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Biomedical subjects

T Kondo

Publications and source records attributed to T Kondo.

At least 145 records · Page 8Linked to original sources
PubMed2001

Hammerhead ribozyme against gamma-glutamylcysteine synthetase sensitizes human colonic cancer cells to cisplatin by down-regulating both the glutathione synthesis and the expression of multidrug resistance proteins.

Multidrug resistance in cancer cells is often associated with an elevation in the concentration of glutathione (GSH) and the expression of gamma-glutamylcysteine synthetase (gamma-GCS), a rate-limiting enzyme for GSH. We constructed a hammerhead ribozyme against a gamma-GCS heavy subunit (gamma-GCSh) mRNA transcript and transfected it to human colonic cancer cells (HCT8DDP) resistant to cisplatin (CDDP). The effect of the ribozyme transfection on the drug resistance of cancer cells was studied. (a) Transfection of the ribozyme decreased the GSH level and the efflux of CDDP-GSH adduct, resulting in higher sensitivity of the cells to CDDP. (b) The transfection suppressed the expression of ATP-binding cassette (ABC) family of transporters such as MRP1, MRP2, and MDR1, and stimulated the expression of mutant p53. (c) An electrophoretic mobility shift assay showed that mutant p53 suppresses the SP1-DNA binding activity, suggesting that this mutant p53 is functional and it, in turn, suppresses the expression of ABC transporters. Collectively, transfection of anti-gamma-GCSh ribozyme reduced the synthesis of GSH and the expression of ABC transporters, which causes an increase in the sensitivity of cancer cells to anticancer drugs. Suppression of the SP1-DNA binding activity by p53 may be a factor of down-regulation of ABC transporters.

Antineoplastic Agents↗
PubMed2001

Estimation of age of human cadavers by immunohistochemical assessment of advanced glycation end products in the hippocampus.

AIMS: Advanced glycation end products (AGEs) are known to accumulate in long-lived tissue proteins during normal ageing. In this study, we examined the expression of AGEs in human hippocampus using immunohistochemistry and determined its utility for estimating the age of cadavers of unknown age. METHODS AND RESULTS: Hippocampus tissues were obtained at autopsy from 31 individuals, including 10 fire victims, aged 0--96 years within 3 days postmortem. Immunostaining using anti-AGE antibody demonstrated that the perikarya of pyramidal neurones in the hippocampus was immunoreactive for the anti-AGE antibody, and the immunoreactivity was increased with age. Quantitative analysis of the AGE-immunoreactivity in the pyramidal neurones of the CA4 region revealed a significant correlation between the AGE-immunoreactivity and the age in nonfire death cases with a correlation coefficient of 0.91 (P < 0.01). The significant correlation could be obtained even in fire death cases affected by the unusual environmental condition. CONCLUSIONS: These results suggest that the immunohistochemical analysis of AGEs in human hippocampus may be useful for the age estimation of cadavers with unknown age.

Adolescent↗
PubMed2001

Purification and cDNA cloning of nitric oxide reductase cytochrome P450nor (CYP55A4) from Trichosporon cutaneum.

Cytochrome P450nor is involved in fungal denitrification as nitric oxide (NO) reductase. Although the heme protein has been known to occur in restricted species of fungi that belong to ascomycotina, we have previously suggested that it would also occur in the yeast Trichosporon cutaneum, which is phylogenetically far from those P450nor-producing ascomycetous fungi. Here we isolated and characterized the heme protein from the basidiomycetous yeast T. cutaneum. P450nor of the yeast (TcP450nor) exhibited properties in terms of catalysis, absorption spectrum and molecular mass that are almost identical to those of its counterparts in ascomycetous fungi. We also isolated and sequenced its cDNA. The predicted primary structure of TcP450nor showed high sequence identities (around 65%) to those of other P450nors, indicating that they belong to the same family. TcP450nor protein cofractionated with cytochrome c oxidase by subcellular fractionation and its predicted primary structure contained an extension on its amino terminus that is characteristic of a mitochondrial-targeting signal, indicating that it is a mitochondrial protein like some of the isoforms of other fungi. On the other hand, TcP450nor was unique in that inducers such as nitrate, nitrite, or NO were not required for its production in the cells. The occurrence of P450nor across the subdivisions of eumycota suggests that P450nor and denitrification are distributed more universally among fungi than was previously thought.

