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Introduction: Dental problems may have a great impact on military mission effectiveness, as such, evidence-based dental classification guidelines are required for minimizing the occurrence of dental problems. The aim of this study is to elucidate the independent contribution of each oral disease to the perception of dental problems among Japan Maritime Self-Defense Force (JMSDF) personnel in order to make the dental classification guidelines more precise for the prediction of future dental problems.Materials and Methods: Japan Maritime Self-Defense Force personnel who were examined during the annual dental checkup in 2013 answered questions about the experience of dental problems within the last 12 months in 2014. The associations between the items of a dental checkup and the perception of dental problems were examined using multiple logistic regression analysis with a stepwise procedure to calculate odds ratios (ORs) and 95% CIs.Results: The data of a total of 22,441 subjects were included in the analysis. Those who declared to have perceived dental problems within the last 12 months were 5,088 (22.7%). The multiple logistic regression analysis showed that personnel who had decayed teeth had a higher chance of experiencing dental problems than those who had no dental caries. Personnel whose periodontal disease was judged to be more severe in a dental examination had a greater OR for the perception of dental problems.Conclusion: These results may become recommendations for operations in the JMSDF dental classification system. [ABSTRACT FROM AUTHOR]

We have performed a Zero-K Monte Carlo simulation for F/AF coupled systems of simple cubic structure. No combination of parameters, J[SUBF-AF]/J[SUBF-F] and J[SUBAF-AF]/J[SUBF-F] (J[SUBF-F], J[SUBAF-AF] and J[SUBF-AF] are exchange constant between F-F, AF-AF, and F-AF spins, respectively) ranging between 0.1 and 1 has been found, assuming K[SUBu]/J[SUBF-F] = 0.01 (K[SUBu]: uniaxial anisotropy coefficient), which gives unidirectional anisotropy in the sense that the energy exhibits 360° symmetry dependence on the F-magnetization direction. However, by assuming the existence of a plane in the AF-layer across which the AF-spins couple loosely with each other, it is demonstrated that a typical 360° symmetry anisotropy appears without assuming any AF-spin constraint in the plane. [ABSTRACT FROM AUTHOR]

Electrical resistivity and its thermal coefficient (TCR) of TiW alloy thin films which were prepared by using two different sputtering systems have been investigated. System A is a DC-magnetron sputtering system equipped with a single composite-target that allows the contents controllable by an external field of solenoid as reported in previous papers (Sakurai and Takeda, Abstract of E-MRS 2005 Fall Meeting [1] and Sakurai et al., Solid State Phenom. 154, 175 (2009) [2]). The system A prepared specimens with the range of 21.6 to 36.6 at% of W-contents. The TCR varies from minus to plus at 32 at% of W-content. On the other hand, System B is a RF-magnetron sputtering system equipped with multi-targets and multi-sputtering-sources. The system B covered the whole binary composition ranges by controlling power ratio for two independent sputtering sources. The resistivity characteristics show a parabolic curve with the maximum value on Ti-rich contents. The TCR decreases at the contents that shows the maximum resistivity, but the TCR is always plus and does not cross zero. Difference of the properties by using the two systems will be discussed. In the system A, the background is exhausted by an oil diffusion pump and the pressure is higher (lower vacuum degree) than the background in the system B with a turbo molecular pump. This suggests that zero TCR would be achieved by introducing the controlled impurities (O2 or N2) into the binary alloy films. (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [ABSTRACT FROM AUTHOR]

Since its discovery, unidirectional anisotropy appearing in exchange coupled ferromagnetic (F)/antiferromagnetic (AF) layers has been used to pin ferromagnetic layers of various spin devices. However, a fundamental understanding is still lacking. The author has already demonstrated a mechanism based on simply assuming a loosely coupled layer in the AF region, without imposing any restrictions on the classical Heisenberg spins, with perfect compensated and uncompensated AF interfaces on the simple cubic (sc) lattice. The difference between compensated and uncompensated is only the F/AF coupling form (spin flop or collinear) interaction, and unidirectional anisotropy does not depend on the compensated or uncompensated case, but appears as a result of introducing loose coupling in the AF region. The unidirectional anisotropy energy does not come from the F/AF interfaces, but from the inner AF coupling defects. As reported in our previous papers, a large decrease in AF interaction from 1/10 to 1/1000 of the usual AF interaction was necessary in order to obtain unidirectional anisotropy in the systems. Correspondence between loose coupling and the defect mode, cell size dependency in the fcc system, and thickness dependency are topics for future investigation. © 2011 Wiley Periodicals, Inc. Electron Comm Jpn, 94(9): 36-44, 2011; Published online in Wiley Online Library (). DOI 10.1002/ecj.10352 [ABSTRACT FROM AUTHOR]

Abstract: Objective: To investigate associations between blood low-density lipoprotein cholesterol (LDL-C) levels and the prevalence of acquired color vision impairment (ACVI) in middle-aged Japanese men. Methods: Participants in this cross-sectional study underwent color vision testing, ophthalmic examination, a standardized interview and examination of venous blood samples. Ishihara plates, a Lanthony 15-hue desaturated panel, and Standard pseudoisochromatic Plates part 2 were used to examine color vision ability. The Farnsworth–Munsell 100-hue test was performed to define ACVI. Smoking status and alcohol intake were recorded during the interview. We performed logistic regression analysis adjusted for age, LDL-C level, systemic hypertension, diabetes, cataract, glaucoma, overweight, smoking status, and alcohol intake. Adjusted odds ratios for four LDL-C levels were calculated. Results: A total of 1042 men were enrolled, 872 participants were eligible for the study, and 31 subjects were diagnosed with ACVI. As compared to the lowest LDL-C category level (<100mg/dl), the crude OR of ACVI was 3.85 (95% confidence interval [CI], 1.24–11.00) for the 2nd highest category (130–159mg/dl), and 4.84 (95% CI, 1.42–16.43) for the highest level (≥160mg/dl). The multiple-adjusted ORs were 2.91 (95% CI, 0.87–9.70) for the 2nd highest category and 3.81 (95% CI, 1.03–14.05) for the highest level. Tests for trend were significant (P <0.05) in both analyses. Conclusions: These findings suggested that the prevalence of ACVI is higher among middle-aged Japanese men with elevated LDL-C levels. These changes might be related to deteriorated neurologic function associated with lipid metabolite abnormalities. [Copyright &y& Elsevier]

