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51.
Shimizu M Tatsumi K Miwa Y Shima T Okada T Minami H Mukohara N 《Journal of cardiology》2004,43(2):81-86
A 76-year-old man with previous antero-septal myocardial infarction and aorto-coronary bypass surgery developed exertional dyspnea. Echocardiography revealed diffuse left ventricular hypokinesis and aortic stenosis with a mean pressure gradient of 29 mmHg. Coronary angiography showed no significant lesions in the bypass grafts and total occlusions of the proximal left anterior descending artery and mid circumflex artery. Dobutamine stress echocardiography was performed to evaluate the severity of aortic stenosis and left ventricular functional reversibility. Administration of dobutamine increased the mean pressure gradients to 48 mmHg and increased the stroke volume by 28% without change in aortic valve area of about 0.5 cm2. We considered that our patient had severe aortic stenosis with contractile reserve. After aortic valve replacement, he improved with better left ventricular function. 相似文献
52.
Hiroyuki?Takahama Masanori?Asakura Yukio?Abe Masayoshi?Ajioka Kazutaka?Aonuma Toshihisa?Anzai Takaharu?Hayashi Shinya?Hiramitsu Hiroya?Kawai Hidetaka?Kioka Kazuo?Kimura Young-Jae?Lim Ken?Matsuoka Hirohiko?Motoki Yoji?Nagata Sunao?Nakamura Nobuyuki?Ohte Yukio?Ozaki Taishi?Sasaoka Shunsuke?Tamaki Toshimitsu?Hamasaki Masafumi?Kitakaze 《Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy》2018,32(4):381-388
Background
Previous studies suggest that the pathophysiology of heart failure with preserved ejection fraction (HFpEF) is characterized not only by high ventricular stiffness, but also by vascular stiffness. Azilsartan has higher vascular affinity compared with other angiotensin II receptor blockers (ARBs), which were proven to have no beneficial effects on clinical outcomes in patients with HFpEF in earlier clinical trials. We aimed to test the hypothesis that azilsartan may improve left ventricular diastolic function in HFpEF patients with hypertension in this trial.Methods
The Effects of Angiotensin Receptor Blockers on Diastolic Function in Patients Suffering from Heart Failure with Preserved Ejection Fraction: J-TASTE trial is a multicenter, randomized, open-labeled, and assessor(s)-blinded, active controlled using candesartan, parallel-group clinical trial, to compare changes in left ventricular (LV) diastolic dysfunction between HFpEF patients with hypertension who have received candesartan or azilsartan for 48 weeks. The primary endpoint is the change in early diastolic wave height/early diastolic mitral annulus velocity (E/e’) assessed by echocardiography from the baseline to the end of the study (48 weeks). A total of 190 patients will be recruited into the study.Conclusions
The design of the J-TASTE trial will provide data on whether differences between the effects of the two tested drugs on LV diastolic function exist in HFpEF patients with hypertension and will improve understanding of the pathophysiological role of vascular stiffness on diastolic function.53.
The present study was performed to examine whether the expression of CD64 Fc gamma receptor type I (FcgammaRI) on both neutrophils and monocytes can be modulated by multiple daily administrations of granulocyte colony-stimulating factor (G-CSF) to patients with non-Hodgkin's lymphoma in neutropenia caused by CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. The expression of CD64 was determined by flow cytometric analysis at the following time points: before chemotherapy, at the nadir of the neutrophil count, at the fifth day after the start of G-CSF administration, and at more than 8 days after the start of G-CSF administration. CD64 expression was enhanced in patients given G-CSF during CHOP treatment, whereas CD64 expression remained unchanged in patients not given G-CSF CD64 expression levels on both neutrophils and monocytes were significantly up-regulated by the daily administration of G-CSF and reached peak levels at day 5 (P = .0007). Thereafter, expression on both cell types remained at almost the same levels as on day 5 for the rest of the treatment course, even though G-CSF therapy continued for 3 to 5 more days. Interestingly, CD64 expression on monocytes was already increased significantly (P = .0001) at the nadir of the neutrophil count relative to the baseline before chemotherapy and then was additionally up-regulated by day 5 after the start of G-CSF injections (P = .019). In antibody-dependent cellular cytotoxicity assays, we found that rituximab-mediated cell lysis was significantly enhanced at day 5 after the start of G-CSF treatment (P = .01). In conclusion, this study shows that multiple doses of G-CSF administered to lymphoma patients with neutropenia due to CHOP chemotherapy can enhance CD64 expression on both neutrophils and monocytes. Peak CD64 levels are reached at day 5 of G-CSF treatment, resulting in an activation of the rituximab-mediated antitumor ability of these effector cells. This finding may be useful in determining the optimal timing of administration for an antibody such as rituximab in a chemotherapeutic strategy designed to exert a maximal effect against tumor cells. 相似文献
54.
