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Biomedical subjects

T Kondo

Publications and source records attributed to T Kondo.

At least 343 records · Page 19Linked to original sources
PubMed1999

The prevention of postoperative intraperitoneal adhesions by tranilast: N-(3',4'-dimethoxycinnamoyl)anthranilic acid.

The development of postoperative intraperitoneal adhesions continues to be a major concern for surgeons. The purpose of this study was to establish a postoperative adhesion model in rats, and to assess the effectiveness of tranilast (N-(3',4'-dimethoxycinnamoyl)anthranilic acid) in preventing postoperative adhesion formation. The adhesion model was established in 12 male Donryu rats. This involved two essential factors, drying and bleeding. Another 22 male Donryu rats were used to study the prevention of intraperitoneal adhesions. Tranilast was administered orally pre- and postoperatively. Adhesion strength was evaluated by grading, and basic fibroblast growth factor (bFGF) and transforming growth factor-beta-1 (TGF-beta1) concentration were measured. Postoperative intraperitoneal adhesions were seen in all rats, but the adhesions in the tranilast group were significantly less severe than those in the control group. Serum bFGF and TGF-beta1 levels in the tranilast group were lower at the time of surgery than those in the control group, and bFGF levels were lower at the endpoint of this study in the tranilast group than in the control group. The TGF-beta1 levels at the end-point did not differ between the two groups. These findings demonstrated that tranilast significantly reduced postoperative intraperitoneal adhesion formation.

Abdomen↗
PubMed1999

Involvement of the #12u lymph nodes around the upper lobe bronchi in patients with lung cancer of the right middle lobe, right lower lobe, or left lower lobe.

In Japan, the lymph nodes around the upper lobe bronchi, known as the #12u nodes, are not included in the nodes recommended for dissection in patients with right middle lobe carcinoma, right lower lobe carcinoma, or left lower lobe carcinoma. However, histologic examination has revealed involvement of these nodes in pneumonectomy patients whose carcinoma originated in the right lower lobe. We histologically examined the lymph nodes from 152 patients with lung cancer to determine the incidence of involvement of the #12u lymph nodes. These nodes were found to be involved in 14 (9.2%) of the 152 patients. The rate of involvement was significantly higher in those with T2-T4 disease than in those with T1 disease, and was also significantly higher in patients with N2 disease than in those with N1 disease. There were two long-term survivors without recurrence, and one other patient who lived for more than 5 years before succumbing to the disease. In conclusion, to ensure removal of all the cancer tissue, it is recommended that the #12u lymph nodes be included in the nodes routinely dissected in patients with right lower lobe carcinoma, right middle lobe carcinoma, or left lower lobe carcinoma.

Bronchi↗
PubMed1999

Effects of itraconazole on the steady-state plasma concentrations of bromperidol and reduced bromperidol in schizophrenic patients.

RATIONALE: A previously reported pharmacokinetic interaction between bromperidol and carbamazepine, an inducer of cytochrome P450 (CYP) 3A4, suggests possible involvement of CYP3A4 in the metabolism of bromperidol. OBJECTIVE: We investigated pharmacokinetic interaction between bromperidol and itraconazole, a potent inhibitor of CYP3A4, to clarify the involvement of CYP3A4 in the metabolism of bromperidol and its reduced metabolite. METHODS: Itraconazole 200 mg/day for 7 days was coadministered to eight schizophrenic patients treated with a fixed dose of bromperidol 12 or 24 mg/day for at least 2 weeks. Blood samples were taken before and 1 week after itraconazole coadministration and 1 week after its discontinuation, together with clinical assessments using the Brief Psychiatric Rating Scale (BPRS) and the Udvalg for Kliniske Undersøgelser (UKU) Side Effect Rating Scale. RESULTS: Plasma concentrations of bromperidol during itraconazole coadministration (16.7+/-4.9 ng/ml) were significantly higher (P<0.01) than before itraconazole coadministration (8.9+/-4.4 ng/ml) and 1 week after its discontinuation (9.9+/-4.3 ng/ml). Plasma concentrations of reduced bromperidol during itraconazole coadministration (3.6+/-2.9 ng/ml) were significantly higher (P<0.01) than before itraconazole coadministration (1.8+/-1.3 ng/ml). No changes were observed in BPRS and UKU scores throughout the study. CONCLUSIONS: The pharmacokinetic interaction between bromperidol and itraconazole is probably due to the inhibitory effect of itraconazole on the metabolism of bromperidol. This study provides in vivo evidence of involvement of CYP3A4 in the metabolism of bromperidol and reduced bromperidol.

