No abstract available.
Percutaneous Coronary Intervention ; Tetrazoles ; Valine ; Ventricular Function, Left ; Valsartan

A 1-year-old female with maple syrup urine disease presenting with erythematous, partially eroded plaques on the trunk, anogenital area, and extremities experienced metabolic crisis. The skin lesions appeared at 11 months of age and was thought to result from amino acid imbalance secondary to erratic supplementation of specialized milk formula devoid of isoleucine, leucine, and valine. Serial urine monitoring showed persistent ketones and elevated serum leucine and valine. The patient was managed with emollients, intralipid 20%, and addition of isoleucine and valine supplements to counter the neurotoxic effect of leucine. After 8 days of proper feeding and continuous emollient application, the lesions improved and skin biopsy revealed superficial perivascular dermatitis. Although a decrease in erythema and desquamation was noted, the patient had persistent cerebral edema and continued to deteriorate.

BACKGROUND AND OBJECTIVES: Angiotensin-receptor blockers (ARBs) have beneficial effects on cardiovascular, metabolic, and inflammatory parameters in addition to controlling blood pressure (BP). However, few comparative clinical studies have been conducted with different ARBs. We compared these effects in patients with uncomplicated hypertension who were receiving telmisartan or valsartan. SUBJECTS AND METHODS: The subjects were patients with essential hypertension (48.4+/-9.6 years) who were randomly assigned to take either telmisartan (80 mg/day, n=30) or valsartan (160 mg/day, n=30) for 12 weeks. Their anthropometric, laboratory, vascular, and echocardiographic data were measured at baseline and at the end of the study. RESULTS: Baseline characteristics were not significantly different between the two groups, except for the carotid-femoral pulse wave velocity (cfPWV; telmisartan group vs. valsartan group; 841.2+/-131.0 vs. 761.1+/-104.4 cm/s, p<0.05). After 12 weeks, BP had fallen to a similar extent with mean reductions in the systolic and diastolic BP of 20.7+/-18.1 and 16.3+/-13.0 mm Hg (p<0.001, respectively) for the telmisartan and 22.5+/-17.0 and 16.8+/-9.3 mm Hg (p<0.001, respectively) for the valsartan group. Although the cfPWV and left ventricular mass index (LVMI) fell significantly only with the administration of telmisartan, they were not significantly different when baseline cfPWV was considered. The differences in the cfPWV and LVMI changes from baseline between the two groups were also not significant after adjusting for baseline cfPWV. No significant changes in other vascular, metabolic, or inflammatory parameters were observed with either treatment. CONCLUSION: The effects of a 12-week treatment with the two ARBs, telmisartan and valsartan, on cardiovascular, metabolic, and inflammatory parameters were not different in patients with uncomplicated hypertension.
Benzimidazoles ; Benzoates ; Blood Pressure ; Humans ; Hypertension ; Pulse Wave Analysis ; Tetrazoles ; Valine ; Valsartan

OBJECTIVES: Catechol-O-methyltransferase (COMT) gene has been identified as a positional and functional candidate gene of schizophrenia. Although specific mechanism of increasing schizophrenia susceptibility by this gene has not been well described yet, recent studies suggest that the valine allele of COMT Val158Met polymorphism may contribute to cognitive decline in schizophrenia. The present study investigated the association between this polymorphism of COMT gene and cognitive markers related to schizophrenia in both schizophrenia patients and normal controls. METHODS: The subjects were 78 patients with schizophrenia diagnosed by DSM-IV and 97 normal controls. Comprehensive neurocognitive tests for which performance deficits have been reported in schizophrenia were administered. Genotyping for COMT Val158Met polymorphism was done with SNapShot method. Association analyses between genotype and cognitive functions were performed using ANCOVA and MANCOVA. RESULTS: In the comparison of allele frequencies between patient and control groups, no significant association between the polymorphism and schizophrenia was observed. Significant differences of cognitive performance among genotype groups were not identified in control group. This trend was also observed in the patient group. In the combined analysis of both patient and control groups, there was no significant genotype or genotype-by group effect on any cognitive function measure. CONCLUSION: These findings do not support a major role of COMT gene in the regulation of the cognitive processes of schizophrenia.
Alleles ; Catechol O-Methyltransferase ; Cognition ; Diagnostic and Statistical Manual of Mental Disorders ; Gene Frequency ; Genotype ; Humans ; Schizophrenia ; Valine

