Search

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.

Programmed cell death protein (PD)-1 is a coinhibitory molecule that suppresses immune response and maintains immune homeostasis. Moreover, the PD-1 pathway blocks cancers from being attacked by immune cells. Anti–PD-1 antibody therapy such as nivolumab improves survival in cancer patients. However, the occurrence of autoimmune inflammatory disorders in various organs has been increasingly reported as an adverse effect of nivolumab. Of the disorders associated with nivolumab, Sicca syndrome occurs in 3% to 11% of cases and has unknown pathologic mechanisms. Whether the absence of the PD-1 pathway causes functional and morphologic disorders in lacrimal glands was determined by analyzing PD-1 gene–knockout (Pdcd1−/−) mice. Histopathologic analysis showed that Pdcd1−/− mice developed dacryoadenitis beginning at 3 to 4 months of age, and deteriorated with age. Flow-cytometric analysis confirmed that cells infiltrating the affected lacrimal glands consisted mainly of CD3+ T cells and only a small proportion of CD19+ B cells. Among infiltrating T cells, the CD4+ Th-cell subset consisted of Th1 cells producing interferon-γ in an early stage of dacryoadenitis in Pdcd1−/− mice. Experiments of lymphocyte transfer from Pdcd1−/− into irradiated wild-type mice confirmed that CD4+ T cells from Pdcd1−/− mice induced dacryoadenitis. These results indicate that PD-1 plays an important role in the prevention of autoimmune inflammatory disorders in lacrimal glands caused by activated CD4+ Th1 cells.

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.

An oral infectious disease, dental caries, is caused by the cariogenic streptococci Streptococcus mutans. The expected preventive efficiency for prophylactics against dental caries is not yet completely observed. Nisin, a bacteriocin, has been demonstrated to be microbicidal against S. mutans, and liposome-encapsulated nisin improves preventive features that may be exploited for human oral health. Here we examined the bactericidal effect of charged lipids on nisin-loaded liposomes against S. mutans and inhibitory efficiency for insoluble glucan synthesis by the streptococci for prevention of dental caries. Cationic liposome, nisin-loaded dipalmitoylphosphatidylcholine/phytosphingosine, exhibited higher bactericidal activities than those of electroneutral liposome and anionic liposome. Bactericidal efficiency of the cationic liposome revealed that the vesicles exhibited sustained inhibition of glucan synthesis and the lowest rate of release of nisin from the vesicles. The optimizing ability of cationic liposome-encapsulated nisin that exploit the sustained preventive features of an anti-streptococcal strategy may improve prevention of dental caries.

Background Tuberculosis (TB)-associated uveitis presents periphlebitis, occasionally causing central retinal vascular occlusion (CRVO). Intravitreal injection of ranibizumab (IVR) is an effective treatment for CRVO, which improves macular edema (ME) by reducing vascular permeability and prevents progression of retinal nonperfusion in CRVO. We report a case of CRVO due to TB-associated uveitis, which initially remitted by repeated IVR as an adjunct to anti-TB therapy and systemic corticosteroids, but subsequently led to severe vitreous hemorrhage (VH). Case presentation A 28-year-old man was referred to our hospital with a 2-week history of uveitis in his right eye. Ophthalmoscopic examination of the right eye revealed fine keratoprecipitates and moderate cell infiltration into the anterior chamber and vitreous. No obvious retinal lesion was observed. Despite initiation of topical corticosteroids, CRVO developed a few weeks later in the right eye. TB-associated uveitis was diagnosed based on a positive tuberculin skin test and interferon-γ release assay in addition to the ocular findings. Anti-TB therapy together with IVR and systemic corticosteroids was initiated. Although fundus findings associated with CRVO gradually improved, CRVO with VH recurred before the fourth IVR. Although IVR was continued, VH progressed to obscure fundus observation. Therefore, vitrectomy and panretinal photocoagulation were performed. After surgery, ocular inflammation was controlled, and anti-TB therapy was continued for 6 months and was suspended. Conclusion In addition to anti-TB therapy with or without corticosteroids, panretinal photocoagulation for retinal nonperfusion area in TB-associated uveitis should be performed for preventing neovascularization that may cause VH, and this role of panretinal photocoagulation cannot be replaced by anti-VEGF therapy.

