<ORIGINAL ARTICLE>Establishment and characteristics of a cell line derived from osteosarcoma induced by ^<32>P in the rat.

骨肉腫細胞株はヒト骨肉腫治療の実験モデルになるばかりでなく,骨形成を示すため骨代謝の研究に対しても有用な実験モデルとなりうる。しかし,可移植性骨肉腫株やその細胞株は今日においても非常に少ない。われわれはすでに^Pで誘発した可移植性骨肉腫を報告した。この腫瘍は継代移植においても骨形成能を維持している。今回の実験はこの骨腫瘍の細胞株を樹立すること,ならびにその生物学的特長を検索することである。その結果,1.ラット骨肉腫の細胞株(MSK,武藤-佐藤-金沢)が樹立された。2.この細胞株はin vitroにおいて強いアルカリフォスファターゼ活性とコラーゲン形成能を示した。3.MSK細胞を同系ラットの背部皮下に移植すると骨形成能を示した。4.ミリポアフィルターを用いたin VIVO骨形成実験では,フィルターの外側に骨形成が認められた。5.以上の結果より,MSK細胞は骨形成能を示すだけでなく骨誘導能の可能性が示唆された。それゆえ,この細胞株は骨芽細胞の特性の検索ばかりでなく骨誘導の研究にも有用なモデルであると考える。To study the medical treatment of human osteosarcoma there is a need for experimental tumor models Moreover, osteoblastic cell line is a useful model for research of the bone and mineral metabolism. Even today, a few transplantable bone-forming osteosarcomas and their cell lines are available Previously we have reported transplantation of osteosarcoma induced by administration of ^P This tumor retains the osteoid-forming ability even in serial transplantations In the present study, we established the cell line of our transplantable ratosteosarcoma and investigated the characteristics of the cell line The results were as follows 1. A cell line (MSK, Muto-Sato-Kanazawa) of rat osteosarcoma was established 2. The cell line showed intense staining of alkaline phosphatase and collagen synthesis in vitro. 3. MSK cell line also maintained the bone-forming ability when it was inoculated sub cutaneously into the back of syngenic rats 4. Osteogenesis outside a Millipore filter by MSK cells was demonstrated in vivo. 5. It was suggested that MSK cells had not only bone-forming ability but also bone-inductive ability. Therefore, MSK cell line would be a useful model for the study on the property of osteoblast and bone inductio

<ORIGINAL ARTICLE>The effects of sagittal ramus osteotomy for mandibular prognathism on maximum mouth opening and condylar movement

Maximum mouth opening and condylar movement before and more than 6 months after surgery were analyzed in 23 cases of sagittal ramus osteotomy of the mandible for correction of mandibular prognathism. Condylar movement (translation and rotation) did not show postoperatively a significant difference pre-and postoperatively, and then was a tendency to a reduction of maximum mouth opening was found

<CLINICAL REPORT>A case of inverted papilloma of the maxillary sinus

A case of inverted papilloma arising in the maxillary sinus is described. The first symptoms were rhinorroea and discomfort of the left infraorbital region. A biopsy obtained by penetration into the maxillary sinus resulted in a diagnosis of chronic sinusitis. However, the surgical specimen showed characteristic inverted epithelial proliferation. Two years after operation by the Caldwell-Luc method, there are no signs of recurrence. The diagnosis and treatment of inverted papilloma are discussed

Cardiorespiratory fitness, body mass index, and cancer mortality: a cohort study of Japanese men

