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T Kondo

Publications and source records attributed to T Kondo.

At least 55 records · Page 3Linked to original sources

Negative regulatory effect of an oligodendrocytic bHLH factor OLIG2 on the astrocytic differentiation pathway.

In the developing vertebrate nervous system, multipotent neural stem cells produce both neurons and glia. OLIG2 is a basic helix-loop-helix transcription factor that plays critical roles in oligodendrocyte and motor neuron development; however, its role in astrocytic development remains elusive. In this study, we analyzed an effect of OLIG2 on cytokine-induced astrocytic differentiation from mouse telencephalic neuroepithelial cells. We show that the presence of OLIG2 protein leads to inhibition of the promoter activation of astrocyte-specific glial fibrillary acidic protein gene. We found that OLIG2 abolishes complex formation between a transcriptional coactivator p300 and a transcription factor, signal transducer and activator of transcription 3 (STAT3), which is activated by astrocytic differentiation-inducing cytokines, such as leukemia inhibitory factor (LIF). The enforced expression of OLIG2 in neuroepithelial cells inhibits the LIF-induced astrocytic differentiation. We also show that the OLIG2 protein in the nuclei of neural precursor cells disappears in accordance with astrocytic differentiation during culture with LIF. Together, these results reveal a novel molecular function of OLIG2 on the astrocyte development. Cell Death and Differentiation (2004) 11, 196-202. doi:10.1038/sj.cdd.4401332 Published online 24 October 2003

Animals↗

Regulation of Chk2 gene expression in lymphoid malignancies: involvement of epigenetic mechanisms in Hodgkin's lymphoma cell lines.

The tumor suppressor Chk2 kinase plays crucial roles in regulating cell-cycle checkpoints and apoptosis following DNA damage. We investigated the expression levels of the genes encoding Chk2 and several cell-cycle regulators in nine cell lines from lymphoid malignancies, including three Hodgkin's lymphoma (HL) lines. We found that all HL cell lines exhibited a drastic reduction in Chk2 expression without any apparent mutation of the Chk2 gene. However, expression of Chk2 in HL cells was restored following treatment with the histone deacetylase inhibitors trichostatin A (TsA) and sodium butyrate (SB), or with the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5Aza-dC). Chromatin-immunoprecipitation (Chip) assays revealed that treatment of HL cells with TsA, SB or 5Aza-dC resulted in increased levels of acetylated histones H3 and H4, and decreased levels of dimethylated H3 lysine 9 at the Chk2 promoter. These results indicate that expression of the Chk2 gene is downregulated in HL cells via epigenetic mechanisms.

Acetylation↗

A prospective study of body size and colon cancer mortality in Japan: The JACC Study.

OBJECTIVE: To determine whether body size measurements are risk factors for colon cancer death among the Japanese. DESIGN AND SUBJECTS: A nationwide prospective study, the Japan Collaborative Cohort (JACC) Study from 1988 to 1999. The present analysis included 43 171 men and 58 775 women aged 40-79 y who respond to a questionnaire on current weight and height, weight around 20 y of age, and other lifestyle factors. Body mass index (BMI) at baseline and 20 y of age (B-BMI and 20-BMI, respectively) were calculated. RESULTS: We identified 127 deaths from colon cancer during the follow-up of 424 698 person-years among men and 122 deaths during the follow-up of 591 787 person-years among women. After adjustments for the lifestyle factors known to modify the risk of colon cancer, weight at baseline showed a significant positive association in women, while no such association was seen in men. There was also a significant trend of increasing risk with the increase in B-BMI among women. Women with B-BMI >/=28 kg/m(2) had a relative risk (RR) of 3.41 (95% confidence interval (CI): 1.44-8.06) compared with those with BMI of 20-<22 kg/m(2). 20-BMI also presented the same trend of increasing risk as B-BMI. Women with 20-BMI of <22 and B-BMI of >26 kg/m(2), that is, excessive BMI gain, had a high RR of 3.41 (95% CI 1.29-9.02) compared with those with 20-BMI of <22 and B-BMI of <22 kg/m(2). There were no corresponding trends of colon cancer risk for B-BMI, 20-BMI, or BMI change among men. CONCLUSIONS: These study data suggest that obesity and excessive weight gain are associated with the risk of colon cancer death in Japanese women but no such relationship was found in Japanese men.

Adult↗

Enhanced ultrasound-induced apoptosis and cell lysis by a hypotonic medium.

