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Biomedical subjects

S Kitamura

Publications and source records attributed to S Kitamura.

At least 199 records · Page 11Linked to original sources

Effects of long-term administration of erythromycin on cytokine production in rat alveolar macrophages.

Low-dose long-term erythromycin treatment has recently been reported to be very effective in patients with chronic respiratory infection and inflammation. This effect of erythromycin was thought to be not antibacterial but anti-inflammatory. However, the exact mechanism of the effect of erythromycin has not yet been clarified. The aims of this study were to investigate the effects of erythromycin on cytokine production and its mechanisms of actions in rat alveolar macrophages. Using rats with or without administration of erythromycin for 3 months, the production of the cytokines tumour necrosis factor-or (TNF-alpha), cytokine-induced neutrophil chemoattractant (CINC)-1 and CINC-2alpha by enzyme-linked immunosorbent assay and the expression of TNF-alpha and CINC-1 messenger ribonucleic acid (mRNA) by Northern blotting in rat alveolar macrophages were analysed. CINC-1 is the rat counterpart of human interleukin-8, and CINC-2alpha of human macrophage inflammatory peptide-2. Erythromycin reduced cytokine production and secretion when cytokines was induced by lipopolysaccharide treatment. Conversely, erythromycin slightly upregulated the expression of cytokine mRNA. These results suggest that erythromycin inhibits cytokine production and exhibits anti-inflammatory effects by means of a translational and/or posttranslational mechanism.

Animals↗

Debromination of (alpha-bromoiso-valeryl)urea catalysed by rat blood.

(Alpha-bromoiso-valeryl) urea, a sedative or hypnotic, is metabolized to (3-methylbutyryl)urea by reductive debromination. This study was designed to evaluate the role of blood in the debromination of (alpha-bromoiso-valeryl) urea. Rat blood containing an electron donor had significant debrominating activity toward (alpha-bromoiso-valeryl)urea. This debromination proceeded by enzymatic and non-enzymatic processes which required both NADH (or NADPH) and flavin mononucleotide (FMN), under anaerobic conditions. The debrominating activity was sensitive to inhibition by carbon monoxide, and the pH optimum was 8.5. When FMN was replaced by flavin adenine dinucleotide (FAD) or riboflavin, similar results were obtained. The optimum concentration of flavins was 10(-4) M. The reductive debromination was also mediated by rat erythrocytes, but not by plasma. When the blood or erythrocytes were boiled, the debrominating activity was not abolished, but was enhanced, suggesting that the activity arises from the haemoglobin in erythrocytes, and haemoglobin had debrominating activity when supplemented with both a reduced pyridine nucleotide and a flavin. Furthermore, haematin had significant debrominating activity in the presence of these cofactors. The activity of haematin was also observed with the photochemically reduced form of FMN. The results imply that the debromination proceeds in two steps--enzymatic or non-enzymatic reduction of a flavin such as FAD, FMN or riboflavin by NADPH or NADH, then non-enzymatic reductive debromination of (alpha-bromoiso-valeryl)urea to (3-methylbutyryl)urea catalysed by the haem group of rat haemoglobin in the presence of the reduced flavin.

Animals↗

Reductive debromination of (alpha-bromoiso-valeryl)urea by intestinal bacteria.

The reductive debromination of the hypnotic (alpha-bromoiso-valeryl)urea to (3-methylbutyryl)urea by intestinal bacteria has been studied. The caecal contents of rats, mice, hamsters, guinea-pigs and rabbits had significant debrominating activity toward (alpha-bromoiso-valeryl)urea. The cell-free extract of intestinal bacteria from the caecal contents of rats had debrominating activity in the presence of both flavin mononucleotide (FMN) and NADH (or NADPH) under anaerobic conditions. Seven pure strains of intestinal bacteria were also tested and the highest activity was observed with Clostridium sporogenes. The cell-free extract of Clostridium sporogenes had debrominating activity in the presence of both FMN and NADH (or NADPH), and this activity was inhibited by sodium arsenite and potassium cyanide. The activity of the cell-free extract was also supported by the photochemically reduced form of FMN. The debromination in intestinal bacteria seems to proceed in two steps--reduction of flavins by bacterial flavin reductase(s) in the presence of NADPH or NADH, and then the reductive debromination of (alpha-bromoiso-valeryl)urea to (3-methylbutyryl)urea by bacterial dehalogenase(s) using the reduced flavins as an electron donor. These results indicate that intestinal bacteria play a role in the reductive debromination of (alpha-bromoiso-valeryl)urea to (3-methylbutyryl)urea in animals. The debromination is inhibited by oxygen and dependent on flavins.