Background: The aim of this study is to investigate the independent and joint effects of cardiorespiratory fitness (CRF) and body mass index (BMI) on cancer mortality in a low body mass index population. Methods: We evaluated CRF and BMI in relation to cancer mortality in 8760 Japanese men. The median BMI was 22.6 kg/m2 (IQR: 21.0-24.3). The mean follow-up period was more than 20 years. Hazard ratios and 95% CI were obtained using a Cox proportional hazards model while adjusting for several confounding factors. Results: Using the 2nd tertile of BMI (21.6-23.6 kg/m2) as reference, hazard ratios and 95% CI for the lowest tertile of BMI (18.5-21.5) were 1.26 (0.87–1.81), and 0.92 (0.64–1.34) for the highest tertile (23.7-37.4). Using the lowest tertile of CRF as reference, hazard ratios and 95% CIs for 2nd and highest tertiles of CRF were 0.78 (0.55–1.10) and 0.59 (0.40–0.88). We further calculated hazard ratios according to groups of men cross-tabulated by tertiles of CRF and BMI. Among men in the second tertile of BMI, those belonging to the lowest CRF tertile had a 53% lower risk of cancer mortality compared to those in the lowest CRF tertile (hazard ratio: 0.47, 95% CI: 0.23-0.97). Among those in the highest BMI tertile, the corresponding hazard ratio was 0.54 (0.25-1.17). Conclusion: These results suggest that high CRF is associated with lower cancer mortality in a Japanese population of men with low average BMI

Neuronal surface antigen-specific immunostaining pattern on a rat brain immunohistochemistry in autoimmune encephalitis

A variety of neuronal surface (NS) antibodies (NS-Ab) have been identified in autoimmune encephalitis (AE). Tissue-based assay (TBA) using a rodent brain immunohistochemistry (IHC) is used to screen NS-Ab, while cell-based assay (CBA) to determine NS antigens. Commercial rat brain IHC is currently available but its clinical relevance remains unclear. Immunostaining patterns of NS antigens have not been extensively studied yet. To address these issues, we assessed a predictive value of “neuropil pattern” and “GFAP pattern” on commercial IHC in 261 patients, and characterized an immunostaining pattern of 7 NS antigens (NMDAR, LGI1, GABAaR, GABAbR, AMPAR, Caspr2, GluK2). Sensitivity and specificity of “neuropil pattern” for predicting NS-Ab were 66.0% (95% CI 55.7-75.3), and 98.2% (95% CI 94.8-99.6), respectively. False-positive rate was 1.8% (3/164) while false-negative rate was 34.0% (33/97). In all 3 false-positive patients, neuropil-like staining was attributed to high titers of GAD65-Ab. In 33 false-negative patients, NMDAR was most frequently identified (n=18 [54.5%], 16/18 [88.9%] had low titers [&lt; 1:32]), followed by GABAaR (n=5). Of 261 patients, 25 (9.6%) had either GFAP (n=21) or GFAP-mimicking pattern (n=4). GFAP-Ab were identified in 21 of 31 patients examined with CBA (20 with GFAP pattern, 1 with GFAP-mimicking pattern). Immunostaining pattern of each NS antigen was as follows: 1) NMDAR revealed homogenous reactivity in the dentate gyrus molecular layer (DG-ML) with less intense dot-like reactivity in the cerebellar granular layer (CB-GL); 2) both GABAaR and GluK2 revealed intense dot-like reactivity in the CB-GL, but GABAaR revealed homogenous reactivity in the DG-ML while GluK2 revealed intense reactivity along the inner layer of the DG-ML; and 3) LGI1, Caspr2, GABAbR, and AMPAR revealed intense reactivity in the cerebellar ML (CB-ML) but LGI1 revealed intense reactivity along the middle layer of the DG-ML. Whereas, Caspr2, GABAbR, and AMPAR revealed similar reactivity in the DG-ML but some difference in other regions. TBA is useful not only for screening NS- or GFAP-Ab but also for estimating NS antigens; however, negative results should be interpreted cautiously because “neuropil pattern” may be missed on commercial IHC when antibody titers are low. Antigen-specific immunoreactivity is a useful biomarker of AE

Arabidopsis RPT2a, 19S Proteasome Subunit, Regulates Gene Silencing via DNA Methylation