Rationale Choroidal detachment is a major postoperative complication of trabeculectomy. Postoperative choroidal detachment occurs with low intraocular pressure (IOP), and is naturally resolved by elevation of IOP. We report a case of chronic chorioretinal detachment (CRD) in the eye with uveitic glaucoma after trabeculectomy which persisted with normal IOP resistant for medication and required surgery. Patient concerns A 63-year-old man was referred to our department with uncontrolled uveitic glaucoma in his right eye. At first presentation, IOP was 62 mm Hg in the right eye with opened angle, and active ocular inflammation was presented by moderate cell infiltration to the anterior chamber. Diagnosis Uveitic glaucoma. Interventions Trabeculectomy with mitomycin-C combined with phacoemulsification were performed without any surgical trouble. Postoperative inflammation in the anterior segment was mild, and IOP decreased to the middle-teen. Outcomes At 19 days after surgery, the depth of the anterior chamber changed to shallow and CRD occurred in the inferior quadrant area. This complication could not be resolved by additional systemic corticosteroid medication and scleral fenestration. Although IOP was maintained in middle-teen range, suture fixation of the sclera flap and additional scleral fenestration were necessary to resolve CRD at 191 days after primary surgery. Lessons In uveitic eye with uncontrolled ocular hypertension, severe CRD after trabeculectomy is able to occur even with normal IOP, which requires surgical procedure in addition to the medical treatment.

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.

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 r 2 = 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.

Vitreous opacity (VO) is a common feature of intermediate uveitis, posterior uveitis, and panuveitis. Fundus observation is critical for determining the etiology of uveitis, however, is often interfered with VO. In these clinical settings, vitrectomy contributes to a correct diagnosis and guides alternative management strategies. The purpose of this study was to evaluate the diagnostic yield and surgical outcome of vitrectomy in uveitic patients with VO and compare the visual outcome between infectious and noninfectious uveitis. Forty-five eyes with uveitis-associated VO underwent diagnostic and therapeutic vitrectomy, and etiological diagnosis of uveitis was confirmed in 34 of 45 eyes (75.6%). The diagnoses were infectious uveitis in 13 eyes (28.9%), noninfectious uveitis in 21 eyes (46.7%), and unidentified uveitis in 11 eyes (24.4%). Visual acuity (VA) improvement rates at 6 months after surgery were 69.2%, 76.2%, and 90.9% in the infectious, noninfectious, and unidentified uveitis groups, with no significant difference among 3 groups. Significant decrease in inflammation score after vitrectomy was observed only in the infectious uveitis group. This study demonstrated that diagnostic vitrectomy for inflammatory eyes with VO of unknown etiology was effective in infectious and noninfectious uveitis, and the therapeutic effect of VA improvement was observed in both types of uveitis.

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.

Background The epidemiological patterns of musculoskeletal injuries or disorders in military personnel have not been well documented and a better understanding is required for proper preventative measures and treatment. Here, we investigated musculoskeletal injuries or disorders among members of the Japan Self-Defense Forces. Methods All orthopedic patients (n = 22,340) who consulted to Japan Self-Defense Forces Hospitals were investigated for their type of injury or disorder, the injured body part, the mechanism, and the cause of injuries. Results Thirty-nine percent of the cases were classified as traumatic injuries, and 61% were classified as non-traumatic disorders. Of the traumatic injury patients, the injured body part was the upper extremity in 32%, the trunk in 23%, and the lower extremities in 45% of the cases. The most common injured body location was the knee followed by the hand/finger and ankle. Exercise was the most common cause of injury, followed by traffic accident and military training. Contusions were the most common traumatic injuries, followed by sprains and fractures. Of non-traumatic disorders, the lower extremities were reported as the injured part in 43% of the disorders. Lumbar spine disorders were the most common non-traumatic disorders, followed by tendon and joint disorders. Conclusions Over one-third of orthopedic cases among members of the Japan Self-Defense Forces are traumatic injuries, with the knee being the body part most commonly injured and exercise being the leading cause of injury.