Adult↗
PubMed1999

Genomic organization and expression analysis of the mouse qkI locus.

qkI, encoding a KH domain-containing RNA binding protein, has been isolated as a candidate gene for the mouse neurological mutation quaking. Here, we describe detailed studies on its genomic structure and expression pattern. We isolated approximately 1 Mb of genomic region containing the quaking locus and determined its genomic organization. The qkI locus contains at least 9 exons spanning approximately 65 kb of DNA. It gives rise to six distinct transcripts encoding, theoretically, five different protein isoforms. Exons 1 through 4 are shared by all the transcripts, whereas coding exons and two distinct 3'-UTRs downstream to the exon 4 are differentially utilized. One isoform has a truncated KH domain and may act as an antagonist to the others. These findings and identification of a single transcription initiation site suggest that differential expression of each transcript is regulated by alternative splicing. Expression of each alternative transcript and protein product was also examined. Two types of transcripts, 5 kb-A and B, are most abundant in the brain of newborn mice and are gradually downregulated thereafter. In contrast, the other three messages, 6 kb, 7 kb-A and B, increase as myelination proceeds and peak at 2 weeks of age, corresponding to the most active stage of myelination. Although the qkI messages and their products are abundant in brain and heart, a lower level of expression was found in various other tissues tested. Alternative transcripts that share the same 3'-UTR showed very similar expression patterns, suggesting a regulatory role of the 3'-UTRs in qkI gene expression.

3' Untranslated Regions↗
PubMed1999

Immunohistochemical and morphometrical study on the temporal expression of interleukin-1alpha (IL-1alpha) in human skin wounds for forensic wound age determination.

An immunohistochemical and morphometrical study on the temporal expression of interleukin-1alpha (IL-1alpha) was performed on 40 human skin wounds with different wound ages. Immunohistochemically, polymorphonuclear neutrophils mainly showed positive reactions for IL-1alpha in wounds aged between 4 h and 1 day, but with increasing wound age, neutrophils were no longer present, and macrophages and fibroblasts were positively stained. Morphometrically, the ratio of the number of IL-1alpha-positive infiltrating cells to the total number of infiltrating cells was evaluated. A considerable increase in the IL-1alpha-positive cell ratio was observed in wound specimens aged 4 h to 1 day, and the maximum ratio was 46.5% in a 7 hold wound. The mean value of the IL-1alpha-positive ratio in 10 wound specimens with different wound ages between 4 h and 1 day was 32.8 +/- 9.7%. In most cases the ratio of IL-1alpha-positive cells gradually decreased in wounds aged between 1.5 and 21 days to less than 30%, and the mean value was 17.5 +/- 7.2% (n = 27). These results suggest that ratios of IL-1alpha-positive cells considerably exceeding 30%, indicate a postinfliction interval of 1 day or less.

Adolescent↗
PubMed1999

Effects of aging and gastric lipolysis on gastric emptying of lipid in liquid meal.

