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Biomedical subjects

S Kitamura

Publications and source records attributed to S Kitamura.

At least 361 records · Page 20Linked to original sources

Purification of an alpha,beta-ketoalkene double bond reductase from Salmonella typhimurium.

An alpha, beta-ketoalkene double bond reductase was purified from the cell-free extract of Salmonella typhimurium. The purified enzyme was homogeneous by the criterion of sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The molecular weight of the enzyme was estimated to be 24,700 by the electrophoresis and 23,900 by HPLC gel filtration, respectively. The isoelectric point is pH 7.2. The enzyme in the presence of NAD(P)H exhibited double bond reductase activity toward alpha, beta-ketoalkenes such as trans-phenyl-1-propenyl ketone, trans-benzylideneacetophenone and 15-ketoprostaglandins. The enzyme activity was markedly inhibited by dicumarol.

Alprostadil↗

Acute aortic dissection with intramural hematoma: possibility of transition to classic dissection or aneurysm.

Acute aortic dissection with intramural hematoma has been believed to have a good prognosis, but we have encountered the transition of this entity to a classic dissection or aneurysm. We report the serial computed tomography (CT) features in 27 cases of acute aortic dissection with intramural hematoma. Eleven patients (40.7%) developed a classic dissection or aneurysm during follow-up. Four patients (14.8%) showed transition to a classic dissection without resolution of the intramural hematoma; each had a dilated ascending aorta measuring > 5 cm in diameter on the initial CT. One case (3.7%) developed an enlarging aneurysm without resolution of the intramural hematoma. In 19 cases (70.4%), the hematoma resolved; among these 19, the aortic diameter was significantly larger (p < 0.01) than those in a normal control group. Two of these 19 later developed an aneurysm, and four developed a classic dissection. This entity often (40.7%; 11 of 27) required surgical intervention or periodic follow-up CT examinations, particularly with a dilated ascending aorta of > 5 cm in diameter.

Acute Disease↗

Changes in platelet, granulocyte, and complement activation during cardiopulmonary bypass using heparin-coated equipment.

The effects of heparin-coated cardiopulmonary bypass (CPB) systems on platelet, granulocyte, and complement activation were investigated during cardiopulmonary bypass. Thirty patients underwent coronary artery bypass surgery with a heparin-coated (Carmeda Bio-Active Surface, CBAS, Medtronic, U.S.A.) CPB system (HC group, n = 10), a heparin-coated oxygenator and uncoated CPB circuit (HO group, n = 10), or an uncoated system (UC group, n = 10). In the HO group, plasma C3a (1667 +/- 632 ng/ml) and C4a (1088 +/- 319 ng/ml) concentrations were significantly (p < 0.05) lower than in the UC group (2846 +/- 1045 ng/ml and 1494 +/- 480 ng/ml, respectively) 10 min after the administration of protamine, but there were no significant differences in the platelet or granulocyte counts. In the HC group, granulocyte elastase concentrations 120 min after the onset of CPB (365 +/- 177 micrograms/L) and 10 min after the administration of protamine (676 +/- 314 micrograms/L) were significantly (p < 0.05) lower than in the other 2 groups (820 +/- 341 and 893 +/- 303 micrograms/L and 1365 +/- 595 and 1,258 +/- 622 micrograms/L). In addition, the increase in the plasma C3a concentration in the HC group 60 (p < 0.05) and 120 min after the onset of CPB (p < 0.05) was significantly less than in the other 2 groups. The C3a and C4a concentrations 10 min after the administration of protamine were significantly (p < 0.005 and p < 0.05) less in the HC group than in the UC group. Platelet counts 10 min after the administration of protamine were significantly higher (p < 0.05) and plasma beta-thromboglobulin concentrations during CPB were significantly lower in the HC group than in the other 2 groups 5 (p < 0.05), 60, and 120 min (p < 0.005) after the onset of CPB. Postoperative blood loss during the first 12 h in the HC group was significantly (p < 0.05) less than that in the UC group. The heparin-coated oxygenator and uncoated CPB circuit reduced complement activation but demonstrated no significant effects on the platelet and granulocyte systems. However, the heparin-coated CPB circuit (with all components making blood contact) reduced platelet, granulocyte, and complement activation and significantly reduced postoperative blood loss. Therefore, heparin coating of CPB systems improves biocompatibility.

