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Background Fibroblast growth factor 23 (FGF23) plays an important role in chronic kidney disease (CKD)‐related mineral and bone disorders. High FGF23 levels are associated with increased risk of anaemia in non‐haemodialysis CKD patients. FGF23 also negatively regulates erythropoiesis in mice. We hypothesized that higher FGF23 levels are associated with increased erythropoietin hyporesponsiveness among haemodialysis patients. Methods The study included 1044 patients from the Japanese Dialysis Outcomes and Practice Patterns Study (J‐DOPPS) phase 5 (2012‐2015). The outcome was erythropoiesis‐stimulating agent hyporesponsiveness (ESA‐hypo), defined as mean Hgb 6000 u/week over 4 months following FGF23 measurement. The association between ESA‐hypo and FGF23 was estimated using multivariable‐adjusted logistic generalized estimating equation regression models. Results Patients with higher levels of FGF23 were younger and had higher levels of serum albumin, creatinine, albumin‐corrected calcium, phosphorus, PTH, 25(OH)‐vitamin D, and had higher percentages of intravenous (IV) iron, IV vitamin D and cinacalcet use. ESA‐hypo was present in 144 patients (13.8%). Compared with the third quintile of FGF23 levels, the odds ratio (95% CI) of ESA‐hypo was 2.14 (0.99, 4.62) and 1.74 (0.74, 4.11) for the first and fifth quintiles, respectively. Conclusion The lowest and highest levels of FGF23 were associated with higher odds of ESA‐hypo in patients on maintenance haemodialysis, although the associations were not statistically significant. The relationship between FGF23 and anaemia, and particularly the increased risks of ESA‐hypo at low FGF23 levels which might be the result of energy saving, must be confirmed in larger clinical studies., SUMMARY AT A GLANCE The study included 1044 patients in Japan from J‐DOPPS and found that the lowest and highest levels of serum FGF‐23 were associated with increased odds of ESA‐hyporesponsiveness in patients on maintenance haemodialysis, though this did not reach statistical significance. Further study is needed to address the relationship between circulating FGF‐23 and anaemia in dialysis patients.

In the largest retrospective study of adrenal incidentalomas (AIs) in Japan between 1999 and 2004, adrenal tumors detected during secondary hypertension (HT) screening were included. The characteristics of patients with adrenal tumors detected during HT screening may differ from those of patients with AIs. This study aimed to compare the characteristics of patients with AIs with those of patients with adrenal tumors detected during HT screening. We retrospectively analyzed patients referred to our division for detailed examination of adrenal tumors between April 2009 and April 2017. When the purposes of imaging tests included HT screening, we defined adrenal tumors as HT associated, otherwise as strictly defined AIs. We reviewed data on age, sex, purpose and modality of imaging, location of tumor, tumor diameter, and hormonal evaluation. We identified 104 patients with HT-associated adrenal tumors and 413 with AIs. Patients with HT-associated adrenal tumors were younger (54.2 years vs. 61.7 years, p < 0.001) and had smaller tumor diameters (1.3 cm vs. 1.9 cm, p < 0.001), lower prevalence of nonfunctioning tumors (24.0% vs. 67.6%, p < 0.001), and higher prevalence of primary aldosteronism (58.7% vs. 4.8%, p < 0.001) than those with AIs. There were no differences in terms of tumor location and prevalence of subclinical Cushing's syndrome, Cushing's syndrome, and pheochromocytoma (18.3% vs. 16.0%, 7.7% vs. 8.0%, and 2.9% vs. 4.6%, respectively). In conclusion, patients with HT-associated tumors were younger and had a smaller tumor with higher prevalence of primary aldosteronism than those with AIs.

Introduction The usefulness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests in asymptomatic individuals has not been well validated, although they have satisfied sensitivity and specificity in symptomatic patients. In this study, we investigated the significance of IgM and IgG antibody titers against SARS-CoV-2 in the serum of asymptomatic healthy subjects. Methods From June 2020, we recruited 10,039 participants to the project named the University of Tokyo COVID-19 Antibody Titer Survey (UT-CATS), and measured iFlash-SARS-CoV-2 IgM and IgG (YHLO IgM and IgG) titers in the collected serum. For the samples with increased IgM or IgG titers, we performed additional measurements using Elecsys Anti-SARS-CoV-2 Ig (Roche total Ig) and Architect SARS-CoV-2 IgG (Abbott IgG) and investigated the reactivity to N, S1, and receptor binding domain (RBD) proteins. Results After setting the cutoff value at 5 AU/mL, 61 (0.61%) were positive for YHLO IgM and 104 (1.04%) for YHLO IgG. Few samples with elevated YHLO IgM showed reactivity to S1 or RBD proteins, and IgG titers did not increase during the follow-up in any samples. The samples with elevated YHLO IgG consisted of two groups: one reacted to S1 or RBD proteins and the other did not, which was reflected in the results of Roche total Ig. Conclusions In SARS-CoV-2 seroepidemiological studies of asymptomatic participants, sufficient attention should be given to the interpretation of the results of YHLO IgM and IgG, and the combined use of YHLO IgG and Roche total Ig might be more reliable.