Lipid delays gastric emptying, and aging is associated with changes in gastric motor function and transit. However, little is known about the effect of lipid on gastric emptying time in the elderly. To determine the effect of aging on lipid gastric emptying, we used electrical impedance tomography (EIT) to study gastric emptying of liquid meals with or without lipid in five young (23.0 +/- 0.6 years, mean +/- SEM) and six elderly (73.3 +/- 1.6 years) healthy male volunteers. These subjects drank 400 ml of non-lipid soup (triglycerides, 0 g) or lipid soup (triglycerides, 24.6g) in liquid test meals. To study the effect of lipolysis in the stomach, a liquid test meal containing 240mg of lipase in the lipid soup was also administered. Plasma cholecystokinin (CCK) concentration was measured by specific radioimmunoassay before and 30 min after the ingestion of a test meal. The gastric emptying time of the lipid soup was longer in the elderly than in the young subjects, and the time was significantly longer for lipid soup than for nonlipid soup (P < 0.05) in both the young and elderly subjects. Gastric emptying time for non-lipid soup was not significantly different between the elderly and young subjects. The administration of lipase shortened the gastric emptying time for lipid in both the elderly and the young subjects. Basal CCK concentration was significantly higher in the elderly than in the young subjects. However, there was no relationship between gastric emptying time and plasma CCK concentration after the ingestion of a test meal in the subjects overall. In conclusion, the delaying effect of lipid on gastric emptying is increased in the elderly, and the administration of lipase accelerates the emptying of lipid from the stomach.

Adult↗
PubMed1999

Effects of the CYP2D6*10 allele on the steady-state plasma concentrations of haloperidol and reduced haloperidol in Japanese patients with schizophrenia.

BACKGROUND: The CYP2D6*10 (*10) allele that causes decreased CYP2D6 activity is present in Asians with a high frequency of about 50%. In this study we studied the effects of the *10 allele on the steady-state plasma concentrations (Css) of haloperidol and reduced haloperidol. METHODS: The subjects were 67 Japanese inpatients with schizophrenia who had only the wild-type or *10 alleles. Thirty-four patients were homozygous for the wild-type allele, and 26 were heterozygous and 7 were homozygous for the *10 allele. All patients had been receiving 12 mg/day haloperidol for at least 2 weeks. Plasma concentrations of haloperidol and reduced haloperidol were measured by HPLC. RESULTS: The mean +/- SD values of haloperidol Css in the patients with 0, 1, and 2 *10 alleles were 22.8+/-11.0, 30.1+/-10.6, and 31.2+/-21.2 nmol/L, respectively, and those values for reduced haloperidol were 6.1+/-2.9, 9.5+/-3.7, and 9.9+/-6.2 nmol/L, respectively. The mean haloperidol Css was significantly (P < .05) higher in the patients with 1 *10 allele than in those with no *10 alleles. The mean Css of reduced haloperidol was significantly (P < .05) higher in the patients with 1 and 2 *10 alleles than in those with no *10 alleles. CONCLUSION: This study suggests that the *10 allele plays an important role in controlling the Css of both haloperidol and reduced haloperidol, especially in Asian subjects.

Adult↗
PubMed1999

Serum hyaluronic acid levels during pregnancy and labor.

OBJECTIVE: To study the changes in concentrations of serum hyaluronic acid in uncomplicated human pregnancies. METHODS: We determined the concentrations of serum hyaluronic acid, using a specific enzyme-linked immunosorbent assay, in 70 nonpregnant women, 250 women during their pregnancies, and 68 women at the time of parturition. Results were analyzed for statistical significance with Scheffé test for multiple comparisons. RESULTS: During pregnancy, mean (+/- standard deviation) serum hyaluronic acid levels were 11.4 +/- 4.5, 13.6 +/- 2.8, 20.6 +/- 1.5, and 46.9 +/- 7.9 ng/mL at 5-14 (n = 47), 15-26 (n = 46), 27-37 (n = 58), and 38-40 (n = 99) weeks' gestation, respectively. Pregnant women in labor (n = 68) had significantly higher levels (100.4 +/- 11.3 ng/mL) than did women at term but not in labor (P < .01). CONCLUSION: Maternal serum hyaluronic acid concentrations increase as pregnancy progresses and serum levels increase significantly at term. Hyaluronic acid may be associated with cervical ripening during parturition.