Amino Acid Sequence↗
PubMed2001

Isolated unilateral absence of a pulmonary artery: influence of systemic circulation on alveolar capillary vessels.

We report a case of isolated unilateral absence of a pulmonary artery. The first clinical symptom that was manifested in the patient was recurrent hemoptysis, and subsequent angiography revealed that the main pulmonary artery was absent in the right lung, which was being fed only from the systemic circulation. Right pneumonectomy was performed, and neither the main pulmonary artery nor its remnant was detected in the resected right lung. Histologically, there were many muscular vessels in the resected lung, with intimal proliferation, or with plexiform-like lesions. The alveolar septum was moderately thickened and alveolar capillary vessels were dilated. We examined the alveolar capillary endothelial cells of the resected lung for immunoreactivity to thrombomodulin (TM) and von Willebrand factor (vWF). The endothelial cells were negative for TM and positive for vWF, while in the normal lung control group, these cells were positive for TM and negative for vWF. We considered that the hemodynamics of the systemic circulation in the resected lung caused the alteration of immunohistochemical characteristics in alveolar capillary endothelial cells.

Adult↗
PubMed2001

Re-evaluation of the latent period of bladder cancer in dyestuff-plant workers in Japan.

BACKGROUND: The carcinogenesis of benzidine (BZ) and beta-naphthylamine (BNA) for bladder is well known. Although it was thought to be rare to develop occupational bladder cancer more than 20 years after the exposure to these chemicals, there are still new clinical cases even 30 years after exposure. The purpose of this study was to re-evaluate the latent carcinogenic period of BZ and BNA, in order to set the safety period after exposure for the health surveillance system. METHODS: The subjects were 236 dyestuff-plant workers in Tokyo, who had been exposed to these dyestuffs. The incidence of bladder cancer and its histopathology in this group was surveyed in the period from 1962 to 1996. RESULTS: Nineteen workers (8.1%) were found to have bladder cancers. The exposure period for these 19 patients was 82.0 +/- 50.2 months. The mean +/- SD latent period from the subjects' initial and final exposure until tumor development was 29.5 +/- 8.2 years and 20.1 +/- 10.6 years, respectively. Significantly, a negative correlation (Pearson) was observed between the exposure period and the latent period from the end of exposure to cancer onset (R = -0.544, P < 0.05). All tumors except one were transitional cell carcinoma. Flow cytometric analysis was performed in 11 patients and all of these patients had DNA aneuploidy. CONCLUSIONS: The latent periods of bladder cancer caused by BZ and BNA were longer than previously expected. It is necessary to survey the onset of bladder cancer in exposed workers more than 30 years after the initial exposure.

2-Naphthylamine↗
PubMed2001

Prolongation of activation-recovery interval over a preexcited region before and after catheter ablation in patients with Wolff-Parkinson-White syndrome.

INTRODUCTION: Preexisting changes in repolarization properties play an important role in T wave abnormalities (cardiac memory) after ablation in patients with Wolff-Parkinson-White (WPW) syndrome. However, no report has provided direct evidence for prolongation of action potential duration (APD) over a preexcited region before and after ablation. METHODS AND RESULTS: We studied 10 patients with ventricular preexcitation due to a left-sided accessory pathway (AP) (group M) and 12 patients with concealed left-sided AP (group C) to clarify prolongation of APD using activation-recovery intervals (ARIs) from epicardial and endocardial unipolar electrograms in patients with WPW syndrome. ARI was calculated from unipolar electrograms at the His bundle and the coronary sinus adjacent to the AP during atrial pacing (100 beats/min) before and 30 minutes after ablation. Before ablation, ARIs at the AP site were significantly longer in group M than in group C (255+/-21 msec vs 211+/-24 msec; P < 0.01), whereas ARIs at the His bundle did not differ between the two groups (255+/-20 msec vs 245+/-27 msec; P = NS). After ablation, group M showed no significant changes in ARIs at the AP and His bundle (256+/-19 msec and 253+/-15 msec) compared with before ablation. CONCLUSION: We found by direct analysis of ARIs from the epicardium that APD prolongation over the preexcited region was present before catheter ablation and persisted after catheter ablation. The gradual changes in repolarization properties, including APD prolongation after discontinuation of AP, may be one mechanism of cardiac memory after catheter ablation in patients with WPW syndrome.

