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Biomedical subjects

K Harada

Publications and source records attributed to K Harada.

At least 325 records · Page 18Linked to original sources
PubMed1998

Cerebral blood flow and metabolism in multiple system atrophy of the Shy-Drager syndrome type: a PET study.

To investigate the role of the autonomic nervous system in cerebral blood flow (CBF) and metabolism, CBF and oxygen metabolism in patients with multiple system atrophy of the Shy-Drager syndrome type were examined. Seven patients with Shy-Drager syndrome were imaged using positron emission tomography and 15O-labeled gases. There was excellent local coupling between CBF and the cerebral metabolic rate of oxygen in the resting state. Elevation of blood pressure induced by leg raising increased CBF. The inhalation of CO2 also increased CBF in the Shy-Drager patients. These results showed that autoregulation is impaired in Shy-Drager syndrome, but local metabolic-flow coupling in the resting state and the CBF response to CO2 inhalation are spared. We conclude that the autonomic nervous system plays an important role in autoregulation, but not in local metabolic-flow coupling in the resting state. We suggest that metabolic mechanisms may mediate resting metabolic-flow coupling.

Aged↗
PubMed1998

Pressure overload induces cardiac hypertrophy in angiotensin II type 1A receptor knockout mice.

BACKGROUND: Many studies have suggested that the renin-angiotensin system plays an important role in the development of pressure overload-induced cardiac hypertrophy. Moreover, it has been reported that pressure overload-induced cardiac hypertrophy is completely prevented by ACE inhibitors in vivo and that the stored angiotensin II (Ang II) is released from cardiac myocytes in response to mechanical stretch and induces cardiomyocyte hypertrophy through the Ang II type 1 receptor (AT1) in vitro. These results suggest that the AT1-mediated signaling is critical for the development of mechanical stress-induced cardiac hypertrophy. METHODS AND RESULTS: To determine whether AT1-mediated signaling is indispensable for the development of pressure overload-induced cardiac hypertrophy, pressure overload was produced by constricting the abdominal aorta of AT1A knockout (KO) mice. Quantitative reverse transcriptase-polymerase chain reaction revealed that the cardiac AT1 (probably AT1B) mRNA levels in AT1A KO mice were <10% of those of wild-type (WT) mice and were not affected by pressure overload. Chronic treatment with subpressor doses of Ang II increased left ventricular mass in WT mice but not in KO mice. Pressure overload, however, fully induced cardiac hypertrophy in KO as well as WT mice. There were no significant differences between WT and KO mice in expression levels of fetal-type cardiac genes, in the left ventricular wall thickness and systolic function as revealed by the transthoracic echocardiogram, or in the histological changes such as myocyte hypertrophy and fibrosis. CONCLUSIONS: AT1-mediated Ang II signaling is not essential for the development of pressure overload-induced cardiac hypertrophy.

Angiotensin II↗
PubMed1998

Maturational changes in left ventricular contractile state.

It has been suggested from animal and human studies that age-related alterations in left ventricular contractility occur. However, there is little information about growth-related changes in left ventricular performance from preterm infants to older children. In 22 preterm infants, 23 fullterm infants, and 35 children, left ventricular contractility was evaluated by two-dimensional and M-mode echocardiography. The rate-corrected mean velocity of fiber shortening (mVcfc)-end-systolic wall stress (ESS) relation was used as an index of contractility. There were significant inverse linear correlations between ESS and mVcfc in the three groups (all P<0.01). The slopes and y-intercepts of the regression lines of mVcfc-ESS relation were both significantly greater in the premature infants (mVcfc=-0.0133 ESS+1.62) and neonates (mVcfc=-0.0107 ESS+1.55) than those in the children (mVcfc=-0.0047+1.29). However, there were no significant differences between the premature and fullterm infants. Thus, these findings suggest that the contractility and afterload sensitivity of the left ventricle in the premature infants may be similar to those in the fullterm infants. In addition, our serial study in the premature infants showed that the ESS increased significantly with growth while the mVcfc did not change, suggesting that the left ventricular performance in the premature infants during early life was preserved in the setting of a lower afterload.

Analysis of Variance↗
PubMed1998

Effect of continuous infusion of vasopressin on glomerular growth response in spontaneously hypertensive rats.

