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Biomedical subjects

H Horie

Publications and source records attributed to H Horie.

At least 37 records · Page 2Linked to original sources
PubMed2001

Localization of Shiga toxins of enterohaemorrhagic Escherichia coli in kidneys of paediatric and geriatric patients with fatal haemolytic uraemic syndrome.

Haemolytic uraemic syndrome (HUS) is characterized by haemolytic anaemia, thrombocytopenia and renal failure. Infection with enterohaemorrhagic Escherichia coli (EHEC), mainly O157:H7, has been strongly implicated as the major cause of HUS in children. The pathogenesis of HUS caused by the infection is not well understood and the defined sites of Stx in kidney of EHEC-infected humans has not been clearly demonstrated. The aim of this study was to investigate and compare the locations of Stx deposition in kidneys of paediatric and geriatric patients who died from enterohaemorrhagic E. coli O157 (EHEC) associated HUS, using an immunoperoxidase staining of the tissues. The study revealed that binding of Stx was relatively less and limited only to the renal tubules of an adult case (81 years old), while more binding was found at both renal tubules and glomeruli of an infant case (21 months old). The Stx binding in the infant's glomeruli was at podocytes, mesangial and endothelial cells. It has been known that young children are more susceptible than adults to HUS. One possibility for this is that the more extensive binding of the Stx to the kidney tissue of the paediatric patient might be due to the higher synthesis and expression of Stx receptors, i.e. Gb(3), in infants and less so in the aged individuals. However, other alternatives are possible, for example, the difference in stage of HUS in individual patients. Thus it is too early to draw any conclusion on this enigma and further investigation is required.

Aged↗
PubMed2001

Bradykinin stimulates the release of tissue plasminogen activator in human coronary circulation: effects of angiotensin-converting enzyme inhibitors.

OBJECTIVES: The goal of this study was to determine: 1) whether bradykinin (BK) directly stimulates tissue plasminogen activator (tPA) secretion in human coronary circulation, and 2) whether angiotensin-converting enzyme (ACE) inhibition favorably alters the fibrinolytic balance regulated by BK. BACKGROUND: Bradykinin is a potent stimulator of tPA secretion in endothelial cells; however, the effect of BK on tPA release in the human coronary circulation has not been studied. METHODS: Fifty-six patients with atypical chest pain were randomly assigned to two groups: 25 patients were treated with the ACE inhibitor enalapril (ACE inhibitor group), and 31 were not treated with ACE inhibitors (non-ACE inhibitor group). Graded doses of BK (0.2, 0.6, 2.0 microg/min), acetylcholine (ACh) (30 microg/min) and papaverine (PA) (12 mg) were administered into the left coronary artery. Coronary blood flow (CBF) was evaluated by Doppler flow velocity measurement. Blood samples were taken from the aorta (Ao) and the coronary sinus (CS). RESULTS: Bradykinin induced similar increases in CBF in both groups. The net tPA release induced by BK was dose-dependently increased in both groups, and the extent of that increase in the ACE inhibitor group was greater than that in the non-ACE inhibitor group. Bradykinin did not alter plasminogen activator inhibitor-1 (PAI-1) levels in the Ao or CS in either group. Neither ACh nor PA altered tPA levels or PAI-1 levels in either group. CONCLUSIONS: Intracoronary infusion of BK stimulates tPA release without causing any change in PAI-1 levels in the human coronary circulation. In addition, this effect of BK is augmented by an ACE inhibitor.

Acetylcholine↗
PubMed2001

Coronary vasomotor responses to bradykinin and acetylcholine in patients with coronary spastic angina.

It is unclear whether coronary endothelial function is linked to the pathogenesis of coronary spastic angina (CSA), so the present study examined the coronary vasomotor responses to acetylcholine (ACh) and bradykinin (BK) in 23 patients with CSA, 26 patients with CSA+coronary artery disease (CAD), and 21 control patients. Acetylcholine induced vasospasm of the left coronary artery in all of the patients with CSA, but not in any of the control patients. The changes in dilatation of the left coronary artery in response to bradykinin at doses of 0.2, 0.6 and 2.0 microg/min in the CSA group were significantly greater than those in the other 2 groups. The ratio of epicardial coronary vasodilations induced by BK to those induced by nitroglycerin did not differ among any of the groups. Bradykinin caused a similar increase in coronary blood flow in the control group and CSA group, but had less of an effect in the CSA+CAD group. In conclusion, the vasorelaxing effect of BK was preserved not only in epicardial spasm coronary arteries induced by ACh, but also in resistance coronary arteries distal to the spasm arteries in patients with CSA. The coronary vasodilation response induced by BK may not deteriorate until coronary atherosclerosis advances in patients with CSA.

