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Biomedical subjects

Yasuhiro Hasegawa

Publications and source records attributed to Yasuhiro Hasegawa.

At least 19 recordsLinked to original sources
PubMed2006

Acute exacerbation of hepatitis in a boy with chronic HCV genotype-2 infection after a 9-year period of normal transaminases levels.

We report on a boy with HCV genotype-2a infection who presented with a severe degree of ALTflare after 9 years of asymptomatic period and was treated with pegylated interferon and ribavirin. We suggest that children with HCV genotype-2 infection who show a significant ALT flare should be treated with anti-viral therapies in order to avoid progression of hepatic fibrosis.

Acute Disease↗
PubMed2006

Overexpression of mitochondrial peroxiredoxin-3 prevents left ventricular remodeling and failure after myocardial infarction in mice.

BACKGROUND: Mitochondrial oxidative stress and damage play major roles in the development and progression of left ventricular (LV) remodeling and failure after myocardial infarction (MI). We hypothesized that overexpression of the mitochondrial antioxidant, peroxiredoxin-3 (Prx-3), could attenuate this deleterious process. METHODS AND RESULTS: We created MI in 12- to 16-week-old, male Prx-3-transgenic mice (TG+MI, n=37) and nontransgenic wild-type mice (WT+MI, n=39) by ligating the left coronary artery. Prx-3 protein levels were 1.8 times higher in the hearts from TG than WT mice, with no significant changes in other antioxidant enzymes. At 4 weeks after MI, LV thiobarbituric acid-reactive substances in the mitochondria were significantly lower in TG+MI than in WT+MI mice (mean+/-SEM, 1.5+/-0.2 vs 2.2+/-0.2 nmol/mg protein; n=8 each, P<0.05). LV cavity dilatation and dysfunction were attenuated in TG+MI compared with WT+MI mice, with no significant differences in infarct size (56+/-1% vs 55+/-1%; n=6 each, P=NS) and aortic pressure between groups. Mean LV end-diastolic pressures and lung weights in TG+MI mice were also larger than those in WT+sham-operated mice but smaller than those in WT+MI mice. Improvement in LV function in TG+MI mice was accompanied by a decrease in myocyte hypertrophy, interstitial fibrosis, and apoptosis in the noninfarcted LV. Mitochondrial DNA copy number and complex enzyme activities were significantly decreased in WT+MI mice, and this decrease was also ameliorated in TG+MI mice. CONCLUSIONS: Overexpression of Prx-3 inhibited LV remodeling and failure after MI. Therapies designed to interfere with mitochondrial oxidative stress including the antioxidant Prx-3 might be beneficial in preventing cardiac failure.

Animals↗
PubMed2006

Transrectal ultrasound-guided 10-core biopsy of the prostate for Japanese patients.

To determine the utility of transrectal ultrasound (TRUS)-guided 10-core prostate biopsy (sextant plus 4 far lateral cores) for Japanese patients, we compared it with the standard sextant for detection of prostate cancer. The study patients were 564 consecutive Japanese men (median age 71 years) who underwent 10-core biopsy because of PSA values of > or = 2.0 ng/ml at Hiroshima University Hospital between March 2000 and December 2004. The overall cancer detection rate for the 10-core biopsy was 42.6% (240/564), which was significantly higher than the 36.3% (205/564) for the standard sextant biopsy (P=0.0330), with a 14.6% (35/240) improvement. The 10-core biopsy also detected a significant number of additional cancers in the sub-groups of patients with PSA values of 2 to approximately 10 ng/ml (P=0.0275), a prostate volume of > 20 cc (P=0.0440), or normal findings of digital rectal examination (P=0.0304). The 10-core biopsy scheme detected 9.6% and 2.1 to approximately 8.3% more cancers than the lateral sextant (apex, lateral mid portion, and lateral base) and the probable different combinations of 8-core biopsy designs, respectively. Compared to the standard sextant biopsy, the 10-core biopsy did not detect an increased proportion of clinically insignificant cancers. There was no severe morbidity, and only 2 patients (0.4%) were briefly hospitalized due to high fever. These results show that the TRUS-guided 10-core biopsy yields a better prostate cancer detection rate than the 6-core or 8-core protocol without severe complications. Therefore, it seems to be practicable for Japanese patients.

Adult↗
PubMed2006

[PROGRESS].

Explore the source record for details and available documents.

Activities of Daily Living↗
PubMed2005

The effect of weekends and holidays on stroke outcome in acute stroke units.