Vasopressin (VP) is thought to play an important role in the pressor and proliferative responses of renal glomeruli. We have utilized the spontaneously hypertensive rat (SHR) model to determine if glomerular proliferation is induced by chronic infusion of exogenous VP. SHR were continuously infused with 0.1 ng/kg/min VP (H-VP group), 1.0 ng/kg/min (H-VP group), or vehicle alone (control group) for fifteen days using osmotic minipumps, and the histological alterations and level of expression of platelet-derived growth factor B-chain (PDGF-B) and transforming growth factor (TGF)-beta1 mRNA were determined. We observed no significant differences in systolic blood pressure, heart rate, serum electrolytes, protein and creatinine among the three groups of rats, but urine volume was found to be significantly decreased, and urine osmolality significantly increased, in the H-VP group. Kidney weight was significantly higher in the H-VP and L-VP groups than in the control group, and glomerular diameter was higher in the H-VP group. When we measured mesangial injury score and cellularity in the glomeruli of these animals, we observed VP dose-dependent proliferative changes. In the immunofluorescence study, although we did not find an obvious difference in depositions of collagen types III, IV and VI, alpha-smooth muscle actin and PDGF-B among the groups, the collagen type I and TGF-beta1 increased in several glomeruli in the H-VP group. Reverse transcription polymerase chain reaction (RT-PCR) revealed no significant differences in the glomerular levels of PDGF-B mRNA among the three groups of rats, but the level of expression of TGF-beta1 mRNA was significantly higher in the L-VP and H-VP groups than in the control group. These findings suggest that VP may contribute to glomerular proliferation, and that VP may exert its effects in part through the induction of TGF-beta1 expression. These results also raise the possibility that blockade of VP receptors may be useful in the treatment of some forms of glomerular disease.

Animals↗
PubMed1998

Acute pressure overload could induce hypertrophic responses in the heart of angiotensin II type 1a knockout mice.

Increasing evidence has suggested that locally produced angiotensin II (Ang II) plays an important role in the development of cardiac hypertrophy through the Ang II type 1 receptor (AT1). We and others have recently reported that Ang II is critical for mechanical stress-induced hypertrophic responses in vitro. Using AT1a knockout (KO) mice, we examined whether Ang II is indispensable for pressure overload-induced cardiac hypertrophy in the present study. Reverse-transcriptase polymerase chain reaction analysis revealed that AT1 mRNA levels were <10% in the heart of KO mice compared with wild-type (WT) mice, but the Ang II type 2 receptor gene was expressed at almost the same levels in the hearts of both mice. Intravenous infusion of subpressor dose of Ang II induced c-fos gene expression in the hearts of WT mice but not KO mice. Acute pressure overload, however, induced expressions of immediate-early response genes and activations of mitogen-activated protein kinases in the hearts of KO mice as well as WT mice. Both basal and activated levels of all these responses were significantly higher in KO mice than in WT mice. Pressure overload markedly increased the heart weight-to-body weight ratio in both mice strains at 14 days after aortic banding. These results suggest that acute hypertrophic responses could be induced by pressure overload in the in vivo heart without AT1 signaling.

Angiotensin II↗
PubMed1998

Angiotensin II type 1a receptor is involved in the occurrence of reperfusion arrhythmias.

BACKGROUND: A growing body of evidence has suggested that the renin-angiotensin system plays an important role in the development of cardiac hypertrophy induced by hemodynamic overload and left ventricular remodeling after myocardial infarction. The role of the renin-angiotensin system in ischemia-reperfusion (IR) injury, however, has not been established. METHODS AND RESULTS: To determine the role of angiotensin II (Ang II) in IR injury, we examined infarct size and arrhythmias after IR using Ang II type 1a receptor (AT1a) knockout mice. The left coronary artery was occluded for 30 minutes followed by reperfusion for 120 minutes. There were no significant differences in infarct size between wild-type and knockout mice determined by dual staining with triphenyltetrazolium chloride and Evans blue dye. The number of ventricular premature beats after reperfusion in knockout mice, however, was much less than in wild-type mice. Treatment with a selective AT1 antagonist, CV-11974, before ischemia blocked reperfusion arrhythmias in wild-type mice but had no effects on infarct size. CONCLUSIONS: Ang II may be critically involved in the induction of ventricular arrhythmias but not in the determination of infarct size after IR.

