IgE sensitization to food allergens and airborne allergens in relation to biomarkers of type 2 inflammation in asthma.

BACKGROUND: We have recently reported that sensitization to food allergens and sensitization to airborne allergens had independent associations with increased fraction of exhaled nitric oxide (FeNO) and blood eosinophils in middle-aged adults and in young subjects with asthma. OBJECTIVE: To investigate the relation between IgE sensitization and several type 2 inflammation biomarkers in adult asthmatics. METHODS: FeNO, urinary eosinophil-derived neurotoxin (U-EDN), serum eosinophil cationic protein (S-ECP) and periostin were measured in 396 asthmatics, aged 17-76 years, from the Swedish GA2LEN study. Sensitization to airborne allergens was examined with skin prick tests (≥3 mm wheal) and sensitization to food allergens with measurement of specific IgE (≥0.35 kU/L). RESULTS: Asthmatics sensitized to food allergens had higher FeNO, 22.3 ppb (18.6, 26.7) vs 16.1 ppb (14.2, 18.2) (P = .005), S-ECP, 17.7 mg/L (14.8, 21.1) vs 12.8 mg/L (10.9, 14.9) (P = .01), and periostin, 73.7 (67.5, 80.3) ng/mL vs 59.9 (55.8, 64.2) ng/mL (P = .003), than non-sensitized subjects. Periostin levels in this group were also significantly higher than in the group sensitized only to airborne allergens (P = .01). Sensitization to food allergens related independently to FeNO (P = .02), S-ECP (P = .006) and periostin (P = .004), whereas sensitization only to airborne allergens related only to FeNO (P = .02) after adjustments for age, sex, height, weight and smoking history. FeNO correlated weakly with S-ECP (r = .17, P < .001), periostin (r = .19, P < .001) and U-EDN (0.16, P < .001). S-ECP also correlated weakly with U-EDN (r = .12, P = .02). None of the correlations between the remaining pairs of markers of type 2 inflammation were significant. CONCLUSIONS & CLINICAL RELEVANCE: Sensitization to food allergens related to several local and systemic type 2 inflammation markers, such as FeNO, S-ECP and periostin. Assessing the profile of allergic sensitization, including to food allergens, might improve the understanding and interpretation of inflammatory markers and potentially improve asthma management.

Prospective predictors of exacerbation status in severe asthma over a 3-year follow-up.

BACKGROUND: A predisposition to exacerbations is being recognized as a distinct phenotype with "previous exacerbations" representing the strongest clinical factor associated with future exacerbation. Thus, to identify additional novel biomarkers associated with asthma exacerbations, "past exacerbation status" must be included as a confounding factor. OBJECTIVE: This study aimed to characterize the clinical and biomarker features associated with asthma exacerbations in severe asthma. METHODS: We evaluated clinical parameters from 105 severe asthmatics yearly for 3 years, as well as their exacerbation status. We classified the subjects into 3 groups: (i) consistent non-exacerbators (CNE, subjects who did not experience any exacerbation over the 3-year period); (ii) consistent frequent exacerbators (CFE, subjects with frequent exacerbation, defined as those who had 2 or more exacerbations within 1 year, throughout the 3-year period); and (iii) intermittent exacerbators (IE). We conducted multivariate analysis for comparisons among the groups for multiple factors, including several Th2-related biomarkers, in addition to the "past exacerbation status." RESULTS: Thirty-nine subjects were classified as CNE, 15 as CFE, and 51 as IE. Frequent exacerbations in the previous year predicted exacerbations for the following year (P < .001). Among the several Th2-related biomarkers, only FeNO was associated with exacerbation status. When we analysed the data after the second visit, the impact of FeNO on predicting future exacerbation remained significant, even after considering the exacerbation status during the first year (P < .05). CONCLUSIONS AND CLINICAL RELEVANCE: Measurement of FeNO has a significant potential to predict future asthma exacerbation, which is independent of the "past exacerbation history."

Si-based Mach-Zehnder wavelength/mode multi/demultiplexer for a WDM/MDM transmission system.