PURPOSE: To test the hypothesis that non-lethal hypotonia will enhance ultrasound-induced cell killing in vitro and that the mechanism is mechanical in nature. MATERIALS AND METHODS: Hypotonic RPMI medium (146 mOsm) was used to induce non-lethal osmotic swelling of human myelomonocytic leukaemia U937 cells. Hypotonia for 10 min was started just before exposure to 1 MHz ultrasound at 0.5 or 1.0 Wcm(-2) for 10 min, or 5 min before exposure to 2.0 Wcm(-2) for 1 min. Surviving intact cells were then determined by the trypan blue dye exclusion test immediately after treatment. After 6-h incubation of the treated cells, early apoptosis and secondary necrosis were measured using a flow cytometer. Intracellular free calcium ion imaging by Fura-2 fluorescence and cellular ion scanning using a secondary ion mass spectrometer were also performed. RESULTS: Enhancement of ultrasound-induced cell lysis was observed at all intensities, and most prominently at 2.0 Wcm(-2), while apoptosis induction was significantly enhanced at intensities of 0.5 and 1.0 Wcm(-2), but not at 2.0 Wcm(-2). The enhanced cell lysis is attributed to the increased susceptibility of the cells to mechanical damage. This is consistent with previous reports describing the effects of mechanical stresses on cell membranes. Cellular ion scanning images also suggest that hypotonia has an effect on the membrane damage-and-repair mechanism of the cells. CONCLUSIONS: The results support the hypothesis that non-lethal hypotonia can enhance ultrasound-induced cell killing. These findings also suggest the 'sonomechanical' nature of the effects on the cells.

Apoptosis↗

Effect of itraconazole on the pharmacokinetics and pharmacodynamics of a single oral dose of brotizolam.

AIMS: To assess the effect of itraconazole, a potent inhibitor of cytochrome P450 (CYP)3A4, on the single oral dose pharmacokinetics and pharmacodynamics of brotizolam. METHODS: In this randomized, double-blind, cross-over trial 10 healthy male subjects received either itraconazole 200 mg or matched placebo once daily for 4 days. On day 4, a single 0.5 mg dose of brotizolam was administered orally. Plasma concentrations of brotizolam were followed up to 24 h, together with assessment of psychomotor function measured by the digit symbol substitution test (DSST), visual analogue scales and UKU side-effect rating scale. RESULTS: Itraconazole significantly (P < 0.001) decreased the apparent oral clearance (CL/F) (16.47 +/- 4.3 vs 3.91 +/- 2.1), increased the area under the concentration-time curves (AUC) from 0 h to 24 h (28.37 +/- 10.8 vs 68.71 +/- 24.1 ng ml h(-1)), and prolonged the elimination half-life (4.56 +/- 1.4 vs 23.27 +/- 10.3 h) of brotizolam. The AUC(0,24 h) of the DSST (P < 0.001) and the item 'sleepiness' of UKU (P < 0.05) were significantly decreased. CONCLUSIONS: Itraconazole increases plasma concentrations of brotizolam probably via its inhibitory effect on CYP3A4 brotizolam metabolism.

Administration, Oral↗

Cry j 1 isoforms derived from Cryptomeria japonica trees have different binding properties to monoclonal antibodies.

BACKGROUND: We identified five Cryptomeria japonica trees producing Cry j 1 isoforms that cannot be detected in a sandwich ELISA using two monoclonal antibodies, J1B01 and J1B07, suggesting that the binding affinity of these isoforms for both monoclonal antibodies is low. OBJECTIVES: The binding properties of the Cry j 1 isoforms produced by five trees to J1B07 and J1B01 were examined. The complementary DNA (cDNA) sequences of the Cry j 1 isoforms were also determined. METHODS: To clarify the binding properties of these Cry j 1 isoforms to J1B01 and J1B07, Cry j 1 was quantified in pollen samples collected from each of the five trees, by sandwich ELISAs using polyclonal antibodies and either J1B01 or J1B07. The cDNA sequences of isoforms with different binding properties were determined. To test the assumption that amino acid substitutions affect the binding affinities of Cry j 1 isoforms for monoclonal antibodies, cleaved amplified polymorphic sequences (CAPS) markers representing the putative polymorphisms were used to analyse additional trees. RESULTS: Four of the five trees produced Cry j 1 isoforms with extremely low binding affinity for J1B07, whereas the other tree produced two different isoforms with low binding affinity for either J1B01 or J1B07. Cry j 1-encoding cDNA sequences for one of the four trees and for the exceptional fifth tree indicate that amino acid substitutions at positions 55 and 352 in mature Cry j 1 affect its binding to J1B01 and J1B07, respectively. This was supported by the results of CAPS analysis. CONCLUSION: The existence of Cry j 1 isoforms with low binding affinity for either J1B01 or J1B07 was established. Furthermore, a single amino acid substitution is involved in this difference in binding affinity for each monoclonal antibody.

Allergens↗

Effects of antiplatelet agents on pulmonary haemodynamic response to fMLP in endotoxin primed rats.

BACKGROUND: The interaction between neutrophils and platelets may be important in the modulation of pulmonary haemodynamics under systemic inflammatory conditions. A study was undertaken to examine whether antiplatelet agents inhibit platelet-neutrophil adherence and ameliorate the pulmonary haemodynamic response to fMLP by inhibiting thromboxane release in endotoxin primed lungs. fMLP stimulates neutrophils but not platelets; however, thromboxane synthesis in neutrophils is very low. METHODS: Rats were pretreated with either cilostazol (300 mg/kg) or aspirin (50 mg/kg) before endotoxin priming (5 mg/kg). Platelets in the lung were identified by fluorescent immunohistochemistry. Platelet-neutrophil adherence was analysed by flow cytometry of the lung vascular flush. The effect of fMLP (10(-6) M) on thromboxane release, lung weight (an indicator of pulmonary vasoconstriction), and lung filtration coefficient was determined in an isolated lung system perfused at a constant pressure difference. RESULTS: Endotoxin induced platelet accumulation and platelet-neutrophil adherence in the lung capillary were completely inhibited by cilostazol and aspirin while neutrophil recruitment was not affected. The fMLP challenge caused a significant increase in thromboxane B2 levels in endotoxin primed lungs. The fMLP induced decrease in lung weight was enhanced by endotoxin priming (from -4.9 to -63.9 mg, 95% CI of mean difference -99.5 to -10.5 mg, p<0.05). The fMLP induced increase in the lung filtration coefficient was also enhanced by endotoxin priming (from 0.63 to 2.40 mg/min/cm H2O/g, 95% CI of mean difference 1.17 to 2.37 mg/min/cm H2O/g, p<0.05). Treatment with cilostazol and aspirin completely inhibited the enhanced pulmonary haemodynamic response to fMLP. CONCLUSION: The neutrophil-platelet interaction is of critical importance in the modulation of pulmonary haemodynamics via thromboxane.

Animals↗

[New surgical technique of pulmonary segmentectomy by ultrasonic scalpel and absorbable sealing materials].

We developed new surgical technique of pulmonary segmentectomy by ultrasonic scalpel to sever intersegmental pulmonary tissue and absorbable sealing materials to cover the cut surface of lung. This method is expected to preserve more anatomical lung volume than the segmentectomy with surgical stapler. Two cases of post surgical recurrent lung cancer, 3 cases of pulmonary metastasis and 4 cases of primary lung cancer were applied this technique to preserve function. Among 3 materials examined, best result was obtained with polyglycolic acid felt (PGAF:Neoveil). PGAF is a very soft and thin (0.15 mm depth) new absorbable material that is able to closely adhere to irregular sections of the lung with fibrin glue and effectively seals air leakage. Mean chest drainage period after surgery in 6 cases with PGAF was 3.3 days. Excellent lung expansion was obtained immediately after the surgery and PGAF was disappeared completely on chest CT within 1 year. Although the possible superiority of this method is suggested in the present study, further comparative study is necessary to clarify the advantage of this new technique.

Absorbable Implants↗

[Preoperative evaluation for lung resection using right ventricular hemodynamic functions by unilateral pulmonary arterial occlusion test].

We performed a unilateral pulmonary arterial occlusion (UPAO) test for the preoperative evaluation of right ventricular functions as a loading test in patients undergoing a lung resection without cardiac complications preoperatively. We investigated the relationship between changes in right ventricular hemodynamic functions and postoperative cardiac complications, namely right heart failure or arrhythmia. To evaluate the right ventricular hemodynamic function test, we measured the mean pulmonary arterial pressure, cardiac index, right ventricular ejection fraction end-diastolic volume, and stroke volume before and during the UPAO test using the thermodilution method, and calculated the total pulmonary vascular resistance and right ventricular stroke work indexes. The incidence of postoperative cardiac complications was not related to the changes in the total pulmonary vascular resistance index. However, the postoperative cardiac complications were common in patients whose right ventricular end-diastolic volume index was increased by more than 20% during the UPAO test. These results suggest that the changes in the right ventricular end-diastolic volume index during the UPAO test can predict postoperative cardiac complications in patients undergoing a pulmonary resection.

Arrhythmias, Cardiac↗

[An adult congenital bronchoesophageal fistula with massive hemoptysis; report of a case].

A 67-year-old female was referred to our hospital because of bronchoesophageal fistula detected by upper gastro-intestinal series for cancer screening. The patient has had a history of coughing on liquid ingestion since childhood and she has been hospitalized 4 times for treatment of pneumonia during the past 20 years. While waiting the treatment, she was emergently admitted to the hospital because of massive hemoptysis. Transcatheter embolization of feeding arteries including the right inferior phrenic artery successfully controlled her hemoptysis. After reembolization of the feeding arteries for preventing massive hemorrhage during operation, posterolateral thoracotomy was performed. Surgical findings disclosed the bronchoesophageal fistula without inflammatory changes. She underwent fistulectomy combined resection of the middle and lower lobes which were destroyed by the repeated pneumonia. This case was considered type I congenital bronchoesophageal fistula according to Braimbridge and Keith classification because of the presence of diverticular projection which connected to the bronchus. Early diagnosis and rapid treatment are thought to be important for treating this disease.

Aged↗

Identification of AFLP markers linked to a resistance gene against pine needle gall midge in Japanese black pine.

Bulked segregant and AFLP analyses of two mapping populations (R17 x S6 and R17 x S1) were used to identify markers linked to Rpgm, the only known gene responsible for resistance to pine needle gall midge in Pinus thunbergii Parl. Rpgm was found to be bracketed by ACCC/CCTTT(190) on one side at a distance of 6.6 cM and ACGT/CCCGC(250) at 15.3 cM on the other side. The segregation of these markers was analyzed in two other families in order to determine their phase and transferability. One of the two additional resistant parents carried ACCC/CCTTT(190) in the homozygous state while the marker was in coupling (plus marker allele linked with an R allele) in a resistant parent, R17. The marker ACGT/CCCGC(250) was in a repulsion phase in R17 and was not detected in the other two resistant pine trees. Out of four AFLP markers identified, only ACGT/CCAAT(290) was transferable in all resistant trees tested, although its phase was opposite for different trees. These results indicate that in applying those markers to select resistant trees, the phase state of the markers in each resistant tree with respect to Rpgm needs to be considered.

Animals↗

The risk of persistent carriage of methicillin-resistant Staphylococcus aureus in hematopoietic stem cell transplantation.

The clinical course of hematopoietic stem cell transplantation (HSCT) recipients was retrospectively analyzed to determine whether carriage of methicillin-resistant Staphylococcus aureus (MRSA) is a risk factor for MRSA infection during the neutropenic period. We studied four patients in whom MRSA colonies developed before HSCT. Two patients were previously diagnosed as having MRSA infection and two were carriers of MRSA. We tried to eliminate MRSA before HSCT and succeeded in eradication in two patients. MRSA infection did not develop in one patient who received prophylactic administration of vancomycin (VCM), but MRSA-induced phlegmon developed during neutropenia in one patient who did not receive prophylaxis. Of the other two patients who had been persistently positive for MRSA, MRSA did not develop in one patient who received prophylaxis, but the another patient who did not receive prophylaxis died from MRSA-induced sepsis in the early post-transplant period. We therefore recommend that MRSA be eliminated by prophylactic administration of anti-MRSA drugs such as VCM before HSCT when patients have persistent MRSA.

Adolescent↗

Role of cystine transport in intracellular glutathione level and cisplatin resistance in human ovarian cancer cell lines.

Transport system x(c)(-) is a member of plasma membrane heterodimeric amino-acid transporters and consists of two protein components, xCT and 4F2hc. This system mediates cystine entry coupled with the exodus of intracellular glutamate and regulates the intracellular glutathione (GSH) levels in most mammalian cultured cells. We studied the activity of system x(c)(-) and GSH content in human ovarian cancer cell line (A2780) and its cisplatin (CDDP)-resistant variant (A2780DDP). The rate of cystine uptake was approximately 4.5-fold higher in A2780DDP cells than in A2780 cells and the cystine uptake in A2780DDP cells was mediated by system x(c)(-). Intracellular GSH content was much higher in A2780DDP cells but it fell drastically in the presence of excess glutamate, which inhibited the cystine uptake competitively. xCT and 4F2hc mRNAs were definitely expressed in A2780DDP cells, but far less in A2780 cells. Expression of system x(c)(-) activity by transfection with cDNAs for xCT and 4F2hc made A2780 cells more resistant to CDDP. Similar results on the cystine uptake were obtained in human colonic cancer cell lines. These findings suggest that the system x(c)(-) plays an important role in maintaining the higher levels of GSH and consequently in CDDP resistance in cancer cell lines.

Amino Acid Transport Systems↗

Flavone C-glycoside, phenolic acid, and nitrogen contents in leaves of barley subject to organic fertilization treatments.

From the leaves of barley, Hordeum vulgare, one new flavone C-glucoside and three known flavone glucosides were isolated and characterized by (1)H and (13)C NMR and MALDI-TOF-MS. The novel flavone C-glucoside was isovitexin 7-O-beta-[6' "-O-(E)-p-coumaroyl]glucoside (6' "-coumaroylsaponarin), and the known compounds were isovitexin 7-O-beta-[6' "-O-(E)-feruloyl]glucoside, isoorientin 7-O-beta-[6' "-O-(E)-feruloyl]glucoside, and tricin 7-O-beta-glucoside. The sum of all the flavone glycosides and soluble phenolic acids in the leaves decreased with increased rate of plant nutrients given in animal manure and with increased crop yield. All of the major phenylpropanoids showed the same general response to nutrient level. The concentration of nitrogen in the leaves was not directly related to nutrient application or to contents of phenylpropanoids.

Fertilizers↗

Platelet recovery in patients with idiopathic thrombocytopenic purpura after eradication of Helicobacter pylori.

The relationship between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) has been investigated in several studies. We investigated the prevalence of H. pylori infection and the clinical effects of eradication in 22 Japanese patients with chronic ITP. H. pylori infection was found in 14 (63.6%) of the patients by histologic and culture examinations of biopsy samples obtained by gastrointestinal endoscopy. H. pylori was eradicated by proton pump inhibitors and 2 kinds of antibiotics in 13 (92.9%) of the 14 patients in whom the results of treatment could be evaluated. Five (38.4%) of those 13 patients had platelet recovery (platelet count of more than 100 x 10(9)/L and an increase of more than 30 x 10(9)/L with respect to the baseline value) after eradication. The median follow-up period was 15 months. One patient who had a complete response had a partial relapse after cessation of prednisolone treatment without any evidence of H. pylori reinfection. Another patient, in whom H. pylori was not eradicated even after 2 treatment sessions, had a partial response after treatment. A screening examination for H. pylori infection may be necessary for Japanese patients with newly diagnosed ITP. Although the exact mechanism underlying platelet recovery after H. pylori eradication is not clear, the results of this study indicated that H. pylori eradication treatment is a good option for some patients with chronic ITP.

Adult↗

Prolonged effects of polyriboinosinic:polyribocytidylic acid on spontaneous running wheel activity and brain interferon-alpha mRNA in rats: a model for immunologically induced fatigue.

Following 2 weeks acclimation to the running wheel in the home cages, an i.p. injection of a synthetic double-stranded RNA, polyriboinosinic:polyribocytidylic acid (poly I:C, 3 mg/kg), was performed to produce the immunologically induced fatigue in rats. The daily amounts of spontaneous running wheel activity decreased to about 40-60% of the preinjection level until day 9 with normal circadian rhythm, then gradually returned to the baseline level by day 14. Rats given a heat exposure (36 degrees C for 1 h) for the consecutive 3 days showed an increase in activity except for the first day. In the open field test, the total moving distance and the number of rearing of the poly I:C-injected rats decreased on day 1, but they were not different from the saline-injected group on day 7, suggesting that the poly I:C-induced fatigue on day 7 was not due to the peripheral problems such as muscle/joint pain, but involved the CNS. Quantitative analysis of mRNA levels using a real-time capillary reverse transcriptase-polymerase chain reaction (RT-PCR) method revealed that interferon-alpha (IFN-alpha) mRNA contents in the cortex, hippocampus, hypothalamic medial preoptic, paraventricular, and ventromedial nuclei were higher in the poly I:C group than those in the saline and heat-exposed groups on day 7, although the amount of interleukin-1 beta mRNA showed no differences. Serum adrenocorticotropic hormone and catecholamine levels were not significantly different between groups. The present results indicate that the prolonged fatigue induced by poly I:C, which is evaluated by the spontaneous running wheel activity, can be used as an animal model for the immunologically induced fatigue associated with viral infection, and suggest that brain IFN-alpha may play a role in this model.

Adrenocorticotropic Hormone↗