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Biomedical subjects

H Yoshimura

Publications and source records attributed to H Yoshimura.

At least 127 records · Page 7Linked to original sources

Enhanced magnetic resonance imaging of leptomeningeal angiomatosis.

We present two patients with unilateral occipital gyriform calcification and seizures. Gyriform or serpentine calcification as revealed by computed tomography (CT) scan is rare and is a characteristic finding of Sturge-Weber syndrome (SWS) and celiac disease (CD). These patients had neither the facial nevus flammeus or neurological deficits characteristic of SWS, nor the gastrointestinal symptoms characteristic of CD. CD is often accompanied by cerebral occipital calcification indistinguishable from that of SWS. We demonstrate the presence of cerebral leptomeningeal angiomatosis (LA) by Gadolinium-DTPA-enhanced magnetic resonance imaging (MRI) but could not detect LA by either CT scanning or angiography. It has been reported that contrast-enhanced MRI is useful to detect LA in SWS. However, we found no reports of enhanced MRI in patients with SWS without facial angioma. If future studies can demonstrate the absence of cortical enhancement by contrast-enhanced MRI in CD with cerebral calcifications, enhanced MRI would become an important tool for differentiating CD from SWS.

Angiomatosis↗

The relaxant effect of adrenomedullin on particular smooth muscles despite a general expression of its mRNA in smooth muscle, endothelial and epithelial cells.

1. By use of the reverse transcription polymerase chain reaction (RT-PCR), we determined the expression of adrenomedullin (AM) mRNA in the various tissues of the pig. To evaluate the significance of the expression of AM mRNA, we also determined the effects of AM on the cytosolic Ca2+ concentration ([Ca2+]i) and tension development of the porcine smooth muscle strips obtained from the coronary artery, pulmonary vein, trachea, ileum and urinary bladder. 2.AM mRNA was widely expressed in the porcine tissues examined, which included myocardium (left and right ventricle and right atrium), kidney, lung, endothelial cells (aorta and aortic valve), smooth muscles (aorta, main pulmonary artery, pulmonary vein, renal artery and vein, coronary artery, ileum, trachea and urinary bladder) and epithelial cells (trachea and urinary bladder). 3. AM induced a decrease in [Ca2+]i and tension of the coronary artery, but not the pulmonary vein. AM had no effects on either the [Ca2+]i or tension of the trachea and urinary bladder strips or on the tension development of strips of ileum. 4. These results indicated that AM has a role as an autocrine and/or paracrine regulator of the coronary arterial tone. AM probably does not have an important role in the regulation of the pulmonary venous, tracheal, ileac and urinary bladder smooth muscle tone, even though AM mRNA is expressed in these tissues; the functional significance of AM in these smooth muscles remains to be determined.

Adrenomedullin↗

Metabolism of 2,4,5,2',4',5'-hexachlorobiphenyl (PCB153) in guinea pig.

1. The in vitro and in vivo metabolism of 2,4,5,2',4',5'-hexachlorobiphenyl (PCB153) in guinea pig has been studied. 2. Seven metabolites were detected in the faeces of PCB153-treated animals and three were identical to those produced by dog liver microsomes. The detection of a metabolite where a chlorine atom was shifted from the 2- to 3-position strongly suggested the involvement of 2,3-arene oxide intermediate, and evidence for the concomitant formation of a 3,4-arene oxide intermediate was provided by identifying other two minor metabolites which were dechlorinated at the 4-position. 3. In vitro studies using liver microsomes from guinea pigs revealed that the 2,3-arene oxide and 3-hydroxylation pathways are the predominant metabolic routes compared with the 3,4-arene oxide pathway. Although the guinea pig is an another species that can metabolize PCB153 mainly to the 2,3-arene oxide intermediate, the rate of formation was only about one-tenth of the dog. 4. These results indicate that the ability to form this unusual 2,3-arene oxide intermediate may not be responsible for high excretion rate of this congener. Our data also suggest that the cytochrome P450-catalysed metabolism of PCB153 in the guinea pig and dog are similar, whereas for post-cytochrome P450 metabolism, the guinea pig resembles the rabbit.