Adult↗

Effects of endothelin B antagonist RES-701-1 on endothelin-induced contractile responses in-vivo and in-vitro in guinea-pigs.

The effects of an endothelin (ET)-receptor B-specific antagonist, RES-701-1, on ET-induced contraction of guinea-pig trachea and on ET-induced bronchoconstriction in anaesthetized guinea-pigs were investigated. In the epithelium-removed tracheal preparation, 1 x 10(-5) M RES-701-1 inhibited contractions induced by the ETB-specific agonist sarafotoxin S6c (pKB = 6.10). In the epithelium-intact tracheal preparation, RES-701-1 (1 x 10(-5) M)inhibited the ET-3-induced contraction (pKB = 5.27), but enhanced the ET-1-induced contraction significantly and shifted the concentration-response curve to the left. The maximal responses of ET-1- and ET-3-induced contraction were augmented by epithelium removal by 1.5 and 1.8-fold, respectively. Against ET-3-induced contraction in the tracheal preparation without epithelium, RES-701-1 (0.3-10 x 10(-6)M) antagonized the contraction in a concentration-dependent manner (pA2 = 5.9). On the other hand, RES-701-1 (1 x 10(-5)M) did not affect ET-1-evoked responses in the trachea without epithelium. The intravenous administration of ET-1 (1.5 nmol/kg-1) or ET-3 (1.5 nmol/kg-1) evoked a biphasic, fast and sustained bronchoconstriction in anaesthetized guinea-pigs pretreated with propranolol (1.0 mg/kg-1). when administered intravenously, RES-701-1 (0.3 or 1.0 mg/kg-1) showed significant reduction in both phases of bronchoconstriction induced by ET-3. As in the case of ET-1-induced bronchoconstriction, rES-701-1 augmented the sustained phase although a significant reduction of the fast phase was observed. These results indicate that RES-701-1 can inhibit the ET-3 induced airway responses not only in-vitro but also in-vivo.

Animals↗

Involvement of a cytochrome P450 system in microsomal debromination of alpha-(bromisovaleryl)urea.

The reductive debromination of a hypnotic, (alpha-bromisovaleryl)urea to (3-methylbutyryl)urea by rat liver microsomes was studied. Pretreatment of rats with cytochrome P450 inducers such as phenobarbitone, 3-methylcholanthrene, acetone and pregnenolone-16 alpha-carbonitrile enhanced the debromination of (alpha-bromisovaleryl)urea by liver microsomes. Microsomal debromination was inhibited by cytochrome P450 inhibitors such as metyrapone, alpha-naphthoflavone, SKF 525-A and carbon monoxide. Microsomal debromination was enhanced by addition of NADPH-cytochrome P450 reductase and inhibited by addition of an antibody against the flavo enzyme to the liver microsomes. A reconstituted cytochrome P450 system containing NADPH-cytochrome P450 reductase, and cytochrome P450 1AI or P450 2BI exhibited debrominating activity toward the hypnotic. These results indicated that a cytochrome P450 system plays an essential role in the microsomal debromination of (alpha-bromisovaleryl)urea.

Animals↗

Increased production of interleukin 1 beta and hepatocyte growth factor may contribute to foveolar hyperplasia in enlarged fold gastritis.