Objective. The Japanese have a higher intake of fish and a lower incidence of asthma than occupants of western countries. The present epidemiological study investigated the relationship between dietary fish intake and the prevalence of asthma among a childhood population.Methods. Subjects represented all public elementary and junior high schools in Tokorozawa City in Japan (age range: 6–15 years old). The study population included 1,673 currently asthmatic students and 22,109 controls. Participants'' parents completed the Japanese version of American Thoracic Society and Division of Lung Diseases, National Heart, Lung, and Blood Institute questionnaire for children, adopted by the Japan Environment Agency. We added supplementary questions (e.g., parental history of asthma and questions about frequency of foods eaten, including frequency of fish intake). Odds ratios for cases of current asthma according to frequency of fish intake were calculated, and a logistic regression analysis was used to adjust for possible confounding variables.Results. After adjustments for age, gender, parental history of asthma, and vegetables and fruits intake, a significantly higher prevalence of asthma was noted among subjects who ate fish one to two times a week than among those who ate fish one to two times a month (adjusted odds ratio: 1.117; 95% confidence interval: 1.005–1.241; P = 0.041). The risk increased gradually with increasing frequency of fish intake, and the positive trend was statistically significant.Conclusions. The results indicated that frequency of fish intake was positively related to the prevalence of asthma. This result might have important implications for health. [Copyright &y& Elsevier]

In a ferromagnetic (F)/antiferromagnetic (AF) exchange coupled bilayer, we have recently demonstrated by 0 K Monte Carlo simulation using classical nearest neighbor Heisenberg model for an sc lattice system that a typical unidirectional anisotropy can be induced, even for the compensated AF interface, by just assuming a loosely coupled interface within the AF-layer. In this study, we have applied the loosely coupled layer model to FCC(0 0 1) and FCC(1 1 1) AF-interfaces. It has turned out that the model can cause a unidirectional anisotropy for (1 1 1) interfaces, but not for (0 0 1). The unidirectional anisotropy can be attributed to loosely coupled FCC(1 1 1) AF-interface energy, but almost no interface energy is generated in case of FCC(0 0 1) since the nearest-neighbor exchange coupling is canceled out leaving substantially weak exchange coupling between them. [Copyright &y& Elsevier]

Inflammation is known to be involved in the progression of diabetic retinopathy. We have recently reported that vitreous levels of IL-4, IL-17A, IL-22, IL-31, and TNFα are higher than the respective serum levels in proliferative diabetic retinopathy (PDR) patients, and that vitreous levels of these cytokines are higher in PDR than in other non-inflammatory vitreoretinal diseases or uveitis associated with sarcoidosis. In the present study, we investigated inflammatory cytokines including Th17 cell-related cytokines in aqueous humor samples obtained from eyes with PDR, and analyzed the association between the aqueous humor and vitreous fluid levels of individual cytokines. The study group consisted of 31 consecutive type 2 diabetic patients with PDR who underwent cataract surgery and vitrectomy for vitreous hemorrhage and/or tractional retinal detachment. Undiluted aqueous humor was collected during cataract surgery, and then vitreous fluid was obtained using a 25G vitreous cutter inserted into the mid-vitreous cavity at the beginning of vitrectomy. IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, soluble CD40 ligand (sCD40L), and TNFα levels in the aqueous humor and vitreous fluid were measured using a beads-array system. Although IL-17A was detected in the aqueous humor of eyes with PDR and the level correlated with IL-17A level in the vitreous fluid, both percent detectable and level of IL-17A in the aqueous humor were significantly lower than those in the vitreous fluid. Vitreous IL-17A level was related significantly to IL-10, IL-22, and TNFα levels in aqueous humor as well as in vitreous fluid, On the other hand, aqueous IL-17A level was not related significantly to aqueous or vitreous levels of IL-10, IL-22 or TNFα level. The present study demonstrated that IL-17A level and detectable rate in the aqueous humor of patients with PDR are markedly lower than those in the vitreous fluid and aqueous IL-17A does not correlate with vitreous levels of other cytokines, and hence should not be used as a surrogate for IL-17A in the vitreous fluid. [ABSTRACT FROM AUTHOR]

Context: Dental caries are an infectious oral bacterial disease caused by cariogenic streptococci. These streptococci inhabit dental biofilms which comprise insoluble glucans. Objective: To prevent dental caries, nisin, a suitable agent active against Gram-positive bacteria, was examined in vitro for its ability to suppress insoluble glucan-biofilm synthesis by cariogenic streptococci. Materials and methods: To investigate glucan-biofilm synthesis by a typical cariogenic streptococcus, Streptococcus mutans 10449, the naked form of nisin was loaded onto a 96-well microplate in vitro model. To prolong the efficacy of nisin as a preventive agent, liposome-encapsulated nisin (nisin-liposome) was examined for its ability to inhibit the synthesis of glucan-biofilms on microplates. Results: Naked nisin (100 pmol) completely suppressed insoluble glucan-biofilm synthesis by S. mutans 10449 following 1 h cultivation in 96-well microplates. The concentration of nisin-liposome required for the efficacious inhibition of glucan-biofilm synthesis was four times lower than that of naked nisin following 2 h cultivation. In particular, nisin-liposome (30 pmol nisin equivalent) prolonged the inhibitory activity of nisin against glucan-biofilm synthesis by S. mutans 10449 for up to 6 h, while naked nisin (30 pmol) gradually lost this inhibitory activity over the same period. In vitro release assay of nisin from the liposome showed that 76% nisin was released within 6 h. Discussion and conclusion: The findings indicate the usefulness of nisin-liposome for the sustained release of nisin. Thus, nisin-liposome could play a potential role in preventive medicine as an inhibitor of the glucan-biofilm synthesis. [ABSTRACT FROM AUTHOR]

