Biomedical subjects

I Yamaguchi

Publications and source records attributed to I Yamaguchi.

At least 55 records · Page 3Linked to original sources

PubMed2000

Diffuse and marked breast uptake of both 123I-BMIPP and 99mTc-TF by myocardial scintigraphy.

Unexpected breast uptake was observed in a 32-year-old woman referred for evaluation of hypertrophic cardiomyopathy. Diffuse and marked bilateral breast uptake of 123I-BMIPP and 99mTc-TF was shown by both planar and SPECT imaging during the first study, and the uptake of both radionuclides had decreased significantly eleven months later. At the time of the first radionuclide examination, she was occasionally breast feeding her 2-year-old child and had small amounts of milk production. At the follow up examination, the frequency of breast feeding was significantly reduced and she produced only small amounts of milk. Therefore, the uptake of 123I-BMIPP and 99mTc-TF may have been caused by lactation.

Adult↗

PubMed2000

Correlation between the expression of methionine adenosyltransferase and the stages of human colorectal carcinoma.

Methionine adenosyltransferase (MAT) catalyzes the synthesis of S-adenosylmethionine (AdoMet) from ATP and L-methionine. AdoMet is the major methyl donor in most transmethylation reactions in vivo, and it is also the propylamino donor in the biosynthesis of polyamines. In the present study, we assessed MAT activity in human colons with colorectal carcinoma and the values were compared with those of morphologically normal adjacent mucosa. Higher levels of MAT activity were observed in the colorectal carcinoma than in the normal colon. The ratio of MAT activity in tumor tissue versus normal tissue seemed to be correlated well will the stage of the colorectal tumor. Furthermore, immunoblot analysis showed that the high levels of MAT activity observed in colorectal carcinoma were due to the increased amounts of MAT protein. Immunohistochemical analysis revealed that MAT was most abundant in goblet cells, particularly in granules in the supranuclear area of these cells. In the colorectal carcinoma tissues, MAT was strongly stained in the cancerous cells and localized in granules in the supranuclear region. The results of this preliminary study suggest that determination of the relative ratio of MAT activity in both normal and tumor regions in human colorectal carcinoma could be a clinically useful tool for determining the stage of malignancy of colorectal carcinomas.

Adenocarcinoma↗

PubMed2000

A dopamine D(1/5) receptor antagonist, SCH23390, prevents stress-induced sudden death in cardiomyopathic hamsters.

Stress is known to have an impact on the development of life-threatening cardiovascular dysfunction. We have previously demonstrated that repeated exposure to cold-immobilization stress had lethal effects on cardiomyopathic Syrian hamsters (BIO 14.6), and that stress-induced sudden death was prevented by daily treatment with propranolol, suggesting an important role of sympathetic nerves in the etiology of stress-induced cardiac sudden death. In an attempt to clarify further the mechanisms of the sudden death, in the present study we investigated the effects of D(1/5) receptor blockade by SCH23390 on the sudden death of cardiomyopathic hamsters. In accordance with our previous results, repeated exposure for 5 days to cold-immobilization stress induced a lethal effect in the cardiomyopathic hamsters but not in control healthy hamsters. SCH23390 (0.1-10 mg/kg, IP), administered just before the exposure for 5 consecutive days, dose-dependently and significantly prevented the lethal effects of the stress. Furthermore, it was demonstrated that the drug significantly reduced the increase in the weights of the adrenal and kidneys observed in the stressed-cardiomyopathic hamsters. On the other hand, specific D(2) antagonist haloperidol (0. 1-10 mg/kg) failed to prevent the stress-induced sudden death and minimally affected the increase in organ weights. Collectively, these results suggest that D(1/5) receptors had an important role in the etiology of stress-induced cardiac sudden death of the cardiomyopathic hamsters, and provide the first experimental evidence of the potential therapeutic values of D(1/5) antagonists against cardiac sudden death associated with stress.

Animals↗

PubMed2000

An iso-integral mapping technique using magnetocardiogram, and its possible use for diagnosis of ischemic heart disease.

