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121.
Morteza Izadi Nematollah Jonaidi‐Jafari Amin Saburi Hossein Eyni Mohammad‐Reza Rezaiemanesh Reza Ranjbar 《Microbiology and immunology》2012,56(12):836-842
Cryptosporidium spp. is a major cause of diarrhea in developing countries, mainly affecting people with compromised immune systems in general and HIV‐infected individuals with low CD4 + T‐cell counts in particular. This infection is self‐limiting in healthy persons; however, it can be severe, progressive and persistent in those who are immunocompromised. There are few published studies concerning cryptosporidiosis and Cryptosporidium genotypes in Iranian immunocompromised patients and none of them describe risk factors. This study was undertaken to identify prevalence, genotypes and risk factors for cryptosporidiosis in immunocompromised patients. Three fecal samples were obtained at two day intervals from each of the 183 patients and processed with modified Ziehl–Neelsen staining methods and 18S rRNA gene amplification and sequencing. The overall infection prevalence was 6%. Cryptosporidium parvum was identified in isolates from five HIV‐infected patients, one patient who had undergone bone marrow transplantation and one with chronic lymphocytic leukemia. Cryptosporidium hominis was identified in isolates from two HIV‐infected patients and two patients with acute lymphocytic leukemia. According to univariate analysis, the statistically significant factors were diarrhea (OR = 21.7, CI = 2.83–78.4, P= 0.003), CD4 + lymphocytes less than 100 cells/mm3 (OR = 41.3, CI = 13.45–114.8, P < 0.0001), other microbial infections (OR = 7.1321.7, CI = 1.97–25.73, P = 0.006), weight loss (OR = 73.78, CI = 15.5–350, P < 0.0001), abdominal pain (OR = 10.29, CI = 2.81–37.74.4, P= 0.001), dehydration (OR = 72.1, CI = 17.6–341.5, P < 0.0001), vomiting (OR = 4.87, CI = 1.4–16.9, P= 0.015), nausea (OR = 9.4, CI = 2.38–37.2, P < 0.001), highly active antiretroviral therapy (OR = 0.089, CI = 0.01–0.8, P= 0.015) and diarrhea in household members (OR = 7.37, CI = 2.04–26.66, P= 0.001). After multivariate analysis and a backward deletion process, only < 100 CD4 + T‐lymphocytes/mm3 maintained a significant association with infection. The authors recommend that this infection should be suspected in patients with diarrhea, weight loss and dehydration in general and in diarrheal individuals with < 100 CD4 + T‐lymphocytes/mm3. 相似文献
122.
Gajewski S Comeaux EQ Jafari N Bharatham N Bashford D White SW van Waardenburg RC 《Journal of molecular biology》2012,415(4):741-758
Tyrosyl-DNA phosphodiesterase I (Tdp1) is a member of the phospholipase D superfamily that hydrolyzes 3'-phospho-DNA adducts via two conserved catalytic histidines-one acting as the lead nucleophile and the second acting as a general acid/base. Substitution of the second histidine specifically to arginine contributes to the neurodegenerative disease spinocerebellar ataxia with axonal neuropathy (SCAN1). We investigated the catalytic role of this histidine in the yeast protein (His432) using a combination of X-ray crystallography, biochemistry, yeast genetics, and theoretical chemistry. The structures of wild-type Tdp1 and His432Arg both show a phosphorylated form of the nucleophilic histidine that is not observed in the structure of His432Asn. The phosphohistidine is stabilized in the His432Arg structure by the guanidinium group that also restricts the access of nucleophilic water molecule to the Tdp1-DNA intermediate. Biochemical analyses confirm that His432Arg forms an observable and unique Tdp1-DNA adduct during catalysis. Substitution of His432 by Lys does not affect catalytic activity or yeast phenotype, but substitutions with Asn, Gln, Leu, Ala, Ser, and Thr all result in severely compromised enzymes and DNA topoisomerase I-camptothecin dependent lethality. Surprisingly, His432Asn did not show a stable covalent Tdp1-DNA intermediate that suggests another catalytic defect. Theoretical calculations revealed that the defect resides in the nucleophilic histidine and that the pK(a) of this histidine is crucially dependent on the second histidine and on the incoming phosphate of the substrate. This represents a unique example of substrate-activated catalysis that applies to the entire phospholipase D superfamily. 相似文献
123.