We propose and experimentally demonstrate a low-loss and low-crosstalk Mach-Zehnder mode/wavelength multi/demultiplexer for WDM/MDM transmission based on a Si-photonics platform. A broadband 3-dB mode divider, which is also newly devised here, makes it possible to compose a Mach-Zehnder filter for "mode" and "wavelength" simultaneously. Transmission characteristics of fabricated 3-dB mode dividers are in excellent agreement with theoretical results. Mach-Zehnder filters using the 3-dB mode divider with a free spectral range (FSR) of 20 and 1 nm are also fabricated and the modal crosstalk is less than -24 dB in the 40-nm wavelength range for the MZ filter with an FSR of 20 nm. The tuning of the peak wavelength position by the TiN heater is also demonstrated.

IL4Rα and ADAM33 as genetic markers in asthma exacerbations and type-2 inflammatory endotype.

BACKGROUND: Genetic markers of susceptibility to asthma exacerbations in adults remain unclear. OBJECTIVE: To identify genetic markers of asthma exacerbations, particularly in patients with type-2 inflammatory endotype. METHODS: In this observational study of patients enrolled in the Kinki Hokuriku Airway disease Conference multicenter study, frequency of exacerbations requiring systemic corticosteroids during 2 years after enrolment and associated risk factors was determined. For genetic marker analysis, interleukin-4 receptor α (IL4RA) rs8832 and a disintegrin and metalloprotease 33 (ADAM33) S_2 (rs528557), T_1 (rs2280091), T_2 (rs2280090), and V_4 (rs2787094) variants were included. Elevated serum periostin levels at enrolment (≥95 ng/mL, defined as type-2 inflammatory endotype) were considered in the analysis. RESULTS: Among 217 patients who were successfully followed up for 2 years after enrolment, 60 patients showed at least one asthma exacerbation during the 2 years. Airflow limitation (%FEV1 <80%) and recent exacerbations but not genetic variants were identified as risk markers of exacerbations. A total of 27 patients showed type-2 inflammatory endotype (serum periostin ≥95 ng/mL at enrolment) and subsequent exacerbations; risk factors in these patients were airflow limitation (odds ratio, 6.51; 95% confidence interval (CI): 2.37-18.6; P=.0003), GG genotype of IL4RA rs8832 (odds ratio, 4.01; 95% CI: 1.47-11.0; P=.007), and A allele of ADAM33 T_2 (odds ratio, 2.81; 95% CI: 1.05-7.67; P=.04) by multivariate analysis. In addition, GG genotype of IL4RA rs8832 was associated with type-2 endotype, whereas A allele of ADAM33 T_2 was associated with mixed type of eosinophilic/type-2 and neutrophilic inflammations. CONCLUSIONS AND CLINICAL RELEVANCE: IL4RA and ADAM33 variants may be risk markers of asthma exacerbations in type-2 inflammatory endotype. Precise endotyping may facilitate the identification of genetic risk markers of asthma exacerbations.

Pancreatoduodenectomy with portal vein resection for distal cholangiocarcinoma.

BACKGROUND: Little is known about the value of portal vein (PV) resection in distal cholangiocarcinoma. The aim of this study was to evaluate the clinical significance of PV resection in distal cholangiocarcinoma. METHODS: Patients who underwent pancreatoduodenectomy (PD) for distal cholangiocarcinoma between 2001 and 2010 at one of 31 hospitals in Japan were reviewed retrospectively with special attention to PV resection. Short- and long-term outcomes were evaluated. RESULTS: In the study interval, 453 consecutive patients with distal cholangiocarcinoma underwent PD, of whom 31 (6·8 per cent) had combined PV resection. The duration of surgery (510 versus 427 min; P = 0·005) and incidence of blood transfusion (48 versus 30·7 per cent; P = 0·042) were greater in patients who had PV resection than in those who did not. Postoperative morbidity and mortality were no different in the two groups. Several indices of tumour progression, including high T classification, lymphatic invasion, perineural invasion, pancreatic invasion and lymph node metastasis, were more common in patients who had PV resection. Consequently, the incidence of R1/2 resection was higher in this group (32 versus 11·8 per cent; P = 0·004). Survival among the 31 patients with PV resection was worse than that for the 422 patients without PV resection (15 versus 42·4 per cent at 5 years; P < 0·001). Multivariable analyses revealed that age, blood loss, histological grade, perineural invasion, pancreatic invasion, lymph node metastasis and surgical margin were independent risk factors for overall survival. PV resection was not an independent risk factor. CONCLUSION: PV invasion in distal cholangiocarcinoma is associated with locally advanced disease and several negative prognostic factors. Survival for patients who have PV resection is poor even after curative resection.