Acetylcholine↗
PubMed2001

Angiographically documented coronary steal phenomenon evoked by the intracoronary infusion of bradykinin.

While studying flow-dependent coronary dilation using a Doppler flow velocity guidewire, total occlusion of a stenosed segment of the left circumflex artery during the intracoronary infusion of bradykinin was angiographically documented. Total occlusion was not demonstrated during intracoronary infusion of bradykinin after angioplasty. This is angiographic confirmation of the coronary steal phenomenon that has been previously described in the field of stress scintigraphy.

Aged↗
PubMed2001

Frequent deletions and mutations of the beta-catenin gene are associated with overexpression of cyclin D1 and fibronectin and poorly differentiated histology in childhood hepatoblastoma.

Hepatoblastoma (HBL) is the most common malignant liver tumor in young children. Recent reports have shown that the beta-catenin gene was frequently mutated or deleted in HBLS: To elucidate the role of beta-catenin abnormalities in HBLs, we searched for mutations of beta-catenin and APC as well as expression of the target genes, cyclin D1, c-myc, and fibronectin, in 68 primary HBLS: The mutation analysis revealed that 44 (65%) tumors carried missense mutations or deletions of beta-catenin, all of which were somatic and targeted to the exon 3 encoding the amino acid residues involved in its degradation. However, no loss of function mutation of the APC gene was detected by the yeast functional assay. Of interest, beta-catenin mutation was significantly correlated with overexpression of the target genes, cyclin D1 and fibronectin, but not with that of c-myc in HBLs as measured by quantitative real-time reverse transcription-PCR. The immunohistochemical studies in 15 HBLs demonstrated that the nuclear/cytoplasmic accumulation of beta-catenin was positive in 13 tumors, 9 of which had the deletion or mutation of the gene. The significant correlation between the beta-catenin gene abnormality and the positive staining of cyclin D1 was also confirmed. Furthermore, the nuclear accumulation of beta-catenin was strongly associated with the poorly differentiated tumor cell components as well as with the positive staining of cyclin D1 within the tumor. Thus, our present results suggested that the gain of function mutation of beta-catenin played a crucial role in the malignant progression of HBL in vivo.

Adenomatous Polyposis Coli Protein↗
PubMed2001

Progress with inactivated poliovirus vaccines derived from the Sabin strains.

To produce a safe and effective inactivated poliovirus vaccine (IPV), we have developed S-IPV using Vero cells infected with the Sabin strains in a semi-production scale. All production steps including virus culture on microcarrier beads were highly reproducible. Mean recovery percents of infectious viruses or D-antigens during all processes for concentration, purification and inactivation were 30-50% in the three types. The S-IPV potency was adjusted for D-antigen content as determined by in-house ELISA and was comparable to WHO reference IPV derived from the virulent strains in immunogenicity tests in rats. Antibody development in more than 30 seronegative infant volunteers after two shots of S-IPV at four-week interval were 100% without notable adverse reactions. The mean antibody titres (log2) to Sabin 1, 2 and 3 viruses were 11.1, 8.3 and 8.9, respectively. The antibodies neutralized the Mahoney, MEF-1, and Saukett virulent strains with slightly inferior titres to those of the Sabin strains. D-antigens for each type of S-IPV were stable at 4 degrees C without any significant decrease over more than two years.

Adult↗
PubMed2000

Characterisation of vaccine-derived polioviruses isolated from sewage and river water in Japan.

