gadd45beta-luc transgenic mouse using a non-invasive imaging system (IVIS Imaging System, Xenogen Corporation). We found that a number of agents that induce oxidative stress, such as sodium arsenite, CCl4, lipopolysaccharide (LPS), or tumor necrosis factor-alpha, are able to induce luciferase expression throughout the entire animal. In liver, spleen, lung, intestine, kidney, and heart, we observed an induction of luciferase activity after LPS treatment, which correlates with an increase of GADD45beta mRNA in these tissues. Processes that induce DNA damage activate the NF-kappaB signaling pathway. Several inhibitors of the NF-kappaB signaling pathway, including dexamethasone, thalidomide, and a proteasome inhibitor, bortezomib, showed inhibitory effects on LPS-induced GADD45beta expression as indicated by a decrease of the luciferase activity. Northern blot analysis confirmed a broad inhibitory effect of bortezomib on LPS-induced GADD45beta mRNA expression in spleen, lung, and intestine. In liver of bortezomib-treated mice, we observed a reverse correlation between the luciferase activity and the GADD45beta mRNA level. We speculate that such a discrepancy could be due to severe liver toxicity caused by bortezomib and LPS co-treatment. MAPK inhibitors had transient and inconsistent effects on LPS-induced luciferase expression. Our data are consistent with the notion that NF-kappaB, but not the MAPK signaling pathways, is involved in the in vivo regulation of GADD45beta expression. Thus, NF-kappaB signaling involves induction of GADD45beta expression, which supports the proposed role of GADD45beta in protecting cells against DNA damaged under various stress conditions. 相似文献
89.
Atlante A de Bari L Valenti D Pizzuto R Paventi G Passarella S 《Biochimica et biophysica acta》2005,1708(1):13-22
We report here initial studies on D-lactate metabolism in Jerusalem artichoke. It was found that: 1) D-lactate can be synthesized by Jerusalem artichoke by virtue of the presence of glyoxalase II, the activity of which was measured photometrically in both isolated Jerusalem artichoke mitochondria and cytosolic fraction after the addition of S-D-lactoyl-glutathione. 2) Externally added D-lactate caused oxygen consumption by mitochondria, mitochondrial membrane potential increase and proton release, in processes that were insensitive to rotenone, but inhibited by both antimycin A and cyanide. 3) D-lactate was metabolized inside mitochondria by a flavoprotein, a putative D-lactate dehydrogenase, the activity of which could be measured photometrically in mitochondria treated with Triton X-100. 4) Jerusalem artichoke mitochondria can take up externally added D-lactate by means of a D-lactate/H(+) symporter investigated by measuring the rate of reduction of endogenous flavins. The action of the d-lactate translocator and of the mitochondrial D-lactate dehydrogenase could be responsible for the subsequent metabolism of d-lactate formed from methylglyoxal in the cytosol of Jerusalem artichoke. 相似文献
90.
The peroxidase-like activity of cytochrome c is considerably increased by unfolding of the protein. The enhancement of the activity is due to the higher reaction rate of unfolded cytochrome c with hydrogen peroxide, which is the rate-determining step in the peroxidase cycle of cytochrome c (Gebicka, L., 2001, Res Chem Intermed 27, 717-23). In this study we checked whether combined action of two unfolding factors, SDS and peroxynitrite or radiation (hydroxyl radicals), increases the peroxidase-like activity of cytochrome c more than any single treatment alone. Peroxynitrite reacts with SDS-modified cytochrome c in the same way as with native cytochrome c, via intermediate radical products, *OH/*NO2, arising from peroxynitrite homolysis. We found that SDS-modified cytochrome c is much more sensitive to oxidative damage than the native protein. Partial unfolding of cytochrome c by SDS causes the peroxide substrate to have a better access to the heme center. On the other hand, the amino acids located in the vicinity of the active site and/or heme group become accessible for oxidizing radicals. The overall effect observed is that the peroxidase-like activity of SDS-modified cytochrome c decreases with an increase of the concentration of the oxidizing species (peroxynitrite or radiolytically generated hydroxyl radicals). The damage of SDS-modified cytochrome c caused by irradiation is much more significant than that observed after peroxynitrite treatment. 相似文献