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T Ueda

Publications and source records attributed to T Ueda.

1,779 records · Page 99Linked to original sources
PubMedDate not supplied

Reverse effect of guanine on the inhibitory action of mycophenolic acid during nucleic acid synthesis.

Mycophenolic acid (MPA) was demonstrated to inhibit DNA and RNA synthesis in L1210 cells strongly; however these effects were remarkably reduced by guanine. The presence of MPA in the medium decreased the guanine nucleotide contents (GMP, GDP, GTP) of the cells, but the addition of guanine reversed this effect. We have reported previously that MPA had no inhibitory effect on hypoxanthine guanine phosphoribosyltransferase (HGPRTase) activity. Together these findings suggest that the decrease of guanine nucleotides induced by MPA is restored by GMP, which is formed from guanine by HGPRTase in the cells. It is speculated that a suppressor of HGPRTase activity, such as 6-mercaptopurine, may protect the antitumor activity of MPA by preventing the conversion of guanine to GMP.

Animals↗
PubMedDate not supplied

Quantitative description of morphologic changes effected by antileukemic agents in L1210 leukemia cells.

The effect of antileukemic agents is explained mainly by the inhibition of DNA synthesis, which may reflect the structural alteration of the target cells. To identify such cellular alterations, in particular morphologic changes associated with the exposure to antileukemic agents were investigated in the murine leukemic L1210 cell line using flow cytometry and image analysis. Cells were cultured with eight kinds of antileukemic agents in cytostatic concentrations which are clinically achievable. Living cells were observed in culture without fixation or staining. Two parameters related to cell size and shape were measured simultaneously by the image analysing computer. These parameters provided us with different criteria for characterizing the antimetabolites, DNA-strand-damage inducers and other agents tested. Such morphologic studies may make it possible to estimate the characteristics of various antileukemic agents.

Animals↗
PubMedDate not supplied

Pharmacokinetic and clinical pilot study of high-dose intermittent ubenimex treatment in patients with myelodysplastic syndrome.

Ubenimex is an orally active aminopeptidase inhibitor with an immunomodulating action. A pharmacokinetic and clinical pilot study of high-dose intermittent ubenimex was performed in patients with myelodysplastic syndrome. Ubenimex (150 mg/body) was administered orally, twice per day (at a 3 hr interval), twice a week, for at least 8 weeks. The concentrations of ubenimex and p-OH ubenimex, another active metabolite, increased gradually up to 7.1 +/- 4.7 micrograms/ml (mean +/- SD) at 5 hr and 0.25 +/- 0.15 mu/ml at 6 hr. The low percentage (4.2%) of the AUC ratio (p-OH ubenimex/ubenimex) suggested minimal metabolism. The plasma half-life of ubenimex was 2.1 +/- 0.7 hr and the total urinary recovery of both was 71.4% in 48 hr. Among 8 patients clinically studied, one achieved good response and another achieved minor response. These findings suggested good bioavailability, and a certain effectiveness of ubenimex in this administration method, which was worth trying, at least in restricted cases, such as cases with refractory disease or with a poor performance status.

Adult↗
PubMedDate not supplied

Effect of harringtonine on apoptotic cell death and cell cycle progression in human leukemia HL60 cells.

The mechanism of cell killing induced by harringtonine (HT) was investigated in HL60 cells by metabolic labeling studies, light and transmission electron microscopy, agarose gel electrophoresis of DNA and flow cytometry. At concentrations higher than 0.02 microM HT showed significant inhibition on cell growth and protein and DNA synthesis. Following exposure to HT, typical apoptotic cell death was observed from 1.5 to 4 h and it increased in both dose-and time-dependent fashion. This process was prevented by an intracellular calcium ion chelator. In addition, at 0.04 microM of HT the nonapoptotic cells delayed the progression of cell cycle through S and G2 phase and finally arrested in G1 phase. These results are important to understand the mechanism of action of HT and to improve the effect of HT in cancer chemotherapy.

Apoptosis↗
PubMedDate not supplied

[Induction of coronary artery spasm by combined cold pressor and hyperventilation test in patients with variant angina].

