Segmental mobility with spondylolisthesis

Purpose : To evaluate segmental mobility with degenerative lumbar spondylolisthesis (DLS), upright lateral flexion-extension radiographs (FE) are widely used. However, some authors have described that a combination of lateral radiographs in the standing position and supine sagittal image (SS) reveal more segmental mobility than FE. The purpose of this study was to investigate the optimal method for evaluating segmental mobility with DLS. Methods : We included 92 consecutive Japanese patients diagnosed with DLS. Sagittal translation (ST) determined by FE and SS were compared. Pathological instability was defined as ST more than 8% of the upper vertebra. Patients were divided into those diagnosed with pathological instability in FE (PI-FE) and those diagnosed with SS (PI-SS), and lumbar lordosis (LL) in the standing position in each group were compared. Results : ST in FE was significantly greater than in SS. Of 92 patients, 31 had pathological instability in FE or SS ; 17 patients had PI-FE, and 10 patients had PI-SS. LL in the standing position in PI-FE was significantly smaller than in PI-SS. Conclusions : ST in FE was greater than that in SS, contrary to previous studies’ reports on Caucasians. Since Japanese individuals have smaller LL than Caucasians, FE tends to reveal more segmental mobility than SS

Rad51 Expression Is a Useful Predictive Factor for the Efficacy of Neoadjuvant Chemoradiotherapy in Squamous Cell Carcinoma of the Esophagus

BACKGROUND: Neoadjuvant chemoradiotherapy (NACRT) for esophageal squamous cell carcinoma (ESCC) is beneficial in the setting of a complete pathological response. Rad51 expression affects both chemo- and radiosensitivity in many cancers; however, its role in ESCC is unclear. METHODS: Rad51 expression was investigated by immunohistochemical staining with resected specimens in 89 ESCC patients who underwent surgery without preoperative therapy. The association with Rad51 and clinicopathological factors was assessed. The expression of Rad51 was also investigated in pretreatment biopsy specimens in 39 ESCC patients who underwent surgery after NACRT and compared with the pathological response to NACRT. RESULTS: Lymph node metastasis was more frequently observed in Rad51-positive cases than negative cases (58.5 vs. 30.6 %, P = 0.0168) in patients treated with surgery alone. Disease-specific survival was decreased in Rad51-positive cases compared to Rad51-negative cases (5 year survival: 79.6 vs. 59.3 %, P = 0.0324). In NACRT patients, completed pathological responses were more frequently observed in Rad51-negative cases than in Rad51-positive cases (68.8 vs. 46.5 %, P = 0.0171). CONCLUSIONS: Rad51 expression in ESCC was associated with lymph node metastasis and poor survival. Additionally, Rad51 expression in pretreatment biopsy specimens was a predictive factor for the response to NACRT. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1245/s10434-013-3220-2) contains supplementary material, which is available to authorized users

乳腺腺様嚢胞癌においてサイトケラチン5/6の腺腔形成細胞の染色性は類似病変との鑑別に有用である

Adenoid cystic carcinoma (AdCC) of the breast is an uncommon but distinct neoplasm composed of a dual cell population polarized around true glandular (luminal) spaces and pseudolumina. The aim of this study was to clarify whether various immunohistochemical markers (CK7, EMA, CD117, p63, calponin, CD10, S100, CK5/6, CK14, vimentin, and type IV collagen) can distinguish between the two cell types in classical AdCC (n = 14) and in collagenous spherulosis (n = 5). The sensitivity and specificity of these 11 markers to distinguish luminal from abluminal cells were evaluated using a curve created by plotting the true-positive rate (sensitivity) against the false-positive rate (1 - specificity) at threshold settings of 0, 10, 50, and 70 %. The most sensitive and specific markers for luminal cells in AdCC were CK7 and EMA; those for abluminal cells were type IV collagen, p63, and vimentin. CD10 and S100 did not act as abluminal markers in AdCC. CK5/6, one of the basal/myoepithelial markers, was expressed more frequently in luminal than in abluminal cells of AdCC. Thus, CK5/6 immunostaining resulted in a reverse expression pattern, analogous to what we recently documented in clear cells in mammary adenomyoepithelioma. In conclusion, compared with myoepithelial/abluminal cells of normal breast or collagenous spherulosis, the neoplastic abluminal cells of classical AdCC are characterized by enhanced vimentin and attenuated CD10 and S100. Furthermore, the luminal cells of AdCC show a unique aberrant staining pattern for CK5/6 that may aid in the differential diagnosis.博士（医学）・乙第1389号・平成28年11月24日© Springer-Verlag Berlin Heidelberg 2016The final publication is available at Springer via http://dx.doi.org/10.1007/s00428-016-1963-