Serum periostin relates to type-2 inflammation and lung function in asthma: Data from the large population-based cohort Swedish GA(2)LEN.

BACKGROUND: Periostin has been suggested as a novel, phenotype-specific biomarker for asthma driven by type 2 inflammation. However, large studies examining relationships between circulating periostin and patient characteristics are lacking and the suitability of periostin as a biomarker in asthma remains unclear. AIM: To examine circulating periostin in healthy controls and subjects with asthma from the general population with different severity and treatment profiles, both with and without chronic rhinosinusitis (CRS), in relation to other biomarkers and clinical characteristics. METHODS: Serum periostin was examined by ELISA in 1100 subjects aged 17-76 from the Swedish Global Allergy and Asthma European Network (GA(2)LEN) study, which included 463 asthmatics with/without chronic rhinosinusitis (CRS), 98 individuals with CRS only, and 206 healthy controls. Clinical tests included measurement of lung function, Fraction of exhaled NO (FeNO), IgE, urinary eosinophil-derived neurotoxin (U-EDN), and serum eosinophil cationic protein (S-ECP), as well as completion of questionnaires regarding respiratory symptoms, medication, and quality of life. RESULTS: Although median periostin values showed no differences when comparing disease groups with healthy controls, multiple regression analyses revealed that periostin was positively associated with higher FeNO, U-EDN, and total IgE. In patients with asthma, an inverse relationship with lung function was also observed. Current smoking was associated with decreased periostin levels, whereas increased age and lower body mass index (BMI) related to higher periostin levels in subjects both with and without asthma. CONCLUSION: We confirm associations between periostin and markers of type 2 inflammation, as well as lung function, and identify novel constitutional factors of importance to the use of periostin as a phenotype-specific biomarker in asthma.

Utility of serum periostin and free IgE levels in evaluating responsiveness to omalizumab in patients with severe asthma.

BACKGROUND: Omalizumab, a humanized anti-IgE monoclonal antibody, has demonstrated efficacy in patients with severe allergic asthma. However, treatment responses vary widely among individuals. Despite a lack of data, free serum IgE levels following omalizumab treatment have been proposed as a marker of treatment responsiveness. METHODS: In this prospective, observational study, we assessed the utility of biomarkers of type 2 inflammation in predicting omalizumab treatment responses, as determined by the absence of asthma exacerbation during the first year of treatment. Free serum IgE levels were monitored for 2 years to examine their association with baseline biomarker levels and the number of exacerbations. RESULTS: We enrolled thirty patients who had been treated with omalizumab for at least 1 year, of whom 27 were treated for 2 years. Baseline serum periostin levels and blood eosinophil counts were significantly higher in patients without exacerbations during the first year of treatment than in patients with exacerbations. Baseline serum periostin levels, but not eosinophil counts, were negatively associated with free serum IgE levels after 16 or 32 weeks of treatment. Reduced free serum IgE levels during treatment from those at baseline were associated with reduced exacerbation numbers at 2 years. In 14 patients who continued to have exacerbations during the first year of treatment, exacerbation numbers gradually and significantly decreased over the 2-year study period, with concurrent significant reductions in free serum IgE levels. CONCLUSION: Baseline serum periostin levels and serum free IgE levels during treatment follow-up may be useful in evaluating responses to omalizumab treatment.

Elevation of serum squamous cell carcinoma antigen 2 in patients with psoriasis: associations with disease severity and response to the treatment.

