Tsukuba Medical Center

Tsukuba, Japan

Tsukuba Medical Center

Tsukuba, Japan
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Iijima H.,Tsukuba Medical Center | Naito T.,Tsukuba Medical Center | Konno S.,Hokkaido University | Nishimura M.,Hokkaido University | Noguchi E.,University of Tsukuba
Allergology International | Year: 2013

Background: Cluster analyses were previously performed to identify asthma phenotypes underlying asthma syndrome. Although a large number of patients with asthma develop the disease later in life, these previous cluster analyses focused mainly patients with younger-onset asthma. Methods: Cluster analysis examined the existence of distinct phenotypes of late-onset asthma in Japanese patients with adult asthma. We then associated genotypes at the CCL5, TSLP, IL4, and ADRB2 genes with the clusters of asthma identified. Results: Using the 8 variables of age, sex, age at onset of the disease, smoking status, total serum IgE, %FEV1, FEV1/FVC, and specific IgE responsiveness to common inhaled allergens, two-step cluster analysis of 880 Japanese adult asthma patients identified 6 phenotypes: cluster A (n = 155): older age at onset, no airflow obstruction; cluster B (n = 170): childhood onset, normal-to-mild airflow obstruction; cluster C (n = 119): childhood onset, the longest disease duration, and moderate-to-severe airflow obstruction; cluster D (n = 108): older age at onset, severe airflow obstruction; cluster E (n = 130): middle-age at onset, no airflow obstruction; and cluster F (n = 198): older age at onset, mild-to-moderate airflow obstruction. The CCL5-28C>G genotype was significantly associated with clusters A, B and D (OR 1.65, p = 0.0021; 1.67, 0.018; and 1.74, 0.011, respectively). The ADRB2 Arg16Gly genotype was also associated with clusters B and D (OR 0.47, p = 0.0004; and 0.63, 0.034, respectively). Conclusions: The current cluster analysis identified meaningful adult asthma phenotypes linked to the functional CCL5 and ADRB2 genotypes. Genetic and phenotypic data have the potential to elucidate the phenotypic heterogeneity and pathophysiology of asthma. © 2013 by Japanese Society of Allergology.


Okuda T.,Nippon Medical School | Shiotani S.,Tsukuba Medical Center | Sakamoto N.,Hirosaki University | Kobayashi T.,Tsukuba Medical Center
Forensic Science International | Year: 2013

There is a low autopsy rate and wide distribution of computed tomography (CT) and magnetic resonance imaging (MRI) scanners in Japan. Therefore, many Japanese hospitals, including 36% of the hospitals with in-patient facilities and 89% of large hospitals with ER facilities conduct postmortem imaging (PMI), use clinical scanners to screen for causes in unusual deaths as an alternative to an autopsy or to determine whether an autopsy is needed. The Japanese PMI examination procedure is generally referred to as " autopsy imaging" (Ai) and the term " Ai" is now commonly used by the Japanese government. Currently, 26 of 47 Japanese prefectures have at least one Ai Center with scanners that are dedicated for PMI. Here, we briefly review the history of Japanese PMI (Ai) from 1985 to the present. © 2012 Elsevier Ireland Ltd.


Nakayama H.,University of Tsukuba | Nakayama H.,Tsukuba Medical Center | Sugahara S.,University of Tsukuba | Tokita M.,Brown University | And 5 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2010

Purpose: To evaluate in a retrospective review the role of proton beam therapy for patients with medically inoperable Stage I non-small-cell lung cancer (NSCLC). Patients and Methods: From November 2001 to July 2008, 55 medically inoperable patients with Stage I NSCLC were treated with proton beam therapy. A total of 58 (T1/T2, 30/28) tumors were treated. The median age of study participants was 77 years (range, 52-86 years). A total dose of 66 GyE in 10 fractions was given to peripherally located tumors and 72.6 GyE in 22 fractions to centrally located tumors. Results: The rates (95% confidence interval) of overall and progression-free survival of all patients and of local control of all tumors at 2 years were 97.8% (93.6-102.0%), 88.7% (77.9-99.5%), and 97.0% (91.1-102.8%), respectively. There was no statistically significant difference in progression-free rate between T1 and T2 tumors (p = 0.87). Two patients (3.6%) had deterioration in pulmonary function, and 2 patients (3.6%) had Grade 3 pneumonitis. Conclusion: Proton beam therapy was effective and well tolerated in medically inoperable patients with Stage I NSCLC. Copyright © 2010 Elsevier Inc. Printed in the USA. All rights reserved.


