Analysis of heat shock proteins and cytokines expressed during early stages of osteoarthritis in a mouse model

SummaryObjective:Osteoarthritis (OA) is a debilitating disease of the joints. The joints of affected individuals are characterized by a progressive degeneration of articular cartilage leading to inflammation and pain. The expression of heat shock proteins (HSPs) is a ubiquitous self-protective mechanism of all cells under stress, furthermore, the synovium of osteoarthritic individuals contains high levels of cytokines. This study seeks to establish the role of HSPs and cytokines in OA.Methods:We have investigated the presence of HSPs and cytokines in articular cartilage during early stages of OA in a mouse that is known to develop spontaneous OA lesions (C57 black mouse). The articular cartilage from closely related mice (C57BL/6) was used as control. Messenger RNAs (mRNAs) for HSPs (HSP32, HSP47, HSP60, HSP70, HSP84 and HSP86) and cytokines [interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)] were detected by reverse transcription-polymerase chain reaction (RT-PCR).Results:The mRNA levels of HSP47, HSP70, HSP86, IL-6, and IFN-γ were up-regulated in the cartilage of C57 black mice, whereas, the level of expression of HSP32, HSP60, HSP84 and IL-1β remained unchanged. Furthermore, the expression of IL-1β, IL-6, TNF-α and IFN-γ mRNA was associated with expression of HSP60, HSP47, HSP70 and HSP70/HSP86 mRNA, respectively.Conclusions:The findings in this study suggest that chondrocytes are conditioned under non-physiological stress during early stages of OA, In addition, among HSPs, HSP70 was associated with two different highly expressed cytokines in C57 black mice, indicating the possible role of HSP70 as a characteristic indicator of early stage of OA

半側空間無視症例の正中認知に与えるヘッドマウントディスプレイアダプテーションの即時効果

東京都立大

Changes of tumor and normal structures of the neck during radiation therapy for head and neck cancer requires adaptive strategy

The treatment period over which radiation therapy is administered extends over several weeks. Since tumor shrinkage in response to radiation therapy and weight loss due to radiation-induced mucositis may impact on the dose distribution in both target and organ at risk in patients with head and neck cancer, the anatomical changes of tumor and neck volumes during this period should be taken into consideration. We investigated the anatomical changes that occurred in the target and normal structure of the neck during radiation therapy for pharyngeal cancer, and evaluated the necessity of an adaptive strategy. Ten patients with pharyngeal cancer who underwent radical chemoradiation therapy using 3-dimensional conformal radiation therapy RT (66-70 Gy in 33-35 fractions) between April 2009 and September 2010 were enrolled in the study. Patients underwent CT scans every week during their course of treatment. We analyzed the CT data in the radiation treatment planning system and measured changes of tumor, organ at risk, and neck volume. Gross tumor volume (GTV) was rapidly reduced by 28% of the original volume on average in the first 3 weeks. The right and left submandibular glands volume decreased to 70% and 63% of their initial volumes on average, respectively. The volume of the neck in the radiation fields decreased to 89% of its initial volume on average by the sixth week mainly caused by body weight loss due to acute radiation morbidity. Considerable anatomical change in the radiation filed that will affect dose distribution of the target and organ at risk was observed during radiation therapy for head and neck cancer

Tumor-Infiltrating Lymphocytes and Macrophages as a Significant Prognostic Factor in Biliary Tract Cancer

Background: The impact of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs) on the prognosis of biliary tract cancer (BTC) is not completely understood. Therefore, in our study, we investigated the effects of the various immune cells infiltration in tumor microenvironment (TME). Methods: A total of 130 patients with BTC who underwent surgical treatment at our institution were enrolled in this study. We retrospectively evaluated TILs and TAMs with immunohistochemical staining. Results: With CD8-high, CD4-high, FOXP3-high, and CD68-low in TME as one factor, we calculated Immunoscore according to the number of factors. The high Immunoscore group showed significantly superior overall survival (OS) and recurrence-free survival (RFS) than the low Immunoscore group (median OS, 60.8 vs. 26.4 months, p = 0.001; median RFS not reached vs. 17.2 months, p \u3c 0.001). Also, high Immunoscore was an independent good prognostic factor for OS and RFS (hazards ratio 2.05 and 2.41 and p = 0.01 and p = 0.001, respectively). Conclusions: High Immunoscore group had significantly superior OS and RFS and was an independent good prognostic factor for OS and RFS

Phamacogenomics of Clozapine-Induced Agranulocytosis

Background: Clozapine-induced agranulocytosis (CIA)/clozapine-induced granulocytopenia (CIG) (CIAG) is a life-threatening event for schizophrenic subjects treated with clozapine. Methods: To examine the genetic factor for CIAG, a genome-wide pharmacogenomic analysis was conducted using 50 subjects with CIAG and 2905 control subjects. Results: We identified a significant association in the human leukocyte antigen (HLA) region (rs1800625, p = 3.46 × 10−9, odds ratio [OR] = 3.8); therefore, subsequent HLA typing was performed. We detected a significant association of HLA-B*59:01 with CIAG (p = 3.81 × 10−8, OR = 10.7) and confirmed this association by comparing with an independent clozapine-tolerant control group (n = 380, p = 2.97 × 10−5, OR = 6.3). As we observed that the OR of CIA (OR: 9.3~15.8) was approximately double that in CIG (OR: 4.4~7.4), we hypothesized that the CIG subjects were a mixed population of those who potentially would develop CIA and those who would not develop CIA (non-CIA). This hypothesis allowed the proportion of the CIG who were non-CIA to be calculated, enabling us to estimate the positive predictive value of the nonrisk allele on non-CIA in CIG subjects. Assuming this model, we estimated that 1) ~50% of CIG subjects would be non-CIA; and 2) ~60% of the CIG subjects without the risk allele would be non-CIA and therefore not expected to develop CIA. Conclusions: Our results suggest that HLA-B*59:01 is a risk factor for CIAG in the Japanese population. Furthermore, if our model is true, the results suggest that rechallenging certain CIG subjects with clozapine may not be always contraindicated

Atomic-scale visualization of initial growth of homoepitaxial SrTiO3 thin film on an atomically ordered substrate

The initial homoepitaxial growth of SrTiO3 on a (\surd13\times\surd13) - R33.7{\deg}SrTiO3(001) substrate surface, which can be prepared under oxide growth conditions, is atomically resolved by scanning tunneling microscopy. The identical (\surd13\times\surd13) atomic structure is clearly visualized on the deposited SrTiO3 film surface as well as on the substrate. This result indicates the transfer of the topmost Ti-rich (\surd13\times\surd13) structure to the film surface and atomic-scale coherent epitaxy at the film/substrate interface. Such atomically ordered SrTiO3 substrates can be applied to the fabrication of atom-by-atom controlled oxide epitaxial films and heterostructures