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Biomedical subjects

H Izawa

Publications and source records attributed to H Izawa.

At least 19 recordsLinked to original sources
PubMed2003

Combined study with FDG PET and Tl SPECT in patients with idiopathic dilated cardiomyopathy.

This study aimed to determine whether combined examinations of myocardial 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) and stress-redistribution 201Tl single-photon emission computed tomography (Tl SPECT) were useful in clarifying myocardial ischaemia and evaluating the prognosis in patients with idiopathic dilated cardiomyopathy (IDCM). Twenty-two patients with IDCM underwent echocardiography, cardiac catheterization, FDG PET, and Tl SPECT. In scintigraphic analysis, the total defect score (TDS) was semiquantitatively determined as the sum of scores of the 17 left ventricular (LV) segments with a 5-point scale (0 as normal to 4 as absent). Patients were classified according to the scintigraphic findings as follows: eight patients with small defects on Tl and FDG (TDS < or = 20) (group I), eight patients with small defects on FDG (TDS < or = 20) with FDG uptake increased relative to Tl or 'mismatch' (group II), and six patients with large defects on FDG and Tl (TDS >20) (group III). Eleven patients (50%) showed reversible defects on Tl and all showed preserved FDG uptake. The patients in group III had significantly lower LV ejection fraction (LVEF) (P<0.05, respectively) and a poorer prognosis as shown by the Kaplan-Meier event-free curve compared with those in groups I and II (P<0.01, respectively). Although patients in group II had significantly greater TDS on Tl compared with those in group I (P<0.01), no significant differences in LVEF and prognosis were found between patients in groups I and II. In multivariate analysis, a TDS on FDG revealed an independent predictor of subsequent cardiac events. In conclusion, such mismatched areas can be assumed to consist of impaired but viable myocardium, and may be associated with ischaemia of the microvasculature. Impaired myocardial glucose metabolism is a more powerful predictor of future cardiac events than perfusion abnormality in patients with IDCM.

Age Factors↗
PubMed2001

Syntheses and properties of ditelluroxanes and oligochalcogenoxanes: hypervalent oligomers with Te-O apical linkages in the main chain.

The reaction of ditelluroxanes [Ar2Te-O-TeAr]2+[X]2- (2) (Ar = p-tolyl) with a telluroxide 1, a selenoxide 7, or a carboxylate 10 to produce oligochalcogenoxanes with hypervalent Te-O apical linkages in their main chain is described. The 125Te NMR chemical shifts of 2 (2a: X- = CF3SO3-, 2b: X- = CF3CO2-, 2c: X- = CH3CO2-, 2d: X- = Cl-) are shifted downfield with decreasing nucleophilicity of the counteranions. This result reflects both the cationic character and the reactivity of the Te atoms of 2. The reaction of 2a with one, two, three, or four equivalents of telluroxide 1a (Ar = p-tolyl) selectively gave a tritelluroxane 3a, tetratelluroxane 4a, pentatelluroxane 5a, and hexatelluroxane 6a, respectively. In contrast, the reaction of 2b with an excess of 1a produced only tritelluroxane 3b. An equilibrium between the oligotelluroxanes was confirmed by crossover experiments of the reactions of 2a with 4a and of 2a with 1b (Ar = Ph). The selective equilibrium formation of a selenoxaditelluroxane 8 or a bis(selenoxa)ditelluroxane 9 was achieved by the reaction of 2a with one or two equivalents of selenoxide 7, respectively. The association constant of 2a with 7 to form 8 was estimated to be Ka = (2.18+/-0.12) x 10(4) M(-1) in CD3CN at -40 degrees C. The reaction of 2a with two equivalents of carboxylates 10a-d gave a mixture of bis(carboxylate)ditelluroxanes and diaryldicarboxytelluranes 12b-d, respectively, in which the product ratio of these depended upon the electron-withdrawing ability of 10. The reaction of 3a with two equivalents of 10a-d afforded 11a-d in all cases. The present results suggest that the sigma*-n orbital interaction plays an essential role in the reactivity of ditelluroxanes and in the formation of self-assembled oligochalcogenoxanes, and that a hypervalent bond via a sigma*-n orbital interaction is viable as a new supramolecular synthon for molecular assembly.

