Biomedical subjects

S Inoue

Publications and source records attributed to S Inoue.

At least 235 records · Page 13Linked to original sources

PubMed2000

Interleukin-8 gene repression by clarithromycin is mediated by the activator protein-1 binding site in human bronchial epithelial cells.

Macrolide antibiotics are known to be effective for the treatment of chronic inflammatory airway diseases including diffuse panbronchiolitis, chronic bronchitis, and bronchial asthma. Other than having antimicrobial activities, macrolides have antiinflammatory effects, such as the inhibition of cytokine production. In the present study we investigated the effects of clarithromycin (CAM) on interleukin (IL)-8 gene expression and protein levels, using the human bronchial epithelial cell line BET-1A. Northern blot analyses showed that CAM inhibited tumor necrosis factor (TNF)-alpha-induced IL-8 gene expression in a dose- and incubation time-dependent manner. The half-life of IL-8 messenger RNA transcripts in TNF-alpha-treated BET-1A cells did not change with CAM. Transfection studies with BET-1A cells, using fusion genes composed of the 5'-flanking sequences of the IL-8 gene and a luciferase reporter gene, demonstrated potent promoter activity in a 174-bp segment (-130 to +44 bp relative to the transcription start site). This segment includes activator protein (AP)-1 and nuclear factor (NF)-kappaB-like sites, and exhibited its strongest response to TNF-alpha. TNF-alpha-induced promoter activity in this segment showed a significant repression by CAM. However, a 156-bp segment (-112 to +44 bp) that does not include an AP-1 site but includes an NF-kappaB-like site did not show a significant repression of TNF-alpha-induced promoter activity by CAM. Mutation of the AP-1 binding site abrogated the suppression by CAM of TNF-alpha-induced enhancement of luciferase activity. In accord with promoter analyses, an electrophoretic mobility shift assay showed that CAM repressed AP-1 binding in TNF-alpha-treated BET-1A cells; however, TNF-alpha induced both AP-1 and NF-kappaB binding activities in BET-1A cells. These data suggest that macrolides such as CAM repress IL-8 gene transcription mainly via the AP-1 binding site in human bronchial epithelial cells. Our findings provide a novel mechanism for the antiinflammatory function of macrolides, implicating a target for the development of new drugs for treating chronic airway inflammation.

5' Untranslated Regions↗

PubMed2000

Risk factors for death rattle in terminally ill cancer patients: a prospective exploratory study.

Death rattle is frequently observed in cancer patients whose death is impending and may contribute to the severe distress of patients and their family members. To identify risk factors for development and persistency of death rattle, a prospective study was performed on 245 hospice inpatients. One-hundred-and-seven patients (44%) developed death rattle, 71% of whom achieved satisfactory symptom palliation until death. A multiple regression analysis identified neoplasms of brain and lung as independent risk factors for development of death rattle, while refractory symptoms were significantly associated with pulmonary neoplasms and infection/oedema. In conclusion, development of death rattle was influenced by both brain and lung malignancies, while its persistency was mainly determined by pulmonary pathology. A clinical classification of death rattle based on these factors would be established by a further confirmatory study.

Aged↗

PubMed2000

Ontogenetic changes in the expression of estrogen receptor alpha and beta in rat pituitary gland detected by immunohistochemistry.

The physiological effects of estrogen on the pituitary, including cellular proliferation and regulation of hormone synthesis, are mediated by the nuclear estrogen receptor (ER). The purpose of this study was to determine ontogenetic expression of two types of ERs (ERalpha and ERbeta) in the pituitary using specific antibodies, monoclonal antibody (1D5) for ERalpha and polyclonal antibody generated against ERbeta. First, we confirmed the detection of 66- and 55-kDa bands for ERalpha and ERbeta, respectively, in the rat pituitary extract by Western blotting. Then immunostaining with these antibodies was performed using fetal and adult Wistar rat tissues, combined with PRL or LHbeta immunohistochemistry. Intense ERbeta signal was detected throughout the pituitary from day 12 of gestation. However, staining for ERalpha only became detectable from day 17 of gestation. In contrast with the fetal period, nuclei stained for ERalpha were widely distributed in the anterior lobe in the adult rat, whereas ERbeta-positive cells were restricted in the anterior lobe. LHbeta, but not PRL, was colocalized in ERbeta-positive cells. Our results indicated that the major population of ER subtypes in the rat pituitary gland has changed around the day of birth and that the expression of ERbeta may be involved in the differentiation of pituitary cell function to synthesize a specific hormone.