Animals↗

Major role of the CYP2C isozymes in deamination of amphetamine and benzphetamine: evidence for the quinidine-specific inhibition of the reactions catalysed by rabbit enzyme.

1. The cytochrome P450 isozymes involved in the deamination of amphetamine (AP) and benzphetamine (BZP) have been studied in liver microsomes from rabbit and rat using isozyme-specific inhibitors. 2. Metabolism of BZP in rat yielding phenylacetone and formaldehyde was moderately inhibited by testosterone and chloramphenicol. N-Debenzylation was thought to be P450-dependent, but all inhibitors except for a non-specific inhibitor, SKF-525A, failed to inhibit this reaction. 3. In rabbit, quinidine and testosterone were potent inhibitors of both BZP deamination and dealkylation. Deamination of AP in rabbit was extensively inhibited only with quinidine. 4. AP deamination with purified rabbit CYP2C3, which was previously identified as the major isozyme responsible for this metabolism, was extensively inhibited with quinidine, previously thought to be a specific inhibitor of CYP2D. 5. These results strongly support the notion that the CYP2C isozymes play a major role in the deamination of both AP and BZP, but not for N-debenzylation of BZP in rat. However, on the basis of different sensitivities toward inhibitors, multiple isozymes seem to be involved in BZP deaminations in both species.

Amphetamine↗

Expression and function of endothelins, endothelin receptors, and endothelin converting enzyme in the porcine trachea.

Endothelins (ETs) can modulate the airway smooth muscle tone. Using simultaneous measurements of cytosolic Ca2+ concentration ([Ca2+]i) and tension as well as the reverse transcription polymerase chain reaction (RT-PCR), we examined ET systems in the porcine trachea. In the functional study, the application of ET-1, ET-3 or sarafotoxin S6c (S6c) caused increases in [Ca2+]i and tension, in a concentration-dependent manner. These ET ligands were found to increase the Ca2+ sensitivity of the myofilament of the tracheal smooth muscle cells (SMCs). The contractions induced by ET-1 (10(-7) M), an ET receptor (ET-R) non-selective agonist, were much greater than those induced by S6c, an ET(B)-R selective agonist. BQ-123 (10(-6) M), an ET(A)-R antagonist, inhibited the ET-1 induced contraction. These functional experiments suggested the presence of both functioning ET(A)- and ET(B)-Rs in tracheal SMCs. RT-PCR experiments revealed that the tracheal SMCs expressed both ET(A)-R and ET(B)-R mRNAs, while tracheal epithelial cells (EpCs) predominantly expressed ET(A)-R mRNA. The porcine tracheal SMCs and EpCs also expressed pre-pro ET-1 (ppET-1), ppET-3, and endothelin converting enzyme-1 (ECE-1) mRNAs. These results suggested that ETs induce contraction of porcine tracheal SMCs not only by increasing [Ca2+]i but also increasing the Ca2+ sensitivity of the myofilament and that ETs could potentially be the autocrine and/or paracrine transmitters to regulate the contraction in the porcine airway smooth muscle.

Animals↗

Involvement of a novel mouse hepatic microsomal esterase, ES46.5K, in the hydrolysis of phthalate esters.

ES46.5K, a novel esterase from mouse hepatic microsomes (Watanabe K., et al., Biochem. Mol. Biol. Int., 31, 25-30 (1993)), catalyzed hydrolysis of phthalate esters. ES46.5K and mouse hepatic microsomes hydrolyzed diethyl-, dibutyl-, diisobutyl-, dioctyl- and diethylhexyl phthalates, whereas dicyclohexyl- and diphenyl phthalates having ring structure were not hydrolyzed by the enzymes. Vmax (mumol/min/mg protein)/K(m) (microM) ratios of ES46.5K for diethyl-, dibutyl-, diisobutyl-, dioctyl- and diethylhexyl phthalates were 291, 2786, 565, 51 and 57, respectively, while those of microsomes were 0.58, 0.83, 1.71, 0.05 and 1.10, respectively. The hydrolytic activity of ES46.5K was inhibited by diisopropylfluorophosphate and bis-p-nitrophenylphosphate. These results suggest that ES46.5K has high catalytic activity for phthalate esters and some role in the metabolism of phthalate esters in mice.

