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61.
Doxorubicin (DOX) is a broad-spectrum anthracycline antibiotic that has cardiotoxicity as a major side effect. One mechanism of this toxicity is believed to involve the reactive oxygen radical species (ROS); these agents likely account for the pathophysiology of DOX-induced cardiomyopathy. Aminoguanidine (AG) is an effective antioxidant and free radical scavenger which has long been known to protect against ROS formation. We investigated the effects of AG on DOX-induced changes in thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) content. The rats were divided into four groups:1) Control; 2) DOX group; injected intraperitoneally (i.p.) with DOX 20 mg/kg in a single dose 3) AG-treated group; injected i.p. in single dose of 20 mg/kg DOX plus 100 mg/kg AG 1 h before the DOX for 3 days, 4) AG group; injected i.p. with AG 100 mg/kg for 3 days. DOX administration to control rats increased TBARS and decreased GSH levels. AG administration before DOX injection caused significant decrease in TBARS and increase in GSH levels in the heart tissue when compared with DOX only. Morphological changes, including severe myocardial fibrosis and inflammatory cell infiltration were clearly observed in the DOX-treated heart. AG reversed the DOX-induced heart damage. Therefore AG could protect the heart tissue against free radical injury. The application of AG during cancer chemotherapy may attenuate tissue damage and improve the therapeutic index of DOX.  相似文献   
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It has been argued that downstream enzymes in metabolic pathways are expected to be subject to reduced selective constraint, while upstream enzymes, particularly those at pathway branch points, are expected to exhibit more frequent adaptive substitution than downstream enzymes. We examined whether these expectations are met for enzymes in the anthocyanin biosynthetic pathway in Ipomoea. Previous investigations have demonstrated that downstream enzymes in this pathway have substantially higher rates of nonsynonymous substitution than upstream enzymes. We demonstrate here that the difference in rates between the most upstream enzyme (CHS) and the two most downstream enzymes (ANS and UFGT) is explained almost entirely by differences in levels of selective constraint. Adaptive substitutions were not detected in any of these genes. Our results are consistent with suggestions that constraint is greater on enzymes with greater connectivity.  相似文献   
64.
Evolutionary theory predicts that interactions between species such as resource competition or reproductive interference will generate selection for character displacement where similar species co-occur. However, the rate and direction of character displacement will depend not only on the strength of selection for trait divergence, but also on the amount of genetic variation for selected traits and the nature of genetic correlations between them. To assess the importance of genetic constraints for the evolution of character displacement, we examined the genetic architecture of a suite of floral traits previously shown to be under selection in the annual plant Ipomoea hederacea when this species co-occurs with Ipomoea purpurea. We found that the six floral traits we measured are all positively genetically correlated. We also demonstrate, using new statistical approaches, that the predicted response to selection for four of these six traits is substantially constrained by their genetic correlation structure. Most notably, the response to selection for reduced separation of the tallest and shortest anthers, which reduces the degree of detrimental heterospecific pollen flow, is substantially constrained. Our results suggest that the rate of evolution of reproductive character displacement in I. hederacea is limited by the genetic architecture of floral traits.  相似文献   
65.
In self-compatible, hermaphroditic plants, display size-the number of flowers open on a plant at one time-is believed to be influenced by trade-offs between increasing geitonogamous selfing and decreasing per-flower pollen export as display size increases. Experimental results presented here indicate that selection through male function favors smaller display sizes in Ipomoea purpurea. In small arrays, plant display size was manipulated experimentally, and female selfing rate, male outcross success, and total male fitness were estimated using genetic markers and likelihood and regression analyses. As would be expected if larger displays experience greater geitonogamy, selfing rate increased with display size. However, the per-flower amount of pollen exported to other plants decreased with display size. The magnitude of this effect is more than sufficient to offset the increase in selfing rate, resulting in reduced per-flower total male fitness with increasing display size. The low values of inbreeding depression previously reported for this species would enhance this effect.  相似文献   
66.

Background  

A prospective observational study was done to describe nonbacterial pulmonary complications in hospitalized patients with human immunodeficiency virus (HIV) infection.  相似文献   
67.
