Background:Reports on the aquaporin-4 immunoglobulin G (AQP4-IgG) status for cognitive performance and neuroimaging correlations are limited in neuromyelitis optica (NMO) and multiple sclerosis (MS) literature. Methods: Cognitive results of 19 MS and 15 NMO patients were compared with 47 agematched controls. Apparent diffusion coeffi cient (ADC) values were used to delineate gray matter and white matter damages and correlate with neuropsychological results. Results: Verbal memory test showed signifi cant differences between MS and NMO in the late registration, early and delay recall (p<0.05), while their retention rates were even. In MS, ADC values were signifi cantly elevated in the dorsolateral prefrontal and occipital gray matter which was in contrast with NMO group that showed elevation in the dorsolateral prefrontal gray matter and parieto-occcipital white matter. AQP4-IgG status exerted a limited effect on ADC values and neuropsychological results. Conclusions: Verbal memory test might be helpful in differentiating NMO and MS. ADC values can be used as a surrogate marker for tissue injury in NMO and MS since they were in line with the cognition scores. Anatomical regions with elevated ADC values were different in NMO and MS.

Background: Compared with the Western population, central demyelinating disorders are relatively rare while the data on the prognostic value of autoantibodies together with clinical characteristics and cognitive dysfunction has rarely been explored in neuromyelitis optica (NMO) and multiple sclerosis (MS). Methods: Nineteen patients with MS and 14 with NMO underwent clinical profiling and cognitive assessment. According to serology tests, they are divided into four subgroups for further analysis. Results: There was higher frequency of aquaporin-4 immunoglobulin G. sero-positivity (64.3% vs. 10.5%; p=0.003) and antinuclear antibodies (ANA) and/or antibodies to extractable nuclear antigens (anti-ENA) in NMO compared to MS (42.9% vs. 5.2%; p=0.026). The presence of anti-ENA represented a unique clinical phenotype, with longer segment of myelitis (p=0.049), female preponderance, and an inverse correlation between age-of-onset and annual relapse rate (ρ= -0.88, p=0.021). Among patients with anti-ENA positivity, comprehensive serology panels revealed Sjögren’s syndrome A antibodies as the most common (83%), in contrast to limited clinical documentation of Sjögren’s syndrome (16%). There was no significant difference in cognitive assessment by anti-ENA status. MS and NMO represent two different serologic entities. Conclusions: Anti-ENA may have prognostic value for its linkage to a unique clinical phenotype, which has longer initial segment of myelitis, female preponderance, and higher annual relapse rate on earlier age-of-onset, but has limited clinical impact on cognition. Further studies are warranted to investigate whether anti-ENA represents an epiphenomenon of myelitis or simply a systemic inflammatory state.

Purpose: Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized. Methods: Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection. Results: Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20. Conclusion Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.

Purpose: Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized. Methods: Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection. Results: Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20. Conclusion Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.

Purpose: Zinc finger protein 639 (ZNF639) is often found within the overlapping amplicon of PIK3CA, and previous studies suggest its involvement in the pathogenesis of esophageal and oral squamous cell carcinomas. However, its expression and significance in breast cancer remain uncharacterized. Methods: Immunohistochemical analysis of ZNF639 was performed using tissue microarrays.Functional studies, including colony formation, Transwell cell migration, and in vivo metastasis, were conducted on breast tumor cells with ZNF639 knockdown via small interfering RNA transfection. Results: Reduced ZNF639 immunoreactivity was observed in 82% of the breast cancer samples, independent of hormone receptor and human epidermal growth factor receptor 2 status. In multivariate Cox regression analyses, ZNF639 expression was associated with favorable survival outcomes, including recurrence-free survival (hazard ratio, 0.35; 95% confidence interval [CI], 0.14–0.89) and overall survival (hazard ratio, 0.41; 95% CI, 0.16– 1.05). ZNF639 knockdown increased clonogenicity, cell motility, and lung metastasis in NOD/ SCID mice. Following the ZNF639 knockdown, the expression of Snail1, vimentin, and C-C chemokine ligand 20 (CCL20) was upregulated, and the changes in cell phenotype mediated by ZNF639 were reversed by the subsequent knockdown of CCL20. Conclusion Low ZNF639 expression is a novel prognostic factor for recurrence-free survival in patients with breast cancer.

