C-reactive protein levels are associated with cerebral small vessel-related lesions.

OBJECTIVE: Inflammation has received increasing attention as a cause of stroke. Although several lines of evidence suggest that inflammatory processes have a role in arteriosclerotic vascular events, their involvement remains to be determined. The purpose of this study was to examine the associations between serum high-sensitive C-reactive protein (hs-CRP) levels and cerebral small vessel (CSV)-related lesions as a manifestation of arteriosclerosis. MATERIALS AND METHODS: Neurologically normal subjects without any history of neurologic or psychiatric diseases were enrolled (n = 519). All the participants underwent magnetic resonance imaging (MRI), and their CSV-related lesions (i.e., lacunar infarcts, cerebral microbleeds, deep white matter hyperintensity, and periventricular hyperintensity) were evaluated. The serum levels of hs-CRP were evaluated as common inflammatory markers. RESULTS: Subjects with higher C-reactive protein (CRP) levels had more lacunar infarcts (P = 0.02). After adjusting for the traditional cardiovascular risk factors, higher hs-CRP levels were still associated with the presence of lacunar infarcts [odds ratio for the highest vs the lowest tertile of hs-CRP, 3.57 (95% confidence interval: 1.30-9.80)]. These associations did not change when the logarithmically transformed values for hs-CRP were included. Furthermore, subjects with higher CRP levels had more cerebral microbleeds (P = 0.03), more severe deep white matter hyperintensity (P = 0.04), and periventricular hyperintensity (P = 0.04); however, these associations were not observed after adjusting for the cardiovascular risk factors. CONCLUSIONS: Higher levels of hs-CRP were associated with lacunar infarcts. Thus, inflammatory processes may be involved in the pathogenesis of small-vessel disease.

Relationship between DNA degradation ratios and the number of loci detectable by STR kits in extremely old seminal stain samples.

The relationships between DNA degradation ratios and the number of detected loci were explored in extremely old seminal stains evaluated using three short tandem repeat (STR) kits: the AmpFlSTR® Identifiler™ PCR Amplification Kit (Identifiler), the AmpFlSTR® Yfiler™ PCR Amplification Kit (Yfiler), and the AmpFlSTR® MiniFiler™ PCR Amplification Kit (MiniFiler). DNA degradation ratios based on 41, 129, and 305bp DNA fragments were calculated (129:41 and 305:41), and the relationships between the ratios and storage duration were also explored. Using the Identifiler kit, the number of loci detected was strongly correlated with the 129:41 ratio (r=0.887), whereas the correlation with the 305:41 ratio was moderate (r=0.656). Using the Yfiler kit, the DYS385 amplicon was detected in all samples, suggesting that DYS385 may be resistant to degradation. The number of detected loci was strongly correlated with the 129:41 ratio (r=0.768), and moderately so with the 305:41 ratio (r=0.515). MiniFiler detected at least seven loci in all samples. In samples that did not yield full profiles, the undetected loci were D7S820 and D21S11, or D21S11 only, suggesting that these loci might be easily degraded. The number of loci detected using STR kits correlated with the DNA degradation ratios. In particular, the 129:41 ratio was particularly useful for estimating the number of loci detectable by STR kits. On the other hand, we suggest that storage duration cannot be accurately estimated using DNA degradation ratios; these ratios were not strongly correlated with storage duration (129:41; r=-0.698, 305:41; r=-0.550). However, the ratios may allow the identification of samples that have been stored for more than 40years.

Lysophosphatidylcholine increases the neurotoxicity of Alzheimer's amyloid ß1-42 peptide: role of oligomer formation.

