Biomedical subjects

Y Hara

Publications and source records attributed to Y Hara.

At least 253 records · Page 14Linked to original sources

PubMed1998

[Histopathological examination of transurethral electrovaporization of the prostate].

Transurethral electrovaporization of the prostate (TVP) has been devised to eliminate prostatic tissue by electric vaporization and to create a dry coagulation layer beneath to minimize bleeding from the site of TVP. However, vaporization induces degeneration due to thermal coagulation deep in the tissue beneath the vaporized layer, and local tissue damage is thus greater than that caused by the standard transurethral resection of prostate (TURP) loop. Since this results in difficulty with histopathological examination, the percentages of tissue-diagnosable area were determined in sections resected using various vaporization electrodes (Roller Loop, Band & Wedge Loop). The percentage of tissue-diagnosable area was 92.0 +/- 3.3% with the standard TUR loop, 2.4 +/- 0.9% with the Roller Loop, 42.7 +/- 21.1% with the Band Loop, and 39.7 +/- 24.4% with the Wedge Loop. Concerning speed of resection, the best vaporization effect was obtained when the speed of operation was 1/2 or 1/3 that with the standard TUR loop. Since the region in which tissue diagnosis was smaller with the vaporization electrode than with standard TURP, more careful examination was required for diagnosis of incidental cancers. Therefore, postoperative observation by PSA measurement appeared to be important.

Aged↗

PubMed1997

The Clinical Value of Microsatellite Instability and a Loss in Heterozygosity in Sporadic Breast Cancers.

We analyzed loss of heterozygosity (LOH) and microsatellite instability (MI) in 108 cases of sporadic breast cancers using 22 microsatellite markers on 12 chromosomes. LOH was frequently seen in 1p(13%), 6p(18%), 8p(11%), 11p(18%), 13q(21%),16q(31%), 17p(44%) and 17q(29%). Individual patients were scored according to the degree of LOH at the above eight chromosomal markers. Patients with no LOH were scored as 1, patients with one to three LOH were scored as 2, and patients with four or more LOH were scored as 3. A high LOH score correlated with a high histological grade (p=0.019) and a poor prognosis (p=0.0035). Eleven(10.2%) of 108 patients with breast cancer showed MI, with 6 cases showing MI at a single locus and 5 at multiple loci. Of the 11 MI-positive patients only one had lymph node involvement(p=0.015), none had histological grade 3 disease, and MI-positive patients tended to have a better prognosis than MI-negative ones. These data suggest that MI may be an early event in mammary tumorigenesis, and that LOH occurs at a later stage. The LOH score may be a useful prognostic marker of operable breast cancer.

Journal Article↗

PubMed1997

Cloning and characterization of murine glial cell-derived neurotrophic factor inducible transcription factor (MGIF).

The potent neurotrophic factor glial cell-derived neurotrophic factor (GDNF) is a distant member of the transforming growth factor-beta (TGF-beta) superfamily of proteins. We report a transcription factor that is the first nuclear protein known to be induced by GDNF, thus designated murine GDNF inducible factor (mGIF). The cDNA was cloned in the course of investigating transcription factors that bind to Sp1 consensus sequences, using the in situ filter detection method, and it was found to encode a protein having the same C2-H2 zinc finger motif as Sp1. Sequence analysis indicated that mGIF is homologous to the human TGF-beta inducible early gene (TIEG) and human early growth response gene-alpha (EGR-alpha). mGIF is widely distributed in the adult mouse with high mRNA levels in kidney, lung, brain, liver, heart, and testis. In the adult brain, mGIF is abundantly expressed in hippocampus, cerebral cortex, cerebellum, and amygdala with lower amounts in striatum, nucleus accumbens, olfactory tubercle, thalamus, and substantia nigra. During development, mGIF mRNA also has a wide distribution, including in cerebral cortex, cerebellar primordium, kidney, intestine, liver, and lung. GDNF induces the expression of mGIF rapidly and transiently both in a neuroblastoma cell line and in primary cultures of rat embryonic cortical neurons. Co-transfection of the Drosophila SL2 cells using mGIF expression plasmid and reporter constructs having Sp1 binding sites indicated that mGIF represses transcription from a TATA-containing as well as from a TATA-less promoter. These observations suggest that the zinc finger transcription factor mGIF could be important in mediating some of the biological effects of GDNF.

