St Lukes Life Science Institute

Science, Japan

St Lukes Life Science Institute

Science, Japan
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Urayama K.Y.,University of California at Berkeley | Urayama K.Y.,St Lukes Life Science Institute | Thompson P.D.,University of Manchester | Taylor M.,Handforth | And 2 more authors.
Frontiers in Oncology | Year: 2013

The enduring suspicion that infections and immunologic response may play a role in the etiology of childhood leukemia, particularly acute lymphoblastic leukemia (ALL), is now supported, albeit still indirectly, by numerous epidemiological studies. The cumulative evidence includes, for example, descriptive observations of a peculiar peak incidence at age 2-5 years for ALL in economically developed countries, clustering of cases in situations of population mixing associated with unusual patterns of personal contacts, associations with various proxy measures for immune modulatory exposures early in life, and genetic susceptibility conferred by variation in genes involved in the immune system. In this review, our focus is the extended major histocompatibility complex (MHC), an approximately 7.6 Mb region that is well-known for its high-density of expressed genes, extensive polymorphisms exhibiting complex linkage disequilibrium patterns, and its disproportionately large number of immune-related genes, including human leukocyte antigen (HLA). First discovered through the role they play in transplant rejection, the classical HLA class I (HLA-A, -B, and -C) and class II (HLA-DR, HLA-DQ, and HLA-DP) molecules reside at the epicenter of the immune response pathways and are now the targets of many disease susceptibility studies, including those for childhood leukemia. The genes encoding the HLA molecules are only a minority of the over 250 expressed genes in the xMHC, and a growing number of studies are beginning to evaluate other loci through targeted investigations or utilizing a mapping approach with a comprehensive screen of the entire region. Here, we review the current epidemiologic evidence available to date regarding genetic variation contained within this highly unique region of the genome and its relationship with childhood ALL risk. © 2013 Urayama, Thompson, Taylor, Trachtenberg and Chokkalingam.

Sugiyama T.,University of California at Los Angeles | Sugiyama T.,University of Tokyo | Sugiyama T.,National Center for Global Health and Medicine | Tsugawa Y.,Harvard Interfaculty Initiative in Health Policy | And 4 more authors.
JAMA Internal Medicine | Year: 2014

IMPORTANCE: Both dietary modification and use of statins can lower blood cholesterol. The increase in caloric intake among the general population is reported to have plateaued in the last decade, but no study has examined the relationship between the time trends of caloric intake and statin use. OBJECTIVE: To examine the difference in the temporal trends of caloric and fat intake between statin users and nonusers among US adults. DESIGN, SETTING, AND PARTICIPANTS: A repeated cross-sectional study in a nationally representative sample of 27 886 US adults, 20 years or older, from the National Health and Nutrition Examination Survey, 1999 through 2010. EXPOSURES: Statin use. MAIN OUTCOMES AND MEASURES: Caloric and fat intake measured through 24-hour dietary recall. Generalized linear models with interaction term between survey cycle and statin use were constructed to investigate the time trends of dietary intake for statin users and nonusers after adjustment for possible confounders.We calculated model-adjusted caloric and fat intake using these models and examined if the time trends differed by statin use. Body mass index (BMI) changes were also compared between statin users and nonusers. RESULTS: In the 1999-2000 period, the caloric intake was significantly less for statin users compared with nonusers (2000 vs 2179 kcal/d; P = .007). The difference between the groups became smaller as time went by, and there was no statistical difference after the 2005-2006 period. Among statin users, caloric intake in the 2009-2010 period was 9.6% higher (95% CI, 1.8-18.1; P = .02) than that in the 1999-2000 period. In contrast, no significant change was observed among nonusers during the same study period. Statin users also consumed significantly less fat in the 1999-2000 period (71.7 vs 81.2 g/d; P = .003). Fat intake increased 14.4% among statin users (95% CI, 3.8-26.1; P = .007) while not changing significantly among nonusers. Also, BMI increased more among statin users (+1.3) than among nonusers (+0.4) in the adjusted model (P = .02). CONCLUSIONS AND RELEVANCE: Caloric and fat intake have increased among statin users over time, which was not true for nonusers. The increase in BMI was faster for statin users than for nonusers. Efforts aimed at dietary control among statin users may be becoming less intensive. The importance of dietary composition may need to be reemphasized for statin users. Copyright 2014 American Medical Association. All rights reserved.