Animals↗

Purification and some properties of hamster liver aldehyde oxidase.

Aldehyde oxidase was purified from hamster liver cytosol by ammonium sulfate fractionation, chromatography on DEAE-cellulose and Phenyl-Toyopearl, and HPLC-gel filtration on TSK-gel G3000SW(XL) column. The purified enzyme was homogeneous by the criterion of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Its molecular weight was determined to be 144800 by SDS-PAGE and 288000 by HPLC gel filtration. The isoelectric point was pH 5.1. The apparent Km and Vmax for benzaldehyde and 2-hydroxypyrimidine were 19.0 and 4.4 microM, and 165 and 211 nmol/min/mg protein, respectively. The benzaldehyde oxidase activity was markedly inhibited by menadione and chlorpromazine. The substrate specificity was different from those of the enzymes from other animals.

Aldehyde Oxidase↗

Conversion of dieldrin to aldrin by intestinal bacteria in rats.

The present study provides the evidence that dieldrin is reductively metabolized to aldrin by intestinal bacteria in rats. When dieldrin was incubated with the cecal contents of rats, aldrin, a reduced metabolite of the epoxide, was isolated from the incubation mixture. The metabolite was identified unequivocally by UV and mass spectral comparison with an authentic sample, and on the basis of its TLC and HPLC behavior. The cecal contents of rats exhibited epoxide reductase activity toward dieldrin under anaerobic conditions. However, only marginal activity was observed under aerobic conditions. Four pure strains of intestinal bacteria exhibited epoxide reductase activities to varying degrees under anaerobic conditions. The highest activity was observed in Clostridium sporogenes. Cell-free extracts of the intestinal bacteria in rat cecal contents showed reductase activity when supplemented with both NAD(P)H and FMN under anaerobic conditions.

Aldrin↗

DT-diaphorase-like quinone reductase in rat plasma.

The present study provides the evidence that DT-diaphorase-like quinone reductase exists in rat plasma. The quinone reductase activity toward menadione was found in rat plasma in the presence of NADH or NADPH. The enzyme activity was induced by pretreatment with 3-methylcholanthrene, but was not affected by phenobarbital. The 3-methylcholanthrene-induced quinone reductase activity was separated into three fractions (F1, F2, and F3) by gel filtration, which showed NAD(P)H-linked, NADH-linked, and NAD(P)H-linked activities, respectively. F1, which was induced by 3-methylcholanthrene, was inhibited by dicumarol, and cross-reacted with rat liver DT-diaphorase antibody.

Animals↗

Pronounced palatal and mandibular tori observed in a patient with chronic phenytoin therapy: a case report.

Phenytoin, an anticonvulsant drug for epileptic patients, has many adverse effects, including calvarial thickening and coarsening of the facial features. Previous studies have demonstrated that phenytoin has an anabolic action on bone cells. This report describes pronounced palatal and mandibular tori found in a 45-year-old Japanese man undergoing chronic phenytoin therapy. The tori were extremely large, lobular, and symmetrical. A palatal torus appeared along the middle of the hard palate and mandibular tori consisted of 2 pairs of nodular masses extensively filling the lingual floor of the oral cavity. Pronounced osseous outgrowth occurred for the duration of a dose-increase of phenytoin from 1985 to 1997. His parents did not have any palatal or mandibular tori. These facts suggest that these unusual tori may have been the result of chronic phenytoin therapy, rather than association with the familial background.

Anticonvulsants↗

New index for oxygen cost of contractility from curved end-systolic pressure-volume relations in cross-circulated rat hearts.

