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Background: Health-related patient-reported outcomes (HR-PROs) are crucial for assessing the quality of life among individuals experiencing low back pain. However, manual data entry from paper forms, while convenient for patients, imposes a considerable tallying burden on collectors. In this study, we developed a deep learning (DL) model capable of automatically reading these paper forms., Methods: We employed the Japanese Orthopaedic Association Back Pain Evaluation Questionnaire, a globally recognized assessment tool for low back pain. The questionnaire comprised 25 low back pain-related multiple-choice questions and three pain-related visual analog scales (VASs). We collected 1305 forms from an academic medical center as the training set, and 483 forms from a community medical center as the test set. The performance of our DL model for multiple-choice questions was evaluated using accuracy as a categorical classification task. The performance for VASs was evaluated using the correlation coefficient and absolute error as regression tasks., Result: In external validation, the mean accuracy of the categorical questions was 0.997. When outputs for categorical questions with low probability (threshold: 0.9996) were excluded, the accuracy reached 1.000 for the remaining 65 % of questions. Regarding the VASs, the average of the correlation coefficients was 0.989, with the mean absolute error being 0.25., Conclusion: Our DL model demonstrated remarkable accuracy and correlation coefficients when automatic reading paper-based HR-PROs during external validation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Patients undergoing massive tumor resection and total femur replacement (TFR) face a substantial risk of hip dislocation and infection, often resulting in multiple implant revisions or hip disarticulation. These complications can impact their independence and prognosis. Additionally, their shorter life expectancy is influenced by challenges in achieving local radical resection and controlling metastases. Identifying suitable candidates for TFR is vital, necessitating investigations into dislocation, infection, implant failure rates, local recurrence, overall survival, and associated factors., Questions/purposes: (1) What is the postsurgical complication (hip dislocation and infection) rate and factors associated with postsurgical complications in patients who underwent TFR after tumor resection? (2) What is the local recurrence rate, implant failure rate, overall survival rate, and factors associated with local recurrence and implant failure?, Methods: We retrospectively evaluated 42 patients (median [range] age 47 years [10 to 79 years]) who underwent TFR and tumor resection at the time of the same surgical procedure between 1990 and 2020 at 12 registered institutions that specialized in tumor treatment in Japan. A total of 55% (23) of the patients were men, and 79% (33) had bone sarcoma. The median (range) follow-up period was 36.5 months (2 to 327 months). Of the 42 patients, 12% (5) were lost to follow-up before 2 years without meeting a study endpoint (postsurgical complications, revision, or amputation), and another 19% (8) died before 2 years with implants intact, leaving 69% (29) of the original group who had either follow-up of at least 2 years or met a study endpoint before the minimum surveillance duration. Another 10% (4) had a minimum of 2 years of follow-up but had not been seen in the past 5 years. Infection was defined as deep-seated infection involving soft tissues, bones, joints, and the area around the implant. We did not consider superficial infections. Implant failure was defined when a patient underwent reimplantation or amputation. The complication and implant failure rates were assessed by the cumulative incidence function method, considering competing events. The Kaplan-Meier method was used to estimate the overall survival rate., Results: The 1-month, 6-month, 1-year, and 2-year dislocation rates were 5%, 12%, 14%, and 14%, respectively. The 1-month, 6-month, 1-year, and 2-year infection rates were 5%, 7%, 10%, and 15%, respectively. Multivariable analyses for hip dislocation and infection revealed that resection of the abductor muscles and large tumor size were positively associated with hip dislocation. The 6-month, 1-year, and 2-year local recurrence rates were 5%, 15%, and 15%, respectively. The 6-month, 1-year, 2-year, and 5-year implant failure rates were 5% (95% confidence interval 1% to 15%), 7% (95% CI 2% to 18%), 16% (95% CI 6% to 29%), and 16% (95% CI 6% to 29%), respectively. Multivariable analyses of local recurrence and implant failure that led to reimplantation or amputation revealed that a positive surgical margin was positively associated with local recurrence. The 1-year, 2-year, and 5-year overall patient survival rates were 95% (95% CI 87% to 102%), 77% (95% CI 64% to 91%), and 64% (95% CI 48% to 81%), respectively., Conclusion: Hip dislocation, infection, and local recurrence were frequently observed in patients who received massive tumor resection and TFR in our study, eventually leading to reimplantation or amputation. Preserving the abductor muscles and resecting the tumor with a wide margin can prevent postoperative dislocation and local recurrence. Future research should focus on patient selection criteria, prevention of hip dislocation, and innovative treatments., Level of Evidence: Level IV, therapeutic study., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research ® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2023 by the Association of Bone and Joint Surgeons.)