Journal Article↗
PubMed2001

Reduced myocardial sarcoplasmic reticulum Ca(2+)-ATPase mRNA expression and biphasic force-frequency relations in patients with hypertrophic cardiomyopathy.

BACKGROUND: The relationship between left ventricular (LV) contractile functional reserve and gene expression of Ca(2+)-handling proteins in patients with hypertrophic cardiomyopathy (HCM) remains to be clarified. METHODS AND RESULTS: We calculated the maximum first derivative of LV pressure (LV dP/dt(max)) and the LV pressure half-time (T(1/2)) during pacing in 14 patients with nonobstructive HCM (LV ejection fraction >55%) and 7 control subjects. Endomyocardial tissue was obtained, and mRNA levels of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2), ryanodine receptor-2, phospholamban, calsequestrin, and Na(+)/Ca(2+) exchanger were quantified by use of a real-time quantitative reverse transcription-polymerase chain reaction method. Group A consisted of 7 HCM patients who showed a progressive rise in the LV dP/dt(max) with increased heart rate. Group B consisted of 7 HCM patients in whom the heart rate-LV dP/dt(max) relation was biphasic at physiological pacing rates. Both the mean maximal wall thickness and the LV hypertrophy score in group B were greater than in group A (20+/-5 versus 15+/-3 mm and 7+/-1 versus 5+/-2 points, respectively). SERCA2 mRNA levels were significantly lower in group B (SERCA2/GAPDH ratio 0.34+/-0.15) compared with group A (0.72+/-0.27) and control subjects (0.85+/-0.47), whereas the mRNA expression of ryanodine receptor-2, phospholamban, calsequestrin, and Na(+)/Ca(2+) exchanger were similar in all groups. CONCLUSIONS: These results suggest that downregulation of SERCA2 mRNA, resulting in altered Ca(2+) handling, may contribute to impaired LV contractile reserve in HCM patients with severe hypertrophy, even in the absence of detectable baseline systolic dysfunction.

Adult↗
PubMed2001

Association of a G994 --> T (Val279 --> Phe) polymorphism of the plasma platelet-activating factor acetylhydrolase gene with myocardial damage in Japanese patients with nonfamilial hypertrophic cardiomyopathy.

Plasma platelet-activating factor acetylhydrolase (PAF-AH) acts as a key defense against oxidative stress by hydrolyzing PAF and oxidized phospholipids. Deficiency of the activity of this enzyme may thus potentially result in predisposition to myocardial damage. The possible role of the G994 (V allele) --> T (F allele) polymorphism of the PAF-AH gene in modulating cardiac function was investigated in 142 Japanese subjects with nonfamilial hypertrophic cardiomyopathy (HCM). Logistic regression analysis adjusted for age, sex, height, and body weight revealed that the frequency of the F allele was significantly higher in HCM patients than in 284 healthy controls. Echocardiographic examination revealed that left ventricular (LV) end-diastolic and end-systolic dimensions were significantly greater in HCM patients with the FF genotype than in those with the VV genotype. Cardiac catheterization revealed that LV end-diastolic pressure was significantly higher, whereas the LV ejection fraction was significantly smaller, for HCM patients with the F allele than for those with the VV genotype. Interstitial fibrosis was significantly more severe in HCM subjects with the FF genotype than in those with the VV genotype. These results suggest that the G994 --> T (Val279 --> Phe) polymorphism in the plasma PAF-AH gene may exacerbate cardiac damage in Japanese individuals with nonfamilial HCM, although this polymorphism is unlikely to be a causative factor for this condition.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2001

Biphasic changes in left ventricular end-diastolic pressure during dynamic exercise in patients with nonobstructive hypertrophic cardiomyopathy.