Aging↗

PubMed2000

Goosecoid suppresses cell growth and enhances neuronal differentiation of PC12 cells.

In all vertebrate species, the homeobox gene goosecoid serves as a marker of the Spemann organizer tissue. One function of the organizer is the induction of neural tissue. To investigate the role of goosecoid in neuronal differentiation of mammalian cells, we have introduced goosecoid into PC12 cells. Expression of goosecoid resulted in reduced cell proliferation and enhanced neurite outgrowth in response to NGF. Expression of goosecoid led to a decrease in the percentage of S-phase cells and to upregulation of the expression of the neuron-specific markers MAP-1b and neurofilament-L. Analysis of goosecoid mutants revealed that these effects were independent of either DNA binding or homodimerization of Goosecoid. Coexpression of the N-terminal portion of the ets transcription factor PU.1, a protein that can bind to Goosecoid, repressed neurite outgrowth and rescued the proliferation of PC12 cultures. In contrast, expression of the bHLH transcription factor HES-1 repressed goosecoid-mediated neurite outgrowth without changing the proportion of S-phase cells. These results suggest that goosecoid is involved in neuronal differentiation in two ways, by slowing the cell cycle and stimulating neurite outgrowth, and that these two events are separately regulated.

Animals↗

PubMed2000

Effect of beta-blocker therapy on severe ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy.

Beta-blocker therapy has been shown to improve cardiac function and prognosis in patients with idiopathic dilated cardiomyopathy (DCM). However, whether beta-blockers reduce severe ventricular arrhythmias and sudden cardiac death has not been clarified. The present study was designed to investigate the effects of beta-blockers on non-sustained ventricular tachycardia (VT) and sudden cardiac death in patients with DCM. Sixty-five patients with DCM treated with diuretics, digitalis and angiotensin-converting enzyme inhibitors were assigned to receive beta-blockers (n = 33) or not (n = 32). Mean follow-up was 53+/-30 months. The echocardiographic indices of cardiac function, the incidence of non-sustained VT on Holter monitoring electrocardiograms, and sudden cardiac death rate were compared between the 2 groups. Comparable improvement in cardiac function on echocardiograms was found in the 2 treatment groups. The patient group treated with beta-blockers showed a significant reduction in the prevalence of VT (from 43 to 15%, p<0.05) and the development of new episodes of VT (5 vs. 16%) compared to the group without beta-blockers. The sudden cardiac death rate did not differ between the 2 groups. The results of the present study suggest that beta-blockers are effective in reducing severe ventricular arrhythmias in patients with DCM.

Adrenergic beta-Antagonists↗

PubMed2000

U-46619, a selective thromboxane A2 mimetic, inhibits the release of endogenous noradrenaline from the rat hippocampus in vitro.

Possible roles of thromboxane A2 (TXA2) in the release mechanism of hippocampal noradrenaline (NA) were examined in vitro. Slices or crude synaptosomes prepared from the rat hippocampus were superfused with modified Krebs-Ringer solution. Application of 20 mM KCl for 5 min increased the release of NA from the slices, and this release was consistently reproduced. Application of U-46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxy prostaglandin F2alpha), a specific TXA2 mimetic, just before the second KCl (20 mM) stimulation decreased the KCl-evoked NA release in a concentration-dependent manner (10-100 microM). This U-46619 (50 microM)-induced inhibition of NA release was abolished by 10 microM SQ29548, a specific TXA2 receptor antagonist. In experiments with hippocampal crude synaptosomes, however, KCl (20 and 40 mM)-evoked release of NA was not attenuated by U-46619 (100 microM). Furthermore, the inhibitory effect of U-46619 (50 microM) in the sliced preparations was not modified by 100 microM (-)-bicuculline, a GABA(A)-receptor antagonist. The present results indicate that U-46619 inhibits the release of NA from the rat hippocampus by activation of TXA2 receptors. Activation of TXA2 receptors probably excites an unidentified but not GABAergic neuron system, thereby inhibiting the NA release from the rat hippocampus.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed2000

Involvement of complexin II in synaptic plasticity in the CA1 region of the hippocampus: the use of complexin II-lacking mice.