BACKGROUND: A nucleotide change from U to C at position 472 in the 5' non-coding region of the type 3 poliovirus is associated with increased neurovirulence. Moreover, the proportion of type 3 polioviruses containing this mutation (472-C revertants) correlates with the neurovirulence of a particular sample. We used mutant analysis by PCR and restriction-enzyme cleavage (MAPREC) to estimate the neurovirulence of environmental samples obtained from Toyama prefecture, Japan. METHODS: Sewage and river water were collected between October, 1993, and September, 1995, and concentrated samples were inoculated into three different cell types. Isolated type 3 viruses were analysed to determine whether they were derived from the live oral poliovirus vaccine strain; they were then tested for neurovirulence by MAPREC. RESULTS: 29 type 3 strains were isolated--all of which were vaccine-derived. 16 (55%) comprised between 2% and 91% 472-C revertants by MAPREC and were expected to have high neurovirulence. The remaining strains included less than 0.25% revertants, and were regarded as attenuated viruses. Both types were isolated about 3 months after routine oral poliovirus vaccine administrations in May and October. Three strains isolated from river water were of the virulent type. INTERPRETATION: Our results emphasise that there is an environmental risk of vaccine-associated paralytic poliomyelitis as long as live oral poliovirus vaccine is not replaced by inactivated polio vaccine.

DNA, Complementary↗
PubMed2000

Transcardiac extraction of circulating endothelin-1 across the failing heart.

To determine the transcardiac gradient of plasma endothelin-1 (ET-1) in patients with congestive heart failure (CHF), we measured plasma levels of ET-1 in both the aortic root and the coronary sinus in 14 normal subjects and 79 consecutive patients with CHF. In normal subjects, plasma ET-1 was significantly higher in the coronary sinus than in the aortic root; these findings were also shown in patients with mild CHF, suggesting that there was ET-1 spillover across the heart. In contrast, plasma ET-1 was significantly lower in the coronary sinus than in the aortic root in patients with severe CHF, suggesting there was ET-1 extraction across the heart in patients with severe CHF. The transcardiac gradient of plasma ET-1 was correlated with the left ventricular end-diastolic volume index (r = 0.501, p <0.0001) and plasma level of procollagen type III amino terminal peptide in the coronary sinus (r = 0.54, p = 0.0008), a marker of myocardial fibrosis. Stepwise multivariate analysis showed that the transcardiac gradient of plasma ET-1 was an independent and significant relation with the left ventricular end-diastolic volume index in patients with CHF (r = 0.665, p <0.0001). These findings suggest that elevated circulating ET-1 is extracted across the failing heart with a significant correlation between the transcardiac gradient of plasma ET-1 and the left ventricular end-diastolic volume index, suggesting that ET receptors are upregulated in the failing ventricle and that the elevated circulating ET-1 might stimulate the process of left ventricular remodeling in patients with severe CHF.

Angiotensin II↗
PubMed2000

Analysis of tea components by high-performance liquid chromatography and high-performance capillary electrophoresis.

Tea is one of the most popular beverages in the world. The number of reports on the analysis of tea components, especially for catechins, has recently been increasing. We review the recent reports on the analysis of tea components using the analytical methods of high-performance liquid chromatography and high-performance capillary electrophoresis.

Chromatography, High Pressure Liquid↗
PubMed2000

Identification of oxidized galectin-1 as an initial repair regulatory factor after axotomy in peripheral nerves.

Various neurotrophic factors that promote axonal regeneration have been investigated in vivo, but the signals that prompt the axons to send out processes in peripheral nerves after axotomy are not well understood. We have shown using two specific strategies that galectin-1 can play an important role in this initial stage. One used an in vitro nerve regeneration model that allowed us to monitor the initial axon and support cell outgrowth from the proximal nerve stump comparable to the initial stages of nerve repair. The other strategy was to clarify the axonal regeneration-promoting factor from kidney-derived cells. Using these strategies, we discovered that oxidized galectin-1 from the cell (COS1 cell) conditioned media acts as an axonal regeneration-promoting factor without the lectin activity. Oxidized recombinant human galectin-1 (rhGAL-1/Ox) showed the same activity at low concentrations (pg/ml range). A similarly low concentration also effectively promoted axonal regeneration in both transection and crush experiments in vivo. Moreover, the application of functional anti-galectin-1 antibody strongly inhibited the regeneration in vivo. Since galectin-1was shown to be secreted and localized in the regenerating sciatic nerve, this suggests that secreted galectin-1 may be oxidized and change its molecular structure to regulate initial repair after axotomy as a kind of cytokine.

Animals↗
PubMed2000

Spironolactone inhibits the transcardiac extraction of aldosterone in patients with congestive heart failure.