OBJECTIVES: The aim of this study was to clarify the serial changes in left ventricular (LV) end-diastolic pressure (LVEDP) during dynamic exercise in patients with hypertrophic cardiomyopathy (HCM). BACKGROUND: Although HCM is characterized by impaired resting LV diastolic function, serial changes in LVEDP during exercise have not been characterized. METHODS: We simultaneously measured LV pressure and LV dimensions during symptom-limited supine bicycle exercise in 5 healthy individuals and 20 patients with HCM. Exercise thallium-201 scintigraphic studies were also performed. RESULTS: The LVEDP (baseline: 12 +/- 5 mm Hg) progressively increased to a maximum value at peak exercise (28 +/- 8 mm Hg) in 11 patients with HCM (group I). In the remaining nine patients with HCM (group II), changes in LVEDP during exercise were biphasic, with an initial progressive increase and a subsequent gradual decline up to peak exercise (14 +/- 4 mm Hg at baseline, 27 +/- 5 mm Hg at the critical heart rate, 16 +/- 3 mm Hg at peak exercise). Exercise-induced changes in LV dimensions and LV peak systolic pressures were similar in both groups. However, the maximum first derivative of LV pressure was greater and the LV pressure half-time was shorter in group II than in group I at a similar peak exercise heart rate. The biphasic changes in LVEDP disappeared by pretreatment with propranolol. The LV hypertrophy scores were higher in group I than in group II. Exercise thallium-201 images showed more severe perfusion defects in group I than in group II patients. CONCLUSIONS: The biphasic changes in LVEDP seen during exercise may be related to improved coronary microcirculation in response to beta-adrenergic stimulation in patients with mild to moderate HCM.

Adult↗
PubMed2001

The effect of heat-treated human bone morphogenetic protein on clinical implantation.

For the clinical usage of human-derived bones, it is necessary to treat bones to reduce the risk of contamination by microorganisms. Bone morphogenetic protein is vulnerable to chemicals, but shows resistance to thermal heat to 70 degrees C in a short time. In this experiment, crude human bone morphogenetic protein was extracted from heat-treated bones at 60 degrees C for 10 hours and from nonheated bones. Sodium dodecyl sulfate polyacrylamide gel electrophoresis for these specimens was done. Gelatin capsules containing 5 mg of crude human bone morphogenetic protein extracted from heated and nonheated bones were implanted into thigh muscle pouches of five mice. At 20 days after implantation, the heterotopic bone formation was compared by evaluating the radiographic and histologic analyses. The sodium dodecyl sulfate polyacrylamide gel electrophoresis pattern of the human bone morphogenetic proteins showed five main bands (16, 22, 28, 35, and 67 kDa) that were almost identical. Heterotopic bone formation observed on the radiograph was induced by crude human bone morphogenetic protein from heated bones in a manner similar to that used for nonheated bones. The results from this study show that heat-treated bone preserves osteoinduction.

Animals↗
PubMed2001

Cardiac functional and structural alterations induced by endotoxin in rats: importance of platelet-activating factor.

