STAT6 and IL-10 are required for the anti-arthritic effects of Schistosoma mansoni via different mechanisms.

To investigate possible roles of T helper type 2 (Th2) cytokines in the anti-arthritic effects of a blood fluke, Schistosoma mansoni (Sm), for mouse collagen-induced arthritis (CIA), wild-type (WT), signal transducer and activator of transcription 6 (STAT6) knock-out (KO) and interleukin (IL)-10 KO mice were infected with Sm. Three weeks after infection, the mice were immunized with bovine type II collagen (IIC). Arthritis severity was monitored by scoring, measurement of paw thickness and the presence of ankylosis. Serum anti-IIC IgG levels, splenic cytokine production and cytokine gene expression in the popliteal lymph nodes (PLNs) were measured and compared among WT and gene-KO mice. Consistent with our previous findings, Sm infection reduced the arthritis severity in WT mice. Splenic production of IL-17A and tumor necrosis factor (TNF)-α was reduced by the infection. In contrast, Sm infection markedly exacerbated CIA in STAT6 KO mice. In the KO mice, IL-17A production was increased by the infection. Conversely, Sm infection did not affect the exacerbated arthritis in IL-10 KO mice, although IL-17A production was reduced by the helminth. Our results suggest that signaling via STAT6 (presumably IL-4 and/or IL-13) and IL-10 is required for the suppression of CIA by Sm infection, but through different mechanisms. STAT6 was essential for helminth-induced reduction of IL-17A, whereas regulation of the basal arthritis severity by IL-10 was needed in order for it to be sufficiently suppressed by the helminth.

An economic assessment of foot and mouth disease in Japan.

A large-scale foot and mouth disease (FMD) epidemic in Japan in 2010 caused severe economic losses for livestock and related industries. In this paper, the authors develop a clear and usable framework to estimate the economic impact of this FMD outbreak. An economic analysis is then conducted by combining this framework with an epidemiological model. The framework estimates the direct and indirect costs to livestock and related industries by applying an input-output model, as well as by addressing expenditure on disease control. The direct cost to the livestock industry was estimated at 51.2 billion Japanese yen (JPY), engendering an indirect cost to related industries of JPY 25.5 billion. The expenditure for disease control activities was estimated at JPY 8.2 billion. The total impact of the 2010 FMD epidemic was estimated at almost JPY 85 billion. Within the economic analysis, the authors evaluate several control measure scenarios: a baseline scenario, which assumes that the rapid disease spread observed in the early phase of the 2010 FMD epidemic would continue; prompt culling within 24 hours; early detection of the first case; and emergency vaccination within a radius of 10 km around the affected farms in either seven or 28 days. Prompt culling and early detection were superior from an economic point of view, reducing the total economic impact to 30% and 2% of that in the baseline scenario, respectively. Compared with these scenarios, vaccination was less cost effective. However, vaccination suppressed the speed of disease spread and shortened the duration of the epidemic, suggesting its potential effectiveness in curbing rapid disease spread in a densely populated area.

Une épizootie de fièvre aphteuse de grande envergure survenue au Japon en 2010 a entraîné de graves pertes économiques pour la filière de l'élevage et les secteurs connexes. Les auteurs proposent un cadre d'évaluation clair pour estimer l'impact économique de ce foyer de fièvre aphteuse. Ils effectuent ensuite une analyse économique dans laquelle ce cadre d'évaluation est relié à un modèle épidémiologique. Les coûts directs et indirects subis par la filière de l'élevage et par les secteurs connexes sont évalués dans ce cadre en appliquant un modèle entrées­sorties (input­output) et en prenant en compte les dépenses liées à la lutte contre la maladie. Le coût direct de la maladie pour la filière de l'élevage a été estimé à 51,2 milliards de yens japonais, auxquels s'ajoute le coût indirect pour les secteurs connexes estimé à 25,5 milliards de yens japonais. Les dépenses induites par la lutte contre la maladie s'élèvent à 8,2 milliards de yens japonais. L'impact total de l'épizootie de fièvre aphteuse de 2010 est estimé à près de 85 milliards de yens japonais. Dans leur analyse économique, les auteurs ont évalué plusieurs scénarios relatifs aux mesures de lutte appliquées : un scénario de base, qui suppose une propagation de la maladie au même rythme que durant la phase initiale de l'épidémie de 2010 ; l'abattage rapide des animaux en 24 heures ; la détection précoce du premier cas ; l'application de la vaccination d'urgence dans un périmètre de 10 km autour des exploitations affectées et dans un délai de sept ou de 28 jours. Par rapport au scénario de base, l'abattage rapide et la détection précoce sont les meilleurs scénarios du point de vue économique, réduisant l'impact économique total respectivement à 30 % et 2 % de celui du scénario de base. Comparativement à ces scénarios, la vaccination est la solution la moins efficiente économiquement. Néanmoins, la vaccination a freiné la propagation de la maladie et limité la durée de l'épidémie, ce qui laisse penser qu'elle permettrait d'infléchir la courbe de propagation de la maladie dans les zones à forte densité de bétail.