The ubiquitin/proteasome pathway plays a crucial role in many biological processes. Here we report a novel role for the Arabidopsis 19S proteasome subunit RPT2a in regulating gene activity at the transcriptional level via DNA methylation. Knockout mutation of the RPT2a gene did not alter global protein levels; however, the transcriptional activities of reporter transgenes were severely reduced compared to those in the wild type. This transcriptional gene silencing (TGS) was observed for transgenes under control of either the constitutive CaMV 35S promoter or the cold-inducible RD29A promoter. Bisulfite sequencing analysis revealed that both the transgene and endogenous RD29A promoter regions were hypermethylated at CG and non-CG contexts in the rpt2a mutant. Moreover, the TGS of transgenes driven by the CaMV 35S promoters was released by treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine, but not by application of the inhibitor of histone deacetylase Trichostatin A. Genetic crosses with the DNA methyltransferase met1 single or drm1drm2cmt3 triple mutants also resulted in a release of CaMV 35S transgene TGS in the rpt2a mutant background. Increased methylation was also found at transposon sequences, suggesting that the 19S proteasome containing AtRPT2a negatively regulates TGS at transgenes and at specific endogenous genes through DNA methylation

A diagnostic marker for superficial urothelial bladder carcinoma : lack of nuclear ATBF1 (ZFHX3) by immunohistochemistry suggests malignant progression

Background: Pathological stage and grade have limited ability to predict the outcomes of superficial urothelial bladder carcinoma at initial transurethral resection (TUR). AT-motif binding factor 1 (ATBF1) is a tumor suppressive transcription factor that is normally localized to the nucleus but has been detected in the cytoplasm in several cancers. Here, we examined the diagnostic value of the intracellular localization of ATBF1 as a marker for the identification of high risk urothelial bladder carcinoma. Methods: Seven anti-ATBF1 antibodies were generated to cover the entire ATBF1 sequence. Four human influenza hemagglutinin-derived amino acid sequence-tagged expression vectors with truncated ATBF1 cDNA were constructed to map the functional domains of nuclear localization signals (NLSs) with the consensus sequence KR[X10-12]K. A total of 117 samples from initial TUR of human bladder carcinomas were analyzed. None of the patients had received chemotherapy or radiotherapy before pathological evaluation. Results: ATBF1 nuclear localization was regulated synergistically by three NLSs on ATBF1. The cytoplasmic fragments of ATBF1 lacked NLSs. Patients were divided into two groups according to positive nuclear staining of ATBF1, and significant differences in overall survival (P = 0.021) and intravesical recurrence-free survival (P = 0.013) were detected between ATBF1+ (n= 110) and ATBF1− (n=7) cases. Multivariate analysis revealed that ATBF1 staining was an independent prognostic factor for intravesical recurrence-free survival after adjusting for cellular grading and pathological staging (P = 0.008). Conclusions: Cleavage of ATBF1 leads to the cytoplasmic localization of ATBF1 fragments and downregulates nuclear ATBF1. Alterations in the subcellular localization of ATBF1 due to fragmentation of the protein are related to the malignant character of urothelial carcinoma. Pathological evaluation using anti-ATBF1 antibodies enabled the identification of highly malignant cases that had been overlooked at initial TUR. Nuclear localization of ATBF1 indicates better prognosis of urothelial carcinoma

口腔粘膜に多数の小腫瘤を形成したアミロイドーシスの1例

A 75-year-old female reported to our hospital complaining of numerous nodules on the oral mucous membrane. Oral examination revealed an enlarged tongue with multiple nodules on the lateral surfaces and yellow soft excrescences on the undersurface. The buccal and labial mucosa was noted to have numerous nodules. Further examination resulted in a diagnosis of generalized primary amyloidosis

Researching peers and disaster vulnerable communities: an insider perspective

Conducting research among peers and communities that a researcher also serves may be both daunting and rewarding. Researching peers may make the researcher feel uncomfortable raising certain questions that are sensitive or that could be construed to be testing their competencies. This paper is inclined more towards showing that it is advantageous to be an insider, whose position can facilitate collection of information that could not have been accessed, or revealed to an outsider. The paper reports on fieldwork conducted in a low-income country in Sub-Sahara Africa as part of a doctoral study with communities affected by disasters and those that work with such communities. The paper demonstrates the complexities of conducting such research and provides some insights that may be useful to insiders, outsiders or “in-betweeners” embarking on fieldwork in low-income countries and among vulnerable population struggling with manifold stresses and shocks