OBJECTIVE: In this study, we evaluated the time course of the alterations in left ventricular (LV) dimensions, LV wall thickness, and LV systolic function in rats with endotoxemia by using echocardiography as well as myocardial histopathologic assessments. Our second goal was to examine whether pretreatment with a platelet-activating factor (PAF) antagonist would ameliorate the lipopolysaccharide (LPS)-induced cardiovascular collapse during the early phase. DESIGN: A prospective, controlled, in vivo animal laboratory study. SETTING: Research laboratory at a university. SUBJECTS: Male, Wistar rats (8-9 wks old; n = 83). INTERVENTIONS: In pentobarbital-anesthetized rats, the right carotid artery was cannulated to measure the arterial blood pressure and to sample blood. The right jugular vein also was catheterized for the administration of drugs. LPS (2 mg/kg) derived from Klebsiella pneumoniae or physiologic saline was administered in the presence or absence of pretreatment with TCV-309, a specific potent PAF antagonist. Echocardiographic studies were performed with an 8- to 13-MHz transducer. MEASUREMENTS AND MAIN RESULTS: LPS administration immediately induced progressive hypotension. The maximal hypotensive response was observed at 10 mins after LPS infusion with mean arterial pressure decreasing from 119 +/- 2 to 56 +/- 3 mm Hg (p < .001). LV end-diastolic internal dimensions decreased from 6.4 +/- 0.1 to 3.1 +/- 0.1 mm (p < .001) at 30 mins after LPS and remained significantly reduced compared with control rats. LV end-systolic dimensions also decreased dramatically from 3.5 +/- 0.2 to 0.5 +/- 0.1 mm (p < .001) at 30 mins after LPS and remained significantly reduced throughout the experiment. LV fractional shortening increased from 45 +/- 1% to 84 +/- 2% (p < .001) at 30 mins after LPS and remained elevated compared with control rats. LV wall thickness increased strikingly from 15 mins until 2 hrs after LPS infusion. Pathologic studies demonstrated marked congestion of capillaries and mild edema in the LV myocardium. The hematocrit increased after the administration of LPS. LPS markedly increased sympathetic tone as demonstrated by the elevation of plasma concentrations of epinephrine and norepinephrine. There was no elevation of concentrations of nitrite and nitrate. Pretreatment with TCV-309, a specific potent PAF antagonist, reduced LPS-induced hypotension and attenuated LV functional and structural changes. TCV-309 administration reduced the LPS-induced adrenergic activation and hemoconcentration. CONCLUSIONS: The hypotension that occurred during the initial phase of LPS-induced shock was accompanied by LV functional and structural alterations. The marked increase in LV wall thickness can be ascribed to the congestion of capillaries and edema in the LV myocardium. Pretreatment with a PAF antagonist reduced LPS-induced alterations. PAF may play a pivotal role during the initial phase of LPS-induced cardiovascular responses.

Animals↗
PubMed2001

Carboxy-terminal region involved in activity of Escherichia coli TolC.

The Escherichia coli TolC acts as a channel tunnel in the transport of various molecules across the outer membrane. Partial-deletion studies of tolC revealed that the region extending from the 50th to the 60th amino acid residue from the carboxy terminus plays an important role in this transport activity of TolC.

Bacterial Outer Membrane Proteins↗
PubMed2000

Synthesis of optically active 5-substituted-2-pyrrolidinone derivatives having atropisomeric structure and 3,5-cis-selective reaction of their enolates with electrophiles

Optically pure forms (>/=98% ee) of N-(o-tert-butylphenyl)-5-(methoxymethyl)-2-pyrrolidinone having atropisomerism and N-(o-tert-butyldiphenylsiloxyphenyl)-5-(methoxymethyl)-2-pyrrolidinon e having an atropisomerism-like structure were prepared from ortho-substituted aniline derivatives and (S)-5-(methoxymethyl)butyrolactone in a stereoselective manner. The reactions of Li-enolates from these lactams with various electrophiles and subsequent dearylation of the products gave 3, 5-cis-disubstituted-2-pyrrolidinone derivatives.

Journal Article↗
PubMed2000

Different beta-adrenergic regulation of myocardial contraction and relaxation between apical and nonobstructive hypertrophic cardiomyopathy.

BACKGROUND: The impaired adrenergic control of both inotropic and lusitropic reserves has been evaluated in patients with hypertrophic cardiomyopathy (HCM) but not in those with apical HCM (APH). OBJECTIVES: We examined the influence of increases in heart rate and adrenergic stimulation on inotropic and lusitropic reserves in HCM and APH with normal resting left ventricular (LV) systolic function. METHODS: We evaluated LV isovolumic contraction and relaxation during atrial pacing and during supine leg exercise in 7 patients with APH and in 8 patients with HCM. RESULTS: Heart rate was significantly correlated with LV isovolumic contraction and relaxation during pacing and exercise in all patients. In all patients with APH, the increase in LV isovolumic contraction was greater during exercise (101%) than pacing alone (27%) for similar increase in heart rate. In 5 patients with HCM, the increase in LV isovolumic contraction was greater during exercise (83%) than pacing alone (24%), whereas in 3 patients with HCM the increase in LV isovolumic contraction was similar between during exercise (25%) and during pacing alone (22%). In all patients with APH, relaxation was shorter during exercise (39%) than pacing alone (16%). Conversely, in patients with HCM relaxation was similarly shortened between during pacing alone (20%) and during exercise (19%). CONCLUSIONS: The force-frequency and the relaxation-frequency relations were well-preserved in all patients. In patients with HCM, the adrenergic enhancement of force-frequency relation and/or relaxation-frequency relation was impaired. In patients with APH, however, adrenergic control of both force-frequency and relaxation-frequency relations was well-preserved, which may indicate a preserved beta-adrenergic signaling pathway.