En 2010 se produjo en el Japón una epidemia de fiebre aftosa de grandes proporciones, que causó graves pérdidas económicas a la industria ganadera y demás sectores conexos. Los autores describen un método claro para estimar el impacto económico de dicho brote. Acto seguido, llevan a cabo un análisis económico combinando este método con un modelo epidemiológico. El método permite estimar los costos directos e indirectos que soportan la industria ganadera y demás sectores conexos aplicando un modelo de «insumoproducto ¼ (input­output) y teniendo también en cuenta los gastos ligados al control de la enfermedad. Según los cálculos, el costo directo para la industria ganadera fue de 51 200 millones de yenes japoneses y el costo indirecto para los sectores conexos fue de 25 500 millones de yenes. Se estimó que las actividades de lucha contra la enfermedad supusieron gastos por valor de 8 200 millones. En total, pues, según estas estimaciones, el impacto económico de la epidemia de fiebre aftosa de 2010 se cifra en casi 85 000 millones de yenes. Como parte del análisis económico, los autores evalúan varias hipótesis relativas a las medidas de control: una hipótesis básica, en la cual prosigue sin trabas la veloz propagación de la enfermedad observada en la primera fase de la epidemia de 2010; la rápida implantación, en un plazo de 24 horas, de medidas de sacrificio sanitario; la pronta detección del primer caso; y la vacunación de emergencia dentro de un radio de 10 km alrededor de las explotaciones afectadas, en un plazo de siete días o en un plazo de 28 días. Desde un punto de vista económico, el rápido sacrificio sanitario y la pronta detección ofrecían mejores resultados, pues reducían el impacto económico total hasta un 30% y un 2%, respectivamente, del registrado en la hipótesis básica. En comparación con esas dos hipótesis, la vacunación ofrecía menos eficacia en relación con el costo, aunque frenaba la rápida propagación de la enfermedad y abreviaba la epidemia, de donde se infiere que puede resultar eficaz para contener la rápida dispersión de la enfermedad en áreas densamente pobladas.

Population-based study of asymptomatic infection with Chlamydia trachomatis among female and male students.

There are few epidemiological studies of asymptomatic chlamydial infection among students in non-medical settings with minimal bias and improved accuracy; thus, useful data from screening among students are limited. We aimed to obtain accurate epidemiological information about asymptomatic chlamydial infection among students in non-medical settings. A population-based cross-sectional survey of 10,440 >or=18-year-old asymptomatic students who volunteered for a urine screening test for chlamydia was conducted. The prevalences of asymptomatic infection were 9.5% for women and 6.7% for men. Multivariate analysis revealed the risk factors to be a lifetime history of >or=4 sexual partners for women (odds ratio [OR] 3.17) and inconsistent condom use for men (OR 4.18). For both sexes, younger age at first intercourse was associated with a higher rate of inconsistent condom use. This study produced accurate epidemiological information on asymptomatic chlamydial infection. These results may contribute to the establishment of preventive countermeasures against such infection.

Antifouling activity of synthetic polymer gels against cyprids of the barnacle (Balanus amphitrite) in vitro.

Barnacle (Balanus amphitrite) settlement on synthetic hydrogels with various chemical structures was tested in laboratory assays. The results demonstrated that cyprids settle less or not at all on hydrogels and PDMS elastomer compared with the polystyrene control. The low settlement on gels is most likely due to the 'easy release' of initially attached cyprids from the gel surfaces. This low adhesion of cyprids is independent of surface hydrophilicity or hydrophobicity, and of surface charge. The results also revealed that hydrogels can be categorized into two groups. One group showed an extremely strong antifouling (AF) performance that was independent of the elasticity (E) or swelling degree (q) of the gels. The second group showed relatively less strong AF performance that was E- or q-dependent. In the latter case, E, rather than the q, may be the more important factor for cyprid settlement.

