Association between dry eye and periodontal disease in community-dwelling Japanese adults: data from the Uonoma cohort study.

BACKGROUND: While research has explored the risk of periodontal disease in various eye conditions, the link between dry eye and periodontal disease remains underexplored, especially in Japanese adults. This study aims to investigate the association between dry eye and periodontal disease in community-dwelling Japanese adults. METHODS: This study is a subset of the Uonuma cohort study, which includes Japanese adults aged 40 years and older residing in the Uonuma area of Niigata Prefecture, Japan. Participants completed a self-administered, paper-based questionnaire. Statistical analyses, including the chi-square test, independent t test, ANOVA test, and logistic regressions, were employed to assess the association of periodontal disease with independent variables. RESULTS: Among 36,488 participants (average age 63.3 years, 47.4% men), 39.3% had a history of periodontal disease, and gender differences were statistically significant (p < 0.001). Significant associations were found between periodontal disease and dry eye diagnosis or symptoms. Univariable logistic regression revealed links between periodontal disease and age, gender, living status, alcohol consumption, remaining teeth, bite molar availability, and history of dry eye disease or symptoms. Multiple-adjusted regression found that doctor-diagnosed dry eye was associated with a higher likelihood of periodontal disease (odds ratio, 1.12; 95% confidence interval, 1.03-1.22). Participants who never experienced dryness or foreign body sensation had lower ORs of periodontal disease than those who always experienced such symptoms across all models. CONCLUSION: A significant correlation was found between dry eye and periodontal disease in Japanese adults. Regular check-ups, early detection, and effective management of both conditions are strongly recommended.

Chronic kidney disease awareness and its determinants in middle-aged and older Japanese adults: Observations from a 5-year follow-up of the Uonuma cohort study.

AIM: Despite global efforts in public health campaigns concerning chronic kidney disease (CKD), awareness of the condition remains low. We evaluated CKD awareness and related factors to identify an effective way to raise awareness. METHODS: This study assessed laboratory-confirmed CKD and self-reported CKD using a population-based cohort (baseline from 2012 to 2014, age ≥40 years) in Niigata, Japan. Self-reported CKD was obtained at a 5-year follow-up survey and laboratory-confirmed CKD was diagnosed when an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or dipstick urinary protein ≥1+ was observed in at least two health check-ups during the 5-year period. CKD awareness was defined as a match between laboratory-confirmed and self-reported CKD. The association between characteristics and CKD awareness was tested by multivariable logistic regression analysis with adjustment for eGFR and other potential confounders. RESULTS: The analytic population comprised 7472 individuals (mean age, 65.6 years old, 51.2% women) and 19.4% with laboratory-confirmed CKD. The sensitivity and specificity of the survey question concerning self-reported CKD were 12.4% and 98.2%, respectively. Among the participants with laboratory-confirmed CKD, significant factors associated with CKD awareness were male sex (adjusted odds ratio [95% confidence interval], 1.81 [1.27, 2.59]), a history of urinary tract stone (1.86 [1.06, 3.26]), age (0.97 [0.95, 0.99]), and married status (0.66 [0.44, 0.99]). CONCLUSION: Our findings suggest that known lifestyle-related diseases that could cause CKD are not associated with CKD awareness independently of kidney function and that a sex-dependent approach may help to raise CKD awareness in community-dwelling Japanese adults.

Association between Physical Activity in Rural Life and Sarcopenia in Community-Dwelling Middle-Aged and Older Japanese Adults: A Cross-Sectional Study.

Physical activity is crucial to prevent sarcopenia, but there is scant data on the link between sarcopenia and physical activity in rural communities. Therefore, this study investigated associations of farming activity and snow removal with sarcopenia in a middle-aged and older population in rural Japan. This cross-sectional study enrolled 3,056 residents aged ≥ 40 years (49.2% men; mean age, 64.2 years) in Yuzawa, Japan. Information on farming activity and snow removal were collected via questionnaire from May through November and from December through April, respectively. Sarcopenia was assessed by the SARC-F (strength, ambulation, rising from a chair, stair climbing, and history of falling) score. Associations of farming activity and snow removal with sarcopenia were assessed using multivariable logistic regression analysis with adjustment for potential confounders. Participants who engaged in farming activity, snow removal, and both accounted for 3.8%, 40.5%, and 29.4% of the total, respectively. In the multivariable logistic regression analysis, adjusted odds ratios [95% confidence intervals (CI)] of sarcopenia for farming activity and snow removal were 0.80 (0.63-1.03) and 0.68 (0.53-0.87), respectively. Compared with participants who did not engage in farming activity or snow removal, participants who engaged in both had a significantly lower adjusted odds ratio of sarcopenia [0.63 (95% CI 0.47-0.86)]. Participants who engaged in snow removal and those who engaged in both farming activity and snow removal showed inverse associations with sarcopenia. Our findings further support the importance of physical activity in preventing or mitigating sarcopenia in rural communities.

