研究者詳細 - 森田　伸也

論文 - 森田　伸也

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Successful low-dose leflunomide treatment for ganciclovir-resistant cytomegalovirus infection with high-level antigenemia in a kidney transplant: A case report and literature review

Morita, S., Shinoda, K., Tamaki, S., Kono, H., Asanuma, H., Nakagawa, K. and Oya, M.

J Clin Virol 82 133 - 138 2016年09月

ISSN 1873-5967

Ganciclovir-resistant cytomegalovirus infection is sometimes life-threatening for organ transplant recipients. Foscarnet is an alternative, although it may potentially worsen the preexistent impaired renal function. Here we report the case of a successful low-dose leflunomide treatment in a kidney transplant recipient with very high viral replication, who underwent kidney transplantation 10 years before. Administering 10mg leflunomide daily for 5 months without a loading dose completely cleared the ganciclovir-resistant cytomegalovirus strains.

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A Case of Gemcitabine and Cisplatin Chemotherapy in a Patient With Metastatic Urothelial Carcinoma Receiving Hemodialysis

Ezaki, T., Matsumoto, K., Morita, S., Shinoda, K., Mizuno, R., Kikuchi, E. and Oya, M.

Clin Genitourin Cancer 14 （ 4 ） e413 - 6 2016年08月

ISSN 1938-0682

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Human Adrenocortical Remodeling Leading to Aldosterone-Producing Cell Cluster Generation

Nishimoto, K., Seki, T., Hayashi, Y., Mikami, S., Al-Eyd, G., Nakagawa, K., Morita, S., Kosaka, T., Oya, M., Mitani, F., Suematsu, M., Kabe, Y. and Mukai, K.

Int J Endocrinol 2016 7834356 2016年

ISSN 1687-8337

Background. The immunohistochemical detection of aldosterone synthase (CYP11B2) and steroid 11beta-hydroxylase (CYP11B1) has enabled the identification of aldosterone-producing cell clusters (APCCs) in the subcapsular portion of the human adult adrenal cortex. We hypothesized that adrenals have layered zonation in early postnatal stages and are remodeled to possess APCCs over time. Purposes. To investigate changes in human adrenocortical zonation with age. Methods. We retrospectively analyzed adrenal tissues prepared from 33 autopsied patients aged between 0 and 50 years. They were immunostained for CYP11B2 and CYP11B1. The percentage of APCC areas over the whole adrenal area (AA/WAA, %) and the number of APCCs (NOA, APCCs/mm(2)) were calculated by four examiners. Average values were used in statistical analyses. Results. Adrenals under 11 years old had layered zona glomerulosa (ZG) and zona fasciculata (ZF) without apparent APCCs. Some adrenals had an unstained (CYP11B2/CYP11B1-negative) layer between ZG and ZF, resembling the rat undifferentiated cell zone. Average AA/WAA and NOA correlated with age, suggesting that APCC development is associated with aging. Possible APCC-to-APA transitional lesions were incidentally identified in two adult adrenals. Conclusions. The adrenal cortex with layered zonation remodels to possess APCCs over time. APCC generation may be associated with hypertension in adults.

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[Clinical Background Analysis About Transurethral Electrocoagulation]

Katsui, M., Kikuchi, E., Yazawa, S., Hagiwara, M., Morita, S., Shinoda, K., Kosaka, T., Mizuno, R., Shinojima, T., Asanuma, H., Miyajima, A. and Oya, M.

