Gunma, Japan
Gunma, Japan

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Sato K.,Gunma University | Hosonuma K.,Toho hospital | Yamazaki Y.,Gunma University | Kobayashi T.,Gunma University | And 7 more authors.
Tohoku Journal of Experimental Medicine | Year: 2017

Hepatitis C virus (HCV) infection is common in dialysis patients worldwide and nosocomial HCV spread within dialysis facilities continues to develop. Combination therapy with daclatasvir and asunaprevir (DCV/ ASV) that has proven efficacy for dialysis patients infected with genotype 1b HCV (HCV/1b) has several concerns in Japan. The recently available combination therapy with ombitasvir, paritaprevir, and ritonavir (OBV/PTV/r) is not contraindicated in patients with chronic renal failure and has more safety profile and shorter treatment period than that with DCV/ASV. We evaluated the effects of combination therapy with OBV/PTV/r in four dialysis patients infected with HCV/1b, who were eligible for our study. On-treatment assessments included standard laboratory testing, serum HCV RNA and symptom-directed physical examinations. Three patients had a sustained virological response at 12 weeks after treatment, but one remaining patient had viral breakthrough. Notably, the patient with viral breakthrough had been coinfected with HCV/1b and HCV/2b; namely, HCV/2b with resistance-associated variations was not eradicated by the combination therapy. Among the three patients responsive to the combination therapy, one patient complained of appetite loss and itching, while in another patient the therapy was discontinued due to itching, exacerbation of wamble, and a falling tendency probably due to interaction with valsartan. These AEs were ameliorated or disappeared after the completion of the therapy. The significance of our study is persuasive virological evaluation associated to the combination therapy and reasonable interpretation of AEs. In conclusion, combination therapy with OBV/PTV/r may have promise as an efficacious therapy, but caution regarding AEs should be practiced. © 2017 Tohoku University Medical Press.


Kojima M.,Dokkyo Medical University | Nakamura N.,Tokai University | Tsukamoto N.,Gunma University | Yokohama A.,Gunma University | And 5 more authors.
Lupus | Year: 2011

We present here seven cases of idiopathic multicentric Castleman's disease (MCD) showing effusion at the initial clinical presentation. This series includes a high proportion of middle-aged and elderly females (5/7). Various autoantibodies were detected in six cases. Anemia (Hb < 10 g/dl) was detected in four cases, leukocytosis (WBC > 10 × 109/l) in three and thrombycytopenia (<100 × 109/l) in five. Positivity for C-reactive protein or elevated erythrocyte sedimentation rate was recorded in all seven cases. Elevated serum IgG level (>2000 mg/dl) was recorded in only three cases. Elevated serum interleukin-6 level was recorded in all four cases examined. At the onset of disease, four cases were associated with idiopathic thrombocytic purpura. During the course of disease, one case each was diagnosed as systemic sclerosis + Sjögren's syndrome (SJS) and SJS. Histologically, five lesions exhibited a mixed type of Castleman's disease, and one case each exhibited a hyaline-vascular type and plasma cell type. The non-neoplastic nature of the B-lymphocytes was demonstrated by immunohistochemistry and polymerase chain reaction. There were no human herpes type-8 virus-positive cells in any of the seven lesions. Good responsiveness to glucocorticoid therapy has been seen in all six cases treated. From a therapeutic perspective, it is important to discriminate this subtype of MCD. Lupus (2011) 20, 44-50. © The Author(s), 2011.


Shimizu H.,International University of Health and Welfare | Akiyama H.,Toho Hospital | Kakishita H.,Motojima General Hospital | Uehara K.,Uehara Clinic of Internal Medicine | And 3 more authors.
Therapeutic Research | Year: 2014

GLP-1 analogue, liraglutide, improves glycemic control by stimulating endogenous insulin secretion in a glucose-dependent manner, and inhibiting excessive caloric intake in type 2 diabetic(T2DM) patients. We retrospectively evaluated efficacy of liraglutide associated with body mass index (BMI) in Japanese T2DM patients treated with liraglutide over 12 weeks. The average of total daily dose of insulin was 11.8±5.4U/day before switching to liraglutide. The average regimen of insulin injection was 2.4±1.2 times/day. Liraglutide in the patients with no previous treatment or treated with oral hypoglycemic agents showed greater efficacy on glycemic control estimated by HbAlc(NGSP)than that in patients switching from insulin, but not on body weight reduction. BMI did not affect efficacy of liraglutide on body weight reduction and glycemic control in the patients with no previous treatment or treated with oral hypoglycemic agents. In contrast, body weight reduction by liraglutide was significantly higher in the obese patients (30kg/m2 ^ BMI) switching from insulin than the patients with normal BMI. We demonstrated efficacy of liraglutide on glycemic control and body weight reduction and the association with BMI in Japanese T2DM patients.