Adult↗
PubMed2000

Acute effects of a single low oral dose of pimobendan on left ventricular systolic and diastolic function in patients with congestive heart failure.

A recent long-term multicenter trial has shown that pimobendan is more effective when administered in low doses. However, no data are available concerning the effect of a low dose of pimobendan on the systolic and diastolic pressure-volume relations in patients with heart failure. Therefore we examined the effects of a single low dose of oral pimobendan, a calcium sensitizer, on systolic and diastolic hemodynamics in patients with cardiomyopathy and congestive heart failure. We measured the left ventricular (LV) pressure-volume relations using a conductance catheter with a micromanometer tip in 10 patients with chronic congestive heart failure resulting from idiopathic cardiomyopathy before and 45 and 90 min after administration of a single oral dose of 2.5 mg of pimobendan. End-systolic elastance was used as an index of LV contractility and was measured during transient occlusion of the inferior vena cava. End-systolic elastance increased significantly by 25% at 45 min (p < 0.05) and by 55% at 90 min (p < 0.01) without an increase in myocardial oxygen consumption. The inotropic effect was accompanied by improved ventriculoarterial coupling. This effect was attenuated in patients with severely impaired myocardial contractility. LV relaxation, assessed by the time constant of isovolumic pressure decay (T(1/2)), was significantly shortened at 90 min (from 47.7 +/- 1.9 to 41.2 +/- 1.7 ms; p < 0.01), although it remained unchanged at 45 min. The diastolic pressure-volume relation showed a leftward and downward shift in all patients. These results indicate that low-dose oral pimobendan had favorable short-term inotropic and lusitropic effects in patients with congestive heart failure caused by idiopathic dilated cardiomyopathy, and may thus be a useful alternative to traditional agents. Further study in a large-scale trial is merited.

Administration, Oral↗
PubMed1999

Impaired force-frequency relations in patients with hypertensive left ventricular hypertrophy. A possible physiological marker of the transition from physiological to pathological hypertrophy.

BACKGROUND: The extent to which force-frequency and relaxation-frequency relations (FFR and RFR, respectively) and exercise-induced adrenergic stimulation affect myocardial inotropic and lusitropic reserves has not been established in patients with left ventricular (LV) hypertrophy (LVH). METHODS AND RESULTS: We calculated the maximum first derivative of LV pressure (LV dP/dtmax) and the LV pressure half-time (T1/2) during pacing, exercise, and isoproterenol infusion in 17 patients with hypertensive LVH and 9 control subjects to investigate the influence of increases in heart rate (HR) and adrenergic stimulation on inotropic and lusitropic reserves. Group A consisted of 10 LVH patients who showed a progressive increase in the HR-LV dP/dtmax relation. Group B consisted of 7 LVH patients in whom the HR-dP/dtmax relation at physiological pacing rates was biphasic. The LV mass index was larger and the LV ejection fraction was smaller in group B than in group A (244+/-72 g/m2 versus 172+/-22 g/m2 and 55+/-18% versus 72+/-6%, respectively; both P<0.05). The increase in LV dP/dtmax was greater during exercise than pacing alone for similar increases in HR in all groups (P<0.05) (group A, 111+/-22% versus 25+/-14%; group B, 105+/-35% versus 14+/-10%; control, 111+/-24% versus 25+/-12%). T1/2 was shorter (P<0.05) during exercise than with pacing alone in all groups (group A, 41+/-6% versus 11+/-3%; group B, 38+/-9% versus 14+/-4%; control, 44+/-6% versus 12+/-5%). Isoproterenol infusion caused similar increases in LV dP/dtmax and similar decreases in T1/2 in all groups. CONCLUSIONS: The FFR was biphasic in patients with severe LVH irrespective of LV function but was preserved in patients with less severe LVH and control subjects. Importantly, the RFR and adrenergic control of both inotropic and lusitropic reserves were well preserved in all LVH patients. A biphasic FFR at physiological pacing rates may be one of the earliest markers of the transition from physiological adaptation to the pathological process in LVH patients.