Associations of Urinary and Dietary Sodium-To-Potassium Ratios with Albuminuria in Community-Dwelling Japanese Adults: A Cross-Sectional Study.

INTRODUCTION: The urinary sodium-to-potassium ratio is an indicator of dietary sodium intake and has been associated with reduced kidney function. However, less is known about its association with albuminuria, the other key component of chronic kidney disease, in the community-dwelling adult population. We examined the association of the spot urinary sodium-to-potassium ratio with albuminuria and compared spot urinary and dietary sodium-to-potassium ratios. METHODS: We quantified the association of the urinary sodium-to-potassium ratio with albuminuria in 6,274 Japanese adults (aged 40-97 years; 50.9% women) based on spot urine samples. We performed linear and logistic regression modeling to account for potential confounders. Elevated albuminuria was defined as a spot urinary albumin-to-creatinine ratio (ACR) ≥30 mg/g. We secondarily evaluated the dietary sodium-to-potassium ratio based on a food-frequency questionnaire. RESULTS: The median spot urinary and dietary sodium-to-potassium ratios were 2.70 (interquartile interval, 1.87-3.83) and 1.50 (1.21-1.84), respectively. The median ACR was 11.0 (6.0-24.0) mg/g. In a multivariable linear regression model, the spot urinary sodium-to-potassium ratio (per increment) was significantly associated with the natural logarithm of the ACR (regression coefficient, 0.023 [95% confidence interval {95% CI}, 0.007-0.038]). This result was consistent in a multivariable logistic regression model (adjusted odds ratio, 1.08 [95% CI: 1.04-1.12]). The corresponding estimates for the dietary sodium-to-potassium ratio were 0.139 (95% CI: 0.087-0.191) and 1.28 (95% CI: 1.14-1.45), respectively. CONCLUSIONS: Both spot urinary and dietary sodium-to-potassium ratios were associated with elevated albuminuria in community-dwelling Japanese adults. Our findings further support the potential usefulness of the spot urinary sodium-to-potassium ratio as an indicator of sodium intake and suggest a link between sodium intake and kidney damage.

Association between Sarcopenia and Depressive Symptoms in Community-Dwelling People Aged 40 Years and Older.

Several studies have reported an association between sarcopenia and depression. Their results, however, are inconsistent, partly due to small sample sizes and lack of consideration of important confounders. The present study aimed to cross-sectionally examine this association in community-dwelling people in Japan. This study used baseline data from the Yuzawa cohort study (age ≥ 40 years), with the final analysis population comprising 2,466 participants. A self-administered questionnaire was used to elicit information related to sarcopenia, depressive symptoms, demographic characteristics, anthropometrics, disease history, and lifestyles. Sarcopenia was diagnosed using SARC-F, a validated questionnaire including components of Strength, Assistance in walking, Rising from a chair, Climbing stairs, and Falls. Depressive symptoms were assessed using the 11-item version of the Center for Epidemiologic Studies Depression Scale (CES-D). For depressive symptoms, prevalence ratios (PRs) were calculated, and odds ratio (ORs) were obtained using simple and multiple logistic regression analyses. Mean age of participants was 61.7 years (standard deviation = 11.8), and 10.5% and 34.7% had sarcopenia and depressive symptoms, respectively. Sarcopenic individuals had a significantly higher PR (2.00), unadjusted OR (3.67), and adjusted OR (4.96) compared to non-sarcopenic individuals, with an estimated adjusted PR of 2.7. There was a significant dose-dependent association between SARC-F scores and depressive symptoms in sarcopenic individuals (adjusted P for trend = 0.0028). In conclusion, sarcopenia and depressive symptoms were robustly associated in community-dwelling, middle-aged and older people in Japan. However, the direction of this association is unclear, and a future cohort study will be needed to determine causality.