BACKGROUND AND PURPOSE: In almost all acute stroke units in Japan, staffing level is lower on weekends and holidays and rehabilitative services are provided only on weekdays. We sought to investigate the effects of low-volume care early after stroke resulting from weekends and holidays on the outcome of stroke. METHODS: Patients with completed stroke within 72 h of onset were prospectively registered by 10 acute stroke units in Japan. Main outcome measures were favorable outcomes as indicated by a score of 0-1 on the modified Rankin scale (mRS01) on their 21st hospital day and at discharge and case fatality during the hospital stay. Cox proportional hazardsmodels were used to identify the effects of weekday admission and a weekday ratio (a number of weekdays / total length of hospital stay, or 21 days if hospitalization was longer than 21 days) on the main outcome measures. RESULTS: In a total of 1,134 patients, Cox proportional hazards regression analyses demonstrated that the weekday admission was significantly associated with mRS01 at discharge (hazard ratio, HR: 1.385, 95% CI: 1.087-1.764) and case fatality (HR: 0.477, 95% CI: 0.285-0.798). In 858 patients with rehabilitative therapy, the weekday ratio was significantly associated with mRS01 at discharge (p = 0.014). Compared with the lowest tertile of weekday ratio (<66.6%), the highest tertile (>71.4%) was significantly positively associated with mRS01 at discharge (HR: 1.524, 95% CI: 1.053-2.206; p < 0.026). CONCLUSIONS: Weekday admission was an independent negative predictor of case fatality and a positive predictor of favorable outcome (mRS01) at discharge from acute stroke units. In patients with rehabilitative therapy, a reduction in the weekday ratio was also associated with unfavorable outcome, probably due to a reduction in multidisciplinary care.

Acute Disease↗
PubMed2005

[A case of acute cervical epidural hematoma mimicking medial medullary infarction complicated by arterial dissection].

A 67-year woman with hypertension rapidly noted weakness of the right upper and lower extremities with posterior cervical pain. At admission to our hospital, she showed right hemiparesis without facial palsy, and bilateral pathological reflex. Chest X-ray demonstrated enlargement of the mediastinal shadow. We suspected that she developed aortic arch dissection extending into the vertebral arteries and subsequent medial medullary infarction. However, enhanced thoracic CT, brain MRI-DWI and MRA examinations were negative. Her symptoms rapidly recovered three hours after the onset. A cervical MRI study revealed cervical epidural hematoma locating between the C3 and C6, which suppressed right side of the spinal cord. In conclusion, cervical epidural hematoma as well as medial medullary infarction complicated by the vertebral arterial dissection should be urgently explored when a patient had a sudden onset of cervical pain and hemiparesis without facial palsy.

Aged↗
PubMed2004

Hospital cost of ischemic stroke and intracerebral hemorrhage in Japanese stroke centers.

BACKGROUND: In Japan, the healthcare expenditure has increased to 8.0% of the gross domestic products in 2001. Stroke care is costly. OBJECTIVE: To examine hospital costs and clinical outcomes of ischemic stroke (IS) and intracerebral hemorrhage (ICH) in Japanese stroke centers. DESIGN: A prospective non-interventional multi-center study. SETTING: Ten Japanese stroke centers. STUDY PERIOD: Fourteen months between October 2000 and December 2001. PATIENTS: Patients were those who were consecutively hospitalized with acute IS or ICH within 72 h of onset, excluding subarachnoid hemorrhage. Stroke was defined as focal neurological deficits lasting more than 24 h and the relevant lesions were to be confirmed by brain CT and/or MRI. METHODS: We examined demography, in-hospital cares, length of hospital stay, clinical outcomes at discharge, and direct hospital medical costs including physician's fees. The hospital medical cost data were collected from official hospital medical cost charts for reimbursement to the healthcare insurance systems. RESULTS: There were a total of 1113 patients with a mean age of 70 years, of whom 913 (82%) patients had an IS and 200 (18%) patients had an ICH. The 317 patients (28%) experienced a recurrent stroke. Patients with ICH had the higher baseline stroke severity, resulting in longer hospitalization (39 days for IS and 46 days for ICH; P<0.001), lower independence rate at discharge (55 and 40%; P<0.001), higher mortality rate (5 and 10%; P=0.03), and higher medical costs (US dollar 8662 and US dollar 10,260; P<0.001) than those with IS. Patients with recurrent stroke had significantly older age, higher stroke severity, and lower independence rate at discharge than those with first-ever stroke. The length of stay, in-hospital mortality, and hospital medical costs were similar among first-ever and recurrent strokes. In subtype of IS, patients with cardioembolic stroke had the worst neurological deficits, poorest outcomes, and highest medical costs. The hospital costs had a greatest association with length of stay. CONCLUSIONS: Stroke care is costly in Japan. ICH is more likely to impose substantial physical and economic burden than IS. Because the cares of both first-ever and recurrent stroke were costly, primary and secondary prevention of stroke is important on the healthcare aspects.