Animals↗

Novel extracellular alkaline metalloendopeptidases from Vibrio sp. NUF-BPP1: purification and characterization.

We found two types of novel alkaline metalloendopeptidases (AP1 and AP2) from a marine bacterium, isolated from the intestine of a five-barred goatfish (Parupeneus trifasciatus) and identified as Vibrio sp. (NUF-BPP1). We studied the structure-function relationship of these marine bacterial proteases. The electrophoretically homogeneous proteases had a molecular mass of 48 kDa for AP1 and 36 kDa for AP2 on SDS-PAGE, and showed optimum activity at around pH 9.5-10.0 (casein as substrate). Calcium chloride (5 mM) stabilized the activities over pH 6-11, but o-phenanthroline and EDTA inhibited the activities of both AP1 and AP2. The EDTA-inactivated proteases were partly restored to activity by addition of either zinc or calcium. Sodium chloride (3.5 M) increased the activities toward Z-Gly-Leu-NH2. N-Terminal sites of hydrophobic amino acid residues (Leu, Ile, Phe, Tyr, and Trp) of the peptide substrates were cleaved by AP1 and by AP2. Autolysis of AP1 in the absence of calcium ion probably produced AP2 by releasing a fragment (molecular mass of about 12 kDa) from the C-terminal end of AP1.

Amino Acid Sequence↗

Deamination of amphetamines by cytochromes P450: studies on substrate specificity and regioselectivity with microsomes and purified CYP2C subfamily isozymes.

Deamination or oxidative cleavage of the carbon-nitrogen bond in various phenylisopropylamines was examined in liver microsomes from rabbits and rats, and in reconstituted systems containing CYP2C subfamily isozymes. Kinetic studies of phenylacetone formation from six amphetamine (AP) derivatives, catalyzed by rabbit liver microsomes, indicated that AP had the highest apparent affinity (lowest K(m)) and increasing the size of the substituent on the nitrogen atom decreased the affinity. The values of maximal velocity increased with increasing size of the substituent. Experiments with purified CYP2C3 from rabbit liver gave similar results: this enzyme showed the highest activity for phenylacetone formation from benzphetamine (BZP) and showed lower activities with compounds having smaller nitrogen substituents. Based on these results, we conclude that among a series of AP derivatives, the parent phenylisopropylamine has the highest affinity for rabbit liver deaminase, where as BZP has the highest turnover. However, the intrinsic clearance (Vmax/K(m)) values for the individual reactions tended to be comparable. The rates of BZP and deprenyl N-demethylation by rat CYP2C11 and 2C13 were far greater than those of the reactions at other N-alpha-positions. This result indicated that rat CYP2C enzymes have a more rigid regioselectivity than rabbit CYP2C3 for the deamination/N-dealkylation of phenylisopropylamines.

Amphetamines↗

[Effect of worksite dental health program on periodontal status--evaluation by CPITN and bleeding on probing at each tooth].

A dental health promotion program which aimed to prevent periodontal disease was carried out at a shipyard in Nagasaki Prefecture. Repeated tooth cleaning instruction and prophylaxis were conducted in order to adopt proper oral hygiene habits. The first 3 months of this program included 'Initial instruction,' and 'Regular instruction' were given every 6 months in following 2 years. The oral examination was carried out before and after Initial instruction, and at each Regular instruction. The effect of this program was evaluated by 2 measures: CPITN and Bleeding on probing. After this program, the rate of teeth with pockets 4 -5 mm deep or deeper (CPITN 3, 4) was decreased. In contrast, the rate of teeth with no sign of periodontal disease (CPITN 0) was increased remarkably: the percentage increased from 8% preinitial instruction to 40% with regular instruction. Both the rate and grade of teeth with bleeding on probing were decreased. These results indicated that this program was helpful in improving the periodontal status. CPITN and Bleeding on probing at each tooth as an evaluation measure made our analysis more detailed.