Background: Tumor-devitalized autografts treated with deep freezing, pasteurization, and irradiation are biological reconstruction methods after tumor excision for aggressive or malignant bone or soft tissue tumors that involve a major long bone. Tumor-devitalized autografts do not require a bone bank, they carry no risk of viral or bacterial disease transmission, they are associated with a smaller immunologic response, and they have a better shape and size match to the site in which they are implanted. However, they are associated with disadvantages as well; it is not possible to assess margins and tumor necrosis, the devitalized bone is not normal and has limited healing potential, and the biomechanical strength is decreased owing to processing and tumor-related bone loss. Because this technique is not used in many countries, there are few reports on the results of this procedure such as complications, graft survival, and limb function., Questions/purposes: (1) What was the rate of complications such as fracture, nonunion, infection, or recurrence in a tumor-devitalized autograft treated with deep freezing, pasteurization, and irradiation, and what factors were associated with the complication? (2) What were the 5-year and 10-year grafted bone survival (free from graft bone removal) of the three methods used to devitalize a tumor-containing autograft, and what factors were associated with grafted bone survival? (3) What was the proportion of patients with union of the tumor-devitalized autograft and what factors were associated with union of the graft-host bone junction? (4) What was the limb function after the tumor-devitalized autograft, and what factors were related to favorable limb function?, Methods: This was a retrospective, multicenter, observational study that included data from 26 tertiary sarcoma centers affiliated with the Japanese Musculoskeletal Oncology Group. From January 1993 to December 2018, 494 patients with benign or malignant tumors of the long bones were treated with tumor-devitalized autografts (using deep freezing, pasteurization, or irradiation techniques). Patients who were treated with intercalary or composite (an osteoarticular autograft with a total joint arthroplasty) tumor-devitalized autografts and followed for at least 2 years were considered eligible for inclusion. Accordingly, 7% (37 of 494) of the patients were excluded because they died within 2 years; in 19% (96), an osteoarticular graft was used, and another 10% (51) were lost to follow-up or had incomplete datasets. We did not collect information on those who died or were lost to follow-up. Considering this, 63% of the patients (310 of 494) were included in the analysis. The median follow-up was 92 months (range 24 to 348 months), the median age was 27 years (range 4 to 84), and 48% (148 of 310) were female; freezing was performed for 47% (147) of patients, pasteurization for 29% (89), and irradiation for 24% (74). The primary endpoints of this study were the cumulative incidence rate of complications and the cumulative survival of grafted bone, assessed by the Kaplan-Meier method. We used the classification of complications and graft failures proposed by the International Society of Limb Salvage. Factors relating to complications and grafted autograft removal were analyzed. The secondary endpoints were the proportion of bony union and better limb function, evaluated by the Musculoskeletal Tumor Society score. Factors relating to bony union and limb function were also analyzed. Data were investigated in each center by a record review and transferred to Kanazawa University., Results: The cumulative incidence rate of any complication was 42% at 5 years and 51% at 10 years. The most frequent complications were nonunion in 36 patients and infection in 34 patients. Long resection (≥ 15 cm) was associated with an increased risk of any complication based on the multivariate analyses (RR 1.8 [95% CI 1.3 to 2.5]; p < 0.01). There was no difference in the rate of complications among the three devitalizing methods. The cumulative graft survival rates were 87% at 5 years and 81% at 10 years. After controlling for potential confounding variables including sex, resection length, reconstruction type, procedure type, and chemotherapy, we found that long resection (≥ 15 cm) and composite reconstruction were associated with an increased risk of grafted autograft removal (RR 2.5 [95% CI 1.4 to 4.5]; p < 0.01 and RR 2.3 [95% CI 1.3 to 4.1]; p < 0.01). The pedicle freezing procedure showed better graft survival than the extracorporeal devitalizing procedures (94% versus 85% in 5 years; RR 3.1 [95% CI 1.1 to 9.0]; p = 0.03). No difference was observed in graft survival among the three devitalizing methods. Further, 78% (156 of 200 patients) of patients in the intercalary group and 87% (39 of 45 patients) of those in the composite group achieved primary union within 2 years. Male sex and the use of nonvascularized grafts were associated with an increased risk of nonunion (RR 2.8 [95% CI 1.3 to 6.1]; p < 0.01 and 0.28 [95% CI 0.1 to 1.0]; p = 0.04, respectively) in the intercalary group after controlling for confounding variables, including sex, site, chemotherapy, resection length, graft type, operation time, and fixation type. The median Musculoskeletal Tumor Society score was 83% (range 12% to 100%). After controlling for confounding variables including age, site, resection length, event occurrence, and graft removal, age younger than 40 years (RR 2.0 [95% CI 1.1 to 3.7]; p = 0.03), tibia (RR 6.9 [95% CI 2.7 to 17.5]; p < 0.01), femur (RR 4.8 [95% CI 1.9 to 11.7]; p < 0.01), no event (RR 2.2 [95% CI 1.1 to 4.5]; p = 0.03), and no graft removal (RR 2.9 [95% CI 1.2 to 7.3]; p = 0.03) were associated with an increased limb function. The composite graft was associated with decreased limb function (RR 0.4 [95% CI 0.2 to 0.7]; p < 0.01)., Conclusion: This multicenter study revealed that frozen, irradiated, and pasteurized tumor-bearing autografts had similar rates of complications and graft survival and all resulted in similar limb function. The recurrence rate was 10%; however, no tumor recurred with the devitalized autograft. The pedicle freezing procedure reduces the osteotomy site, which may contribute to better graft survival. Furthermore, tumor-devitalized autografts had reasonable survival and favorable limb function, which are comparable to findings reported for bone allografts. Overall, tumor-devitalized autografts are a useful option for biological reconstruction and are suitable for osteoblastic tumors or osteolytic tumors without severe loss of mechanical bone strength. Tumor-devitalized autografts could be considered when obtaining allografts is difficult and when a patient is unwilling to have a tumor prosthesis and allograft for various reasons such as cost or socioreligious reasons., Level of Evidence: Level III, therapeutic study., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2023 by the Association of Bone and Joint Surgeons.)

Background: Low-grade osteosarcomas, namely parosteal osteosarcoma (POS) and low-grade central osteosarcoma (LGCOS), occasionally dedifferentiate into high-grade malignancy, referred to as dedifferentiation in low-grade osteosarcoma (DLOS). This study aimed to elucidate the clinicopathologic features of DLOS, which are poorly described to date due to the extreme rarity of the disease., Methods: A total of 33 patients with DLOS were included. Clinical characteristics, including the diagnostic accuracy of tumor biopsy, multimodal treatments, and clinical course, were retrospectively reviewed. Univariate analysis was performed to identify prognostic factors associated with overall survival (OS) and metastasis-free survival (MFS)., Results: The tumor subtypes comprised 10 cases (30.3%) of LGCOS and 23 cases (69.7%) of POS. The timing of dedifferentiation was synchronous in 25 (75.8%) and metachronous in 8 (24.2%) patients. The rates of preoperative diagnosis of DLOS were 40.0% and 65.4% for core needle biopsy and incisional biopsy, respectively. All patients underwent surgery and 25 patients received perioperative chemotherapy. Of the 13 patients who received neoadjuvant chemotherapy, 11 exhibited a poor histological response. The 5-year OS and MFS rates were 88.1% and 77.7%, respectively. Univariate analysis revealed that local recurrence was associated with poor OS (P < 0.01) and MFS (P < 0.01). Perioperative chemotherapy did not affect OS or MFS., Conclusions: The diagnostic accuracy of tumor biopsy for DLOS was lower than that for bone sarcomas, as reported previously. In contrast to conventional osteosarcomas with high chemosensitivity, both histological responses and survival analysis revealed low efficacy of chemotherapy for DLOS., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Objective This study examined whether or not the disease control in Japanese patients with systemic lupus erythematosus (SLE) had improved in recent years and its possible association with altered balance between the use of glucocorticoids and immunosuppressants. Methods We enrolled Japanese patients with SLE who visited our medical center during 2013-2017 (Group A, 75 patients) and compared them with patients encountered during 1999-2003 (Group B, 69 patients; not overlapping with Group A). Patient background characteristics, doses of glucocorticoids, and the use of immunosuppressants at the times of SLE onset and disease flares were reviewed from the medical records. Disease flare was defined as new British Isles Lupus Assessment Group 2004 A or B scores in at least one system. Results Lupus nephritis and neuropsychiatric manifestations were less frequently observed in Group A than in Group B (p=0.042 and p=0.045, respectively). Although the initial glucocorticoid dosage was similar between the groups, the inclusion rate of immunosuppressants in the initial SLE treatment was significantly higher in Group A than in Group B (56% vs. 6% in Group B, p<0.001). The median number of SLE flares per person-year was significantly lower in Group A than in Group B (0 vs. 0.3, respectively, p<0.001), and a propensity score-matched analysis indicated the association of SLE flare with the non-use of immunosuppressants in the initial treatment (p=0.012). The rates of infectious diseases and other complications were similar between the groups. Conclusion The recent aggressive use of immunosuppressants in Japan resulted in a reduction in the rate of SLE flare.