OBJECTIVES: The study evaluated the transcardiac extraction or spillover of aldosterone (ALDO) in normal subjects and in patients with congestive heart failure (CHF). BACKGROUND: Aldosterone promotes collagen synthesis and structural remodeling of target organs such as the heart. Spironolactone, an ALDO receptor antagonist, has recently been reported to reduce the mortality of patients with CHF; however, the effects of spironolactone on the transcardiac gradient of ALDO have not been clarified. METHODS: We measured plasma ALDO in the aortic root (AO) and coronary sinus (CS) in normal subjects and 113 consecutive CHF patients and also measured plasma procollagen type III aminoterminal peptide (PIIINP) in CS, a biochemical marker of myocardial fibrosis. RESULTS: Plasma ALDO was significantly lower in the CS than in the AO in normal subjects (n = 15; 61.2 +/- 9.3 vs. 83.1 +/- 11.8 pg/ml, p < 0.0001). In 96 CHF patients who did not receive spironolactone, plasma ALDO was significantly lower in the CS than in the AO (59.3 +/- 3.9 vs. 73.8 +/- 4.9 pg/ml, p < 0.0001). In contrast to the difference in these 96 patients, there was no significant difference in ALDO between the AO and CS in 17 patients who received spironolactone (127.4 +/- 20 vs. 124.0 +/- 19 pg/ml, p = 0.50). Stepwise multivariate analyses showed that spironolactone therapy had an independent and significant negative relationship with the transcardiac gradient of plasma ALDO in patients with CHF. In addition, significant positive correlations were seen between the transcardiac gradient of plasma ALDO and PIIINP (r = 0.565, p < 0.0001) and the left ventricular end-diastolic volume index (r = 0.484, p < 0.0001). CONCLUSIONS: These results indicate that plasma ALDO is extracted through the heart in normal subjects and in CHF patients who do not receive spironolactone and that spironolactone inhibits the transcardiac extraction of ALDO in CHF patients, suggesting that spironolactone blocks the effects of ALDO on the failing heart in patients with CHF.

Adolescent↗
PubMed2000

Oxidized galectin-1 promotes axonal regeneration in peripheral nerves but does not possess lectin properties.

Galectin-1 has recently been identified as a factor that regulates initial axonal growth in peripheral nerves after axotomy. Although galectin-1 is a well-known beta-galactoside-binding lectin, its potential to promote axonal regeneration as a lectin has not been reported. It is essential that the process of initial repair in peripheral nerves after axotomy is well clarified. We therefore undertook to investigate the relation between the structure and axonal regeneration-promoting activity of galectin-1. Recombinant human galectin-1 secreted into the culture supernatant of transfected COS1 cells (rhGAL-1/COS1) was purified under nonreducing conditions and subjected to structural analysis. Mass spectrometric analysis of peptide fragments from rhGAL-1/COS1 revealed that the secreted protein exists as an oxidized form containing three intramolecular disulfide bonds (Cys2-Cys130, Cys16-Cys88 and Cys42-Cys60). Recombinant human galectin-1 (rhGAL-1) and a galectin-1 mutant in which all six cysteine residues were replaced by serine (CSGAL-1) were expressed in and purified from Escherichia coli for further analysis; the purified rhGAL-1 was subjected to oxidation, which induced the same pattern of disulfide linkages as that observed in rhGAL-1/COS1. Oxidized rhGAL-1 enhanced axonal regeneration from the transected nerve sites of adult rat dorsal root ganglion explants with associated nerve stumps (5.0-5000 pg. mL-1), but it lacked lectin activity. In contrast, CSGAL-1 induced hemagglutination of rabbit erythrocytes but lacked axonal regeneration-promoting activity. These results indicate that galectin-1 promotes axonal regeneration only in the oxidized form containing three intramolecular disulfide bonds, not in the reduced form which exhibits lectin activity.

Animals↗
PubMed2000

Expression of tumor necrosis factor-alpha protein in the myocardium in fatal myocarditis.

BACKGROUND: Tumor necrosis factor (TNF)-alpha is the most studied cytokine in the failing human heart and in experimental murine myocarditis. We have investigated the expression of TNF-alpha in the myocardium in human myocarditis. METHODS: We examined endomyocardial biopsy (n = 4) and autopsy (n = 5) tissues obtained from nine patients diagnosed with myocarditis by the Dallas criteria. Expression of TNF-alpha in the hearts was immunohistochemically studied using monoclonal antibodies against human TNF-alpha. RESULTS: Tumor necrosis factor-alpha protein was expressed in the myocardium of six of the nine patients studied. Four of five fatal patients showed intense immunoreactivity for TNF-alpha compared with survivors. Furthermore, left ventricular systolic function was reduced in patients with TNF-alpha-positive hearts. CONCLUSIONS: These findings may support the suggestion that TNF-alpha plays an important role in cardiac dysfunction and myocytic damage in fatal human myocarditis.