BACKGROUND: Squamous cell carcinoma antigen (SCCA) belongs to the ovalbumin-serpin family and is a known tumour marker. Expression of SCCA is upregulated in the serum and skin of patients with psoriasis. OBJECTIVES: The aim of this study was to determine SCCA2 levels in association with disease severity and treatment efficacy in patients with psoriasis. MATERIALS AND METHODS: Patients with psoriasis (n = 123) and healthy controls (n = 25) were enrolled in this prospective cross-sectional study. Enzyme-linked immunosorbent assay (ELISA) analysis was performed to determine serum SCCA2 levels. SCCA2 expression in skin was evaluated using immunohistochemical analysis. Serum SCCA2 levels were compared with Psoriasis Area Severity Index (PASI) scores. The effect of treatment on serum SCCA2 levels was assessed using serial examinations. Induction of SCCA2 by several psoriatic cytokines in human keratinocytes was evaluated. RESULTS: The serum levels of SCCA2 were significantly higher in patients with psoriasis than healthy controls and correlated well with disease severity. Increased SCCA2 staining was observed in lesional skin but not in nonlesional skin of patients with psoriasis. In addition, SCCA2 expression levels in skin correlated with serum concentrations of SCCA2. SCCA2 significantly decreased according to improvement of PASI scores. Interleukin (IL)-17 and IL-22 synergistically increased the production of SCCA2 at both mRNA and protein levels in human keratinocytes. CONCLUSIONS: Significant elevation of SCCA2 is associated with disease severity and reflects treatment efficacy. SCCA2 may be a useful biomarker in psoriasis, reflecting T-helper 17-type inflammation - the main determinant of the severity of psoriasis.

Influenza 2014-2015 among pregnant Japanese women: primiparous vs multiparous women.

This study was performed to determine whether multiparous pregnant women are prone to influenza. A questionnaire survey was conducted at 19 centres located throughout Japan, targeting all 6,694 postpartum women within 7 days after birth before leaving the hospital. All women gave birth during the study period between March 1, 2015, and July 31, 2015. Data regarding vaccination and influenza infection in or after October 2014, age, previous experience of childbirth, and number and ages of cohabitants were collected. Seventy-eight percent (n = 51,97) of women given questionnaires responded. Of these, 2,661 (51 %) and 364 (7.0 %) women reported having been vaccinated and having contracted influenza respectively. Multiparous women had a higher risk of influenza regardless of vaccination status (8.9 % [121/1362] vs 5.7 % [74/1299], relative risk [95 % confidence interval], 1.80 [1.36 to 2.38] for vaccinated and 9.3 % [112/1198] vs 4.3 % [57/1328], 2.18 [1.60 to 2.97] for unvaccinated women) compared to primiparous women. The risk of influenza increased with increasing number of cohabitants: 4.8 % (100/2089), 7.5 %, (121/1618), 9.0 %, (71/785), and 10.4 % (58/557) for women with 1, 2, 3, and ≥4 cohabitants respectively. Family size is a risk factor for influenza infection in pregnancy.

GLCCI1 variant accelerates pulmonary function decline in patients with asthma receiving inhaled corticosteroids.

BACKGROUND: In steroid-naive patients with asthma, several gene variants are associated with a short-term response to inhaled corticosteroid (ICS) treatment; this has mostly been observed in Caucasians. However, not many studies have been conducted for other ethnicities. Here, we aimed to determine the relationship between the annual decline in forced expiratory flow volume in one second (FEV1 ) and the variant of the glucocorticoid-induced transcript 1 gene (GLCCI1) in Japanese patients with asthma receiving long-term ICS treatment, taking into account the effect of high serum periostin levels, a known association factor of pulmonary function decline and a marker of refractory eosinophilic/Th2 inflammation. METHODS: In this study, 224 patients with asthma receiving ICS treatment for at least 4 years were enrolled. The effects of single-nucleotide polymorphisms (SNPs) in GLCCI1, stress-induced phosphoprotein 1 (STIP1), and T gene on the decline in FEV1 of 30 ml/year or greater were determined. RESULTS: Besides the known contributing factors, that is, the most intensive treatment step, ex-smoking, and high serum periostin levels (≥95 ng/ml), the GG genotype of GLCCI1 rs37973, and not other SNPs, was independently associated with a decline in FEV1 of 30 ml/year or greater. When patients were stratified according to their serum periostin levels, the GG genotype of rs37973 was significantly associated with blood eosinophilia (≥250/µl) in the high serum periostin group. CONCLUSIONS: A GLCCI1 variant is a risk factor of pulmonary function decline in Japanese patients with asthma receiving long-term ICS treatment. Thus, GLCCI1 may be associated with response to ICS across ethnicities.