Health Education, Dental↗

[A case of bilateral pneumothorax successfully treated with surgery associated with amyotrophic lateral sclerosis having been controlled with artificial ventilation].

We reported a case of bilateral pneumothorax, which was successfully treated with surgery, associated with amyotrophic lateral sclerosis (ALS). The patient had been controlled with artificial ventilation at the time of surgery. Prognosis of ALS is absolutely poor, and the life expectancies for patients with ALS are presumed several years, even though they are controlled with artificial ventilation. We applied a surgical treatment for a patient with ALS who developed bilateral pneumothorax as a life saving procedure.

Amyotrophic Lateral Sclerosis↗

[A case of the old injured vena cava superior found during the operation of lung cancer].

We operated a 78-year-old male with lung cancer and unstable angina pectoris. During the operation of right upper lobe, a mass, with size of 2 cm in diameter was detected on the right postero-lateral side of the superior vena cava, and was resected. Postoperative pathological examination suggested that the mass resulted from an injury made by a Swan-Ganz catheter used before operation. Thus, as insertion of a Swan-Ganz catheter through the right subclavian vein may involve risk, so we concluded that the right internal jugular vein or femoral vein may be preferable as a route of first choice for insertion.

Aged↗

[A case of cardiovascular Behçet's disease detected as multiple nodular shadows on chest X-ray].

A case of cardiovascular Behçet's disease is reported. A 30-year-old man was admitted to our hospital with a high fever. Multiple nodular shadows were revealed on chest X-ray. Echocardiography revealed a mural thrombus in the right ventricle. A diagnosis of multiple pulmonary septic embolisms was made, and antibiotics were administered. The mural thrombus soon resolved, but later recurred in the same location. On the 90th day after admission. The mural thrombus was surgically removed. Histologically, the thrombus consisted of numerous neutrophils and fibrin. Examination of the endocardium attached to the thrombus revealed nonspecific inflammation, with fibrotic change and necrosing granulation present. A diagnosis of cardiovascular Behçet's disease was made based on the following findings: oral ulcerations, acneiform nodules, thrombophlebitis, bilateral uveitis, and positive HLA-B51. After treatment with steroid hormones and cyclosporine, the thrombus resolved completely, and inflammatory signs diminished. Though various clinical and pathological characteristics of cardiovascular Behçet's disease have been reported, it is rare for a mural thrombus to produce multiple pulmonary septic embolisms.

Adult↗

[The outcome of adjusted accumulation dose of treatment of Graves' disease].

We evaluated the outcome of 131I treatment of Graves' disease in two different protocols (old and new protocol) of adjusted accumulation dose from 1988 to 1995. Adjusted accumulation doses of patients with above 50 g thyroid weights were increased by 5-20 Gy/g tissue in new protocol compared to those in old one. In 166 patients treated with single and plural doses of 131I treatment in 1990 (Group In), the therapeutic doses were calculated according to new protocol and in 130 patients in 1988 (Group Io), according to old one, modification of Quimby's formula. The patients treated with plural doses were classified as hyperthyroidism because the efficacies of the first treatments with 131I were insufficient. At the 5-yr follow up, the incidence of hypothyroid in Group In was 9%, subclinical hypothyroid 17%, euthyroid 30%, subclinical hyperthyroid 7%, hyperthyroid 37%. In Group Io, 11% of the patients were hypothyroid, 6% subclinical hypothyroid, 29% euthyroid, 3% subclinical hyperthyroid, 51% hyperthyroid. The incidence of hyperthyroid in Group In was lower than that in Group Io (p < 0.05). There were no significant differences in hypothyroid and euthyroid. In conclusion, we suggest that an adjusted dose of 131I in relation to the patients' thyroid weight shows some room for improvement.

Adult↗

Attenuation of Mg2(+)-block of synaptic N-methyl-D-aspartate receptors in the visual cortex of rats raised under optic nerve blockade.