Urine dipstick tests are often used to evaluate proteinuria during health checkups. We examined the dipstick’s accuracy in assessing the proteinuria levels among Japanese workers. We assessed subjects aged ≥ 18 years who had a health checkup at the University of Tokyo in 2016 or 2017 (n = 5383). Proteinuria was stratified by urine protein-to-creatinine ratio (PCR): A1

Purpose Beta2-microglobulin (β2-M) is recognized as a surrogate marker relating to the mechanisms of dialysis-associated amyloidosis. Few studies have evaluated the association of serum β2-M with clinical outcome in hemodialysis patients using high-flux type. However, study on patients using low-flux dialyzer reuse has not been done yet. Patients and methods Using serum β2-M level on predicting long-term mortality of hemodialysis patients was examined in 326 prevalent hemodialysis patients (45.59±14.46 years, hemodialysis duration of 47.5 (26-79) months, 186 males and 140 females). The patients were divided into 3 groups with equal number of patients, according to their serum β2-M levels: group A (n=109, serum β2-M concentration ≤55.7 mg/L), group B (n=109, serum β2-M level from 55.8 mg/L to 75.4 mg/L) and group C (n=108, serum β2-M concentration >75.4 mg/L). Results During the follow-up period of 5 years, there were 75 all-cause deaths (23.0%). Kaplan-Meier analysis revealed that all-cause mortality in the higher β2-M group was significantly higher compared to that in the lower β2-M groups (p

Early enteral nutrition (EN) is recommended for critically ill patients; however, few reports have examined early EN for patients who received targeted temperature management (TTM) after out-of-hospital cardiac arrest (OHCA). We investigated the effectiveness and safety of early EN for patients who received TTM after OHCA.We used a nationwide Japanese administrative database to identify OHCA patients who received TTM from April 2008 to March 2017. The primary outcome was 30-day mortality; secondary outcomes were incidences of all-cause infection, pneumonia, and intestinal ischemia.Of the 1932 OHCA patients who received TTM, 1682 met the inclusion criteria. Of these, 294 received early EN within 2 days from the initiation of TTM and 266 propensity-score matched pairs were generated. Cox regression analyses revealed no significant difference in 30-day mortality between groups (hazard ratio (HR): 0.90; 95% confidence interval (95% CI): 0.65-1.25). There was no significant difference in the incidence of all-cause infection (odds ratio (OR): 0.98; 95% CI: 0.66-1.46) or pneumonia (OR: 1.02; 95% CI: 0.68-1.55). Subgroup analyses of patients with a low body mass index (BMI; kg/m2) (18.5) revealed a significant decrease of 30-day mortality in the early EN group (HR: 0.30; 95% CI: 0.092-0.97) but no significant difference among patients with a BMI ≥ 18.5 (HR: 1.01; 95% CI: 0.72-1.43).Among patients who received TTM after OHCA, there was no significant association between early EN and 30-day mortality; however, early EN could be beneficial for patients with a low BMI.

We performed this study to evaluate serum iron and ferritin concentrations, serum total iron-binding capacity (TIBC), and proportion of overall iron deficiency among patients with non-dialysisdependent chronic kidney disease (ND-CKD).A hospital-based cross-sectional observational study was conducted on 175 adult patients with stage 3-5 chronic kidney disease (CKD) by using 51 healthy age-sex-matched Vietnamese adults as the control group. We next examined the prevalence of anemia and determined the serum iron and ferritin concentrations and TIBC. Anemia in CKD was defined as hemoglobin levels13 g/dL in men and12 g/dL in women. Transferrin saturation (TSAT, %) was calculated as (serum iron x 100)/TIBC. Functional iron deficiency was defined as serum ferritin100 ng/mL and TSAT20%, and absolute iron deficiency was defined as serum ferritin100 ng/mL and TSAT20%. Overall iron deficiency was defined as the presence of either absolute or functional iron deficiency.Anemia prevalence in our study was approximately 88.6% with a mean hemoglobin concentration of 9.71±2.26 g/dL. The median serum TIBC was lower in the CKD group (50.4 μmol/L) than in the control group (66.0 μmol/L; p0.001). The proportion of overall iron deficiency was 44.0%. TIBC had a diagnostic value for overall iron deficiency (area under the ROC curve=0.81; p0.001).Anemia and iron deficiency are common in Vietnamese patients with NDCKD. TIBC had diagnostic value for overall iron deficiency.

