Association between copy number variation of complement component C4 and Graves' disease

<p>Abstract</p> <p>Background</p> <p>Gene copy number of complement component <it>C4</it>, which varies among individuals, may determine the intrinsic strength of the classical complement pathway. Presuming a major role of complement as an effecter in peptide-mediated inflammation and phagocytosis, we hypothesized that <it>C4 </it>genetic diversity may partially explain the development of Graves' disease (GD) and the variation in its outcomes.</p> <p>Methods</p> <p>A case-control study including 624 patients with GD and 160 healthy individuals were enrolled. CNV of <it>C4 </it>isotypes (<it>C4A </it>and <it>C4B</it>) genes were performed by quantitative real-time polymerase chain reaction analysis. Statistical comparison and identification of CNV of total <it>C4, C4 </it>isotypes (<it>C4A </it>and <it>C4B</it>) and <it>C4 </it>polymorphisms were estimated according to the occurrence of GD and its associated clinical features.</p> <p>Results</p> <p>Individuals with 4, 2, and 2 copies of <it>C4</it>, <it>C4A </it>and <it>C4B </it>genes, especially those with A2B2 polymorphism may associate with the development of GD (p = 0.001, OR = 10.994, 95% CI: 6.277-19.255; p = 0.008, OR = 1.732, 95% CI: 1.190-2.520; p = 2.420 × 10-5, OR = 2.621, 95% CI: 1.791-3.835; and <it>p </it>= 1.395 × 10^-4, OR = 2.671, 95% CI: 1.761-4.052, respectively). Although the distribution of copy number for total <it>C4</it>, <it>C4 </it>isotypes as well as <it>C4 </it>polymorphisms did not associate with the occurrence of goiter, nodular hyperplasia, GO and myxedema, <2 copies of <it>C4A </it>may associate with high risk toward vitiligo in patients with GD (<it>p </it>= 0.001, OR = 5.579, 95% CI: 1.659-18.763).</p> <p>Conclusions</p> <p>These results may be further estimated for its clinical application on GD and the vitiligo in patients with GD.</p

Nonsteroidal Anti-Inflammatory Drugs for Wounds: Pain Relief or Excessive Scar Formation?

The inflammatory process has direct effects on normal and abnormal wound healing. Hypertrophic scar formation is an aberrant form of wound healing and is an indication of an exaggerated function of fibroblasts and excess accumulation of extracellular matrix during wound healing. Two cytokines—transforming growth factor-β (TGF-β) and prostaglandin E2 (PGE2)—are lipid mediators of inflammation involving wound healing. Overproduction of TGF-β and suppression of PGE2 are found in excessive wound scarring compared with normal wound healing. Nonsteroidal anti-inflammatory drugs (NSAIDs) or their selective cyclooxygenase-2 (COX-2) inhibitors are frequently used as a pain-killer. However, both NSAIDs and COX-2 inhibitors inhibit PGE2 production, which might exacerbate excessive scar formation, especially when used during the later proliferative phase. Therefore, a balance between cytokines and medication in the pathogenesis of wound healing is needed. This report is a literature review pertaining to wound healing and is focused on TGF-β and PGE2

Genetic copy number variants in sib pairs both affected with schizophrenia

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is a complex disorder with involvement of multiple genes.</p> <p>Methods</p> <p>In this study, genome-wide screening for DNA copy-number variations (CNVs) was conducted for ten pairs, a total of 20 cases, of affected siblings using oligonucleotide array-based CGH.</p> <p>Results</p> <p>We found negative symptoms were significantly more severe (p < 0.05) in the subgroup that harbored more genetic imbalance (n ≧ 13, n = number of CNV-disrupted genes) as compared with the subgroup with fewer CNVs (n ≦ 6), indicating that the degree of genetic imbalance may influence the severity of the negative symptoms of schizophrenia. Four central nervous system (CNS) related genes including CCAAT/enhancer binding protein, delta (<it>CEBPD</it>, 8q11.21), retinoid × receptor, alpha (<it>RXRA</it>, 9q34.2), LIM homeobox protein 5 (<it>LHX5</it>, 12q24.13) and serine/threonine kinase 11 (<it>STK11</it>, 19p13.3) are recurrently (incidence ≧ 16.7%) disrupted by CNVs. Two genes, <it>PVR </it>(poliovirus receptor) and <it>BU678720</it>, are concordantly deleted in one and two, respectively, pairs of co-affected siblings. However, we did not find a significant association of this <it>BU678720 </it>deletion and schizophrenia in a large case-control sample.</p> <p>Conclusions</p> <p>We conclude that the high genetic loading of CNVs may be the underlying cause of negative symptoms of schizophrenia, and the CNS-related genes revealed by this study warrant further investigation.</p