An electrophysiological study was performed with mice lacking complexin II, a presynaptic protein. The long-term potentiation (LTP) by high-frequency stimulation, recorded in the hippocampal CA1 area, was decreased in complexin II-lacking mice (CPXII KO mice). The overall postsynaptic currents elicited by low frequency stimulation on the Schaffer collateral/commissural fibers in the hippocampal CA1 pyramidal cells were not different between wild-type and mutant mice. Excitatory postsynaptic currents (EPSCs) recorded in the presence of 50 microM bicuculline and inhibitory postsynaptic currents (IPSCs) recorded in the presence of 50 microM AP-5 (DL-2-amino-5-phosphonopentanoic acid) + 30 microM CNQX (6-cyano-7-nitroquinoxaline-2,3-dione) were also identical between wild-types and mutants. Furthermore, the EPSCs following repetitive stimulation (10 Hz) in CPXII KO mice did not show any difference with wild-types. These findings suggest that complexin II does not play a crucial role in ordinary neural transmission, short-term synaptic plasticity or synaptic transmission during high-frequency repetitive stimulation. Therefore, the protein is thought to be involved in the LTP process following tetanic stimulation, including the induction and/or maintenance of the LTP.

Adaptor Proteins, Vesicular Transport↗

PubMed2000

Effect of oxidized cholesterol on age-associated changes to immune parameters in spleen lymphocytes and peritoneal exudate cells derived from rats.

The effects of oxidized cholesterol on immune parameters were examined by using spleen lymphocytes and peritoneal exudate cells (PEC) derived from 5-week- (Young) and 9-month-old (Adult) rats. The immunoglobulin (Ig) G and IgM production was inhibited by oxidized cholesterol in the rats of both ages when lymphocytes were exposed to 30 micrograms/ml of oxidized cholesterol for 24 hr. The intracellular IgA level was also lowered by 30 micrograms/ml of oxidized cholesterol, irrespective of age. In contrast, IgE production was significantly increased by the addition of 30 micrograms/ml of oxidized cholesterol in only young lymphocytes. Moreover, oxidized cholesterol enhanced the intracellular histamine accumulation in only adult PEC, although the total histamine level produced by PEC was similar in the rats of both ages. These results thus suggest the possibility that oxidized cholesterol can have different effects on the age-related modulation of immune functions such as Igs production and histamine release.

Aging↗

PubMed2000

Substrate specificity of regiospecific desaturation of aliphatic compounds by a mutant Rhodococcus strain.

Substrate specificity of cis-desaturation of alipahtic compounds by resting cells of a mutant, Rhodococcus sp. strain KSM-MT66, was examined. Among substrates tested, the rhodococcal cells were able to convert n-alkanes (C13-C19), 1-chloroalkanes (C16 and C18), ethyl fatty acids (C14-C17) and alkyl (C1-C4) esters of palmitic acid to their corresponding unsaturated products of cis configuration. The products from n-alkanes and 1-chloroalkanes had a double bond mainly at the 9th carbon from their terminal methyl groups, and the products from acyl fatty acids had a double bond mainly at the 6th carbon from their carbonyl carbons.

Fatty Acids↗

PubMed2000

Production of isopropyl cis-6-hexadecenoate by regiospecific desaturation of isopropyl palmitate by a double mutant of a Rhodococcus strain.