ObjectiveGout, caused by hyperuricaemia, is a multifactorial disease. Although genome-wide association studies (GWASs) of gout have been reported, they included self-reported gout cases in which clinical information was insufficient. Therefore, the relationship between genetic variation and clinical subtypes of gout remains unclear. Here, we first performed a GWAS of clinically defined gout cases only.MethodsA GWAS was conducted with 945 patients with clinically defined gout and 1213 controls in a Japanese male population, followed by replication study of 1048 clinically defined cases and 1334 controls.ResultsFive gout susceptibility loci were identified at the genome-wide significance level (p−8), which contained well-known urate transporter genes (ABCG2 and SLC2A9) and additional genes: rs1260326 (p=1.9×10−12; OR=1.36) of GCKR (a gene for glucose and lipid metabolism), rs2188380 (p=1.6×10−23; OR=1.75) of MYL2-CUX2 (genes associated with cholesterol and diabetes mellitus) and rs4073582 (p=6.4×10−9; OR=1.66) of CNIH-2 (a gene for regulation of glutamate signalling). The latter two are identified as novel gout loci. Furthermore, among the identified single-nucleotide polymorphisms (SNPs), we demonstrated that the SNPs of ABCG2 and SLC2A9 were differentially associated with types of gout and clinical parameters underlying specific subtypes (renal underexcretion type and renal overload type). The effect of the risk allele of each SNP on clinical parameters showed significant linear relationships with the ratio of the case–control ORs for two distinct types of gout (r=0.96 [p=4.8×10−4] for urate clearance and r=0.96 [p=5.0×10−4] for urinary urate excretion).ConclusionsOur findings provide clues to better understand the pathogenesis of gout and will be useful for development of companion diagnostics.

Background Coxsackieviruses are members of a group of viruses called the enteroviruses, which may cause respiratory and gastrointestinal symptoms, erythema, meningoencephalitis, myocarditis, pericarditis, and myositis. Unilateral acute idiopathic maculopathy caused by coxsackievirus A16 has been associated with hand, foot, and mouth disease, but only a few reports describe retinitis associated with coxsackievirus serotype B3 or B4. We report a case of bilateral multifocal obstructive retinal vasculitis that developed after coxsackievirus A4 infection. Case presentation A 60-year-old woman was referred to our department with bilateral visual disturbance that developed following flu-like symptoms. At the initial examination, best corrected visual acuity was 20/200 in the right eye and 20/50 in the left eye. The critical flicker frequency (CFF) was 23 Hz in the right eye and 27 Hz in the left eye. Fine white keratic precipitates with infiltrating cells were presented in the anterior chamber of both eyes, and multifocal retinal ischemic lesions were observed in the macula and posterior pole of both eyes. The retinal lesions corresponded with scotomas observed in Goldmann visual field test. On spectral domain-optical coherence tomography (SD-OCT), retinal lesions were depicted as hyper-reflective regions in the inner retina layers in both eyes, and disruption of ellipsoid line in the left eye., Fluorescein angiography exhibited findings indicative of multifocal obstructive retinal vasculitis. The patient had a history of current hypertension treated with oral therapy and glaucoma treated with latanoprost eye drops. Blood test for coxsackievirus antibody titers revealed that A4, A6, A9, B1, B2, B3, and B5 were positive (titers: 8–32). Abdominal skin biopsy of necrotic tissue suggested vascular damage caused by coxsackievirus. The general symptoms improved after 6 weeks, and the multifocal retinal ischemic lesions were partially resolved with residual slightly hard exudates. Only coxsackievirus A4 antibody titer increased from 4 to 32-fold after 14 months. However, hyper-reflective regions and disruption of the inner retinal layers on SD-OCT persisted especially in the right eye, and residual paracentral scotoma was observed in the right eye. Conclusion The present case suggests that coxsackievirus A4 causes bilateral multifocal obstructive retinal vasculitis with irreversible inner retinal damage.