Action Potentials↗
PubMed2001

Modulation of transalveolar fluid absorption by endogenous aldosterone in adult rats.

We examined whether transalveolar fluid transport is modulated by aldosterone in adult rats. Because colocalization of mineralocorticoid receptors (MR) with 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) is important for aldosterone specific action, we first determined the immunohistochemical distribution of MR and 11betaHSD2 in the lung. We found that alveolar epithelial cells express both MR and 11betaHSD2. Reverse transcriptase polymerase chain reaction (RT-PCR) demonstrated that rat alveolar type II epithelial cells express both MR and 11betaHSD2. We then measured alveolar fluid clearance in rats treated with chronic low-sodium diet. A low-sodium diet (0.1% NaCl for 12 to 14 days) caused hyperaldosteronism accompanied by hypokalemia, whereas serum corticosterone and adrenaline levels remained normal. We found that hyperaldosteronism was associated with significantly higher alveolar fluid clearance and that this increase was related to the amiloride-sensitive component. In addition, the increase in alveolar fluid clearance was inhibited by spironolactone. Our results show that aldosterone is able to stimulate Na+ channels of alveolar epithelial cells. We conclude that alveolar epithelium is a physiological target tissue for aldosterone and transalveolar fluid absorption could in part be modulated by endogenous aldosterone acting via MR.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗
PubMed2001

Alteration of antioxidants during the progression of heart disease in streptozotocin-induced diabetic rats.

Involvement of oxidative stress is implicated in the progression of complication of diabetes mellitus. With respect to heart diseases, we have studied role of oxidative stress/antioxidants using rats treated with streptozotocin to induce diabetes (DM). Hemodynamic and echocardiographic measurements showed thickening of the wall and an increase in the internal dimension of the left ventricle (LV) in DM rats at 8th week. Decrease in diastolic posterior wall velocity and rate of LV pressure change, and increase in LV end diastolic pressures also proved cardiac dysfunction. These changes were further developed in DM rats after 12 weeks. Utilizing rat hearts at 8th and 12th weeks, the following estimations were performed. There was a decrease in the activity of Mn-superoxide dismutase (SOD), suggesting abnormal mitochondrial metabolism of reactive oxygen species. The level of glutathione (GSH) decreased concomitant with a decrease in the expression of gamma-glutamylcysteine synthetase (gamma-GCS). The expression of transforming growth factor-beta1 (TGF-beta1), known as a growth factor and a suppressor of GSH synthesis, elevated in DM rat hearts. Immunohistochemical estimation showed an increase in type IV collagen in DM hearts. Collectively, it was suggested a linkage between mitochondrial damage to generate reactive oxygen species and inactivation of Mn-SOD and elevation of the expression of TGF-beta1 to lead suppression of GSH synthesis and induction of fibrous change for the consequent cardiac dysfunction in DM.

Animals↗
PubMed2001

Enhancement of hyperthermia-induced apoptosis by a free radical initiator, 2,2'-azobis (2-amidinopropane) dihydrochloride, in human histiocytic lymphoma U937 cells.