Resting cells of a double mutant noted as KSM-MT66, derived from Rhodococcus sp. strain KSM-B-3 by UV irradiation, were found to cis-desaturate isopropyl hexadecanoate, yielding isopropyl cis-6-hexadecenoate. Addition of sodium glutamate (1.0%), Mg SO4 (2 mM), and thiamine (2 mM) increased the productivity of the unsaturated product in phosphate buffer. Optimal temperature and pH for the reaction were around 26 degrees C and 7, respectively. Under the optimized conditions, more than 50 g/l of isopropyl cis-6-hexadecenoate was produced after a 3-day incubation by resting cells of the mutant. Thus, cis-6-hexadecenoic acid, the main component of human sebaceous lipids, can be manufactured economically by the rhodococcal bioconversion.

Amino Acids↗

PubMed2000

Pravastatin attenuates cardiovascular inflammatory and proliferative changes in a rat model of chronic inhibition of nitric oxide synthesis by its cholesterol-lowering independent actions.

Recent studies suggest that some of the beneficial effects of 3-hydroxyl-3-methylglutaryl (HMG)-CoA reductase inhibitors such as pravastatin may be through their cholesterol-lowering independent effects on the blood vessels. We have recently reported that chronic inhibition of nitric oxide (NO) synthesis with N(omega)nitro-L-arginine methyl ester (L-NAME) increases systolic blood pressure and induces coronary vascular inflammatory changes in rats. We designed this study to investigate whether treatment with pravastatin attenuates such proarteriosclerotic changes through their cholesterol-lowering independent effects. Several groups of Wistar-Kyoto rats were studied: the control group, L group received L-NAME in their drinking water (100 mg/kg per day) and L+Px group received L-NAME plus pravastatin (50, 100 or 250 mg/kg per day). We observed marked increases in monocyte infiltration into the coronary arteries, proliferative cell nuclear antigen-positive cells, and monocyte chemoattractant protein-1 (MCP-1) expression in the heart on day 3 after L-NAME administration began. Treatment with pravastatin did not affect serum cholesterol levels or systolic blood pressure but did reduce the L-NAME induced inflammatory and proliferative changes. Pravastatin also attenuated the MCP-1 gene expression induced by L-NAME. In summary, pravastatin inhibited the inflammatory and proliferative changes in the coronary vessels through their cholesterol-independent effects in this model, which may provide an insight into the mechanisms of anti-inflammatory or anti-arteriosclerotic actions of pravastatin.

Animals↗

PubMed2000

Effects of medical education on attitudes towards mental illness among medical students: a five-year follow-up study.

In order to clarify the effects of medical education on attitudes towards mental illness among medical students, a follow-up study was conducted. All 100 students entering Kochi Medical School in 1988 were subjects. The initial questionnaire survey was conducted in 1988, and followed up in 1993. Response rate was 69% in the initial survey, and 83% in the follow-up study. By the time of the follow-up, all of the students had completed their medical education, including courses in psychiatry and mental health. Results were as follows: At the follow-up study, 1) a significantly higher percentage of students replied that they accepted the mentally ill as co-workers; 2) significantly favorable changes were observed in attitudes towards psychiatric services; 3) optimism about the effectiveness of treatment for mental illness at an early stage and prevention of mental illness had decreased; and 4) no change was observed in attitudes toward human rights of the mentally ill, except in the case of one item stating that the mentally ill should not have children in order to avoid hereditary handicaps, with which a lower percentage agreed. Conclusively, medical education can play an important role in attitudes towards mental illness.

Attitude of Health Personnel↗

PubMed2000

Lack of integrative control of body temperature after capsaicin administration.