To examine whether or not a combination of nonpharmacologic provocative tests potentiated the occurrence of coronary spasm, the cold pressor test combined with hyperventilation was studied in 22 consecutive patients with variant angina admitted to our hospital. After a 12-lead electrocardiogram and blood pressure were recorded, the patient was asked to hyperventilate vigorously at a rate of 30 respirations per min for 6 min under continuous electrocardiographic monitoring. Immediately after hyperventilation, the cold pressor test was performed with the patient's right hand submerged in ice water for 2 min. In some patients who showed a positive response to the combined test, a hyperventilation and cold pressor test was performed on another day. Positive response (ST segment elevation > or = 0.1 mV) to the combination test was seen in 18 of 22 patients (82%). Positive response to the hyperventilation test was seen in seven of 11 patients (64%). The response to cold pressor test was all negative in seven patients. The onset of electrocardiographic changes by the combined test occurred an average of 120 sec (30-240 sec) after the end of hyperventilation, whereas the onset by hyperventilation test occurred an average of 210 sec later (60-370 sec). These results suggest the combination of the cold pressor test and hyperventilation test potentiated the occurrence of coronary spasm. The combined cold pressor and hyperventilation test is a powerful and useful nonpharmacologic provocative test for coronary artery spasm in patients with variant angina.

Adult↗
PubMedDate not supplied

Development of a chronic endothelialized transcatheter implantable intra-aortic graft.

The authors developed a new intraluminal aortic prosthesis (IA graft) for internal obliteration of Stanford type B dissection. The newly devised intraluminal aortic graft is a self-expandable metallic stent (Gianturco stent) outer-jacketed with a thin open-cell structured microporous film made of segmental polyurethane (0.2 mm thick, 0.1 mm pore size). Through the femoral artery, the intraluminal aortic grafts (14-20 mm diameter-, 4 cm long) were inserted into a 12 Fr catheter sheath by compression, were implanted into the descending thoracic aortas of five mongrel dogs; they were removed at the projected times of death ranging from 1 to 6 months after implantation. Histopathologic examination revealed that an elastic fiber layer had regenerated and that on the inner surface of the graft adherent and proliferating endothelial cells were observed, even at 1 month after graft implantation. Complete epithelialization was observed over the entire inner surface of the graft within 4 months after implantation. This healing process suggests that the intraluminal aortic graft is highly biocompatible and might be stable in chronic use after the obliteration of acute Stanford type B dissections.

Aortic Dissection↗
PubMedDate not supplied

Development of an expandable intra-aortic prosthesis for experimental aortic dissection.

To achieve transcatheter entry obliteration for Stanford type B dissection, the authors devised and developed a self-expandable intra-aortic prosthesis (IA graft). This graft consisted of a microporous polyurethane graft (wall thickness: 0.2 mm; average pore size: 0.1 mm) and an expandable metallic stent (Gianturco double stent) attached to the lumen surface of the polyurethane graft. Experimental dissections in the descending aorta of mongrel dogs were prepared. An IA graft was inserted through a femoral artery by a catheter sheath into which a compressed IA graft was installed and expanded at the entry site. After 30 min of graft implantation, closure of all the entry sites in four dogs was confirmed by aortography. The results suggest that the newly devised IA graft is extremely useful as a non invasive treatment for Stanford type B dissection.

Aortic Dissection↗
PubMedDate not supplied

Evaluation of oral aclarubicin treatment for tumors of the gastrointestinal track.

Aclarubicin (ACR), a drug useful for the treatment not only of tumors of the hematopoietic system but also of those of the gastrointestinal tract, has been administered invariably by the intravenous route. We attempted oral administration of ACR to increase its specificity in the treatment of gastrointestinal tumors. Oral administration resulted in a much higher intratumor concentration but lower peripheral blood cell or bone marrow cell concentration of the drug as compared with intravenous administration. The reduced peripheral cell inhibition and bone marrow suppression permits the administration of the drug in higher doses, and the absence of the drug in the plasma suggests a reduced likelihood of myocardial cell injury and hepatocyte impairment. These favorable findings are considered to warrant early clinical trial of the treatment.

Aclarubicin↗
PubMedDate not supplied

Establishment of a daunorubicin-resistant cell line which shows multi-drug resistance by multifactorial mechanisms.

We established a daunorubicin (DNR)-resistant cell line derived from human leukemia cell line K562, (K562/D1-9), which also shows multidrug resistance (MDR). K562 cells were cultured with serially increasing concentrations up to 1.0 microM of DNR and then cloned by the limiting dilution method. K562/D1-9 cells were found to be 28 times more resistant to DNR than their its parent cells. Intracellular accumulation of DNR in K562/D1-9 was less than in the wild type, and P-glycoprotein (PGP) was overexpressed. Both DNR resistance and its intracellular accumulation were partially reversed by addition of verapamil to K562/D1-9 cells, but not to K562 cells. Topoisomerase II (Topo II) activity was decreased in K562/D1-9 cells. In contrast to other drugs, such as doxorubicin and vincristine, verapamil could not reverse drug resistance to VP-16 in the K562/D1-9 cell line, suggesting the importance of Topo II as the target of MDR. Protein kinase C (PKC) level was higher in K562/D1-9 than in K562. These findings suggested that the mechanism of MDR in this cell line might be multifactorial, including PGP, topo II and PKC. The K562/D1-9 cell line may be a good model for studying drug resistance in leukemia chemotherapy.