Prevalence of Mycoplasma genitalium among female students in vocational schools in Japan.

OBJECTIVE: In Japan it was reported that about 9% of sexually active female teenagers had Chlamydia trachomatis. Most of them were asymptomatic, which may lead to continuing spread of the infection. Like C trachomatis, Mycoplasma genitalium is a pathogen in male non-gonococcal urethritis. However, few studies of the prevalence of M genitalium in the general population have been reported. The objective of this study was to determine the prevalence of M genitalium infection among younger females and to determine risk factors for this infection. METHODS: The study was conducted between October 2005 and January 2006 using first voided urine specimens and questionnaires from female students of three vocational schools in the Miyazaki prefecture, Japan. C trachomatis was detected with Amplicor PCR. M genitalium was detected with inhibitor controlled real-time TaqMan PCR detecting the MgPa adhesion gene and with a PCR detecting the 16S rRNA. Risk factors associated with infection of M genitalium or C trachomatis were analysed with Fisher's exact test. RESULTS: Among 298 female, 249 (84%) had had experience of sexual intercourse. The prevalence of M genitalium was 2.8% (95% CI 0.76% to 4.86%) and the prevalence of C trachomatis was 8.8% (95% CI 5.31% to 12.36%). CONCLUSIONS: The risk factors of infection with M genitalium were more than five lifetime sexual partners and co-infection with C trachomatis.

Identification and characterization of Birt-Hogg-Dubé associated renal carcinoma.

The Birt-Hogg-Dubé (BHD) gene is responsible for BHD syndrome, a rare autosomal dominant disease, characterized by benign hair follicle tumours, spontaneous pneumothorax and renal neoplasms with diverse histology. To elucidate its involvement in the development of renal neoplasms, we examined a total of 100 sporadic renal tumours with various histological subtypes for BHD mutation by SSCP-sequencing analyses. We found one germline insertion mutation in the C8 hotspot of exon 11 (c.1733insC), which is known to have a strong association with renal tumour occurrence. The germline-mutated patient suffered from solitary renal cell carcinoma (RCC) but did not have any other BHD manifestations or family history. The tumour revealed heterogeneous cytomorphology, mainly a mixture of eosinophilic and focally clear cells with tubulopapillary architecture. In this tumour, both BHD alleles were inactivated by germline mutation concomitant with loss of heterozygosity, and the amount of BHD mRNA detected by real-time quantitative PCR (RQ-PCR) was very low. Renal tumour subtype/nephron segment-specific gene expression detected by RQ-PCR demonstrated that the tumour expressed relatively high amounts of alpha-methylacyl-CoA racemase (AMACR) and the KIT oncogene, but relatively low amounts of carbonic anhydrase IX (CA9), aquaporin 1 (AQP1), claudin 7 (CLDN7), parvalbumin (PVALB), chloride channel Kb (CLCNKB) and 11-beta-hydroxysteroid dehydrogenase 2 (HSD11B2), suggesting diverse mRNA signatures. Further clustering analysis of 88 renal tumours based on expression of these eight genes sub-classified the tumour as close to oncocytomas and chromophobe RCCs, which are considered distal nephron-associated tumours. These data suggest that somatic mutation of BHD is relatively rare in Japanese patients. The BHD-mutated RCC identified in this study, which exhibits heterogeneous biological features in both morphology and gene expression signatures, seems to deviate from our current understanding of renal tumour classification.

Glutathione S-transferase (GST) M1, T1 and N-acetyltransferase 2 (NAT2) polymorphisms and urothelial cancer risk with tobacco smoking.