To elucidate the mechanism how a free radical initiator, 2,2'-azobis (2-amidinopropane) dihydrochloride (AAPH), induces cell death at hyperthermic temperatures, apoptosis in a human histiocytic lymphoma cell line, U937, was investigated. Free radical formation deriving from the thermal decomposition of AAPH was examined by spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). An assay for DNA fragmentation, observation of nuclear morphological changes, and flow cytometry for phosphatidylserine (PS) externalization were used to detect apoptosis and revealed enhancement of 44.0 degrees C hyperthermia-induced apoptosis by free radicals due to AAPH. However, free radicals alone derived from AAPH did not induce apoptosis. Hyperthermia induced the production of lipid peroxidation (LPO), an increase in intracellular Ca2+ concentration ([Ca2+]i) and enhanced expression of the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1). The effects of hyperthermia on LPO and [Ca2+]i were enhanced markedly by the combination with AAPH. A significant decrease in Bcl-2 expression, increase in Bax expression, a loss of mitochondrial membrane potential (delta psi m) and a marked increase in cytochrome c expression were found only in cells treated with hyperthermia and AAPH. Although an intracellular Ca2+ ion chelator, BAPTA-AM, completely inhibited DNA fragmentation, water-soluble vitamin E, Trolox, only partially suppressed DNA fragmentation and the increase in [Ca2+]i. In contrast, LPO was inhibited completely by Trolox, but no inhibition by BAPTA-AM was found. These results suggest that apoptosis induced by hyperthermia alone is due to the increase in [Ca2+]i arising from increased expression of IP3R1 and LPO. Additional increase in [Ca2+]i due to increased LPO and the activation of mitochondria-caspase dependent pathway play a major role in the enhancement of apoptosis by the combination with hyperthermia and AAPH.

Amidines↗
PubMed2001

Relationship between thrombolytic therapy and perfusion defect detected by Gd-DTPA-enhanced fast magnetic resonance imaging in acute myocardial infarction.

To study whether thrombolytic therapy affects Gd-DTPA-enhanced pattern and whether its pattern indicates myocardial viability, Gd-DTPA-enhanced magnetic resonance imaging (MRI) was performed in 43 patients with reperfused acute myocardial infarction 14.8+/-5.0 days after onset with breathhold scanning on a 1.5-T whole body system. The hypoenhanced area at 90 sec after contrast injection was defined as a perfusion defect (PD). Patients were divided into PD(+) and PD(-) groups. The PD was detected in 77.8% of patients treated with direct percutaneous transluminal coronary angioplasty (PTCA) and in 28.6% of patients treated by thrombolytic therapy with or without PTCA in the thrombolysis in myocardial infarction grade 3 group (p < 0.05). The myocardial wall was divided into seven segments based on the American Heart Association committee report. Wall motion of each segment was classified by one of six patterns (wall motion score [WMS]: dyskinesis, -1; akinesis, 0; severe hypokinesis, 1; hypokinesis, 2; slight hypokinesis, 3; normal, 4). By echocardiography, the average WMS and ejection fraction were similar between the PD(+) group and the PD(-) group on admission. Those parameters were significantly worse in the PD(+) group than in PD(-) group 1 month after onset. The change in WMS was significantly lower in the PD(+) group than in the PD(-) group. The number of patients and segments with more than two grades of improvement of WMS in the PD(+) group was significantly lower than that in the PD(-) group. Angiographically, left ventricular ejection fraction and WMS of the PD(+) group were significantly lower than those of the PD(-) group 3 months later. PDs were detected significantly less frequently in patients treated with thrombolytic therapy, suggesting that microvascular embolization related to formation of the no-reflow phenomenon.

Aged↗
PubMed2001

A resin veneer for enamel protection during orthodontic treatment.

