Comparative pharmacokinetics of new curcumin preparations and evidence for increased bioavailability in healthy adult participants.

OBJECTIVE: Theracurmin, which contains the curcumin composition, CR-033P, has been demonstrated to be highly bioavailable. To compare the pharmacokinetics of the three compositions, CR-033P, CR-043P using modified starch as an alternative to the dispersant gum ghatti used in the CR-033P, and TS-P1 containing the newly developed amorphous curcumin, a randomized double-blind crossover study (3-way, 3-period) was conducted. MATERIALS AND METHODS: A single dose of the curcumin capsules (TS-P1 45 mg, CR-033P 90 mg, and CR-043P 90 mg) was administered to healthy adult participants. Blood sampling was performed 24 hours after capsule administration, and the plasma concentration of total curcumin was determined using high-performance liquid chromatography coupled with tandem mass spectrometry. RESULTS: TS-P1 and CR-043P tended to have a slightly lower area under the concentration time curve (AUC) 0-24h than CR-033P, while TS-P1 displayed bioequivalence to CR-043P. Further, TS-P1 displayed bioequivalence to CR-033P in terms of AUC0-12h, while that of CR-043P tended to be lower than that of CR-033P. TS-P1 had a higher AUC0-12h than CR-043P. A statistically significant difference (p < 0.001) was found between the preparations in terms of Cmax. TS-P1 tended to have a higher Cmax than CR-033P, CR-043P tended to have a slightly lower Cmax than CR-033P, and TS-P1 tended to have a higher Cmax than CR-043P. CONCLUSION: The newly developed TS-P1 composition seemed to display similar curcumin systemic exposure except for a higher plasma concentration than the CR-033P composition. Further, only a few significant differences were found between CR-043P and CR-033P.

Optimal lesion size index to prevent conduction gap during pulmonary vein isolation.

INTRODUCTION: A novel real-time lesion size index (LSI) that incorporates contact force (CF), time, and power has been developed for safe and effective catheter ablation. The optimal LSI was evaluated to eliminate gap formation during pulmonary vein isolation (PVI). METHODS AND RESULTS: Consecutive patients were enrolled, who underwent their first PVI using a fiber-optic CF-sensing catheter for atrial fibrillation between December 2016 and October 2017. The CF parameters, force-time integral (FTI), and LSI for 3095 ablation points in 34 patients were evaluated. The FTI and LSI in the lesions with gaps or dormant conduction (gaps/DC) were significantly lower than those in the lesion without gaps/DC (FTI: 140.5 ± 54.5 and 232.4 ± 121.4 g s, P < 0.0001; LSI: 4.0 ± 0.6 and 4.7 ± 0.9, P < 0.0001, respectively). On receiver operating characteristic curve analysis, the optimal LSI threshold was 4.05 (sensitivity, 63.4%; specificity, 76.3%). The LSI of <5.25 predicted a gap or DC with a high sensitivity (sensitivity, 97.6%; specificity, 25.7%). In the posterior wall, which was 37% thinner than the nonposterior wall, a lower LSI of <3.95 showed a relatively high sensitivity (92.3%) and specificity (65.6%). CONCLUSIONS: The LSI can be used to predict gaps/DC during the PVI procedure. An LSI of 5.2 may be a suitable target for effective lesion formation. An LSI of 4.0 may be acceptable in the posterior wall, especially in areas adjacent to the esophagus.

General anesthesia improves contact force and reduces gap formation in pulmonary vein isolation: a comparison with conscious sedation.

Compared to conscious sedation (CS), the use of general anesthesia (GA) in pulmonary vein isolation (PVI) is associated with a lower recurrence rate of atrial fibrillation (AF). GA may improve catheter stability and mapping system accuracy compared to CS, but its influence on contact force (CF) parameters during ipsilateral PVI has not previously been investigated. The study population comprised 176 consecutive patients (107 in GA group and 69 in CS group) with AF who underwent their first PVI procedure. We retrospectively assessed CF parameters, force-time integral (FTI), FTI/wall thickness during anatomical ipsilateral PVI and long-term outcome after ablation. Complete PVI with single continuous circular lesions around the ipsilateral PVs was achieved in 54 patients (50.5%) in the GA group but only 24 patients (34.8%) in the CS group (P = 0.04). The distribution of gaps did not differ between the groups. All CF parameters were significantly higher in the GA group than in the CS group (average CF: 19.4 ± 8.7 vs. 16.7 ± 7.7 g, P < 0.0001; FTI: 399.0 ± 262.5 vs. 293.9 ± 193.4 gs, P < 0.0001; FTI/wall thickness: 155.5 ± 106.1 vs. 115.7 ± 85.5 gs, P < 0.0001). GA was associated with lower AF recurrence rate in patients with paroxysmal AF but not with persistent AF. Compared with CS, GA improves CF parameters, FTI and FTI/wall thickness, and reduced gap formation after ipsilateral PVI.