Oligomer formation is considered as a critical process for the neurotoxic effects of Alzheimer's amyloid ß (Aß) peptide. Previously we have demonstrated that lysophosphatidylcholine (LPC) increases the oligomer formation of Aß1-42, the major Aß peptide found Alzheimer's disease (AD) lesions. In this study, we have investigated whether LPC affects the neurotoxic effects of Aß1-42 in a neuronal cell line (A1) culture. Dimethyl thiazolyl diphenyl tetrazolium (MTT) assay revealed that up to 10µM concentration, LPC did not affect A1 cell viability. Aß1-42 decreased the cell viability, and such effect was dose dependently enhanced by LPC. However, neither LPC nor Aß1-42, alone or in combination increased lactate dehydrogenase (LDH) release from A1 cells after 24-h treatment. Terminal deoxynucleotidyl transferase dUTP-biotin nick-end-labeling (TUNEL) assay showed that LPC increased Aß1-42-induced apoptotic cell number. To determine the underlying mechanisms, the proteins implicated in apoptosis pathways including Bcl-2- and caspase-family were analyzed by Western blotting. The results demonstrated that Aß1-42 decreased Bcl-2 in A1 cells at 24h, whereas LPC had no effect at any time point. Both LPC and Aß1-42 increased Bax level at 24h, and their combined stimulation showed a synergistic effect. Similar synergistic effect of LPC and Aß1-42 on caspase9 activation was observed. Dot blot immunoassay and Western blotting showed that LPC augmented Aß1-42 oligomer formation in cell culture medium. Removing LPC-induced early-formed Aß1-42 oligomer from the culture medium by immunoprecipitation decreased active caspase9 level and neurotoxicity, as revealed by Western blotting and MTT assay. Furthermore, dihydroethidium (DHE) assay showed that Aß1-42 increased reactive oxygen species level in A1 cells, such effect was further enhanced by LPC. Thus, our results demonstrated that LPC increased the oligomer formation process of Aß1-42 peptide in culture condition, and consequently increased apoptotic neuronal death. Such process might be important for the pathogenesis of AD, and inhibition of LPC generation could be a therapeutic target for the disease.

Dielectric properties of fluorine substituted hydroxyapatite: the effect of the substitution on configuration of hydroxide ion chains.

Hydroxyapatite (HAp) [Ca5(PO4)3OH] is an extremely popular biomaterial. Moreover, HAp durability is well-known to be enhanced by fluoridation. We prepared fluoridated HAp (F-HAp; Ca5(PO4)3(OH)1-xFx) ceramics by substituting F- ions for OH- ions of HAp. F-substitution dependence of dielectric properties in F-HAp was measured to detect the configuration change of OH- ion chains. Dielectric relaxation of two kinds was observed. Each kind had a different relaxation time. Faster relaxation, which is associated with the reorientation motion of OH- ions, was only observed at the low F-substitution range (0 ≤x < 0.35). The relaxation strength decreased as the F-substitution increased. It became zero at x = 0.35, suggesting that F-substitution induces hydrogen bonds. One F- ion substituted for an OH- ion forms two hydrogen bonds with the two neighboring OH- ions and inhibits the motion of OH- ions, which results in some kind of ordered configuration in F-HAp. The configuration might be an origin that enhances the durability of the F-HAp.

Impact of five SNPs in dopamine-related genes on executive function.

OBJECTIVES: Dopamine neurotransmission is a critical factor for executive function, which is controlled by the prefrontal cortex in humans. Although the contribution of genetic factors to the regulation of brain dopaminergic activity is widely acknowledged, identification of a genotype-phenotype association has not yet been clearly established. In this study, we therefore evaluated the effects of five functional single-nucleotide polymorphisms (SNPs) in specific genes related to dopamine neurotransmission on executive function in a general population. MATERIALS AND METHODS: Participants of the health examination at the Shimane Institute of Health Science were recruited for this study (n = 964). To evaluate executive function, the Frontal Assessment Battery (FAB) was administered. SNPs were genotyped using the TaqMan method. RESULTS: A significant association was found between an SNP in the catechol-O-methyltransferase (COMT) gene (rs4680) encoding the low-activity Met allele and FAB score (P = 0.003). Of note, the flexibility subset of the FAB was associated with the SNP in COMT (P = 0.003) after adjustment for confounding factors. The generalized multifactor dimensionality reduction method identified that the combination of two SNPs in the COMT gene (rs4680) and the dopamine D4 receptor gene (rs1800955) had a significant effect on FAB score. CONCLUSIONS: Our study indicates a contribution of rs4680 in the COMT gene to the variability in executive function, as assessed by the FAB. In addition, we have indicated that a complex gene-gene interaction between SNPs in the genes related to dopamine neurotransmission may influence executive function in a general population.