: PurposeOther than age, the risk factors for postherpetic neuralgia are not well established. We studied whether the concentration of interleukin 8 in the cerebrospinal fluid is associated with the risk of postherpetic neuralgia.: MethodsWe enrolled 170 patients more than 50 years old who had a typical painful and nontrigeminal herpetic rash. Patients were treated with acyclovir; no corticosteroids were given. Cerebrospinal fluid was taken for analysis of interleukin 8 during and at full crusting of the herpetic rash. Age, sex, comorbid conditions, prodromal pain, localization and severity of herpetic rash, number of skin lesions, and degree of pain were recorded. We used multivariate logistic regression modeling to identify significant predictive factors. Receiver operating characteristic (ROC) curves were evaluated to determine the contribution of each factor.: ResultsSix months after healing, 31 patients (18%) had postherpetic neuralgia; 27 patients still had it after 1 year. Only three variables—age (odds ratio [OR] = 2.7 per 10-year increase; 95% confidence interval [CI]: 1.2 to 6.2), acute pain (OR = 1.8 per unit increase in visual analog scale; 95% CI: 1.2 to 2.8), and interleukin 8 concentration in the cerebrospinal fluid at full crusting of the herpetic rash (OR = 1.6 per 20-μg/L increase; 95% CI: 1.3 to 2.0)—were significant predictors of postherpetic neuralgia at 1 year. Interleukin 8 concentration also had the highest area under the ROC curve at these evaluation points (P <0.001).: ConclusionOur results suggest that interleukin 8 concentration in the cerebrospinal fluid at full crusting of herpetic rash may be useful for identifying patients who are likely to develop intractable postherpetic neuralgia. [Copyright &y& Elsevier]

Purpose: To evaluate real‐world evidence for young Japanese patients with rhegmatogenous retinal detachment (RRD) by retrospectively examining surgical procedures and clinical outcomes in the Japan Clinical Retina Study group. Methods: This was a multicentre retrospective study of the medical records of 562 young patients (384 males and 178 females; mean age: 33.0 ± 11.8 years) who had been diagnosed with RRD and who underwent surgical procedures in participating centres during the period between April 2013 and August 2016. Results: The selected surgeries were scleral buckling (SB) for 295 eyes (49.7%) and pars plana vitrectomy (PPV) for 262 eyes (44.1%). Between the two surgical procedures, there was no significant difference in the primary anatomical reattachment rate (PARR, SB = 92.2%, PPV = 93.9%); improvements in vision were noted in both groups. The incidences of proliferative vitreoretinopathy and cataract formation within 1 year of PPV were 2.3% (p = 0.0047) and 6.5% (p = 0.0005), whereas they were 0% and 1.0% in the SB group, respectively. Conclusion: Scleral buckling (SB) and PPV were chosen with almost equal frequency for young patients with RRD. Clinical outcomes for SB and PPV exhibited a similar PARR. The incidence of cataract formation after PPV may constitute an important limitation of the procedure. [ABSTRACT FROM AUTHOR]

The distribution of age at diagnosis in ocular sarcoidosis has shifted towards the older age groups in developed countries. In systemic sarcoidosis, age-related differences in the clinical presentation, which reflect the therapeutic strategies, was reported. We retrospectively compared 100 consecutive patients from April 2010 to March 2016 who were initially diagnosed with ocular sarcoidosis by International Workshop on Ocular Sarcoidosis criteria. They were classified into elder (>65 years: 50 patients) and younger (≤65 years: 50 patients) groups by the age at diagnosis of uveitis associated with sarcoidosis. All patients received ophthalmic examination to assess the presence of seven intraocular signs and 4 laboratory parameters. Significantly fewer ocular signs (2.8 ± 1.5 and 3.6 ± 1.5; P = 0.0034) and abnormal laboratory results (1.5 ± 1.2 and 2.0 ± 1.2; P = 0.023) were detected in the elder group than in the younger group; statistical differences were found between the groups regarding the frequencies of mutton-fat keratic precipitates (40% and 64%; P = 0.012), vitreous opacities (60% and 78%; P = 0.0059), bilateral inflammation (64% and 80%; P = 0.012), and bilateral hilar lymphadenopathy between the groups (52% and 78%; P < 0.001). Multiple linear regression analysis showed negative correlations between age and number of detected ocular signs (r = −0.36, P < 0.001) and laboratory results (r = −0.20, P = 0.023). The characteristic ocular signs and abnormal laboratory results had a lower frequency in the elder patients compared with the younger patients. Probable or possible ocular sarcoidosis by the international criteria should increase with increased life expectancy in developed countries. [ABSTRACT FROM AUTHOR]

Purpose: We report a case of topical corticosteroid treatment-resolved rubeosis iridis with neovascular glaucoma (NVG) caused by noninfectious granulomatous uveitis. Case Report: A 61-year-old woman with left ocular pain and blurred vision was referred to our department. Visual acuity and intraocular pressure (IOP) were 20/60 and 37 mm Hg in the left eye, respectively. Inflammatory cells, hyphema, and rubeosis iridis were observed. All laboratory tests, including multiplex polymerase chain reaction for infection using aqueous humor, were negative, and there was neither retinal occlusive vasculitis nor retinal ischemia in the fundus. Our diagnosis was noninfectious granulomatous anterior uveitis-associated NVG. Topical corticosteroid treatment and anti-glaucoma agents resolved inflammation, rubeosis iridis, and NVG. IOP had decreased to 13 mm Hg by 1 month of treatment, and no recurrence was observed. Conclusion: Topical corticosteroid could resolve rubeosis iridis and NVG in an eye with noninfectious anterior uveitis. The pathogenesis of NVG in eyes with uveitis is still unknown, but inflammation might have a part in angiogenesis. Anti-inflammatory treatment can be selected as the first choice for anterior uveitis-associated NVG. [ABSTRACT FROM AUTHOR]