BACKGROUND/AIMS: Hematological abnormalities during hepatitis C virus (HCV) combination therapy with pegylated interferon alpha and ribavirin often necessitate dose reduction. Variants of the ITPA gene have been reported to protect against anemia during the early stages of HCV combination treatments but have also been associated with larger decreases in platelet counts. We aimed to identify the association between specific ITPA gene polymorphisms and hematological abnormalities in patients undergoing HCV combination therapy. METHODS: In this retrospective study, 175 patients treated with HCV combination therapy were enrolled at St. Martin De Porres Hospital in Taiwan between 2006 and 2012. Two single nucleotide polymorphisms (SNP) within or adjacent to the ITPA gene (rs1127354, rs6051702) were genotyped. We investigated the effect of ITPA gene variants on hematological abnormalities during the therapy. RESULTS: The ITPA rs1127354 minor variants were significantly associated with protection against anemia at week 4 (p=1.86 x 10(-6)) and with more severe decreases in platelet counts during HCV combination therapy. SNP rs6051702 was not associated with the hemoglobin decline to >3 g/dL at week 4 in our study (p=0.055). CONCLUSIONS: The ITPA SNP rs1127354 is a useful predictor of ribavirin-induced anemia in Taiwanese patients and may be related to more severe decreases in platelet counts during the early stage of HCV combination therapy.
Adult ; Aged ; Anemia/chemically induced/genetics ; Antiviral Agents/*adverse effects ; Cross-Sectional Studies ; Drug Therapy, Combination/adverse effects ; Female ; Hematologic Diseases/*chemically induced/genetics ; Hepacivirus ; Hepatitis C/*drug therapy ; Humans ; Interferon-alpha/adverse effects ; Male ; Middle Aged ; *Polymorphism, Single Nucleotide ; Pyrophosphatases/*genetics ; Retrospective Studies ; Ribavirin/adverse effects ; Taiwan ; Thrombocytopenia/chemically induced/genetics

BACKGROUND/AIMS: Hematological abnormalities during hepatitis C virus (HCV) combination therapy with pegylated interferon alpha and ribavirin often necessitate dose reduction. Variants of the ITPA gene have been reported to protect against anemia during the early stages of HCV combination treatments but have also been associated with larger decreases in platelet counts. We aimed to identify the association between specific ITPA gene polymorphisms and hematological abnormalities in patients undergoing HCV combination therapy. METHODS: In this retrospective study, 175 patients treated with HCV combination therapy were enrolled at St. Martin De Porres Hospital in Taiwan between 2006 and 2012. Two single nucleotide polymorphisms (SNP) within or adjacent to the ITPA gene (rs1127354, rs6051702) were genotyped. We investigated the effect of ITPA gene variants on hematological abnormalities during the therapy. RESULTS: The ITPA rs1127354 minor variants were significantly associated with protection against anemia at week 4 (p=1.86 x 10(-6)) and with more severe decreases in platelet counts during HCV combination therapy. SNP rs6051702 was not associated with the hemoglobin decline to >3 g/dL at week 4 in our study (p=0.055). CONCLUSIONS: The ITPA SNP rs1127354 is a useful predictor of ribavirin-induced anemia in Taiwanese patients and may be related to more severe decreases in platelet counts during the early stage of HCV combination therapy.
Adult ; Aged ; Anemia/chemically induced/genetics ; Antiviral Agents/*adverse effects ; Cross-Sectional Studies ; Drug Therapy, Combination/adverse effects ; Female ; Hematologic Diseases/*chemically induced/genetics ; Hepacivirus ; Hepatitis C/*drug therapy ; Humans ; Interferon-alpha/adverse effects ; Male ; Middle Aged ; *Polymorphism, Single Nucleotide ; Pyrophosphatases/*genetics ; Retrospective Studies ; Ribavirin/adverse effects ; Taiwan ; Thrombocytopenia/chemically induced/genetics