Ohigashi S.,St Lukes International Hospital | Sudo K.,St Lukes International Hospital | Kobayashi D.,St Lukes International Hospital | Takahashi O.,St Lukes Life Science Institute | And 4 more authors.
Digestive Diseases and Sciences | Year: 2013

Background: New molecular biology-based methods of bacterial identification are expected to help elucidate the relationship between colorectal cancer (CRC) and intestinal microbiota. Although there is increasing evidence revealing the potential role of microbiota in CRC, it remains unclear whether microbial dysbiosis is the cause or the result of CRC onset. Aim: We investigated the changes of intestinal environments in CRC or adenoma. Methods: We analyzed 13 groups of microbiota, 8 types of organic acids, and pH in feces obtained from the following 3 groups: individuals with CRC, adenoma, and non-adenoma. Ninety-three patients with CRC and 49 healthy individuals (22 with adenoma and 27 without adenoma) were enrolled. Results: The counts of total bacteria (10.3 ± 0.7 vs. 10.8 ± 0.3 log10 cells/g of feces; p < 0.001), 5 groups of obligate anaerobe, and 2 groups of facultative anaerobes were significantly lower in the CRC group than in the healthy individuals. While the concentrations of short chain fatty acids (SCFAs) were significantly decreased in the CRC group, the pH was increased in the CRC group (7.4 ± 0.8 vs. 6.9 ± 0.6; p < 0.001). Comparison among the CRC, adenoma, and non-adenoma groups revealed that fecal SCFAs and pH in the adenoma group were intermediate to the CRC group and the non-adenoma group. Within the CRC group, no differences in microbiota or organic acids were observed among Dukes stages. Conclusions: CRC patients showed significant differences in the intestinal environment, including alterations of microbiota, decreased SCFAs, and elevated pH. These changes are not a result of CRC progression but are involved in CRC onset. © 2013 Springer Science+Business Media New York.

Tsugawa Y.,Harvard Interfaculty Initiative in Health Policy | Tsugawa Y.,St Lukes Life Science Institute | Kumamaru H.,Harvard University | Yasunaga H.,University of Tokyo | And 3 more authors.
Medical Care | Year: 2013

BACKGROUND: The association between hospital volume and patient outcomes remains unclear for stroke. Little is known about whether these relationships differ by stroke subtypes. OBJECTIVES: To examine the association of hospital volume with in-hospital mortality and costs of care for stroke. RESEARCH DESIGN: Secondary data analysis of national hospital database. SUBJECTS: A total of 66,406 patients admitted between July 1 and December 31, 2010 with primary diagnosis of stroke at 796 acute care hospitals in Japan were included. MEASURES: We used a locally weighted scatter-plot smoothing method to test the relationship between hospital volume and outcomes. On the basis of these results, we categorized patient volume into 3 groups (10-50, 51-100, and >100 discharges/6 mo). We tested the volume-outcome relationship using multivariable regression models adjusting for patient and hospital characteristics. Subgroup analysis was conducted by stratifying on stroke subtype. RESULTS: Compared with those treated at high-volume hospitals (>100 discharges), patients admitted to low-volume hospitals (10-50 discharges) had higher in-hospital mortality (adjusted odds ratio, 1.45; 95% CI, 1.23-1.71, P<0.0001). In the lowest volume hospitals, adjusted costs of care per discharge were 8.0% lower (95% CI, -14.1% to -1.8%, P=0.01) compared with the highest volume hospitals. The volume-mortality association was significant across all stroke subtypes. Highest volume hospitals had higher costs than lowest volume hospitals for subarachnoid hemorrhage, but this association was nonsignificant for ischemic and hemorrhagic stroke. CONCLUSIONS: Highest volume hospitals had lower mortality than the lowest volume hospitals for stroke in Japan. Highest volume hospitals had higher costs for subarachnoid hemorrhage, but not for ischemic and hemorrhagic stroke. Copyright © 2013 by Lippincott Williams & Wilkins.