Gout is caused by hyperuricemia, with alcohol consumption being an established risk factor. Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are crucial enzymes for alcohol metabolism. We recently performed a genome-wide association study of gout and a subsequent fine-mapping study which identified rs671 of ALDH2 as a gout locus. However, the association between gout and common variants of ADH1B has hitherto remained unreported, prompting us to investigate the association between gout and common dysfunctional variants of ADH1B (rs1229984) and ALDH2 (rs671). We used 1,048 clinically defined gout cases and 1,334 controls of Japanese male. The “His carrier” (His/His or His/Arg) of rs1229984 (His48Arg) of ADH1B significantly increased gout risk (P = 4.3 × 10−4, odds ratio = 1.76), as did the “non-Lys carrier (Glu/Glu)” of rs671 (Glu504Lys) of ALDH2. Furthermore, common variants of ADH1B and ALDH2 are independently associated with gout. Our findings likewise suggest that genotyping these variants can be useful for the evaluation of gout risk.

Purpose High-mobility group box-1 (HMGB1) is a nonhistone DNA-binding nuclear protein released from necrotic cells, which is also secreted by activated leukocytes and acts as a primary proinflammatory cytokine. In this study, we compared vitreous HMGB1 levels in ocular sarcoidosis with those in noninflammatory vitreoretinal diseases and evaluated its association with Th cell-related and proinflammatory cytokines. Methods The study group consisted of 24 patients with ocular sarcoidosis. The control group consisted of 27 patients with proliferative diabetic retinopathy (PDR) and 24 with idiopathic epiretinal membrane (ERM). Vitreous fluid samples were obtained at the beginning of vitrectomy. Vitreous levels of HMGB1 and 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 were measured. Results High-mobility group box-1 was detected in the vitreous of 23 of 24 patients (95.8%) with ocular sarcoidosis. Mean vitreous level of HMGB1 was the highest in the sarcoidosis group, followed by the PDR and ERM groups, with significant differences between the three groups. In the sarcoidosis group, vitreous levels of IL-6, IL-10, IL-31, IFN-γ, sCD40L, and TNFα were significantly higher than those in the idiopathic ERM group, and IFN-γ and sCD40L were significantly higher than those in the PDR group. Vitreous HMGB-1 level correlated significantly with IL-10, IFN-γ, and sCD40L levels but not with IL-6, IL-17, IL-31, or TNFα levels. Conclusions The vitreous level of HMGB1 is elevated in ocular sarcoidosis and is associated with vitreous levels of Th1- and regulatory T-related cytokines, but not with proinflammatory or Th17-related cytokines.

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.

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.

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.