Endotoxin shock is a major cause of death in patients with septicemia. Endotoxin induces nitric oxide (NO) production and causes tissue damage. In addition, the release of oxygen free radicals has also been observed in endotoxin shock and was found to be responsible for the occurrence of multiple organ failure. The purpose of the present study was to evaluate suitable indicators for early and late stages of endotoxin shock. The experiments were designed to induce endotoxin shock in conscious rats by means of anEscherichia coli lipopolysaccharide (LPS) injection. Arterial pressure (AP) and heart rate (HR) were continuously monitored for 72 h after LPS administration. The maximal decrease in AP and increase in HR and nitrate/nitrite level occurred at 9–12 h following LPS administration. The white blood cell (WBC) count had decreased at 3 h. Hydroxyl radical (methyl guanidine, MG) decreased rapidly after LPS administration. Plasma levels of blood urea nitrogen (BUN), creatinine (Cr), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), and glutamic oxaloacetic transaminase increased before the rise of amylase. Our results suggest that changes in AP, HR, WBC, free radicals, and chemical substances (BUN, Cr) can possibly serve as approximate indicators for the early stage of endotoxin shock. Severe multiple organ damage may be caused by amylase release in the late stage of endotoxin shock.  相似文献   
68.
Lysosome-associated membrane protein (LAMP)-1, one of the major protein components of the lysosomal membrane, is upregulated in the human glioblastoma cell lines, U-373 MG and LN-Z308, which undergo cisplatin-induced apoptosis. These human brain tumor cell lines demonstrated apoptosis in response to cisplatin/nifedipine treatment. Both cell lines demonstrated an apoptotic response by more than one criterion. Apoptosis was demonstrated by DNA fragmentation techniques such as DNA laddering, ApopTag in situ labeling, and an ELISA-based method of detecting liberated oligosomes. These cells also had characteristic morphologic changes and upregulation of bax consistent with apoptosis. LAMP-1 expression at the protein and mRNA level was examined and found to increase with cisplatin/nifedipine treatment. LAMP-1 expression was examined using indirect immunofluorescent staining, Northern blot analysis and Western blot analysis. The finding of an augmentation of LAMP-1 in these cells induced to die is enigmatic. These findings raise the possibility of LAMP-1 involvement in the apoptotic process.  相似文献   
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70.
M. Claustres PU PH  MD  PhD 《Andrologie》2001,11(4):195-203
Over the last decade, the genetic basis for CBAVD has been identified by its association with CFTR gene mutations, and CBAVD is now generally considered to be a mild or incomplete form of CF. In this review, the author summarizes the main results of compilation of CFTR gene analysis conducted in French laboratories for 3,923 patients with CF and 800 males with CABVD. The degree of clinical expression can be affected by several variables, including the molecular mechanisms by which the various CFTR mutations impair or disrupt the function of the CFTR chloride channel. Phenotypic expression of CFTR mutational genotypes varies from severe, progressive pulmonary disease with pancreatic insufficiency (CF-PI), to mild pulmonary disease with pancreatic sufficiency (PS) or singleorgan forms of “CFTR-opathies”. In CF, a total of 310 different CFTR mutations accounting for 94% of 7,846 CF alleles have generated almost 500 different genotypes, comprising 2 severe mutations in 88% of cases (CF-PI), one severe mutation in trans to a mild mutation in 11% (CF-PS), and 2 mild mutations in 1% of identified genotypes. In CBAVD, 137 mutations scattered over the whole gene were identified in 60% of 1,600 CBAVD alleles during the study. Among the 150 characterized mutational CFTR genotypes, compound heterozygosity was the rule, and the most frequent CBAVD combinations were ΔF508/5T (35%), ΔF508/other mutation (30%, including ΔF508/R117H-7T: 5,6%), and 5T/other mutation (17%). No combination of two severe mutations was found in CBAVD (0%); by contrast with the CF population, 88% of genotypes identified in CBAVD comprised a severe mutation in trans to a mild mutation, and 12% consisted of 2 mild mutations. A total of 22 genotypes were shared by both CF and CBAVD. The role of the 5T allele as a splicing variant with variable, incomplete disease penetrance in CBAVD is reviewed. Other haplotype backgrounds, such as the TG12 sequence and the M470V polymorphism, may influence CFTR splicing and/or function. This study confirms the high molecular heterogeneity of CFTR mutations in CBAVD and emphasizes the importance of extensive CFTR analysis in these patients. Longterm follow-up studies of CBAVD patients are necessary in order to predict the phenotypic consequences of numerous CFTR mutational genotypes.  相似文献   
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