Background: Diagnosing heart failure with preserved ejection fraction (HFpEF) is challenging. Although the H 2 FPEF score and HFA-PEFF algorithm have been proposed for diagnosing HFpEF, previous validation studies were conducted in stable chronic heart failure (HF). Moreover, information on their applicability in the Asian population is limited. We sought to investigate these scores' diagnostic performance for HFpEF in Japanese patients recently hospitalized due to acute decompensated HF., Methods: We examined patients with HFpEF recently hospitalized with acute decompensated HF from a nationwide HFpEF-specific multicenter registry (HFpEF group) and control patients who underwent echocardiography to investigate the cause of dyspnea in our hospital (Non-HFpEF group)., Results: The studied population included 372 patients (194 HFpEF group and 178 Non-HFpEF group; HFpEF prevalence, 52%). A high H 2 FPEF score (6-9 points) could diagnose HFpEF with a high specificity of 97% and a positive predictive value (PPV) of 94%, and a low H 2 FPEF score (0-1 point) could rule out HFpEF with a high sensitivity of 97% and a negative predictive value (NPV) of 93%. HFpEF could be diagnosed with a high HFA-PEFF score (5-6 points) (specificity, 84%; PPV, 82%) or ruled out with a low HFA-PEFF score (0-1 point) (sensitivity, 99%; NPV, 89%). The H 2 FPEF score was significantly superior to the HFA-PEFF score in diagnostic accuracy (area under the curve: 0.89 vs. 0.82, respectively, p = 0.004)., Conclusions: The H 2 FPEF and the HFA-PEFF scores had acceptable diagnostic accuracy in diagnosing HFpEF in Japanese patients., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: This study aimed to assess, among Japanese patients with cardiac sarcoidosis (CS), the implantable cardioverter-defibrillator (ICD) recommendations from the 2017 American Heart Association/American College of Cardiology/Heart Rhythm Society (AHA/ACC/HRS) guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death (SCD)., Background: Although ICDs are used to prevent SCD from ventricular tachycardia or ventricular fibrillation (VT/VF) in patients with CS, the generalizability of the AHA/ACC/HRS guidelines for Japanese patients with CS remains unclear., Methods: This study examined 188 consecutive patients with CS in 2 tertiary hospitals between 1979 and 2020. Patients were followed for a primary outcome of VT/VF or SCD., Results: During a median follow-up of 5.68 years, the primary outcome occurred in 44 patients (23%). Patients with a Class I recommendation for ICD implantation showed the highest incidence of the primary outcome among patients in whom the guideline recommendations for ICD implantation were used (log-rank test; p = 0.03). However, compared with patients with left ventricular ejection fractions (LVEFs) ≤35%, there was no significant difference in the incidence of the primary outcome among patients with LVEFs >35% and those who required a permanent pacemaker (p = 0.31); similar results were observed in those with LVEFs >35% and late gadolinium enhancement during cardiovascular magnetic resonance imaging (p = 0.22)., Conclusions: The American guideline recommendations for ICD implantation might be applicable to Japanese patients with CS. Implantation of an ICD may need to be considered in these patients if they require a permanent pacemaker or have late gadolinium enhancement, regardless of LVEF., Competing Interests: Funding Support and Author Disclosures Dr. Nagai was supported by a Grant-in-Aid for Young Scientists from the Japan Society for the Promotion of Science (15K19402) and by a grant from the Japan Heart Foundation. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

We elucidated clinicopathological characteristics of giant cell tumor of bone (GCTB) in Japan, and significant clinicopathological factors for predicting local recurrence. Clinicopathological profiles of 213 patients with GCTB (100 male, 113 female) involving extra-craniofacial bones were retrieved. Pathological slides obtained at the initial surgery were reviewed. Fourteen pathological and five clinical features were statistically analyzed to disclose prognostic significance. Patient age ranged from 12-80 years (Average 38.7). Long bones were most frequently affected (86.4%), especially around the knee (62.9%). Histological features are basically similar to those previously reported. Within a follow-up period (24-316 months, average 106.1 months), the local recurrence rate is 29.1%. Metastasis has occurred in 9 patients. Cox regression analysis of representative clinicopathological features shows that younger age, higher mitotic count, smaller zones of stromal hemorrhage, considerable vascular invasion and absence of ischemic necrosis are significant predictors for local recurrence. Initial operative method (curettage) is a significant risk factor in univariate analysis but not by multivariate analysis (P = 0.053). Denosumab administration increases risk but not significantly (P = 0.053). Histone 3.3 G34W immunopositivity is not significant for predicting local recurrence., (© 2021 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.)

Background: Although the unpredictable malignant behavior of solitary fibrous tumors (SFTs) has been recognized, the clinical features and prognosis of metastatic SFTs have not been well documented due to the extreme rarity of these cases. The aim of this study is to investigate the clinical features, prognostic factors, and optimal management of patients with metastatic SFTs., Patients and Methods: Sixty patients with metastatic SFT were retrospectively reviewed. Univariate and multivariate analyses were performed to identify the factors associated with survival. Time to next treatment (TNT) was used to evaluate the effects of various chemotherapy regimens., Results: A total of 34 male and 26 female patients (median age 55 years, range, 23-87 years) were included in the study. The median follow-up period after metastasis was 32 months (range 1-126 months). Tumor location and local recurrence were correlated with late metastasis. The 3- and 5-year overall survival rates were 72.7% and 49.2%, respectively. Primary tumor location, number of metastases, and metastasectomy were significantly associated with survival. Metastasectomy was the only significant variable on multivariate analysis. The TNT was significantly different among the various regimens., Conclusions: Patients with metastatic SFTs had relatively longer survival periods compared with those with other metastatic soft-tissue sarcomas. Tumor location and number of metastases was associated with survival. Surgical resection of the metastatic lesions offers the best chance of survival, however further studies are warranted to define patients who would benefit from metastasectomy, and the most effective chemotherapeutic regimen for patients with metastatic SFTs remains unknown.