Periostin levels correlate with disease severity and chronicity in patients with atopic dermatitis.

BACKGROUND: Recent findings indicate that periostin, an extracellular matrix protein induced by T helper 2 cytokines, plays a critical role in the pathogenesis of atopic dermatitis (AD). OBJECTIVES: To determine whether serum periostin level is associated with clinical phenotype in adult patients with AD. METHODS: An enzyme-linked immunosorbent assay was performed to determine serum periostin levels in 257 adult patients with AD, 66 patients with psoriasis vulgaris (PV) as a disease control and 25 healthy controls. Serum periostin levels were analysed together with clinical characteristics and laboratory parameters, including thymus and activation-regulated chemokine (TARC), lactate dehydrogenase (LDH), blood eosinophil count and total IgE. Immunohistochemical analysis evaluated the expression of periostin in association with various clinical phenotypes of AD. The effect of treatment on serum periostin level was also assessed. RESULTS: Serum periostin was significantly higher in patients with AD than in patients with PV and healthy controls. Periostin level was found to be positively correlated with disease severity, TARC level, LDH level and eosinophil count, but not with IgE level. Higher serum periostin level was observed in patients with extrinsic AD compared with patients with intrinsic AD; the positive correlation of disease severity disappeared in patients with intrinsic AD. Robust expression of periostin was detected in the dermis of patients with AD with erythroderma, lichenification and, to a lesser extent, scaly erythema. Serial measurement of serum periostin revealed decreased levels of periostin after treatment for AD. CONCLUSIONS: Periostin may play a critical role in disease severity and chronicity in the pathogenesis of AD.

Serum periostin levels are correlated with progressive skin sclerosis in patients with systemic sclerosis.

BACKGROUND: Periostin, a matricellular protein, serves as a regulator of wound healing and fibrosis. The role of periostin in the pathogenesis of systemic sclerosis (SSc) is unknown. OBJECTIVE: To determine periostin levels in association with severity of skin fibrosis in patients with SSc. METHODS: Expression of periostin was immunohistochemically examined in skin obtained from patients with SSc and healthy controls. Enzyme-linked immunosorbent assay was performed to evaluate serum periostin levels in association with clinical characteristics in 56 patients with SSc [diffuse cutaneous SSc (dSSc), n=16; and limited cutaneous SSc (lSSc), n=40] and 66 healthy controls. RESULTS: Periostin was strongly expressed in the affected dermis from patients with SSc. Periostin was colocalized in α-smooth muscle actin-positive myofibroblasts and platelet endothelial cell adhesion molecule-1-positive endothelial cells in SSc dermis. Serum levels of periostin in patients with dSSc were markedly elevated compared with those in patients with lSSc and control subjects. Patients with lSSc had increased periostin levels compared with healthy controls. In addition, significantly higher levels of periostin were observed in patients with dSSc with disease duration ≤5 years compared with those with disease duration >5 years. Furthermore, the modified Rodnan total skin thickness score (MRSS) was positively correlated with periostin levels in patients with SSc. Serial analysis revealed a correlation between periostin and MRSS; namely, MRSS decreased in line with decreased periostin levels in some patients with dSSc as the disease progressed. CONCLUSION: An elevated periostin level in patients with SSc is associated with severity of skin sclerosis. Periostin may be a potential biomarker for progressive skin fibrosis in SSc.

The gene for Machado-Joseph disease maps to human chromosome 14q.

Machado-Joseph disease (MJD) is an autosomal dominant, multisystem neurodegenerative disorder involving predominantly cerebellar, pyramidal, extrapyramidal, motor neuron and oculomotor systems. Although it was first reported in families of Portuguese-Azorean descent, MJD has also been described in non-Azorean families from various countries, being one of the most common hereditary spinocerebellar degenerations. With the use of highly polymorphic microsatellite DNA polymorphisms, we have assigned the gene for MJD to the long arm of chromosome 14 (14q24.3-q32) by genetic linkage to microsatellite loci D14S55 and D14S48 (multipoint lod score Zmax = 9.719).

Topical application of the antiapoptotic TAT-FNK protein prevents aminoglycoside-induced ototoxicity.