Aim Proteinuria is known to be an independent risk factor of end-stage renal disease (ESRD). But the associations between changes in dipstick proteinuria and the risk of ESRD in the general population and its appropriate observation period to predict incident ESRD are unknown. Methods We assessed the changes in dipstick proteinuria in 69021 subject aged ≥20 years who participated in health check-up from 1993 and more than once until 1996 in Okinawa, Japan. Development of ESRD until 2011 was identified using dialysis registry. Cox proportional hazards model and receiver operating characteristic (ROC) curve were used. Results At baseline, proteinuria (±) and ≥(1+) were observed in 2.4% and 1.2% of total subjects. 1.5% of subjects had decreased and 9.4% of subjects had increased their proteinuria level after 2-year. After adjustment for confounding factors, hazard ratios (95% confidence interval) of ESRD for subjects with proteinuria change ≤-1, +1, +2, +3, and +4 level during 2-year compared to subjects with no change were 0.89 (0.43-1.87), 3.18 (2.21-4.60), 8.01 (5.55-11.55), 11.17 (6.59-19.95), and 16.59 (5.95-46.25), respectively. Heterogeneity existed between changes in proteinuria level during 1- or 3-year and the risk of ESRD among baseline proteinuria. Area under the ROC curve (95%CI) to predict ESRD by increase in proteinuria level during 1-, 2-, and 3-year were 0.650 (0.623-0.679), 0.779 (0.751-0.808), and 0.778 (0.748-0.808), respectively. Conclusions The changes in dipstick proteinuria were an independent predictor of ESRD in the general population. Changes in proteinuria during 2-year may be appropriate for the risk prediction of ESRD.

Background Atypical hemolytic uremic syndrome (aHUS) is caused by complement overactivation, and its presentation and prognosis differ according to the underlying molecular defects. The aim of this study was to characterize the genetic backgrounds of aHUS patients in Japan and to elucidate the associations between their genetic backgrounds, clinical findings, and outcomes. Methods We conducted a nationwide epidemiological survey of clinically diagnosed aHUS patients and examined 118 patients enrolled from 1998 to 2016 in Japan. We screened variants of seven genes related to complement and coagulation, as well as positivity for anti-CFH antibodies, and assessed clinical manifestations, laboratory findings, and clinical course. Results The most frequent genetic abnormalities were in C3 (31%) and the frequency of CFH variants was relatively low (10%) compared to Western countries. The predominant variant in this cohort was C3 p.I1157T (23%), which was related to favorable outcomes despite frequent relapses. A total of 72% of patients received plasma therapy, while 42% were treated with eculizumab. The prognosis of Japanese aHUS patients was relatively favorable, with a total mortality rate of 5.4% and a renal mortality rate of 15%. Conclusions The common occurrence of genotype C3, especially the p.I1157T variant was the characteristic of the genetic backgrounds of Japanese aHUS patients that differed from those of Caucasian patients. In addition, the favorable prognosis of patients with the unique C3 p.I1157T variant indicates that understanding the clinical characteristics of individual gene alterations is important for predicting prognosis and determining therapeutic strategies in aHUS.

AIM The clinical course of idiopathic membranous nephropathy (IMN) varies from spontaneous remission of nephrotic syndrome (NS) to end-stage renal disease (ESRD). The aim of the study was baseline identification of patients with high risk of progression for which immunosuppressive therapy is mandatory. METHODS Eighty-six IMN subjects were followed for a median of 69 months (range 6-253). Receiver operating characteristic curve and Cox proportional hazards model were used to evaluate prognostic factors for progression, defined as ESRD or estimated glomerular filtration rate (eGFR) reduction ≥50% of baseline. RESULTS Among all, 24 subjects had progression. Area under the ROC curve of N-acetyl-β-glucosaminidase/creatinine ratio (NAG/C) were significantly higher than proteinuria/24 h (0.770 and 0.637 respectively, P = 0.018). In Cox proportional hazards regression analysis, NAG/C and eGFR were independent predictors of progression. Compared to lowest tertile of NAG/C (