BACKGROUND AND AIMS: It has been reported that eradication of Helicobacter pylori improves fold width in H pylori associated enlarged fold gastritis. The aim of this study was to clarify the mechanism of fold thickening in this condition. PATIENTS AND METHODS: In eight patients with enlarged fold gastritis and 13 patients without enlarged folds, the presence of H pylori infection, inflammatory infiltrates, mucosal plasia, and epithelial cell proliferation in the body mucosa were investigated, and production of transforming growth factor alpha (TGF alpha), hepatocyte growth factor (HGF), and interleukin 1 beta (IL 1 beta) was determined by a competitive reverse transcription/polymerase chain reaction method and in vitro short-term culture of biopsy specimens. RESULTS: In the patients with enlarged fold gastritis, inflammatory infiltrates including macrophages increased with H pylori colonisation in the body. Foveolar thickness and proliferating cell nuclear antigen (PCNA) labelling index were increased. Messenger RNA levels of HGF, but not TGF alpha, were increased, and release of HGF and IL 1 beta was increased. HGF release, which was positively correlated with IL 1 beta release and foveolar thickness, decreased in the presence of IL 1 receptor antagonist. After eradication of H pylori, inflammatory infiltrates, IL 1 beta and HGF release decreased with concomitant decreases in PCNA labelling index, foveolar thickness and fold width. CONCLUSIONS: Increased IL 1 beta and HGF production caused by H pylori infection may contribute to fold thickening of the stomach by stimulating epithelial cell proliferation and foveolar hyperplasia in patients with enlarged fold gastritis.

Adult↗

KW-4679, an antiallergic drug, inhibits the production of inflammatory lipids in human polymorphonuclear leukocytes and guinea pig eosinophils.

The effects of (Z)-11-[(3-dimethylamino)propylidene]-6,11-dihydrodibenz [b.e.]oxepin-2-acetic acid monohydrochloride (KW-4679), an orally active antiallergic drug, on the production of platelet-activating factor (PAF), leukotriene (LT) and thromboxane (TX) induced by Ca2+ ionophore A23187 were examined. KW-4679 at 10 microM reduced the amount of cell-associated PAF by 52.8% in human polymorphonuclear leukocytes (PMNs). KW-4679 (1-100 microM) also inhibited the release of both LTB4 and TXB2, a stable metabolite of TXA2, by human PMNs in a concentration-dependent manner, but did not influence the release of beta-glucuronidase. The 50% inhibitory concentration (IC50) values for LTB4 and TXB2 release were 5.9 and 6.0 microM, respectively. In guinea pig eosinophils, KW-4679 inhibited the release of peptide LTs at a concentration higher than 10 microM (IC50 = 66.9 microM). KW-4679 failed to inhibit PAF acetyltransferase, 5-lipoxygenase and TX synthase, but inhibited the arachidonic acid release by human PMNs in a concentration-dependent manner in a similar concentration as that inhibiting production or release of lipid mediators (IC50 = 19.5 microM). These results indicate that KW-4679 suppresses LTs and TX release and PAF formation by reducing arachidonic acid release from phospholipids, probably through interference with phospholipase A2. The inhibitory action of KW-4679 on PAF, LT and TX production is a beneficial effect of an antiallergic drug.

Acetyltransferases↗

Effects of KW-4679, a new orally active antiallergic drug, on antigen-induced bronchial hyperresponsiveness, airway inflammation and immediate and late asthmatic responses in guinea pigs.

We investigated the effects of KW-4679, an antiallergic drug, on the development of bronchial hyperresponsiveness, airway inflammation and early and late asthmatic responses following aerosol antigen challenge in guinea pigs actively sensitized by the inhalation of aerosolized ovalbumin. Pretreatment with KW-4679 (10 mg/kg, p.o.) 1 h before antigen challenge prevented the development of bronchial hyperresponsiveness to inhaled methacholine. Examination of the bronchoalveolar lavage fluid 24 h after antigen challenge revealed the inhibitory effect of KW-4679 on the infiltration of eosinophils into the airway. Treatment with KW-4679 significantly inhibited both the immediate and late asthmatic responses. These results indicate that KW-4679 could be useful in the treatment of allergic diseases such as bronchial asthma.

Administration, Oral↗

Role of the nondominant hemisphere and undamaged area during word repetition in poststroke aphasics. A PET activation study.