BACKGROUND: Body temperature is usually regulated by opposing controls of heat production and heat loss. However, systemic administration of capsaicin, the pungent ingredient of hot peppers, facilitated heat production and heat loss simultaneously in rats. We recently found that the capsaicin-induced heat loss and heat production occur simultaneously and that the biphasic change in body temperature is a sum of transient heat loss and long-lasting heat production. Moreover, suppression of the heat loss response did not affect capsaicin-induced heat production and suppression of heat production did not affect capsaicin-induced heat loss. These observations suggest the independent peripheral mechanisms of capsaicin-induced thermal responses. Thus, the capsaicin-induced thermal responses apparently lack an integrated control. METHODS: Male Wistar rats were maintained at an ambient temperature of 24 +/- 1 degrees C on a 12 h on-off lighting schedule at least for two weeks before the experiments. They were anesthetized with urethane (1.5 g/kg, i.p.) and placed on a heating pad, which was kept between 29 and 30 degrees C. Skin temperature(Ts) was measured with a small thermistor, which was taped to the dorsal surface of the rat's tail, to assess vasoactive changes indirectly. Colonic temperature(Tc) was measured with another thermistor inserted about 60 mm into the anus. O2 consumption was measured by the open-circuit method, and values were corrected for metabolic body size (kg0.75). Capsaicin (Sigma) was dissolved in a solution comprising 80% saline, 10% Tween 80, and 10% ethanol, and injected subcutaneously at a dose of 5 mg/kg. Each rat received a single injection of capsaicin because repeated administration of capsaicin renders an animal insensitive to the subsequent administration of capsaicin. Laminectomy was performed at the level of the first and second cervical vertebrae to expose the cervical spinal cord for sectioning. The brain was transected at 4-mm rostral from the interaural line with an L-shaped knife. RESULTS: After administration of capsaicin, O2 consumption increased from 13.5 +/- 0.4 mL/min/kg0.75 at 0 min to a peak of 15.9 +/- 0.4 mL/min/kg0.75 at 71 min and gradually declined but remained higher than the basal value until the end of the 4-h observation period. Ts also immediately increased from 27.7 +/- 0.2 degrees C to 31.9 +/- 0.3 degrees C at 39 min, and it returned to the baseline level within 90 min after the capsaicin administration. Tc initially decreased from 37.1 +/- 0.1 degrees C to 36.8 +/- 0.2 degrees C at 43 min and then gradually increased over the baseline level and remained at 37.6 +/- 0.2 degrees C until the end of the experiment. In spinalized rats, the capsaicin-induced increases in O2 consumption was largely attenuated, while the basal O2 consumption was similar to that of control rats. The basal Ts of spinalized rats was 32.4 +/- 0.3 degrees C, which was higher than that of control rats. Capsaicin increased Ts by less than 1 degree C, and Tc did not change after the capsaicin administration. O2 consumption of decerebrated rats was statistically higher than that of control rats after the injection of capsaicin. However, capsaicin did not increase Ts, showing a lack of a vasodilatory response. Decerebration between the hypothalamus and midbrain prevented the capsaicin-induced heat loss but not the heat production response. CONCLUSION: These results show that the capsaicin-induced heat production and heat loss are controlled separately by the brainstem and by the forebrain, respectively, and suggest that the body temperature regulation is performed without an integrative center.

Animals↗

PubMed2000

[Optimal dose of indocyanine-green injected from the peripheral vein in cardiac output measurement by pulse dye-densitometry].

Cardiac output is measured by pulse dye-densitometry using indocyanine-green (ICG). This cardiac output is estimated by correlating with the cardiac output measured by pulmonary artery catheter using thermodilution method. Twenty-four patients scheduled for elective cardiovascular surgeries under general anesthesia were studied. The pulse dye-densitometry monitoring system used was DDG-2001 (Nihon Kohden, Japan). In group A (13 patients: 19 times), ICG was administered from the peripheral vein as bolus doses of 5, 10 or 20 mg (5 mg.ml-1 water solution). In group B (11 patients: 12 times), ICG was administered from the peripheral vein as bolus doses of 20, 10 or 5 mg (5 mg.ml-1 water solution). The correlation (Pearson's correlation coefficient) and precision (the method proposed by Bland and Altman) compared with cardiac output measured by pulmonary artery catheter were examined. Better correlation and precision were recognized after 20 mg ICG injection than 5 or 10 mg ICG injection. In conclusion, the measurement of cardiac output by pulse dye-densitometry with peripheral vein ICG injection was useful using a bolus dose of ICG 20 mg.