Background: Postoperative recovery of activities of daily living after surgery in elderly patients often takes a longer time because of their frailty. However, it is unclear how long it takes for patients with adult spinal deformity (ASD) to recover their abilities to live their daily lives in their home after corrective fusion surgery. This study aimed to investigate the length of hospital stay required to perform activities of daily living (ADL) in patients undergoing two-stage corrective fusion surgery for ASD in our institution and to detect factors associated with the length of hospital stay., Methods: Thirty-four consecutive female ASD patients (median age, 70 years) who underwent two-stage corrective fusion surgery (lateral lumbar interbody fusion at the first stage and posterior corrective fusion at the second stage) from T9 or T10 to the pelvis were included. The length of hospital stay from admission to return home was determined, and correlations between length of hospital stay and demographics, skeletal muscle mass, operative invasion and perioperative complications, and spino-pelvic alignment were investigated., Results: The median length of hospital stay was 51 days, exceeding 100 days in 25% of cases. Age at surgery (ρ = 0.545, p = 0.001), estimated glomerular filtration rate (ρ = -0.603, p < 0.001), age-adjusted Charlson comorbidity index (ρ = 0.437, p = 0.01), and preoperative pelvic incidence (ρ = 0.356, p = 0.04) were correlated with length of hospital stay. Preoperative skeletal muscle mass, preoperative spinal imbalance, perioperative changes in spino-pelvic alignment, operative invasion, and perioperative complications were not correlated with length of hospital stay., Conclusions: After >50 days, ADL performance of each patient reached the extent required for daily living to return home after two-stage corrective fusion surgery for ASD. Factors related to length of hospital stay were age and indices related to frailty., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Sarcoidosis is a genetically complex systemic inflammatory disease that affects multiple organs. We present a GWAS of a Japanese cohort (700 sarcoidosis cases and 886 controls) with replication in independent samples from Japan (931 cases and 1,042 controls) and the Czech Republic (265 cases and 264 controls). We identified three loci outside the HLA complex, CCL24, STYXL1-SRRM3, and C1orf141-IL23R, which showed genome-wide significant associations (P < 5.0 × 10 -8 ) with sarcoidosis; CCL24 and STYXL1-SRRM3 were novel. The disease-risk alleles in CCL24 and IL23R were associated with reduced CCL24 and IL23R expression, respectively. The disease-risk allele in STYXL1-SRRM3 was associated with elevated POR expression. These results suggest that genetic control of CCL24, POR, and IL23R expression contribute to the pathogenesis of sarcoidosis. We speculate that the CCL24 risk allele might be involved in a polarized Th1 response in sarcoidosis, and that POR and IL23R risk alleles may lead to diminished host defense against sarcoidosis pathogens.

Decreasing the transfer of radioactive cesium (RCs) from soil to crops has been important since the deposition of RCs in agricultural soil owing to the Fukushima nuclear power plant accident of 2011. We investigated the genotypic variation in RCs accumulation in 234 and 198 hexaploid wheat (Triticum spp.) varieties in an affected field in 2012 and 2013, respectively. The effects of soil exchangeable potassium (ExK) content to RCs accumulation in wheat varieties were also evaluated. A test field showed fourfold differences in soil ExK contents based on location, and the wheat varieties grown in areas with lower soil ExK contents tended to have higher grain RCs concentrations. RCs concentrations of shoots, when corrected by the soil ExK content, were positively significantly correlated between years, and RCs concentrations of shoots were significantly correlated with the grain RCs concentration corrected by the soil ExK content. These results indicated that there were genotypic variations in RCs accumulation. The grain to shoot ratio of RCs also showed significant genotypic variation. Wheat varieties with low RCs accumulations were identified. They could contribute to the research and breeding of low RCs accumulating wheat and to agricultural production in the area affected by RCs deposition.

Since vitamin E is one of the most potent antioxidant and anti-inflammatory agents, vitamin E can play a role against arteriosclerosis through various actions. Then, we have studied the relationship between serum vitamin E status and risk factors for arteriosclerosis in Japanese postmenopausal women. One hundred and seven subjects (70.0±7.7 y) were evaluated for vitamin E status by measuring serum α- and γ-tocopherol (αT and γT) levels. The number of arteriosclerosis risk factors was defined by the existence of high blood pressure, hyperglycemia, and dyslipidemia. Median serum αT and γT concentrations were 24.32 and 2.79 μmol/L, respectively. In none of the subjects, serum αT level was below the cutoff value (<12 μmol/L) for vitamin E deficiency which causes fragile erythrocyte and hemolysis. While no significant differences were found in serum levels of αT and γT between the groups categorized by the number of arteriosclerosis risks, serum levels of αT adjusted by serum total cholesterol (TC) and triglyceride (TG) decreased with an increasing number of arteriosclerotic risk factors (p=0.074). Serum αT level adjusted by serum TC and TG was also a negative significant predictor for the number of arteriosclerosis risk factors controlled by covariates associated with arteriosclerosis. The present study described that serum vitamin E level was positively associated with a lower number of arteriosclerotic risks, and its role for preventing noncommunicable diseases was suggested.