PURPOSE: In spite of an extensive vaccination program, parvoviral infections still pose a major threat to the health of dogs. MATERIALS AND METHODS: We isolated a novel canine parvovirus (CPV) strain from a dog with enteritis. Nucleotide and amino acid sequence analysis of the isolate showed that it is a novel type 2b CPV with asparagine at the 426th position and valine at the 555th position in VP2. To develop a vaccine against CPV infection, we passaged the isolate 4 times in A72 cells. RESULTS: The attenuated isolate conferred complete protection against lethal homologous CPV infection in dogs such that they did not develop any clinical symptoms, and their antibody titers against CPV were significantly high at 7-11 days post infection. CONCLUSION: These results suggest that the virus isolate obtained after passaging can be developed as a novel vaccine against paroviral infection.
Animals ; Asparagine ; Dogs ; Enteritis ; Parvovirus, Canine ; Sequence Analysis, Protein ; Sprains and Strains ; Vaccination ; Vaccines ; Valine ; Viruses

BACKGROUND: ras gene mutations have been described in various human malignancies, suggesting that their activation may play a role in oncogenesis. However, there are few reports concerning ras gene alterations in malignant fibrous histiocytomas. We therefore designed a study to determine the prevalence and type of mutations in the first exons of H-ras and K-ras genes in these tumors. METHODS: Twenty-seven malignant fibrous histiocytomas were investigated by direct sequencing analysis with the automated DNA sequencing of polymerase chain reaction-amplified ras sequences. RESULTS: Twenty-four mutations were found in 18 (67%) of the tumors: GGC to GAC transition mutations at codon 13 of K-ras (coding for aspartic acid instead of glycine) in 18 of the samples and GGC to GTC transversions at codon 12 of H-ras (coding for valine instead of glycine) in six of the lesions. CONCLUSIONS: Our data suggest an involvement of the ras gene mutation in conjunction with other yet unknown events in the tumorigenesis and/or progression of malignant fibrous histiocytomas. The K-ras gene activation predominated in these tumors by a mutation at codon 13. It is noteworthy that H-ras mutations were detected only in association with the lesions containing K-ras mutated genes, the significance of which remains to be determined.
Aspartic Acid ; Carcinogenesis ; Codon ; Exons ; Genes, ras* ; Histiocytoma, Malignant Fibrous* ; Humans ; Prevalence ; Sequence Analysis, DNA ; Valine

BACKGROUND AND OBJECTIVES: Phenylthiocarbamide (PTC) and its chemically related compound,6-n-propylthiouracil (PROP), both produce a taste that is extremely bitter to some subjects (tasters) but tasteless or only slightly bitter to others (non-tasters). Earlier studies had used PTC, but most investigators have switched to PROP because of its several advantages. Recently, three single nucleotide polymorphisms in the TAS2R38 gene were identified and several studies have demonstrated a strong association between these genes with taster status. The aim of this study was to investigate the relationship between taste thresholds of PTC and PROP and their correlation with the TAS2R38 genotype. SUBJECTS AND METHOD: Seventy-five healthy normal volunteers were included. Taster status was determined using successive solutions of PTC and PROP, which comprised a total of 15 grades. All participants were genotyped for polymorphism of the TAS2R38 gene that affects taste sensitivity to PTC and PROP. RESULTS: PTC taste thresholds showed 96% correlation with the taste thresholds for PROP. Non-tasters defined by the PTC threshold test were the exactly the same with those identified as AVI (alanine, valine, isoleucine) homozygous, but taster status determined by the PROP threshold test showed 96% correlation with the genotypes. CONCLUSION: The PTC threshold test was more reliable for determining taste blindness than the PROP threshold test.
Ageusia ; Factor IX ; Genotype ; Humans ; Phenylthiourea ; Polymorphism, Single Nucleotide ; Research Personnel ; Taste Threshold ; Valine