Aged↗
PubMed2004

Periostin as a novel factor responsible for ventricular dilation.

BACKGROUND: Periostin is highly expressed in the myocardium in patients with heart failure. However, no report has documented the function of periostin. To identify the function of periostin in the pathophysiology of heart failure, overexpression or loss of function of the periostin gene was examined by direct transfection into the rat heart. METHODS AND RESULTS: Rats transfected with the periostin gene by the HVJ-liposome method showed left ventricular (LV) dilation as assessed by echocardiography, accompanied by an increase in periostin expression. Consistently significant differences were observed in LV pressure, LV end-diastolic pressure, LV dP/dt(max), and LV dP/dt(min) at 6 and 12 weeks after transfection in rats transfected with the periostin gene, accompanied by a decrease in cardiac myocytes and an increase in collagen deposition. Importantly, periostin has the ability to inhibit the spreading of myocytes and the adhesion of cardiac fibroblasts with or without fibronectin. Markers of cardiac dysfunction such as brain natriuretic peptide and endothelin-1 gene expression were significantly increased after transfection in the LV of rats transfected with the periostin gene. These data demonstrate that overexpression of the periostin gene led to cardiac dysfunction. Thus, we examined the inhibition of periostin in Dahl salt-sensitive rats by an antisense strategy because periostin is highly expressed in heart failure. Importantly, inhibition of periostin gene expression resulted in a significant increase in survival rate, accompanied by an improvement of LV function. CONCLUSIONS: The present study demonstrates the contribution of the periostin gene to cardiac dilation in animal models. Inhibition of periostin might become a new therapeutic target for the treatment of heart failure.

Animals↗
PubMed2004

Long-term prognosis, by stroke subtypes, after a first-ever stroke: a hospital-based study over a 20-year period.

BACKGROUND AND PURPOSE: The influence of stroke subtype on recurrence, and determinants of recurrence-free survival after a first-ever stroke are not fully understood. We aimed to clarify the long-term prognosis by stroke subtypes and to identify determinants for recurrence and death after a first-ever stroke. METHODS: We enrolled 1,732 consecutive patients (men/women = 1,134/598, mean age of 65 years) with a first-ever acute stroke who were admitted to our Stroke Care Unit during a period of 20 years. Stroke subtypes were classified as atherothrombotic brain infarction, lacunar infarction, cardioembolic infarction, other type of infarction, and brain hemorrhage. The prognosis was assessed by stroke subtypes. RESULTS: During the hospital stay (mean 61 days), 99 patients died: 73 died directly from stroke. A total of 198 patients had recurrent strokes, and 286 died within 3 years after the index stroke. The overall recurrence rate within the first year was 6.5%, which was different among stroke subtypes. Patients with cardioembolic infarction (9.0%) as well as other type of infarction (9.1%) had more recurrent strokes within the initial year compared with the other subtypes. A history of transient ischemic attack (relative risk = 1.38), atrial fibrillation (1.52), ischemic heart disease (1.40), and disability at discharge (2.64) were independent predictors for the recurrence and death within 3 years after the first-ever stroke. CONCLUSIONS: The recurrence rate was different among stroke subtypes within 1 year after the index stroke. Atrial fibrillation, ischemic heart disease, history of transient ischemic attack, and disability at discharge were important determinants for stroke recurrence and death.

Acute Disease↗
PubMed2004

Transcriptional regulation of human angiopoietin-2 by transcription factor Ets-1.

Angiopoietin-2 (Ang-2) plays an important role in destabilizing vessels for angiogenesis, however its transcriptional regulation has not been determined. Here we isolated about 3.2kb of the 5' upstream of the human Ang-2 gene and further characterized the transcriptional regulation of Ang-2. We found 10 Ets binding sites (EBSs) in this region. Ets-1 and Ets-2 but not Erg-1 augmented its promoter activity. Sequential deletion of EBSs and mutation analysis revealed that EBS8 located at -416/-406 from the translation initiation site was critical for Ets-1- or Ets-2-stimulated promoter activity. VEGF induced the expression of Ets-1 and Ang-2 in human umbilical vein endothelial cells (HUVECs). Electrophoretic mobility shift and chromatin immunoprecipitation assays showed that Ets-1 bound to EBS8 in HUVECs. Moreover, synthetic double-strand oligonucleotides containing corresponding EBS8 abrogated the induction of Ang-2 by VEGF in HUVECs. These results indicate that Ets-1 and the corresponding EBS are critical for the induction of Ang-2.