Amino Acid Sequence↗

PubMed1997

PTH-related peptide-like immunoreactivity in the median emminence, paraventricular and supraoptic nuclei in colchicine-treated rats.

The existence of PTH-related peptide (PTHrP) in the hypothalamus was examined by immunohistochemistry in colchicine-treated rats. Two days after intracerebroventricular administration of colchicine dense PTHrP-like immunoreactivity (LI) was observed in the external zone of the median emminence (ME). PTHrP-LI cells were found in the paraventricular nucleus, the supraoptic nucleus and the periventricular region of the third ventricule. The effects of PTHrP on intracellular Ca2+ concentrations ([Ca2+]i) were examined by a Ca2+ imaging method using fura-2 in perifused preparations of isolated rat anterior pituitary cells. The rise in [Ca2+]i induced by PTHrP was found in approximately 17% of the cells examined. These results suggest that PTHrP-LI cells in the hypothalamus may project to the ME and contribute to the anterior pituitary function.

Animals↗

PubMed1997

Pirmenol inhibits muscarinic acetylcholine receptor-operated K+ current in the guinea pig heart.

We examined the effects of pirmenol and disopyramide on the muscarinic acetylcholine receptor-operated K+ current (I[K.ACh]) in atrial cells and on experimental atrial fibrillation in isolated guinea-pig hearts. In isolated atrial myocytes, both pirmenol and disopyramide concentration-dependently inhibited the I(K.ACh) induced by carbachol or intracellular loading of GTPgammaS. Their inhibitory effects on the carbachol-induced current were more potent than those on GTPgammaS-induced current, suggesting that these drugs inhibit I(K.ACh) mainly by blocking muscarinic receptors. In Langendorff-perfused hearts these drugs reversed the carbachol-induced decreases in effective refractory periods and atrial fibrillation threshold. These drugs may be useful for the prevention of vagally induced atrial fibrillation.

Action Potentials↗

PubMed1997

Class Ia antiarrhythmic drug cibenzoline: a new approach to the medical treatment of hypertrophic obstructive cardiomyopathy.

BACKGROUND: The class Ia antiarrhythmic drug disopyramide relieves the outflow tract obstruction of hypertrophic obstructive cardiomyopathy (HOCM). Disopyramide, however, has several adverse effects, such as dysuria and thirst, resulting from its anticholinergic activity. A new class Ia antiarrhythmic drug, cibenzoline, has little anticholinergic activity. The aim of this study is to elucidate whether cibenzoline attenuates left ventricular pressure gradient (LVPG) in patients with HOCM. METHODS AND RESULTS: Ten patients with HOCM (mean age, 59+/-12 years) participated in this study. LVPG and left ventricular functions were measured before and 2 hours after administration of a single oral dose of 150 or 200 mg cibenzoline. LVPG decreased from 123+/-60 to 39+/-33 mm Hg (P=.0026). The E/A ratio in transmitral Doppler flow increased from 1.20+/-0.84 to 2.00+/-1.72 (P=.029). Isovolumic relaxation time increased from 73+/-16 to 101+/-23 ms (P=.0026). Left ventricular diastolic dimension remained unchanged, but left ventricular systolic dimension enlarged significantly, from 21.6+/-2.4 to 26.2+/-3.3 mm (P=.0004). Fractional shortening decreased from 47.6+/-6.1% to 34.6+/-8.8% (P=.0007). Left ventricular ejection time index decreased significantly, and preejection period index increased in all the patients. Decreased LVPG remained maintained even in the long-term treatment with cibenzoline. Conclusions These results indicate that cibenzoline can markedly attenuate LVPG in patients with HOCM. A decrease in myocardial contractility seems to be closely related to a marked decrease in LVPG.

