Selection of common markers for bone marrow stromal cells from various bones using real-time RT-PCR: effects of passage number and donor age

Bone marrow stromal cells (BMSCs) are valuable in tissue engineering and cell therapy, but the quality of the cells is critical for the efficacy of therapy. To test the quality and identity of transplantable cells, we identified the molecular markers that were expressed at higher levels in BMSCs than in fibroblasts. Using numerous BMSC lines from tibia, femur, ilium, and jaw, together with skin and gum fibroblasts, we compared the gene expression profiles of these cells using DNA microarrays and low-density array cards. The differentiation potential of tibia and femur BMSCs was similar to that of iliac BMSCs, and different from jaw BMSCs, but all BMSC lines had many common markers that were expressed at much higher levels in BMSCs than in fibroblasts; several BMSC markers showed discrete expression patterns between jaw and other BMSCs. The common markers are probably useful in routine tests, but their efficacy may depend upon the passage number or donor age. In our study the passage number markedly altered the expression levels of several markers, while donor age had little effect on them. Considering the effects of in vivo location of BMSCs and passage, magnitude of increase in expression levels, and interindividual differences, we identified several reliable markers -- LIF, IGF1, PRG1, MGP, BMP4, CTGF, KCTD12, IGFBP7, TRIB2, and DYNC1I1 -- among many candidates. This marker set may be useful in a routine test for BMSCs in tissue engineering and cell therapy.     

Cardiovascular changes after pulmonary embolism from injecting calcium phosphate cement

Concerns have been raised that the use of calcium phosphate (CaP) cements for the augmentation of fractured, osteoporotic bones may aggravate cardiovascular deterioration in the event of pulmonary cement embolism by stimulating coagulation. The aim of the present study was therefore to investigate the cardiovascular changes after pulmonary embolism of CaP cement using an animal model. In 14 sheep, 2.0 mL CaP or polymethylmethacrylate cement were injected intravenously. Cardiovascular parameters and antithrombin levels were monitored until 60 min postinjection. Postmortem, lungs were subjected to CT scanning, and 3D reconstruction of the cement was performed. Intravenous injection of CaP cement resulted in a more severe increase in pulmonary arterial pressure and decrease in arterial blood pressure. Disintegration of the CaP cement seemed to be the reason for the more severe reaction. There was no evidence of thromboembolism. Disintegration of CaP cement in circulating blood does not only compromise the mechanical properties, but also represents a risk of cardiovascular complications. Reliable cohesion of CaP cements in an aqueous environment is essential for clinical applications such as osteoporotic bone augmentation.     

Is SS-A/Ro52 a hydrogen peroxide-sensitive signaling molecule?

SS-A/Ro52 (Ro52) protein is one of the targets of autoantibodies in Sjogren's syndrome and systemic lupus erythematosus. Ro52 structurally belongs to the RING-B-box/coiled-coil family, which appears to carry out diverse functions, but the physiological function of Ro52 remains largely unknown. Here, the authors demonstrate that hydrogen peroxide but not other oxidative stressors induced translocation of Ro52 protein from the cytoplasm to the nucleus and this phenomenon was attenuated by inhibition of MAP kinases, ERK in particular. These findings raise the possibility that SS-A/Ro52 may function as a hydrogen peroxide-selective, oxidative stress-sensitive signaling molecule that is activated via the MAP kinase pathway.     

Neighborhood walkability and TV viewing time among Australian adults

BACKGROUND: Built-environment attributes of a neighborhood are associated with participation in physical activity and may also influence time spent in sedentary behaviors. Associations of neighborhood walkability (based on dwelling density, street connectivity, land-use mix, and net retail area) and television viewing time were compared in a large, spatially-derived sample of Australian adults. METHODS: Neighborhood-level variables (walkability and socioeconomic status [SES]) were calculated in 154 Australian census collection districts using Geographic Information Systems. Individual-level variables (TV viewing time, time spent in leisure-time physical activity, height, weight, and sociodemographic variables) were collected from adults living in urban areas of Adelaide, Australia using a mail survey (N=2224) in 2003-2004. Multilevel linear regression analysis was conducted in 2006 separately for men and women to examine variations in TV viewing time across tertiles of walkability. RESULTS: Neighborhood walkability was negatively associated with TV viewing time in women, but not in men. After controlling for neighborhood SES, body mass index, physical activity, and sociodemographic variables, women living in medium- and high-walkable neighborhoods reported significantly less TV viewing time per day (14 minutes and 17 minutes, respectively) compared to those residing in low-walkable neighborhoods. CONCLUSIONS: Built-environment attributes of neighborhoods that are related to physical activity also may play an important role in influencing sedentary behavior, particularly among women. Considering the effects of prolonged sedentary time on health risks, which are independent of physical activity, there is the need for further research to explore how environmental characteristics may contribute to the amount of time spent in sedentary behavior.     