Retinoid X receptor agonists modulate Foxp3⁺ regulatory T cell and Th17 cell differentiation with differential dependence on retinoic acid receptor activation.

Retinoic acid (RA) enhances TGF-ß-dependent differentiation of Foxp3(+) inducible regulatory T cells (iTregs) and inhibits Th17 differentiation by binding to the RA receptor (RAR)/retinoid X receptor (RXR) heterodimer. The major physiologic RA, all-trans-RA, binds to RAR but not to RXR at physiological concentrations. It remained unclear whether RXR-mediated stimulation affected the iTregs and Th17 differentiation. We found in this study that the RXR agonists, PA024 and tributyltin, augmented the ability of all-trans-RA or the RAR agonist Am80 to enhance CD4(+)CD25(-) T cells to acquire Foxp3 expression and suppressive function. However, they failed to enhance Foxp3 expression in the presence of the RAR antagonist LE540, suggesting that the effect depends on RAR-mediated signals. They exerted the effect largely by augmenting the ability of all-trans-RA to suppress the production of IL-4, IL-21, and IFN-γ that inhibited Foxp3 expression. Agonists of peroxisome proliferator-activated receptors and liver X receptors (LXRs), permissive partners of RXR, failed to enhance Foxp3 expression. In contrast, RXR agonists and LXR agonists suppressed IL-17 expression. The RXR-mediated suppression was not canceled by blocking RAR stimulation but was likely to involve permissive activation of LXRs. All-trans-RA and an agonist of RXR or LXR additively suppressed IL-17 expression when the all-trans-RA concentration was low. RXR agonists also suppressed Ccr6 expression that is essential for Th17 cells to enter the CNS. Accordingly, tributyltin treatment of mice ameliorated experimental autoimmune encephalomyelitis through regulating Th17 cell activities. These results suggest that RXR stimulation modulates Foxp3(+) iTreg and Th17 differentiation with differential dependence on RAR-mediated stimulation.

Loneliness Factors in Older People and the Influence on Attitudes Toward Informal Care: A Study of Older Chinese People in Urban Areas.

OBJECTIVES: Loneliness is thought to be more likely to occur in older people and influences their lives. This study aimed to verify the influence of loneliness in older Chinese people on their attitudes toward informal care, as well as the demographic, social, and economic factors that may cause loneliness. METHODS: Data was collected from older P (age: >60 years) using an online questionnaire. Hierarchical linear regression was used to analyze the associations between demographic, social, and economic factors, loneliness, and attitudes toward informal care. RESULTS: Results have shown that cohabitation and family savings could significantly negatively influence loneliness. Educational background and cohabitation could significantly positively influence attitudes toward informal care. However, loneliness could significantly negatively influence attitudes toward informal care. CONCLUSION: Older people living alone and with worse economic conditions may need attention from the community and society because they are more likely to suffer from loneliness. Loneliness may also significantly impact older people's attitudes toward long-term care. Older people are more likely to feel lonely may have more negative attitudes toward informal care. Communities need to make more efforts to improve community health services or formal care services for these older people to address situations where informal care is not sufficiently provided.

Helicobacter pylori Reinfection Diagnosed by Endoscopic and Histologic Recurrence in a Patient with Gastric Mucosa-Associated Lymphoid Tissue Lymphoma.