Dental Arch Relationship Outcomes Following 2-Stage Palatoplasty for Japanese Patients With Complete Unilateral Cleft Lip and Palate: A 3-Center Study.

OBJECTIVE: To compare dental arch relationship outcomes following 3 different 2-stage palatal repair protocols. DESIGN: Retrospective, cross sectional. SETTING: Three cleft palate centers (A, B, C) in Japan. PATIENTS: Ninety (A: 39, B: 26, C: 25) consecutively treated Japanese patients with complete unilateral cleft lip and palate. INTERVENTIONS: In A, the soft palate and the posterior half of the hard palate were repaired at a mean age of 1 year 7 months. In B, the soft palate and hard palate were closed separately at a mean age of 1 year 6 months and 5 years 8 months, respectively. In C, the soft palate and hard palate were closed at a mean age of 1 year and 1 year 5 months, respectively. MAIN OUTCOME MEASURES: Dental arch relationships were assessed using the 5-Year-Olds' (5-Y) index by 5 raters and the Huddart/Bodenham (HB) index by 2 raters. RESULTS: Intra- and inter-rater reliabilities showed substantial or almost perfect agreement for the 5-Y and HB ratings. No significant differences in mean values and distributions of 5-Y scores were found among the 3 centers. The mean HB index scores of molars on the minor segment were significantly smaller in C than those in A and B (P < .05). CONCLUSIONS: There were no significant differences in dental arch relationships at 5 years among the times and techniques of hard palate closure. However, further analysis of the possible influence of infant cleft size as a covariable on a larger sample size is needed.

Plasma Globotriaosylsphingosine and α-Galactosidase A Activity as a Combined Screening Biomarker for Fabry Disease in a Large Japanese Cohort.

Fabry disease is an X-linked disorder of α-galactosidase A (GLA) deficiency. Our previous interim analysis (1 July 2014 to 31 December 2015) revealed plasma globotriaosylsphingosine as a promising primary screening biomarker for Fabry disease probands. Herein, we report the final results, including patients enrolled from 1 January to 31 December 2016 for evaluating the potential of plasma globotriaosylsphingosine and GLA activity as a combined screening marker. We screened 5691 patients (3439 males) referred from 237 Japanese specialty clinics based on clinical findings suggestive of Fabry disease using plasma globotriaosylsphingosine and GLA activity as primary screening markers, and GLA variant status as a secondary screening marker. Of the 14 males who tested positive in the globotriaosylsphingosine screen (≥2.0 ng/mL), 11 with low GLA activity (<4.0 nmol/h/mL) displayed GLA variants (four classic, seven late-onset) and one with normal GLA activity and no pathogenic variant displayed lamellar bodies in affected organs, indicating late-onset biopsy-proven Fabry disease. Of the 19 females who tested positive in the globotriaosylsphingosine screen, eight with low GLA activity displayed GLA variants (six classic, two late-onset) and five with normal GLA activity displayed a GLA variant (one classic) and no pathogenic variant (four late-onset biopsy-proven). The combination of plasma globotriaosylsphingosine and GLA activity can be a primary screening biomarker for classic, late-onset, and late-onset biopsy-proven Fabry disease probands.

Association of coexisting anti-ribosomal P and anti-dsDNA antibodies with histology and renal prognosis in lupus nephritis patients.

OBJECTIVES: Anti-ribosomal P protein autoantibodies (anti-P) specifically develop in patients with systemic lupus erythematosus. Associations of anti-P with lupus nephritis (LN) histological subclass and renal outcome remain inconclusive. We sought to determine the association of anti-P and anti-double-stranded DNA antibody (anti-dsDNA) with renal histology and prognosis in LN patients. METHODS: Thirty-four patients with LN, having undergone kidney biopsy, were included. The 2018 revised ISN/RPS classification system was used for pathophysiological evaluation. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m2 for > 3 months. RESULTS: Six patients (17.6%) were positive for anti-P and 26 (76.5%) for anti-dsDNA. Among the six patients with anti-P, one did not have anti-dsDNA, but did have anti-Sm antibody, and showed a histological subtype of class V. This patient maintained good renal function for over 14 years. The remaining five patients, who had both anti-P and anti-dsDNA, exhibited proliferative nephritis and were associated with prolonged hypocomplementemia, and the incidence of CKD did not differ from patients without anti-P. CONCLUSION: Although this study included a small number of patients, the results indicated that histology class and renal prognosis associated with anti-P depend on the coexistence of anti-dsDNA. Further studies with a large number of patients are required to confirm this conclusion.