Aged↗

PubMed1997

Increase of urocortin-like immunoreactivity in the rat supraoptic nucleus after dehydration but not food deprivation.

The effects of dehydration and food deprivation on urocortin-like immunoreactivity (Ucn-IR) in the rat supraoptic nucleus (SON) and the paraventricular nucleus (PVN) were examined by immunohistochemistry. Water deprivation for 48 h caused a significant increase in the number of Ucn-IR neurons in the SON, compared with control. Ucn-IR fibers and varicosities in the SON and the internal zone of the median eminence (ME) were increased, but a few and faint Ucn-IR neurons and fibers were observed in the PVN. On the other hand, food deprivation for 48 h caused a significant decrease in the number of Ucn-IR neurons in the SON, compared with control. Ucn-IR fibers and varicosities in the SON and the ME were fewer than those in controls. Ucn-IR neurons and fibers in the PVN were not detected after food deprivation. These results suggest that Ucn in the SON may be involved in the central regulation of water balance and nutrient homeostasis.

Animals↗

PubMed1997

Increase of urocortin-like immunoreactivity in the rat hypothalamo-neurohypophysial system after salt loading and hypophysectomy.

The effect of chronic salt loading on urocortin-like immunoreactivity (Ucn-IR) was investigated in the rat hypothalamo-neurohypophysial system. In control rats a few Ucn-IR neurons were observed scattered throughout the supraoptic nucleus (SON) and few in the paraventricular nucleus (PVN). A small number of Ucn-IR fibers were observed scattered in the median eminence (ME) and the posterior pituitary. However, after 5 days of chronic administration of 2% saline, a marked increase in the number of Ucn-IR perikarya and fibers was observed in the PVN and the SON. Additionally, Ucn-IR varicosities and fibers were found in the internal zone of the ME and in the posterior pituitary. To confirm the findings and examine the possible involvement of anterior pituitary function in synthesis of Ucn, surgical hypophysectomized rats were used. Five days after hypophysectomy, a marked increase in Ucn-IR was observed in the PVN, the SON, and both the internal and the external zone of the ME. These results suggest that Ucn in the hypothalamo-neurohypophysial system may be involved in the regulation of salt balance, and possibly in the stimulation of ACTH release from the anterior pituitary.

Animals↗

PubMed1997

Dual effects of extracellular ATP on the muscarinic acetylcholine receptor-operated K+ current in guinea-pig atrial cells.

Adenosine 5'-triphosphate (ATP) is stored in sympathetic and parasympathetic nerve terminals and co-released with norepinephrine and acetylcholine during nerve stimulation. In the heart in situ parasympathetic nerve is tonically stimulated and the activated muscarinic acetylcholine-receptor-operated K+ current (I(K,ACh)) plays an important role in the repolarization of the atrial action potential, the sinoatrial node automaticity and the atrioventricular conduction. In the present study, effects of extracellular ATP on the I(K,ACh) activated by carbachol or adenosine were examined in isolated guinea-pig atrial cells by use of the patch-clamp technique. ATP (10 microM) per se produced a transient activation of I(K,ACh) in atrial cells held at -40 mV. When I(K,ACh) was preactivated by 1 microM carbachol or 10 microM adenosine, ATP (1-100 microM) produced a transient increase followed by a sustained decrease of the current. These ATP-induced biphasic changes of I(K,ACh) were abolished by suramin (100 microM) or reactive blue-2 (30 microM), but not by theophylline (500 microM), indicating the involvement of P2 purinoceptors. ATP also enhanced and then partially reversed the action potential shortening induced by carbachol or adenosine in current-clamped atrial cells. Extracellular ATP did not increase but decreased the openings of the single K(ACh) channel that were recorded by use of a pipette solution containing 1 microM carbachol in the cell-attached mode. Thus, P2 purinoceptor stimulation produces dual effects of ATP on the pre-activated I(K,ACh) and may modulate the chronotropic and inotropic responses during autonomic nerve stimulation.