Although the effects of dipeptidyl peptidase 4 (DPP-4) inhibitors beyond their hypoglycemic action have been reported, whether these inhibitors have renoprotective effects in nondiabetic chronic kidney disease (CKD) is unclear. We examined the therapeutic effects of DPP-4 inhibition in mice with unilateral ureteral obstruction (UUO), a nondiabetic model of progressive renal fibrosis. After UUO surgery, mice were administered either the DPP-4 inhibitor alogliptin or a vehicle by oral gavage once a day for 10 days. Physiological parameters, degrees of renal fibrosis and inflammation, and molecules related to renal fibrosis and inflammation were then evaluated using sham-operated mice as controls. Positive area of α-smooth muscle actin was significantly smaller and expression of transforming growth factor β messenger RNA was significantly lower in the alogliptin-treated group than in the vehicle-treated group. Renal total collagen content was also significantly lower in the alogliptin-treated group than in the vehicle-treated group. These results suggest that alogliptin exerted renoprotective antifibrotic effects. The positive area of F4/80 was significantly smaller and expression of CD68 messenger RNA was significantly lower in the alogliptin-treated group than in the vehicle-treated group, suggesting an anti-inflammatory action by the DPP-4 inhibitor. Compared to the results for the vehicle-treated group, expression of markers for M1 macrophages tended to be lower in the alogliptin-treated group, and the relative expression of M2 macrophages tended to be higher. These data indicate the various protective effects of DPP-4 inhibition in nondiabetic mice with UUO. DPP-4 inhibitors may therefore be promising therapeutic choices even for nondiabetic CKD patients. [ABSTRACT FROM PUBLISHER]

Purpose: To compare latanoprost/timolol (LT) versus travoprost/timolol (TT) fixed combinations for ocular hypertension (OHT) associated with uveitis.Methods: Thirty-six patients (55 eyes) who were treated with LT (28 eyes) or TT (27 eyes) for OHT associated with uveitis were reviewed retrospectively. Intraocular pressure (IOP) and inflammation scores at the initiation of treatment and at the last visit during therapy were analyzed.Results: Although IOP was reduced significantly in both LT and TT groups, the reduction rate was significantly greater with TT group than with LT. The differences in the reduction of IOP between the groups remained significant when the cases were classified into inflammation-induced OHT and steroid-induced OHT. Inflammation score was not exacerbated by LT or TT treatment.Conclusions: Both LT and TT are safe and effective for the treatment of OHT associated with uveitis and greater IOP reduction may be achieved by TT than by LT treatment. [ABSTRACT FROM AUTHOR]

Little is known regarding the incidence of the shoulder instability in Japan. The aim of this study was to evaluate the incidence of traumatic shoulder instability among Japanese military cadets. A prospective cohort study was performed to capture all traumatic shoulder instability events between 2009 and 2012 among cadets in a military educational academy of the Japan Self Defense Forces. The total number of cadets in the cohort was 5,402 (average age 20.6 years). The incidence of instability events, including dislocation or subluxation, was calculated. Chronicity, demographics of participants, mechanism of injury, and athletic events were also evaluated. The incidence of traumatic dislocation was 4.1/1,000 person-years and that of subluxation was 6.1/1,000 person-years. The incidence of primary dislocation or subluxation was 5.4/1,000 person-years and that of recurrent dislocation or subluxation was 4.7/1,000 person-years. Of first dislocations or subluxations, 92% occurred during sports activities, including after-school sports activities, military training, and gym classes. In conclusion, the overall incidence of shoulder instability events among Japanese military cadets was 10.3/1,000 person-years, and was extremely high. Most shoulder instability events occurred during sports activities, and a program to prevent such injuries during sports activities is necessary for young participants. [ABSTRACT FROM AUTHOR]

Macrophages are involved in low-grade inflammation in diabetes, and play pathogenic roles in proliferative diabetic retinopathy (PDR) by producing proinflammatory cytokines. T cells as well as other cells are also activated by proinflammatory cytokines, and infiltration into the vitreous of patients with PDR has been shown. In this study, we measured helper T (Th) cell-related cytokines in the vitreous of PDR patients to define the characteristics of Th-mediated immune responses associated with PDR. The study group consisted of 25 type 2 diabetic patients (25 eyes) with PDR. The control group consisted of 27 patients with epiretinal membrane (ERM), 26 patients with idiopathic macular hole (MH), and 26 patients with uveitis associated with sarcoidosis. Vitreous fluid was obtained at the beginning of vitrectomy, and centrifuging for cellular removals was not performed. Serum was also collected from PDR patients. IL-1β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, IFN-γ, soluble sCD40L, and TNFα in the vitreous and serum samples were measured. Both percent detectable and levels of IL-4, IL-6, IL-17A, IL-21, IL-22, and TNFα in the vitreous were significantly higher than those in the serum in PDR patients. Vitreous levels of these cytokines and IL-31 were significantly higher in PDR than in ERM or MH patients. Vitreous levels of IL-4, IL-17A, IL-22, IL-31, and TNFα in PDR patients were also significantly higher than those of sarcoidosis patients. In PDR patients, vitreous IL-17A level correlated significantly with vitreous levels of IL-22 and IL-31, and especially with IL-4 and TNFα. Although it is unclear whether these cytokines play facilitative roles or inhibitory roles for the progression of PDR, the present study indicated that Th2- and Th17-related immune responses are involved in the pathogenesis of PDR. [ABSTRACT FROM AUTHOR]