The aims of this study were to test the tensile bond strength of a recently developed veneer. Sound premolar teeth (120) extracted for orthodontic purposes were divided into two experimental and two control groups. In one experimental group (V1) 4-META/MMA-TBB resin (4META) was used on the surface veneer prepared with micro particle filled resin (MFR) as an adhesive for bracketing and in the second group (V2) 4META was applied on the surface veneer with the trial resin. For the controls, in group R 4META was used on the enamel surface without veneer and in group G light-cured glass ionomer cement was applied. The 30 samples in each group were divided into three groups of 10 samples and thermal cycled (TC) at 3000, 10,000 or left uncycled. Tensile testing was carried out using an Instron machine. After tensile testing the bond failures in the experimental groups were recorded using a stereomicroscope. Statistical analysis was performed using ANOVA. In group V2 the resin veneer was able to maintain sufficient bond force to enamel during clinical use. The bond strength of group V1 was significantly higher than that of groups R (P < 0.05) and G (P < 0.01) at TC 0, but for both TC 3000 and 10,000, the bond strength of group V1 was lower than groups R and G, respectively. There were significant differences between groups V1 and R (P < 0.01) for TC 3000, and between groups V1 and R and G (P < 0.01) at TC 10,000. The bond strength of group V2 was almost equal to that of group R at TC 0. At TC 3000, group V2 showed significantly lower bond strength than group R (P < 0.05), but no significant difference was found compared with group G. At TC 10,000, there were no significant differences between groups V2, R or G. When comparing groups V1 and V2, the bond strength of group V1 was significantly higher than that of group V2 (P < 0.01) at TC 0, but the bond strength of group V1 was significantly lower than that of group V2 for both TC 3000 (P < 0.05) and TC 10,000 (P < 0.01). Comparison between groups R and G, showed that the bond strength of group R was significantly higher than that of group G for both TC 0 (P < 0.01) and TC 3000 (P < 0.01), but no significant difference was found for TC 10,000. In group V2, nine samples showed adhesive failure between the veneer surface and bracket adhesive before thermal cycling. There were significant differences between the MFR and both trial resin and glass ionomer cement (P < 0.01) when examining thermal expansion. No significant difference was found between the trial resin and glass ionomer cement. It is suggested that application of a resin veneer prior to bracket bonding is suitable for clinical application to protect the teeth and to prevent decalcification and caries.

Acrylic Resins↗
PubMed2001

Ethylenediamine-N,N,N',N'-tetraacetic acid induces parthenogenetic activation of porcine oocytes at the germinal vesicle stage, leading to formation of blastocysts.

The present study showed that treatment with a cell membrane-impermeable metal ion chelator, EDTA, of porcine oocytes at the germinal vesicle (GV) stage collected from follicles 2-6 mm in diameter induced artificial activation followed by formation of a pronucleus (PN). When the oocytes were cultured for 48 h in medium containing 0.1 to 2 mM EDTA disodium salt (Na-EDTA), they were activated to form PN, and the maximum PN formation rate (63%, n = 68) was achieved in oocytes cultured with 1 mM Na-EDTA. More than 90% of oocytes activated by 1 mM Na-EDTA treatment formed 1 PN without emission of the first and the second polar bodies (PB). This result suggests that EDTA at 1 mM may force the maturing (meiosis I) oocytes to form a PN without chromosome segregation. When oocytes at the GV stage that had been cultured with 1 mM Na-EDTA for 48 h were further cultured in 0.4% BSA-containing NCSU23 medium for 144 h, blastocysts that appeared to be morphologically normal were formed at the rate of 10%, whereas no blastocysts were formed from oocytes that had not been cultured with Na-EDTA. Next we examined the effects of Ca2+, Zn2+, Fe3+, or Cu2+-saturated EDTA (Ca-EDTA, Zn-EDTA, Fe-EDTA, and Cu-EDTA, respectively), and a Ca2+-specific chelator, EGTA, at a concentration of 1 mM. The Ca-EDTA, Fe-EDTA, and Cu-EDTA, but not Zn-EDTA or EGTA, had the ability to activate the oocytes. From these results, it is suggested that extracellular chelation of Zn2+ with EDTA of maturing (meiosis I) porcine oocytes results in parthenogenetic activation of the oocytes, which induces PN formation followed by development to blastocysts.

Animals↗
PubMed2001

Doxorubicin-induced DNA intercalation and scavenging by nuclear glutathione S-transferase pi.