We have developed an iso-integral mapping technique that uses magneto-cardiogram (MCG) data to obtain a map as projected total current image on the torso from the heart. We have also investigated the applicability of iso-integral mapping to the diagnosis of ischemic heart disease. We simulated and measured the characteristics of two types of iso-integral maps: one using tangential (Bxy) components, and one using the normal component (Bz). Each vector component was measured by two types of superconducting quantum interference device (SQUID) system to determine the tangential and normal components. The tangential component of the magnetic field appeared to be equivalent to the current image in the myocardium projected on the observing plane, and we were able to obtain a projected total current image by integration of the tangential components during the depolarization and repolarization processes. And we found that the iso-integral maps of normal hearts showed similar pattern in both processes; however, those of ischemic hearts showed different patterns.

Action Potentials↗

PubMed2000

Role of mast cells in the onset of IgE-mediated late-phase cutaneous response in mice.

BACKGROUND: In mice that are passively sensitized to IgE, cutaneous antigen challenge produces a biphasic response with peaks at 1 and 24 hours after challenge. OBJECTIVE: We investigated the role of mast cells in the IgE-mediated late-phase reaction in mice. METHODS: We histologically and ultrastructurally investigated the morphologic changes of mast cells during the biphasic responses. RESULTS: Degranulation of mast cells, which was observed between 4 and 24 hours after challenge, reached a peak at 8 hours. Piecemeal degranulation was seen during the immediate phase reaction. The number of IL-6-positive mast cells was increased after 4 hours in both IgE-sensitized and unsensitized mice, but positive cells showed a greater increase in sensitized mice and reached a peak after 8 hours. With in situ hybridization experiments, mast cells were positive for IL-6 messenger RNA at 6 hours after challenge. CONCLUSION: These findings indicate that anaphylactic degranulation of mast cells and the expression of IL-6 mRNA within 4 hours after antigen challenge are important for the onset of the late-phase allergic cutaneous reaction in mice.

Animals↗

PubMed2000

Expression, purification, and characterization of blasticidin S deaminase (BSD) from Aspergillus terreus: the role of catalytic zinc in enzyme structure.

We established an efficient overproduction-purification system for blasticidin S deaminase (BSD) using the cDNA cloned from Aspergillus terreus. The estimated molecular mass of the purified enzyme indicated BSD was a tetramer. This tetrameric form was very resistant to denaturation by SDS and showed heat-modifiable behavior on SDS-PAGE; i.e., BSD migrated much slower (as a single band of 36 kDa) in its active conformation than its completely denatured polypeptide (13 kDa) if heat treatment in 2% SDS was not performed before electrophoresis. As predicted from the presence of the catalytic zinc-coordinating sequence motif conserved in the cytosine nucleoside/nucleotide deaminase family, BSD also contained one zinc per deaminase subunit. However, the predicted catalytic function appeared not to be the only role of this zinc in the enzyme. First, titration of the zinc-chelating -SH groups with p-hydroxymercuriphenylsulfonate led to dissociation of the BSD tetramer into unstable monomers or dimers. Second, depletion of zinc on reconstitution of chemically denatured BSD (with either guanidine-HCl or acidic pH) resulted in improper folding of the polypeptide. These results suggest that zinc also plays a structural role in maintenance of the protein structure. When we introduced mutations at Glu-56 (the proposed active site) and Cys-91 (a proposed catalytic zinc-binding Cys) in BSD, none of the resulting mutants (E56D, E56Q, C91A, C91S, and C91H) showed any detectable activity, as judged with the spectrophotometric assay. Replacements of Cys-91 resulted in gross perturbation of the enzyme structure although the catalytically essential Glu-56 was not necessarily required for proper folding of the enzyme. These results further support our proposal that the catalytic zinc coordinated by the conserved sequence motif is also structural in BSD.

Amino Acid Motifs↗

PubMed2000

Mating-type genes from asexual phytopathogenic ascomycetes Fusarium oxysporum and Alternaria alternata.