Nihon Hinyokika Gakkai Zasshi 106 （ 4 ） 255 - 63 2015年10月

ISSN 0021-5287

PURPOSE: Transurethral electrocoagulation (TUC) is a rare event but occurs in a constant manner with various causes or disorders and reduces patient quality of life. So far there have been no reports focusing on the details of TUC. We focused on the clinical background and related causes in cases of TUC in our institution. PATIENTS AND METHODS: We identified 76 cases (65 patients) who underwent TUC at Keio University Hospital between April 2001 and March 2011. We focused on patient background, especially with respect to the primary disease, treatment modality, use of antiplatelet or anticoagulant agent, timing of TUC, type of electrosurgical device, and the incidence of transfusion. RESULTS: The primary disease for TUC included bladder tumor (BT) in 31 cases, benign prostate hyperplasia (BPH) in 13, prostate cancer (PCa) in 13, idiopathic bladder bleeding in 4, periarteritis nodosa in 3, uterine cervical cancer in 3, and others in 9. TUC after transurethral resection (TUR) was found in 38 cases, including transurethral resection of bladder tumor (TURBT) in 26 of 31 BT cases and transurethral resection of prostate (TURP) in 12 of 13 BPH cases. After TURBT, TUC was performed before removal of a urethral catheter in 7 cases, and after removal of a urethral catheter in 19 cases. With regard to TUC associated with TURP, the average estimated prostate volume in TUC cases before removal of the urethral catheter was 66.2 ml, which was significantly larger than that in TUC cases after removal of the urethral catheter (46.1 ml, p = 0.045). TUC after the radiation therapy was observed in 21 cases, and the average time from the radiation therapy to TUC was 3.4 years (7 months-10 years). CONCLUSION: TUC was caused by multiple causes or disorders, and 75% of our TUC was associated with BT, BPH or PCa. TUC associated with TURBT frequently occurred within 1 week after TURBT but was still observed after 1 month following the operation. All TUC associated with TURP occurred within 3 weeks after operation. The average period from radiation therapy to TUC was 3.4 years (7 months-10 years) and TUC associated with radiation cystitis could occur beyond 5 years after radiation.

Predictive factors for severe and febrile neutropenia during docetaxel chemotherapy for castration-resistant prostate cancer

Shigeta Keisuke, Kosaka Takeo, Yazawa Satoshi, Yasumizu Yota, Mizuno Ryuichi, Nagata Hirohiko, Shinoda Kazunobu, Morita Shinya, Miyajima Akira, Kikuchi Eiji, Nakagawa Ken, Hasegawa Shintaro, Oya Mototsugu

International Journal of Clinical Oncology 20 （ 3 ） 605 - 612 2015年06月

ISSN 1341-9625

Background: The aim of this study is to identify factors that increase the occurrence of severe neutropenia (SN) and febrile neutropenia (FN) during docetaxel treatment for castration-resistant prostate cancer (CRPC). Methods: We retrospectively reviewed 258 courses during the first three cycles among 95 patients. Docetaxel at a dose of 75 mg/m2 was administered every 3 or 4 weeks. Patient background, laboratory data, and bone scan results were collected to assess predictive factors for SN and FN. We defined SN as an absolute neutrophil count (ANC) of <500/mm3 and defined FN as an ANC of <1000/mm3 with a body temperature of >38.3 °C. Results: The mean age of the patients was 72.6 ± 6.4 years and the mean prostate-specific antigen was 135.4 ± 290.9 ng/ml. During the first three courses of treatment, SN occurred in 72.6 % of patients and FN occurred in 9.5 % of patients. Univariate analysis demonstrated that age ≥75 years (p = 0.002), number of comorbidities ≥1.2 (p = 0.008 and p = 0.006) and previous external beam radiation therapy (EBRT) (p = 0.001) were predictive factors for the development of SN or FN. In multivariate analysis, significant predictors of SN or FN were age ≥75 years (hazard ratio [HR] 5.77; p = 0.004) and previous EBRT (HR 14.5; p = 0.012). According to the subgroup analysis dividing SN and FN separately, multivariate analysis also revealed that age ≥75 years and previous EBRT were also significant predictors for developing SN (HR 5.09; p = 0.023, HR 12.7; p = 0.020, respectively) and for developing FN (HR 5.45; p = 0.042, HR 7.72; p = 0.015, respectively). Conclusions: Patients aged ≥75 years and with a history of localized radiation therapy are at higher risk for significant neutropenic events and require closer surveillance.

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Water-Permeable Dialysis Membranes for Multi-Layered Microdialysis System

To, N., Sanada, I., Ito, H., Prihandana, G. S., Morita, S., Kanno, Y. and Miki, N.