The objective of this study was to examine the association between the genetic polymorphism of glutathione S-transferase (GST) M1, T1 and N-acetyltransferase 2 (NAT2) genes and urothelial cancer risk in relation to smoking status. In this study, 325 Japanese patients with urothelial transitional cell carcinoma and 325 healthy controls were compared for frequencies of GSTM1, T1 and NAT2 genotypes. The frequencies of GSTM1 null genotype and NAT2 slow genotype were significantly higher in the cases than in the controls (adjusted odds ratio (OR) 1.37, 95% confidence interval (CI) 1.01-1.87, adjusted OR 3.09, 95% CI 1.69-5.63, individually). Furthermore, the risk of GSTM1 null genotype and NAT2 slow genotype was higher among smokers (adjusted OR 1.48, 95% CI 1.01-2.15, adjusted OR 4.28, 95% CI 1.96-9.36, individually). The regression analysis of cancer risk as a function of the amount of smoking showed that the susceptibility of people who had GSTM1 null genotype increased from 45 pack-years, while the susceptibility of people with NAT2 intermediate or slow genotype increased rapidly from 25 pack-years, compared with non-smokers. A multiplicative interaction between NAT2 intermediate or slow genotype and pack-years of smoking was found (P<0.001), but GSTM1 null genotype was not (P=0.06). Our results indicate that the GSTM1 null genotype and NAT2 intermediate or slow genotype are associated with an increased risk of urothelial cancer in relation to smoking amounts. Furthermore, the interaction between NAT2 intermediate or slow genotype and pack-years of smoking has a strong impact on urothelial cancer.

Infant schistosomiasis in Ghana: a survey in an irrigation community.

We used a rapid, visually read, field applicable monoclonal antibody (MoAb)-dipstick assay for specific diagnosis of urinary schistosomiasis together with microscopy to determine the prevalence of infant schistosomiasis in a community in the Awutu-Efutu Senya District in the Central Region of Ghana. The study group consisted of 97 infants (51 males and 46 females) aged 2 months to 5 years. A total of 75 of 97 (77.3%) subjects submitted stool samples; none had Schistosoma mansoni. Three individuals (3.1%) had hookworms but there were no other intestinal helminths. The urinary schistosomiasis prevalence by MoAb-dipstick (30%) was higher (P < 0.05) than that estimated by microscopy (11.2%). However, three of nine (33.3%) microscopically confirmed cases tested MoAb-dipstick positive after pre-treatment of the urine specimen with heat. The youngest infant to be found infected with S. haematobium microscopically was 4 months old. Fifteen of 71 S. haematobium egg negative individuals tested dipstick positive, giving a dipstick specificity of 78.9% as compared with microscopy as gold standard test. The relative sensitivity of the dipstick was 100%.

The antibody responses to adult-worm antigens of Schistosoma haematobium, among infected and resistant individuals from an endemic community in southern Ghana.

Antibody responses to antigens from adult Schistosoma haematobium were investigated in an endemic community in Ghana, using microplate-ELISA. The results of a survey of egg output in urine and of a questionnaire-based investigation of water-contact activities were used to select 'endemic normal' (EN) and patently infected (PI) individuals as subjects. The plasma levels of antibodies reacting with the adult-worm antigens were determined and compared and the correlations between these levels and the age, water-contact index and egg output of each subject were evaluated. Compared with the EN subjects, the PI generally had higher levels of anti-worm IgG and IgE but lower levels of anti-worm IgA. When the data for the EN and PI groups were combined, the levels of anti-worm IgG and IgE were found to be positively correlated with egg output and with each other. Whichever the antibody class considered, levels of anti-worm antibodies were never negatively correlated with egg output. These results indicate that anti-worm IgE and IgG could be used as markers to reflect current infection intensity, and that anti-worm antibodies may not act as protective antibodies in the natural course of urinary schistosomiasis.

Fluorescence study of Cu(2+)-induced interaction between albumin and anionic polyelectrolytes.

The Cu(2+)-induced complex formation of bovine serum albumin (BSA) with anionic polyelectrolytes (PEs) (polyacrylic acid (PAA), poly(N-isopropylacrylamide) [poly[NIPAAm]], and copolymers of N-isopropylacrylamide (NIPAAm) and acrylic acid) in aqueous solution was studied by a fluorescence technique and high-performance liquid chromatography analysis. The character of the interactions depends on the monomer composition (r = [COOH]/[NIPAAm]), [Cu(2+)]/[PE], and [BSA]/[PE] ratios and solution pH. Two types of ternary polycomplex (polymer + Cu(2+) + BSA) particles are formed depending on the monomer composition r of the copolymer. At r from 1/3 to 1/1, the protein molecules in the structure of ternary polycomplex particles are densely covered by the shell of a polymer coil and practically "fenced off" from the water environment. At r > or = 3/1 ternary polycomplex PAA-Cu(2+)-BSA particles have more friable structures in which protein molecules are practically exposed to the solution. At low polymer concentration, an intrapolymer ternary polycomplex is formed. This complex aggregates to an interpolymer species upon increase in polymer concentration. Fluorescence data indicate that in ternary complex polymer interacts through Cu(2+) ions with BSA preferentially at the site close to the location of "cleft" tryptophan residue. This leads to static quenching of this tryptophan fluorescence. Cu(2+)-induced complex formation is an equilibrium reaction.

[An epidemiological study regarding the hearing acuity of residents in the area with high level of aircraft noise: results of hearing tests conducted in the vicinity of Kadena Air Base].

Hearing tests, primary and secondary, were conducted in two communities vicinal to Kadena US Air Base in Okinawa from May 1996 to July 1998. The noise exposure expressed in WECPNL as designated by the Defense Facilities Administration Agency ranged from 85 to 95 and above. A total of 2035 subjects aged between 25 and 69 years inclusive were considered eligible for inclusion in this study and among them 137 males and 206 females underwent the primary test. Before the test, subjects were asked about hearing difficulty, tinnitus, otological anamnesis and past experience of noise exposure at work and/or hobbies. The primary test was a pure tone audiometry using the ascending method of limits with 5 dB step at 7 test frequencies of 0.5 to 8 kHz. Forty individuals who were judged to have possible noise induced hearing loss were sent to Okinawa Chubu Hospital as subjects for the secondary test. The secondary test consisted of pure tone audiometry with 1 dB step at 9 test frequencies with the addition of 3 kHz and 6 kHz to the primary test frequencies, a Short Increment Sensitivity Index (SISI), test, tympanometry and audioscan audiometry. Based on test findings 12 subjects were considered to have noise induced hearing loss. The examiners interviewed the 12 subjects again to confirm that they had not experienced habitual or repeated intense noise exposure other than aircraft noise exposure around their homes. The geographical distribution of the subject's residences showed their proximity to the airfield, which strongly suggests that the cause of hearing loss may be exposure to aircraft noise from Kadena Air Base.

[Diagnosis of prostate capsular invasion by pelvic magnetic resonance imaging and serum level of prostate specific antigen].

Transrectal ultrasonography (TRUS), computed tomography (CT), and magnetic resonance imaging (MRI) are employed to diagnose the clinical stage of prostate cancer. However, several cases are diagnosed as pathological stage pT3 after total prostatectomy. We investigated the accuracy of the evaluation of pathologic capsular penetration by preoperative pelvic MRI and preoperative serum PSA level and capsular penetration. The diagnostic accuracy of capsular penetration by MRI was 63.3%. On the other hand, the diagnostic accuracy of capsular penetration by preoperative PSA was 89.7% when its cut off value was 17 ng/ml. We conclude that preoperative serum PSA level could be more useful to diagnose accurately stage of prostate cancer than pelvic MRI.

Water-soluble covalent conjugates of bovine serum albumin with anionic poly(N-isopropyl-acrylamide) and their immunogenicity.

We have conjugated bovine serum albumin (BSA) to poly(N-isopropylacrylamide-co-acrylic acid) (poly(NIPAAm-AA)) by using water-soluble carbodiimide, and the effects of the bulk mass ratio of protein to polymer (r) on the formation of polymer-protein conjugates have been studied. HPLC, electrophoresis, viscosimetry and fluorescence spectroscopy suggest that the mode of covalent binding of BSA to poly(NIPAAm-AA) depends upon the weight concentration ratio (r) of BSA to poly(NIPAAm-AA). At r < or = 1, free poly(NIPAAm-AA) molecules coexist with conjugate, and when r reaches 1 the amount of free polymer is too small to be observed. It is shown that depending on the ratio r, two types of conjugate particles were formed: at r < 1, the protein molecules in the structure of conjugate particles are densely covered as a shell by polymer chain and practically "fenced off" from water environment; at r > 1 the conjugate-forming particles possess more friable structures in which protein molecules are practically exposed to the solvent. The complex formation involving electrostatic interactions between BSA and carbodiimide activated polymer are proposed as the driving force for the covalent binding of BSA to polymer macromolecules. The coil-globule transition of macromolecules in low and thermally induced precipitation in more concentrated solutions of bioconjugates was observed. The immunogenic properties of covalent conjugates of CP-BSA were investigated and the temperature-modulated solubility-immunogenicity alterations was analyzed. A single immunization of mice with conjugates at the thermally precipitating concentration without an adjuvant evoked increased specific immune response to BSA, which practically did not depend on the initial conjugation ratio of components. Such a modulated system is attractive for application as a novel immunogenic system in vaccine technology.

Prophylactic intravesical instillation of mitomycin C and cytosine arabinoside for prevention of recurrent bladder tumors following surgery for upper urinary tract tumors: a prospective randomized study.

BACKGROUND: A recurrence of bladder tumors following surgery for transitional cell carcinoma of the upper urinary tract is not rarely observed. A prospective randomized study was conducted to examine the significance of prophylactic intravesical instillation of mitomycin C (MMC) and cytosine arabinoside (Ara-C) to prevent recurrent bladder tumors after surgery for superficial transitional cell carcinoma of the upper urinary tract. METHODS: The patients were randomized into an instillation group, who received postoperative intravesical instillation of MMC (20 mg) and Ara-C (200 mg) 28 times over a period of 2 years, and a non-instillation group. The non-recurrence rate was then compared between the groups. RESULTS: Of the 27 patients registered, 25 patients (13 with instillation and 12 without instillation) were able to be evaluated, with a median follow-up period of 45 months. The non-recurrence rate of bladder tumors in the instillation group was higher than that in the non-instillation group. Although the difference was not statistically significant, the P-value (P = 0.079) demonstrated a strong trend. When any possible bias was allowed for a multivariate analysis, the difference was almost significant (P = 0.0567). No patients withdrew from this study due to any side-effects. CONCLUSION: The postoperative instillation of MMC and Ara-C may be a useful approach for reducing the recurrence of bladder tumors after surgery for upper urinary tract tumors.

[Small cell carcinoma of the prostate: a case report].

A 81-year-old man was admitted to our department with the chief complaints of pollakisuria and difficulty in voiding. He presented with increased serum PSA level (over 100 ng/ml). We performed biopsy of the prostate and found a moderately differentiated adenocarcinoma. Various urological examinations showed metastases to paraaortic lymph nodes and systemic bones. He was started-on hormonal therapy. Nine months from the start of hormonal therapy, this therapy was effective and the serum PSA level was decreased to 14 ng/ml. Thereafter, the serum PSA level and the tumor volume were increased and he died 29 months from the start of treatment. The autopsy revealed small cell carcinoma with adenocarcinoma of the prostate.

Protective immunity to Schistosoma japonicum infection depends on the balance of T helper cytokine responses in mice vaccinated with gamma-irradiated cercariae.

Although the strain difference in protection of mice to Schistosoma mansoni infection has been described, limited information is available in the case of Schistosoma japonicum. In the present study, we compared the protective immunity to S. japonicum infection and cytokine production in various strains of mice vaccinated with gamma-irradiated cercariae. A significant reduction in worm recovery was observed in male and female mice of DBA/2 at a 6-week interval between vaccination and a challenge infection, whereas vaccinated mice of C57BL/6, C57BL/10, (C57BL/6 x DBA/2) F1 (B6D2F1) and (C57BL/10 x DBA/2) F1 (B10D2F1) showed no detectable level of protection. No sex-linked difference in development of resistance was observed in any of the strains so far examined. Vaccination with gamma-irradiated cercariae twice with a 3-week interval also induced significant protection against a challenge infection in DBA/2 but not in BALB/c or C57BL/6 strains. Further studies demonstrated that spleen cells of vaccinated C57BL/6 mice produced lower levels of IFN-gamma compared to the cells of vaccinated BALB/c and DBA/2. On the other hand, production of IL-10 by spleen cells was relatively higher in BALB/c mice than in the other two strains. Macrophages that had been stimulated with spleen cell culture supernatants derived from vaccinated DBA/2 damaged schistosomula more effectively than cells stimulated with supernatants derived from the other strains. These results suggest that different levels of protection observed among strains of mice depend on the balance of cytokine responses which consequently activate or suppress macrophage-mediated damage to schistosomula.