Masuko H.,University of Tsukuba | Sakamoto T.,University of Tsukuba | Kaneko Y.,University of Tsukuba | Iijima H.,Tsukuba Medical Center | And 5 more authors.
International Journal of COPD | Year: 2011

Few studies have investigated the significance of decreased FEV 1 in non-COPD, nonasthmatic healthy subjects. We hypothesized that a lower FEV 1 in these subjects is a potential marker of an increased susceptibility to obstructive lung disease such as asthma and COPD. This was a cross-sectional analysis of 1505 J apanese adults. We divided the population of healthy adults with no respiratory diseases whose FEV 1/FVC ratio was ≥70% (n = 1369) into 2 groups according to their prebronchodilator FEV 1 (% predicted) measurements:<80% (n = 217) and ≥80% (n = 1152). We compared clinical data - including gender, age, smoking habits, total IgE levels, and annual decline of FEV 1 - between these 2 groups. In addition, as our group recently found that TSLP variants are associated with asthma and reduced lung function, we assessed whether TSLP single nucleotide polymorphisms (SNPs) were associated with baseline lung function in non-COPD, nonasthmatic healthy subjects (n = 1368). Although about half of the subjects with lower FEV 1 had never smoked, smoking was the main risk factor for the decreased FEV 1 in non-COPD, nonasthmatic subjects. However, the subjects with lower FEV 1 had a significantly higher annual decline in FEV 1 independent of smoking status. Airflow obstruction was associated with increased levels of total serum IgE (P = 0.029) and with 2 functional TSLP SNPs (corrected P = 0.027-0.058 for FEV 1% predicted, corrected P = 0.015-0.033 for FEV 1/FVC). This study highlights the importance of early recognition of a decreased FEV 1 in healthy subjects without evident pulmonary diseases because it predicts a rapid decline in FEV 1 irrespective of smoking status. Our series of studies identifed TSLP variants as a potential susceptibility locus to asthma and to lower lung function in non-COPD, nonasthmatic healthy subjects, which may support the contention that genetic determinants of lung function infuence susceptibility to asthma. © 2011 Masuko et al, publisher and licensee Dove Medical Press Ltd.


Shiotani S.,Tsukuba Medical Center | Kobayashi T.,Tsukuba Medical Center | Hayakawa H.,Tsukuba Medical Examiners Office | Kikuchi K.,Tsukuba Medical Center | Kohno M.,Tsukuba Medical Center
Legal Medicine | Year: 2011

Objective: Postmortem CT (PMCT) findings may change with the passage of time after death. The aim of this study was to investigate time-dependent PMCT findings of the lung in order to aid the interpretation of postmortem images obtained at various times. Materials and methods: Our subjects were three non-traumatically deceased male subjects (25, 44, and 76. years old) who underwent whole body PMCT scan at two time points: one immediately after death and the other several hours after death but before the autopsy. The causes of death of the subjects were acute cardiac insufficiency (so-called sudden manhood death syndrome, 2 subjects), ischemic heart disease (acute coronary syndrome, 1 subject). The immediate and delayed PMCT findings of the lung were compared, and the differences between them were investigated. Results: Compared with immediate PMCT, delayed PMCT showed advanced dependent opacity and consolidation corresponding to congestive pulmonary edema. Conclusion: PMCT images of the lung change as the time after death increases due to the natural postmortem changes of the corpse. Immediate PMCT is more suitable than delayed PMCT for discerning cause of death. Delayed PMCT reflects the autopsy findings more accurately than immediate PMCT. © 2011 Elsevier Ireland Ltd.