Fluvastatin improves arterial stiffness in patients with coronary artery disease and hyperlipidemia: a 5-year follow-up study. 总被引:1,自引:0,他引:1
Minoru Hongo Hiroshi Tsutsui Eiichiro Mawatari Hiroya Hidaka Setsuo Kumazaki Yoshikazu Yazaki Masafumi Takahashi Osamu Kinoshita Uichi Ikeda 《Circulation journal》2008,72(5):722-728
BACKGROUND: The present study was designed to test the hypothesis that fluvastatin might improve arterial stiffness, as assessed with pulse wave velocity (PWV), in patients with coronary artery disease (CAD) and hyperlipidemia over the long term. METHODS AND RESULTS: Ninety-three patients were randomly assigned to either fluvastatin (group A, n=50) or bezafibrate (group B, n=43) and followed for 5 years. There was no difference in the clinical findings between the 2 groups. In group A, there was a progressive reduction in the brachial-ankle PWV along with a decrease in serum low-density lipoprotein-cholesterol (LDL-C) and C-reactive protein (CRP) by 12 months after fluvastatin, and the improvement was maintained until 5 years after treatment. In group B, despite identical lowering of the serum lipid, PWV was progressively increased. In group A, the percentage change in PWV correlated significantly with that of the serum CRP (r=0.49, p<0.001), but not with that of the serum LDL-C after treatment. CONCLUSIONS: The beneficial vascular effects of fluvastatin persisted for a long period in patients with CAD and hyperlipidemia. Its anti-inflammatory action might contribute to the favorable effects on arterial stiffness. 相似文献
55.
Hiroshi Okada Michiaki Fukui Muhei Tanaka Shinobu Matsumoto Kanae Kobayashi Hiroya Iwase Kiichiro Tomiyasu Koji Nakano Goji Hasegawa Naoto Nakamura 《Metabolism: clinical and experimental》2014
Objective
Bilirubin has been recognized as an important endogeneous antioxidant. Previous studies reported that bilirubin could prevent atherosclerosis. The aim of this study was to investigate if serum bilirubin concentration could be a predictor for the development of albuminuria in patients with type 2 diabetes.Materials and Methods
We measured serum bilirubin in 320 consecutive patients with normoalbuminuria. We performed follow-up study to assess the development of albuminuria, mean interval of which was 3.2 ± 0.9 years. Cox proportional hazards regression was used to examine the relationship between serum bilirubin concentration and the development of albuminuria.Results
During follow-up duration, 43 patients have developed albuminuria. In multivariate analysis, after adjusting for comprehensive risk factors, the risk of developing albuminuria was higher in the lowest quartile of serum bilirubin concentrations than that in the highest quartile of serum bilirubin concentrations (Hazard ratio, 5.76; 95% CI, 1.65 to 24.93).Conclusions
Low serum bilirubin concentration could be a novel risk factor for the development of albuminuria in patients with type 2 diabetes. 相似文献56.
Hiroya Kuwahara Kuniaki Tsuchiya Zen Kobayashi Akira Inaba Haruhiko Akiyama Hidehiro Mizusawa 《Neuropathology》2014,34(1):45-48
Cryptococcal meningitis is rarely complicated by immune‐mediated leukoencephalopathy, but the precise pathomechanism is uncertain. A 72‐year‐old Japanese man treated with prednisolone for Sweet disease developed a subacute progression of meningitis, which was considered as neuro‐Sweet disease. A treatment by methylprednisolone rapidly improved CSF findings with a remarkable decrease in lymphocyte numbers in the blood, but the patient's consciousness still worsened after the cessation of the treatment. The patient developed cryptococcal meningitis and MRI showed abnormal intensities predominantly in the cerebral deep white matter along with the recovery of lymphocyte numbers in the blood, which resulted in death. A postmortem examination of the brain revealed degenerative lesions, especially at the cerebral white matter and cortex adjacent to the leptomeninges abundantly infiltrated by Cryptococcus neoformans. In the affected cerebral deep white matter, perivascular infiltration of lymphocytes was prominent in coexistence with reactive astrocytes and vascular proliferation, but these findings were not observed in the subcortical and cortical lesions. Cryptococcus neoformans was not present within the brain parenchyma. This is the first report of a case suggesting that cryptococcal meningitis can accompany lymphocytic inflammation predominantly in cerebral deep white matter as a possible manifestation of immune reconstitution inflammatory syndrome. 相似文献
57.