Activating HRAS mutation in a case of inverted ductal papilloma of the salivary gland.

Inverted ductal papilloma (IDP) is one of the least common benign papillary/cystic neoplasms of the salivary duct system, being characterized histologically by florid hyperplasia of duct-type epithelial cells into a cystic lumen near the orifice with occasional endophytic growth of the surface squamous epithelium along the terminus of the affected excretory duct. Given its rarity, the exact etiology of IDP remains to be defined. We herein present the first evidence of oncogenic HRAS mutation in a case of oral IDP. This finding, together with the frequent and specific BRAF mutations in sialadenoma papilliferum reported in the recent literature, supports an active role of the MAP-kinase cascade in the pathogenesis of benign papillary neoplasms of terminal duct origin.

Education, household income, and depressive symptoms in middle-aged and older Japanese adults.

BACKGROUND: Income inequality has dramatically increased worldwide, and there is a need to re-evaluate the association between socio-economic status (SES) and depression. Relative contributions of household income and education to depression, as well as their interactions, have not been fully evaluated. This study aimed to examine the association between SES and depressive symptoms in Japanese adults, focusing on interactions between education and household income levels. METHODS: This cross-sectional study used data from baseline surveys of two cohort studies. Participants were 38,499 community-dwelling people aged 40-74 years who participated in baseline surveys of the Murakami cohort study (2011-2012) and Uonuma cohort study (2012-2015) conducted in Niigata Prefecture, Japan. Information regarding marital status, education level, household income, occupation, activities of daily living (ADL), and history of cancer, myocardial infarction, stroke, and diabetes was obtained using a self-administered questionnaire. Depressive symptoms were examined using the Center for Epidemiologic Studies Depression Scale (CES-D). Logistic regression analysis was used to obtain odds ratios (ORs). Covariates included age, sex, marital status, education, household income, occupation, ADL, and disease history. RESULTS: Individuals with higher education levels had lower ORs (adjusted P for trend = 0.0007) for depressive symptoms, independently of household income level. The OR of the university-or-higher group was significantly lower than that of the junior high school group (adjusted OR = 0.79). Individuals with lower household income levels had higher ORs (adjusted P for trend< 0.0001) for depressive symptoms, independently of education level. The type of occupation was not associated with depressive symptoms. In subgroup analyses according to household income level, individuals with higher education levels had significantly lower ORs in the lowest- and lower-income groups (adjusted P for trend = 0.0275 and 0.0123, respectively), but not in higher- and highest-income groups (0.5214 and 0.0915, respectively). CONCLUSIONS: Both education and household income levels are independently associated with the prevalence of depressive symptoms, with household income levels showing a more robust association with depressive symptoms than education levels. This suggests that a high household income level may offset the risk of depressive symptoms from having a low education level.

Distinct clonal evolution in a case with anaplastic embryonal rhabdomyosarcoma.

BACKGROUND: Clonal evolution of malignancy is a complex process related to intratumoral heterogeneity, as recent studies have also demonstrated in rhabdomyosarcoma. The purpose of this study is to present a distinct clonal feature of a case with anaplastic embryonal type rhabdomyosarcoma (ERMS) using molecular analysis. METHODS: A five-year-old girl developed a metastatic pelvic tumor. We cultured neoplastic cells isolated from the biopsy sample. Next, to characterize the current case, we analyzed the biopsy sample, autopsy sample, and established cell line using combined modalities, including histopathological, cytogenetic, and molecular assay. We also undertook the backtrack mutation-specific polymerase chain reaction to reveal clonal composition. RESULTS: The histology of the biopsy sample was consistent with ERMS with focal anaplasia. We established a permanently growing cell line, ICH-ERMS-1, from the biopsy sample. On molecular analysis, the biopsied tissue revealed a missense mutation at codon 245 of TP53. In contrast, the autopsy tumor tissue and the cell line established from the biopsied tissue showed a missense mutation at codon 248. A backtrack study using mutation-specific polymerase chain reaction detected a TP53 codon 248 mutation in the original biopsy sample. All the specimens examined had a missense mutation at PTPN11 codon 69. CONCLUSIONS: This study highlights intratumoral heterogeneity and distinct clonal change related to the functional context in our anaplastic ERMS case, supporting the concept of intratumoral heterogeneity and clonal evolution. It requires further case collection to reveal whether p14ARF-p53-MDM2 tumor suppressor pathway alteration, considered a late event in ERMS tumorigenesis, is responsible for anaplasia in ERMS.