Ohigashi S.,St Lukes International Hospital | Hoshino Y.,Keio University | Ohde S.,St Lukes Life Science Institute | Onodera H.,St Lukes International Hospital
Surgery Today | Year: 2011

Purpose: We investigated the functional outcome and health-related quality of life (QOL) of patients who underwent a surgical resection of colorectal cancer, and reviewed the efficacy of probiotics for improving bowel function. Methods: A questionnaire was mailed to 193 patients. Questionnaires contained the Medical Outcomes Study Short-Form 36-Item Health Survey and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 as QOL scores, the Wexner incontinence score, and original questionnaire items about bowel functions. Probiotics, containing Bacillus natto and Lactobacillus acidophilus, were given to 77 patients for 3 months; after 3 months of treatment, the same questionnaire was administered. The results were analyzed by location of the resected cancer: rectal, colonic, right, and left. Results: In the rectal group, defecation frequency, anal pain, and the Wexner score were significantly worse than in the colonic group. In the right group, the fecal form was looser and nighttime defecation frequency was higher than those of the left group. Three items in the QOL score of the right group were significantly worse compared with the left group. Functional outcome including defecation frequency, feeling of incomplete defecation, and five items in the QOL score were significantly improved after taking probiotics. Improvement in functional outcome and/or QOL was observed in all groups. Conclusions: Not only rectal resection but also rightside colectomy affected bowel dysfunction. Probiotics could be an effective treatment for improvement in functional outcome and QOL after colorectal resection. © 2011 Springer.

Urayama K.Y.,St Lukes Life Science Institute | Chokkalingam A.P.,University of California at Berkeley | Manabe A.,St Lukes International Hospital | Mizutani S.,Tokyo Medical and Dental University
International Journal of Hematology | Year: 2013

Acute lymphoblastic leukemia (ALL) is the most common cancer in children, and efforts to understand its etiology has followed a paradigm that common genetic variation in the presence of modifiable environmental factors contribute to disease risk. To date, there are numerous reports of candidate gene association studies suggesting an involvement of genetic loci in childhood ALL risk, but the general lack of consistency in results has underscored the need for careful interpretation and confirmation in additional well-designed studies. Complementary efforts using the genome-wide association study approach have shown indisputable evidence that common low penetrance genetic polymorphisms contribute to childhood ALL risk. However, current calculations show that these established disease loci only explain a portion of the total estimated contribution of common genetic variation on childhood ALL risk. Certain candidate gene loci previously examined likely contribute to this unexplained variation in risk, but the challenge moving forward will be to establish which ones based on the accumulating evidence. In this review, we describe the results of the most recent gene association studies in childhood ALL and discuss options for future efforts to advance this area of research. © 2012 The Japanese Society of Hematology.

Ward A.M.,University of Oxford | Takahashi O.,St Lukes Life Science Institute | Stevens R.,University of Oxford | Heneghan C.,University of Oxford
Journal of Hypertension | Year: 2012

Objective: Examine the relationship between home blood pressure (BP) and risk for all-cause mortality, cardiovascular mortality and cardiovascular events. Methods: We conducted a systematic review and meta-analysis of prospective studies of home BP. Primary outcomes were all-cause mortality, cardiovascular mortality and cardiovascular events. We extracted hazard ratios and 95% confidence intervals (CIs) which were pooled with a random-effects model. Heterogeneity was assessed using the I statistic. Results: We identified eight studies with 17 698 participants. Follow-up was 3.2-10.9 years. For all-cause mortality (n = 747) the hazard ratio for home BP was 1.14 (95% CI 1.01-1.29) per 10 mmHg increase in systolic BP compared to 1.07 (0.91-1.26) for office BP. For cardiovascular mortality (n = 193) the hazard ratio for home BP was 1.29 (1.02-1.64) per 10 mmHg increase in systolic BP compared to 1.15 (0.91-1.46) for office BP. For cardiovascular events (n = 699) the hazard ratio for home BP was 1.14 (1.09-1.20) per 10 mmHg increase in systolic BP compared to 1.10 (1.06-1.15) for office BP. In three studies which adjusted for office and home BP the hazard ratio was 1.20 (1.11-1.30) per 10 mmHg increase in systolic BP for home BP adjusted for office BP compared to 0.99 (0.93-1.07) per 10 mmHg increase in systolic BP for office BP adjusted for home BP. Diastolic results were similar. Conclusions: Home BP remained a significant predictor of cardiovascular mortality and cardiovascular events after adjusting for office BP suggesting it is an important prognostic variable over and above that of office BP. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Okada K.,St Lukes International Hospital | Ohde S.,St Lukes Life Science Institute | Otani N.,St Lukes International Hospital | Sera T.,St Lukes International Hospital | And 3 more authors.
Resuscitation | Year: 2012