Rika Watarai Koji Suzuki Naohiro Ichino Keisuke Osakabe Keiko Sugimoto Hiroya Yamada Takeshi Hamajima Nobuyuki Hamajima Takashi Inoue 《Journal of epidemiology / Japan Epidemiological Association》2014,24(3):250-257
Background
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelium nitric oxide synthase (NOS). ADMA binds to a substrate-binding site of NOS and then inhibits nitric oxide production from vascular endothelial cells. Elevated ADMA levels are a risk factor for cardiovascular disease. Recently, it was reported that plasma ADMA levels were negatively correlated with vegetable and fruit consumption. The purpose of this study was to examine the association between serum levels of carotenoids and serum ADMA levels in Japanese subjects.Methods
We conducted a cross-sectional study of 470 subjects (203 men and 267 women) who attended a health examination in August 2011. Serum levels of several carotenoids were separately measured by high-performance liquid chromatography. Serum ADMA levels were determined by using an enzyme-linked immunosorbent assay kit.Results
In women, the multivariate-adjusted odds ratios (ORs) of elevated serum ADMA levels were significantly decreased in the highest tertile for β-cryptoxanthin (OR 0.47, 95% CI 0.23–0.95), α-carotene (OR 0.39, 95% CI 0.18–0.79), and β-carotene (OR 0.36, 95% CI 0.17–0.73) compared to the lowest tertile. In men, significantly decreased ORs were observed in the highest tertiles of serum zeaxanthin/lutein (OR 0.23, 95% CI 0.06–0.69) and α-carotene (OR 0.26, 95% CI 0.07–0.82), and in the middle and the highest tertiles of serum β-carotene (OR 0.27, 95% CI 0.09–0.74 and OR 0.20, 95% CI 0.03–0.88, respectively) when the tertile cutoff points of women were extrapolated to men.Conclusions
Higher serum levels of carotenoids, such as α-carotene and β-carotene, may help to prevent elevated serum ADMA levels in Japanese subjects.Key words: asymmetric dimethylarginine, carotenoids, cross-sectional study 相似文献58.
Daisuke Ishibashi Takeshi Ishikawa Satoshi Mizuta Hiroya Tange Takehiro Nakagaki Tsuyoshi Hamada Noriyuki Nishida 《Neurotherapeutics》2020,17(4):1836
The accumulation of abnormal prion protein (PrPSc) produced by the structure conversion of PrP (PrPC) in the brain induces prion disease. Although the conversion process of the protein is still not fully elucidated, it has been known that the intramolecular chemical bridging in the most fragile pocket of PrP, known as the “hot spot,” stabilizes the structure of PrPC and inhibits the conversion process. Using our original structure-based drug discovery algorithm, we identified the low molecular weight compounds that predicted binding to the hot spot. NPR-130 and NPR-162 strongly bound to recombinant PrP in vitro, and fragment molecular orbital (FMO) analysis indicated that the high affinity of those candidates to the PrP is largely dependent on nonpolar interactions, such as van der Waals interactions. Those NPRs showed not only significant reduction of the PrPSc levels but also remarkable decrease of the number of aggresomes in persistently prion-infected cells. Intriguingly, treatment with those candidate compounds significantly prolonged the survival period of prion-infected mice and suppressed prion disease-specific pathological damage, such as vacuole degeneration, PrPSc accumulation, microgliosis, and astrogliosis in the brain, suggesting their possible clinical use. Our results indicate that in silico drug discovery using NUDE/DEGIMA may be widely useful to identify candidate compounds that effectively stabilize the protein.Electronic supplementary materialThe online version of this article (10.1007/s13311-020-00903-9) contains supplementary material, which is available to authorized users. 相似文献
59.