Helicobacter pylori infection is a major cause of gastric mucosa-associated lymphoid tissue (MALT) lymphoma. Successful H. pylori eradication can induce a complete remission (CR); however, it takes a long time. In this case, the recurrence of gastric MALT lymphoma was observed by endoscopic and histologic findings during a 11-year follow-up and due to H. pylori reinfection twice. After the first successful eradication and achieving histologic CR, the patient was starting to work at a nursing home for older adults, where she frequently came in contact with their vomitus or feces. In the examinations 2 years later after the first successful eradication, endoscopic and histologic findings have demonstrated deterioration. Similar findings were continuously observed in the examinations 3 months later, and H. pylori reinfection was confirmed by the rapid urease test. After the second successful eradication, endoscopic and histologic CR of gastric MALT lymphoma was achieved. However, endoscopic and histologic findings have shown deterioration again 1 year later after the histologic CR and at 3.5 years later after the second successful eradication. H. pylori reinfection was confirmed by the repeated urea breath test, and the patient had received the third eradication treatment; and the patient had achieved successful eradication. In addition, proper hygiene practices were advised to avoid H. pylori reinfection. H. pylori reinfection is very rare in adults after successful eradication in developed countries. After successful eradication and proper hygiene practice, endoscopic and histologic CR has been maintained for 2 years up to the present.

Continuous drainage for the treatment of gastric cancer with pericardial metastasis and cardiac tamponade: A case report.

Key Clinical Message: Signet-ring cell gastric carcinomas presenting as pericardial effusion early in diagnosis are rare and associated with high mortality and a poor prognosis. There are two interesting aspects of this case: primary gastric carcinoma presenting as cardiac tamponade and the metastatic behavior of gastric signet-ring cell carcinoma. Abstract: This report describes an 83-year-old man diagnosed to have cardiac tamponade due to massive pericardial effusion. A cytological analysis of the pericardial effusion disclosed adenocarcinoma. The patient was treated with continuous pericardial drainage and the amount of pericardial effusion decreased.

Efficient induction of CCR9 on T cells requires coactivation of retinoic acid receptors and retinoid X receptors (RXRs): exaggerated T Cell homing to the intestine by RXR activation with organotins.

The active vitamin A metabolite retinoic acid (RA) imprints gut-homing specificity on lymphocytes upon activation by inducing the expression of α4ß7 integrin and CCR9. RA receptor (RAR) activation is essential for their expression, whereas retinoid X receptor (RXR) activation is not essential for α4ß7 expression. However, it remains unclear whether RXR activation affects the RA-dependent CCR9 expression on T cells and their gut homing. The major physiological RA, all-trans-RA, binds to RAR but not to RXR at physiological concentrations. Cell-surface CCR9 expression was often induced on a limited population of murine naive CD4(+) T cells by all-trans-RA or the RAR agonist Am80 alone upon CD3/CD28-mediated activation in vitro, but it was markedly enhanced by adding the RXR agonist PA024 or the RXR-binding environmental chemicals tributyltin and triphenyltin. Accordingly, CD4(+) T cells treated with the combination of all-trans-RA and tributyltin migrated into the small intestine upon adoptive transfer much more efficiently than did those treated with all-trans-RA alone. Furthermore, naive TCR transgenic CD4(+) T cells transferred into wild-type recipients migrated into the small intestinal lamina propria following i.p. injection of Ag, and the migration was enhanced by i.p. injection of PA024. We also show that PA024 markedly enhanced the all-trans-RA-induced CCR9 expression on naturally occurring naive-like regulatory T cells upon activation, resulting in the expression of high levels of α4ß7, CCR9, and Foxp3. These results suggest that RXR activation enhances the RAR-dependent expression of CCR9 on T cells and their homing capacity to the small intestine.

Intramammary infection caused by Staphylococcus aureus increases IgA antibodies to iron-regulated surface determinant-A, -B, and -H in bovine milk.

The aim of this study was to identify virulence factors that have high immunogenicity. An in vivo-expressed Staphylococcus aureus antigen was identified by probing bacteriophage expression libraries of S. aureus with antibodies in bovine mastitis milk. Eighteen clones were isolated, and their proteins were identified as 5 characterised proteins (IsdA, Protein A, IsdB, autolysin, and imidazole glycerol phosphate dehydratase) and 13 hypothetical proteins. We focused on IsdA, IsdB, and IsdH as virulence factors that have a high immunogenicity and are capable of inducing a specific humoral immune response in S. aureus-infected quarters. The optical density (OD) values of IsdA and IsdB IgA and IgG antibodies in milk affected by naturally occurring mastitis caused by S. aureus increased significantly compared to those in healthy milk. In the experimental infection study, the OD values of IsdA- and B-specific IgA and IgG antibodies were significantly increased from 2 to 4 weeks after S. aureus infection compared to day 0 (P < 0.05). On the other hand, we demonstrated that milk from natural and experimental intramammary infections caused by S. aureus are associated with significantly higher IgA levels against IsdH (P < 0.05), but no significant change in IgG levels. Our findings facilitated our understanding of the pathogenicity of S. aureus in bovine mastitis, as well as the mechanisms by which specific humoral immune responses to S. aureus infection are induced. In addition, the results obtained could provide insight into how bovine mastitis can be controlled, for example, through vaccination.