Background Because of the necessity for extended period and large costs until the event occurs, surrogate endpoints are indispensable for implementation of clinical studies to improve chronic kidney disease (CKD) patients’ prognosis. Methods Subjects with serum creatinine level for a baseline period over 1–3 years were enrolled (n = 69,238) in this community-based prospective cohort study in Okinawa, Japan, and followed up for 15 years. The endpoint was end-stage renal disease (ESRD). The percent of estimated glomerular filtration rate (%eGFR) change was calculated on the basis of the baseline period. Results Subjects had a mean ± SD age, 55.59 ± 14.69 years; eGFR, 80.15 ± 21.15 ml/min/1.73 m2. Among the subjects recruited, 15.81% had a low eGFR (

Aim: It is not clear whether elevated serum non-high-density lipoprotein cholesterol (non-HDL-C) levels are a risk factor for cardiovascular disease (CVD) in subjects with chronic kidney disease (CKD) in the general population. Methods: A total of 2,630 community-dwelling Japanese subjects (1,107 men and 1,523 women) without history of CVD and aged ≥ 40 years were prospectively followed up for an average of 19 years, and the association between serum non-HDL-C levels and the incidence of type-specific CVD was estimated using a Cox proportional hazards model. CKD was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m2 or proteinuria (≥ 1 + on dipstick). Results: At baseline, 357 subjects had CKD. During the follow up, 186 coronary heart disease (CHD) and 277 stroke events occurred. The age- and sex-adjusted incidence of CHD was significantly higher in subjects with higher non-HDL-C levels, both in those with and without CKD. In the CKD group, the risk of CHD was significantly higher in those with non-HDL-C levels of 150–189 mg/dL [adjusted hazard ratio (HR), 2.23; 95% confidence interval (CI), 1.04–4.77] and those with levels ≥ 190 mg/dL (adjusted HR, 3.20; 95% CI, 1.46–7.03) than in those with levels < 150 mg/dL. In the non-CKD group, the risk of CHD was significantly higher only in those with non-HDL-C levels ≥ 190 mg/dL (adjusted HR, 2.12; 95% CI, 1.33 –3.38). However, no such association was observed for the risk of stroke. Conclusions: Our findings suggest that higher serum non-HDL-C levels are associated with greater risk of CHD in subjects with and without CKD and that this association is greater in subjects with CKD than in those without CKD.

Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine produced during acute inflammation. Few studies have evaluated the association between serum TNF-α and its receptors and their clinical outcomes in hemodialysis patients. However, a study assessing patients using a low-flux dialyzer reuse has not been conducted yet. The serum TNF-α concentrations of 319 prevalent hemodialysis patients (mean age, 45 ± 15 years; median duration of hemodialysis, 48 [interquartile range, 26-79] months; 185 males and 134 females) was examined to predict their 3-year mortality. The patients were divided into tertiles according to their serum TNF-α concentrations: T1 (n = 106; serum TNF-α concentration

The appropriate blood pressure target to prevent end-stage renal disease (ESRD) is controversial. We examined the association between systolic blood pressure (SBP) changes and ESRD incidence in 69,575 participants from the Okinawa general population aged ≥ 20 years who underwent health check-ups in 1993 and more than once in 1994–1996. ESRD incidence was identified using dialysis registry until 2011. Cox proportional hazards model was used to estimate hazard ratio (95% confidence interval) with confounding factor adjustment. At baseline, 29.9%, 22.1%, 20.6%, and 27.5% of subjects had SBP

Background and objectives: There is insufficient epidemiological knowledge of hypouricemia. In this study, we aimed to describe the distribution and characteristics of Japanese subjects with hypouricemia. Materials and Methods: Data from subjects who underwent routine health checkups from January 2001 to December 2015 were analyzed in this cross-sectional study. A total of 246,923 individuals, which included 111,117 men and 135,806 women, met the study criteria. The participants were divided into quartiles according to their serum uric acid (SUA) levels. We subdivided the subjects with hypouricemia, which was defined as SUA level &le, 2.0 mg/dL, into two groups and compared their characteristics, including their cardiovascular risks. Results: The hypouricemia rates were 0.46% overall, 0.21% for the men and 0.66% for the women (P &lt, 0.001). The number of the subjects with hypouricemia showed two distributions at SUA levels of 0.4&ndash, 1.1 mg/dL (lower hypouricemia group), which included a peak at 0.7&ndash, 0.8 mg/dL, and at SUA levels of 1.4&ndash, 2.0 mg/dL (higher hypouricemia group). The men in the higher hypouricemia group had lower body mass indexes (BMI) and triglyceride (TG) levels and had higher fasting blood glucose levels than those in the lower hypouricemia group. The women in the higher hypouricemia group were younger, had lower BMI, total protein, TG, total cholesterol and low-density lipoprotein cholesterol levels, and had higher estimated glomerular filtration rates levels compared to those in the lower hypouricemia group. Conclusions: The characteristics of the individuals in the lower and higher hypouricemia groups differed significantly, indicating different pathophysiologies within each group.

