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Biomedical subjects

H Yoshimura

Publications and source records attributed to H Yoshimura.

At least 109 records · Page 6Linked to original sources

Surgically curable and incurable scirrhous carcinomas of the stomach.

BACKGROUND AND OBJECTIVES: The purpose of this study was to identify a subgroup of patients with scirrhous carcinoma of the stomach who are more suitable for surgery by analysis of their clinicopathologic characteristics. METHODS: Seventy-three patients with scirrhous gastric carcinoma who underwent gastrectomy between 1979 and 1994 were included in the study. Clinicopathological characteristics of 5-year survivors and nonsurvivors were compared. A multivariate analysis of various prognostic factors was performed. RESULTS: The 5-year survival rate was 31.4%; 78% (28/36) of nonsurvivors died of malignant ascites and only 8% (3/36) died of hepatic or lung metastasis. When clinicopathologic parameters of 5-year survivors and nonsurvivors were compared, age, tumor size, macroscopic appearance, pT, pN, pM, stage, peritoneal lavage cytology, residual tumor, extent of gastric resection, operation time, volume of blood loss, and transfusion were significantly different. By the multivariate analysis, residual tumor, pathological depth of tumor infiltration, blood transfusion, and histological type were the independent prognostic factors. CONCLUSIONS: The prognosis of scirrhous carcinoma of the stomach is mainly determined by the depth of penetration and curability. In order to obtain better survival, early detection of tumor while it is limited to T2 stage appeared most important. Aggressive surgery would be indicated for T3 tumors, but in the case of T4 tumors, extent of operation should be determined by other factors such as extent of nodal metastasis or presence of distant metastasis.

Adenocarcinoma, Scirrhous↗

Thyroid-stimulating antibody and TSH-binding inhibitor immunoglobulin in 277 Graves' patients and in 686 normal subjects.

TSH receptor antibodies (TRAb) are believed to cause hyperthyroidism of Graves' disease. Thyroid-stimulating antibody (TSAb) and TSH-binding inhibitor immunoglobulin (TBII) have been measured as TRAb to diagnose Graves' disease and to follow Graves' patients. We intended to evaluate the clinical value of TRAb (TSAb and TBII) assay in establishing the diagnosis of Graves' disease and in predicting its clinical course. TSAb and TBII were studied in 686 normal subjects and in 277 Graves' patients before antithyroid drug therapy. We followed serial changes of TSAb and TBII in 30 Graves' patients before, during and after antithyroid drug therapy over 3.5-9 yr. We measured TSAb as a stimulator assay and TBII as a receptor assay. Both TSAb and TBII were distributed normally in 686 normal subjects. ROC curves demonstrated that both TSAb and TBII had high sensitivity and specificity for the diagnosis of Graves' disease, and were equally sensitive and specific; 150% was chosen as cut-off value for TSAb and 10% for TBII. Of the 277 untreated Graves' patients, 254 (92%) had positive TSAb and positive TBII. All of the 277 untreated Graves' patients had positive TRAb (TSAb and/or TBII). We followed the serial changes of TSAb and TBII in 30 Graves' patients over 3.5-9 yr. During antithyroid drug therapy, TSAb and TBII activities decreased and disappeared in 27 patients (Group A), but continued to be high in the other 3 (Group B). The former 27 Group A patients achieved remission, but the latter 3 Group B patients continued to have hyperthyroidism. Of the 27 Group A patients, 16 (59%) had parallel decreases of TSAb and TBII activities; in 6, the changes were predominantly observed in either TSAb or TBII, and in 4, complex changes in TSAb and TBII activities were observed. Disappearance of TSAb and appearance of TSBAb was seen in one. The other 3 Group B patients continued to have high TSAb and TBII activities and to have hyperthyroidism. In conclusion, TSAb and TBII are of clinical value in establishing the diagnosis of Graves' disease and in predicting its clinical course. We clearly demonstrated its diagnostic usefulness. Both TSAb and TBII have high sensitivity and specificity. All of the 277 untreated Graves' patients had TRAb (TSAb and/or TBII). Serial changes of TSAb and TBII during therapy differ from one patient to another, and can be classified into several groups. Changes in TSAb and TBII activities reflect the clinical courses of Graves' patients. The simultaneous measurement of both TSAb and TBII is clinically useful, since TSAb and TBII reflect two different aspects of TRAb. TSAb and TBII are different.

Adolescent↗

An animal model of copulatory disorder induced by social stress in male mice: effects of apomorphine and L-dopa.