Adult↗
PubMed1999

Flavonol glycosides from flowers of Crocus speciosus and C. antalyensis.

From the flower extracts of Crocus speciosus and C. antalyensis nine flavonol glycosides have been isolated. One of these products is a new flavonol glycoside identified as kaempferol 3-O-alpha-(2,3-di-O-beta-D-glucopyranosyl)rhamnopyranoside by UV, mass and NMR spectroscopy.

Carbohydrate Conformation↗
PubMed1999

Quantitative analysis for the cellulose I alpha crystalline phase in developing wood cell walls.

FT-IR and X-ray analyses were employed to determine the relative ratio of cellulose Ialpha and Ibeta crystalline phases present in each developmental stage of coniferous tracheid cell wall formation. The IR spectra showed that initially the Ialpha phase occupies 50% of the crystalline regions in the primary cell wall cellulose and this value drops to 20% after ceasing of the cell enlarging growth for the formation of the secondary wall cellulose (the remaining regions are composed of the Ibeta phase). Although it is reasonable that the content for Ibeta, which is stress-reduced crystalline form, was higher in the secondary wall formation (Kataoka Y, and Kondo T. Macromolecules 1996;29:6356 6358) it is more interesting that during the crystallization of stress-induced Ialpha cellulose for the primary wall the stress-reduced Ibeta, is also possible to be crystallized in an alternative way. This means that throughout the period the Ialpha-causing stress may not be necessarily kept loaded. In light of our previously reported hypothesis (Kataoka Y. and Kondo T. Macromolecules 1998;31:760-764) for the formation of Ialpha phase due to cellular growing stresses in the primary wall cellulose, such an alternating on-off stress effect to account for the occurrence of both Ialpha and Ibeta phases might be related to a biological growth system in coniferous wood cells.

Cell Division↗
PubMed1999

Cold injury in mice: a model to study mechanisms of brain edema and neuronal apoptosis.

Small rodents, mice in particular, have been widely used for genetic manipulation because of the extensive knowledge in development, embryology and other molecular aspects of this species. However, the use of mice for neurobiology research in the area of brain edema and neuronal injury has not been common. Here we summarize the studies of cold injury-induced brain edema and neuronal apoptosis using mice. Blood-brain barrier (BBB) permeability, demonstrated by extravasation of a serum albumin tracer, Evans Blue, was increased immediately after the injury and returned to the control level by 24 hr. Water content was maximized at 24 hr, whereas a secondary lesion gradually progressed up to 72 hr after cold injury. The mechanism of the development of the cold injury-induced edema and the secondary lesion, involving of oxygen radicals in particular, was determined using superoxide dismutase (SOD)-1 transgenic (Tg) mice with overexpressed copper, zinc-SOD. All of the parameters, BBB permeability, water content and secondary lesion, were attenuated in the Tg mice as compared to littermate non-Tg mice. This clearly demonstrates that oxygen radicals, superoxide anion in particular, mediate cold injury. We also studied whether apoptosis contributes to brain injury following cold injury. Staining with terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end labeling showed the apoptotic cells widespread throughout the entire lesion while still remaining in the margin. DNA laddering was exhibited by gel electrophoresis. These studies indicate that oxidative mediates the development of cold injury-induced edema and the secondary injury, and induces apoptotic cell death. We believe that cold injury in mice provides a simple animal model to study the pathogenesis of brain edema and apoptosis in genetically altered animals.

Animals↗
PubMed1999

P-selectin inhibition prevents early neutrophil activation but provides only modest protection against myocardial injury in dogs with ischemia and forty-eight hours reperfusion.