Mating-type (MAT) loci were cloned from two asexual (mitosporic) phytopathogenic ascomycetes, Fusarium oxysporum (a pyrenomycete) and Alternaria alternata (a loculoascomycete), by a polymerase chain reaction (PCR)-based strategy. The conserved high mobility group (HMG) box domain found in the MAT1-2-1 protein was used as a starting point for cloning and sequencing the entire MAT1-2 idiomorph plus flanking regions. Primer pairs designed to both flanking regions were used to amplify the opposite MAT1-1 idiomorph. The MAT1-1 and MAT1-2 idiomorphs were approximately 4.6 and 3.8 kb in F. oxysporum and approximately 1.9 and 2.2 kb in A. alternata, respectively. In both species, the MAT1-1 idiomorph contains at least one gene that encodes a protein with a putative alpha box domain and the MAT1-2 idiomorph contains one gene that encodes a protein with a putative HMG box domain. MAT-specific primers were used to assess the mating type of F. oxysporum and A. alternata field isolates by PCR. MAT genes from A. alternata were expressed. The A. alternata genes were confirmed to be functional in a close sexual relative, Cochliobolus heterostrophus, by heterologous expression.

Alternaria↗

PubMed2000

Norepinephrine release is increased in the hibernating heart, studied in a chronic canine model of myocardial hibernation.

We examined the change in cardiac sympathetic function in the hibernating heart. To induce hibernating hearts in dogs, we placed a nylon tube via the carotid artery in the left circumflex artery (LCx) and obstructed the LCx flow. The plasma norepinephrine (NE) and epinephrine (E) concentrations in the coronary sinus and the aorta were measured before and 1 week after the tube placement to evaluate the catecholamine release from the heart. The wall motion was followed by echocardiography and. 1 week after the tube placement, regional myocardial blood flow (RBF) was measured using colored microspheres. Also. the restorability of myocardial dysfunction was examined in other dogs by extracting the LCx tube 1 week after the placement. Finally, the heart was removed for pathological observation and dogs showing myocardial infarction were excluded. One week after placing the tube, wall thickening was reduced in the LCx area, but was not in the left anterior descending (LAD) area. Compared with the LAD area, RBF in the LCx area was decreased in the endocardium (p < 0.05), but was not in the epicardium. In other dogs, the reduced wall thickening in the LCx area was restored to normal levels 1 or 2 weeks after the tube extraction. Thereby, our dogs with the tube placed were considered to be models of myocardial hibernation. The plasma NE and E concentrations were not significantly changed by placing the tube, but NE release from the heart was increased after the tube placement (p < 0.05). E uptake from the heart did not differ. Therefore, it is suggested that NE release is increased in the hibernating heart and may contribute to its mechanism.

Animals↗

PubMed2000

Hypotensive effect of endothelin-1 via endothelin-B-receptor pathway on pulmonary circulation is enhanced in rats with pulmonary hypertension.

The pharmacological characterization of endothelin-1 (ET-1) in the pulmonary circulation in pulmonary hypertension (PH) is not known precisely. We investigated the effect of intravenous injection of ET-1 (1000 pmol/kg) on right ventricular systolic pressure (RVSP) (which is equal to systolic pulmonary arterial pressure) in rats with monocrotaline-induced PH. ET-1 decreased RVSP in PH rats; however, ET-1 did not alter RVSP in control rats, suggesting that ET-1 causes dilatation of the pulmonary artery in PH rats. Under pretreatment with the endothelin-A- (ET(A)) receptor antagonist BMS 193884, ET-1 decreased RVSP in PH rats more than in control rats, suggesting that pulmonary vasodilator action of ET-I mediated via the ET(B)-receptor pathway is augmented in PH rats. Under pretreatment with the ET(A/B)-receptor antagonist SB 209670, the effect of ET-1 in lowering pulmonary arterial pressure was abolished in both groups of rats. These results suggest that the hypotensive effect of ET-1 on pulmonary circulation mediated via the ET(B)-receptor pathway is enhanced in PH rats compared with control normal rats. It is considered that the blockade of only the ET(A)-receptor pathway is preferable to the blockade of both the ET(A)- and ET(B)-receptor pathways in the treatment of PH.

Animals↗

PubMed2000

Impairment of cardiac energy metabolism in vivo causes hemodynamic abnormality and increases cardiac expression of preproendothelin-1 mRNA.