ATP-binding cassette transporter, sub-family G, member 2 (ABCG2/BCRP) is identified as a high-capacity urate exporter, and its dysfunction has an association with serum uric acid levels and gout/hyperuricemia risk. Generally, hyperuricemia has been classified into urate “overproduction type,” “underexcretion type,” and “combined type” based on only renal urate excretion, without considering an extra-renal pathway such as gut excretion. In this study, we investigated the effects of ABCG2 dysfunction on human urate handling and the mechanism of hyperuricemia. Clinical parameters for urate handling including urinary urate excretion (UUE) were examined in 644 Japanese male outpatients with hyperuricemia. The severity of their ABCG2 dysfunction was estimated by genotype combination of two common ABCG2 variants, nonfunctional Q126X (rs72552713) and half-functional Q141K (rs2231142). Contrary to the general understanding that ABCG2 dysfunction leads to decreased renal urate excretion, UUE was significantly increased by ABCG2 dysfunction (P = 3.60 × 10−10). Mild, moderate, and severe ABCG2 dysfunctions significantly raised the risk of “overproduction” hyperuricemia including overproduction type and combined type, conferring risk ratios of 1.36, 1.66, and 2.35, respectively. The present results suggest that common dysfunctional variants of ABCG2 decrease extra-renal urate excretion including gut excretion and cause hyperuricemia. Thus, “overproduction type” in the current concept of hyperuricemia should be renamed “renal overload type,” which is caused by two different mechanisms, “extra-renal urate underexcretion” and genuine “urate overproduction.” Our new concept will lead to a more accurate diagnosis and more effective therapeutic strategy for hyperuricemia and gout. [ABSTRACT FROM AUTHOR]

Background The therapeutic effect of tonsillectomy for immunoglobulin A nephropathy (IgAN) has been widely recognized, but the mechanism by which tonsillar immunity leads to glomerulonephritis has been unclear. We investigated subtypes and localization of dendritic cells (DCs) in tonsils and looked for relationships between the tonsillar DCs and the clinical features and renal histological changes of patients with IgAN. Methods We examined tonsils from 33 IgAN patients, using as control tonsillar specimens from subjects without glomerulonephritis. Five distinct markers of DCs (CD303, CD1c, CD209, CD208 and CD1a) were analyzed by immunohistochemistry and flow cytometry. The mRNA levels of these DC markers were evaluated using real-time polymerase chain reaction. The clinical data and histological results obtained evaluating renal biopsy tissues were statistically compared with immunological data. Results Of the five subtypes of DCs, CD208+ DCs were significantly increased in the tonsils of IgAN patients compared with that of controls. Furthermore, the number of CD208+ DCs in the tonsils was positively and linearly correlated with the proportion of crescentic glomeruli in renal biopsy tissues and with the urinary protein level. Only few CD208+ cells, however, were found in the kidney biopsy specimens of IgAN patients. Conclusions These observations suggest that increased CD208+ DCs in tonsils may play a directive role in the pathogenesis of IgAN. The present results support the therapeutic significance of tonsillectomy for IgAN patients. [ABSTRACT FROM AUTHOR]

The protective effects of Rho kinase inhibitor fasudil against renal diseases have recently been reported. We compared the therapeutic effects of fasudil on the spontaneously hypercholesterolemic (SHC) rat, a model of chronic kidney disease (CKD) with proteinuria, with those of the angiotensin receptor blocker olmesartan (OL) by paying attention to the proteinuria and the macrophage phenotype. SHC rats were allocated to six treatment groups: a vehicle (Ve) group, a low-dose fasudil (FL) group, a high-dose fasudil (FH) group, an OL group, a combination of low-dose fasudil and OL (CL) group, and a combination of high-dose fasudil and OL (CH) group. Sprague-Dawley rats treated with vehicle served as a control (n 7/each). The rats were treated for 24 wk. Compared with the Ve group, proteinuria was significantly decreased in the FH, OL, and CL groups, and it completely disappeared in the CH group. Glomerular stainings of nephrin and F-actin were focally impaired in the Ve group but were restored in the CH group. Western blotting showed that the CH group had significantly increased renal nephrin expression compared with the Ve group. Interstitial infiltration of macrophages was significantly increased in the Ve group, which was significantly attenuated in all treatment groups. The ratio of CD206 (M2 macrophage marker) to CD68 mRNA was significantly greater in the CH group than in the Ve group. These results indicate that fasudil with OL reduces proteinuria by protecting podocyte integrity and alters the interstitial macrophage density/phenotype, thereby exerting renoprotective effects against CKD. [ABSTRACT FROM AUTHOR]

Aims Endothelin-1 (ET-1) contributes to the pathogenesis of cardiovascular diseases with multiple properties such as vasoconstriction. Human ET-1 gene expression is up-regulated by the transcription factor hypoxia-inducible factor-1 (HIF-1) through hypoxia response element (HRE). Although previous studies suggested that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) alter HIF-1-related gene expression, it remained unclear whether statins modulate HIF-1-mediated ET-1 expression. Therefore, we investigated the effect of fluvastatin on hypoxia-induced human ET-1 expression in vascular smooth muscle cells (VSMC). Methods and results Hypoxia (1% O2), compared with the normoxic condition (21% O2), significantly induced the expression of preproET-1 mRNA, ET-1 protein, and ET-1 secretion in VSMC. Hypoxia induced a 2.3-fold increase in HRE-dependent ET-1 reporter gene activation. Under concentrations of 1 µmol/L or greater, fluvastatin attenuated the hypoxia-induced ET-1 gene expression through the accelerated ubiquitin/proteasome-dependent degradation of HIF-1α, thus consequently attenuating HIF-1α binding to the HRE of the ET-1 gene. These inhibitory effects of fluvastatin were cancelled by concomitant treatment with mevalonate, farnesyl pyrophosphate, or geranylgeranyl pyrophosphate, but not squalene. Conclusion The present study suggests that fluvastatin attenuates HIF-1-dependent ET-1 gene expression in conjunction with the stimulation of HIF-1α ubiquitin/proteasome-dependent degradation via isoprenoid-dependent mechanisms. [ABSTRACT FROM PUBLISHER]