We have already reported the linear oxygen consumption per beat (VO(2))-systolic pressure-volume area (PVA) relation from the curved left ventricular (LV) end-systolic pressure-volume relation (ESPVR) in the cross-circulated rat heart. The VO(2) intercept (PVA-independent VO(2)) is primarily composed of VO(2) for Ca(2+) handling in excitation-contraction (E-C) coupling and basal metabolism. The aim of the present study was to obtain the oxygen cost of LV contractility that indicates VO(2) for Ca(2+) handling in E-C coupling per unit LV contractility change in the rat heart. Oxygen cost of LV contractility is obtainable as a slope of a linear relation between PVA-independent VO(2) and LV contractility. We obtained a composite VO(2)-PVA relation line at a mid-range LV volume (mLVV) under gradually enhanced LV contractility by stepwise increased Ca(2+) infusion and thus the gradually increased PVA-independent VO(2) values. As a LV contractility index, we could not use E(max) (ESP-V ratio; ESP/ESV) for the linear ESPVR because of the curved ESPVR in the rat LV. A PVA at a mLVV (PVA(mLVV)) has been proposed as a good index for assessing rat LV mechanoenergetics. Since the experimentally obtained PVA(mLVV) was not triangular due to the curved ESPVR, we propose an equivalent ESP-V ratio at a mLVV, (eESP/ESV)(mLVV), as a LV contractility index. This index was calculated as an ESP-V ratio of the specific virtual triangular PVA(mLVV) that is energetically equivalent to the real PVA(mLVV). The present approach enabled us to obtain a linear relation between PVA-independent VO(2) and (eESP/ESV)(mLVV) and the oxygen cost of LV contractility as the slope of this relation.

Animals↗

Very late-onset symptomatic cerebral vasospasm caused by a large residual aneurysmal subarachnoid hematoma--case report.

A 70-year-old female developed delayed ischemic neurological deficits at 35 days after subarachnoid hemorrhage (Hunt and Kosnik grade III, Fisher group 4) caused by a ruptured aneurysm of the left middle cerebral artery. Angiography indicated late-onset cerebral vasospasm probably due to the mass effect of a large hematoma remaining in the sylvian fissure and an intracerebral hematoma after surgery. Patients with a large subarachnoid hematoma after subarachnoid hemorrhage should receive therapy to prevent cerebral vasospasm until the mass effect of the hematoma has diminished.

Activities of Daily Living↗

[Congenital ventricular diverticulum in a neonate: anesthetic considerations].

Congenital diverticulum of the ventricle is a rare cardiac malformation and the reports of its surgical repair are scarce. We experienced anesthesia for a neonate with an isolated congenital left ventricular diverticulum diagnosed in utero. A male infant presented with ventricular arrhythmias and congestive heart failure. At 9 days of life the resection of the diverticulum was performed under moderately hypothermic cardio-pulmonary bypass (CPB) Major anesthetic considerations include the possible life-threatening arrhythmias, cardiac failure due to diverticulum and cardiac dysfunction after resection. Premature ventricular contractions were noted before CPB but greatly decreased under anesthesia. The operation was performed safely and arrhythmias disappeared completely after resection. Intra- and post-operative course was uneventful without any sign of cardiac dysfunction.

Anesthesia, Inhalation↗

Expression of vascular endothelial growth factor and its receptors during lung carcinogenesis by N-nitrosobis(2-hydroxypropyl)amine in rats.

The expression of vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), VEGFR-1/Flt-1 and VEGFR-2/Flk-1, was investigated by immunohistochemical and northern blot analysis during lung carcinogenesis by N-nitrosobis(2-hydroxypropyl)amine (BHP) in male Wistar rats. After BHP was given in the drinking water for 12 wk, the rats were maintained without further treatment until they were killed at 20-28 wk. Immunohistochemical studies revealed VEGF expression in almost all malignancies, the reaction being strongly positive in most adenocarcinomas (15 of 18; 83.3%) and squamous cell carcinomas (four of five; 80.0%), but less so in a total of 120 adenomas and 136 alveolar hyperplasias. In addition, VEGF mRNA and VEGFR mRNAs were found to be overexpressed in most adenocarcinomas and squamous cell carcinomas as well as in one to three of the five adenomas tested. The results indicated that VEGF and VEGFRs play important roles in the acquisition of malignant potential by preneoplastic lung lesions induced by BHP in rats. Moreover, overexpression of VEGF was related to upregulation of VEGFR-1/Flt-1 and VEGFR-2/Flk-1 expression in malignant and premalignant lung lesions.