Front Bioeng Biotechnol 3 70 2015年

ISSN 2296-4185

This paper presents the development of water-permeable dialysis membranes that are suitable for an implantable microdialysis system that does not use dialysis fluid. We developed a microdialysis system integrating microfluidic channels and nanoporous filtering membranes made of polyethersulfone (PES), aiming at a fully implantable system that drastically improves the quality of life of patients. Simplicity of the total system is crucial for the implantable dialysis system, where the pumps and storage tanks for the dialysis fluid pose problems. Hence, we focus on hemofiltration, which does not require the dialysis fluid but water-permeable membranes. We investigated the water permeability of the PES membrane with respect to the concentrations of the PES, the additives, and the solvents in the casting solution. Sufficiently, water-permeable membranes were found through in vitro experiments using whole bovine blood. The filtrate was verified to have the concentrations of low-molecular-weight molecules, such as sodium, potassium, urea, and creatinine, while proteins, such as albumin, were successfully blocked by the membrane. We conducted in vivo experiments using rats, where the system was connected to the femoral artery and jugular vein. The filtrate was successfully collected without any leakage of blood inside the system and it did not contain albumin but low-molecular-weight molecules whose concentrations were identical to those of the blood. The rat model with renal failure showed 100% increase of creatinine in 5 h, while rats connected to the system showed only a 7.4% increase, which verified the effectiveness of the proposed microdialysis system.

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[Copper deficiency anemia morphologically mimicking myelodysplastic syndrome]

Kikuchi, T., Mori, T., Shimizu, T., Morita, S., Kono, H., Nakagawa, K., Mitsuhasi, T., Murata, M. and Okamoto, S.

Rinsho Ketsueki 55 （ 3 ） 345 - 9 2014年03月

ISSN 0485-1439

A 64-year-old man underwent kidney transplantation for progressive chronic renal failure which had developed 8 years after allogeneic bone marrow transplantation for acute myeloid leukemia. Because of post-operative complications, he had been placed on intravenous hyperalimentation. Three months after the transplantation, anemia rapidly progressed (hemoglobin, 7.9 g/dl). The proportion of reticulocytes was 0.2%, but white blood cell and platelet counts remained within normal ranges. Serum iron, vitamin B12, and folate levels were normal. Bone marrow examination showed the presence of ringed sideroblasts and cytoplasmic vacuoles in a fraction of erythroid cells. Megakaryocytes were adequate in number with normal morphology. Although the findings were consistent with refractory anemia with ringed sideroblasts according to the WHO classification, cytoplasmic vacuolations were also observed in myeloid cells, suggesting copper deficiency. Indeed, serum copper and ceruloplasmin levels were found to be low (33 mug/dl and 11 mg/dl, respectively), and oral copper supplementation at a daily dose of 1 mg was initiated. There was a prompt increase in reticulocytes, and the hemoglobin level was normalized within one month, in response to this regimen. In progressive anemia cases with ringed sideroblasts in the bone marrow, copper deficiency should be considered in the differential diagnosis.

The implications of prostate-specific antigen density to predict clinically significant prostate cancer in men </= 50 years

Kosaka, T., Mizuno, R., Shinojima, T., Miyajima, A., Kikuchi, E., Tanaka, N., Shinoda, K., Morita, S., Mikami, S. and Oya, M.

Am J Clin Exp Urol 2 （ 4 ） 332 - 6 2014年

ISSN 2330-1910

To investigate the appropriate cut-off level of PSA or other clinical parameters at aged </= 50 years. The rate of detection of PCa in young men will continue to rise associated with the advancement of the current and evolving practices of screening and detection. In this study, we determined whether to investigate the appropriate cut-off level of PSA or other clinical parameters at aged </= 50 years. The study population included 106 patients aged </= 50 years who had prostate biopsy at our institute. The differences of clinical variables including various PSA related parameters between the patients with significant PCa and insignificant PCa were analyzed. Receiver operating characteristics (ROC) curves and the corresponding areas under the ROC curves (AUC) were calculated. There were no significant differences between no-PCa and PCa patients regarding PSA value, prostate volume (P vol), PSA density (PSAD), transition zone volume (TZ vol), PSATZ density (PSATZD). When the patients meeting the following criteria, Gleason score was </= 6 with less than 2 positive biopsy cores, were classified as having insignificant prostate cancer, PSAD could become a useful predictor of significant PCa in men. The AUC was significantly greater in PSAD (0.801) than for the other parameters. The sensitivity and specificity of a PSAD threshold of 0.32 were 85.7% and 77.8%, respectively. In conclusion, PSAD can be a useful and very effective predictor in a man aged </= 50 and we can counsel patients with discretion regarding the likelihood of significant PCa.