Background: There have been few reports on the incidence and risk factors of the complications after spinal fixation surgery for osteoporotic vertebral collapse (OVC) with neurological deficits. This study aimed to identify the incidence and risk factors of the complications after OVC surgery., Methods: In this retrospective multicenter study, a total of 403 patients (314 women and 89 men; mean age 73.8 years) who underwent spinal fixation surgery for OVC with neurological deficits between 2005 and 2014 were enrolled. Data on patient demographics were collected, including age, sex, body mass index, smoking, steroid use, medical comorbidities, and surgical procedures. All postoperative complications that occurred within 6 weeks were recorded. Patients were classified into two groups, namely, complication group and no complication group, and risk factors for postoperative complications were investigated by univariate and multivariate analyses., Results: Postoperative complications occurred in 57 patients (14.1%), and the most common complication was delirium (5.7%). In the univariate analysis, the complication group was found to be older (p = 0.039) and predominantly male (p = 0.049), with higher occurrence rate of liver disease (p = 0.001) and Parkinson's disease (p = 0.039) compared with the no-complication group. In the multivariate analysis, the significant independent risk factors were age (p = 0.021; odds ratio [OR] 1.051, 95% confidence interval [CI] 1.007-1.097), liver disease (p < 0.001; OR 8.993, 95% CI 2.882-28.065), and Parkinson's disease (p = 0.009; OR 3.636, 95% CI 1.378-9.599)., Conclusions: Complications after spinal fixation surgery for OVC with neurological deficits occurred in 14.1%. Age, liver disease, and Parkinson's disease were demonstrated to be independent risk factors for postoperative complications., (Copyright © 2019 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: The JOA (Japan Orthopaedic Association) score has been a standard outcome measure to evaluate cervical myelopathy in Japan. Despite its reliability and convenience, there can be a rating bias in the JOA score. The current study was conducted to delineate the rater's bias of the JOA score by comparing it with a new objective outcome measure., Methods: Two hundred and thirty four operative candidates with cervical myelopathy were included in the study. The patients were divided into four groups according to the surgeon (92 patients in group A, 60 patients in group B, 38 patients in group C and 44 patients in group D). Each patient's preoperative JOA score was exclusively recorded by the surgeon himself, while JOACMEQ (Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire) was recorded by each patient. Disease severity, the most important prognostic factor, was equalized between patient groups by a special statistical method called inverse-probability weighting (IPW). To define similarity of the two groups, Cohen's d was used., Results: After the adjustment, the differences of the JOA score were only 0.1 between groups A and D and 0 between groups B and C. The values of Cohen's d were also very small both between groups A and D (3%), and between groups B and C (0.3%). The averaged JOA scores of groups A and D were higher by 0.4-0.8 than those of groups B and C, while the averaged JOA scores were almost the same both between groups A and D, and between groups B and C. Surgeons A and D had the same tendency to give higher JOA scores than surgeons B and C did., Conclusions: The current study confirmed there is a definite rater's bias in the JOA score. JOACMEQ is to be applied as a more reliable outcome measure to evaluate myelopathy patients., (Copyright © 2018 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Objective: To assess the safety and efficacy of infliximab (IFX) for the treatment of patients with Kawasaki disease (KD)., Study Design: This was a nationwide survey of 274 Japanese institutions exploring how IFX was used to treat patients with KD. The patients' sex, age, treatment course, pre- and post-IFX therapy blood test results, coronary artery lesions (CALs), and adverse events (AEs) were evaluated., Results: We analyzed 434 patients with KD who received IFX between March 2005 and November 2014. The median age at onset was 33 months (range 1-138), and 66 patients (15.2%) were under 1 year old. In all cases, IFX was administered as additional treatment. The median days of illness at the initiation of IFX was 9 days. In 275 patients (63.4%), IFX was administered as third-line treatment, and in 106 patients (24.4%), IFX was administered as fourth-line treatment. Single dose IFX 5 mg/kg was administered to 412 patients (94.9%). After IFX, 363 patients (83.6%) became afebrile within 2 days, and the white blood cell count, percentage of neutrophils, and serum C-reactive protein levels significantly decreased (P < .001), although 119 patients (27.4%) received additional treatment. Before IFX, 132 patients (30.4%) had already developed CALs. In patients without CALs before IFX, 31 patients (10.3%) newly developed CAL after IFX, whereas 32 patients (24.2%) with CAL before IFX showed increased CAL severity. Eighty AEs were observed in 69 patients (15.9%); however, serious AEs were few and reversible., Conclusions: IFX might be an effective and tolerable treatment for refractory KD., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The incidence of Ewing sarcoma is lower in non-Caucasian populations, compared with Caucasian populations, for unknown reasons. Most studies from western countries have reported improvement in outcomes following multi-agent chemotherapy, with no difference in outcome between skeletal and extraskeletal Ewing sarcoma. However, there are few studies of Ewing sarcoma in non-Caucasian populations, with especially few comparing outcomes between skeletal and extraskeletal Ewing sarcoma. Thus, the purpose of this study is to determine whether the outcomes and prognostic factors of Ewing sarcoma in the Japanese population are similar to those in Caucasian populations and to determine whether skeletal and extraskeletal Ewing sarcoma have similar outcomes in Japanese patients., Methods: We retrospectively evaluated the outcomes of 74 Japanese patients with Ewing sarcoma treated between 1981 and 2011 from the Osaka University Orthopaedic Oncology Group., Results: Extraskeletal Ewing sarcoma, tumors in the extremities, localized disease at presentation and diagnosis after 2000 were significantly associated with a favorable outcome. Among patients with localized disease at presentation, a significantly better outcome was observed for those with extraskeletal Ewing sarcoma, those who underwent a VDC/IE based or VAIA chemotherapy protocol, and those who were diagnosed after 2000. In the multivariable analyses, extraskeletal Ewing sarcoma was an independent predictor of increased overall survival among all patients and the subset of patients with localized disease., Conclusions: The outcome of patients with Ewing sarcoma in Japan has improved in the last decade. The outcomes and prognostic factors are similar for Japanese and Caucasian patients, though in this series of Japanese patients, a better prognosis was observed for patients with extraskeletal rather than skeletal Ewing sarcoma., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

An increasing number of Shiga toxin 2f-producing Escherichia coli (STEC2f) infections in humans are being reported in Europe, and pigeons have been suggested as a reservoir for the pathogen. In Japan, there is very little information regarding carriage of STEC2f by pigeons, prompting the need for further investigation. We collected 549 samples of pigeon droppings from 14 locations in Kyushu, Japan, to isolate STEC2f and to investigate characteristics of the isolates. Shiga toxin stx 2f gene fragments were detected by PCR in 16 (2.9%) of the 549 dropping samples across four of the 14 locations. We obtained 23 STEC2f-isolates from seven of the original samples and from three pigeon dropping samples collected in an additional sampling experiment (from a total of seven locations across both sampling periods). Genotypic and phenotypic characteristics were then examined for selected isolates from each of 10 samples with pulsed-field gel electrophoresis profiles. Eight of the stx 2f gene fragments sequenced in this study were homologous to others that were identified in Europe. Some isolates also contained virulence-related genes, including lpfA O26, irp 2, and fyuA, and all of the 10 selected isolates maintained the eae, astA, and cdt genes. Moreover, five of the 10 selected isolates contained sfpA, a gene that is restricted to Shiga toxin-producing E. coli O165:H2 and sorbitol-fermenting Shiga toxin-producing E. coli O157:NM. We document serotypes O152:HNM, O128:HNM, and O145:H34 as STEC2f, which agrees with previous studies on pigeons and humans. Interestingly, O119:H21 was newly described as STEC2f. O145:H34, with sequence type 722, was described in a German study in humans and was also isolated in the current study. These results revealed that Japanese zoonotic STEC2f strains harboring several virulence-related factors may be of the same clonal complexes as some European strains. These findings provide useful information for public health-related disease management strategies in Japan.