We previously demonstrated that an artificial protein, TAT-FNK, has antiapoptotic effects against cochlear hair cell (HC) damage caused by ototoxic agents when applied systemically. To examine the feasibility of topical protein therapy for inner ear disorders, we investigated whether gelatin sponge soaked with TAT-FNK and placed on the guinea pig round window membrane (RWM) could deliver the protein to the cochlea and attenuate aminoglycoside (AG)-induced cochlear damage in vivo. First, we found that the immunoreactivity of TAT-myc-FNK was distributed throughout the cochlea. The immunoreactivity was observed from 1-24 h after application. When Tat-FNK was applied 1 h before ototoxic insult (a combination of kanamycin sulfate and ethacrynic acid), auditory brainstem response threshold shifts and the extent of HC death were significantly attenuated. When cochlear organotypic cultures prepared from P5 rats were treated with kanamycin, TAT-FNK significantly reduced the extent of caspase-9 activation and HC death. These findings indicate that TAT-FNK topically applied on the RWM can enter the cochlea by diffusion and effectively prevent AG-induced apoptosis of cochlear HCs by suppressing the mitochondrial caspase-9 pathway.

A change of osteocalcin (OC) and tartrate resistant acid phosphatase 5b (TRACP-5b) with the menstrual cycle.

Bone metabolism markers associated with 4 menstrual cycle phases were evaluated in 14 healthy young females without menstrual disorder. Menstrual cycle phases were confirmed with basal body temperature for 3 months, luteinizing hormone kits, and sexual hormone concentrations of serum. The bone metabolism markers used were osteocalcin (OC), which was measured by immunoradiometric assay (IRMA), and tartrate resistant acid phosphatase 5b (TRACP-5b), which was measured by enzyme immunometric assay (EIA). The highest values of OC and TRACP-5b were observed in the ovulation phase, and TRACP-5b increased significantly when compared with levels in the menstrual phase (p<0.05). Furthermore, the changes in sex-hormone secretion involved in OC and TRACP-5b showed specific patterns during the menstrual cycle. In other words, TRACP-5b levels are influenced by sex hormones produced during the menstrual period and are based on the bone-formation status. Therefore, it is presumed that the TRACP-5b levels during ovulation play a central role in bone formation and bone metabolism.

Periostin, a matrix protein, is a novel biomarker for idiopathic interstitial pneumonias.

Idiopathic interstitial pneumonias (IIPs) are histopathologically classified into several types, including usual interstitial pneumonia (UIP), nonspecific interstitial pneumonia (NSIP) and cryptogenic organising pneumonia (COP). We investigated whether periostin, a matrix protein, could be used as a biomarker to assess histopathological types of IIPs. We performed immunohistochemical analyses in each histopathological type of IIP, examined serum levels of periostin in IIP patients and analysed the relationship between serum levels of periostin and the pulmonary functions in patients with idiopathic pulmonary fibrosis (IPF). Periostin was strongly expressed in lungs of UIP and fibrotic NSIP patients, whereas expression of periostin was weak in the lungs of cellular NSIP and COP patients, as well as in normal lungs. Serum levels of periostin in IPF were significantly higher than those of healthy subjects and COP patients. Furthermore, periostin levels in IPF patients were inversely correlated with their pulmonary functions. Thus, we have found that periostin is a novel component of fibrosis in IIP. Periostin may be a potential biomarker to distinguish IIP with fibrosis.

Effect of tiotropium bromide on airway inflammation and remodelling in a mouse model of asthma.

