Ribosomal protein mutations in Korean patients with Diamond-Blackfan anemia

Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome characterized by hypoproliferative anemia, associated physical malformations and a predisposition to cancer. DBA has been associated with mutations and deletions in the large and small ribosomal protein genes, and genetic aberrations have been detected in ∼50–60% of patients. In this study, nine Korean DBA patients were screened for mutations in eight known DBA genes (RPS19, RPS24, RPS17, RPS10, RPS26, RPL35A, RPL5 and RPL11) using the direct sequencing method. Mutations in RPS19, RPS26 and RPS17 were detected in four, two and one patient, respectively. Among the mutations detected in RPS19, two mutations were novel (c.26T>A, c.357-2A>G). For the mutation-negative cases, array-CGH analysis was performed to identify copy-number variations, and no deletions involving the known DBA gene regions were identified. The relative mRNA expression of RPS19 estimated using real-time quantitative PCR analysis revealed two- to fourfold reductions in RPS19 mRNA expression in three patients with RPS19 mutations, and p53 protein expression analysis by immunohistochemistry showed variable but significant nuclear staining in the DBA patients. In conclusion, heterozygous mutations in the known DBA genes RPS19, RPS26 and RPS17 were detected in seven out of nine Korean DBA patients. Among these patients, RPS19 was the most frequently mutated gene. In addition, decreased RPS19 mRNA expression and p53 overexpression were observed in the Korean DBA patients, which supports the hypothesis that haploinsufficiency and p53 hyperactivation represent a central pathway underlying the pathogenesis of DBA.     

血液透析联合血液灌流治疗急性肾功能衰竭的临床效果分析

目的分析急性肾功能衰竭采取血液透析联合血液灌流治疗的临床效果。方法选取2010年1月—2015年1月期间惠州市中医医院收治的24例急性肾功能衰竭患者作为研究对象,按治疗方法的不同将本组患者分为两组,对照组12例患者接受单纯血液透析治疗,观察组12例患者接受血液透析联合血液灌流治疗,治疗2个月后,对两组患者的临床指标及临床效果进行统计对比。结果观察组治疗后CRP、Cr、BUN、MMS指标优于对照组,差异有统计学意义(P0.05);观察组治疗有效率为91.67%(11/12),高于对照组75.00%(9/12),差异有统计学意义(P0.05)。结论对急性肾功能衰竭患者的治疗,采取血液透析联合血液灌流治疗的临床效果显著,促进患者康复,在临床中具有良好的应用价值。     

Protective Effect of Thymus serrulatus Essential Oil on Cadmium-Induced Nephrotoxicity in Rats,through Suppression of Oxidative Stress and Downregulation of NF-κB,iNOS, and Smad2 mRNA Expression

The purpose of the research was to examine the protective effect of essential oil from Thymus serrulatus Hochst. ex Benth. (TSA oil) against cadmium (Cd)-induced renal toxicity. The experimental protocol was designed using 30 healthy adult Wistar albino rats allocated into five groups containing six animals in each group. Group 1 was treated as normal control and groups 2, 3, 4, and 5 were treated with cadmium chloride (CdCl₂, 3 mg/kg, IP) for 7 days. Group 3 was also treated with silymarin (100 mg/kg, PO) as a standard group, while groups 4 and 5 were administered with TSA oil at doses of 100 and 200 mg/kg PO, respectively. The nephrotoxicity was measured with various parameters such as kidney function markers, oxidative stress markers (glutathione (GSH) and malondialdehyde (MDA)), and messenger ribonucleic acid (mRNA) expression levels of inflammatory factors. The histological studies were also evaluated in the experimental protocol. The CdCl₂-treated groups showed a significant increase in the levels of serum kidney function markers along with MDA levels in kidney homogenate. However, renal GSH level was found to be reduced significantly. It was found that CdCl₂ significantly upregulated the nuclear factor levels of kappaB (NF-κB p65), inducible nitric oxide synthase (iNOS), and small mothers against decapentaplegic (Smad2) as compared to the normal control group. On the other hand, TSA oil significantly improved the increased levels of serum kidney function markers, non-enzymatic antioxidants, and lipid peroxidation. In addition, TSA oil significantly downregulated the increased expression of NF-κB p65, iNOS, and Smad2 in Cd-intoxicated rats. Moreover, the histological changes in the tissue samples of the kidney of Cd-treated groups were significantly ameliorated in the silymarin- and TSA-oil-treated groups. The present study reveals that TSA oil ameliorates Cd-induced renal injury, and it is also proposed that the observed nephroprotective effect could be due to the antioxidant potential of TSA oil and healing due to its anti-inflammatory action.     

Screening disrupted molecular functions and pathways associated with clear cell renal cell carcinoma using Gibbs sampling

ObjectiveTo explore the disturbed molecular functions and pathways in clear cell renal cell carcinoma (ccRCC) using Gibbs sampling.MethodsGene expression data of ccRCC samples and adjacent non-tumor renal tissues were recruited from public available database. Then, molecular functions of expression changed genes in ccRCC were classed to Gene Ontology (GO) project, and these molecular functions were converted into Markov chains. Markov chain Monte Carlo (MCMC) algorithm was implemented to perform posterior inference and identify probability distributions of molecular functions in Gibbs sampling. Differentially expressed molecular functions were selected under posterior value more than 0.95, and genes with the appeared times in differentially expressed molecular functions ≥5 were defined as pivotal genes. Functional analysis was employed to explore the pathways of pivotal genes and their strongly co-regulated genes.ResultsIn this work, we obtained 396 molecular functions, and 13 of them were differentially expressed. Oxidoreductase activity showed the highest posterior value. Gene composition analysis identified 79 pivotal genes, and survival analysis indicated that these pivotal genes could be used as a strong independent predictor of poor prognosis in patients with ccRCC. Pathway analysis identified one pivotal pathway − oxidative phosphorylation.ConclusionsWe identified the differentially expressed molecular functions and pivotal pathway in ccRCC using Gibbs sampling. The results could be considered as potential signatures for early detection and therapy of ccRCC.     

