Physical activity, body composition, thigh composition and structural changes in the knees of older adults

Osteoarthritis of the knee (knee OA) is a major cause of disability. The effect of physical activity and sedentary time on knee structural changes in older adults has not been established. Recent studies highlight the metabolic aspect of knee OA, but whether higher weight or metabolic mechanisms are more important is unknown. First, physical activity level was defined based on subjectively measured energy expenditure in total and for exercise in the Health, Aging and Body Composition Study. In older adults without knee pain, being lifestyle active or an exerciser was associated with two times higher odds of severe cartilage damage in the medial tibiofemoral joint compared with being inactive, suggesting vulnerability of knee cartilage to higher physical activity levels. In older adults with knee pain, those watching TV for ≥7 hours/week had over two times higher odds of bone marrow lesion (BML) in the whole knee, and ≥14 hours/week with 2.6 times higher odds of severe cartilage damage in the medial compartment compared with <7 hours/week. Next, body composition from DXA, and abdominal subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) areas on CT were examined. Higher appendicular lean mass rather than total body fat mass was associated with knee structural changes. Greater VAT area per weight was not positively associated with knee outcomes. Significant associations between greater SAT area and higher odds of knee structural changes found only in women were not explained by inflammatory markers, adipokines, or cardiometabolic risk factors. Lastly, thigh fat composition on CT and knee extensor strength were examined. Higher thigh density reflecting lower intramuscular fat, specifically quadriceps in men and hamstring in women, and higher knee extensor strength per quadriceps area in women were associated with lower odds of structural changes. Generally, no association with structural change was found for thigh intermuscular adipose tissue area or thigh SAT area. These findings support the importance of mechanical mechanisms rather than metabolic mechanisms. This dissertation has the important public health implication that weight control, good muscle quality and proper levels of physical activity are recommended for knee OA prevention and control in older adults

Levels of Octachlorostyrene in Mothers' Milk and Potential Exposure Among Infants in Sendai City, Japan 2012

Persistent organic pollutants can accumulate inside the human body, including in mothers’ milk, which may affect infant development. This cross-sectional study aimed to examine selected persistent organic pollutants in the milk of 100 mothers in Sendai city, Miyagi Prefecture, Japan. We used gas-chromatography-electron capture negative chemical ionization-mass spectrometry to check for octachlorostyrene, dechlorane (Dec) plus, Dec 602, Dec 603, and Dec 604. Octachlorostyrene was detected in 86 samples at more than the method detection limit (84 pg g-lipid⁻¹) but no dechloranes were above the method detection limit (1 ng mL⁻¹ for dechlorane plus, Dec 602, and Dec 603; 20 ng mL⁻¹ for Dec 604). The mean octachlorostyrene concentration was 461 pg g-lipid−1, the median was 337 pg g-lipid⁻¹, and the standard deviation 450 pg g-lipid⁻¹. No baseline characteristics were associated with octachlorostyrene level except for mother’s occupation (stay-at-home mother, 353 ± 327 pg g-lipid⁻¹; others, 531 ± 509 pg g-lipid⁻¹). Octachlorostyrene was also significantly negatively correlated with lipid content (r = −0.35, p = 0.0004). However, the maximum intake of octachlorostyrene among infants in this study (3.5 ng/kg/day) was under the acceptable daily intake (30 ng/kg/day, derived from 12−month study in rats), and is therefore unlikely to pose a health risk

Tensile strain increases expression of CCN2 and COL2A1 by activating TGF-beta-Smad2/3 pathway in chondrocytic cells

Physiologic mechanical stress stimulates expression of chondrogenic genes, such as multifunctional growth factor CYR61/CTGF/NOV (CCN) 2 and alpha 1(II) collagen (COL2A1), and maintains cartilage home-ostasis. In our previous studies, cyclic tensile strain (CTS) induces nuclear translocation of transforming growth factor (TGF)-beta receptor-regulated Smad2/3 and the master chondrogenic transcription factor Srytype HMG box (SOX) 9. However, the precise mechanism of stretch-mediated Smad activation remains unclear in transcriptional regulation of CCN2 and COL2A1. Here we hypothesized that CTS may induce TGF-beta 1 release and stimulate Smad-dependent chondrogenic gene expression in human chondrocytic SW1353 cells. Uni-axial CTS (0.5 Hz, 5% strain) stimulated gene expression of CCN2 and COL2A1 in SW1353 cells, and induced TGF-beta 1 secretion. CCN2 synthesis and nuclear translocalization of Smad2/3 and SOX9 were stimulated by CTS. In addition, CTS increased the complex formation between phosphorylated Smad2/3 and SOX9. The CCN2 promoter activity was cooperatively enhanced by CIS and Smad3 in luciferase reporter assay. Chromatin immunoprecipitation revealed that CTS increased Smad2/3 interaction with the CCN2 promoter and the COL2A1 enhancer. Our results suggest that CTS epigenetically stimulates CCN2 transcription via TGF-beta 1 release associated with Smad2/3 activation and enhances COL2A1 expression through the complex formation between SOX9 and Smad2/3