BACKGROUND AND PURPOSE: Although the resting regional cerebral blood flow (rCBF) in aphasic patients has been thoroughly investigated with positron emission tomography (PET) and single-photon emission CT, and PET studies in normal subjects have elucidated the functional localization of language processing, little is known about the activation pattern of language processing in aphasic patients. METHODS: We measured the changes in rCBF during a repetition task (hearing a single word and repeating it aloud) and the resting state using the H2(15)O PET activation technique in 6 normal subjects (mean +/- SD age, 58.3 +/- 8.1 years) and 16 aphasic patients: 10 fluent aphasics (age, 60.3 +/- 12.5 years) and 6 nonfluent aphasics (age, 50.5 +/- 8.3 years). RESULTS: In normal subjects, the posteroinferofrontal area (PIF) including Broca's area, the posterosuperotemporal area (PST) including Wernicke's area, the rolandic areas, and a few other areas were activated with left side dominance by the repetition task. In the resting state, the rCBF in the left PIF and the left posterotemporal area was reduced in both fluent and nonfluent aphasics. In aphasic patients, the magnitude of activation in the right PIF and PST by the repetition task was greater than in normal subjects. The increase in rCBF during the repetition task in the left PIF correlated with the Western Aphasia Battery score of spontaneous speech in the nonfluent aphasics with a left inferofrontal lesion. CONCLUSIONS: This study shows the importance in aphasic patients of the mirror regions of the left PIF and PST in the nondominant (right) hemisphere for performing the word repetition task. The results also show the importance for nonfluent aphasic patients of the recruitment of the undamaged PIF for spontaneous speech.

Adult↗

Metabolism in vivo of 1-nitropyrene, an environmental pollutant, in fish.

The in vivo metabolism of 1-nitropyrene, an important environmental pollutant, was examined in fish, focusing on nitroreduction followed by acylation. When goldfish were bathed in a solution of 1-nitropyrene or its reduction product, 1-aminopyrene, one or two metabolites were isolated from the solution, respectively. The former metabolite was identified as 1-aminopyrene and the latter two metabolites as 1-acetylaminopyrene and 1-formylaminopyrene by comparing their mass and UV spectra, and their behaviors in HPLC and TLC, with those of authentic samples.

Animals↗

Further metabolism of 2-formylaminofluorene, a metabolite of 2-aminofluorene, in rats.

The further in vivo metabolism of 2-formylaminofluorene (FAF), which is a metabolite of 2-aminofluorene, was examined in rats. The 48 h urine collected following oral administration of FAF to rats was treated with beta-glucuronidase/arylsulfatase and extracted with benzene. When the benzene extract was subjected to HPLC, ten peaks due to FAF and its metabolites were detected. Among these metabolites, major metabolites 1, 2, 4 and 5 were isolated and identified unequivocally as 7-hydroxy-2-formylaminofluorene, 7-hydroxy-2-acetylaminofluorene, 5-hydroxy-2-formylaminofluorene and 5-hydroxy-2-acetylaminofluorene, respectively, by comparing their MS and UV spectra, and HPLC and TLC behavior with that of authentic specimens. Minor metabolites, 7-hydroxy-2-aminofluorene, 5-hydroxy-2-aminofluorene, 2-acetylaminofluorene and 2-aminofluorene together with the parent compound were detected by HPLC. These metabolites of FAF were also detected in the feces of rats given FAF.

Animals↗

Human T-cell lymphotropic virus type-I associated myelopathy complicated by optic neuritis.

A 48-year-old Japanese woman from Kyushu was admitted to the Nippon Medical School First Hospital with complaints of numbness in both legs, gait disturbance, and urinary problems. On examination, her lower extremities were spastic with increased reflexes and positive Babinski sign. Sensation was absent below the T4 spinal level. The cerebrospinal fluid contained HTLV-I antibodies and she was diagnosed with HTLV-I associated myelopathy. Her symptoms were resolved with prednisolone, but six months later a visual disturbance of the left eye edema developed. Orbital CT scans showed that left optic nerve was edematous. T2 enhanced MRI revealed a high intensity lesion of the left optic nerve. ERG was normal and no VEP was detected in response to flashing stimulation to the left eye. The HTLV-I antigen titer of CBF was very high. Her optic neuritis improved following oral administration of prednisolone and retrobulbar injections of dexamethasone. This is the first case report of HTLV-I associated myelopathy complicated by optic neuritis.

