Iida A.,RIKEN |
Hosono N.,RIKEN |
Sano M.,Chibanishi General Hospital |
Kamei T.,Chigasaki Tokushukai General Hospital |
And 6 more authors.
Neurobiology of Aging | Year: 2012
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by selective motor neuron death in the brain and spinal cord. Many disease genes for ALS have been identified; however, each disease gene is responsible for very small fractions of ALS. Recently, mutations of the gene encoding optineurin (. OPTN) are reported in familial and sporadic ALS. . OPTN is also responsible for a small number of ALS, 3.8% of familial and 0.29% of sporadic ALS in Japanese. The low prevalence may be an underestimation due to incomplete screening of the mutation. To examine . OPTN mutations more extensively, we screened the . OPTN deletions using a quantitative PCR system. We examined 710 Japanese ALS subjects who had previously been found to have no . OPTN mutations by a screening using a PCR-direct sequence strategy. We identified 3 kinds of deletions in 5 patients; one was homozygous, and the remaining were heterozygous. All deletions occurred due to the Alu-mediated recombination and are expected to result in null alleles. Our results suggest that the . OPTN deletion mutation in ALS is not infrequent and the prevalence of the . OPTN mutation in Japanese sporadic ALS is considerably high. © 2012 Elsevier Inc..
Iida A.,RIKEN |
Kamei T.,Chigasaki Tokushukai General Hospital |
Sano M.,Chibanishi General Hospital |
Oshima S.,Chiba Tokushukai Hospital |
And 4 more authors.
Neurobiology of Aging | Year: 2012
Mutations in TARDBP encoding TDP (TAR DNA binding protein)-43 have been reported in familial and sporadic amyotrophic lateral sclerosis (ALS), but mostly in Caucasians. In other ethnic groups, four types of mutations are found in familial ALS. In sporadic ALS, the TARDBP mutations frequency is low in Caucasians (0-5%) and no mutation has been found in other ethnic groups. To examine spectrum of TARDBP mutations and its frequency in Japanese, we screened the TARDBP mutation in 721 Japanese ALS by direct sequencing. We identified a novel mutation, c.1069G > A (p.Gly357Ser) and a known mutation in sporadic ALS. One patient was homozygous for p.Gly357Ser, which was the first for TARDBP mutation. Our study showed that TARDBP mutations also occur in non-Caucasian sporadic ALS. The estimated frequency of the TARDBP mutation in sporadic ALS is 0.29% in Japanese. The mutation frequency in familial ALS in Japanese is also similar to that in Caucasian, and is ~10 times higher than that in Japanese sporadic ALS. © 2012 Elsevier Inc.
PubMed | Red Cross, Fukuoka University, Lin Kou Chang Gung Memorial Hospital, Yokohama City University and 41 more.
Type: Journal Article | Journal: Journal of hepato-biliary-pancreatic sciences | Year: 2016
Serious complications continue to occur in laparoscopic cholecystectomy (LC). The commonly used indicators of surgical difficulty such as the duration of surgery are insufficient because they are surgeon and institution dependent. We aimed to identify appropriate indicators of surgical difficulty during LC.A total of 26 Japanese expert LC surgeons discussed using the nominal group technique (NGT) to generate a list of intraoperative findings that contribute to surgical difficulty. Thereafter, a survey was circulated to 61 experts in Japan, Korea, and Taiwan. The questionnaire addressed LC experience, surgical strategy, and perceptions of 30 intraoperative findings listed by the NGT.The response rate of the survey was 100%. There was a statistically significant difference among nations regarding the duration of surgery and adoption rate of safety measures and recognition of landmarks. The criteria for conversion to an open or subtotal cholecystectomy were at the discretion of each surgeon. In contrast, perceptions of the impact of 30 intraoperative findings on surgical difficulty (categorized by factors related to inflammation and additional findings of the gallbladder and other intra-abdominal factors) were consistent among surgeons.Intraoperative findings are objective and considered to be appropriate indicators of surgical difficulty during LC.
PubMed | Saiseikai Yokohamashi Tobu Hospital, Hakujikai Memorial Hospital, Chiba Tokushukai Hospital, Jikei University School of Medicine and 5 more.