Adenosine Triphosphate↗

PubMed1997

Ca2+ overloading causes the negative inotropic effect of doxorubicin in myocytes isolated from guinea-pig hearts.

We reported previously that conditions shown to increase Ca2+ loading augment the negative inotropic effect of doxorubicin: To examine if the negative inotropic effect is caused by Ca2+ overloading doxorubicin-induced changes in diastolic and systolic Ca2+ concentrations and twitch contractions were studied under altered Ca2+ loading. Intracellular Ca2+ concentrations ([Ca2+]i) were monitored in fura-2-loaded myocytes isolated from the ventricular muscle of guinea-pig hearts. Twitch contractions were estimated from the shortening of myocytes. In myocytes incubated at 34 degrees C a medium containing 1.2 mM CaCl2 (standard conditions), doxorubicin (100 microM) caused a significant decrease in diastolic length, and an increase in the amplitude of contraction. The positive inotropic effect of doxorubicin was followed by a negative effect. Concomitant with these changes in myocyte contractions, a monophasic increase in diastolic Ca2+ and an increase and a subsequent decrease in the amplitude of Ca2+ transients (peak [Ca2+]i minus diastolic [Ca2+]i) were observed. When the Ca2+ load of myocytes was increased by an incubation at a low temperature (25 degrees C) or in the presence of high Ca2+ in the incubation medium (2.4 mM CaCl2), diastolic [Ca2+]i was elevated. Doxorubicin further increased diastolic [Ca2+]i. Under these conditions, the doxorubicin-induced increase in the twitch contraction lasted a shorter period of time and the subsequent decrease in contraction was significantly enhanced. The peak [Ca2+]i initially increased slightly and then decreased. Thus, the decrease in the amplitude of Ca2+ transients, as well as myocyte contraction was greater compared to the corresponding values observed under the standard conditions. These changes in the contraction and Ca2+ transient developed with the same time course. The effects of the low temperature incubation were antagonized by verapamil. These results indicate that the negative inotropic effect of doxorubicin results from a decrease in the amplitude of Ca2+ transients caused by an increased diastolic [Ca2+]i and a decreased peak [Ca2+]i. These changes are likely to be caused by myocardial Ca2+ overload.

Animals↗

PubMed1997

Inhibition of PhIP mutagenicity by catechins, and by theaflavins and gallate esters.

Aqueous solutions of gallic acid, methyl gallate, catechins, theaflavins and tannic acid were tested for inhibition of the mutagenicity of PhIP in the Salmonella typhimurium TA98 assay with an S9 fraction from the liver of rats induced with alpha-naphthoflavone and phenobarbital. The IC50S were in the 80-250 microM range for the gallated catechins, theaflavins and tannic acid. No inhibition could be found with these compounds when a direct acting mutagen was used. This indicates that the anti-mutagenic properties of these phenolic compounds may be due to their inhibition of the cytochrome P-450 enzymes.

Animals↗

PubMed1997

The origin of chlorarachniophyte plastids, as inferred from phylogenetic comparisons of amino acid sequences of EF-Tu.