BACKGROUND The independent role of serum triglyceride (TG) levels as a cardiovascular risk factor is still not elucidated. We aimed to investigate if the effect of TG on arterial stiffness is influenced by the serum level of low-density lipoprotein cholesterol (LDL-C). Methods and Results: We studied 11,640 subjects who underwent health checkups. They were stratified into 4 groups according to LDL-C level (≤79, 80-119, 120-159, and ≥160 mg/dL). Arterial stiffness was evaluated by brachial-ankle pulse wave velocity (baPWV). In each group, univariate and multivariete logistic regression analyses were performed to investigate the association between high TG (≥150 mg/dL) and high baPWV (>1,400 cm/s). In the univarite analysis, high TG was significantly associated with high baPWV in LDL-C

This study investigated the real-world persistence rate and switches of teriparatide-treated patients using a claims database in Japan. The persistence rate of teriparatide at 12 months was 34.9%, and approximately one-third of the patients were not treated with any osteoporosis drugs after teriparatide. Improvement in persistence and switches are desired. We aimed to elucidate the persistence rates and switches before and after teriparatide treatment in real-world osteoporosis patients based on data from a medical claims database in Japan. We reviewed the records of patients with diagnoses of osteoporosis who were prescribed teriparatide at least once from January 2005 to June 2017. Patients with a follow-up ≤ 90 days before the first and ≤ 90 days after the last prescription of teriparatide were excluded. Discontinuation was defined as no treatment for > 90 days. We investigated treatment duration, compared characteristics of patients with persistence ≤ 12 and > 12 months, and osteoporotic medications before and after teriparatide by weekly or daily teriparatide. Among the 553 patients extracted for the study, 81.9% were women, 45.6% were aged ≥ 65 years, and 67.3% had a fracture. The most common fracture site was the spine (39.2%). The overall persistence rate of teriparatide > 12 months was 34.9% (weekly, 23.5%; daily, 43.1%). The subjects with persistence > 12 months comprised a higher proportion of women and they had a higher prevalence of rib and sternum fractures than those with ≤ 12 months. After teriparatide, 38.2% were switched to active vitamin D3, 35.1% to bisphosphonates, and 13.7% to denosumab allowing duplication. However, 34.0% of the patients were not switched to any subsequent medication for osteoporosis. Persistence rate over 12 months of teriparatide treatment was 34.9% in Japan. Approximately one-third of patients had no subsequent treatment immediately after teriparatide. Monitoring persistence and considering subsequent drugs for osteoporosis are necessary for teriparatide treatment.

Aim Proteinuria is known to be an independent risk factor of end‐stage renal disease (ESRD). But the associations between changes in dipstick proteinuria and the risk of ESRD in the general population and its appropriate observation period to predict incident ESRD are unknown. Methods We assessed the changes in dipstick proteinuria in 69 021 participants aged ≥20 years who participated in health check‐ups from 1993 and more than once until 1996 in Okinawa, Japan. Development of ESRD until 2011 was identified using dialysis registry. Cox proportional hazards model and receiver operating characteristic (ROC) curve were used. Results At baseline, proteinuria (±) and ≥(1+) were observed in 2.4% and 1.2% of total subjects. 1.5% of subjects had decreased and 9.4% of subjects had increased their proteinuria level after 2 years. After adjustment for confounding factors, hazard ratios (95% confidence interval) of ESRD for subjects with proteinuria change ≤ − 1, +1, +2, +3, and +4 level during 2 years compared to subjects with no change were 0.89 (0.43–1.87), 3.18 (2.21–4.60), 8.01 (5.55–11.55), 11.17 (6.59–19.95), and 16.59 (5.95–46.25), respectively. Heterogeneity existed between changes in proteinuria level during 1 or 3 years and the risk of ESRD among baseline proteinuria. Area under the ROC curve (95%CI) to predict ESRD by increase in proteinuria level during 1, 2, and 3 years were 0.650 (0.623–0.679), 0.779 (0.751–0.808), and 0.778 (0.748–0.808), respectively. Conclusions The changes in dipstick proteinuria were an independent predictor of ESRD in the general population. Changes in proteinuria over 2 years may be appropriate for the risk prediction of ESRD., Summary at a Glance Changes in dipstick proteinuria were an independent predictor of ESRD in the general population. This study on a large Japanese population of CKD with proteinuria shows that increase in dipstick proteinuria over 2 years may be appropriate for risk prediction of ESRD.