Angiopoietin-2↗
PubMed2004

Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis.

Negative feedback is a crucial physiological regulatory mechanism, but no such regulator of angiogenesis has been established. Here we report a novel angiogenesis inhibitor that is induced in endothelial cells (ECs) by angiogenic factors and inhibits angiogenesis in an autocrine manner. We have performed cDNA microarray analysis to survey VEGF-inducible genes in human ECs. We characterized one such gene, KIAA1036, whose function had been uncharacterized. The recombinant protein inhibited migration, proliferation, and network formation by ECs as well as angiogenesis in vivo. This inhibitory effect was selective to ECs, as the protein did not affect the migration of smooth muscle cells or fibroblasts. Specific elimination of the expression of KIAA1036 in ECs restored their responsiveness to a higher concentration of VEGF. The expression of KIAA1036 was selective to ECs, and hypoxia or TNF-alpha abrogated its inducible expression. As this molecule is preferentially expressed in ECs, we designated it "vasohibin." Transfection of Lewis lung carcinoma cells with the vasohibin gene did not affect the proliferation of cancer cells in vitro, but did inhibit tumor growth and tumor angiogenesis in vivo. We propose vasohibin to be an endothelium-derived negative feedback regulator of angiogenesis.

Amino Acid Sequence↗
PubMed2004

Effects of perindopril-based blood pressure lowering and of patient characteristics on the progression of silent brain infarct: the Perindopril Protection against Recurrent Stroke Study (PROGRESS) CT Substudy in Japan.

Controversy persists as to whether reducing the blood pressure of patients with a history of stroke leads to an increased risk of silent brain infarct (SBI) and dementia. A total of 667 patients were randomized to receive the angiotensin-converting enzyme (ACE) inhibitor perindopril (4 mg daily), with or without the diuretic indapamide (2 mg daily) or matching placebo(s). Brain CT scanning was performed annually over the mean follow-up period of 3.9 years. Active treatment reduced the blood pressure (systolic/diastolic) by 5.2/2.6 mmHg over the follow-up period. A total of 119 new SBI were detected and 92% of them were lacunar type small infarcts. The frequency of reaching the primary end-point (recurrent symptomatic stroke or new SBI) was similar in the placebo group (26.5%) and in the active treatment group (25.9%). There was no significant difference in brain atrophy indices between two groups. In the subgroup with a history of large artery infarction, 7 out of 55 patients from the placebo group developed new SBI, while none of the 40 patients from the active treatment group did so (p = 0.020). The baseline diastolic blood pressure was significantly associated with the risk of new SBI (p = 0.004), but the stroke subtype was not. In conclusion, blood pressure-lowering with a perindopril-based regimen did not increase the risk of SBI and brain atrophy in patients with a history of stroke. The baseline diastolic blood pressure was an independent predictor of new SBI, but the index stroke subtype did not influence the risk of SBI.

Aged↗
PubMed2004

[Brain hemorrhage with medical treatment: prediction of early outcome and production of critical paths].

The first purpose of this study was to detect clinical and radiological factors on admission which predict early outcome of patients in brain hemorrhage with medical treatment. For 50 consecutive patients in our Cerebrovascular Center, NIH Stroke Scale score was a useful indicator for prediction of independent daily life, discharge to home, and death in the acute stage; the score < or = 4, < or = 7, and > or = 23 were the most appropriate cut-off values for the above events, respectively. The second purpose of this study was to produce critical paths of medical management for brain hemorrhage based on the above results. We prepared three courses of paths according to clinical severity. As inclusion criteria for each course, we used the above three cut-off values and hematoma volume. Duration of hospitalization of the three courses was 16, 20, and 28 days. When we applied the paths to 200 patients with brain hemorrhage who were enrolled in the research grant supported by the Japanese ministry of health, labor and welfare (12C-10), duration of hospitalization for the majority of the patients were 5 days or more than the planned duration in the paths. It is indispensable to manage acute stroke patients according to critical paths, because standard and efficient strategies of clinical medicine have been stressed these years. We will immediately apply the new paths in this study to patients in our center, and renew them at short intervals. We think that we can contribute to new evidences for standard medical management of brain hemorrhage by our approach to the critical paths.

