Decreased levels of insulin-like growth factor-1 and vascular endothelial growth factor relevant to the ossification disturbance in femoral heads spontaneous hypertensive rats.

Ossification disturbance in femoral head reportedly is seen in the Spontaneously Hypertensive rats (SHR) between ages of 10 and 20 weeks. We investigated serum and tissue levels of insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) in SHR relevant to the ossification disturbance and osteonecrosis of the femoral head. Serum levels of IGF-1 and VEGF were significantly lower in SHR than in Wistar Kyoto rats (WKY) at weeks 5, 10, 15 and 20 (p<0.005). The incidence of histological ossification disturbance of the femoral head was higher in SHR (59%) than in WKY (40%) at week 20. Lower serum and local levels of VEGF in SHR appeared to be related to the incomplete ossification of the femoral heads. Immunohistochemical study showed significantly lower numbers of IGF-1 and VEGF positive chondrocytes in the femoral epiphyseal cartilage of SHR than in those of WKY at weeks 10, 15 and 20. Our results suggest that local and/or systemic levels of IGF-1 and VEGF between ages of 5 and 20 weeks might play roles in the pathogenesis of ossifi cation disturbance of the femoral head in SHR

Formation of meso, N-diphenylprotoporphyrin IX by an aerobic reaction of phenylhydrazine with oxyhemoglobins.

Administration of phenylhydrazine to rabbits resulted in the denaturation of hemoglobins in erythrocytes, causing the formation of intracellular precipitates known as Heinz bodies, severe hemolytic anemia, and reticulocytosis. To elucidate the molecular mechanism of the destabilization, we allowed human oxyhemoglobins to react aerobically with phenylhydrazine. After treatment with acetic acid/HCl and H2SO4/methanol, the chloroform extract contained blue-green pigments of major products accompanied by different minor products. Each product was isolated by column chromatography. By fast-atom-bombardment mass spectrometry (FAB-MS) and proton nuclear magnetic resonance (1H-NMR) spectrometry, dimethyl esters of N-phenylprotoporphyrin IX and meso, N-diphenylprotoporphyrin IX were determined. Other major products also were determined to be dimethyl esters of triphenyl-and tetraphenyl-substituted protoporphyrins by FAB-MS. The formation of meso, N-diphenylprotoporphyrin indicated that the addition of a phenyl radical to the meso-carbon atom of the protoporphyrin ring occurred. Triphenyl and tetraphenyl adducts also indicated the formation of phenyl radicals in the aerobic reaction of phenylhydrazine with oxyhemoglobins. From these results, we suggest that the formation of phenyl radicals and the replacement of heme with phenyl-substituted protoporphyrins cause the destabilization of hemoglobins to induce Heinz bodies and hemolytic anemia with phenylhydrazine.</p

A case of placenta previa accreta successfully treated by open infrarenal aortic clamping

Open infrarenal aortic clamping has been performed for traumatic pelvic hemorrhage or aortic rupture, and there are few reports of its use in the field of obstetrics and gynecology1). We report a patient with placenta previa accreta who was successfully treated by open infrarenal aortic clamping

骨卒中予防みそ汁が握力と血清25(OH)D濃度に及ぼす影響

We examined the nutritional effects of miso soup supplemented with vitamin D on serum level of ２５‐hydroxyvitamin D（２５（OH）D）and grip strength in sixty-seven inpatients（２６ males, ４１ females）of vitamin D insufficiency. The average age was ８４．６ years old and average body mass index was ２０．５kg/m２. These inpatients were divided into two groups, miso soup supplemented with vitamin D group（D group）（n=３５）and control group（n＝３２）. Nyucal Kouso FiberⓇ, NUTRI Co, Ltd, easily dissolved in miso soup. The D group ingested ２g of Nyucal Kouso FiberⓇ containing １０μg of vitamin D once a day. The daily diet included １７．５μg of vitamin D. As a result, D group and control group ingested ２７．５ μg and １７．５ μg per day of vitamin D, respectively. These results showed that both serum level of ２５（OH）D and grip strength of D group were significantly higher for one month than before（p<0.001）. In contrast, in control group, serum level of ２５（OH）D also higher than before, whereas grip strength did not change so much. These findings suggest that vitamin D-added diet is nutritionally effective to improve serum level of ２５（OH）D and grip strength of patients with vitamin D insufficiency

LRRN4 and UPK3B Are Markers of Primary Mesothelial Cells

Mesothelioma is a highly malignant tumor that is primarily caused by occupational or environmental exposure to asbestos fibers. Despite worldwide restrictions on asbestos usage, further cases are expected as diagnosis is typically 20–40 years after exposure. Once diagnosed there is a very poor prognosis with a median survival rate of 9 months. Considering this the development of early pre clinical diagnostic markers may help improve clinical outcomes.Microarray expression arrays on mesothelium and other tissues dissected from mice were used to identify candidate mesothelial lineage markers. Candidates were further tested by qRTPCR and in-situ hybridization across a mouse tissue panel. Two candidate biomarkers with the potential for secretion, uroplakin 3B (UPK3B), and leucine rich repeat neuronal 4 (LRRN4) and one commercialized mesothelioma marker, mesothelin (MSLN) were then chosen for validation across a panel of normal human primary cells, 16 established mesothelioma cell lines, 10 lung cancer lines, and a further set of 8 unrelated cancer cell lines.Within the primary cell panel, LRRN4 was only detected in primary mesothelial cells, but MSLN and UPK3B were also detected in other cell types. MSLN was detected in bronchial epithelial cells and alveolar epithelial cells and UPK3B was detected in retinal pigment epithelial cells and urothelial cells. Testing the cell line panel, MSLN was detected in 15 of the 16 mesothelioma cells lines, whereas LRRN4 was only detected in 8 and UPK3B in 6. Interestingly MSLN levels appear to be upregulated in the mesothelioma lines compared to the primary mesothelial cells, while LRRN4 and UPK3B, are either lost or down-regulated. Despite the higher fraction of mesothelioma lines positive for MSLN, it was also detected at high levels in 2 lung cancer lines and 3 other unrelated cancer lines derived from papillotubular adenocarcinoma, signet ring carcinoma and transitional cell carcinoma