Background: Recent evidence indicates that vitamin D deficiency is associated with an increased risk of renal impairment, but studies addressing the influence of vitamin D deficiency on the development of chronic kidney disease (CKD) in the general Asian population have been few. Methods and Results: A total of 2,417 community-dwelling individuals without CKD stage 3–5 aged ≥40 years were followed for 5 years (mean age, 60 years; women, 59.1%). The cumulative incidence of CKD stage 3–5, defined as estimated glomerular filtration rate (eGFR)

BACKGROUND Angiopoietin-like protein 2 (Angptl2) is an adipokine that promotes inflammation and endothelial dysfunction of the vessels. The aim of this study was to investigate the relationship between serum Angptl2 level and chronic kidney disease (CKD). METHODS AND RESULTS A total of 3,169 community-dwelling subjects aged ≥40 years were divided into quintiles by Angptl2 level. CKD was defined as the presence of albuminuria (urine albumin-creatinine ratio ≥30.0mg/g) or decreased estimated glomerular filtration rate (eGFR

The clinical course of idiopathic membranous nephropathy (IMN) varies from spontaneous remission of nephrotic syndrome (NS) to end-stage renal disease (ESRD). The aim of the study was baseline identification of patients with high risk of progression for which immunosuppressive therapy is mandatory.Eighty-six IMN subjects were followed for a median of 69 months (range 6-253). Receiver operating characteristic curve and Cox proportional hazards model were used to evaluate prognostic factors for progression, defined as ESRD or estimated glomerular filtration rate (eGFR) reduction ≥50% of baseline.Among all, 24 subjects had progression. Area under the ROC curve of N-acetyl-β-glucosaminidase/creatinine ratio (NAG/C) were significantly higher than proteinuria/24 h (0.770 and 0.637 respectively, P = 0.018). In Cox proportional hazards regression analysis, NAG/C and eGFR were independent predictors of progression. Compared to lowest tertile of NAG/C (9.4 UI/gC) or highest tertile of eGFR (≥88 mL/min per 1.73mIdiopathic membranous nephropathy subjects with high NAG/C and low eGFR have greater risk of progression, and immunosuppressive treatment is suggested at diagnosis.

Aims: To elucidate the relationship between albuminuria and the prevalence of peripheral arterial disease (PAD), and to examine the effect of albuminuria on the ability to assess the likelihood of PAD in a general Japanese population.Methods: In 3,061 community-dwelling subjects aged. 40 years, we investigated the association of urinary albumin-creatinine ratio (UACR) levels with the prevalence of PAD, defined as an ankle-brachial index 300.0 mg/g, being 0.34, 0.80, 2.02, 2.50, and 2.53%, respectively (p for trend

The purpose of this study was to investigate the correlation between dental conditions and comorbidities in an elderly population in Japan.A database constructed using data obtained from 12 nursing homes in Japan was used in this study. The study period ranged from January 2014 to December 2

Background: Rush immunotherapy (RIT) can confer rapid clinical benefit on patients with allergic rhinitis or asthma. However, biomarkers representing mechanisms for the efficacy of RIT are still to be established. CD203c is a basophil activation marker known to be upregulated by cross-linking of the FcΕRIα receptor and may serve as a useful marker. Objective: We sought to investigate the changes in allergen-induced CD203c expression in patients with Japanese cedar pollen (JCP) pollinosis who received RIT. Methods: Nine patients treated with RIT were enrolled in the study. Whole blood was incubated with various concentrations of JCP extract. CD203c expression on basophils was quantitated by means of flow cytometry. JCP-specific IgG4 levels in sera were measured with ELISA. Basophil histamine release, CAP-RAST to JCP (JCP-IgE) and total IgE were also examined. The biomarkers listed above were evaluated before and sequentially after RIT. Symptom and quality of life scores were obtained during pre- and posttreatment pollen seasons. Results: All patients showed significant improvement in symptom and quality of life scores after RIT. Serum JCP-specific IgG4 titers were significantly elevated at 1 month and remained at high levels 12 months after the treatment. Stimulation with JCP extract induced enhancement of basophil CD203c expression in a concentration-dependent manner except for 2 subjects in whom no increase in CD203c by an anti-IgE antibody was observed (nonresponders). Significant reductions in the responses were observed in 4 subjects after RIT (reduction in CD203c expression, RCE) whereas no changes were seen in 3 subjects (non-RCE). RCE subjects were older than non-RCE counterparts, with mean ages of 20 and 12 years, respectively. No significant changes in JCP-specific IgE and total IgE levels were seen before and after RIT. Conclusion: Allergen-induced CD203c expression in basophils may represent, at least in part, the cellular mechanism for the therapeutic responses to RIT for JCP pollinosis. However, further larger-scale studies to confirm the utility of the test are necessary.