We investigated the possible role of dopamine receptors in the mediation of copulatory disorder induced by defeat experience in male mice, using L-dopa and apomorphine. To generate the copulatory disorder, male mice were attacked 20 times daily for 5 consecutive days, as intruders in confrontation with an aggressive resident. Following the repeated exposure to defeat, virtually all intruder males failed to display copulatory behavior towards estrous females. Acute injection of apomorphine (25, 50, 75 micrograms/kg, s.c.) significantly increased both the incidence and the frequency of copulatory elements (mounting and intromission) in a dose-dependent manner. The combination of L-dopa with carbidopa, a dopa decarboxylase inhibitor, also increased significantly copulatory behavior, revealing an inverted U-shaped dose-effect curve. In both cases, locomotion and digging frequencies were significantly decreased. This evidence suggests that dopaminergic mechanisms are involved in the mediation of social stress-induced copulatory disorder.

Aggression↗

Clinicopathological features of superficial squamous cell carcinoma of the esophagus.

BACKGROUND: The depth of penetration is the crucial factor determining the prognosis of esophageal carcinoma patients. Patients with superficial esophageal carcinoma have a significantly favorable clinical course compared with those with advanced cancers. The outcome for patients with mucosal cancer is excellent with a 5-year survival rate exceeding 80%. On the other hand, submucosal cancer often metastasizes to lymph nodes or other organs, and the prognosis of these patients is far from satisfactory. METHODS: Among 165 patients with squamous cell carcinoma of the esophagus, surgically resected between December 1979 and April 1995, 30 patients (18.2%) had superficial esophageal carcinoma (SEC) confined to the epithelium, lamina propria mucosa, or submucosa. Disease profile and clinicopathological characteristics of these 30 patients were studied. RESULTS: The incidence of SEC has increased from 6.3% (2 of 32) in the first 5-year period (1979 to 1984) to 27.4% (20 of 73) in the recent 5-year period (1991 to 1995). Subjective symptoms were present in 2 (13.3%) with 15 mucosal cancers and in 4 (26.7%) with 15 submucosal cancers. The remaining 24 patients (80%) had no subjective symptoms. Twenty-two patients (73.3%) were diagnosed to have the lesions by endoscopic examination at the time of screening for gastric problems, and only 3 were detected by gastrointestinal series. None of the 15 patients with mucosal cancer had lymphatic invasion, venous invasion, or lymph node metastasis. On the other hand, in those with submucosal cancers, 9 (60%) had lymphatic invasion, 5 (33.3%) venous invasion, and 8 (53.3%) lymph node metastases. Twenty-two patients are alive without recurrence. The 3- and 5-year survival rates are 86.7% and 86.7% for patients with mucosal cancer and 72.2% and 65.0% for those with submucosal cancer, respectively. CONCLUSION: Esophagectomy with wide lymphadenectomy should be carried out for submucosal cancer, whereas esophagectomy with moderate lymphadenectomy can be preferred for mucosal cancer.

Carcinoma, Squamous Cell↗

Specific expression of ES46.5K, a novel microsomal esterase, in the mouse liver and its catalytic activity for xenobiotic amide and esters.

ES46.5K, a novel esterase, was found in mouse hepatic microsomes. The enzyme catalyzed hydrolysis of 2-acetylaminofluorene and cannabinoid esters. In latter case, the enzyme regioselectively hydrolyzed acetates of 11-hydroxy-delta8-tetrahydrocannabinol. Western immunoblotting analysis demonstrated that none of immuno-reactive proteins against ES46.5K were present in hepatic microsomes from rats, guinea-pigs, monkeys and humans. Rabbit hepatic microsomes contained an immuno-reactive protein, although molecular weight of the protein was rather high (50 kDa) by SDS-PAGE. Esterase activity stained after PAGE demonstrated that ES46.5K retained at origin. Hepatic microsomes of above animal species contained several activity bands on the PAGE, while only mouse hepatic microsomes exhibited significant activity at origin. In mice, liver was only an organ containing ES46.5K by analyzing Western immunoblotting. These results indicate that distribution of ES46.5K is quite different from known carboxylesterases, and suggest that the enzyme has some role in the biotransformation of xenobiotic amide and esters.

Adolescent↗

Two-dimensional crystals of apoferritin.

A simple 2D crystallization method using unfolded protein film as a supporting film of crystals was described, which allows modification of protein surfaces by injecting chemical reagents into the subphase after the crystal formation. As an example, glutaraldehyde was used to cross-link adjacent proteins and then stabilize protein crystals. The second layer of other proteins can also be formed on the apoferritin array using cross-linkers. The array of apoferritin is not only beneficial for electron crystallography but also for practical applications. For example, apoferritin produces a mineral core with a size which can be adjusted by the size to the cavity (i.e. 6 nm). Fabrication of such a small size of well defined fine particles is currently not easy using physical or chemical procedures. Using apoferritin, however, it is easy to produce uniform fine particles. If the core is designed to add interesting properties such as magnetism it is possible to make the highest class of magnetic film with ferritin 2D crystals. Basic researches toward practical applications of 2D protein crystal is now under way in various fields. The well defined size and function of protein molecules will benefit to many applications. The function and crystalline order can be designed by site-directed mutagenesis with the development of protein engineering.

Animals↗

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↗