Selection of immunobiotic ligilactobacillus salivarius strains from the intestinal tract of wakame-fed pigs: Functional and genomic studies

In this article, Ligilactobacillus salivarius FFIG strains, isolated from the intestinal tract of wakame-fed pigs, are characterized according to their potential probiotic properties. Strains were evaluated by studying their interaction with porcine intestinal epithelial (PIE) cells in terms of their ability to regulate toll-like receptor (TLR)-3- or TLR4-mediated innate immune responses, as well as by assessing their adhesion capabilities to porcine epithelial cells and mucins. These functional studies were complemented with comparative genomic evaluations using the complete genome sequences of porcine L. salivarius strains selected from subgroups that demonstrated different ‘immune’ and ‘adhesion’ phenotypes. We found that their immunomodulatory and adhesion capabilities are a strain-dependent characteristic. Our analysis indicated that the differential immunomodulatory and adhesive activities of FFIG strains would be dependent on the combination of several surface structures acting simultaneously, which include peptidoglycan, exopolysaccharides, lipoteichoic acid, and adhesins. Of note, our results indicate that there is no correlation between the immunomodulatory capacity of the strains with their adhesion ability to mucins and epithelial cells. Therefore, in the selection of strains destined to colonize the intestinal mucosa and modulate the immunity of the host, both properties must be adequately evaluated. Interestingly, we showed that L. salivarius FFIG58 functionally modulated the innate immune responses triggered by TLR3 and TLR4 activation in PIE cells and efficiently adhered to these cells. Moreover, the FFIG58 strain was capable of reducing rotavirus replication in PIE cells. Therefore, L. salivarius FFIG58 is a good candidate for further in vivo studying the protective effect of lactobacilli against intestinal infections in the porcine host. We also reported and analyzed, for the first time, the complete genome of several L. salivarius strains that were isolated from the intestine of pigs after the selective pressure of feeding the animals with wakame. Further genomic analysis could be of value to reveal the metabolic characteristics and potential of the FFIG strains in general and of the FFIG58 strain, in particular, relating to wakame by-products assimilation.Fil: Zhou, Binghui. Tohoku University; JapónFil: Albarracín, Leonardo Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Universidad Nacional de Tucumán. Facultad de Ciencias Exactas y Tecnología. Departamento de Ciencias de la Computación; Argentina. Tohoku University; JapónFil: Indo, Yuhki. Tohoku University; JapónFil: Arce, Lorena Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Tohoku University; JapónFil: Masumizu, Yuki. Tohoku University; JapónFil: Tomokiyo, Mikado. Tohoku University; JapónFil: Islam, Md Aminul. Bangladesh Agricultural University; Bangladesh. Tohoku University; JapónFil: Garcia Castillo, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University; JapónFil: Ikeda Ohtsubo, Wakako. Tohoku University; JapónFil: Nochi, Tomonori. Tohoku University; JapónFil: Morita, Hidetoshi. Okayama University; JapónFil: Takahashi, Hideki. Tohoku University; JapónFil: Kurata, Shoichiro. Tohoku University; JapónFil: Villena, Julio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina. Tohoku University; JapónFil: Kitazawa, Haruki. Tohoku University; Japó

Recombinant human FGF-2 for the treatment of early-stage osteonecrosis of the femoral head: TRION, a single-arm, multicenter, Phase II trial

Aim: This study aimed to evaluate the 2-year outcomes from a clinical trial of recombinant human FGF-2 (rhFGF-2) for osteonecrosis of the femoral head (ONFH). Patients & methods: Sixty-four patients with nontraumatic, precollapse and large ONFHs were percutaneously administered with 800 μg rhFGF-2 contained in gelatin hydrogel. Setting the end point of radiological collapse, we analyzed the joint preservation period of the historical control. Changes in two validated clinical scores, bone regeneration and safety were evaluated. Results: Radiological joint preservation time was significantly higher in the rhFGF-2 group than in the control group. The ONFHs tended to improve to smaller ONFHs. The postoperative clinical scores significantly improved. Thirteen serious adverse events showed recovery. Conclusion: rhFGF-2 treatment increases joint preservation time with clinical efficacy, radiological bone regeneration and safety