A molecular phylogenetic analysis of elongation factor Tu (EF-Tu) proteins from plastids was performed in an attempt to identify the origin of chlorarachniophyte plastids, which are considered to have evolved from the endosymbiont of a photosynthetic eukaryote. Partial sequences of the genes for plastid EF-Tu proteins (1,080-1,089 bp) were determined for three algae that contain chlorophyll b, namely, Gymnochlora stellata (Chlorarachniophyceae), Bryopsis maxima (Ulvophyceae), and Pyramimonas disomata (Prasinophyceae). The deduced amino acid sequences were used to construct phylogenetic trees of the plastid and bacterial EF-Tu proteins by the maximum likelihood, the maximum parsimony, and the neighbor joining methods. The trees obtained in the present analysis suggest that all plastids that contain chlorophyll b are monophyletic and that the chlorarachniophyte plastids are closely related to those of the Ulvophyceae. The phylogenetic trees also suggest that euglenophyte plastids are closely related to prasinophycean plastids. The results indicate that the chlorarachniophyte plastids evolved from a green algal endosymbiont that was closely related to the Ulvophyceae and that at least two secondary endosymbiotic events have occurred in the lineage of algae with plastids that contain chlorophyll b.

Amino Acid Sequence↗

PubMed1997

Suppressed alloreactivity and mixed chimerism in rats with accepted cardiac allografts by intrathymic injection of donor bone marrow cells.

Intrathymic injection of donor bone marrow cells (ITBMCs) at the time of transplantation and treatment with antilymphocyte serum (ALS) permitted the indefinite survival of Brown Norway (BN, RT1n) rat heart grafts in 6 out of 8 Lewis (LEW, RT1l) rat recipients, LEW recipients with long-surviving BN heart grafts (LSGs) also accepted additional BN heart grafts without further immunosuppression, though they rejected Piebald Virol Glaxo (PVG, RT1c) rat heart grafts in the usual fashion. In the in vitro study, the proliferative response of the lymphocytes from LEW recipients with LSGs remained suppressed when they were stimulated by BN spleen cells, but not when stimulated by PVG cells. Bone marrow cells (BMCs) from LEW rats with LSGs showed strong, nonspecific, suppressive effects on the proliferative response in the mixed lymphocyte culture reaction, suggesting that one of the possible explanations for tolerance might be the involvement of a suppressor mechanism.

Animals↗

PubMed1997

Coincident induction of K rev-1/rap 1A, rap 1B and H-ras mRNAs in the rat spinal cord by noxious stimulation.

Two cDNA fragments, K rev-1/rap 1A and rap 1B, were amplified from total cellular RNA of the rat spinal cord by reverse transcription-polymerase chain reaction with a set of oligonucleotide primers specific for the human rap 1A cDNA. We report here using Northern blot analysis with these cDNA probes that noxious stimulation causes a marked and coincident increase in rap 1A, rap 1B and H-ras mRNAs in the rat spinal cord. This suggests that Rap 1 participates in sensory processing in spinal neurons in parallel with Ras.

Amino Acid Sequence↗

PubMed1997

Erythrocyte-dependent mitogenic activity of epigallocatechin gallate on mouse splenic B cells.

We previously reported that epigallocatechin gallate (EGCg), the main constituent of tea catechins, displays mitogenic effect on mouse splenic B cells. During research into the mechanism(s), it was found that the mitogenic activity of EGCg was dependent on the presence of red blood cells (RBC). When RBC in T cell-depleted spleen cells were removed, EGCg did not enhance the proliferation of B cells and even showed toxic effect at 25-50 micrograms/ml. When mouse, rabbit or sheep RBC as well as RBC-ghosts were added into the cultures, EGCg showed the mitogenic activity at a range of 1-50 micrograms/ml. Thereafter, we preincubated RBC with EGCg at 4 degrees C for various times and then washed the RBC to remove free EGCg in the suspensions. The EGCg-preincubated RBC also enhanced B cell proliferation. As short as ten minutes was sufficient for EGCg to bind to RBC membrane. These results indicate that EGCg first attached to the membrane of RBC and then stimulated B cell proliferation. The above results suggest an important immunoregulatory function of RBC.

Animals↗

PubMed1997

Epigallocatechin gallate-induced histamine release in patients with green tea-induced asthma.