PURPOSE: Cancer cells develop acquired resistance induced by chemotherapeutic drugs. In this study, we investigated the effects of brief treatment with cytotoxic drugs on the phenotype of breast cancer cells. METHODS: Breast cancer cells MCF7 and BT-474 were briefly treated with paclitaxel or doxorubicin. Clonogenic, migration, and invasion assays were performed on the treated cells. Western blot analysis and RhoA activity assay were also performed. RESULTS: Breast cancer cells when briefly treated with paclitaxel or doxorubicin showed reduced clonogenic ability. Doxorubicin, but not paclitaxel, augmented cell migration and invasion. The invasion-promoting effects of doxorubicin were lost when the two drugs were sequentially used in combination. Myosin light chain (MLC) 2 phosphorylation and RhoA activity were upregulated by doxorubicin and downregulated by paclitaxel. Pretreatment with RhoA inhibitors abolished the migration- and invasion-promoting effects of doxorubicin. CONCLUSION: Doxorubicin activates the RhoA/MLC pathway and enhances breast cancer cell migration and invasion. Therefore, this pathway might be explored as a therapeutic target to suppress anthracycline-enhanced tumor progression.
Blotting, Western ; Breast Neoplasms ; Breast ; Cell Movement ; Doxorubicin ; Myosin Light Chains ; Paclitaxel ; Phenotype ; Phosphorylation ; Up-Regulation

This study evaluated the value of procalcitonin (PCT) levels in pleural effusion to differentiate the etiology of parapneumonic effusion (PPE). Forty-one consecutive PPE patients were enrolled and were divided into bacterial and non-bacterial PPE. Blood and pleural effusion samples were collected for PCT measurement on admission and analyzed for diagnostic evaluation. PCT of pleural fluid was significantly increased in the bacterial PPE group (0.24 ng/mL) compared to the non-bacterial PPE group (0.09 ng/mL), but there was no significant difference for serum PCT. A PCT concentration of pleural fluid >0.174 ng/mL (best cut-off value) was considered positive for a diagnosis of bacterial PPE (sensitivity, 80%; specificity, 76%; AUC, 0.84). Pleural effusion PCT in the bacterial PPE is significantly different from those of the non-bacterial PPE and control groups, so the diagnostic use of PCT still warrants further investigation.
Aged ; Bacterial Infections/*diagnosis ; Calcitonin/*analysis/blood ; Diagnosis, Differential ; Female ; Humans ; Male ; Middle Aged ; Pleural Effusion/*diagnosis ; Pneumonia/*diagnosis ; Predictive Value of Tests ; Protein Precursors/*analysis/blood ; ROC Curve

AIMTo complete comprehensive haplotype analysis of USP26 for both fertile and infertile men.

METHODSTwo hundred infertile men with severe oligospermia or non-obstructive azoospermia were subjected to sequence analysis for the entire coding sequences of the USP26 gene. Two hundred men with proven fertility were genotyped by primer extension methods. Allele/genotype frequencies, linkage disequilibrium (LD) characteristics and haplotypes of fertile men were compared with infertile men.

RESULTSThe allele frequencies of five single nucleotide polymorphisms (370-371insACA, 494T>C, 576G>A, ss6202791C>T, 1737G>A) were significantly higher in infertile patients than control subjects. The major haplotypes in infertile men were TACCGA (28% of the population), TGCCGA (15%), TACCAA (8%), TGCCAA (6%), TATCAA (5%) and CATCAA (5%). The major haplotypes for the control subjects were TACCGA (58% of the population), CACCGA (7%), CATCGA (6%) and TGCCGA (5%). Haplotypes TGCCGA, TATCAA, CATCAA, CATCGC, TACCAA and TGCCAA were over-transmitted in patients with spermatogenic defect, whereas haplotypes TACCGA, CACCGA, and CATCGA were under-transmitted in these patients.

CONCLUSIONSome USP26 alleles and haplotypes are associated with spermatogenic defect in the Han nationality in Taiwan, China.

Adult ; Alleles ; Azoospermia ; epidemiology ; genetics ; Cysteine Endopeptidases ; genetics ; DNA Primers ; Gene Frequency ; Genetic Variation ; Genotype ; Haplotypes ; Humans ; Infertility, Male ; epidemiology ; genetics ; Linkage Disequilibrium ; Male ; Multigene Family ; Oligospermia ; epidemiology ; genetics ; Polymorphism, Genetic ; Spermatogenesis ; genetics ; physiology ; Taiwan ; epidemiology