Expression of Grainyhead-like 2 in the Process of Ductal Development of Mouse Mammary Gland.

Grainyhead-like 2 (Grhl2) is a transcription factor regulating cell adhesion genes. Grhl2 acts as an epithelial-mesenchymal transition suppressor, and it is a proto-oncogene involved in estrogen-stimulated breast cancer proliferation. However, its expression during ovarian hormone-dependent mammary ductal development remains obscure. We here examined Grhl2 expression in the mammary gland of normal and steroid-replaced ovariectomized mice. Grhl2 protein signals were detected in both the mammary luminal epithelial and myoepithelial nuclei. The ratio and density of Grhl2-positive nuclei increased after the onset of puberty and progressed with age, whereas Grhl2-negative epithelial cells were detected in mature ducts. Claudin 3, claudin 4, claudin 7, and E-cadherin gene expression in the mammary gland was upregulated, and their expression was highly correlated with Grhl2 gene expression. Furthermore, Grhl2 mRNA expression and ductal lumen width were significantly increased by the combined treatment of estrogen and progesterone compared with estrogen alone. These results suggest that Grhl2 expressed in the luminal epithelial and myoepithelial cells from the early phase of ductal development, controlling the expression of cell adhesion molecules to establish functional ducts.

Evaluating the usefulness of breast strain elastography for intraductal lesions.

PURPOSE: Strain elastography for imaging lesion stiffness is being used as a diagnostic aid in the malignant/benign discrimination of breast diseases. While acquiring elastography in addition to B-mode images has been reported to help avoid performing unnecessary biopsies, intraductal lesions are difficult to discriminate whether they are malignant or benign using elastography. An objective evaluation of strain in lesions was performed in this study by measuring the elasticity index (E-index) and elasticity ratio (E-ratio) of lesions as semi-quantitative numerical indicators of the color distribution of strain. We examined whether ductal carcinoma in situ (DCIS) and intraductal papilloma could be distinguished using these semi-quantitative numerical indicators. METHODS: In this study, 170 ultrasonographically detected mass lesions in 162 cases (106 malignant lesions and 64 benign lesions)-in which tissue biopsy by core needle biopsy and vacuum-assisted biopsy, or surgically performed histopathological diagnosis, was performed-were selected as subjects from among 1978 consecutive cases (from January 2014 to December 2016) in which strain elastography images were acquired, in addition to standard B-mode breast ultrasonography, by measuring the E-index and E-ratio. RESULTS: The cut-off values for E-index and E-ratio in the malignant/benign discrimination of breast lesions were determined to be optimal values at 3.5 and 4.2, respectively, based on receiver operating characteristic (ROC) curve analysis. E-index sensitivity, specificity, accuracy, and AUC value (area under the curve) were 85%, 86%, 85%, and 0.860, respectively, while those for E-ratio were 78%, 74%, 74%, and 0.780, respectively. E-index yielded superior results in all aspects of sensitivity, specificity, accuracy, and AUC values, compared to those of E-ratio. The mean E-index values for malignant tumors and benign tumors were 4.46 and 2.63, respectively, indicating a significant difference (P < 0.001). E-index values of 24 DCIS lesions and 25 intraductal papillomas were 3.88 and 3.35, respectively, which showed a considerably close value, while the false-negative rate for DCIS was 29.2%, and the false-positive rate for intraductal papilloma was as high as 32.0%. CONCLUSION: E-index in strain elastography yielded better results than E-ratio in the malignant/benign discrimination of breast diseases. On the other hand, E-index has a high false-negative rate and false-positive rate for intraductal lesions, a factor which should be taken into account when making ultrasound diagnoses.

GM-CSF and IL-4 synergistically trigger dendritic cells to acquire retinoic acid-producing capacity.