Type: Journal Article | Journal: Hepatology research : the official journal of the Japan Society of Hepatology | Year: 2016
Protease inhibitors with pegylated interferon (PEG IFN)/ribavirin improve a sustained virological response (SVR) rate to approximately 90% in chronic hepatitis C genotype 1b patients with IL28B rs8099917 genotype TT, but yield only approximately 50% in those with the unfavorable non-TT. Among such treatment-refractory patients, serum vitamin D levels could influence the SVR rate. This randomized controlled trial was conducted to assess the effect of native vitamin D supplementation in simeprevir with PEG IFN/ribavirin for 1b patients with non-TT.Patients were randomly assigned to receive simeprevir (100mg/day) for 12weeks plus PEG IFN/ribavirin for 24weeks (control group, n=58), or vitamin D (2000IU/day) for 16weeks including a lead-in phase plus PEG IFN/ribavirin for 24weeks (vitamin D group, n=57). The primary end-point was sustainably undetectable viremia 24weeks after the end of treatment (SVR).SVR rates were 37.9% in the control group and 70.2% in the vitamin D group. In subgroup analysis, SVR rates of prior null responders were 11.8% and 54.5%, respectively. SVR rates for advanced fibrosis were 28.6% and 65.4%. SVR rates for patients with vitamin D3 deficiency at the baseline were 25.0% in the control group and 66.7% in the vitamin D group. Overall, the SVR rate was significantly higher in patients with high serum 25(OH)D3 levels at the beginning of combination therapy than in those with low serum 25(OH)D3 levels.Native vitamin D3 supplementation improved SVR rates in simeprevir with PEG IFN/ribavirin for chronic hepatitis C genotype 1b patients with refractory factors.
PubMed | Saiseikai Yokohamashi Tobu Hospital, Chiba Tokushukai Hospital, Jikei University School of Medicine, Tokyo Metropolitan Bokutoh Hospital and 5 more.
Type: | Journal: BMC infectious diseases | Year: 2015
Serum 25-hydroxyvitamin D3 levels are generally lower in chronic hepatitis C patients than in healthy individuals. The purpose of this study is to clarify the factors which affect serum 25-hydroxyvitamin D3 levels using data obtained from Japanese chronic hepatitis C patients.The subjects were 619 chronic hepatitis C patients. Serum 25-hydroxyvitamin D3 levels were measured by using double-antibody radioimmunoassay between April 2009 and August 2014. Serum 25-hydroxyvitamin D3 levels of 20 ng/mL or less were classified as vitamin D deficiency, and those with serum 25-hydroxyvitamin D3 levels of 30 ng/mL or more as vitamin D sufficiency. The relationship between patient-related factors and serum 25-hydroxyvitamin D3 levels was analyzed.The cohort consisted of 305 females and 314 males, aged between 18 and 89 years (median, 63 years). The median serum 25-hydroxyvitamin D3 level was 21 ng/mL (range, 6-61 ng/mL). On the other hand, the median serum 25-hydroxyvitamin D3 level in the healthy subjects was 25 ng/mL (range, 7-52), being significantly higher than that those in 80 chronic hepatitis C patients matched for age, gender, and season (p = 1.16 10(-8)). In multivariate analysis, independent contributors to serum 25-hydroxyvitamin D3 deficiency were as follows: female gender (p = 2.03 10(-4), odds ratio = 2.290, 95 % confidence interval = 1.479-3.545), older age (p = 4.30 10(-4), odds ratio = 1.038, 95 % confidence interval = 1.017-1.060), cold season (p = 0.015, odds ratio = 1.586, 95 % confidence interval = 1.095-2.297), and low hemoglobin level (p = 0.037, odds ratio = 1.165, 95 % confidence interval = 1.009-1.345). By contrast, independent contributors to serum 25-hydroxyvitamin D3 sufficiency were male gender (p = 0.001, odds ratio = 3.400, 95 % confidence interval = 1.635-7.069), warm season (p = 0.014, odds ratio = 1.765, 95 % confidence interval = 1.117-2.789) and serum albumin (p = 0.016, OR = 2.247, 95 % CI = 1.163-4.342).Serum 25-hydroxyvitamin D3 levels in chronic hepatitis C Japanese patients were influenced by gender, age, hemoglobin level, albumin and the season of measurement.
Nakada T.,Kuriyama Central Hospital |
Nakada H.,Doai Kinen Hospital |
Yoshida Y.,Chiba Tokushukai Hospital |
Nakashima Y.,Kuriyama Central Hospital |
And 3 more authors.
Urologia Internationalis | Year: 2012
Objective: To assess the safety and efficacy of hyperbaric oxygen (HBO) for treating radiation cystitis a long-term follow-up study was done in patients with prostate cancer, the second most common malignancy in Japan. Patients and Methods: A total of 38 patients at an age of 68 ± 8 years with radiation cystitis following irradiation of prostate cancer were treated with HBO at 2 absolute atmospheric pressures for 90 min daily. The average number of HBO treatment sessions in each patient was 62 ± 12. The follow-up period was 11.6 ± 3.7 years. We evaluated objective and subjective symptoms periodically with special reference to the initiation timing of HBO therapy. Results: High efficacy ratios of objective and subjective findings were obtained at 2 and 4 (79-95%) years, respectively. After 7 years' follow-up, these ratios decreased slightly (72-83%) but still remained stable thereafter (75-88%) without any serious accident. Comparison of late morbidity scores before and 11.6 years after HBO therapy showed significant improvement (p < 0.0005). Twenty-eight patients (74%) obtained nonrecurrent outcome. They had received 18% lower (p < 0.001) radiation dosage than recurrent patients. The interval between the onset of hematuria and start of HBO treatment in nonrecurrent patients was 30% shorter (p < 0.001) than that of recurrent patients. Conclusions: We elucidated the long-term safety and beneficial effect of HBO therapy of radiation cystitis in patients with prostate cancer. Early application of HBO treatment after the onset of hematuria appears to produce favorable outcome. Copyright © 2012 S. Karger AG, Basel.