Feasibility of similarity coefficient map for improving morphological evaluation of T2* weighted MRI for renal cancer

The purpose of this paper is to investigate the feasibility of using a similarity coefficient map(SCM) in improving the morphological evaluation of T2* weighted(T2*W) magnatic resonance imaging(MRI) for renal cancer.Simulation studies and in vivo 12-echo T2*W experiments for renal cancers were performed for this purpose.The results of the first simulation study suggest that an SCM can reveal small structures which are hard to distinguish from the background tissue in T2*W images and the corresponding T2* map.The capability of improving the morphological evaluation is likely due to the improvement in the signal-to-noise ratio(SNR) and the carrier-to-noise ratio(CNR) by using the SCM technique.Compared with T2* W images,an SCM can improve the SNR by a factor ranging from 1.87 to 2.47.Compared with T2* maps,an SCM can improve the SNR by a factor ranging from 3.85 to 33.31.Compared with T2*W images,an SCM can improve the CNR by a factor ranging from 2.09 to 2.43.Compared with T2* maps,an SCM can improve the CNR by a factor ranging from 1.94 to 8.14.For a given noise level,the improvements of the SNR and the CNR depend mainly on the original SNRs and CNRs in T2*W images,respectively.In vivo experiments confirmed the results of the first simulation study.The results of the second simulation study suggest that more echoes are used to generate the SCM,and higher SNRs and CNRs can be achieved in SCMs.In conclusion,an SCM can provide improved morphological evaluation of T2*W MR images for renal cancer by unveiling fine structures which are ambiguous or invisible in the corresponding T2*W MR images and T2* maps.Furthermore,in practical applications,for a fixed total sampling time,one should increase the number of echoes as much as possible to achieve SCMs with better SNRs and CNRs.     

Anti-tumor Effects of a Recombinant Fowlpox Virus Expressing Apoptin on Human Cervical Carcinoma in Vivo and in Vitro

Apoptin is a chicken anemia virus-derived,p53-independent,bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis of various human tumor cells,but not of normal diploid cells.To explore the application of apoptin in tumor gene therapy,we used a recombinant fowlpox virus expressing apoptin protein (vFV-Apoptin) to investigate the anti-tumor effectes of vFV-Apoptin on human cervical carcinoma(HeLa) cells in vivo and in vitro through 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetraz...     

Copper(II) Complexes of N-(Hydroxyethyl)Salicylideneimines

Abstract

Two groups of workers^1,2 have described the synthesis of Cu(sal:propanolamine). The compound is a dimer in chloroform and has a magnetic moment of 0.49 BM at room temperature.² There is no report in the literature on the synthesis of Cu(sal:ethanolamine). Apparently several groups have tried to synthesize the compound without success.^2,3 This communication describes the successful synthesis and characterization of Cu(sal:ethanolamine) and Cu(5-Br-sal:ethanolamine).     

Hepatorenal tyrosinemia

In 1957 Sakai and Kitagawa in Japan reported the clinical and biochemical findings in a patient with tyrosinemia, tyrosyluria, liver cirrhosis, and renal rickets. Subsequently, reports were published from various countries of other patients with hepatorenal tyrosinemia (HRT). 4-Hydroxyphenylpyruvate dioxygenase deficiency was originally proposed as the cause of HRT. However, in 1977 Lindblad et al. found that succinylacetone, which accumulates in the serum and urine from patients with HRT, inhibits delta-aminolevulinic acid (ALA) dehydratase in vitro. They suggested that the primary enzyme deficiency in patients with HRT was fumarylacetoacetate hydrolase, and this was soon confirmed. Thus, the elucidation of the pathogenesis of this disease has led to the possibility that, if a reliable newborn screening method could be developed, the prognosis of these patients would be improved. Early treatment would require a diet low in phenylalanine and tyrosine, administration of 2-(2-nitoro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), and liver transplantation.     

Hydrodynamics of viscous fluid through porous slit with linear absorption

The exact solutions for the viscous fluid through a porous slit with linear ab-sorption are obtained. The Stokes equation with non-homogeneous boundary conditions is solved to get the expressions for the velocity components, pressure distribution, wall shear stress, fractional absorption, and leakage flux. The volume flow rate and mean flow rate are found to be useful in obtaining a convenient form of the longitudinal velocity component and pressure difference. The points of the maximum velocity components for a fixed axial distance are identified. The value of the linear absorption parameter is ran-domly chosen, and the rest available data of the rat kidney to the tabulate pressure drop and fractional absorption are incorporated. The effects of the linear absorption, uniform absorption, and flow rate parameters on the flow properties are discussed by graphs. It is found that forward flow occurs only if the volume flux per unit width is greater than the absorption velocity throughout the length of the slit, otherwise back flow may occur. The leakage flux increases with the increase in the linear absorption parameter. Streamlines are drawn to help the analysis of the flow behaviors during the absorption of the fluid flow through the renal tubule and purification of blood through an artificial kidney.