Glutathione S-transferase (GST) functions in xenobiotic biotransformation and drug metabolism. Increased expression of GSTpi, an isozyme of GST, has been found in cancer cells resistant to doxorubicin hydrochloride (DOX) or cis-diamminedichloroplatinum (II) (CDDP), and this increase was believed to be correlated with drug resistance of cancer cells. GST is mainly expressed in the cytoplasm; GSTpi in the nucleus has been reported in cancer cells, but the meaning of this result is not known. Here, we studied changes in the amount of nuclear GSTpi after exposure of cancer cells to anticancer drugs, and role of the nuclear GSTpi in drug resistance. We found nuclear GSTpi in cancer cells resistant to DOX, and the amount of nuclear GSTpi was enhanced by treatment of the cancer cells with DOX or CDDP. We also found that a mushroom lectin, an inhibitor of nuclear transport, inhibited the nuclear transfer of GSTpi, suggesting the existence of a specific transport system for the nuclear transfer of GSTpi. Nuclear GSTpi protected DNA against damage by anticancer drugs. These results suggest a possible role of GSTpi in the acquisition of resistance to anticancer drugs by cancer cells.

Antineoplastic Agents↗
PubMed2001

The -141C Ins/Del polymorphism in the dopamine D2 receptor gene promoter region is associated with anxiolytic and antidepressive effects during treatment with dopamine antagonists in schizophrenic patients.

Previous studies have demonstrated a lower density of dopamine D2 receptor (DRD2) in subjects without Del alleles of the -141C Ins/Del polymorphism in DRD2 gene promoter region than in those with one or two Del alleles. The present study aimed to examine whether the -141C Ins/Del DRD2 promoter polymorphism is related to therapeutic response to selective DRD2 antagonists in the treatment of schizophrenia. Subjects consisted of 49 acutely exacerbated schizophrenic inpatients treated with bromperidol (30 cases, mean dose +/- SD: 11.4 +/- 4.8 mg/day) or nemonapride (19 cases, 18 mg/day). Clinical symptoms were evaluated by the Brief Psychiatric Rating Scale (BPRS) before and 3 weeks after the treatment. The -141C Ins/Del DRD2 genotypes, the Ins and Del alleles, were determined by a polymerase chain reaction method. Thirty-five patients were homozygous for the Ins allele and 14 were heterozygous for the Del and Ins alleles. The patients without Del allele showed a higher percentage of improvement in anxiety-depression symptoms than those with Del allele (58.5 +/- 44.5% versus 24.1 +/- 48.2%) after 3 weeks of treatment while percentage improvement in total BPRS or other subgrouped symptoms (positive, negative, excitement and cognitive symptoms) was similar between the two genotype groups. The present results suggest that the -141C Ins/Del DRD2 polymorphism is associated with anxiolytic and antidepressive effects of neuroleptic treatment in schizophrenic patients.

Adult↗
PubMed2001

Decrease in risk of lung cancer death in males after smoking cessation by age at quitting: findings from the JACC study.

To evaluate the impact of smoking cessation in individuals and populations, we examined the decrease in risk of lung cancer death in male ex-smokers by age at quitting in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk Sponsored by Monbusho (JACC Study), which was initiated from 1988 to 1990 in Japan. For simplicity, subjects were limited to male non-smokers, and former / current smokers who started smoking at ages 18 - 22, and 33654 men aged 40 - 79 years were included. We modeled the mortality rates in non-smokers and current smokers, and compared the rates in ex-smokers with those expected from the model if they had continued smoking. During the mean follow-up of 8.0 years, 341 men died from lung cancer. The mortality rate ratio for current smokers, compared to non-smokers, was 5.16, and those for ex-smokers who had quit smoking 0 - 4, 5 - 9, 10 - 14, 15 - 19 and > or = 20 years before were 4.84, 3.19, 2.03, 1.29 and 0.99, respectively. The functions of 3.20 x 10(-7) x (age)(4.5) and 1.96 x 10(-5) x (age - 29.6)(4.5) fitted the observed mortality rates (per 100000 person-years) in non-smokers and continuing smokers, respectively. A greater decrease in lung cancer mortality was estimated among those who quit smoking at younger ages. Stopping smoking earlier in life appears preferable to keep the individual risk low. The absolute rate, however, substantially decreased after smoking cessation even in those who quit at ages 60 - 69, reflecting the high mortality rate among continuing smokers in the elderly.

Adult↗