BACKGROUND AND OBJECTIVE: Epigallocatechin gallate is the causative agent of green tea-induced asthma. To determine whether an IgE-mediated mechanism plays a pathogenetic role in this disorder, we measured histamine release after in vitro exposure to epigallocatechin gallate. METHODS: Subjects included eight patients (four men and four women) with green tea-induced asthma, who had been diagnosed by skin test and inhalation challenge, and eight controls (four asthmatic subjects with no previous exposure tea dust and four healthy volunteers). Heparinized whole blood samples were taken and incubated with epigallocatechin gallate at various concentrations (final concentration range, 0.003 to 300 micrograms/mL) for 30 minutes at 37 degrees C. After centrifugation, histamine was measured in the cell-free supernatants by radioimmunoassay. Histamine release was expressed as a percentage of total histamine. A result higher than 10% was considered positive. RESULTS: In one of the tea-sensitive patients, epigallocatechin gallate did not cause histamine release. Five of the other seven patients (71%) demonstrated a positive, dose-dependent histamine release to epigallocatechin gallate. In asthmatic and normal controls, histamine release was not observed at any epigallocatechin gallate concentration. Furthermore, a significant correlation was noted between the maximum percentage histamine release and the threshold epigallocatechin gallate concentration for intradermal skin testing. CONCLUSION: These results indicate that an IgE-mediated response is the basis for green tea-induced asthma.

Adult↗

PubMed1997

Pharmacokinetics of ozagrel and its metabolites after intravenous and oral administrations.

The pharmacokinetics of ozagrel, a selective thromboxane A2 synthetase inhibitor, and its metabolites (M1 and M2) was investigated in rats. The plasma concentration-time profile of ozagrel was biexponential with a rapid terminal decay (t1/2beta, 0.173 and 0.160 h at doses of 15 and 45 mg/kg, respectively). Metabolites M1 and M2 appeared in plasma immediately after intravenous (iv) dosing of the parent drug. Similar patterns of metabolites were observed in plasma after oral dosing, although concentrations of M2 were higher than those of M1, indicating the metabolic conversion of ozagrel to M2 and M1. However, a saturable first-pass clearance was seen at a high dose (60 mg/kg) of oral ozagrel. When M2 was administered iv, M1 appeared in the circulation system at appreciable levels, providing the first evidence of metabolic conversion of M2 to M1 in the systemic circulation. Ozagrel was partly metabolized to M2 and M1 in rat intestinal mucosa, although the main metabolic site might be in the liver. The results indicate that the metabolic pathway of ozagrel in rats is the conversion of the parent drug to M2 and M1 and the conversion of M2 to M1.

Administration, Oral↗

PubMed1997

Alterations of platelet, coagulation, and fibrinolysis markers in patients with acute ischemic stroke.

Alterations of platelet, coagulation, and fibrinolysis markers were investigated to determine the indications for antithrombotic therapy in patients with different clinical categories of acute cerebral infarction. Marked platelet activation was observed in platelet function tests, including measurements of platelet-specific proteins and platelet survival, platelet scintigraphy in the brain, and platelet fibrinogen binding assay, in patients with atherothrombotic stroke. Among patients with atherothrombotic stroke, increases of thrombin-antithrombin III complex (TAT) and D-dimer were frequent in addition to the findings of platelet activation in patients showing progressing stroke. Patients with cardioembolic stroke demonstrated marked elevation of coagulation markers, TAT and fibrinopeptide A, and fibrinolysis markers, D-dimer and plasmin-alpha2-plasmin inhibitor complex, as well as platelet activation. In contrast, neither activation was seen in patients with lacunar stroke. On the basis of these findings, antiplatelet therapy is indicated for stable or improving stroke, whereas anticoagulant therapy is indicated for progressing stroke among patients with atherothrombotic stroke. In patients with cardioembolic stroke, anticoagulant therapy should be started as soon as possible, or should be followed by thrombolytic therapy in the hyperacute phase. However, further investigation appears necessary for recommendations for patients with lacunar stroke.

Acute Disease↗