Retinoic acid (RA) produced by intestinal dendritic cells (DCs) imprints gut-homing specificity on lymphocytes and enhances Foxp3(+) regulatory T-cell differentiation. The expression of aldehyde dehydrogenase (ALDH) 1A in these DCs is essential for the RA production. However, it remains unclear how the steady-state ALDH1A expression is induced under specific pathogen-free (SPF) conditions. Here, we found that bone marrow-derived dendritic cells (BM-DCs) generated with granulocyte-macrophage colony-stimulating factor (GM-CSF) expressed Aldh1a2, an isoform of Aldh1a, but that fms-related tyrosine kinase 3 ligand-generated BM-DCs did not. DCs from mesenteric lymph nodes (MLN) and Peyer's patches (PP) of normal SPF mice expressed ALDH1A2, but not the other known RA-producing enzymes. Employing a flow cytometric method, we detected ALDH activities in 10-30% of PP-DCs and MLN-DCs. They were CD11c(high)CD4(-/low)CD8alpha(intermediate)CD11b(-/low) F4/80(low/intermediate)CD45RB(low)CD86(high)MHC class II(high)B220(-)CD103(+). Equivalent levels of aldehyde dehydrogenase activity (ALDHact) and ALDH1A2 expression were induced synergistically by GM-CSF and IL-4 in splenic DCs in vitro. In BM-DCs, however, additional signals via Toll-like receptors or RA receptors were required for inducing the equivalent levels. The generated ALDH1A2(+) DCs triggered T cells to express gut-homing receptors or Foxp3. GM-CSF receptor-deficient or vitamin A-deficient mice exhibited marked reductions in the ALDHact in intestinal DCs and the T cell number in the intestinal lamina propria, whereas IL-4 receptor-mediated signals were dispensable. GM-CSF(+)CD11c(-)F4/80(+) cells existed constitutively in the intestinal tissues. The results suggest that GM-CSF and RA itself are pivotal among multiple microenvironment factors that enable intestinal DCs to produce RA.

Comparison of monoclonal antibody-based stool antigen tests to determine the results of Helicobacter pylori eradication therapy.

OBJECTIVE: Stool antigen tests using monoclonal antibody are used to test the results of eradication therapy of Helicobacter pylori. A newly developed test using multiple monoclonal antibodies is considered to have higher sensitivity. The aim of this study was to examine whether monoclonal antibody-based stool antigen tests are equally applicable to determine the results of eradication therapy. MATERIALS AND METHODS: Stool specimens obtained from patients infected with H. pylori were diluted by human stool and tested by both Testmate pylori antigen enzyme immunoassay (TPAg EIA) and Premier Platinum HpSA PLUS (HpSA ELISA II). A total of 239 patients infected with H. pylori received eradication therapy and 5-8 weeks after finishing the treatment, stool samples were tested by TPAg EIA and HpSA ELISA II. On the same day of stool collection, all the patients received (13)C-urea breath test (UBT). RESULTS: After 5× dilution, optical density (OD) values of TPAg EIA were significantly reduced and three out of four stool specimens were tested negative after 10× dilution. By contrast, three specimens were tested positive even after 100× dilution by HpSA ELISA II. In the determination of eradication therapy, accordance between the two tests was 95.8%. Among 199 patients who tested negative by both stool antigen tests, 10 patients were positive by UBT. Overall accordance of TPAg EIA and HPSA ELISA II to UBT was 91.2% and 95.4%, respectively (NS). CONCLUSIONS: Although reduction of OD values was seen in TPAg EIA, it did not seem to cause false negative results in stool samples after eradication therapy. Both TPAg EIA and HpSA ELISA II were equally useful to determine the results of eradication therapy comparing with UBT.

Author Correction: A spatial similarity of stereochemical environments formed by amino acid residues defines a common epitope of two non-homologous proteins.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Applicability of a monoclonal antibody-based stool antigen test to evaluate the results of Helicobacter pylori eradication therapy.

The (13)C-urea breath test (UBT) is widely used to examine the results of eradication therapy for Helicobacter pylori. We examined whether a stool antigen test can be used as efficiently as UBT. (i) Ninety-four patients infected with H. pylori underwent eradication therapy. Six or eight weeks after the completion of treatment, the results were evaluated by UBT and a stool antigen test (TPAg). In 77 out of 78 patients who had negative UBT results, the TPAg results were also negative. Among the 16 UBT-positive patients, 12 were also positive by TPAg. Agreement of UBT and TPAg was 94.7%. (ii) Twenty-two patients with peptic ulcers in the active stage also received eradication therapy followed by proton pump inhibitor (PPI) administration. TPAg and UBT were performed to examine the results of eradication therapy at the end of PPI administration and at least 7 days after its discontinuation. Of the 22 patients taking PPIs, TPAg evaluated the results of eradication therapy accurately in 21 patients. TPAg appears to be an accurate test for evaluating the results of H. pylori eradication therapy, and to be as efficient as (13)C-UBT. Use of the stool antigen test should be considered as an alternative, particularly in patients who have to take PPIs in order to avoid the risk of peptic ulcers.