PURPOSE Validated questionnaire for evaluation of pediatric lower urinary tract symptoms (LUTS) is of a great need. We performed cross-cultural validated adaptation of Dysfunctional Voiding Symptom Score (DVSS) to Japanese language, and assessed whether children understand and respond to questionnaire correctly, using cognitive linguistic approach. METHODS We translated DVSS into two Japanese versions according to a standard validation methodology: translation, synthesis, back-translation, expert review, and pre-testing. One version was written in adult language for parents, and the other was written in child language for children. Pre-testing was done with 5 to 15-year-old patients visiting us, having normal intelligence. A specialist in cognitive linguistics observed the response by children and parents to DVSS as an interviewer. When a child could not understand a question without adding or paraphrasing the question by the parents, it was defined as 'misidentification'. RESULTS We performed pretesting with 2 trial versions of DVSS before having the final version. The pre-testing for the first trial version was done for 32 patients (male to female ratio was 19 : 13). The pre-testing for the second trial version was done for 11 patients (male to female ratio was 8 : 3). In DVSS in child language, misidentification was consistently observed for representation of time or frequency. We completed the formal validated translation by amending the problems raised in the pre-testing. CONCLUSION The cross-cultural validated adaptation of DVSS to child and adult Japanese was completed. Since temporal perception is not fully developed in children, caution should be taken for using the terms related with time or frequency in the questionnaires for children.

To elucidate the relationship between albuminuria and the prevalence of peripheral arterial disease (PAD), and to examine the effect of albuminuria on the ability to assess the likelihood of PAD in a general Japanese population.In 3,061 community-dwelling subjects aged. 40 years, we investigated the association of urinary albumin-creatinine ratio (UACR) levels with the prevalence of PAD, defined as an ankle-brachial index0.9. The odds ratio for the presence of PAD was estimated using the logistic regression model. To compare the accuracy of the assessment for the likelihood of prevalent PAD between models adjusted for potential risk factors with and without UACR levels, the receiver operating characteristic (ROC) curves were plotted.Overall, 1.47% of the study participants had PAD. The age- and sex-adjusted prevalence of PAD increased linearly for UACR levels of5.6, 5.6-10.8, 10.9-29.9, 30.0-300.0, and300.0 mg/g, being 0.34, 0.80, 2.02, 2.50, and 2.53%, respectively (p for trend0.001). The multivariate-adjusted odds ratio for the presence of PAD was 1.85 (95% confidence interval 1.12-3.06) for every 10-fold increment in UACR. The area under the ROC curve significantly increased when UACR levels were incorporated into a model with potential risk factors for PAD (0.80 vs. 0.77, p= 0.02).Greater UACR levels are associated linearly with a higher prevalence of PAD, even within the normoalbuminuric range, in the general Japanese population, and combining UACR levels with potential risk factors substantially improves the performance to assess the likelihood of PAD.

Location of the type V collagen-binding domain within bovine thrombospondin (TSP) was investigated by using fragments of reduced and alkylated TSP. A fragment of relative molecular mass (19 kDa) was isolated, which inhibited binding of 125I-TSP to type V collagen in a solid-phase binding assay. A direct binding assay using the 125I-labeled fragment confirmed that the fragment actually bound to collagen. The fragment retained specificity for the native structure of type V collagen like the intact TSP molecule. Its binding to the collagen, however, was not inhibited by Ca2+ in contrast to intact TSP. Amino acid sequence analysis of the 19-kDa fragment suggested that this fragment corresponded to Val333-Lys412, a part of the stalklike region in the human TSP primary structure. It was found that the fragment also bound well to heparin in a specific and saturable manner and, furthermore, binding to type V collagen was inhibited by soluble heparin. Removal of the N-linked sugar chain from this fragment resulted in a 14-kDa fragment. The deglycosylated fragment retained the ability to bind to type V collagen as well as heparin. These results suggest that a type V collagen-binding site is present in the 80-residue portion of bovine TSP (Val333-Lys412) and is likely to be identical or lie very close to a heparin-binding site, which exists in the type I repeat structure.