Adrenergic beta-Agonists↗
PubMed1999

Histopathological analysis of apoptosis, and expression of p53, bcl-2, bax, and Ki-67 in laryngeal squamous cell carcinomas and dysplasia.

The growth of neoplasia is determined by the proliferation and loss of cells. The purpose of this study is to determine the frequency of apoptosis in laryngeal carcinomas and to examine its relationship to the pathological parameters, including ki-67 expression, and to expression of p53, bcl-2, and bax protein. The materials are 67 cases of laryngeal squamous cell carcinomas (SCCs) and 22 cases of squamous dysplasia using biopsy and surgery specimens. Apoptotic cells were determined by the modified TUNEL method. Expressions of p53, bcl-2, and bax, i.e. apoptosis-related genes, and ki-67, a proliferation marker, were immunohistochemically examined. The relationships between apoptosis and the clinicopathological findings were studied. The stage of the carcinoma was not related to the apoptotic index. The expression of p53 was frequently detectable in the advanced carcinomas with T3, T4 and N-positive. The apoptotic index was not significantly related to recurrence, metastasis or histological differentiation. Apoptosis occurred frequently in the cornified areas of well differentiated SCCs. The expressions of ki-67 observed in the poorly differentiated SCCs was significantly higher than that observed in the well differentiated SCCs (P< 0.01). The apoptotic index increased after irradiation in the carcinoma. No relationship was found between apoptotic index, ki-67 index, and expression of p53, bcl-2 and bax. The apoptotic index obtained form the SCCs was significantly higher than that obtained form squamous dysplasias (P < 0.05). Various apoptosis-related findings including p53 expression were observed in the advanced type of laryngeal SCCs, and apoptosis of the carcinoma was suggested to be controlled by complicated factors including bcl-2.

Adult↗
PubMed1998

PyNPase expression in human colon cancer.

Although colorectal cancer tissue is rich in pyrimidine nucleoside phosphorylase (PyNPase), there is no consensus as to whether cancer cells or stromal cells predominately express PyNPase. We micro-dissected OCT compound embedded frozen tissue sections into epithelial and stromal components and then analyzed the extracted samples separately. The PyNPase expression level was higher in stromal cells than in cancer cells and the difference increased with inflammation induced by the immunostimulator OK432. These results suggest that stromal cells are the major PyNPase source in colorectal cancer.

Adult↗
PubMed1998

Extraction and analysis of diagnostically useful proteins from formalin-fixed, paraffin-embedded tissue sections.

We describe and discuss a method of protein extraction for Western blot analysis from formalin-fixed, paraffin-embedded tissue sections. From 5-mm2 50-micron-thick tissue sections, an abundance of proteins could be extracted by incubating the sections in lysis buffer containing 2% sodium dodecyl sulfate (SDS) at 100C for 20 min followed by incubation at 60C for 2 hr. Extracts yielded discernible protein bands ranging from 10 kD to 120 kD as identified by SDS-polyacrylamide gel electrophoresis (PAGE). Western blot analysis successfully detected membrane-bound protein such as E-cadherin, cytosolic protein such as beta-catenin, and nuclear proteins including proliferating cell nuclear antigen (PCNA), mutant-type p53, cyclin D1, cyclin E, and cyclin-dependent kinases (CDKs). With this technique, we could examine cyclin D1 and CDK2 expression in small adenomas compared with cancer tissues and normal mucosa. The simple method of protein extraction described here should make it possible to use large-scale archives of formalin-fixed, paraffin-embedded samples for Western blot analysis, and its application could lead to detailed analysis of protein expression. This new technique should yield valuable information for molecular biology.

Adenoma↗