Anti-Cancer Effects of Protein Extracts from Calvatia lilacina, Pleurotus ostreatus and Volvariella volvacea

Calvatia lilacina (CL), Pleurotus ostreatus (PO) and Volvariella volvacea (VV) are widely distributed worldwide and commonly eaten as mushrooms. In this study, cell viabilities were evaluated for a human colorectal adenocarcinoma cell line (SW480 cells) and a human monocytic leukemia cell line (THP-1 cells). Apoptotic mechanisms induced by the protein extracts of PO and VV were evaluated for SW480 cells. The viabilities of THP-1 and SW480 cells decreased in a concentration-dependent manner after 24 h of treatment with the protein extracts of CL, PO or VV. Apoptosis analysis revealed that the percentage of SW480 cells in the SubG1 phase (a marker of apoptosis) was increased upon PO and VV protein-extract treatments, indicating that oligonucleosomal DNA fragmentation existed concomitantly with cellular death. The PO and VV protein extracts induced reactive oxygen species (ROS) production, glutathione (GSH) depletion and mitochondrial transmembrane potential (ΔΨm) loss in SW480 cells. Pretreatment with N-acetylcysteine, GSH or cyclosporine A partially prevented the apoptosis induced by PO protein extracts, but not that induced by VV extracts, in SW480 cells. The protein extracts of CL, PO and VV exhibited therapeutic efficacy against human colorectal adenocarcinoma cells and human monocytic leukemia cells. The PO protein extracts induced apoptosis in SW480 cells partially through ROS production, GSH depletion and mitochondrial dysfunction. Therefore, the protein extracts of these mushrooms could be considered an important source of new anti-cancer drugs

Apoptosis induction in BEFV-infected Vero and MDBK cells through Src-dependent JNK activation regulates caspase-3 and mitochondria pathways

Our previous report demonstrated that bovine ephemeral fever virus (BEFV)-infected cultured cells could induce caspase-dependent apoptosis. This study aims to further elucidate how BEFV activates the caspase cascade in bovine cells. BEFV replicated and induced apoptosis in Vero and Madin-Darby bovine kidney (MDBK) cells, and a kinetic study showed a higher efficiency of replication and a greater apoptosis induction ability of BEFV in Vero cells. Src and c-Jun N-terminal kinase (JNK) inhibitor, but not extracellular signal-regulated kinase (ERK) or p38 inhibitor, alleviated BEFV-mediated cytopathic effect and apoptosis. In BEFV-infected Vero and MDBK cells, BEFV directly induced Src tyrosine-418 phosphorylation and JNK phosphorylation and kinase activity, which was inhibited specifically by SU6656 and SP600125, respectively. The caspase cascade and its downstream effectors, Poly (ADP-ribose) polymerase (PARP) and DFF45, were also activated simultaneously upon BEFV infection. In addition, cytochrome c, but not Smac/DIABLO, was released gradually from mitochondria after BEFV infection. SU6656 suppressed Src, JNK, and caspase-3 and -9 activation, as well as PARP and DFF45 cleavage; SP600125 reduced JNK and caspase-3 and -9 activation, as well as PARP and DFF45 cleavage. Taken together, these results strongly support the hypothesis that a Src-dependent JNK signaling pathway plays a key role in BEFV-induced apoptosis. The molecular mechanism identified in our study may provide useful information for the treatment of BEFV

The effect of adding a home program to weekly institutional-based therapy for children with undefined developmental delay: A pilot randomized clinical trial

AbstractBackgroundEarly rehabilitation for children with developmental delay without a defined etiology have included home and clinic programs, but no comparisons have been made and efficacy is uncertain. We compared a weekly visit for institutional-based therapy (IT) to IT plus a structured home activity program (HAP).MethodsSeventy children who were diagnosed with motor or global developmental delay (ages 6-48 months and mean developmental age 12.5 months) without defined etiology were recruited (including 45 males and 23 females). The outcomes included the comprehensive developmental inventory for infants and toddlers test and the pediatric evaluation of disability inventory.ResultsChildren who received only IT improved in developmental level by 2.11 months compared with 3.11 months for those who received a combination of IT and HAP (p = 0.000). On all domains of the comprehensive developmental inventory for infants and toddlers test, except for self-help, children who participated in HAP showed greater improvements, including in cognition (p = 0.015), language (p = 0.010), motor (p = 0.000), and social (p = 0.038) domains. Except on the subdomain of self-care with caregiver assistance, the HAP group showed greater improvement in all the pediatric evaluation of disability inventory subdomains (p < 0.05).ConclusionEarly intervention programs are helpful for these children, and the addition of structured home activity programs may augment the effects on developmental progression