Paclitaxel plus Carboplatin Chemotherapy for Primary Peritoneal Carcinoma: A Study of 22 Cases and Comparison with Stage III-IV Ovarian Serous Carcinoma.

The aim of this study was to assess the clinical characteristics and outcome of patients with either primary peritoneal carcinoma (PPC) or ovarian serous carcinoma (OSC) treated with paclitaxel plus carboplatin chemotherapy. We retrospectively identified 22 PPC patients and 55 stage III-IV OSC patients treated between 2002 and 2007. After exploratory laparotomy, all patients received paclitaxel and carboplatin every 3 weeks, with the goal of optimal cytoreduction. There were no statistically significant differences between the PPC and OSC groups with regard to tumor stage, residual tumor after debulking surgery (initial or interval), serum cancer antigen (CA) 125 levels at diagnosis, and completion of first-line chemotherapy. The progression-free survival (PFS) durations were 12.7 months (95% CI, 6.3-18.5) in the patients with PPC and 15.9 months (95% CI, 13.3-18.5) in those with OSC (p = 0.016). However, the median survival durations were 26.5 months (95% CI, 14.6-38.3) in the patients with PPC and 38 months (95% CI, 23.8-53.8) in those with OSC (p = 0.188). Survival was longer for all patients whose CA125 levels normalized to 26 U/ml during and after treatment. Overall survival (OS) of the patients with PPC was similar to that of the patients with OSC, suggesting that management for advanced-stage OSC would be similar to that for PPC. The combination of optimal debulking with paclitaxel plus carboplatin chemotherapy may offer patients the most effective treatment. The CA125 nadir after cytoreductive surgery can be considered a prognostic factor for OS and PFS in patients with PPC.

Elevated BAFF levels in the cerebrospinal fluid of patients with neuro-Behçet's disease: BAFF is correlated with progressive dementia and psychosis.

Neuro-Behçet's disease (NBD) is a serious complication of Behçet's disease. Generally, NBD patients with a chronic course are refractory to immunosuppressive treatment, resulting in the deterioration of personality. In this study, levels of B cell-activating factor belonging to the TNF family (BAFF) were measured in the cerebrospinal fluid (CSF) from 18 patients with NBD, 27 patients with epidemic aseptic meningitis (AM), 24 patients with multiple sclerosis (MS) and 34 healthy controls. BAFF levels in patients with NBD were significantly elevated compared with healthy controls, but showed no statistically significant elevation compared with either of the disease controls. In contrast, CSF IL-6 levels were slightly elevated in patients with NBD and significantly elevated in patients with AM and MS compared with healthy controls. Patients with NBD were subdivided into two groups according to their clinical course (eight patients with a slowly progressive course presenting with psychosis and dementia and 10 patients with an acute course including aseptic meningitis, brainstem involvement and myelopathy). BAFF levels were significantly increased in those with a slowly progressive course compared with those with an acute course. CSF BAFF levels did not correlate with serum BAFF levels, CSF cell counts or CSF IL-6 levels in patients with NBD. These data suggested that BAFF was produced within the central nervous system and may be associated with the development of NBD, particularly with a progressive course.

Prevalence and impact of rhinitis in asthma. SACRA, a cross-sectional nation-wide study in Japan.