Background: Anti-tachycardia pacing (ATP) delivered by implantable cardioverter defibrillators (ICD) safely avoids painful shocks with minimum risk of tachycardia acceleration. The etiology of ventricular tachycardia (VT) in those studies, however, was predominantly coronary artery disease (CAD). Patient etiology differs by geography and could affect ATP efficacy rate. The primary objective of this study was to examine how often the first ATP therapy terminates fast VT (FVT) in Japanese ICD patients with regional etiologies. METHODS AND RESULTS: Seven hundred and fifteen patients received ICD or cardiac resynchronization therapy defibrillator with the function of ATP during capacitor charging. The primary endpoint was the first ATP success rate for terminating FVT with cycle length 240-320 ms. During a mean follow-up of 11.3 months, 888 spontaneous VT episodes were detected, including 276 FVT (31.1%) in 42 patients. The first-ATP success rate for FVT in the overall group (41% CAD, 59% non-CAD including 23% idiopathic VT) was 62.1% (61.7% adjusted). Success rate was not different between non-CAD and CAD patients (61.4% adjusted and 57.5% adjusted, respectively, P=0.75). Eight FVT episodes (2.9%) accelerated after the first ATP attempt, all of which were terminated by subsequent device therapy (additional ATP or shock)., Conclusions: ATP efficacy for FVT was similar between ICD patients with and without CAD etiology.

Purpose: Sarcoidosis is a heterogeneous and multisystem granulomatous disorder. The etiology still is uncertain, but the disease currently is thought to be triggered by various genetic as well as environmental factors. Recently, an association between sarcoidosis and the butyrophilin-like 2 (BTNL2) gene located in close proximity to the HLA-DRB1 gene was reported. The purpose of our study was to verify the relationship between BTNL2 and HLA risk alleles for the susceptibility to sarcoidosis, and to assess whether the BTNL2 association is independent of the HLA risk alleles., Methods: In our study, 11 single nucleotide polymorphisms (rs28362677, rs2076533, rs2076530, rs2076529, rs2294881, rs3763304, rs2076523, rs28362682, rs3806156, rs9268499, rs3763317), including the functional rs2076530 (G > A) of the BTNL2 gene, and HLA-DRB1 and -DQB1 alleles, were genotyped in 237 Japanese patients diagnosed with sarcoidosis and 287 healthy Japanese control subjects., Results: In the patient group, the HLA-DRB1*08:03 (P = 6.15 × 10(-5), odds ratio [OR] = 2.43) and BTNL2 rs2076530&#95;A (P = 6.90 × 10(-6), OR = 1.84) were associated with disease susceptibility. Upon stratification analysis in search for a synergistic effect given the extensive linkage disequilibrium between BTNL2 rs2076530&#95;A and HLA-DRB1*08:03, our results suggested that the risk-bearing allele of these two loci interact negatively. No significant differences were observed in allele frequencies for alleles in patients with ocular and other systemic sarcoidosis., Conclusions: Our studies implicated that the HLA-DRB1 allele is a major contributing genetic factor in the development of sarcoidosis in Japan. However, further studies are needed to verify how HLA or BTNL2 alleles confer the disease phenotype, severity of sarcoidosis.

We evaluated the sensitivity and specificity of an immunochromatography kit, Single-path Emetic Tox Mrk (Merck), which targets a marker protein for the detection of Bacillus cereus that produces emetic toxin. Strains were isolated after outbreaks of food poisoning, and from retail prepared foods and food products. The strains were examined for the presence of the emetic toxin-synthetase gene by PCR. All 58 emetic strains isolated from the food poisoning cases showed a positive reaction in the immunochromatography kit. No emetic strains gave false negative result. Among 47 non-emetic strains, only two strains isolated from the food poisonings and one strain isolated from food products showed a false positive reaction in the test. We concluded that this method has high sensitivity and specificity. The test can be used for detection of emetic toxin-producing B. cereus not only from food poisoning cases, but also in food products.

Purpose: Sarcoidosis is a systemic inflammatory disease characterized by the formation of non-caseating granulomas, with varied clinical manifestations. The common etiology of sarcoidosis is uncertain, but it is thought to be triggered by an exogenous antigenic stimulus, such as some bacterial proteins. Toll-like receptors (TLRs) recognize microbial components and elicit innate as well as adaptive immune responses. It has been reported that polymorphisms in TLR2 might be important in a small group of Caucasian sarcoidosis patients. The present study aimed to establish whether these findings are relevant to the Japanese population., Methods: We genotyped 5 single-nucleotide polymorphisms (SNPs) in TLR2 and assessed the allelic diversity between 257 Japanese sarcoidosis patients and 193 Japanese healthy controls., Results: No significant differences in the frequency of TLR2 alleles and haplotypes in the sarcoidosis cases were found in comparison with the controls. However, marginal associations were observed for TLR2 at rs3804099 and rs3804100 in sarcoidosis patients with cutaneous manifestations., Conclusions: Our results suggest that TLR2 polymorphisms are not significantly related to the pathogenesis of sarcoidosis in the Japanese population.