BACKGROUND AND OBJECTIVES: A biallelic A/G polymorphism in the Monocyte chemotactic protein (MCP) -1 at position -2518 has been found to affect the level of MCP-1 expression. To investigate if these polymorphisms in chemokine ligand and receptor genes are relevant for the development of allergic rhinitis, we investigated polymorphisms of MCP-1 and CC chemokine receptor 2 (CCR2) known as the receptor of MCP-1. MATERIALS AND METHOD: Blood samples for genetic analysis were obtained from 198 individuals with allergic rhinitis and from 278 healthy subjects without atopic diseases. Polymerase chain reaction-based assay for MCP-1 -2518 A/G (A/G polymorphism in the MCP-1 at position -2518) and CCR2 V64I polymorphisms (replacement of valine by isoleucine in CCR2 64) was used for genotyping. RESULTS: There were no differences in the frequencies of the genotypes in the controls and patients (p>0.05). The frequencies of the MCP-1 G and CCR2 A alleles were not statistically different between controls and allergic rhinitis patients (p>0.05). The odds ratios (95% confidence interval) of MCP-1 G/G and CCR2 A/A genotypes for allergic rhinitis were not statistically significant, whereas, alleles frequencies of MCP-1 -2518G and CCR2 A of controls were various according to the ethnic background. CONCLUSION: Our result suggests MCP-1 -2518 A/G and CCR2 V64I polymorphisms are not part of the factors contributing to genetical susceptibility in the development of allergic rhinitis in Koreans.
Alleles ; Genetic Predisposition to Disease* ; Genotype ; Humans ; Isoleucine ; Korea ; Monocytes ; Odds Ratio ; Receptors, CCR2 ; Rhinitis* ; Valine

OBJECTIVETo determine the contents of L-enantiomer impurity in valaciclovir hydrochloride.

METHODSValaciclovir enantiomers were separated and determined by using chiral high performance liquid chromatography. Chromatographic conditions were as follows:CROWNPAK(®) CR(+) chiral column (4 mm×150 mm, 5 μm), detection wavelength:254 nm, mobile phase:water-methanol-perchloric acid (19:1:0.1), flow rate:0.75 ml/min, sample injection volume:10 μl.

RESULTSD-valaciclovir was completely separated from L-enantiomer impurity. The contents of L-enantiomer impurity were 0.65%-2.62% on average in 8 batches of valaciclovir hydrochloride.

CONCLUSIONEnantiomeric impurity contents in each batch of products were all meet criteria of United States Pharmacopeia, which can be used in criteria of Chinese Pharmacopeia as references.