BACKGROUND: Asthma and rhinitis are common co-morbidities everywhere in the world but nation-wide studies assessing rhinitis in asthmatics using questionnaires based on guidelines are not available. OBJECTIVE: To assess the prevalence, classification, and severity of rhinitis using the Allergic Rhinitis and its Impact on Asthma (ARIA) criteria in Japanese patients with diagnosed and treated asthma. METHODS: The study was performed from March to August 2009. Patients in physicians' waiting rooms, or physicians themselves, filled out questionnaires on rhinitis and asthma based on ARIA and Global Initiative for Asthma (GINA) diagnostic guides. The patients answered questions on the severity of the diseases and a Visual Analog Scale. Their physicians made the diagnosis of rhinitis. RESULTS: In this study, 1910 physicians enrolled 29,518 asthmatics; 15,051 (51.0%) questionnaires were administered by physician, and 26,680 (90.4%) patients were evaluable. Self- and physician-administered questionnaires gave similar results. Rhinitis was diagnosed in 68.5% of patients with self-administered questionnaires and 66.2% with physician-administered questionnaires. In this study, 994 (7.6%) patients with self-administered and 561 (5.2%) patients with physician-administered questionnaires indicated rhinitis symptoms on the questionnaires without a physician's diagnosis of rhinitis. Most patients with the physician's diagnosis of rhinitis had moderate/severe rhinitis. Asthma control was significantly impaired in patients with a physician's diagnosis of rhinitis for all GINA clinical criteria except exacerbations. There were significantly more patients with uncontrolled asthma as defined by GINA in those with a physician's diagnosis of rhinitis (25.4% and 29.7%) by comparison with those without rhinitis (18.0% and 22.8%). CONCLUSION: Rhinitis is common in asthma and impairs asthma control.

Inhibition of neutrophil elastase-induced goblet cell metaplasia by tiotropium in mice.

Airway occlusion by mucus in chronic obstructive disease (COPD) is associated with a poor prognosis. We hypothesised that tiotropium has the ability to inhibit neutrophil elastase (NE)-induced goblet cell metaplasia in mice and mucin production in vitro. On days 1, 4, and 7, tiotropium or vehicle was administered to C57BL/6 mice by inhalation and they were allowed to intranasally aspirate human NE. Bronchoalveolar lavage fluid (BALF) and lung sections were analysed on days 8, 11 and 14. The effect of late administration of tiotropium on the goblet cell metaplasia by NE aspiration was also assessed. NE-induced MUC5AC production by NCI-H292 cells was measured with ELISA. Repeated NE aspiration induced marked goblet cell metaplasia. The grading of goblet cell metaplasia, neutrophil count and eosinophil count in BALF, keratinocyte-derived chemokine level and leukotriene B(4) level in BALF, and M(3) receptor expression by immunohistochemistry, were lower in the tiotropium group than in the vehicle group. Late administration of tiotropium inhibited the established goblet cell metaplasia. Tiotropium inhibited NE-induced MUC5AC production. Tiotropium inhibited NE-induced goblet cell metaplasia and mucin production, probably mediated by suppression of inflammation and a direct action on epithelial cells. This result suggests that tiotropium may be useful for the treatment of mucus overproduction in COPD.

Cellular expression of the monocarboxylate transporter (MCT) family in the placenta of mice.

Lactate plays an important role as an alternative energy substrate, especially in conditions with a decreased utility of glucose. Proton-coupled monocarboxylate transporters (MCTs) are essential for the transport of lactate, ketone bodies, and other monocarboxylates through the plasma membrane and may contribute to the net transport of lactate through the placental barrier. The present study examined the expression profile and subcellular localization of MCTs in the mouse placenta. An in situ hybridization survey of all MCT subtypes detected intense mRNA expressions of MCT1, MCT4, and MCT9 as well as GLUT1 in the placenta from gestational day 11.5. The expression of MCT mRNAs decreased in the intensity at the end of gestation in contrast to a consistently intense expression of GLUT1 mRNA. Immunohistochemically, MCT1 and MCT4 showed a polarized localization on the maternal side and fetal side of the two cell-layered syncytiotrophoblast, respectively. The membrane-oriented localization of MCTs was supported by the coexistence of CD147 which recruits MCT to the plasma membrane. However, the subcellular arrangement of MCT1 and MCT4 along the trophoblastic cell membrane was completely opposite of that in the human placenta. Although we cannot exactly explain the reversed localization of MCTs between human and murine placentas, it may be related to differences between humans and mice in the origin of lactate and its utilization by fetuses.