Aged↗

PubMed2000

[Prediction of the clinical efficacy of hepatic arterial chemotherapy for metastatic hepatic cancer by intraarterial infusion of 99mTc-MIBI].

SPECT was performed in 11 patients with metastatic hepatic cancer by intraarterial infusion of 99mTc-MIBI before hepatic arterial chemotherapy was started, and the degree of accumulation and clinical efficacy were compared. Early and delayed SPECT images were obtained and various parameters were calculated, including early ratio (ER), delayed ratio (DR), washout rate (WR), and retention index (RI). Judgement of clinical efficacy was made by CT before and after hepatic arterial chemotherapy and was classified as effective, unchanged, and progressive groups. The mean values of ER and DR in the effective group were higher than those in the progressive group. No relationships were noted among the WR and RI values of the groups. The assessment of ER and DR using 99mTc-MIBI intraarterial SPECT is considered to be useful for prediction of the clinical efficacy of hepatic arterial chemotherapy for metastatic hepatic cancer.

Adult↗

PubMed2000

[Anti-emetic treatment for patients with lung cancer after chemotherapy, and usefulness of prochlorperazine for psychiatric emesis].

Clinical study of cisplatin 80 mg/m2 and other agents was undertaken to determine whether they could prevent psychiatric emesis during chemotherapy in 50 patients with lung cancer. YG character tests revealed that 9 patients had a coupled rightward shift in N (nervous) and I (inferior complex) components, and were classified as emotionally unstable. In these 9 cases, addition of 15 mg prochlorperazine to the preventive combined administration of 3 mg granisetoron, 500 mg methylpredonisolon, and 40 mg metoclopramide decreased the post-chemotherapy psychiatric emesis from 100% in 3 control cases to 16.7% in 6 added cases. In the remaining 41 cases, the preventive combined administration alone was effective. The good control of acute emesis is the first priority in emotionally unstable patients. The addition of prochlorperazine might be a useful therapy for psychiatric emesis induced by anticancer agents in emotionally unstable patients.

Aged↗

PubMed2000

[Intraoperative motor evoked potential monitoring: a review of 115 cases].

We reviewed our experiences of intraoperative motor evoked potentials (MEPs) monitoring for 115 operations on the spine or spinal cord. We observed compound muscle action potentials from bilateral anterior tibial muscles by electrical transcranial stimulation of the motor cortex under general anesthesia induced and maintained with intravenous anesthetics (ketamine, propofol, or droperidol), fentanyl, and 50% nitrous oxide. Partial neuromuscular blockade was obtained with continuous infusion of vecuronium. MEPs were recorded bilaterally in 91 cases (79%) and laterally in 18 cases (16%). Postoperative deterioration of motor function was observed in 2 cases and amplitude of MEPs decreased more than 50% of control values in both cases. Intraoperative monitoring of MEPs might be a reliable indicator of spinal cord motor function.

Adult↗

PubMed2000

Sequence analysis of trinucleotide repeat microsatellites from an enrichment library of the equine genome.

Microsatellites are useful tools for the construction of a linkage map and parentage testing of equines, but only a limited number of equine microsatellites have been elucidated. Thus, we constructed the equine genomic library enriched for DNA fragments containing (CAG)n repeats. The enriched method includes hybridization-capture of repeat regions using biotin-conjugated oligonucleotides, nucleotide substrate-biased polymerase reaction with the oligonucleotides and subsequent PCR amplification, because these procedures are useful for the cloning of less abundant trinucleotide microsatellites. Microsatellites containing (CAG)n repeats were obtained at the ratio of one per 3-4 clones, indicating an enrichment value about 10(4)-fold, resulting in less time consumption and less cost for cloning. In this study, 66 different microsatellites, (CAG)n repeats, were identified. The number of complete simple CAG repeats in our clones ranged 4-33, with an average repeat length of 8.8 units. The microsatellites were useful as sequence-tagged site (STS) markers. In addition, some clones containing (CAG)n repeats showed homology to human (CAG)n-containing genes, which have been previously mapped. These results indicate that the clones might be a useful tool for chromosome comparison between equines and humans.

Animals↗