Hyodo I.,University of Tsukuba | Morita T.,Seirei Mikatabara Hospital | Adachi I.,Shizuoka Cancer Center | Shima Y.,Tsukuba Medical Center | And 2 more authors.
Japanese Journal of Clinical Oncology | Year: 2010

Objective: To develop a predicting tool for survival of terminally ill cancer patients. Methods: This prospective, multicenter study was composed of two cohorts of samples: development and test. In the development sample of terminally ill cancer patients, 32 candidate predictors were studied to develop a new tool, Japan Palliative Oncology Study Prognostic Index using the Cox proportional hazard model. Then the test sample was studied to validate Japan Palliative Oncology Study-Prognostic Index and compared it with the conventional predicting tools, such as palliative prognostic score and simplified palliative prognostic index. Results: Five significant predictors, physician's clinical prediction of survival, consciousness, pleural effusion, white blood cell count and lymphocyte % were derived from the analysis of 201 patients, and Japan Palliative Oncology Study-Prognostic Index was developed using these predictors. It could divide patients into three risk groups: low (A), intermediate (B) and high (C). Median survival times for Groups A, B and C were 51, 35 and 16 days, respectively. Survival probability for more than 30 days for Groups A, B and C in the development sample was 78%, 61% and 16%, respectively. Japan Palliative Oncology Study-Prognostic Index was studied in subsequent 208 patients for the test sample, and constant results (median survival times for Groups A, B and C; 67, 31 and 10 days, and survival probability for more than 30 days for Groups A, B and C; 81, 48 and 11%) were obtained. Palliative prognostic score can also predict three risk groups well, but simplified palliative prognostic index could not discriminate low risk from intermediate risk group. Conclusion: Japan Palliative Oncology Study-Prognostic Index, a tool to predict survival, has been developed. Its reliability should be confirmed further in the future study, comparing with palliative prognostic score. © The Author (2010). Published by Oxford University Press. All rights reserved.


Nakayama H.,Tsukuba Medical Center | Nakayama H.,University of Tsukuba | Satoh H.,University of Tsukuba | Kurishima K.,University of Tsukuba | And 4 more authors.
International Journal of Radiation Oncology Biology Physics | Year: 2010

Purpose: To determine the effectiveness of high-dose conformal radiotherapy to the involved field for patients with Stage III non-small-cell lung cancer (NSCLC). Methods and Materials: Between May 1999 and April 2006, a total of 100 consecutive patients with inoperable Stage IIIA or IIIB NSCLC with a performance score of 0 to 2 and treatment by radical radiotherapy combined with chemotherapy were included. Up to August 2002, 33 patients underwent conventional radiotherapy of 56 Gy to 66 Gy using anteroposterior opposite ports to the primary tumor and elective lymph nodes (conventional group). After September 2002, the remaining 67 patients underwent high-dose radiotherapy of 66 Gy to 84 Gy to the involved volume with three-dimensional (3-D) conformal radiotherapy (conformal group). Results: The median survival was 13.2 months (95% confidence interval [CI], 7.5-18.5 months) in the conventional group and 17.3 months (95% CI, 10.7- 24.0 months) in the conformal group. The overall survival at 3 years were 9.1% (95% CI, -0.7-18.9%) in the conventional group and 31.0% (95% CI, 18.9-43.1%) in the conformal group; the conformal group had a significantly better overall survival (p < 0.05). The radiotherapy method (hazard ratio = 0.55, p < 0.05) and performance status (hazard ratio = 1.48, p < 0.05) were shown to be statistically significant independent prognostic factors. Conclusions: Based on the practical experience reported here, 3-D conformal radiotherapy allowed dose escalation without excessive toxicity, and may improve overall survival rates for patients with Stage III NSCLC. © 2010 Elsevier Inc. All rights reserved.