Angiotensin Receptor Antagonists↗
PubMed1998

Changes in superior vena cava velocity patterns in normal neonates.

We demonstrated serial changes in the flow velocity patterns of both the superior vena cava and the tricuspid flow velocity patterns during the first day of life. These changes in waveforms may be related to alterations in loading conditions induced by the closing process of the ductus arteriosus.

Blood Flow Velocity↗
PubMed1998

Age-related changes in the activation of aortic cholesteryl ester hydrolases by protein kinases in rats.

Age-related changes in the activities of acid and neutral cholesteryl ester hydrolases (ACEH and NCEH) and their activation by protein kinase A (PKA) and also by protein kinase C (PKC) were examined in the aortae of 4-, 8-, 12- and 20-week-old rats in relation to their aortic lipid and lipid peroxides and lipid contents. The physiological basal activity as well as total activities of the ACEH and NCEH activated by the two kinases, which were high in the aortae of the 4- and 8-week-old rats, decreased gradually with increasing age to about 40% (ACEH) and 50% (NCEH) by 20 weeks of age. The vitamin E intake and ad libitum-diet intake of the rats each modified the age-related decline of CEH activities. The aortic PKA and PKC activities were reflected by the CEH activities to some degree. The in vitro exposure of the aortic CEH to active oxygen (AO) generators revealed the PKC-mediated activation of CEH, which was inhibited by superoxide dismutase and catalase. These results suggested that the activities of ACEH and NCEH and their regulatory enzymes may be modulated by the dual effect of endogenous AO; an activation of CEH at low doses and an inactivation at high doses, or upon a long-term exposure in aging to a low level of endogenous AO.

Aging↗
PubMed1998

Role of left ventricular mass/volume ratio on transmitral flow velocity patterns from infancy to childhood.

Age-related changes in left ventricular diastolic filling have been reported to occur in normal children in studies using Doppler echocardiographic methods. However, little information currently exists on the relationships between transmitral flow velocity patterns and the left ventricular mass. We measured left ventricular end-diastolic volume, left ventricular mass, mass/volume ratio, and transmitral flow velocity patterns by M-mode and Doppler echocardiography in 165 normal children aged 5 days to 195 months. Subjects were divided into 6 age groups: <1; 1 to <3; 3 to <5; 5 to <7; 7 to <9; and > or = 9 years old. The left ventricular end-diastolic volume and mass increased progressively with increasing age. However, the mass/volume ratio in infants <1 year was significantly higher than that in infants 1 to <3 years (1.32+/-0.25 vs. 1.14+/-0.16, p<0.01) without any changes of the ratio thereafter. The peak E wave in infants <1 year was significantly lower than that in 1 to <3 years (71+/-18 vs. 92+/-13 cm/s, p<0.01) without changes thereafter. As the flow velocity time integral of E wave increased and that of A wave remained constant, the flow velocity time integral of E/A wave increased with increasing age. The early diastolic tilling fraction in infants <1 year was lower than that in infants 1 to 3 years. (0.61+/-0.07 vs. 0.70+/-0.06, p<0.01). The atrial filling fraction in infants <1 year was higher than that in infants 1 to <3 years (0.40+/-0.08 vs. 0.30+/-0.06, p<0.01) with a little decrease thereafter. The peak E wave, early diastolic tilling fraction, and the atrial filling fraction correlated with the logarithm of age (p<0.01). Age-related changes in these Doppler echocardiographic findings suggest reduced left ventricular early diastolic filling patterns. The mass/volume ratio correlated linearly with peak E wave, early diastolic filling fraction, and atrial filling fraction (r=-0.38, -0.33, and 0.26, p<0.01). No significant relationships between mass/volume ratio and the other Doppler indices were found. Thus, the age-related reduction in the mass/volume ratio may be one of the mechanisms underlying age-related changes in the early diastolic ventricular filling as assessed by Doppler echocardiography.