The Trp64Arg polymorphism of the beta-3-adrenergic receptor gene has been studied as a potential genetic factor contributing to the development of obesity. Several studies have investigated whether or not this polymorphism affects weight reduction due to exercise, but the results of these studies have not been consistent. Moreover, information on a population characterized by a wide ranges of physical activities is scarce. Thus, to further understand the impact of this polymorphism, we examined whether the polymorphism modulates the relationship between physical activity due to exercise (PAE) and percentage of body fat (%BF).The study population was 70 Japanese male young adults with a high prevalence of habitual exercise. PAE was estimated by a questionnaire, and %BF was measured by bioelectrical impedance analysis. Genotyping was done by PCR-restriction fragment length polymorphism analysis.The median PAE value of the subjects was 6.9 MET-h/day with an interquartile range of 1.5-10.3 MET-h/day. PAE correlated significantly with %BF in the entire population and within the two subpopulations, namely, carriers or non-carriers of the Arg allele. Multiple regression analysis of PAE, Trp64Arg polymorphism, and the interaction term revealed that while the PAE-derived independent variable was statistically significant, the interaction term was insignificant. When the two regression lines of subjects with and without the Arg allele were considered, the difference between the two slopes did not deviate from zero, nor did the vertical distance of the two regression lines. These findings suggest that the impact of this polymorphism is limited.In our study population of young adult Japanese males, the impact of the Trp64Arg polymorphism on the association between exercise and body composition was weak, if it existed at all.

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.

Urate transporter 1 (URAT1/SLC22A12), a urate transporter gene, is a causative gene for renal hypouricemia type 1. Among several reported nonsynonymous URAT1 variants, R90H (rs121907896) and W258X (rs121907892) are frequent causative mutations for renal hypouricemia. However, no case-control study has evaluated the relationship between gout and these two variants. Additionally, the effect size of these two variants on serum uric acid (SUA) levels remains to be clarified. Here, 1,993 primary gout patients and 4,902 health examination participants (3,305 males and 1,597 females) were genotyped with R90H and W258X. These URAT1 variants were not observed in any gout cases, while 174 subjects had the URAT1 variant in 2,499 health examination participants, respectively (P = 8.3 × 10−46). Moreover, in 4,902 health examination participants, the URAT1 nonfunctional variants significantly reduce the risk of hyperuricemia (P = 6.7 × 10−19; risk ratio = 0.036 in males). Males, having 1 or 2 nonfunctional variants of URAT1, show a marked decrease of 2.19 or 5.42 mg/dl SUA, respectively. Similarly, females, having 1 or 2 nonfunctional variants, also evidence a decrease of 1.08 or 3.89 mg/dl SUA, respectively. We show that URAT1 nonfunctional variants are protective genetic factors for gout/hyperuricemia and also demonstrated the sex-dependent effect size of these URAT1 variants on SUA (P for interaction = 1.5 × 10−12).

Dental caries are an infectious oral bacterial disease caused by cariogenic streptococci. These streptococci inhabit dental biofilms which comprise insoluble glucans.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.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.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.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.

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 CG-treated 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 ± 4.6 cells per field). It was 54.1 ± 3.2 cells per field in the group given 20 mg UC, 43.2 ± 5.2 cells per field in the group given 10 mg LC and 27.2 ± 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 α-smooth muscle actin and in messenger RNA expression for transforming growth factor-β1 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.

Mutanase, α-1,3-glucanase, catalyzes the hydrolysis of α-1,3-glucans, and is expected for preventive medicine, since the enzyme has an ability for hydrolysis of insoluble glucans that are synthesized by cariogenic streptococci. We previously isolated the mutanase of Paenibacillus humicus from fermented soybeans. In the present study, Paenibacillus mutanase was characterized with respect to its hydrolysis efficiency of insoluble glucans, and mode of action on α-1,3-glucan oligosaccharides. Recombinant mutanase hydrolyzed insoluble glucans of cariogenic streptococci efficiently. Enzymatic reaction on hydrolysis of mutan, we assumed that the enzyme cleaved the substrate in an endo-catalytic manner. The hydrolysis of α-1,3-glucan oligosaccharides gave α-1,3-glucan tetrasaccharide as the primary final product but α-1,3-glucan pentasaccharide was the minimal size of substrate on which the enzyme catalyzed. Mutanase hydrolyzed borohydride-treated α-1,3-glucan hexasaccharide into the tetrasaccharide and the disaccharide-alditol. Thus, the enzyme cleaved the fourth α-1,3-glucosidic linkage from the non-reducing end of the oligosaccharides. Mutanase in fermented food should be capable of removing streptococcal insoluble glucans that can induce dental caries.