Temperature dependence of gain shift in gamma-ray spectrometry system involving a long connecting cable.

This work demonstrates the possibility of a gain shift or a peak-shape-deterioration with changes in the temperature of a long connecting cable between a pre-amplifier and a main amplifier in a Ge gamma-ray spectrometry system. The tests were performed for 50m-long RG174/U and RG58C/U cables with and without the termination. Such a temperature effect may cause from the temperature dependence of the resistivity of a central copper wire. In order to minimize such temperature effects in a Ge gamma-ray spectrometry, use of a terminator should be avoided.

Genetic risk factors for periodontitis in a Japanese population.

Genetic variants at multiple loci have been shown to be associated with susceptibility to periodontitis. To better assess the genetic risk factors for periodontitis, we performed a case-control study in 319 Japanese individuals with periodontitis (172 aggressive and 147 chronic disease) and 303 race-matched healthy control individuals. Thirty-five functional gene polymorphisms that had been previously associated with immune responses were genotyped. For all gene polymorphisms tested, no significant differences were observed in the allele frequencies of persons with aggressive, chronic, and combined (aggressive and chronic) periodontitis, compared with control individuals. Multiple logistic regression analysis revealed a significant association of the vitamin D receptor +1056 T/C polymorphism with susceptibility to chronic periodontitis, after adjustment for age, gender, and smoking status (P = 0.002). These results suggest that none of the polymorphisms tested was strongly associated with periodontitis in a Japanese population. However, the vitamin D receptor +1056 polymorphism may be related to chronic periodontitis.

Effects of a leukotriene B4 receptor antagonist on bleomycin-induced pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a devastating disease with poor prognosis. Leukotrienes play an important role in IPF, and leukotriene (LT)B(4) is one of the key eicosanoids in IPF. In this study, we investigated whether ONO-4057, a LTB(4) receptor (BLTR) antagonist is capable of preventing bleomycin-induced pulmonary fibrosis. On day 1, C57BL/6 male mice were given a single intratracheal injection of bleomycin (2.5 mg x kg(-1)), and ONO-4057 (1.0 mg x kg(-1)) or vehicle alone, administered by intraperitoneal injection on days 1-5 each week for 3 weeks after the bleomycin injection. ONO-4057 reduced the total cell count in bronchoalveolar lavage fluid (BALF) on days 7, 14 and 21 and the Ashcroft score and the lung hydroxyproline content on days 14 and 21. The LTB(4), interleukin (IL)-6, IL-13, transforming growth factor (TGF)-beta levels in BALF and the TGF-beta expression in lung tissue, assessed by immunohistochemistry were decreased on day 7, whereas interferon (IFN)-gamma level in BALF was increased on day 14. The results of this study indicated that the BLTR antagonist inhibited the development of bleomycin-induced pulmonary fibrosis in mice by decreasing inflammation and altering TGF-beta, IL-6, IL-13 and IFN-gamma.

Role of epidermal growth factor receptor in maintaining airway goblet cell hyperplasia in rats sensitized to allergen.