Tshilela K.A.,Gunma University | Ikeuchi H.,Gunma University | Matsumoto T.,Toho Hospital | Kuroiwa T.,Gunma Rheumatism Clinic | And 6 more authors.
Clinical and Experimental Nephrology | Year: 2016

Background: Aberrant expression of T helper cell (Th) cytokines is believed to play a central role in the pathogenesis of systemic lupus erythematosus (SLE). While the glomerulus is one of the major targets of lupus inflammation, little is known about the cytokine expression in glomeruli. The current study aimed to explore the profiles of Th cytokine gene expressions in isolated glomeruli of lupus-prone mice. Methods: Glomeruli were purified from lupus-prone MRL/lpr mice using the magnetic microbead method. Expressions of cytokine genes representing the Th subset and FoxP3 were examined using real-time polymerase chain reaction. Serum levels of these cytokines were also measured by enzyme-linked immunosorbent assay. MRL/n mice were used as controls. Histologic glomerular damages were scored semiquantitatively. To examine the role of TNF-α in glomerular damage, we administered etanercept, a TNF-α antagonist, into the subjects. Results: Glomerular gene expressions of TNF-α in lpr mice increased with week postpartum and reached statistically significant levels at 16 weeks compared with those of the glomeruli from control mice. Expressions of IFN-γ, IL-4 and FoxP3 also increased, but the difference was not significant. There was a significant increase in serum levels of TNF-α, IFN-γ, and IL-17 and decrease in those of IL-4. Among the genes examined, TNF-α significantly correlated with glomerular damage score. Administration of etanercept did not affect glomerular cytokine expressions or proteinuria and failed to ameliorate histologic glomerular damages. Conclusion: Our data suggest that Th1 cytokines, especially TNF-α, are dominantly expressed in the glomeruli of lupus-prone mice, but its pathophysiological role remains unclear. © 2015, Japanese Society of Nephrology.


Hosonuma K.,Toho Hospital | Sato K.,Gunma University | Yamazaki Y.,Gunma University | Yanagisawa M.,Heisei hidaka Clinic | And 5 more authors.
American Journal of Gastroenterology | Year: 2015

OBJECTIVES:The aim of this study was to assess the long-term prognosis, efficacy, and safety of combination therapy using ursodeoxycholic acid (UDCA) and bezafibrate (BF) for primary biliary cirrhosis (PBC) patients exhibiting dyslipidemia.METHODS:We performed a prospective, randomized, controlled, multicenter study to compare the long-term clinical results between combination therapy and UDCA monotherapy for patients refractory to UDCA monotherapy. Twenty-seven consecutive PBC patients were enrolled.RESULTS:The median treatment period in the UDCA and UDCA+BF groups was 107 and 110 months, respectively. The serum alkaline phosphatase (ALP) levels and the Mayo risk score in the combination therapy group (mean 290 IU/l and 0.91, respectively) were significantly lower than those in the UDCA monotherapy group (mean 461 IU/l and 1.42, respectively) at 8 years after the beginning of the study (P<0.05). The serum creatinine levels in the combination therapy group (mean 0.94 mg/dl) were significantly higher than those in the UDCA monotherapy group (mean 0.56 mg/dl) at 8 years after the beginning of the study (P<0.05). However, the survival rate was not significantly different between the groups. We observed dose reduction or discontinuation of the administration of BF, but not UDCA, due to renal dysfunction or muscle pain.CONCLUSIONS:Long-term combination therapy significantly improved the serum ALP levels and the Mayo risk score. However, the survival rate was not significantly different between the groups. In addition, long-term combination therapy significantly increased the serum creatinine levels. We should pay close attention to adverse events during this long-term combination therapy. © 2015 by the American College of Gastroenterology.


Hamatani H.,Toho Hospital | Hiromura K.,Gunma University | Kobatake K.,Toho Hospital | Yoshida H.,Toho Hospital | And 7 more authors.
Clinical and Experimental Nephrology | Year: 2010

We report two patients, a daughter and a mother, with lipoprotein glomerulopathy (LPG) who were successfully treated with niceritrol. Both patients carried a mutation in the apolipoprotein E (apoE) gene known as ApoE Tokyo/Maebashi. The daughter was found to have proteinuria at the age of 4 years. Four years later, she was diagnosed as having LPG based on a renal biopsy. She was treated with several medications including pravastatin, ethyl icosapentate, enalapril, warfarin and cyclophosphamide, all of which failed to reduce her proteinuria. At the age of 17 years, she exhibited an increase in proteinuria and a decline in renal function, despite ongoing treatment with pravastatin and enalapril. After switching from pravastatin to niceritrol, a marked reduction in the proteinuria and an improvement in renal function were observed. Her mother was found to have proteinuria at the age of 57 years and was diagnosed as having LPG based on a renal biopsy. She was also treated with niceritrol, resulting in an improvement in her proteinuria and renal function. These cases suggest that niceritrol might be a useful therapeutic option for LPG. © 2010 Japanese Society of Nephrology.