Activities of Daily Living↗
PubMed2003

Extracorporeal double filtration plasmapheresis in acute atherothrombotic brain infarction caused by major artery occlusive lesion.

Extracorporeal double filtration plasmapheresis (EDFP) can quickly lower plasma viscosity and fibrinogen concentration. EDFP has the potential to improve cerebral microcirculation in acute ischemic stroke and ultimately to salvage penumbral tissue. However, no evidence is available to show that EDFP can increase cerebra blood flow (CBF). Therefore, we investigated whether EDFP could increase CBF by quantitative CBF measurements and documented the clinical effects of EDFP in acute ischemic stroke. EDFP was performed ten times in seven patients diagnosed as having acute atherothrombotic brain infarction caused by major artery occlusive lesion. They also fulfilled one of the following entry criteria: 1) diffusion/perfusion mismatch demonstrated by MRI on admission; 2) a hemispheric syndrome, but only a small lesion on diffusion weighted MRI (<25% of MCA territory); or 3) progressing stroke. Exclusion criteria were 1) contraindication of heparin or 2) spontaneous improvement of symptoms. Time from stroke onset to EDFP varied from 5 hr to 7 days. Plasma viscosity was quickly lowered by EDFP without affecting RBC counts, Hb, or Hct in all patients. Positron emission tomography (PET) with 15-O labeled H2O measurements revealed a significant CBF increase from 36.4 +/- 8.3 ml/100 g/min to 40.7 +/- 6.8 ml/100 g/min in the affected hemisphere (P=0.048). Definite CBF improvement was also demonstrated by single photon emission computed tomography (SPECT) in one of two patients who had severe stenosis of the middle cerebral artery. Furthermore, this patient showed remarkable improvement of hemiplegia immediately following EDFP (NIHSS score: 18 to 13). In conclusion, EDFP can increase CBF in ischemic brain tissue in acute atherothrombotic brain infarction. Further clinical studies should focus on the efficacy of EDFP on outcome of patients with this stroke subtype.

Aged↗
PubMed2003

Cyclooxygenase-2 expression associated with spreading depression in a primate model.

The authors previously provided evidence that spreading depression (SD) can be evoked in primates. Cyclooxygenase-2 (COX-2) expression has been found to increase in the rodent cortex undergoing SD, and the authors sought to determine whether this association exists in primate brain. In the present study, neuronal COX-2 expression was induced during SD in the primate cortex. The mean expression ratio of COX-2 messenger RNA in animals with SD was significantly higher than that measured in controls (1.69 vs. 0.5; P = 0.02). Induction of COX-2 in these animals was also detected by human microarray analysis. Results show that, as in rodents, neuronal COX-2 is induced in the primate cortex in response to SD.

Animals↗
PubMed2003

Topographic distribution of misery perfusion in relation to internal and superficial borderzones.

BACKGROUND AND PURPOSE: Whether misery perfusion (MP) commonly accompanies brain borderzones (BZs) in patients with major cerebral artery occlusion remains unclear. We elucidated topographic patterns of chronic hemodynamic failure in such patients. METHODS: Twenty-four patients with unilateral occlusion or severe stenosis (>75% in diameter) of the internal carotid artery (ICA) or middle cerebral arterial (MCA) trunk with minimal or no infarct underwent PET with (15)O-labeled gas inhalation. Mean cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate of oxygen, oxygen extraction fraction (OEF), and CBV/CBF ratio were determined in the superficial BZs, internal BZ, and MCA territory excluding BZs. Values in BZs were standardized and compared with those in controls. Topographic distributions of regions with OEF greater than that in controls were determined. RESULTS: Values in patients and controls were not significantly different. Topographic distributions included matched perfusion in 10 patients, MP in only the ipsilateral internal BZ in four, MP in both ipsilateral internal and superficial BZs in two, MP in the ipsilateral MCA territory including BZs in one, MP in the ipsilateral MCA territory including BZs and contralateral BZs in two, and MP in the ipsilateral MCA territories including BZs in five. CONCLUSION: Only 25% of the patients had MP localized in affected BZs Although localized MP more frequently accompanied the internal BZ than other regions, no patient had elevated OEF in the superficial BZ alone. These results are inconsistent with clinical observations that 80% of BZ infarctions develop superficially. Thus, hemodynamic mechanisms may not cause most superficial BZ infarctions.

Adult↗