The propolypeptide of von Willebrand factor (pp-vWF) was found to serve as a substrate for Factor XIIIa (FXIIIa). FXIIIa catalyzed polymerization of pp-vWF as well as the incorporation of monodansylcadaverine and [14C]putrescine into pp-vWF in a Ca(2+)- and time-dependent manner. The amount of putrescine incorporated into pp-vWF was increased as a function of putrescine concentration and reached a maximum of 3 mol/mol of pp-vWF, indicating that there are at least 3 glutamine residues in the pp-vWF molecule responsible for the reaction. 125I-pp-vWF was incubated with FXIIIa in the presence of various adhesive glycoproteins. Laminin, among the proteins tested, specifically formed a large molecular weight complex with 125I-pp-vWF in a Ca(2+)- and time-dependent manner. It was also found that FXIIIa catalyzed polymerization of laminin as well as the incorporation of monodansylca-daverine into laminin. The high molecular weight complexes of 125I-pp-vWF (or 125I-laminin) formed in the presence of laminin (or pp-vWF) were immunoprecipitated with anti-laminin (or anti-pp-vWF) antibodies. Taking all the data together it can be concluded that both pp-vWF and laminin have glutamine and lysine residues responsive to FXIIIa and make copolymers by virtue of FXIIIa.

We compared the binding of propolypeptide and mature portions of von Willebrand factor of bovine origin to fibrillar type-I collagen obtained from bovine tendon. The propolypeptide (pp-vWF) and the mature portion (m-vWF) of human origin consist of 741 and 2050 amino acids, respectively, and are rather large proteins. The collagen-binding properties of the two proteins of bovine origin were similar in that both bound more avidly to native collagen than to heat-denatured collagen. Bindings was affected similarly by ionic strength but was not modified either by divalent cations or a synthetic peptide containing Arg-Gly-Asp. However, the binding sites in the fibrillar type-I collagen molecule for pp-vWF and m-vWF seem to be different: the two proteins did not effectively compete with each other for binding to collagen. Furthermore, pepsin treatment of fibrillar type-I collagen resulted in a drastic decrease in the binding of pp-vWF, while only a moderate decrease in the binding of m-vWF was observed after the treatment.

Recently we have found that propolypeptide of von Willebrand factor (pp-vWF) obtained from platelets binds to type I collagen. It is known that pp-vWF is present in platelet alpha-granules and is secreted upon activation. In this paper, we demonstrate the two following evidences to show that it is also present on the surface of resting platelets. [1] The antibody against pp-vWF bound to the surface of platelets. [2] The antibody induced aggregation of platelets. The binding of the antibody and the antibody-induced aggregation of platelets were inhibited in a dose-dependent manner by Fab fragment of the antibody. Platelets from von Willebrand disease patients bound less of the antibody and responded weakly to the antibody.

When platelets are activated by the recognition of exposed collagen fibers, they start synthesizing two major arachidonic acid metabolites, i.e. thromboxane A2 and 12S-hydroxyeicosatetraenoic acid (12-HETE) via cyclooxygenase and 12-lipoxygenase pathways, respectively. Although the physiological role of the former is well established, that of the latter has not been fully elucidated. Recently, we have revealed that 12-HETE interferes with collagen-induced platelet aggregation [Sekiya, F. et al. (1990) Biochim. Biophys. Acta 1044, 165-168]. In the present paper, we show that this substance enhances thrombin-induced aggregation of bovine platelets, in sharp contrast with the case of collagen. Additionally, 12-HETE is able to prevent the prostaglandin E1-induced elevation of platelet cAMP level and counteracts its inhibitory effect on platelet aggregations. With these observations, we propose a novel self-regulatory mechanism of platelets where 12-HETE plays a key role; it switches sensitivity of platelets from the primary agonist (collagen) to the secondary one (thrombin), and cancels the inhibitory effect of cAMP elevators.

A new debenzylation method using aluminum chloride in benzene or anisole, which had been developed by us for N-benzyl-2-acyl- and -2-ethoxycarbonylindoles, was applied to benzyl derivatives of other types of indoles and related compounds. Among them, N-benzyl derivatives of fully aromatized indoles, carbazoles and β-carbolines, and some benzamides were debenzylated successfully, whereas those of oxindoles and heterocyclic amides were not. As to the effect of a p-substituent on the benzyl group, it was found that an electron-donating substituent accelerates deprotection, whereas an electron-attracting substituent delays or prevents deprotection.