PubMed | Heisei Hidaka Clinic, Toho Hospital and Gunma University
Type: Comparative Study | Journal: The American journal of gastroenterology | Year: 2015

The aim of this study was to assess the long-term prognosis, efficacy, and safety of combination therapy using ursodeoxycholic acid (UDCA) and bezafibrate (BF) for primary biliary cirrhosis (PBC) patients exhibiting dyslipidemia.We performed a prospective, randomized, controlled, multicenter study to compare the long-term clinical results between combination therapy and UDCA monotherapy for patients refractory to UDCA monotherapy. Twenty-seven consecutive PBC patients were enrolled.The median treatment period in the UDCA and UDCA+BF groups was 107 and 110 months, respectively. The serum alkaline phosphatase (ALP) levels and the Mayo risk score in the combination therapy group (mean 290IU/l and 0.91, respectively) were significantly lower than those in the UDCA monotherapy group (mean 461IU/l and 1.42, respectively) at 8 years after the beginning of the study (P<0.05). The serum creatinine levels in the combination therapy group (mean 0.94mg/dl) were significantly higher than those in the UDCA monotherapy group (mean 0.56mg/dl) at 8 years after the beginning of the study (P<0.05). However, the survival rate was not significantly different between the groups. We observed dose reduction or discontinuation of the administration of BF, but not UDCA, due to renal dysfunction or muscle pain.Long-term combination therapy significantly improved the serum ALP levels and the Mayo risk score. However, the survival rate was not significantly different between the groups. In addition, long-term combination therapy significantly increased the serum creatinine levels. We should pay close attention to adverse events during this long-term combination therapy.


PubMed | Toho Hospital and Gunma University
Type: Journal Article | Journal: Breast cancer (Tokyo, Japan) | Year: 2016

The members of AID/APOBEC protein family possess cytidine deaminase activity that converts cytidine residue to uridine on DNA and RNA. Recent studies have shown the possible influence of APOBEC3B (A3B) as DNA mutators of breast cancer genome. However, the clinical significance of A3B expression in Japanese breast cancer has not been studied in detail.Ninety-three primary breast cancer tissues (74 estrogen-receptor (ER) positive, 3 ER and HER2 positive, 6 HER2 positive, and 10 triple negative) including 37 tumor-normal pairs were assessed for A3B mRNA expression using quantitative real-time RT-PCR. We analyzed the relation between A3B expression, mutation analysis of TP53 and PIK3CA by direct sequencing, polymorphic A3B deletion allele and human papillomavirus (HPV) infection in tumors.A3B mRNA was overexpressed in tumors compared with normal tissue. Patients with high A3B expression were associated with subtype and progression of lymph node metastasis and pathological nuclear grade. However, the expression was not related to any other clinicopathological factors, including mutation of TP53 and PIK3CA, polymorphic A3B deletion allele, HPV infection and survival time.The expression of A3B in breast cancer was higher than in non-cancerous tissues and was related to the lymph node metastasis and nuclear grade, which are reliable aggressive phenotype markers in breast cancer. Evaluation of A3B expression in tumor may be a marker for breast cancer with malignant potential.


Matsumura M.,Toho Hospital | Sasaki H.,Toho Hospital | Sekizuka K.,Toho Hospital | Sano H.,Toho Hospital | And 7 more authors.
International Journal of Artificial Organs | Year: 2010

Background: Intradialytic hypotension (IDH) is a common clinical trait in hemodialysis (HD) which is caused by poor biocompatibility of the dialyzer membrane. Aiming to improve IDH, vitamin E-bonded polysulfone dialyzer (VPS-H) was evaluated in a pilot study. Methods: Eight IDH patients on standard HD were switched from their conventional high-flux dialyzers to VPS-H, and intradialytic blood pressure (BP) was monitored regularly for 10 months. Results: The results showed that hypotension of systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) during the session were improved after changing the dialyzer. Notably, almost all the values recorded from 120 minutes into the session until the end of the treatment in the period between the second and tenth month after treatment were significantly different from the corresponding baseline values. Moreover, after 8 to 10 months, the SBP prior to a dialysis session was significantly reduced compared with baseline values. On the other hand, the pulse rate showed no difference throughout the study period. Conclusions: This study provides early evidence of the beneficial role that vitamin E-bonded dialyzers may have in preventing IDH. Larger controlled trials are needed to confirm this original finding. © 2010 Wichtig Editore.


PubMed | Toho Hospital
Type: Journal Article | Journal: The International journal of artificial organs | Year: 2010

Intradialytic hypotension (IDH) is a common clinical trait in hemodialysis (HD) which is caused by poor biocompatibility of the dialyzer membrane. Aiming to improve IDH, vitamin E-bonded polysulfone dialyzer (VPS-H) was evaluated in a pilot study.Eight IDH patients on standard HD were switched from their conventional high-flux dialyzers to VPS-H, and intradialytic blood pressure (BP) was monitored regularly for 10 months.The results showed that hypotension of systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) during the session were improved after changing the dialyzer. Notably, almost all the values recorded from 120 minutes into the session until the end of the treatment in the period between the second and tenth month after treatment were significantly different from the corresponding baseline values. Moreover, after 8 to 10 months, the SBP prior to a dialysis session was significantly reduced compared with baseline values. On the other hand, the pulse rate showed no difference throughout the study period.This study provides early evidence of the beneficial role that vitamin E-bonded dialyzers may have in preventing IDH. Larger controlled trials are needed to confirm this original finding.

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