We investigated whether impairment of myocardial energy metabolism attenuates cardiac function and increases cardiac endothelin-1 (ET-1) gene expression in rats. Three weeks after commencing administration of cobalt chloride (CoCl2), an inhibitor of mitochondrial function, the peak positive first derivative of left ventricular (LV) pressure, an indicator of myocardial contractility, was significantly decreased in the CoCl2-treated rats. LV end-diastolic pressure and right ventricular systolic pressure were increased in the CoCl2-treated rats. Echocardiography showed that fractional shortening was significantly decreased in the CoCl2-treated rats. Myocardial expressions of acyl-CoA synthase mRNA, an enzyme involved in fatty acid utilization, was markedly decreased in the CoCl2-treated rats. Under such conditions, myocardial expression of preproendothelin-1 mRNA and atrial natriuretic peptide (ANP) mRNA, molecular markers of heart failure, was markedly increased in the CoCl2 rats. In conclusion, the data suggest that impairment of myocardial energy metabolism causes hemodynamic abnormality and increases molecular markers of heart failure (ET-1, ANP mRNA). These data suggest that myocardial energy metabolism is one of the factors involved in the upregulation of ET-1 gene expression in the failing heart.

Animals↗

PubMed2000

Mitochondrial dysfunction of cardiomyocytes causing impairment of cellular energy metabolism induces apoptosis, and concomitant increase in cardiac endothelin-1 expression.

It has been reported that at the end stage, apoptosis is involved in the progression of heart failure. It is suggested that cardiac energy metabolism is impaired during the progression of heart failure. Although the mechanism of induction of apoptosis in the failing heart varies according to the model of heart failure, it is not known whether an impairment of energy metabolism in cardiomyocytes is a primary cause of apoptosis. In this study, we applied mitochondrial inhibitors, such as rotenone, cobalt chloride and antimycin A, which inhibit mitochondrial function at different sites of the mitochondrial respiratory chain, to cardiomyocytes. All these reagents markedly decreased 3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay (MTT) reduction activity, an indicator of mitochondrial function, of cardiomyocytes and greatly increased glucose consumption, suggesting that cardiac energy metabolism is switched from beta-oxidation of fatty acid to glycolysis. It was shown that after 48-72 h of treatment with each reagent, apoptosis was shown to occur by DNA laddering and increase in caspase activity. Interestingly, each reagent with a different action site greatly activated caspase-3, but not caspase-8 activity, suggesting that mitochondria are involved in induction of apoptosis. On the other hand, within 24 h of the treatment, when apoptosis of cardiomyocytes was not observed, the treated cardiomyocytes showed a marked increase in preproendothelin-1 and atrial natriuretic peptide (ANP) gene expressions. In conclusion, the present study suggests that mitochondrial dysfunction with impaired energy metabolism elevates gene expression of cardiac ET-1, an aggravating factor in heart failure, and then finally induces apoptosis in cardiomyocytes. The finding of marked increases in expression of molecular markers (ET-1 mRNA and ANP mRNA) in the failing heart, followed by apoptosis in the treated cardiomyocytes suggests that the inhibition of mitochondrial function of cultured cardiomyocytes provides a possible new in vitro model of heart failure.

Animals↗

PubMed2000

Mitochondrial dysfunction increases expression of endothelin-1 and induces apoptosis through caspase-3 activation in rat cardiomyocytes in vitro.

We have reported that the expression of endothelin-1 (ET-1) increases in the failing heart. With the progress of heart failure, it has been reported that energy metabolism switches from mitochondrial b-oxidation to glycolysis. Furthermore, it has been reported that apoptosis is induced in the failing heart. However, it is not known how the gene expression of preproendothelin-1 and cellular apoptosis are affected by the mitochondrial dysfunction. Therefore, in order to elucidate this problem, we developed an in vitro model of mitochondrial dysfunction using rotenone, a mitochondrial respiratory chain complex I inhibitor, and studied preproendothelin-1 gene expression and apoptosis. Rotenone greatly increased the gene expression of pre-proendothelin-1 in cardiomyocytes. This result suggests that the gene expression of preproendothelin-1 is induced by the mitochondrial dysfunction. Furthermore, treatment of cardiomyocytes with rotenone induced an elevation of caspase-3 activity, and caused a marked increase in DNA laddering, an indication of apoptosis. In conclusion, it is suggested that mitochondrial impairment in primary cultured cardiomyocytes induced by rotenone in vitro, mimics some of the pathophysiological features of heart failure in vivo, and that ET-1 may have a role in myocardial dysfunction with impairment of mitochondria in the failing heart.