Adult↗
PubMed2000

Effects of intravenous nicorandil on coronary circulation in humans: plasma concentration and action mechanism.

We investigated the cardiovascular profile of nicorandil, an antianginal agent, in humans. Pharmacologically, nicorandil acts as both an adenosine triphosphate (ATP)-sensitive K+ (K(ATP)) channel opener and a nitrate. We examined which of these mechanistic components has a predominant vasodilatory effect at clinical doses. Fourteen patients underwent cardiac catheterization. The effects of the continuous intravenous infusion of nicorandil (12 mg/45 min) were examined in angiographically normal coronary arteries. Coronary vascular resistance was calculated from coronary artery diameter and coronary blood flow velocity measured using an intravascular Doppler catheter. We compared the hemodynamic responses to nicorandil with those to the intracoronary injection of nitroglycerin (250 microg) and papaverine (12 mg). The epicardial coronary arteries responded to nicorandil at the lowest plasma concentration examined (dilation of +14.0 +/- 3.3% at approximately 170 ng/ml), whereas dilation of the coronary resistance arteries (i.e., a decrease in coronary vascular resistance) took place only at higher concentrations (>200 ng/ml). Nitroglycerin caused no further changes in coronary artery diameter or coronary vascular resistance. Papaverine caused no further increase in coronary artery diameter, but markedly decreased coronary vascular resistance (1.6 +/- 0.3 to 0.4 +/- 0.1 mm Hg/ml/min; p < 0.05). Nicorandil significantly decreased pulmonary capillary wedge pressure (i.e., reduced cardiac preload) at a plasma level of >200 ng/ml, but did not change either systemic or pulmonary vascular resistance. Thus nicorandil preferentially dilated epicardial coronary arteries rather than coronary resistance arteries, and had a stronger effect on preload than on afterload. These changes in human coronary hemodynamics suggest that the nitrate actions of nicorandil as a coronary vasodilator predominate over those as a K(ATP) opener.

Adult↗
PubMed2000

Assessment of poliovirus eradication in Japan: genomic analysis of polioviruses isolated from river water and sewage in toyama prefecture.

Seventy-eight poliovirus strains isolated from river water and sewage in Toyama Prefecture, Japan, during 1993 to 1995 were characterized by the PCR-restriction fragment length polymorphism (RFLP) method and by partially sequencing the VP3 and VP1 regions of the viral genome. Of these isolates, 36 were identified as Sabin vaccine strains, and 42 were identified as vaccine variant strains that had less than 1.4% nucleotide divergence from the Sabin strains, including 7 isolates with patterns different from those of Sabin strains as determined by PCR-RFLP analysis. These findings suggest that wild-type poliovirus was not circulating in Toyama Prefecture.

Fresh Water↗
PubMed2000

Brain natriuretic peptide predicts chronic atrial fibrillation after ventricular pacing in patients with sick sinus syndrome.

Chronic atrial fibrillation (AF) is one of the main complications of sick sinus syndrome (SSS). As previously reported, plasma brain natriuretic peptide (BNP), reflects hemodynamic changes in different pacing modes, as does plasma atrial natriuretic peptide (ANP), so the present study investigated whether plasma BNP or ANP can predict chronic AF after single-chamber ventricular (VVI) pacemaker implantation in patients with SSS. Plasma ANP and BNP levels were measured before and 1-3 months after implantation in 99 SSS patients. Long-term follow-up was conducted with chronic AF as an endpoint. Chronic AF occurred in 19 patients during a mean follow-up of 5.1 years. Plasma ANP and BNP were significantly higher in the patients who developed chronic AF after implantation than in those who did not, despite similar ANP and BNP levels between the 2 groups before implantation. Post-implant high BNP and a history of paroxysmal AF were independent predictors of chronic AF by a multivariate Cox proportional hazards analysis. Plasma BNP can predict the development of chronic AF after VVI pacemaker implantation in patients with SSS because increased levels may reflect latent hemodynamic abnormalities, which may contribute to the development of AF after VVI pacemaker implantation.

Actuarial Analysis↗