OBJECTIVES: This study was designed to determine whether antibody neutralization of the adhesion protein P-selectin would prevent neutrophil activation and reduce myocardial reperfusion injury. BACKGROUND: Although inhibition of P-selectin markedly reduces short-term myocardial injury after ischemia and reperfusion, it is unknown whether it can provide meaningful long-term protection and preserve left ventricular function. METHODS: Closed-chest dogs underwent 90 min left anterior descending coronary artery occlusion and 48 h reperfusion, and were randomized to 1) a treatment group (n = 11) receiving 1 mg/kg of the blocking anti-P-selectin antibody PB1.3, or 2) a control group receiving 1 mg/kg PNB1.6 (nonblocking antibody against P-selectin, n = 7) or an equivalent volume of saline (n = 2) 10 min before reperfusion. Infarct size was assessed postmortem by triphenyl tetrazolium chloride staining. Contrast left ventriculography was used to measure left ventricular function. Activation of circulating polymorphonuclear neutrophils (PMNs) was assessed by an increase in surface CD18 expression. RESULTS: Neutrophil activation was observed at 30 min after reperfusion in the control group, but was abolished in the treatment group. Infarct size was reduced about 25% in the treatment group after controlling for variations in ischemic blood flow (p = 0.003, by analysis of covariance). However, this protective effect was not associated with preservation of blood flow to the ischemic-reperfused myocardium, nor with any improvement in global or regional left ventricular function. CONCLUSIONS: The anti-P-selectin antibody PB1.3 prevented early PMN activation, but had only a modest long-term infarct-limiting effect over 48 h reperfusion. Adhesion molecules other than P-selectin may mediate delayed PMN activation and accumulation in reperfused myocardium.

Animals↗
PubMed1999

Corneal astigmatism after cataract surgery with 4.1 mm BENT scleral and 4.1 mm plus meridian corneal incisions.

PURPOSE: To determine whether the 4.1 mm BENT (between 9 and 12 o'clock) scleral incision or the 4.1 mm plus meridian corneal incision (PMCI) is better at minimizing postoperative astigmatism. SETTING: Department of Ophthalmology, Kobe City General Hospital, Kobe, Japan. METHODS: This prospective study comprised 58 eyes of 29 consecutive patients with bilateral cataract. One eye was randomly assigned to have cataract surgery with a 4.1 mm BENT scleral incision and the other eye, with a 4.1 mm PMCI. Corneal astigmatism was measured before surgery and 1, 3, 10, 30, and 100 days after surgery. RESULTS: Mean astigmatism preoperatively and on postoperative days 1, 3, 10, 30, and 100 in the BENT scleral incision group was 0.99 +/- 0.66, 1.53 +/- 1.11, 1.12 +/- 0.72, 1.26 +/- 0.81, 1.16 +/- 0.73, and 1.09 +/- 0.64 diopters (D), respectively. Means in the PMCI group were 1.14 +/- 0.79, 1.38 +/- 0.98, 1.17 +/- 0.88, 1.31 +/- 0.77, 1.01 +/- 0.70, and 1.00 +/- 0.60 D. respectively. Astigmatism on days 1 and 10 postoperatively was significantly greater than preoperatively in the BENT group (P < .03) but not in the PMCI group. The changes in astigmatism were less in the PMCI group at every examination and were significantly different 30 days postoperatively (P < .05). The negative correlation between preoperative astigmatism and the final postoperative change was significant in both groups (P < .032); the value of x-intercept of the regression line was 1.37 D in the BENT scleral incision group and 0.82 D in the PMCI group. CONCLUSION: In cataract surgery using a 4.1 mm incision, the PMCI surpassed the BENT scleral incision in minimizing postoperative corneal astigmatism.

Adult↗
PubMed1999

Protective role of glutathione synthesis in response to oxidized low density lipoprotein in human vascular endothelial cells.