A lack of association between genetic polymorphisms in beta-defensins and susceptibility of psoriasis in Taiwanese: A case–control study

AbstractBackgroundGenetic predisposition of the inflammatory-host response may affect the development of psoriasis. Previous studies have shown that copy number variations (CNVs) of β-defensin genes (DEFB) are associated with the susceptibility of psoriasis in Caucasian populations.ObjectivesThis study aimed to assess the role of the CNVs of the DEFB4 gene and functional variants in the DEFB1 gene in Taiwanese patients with psoriasis.MethodsIn total, 196 patients with psoriasis and 196 control individuals were analyzed for the presence of the DEFB4 CNVs using the paralogue ratio test, and also for the DEFB1 polymorphisms rs11362, rs1800972, and rs1799946, using a polymerase chain reaction.ResultsNone of the polymorphisms were found to be associated with psoriasis. The distribution of DEFB4 genomic CNVs did not significantly differ between the control group and psoriasis group. The frequencies of patients who carried a greater than the median (≥ 5) number of copies did not significantly differ in patients with psoriasis and controls. The multivariate analysis similarly revealed that the DEFB4 CNVs were not associated with psoriasis (odds ratio = 1.03, 95% confidence interval = 0.89–1.19, p = 0.720). No significant difference was detected in the genotype and allele distribution for any of the individual DEFB1 polymorphisms between the cases and the controls. Finally, the overall haplotype frequency profiles derived from the three polymorphisms did not significantly differ between the cases and the controls.ConclusionOur results do not suggest that these genetic variants of the β-defensin genes contribute to the genetic background of psoriasis in Taiwanese patients

Taiwanese Version of the EQ-5D: Validation in a Representative Sample of the Taiwanese Population

Background/PurposeWe know of no validated Taiwanese-language instrument to measure a utility of the patient's health. Our aim was to evaluate the reliability and validity of a Taiwanese version of the EuroQol instrument (EQ-5D) in a Taiwanese population.MethodsQuestionnaires containing the Taiwanese versions of the EQ-5D and the Short-Form 12 Health Survey (SF-12) were sent to 12,923 people in Taiwan in December 2002. Concurrent validity of the EQ-5D was analyzed by assuming that subjects with problems in any EQ-5D dimensions had decreased SF-12 scores. Discriminant validity of the EQ-5D was analyzed by assuming that subjects with the following characteristics had lowered EQ-5D indexes and scores on the EQ-5D visual analog scale (VAS): more chronic diseases than others, serious illness, more hospitalizations in the past year than others, poor general health, and more outpatient visits than others. Test—retest reliability was analyzed in a subgroup of respondents who were evaluated twice within a month by using the intraclass correlation coefficient and the k method.ResultsThe general survey response rate was 12.7% (1644 of 12,923). SF-12 scores were lower in subjects reporting problems on EQ-5D dimensions than in others without such problems (p < 0.01). Subjects with more health problems than others had lower EQ-5D indexes and VAS scores (p < 0.01). The physical dimension of the EQ-5D was more strongly correlated with the SF-12 Physical Component Summary than with the Mental Component Summary; this finding satisfied the a priori hypothesis. For test—retest reliability of items on the EQ-5D, k values ranged from 0.49 to 1 (p < 0.001).ConclusionThe Taiwanese EQ-5D instrument appears to be a moderately valid and reliable tool for measuring the health status of the general population in Taiwan

Social skills deficits and their association with Internet addiction and activities in adolescents with attention-deficit/hyperactivity disorder

The aims of this study were to examine the association between social skills deficits and Internet addiction and activities in adolescents with attention-deficit/hyperactivity disorder (ADHD) as well as the moderators for this association. Methods A total of 300 adolescents, aged between 11 and 18 years, who had been diagnosed with ADHD participated in this study. Their Internet addiction levels, social skills deficits, ADHD, parental characteristics, and comorbidities were assessed. The various Internet activities that the participants engaged in were also examined. Results The associations between social skills deficits and Internet addiction and activities and the moderators of these associations were examined using logistic regression analyses. Social skills deficits were significantly associated with an increased risk of Internet addiction after adjustment for the effects of other factors [odds ratio (OR) = 1.049, 95% confidence interval (CI) = 1.030–1.070]. Social skills deficits were also significantly associated with Internet gaming and watching movies. The maternal occupational socioeconomic levels of the participants moderated the association between social skills deficits and Internet addiction. Conclusions Social skills deficits should be considered targets in prevention and intervention programs for treating Internet addiction among adolescents with ADHD