Mutanase is an α-1,3-glucanase that cleaves the α-1,3-glucosidic linkages of glucan polysaccharides termed mutan. There has been interest in mutanase as it has the potential to be considered in preventive medicine. Previously, we identified the mutanase of Paenibacillus humicus from fermented soybeans and observed that the enzyme hydrolyzed insoluble glucans and mutan in vitro. Here we focused on the ability of mutanase in preventing dental caries. We proposed that the enzyme participates in the degradation of insoluble glucan biofilms in microplates, which were used as a model of biofilms on tooth surface. In this study, we investigated the potential of mutanase to hydrolyze insoluble glucan biofilms synthesized by a typical cariogenic streptococcus, Streptococcus mutans 10449, in 96-well microplates. The mutanase specifically hydrolyzed insoluble glucan biofilms composed of insoluble glucans synthesized by S. mutans. The mutanase hydrolyzed approximately 60% of S. mutans glucan biofilms in the wells and liberated oligosaccharides from the glucan films. We observed that recombinant mutanase could hydrolyze mutan biofilms, and the enzyme was characterized as an endo-α-1,3-glucanase because its hydrolysis of mutan biofilms, resulted in the predominant liberation of α-1,3-glucan tetrasaccharides. The present study suggests that Paenibacillus mutanase from fermented soybeans has potential application in preventive medicine because of its ability to degrade oral insoluble glucan biofilms.

There has been much interest in mutanases, α-1,3-glucanases, as they have the potential for preventive agents in the oral cavity. Mutanases have been reported in some bacteria and fungi but remain a relatively uncharacterized family of enzymes. We screened bacterial mutanase in fermented food for the application of the enzyme to preventive medicine. Immersed solutions of fermented soybeans, natto, on mutan-containing agar plates exhibited mutan-hydrolyzing activity after incubation. We isolated a microorganism that hydrolyzed mutan from the fermented soybeans and named it Paenibacillus humicus strain NA1123. The gene for the mutanase was cloned, and the nucleotide sequence of the gene consisted of 3441-bp open reading frame that encoded a predicted 1146-amino acid polypeptide including a 33-amino acid signaling peptide. The predicted molecular mass of the matured enzyme was 115399. The protein is composed of an N-terminal domain and a C-terminal domain, that are connected by a sequence composed of proline and threonine repeats. The deduced amino acid sequence of the present enzyme showed similarity to that of the mutanase MuC1 of strain KSM-M126 and the mutanase MuE of strain KSM-M318 of Paenibacillus sp. with 77.2% and 73.5% identity, respectively. We confirmed that the recombinant mutanase exhibited mutan hydrolyzing activity.

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.

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.

Dental caries is a common oral bacterial infectious disease. Its prevention requires the control of the causative pathogens, such as Streptococcus mutans, that exist within dental plaque. Nisin is a proteinaceous bacteriocin produced by Lactococcus lactis that is used to suppress bacterial infections. It has an inhibitory mode of action on a wide range of gram-positive bacteria. Improvements in the medical benefits of antibacterial agents can be achieved if they can be retained in liposomes for a long period after administration. Liposome systems can increase the ability of the encapsulated compounds, which have been widely used to encapsulate many kinds of compounds in various scientific settings. Liposomes can release labile molecules at a moderate rate. Liposome technologies that effectively protect the encapsulated molecules from decomposition have the potential to improve their preventive and therapeutic effects. Therefore, the use of liposomes to administer antimicrobial agents has spurred research into their utility in preventive medicine. The encapsulation of nisin in liposomes can provide means of improving the stability of nisin and its antibacterial effect against S. mutans. The present chapter will review the prospects for liposome-encapsulated nisin for the prevention of oral infectious diseases.

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

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.