Nakazawa K.,University of Tsukuba | Kurishima K.,University of Tsukuba | Tamura T.,University of Tsukuba | Ishikawa H.,Tsukuba Medical Center | And 2 more authors.
Medical Oncology | Year: 2013

The aim of this study was to examine the survival difference between non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) patients with diabetes mellitus (DM) according to the first-line therapy. All patients with lung cancer diagnosed at our hospitals between April 1999 and March 2011 were retrospectively analyzed. The definition of DM was strictly determined and included fasting plasma glucose and HbA1c levels. The patients were divided into 2 groups: those with DM (DM group) and those without DM (non-DM group). For each treatment type, the survival of these 2 groups was evaluated. For NSCLC patients overall, the difference in survival between the DM group and the non-DM group was not significant (p = 0.112). However, in surgically treated NSCLC patients, the difference in survival between the 2 groups was significant (p = 0.022). In chemotherapy-treated NSCLC patients, the difference in survival between the 2 groups was not significant (p = 0.942). On the other hand, for SCLC patients overall, the difference in survival between the DM group and the non-DM group was significant (p = 0.012). In chemotherapy-treated SCLC patients, the difference in survival between the 2 groups was significant (p = 0.026). The influence of DM may differ between NSCLC and SCLC patients. At the current treatment level for unresectable NSCLC, the influence of DM might not be the same for NSCLC patients treated with surgery as for SCLC patients treated with chemotherapy. Elucidation of the mechanism by which hyperglycemia influences the progression of lung cancer will improve survival in lung cancer patients with DM. © 2013 Springer Science+Business Media New York.


PubMed | University of Tsukuba, Tsukuba Medical Center and Azabu University
Type: Journal Article | Journal: International journal of molecular sciences | Year: 2016

The renal microvasculature is targeted during aging, sometimes producing chronic kidney disease (CKD). Overdiagnosis of CKD in older persons is concerning. To prevent it, a new concept of healthy aging is arising from a healthy renal donor study. We investigated the renal microcirculatory changes of three older persons and compared them with that of one patient with nephrosclerosis using a three-dimensional (3D) reconstruction technique that we previously developed. This method uses a virtual slide system and paraffin-embedded serial sections of surgical material that was double-immunostained by anti-CD34 and anti- smooth muscle actin (SMA) antibodies for detecting endothelial cells and medial smooth muscle cells, respectively. In all cases, the 3D images proved that arteriosclerotic changes in large proximal interlobular arteries did not directly induce distal arterial change or glomerulosclerosis. The nephrosclerotic patient showed severe hyalinosis with luminal narrowing of small arteries directly inducing glomerulosclerosis. We also visualized an atubular glomerulus and intraglomerular dilatation of an afferent arteriole during healthy aging on the 3D image and showed that microcirculatory changes were responsible for them. Thus, we successfully visualized healthy aged kidneys on 3D images and confirmed the underlying pathology. This method has the ability to investigate renal microcirculatory damage during healthy aging.


PubMed | University of Tsukuba and Tsukuba Medical Center
Type: Journal Article | Journal: Molecular and clinical oncology | Year: 2016

Pleomorphic carcinoma of the lung is a rare, highly malignant subtype of lung cancer, with a more aggressive clinical course compared with other types of non-small-cell lung cancer (NSCLC). Pemetrexed and bevacizumab are currently evaluated as two of the most reliable chemotherapeutic drugs for advanced NSCLC. We herein report a case of a 68- and a 46-year-old man with recurrent and chemo-nave pleomorphic carcinoma of the lung, respectively, who were treated with a combination of carboplatin, pemetrexed and bevacizumab. The overall survival after the initiation of chemotherapy was 30 and 8 months, respectively. These cases exhibited a relatively long-term survival with chemotherapy. In the absence of definitive clinical trials, which are unlikely to be performed due to the rarity of this tumor, our cases demonstrated the potential utility of pemetrexed- and bevacizumab-containing chemotherapy. Our results also suggested that pemetrexed-containing chemotherapy may be key to the treatment of pleomorphic carcinoma of the lung.

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