Aging↗
PubMed1998

Expression of co-stimulatory factor B7-2 on the intrahepatic bile ducts in primary biliary cirrhosis and primary sclerosing cholangitis: an immunohistochemical study.

Co-stimulatory factors B7-1 (CD80) and B7-2 (CD86) and their ligands, including CD28, are important for the efficient presentation and persistence of an antigen-specific immune reaction. Hitherto, there has been a paucity of data on the roles of such co-stimulatory factors in immune-mediated biliary diseases. In this investigation, the hepatic immunohistochemical expression of B7-1 and B7-2 has been studied, with emphasis on intrahepatic biliary epithelia, using wedge biopsies from 22 patients with primary biliary cirrhosis (PBC), seven with primary sclerosing cholagitis (PSC), and, as controls, eight cases of extrahepatic biliary obstruction, eight of chronic viral hepatitis C, and three histologically normal livers. In 10/22 (45 per cent) patients with PBC and 3/7 (43 per cent) patients with PSC, B7-2, but not B7-1, was expressed on the epithelial cells of small intrahepatic bile ducts and bile ductules. This expression was manifest as diffuse but variable cytoplasmic staining. Such B7-2-positive bile ducts were not seen in controls. Positive staining was found only in the early stage of PBC and PSC. In PBC and PSC, almost all lymphocytes in the portal tracts, including those around the damaged bile ducts, were positive for CD28, a ligand of B7-2. These results suggest that B7-2 expression on biliary epithelial cells is involved in antigen presentation and perhaps in bile duct destruction in PSC and PBC.

Antigens, CD↗
PubMed1998

Investigation of genetic alterations associated with the grade of astrocytic tumor by comparative genomic hybridization.

Comparative genomic hybridization (CGH) is a technique that allows the detection of losses and gains in DNA copy number across the entire genome. We used CGH to study the genetic alterations that occur in primary astrocytomas, including 14 glioblastomas (GBM), 12 anaplastic astrocytomas (AA), and 7 low-grade astrocytomas (LGA). The average numbers of total aberrations in GBM, AA, and LGA were 9.7, 5.4, and 4.0, respectively. The average number of DNA sequence losses in GBM was significantly higher than that in AA or LGA (P < 0.01). Frequently altered regions (> eight cases) observed in all grades of astrocytoma were 7p13-p12 (gain), 7q31 (gain), 8q24.1-q24.2 (gain), 9p21 (loss), 10p12-p11 (loss), 10q22-qter (loss), 13q21-q22 (loss), and 20q13.1-q13.2 (gain). Loss of 9p, 10p, or 10q, and the gain or amplification of 7p, were observed frequently in GBM (64%, 57%, 64%, and 50% of cases, respectively). Frequent alterations found in AA were losses of 9p, 10q, and 13q, and gains of 1q, chromosome 7, 11q, and Xq. Whereas 7p13-p11 amplification occurred exclusively in cases with the loss of all or part of chromosome 10, this change never occurred in cases having an increase in copy number of 8q, which was the most frequent change observed in LGA (four of seven cases). These results may indicate that an increase in copy number of 8q is an important event in GBM, with a genetic pathway, which is distinct from that in GBM with 7p amplification.

Adult↗
PubMed1998

Increased CD1d expression on small bile duct epithelium and epithelioid granuloma in livers in primary biliary cirrhosis.

Cluster of differentiation 1 (CD1) is a family of four distinct nonpolymorphic major histocompatibility complex class I-like molecules that can present microbial nonpeptide lipid antigens to T cells. Among the CD1 gene family, CD1d is found in a wide range of tissues including the intestine and liver, and has been proposed to play an important role in mucosal immunity. Primary biliary cirrhosis (PBC) is an immune-mediated liver disease involving the intrahepatic small bile ducts, which also belong to the mucosal immune system. In this study, we studied the expression of CD1d in patients with PBC and compared the data with those of patients with hepatic sarcoidosis, primary sclerosing cholangitis (PSC), chronic viral hepatitis (CVH), and normal liver as controls. CD1d was found to be expressed in hepatocytes in all cases examined, and in epithelioid granuloma cells in 19 of 22 PBC livers and in 4 of 4 livers with hepatic sarcoidosis. In addition, CD1d was focally expressed on epithelial cells of the small bile ducts in approximately 50% of the PBC patients but in no controls. Such bile duct epithelial staining of CD1d was seen in early-stage PBC and virtually absent in late-stage PBC. Moreover, there was no evidence of expression of CD1d in large bile duct epithelial cells of PBC. The CD1d on biliary epithelial cells in PBC may be involved in the antigen presentation of microbial lipid antigen(s) to surrounding T cells. Alternatively, modified endogenous lipidic compounds may share analogy with bacterial lipid antigens and explain CD1d expression, a possible epiphenomenon rather than a proof of bacterial involvement.