Background: Dental caries is an infectious oral disease caused by cariogenic Streptococcus mutans. The streptococci inhabit dental-biofilms which comprise insoluble glucans. Objectives: To prevent dental caries, liposome-encapsulated nisin prepared from phosphatidylcholines with different acyl chain lengths were tested for bactericidal activity against cariogenic S. mutans. Materials and Methods: Liposomal nisins prepared from dimyristoylphosphatidylcholine (DMPC), dipalmitoylphosphatidylcholine (DPPC), and distearoyl phoshatidylcholine (DSPC) were tested for their bactericidal activity against S. mutans 10449 and as a consequence, to inhibit the synthesis of insoluble glucan by the streptococci in vitro. Results: The bactericidal activities by minimum inhibitory concentration assay, DSPC-nisin, DPPC-nisin, and DMPC-nisin were higher by factors of 10, 3.3, and 2.5 compared with unencapsulated nisin. Inhibition of glucan synthesis was sustained the longest by DSPC-nisin. On the release assay of these liposomes, nisin was released at the highest and lowest rates from DMPC-nisin and DSPC-nisin, respectively. The highest and most sustained levels of bactericidal activity correlated with the slow release of encapsulated nisin. Conclusion: The DSPC-nisin may be useful for preventing the formation of dental caries due to sustained release of nisin. Thus, prophylaxis with the liposomal nisin may serve to maintain oral health.

BACKGROUND We sought to investigate the association between blood pressure levels and prevalence of acquired color vision impairment in middle-aged Japanese men. METHODS Participants underwent color vision testing, ophthalmological examination, standardized interview, physical record examination, and venous blood examination. Cardiovascular disease risk factors were determined based on blood and physical examination results and the interview. Logistic regression analysis was performed after adjusting for body mass index, systemic dyslipidemia, diabetes, cataract, glaucoma, smoking status, and drinking status. RESULTS Of 1,042 men, 872 were eligible for the study, 130 failed the Lanthony 15-hue desaturated panel (D-15 DS) diagnosed as acquired color vision impairment 15-hue, and 31 failed the Farnsworth-Munsell 100-hue test diagnosed as acquired color vision impairment 100-hue. Diastolic blood pressure was significantly correlated with both acquired color vision impairment in 100-hue patients (adjusted odds ratio (OR) for 10-mm Hg increases = 1.42; 95% confidence interval (CI) = 1.00-2.02) and acquired color vision impairment in 15-hue patients (adjusted OR for 10-mm Hg increases = 1.25; 95% CI = 1.04-1.51). The multiple-adjusted ORs for acquired color vision impairment 100-hue patients and acquired color vision impairment 15-hue patients were 7.13 (95% CI = 1.72-27.88) and 4.37 (95% CI = 1.69-11.03), respectively, for the highest blood pressure category (systolic blood pressure ≥ 160 and diastolic blood pressure ≥ 100 mm Hg) compared with those for the lowest blood pressure category (systolic blood pressure

Objective.Recently, genetic analyses indicated the association between gout and cGMP-dependent protein kinase 2 (cGKII/PRKG2) gene in a Fukien-Taiwanese heritage population. However, no replication study has been reported in other ancestries. Therefore, we investigated this association in a Japanese population.Methods.Genotyping of 4 variants (rs11736177, rs10033237, rs7688672, and rs6837293) of cGKII was performed in 741 male gout patients and 1302 male controls.Results.cGKII variants have no association with gout.Conclusion.Our replication study suggests that cGKII is not involved in gout susceptibility.