Aim: To identify patients who can obtain the full benefit from targeted temperature management (TTM) after out-of-hospital cardiac arrest. Methods: We performed a retrospective observational study of comatose patients treated with TTM after an out-of-hospital cardiac arrest from January 2006 to February 2011. Neurological outcome was evaluated with the Glasgow-Pittsburgh Cerebral Performance category (CPC) at discharge and predictors were determined. Results: Of 66 patients studied, 40 (60.6%) survived to neurologically intact discharge (CPC 1 or 2). According to multivariate analysis, predictors of good neurological outcome included arrest-to-first cardiopulmonary resuscitation attempt interval ≤5. min, ventricular fibrillation or ventricular tachycardia in the first monitored rhythm, absence of re-arrest before leaving the emergency department, arrest-to-return of spontaneous circulation interval ≤30. min and recovery of pupillary light reflex, which were identifiable in the emergency department. Based on this analysis, we developed a seven-point score (5-R score). If the score was ≥5, it predicted good neurological outcome with a sensitivity of 82.5% (95% confidence interval [CI], 67.2-92.7%) and specificity of 92.3% (95% CI, 74.9-99.1%). The negative predictive value of a score ≥4 was 100% (95% CI, 81.5-100%). Our prediction model was validated internally by a bootstrapping technique. Conclusions: The prediction protocol using the 5-R score was associated with good neurological outcome of patients treated with TTM. Therefore, it could be helpful in clinical decision making on whether to initiate cooling. © 2012 Elsevier Ireland Ltd.

Inagaki K.,St Lukes International Hospital | Ohkoshi K.,St Lukes International Hospital | Ohde S.,St Lukes Life Science Institute
Retina | Year: 2012

Purpose: To perform optical coherence tomography imaging of retinal healing after conventional multicolor laser, pattern scanning laser, or micropulse laser treatment and compare the characteristics of each method. Methods: This was a single-center interventional case series study. Twenty-nine patients with macular edema underwent laser photocoagulation. Changes of retinal morphology because of laser-tissue interaction were assessed within 3 months by using a spectral-domain optical coherence tomography. Results: Immediately after conventional multicolor laser or pattern scanning laser treatment, a hyperreflective band appeared at the laser sites. The photoreceptor inner segment-outer segment line disappeared in all the patients treated with a conventional multicolor laser, but was intact in 22.2% (2/9 eyes) after pattern scanning laser. From 1 week to 1 month, the bands resolved. At 3 months, recovery of the inner segment-outer segment line surrounding the laser site was seen in all patients after conventional grid photocoagulation and pattern scanning laser. Retinal morphology did not change at any time during the observation period after subthreshold micropulse diode laser photocoagulation. Conclusion: The characteristic in vivo effects of retinal photocoagulation were monitored over time by spectral-domain optical coherence tomography. Changes of retinal morphology appeared less intense after pattern scanning laser than conventional grid laser treatment.

Nomura A.,St Lukes International Hospital | Omata F.,St Lukes Life Science Institute | Furukawa K.,St Lukes International Hospital
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2010

In-hospital and long-term mortality of infective endocarditis (IE) are well noted, but the studies for mid-term (90-day) mortality of IE is still limited. We determine the mid-term mortality rate of IE and its significant predictors. Seventy patients with IE were hospitalised at St. Luke's International Hospital between January 1996 and March 2009, of whom 62 consecutive patients could be followed up for 90 days after diagnosis. We then calculated Kaplan-Meier (KM) estimates and performed time-to-event analysis. The mean (standard deviation, SD) age was 66.6 (15.3) years. Thirty-five patients (56%) were male. Blood cultures were positive in 87%. Causative microorganisms were: viridans group streptococci (23%), β-streptococci (16%), Staphylococcus aureus (15%), including methicillin-resistant S. aureus (MRSA) (5%). Thirty-three cases (53%) had at least one complication such as heart failure (34%), central nervous system (CNS) complication (29%) or emboli peripheral to CNS (6%). KM estimates (95% CI) of the 90-day mortality was 14.5% (7.8-25%). In multiple regression analysis using the Cox proportional hazards model, hazard ratios of at least one complication for the 90-day mortality was 8.2 (1.4-155). Mid-term mortality of IE continues to be high and the presence of at least one complication may be considered as an independent risk factor of mid-term mortality. © 2010 Springer-Verlag.

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