Identification of an Anti–Integrin αvβ6 Autoantibody in Patients With Ulcerative Colitis

指定難病「潰瘍性大腸炎」の自己抗体発見 --新たな診断や治療開発へ--. 京都大学プレスリリース. 2021-03-09.Background and Aims: Ulcerative colitis is the most frequent type of inflammatory bowel disease and is characterized by colonic epithelial cell damage. Although involvement of autoimmunity has been suggested in ulcerative colitis, specific autoantigens/antibodies have yet to be elucidated. Methods: Using 23 recombinant integrin proteins, we performed enzyme-linked immunosorbent assays on sera from patients with ulcerative colitis and controls. Integrin expression and IgG binding in the colon tissues of patients with ulcerative colitis and controls were examined using immunofluorescence and coimmunoprecipitation, respectively. The blocking activity of autoantibodies was examined using solid-phase binding and cell adhesion assays. Results: Screening revealed that patients with ulcerative colitis had IgG antibodies against integrin αvβ6. In the training and validation groups, 103 of 112 (92.0%) patients with ulcerative colitis and only 8 of 155 (5.2%) controls had anti–integrin αvβ6 antibodies (P < .001), resulting in a sensitivity of 92.0% and a specificity of 94.8% for diagnosing ulcerative colitis. Anti–integrin αvβ6 antibody titers coincided with ulcerative colitis disease activity, and IgG1 was the major subclass. Patient IgG bound to the integrin αvβ6 expressed on colonic epithelial cells. Moreover, IgG of patients with ulcerative colitis blocked integrin αvβ6–fibronectin binding through an RGD (Arg-Gly-Asp) tripeptide motif and inhibited cell adhesion. Conclusions: A significant majority of patients with ulcerative colitis had autoantibodies against integrin αvβ6, which may serve as a potential diagnostic biomarker with high sensitivity and specificity

Field Effect of Alcohol, Cigarette Smoking, and Their Cessation on the Development of Multiple Dysplastic Lesions and Squamous Cell Carcinoma: A Long-term Multicenter Cohort Study

[Background and Aims] Multiple developments of squamous dysplasia and squamous cell carcinoma (SCC) in the upper aerodigestive tract have been explained by field cancerization phenomenon and were associated with alcohol and cigarette use. Second primary SCC development after curative treatment impairs patients’ quality of life and survival; however, how these consumption and cessation affect field cancerization is still unknown. [Methods] This is a multicenter cohort study including 331 patients with superficial esophageal SCC (ESCC) treated endoscopically and pooled data from 1022 healthy subjects for comparison. Physiological condition in the background esophageal mucosa was classified into 3 groups based on the number of Lugol-voiding lesions (LVLs) per endoscopic view: grade A, 0; grade B, 1–9; or grade C, ≥10 LVLs. Lifestyle surveys were conducted using a self-administered questionnaire. Patients were counseled on the need for alcohol and smoking cessation by physicians and were endoscopically surveyed every 6 months. [Results] LVL grades were positively associated with alcohol drinking intensity, flushing reactions, smoking, and high-temperature food and were negatively associated with eating green and yellow vegetables and fruit. Second primary ESCC and head/neck SCC were significantly more prevalent in the grade C LVL (cumulative 5-y incidences 47.1%, 95% confidence interval [CI] = 38.0–57.2 and 13.3%, 95% CI = 8.1–21.5, respectively). Alcohol and smoking cessation significantly reduced the development of second primary ESCC (adjusted hazard ratios 0.47, 95% = CI 0.26–0.85 and 0.49, 95% CI = 0.26–0.91, respectively). [Conclusion] Alcohol drinking, smoking, flushing reaction, and high-temperature food were closely associated with field cancerization, and cessation of alcohol and smoking significantly reduced the risk of development of second primary cancer. UMIN Clinical Trials Registry ID:UMIN000001676

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection