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Biomedical subjects

T Kondo

Publications and source records attributed to T Kondo.

At least 91 records · Page 5Linked to original sources

Lamivudine treatment for reverse seroconversion of hepatitis B 4 years after allogeneic bone marrow transplantation.

Reverse seroconversion of hepatitis B virus (HBV) after allogeneic BMT is rare. We present a case of HBV reactivation late after allogeneic BMT which responded well to lamivudine therapy. A 35-year-old woman with CML received an allogeneic BMT. Before BMT, the patient had immunity to HBV, with serum antibodies against hepatitis B surface antigen (HBsAb), and the donor was completely negative for HBV. Four years after BMT, acute hepatitis occurred with a detectable level of HBV-DNA. Lamivudine rapidly reduced transaminase and bilirubin levels, and serum HBV-DNA decreased to negative. Retrospective analysis revealed that there had been a gradual decrease in serum HBsAb titers after BMT. Administration of lamivudine immediately after HBV replication may be more effective than vaccination of hepatitis B surface antigen-negative donors before BMT.

Adult↗

Control of ceramide-induced apoptosis by IGF-1: involvement of PI-3 kinase, caspase-3 and catalase.

Insulin-like growth factor-1 (IGF-1) inhibited N-acetylsphingosine (C2-ceramide)-induced HL-60 cell apoptosis via relieving oxidative damage. This inhibitory action of IGF-1 was blocked by a phosphatidylinositol-3 (PI-3) kinase inhibitor wortmannin and enhanced by overexpression of the p110 catalytic subunit of PI-3 kinase. Either IGF-1 pretreatment or PI-3 kinase overexpression restored ceramide-depleted catalase function, and this restoration was inhibited by wortmannin. A catalase inhibitor 3-amino-1h-1, 2, 4-triazole (ATZ) blocked the inhibitory action of IGF-1 on ceramide-induced apoptosis, whereas exogenous purified catalase enhanced it. Ceramide-activated caspase-3 was inhibited by IGF-1/PI-3 kinase and enhanced by wortmannin, while the addition of a specific caspase-3 inhibitor DMQD-CHO significantly enhanced the restoration by IGF-1 of ceramide-depleted catalase function. Moreover, IGF-1 inhibited C2-ceramide-induced decrease of mitochondrial membrane potential, and increase of cytochrome c release, caspase-3 cleavage and caspase-3 activity as judged by PhiPhiLux cleaving method. In summary, these results suggest that IGF-1/PI-3 kinase inhibited C2-ceramide-induced apoptosis due to relieving oxidative damage, which resulted from the inhibition of catalase by activated caspase-3.

Androstadienes↗

Ventricular activation and recovery measured in electrocardiographic limb leads correlate with measurements from specific areas in body surface mapping.

AIMS: Dispersion of ventricular depolarization-repolarization in 12-lead electrocardiograms (ECGs) has been reported to provide noninvasive information on arrhythmogenicity. However, there are two methods to calculate the dispersion from ECGs including and excluding limb leads. The aim of this study was to examine whether temporal parameters from limb leads represent activation and repolarization of a particular part of the body surface. METHODS AND RESULTS: We compared the temporal parameters of activation time (AT), activation-recovery interval (ARI), and recovery time (RT) from limb leads of ECGs with those from an 87-lead body surface maps. The study population consisted of 50 normal subjects (25 men and 25 women, 19.4 +/- 1.6 years). The temporal parameters in leads I, II, and III were highly (r > 0.9) correlated with those in unipolar leads over the left lateral, left lower, and right lower chest, respectively. The temporal parameters in leads aVR, aVL, and aVF showed a significant correlation (r > 0.8) with those in unipolar leads over the right upper, left upper, and lower anterior chest, respectively. The mean AT, ARI, and RT from each limb lead of ECG were almost the same as those of unipolar leads over the corresponding areas of the body surface. CONCLUSIONS: These findings suggest that ATs, ARIs, and RTs from limb leads may represent those from unipolar leads of particular areas over the body surface in normal subjects. The temporal parameters from limb leads of ECGs may provide information on activation and repolarization as well as the precordial leads of ECGs.

Adolescent↗

Membrane potential and bicarbonate secretion in isolated interlobular ducts from guinea-pig pancreas.

The interlobular duct cells of the guinea-pig pancreas secrete HCO(3)(-) across their luminal membrane into a HCO(3)(-)-rich (125 mM) luminal fluid against a sixfold concentration gradient. Since HCO(3)(-) transport cannot be achieved by luminal Cl-/HCO(3)(-) exchange under these conditions, we have investigated the possibility that it is mediated by an anion conductance. To determine whether the electrochemical potential gradient across the luminal membrane would favor HCO(3)(-) efflux, we have measured the intracellular potential (V(m)) in microperfused, interlobular duct segments under various physiological conditions. When the lumen was perfused with a 124 mM Cl- -25 mM HCO(3)(-) solution, a condition similar to the basal state, the resting potential was approximately -60 mV. Stimulation with dbcAMP or secretin caused a transient hyperpolarization (approximately 5 mV) due to activation of electrogenic Na+-HCO(3)(-) cotransport at the basolateral membrane. This was followed by depolarization to a steady-state value of approximately -50 mV as a result of anion efflux across the luminal membrane. Raising the luminal HCO(3)(-) concentration to 125 mM caused a hyperpolarization (approximately 10 mV) in both stimulated and unstimulated ducts. These results can be explained by a model in which the depolarizing effect of Cl- efflux across the luminal membrane is minimized by the depletion of intracellular Cl- and offset by the hyperpolarizing effects of Na+-HCO(3)(-) cotransport at the basolateral membrane. The net effect is a luminally directed electrochemical potential gradient for HCO(3)(-) that is sustained during maximal stimulation. Our calculations indicate that the electrodiffusive efflux of HCO(3)(-) to the lumen via CFTR, driven by this gradient, would be sufficient to fully account for the observed secretory flux of HCO(3)(-).

Animals↗

[Metachronous lung cancer: indication and outcome].

Although lobectomy is the standard surgical treatment for primary lung cancer, it is unclear whether lobectomy will be benefit for patients with metachronous lung cancer. The purpose of this study is to evaluate the difference of benefit between lobectomy and limited resection at second lung resection. Forty-eight patients, who had already undergone lobectomy due to primary lung cancer, undergoing second lobectomy (n = 30) or limited resection (n = 18) for metachronous lung cancer were investigated. The over-all 5-year survival rate of second operation was 51.9%. Although there was no significant difference of 5-year survival rates between lobectomy and limited resection, 50.4% and 49.4%, respectively, lobectomy for T1N0 subset prolonged the survival compared to limited resection, 5-year survival rates, 69.6% and 31.7%, respectively. However, lobectomy resulted in more postoperative complications and less preservation of lung function. Lobectomy should be considered the surgical procedure of choice for patients with metachronous T1N0 lung cancer when lung function is preserved.

Aged↗

[Synchronous tumors consisted of bronchial carcinoid and adenocarcinoma of the lung].

We report a case of synchronous tumors consisted of bronchial carcinoid and adenocarcinoma of the lung. A 58-year-old female was referred to our hospital after screening, because an abnormal shadow was noted in the right lung on her computed tomography (CT) of the chest. CT scans showed a peripheral pulmonary mass in the right middle lobe and a nodule around the right lower lobe bronchus. The nodular lesion like swollen lymph node was diagnosed as bronchial carcinoid originated in B6 by bronchoscopy. The pulmonary mass was diagnosed as adenocarcinoma by using core needle biopsy during operation. Right middle and lower bilobectomy and mediastinal lymph node dissection were performed. Coincidence of a bronchial carcinoid and an adenocarcinoma of the same side of the lung is a rare occurrence.

Adenocarcinoma↗

Effects of EDTA saturated with Ca2+ (Ca-EDTA) on pig, bovine and mouse oocytes at the germinal vesicle stage during maturation culture and the involvement of chelation of Zn2+ in pronuclear formation induction by Ca-EDTA.

EDTA saturated with Ca(2+), Fe(3+) or Cu(2+) can induce parthenogenetic activation of pig oocytes at the germinal vesicle stage, whereas EDTA saturated with Zn(2+), which is unable to chelate Zn(2+), does not, indicating that chelation of Zn(2+) with EDTA saturated with Ca(2+) (Ca-EDTA) in maturing pig oocytes plays a pivotal role in the induction of parthenogenetic activation of oocytes. In the present study, the involvement of Zn(2+) chelation in the induction of parthenogenetic activation of pig oocytes at the germinal vesicle stage was confirmed first by examining the effects of concomitant addition of Zn(2+), Cu(2+) or Ni(2+) at various concentrations together with 1 mmol Ca-EDTA l(-1) to the maturation medium. The titration experiments revealed that the pronuclear formation induced by 1 mmol Ca-EDTA l(-1) was completely inhibited by the addition of > 30 micromol Zn(2+) l(-1) to the medium, but not by the addition of Cu(2+) and Ni(2+) at any concentration examined. Second, bovine and mouse oocytes at the germinal vesicle stage were cultured in medium with or without 1 mmol Ca-EDTA l(-1) for 48 h to examine the effects of Ca-EDTA treatment on these oocytes during maturation culture. Most (70-86%) of the bovine oocytes that underwent germinal vesicle breakdown matured to the MII stage via the MI phase, regardless of whether Ca-EDTA was present for the first 24 h of culture. However, 61% of oocytes that had been cultured with Ca-EDTA for 48 h formed a pronucleus without a second polar body, whereas oocytes cultured in the absence of Ca-EDTA were not observed to form a pronucleus at any time during culture. However, even when mouse oocytes at the germinal vesicle stage were cultured for up to 48 h in maturation medium containing Ca-EDTA, pronuclear formation was not observed. Finally, when bovine oocytes that had been cultured with 1 mmol Ca-EDTA l(-1) for 48 h from the germinal vesicle stage were cultured further in medium without Ca-EDTA that was supplemented with 5% fetal calf serum, only 26% of the oocytes developed to the cleaved stage, and none could develop further.

Animals↗

[Platelet activation in obstructive sleep apnea syndrome].

The incidences of cardiovascular and cerebrovascular diseases are reportedly higher in patients with obstructive sleep apnea (OSA) than in OSA-free subjects, though the mechanism remains unknown. Recently, the contribution of activated platelets to a number of pathological conditions such as stroke or ischemic heart disease has been suggested. We hypothesized that the expression of activated platelet markers resulting from OSA might be higher than in healthy subjects. By flow cytometry using monoclonal antibodies, we measured two such markers, PAC-1 and CD 62 P, in OSA patients and healthy subjects. Twelve healthy men (age, 52.7 +/- 12.8 y/o; and body mass index (BMI), 22.2 +/- 16.1 kg/m2; mean +/- S.D.) and 20 male patients with OSA (age, 50 +/- 7.96 y/o; BMI, 28.1 +/- 3.3 kg/m2; apnea hypopnea index (AHI), 38.2 +/- 21.2 times/hr; and lowest SpO2, 75.6 +/- 11.3%) were enrolled in this study. PAC-1 expression was significantly higher in OSA patients (65.1 +/- 17.8%) than in healthy subjects (16.8 +/- 7.4%), as was CD 62 P expression (8.5 +/- 8.8% vs. 0.88 +/- 0.57%). The increase in PAC-1 expression was correlated with AHI and the arousal index. These findings suggest that activated platelet markers could be good indicators for untreated OSA.

Adult↗

[Assessment of mode of recurrence after surgical treatment for thymic carcinoma].

In order to establish an appropriate treatment for thymic carcinoma, clinical courses of 15 patients with type C thymoma of WHO classification were reviewed. Five-years survival rate in all patients was 37.6%. In cases underwent complete resection, survival was 48.5%. The induction chemotherapy was done in 7 cases, and complete resection was possible in all these cases, suggested the possibility of improving the survival by the induction therapy. Upper mediastinal lymph node dissection each performed in 9 cases, and they showed significantly better survival than those without lymph node dissection. In conclusion, we have found that induction chemoradiotherapy and complete tumor resection with lymphnode dissection would contribute to improvement of the results in treatment for thymic carcinoma.

Adult↗

[Dynamic analysis of airway temperature in dogs breathing cold air].

Exercise in cold, dry air induces bronchoconstriction. However, the time course of airway cooling during the breathing of cold air has not been investigated. In this study in dogs, the temperatures of tracheal gas and the tracheal wall were measured continuously while the animal was breathing cold air at approximately 4.5 degrees C. The temperature of the tracheal gas decreased during the inspiratory phase, increase slightly early in the expiratory phase, and then decreased to the level at end-expiration. The lowest temperature of the tracheal gas decreased significantly, from 29.7 +/- 2.4 degrees C (mean +/- SD) to 25.7 +/- 2.8 degrees C. The highest temperature also changed significantly, but the decrease was less than 1 degree C. The lowest temperature of the tracheal wall decreased from 31.1 +/- 2.6 degrees C to 30.5 +/- 2.5 degrees C during cold-air breathing, but the difference was not significant. When a dog inspired deeply during a cough, the temperature of tracheal gas did not decrease linearly with the progression of inspiration. However, the decrease in the tracheal wall temperature was almost directly proportional to inspiratory volume. We concluded that both the tracheal gas and the tracheal wall temperatures were resistant to cooling with cold-air breathing. It remains uncertain whether rapid, deep breathing during exercise decreased the tracheal wall temperature.

Animals↗

Subthalamo-pallido-striatal axis: a feedback system in the basal ganglia.

Systemic administration of a dopamine D2 receptor blocker, haloperidol, but not vehicle, significantly increased the number of c-Fos-immunoreactive neurons in the globus pallidus (GP) in rats. Dual immunohistochemistry, a combination of c-Fos immunohistochemistry and retrograde tracing experiments with cholera toxin B (ChB), revealed that a subset of the c-Fos-immunoreactive GP neurons was pallidostriatal feedback neurons. Lesioning of the subthalamic nucleus (STN) by local injection of ibotenic acid inhibited the haloperidol-induced c-Fos expression in the GP neurons, suggesting that the activation of GP neurons is a result of increased excitatory drives from the STN. Therefore, the present findings are evidence of the existence of the subthalamo-pallido-striatal axis as a feedback system in the internal circuits of the basal ganglia.

Animals↗

Recruitment of Mec1 and Ddc1 checkpoint proteins to double-strand breaks through distinct mechanisms.

In response to DNA damage, eukaryotic cells activate checkpoint pathways that arrest cell cycle progression and induce the expression of genes required for DNA repair. In budding yeast, the homothallic switching (HO) endonuclease creates a site-specific double-strand break at the mating type (MAT) locus. Continuous HO expression results in the phosphorylation of Rad53, which is dependent on products of the ataxia telangiectasia mutated-related MEC1 gene and other checkpoint genes, including DDC1, RAD9, and RAD24. Chromatin immunoprecipitation experiments revealed that the Ddc1 protein associates with a region near the MAT locus after HO expression. Ddc1 association required Rad24 but not Mec1 or Rad9. Mec1 also associated with a region near the cleavage site after HO expression, but this association is independent of Ddc1, Rad9, and Rad24. Thus, Mec1 and Ddc1 are recruited independently to sites of DNA damage, suggesting the existence of two separate mechanisms involved in recognition of DNA damage.

Cell Cycle↗

Synthesis of alkenylene-bridged macrocyclic silsesquioxanes by ruthenium or rhodium-catalyzed ring-closing reactions of bis(allyldimethylsilyl) groups.

Novel alkenylene-bridged oligosilsesquioxanes composed of half-caged structures with 16- or 17-membered rings as well as a titanium-containing molecule with a twisted 21-membered macrocycle have been synthesized by ruthenium or rhodium-catalyzed ring-closing reactions of silsesquioxanes with bis(allyldimethylsilyl) groups.

Journal Article↗

Reversal of cisplatin and multidrug resistance by ribozyme-mediated glutathione suppression.

gamma-Glutamylcysteine synthetase (gamma-GCS) is a key enzyme in glutathione (GSH) synthesis, and is thought to play a significant role in intracellular detoxification, especially of anticancer drugs. Increased levels of GSH are commonly found in the drug-resistant human cancer cells. We designed a hammerhead ribozyme against gamma-GCS mRNA (anti-gamma-GCS Rz), which specifically down-regulated gamma-GCS gene expression in the HCT-8 human colon cancer cell line. The aim of this study was to reverse the cisplatin and multidrug resistance for anticancer drugs. The cisplatin-resistant HCT-8 cells (HCT-8DDP cells) overexpressed MRP and MDR1 genes, and showed resistance to not only cisplatin (CDDP), but also doxorubicin (DOX) and etoposide (VP-16). We transfected a vector expressing anti-gamma-GCS Rz into the HCT-8DDP cells (HCT-8DDP/Rz). The anti-gamma-GCS Rz significantly suppressed MRP and MDR, and altered anticancer drug resistance. The HCT-8DDP/Rz cells were more sensitive to CDDP, DOX and VP-16 by 1.8-, 4.9-, and 1.5-fold, respectively, compared to HCT-8DDP cells. The anti-gamma-GCS Rz significantly down-regulated gamma-GCS gene expression as well as MRP/MDR1 expression, and reversed resistance to CDDP, DOX and VP-16. These results suggested that gamma-GCS plays an important role in both cisplatin and multidrug resistance in human cancer cells.

Antineoplastic Agents↗

A case-control study for evaluating the efficacy of mass screening program for lung cancer in Miyagi Prefecture, Japan.

BACKGROUND: In Miyagi Prefecture, Japan, a mass screening program for lung cancer has been conducted since 1982 (miniature chest X-ray for all screenees and sputum cytology for those with a smoking index > or = 600) [smoking index 600 = 30 pack years, the average number of cigarettes smoked per day multiplied by the number of years of regular smoking]. Over 1500 lung carcinomas, including 250 roentgenographically occult lung tumors, were detected and treated up to 1999. In the current study, a nested case-control study was conducted in the population that was screened in 1989 to evaluate the efficacy of the screening program for lung cancer. METHODS: To reduce self-selection bias, the source population was defined as screenees with negative results in 1989 (284,226 individuals). In the population, 474 individuals died of lung carcinoma during 1992-1994. After exclusion, 328 patients who died of primary lung carcinoma at between ages 40 years and 79 years were defined as the cases. Six controls were supposed to be selected in the source population for each case and matched by gender, year of birth, municipality, and smoking habits. Controls who had died or moved before the matched case was diagnosed were excluded. Finally, 328 cases and 1886 controls were selected. Screening histories were compared, and odds ratios were calculated using conditional logistic regression analysis. RESULTS: Within the 12 months before diagnosis, 241 of 328 cases (73.5%) had attended the screening compared with 1557 of 1886 controls (82.6%). The smoking-adjusted odds ratio was 0.54 (95% confidence interval, 0.41-0.73). CONCLUSIONS: The mass screening program for lung cancer in Miyagi Prefecture was capable of reducing by 46% the risk of death from carcinoma of the lung.

Adult↗

Src-catalyzed phosphorylation of c-Cbl leads to the interdependent ubiquitination of both proteins.

The protooncogene c-Cbl has recently emerged as an E3 ubiquitin ligase for activated receptor tyrosine kinases. We report here that c-Cbl also mediates the ubiquitination of another protooncogene, the non-receptor tyrosine kinase c-Src, as well as of itself. The c-Cbl-dependent ubiquitination of Src and c-Cbl requires c-Cbl's RING finger, Src kinase activity, and c-Cbl's tyrosine phosphorylation, probably on Tyr-371. In vitro, c-Cbl forms a stable complex with the ubiquitin-conjugating enzyme UbcH7, but active Src destabilizes this interaction. In contrast, Src inhibition stabilizes the c-Cbl. UbcH7.Src complex. Finally, c-Cbl reduces v-Src protein levels and suppresses v-Src-induced STAT3 activation. Thus, in addition to mediating the ubiquitination of activated receptor tyrosine kinases, c-Cbl also acts as a ubiquitin ligase for the non-receptor tyrosine kinase Src, thereby down-regulating Src.

Binding Sites↗