Animals↗

PubMed2000

Endothelin-A-receptor antagonist and oral prostacyclin analog are comparably effective in ameliorating pulmonary hypertension and right ventricular hypertrophy in rats.

Pulmonary hypertension (PH) has a poor prognosis and is a drug-resistant disease. Recently, it has been reported that continuous intravenous prostacyclin (PGI2) administration is effective for PH. In this study, we compared the effects of chronic treatment with an endothelin-A- (ETA) receptor antagonist with an oral PGI2 analog on PH in rats. We administered the ETA-receptor antagonist TA-0201 or beraprost sodium (BPS), which is an orally active PGI2 analog, to monocrotaline- (MCT) induced PH rats. Each drug was given orally for 19 days. The rats were divided into the following four groups: (1) normal rats with vehicle (control); (2) PH rats with vehicle treatment (PH + vehicle); (3) PH rats with TA-0201 treatment (0.5 mg/kg/day) (PH + TA-0201); (4) PH rats with BPS treatment (100 microg/kg/day) (PH + BPS). Nineteen days after MCT injection, Pp/Ps [the ratio of right ventricular (RV) systolic pressure to systemic systolic blood pressure) and the ratio of the RV weight to the body weight (RV/BW), indicators of PH and RV hypertrophy. were markedly higher in the PH + vehicle group than in the control (healthy) group. The increase in Pp/Ps and RV/BW was significantly depressed in the PH + TA-0201 group and PH + BPS group to a similar extent. The expression of beta-myosin heavy chain (MHC) mRNA, a molecular marker for cardiac hypertrophy, in the RV was greatly increased in the PH + vehicle group and this increase was inhibited in the PH + TA-0201 group and PH + BPS group to a similar effect. In conclusion, treatment with an ETA-receptor antagonist or an oral PGI2 analog is comparably effective in the prevention of progression of PH and RV hypertrophy.

Administration, Oral↗

PubMed2000

Endothelin-1 and right-sided heart failure in rats: effects of an endothelin receptor antagonist on the failing right ventricle.

The development of pulmonary hypertension (PH) causes right-sided heart failure. We investigated whether chronic treatment with the endothelin-A- (ETA) receptor antagonist BMS-193884 in rats with monocrotaline- (MCT) induced PH improves right-sided heart failure. Administration of BMS-193884 (100mg/kg) was commenced on the day before treatment with MCT. At 19 days, hemodynamics were measured under anesthesia and hearts were removed. The right ventricular systolic pressure (RVSP), an indicator for pulmonary hypertension, was remarkably elevated in the PH group compared with the normal control group. BMS-193884 effectively prevented this elevation. The central venous pressure, an indicator for right-sided heart failure, was markedly increased in the PH group. This increase was reduced to the normal level by BMS-193884. In the failing right ventricle of the PH group, the expression of atrial natriuretic peptide (ANP) mRNA, which is a molecular marker for the failing heart, was markedly increased. BMS-193884 greatly prevented this increase. The present study suggests that ET-1 contributes to the right-sided heart failure caused by PH and that an ETA-receptor antagonist is a beneficial drug which improves both hemodynamics and cardiac gene expression in the failing right ventricle.

Animals↗

PubMed2000

Characterization of brassinazole, a triazole-type brassinosteroid biosynthesis inhibitor.

Screening for brassinosteroid (BR) biosynthesis inhibitors was performed to find chemicals that induce dwarfism in Arabidopsis, mutants that resembled BR biosynthesis mutants that can be rescued by BR. Through this screening experiment, the compound brassinazole was selected as the most potent chemical. In dark-grown Arabidopsis, brassinazole-induced morphological changes were nearly restored to those of wild type by treatment with brassinolide. The structure of brassinazole is similar to pacrobutrazol, a gibberellin biosynthesis inhibitor. However, in assays with cress (Lepidium sativum) plants, brassinazole-treated plants did not show recovery after the addition of gibberellin but showed good recovery after the addition of brassinolide. These data demonstrate that brassinazole is a specific BR biosynthesis inhibitor. Brassinazole-treated cress also showed dwarfism, with altered leaf morphology, including the downward curling and dark green color typical of Arabidopsis BR-deficient mutants, and this dwarfism was reversed by the application of 10 nM brassinolide. This result suggests that BRs are essential for plant growth, and that brassinazole can be used to clarify the function of BRs in plants as a complement to BR-deficient mutants. The brassinazole action site was also investigated by feeding BR biosynthesis intermediates to cress grown in the light.