Gout/hyperuricemia is a common multifactorial disease having typical environmental risks. Recently, common dysfunctional variants of ABCG2, a urate exporter gene also known as BCRP, are revealed to be a major cause of gout/hyperuricemia. Here, we compared the influence of ABCG2 dysfunction on serum uric acid (SUA) levels with other typical risk factors in a cohort of 5,005 Japanese participants. ABCG2 dysfunction was observed in 53.3% of the population investigated, and its population-attributable risk percent (PAR%) for hyperuricemia was 29.2%, much higher than those of the other typical environmental risks, i.e. overweight/obesity (BMI ≥ 25.0; PAR% = 18.7%), heavy drinking (>196 g/week (male) or >98 g/week (female) of pure alcohol; PAR% = 15.4%), and aging (≥60 years old; PAR% = 5.74%). SUA significantly increased as the ABCG2 function decreased (P = 5.99 × 10−19). A regression analysis revealed that ABCG2 dysfunction had a stronger effect than other factors; a 25% decrease in ABCG2 function was equivalent to “an increase of BMI by 1.97-point” or “552.1 g/week alcohol intake as pure ethanol” in terms of ability to increase SUA. Therefore, ABCG2 dysfunction originating from common genetic variants has a much stronger impact on the progression of hyperuricemia than other familiar risks. Our study provides a better understanding of common genetic factors for common diseases.

Gout is a common disease which results from hyperuricemia. We have reported that the dysfunction of urate exporter ABCG2 is the major cause of renal overload (ROL) hyperuricemia, but its involvement in renal underexcretion (RUE) hyperuricemia, the most prevalent subtype, is not clearly explained so far. In this study, the association analysis with 644 hyperuricemia patients and 1,623 controls in male Japanese revealed that ABCG2 dysfunction significantly increased the risk of RUE hyperuricemia as well as overall and ROL hyperuricemia, according to the severity of impairment. ABCG2 dysfunction caused renal urate underexcretion and induced hyperuricemia even if the renal urate overload was not remarkable. These results show that ABCG2 plays physiologically important roles in both renal and extra-renal urate excretion mechanisms. Our findings indicate the importance of ABCG2 as a promising therapeutic and screening target of hyperuricemia and gout.

Rationale and Objectives The purpose of this study was to determine if male radiologists predominantly father daughters and, if so, to investigate the association between this skewed sex ratio of offspring and radiation exposure. Materials and Methods Questionnaires completed by 586 male radiologists in Japan provided data regarding the radiologist's age, length of employment in radiology, if he had ever received radiation doses higher than that recommended by the International Commission on Radiological Protection, the sex of each child fathered, and the birth date of each child. Results As a group, male radiologists tended to father a lower proportion of boys (48.47%) compared with the control group (51.46%), and the relative risk was 1.13 (95% confidence interval [CI]: 1.00, 1.27). Offspring of highly irradiated radiologists, however, had a reduced proportion of males (34.48%), with a significantly (P = .002) increased relative risk of 2.01 (95% CI: 1.29, 3.13). Conclusion X-ray exposure may explain the reduced percentage of sons in the offspring of male radiologists.

BACKGROUND: Despite the westernized lifestyle, most Japanese are not prominently obese. As their obesity may be obscured, we want to further explore central fat distribution and health risks among this population. METHODS: 2668 men (body mass index (BMI) 20–

The body mass index (BMI), waist circumference, waist to hip ratio, waist to height ratio and skinfolds (near-umbilical and iliac areas) in three age groups (35-44, 45-54 and 55-64 years) were compared in 3117 men and 997 women in Tokyo. In both genders, height was significantly shorter, while the waist to hip ratio and waist to height ratio were significantly higher, in the older groups. In the men, there were no significant differences in BMI and waist circumference among the three age groups, but the iliac skinfold was significantly thinner in each older group, and the paraumbilical skinfold was thinner in the group aged 55-64 years. In the women, the paraumbilical skinfold was significantly thicker in each older group, while waist circumference and the iliac skinfold were significantly larger or thicker in the group aged 55-64 years, and BMI was larger in the groups aged 45-54 and 55-64 years. There were age-related discrepancies between BMI and other obesity indices in the different genders, in that only the waist to height ratio and waist to hip ratio increased with age in both genders.