Antipsychotic drugs have various neuropharmacological properties as a result of their structural diversity. Despite their therapeutic benefits, most of the prescribed atypical antipsychotics can induce severe side effects, including weight gain, type II diabetes mellitus, and cardiovascular diseases. Among the developed atypical antipsychotic agents, tetracyclic dibenzodiazepine and thienobenzodiazepine compounds, particularly clozapine and olanzapine, are associated with the greatest weight gain and metabolic disturbances. However, the unique chemical structure of these compounds causes the low risk of side effects reported for typical antipsychotics (e.g. extrapyramidal symptoms and tardive dyskinesia). This report reviews the recent discovery of the potential role of the chemical structure of antipsychotics in their therapeutic properties and metabolic disturbances. By developing structure-activity relationship studies for atypical antipsychotics, we will improve our understanding of the structural modifications of these chemical classes that lead to reduced weight gain, which will be an invaluable step toward the discovery of the next generation of atypical antipsychotics. In this review, we suggest that a novel dibenzodiazepine or thienobenzodiazepine antipsychotic drug with lower affinity for H(1) receptors may significantly advance schizophrenia therapy. 相似文献
124.
125.
Pholcodine is an opiate derivative drug which is widely used in pediatric medicine. In this study, a chemiluminescence (CL) method is described that determines pholcodine in human plasma and syrup samples. This method is based on the fact that pholcodine can greatly enhance the weak CL emission of reaction between tris(1,10 phenanthroline)ruthenium(II), Ru(phen)32+, and acidic Ce(IV). The CL mechanism is described in detail using UV–vis light, fluorescence and CL spectra. Effects of chemical variables were investigated and under optimum conditions, CL intensity was proportional to the pholcodine concentration over the range 4.0 × 10?8 to 8.0 × 10?6 mol L?1. The limit of detection (LOD) (S/N = 3) was 2.5 × 10?8 mol L?1. Percent of relative standard deviations (%RSD) for 3.0 × 10?7 and 3.0 × 10?6 mol L?1 of pholcodine was 2.9 and 4.0%, respectively. Effects of common ingredients were investigated and the method was applied successfully to the determination of pholcodine in syrup samples and human plasma. 相似文献
126.
Yun-Seo Kil Jiyoung Park Mahtab Jafari Hyun Ae Woo Eun Kyoung Seo 《Bioorganic & medicinal chemistry letters》2017,27(14):3065-3070
A new coumarin, (?)-cis-(3′R,4′R)-4′-O-angeloylkhellactone-3′-O-β-d-glucopyranoside (1) and two new chalcones, 3′-[(2E)-5-carboxy-3-methyl-2-pentenyl]-4,2′,4′-trihydroxychalcone (4) and (±)-4,2′,4′-trihydroxy-3′-{2-hydroxy-2-[tetrahydro-2-methyl-5-(1-methylethenyl)-2-furanyl]ethyl}chalcone (5) were isolated from the aerial parts of Angelica keiskei (Umbelliferae), together with six known compounds: (R)-O-isobutyroyllomatin (2), 3′-O-methylvaginol (3), (?)-jejuchalcone F (6), isoliquiritigenin (7), davidigenin (8), and (±)-liquiritigenin (9). The structures of the new compounds were determined by interpretation of their spectroscopic data including 1D and 2D NMR data. All known compounds (2, 3, and 6–9) were isolated as constituents of A. keiskei for the first time. To identify novel hepatocyte proliferation inducer for liver regeneration, 1–9 were evaluated for their cell proliferative effects using a Hep3B human hepatoma cell line. All isolates exhibited cell proliferative effects compared to untreated control (DMSO). Cytoprotective effects against oxidative stress induced by glucose oxidase were also examined on Hep3B cells and mouse fibroblast NIH3T3 cells and all compounds showed significant dose-dependent protection against oxidative stress. 相似文献
127.