It is well known that glomerulonephritis can occur after streptococcal infection, which is classically referred to as acute poststreptococcal glomerulonephritis (APSGN). The pathogenic mechanism of APSGN has been described by so-called immune complex theory, which involves glomerular deposition of nephritogenic streptococcal antigen and subsequent formation of immune complexes in situ and/or the deposition of circulating antigen-antibody complexes. However, the exact entity of the causative antigen has remained a matter of debate.We isolated a nephritogenic antigen for APSGN from the cytoplasmic fractions of group A streptococcus (GAS) depending on the affinity for IgG of APSGN patients. The amino acid and the nucleotide sequences of the isolated protein revealed to be highly identical to those of reported plasmin(ogen) receptor of GAS. Thus, we termed this antigen nephritis-associated plasmin receptor (NAPlr). Immunofluorescence staining of the renal biopsy tissues with anti-NAPlr antibody revealed glomerular NAPlr deposition in essentially all patients with early-phase APSGN. Furthermore, glomerular plasmin activity was detected by in situ zymography in the distribution almost identical to NAPlr deposition in renal biopsy tissues of APSGN patients. These data suggest that NAPlr has a direct, nonimmunologic function as a plasmin receptor and may contribute to the pathogenesis of APSGN by maintaining plasmin activity. [ABSTRACT FROM AUTHOR]

It is well known that glomerulonephritis can occur after streptococcal infection, which is classically referred to as acute poststreptococcal glomerulonephritis (APSGN). The pathogenic mechanism of APSGN has been described by so-called immune complex theory, which involves glomerular deposition of nephritogenic streptococcal antigen and subsequent formation of immune complexes in situ and/or the deposition of circulating antigen-antibody complexes. However, the exact entity of the causative antigen has remained a matter of debate.We isolated a nephritogenic antigen for APSGN from the cytoplasmic fractions of group A streptococcus (GAS) depending on the affinity for IgG of APSGN patients. The amino acid and the nucleotide sequences of the isolated protein revealed to be highly identical to those of reported plasmin(ogen) receptor of GAS. Thus, we termed this antigen nephritis-associated plasmin receptor (NAPlr). Immunofluorescence staining of the renal biopsy tissues with anti-NAPlr antibody revealed glomerular NAPlr deposition in essentially all patients with early-phase APSGN. Furthermore, glomerular plasmin activity was detected by in situ zymography in the distribution almost identical to NAPlr deposition in renal biopsy tissues of APSGN patients. These data suggest that NAPlr has a direct, nonimmunologic function as a plasmin receptor and may contribute to the pathogenesis of APSGN by maintaining plasmin activity. [ABSTRACT FROM AUTHOR]

Background. Long-term peritoneal dialysis (PD) causes morphologic and functional changes in the peritoneum that hamper the continuation of PD therapy. Because macrophages play important roles in the development of peritoneal fibrosis and liposome-encapsulated clodronate (LC) induces macrophage apoptosis, we examined the effect of LC on chlorhexidine gluconate (CG)-induced peritoneal fibrosis in rats. Methods. Fifty Sprague–Dawley rats were randomly allocated into five groups of 10 receiving intraperitoneal (i.p.) injections (1.5 mL/100 g) of either 0.1% CG (four groups) or vehicle (one group) three times a week. Three of the CGtreated groups also received intravenous injections of clodronate twice a week: 10 mg of LC, 20 mg of LC or 20 mg of unencapsulated clodronate (UC20). Twenty-one days after the first i.p. injection, the rats were sacrificed and the parietal peritoneum was harvested. Results. The number of peritoneal macrophages in the rats given clodronate was significantly smaller than that in rats not given clodronate (92.0 6 4.6 cells per field). It was 54.1 6 3.2 cells per field in the group given 20 mg UC, 43.2 6 5.2 cells per field in the group given 10 mg LC and 27.2 6 2.8 cells per field in the group given 20 mg LC. This decrease in macrophage number was paralleled by decreases in peritoneal thickening, in the number of mesothelial cells staining positive for cytokeratin and a-smooth muscle actin and in messenger RNA expression for transforming growth factor-b1 and collagen types I and III. Conclusions. These data suggest that macrophages play a critical role in the development of peritoneal fibrosis and that LC may be useful for treating peritoneal fibrosis in PD patients. [ABSTRACT FROM AUTHOR]

BSTRACT [ABSTRACT FROM AUTHOR]

A total of 300 stool samples collected from 213 Japanese residents of Egypt were examined microscopically. Among these samples, 39 were judged positive for heterophyid eggs. Sixty seven residents were examined repeatedly. The prevalence of heterophyid eggs revealed by the first examination samples was 8.5% (18/213) whereas that revealed by the second follow-up was 24% (16/67). The interval between the first and second examination was one year in 58 cases and 2 years in 9 cases. The association of infection with the length of stay in Egypt was evident. Positivity among new residents (period of stay in Egypt < 1 year) was as low as 3% (2/60). Positive conversion from new residents was observed in 28% (7/25), indicating a positive association between heterophyid infection and the length of stay in Egypt among Japanese residents of that country. [ABSTRACT FROM AUTHOR]

Aim: To examine the additive protective effects of the peroxisome proliferator-activated receptor-γ agonist pioglitazone (Pio) and the angiotensin II receptor blocker candesartan (Cand) in a murine model of renal fibrosis: mice with unilateral ureteral obstruction (UUO). Methods: Mice were randomly assigned into four groups that after UUO received i.p. injections of either Pio (10 mg/kg/day), Cand (1 mg/kg/day), Cand + Pio or vehicle for 10 days. Physiological parameters, the degree of renal fibrosis and molecules related to renal fibrosis were analysed, and sham-operated mice were used as controls. Results: Total collagen assay showed prominent renal fibrosis in the vehicle-treated mice, significantly attenuated renal fibrosis in the Cand-treated and the Pio-treated mice, and further attenuated renal fibrosis in the (Cand + Pio)-treated mice. Real-time reverse transcription polymerase chain reaction revealed that this attenuation pattern was also evident in the expression of the mRNA for transforming growth factor-β, collagens I and III, and plasminogen activator inhibitor-1. Conclusion: Pioglitazone and candesartan have additive protective effects on renal fibrosis due to UUO in mice, suggesting that their use in combination would be an effective treatment for chronic kidney disease. [ABSTRACT FROM AUTHOR]