It has been known that the sensitive period for ocular dominance column plasticity is prolonged in animals raised under light deprivation. We tested whether this prolongation is related to a developmental change in Mg2+ block of N-methyl-D-aspartate (NMDA) receptors. Synaptic potentials were recorded intracellularly from visual cortex slices of rats whose optic nerves were blocked bilaterally by tetrodotoxin injected into the eyes for 2-4 weeks of age. In cells from normal rats, the amplitude of NMDA receptor-mediated synaptic potentials became smaller at more negative membrane potentials, and larger at more positive potentials, even at 0.1 mM [Mg2+]o. In cells from tetrodotoxin-treated rats, the voltage-dependence was significantly weaker than in cells from normal rats at 0.1 mM [Mg2+]o. Thus, Mg(2+)-block of synaptic NMDA receptors in the visual cortex may be regulated by optic nerve activity, and may thereby control the sensitivity to synaptic plasticity in an activity-dependent manner.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Hamster liver cytochrome P450 (CYP2A8) as a 4-hydroxylase for 2,5,2',5'-tetrachlorobiphenyl.

Metabolism of 2,5,2',5'-tetrachlorobiphenyl (TCB) was studied using liver microsomes of hamsters and two hamster P450 isoforms, CYP1A2 and 2A8. CYP2A8 catalyzed selectively 4-hydroxylation of 2,5,2',5-TCB at a rate of 21.7 pmol/min/nmol P450. In contrast, CYP1A2 showed no activity for hydroxylation of 2,5,2',5'-TCB. Immunological study revealed that rabbit antiserum against CYP2A8 almost completely inhibited the microsomal 4-hydroxylation but that against CYP1A2 did not. It was also shown that the induction pattern of CYP2A8 protein by P450 inducer was similar to that of the 4-hydroxylase activity in hamster liver microsomes. These results suggest that CYP2A8 plays a major role in the 4-hydroxylation of 2,5,2',5'-TCB in hamster liver.

Animals↗

Ciliary neurotrophic factor attenuates spatial cognition impairment, cortical infarction and thalamic degeneration in spontaneously hypertensive rats with focal cerebral ischemia.

Ciliary neurotrophic factor (CNTF) has been shown to exhibit potent neurotrophic activity on peripheral and central neurons in vitro and in vivo. However, it remains to be determined whether or not CNTF rescues neuronal loss due to focal cerebral ischemia and prevents ischemia-induced disability of space navigation in rats. In the present in vivo study, we infused CNTF continuously for 4 weeks into the lateral ventricle, starting just after permanent occlusion of the left middle cerebral artery (MCA) of stroke-prone spontaneous hypertensive rats. CNTF infusion prevented the occurrence of ischemia-induced learning disability in a dose-dependent manner in rats subjected to the Morris water maze task. Subsequent histological examinations showed that cortical infarction and retrograde degeneration of the ipsilateral thalamic neurons in ischemic rats infused with CNTF were significantly less severe than those in ischemic rats infused with vehicle alone. These findings suggest that postischemic CNTF treatment prevents the occurrence of spatial learning disability in rats with permanent MCA occlusion, possibly by reducing neuronal damage within the cerebral cortex and secondary retrograde degeneration of the thalamus.

Analysis of Variance↗

Interleukin-6 prevents ischemia-induced learning disability and neuronal and synaptic loss in gerbils.

Interleukin-6 (IL-6) has been shown to have potent neurotrophic activity on peripheral and central neurons in vitro. However, it remains to be determined whether or not IL-6 rescues hippocampal CA1 neurons from lethal ischemia and prevents ischemia-induced learning disability. In the present in vivo study, we infused IL-6 continuously for 7 days into the lateral ventricle of gerbil starting 2 h before 3-min forebrain ischemia. IL-6 infusion prevented the occurrence of ischemia-induced learning disability in a dose-dependent manner as revealed by a step-down passive avoidance task. Subsequent light and electron microscopic examinations showed that pyramidal neurons in the CA1 region of the hippocampus as well as synapses within the strata moleculare, radiatum and oriens of the region were significantly more numerous in gerbils infused with IL-6 than in those receiving vehicle infusion. These findings suggest that IL-6 has a trophic effect on ischemic hippocampal neurons.

Animals↗