BACKGROUND: Tiotropium bromide, a long acting muscarinic receptor inhibitor, is a potent agent for patients with bronchial asthma as well as chronic obstructive pulmonary disease. OBJECTIVE: The aim of this study was to evaluate whether tiotropium bromide can inhibit allergen-induced acute and chronic airway inflammation, T helper (Th)2 cytokine production, and airway remodelling in a murine model of asthma. METHODS: Balb/c mice were sensitized and challenged acutely or chronically to ovalbumin (OVA). The impact of tiotropium bromide was assessed using these mice models by histologic, morphometric, and molecular techniques. Moreover, the effect of tiotropium bromide on Th2 cytokine production from purified human peripheral blood mononuclear cells (PBMCs) was assessed. RESULTS: Treatment with tiotropium bromide significantly reduced airway inflammation and the Th2 cytokine production in bronchoalveolar lavage fluid (BALF) in both acute and chronic models of asthma. The levels of TGF-beta1 were also reduced by tiotropium bromide in BALF in a chronic model. The goblet cell metaplasia, thickness of airway smooth muscle, and airway fibrosis were all significantly decreased in tiotropium bromide-treated mice. Moreover, airway hyperresponsiveness (AHR) to serotonin was significantly abrogated by tiotropium bromide in a chronic model. Th2 cytokine production from spleen cells isolated from OVA-sensitized mice was also significantly inhibited by tiotropium bromide and 4-diphenylacetoxy-N-methylpiperidine methiodide, which is a selective antagonist to the M3 receptor. Finally, treatment with tiotropium bromide inhibited the Th2 cytokine production from PBMCs. CONCLUSION: These results indicate that tiotropium bromide can inhibit Th2 cytokine production and airway inflammation, and thus may reduce airway remodelling and AHR in a murine model of asthma.

Malignant transformation in craniopharyngioma after radiation therapy: a case report and review of the literature.

OBJECTIVE: Craniopharyngioma is a benign epithelial tumor that is thought to arise from the remnant of the Rathke pouch. Malignant transformation in craniopharyngioma is extremely rare. Herein, we report a case of malignant transformation in craniopharyngioma after radiation therapy. MATERIALS AND METHODS: Histopathological and immunohistochemical analyses were carried out for specimens of the suprasellar tumor (from three resections, with the third surgery performed after radiation therapy). RESULTS: The resected tumors from the first and second surgeries comprised islands of loosely cohesive aggregates of epithelial cells, so-called stellate reticulum. At the periphery of the nests, palisaded columnar epithelium was observed. Wet keratins were scattered, and few mitotic figures were seen. The third surgical specimen was composed of irregular large nests of basaloid cells that had large, round to oval nuclei with prominent nucleoli, and mitotic figures were frequently seen (21/10 high power fields). In the center of the nests, eosinophilic ghost cells, resembling wet keratin, were observed. Accordingly, the diagnosis of malignant transformation in craniopharyngioma was made. Immunohistochemical studies revealed that the p53 protein was over-expressed in the malignant component, whereas its expression was much lower in the benign component. CONCLUSIONS: Similar to the ten previously reported cases of malignant transformation in craniopharyngioma, the present case occurred after radiation therapy. p53 protein overexpression was also observed in the earlier cases of malignant craniopharyngioma as well as in the present case (6/6 cases). We concluded that radiation therapy and p53 mutations could be involved in malignant transformation in craniopharyngioma.

Thin film growth of CaAgAs by molecular beam epitaxy.

We have grown thin films of CaAgAs by molecular beam epitaxy, which was theoretically proposed to be a topological insulator. The temperature dependence of resistivity and the carrier concentration at 4 K were similar to the reported results of bulk samples. However, the magnetoresistance exhibited a steep increase at low magnetic fields, a behavior not observed for bulk samples. This steep increase of resistivity is ascribable to the weak antilocalization effect and provides clues to the nature of the topological surface state of CaAgAs.

Follow-up of a self-resolving renal pseudoaneurysm using contrast-enhanced power Doppler ultrasonography.

It has been standard practice to embolise a pseudoaneurysm caused by penetrating trauma whenever it is found, even in the absence of overt symptoms. This is a case report of a renal pseudoaneurysm (RPA) caused by a stab wound, which was safely monitored and followed using colour Doppler ultrasonography. On day 1, angiography showed a pseudoaneurysm of the renal artery in the parenchyma and ultrasonography showed blood flow into the pseudoaneurysm. Although abnormal blood flow into the kidney was seen, there appeared to be no leakage of blood from the pseudoaneurysm. The abnormal flow disappeared on day 12 and the area of the pseudoaneurysm became unclear from day 13. This report suggests the possibility that RPA caused by a stab wound could be an indication for conservative therapy under the following conditions: the RPA is detected initially; close monitoring using a colour Doppler ultrasound is possible; there is no leakage of blood from the right subclavian artery and there is a 2-week period of observation.