Purpose: The clinical features of large cell carcinoma (LCC) of the lung have remained unclear due to the low incidence of the disease. This study investigated the clinicopathological features and the surgical outcome in patients with LCC., Subjects: This study clinicopathologically evaluated 975 patients who had undergone a resection for non-small cell carcinoma between 1994 and 2007. There were 57 (5.8%) patients with LCC among them., Results: The LCC patients included 49 males and 8 females and included 9 patients with large cell neuroendocrine carcinoma. All patients excluding 1 had a smoking habit. The mean smoking pack-year index was 49.9 in the patients with LCC, 27.1 in 625 patients with adenocarcinoma, and 52.5 in 266 patients with squamous cell carcinoma, and this was significantly higher in the patients with LCC than in those with adenocarcinoma. The mean tumor diameter was 38 mm for LCC, 28 mm for adenocarcinoma, and 39 mm for squamous cell carcinoma. The pathological stage was IA in 11 patients, IB in 11, II in 12, IIIA in 16, IIIB in 5, and IV in 2. The post-operative 5-year survival rate was 60.5% for LCC, 64.3% for large cell neuroendocrine carcinoma, 67.0% for adenocarcinoma, and 50.1% for squamous cell carcinoma., Conclusion: The tumor diameter was significantly larger for LCC than for adenocarcinoma at the time of diagnosis. The proportion of smokers and the smoking pack-year index in patients with LCC were significantly higher than those of adenocarcinoma. The surgical results were similar between LCC and other non-small cell lung carcinomas., (Copyright 2010 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Shiga toxin 2f-producing Escherichia coli (O115:HNM) with eae was isolated from a symptomatic patient in Fukuoka Prefecture, Japan. The patient was a 23-year-old male and his symptoms were diarrhea, abdominal pain, headaches and a fever (37.7 degrees C). He had eaten raw chicken meat, raw chicken eggs, cooked chicken meat and raw vegetables about 13 h prior to the onset of the symptoms. The patient's specimen was examined, and no diarrheagenic agents were detected except for Shiga toxin 2f-producing E. coli (STEC(2f)) with eae. This is the first report of the serotype O115:HNM possessing stx(2f). We discuss the necessity of routinely using stx(2f)-detecting PCR primers for detection of this enteric pathogen.

CARD15 was first identified as a susceptibility gene for Crohn's disease. More recently, CARD15 mutations were shown to be associated with the pediatric granulomatous inflammatory diseases, Blau syndrome and early-onset sarcoidosis (EOS). The aim of the present study was to evaluate whether CARD15 variants also play a role in patients with ordinary sarcoidosis other than EOS. We enrolled 135 Japanese sarcoidosis patients with uveitis as well as 95 healthy individuals and performed mutation analysis by direct sequencing of CARD15 exon 4. Direct DNA sequencing in the sarcoidosis patients showed eight CARD15 variants, including five novel mutations (13402C>T, 13543C>T, 13775C>A, 13937G>A, and 14079C>T). Compared with healthy individuals, CARD15 mutations are not common in the Japanese patients with sarcoidosis. Based on the results, we examined the clinical manifestations in patients with sarcoidosis according to their CARD15 mutations. Sarcoidosis patients with these mutations have no specific clinical features with regard to course of the disease or disease severity. Our results indicate that in general, CARD15 mutations may not contribute to the risk of sarcoidosis.

The prognostic implication of SYT-SSX fusion type in synovial sarcomas is still controversial. The aim of this study is to clarify the prognostic impact of fusion type, in association with other clinical factors, in patients with synovial sarcoma in Japan. Data on 108 SYT-SSX fusion transcript-positive patients with synovial sarcoma, treated in 11 tertiary referral cancer centers in Japan, were retrospectively analyzed. The following parameters were examined for their potential prognostic impact: SYT-SSX fusion type, patient age at presentation, sex, primary tumor location, tumor size, histological subtype, histological grade, treatment modalities and disease stage at presentation. Among the patients with localized disease at presentation, 5-year overall survival (OS) for SYT-SSX1 and -2 subgroups were 84.4 and 74.9%, respectively (P=0.244). Five-year metastasis-free survival (MFS) rates were 67.8% for SYT-SSX1 and 68.5% for SYT-SSX2 (P=0.949). Univariate survival analyses for 91 patients with localized disease at presentation showed that tumor size was the only significant prognostic factor for OS (P=0.0033) and MFS (P=0.0029) and the histological grade was marginally significant for MFS (P=0.0785), whereas the SYT-SSX fusion type and other variables were not. Multivariate survival analyses further indicated that tumor size was the most significant independent prognostic factor for OS and MFS and the histological grade was also significant for MFS. In conclusion, the SYT-SSX fusion type is not a significant prognostic factor unlike tumor size, followed by histological grade for patients with localized synovial sarcoma in Japan.

Objective: To clarify the association between the cytochrome P450 (CYP) 1A2 genotype with the CYP1A2 phenotype and to search for the CYP1A2*1K haplotype, which has been shown to decrease CYP1A2 inducibility and/or other functional polymorphisms in Japanese., Methods: Two polymorphisms, CYP1A2*1C and CYP1A2*1F, were genotyped in 126 patients receiving oral slow-release theophylline (TP) therapy and in 224 healthy volunteers. The CYP1A2 phenotype was assessed by the plasma [1-methyluric acid (1U)+3-methylxanthine (3X)]/TP ratio in the patients. The volunteers were given 150 mg caffeine, and the urine [1X+1U+5-acetylamino-6-amino-3-methyluracil (AAMU)]/17U ratio was used for CYP1A2 phenotyping. CYP1A2 intron 1 and six exons (exon 2-exon 7) were sequenced in the patients whose (1U+3X)/TP ratios were below the mean-2SD of those of all patients, and intron 1 was also sequenced in an additional 20 healthy volunteers exhibiting putative low CYP1A2 activities., Results: The individual (1U+3X)/TP ratios ranged from 0.007 to 0.21 (a 30-fold difference) in the patients, and the (1X+1U+AAMU)/17U ratios ranged from 1.6 to 112 (a 70-fold difference) in the healthy volunteers. The CYP1A2 activities were not significantly influenced by CYP1A2*1C or CYP1A2*1F. We found no functional polymorphisms by a sequencing analysis., Conclusion: These results suggest that the CYP1A2*1C and CYP1A2*1F genotypes are not crucial factors for the variability of CYP1A2 activity and that the CYP1A2*1K haplotype is either nil or only shows a very low frequency in Japanese.

Background: It has been reported that recording electrocardiograms (ECGs) in the 3rd intercostal space (ICS) is one method that can be used for detecting Brugada syndrome; however, the prevalence of Brugada-type ECGs recorded in the 3rd ICS and the usefulness of recording the ECG in the 3rd ICS in accordance with recently established electrocardiographic criteria is unknown., Methods and Results: ECGs were recorded in both the 4th and 3rd ICS in 17 Brugada-type ECG patients (group A) and in 206 consecutive male subjects (group B). Brugada-type ECGs were divided into 3 types. In group A, the prevalence of type 1 ECG, which is a coved-type ECG with ST-segment elevation of >/=2 mm, increased from 23.5% to 64.7% when ECG was recorded in the 3rd ICS. The conversion to type 1 ECG was found to be related to induction of ventricular arrhythmia. In group B, the prevalence of Brugada-type ECG increased from 1.5% to 5.8% when the ECG was recorded in the 3rd ICS., Conclusions: Recording the ECG in the 3rd ICS is useful for identifying high-risk patients with Brugada-type ECG and for detecting concealed Brugada-type ECG.