Renal hypouricemia is an inherited disorder characterized by impaired renal urate (uric acid) reabsorption and subsequent low serum urate levels, with severe complications such as exercise-induced acute renal failure and nephrolithiasis. We previously identified SLC22A12, also known as URAT1, as a causative gene of renal hypouricemia. However, hypouricemic patients without URAT1 mutations, as well as genome-wide association studies between urate and SLC2A9 (also called GLUT9), imply that GLUT9 could be another causative gene of renal hypouricemia. With a large human database, we identified two loss-of-function heterozygous mutations in GLUT9, which occur in the highly conserved "sugar transport proteins signatures 1/2." Both mutations result in loss of positive charges, one of which is reported to be an important membrane topology determinant. The oocyte expression study revealed that both GLUT9 isoforms showed high urate transport activities, whereas the mutated GLUT9 isoforms markedly reduced them. Our findings, together with previous reports on GLUT9 localization, suggest that these GLUT9 mutations cause renal hypouricemia by their decreased urate reabsorption on both sides of the renal proximal tubules. These findings also enable us to propose a physiological model of the renal urate reabsorption in which GLUT9 regulates serum urate levels in humans and can be a promising therapeutic target for gout and related cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The profibrotic effect of plasminogen activator inhibitor-i (PAT-i) in renal fibrosis is widely recognized, but its mechanism remains controversial especially in chronic progressive kidney disease. in the present study, pioglitazone (Pio) and candesartan (CD), which are reported to inhibit PAT-I, were administered to spontaneously hypercholesterolemic (SHC) rats, a model of chronic progressive kidney disease. Therapeutic effects and effects on the intrarenal plasmin cascade were examined. Eight-wk-old SHC rats were used as controls. Oral administration of vehicle alone, Pio, or CD was performed starting at 8 wk of age and was continued for 24 wk. The degree of renal fibrosis was evaluated by sirius red staining of kidney sections and by total collagen assay of renal homogenates. The renal PAl-I protein level was assessed by Western blotting, and plasmin activity was analyzed by chromogenic assay and casein gel zymography. Urinary protein and blood urea nitrogen were significantly increased in the vehicle-treated group, but the increase was attenuated in the Pio- and CD- treated groups. This correlated well with the degree of fibrosis as assessed by sirius red staining and total collagen assay. The PAl-1 protein level was also increased significantly in the vehicle-treated group, and the increase was attenuated in the Pio- and CD-treated groups. Despite the presumed plasmin-inhibitory function of PAl- 1, plasmin activity changed in parallel with PAl- 1. These results suggest that Pio and CD inhibit PAT-T and exert renoprotective effects against chronic progressive renal disease, but its action is independent of the regulatory function on plasmin activity. [ABSTRACT FROM AUTHOR]

Purpose: To compare the midterm efficacy and safety of phacoviscocanalostomy (viscocanalostomy, phacoemulsification, and intraocular lens [IOL] implantation) and cataract surgery (phacoemulsification and IOL implantation) in patients with normal-tension glaucoma (NTG) and cataract. Setting: Sensho-kai Eye Institute, Kyoto, Japan. Methods: Thirty-one eyes had phacoviscocanalostomy, and 35 eyes had uncomplicated cataract surgery only. The intraocular pressure (IOP), postoperative antiglaucoma medications, and visual outcomes were compared between groups. Results: The mean follow-up was 34.9 months ± 19.8 (SD) (range 7 to 78 months). At 36 months, the mean preoperative IOP and postoperative IOP were 17.2 ± 1.5 mm Hg and 14.1 ± 1.6 mm Hg, respectively, in the phacoviscocanalostomy group and 16.7 ± 1.4 mm Hg and 15.6 ± 3.4 mm Hg, respectively, in the cataract surgery only group. The differences between groups were significant at all time points (P<.05). The success probabilities of the phacoviscocanalostomy group achieving 20% and 30% IOP reductions with (or without) medications were 78.5% (67.4%) and 35.5% (37.4%) at 24 months and 58.0% (44.2%) and 28.0% (26.6%) at 48 months, which were significantly better than the probabilities in the cataract surgery only group, which were 16.0% (9.5%) and 5.7% (2.9%) at 24 months (P<.001 for each comparison, Kaplan-Meier life-table analysis with log-rank test). Based on the modified Aulhorn-Greve classification, the visual acuity and visual fields did not deteriorate in the phacoviscocanalostomy group; the visual fields deteriorated in 6 eyes in the cataract surgery only group during the follow-up (P = .024). Conclusion: Phacoviscocanalostomy lowered IOP and maintained postoperative visual outcomes; it was safe and effective in elderly patients with coexisting NTG and cataract. [Copyright &y& Elsevier]

Background. Airline flight personnel work in a unique environment with exposure to known or suspected carcinogens and mutagens including ionizing cosmic radiation. A meta-analysis was conducted to study whether the occupational exposure of female flight attendants (FA) increased their relative risk of cancer incidence. Methods. A bibliographical computer search from 1966 to 2005 of cancer incidence cohort studies of female FA was performed. Combined relative risks (RRc) in cancer incidence were calculated by means of meta-analysis. Results. RRc and 95% confidence interval (CI) for malignant melanoma and breast cancer in female FA were 2.13 (95% CI: 1.58–2.88) and 1.41 (1.22–1.62) ( p < 0.0001). Excess risk was not significant for all-site cancer with RRc of 1.10 (0.99–1.21). Conclusions. The meta-analysis confirmed the significantly increased risks for malignant melanoma and breast cancer in female FA. Increased exposure to cosmic radiation during flight has been suggested as a potential occupational risk factor. Ultraviolet radiation exposure on board seems an unlikely occupational risk, but nonoccupational leisure time sun exposure is a possible risk factor. The etiology of the observed increase in incidence of some cancers remains controversial because assessment of possible confounders, especially nonoccupational exposure factors, has thus far been limited. [ABSTRACT FROM AUTHOR]