A spatial similarity of stereochemical environments formed by amino acid residues defines a common epitope of two non-homologous proteins.

It is critical for development of high-quality antibodies in research and diagnostics to predict accurately their cross-reactivities with "off-target" molecules, which potentially induce false results. Herein, we report a good example of such a cross-reactivity for an off-target due to a stereochemical environment of epitopes, which does not simply depend on amino acid sequences. We found that significant subpopulation of a polyclonal peptide antibody against Bcnt (Bucentaur) (anti-BCNT-C antibody) cross-reacted with a completely different protein, glutamine synthetase (GS), and identified four amino acids, GYFE, in its C-terminal region as the core amino acids for the cross-reaction. Consistent with this finding, the anti-BCNT-C antibody strongly recognized endogenously and exogenously expressed GS in tissues and cultured cells by Western blotting and immunohistochemistry. Furthermore, we elucidated that the cross-reaction is caused by a spatial similarity between the stereochemical environments formed by amino acid residues, including the GYFE of GS and the GYIE of Bcnt, rather than by their primary sequences. These results suggest it is critical to comprehensively analyze antibody interactions with target molecules including off-targets with special attention to the physicochemical environments of epitope-paratope interfaces to decrease the risk of false interpretations of results using antibodies in science and clinical applications.

No association between the ryanodine receptor 3 gene and autism in a Japanese population.

AIM: Autism is a neurodevelopmental disorder with a complex genetic etiology. Chromosome 15q11-q14 has been proposed to harbor a gene for autism susceptibility because deletion of the region leads to Prader-Willi syndrome or Angelman syndrome, having phenotypic overlap with autism. Here we studied the association between autism and the ryanodine receptor 3 (RyR3) gene, which is located in the region. This is the first study, to our knowledge, that has investigated the association. METHODS: We genotyped 14 tag single nucleotide polymorphisms (SNPs) in 166 Japanese patients with autism and 375 controls. RESULTS: No significant difference was observed between the patients and controls in allelic frequencies or genotypic distributions of the 14 SNPs. Analysis after confining the subjects to males showed similar results. CONCLUSIONS: The present study provides no positive evidence for the association between the RyR3 gene and autism in the Japanese population.

Association study of the 15q11-q13 maternal expression domain in Japanese autistic patients.

Chromosome 15q11-q13 has been a focus of genetic studies of autism susceptibility, because cytogenetic abnormalities are frequently observed in this region in autistic patients. An imprinted, maternally expressed gene within the region may have a role in autistic symptomatology. In the present study, we investigated the association between autism and the maternal expression domain (MED) in the region, containing the UBE3A and ATP10C genes, and the upstream imprinting center (IC), which mediates coordinate control of imprinted expression throughout the region. We analyzed 41 single nucleotide polymorphisms (SNPs) in 166 patients with autism and 416 controls from a Japanese population. As a result, a statistically significant difference after correction for multiple testing was observed between the patients and controls in the genotypic distribution of SNP rs7164989 (SNP8 in this study) located in SNRPN, whose promoter corresponds to the IC (P = 0.018, corrected for multiple testing). In the analysis of a four-marker haplotype located in ATP10C, a statistically significant difference after correction for multiple testing was observed in the frequency of one haplotype between male patients and controls (permutation P = 0.033, corrected for multiple testing). Thus, the present study may suggest the association between autism and the MED or the upstream IC in chromosome 15q11-q13 in the Japanese population.

No association between the CNTF null mutation and schizophrenia or personality.

The ciliary neurotrophic factor (CNTF) is a neurotrophic cytokine that plays a critical role in neurodevelopment. On the basis of neurodevelopmental hypothesis, the CNTF gene has been a candidate locus for schizophrenia. Several studies have investigated the association between the null mutation of the gene and schizophrenia, however, with inconsistent results. In the present study, we investigated the association in 222 Japanese patients with schizophrenia and 237 controls. The association between the mutation and personality traits was also studied, to investigate the effect of the mutation in participants from the general population. As a result, no association was observed between the mutation and schizophrenia nor personality traits, evaluated by using the Revised NEO Personality Inventory scores. The present study did not provide evidence for the association between the CNTF gene and schizophrenia or personality traits in the Japanese population.