BACKGROUND: Stimulation of epidermal growth factor receptor (EGFR) induces airway goblet cell hyperplasia, but the role of this molecule in the maintenance of this pathologic change remains uncertain. OBJECTIVE: To determine the mechanisms by which goblet cell hyperplasia is maintained in airway epithelium, we investigated EGFR-induced signalling pathways that lead to both mucin production and antiapoptosis in vitro. We also tested whether the inhibition of EGFR tyrosine kinase speeds reversal of established goblet cell hyperplasia to normal epithelial phenotype in vivo. METHODS: MUC5AC production was measured by immunoassay, and antiapoptotic responses were determined by Bcl-2 expression and terminal deoxynucleotidyl transferase-mediated dUTP-biotin Nick End Labelling staining using NCI-H292 cells. The effect of an inhibitor of EGFR tyrosine kinase (AG1478) on goblet cell hyperplasia was also determined in rats sensitized with ovalbumin (OVA). RESULTS: MUC5AC was constitutively expressed and few apoptotic cells were observed in NCI-H292 cells under non-stimulated condition. TGF-alpha increased MUC5AC and Bcl-2 expression, an effect that was prevented by inhibitors of EGFR tyrosine kinase (AG1478), MEK (PD98059), and NF-kappaB (CAPE). After the addition of TGF-alpha, AG1478 and an inhibitor of phosphatidylinositol 3 kinase/Akt (LY294002), but not PD98059, induced a marked apoptotic response, which was prevented by the caspase inhibitor Z-VAD fmk. Goblet cell hyperplasia and EGFR expression in airway epithelium were noted in the OVA-sensitized rats. Intratracheal instillation of AG1478 induced apoptosis of goblet cells, reverting the airway epithelium to normal epithelial phenotype. CONCLUSION: These findings indicate that EGFR plays an important role in the maintenance of goblet cell hyperplasia. We speculate that inhibitors of the EGFR cascade might be an effective therapy of airway remodelling.

Cystatin C expression in ischemic white matter lesions.

OBJECTIVES: To study the involvement of cystatin C in the progression of ischemic white matter lesions (WMLs). MATERIALS AND METHODS: Cystatin C levels in the cerebrospinal fluid (CSF) of patients with cerebrovascular disease, and also in primary and established human neural cell cultures were investigated. For pathologic analysis, cystatin C immunoreactivity was investigated in the white matter of patients with severe WMLs, mild WMLs or controls. RESULTS: Cystatin C levels in the CSF of patients with Fazekas WML grade 3 [14 with hypertension; W/HT(+) and nine without hypertension; W/HT(-)] were lower than those in 38 patients with grade 0-1 (P = 0.0022 and P < 0.0001 respectively). Immunohistochemical study showed that the cystatin C immunoreactivity was found in astrocytes, and the number of astrocytes in the white matter in the severe WML group was decreased when compared with that in controls (P = 0.0027) and in the mild WML group (P = 0.0024). In human neural cell cultures, treatments with thrombin, matrix metalloproteinases and interleukin 1 beta increased the expression of cystatin C mRNA in human astrocytes and hybrid neurons, but an enzyme-linked immunosorbent assay revealed that only thrombin significantly increased the production and secretion of cystatin C in astrocytes. CONCLUSIONS: These results suggest that low levels of CSF cystatin C in ischemic WMLs might be due to the decreased number of astrocytes that secrete cystatin C in response to the stimuli of proteases and inflammatory cytokines.

Chemokine-like factor expression in the idiopathic inflammatory myopathies.

OBJECTIVES: We evaluated the expression of chemokine-like factor (CKLF) in biopsied muscle fibers in inflammatory myopathies, non-inflammatory myopathies and neurologically diseased controls. MATERIALS AND METHODS: We studied the expression of CKLF in 15 polymyositis (PM), five dermatomyositis (DM), 15 non-inflammatory myopathies and nine neurologically diseased patients by immunohistochemistry. RESULTS: Chemokine-like factor was mostly expressed in small diameter muscle fibers surrounded by infiltrated lymphocytes of inflammatory myopathies patients. Parts of them were also positive for the staining of the developmental form of myosin heavy chain, a maker of regenerating muscle fibers. Thrombin immunoreactivity was observed in endomysium in PM and perimysium in DM. In vitro differentiation study showed a constitutive expression of CKLF in myoblasts that was abolished in myotubes during differentiation process and was induced again by thrombin. Thrombin regulates CKLF expression through protease-activated receptor-1 in myotubes. Treatment of a protein kinase C inhibitor partially blocked CKLF expression in myoblasts, while it remarkably inhibited that in myotubes. CONCLUSION: Chemokine-like factor expression is differentially regulated in myoblasts and myotubes. Thrombin could be a strong regulator for its expression. As CKLF is immunohistochemically positive in regenerating muscle fibers, we postulate here that CKLF is a useful marker for regenerating muscle fibers in inflammatory myopathies.