Takeshi Nagashima Ken Yamaguchi Kenichi Urakami Yuji Shimoda Sumiko Ohnami Keiichi Ohshima Tomoe Tanabe Akane Naruoka Fukumi Kamada Masakuni Serizawa Keiichi Hatakeyama Kenya Matsumura Shumpei Ohnami Koji Maruyama Tohru Mochizuki Masatoshi Kusuhara Akio Shiomi Yasuhisa Ohde Masanori Terashima Katsuhiko Uesaka Tetsuro Onitsuka Seiichiro Nishimura Yasuyuki Hirashima Nakamasa Hayashi Yoshio Kiyohara Yasuhiro Tsubosa Hirohisa Katagiri Masashi Niwakawa Kaoru Takahashi Hiroya Kashiwagi Masahiro Nakagawa Yuji Ishida Takashi Sugino Mitsuru Takahashi Yasuto Akiyama 《Cancer science》2020,111(2):687-699
This study aimed to establish the Japanese Cancer Genome Atlas (JCGA) using data from fresh frozen tumor tissues obtained from 5143 Japanese cancer patients, including those with colorectal cancer (31.6%), lung cancer (16.5%), gastric cancer (10.8%) and other cancers (41.1%). The results are part of a single‐center study called “High‐tech Omics‐based Patient Evaluation” or “Project HOPE” conducted at the Shizuoka Cancer Center, Japan. All DNA samples and most RNA samples were analyzed using whole‐exome sequencing, cancer gene panel sequencing, fusion gene panel sequencing and microarray gene expression profiling, and the results were annotated using an analysis pipeline termed “Shizuoka Multi‐omics Analysis Protocol” developed in‐house. Somatic driver alterations were identified in 72.2% of samples in 362 genes (average, 2.3 driver events per sample). Actionable information on drugs that is applicable in the current clinical setting was associated with 11.3% of samples. When including those drugs that are used for investigative purposes, actionable information was assigned to 55.0% of samples. Germline analysis revealed pathogenic mutations in hereditary cancer genes in 9.2% of samples, among which 12.2% were confirmed as pathogenic mutations by confirmatory test. Pathogenic mutations associated with non–cancerous hereditary diseases were detected in 0.4% of samples. Tumor mutation burden (TMB) analysis revealed 5.4% of samples as having the hypermutator phenotype (TMB ≥ 20). Clonal hematopoiesis was observed in 8.4% of samples. Thus, the JCGA dataset and the analytical procedures constitute a fundamental resource for genomic medicine for Japanese cancer patients. 相似文献
60.
Katsuji Kaida Kazuhiro Ikegame Junko Ikemoto Rie Murata Reiko Irie Satoshi Yoshihara Shinichi Ishii Masaya Okada Takayuki Inoue Hiroya Tamaki Toshihiro Soma Yoshihiro Fujimori Shunro Kai Hiroyasu Ogawa 《International journal of hematology》2014,99(4):463-470
In the present study, we analyzed the kinetics of serum soluble interleukin-2 receptor (sIL-2R) using data from 77 patients undergoing HLA-haploidentical transplantation using reduced-intensity conditioning (RIC), who were at an advanced stage or at high risk for relapse, to clarify the usefulness of sIL-2R as a biomarker of acute graft-versus-host disease (GVHD). Anti-T-lymphocyte globulin and methylprednisolone were used as GVHD prophylaxis. While the median sIL-2R in 38 patients not developing GVHD was suppressed at levels <740 U/ml, sIL-2R in 25 patients developing severe GVHD peaked on day 11 (1,663 U/ml), and thereafter decreased to <1,000 U/ml after day 30. The occurrence of GVHD was not limited to times of high sIL-2R level, but occurred at any time point on the sIL-2R curve. Most patients developing GVHD, however, experienced a higher sIL-2R level early in their transplant course. The combination of RIC and glucocorticoids sufficiently suppressed sIL-2R levels after HLA-haploidentical transplantation. In a multivariate analysis to identify factors associated with GVHD, day 7 sIL-2R >810 U/ml was the only factor significantly associated with the occurrence of severe GVHD (p = 0.0101). 相似文献