Adult↗
PubMed1998

An infant with hypereosinophilic syndrome and heart failure markedly responded to prednisolone: serial changes of left ventricular wall thickening and left ventricular diastolic dysfunction observed by echocardiography.

We encountered an infant with congestive heart failure due to idiopathic hypereosinophilic syndrome. The patient showed marked thickening of the left ventricular wall and left ventricular diastolic dysfunction, both of which, shortly after prednisolone therapy, markedly improved together with improvement of the congestive heart failure and hypereosinophilia. Observation of pulmonary venous flow patterns detected by pulsed Doppler echocardiography may be useful for evaluation of left ventricular diastolic function.

Echocardiography, Doppler, Pulsed↗
PubMed1998

Comparison of venodilatory effect of nicardipine, diltiazem, and verapamil in human subjects.

OBJECTIVE: Venodilatory effects of calcium antagonists have not been fully investigated, especially in human subjects. The present study was undertaken to compare the direct venodilatory effects of nicardipine, diltiazem and verapamil using the dorsal hand-vein technique. METHODS: In eight healthy male subjects, increasing doses (0.001, 0.01, 0.1, 1 and 10 microg x min(-1)) of these drugs and saline alone were infused, on four separate occasions, into the dorsal hand vein preconstricted with noradrenaline, and its diameter was measured by a linear-variable differential transformer. RESULT AND CONCLUSIONS: Diltiazem caused significant venodilation at a dose of 0.01 microg x min(-1) or more, while verapamil and nicardipine only caused this effect at 1 microg x min(-1) or more. The potency of the effect was diltiazem > verapamil > nicardipine. The venodilation at a dose of 1 microg x min(-1) was 41.7%, 16.2% and 8.5%, respectively, for each drug. These findings indicate that the venodilatory effect of diltiazem is larger than that of verapamil and nicardipine in human subjects.

Adult↗
PubMed1998

Effects of dopamine on veins in humans: comparison with noradrenaline and influence of age.

OBJECTIVE: To compare the venoconstricting effect of dopamine with that of noradrenaline and to investigate the influence of age on the responsiveness to dopamine in human subjects. METHODS: In eight young and eight elderly male subjects, increasing doses of dopamine or noradrenaline were infused into a dorsal hand vein and its diameter was measured using a linear variable differential transformer. RESULTS: There was no significant difference between the maximum venoconstriction (Emax) for dopamine and that for noradrenaline. The infusion rate to induce 50% of Emax (ED50) for dopamine in the young and elderly subjects was 363 ng x min(-1) and 352 ng min(-1), and the ED50 for noradrenaline was 40.7 ng min(-1) and 43.8 ng x min(-1), respectively. Neither in the Emax nor in the ED50 for these drugs were there significant differences between the young and elderly subjects. CONCLUSION: The venoconstricting effect of dopamine is 5-20 times less than that of noradrenaline, and aging does not influence the responsiveness to dopamine and noradrenaline in human subjects.

Adult↗
PubMed1998

Characteristic MR features of encephalitis caused by Epstein-Barr virus: a case report.

An 8-year-old girl showed symptoms of encephalitis during acute Epstein-Barr virus (EBV) infection. The diagnosis of EB virus infection was made by changes in the titres of EB virus-specific antibody. Cranial MRI demonstrated abnormal low and high signal intensities in the striatal body (putamen and caudate nucleus) on T1-weighted and T2-weighted images, respectively, during the acute phase. These abnormal findings had almost completely resolved 1 month later. EBV infection should be considered when lesions are localised to the basal ganglia.

Caudate Nucleus↗