OBJECTIVES: Multiple myeloma (MM) is a plasma cell malignancy occurring in middle and old age. MM is still an incurable disease due to its frequent recurrence and drug resistance. However, its pathogenesis is still unclear. Abnormal amino acid metabolism is one of the important characteristics of MM, and the important metabolic pathway of amino acids participates in protein synthesis as basic raw materials. Aminoacyl transfer ribonucleic acid synthetase (ARS) gene is a key regulatory gene in protein synthesis. This study aims to explore the molecular mechanism for ARS, a key factor of amino acid metabolism, in regulating amino acid metabolism in MM and affecting MM growth. METHODS: The corresponding gene number was combined with the gene expression profile GSE5900 dataset and GSE2658 dataset in Gene Expression Omnibus (GEO) database to standardize the gene expression data of ARS. GSEA_4.2.0 software was used to analyze the difference of gene enrichment between healthy donors (HD) and MM patients in GEO database. GraphPad Prism 7 was used to draw heat maps and perform data analysis. Kaplan-Meier and Cox regression model were used to analyze the expression of ARS gene and the prognosis of MM patients, respectively. Bone marrow samples from 7 newly diagnosed MM patients were collected, CD138⁺ and CD138^- cells were obtained by using CD138 antibody magnetic beads, and the expression of ARS in MM clinical samples was analyzed by real-time RT-PCR. Human B lymphocyte GM12878 cells and human MM cell lines ARP1, NCI-H929, OCI-MY5, U266, RPMI 8266, OPM-2, JJN-3, KMS11, MM1.s cells were selected as the study objects. The expression of ARS in MM cell lines was analyzed by real-time RT-PCR and Western blotting. Short hairpin RNA (shRNA) lentiviruses were used to construct gene knock-out plasmids (VARS-sh group). No-load plasmids (scramble group) and gene knock-out plasmids (VARS-sh group) were transfected into HEK 293T cells with for virus packaging, respectively. Stable expression cell lines were established by infecting ARP1 and OCI-MY5 cells, and the effects of knockout valyl-tRNA synthetase (VARS) gene on proliferation and apoptosis of MM cells were detected by cell counting and flow cytometry, respectively. GEO data were divided into a high expression group and a low expression group according to the expression of VARS. Bioinformatics analysis was performed to explore the downstream pathways affected by VARS. Gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) and high performance liquid chromatography (HPLC) were used to detect the valine content in CD138⁺ cells and ARP1, OCI-MY5 cells and supernatant of knockdown VARS gene in bone marrow samples from patients, respectively. RESULTS: Gene enrichment analysis showed that tRNA processing related genes were significantly enriched in MM compared with HD (P<0.0001). Further screening of tRNA processing-pathway related subsets revealed that cytoplasmic aminoacyl tRNA synthetase family genes were significantly enriched in MM (P<0.0001). The results of gene expression heat map showed that the ARS family genes except alanyl-tRNA synthetase (AARS), arginyl-tRNA synthetase (RARS), seryl-tRNA synthetase (SARS) in GEO data were highly expressed in MM (all P<0.01). With the development of monoclonal gammopathy of undetermined significance (MGUS) to MM, the gene expression level was increased gradually. Kaplan-Meier univariate analysis of survival results showed that there were significant differences in the prognosis of MM patients in methionyl-tRNA synthetase (MARS), asparaginyl-tRNA synthetase (NARS) and VARS between the high expression group and the low expression group (all P<0.05). Cox regression model multivariate analysis showed that the high expression of VARS was associated with abnormal overall survival time of MM (HR=1.83, 95% CI 1.10 to 3.06, P=0.021). The high expression of NARS (HR=0.90, 95% CI 0.34 to 2.38) and MARS (HR=1.59, 95% CI 0.73 to 3.50) had no effect on the overall survival time of MM patients (both P>0.05). Real-time RT-PCR and Western blotting showed that VARS, MARS and NARS were highly expressed in CD138⁺ MM cells and MM cell lines of clinical patients (all P<0.05). Cell counting and flow cytometry results showed that the proliferation of MM cells by knockout VARS was significantly inhibited (P<0.01), the proportion of apoptosis was significantly increased (P<0.05). Bioinformatics analysis showed that in addition to several pathways including the cell cycle regulated by VARS, the valine, leucine and isoleucine catabolic pathways were upregulated. Non-targeted metabolomics data showed reduced valine content in CD138⁺ tumor cells in MM patients compared to HD (P<0.05). HPLC results showed that compared with the scramble group, the intracellular and medium supernatant content of ARP1 cells and the medium supernatant of OCI-MY5 in the VARS-shRNA group was increased (all P<0.05). CONCLUSIONS MM patients with abnormal high expression of VARS have a poor prognosis. VARS promotes the malignant growth of MM cells by affecting the regulation of valine metabolism.
Humans ; Valine-tRNA Ligase ; Multiple Myeloma/genetics* ; Metabolomics ; Amino Acids ; RNA, Transfer