A prospective randomized comparison of diagnostic efficacy between transperineal and transrectal 12-core prostate biopsy.

The aim of this study is to elucidate the diagnostic efficacy between transperineal and transrectal 12-core prostate biopsy for prostate cancer. We prospectively randomized 200 consecutive men into two groups to undergo systematic prostate biopsy. Overall positivity for cancer was similar (47% by transperineal and 53% by transrectal; P=0.480). However, in case with 'gray zone' PSA (from 4.1 to 10.0 ng/ml), significantly more cores were positive when approach was transperineal, especially among transition zone cores. Therefore, urologist preferences are sufficient for choosing an approach, except for a possible small advantage of transperineal biopsy when PSA is in gray zone.

Interleukin-9 and Interleukin-13 augment UTP-induced Cl ion transport via hCLCA1 expression in a human bronchial epithelial cell line.

BACKGROUND: IL-9 and IL-13 induce airway goblet cell metaplasia, which is associated with expression of a Ca(2+)-activated Cl channel, hCLCA1. OBJECTIVE: As UTP stimulates both mucin secretion and Cl ion transport via a Ca(2+)-dependent pathway, the purpose of this study is to determine whether IL-9 and IL-13 affect UTP-induced Cl ion transport in human bronchial epithelial cell line 16HBE cells, and if they do, to elucidate whether such an effect is associated with hCLCA1 expression. METHODS: The increases in short-circuit current (I(sc)) in response to UTP were measured in the presence of amiloride by the Ussing chamber method. The morphology of epithelial cells was assessed by light microscopic findings, and hCLCA1 expression was investigated by immunocytochemistry and immunoblotting. RESULTS: UTP-induced increases in I(sc) in the cells treated with IL-9 or IL-13 for 48 h were greater than those in non-treated cells, and the potency of IL-13 was greater than that of IL-9. Pre-treatment with Ca(2+)-activated Cl channel inhibitors diisothocyanatostilbene-2, 2-disulphonic acid and niflumic acid completely inhibited the augmenting effects of IL-9 and IL-13 on I(sc). The epithelial layer of the cells treated with IL-9 or IL-13 was thicker than that of non-treated cells. The expression of hCLCA1 protein was induced by IL-13 in a concentration-dependent manner. These effects of IL-13 were more potent than those of IL-9. CONCLUSION: IL-9 and IL-13 augmented UTP-induced Cl ion transport, probably via proliferation of the cells with hCLCA1 expression, and IL-13 was more potent than IL-9 in producing such an effect in 16HBE cells.

Anisotropy and corotation of galactic cosmic rays.

The intensity of Galactic cosmic rays is nearly isotropic because of the influence of magnetic fields in the Milky Way. Here, we present two-dimensional high-precision anisotropy measurement for energies from a few to several hundred teraelectronvolts (TeV), using the large data sample of the Tibet Air Shower Arrays. Besides revealing finer details of the known anisotropies, a new component of Galactic cosmic ray anisotropy in sidereal time is uncovered around the Cygnus region direction. For cosmic-ray energies up to a few hundred TeV, all components of anisotropies fade away, showing a corotation of Galactic cosmic rays with the local Galactic magnetic environment. These results have broad implications for a comprehensive understanding of cosmic rays, supernovae, magnetic fields, and heliospheric and Galactic dynamic environments.