CKM matrix and CP violation in B-mesons

Planned as a review of CPV in B-mesons which covered recent B-factories results these lectures appeared to be a bit wider. It is not natural to be limited by direct CPV and that in mixing in B-mesons and not to speak about the analogous phenomena in K-mesons since it is very useful and interesting to study what is common and what is different in these systems and why. CKM matrix elements are extracted from K and B mixings and decays and the deviation from unitarity of CKM matrix may become a place in which New Physics will show up. So we discuss this simple and elegant piece of Standard Model as well.Comment: 51 pages, 10 figures, to be published in the Proceedings of the XXXI ITEP Winter School, Moscow, Russia, 18-26 February 200

Dynamin 1 is important for microtubule organization and stabilization in glomerular podocytes

Dynamin 1 is a neuronal endocytic protein that participates in vesicle formation by scission of invaginated membranes. Dynamin 1 is also expressed in the kidney; however, its physiological significance to this organ remains unknown. Here, we show that dynamin 1 is crucial for microtubule organization and stabilization in glomerular podocytes. By immunofluorescence and immunoelectron microscopy, dynamin 1 was concentrated at microtubules at primary processes in rat podocytes. By immunofluorescence of differentiated mouse podocytes (MPCs), dynamin 1 was often colocalized with microtubule bundles, which radially arranged toward periphery of expanded podocyte. In dynamin 1-depleted MPCs by RNAi, alpha-tubulin showed a dispersed linear filament-like localization, and microtubule bundles were rarely observed. Furthermore, dynamin 1 depletion resulted in the formation of discontinuous, short acetylated alpha-tubulin fragments, and the decrease of microtubule-rich protrusions. Dynamins 1 and 2 double-knockout podocytes showed dispersed acetylated alpha-tubulin and rare protrusions. In vitro, dynamin 1 polymerized around microtubules and cross-linked them into bundles, and increased their resistance to the disassembly-inducing reagents Ca(2+)and podophyllotoxin. In addition, overexpression and depletion of dynamin 1 in MPCs increased and decreased the nocodazole resistance of microtubules, respectively. These results suggest that dynamin 1 supports the microtubule bundle formation and participates in the stabilization of microtubules

The Endogenous Th17 Response in NO<inf>2</inf>-Promoted Allergic Airway Disease Is Dispensable for Airway Hyperresponsiveness and Distinct from Th17 Adoptive Transfer

Severe, glucocorticoid-resistant asthma comprises 5-7% of patients with asthma. IL-17 is a biomarker of severe asthma, and the adoptive transfer of Th17 cells in mice is sufficient to induce glucocorticoid-resistant allergic airway disease. Nitrogen dioxide (NO2) is an environmental toxin that correlates with asthma severity, exacerbation, and risk of adverse outcomes. Mice that are allergically sensitized to the antigen ovalbumin by exposure to NO2 exhibit a mixed Th2/Th17 adaptive immune response and eosinophil and neutrophil recruitment to the airway following antigen challenge, a phenotype reminiscent of severe clinical asthma. Because IL-1 receptor (IL-1R) signaling is critical in the generation of the Th17 response in vivo, we hypothesized that the IL-1R/Th17 axis contributes to pulmonary inflammation and airway hyperresponsiveness (AHR) in NO2-promoted allergic airway disease and manifests in glucocorticoid-resistant cytokine production. IL-17A neutralization at the time of antigen challenge or genetic deficiency in IL-1R resulted in decreased neutrophil recruitment to the airway following antigen challenge but did not protect against the development of AHR. Instead, IL-1R-/- mice developed exacerbated AHR compared to WT mice. Lung cells from NO2-allergically inflamed mice that were treated in vitro with dexamethasone (Dex) during antigen restimulation exhibited reduced Th17 cytokine production, whereas Th17 cytokine production by lung cells from recipient mice of in vitro Th17-polarized OTII T-cells was resistant to Dex. These results demonstrate that the IL-1R/Th17 axis does not contribute to AHR development in NO2-promoted allergic airway disease, that Th17 adoptive transfer does not necessarily reflect an endogenously-generated Th17 response, and that functions of Th17 responses are contingent on the experimental conditions in which they are generated. © 2013 Martin et al

Yielded to Christ or conformed to this world? Postwar Mennonite responses to labour activism

This is the accepted version of the manuscript.The urbanization of North American Mennonites after the Second World War necessitated a reconsideration of Mennonite religious beliefs. Post-war concerns for social justice led to a greater emphasis on non-violence and agape at the expense of Gelassenheit. The tenor of Mennonite church conference resolutions regarding labour union membership changed; while skepticism remained regarding the wisdom of union involvement, the door was left open for participation in unions. The labour militancy of the 1970s led Manitoba Mennonites to re-examine their engagement with the labour movement, a process that has continued to the present day. Without further research on Mennonite workplaces, it cannot be known exactly how the change in religious emphases has affected Mennonite identity.https://journals.sagepub.com/doi/abs/10.1177/00084298070360020