Asahara S.,Chiba Tokushukai Hospital |
Takeda K.,Juntendo University |
Yamao K.,Aichi Cancer Center Hospital |
Maguchi H.,Teine Keijinkai Hospital |
Yamaue H.,Wakayama Medical University
Journal of Translational Medicine | Year: 2013
Background: We previously developed an immunotherapy treatment utilizing a cancer vaccine reagent KIF20A-66 in order to treat pancreatic cancer. KIF20A-66 is HLA-A24-restricted epitope peptide derived from KIF20A, a member of kinesin super family protein 20A that is significantly transactivated in pancreatic cancer. In this report, we further demonstrated non-randomized, open-label, single centered phase I/II clinical trial of immunotherapy using the KIF20A-66 peptide for the patients with advanced pancreatic cancer.Methods: Vaccination was performed to the patients with metastatic pancreatic cancer, in whom gemcitabine-based therapy had failed. In phase I study, KIF20A-66 peptide was subcutaneously injected weekly in a dose-escalation manner (doses of 1.0 and 3.0 mg/body, 6 patients/1 cohort). After safety was assessed, phase II study was conducted using 3.0 mg of KIF20A-66 peptide.Results: KIF20A-66 peptide vaccination was well tolerated in the doses we examined and tumor responses after 1 month of the treatment were evaluated. Among 29 patients who completed one course of the treatment at least, stable disease (SD) was found in 21 cases, while progressive disease (PD) was found in 8 cases, indicating that the disease control rate was 72%. Objective tumor shrinkage was observed in 8 cases, including 1 case of complete response (CR). The median survival time (MST) and progression free survival time (PFS) were 142 days and 56 days, respectively. These results clearly demonstrate that overall survival of the patients was significantly prolonged, compared to the historical controls of 9 cases with unmatched HLA in the same hospital (MST: 83 days), as well as 81 cases in our and other hospitals (MST: 63 days).Conclusion: The patients vaccinated with KIF20A-66 peptide had better prognosis than the control group with best supportive care (BSC). Thus, we concluded that KIF20A-66 vaccination is significantly effective as an immunotherapy against advanced pancreatic cancer. KIF20A-66 peptide was well tolerable in the dose of either 1.0 mg or 3.0 mg/body, and effectively induced peptide-specific response of cytotoxic T lymphocyte (CTL). Further clinical study using this peptide is a promising approach for advanced pancreatic cancer to achieve high potential benefit for better prognosis.Clinical trial registration: UMIN-CTR, number UMIN000004919. © 2013 Asahara et al.; licensee BioMed Central Ltd.
Shirobe T.,Chiba Tokushukai Hospital |
Maruyama S.,Tamakyuryo Hospital
Surgical Endoscopy and Other Interventional Techniques | Year: 2015
Background: Laparoscopic surgery has been widely employed in the field of digestive surgery, since the minimally invasive procedure provides a significant benefit to patients. However, laparoscopic curative surgery for gallbladder cancer has been rarely described. The aim of this study was to evaluate the effectiveness and validity of laparoscopic radical cholecystectomy with lymph node dissection (Lap-RC) to treat with T1b/T2 gallbladder carcinoma. Methods: A total of 11 patients underwent Lap-RC for gallbladder carcinoma from November 2001 until June 2013. While 4 patients were preoperatively diagnosed with T1b/T2 gallbladder carcinoma, 7 patients were diagnosed with incidental T1b/T2 gallbladder carcinoma by postoperative pathological examination after laparoscopic cholecystectomy. Common bile duct resection and biliary tract reconstruction were performed in 2 cases. End points in this clinical study were tumor recurrence and survival of patients. Results: Mean operative time was 196 min, and average hospital stay after surgery was 6.4 days, excluding 2 cases with biliary tract reconstruction. One patient died of recurrence of cancer 89 months after surgery, and another patient died of other reason with local recurrence 39 months after the operation. The other 9 patients were all alive without recurrence at this writing. The 5-year survival rate was 100 % for T1b patients and 83.3 % for T2. These results indicate that almost equivalent outcomes compared with open surgery in terms of curability were achieved. Conclusions: We conclude that pure laparoscopic radical cholecystectomy with lymph node dissection is safe and beneficial for the patients with T1b/T2 gallbladder carcinoma. © 2014, Springer Science+Business Media New York.