Adenocarcinoma↗

Reductive metabolism In vivo of trans-4-phenyl-3-buten-2-one in rats and dogs.

The reductive metabolism in vivo of a flavoring additive, trans-4-phenyl-3-buten-2-one (PBO; trans-methyl styryl ketone) was investigated in rats and dogs. In both species, the double bond-reduced product, 4-phenyl-2-butanone (PBA), was detected by HPLC as the predominant species in blood after i.v. administration of PBO. PBA detected in rat blood was identified by comparison to the authentic sample. In contrast, the carbonyl-reduced product, trans-4-phenyl-3-buten-2-ol (PBOL) was also detected as a minor metabolite of PBO in both species. The area under the curve of PBOL in rat blood was only 3% of that of PBA. PBO was mutagenic in the Ames test using Salmonella typhimurium TA 100 when S-9 mix was added, but PBA and PBOL were not. It appears that PBO is mainly metabolized to PBA in vivo in rats and dogs as a detoxification pathway.

Animals↗

[Mucosa-associated lymphoid tissue lymphoma with Sjögren's syndrome].

A 68-year-old woman presented with Sjögren's syndrome. Chest X-ray films disclosed consolidated shadows in the right S2 and an infiltration shadow in the right S8 with small nodules. Pathological examination of transbronchial lung biopsy (TBLB) specimens revealed lymphocytic infiltrations that stained positive with UCHL-1 and L 26 in immunohistochemical studies. Lung tissue specimens obtained by video-assisted thoracic surgery showed lympho-epithelial lesions with dense lymphocytic infiltration. Southern blot hybridization and polymerase chain reaction (PCR) assays demonstrated monoclonality and immunoglobulin heavy chain gene rearrangement. These findings yielded a diagnosis of mucosa-associated lymphoid tissue (MALT) lymphoma. The detection of rear-ranged genes encoding for immunoglobulin heavy chains is useful for the diagnosis of primary pulmonary lymphoproliferative disorders, especially malignant lymphomas.

Aged↗

[Anesthetic management of parturients with cerebrovascular diseases].

From January 1992 to December 1997, 13 parturients with cerebrovascular diseases had childbirth at our institution. Among them, 8 patients received anesthesia for delivery. Five patients had a history of ruptured arteriovenous malformation (AVM), cerebral aneurysm, or intraventricular bleeding due to moyamoya disease, and they had radical operations. Of these 5 patients after radical operations, three had a repeat cesarean section under spinal anesthesia, and two had a vaginal delivery under epidural anesthesia to avoid excessive hypertension and hyperventilation. There were two patients with a history of cerebrovascular diseases but had no radical operations. Of these two, one patient who was diagnosed as having aneurysm underwent elective cesarean section under spinal anesthesia, and another patient with a history of cerebral bleeding underwent cesarean section under general anesthesia for abruptio placentae. These 7 patients did well during pregnancy and puerperium. The eighth patient experienced severe headache followed by loss of consciousness caused by ruptured AVM, and required an emergency operation. Simultaneous cesarean section and craniotomy were performed at another hospital. Intrauterine fetal death (IUFD) occurred, but mother survived.

Adult↗

[A case report of emergent CABG after left main trunk occlusion as complication of direct PTCA].

A 38-years-old man was transferred to our hospital because of cardiogenic shock following acute left main trunk (LMT) occlusion as a complication of direct percutaneous transluminal coronary angioplasty (PTCA), and then underwent emergent coronary artery bypass grafting. We successed his life salvage, but he suffers from very severe heart failure following extensive myocardial infarction. Though acute LMT occlusion as a complication of PTCA is rare, a proper treatment has to be started as soon as possible if it occurs. We must make the systems of support for the emergencies among the surrounding hospitals.

Adult↗