The aim of the measurement of Epstein‐Barr virus DNA in hydroa vacciniforme and hypersensitivity to mosquito bites

Epstein‐Barr virus (EBV) DNA load in the blood increases in posttransplant lymphoproliferative disorders and chronic active EBV infection. In this report, we analyzed the EBV DNA load in the peripheral blood mononuclear cells (PBMCs) and plasma of patients with hydroa vacciniforme (HV) and/or hypersensitivity to mosquito bites (HMB) to understand the clinical significance of EBV DNA load. All 30 patients showed high DNA loads in the PBMCs over the cut‐off level. Of 16 plasma samples, extremely high in two samples obtained from patients with hemophagocytic lymphohistiocytosis (HLH). The amount of cell‐free DNA in plasma was correlated to the serum levels of lactate dehydrogenase and inversely correlated to platelet counts. These results indicate that the EBV DNA load in PBMCs can provide one of the diagnostic indicators for HV and HMB and marked elevation of cell‐free EBV DNA in plasma might be related to cytolysis such as that observed in HLH

子宮筋層の内外層に発生する子宮腺筋症おける、それぞれの組織学的特徴

OBJECTIVE: To estimate the phenotypic characterization of fibrotic process in adenomyosis occurring at the inner or the outer myometrium. METHODS: Eight cases of adenomyosis occurring at the inner myometrium (Subtype I) and 10 cases of adenomyosis occurring at the outer myometrium (Subtype II), and 10 normal counterparts were used in this study. A immunohistochemical study for smooth muscle cells (SMCs) was performed using cytoskeletal proteins, Type I and III collagen, TGF-β and its signaling molecules. RESULTS: An increased expression of Type I collagen was observed in the extracellular matrix of adenomyotic foci. In normal uteri, immunostaining of SMC differentiation marker proteins (Desmin, Smoothelin, Myosin heavy chain (MHC)) were absent or only found in low numbers at the inner myometrium, while all of these marker proteins were clearly stained at the outer myometrium. In both types of adenomyotic foci, Desmin, Smoothelin, and MHC commonly showed a negative staining at the adjacent area to the glands. A significant staining of Non-muscle myosin IIB, TGF-β, and phosphorylated TGF-β type I receptors were found only at the SMCs of Subtype II adenomyosis. The Smad3/2 ratio of Subtype II adenomyosis was significantly higher than that of Subtype I. CONCLUSIONS: The inner myometrium of normal uteri was composed of undifferentiated phenotypes of SMCs, while the outer myometrium was composed of terminally differentiated SMCs. Various fibrotic processes have been suggested in the development of uterine adenomyosis. Distinct expression patterns of fibrosis related proteins have been shown to be implicated with differences in the subtypes of adenomyosis.博士（医学）・甲第681号・平成30年3月15日Copyright: © 2017 Kishi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Members of a novel gene family, Gsdm, are expressed exclusively in the epithelium of the skin and gastrointestinal tract in a highly tissue-specific manner

AbstractGasdermin (Gsdm) was originally identified as a candidate causative gene for several mouse skin mutants. Several Gsdm-related genes sharing a protein domain with DFNA5, the causative gene of human nonsyndromic hearing loss, have been found in the mouse and human genomes, and this group is referred to as the DFNA5–Gasdermin domain family. However, our current comparative genomic analysis identified several novel motifs distinct from the previously reported domain in the Gsdm-related genes. We also identified three new Gsdm genes clustered on mouse chromosome 15. We named these genes collectively the Gsdm family. Extensive expression analysis revealed exclusive expression of Gsdm family genes in the epithelium of the skin and gastrointestinal tract in a highly tissue-specific manner. Further database searching revealed the presence of other related genes with a similar N-terminal motif. These results suggest that the Gsdm family and related genes have evolved divergent epithelial expression profiles

Xanthogranulomatous inflammation of the perimetrium with infiltration into the uterine myometrium in a postmenopausal woman: a case report

BACKGROUND: Xanthogranulomatous inflammation is an uncommon form of chronic inflammation that is destructive to the normal tissue of affected organs. Although xanthogranulomatous endometritis and xanthogranulomatous salpingitis of the female genital tract has been described previously, to the best of our knowledge, this is the first report of xanthogranulomatous inflammation with infiltration into the uterine myometrium from the perimetrium without endometritis. CASE PRESENTATION: A 68-year-old Japanese woman with intermittent lower abdominal pain and low-grade fever who was initially treated with antibiotics underwent hysterectomy due to abscess formation in the posterior wall of the myometrium and perimetrium (the outer serosal layer of the uterus). Histopathological findings revealed that the abscess was caused by xanthogranulomatous inflammation with the granulation tissue and chronic inflammatory cells that consisted of focal and sheets of foam cells. The inflammation destroyed the perimetrial elastic lamina, and the myometrium was deeply infiltrated by the xanthoma cells. Neither endometritis nor salpingitis was coexistent with the xanthogranulomatous inflammation. CONCLUSION: The patient was diagnosed as xanthogranulomatous inflammation, most likely arising from the perimetrium. Our findings suggest that the perimetrium, as well as the endometrium and adnexae, is one of the origins of xanthogranulomatous inflammation in female genital tract