Anti-Inflammatory Agents↗

Serum KL-6 for the evaluation of active pneumonitis in pulmonary sarcoidosis.

KL-6, a mucinous high-molecular weight glycoprotein, expressed on type II pneumonocytes, is elevated in the serum of patients with active interstitial pneumonia. Forty-seven patients with histologically confirmed sarcoidosis were analyzed by chest radiography, CT, 67Ga scintigraphy, BAL fluid (BALF), and serum KL-6. Serum KL-6 level was significantly elevated in radiographic type II (945 +/- 725 U/mL; n = 13; p < 0.01) and type III (1,179 +/- 1,320 U/mL; n = 9; p < 0.01), as compared with type 0 (333 +/- 173 U/mL; n = 10) and type I (430 +/- 225 U/mL; n = 15). Serum KL-6 level was significantly elevated in patients with CT findings of irregular small opacities, ground-glass opacities, and thickened bronchovascular bundle (p < 0.01), as compared to those without these findings. Serum KL-6 level was significantly elevated in patients with positive pulmonary accumulation in 67Ga scintigraphy (1,108 +/- 1,044; n = 20; p < 0.001) as compared to those without accumulation (390 +/- 206; n = 27). Serum KL-6 level was elevated in patients with a higher CD4+/CD8+ ratio (> or =3) in BALF, as compared to those with lower ratios. These results suggest that serum KL-6 is a useful marker of sarcoidosis activity.

Adolescent↗

Clinical features of skin metastasis from lung cancer.

Metastasis to the skin from lung cancer is less common than metastasis to other organs. We clinically reviewed 16 cases of skin metastasis. The incidence of skin metastasis was 2.8% among all 579 cases of lung cancer. Large cell carcinoma showed the greatest tendency to spread to the skin and epidermoid carcinoma showed the least tendency. The most common sites for skin lesions were the back. Almost all lesions ranged from 1 to 5 cm in diameter. Clinical manifestation of skin metastasis was nodular type in all cases. At the development of skin metastasis, all cases were accompanied by metastasis to other organs. There was only a slight response to combination chemotherapy carried out 5 cases for lung cancer, and most lesions were progressive. Median survival after skin involvement was approximately 4 months.

Adult↗

[Clinico-pathological evaluation of leukoaraisosis in Alzheimer's disease].

Patients with multi-infarct dementia often have periventricular low density lesions on computed tomography and periventricular hyper-intensity lesions on computed tomography and periventricular hyper-intensity lesions on magnetic resonance imaging. Hachinski called this condition leukoaraiosis and results of previous studies that in multi-infarct dementia leukoaraiosis correlates with cerebral hypoperfusion. Periventricular low-density lesions in the white matter also occur, but their origin and clinical significance insuch patients is unknown. We studied when these lesions develop in patients with Alzheimer's dementia, and whether their presence correlates with clinical findings and cerebral blood flow. The subjects were 37 patients with a probable diagnosis of Alzheimer's dementia, as based on the Neuroepidermilogy Branch of the National Institute of Neurological Disorders and Stroke and the Alzheimer's disease and Related Disorders Association system. Autopsy findings were also available for 2 patients. Patients at higher Functional Assessment Staging of Senile Dementia of Alzheimer Type stages had more extensive periventricular low-density lesions. Patients with the lesions were more likely to have grasp reflex and sucking relex. Blood flow to the frontal and parietal cortices was significantly less in patients with the lesions than in those without the lesions. Neither of the 2 autopsies cases yielded evidence of arteriolosclerosis. Periventricular low-density lesions in Alzheimer's dementia may be closely associated with a degenerative process different from that seen in multi-infarct dementia.

Alzheimer Disease↗