Renal arteriolar injury by salt intake contributes to salt memory for the development of hypertension

Oguchi Hideyo, Sasamura Hiroyuki, Shinoda Kazunobu, Morita Shinya, Kono Hidaka, Nakagawa Ken, Ishiguro Kimiko, Hayashi Kaori, Nakamura Mari, Azegami Tatsuhiko, Oya Mototsugu, Itoh Hiroshi

Hypertension 64 （ 4 ） 784 - 791 2014年

ISSN 0194-911X

The role of salt intake in the development of hypertension is prominent, but its mechanism has not been fully elucidated. Our aim was to examine the effect of transient salt intake during the prehypertensive period in hypertensive model animals. Dahl salt-sensitive rats and spontaneously hypertensive rats were fed from 6 to 14 weeks with lowsalt (0.12% NaCl), normal-salt (0.8% NaCl), high-salt (7% NaCl), or high-sodium/normal-chloride diet and returned to normal-salt diet for 3 months. Rats in the high-salt group saw elevations in blood pressure (BP) not only during the treatment period but also for the 3 months after returning to normal-salt diet. We named this phenomenon salt memory. Renal arteriolar injury was found in the high-salt group at the end of experiment. Dahl salt-sensitive rats were fed from 6 to 14 weeks with high-salt diet with angiotensin receptor blocker, vasodilator, calcium channel blocker, and calcium channel blocker+angiotensin receptor blocker and returned to normal-salt diet. Although BP was suppressed to control levels by vasodilator or calcium channel blocker, elevated renal angiotensin II and renal arteriolar injury were observed, and salt memory did not disappear because of sustained renal arteriolar injury. Calcium channel blocker+angiotensin receptor blocker suppressed renal arteriolar injury, resulting in the disappearance of salt memory. Cross-transplantation of kidneys from Dahl salt-sensitive rats on high salt to control rats caused increase of BP, whereas control kidneys caused reduction in BP of hypertensive rats, inducing the central role of the kidney. These results suggest that renal arteriolar injury through BP and renal angiotensin II elevation plays important roles in the development of salt memory for hypertension.

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Editorial Comment to Salvage of grafts with vascular thrombosis during live donor renal allotransplantation

Morita Shinya

International Journal of Urology 21 （ 10 ） 1004 2014年

ISSN 0919-8172

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Effect of a novel nuclear factor-jb activation inhibitor on renal ischemia-reperfusion injury

Kono Hidaka, Nakagawa Ken, Morita Shinya, Shinoda Kazunobu, Mizuno Ryuichi, Kikuchi Eiji, Miyajima Akira, Umezawa Kazuo, Oya Mototsugu

Transplantation 96 （ 10 ） 863 - 870 2013年

ISSN 0041-1337

Background. In kidney transplantation, the relationship between prolonged warm or cold ischemic storage of kidneys and a higher incidence of delayed graft function is previously known, and delayed graft function has been known to aggravate poor long-term graft survival. We investigated the effect of a novel nuclear factor-JB activation inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on renal ischemia-reperfusion (I/R) injury. Methods. DHMEQ was administered to Lewis rats once just before renal artery clamping (DHMEQ pretreatment group), and the effect on I/R injury was investigated. Results. In the DHMEQ pretreatment group, the 24-hr urine volume on days 1 to 3 after I/R was significantly larger, and the protein concentration of the urine on days 2 to 7 was significantly smaller than in the untreated group. The serum creatinine level was significantly improved, and significantly lower levels of the inflammatory cells and inflammatory cytokines were present in the kidneys on day 1. The relative ratio of nuclear to cytoplasmic nuclear factor-JB and oxidative stress of kidney tissue on day 1 were significantly decreased. Conclusions. Treatment with DHMEQ before renal artery clamping may therefore be useful for renal I/R injury and application to renal transplantation is expected. © 2013 by Lippincott Williams & Wilkins.