Questionnaires were sent to 46 hospitals of all over Japan in order to obtain the clinical data on sarcoidosis patients who were treated with oral corticosteroids. The number of female patients was greater than that of male patients (1.5:1), and the average age was 44.9 +/- 16.5 with peaks at 20 and at 50 to 60. The markers of disease activity were high in serum or bronchoalveolar lavage fluids (BALF): specifically, the serum angiotensin-converting enzyme (sACE) was 27.9 +/- 31.9 IU/ml (n.v. < 21.4), and the CD4/CD8 lymphocyte ratio was 6.5 +/- 5.7. Eye involvement was the most common reason for systemic steroid therapy, followed in order by lung and heart involvement. The main reasons for steroid therapy were the exacerbation of ocular symptoms, visual disturbance, respiratory symptoms, such as cough or exertional dyspnea, progression of chest radiographic findings, heart failure and severe arrhythmia, such as AV block. The initial corticosteroid dose was usually 30 mg of predinisolone per day, but for some refractory cases, a 40-60 mg per day was used. Immunosuppressive drugs, such as methotrexate, were also used in the small number of patients who responded poorly to the steroid. Overall, a good clinical response to the drug was found in 70-80% of the steroid treated patients, but in those with cardiac disease, the response rate was only 48%.

A new method for the detection and quantification of ethephon residues in fruit and vegetables was developed. The present study indicates that fruit and vegetables require a rapid and simple cleanup step before using gas chromatograph/mass spectrometry. The recovery and precision of the new method were evaluated by spiking the fruit and vegetable samples with 0.01-0.1 microg/g of ethephon. The amount of ethephon residue can be determined with good accuracy (recovery, 78.6-109%; coefficient variation, 2.65-6.41%), and the detection limit, defined as the amount of ethephon equivalent to three standard deviations (SD) of the noise level in observations at the baseline level of the selected ion (m/z 110), was 4 pg. The determination limit, defined as the equivalent to 8 SD of the noise level, was 11 pg. The working range was between 10 and 1000 ng/mL, and the correlation coefficient was 0.999 in the five experiments. Ethephon residues were determined between <2 and 97 ng/g in commercial pineapples from Western Japan.

Background: Testicular cancer is one of those cancers for which the prognosis has improved remarkably since the introduction of effective chemotherapy., Methods: Study subjects were 709 testicular cancer patients who were registered to the population-based Osaka Cancer Registry (OCR) as diagnosed between 1975 and 1992. The testicular cancer patients diagnosed/treated in the Osaka Medical Center for Cancer and Cardiovascular Diseases (OMCC) were also analyzed for comparison., Results: The 5-year relative survival was 75.2% for the total of 709 patients and 77.9% for those diagnosed during 1990-92. These figures were much lower than those for patients in the USA and in Europe. In contrast, the 5-year survival of the 113 patients diagnosed in the OMCC during 1975-93 was 91.5% and similar to those in the USA and in Europe., Conclusions: The present study suggests that there are problems in the speed and extent of diffusion of effective chemotherapy for testicular cancer in Osaka.

Vitamin B(12) concentrations of dried green (Enteromorpha sp.) and purple (Porphyra sp.) lavers (nori) were determined by both Lactobacillus leichmannii ATCC 7830 microbiological and intrinsic factor chemiluminescence methods. The values determined by using the microbiological method (63.58 +/- 2.90 and 32.26 +/- 1.61 microg/100 g of dry weight) were identical to those found by using the chemiluminescence method (69.20 +/- 2.21 and 25.07 +/- 0.54 microg/100 g of dry weight) in both dried green and purple lavers, respectively. A silica gel 60 thin-layer chromatography of both laver extracts shows that non-coenzyme forms (hydroxo and cyano forms) of vitamin B(12) predominate in both dried lavers. The dried lavers contained lesser amounts of dietary iodine ( approximately 4-6 mg/100 g of dry weight) relative to other seaweeds, suggesting that excessive intake of the dried lavers is unlikely to result in harmful intake of dietary iodine. These results indicate that the dried lavers (nori) are the most excellent source of vitamin B(12) among edible seaweeds, especially for strict vegetarians.

We isolated several species of bacteria from the surface water of a Japanese lake. Of the isolated bacteria, Pseudomonas aeruginosa was the only species which could degrade microcystin LR in vitro. Microcystin LR decreased to 4.5% of the spiked microcystin LR quantity in the P. aeruginosa culture, and was metabolized to (2S, 3S, 8S)-3-amino-2, 6, 8-trimethyl-10-phenyldeca-4E, 6E-dienoic acid (DmADDA). It was possible that P. aeruginosa hydrolysed nucleophilically the peptide bond of microcystin LR. We examined if pyochelin, pyocyanin and alkaline protease produced by P. aeruginosa affected the reduction of microcystin LR. In the result, DmADDA was produced from microcystin LR in the presence of 100 microM H2O2 and 100 microM each of pyochelin, pyocyanin or both. However, the production of DmADDA was slight (2 to 12 mole%). After treatment with P. aeruginosa alkaline protease, DmADDA was produced 75 mole% from microcystin LR. Therefore, we concluded that microcystin was degraded mainly by the action of P. aeruginosa alkaline protease.

A total of 108 samples of pickles, which were produced in districts with high and low incidences of stomach cancer in Japan, were extracted with methanol-chloroform. The extracts were bioassayed with Salmonella tester strains. The pickles produced in the high-cancer-incidence district were more mutagenic than those produced in the low-incidence district. The most mutagenic sample among 24 pickle specimens collected in the high-incidence district induced 130 revertants/mg of the crude extract for strain TA98. The mutagenic compounds were purified, and 2 flavonols, quercetin and rhamnetin, were identified as the major mutagens in the pickles by gas chromatography-mass spectrometry. The quantities of the 2 compounds were determined as 6.60 mg for quercetin, and 1.96 mg for rhamnetin per gram of the crude extract. The mutagenic activities of the pickles produced in the 2 districts were closely related to the amounts of quercetin in them.