Low serum 25-hydroxyvitamin D is associated with low grip strength in an older Japanese population.

Positive associations between vitamin D levels and hand grip strength have been reported worldwide, but the results are not consistent and few studies on East Asian populations have been published. The aim of this study was to determine whether such an association is present in a community-dwelling Japanese population, including elderly and middle-aged individuals. This study used a cross-sectional design. Participants were 492 community-dwelling individuals aged ≥ 40 years living in Yuzawa Town, Japan. The health check examination was conducted in 2015, and serum 25-hydroxyvitamin D [25(OH)D, an index of vitamin D levels], and hand grip strength were measured. Covariates were serum albumin concentration, body mass index, and physical activity level. The associations of serum 25(OH)D concentrations with hand grip strength and low grip strength (< 26 kg for men and < 18 kg for women) were analyzed using analysis of covariance and multiple logistic regression. Mean (standard deviation) age and serum 25(OH)D were 75.4 (9.0) years and 30.9 (9.1) ng/mL, respectively. The prevalence of serum 25(OH)D < 20, 20-29, and ≥ 30 ng/mL was 7.3%, 37.8%, and 54.9%, respectively. Mean hand grip strength in the 25(OH)D < 20 ng/mL group was significantly lower than that in the ≥ 30 ng/mL group (adjusted P ≤ 0.001). The 25(OH)D < 20 ng/mL group was significantly more likely to have low grip strength than the 25(OH)D ≥ 30 ng/mL group (odds ratio = 4.12). In conclusion, low serum 25(OH)D concentration (< 20 ng/mL) is associated with low grip strength in an older Japanese population.

Study Design and Baseline Profiles of Participants in the Uonuma CKD Cohort Study in Niigata, Japan.

BACKGROUND: Evidence for primary prevention of chronic kidney disease (CKD) is insufficient. The population-based prospective Uonuma CKD cohort study aims to explore associations of lifestyle and other risk factors with CKD. We report here the study design and baseline profiles. METHODS: All 67,322 residents aged ≥40 years in Minamiuonuma City, Uonuma City, and Yuzawa Town, Niigata Prefecture, Japan and 11,406 participants who attended local health-check examinations were targeted for baseline questionnaire and biochemical sampling, respectively. Information was gathered from 43,217 (64.2%) questionnaires and 8,052 (70.6%) biochemical samples; 6,945 participants consented to both questionnaire and biochemical sampling at baseline, conducted between fiscal years 2012 and 2015. Participants provided information regarding sociodemographic, lifestyle, and self-reported outcomes. Urine albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR) were measured. The primary outcome is CKD based on self-report and biochemical/clinical diagnosis. RESULTS: Mean age of questionnaire respondents was 63.3 (standard deviation [SD], 12.5) years for men and 64.3 (SD, 13.3) years for women. Among participants who submitted urine samples, median ACR was 10.0 (interquartile range [IQR], 5.0-24.0) mg/g for men and 13.0 (IQR, 7.7-27.0) mg/g for women, and median eGFR was 73.6 mL/min/1.73 m2 (IQR, 63.5-84.5) for men and 73.5 mL/min/1.73 m2 (IQR, 64.4-83.5) for women. ACR 30 mg/g or more was found in 1,741 participants (21.7%) and eGFR <60 mL/min/1.73 m2 in 1,361 participants (16.9%). CONCLUSION: The Uonuma CKD cohort study was established to investigate the impact of lifestyle on CKD development and to provide data for preventing the onset and progression of CKD.

Epidemiological study of oral allergy syndrome in birch pollen dispersal-free regions.

BACKGROUND: Oral allergy syndrome (OAS) is an immediate allergy caused by a cross-reaction of highly homologous common antigens (pan-allergens) contained in fruits/vegetables and pollen. METHODS: A questionnaire was provided to 6824 outpatient visitors and serum levels of specific IgEs against crude antigens and pan-allergen components were measured to study the relationship between the prevalence of OAS and pollinosis in the Fukui Prefecture where there is almost no dispersal of birch pollen. RESULTS: The prevalence of OAS was 10.8%. The rate of pollinosis complication in the OAS group was 67.4%, and OAS was observed in 16.8% of pollinosis patients. Causative foods in order of frequency were melon, pineapple, kiwi fruit, peach, and apple. A significantly higher number of patients from the OAS group were positive for birch, alder, and timothy grass-specific IgE. The rate of positivity for anti-component IgE corresponding to pollen in OAS group was also significantly higher. Of 34 patients with OAS caused by eating apples, 28 (82.4%) were positive for Mal d1-specific IgE. Of the 52 patients with peach-induced OAS, 41 (78.8%) were positive for Pur p1-specific IgE. The concordance rates between crude antigen-specific IgE and anti-PR-10 component-specific IgE were 87.1% and 93.3% for apple and peach respectively. CONCLUSIONS: In regions where birch pollen is not dispersed, OAS patients have a significant association with the onset of Bet v1-associated allergy. Anti-PR-10 component IgE was useful in diagnosing OAS, and crude antigen-specific IgE was also associated with apple and peach allergies.

Medullary thick ascending limb impairment in the GlatmTg(CAG-A4GALT) Fabry model mice.

A main feature of Fabry disease is nephropathy, with polyuria an early manifestation; however, the mechanism that underlies polyuria and affected tubules is unknown. To increase globotriaosylceramide (Gb3) levels, we previously crossbred asymptomatic Glatm mice with transgenic mice that expressed human Gb3 synthase (A4GALT) and generated the GlatmTg(CAG-A4GALT) symptomatic Fabry model mice. Additional analyses revealed that these mice exhibit polyuria and renal dysfunction without remarkable glomerular damage. In the present study, we investigated the mechanism of polyuria and renal dysfunction in these mice. Gb3 accumulation was mostly detected in the medulla; medullary thick ascending limbs (mTALs) were the most vacuolated tubules. mTAL cells contained lamellar bodies and had lost their characteristic structure ( i.e., extensive infolding and numerous elongated mitochondria). Decreased expression of the major molecules-Na+-K+-ATPase, uromodulin, and Na+-K+-2Cl- cotransporter-that are involved in Na+ reabsorption in mTALs and the associated loss of urine-concentrating ability resulted in progressive water- and salt-loss phenotypes. GlatmTg(CAG-A4GALT) mice exhibited fibrosis around mTALs and renal dysfunction. These and other features were consistent with pathologic findings in patients with Fabry disease. Results demonstrate that mTAL dysfunction causes polyuria and renal impairment and contributes to the pathophysiology of Fabry nephropathy.-Maruyama, H., Taguchi, A., Nishikawa, Y., Guili, C., Mikame, M., Nameta, M., Yamaguchi, Y., Ueno, M., Imai, N., Ito, Y., Nakagawa, T., Narita, I., Ishii, S. Medullary thick ascending limb impairment in the GlatmTg(CAG-A4GALT) Fabry model mice.

Association of estimated dietary acid load with albuminuria in Japanese adults: a cross-sectional study.

BACKGROUND: Acid-base imbalance might promote the progression of chronic kidney disease (CKD), but whether nutrient-derived dietary acid load increases the risk of albuminuria or even high normoalbuminuria is unclear. METHODS: A Japanese cohort comprising 3250 men and 3434 women aged 40-97 years with urine albumin-to-creatinine ratio (ACR) < 33.9 mg/mmol or estimated glomerular filtration rate ≥ 15 ml/min/1.73 m2 were assessed. We performed a cross-sectional evaluation of the association between net endogenous acid production (NEAP), estimated as dietary protein to potassium content ratio, and the presence of high normoalbuminuria (ACR: 1.13-3.38 mg/mmol) or microalbuminuria. RESULTS: Median NEAP was 43.4 (interquartile range (IQR): 34.2-53.4) mEq/day in men and 35.0 (IQR: 27.7-43.6) mEq/day in women. Median ACR was 1.11 (IQR: 0.57-2.49) mg/mmol in men and 1.47 (IQR: 0.82-2.83) mg/mmol in women. In multivariate analysis, the adjusted odds ratio of the highest versus lowest NEAP quartile for microalbuminuria was 1.47 (95% confidence interval (CI): 1.08-1.99) in men and 1.54 (95% CI: 1.11-2.14) in women. For high normoalbuminuria or microalbuminuria, the adjusted odds ratio was 1.28 (95% CI: 1.02-1.59) in men and 1.39 (95% CI: 1.11-1.74) in women. From nutrient composition analysis, subjects with the highest potassium intake, but not protein intake, had lower adjusted odds ratios for the presence of microalbuminuria than those in the lowest quartile for potassium intake. CONCLUSIONS: Higher NEAP was associated with albuminuria and its association might negatively relate to potassium intake in an adult Japanese population.

Tubulointerstitial nephritis with monotypic lympho-plasmacytic infiltrates in a patient with primary Sjögren's syndrome accompanied by IgA-type monoclonal gammopathy.

BACKGROUND: Although most cases of tubulointerstitial nephritis in paraproteinemia are monoclonal light chain deposition-mediated, interstitial nephritis as neoplastic interstitial cell infiltration has rarely been described. On the other hand, lympho-plasma-cell-rich tubulointerstitial nephritis, in which the infiltrative cells are usually polytypic, is often evident in primary Sjögren's syndrome (pSS). Herein we present a rare case of pSS in a patient who had been diagnosed as having IgA kappa-type monoclonal gammopathy of undetermined significance (MGUS) and developed tubulointerstitial nephritis with monotypic (IgA kappa) lympho-plasmacytic infiltrates. CASE PRESENTATION: A 74-year-old Japanese woman with pSS who had been diagnosed as having IgA kappa-type MGUS developed progressive renal dysfunction. Renal biopsy revealed tubulointerstitial nephritis with abundant plasma cell-rich mononuclear cell infiltrates without atypia. Immunohistochemical staining for immunoglobulins and light chains showed that most infiltrates were positive for IgA and kappa. Most of the infiltrative cells were positive for CD38 and CD138, and cells positive for CD 19 and CD 45 were also widely evident. Electron microscopy and immunofluorescence studies revealed no apparent immunological deposits in the glomeruli and tubules. Bone marrow and whole-body radiological examinations revealed no findings suggestive of multiple myeloma or lymphoma. Renal function improved rapidly with prednisolone 40 mg daily and has been maintained at the same level on low-dose prednisolone and azathioprine for 18 months. CONCLUSION: Tubulointerstitial nephritis with monotypic cell infiltrates, without immunological deposits, is a quite rare histological picture in MGUS, and might be a unique renal manifestation in patients with pSS.

Analysis of the prevalence of systemic de novo thrombotic microangiopathy after ABO-incompatible kidney transplantation and the associated risk factors.

OBJECTIVES: To analyze the prevalence of systemic de novo thrombotic microangiopathy in ABO-incompatible kidney transplantation and risk factors associated with this condition. METHODS: A total of 201 patients who received living-donor kidney transplantation (114 patients with ABO-identical kidney transplantation and 87 patients with ABO-incompatible kidney transplantation) were retrospectively analyzed. Systemic de novo thrombotic microangiopathy was diagnosed clinically according to the presence of thrombocytopenia with microangiopathic hemolytic anemia and pathological findings of thrombotic microangiopathy. Anti-A and anti-B antibodies were purified from human plasma, and these antibodies' bindings to human kidney were investigated in vitro. RESULTS: ABO-incompatible kidney transplantation was a significant risk factor of systemic de novo thrombotic microangiopathy (odds ratio 55.9, 95% CI 1.8-8.9, P < 0.001) after transplantation. Multivariate logistic regression analysis showed that non-use of mycophenolate mofetil, pretreatment immunoglobulin G antibody titer ≥64-fold and pretransplant immunoglobulin M antibody titer ≥16-fold were significant risk factors for systemic de novo thrombotic microangiopathy in ABO-incompatible kidney transplantation. Microvascular inflammation of 1-h post-transplant biopsy could be observed more frequently in thrombotic microangiopathy patients than in non-thrombotic microangiopathy patients. Anti-A and anti-B antibodies purified from human plasma showed a strong in vitro reaction against human kidney when the antibody titer was ≥16-fold. CONCLUSIONS: Antibody titer should be decreased to ≤16-fold until the day of ABO-incompatible kidney transplantation by desensitization therapy including mycophenolate mofetil. The 1-h biopsy results might help to diagnose systemic de novo thrombotic microangiopathy.

Suppression of SESN1 reduces cisplatin and hyperthermia resistance through increasing reactive oxygen species (ROS) in human maxillary cancer cells.

INTRODUCTION: Cisplatin is used as a standard chemotherapeutic agent for head and neck cancer treatment. However, some head and neck cancers have cisplatin resistance, leading to difficulty in treatment and poor prognosis. Overcoming cisplatin resistance remains an important strategy to improve prognoses for head and neck cancer patients. OBJECTIVE: Elucidation of the mechanisms underlying cisplatin resistance can suggest novel targets to enhance the anticancer effects of cisplatin for treating head and neck cancers. MATERIAL AND METHODS: We used a cisplatin-resistant human maxillary cancer cell line, IMC-3CR to analyse the cisplatin resistance mechanisms. Cisplatin-induced genes were analysed in IMC-3CR cells using PCR array. Among the genes with expression increased by cisplatin, we specifically examined SESN1. SESN family reportedly regenerates peroxiredoxin and suppresses oxidative DNA injury by reactive oxygen species (ROS), which can be induced by chemotherapeutic agents such as cisplatin, radiation, and hyperthermia. The function of SESN1 in cisplatin resistance and ROS generation were analysed using specific RNAi. RESULTS: Results show that SESN1 was induced by cisplatin treatment in IMC-3CR cells. Suppression of SESN1 by RNAi induced apoptosis and reduced cell viability through enhancement of ROS after cisplatin treatment. Moreover, suppression of SESN1 enhanced the cell-killing effects of hyperthermia with increased ROS, but did not affect the cell-killing effects of radiation. CONCLUSIONS: This study demonstrated the participation of SESN1 in cisplatin and hyperthermia resistance of human head and neck cancers. SESN1 is a novel molecular target to overcome cisplatin resistance and hyperthermia resistance and improve head and neck cancer treatment.

Tubulointerstitial Nephritis with IgM-Positive Plasma Cells.

Infiltration by IgG-positive plasma cells is a common finding in tubulointerstitial nephritis. Indeed, it has been thought that CD138-positive mature plasma cells secrete mainly IgG, and the occurrence of tubulointerstitial nephritis with CD138-positive plasma cells secreting IgM has rarely been reported. Routine immunofluorescence of fresh frozen sections is considered the gold standard for detection of immune deposits. However, the immunoenzyme method with formalin-fixed, paraffin-embedded sections is superior for detecting IgM- or IgG-positive cells within the renal interstitium, thus histologic variants may often go undetected. We recently discovered a case of tubulointerstitial nephritis showing IgM-positive plasma cell accumulation within the interstitium. To further explore the morphologic and clinical features of such cases, we performed a nationwide search for patients with biopsy-proven tubulointerstitial nephritis and high serum IgM levels. We identified 13 patients with tubulointerstitial nephritis and IgM-positive plasma cell infiltration confirmed with the immunoenzyme method. The clinical findings for these patients included a high prevalence of distal renal tubular acidosis (100%), Fanconi syndrome (92%), and anti-mitochondrial antibodies (82%). The pathologic findings were interstitial nephritis with diffusely distributed CD3-positive T lymphocytes and colocalized IgM-positive plasma cells, as well as tubulitis with CD3-positive T lymphocytes in the proximal tubules and collecting ducts. Additionally, levels of H+-ATPase, H+, K+-ATPase, and the HCO3--Cl- anion exchanger were markedly decreased in the collecting ducts. We propose to designate this group of cases, which have a common histologic and clinical form, as IgM-positive plasma cell-tubulointerstitial nephritis.