Antibiotics, Antineoplastic↗
PubMedDate not supplied

Molecular analysis of a case of Philadelphia chromosome-positive acute myeloid leukemia.

This report describes a precise molecular analysis of a rare case of Philadelphia chromosome (Ph) positive acute myeloid leukemia (AML) (FAB classification M2). Phenotypic markers were positive for cells of the myeloid lineage, but negative for B cell and T cell lineage. The leukemic cells carried a Philadelphia chromosome. Major breakpoint cluster region (M-BCR) rearrangement was detected by the Southern blot analysis. Reverse transcriptase polymerase chain reaction analysis revealed the presence of b3a2 BCR/ABL mRNA transcripts. The patient achieved complete remission by conventional remission induction therapy for acute myeloid leukemia. M-BCR rearrangement could not be detected during complete remission. After hematological remission of an 8-month duration, the patient relapsed and died of respiratory distress due to pneumonia. Our case indicate Ph-positive AML with M-BCR rearrangement actually exists. Ph-positive AML carries either M-BCR rearrangement expressing the P210 BCR-ABL or minor breakpoint cluster region (m-BCR) rearrangement producing the P190 BCR-ABL. Therefore, additional other factor (s) apart from the Ph chromosome must be responsible for the acute malignant transformation.

Aged↗
PubMedDate not supplied

Video assisted thoracoscopic and cardioscopic radiofrequency Maze ablation.

The authors examined the feasibility of transthoracic radio frequency Maze ablation of atrial fibrillation using video assisted thoracoscopy and cardioscopy in the experimental setting of a beating porcine heart. In six pigs under general anesthesia, the left atrium was viewed using a video assisted thoracoscopy system (VATS), and radiofrequency linear ablation of the left atrial wall was carried out using a radiofrequency ablation catheter (HAT200S:OSYPKA) inserted through a trocar port. The right atrium was also ablated in the same manner under VATS. In six other pigs, intravenous radiofrequency ablation by cardioscopic catheter device was carried out. Atrial fibrillation was provoked by acetylcholine injection plus rapid atrial pacing. The thoracoscopic visual field created for radiofrequency catheter ablation from a transthoracic approach and the cardioscopic visual field from an intravenous approach were sufficient, and safe positioning of the ablation catheter device on the atrial epicardium and endocardium, which enabled linear ablation of the atrium, was obtained. The Optimal setting for ablation was 70-80 degrees C/ 30 sec duration per each ablation. This process was monitored and documented by a video system through the thoracoscope and cardioscope, and results were confirmed by postmortem macrohistologic examination. In conclusion, the authors' results suggest the potential usefulness of the combination of transthoracic radiofrequency catheter ablation with video assisted thoracoscopic and cardioscopic linear ablation of atrial fibrillation, and the possibility that use of this system might eliminate the need for open heart Maze surgery.

Acetylcholine↗
PubMedDate not supplied

Surgical treatment for severe acute pancreatitis: factors which affect the surgical results.

Surgical treatment for severe acute pancreatitis has not yet yielded satisfactory results. Several factors which might affect the surgical results of severe acute pancreatitis were analyzed in this study. The presence or absence of infection was not important as a factor determining the surgical results. The severity scores and some biochemical parameters such as CRP, IL-6, PMN-E, HGF seemed to be closely related to surgical results. It was likely that a significant decrease in lymphocyte counts in the blood on admission was closely related to the prognosis of the surgical patients. Timing and procedures for surgery should be more seriously considered in the treatment for patients with such poor general conditions.

Acute Disease↗
PubMedDate not supplied

Ascidian mitochondrial tRNA(Met) possessing unique structural characteristics.

Methionine tRNA was purified from muscle mitochondria of the ascidian Halocynthia roretzi and its RNA sequence was determined. Analysis of the nucleotide sequence revealed that unlike most metazoan mitochondrial tRNAs(Met), which have a highly conserved cytidine (C) or C-derivative at the wobble position, the H. roretzi mitochondrial tRNA(Met) possesses 5-carboxymethylaminomethyluridine (cmnm5U) at the first position of the anticodon. This is the first report of a single mitochondrial tRNA(Met) species having uridine (U) or a U-derivative at the wobble position.

Animals↗