The article describes the imported cases of Dermatobia hominis in Japan as shown by a traveler returning from Costa Rica. Myiasis is an infection by a fly maggot in the organs and living or necrotic tissue of vertebrae. Infestation occurred mainly in uncovered parts of the body such as the head, arms and legs. The recommended treatment of the infestation involves using oil which blocks respiration or simple removal of the larva surgically, followed by antibiotic administration to avoid a secondary baterial infection.

We experienced a case of Dermatobia hominis infestation from South America. Here we discuss imported cases of D. hominis in Japan with literature. [ABSTRACT FROM AUTHOR]

The value of fluorescence in situ hybridization (FISH) as an aid to deciding the prognosis for lung carcinoma patients, comparing quantitatively the signal from the p53 gene (17p13.1) on chromosome 17, was studied. A dual-labeling technique was used, using probes for the centromeric region of chromosome 17 and for the p53 gene locus. FISH was used on frozen sections of 68 surgically resected lung carcinoma (20 adenocarcinoma; 37 squamous cell carcinoma; 11 large, small, and other cell carcinoma). Hybridization signals were counted for 100–200 interphase nuclei per specimen using a Zeiss confocal laser scanning microscope (Carl Zeiss, Oberkochen, Germany) equipped with a bandpass filter for diaminophenolindole and a longpass filter for rhodamine. Clinicopathologic data were evaluated using the Statistical Analysis System. Chromosome 17 polysomy (three or more signals) was greater in poorly differentiated than in well-differentiated lung carcinoma ( P < 0.05). p53 deletion correlated with p53 immunostaining ( P < 0.05). Thus, analysis by FISH using DNA probes for chromosome 17 and p53 may be of some, albeit limited, value in determination of prognosis. [ABSTRACT FROM AUTHOR]

Background: Gout is a common disease resulting from hyperuricemia which causes acute arthritis. A recent genome-wide association study (GWAS) of gout identified three new loci for gout in Han Chinese: regulatory factor X3 (RFX3), potassium voltage-gated channel subfamily Q member 1 (KCNQ1), and breast carcinoma amplified sequence 3 (BCAS3). The lack of any replication studies of these three loci using other population groups prompted us to perform a replication study with Japanese clinically defined gout cases and controls. Methods: We genotyped the variants of RFX3 (rs12236871), KCNQ1 (rs179785) and BCAS3 (rs11653176) in 723 Japanese clinically defined gout cases and 913 controls by TaqMan method. rs179785 of KCNQ1 is also evaluated by direct sequencing because of difficulties of its genotyping by TaqMan method. Results: Although the variants of RFX3 and BCAS3 were clearly genotyped by TaqMan method, rs179785 of KCNQ1 was not, because rs179785 (A/G) of KCNQ1 is located at the last nucleotide ("A") of the 12-bp deletion variant (rs200562977) of KCNQ1. Therefore, rs179785 and rs200562977 of KCNQ1 were genotyped by direct sequencing in all samples. Moreover, by direct sequencing with the same primers, we were able to evaluate the genotypes of rs179784 of KCNQ1 which shows strong linkage disequilibrium with rs179785 (D' = 1.0 and r2 = 0.99). rs11653176, a common variant of BCAS3, showed a significant association with gout (P = 1.66 × 10− 3; odds ratio [OR] = 0.80); the direction of effect was the same as that seen in the previous Han Chinese GWAS. Two variants of KCNQ1 (rs179785 and rs179784) had a nominally significant association (P = 0.043 and 0.044; OR = 0.85 and 0.86, respectively), but did not pass the significance threshold for multiple hypothesis testing using the Bonferroni correction. On the other hand, rs200562977 of KCNQ1 and rs12236871 of RFX3 did not show any significant association with gout. Conclusion: BCAS3 is a coactivator of estrogen receptor alpha, and the influence of estrogen to serum uric acid level is well known. Our present replication study, as did the previous gout GWAS, demonstrated the common variant of BCAS3 to be associated with gout susceptibility. [ABSTRACT FROM AUTHOR]

Complete removal of the posterior hyaloid is an important procedure in vitrectomy for various vitreoretinal disorders. Although posterior vitreous detachment (PVD) can be usually induced by active aspiration of vitreous gel, it is difficult in cases where the posterior hyaloid attaches tightly to the retina, especially in minimum incision vitrectomy systems (MIVS) due to the smaller apertures of the instruments. We describe a novel technique of creating PVD without aspiration. In this method, a break in the vitreous cortex is initially made at the posterior precortical vitreous pocket using a diamond dusted membrane scraper. Once a break in the vitreous cortex is induced, the break is extended by continuing the same manipulation. Detachment of the posterior vitreous gradually progresses by the influx of irrigation fluid from the break into the space between the posterior vitreous and the retina. Subsequently, the scraper is inserted under the detached posterior hyaloid from the break in the cortical vitreous, and is lifted upward to complete the PVD. Complete PVD is confirmed by observation of the Weiss ring in front of the retina. Using this technique, PVD can be achieved in vitrectomies using MIVS, even when the posterior hyaloid attaches tightly to the retina. [ABSTRACT FROM AUTHOR]

A response by Robert Wood Johnson to a letter to the editor about his article on the relations between reproductive factors and increased risk for breast cancer in the previous issue is presented.

A correction to the article "Mutations in Glucose Transporter 9 Gene SLC2A9 Cause Renal Hypouricemia" that was published in the December 12, 2008 issue is presented.