Arabidopsis↗

PubMed2000

Repression of shoot growth, a bZIP transcriptional activator, regulates cell elongation by controlling the level of gibberellins.

Cell expansion, a developmental process regulated by both endogenous programs and environmental stimuli, is critically important for plant growth. Here, we report the isolation and characterization of RSG (for repression of shoot growth), a transcriptional activator with a basic leucine zipper (bZIP) domain. To examine the role of RSG in plant development, we generated transgenic tobacco plants expressing a dominant-negative form of RSG, which repressed the activity of full-length RSG. In transgenic plants, this expression severely inhibited stem internode growth, specifically cell elongation. These plants also had less endogenous amounts of the major active gibberellin (GA) in tobacco, GA(1). Applying GAs restored the dwarf phenotypes of transgenic tobacco plants that expressed the dominant-negative form of RSG. To investigate the function of RSG in the regulation of the endogenous amounts of GAs, we identified a target for RSG. RSG bound and activated the promoter of Arabidopsis GA3, one of the genes encoding enzymes involved in GA biosynthesis. Moreover, the dominant-negative form of RSG decreased expression of the GA3 homolog in transgenic tobacco plants. Our results show that RSG, a bZIP transcriptional activator, regulates the morphology of plants by controlling the endogenous amounts of GAs.

Amino Acid Sequence↗

PubMed2000

Intense exercise causes decrease in expression of both endothelial NO synthase and tissue NOx level in hearts.

Cardiac myocytes produce nitric oxide (NO). We studied the effects of intense exercise on the expression of NO synthase (NOS) and the tissue level of nitrite (NO(2)(-))/nitrate (NO(3)(-)) (i.e., NOx), which are stable end products of NO in the heart. Rats ran on a treadmill for 45 min. Immediately after this exercise, the heart was quickly removed. Control rats remained at rest during the same 45-min period. The mRNA level of endothelial NOS (eNOS) in the heart was markedly lower in the exercised rats than in the control rats. Western blot analysis confirmed downregulation of eNOS protein in the heart after exercise. Tissue NOx level in the heart was significantly lower in the exercised rats than in the control rats. The present study revealed for the first time that production of NO in the heart is decreased by intense exercise. Because NO attenuates positive inotropic and chronotropic responses to beta(1)-adrenergic stimulation in the heart, the decrease in cardiac production of NO by intense exercise may contribute to the acceleration of increase in myocardial contractility and heart rate during intense exercise.

Animals↗

PubMed2000

Hemodynamic and thermal responses to a 30-minute constant-workload aerobic exercise in middle- or old-aged patients with cardiovascular diseases.

The aim of the present investigation was to compare the hemodynamic and thermal responses to a 30-min aerobic exercise between middle- or old-aged patients with normal left ventricular function and those with left ventricular dysfunction. Constant-load sitting ergometer exercise of approximately 90% of the subject's oxygen uptake (VO2) at the anaerobic threshold for 30 min was conducted in 21 patients with left ventricular dysfunction (61+/-10 years, left ventricular ejection fraction (LVEF) 35+/-7%) and 24 patients with normal left ventricular function (59+/-9 years, LVEF 71+/-7%). Heart rate (HR), blood pressure, deep temperatures in the forehead and thigh, and forearm skin blood flow (SkBF) were measured every minute, and cardiac output (CO) and stroke volume (SV) were determined every 10 min with the dye-dilution technique during the exercise. Patients of both groups exhibited a progressive elevation in each temperature and an increase in SkBF during the exercise. Although the VO2 and CO remained stable, almost the same magnitude of decrease in SV as increase in HR was seen after the 10th min of exercise in both groups. The magnitude of the decrease in SV was greater in old-aged than middle-aged patients with left ventricular dysfunction. Thus, the downward drift in SV during a 30-min constant-load aerobic exercise might not be influenced by left ventricular function, but intensified by aging in patients with left ventricular dysfunction.

Adult↗