Impairment of endothelial cells by oxidized low density lipoprotein (OxLDL) is believed to be the first step in atherogenesis. It is also believed that oxidative stress/antioxidant imbalance is involved in the cell damage by OxLDL. However, little is known about the interaction between OxLDL and antioxidants. In this study, we show that treatment of human vascular endothelial cells with OxLDL caused a gradual increase of glutathione (gamma-glutamylcysteinyl glycine, GSH) levels in 24 h. OxLDL increased the intracellular levels of reactive oxygen species (ROS) and stimulated the expression of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme for the GSH synthesis, the mitogen-activated protein kinase (MAPK) activity, and the AP-1-DNA binding activity. The luciferase activity of gamma-GCS promoter containing AP-1 site was activated by OxLDL. Collectively, OxLDL induces gamma-GCS expression mediated by AP-1 resulting in an increase of GSH levels. The MAPK activity stimulated by ROS may be involved in the activation of AP-1. The increase in GSH by OxLDL may afford cellular protection against OxLDL-induced oxidative stress.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1999

Melatonin induces gamma-glutamylcysteine synthetase mediated by activator protein-1 in human vascular endothelial cells.

In the present study, we show that melatonin induces the expression of gamma-glutamylcysteine synthetase (gamma-GCS), the rate-limiting enzyme of glutathione (GSH) synthesis, in ECV304 human vascular endothelial cells. One micromolar melatonin induced the expression of gamma-GCS mRNA followed by an increase in the concentration of GSH with a peak at 24 h. An electrophoretic mobility shift assay showed that melatonin stimulates the DNA-binding activity of activator protein-1 (AP-1) as well as retinoid Z receptor/retinoid receptor-related orphan receptor alpha (RZR/RORalpha). ECV304 cells transiently transfected with a plasmid containing the gamma-GCS promoter-luciferase construct showed increased luciferase activity when treated with melatonin. The melatonin-dependent luciferase activity was found in the gamma-GCS promoter containing AP-1 site. The luciferase activity mediated by AP-1 was repressed in the promoter containing RZR/RORalpha site. In addition, cell cycle analysis showed that melatonin increases the number of cells in the G0/G1 phase; however, treatment of the cells with buthionine sulfoximine, a specific inhibitor of gamma-GCS, abolished the effect of melatonin on the cell cycle, suggesting induction of cell arrest by melatonin requires GSH. As conclusion, induction of GSH synthesis by melatonin protects cells against oxidative stress and regulates cell proliferation.

Buthionine Sulfoximine↗
PubMed1999

Biphasic effects of zonisamide on serotonergic system in rat hippocampus.

To study the mechanisms of antiepileptic action of zonisamide (ZNS), we determined the effects of ZNS on extracellular, total levels and re-uptake activity of serotonin (5-HT) in rat striatum and hippocampus. After acute administrations, plasma ZNS concentrations associated with anticonvulsive action (effective concentrations) increased the total levels of 5-HT, its metabolise (5-hydroxyindoleacetic acid: 5-HIAA) and precursor (5-hydroxytryptophan: 5-HTP). After chronic administration of ZNS, effective plasma concentrations also increased the extracellular and total levels of 5-HT, 5-HIAA, and 5-HTP. On the other hand, after both acute and chronic administrations of ZNS, a supra-effective ZNS concentration either decreased or did not affect the total levels of these substances. Therefore, the stimulatory effects of ZNS on the 5-HT system were reduced by an increase in ZNS concentration to supra-effective concentrations. ZNS concentrations of 30-1000 microM did not affect hippocampal 5HT re uptake activity in vitro. These results suggest that ZNS has biphasic effects on the 5-HT system, in that effective concentrations of ZNS enhance and supra-effective concentrations of ZNS reduce the function of the 5-HT system. These biphasic effects of ZNS on the 5-HT system may be involved in the mechanisms of action of the antiepileptic and psychotropic effects, and side effects of ZNS.

5-Hydroxytryptophan↗