Nutrient and food intake in relation to serum leptin concentration among young Japanese women

OBJECTIVE: Little is known about the relation of modifiable dietary factors to circulating leptin concentrations, particularly in young adults and non-Western populations. We examined cross-sectional associations between nutrient and food intake and serum leptin concentration in young Japanese women. METHODS: Subjects were 424 female Japanese dietetic students 18-22 y of age. Intake of macronutrients (protein, total fat; saturated, monounsaturated, and polyunsaturated fatty acids; and carbohydrate), dietary fiber, and 12 food groups was assessed with a validated, self-administered, comprehensive, diet history questionnaire. Fasting blood samples were collected, and serum leptin concentrations were measured by radioimmunoassay. RESULTS: For nutrients, only dietary fiber was a significant determinant of serum leptin concentration. Increasing dietary fiber intake was associated with lower serum leptin concentration independent of potential confounding factors, including body mass index (mean serum leptin concentrations in the lowest and highest quintiles of dietary fiber intake were 8.6 and 7.5 ng/mL, respectively; P for trend = 0.026). Vegetables and pulses were the only foods significantly associated with serum leptin concentration, with higher intakes independently associated with lower concentrations (mean serum leptin concentrations in the lowest and highest quintiles of intake were 8.1 and 7.0 ng/mL, P for trend = 0.007, for vegetables and 8.8 and 7.6 ng/mL, P for trend = 0.019, for pulses, respectively). CONCLUSION: Intake of dietary fiber, vegetables, and pulses showed an independent inverse association with serum leptin concentration in a group of young Japanese women.     

Effectiveness of CT for clinical stratification of occupational lung edema

We treated two occupational lung diseases in different situations during military training. The purpose of this study is to investigate the availability of CT scanning for the evaluation of inhalation pulmonary edema. Two soldiers suffered severe lung edema after using a spray for the daily maintenance of their firearms. Four soldiers suffered severe dyspnea after undertaking drills in a narrow zone where numerous smoke bombs had been used. We evaluated these patients from several aspects. CT scans of the chest of spray-induced patients revealed bilateral infiltration predominantly in the upper lung fields. The patients received steroid pulse treatment and gradually recovered. CT scans of the chest of smoke-induced patients revealed bilateral ground-glass attenuation with peripheral lung sparing. The patients gradually recovered with steroid therapy. In accordance with previous studies, CT scans of the chest in our patients demonstrated that the periphery of the lungs remained normal, except in cases of serious injury. When differential diagnosis is required, we consider that CT scans of the chest are particularly useful; CT findings are useful in determining the severity of lung injury as well as the diagnosis of inhalation pulmonary edema.     

CD24, not CD47, negatively impacts upon response to PD‐1/L1 inhibitors in non–small‐cell lung cancer with PD‐L1 tumor proportion score < 50

CD24, a heavily glycosylated glycosylphosphatidylinositol–anchored surface protein, inhibits phagocytosis as potently as CD47. The relationship between such anti‐phagocytic factors and the immune response with immune–checkpoint inhibitors (ICI) remains unexplored. We evaluated CD24 and CD47 tumor proportion scores (TPS) in 68 of the 106 patients with advanced non–small‐cell lung cancer who participated in a prospective observational study of ICI treatment. We also explored the impact of CD24 TPS and CD47 TPS on ICI efficacy and serum cytokine changes. CD24 positivity (TPS ≥ 1) was negatively associated with progression–free survival (PFS) of ICI when PD‐L1 TPS was < 50 (median PFS; 37 vs 127 d, P = .033), but there was no association when PD‐L1 TPS was ≥ 50 (median PFS; 494 vs 144 d, P = .168). CD24 positivity was also related to significantly higher increase of CCL2 from baseline to 4‐6 wk later, and such increase was notably observed only when PD‐L1 TPS < 50 (P = .0004). CCL2 increase after ICI initiation was negatively predictive for survival after initiation of ICI (median survival time; not reached vs 233 d; P = .028). CD47 TPS high (≥60) significantly suppressed the increase in vascular endothelial growth factor (VEGF)‐A, D and PDGF‐AB/BB after ICI initiation. There was no association, however, between CD47 tumor expression and the efficacy of ICI. In conclusion, CD24, not CD47, is a candidate negative predictive marker of ICI in advanced, non–small‐cell lung cancer with PD‐L1 TPS < 50. Tumor expression of both CD24 and CD47 was associated with changes in factors related to monocytes and angiogenesis after ICI initiation (UMIN000024414).     

Clinical usefulness of cell-free and concentrated ascites reinfusion therapy (CART) in combination with chemotherapy for malignant ascites: a post-marketing surveillance study

International Journal of Clinical Oncology - Cell-free and concentrated ascites reinfusion therapy (CART) has been suggested to be able to treat malignant ascites more safely and effectively with...     

Prognostic significance of third-line treatment for patients with metastatic castration-resistant prostate cancer: comparative assessments between cabazitaxel and other agents

International Journal of Clinical Oncology - Cabazitaxel has played an important role in the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC); however, several...     

SARS-CoV spike protein-expressing recombinant vaccinia virus efficiently induces neutralizing antibodies in rabbits pre-immunized with vaccinia virus

A vaccine for severe acute respiratory syndrome (SARS) is being intensively pursued against its re-emergence. We generated a SARS coronavirus (SARS-CoV) spike protein-expressing recombinant vaccinia virus (RVV-S) using highly attenuated strain LC16m8. Intradermal administration of RVV-S into rabbits induced neutralizing (NT) antibodies against SARS-CoV 1 week after administration and the NT titer reached 1:1000 after boost immunization with RVV-S. Significantly, NT antibodies against SARS-CoV were induced by administration of RVV-S to rabbits that had been pre-immunized with LC16m8. RVV-S can induce NT antibodies against SARS-CoV despite the presence of NT antibodies against VV. These results suggest that RVV-S may be a powerful SARS vaccine, including in patients previously immunized with the smallpox vaccine.