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Metastatic urothelial carcinoma to pericardia manifested by dyspnea from cardiac tamponade during systemic chemotherapy

Hattori Seiya, Miyajima Akira, Maeda Takahiro, Takeda Toshikazu, Morita Shinya, Kosaka Takeo, Kikuchi Eiji, Oya Mototsugu

Journal of the Canadian Urological Association 6 （ 5 ） 2012年10月

ISSN 1911-6470

A 53-year-old man presented for further evaluation due to microscopic hematuria and left lumbar pain. Computed tomography revealed a large tumour in the left renal pelvis with multiple metastases. Despite effective systemic chemotherapy, he developed dyspnea, and was diagnosed with cardiac tamponade. Pericardial involvement in an advanced malignancy is common, but symptomatic cardiac metastasis from urothelial carcinoma is rare. Of the reports of symptomatic cardiac metastasis from urothelial carcinoma, only 3 cases presented as cardiac tamponade. We report here a rare case of cardiac tamponade caused by a renal pelvic carcinoma with positive cytodiagnosis of pericardial effusion. We also summarize and discuss the symptoms, treatment, and prognosis of the pathological condition, and present a brief review of previously published reports. © 2012 Canadian Urological Association.

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Brain metastasis of a papillary renal cell carcinoma, identified as type 2

Hasegawa Masanori, Kikuchi Eiji, Yasumizu Yota, Hattori Seiya, Takeda Toshikazu, Morita Shinya, Kosaka Takeo, Miyajima Akira, Horiguchi Takashi, Mikami Shuji, Oya Mototsugu

International Journal of Clinical Oncology 14 （ 3 ） 270 - 272 2009年06月

ISSN 1341-9625

Papillary renal cell carcinomas (PRCCs) tend to metastasize to lymph nodes, while metastasis to the brain is extremely rare. We report the case of a man who had a brain metastasis of PRCC type 2. He was brought to our hospital due to the sudden onset of convulsions. Diagnostic imaging studies showed a metastatic brain tumor in the left parietal lobe, and a primary renal tumor in the right kidney, with paraaortal lymph node metastases. An excision of brain tumor was performed. The brain tumor had a papillary structure with eosinophilic cytoplasm. Five weeks later nephrectomy was carried out. Histological analysis of the nephrectomy specimen revealed the same papillary structure, which was compatible with PRCC type 2. © 2009 Japan Society of Clinical Oncology.

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Right orbital metastasis from left renal cell carcinoma

Takeda Toshikazu, Yasumizu Yota, Hasegawa Masanori, Morita Shinya, Oya Mototsugu

Japanese Journal of Clinical Urology 62 （ 5 ） 319 - 321 2008年

ISSN 0385-2393

A 76-year-old woman receieved right thyroidectomy for a right thyroid tumor and the histopathological diagnosis was clear cell carcinoma. Radiological examination revealed left renal cell carcinoma with metastasis to the pancreas and left radical nephrectomy was performed. After the operation, IFN therapy was performed. But the tumor recurred at the same region in 2 years and metastasized to the lung in 3 years, to the right orbit in 6 years. Tumorectomy of the orbital tumor was performed and the histopathological diagnosis was suggestive of metastatic tumor from renal cell carcinoma.

Inhibition of inflammatory cytokine secretion from mouse microglia cells by DHMEQ, an NF-κB inhibitor

Takatsuna H., Morita S., Nagatsu T., Sawada M., Umezawa K.

Biomedicine and Pharmacotherapy 59 （ 6 ） 318 - 322 2005年07月

ISSN 0753-3322

Activation of microglia has been implicated in various neurodegenerative disorders, and thus the inhibition of microglial activity may suppress these disorders. Earlier we designed and synthesized an NF-κB inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ) that showed anti-inflammatory and anti-tumor activities in vivo. In the present research, we studied whether DHMEQ would inhibit the activation of mouse microglial cells. DHMEQ inhibited lipopolysaccharide (LPS)-induced activation of NF-κB in an electrophoresis mobility shift assay. It also inhibited LPS-induced secretions of TNF-α and IL-6 from mouse microglial cell line 6-1 cells. © 2005 Elsevier SAS. All rights reserved.

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森田 伸也

論文 - 森田 伸也

森田　伸也

論文 - 森田　伸也