A Chimeric protein of CFA/I,CS6 subunits and LTB/STa toxoid protects immunized mice against enterotoxigenic Escherichia coli
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Narges Zeinalzadeh Ali Hatef Salmanian Goli Goujani Jafar Amani Ghasem Ahangari Asal Akhavian Mahyat Jafari 《Microbiology and immunology》2017,61(7):272-279
128.
Shahram?SadeghiEmail author Mohammadrezaalavian?Ghavanini Alireza?Ashraf Peyman?Jafari 《BMC neurology》2004,4(1):11
Background
central loop of the gastrocnemius-soleus H-reflex latency (Tc) that looks promising in the diagnosis of S1 radiculopathy; has been investigated in a few studies and only two of them have focused on the constitutional factors affecting it. Although leg length has been shown to contribute to the Tc, the role of age is controversial. More confusing, none of the previously performed studies have used strict criteria to rule out subclinical neuropathy, so the results could be misleading. This study has been performed to determine the influence of leg length and age on Tc among a carefully selected group of healthy volunteers. 相似文献129.
Adenovirus type 5 viral particles pseudotyped with mutagenized fiber proteins show diminished infectivity of coxsackie B-adenovirus receptor-bearing cells 总被引:2,自引:0,他引:2
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Jakubczak JL Rollence ML Stewart DA Jafari JD Von Seggern DJ Nemerow GR Stevenson SC Hallenbeck PL 《Journal of virology》2001,75(6):2972-2981
A major limitation of adenovirus type 5 (Ad5)-based gene therapy, the inability to target therapeutic genes to selected cell types, is attributable to the natural tropism of the virus for the widely expressed coxsackievirus-adenovirus receptor (CAR) protein. Modifications of the Ad5 fiber knob domain have been shown to alter the tropism of the virus. We have developed a novel system to rapidly evaluate the function of modified fiber proteins in their most relevant context, the adenoviral capsid. This transient transfection/infection system combines transfection of cells with plasmids that express high levels of the modified fiber protein and infection with Ad5.beta gal.Delta F, an E1-, E3-, and fiber-deleted adenoviral vector encoding beta-galactosidase. We have used this system to test the adenoviral transduction efficiency mediated by a panel of fiber protein mutants that were proposed to influence CAR interaction. A series of amino acid modifications were incorporated via mutagenesis into the fiber expression plasmid, and the resulting fiber proteins were subsequently incorporated onto adenoviral particles. Mutations located in the fiber knob AB and CD loops demonstrated the greatest reduction in fiber-mediated gene transfer in HeLa cells. We also observed effects on transduction efficiency with mutations in the FG loop, indicating that the binding site may extend to the adjacent monomer in the fiber trimer and in the HI loop. These studies support the concept that modification of the fiber knob domain to diminish or ablate CAR interaction should result in a detargeted adenoviral vector that can be combined simultaneously with novel ligands for the development of a systemically administered, targeted adenoviral vector. 相似文献
130.
Four airport malaria cases have been observed in the vicinity of the Roissy-Charles-de-Gaulle International Airport, Paris, France. These cases were geographically very close to each other and clustered in a short period of time during the summer of 1999. The phenotype and genotype of the Plasmodium falciparum isolates obtained from these patients were determined in order to know whether a single mosquito could have infected more than one subject. The genomic characterisation of isolates was performed using the polymorphic markers merozoite surface protein 1 (Msp 1) and merozoite surface protein 2 (Msp 2) genes, the kappa and omega repeats domains of cg2 and the dihydrofolate reductase (DHFR) genotypes. Results showed identical genotypes for isolates 1, 2 and 4 whereas the genotype of isolate 3 differed at one locus. The molecular analysis was consistent with the hypothesis that all patients could have been bitten by the same mosquito and that patient 3, may have received a different clone and an additional species. In vitro susceptibility data did not confirm or rule out this hypothesis because isolates had the same profile of susceptibility to the tested drugs. 相似文献