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Biomedical subjects

K Ueda

Publications and source records attributed to K Ueda.

At least 289 records · Page 16Linked to original sources
PubMed1999

[Report of three cases of emergency operation for acute pulmonary embolism].

Three successful surgical cases of acute pulmonary embolism with severe cardiopulmonary impairment were reported. Currently, thrombolysis is widely accepted as the front-line treatment for most patients with pulmonary embolism. However, treatment failure is high and can lead to death in the most severe cases. If these patients have severe cardiopulmonary impairment, pulmonary embolectomy should be done immediately.

Acute Disease↗
PubMed1999

[The effect of milrinone for the shock patients after cardiac surgery].

The effect of milrinone in the 16 postoperative shock patients of cardiovascular surgery was studied. The preoperative hemodynamic status were 12 of cardiogenic shock, 2 cases of chronic heart failure and 2 cases of unstable angina pectoris. The operative procedure were 8 cases of coronary artery bypass grafting, 4 cases of valvular surgery, 2 cases of closure of ventricular septal perforation, 2 cases of Bentall operation and 1 case of ascending aortic replacement. The postoperative hemodynamic status were 15 cases of cardiogenic shock, 10 cases of hemorrhagic shock and 1 case of septic shock. Continuous intravenous infusion of 0.5 microgram/kg/min without initial bolus loading was administered immediately after the entrance of the intensive care unit. Significant increase in the maximum blood pressure 3 hours after the infusion were observed (84 +/- 17 mmHg vs 94 +/- 12, p = 0.033). The maximum blood pressure was increased gradually until 24 hours after the infusion. Significant increase in the peripheral body temperature 3 hours after the infusion were observed (32.5 +/- 2.0 degrees C vs 35.9 +/- 1.1 degrees C, p = 0.001). The difference between the peripheral temperature and the central body temperature diminished until 24 hours after the infusion. No significant change in the central venous pressure, pulmonary arterial pressure, pulmonary and cardiac index wedge pressure were observed. No significant change in the platelet number was observed until 3 days after the infusion. Twenty patients (75%) were discharged. Four hospital deaths included 1 cardiac and 3 septic cause were seen. These data suggest that the administration of milrinone for the shock patients after cardiac surgery showed safe and that the continuous intravenous infusion of 0.5 microgram/kg/min without bolus loading showed effective for the recovery of the peripheral circulation.

Aged↗
PubMed1999

ATP-Dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P.

Non-P-glycoprotein-mediated multidrug-resistant C-A120 cells that overexpressed multidrug resistance protein (MRP) were 10.8- and 29. 6-fold more resistant to 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and SN-38, respectively, than parental KB-3-1 cells. To see whether MRP is involved in CPT-11 and SN-38 resistance, MRP cDNA was transfected into KB-3-1 cells. The transfectant, KB/MRP, which overexpressed MRP, was resistant to both CPT-11 and SN-38. 2-[4-Diphenylmethyl)-1-piperazinyl]ethyl-5-(trans-4,6-dimethyl-1,3 , 2-dioxaphosphorinan-2-yl)-2, 6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate P-oxide (PAK-104P) and MK571, which reversed drug resistance in MRP overexpressing multidrug-resistant cells, significantly increased the sensitivity of C-A120 and KB/MRP cells, but not of KB-3-1 cells, to CPT-11 and SN-38. The accumulation of both CPT-11 and SN-38 in C-A120 and KB/MRP cells was lower than that in KB-3-1 cells. The treatment with 10 microM PAK-104P increased the accumulation of CPT-11 and SN-38 in C-A120 and KB/MRP cells to a level similar to that found in KB-3-1 cells. The ATP-dependent efflux of CPT-11 and SN-38 from C-A120 and KB/MRP cells was inhibited by PAK-104P. DNA topoisomerase I expression, activity, and sensitivity to SN-38 were similar in the three cell lines. Furthermore, the conversion of CPT-11 to SN-38 in KB-3-1 and C-A120 cell lines was similar. These findings suggest that MRP transports CPT-11 and SN-38 and is involved in resistance to CPT-11 and SN-38 and that PAK-104P reverses the resistance to CPT-11 and SN-38 in tumors that overexpress MRP.

ATP-Binding Cassette Transporters↗
PubMed1999

Serum granulocyte colony-stimulating factor levels in patients with chronic neutropenia of childhood: modulation of G-CSF levels by myeloid precursor cell mass.

The serum G-CSF levels of eight patients with severe congenital neutropenia (SCN) were found to be significantly higher than those of 22 patients with chronic benign neutropenia (CBN). The relative number of cells expressing the G-CSF receptor in light density bone marrow cells (LDBMC) was lower in patients with SCN than in patients with CBN or in normal subjects. When recombinant human G-CSF was incubated with LDBMC, G-CSF levels were decreased by LDBMC from normal subjects and CBN patients, but not by those from SCN patients. Serum G-CSF concentrations, which are affected by mature neutrophils, may also be modulated by myeloid precursor cells in the bone marrow.

Adolescent↗
PubMed1999

[Detection of TTV DNA in hepatocellular carcinoma].

A new hepatitis agent, TTV has been cloned from post-transfusion hepatitis patient sera. This virus has a single stranded DNA as genome, surrounded by viral capsid antigen without envelope. It might be a member of parvoviridae. But genome organization is far from the known parvoviridae such as B19 and adeno-associated virus. Although this virus could be a new causative agent for nonA-nonG hepatitis, high healthy carrier rate, no relation with hepatocellular carcinoma and no evidence of amplification in parencymal hepatocyte might lead to less importance in liver disease. It is necessary to accumulate further knowledge about this new agent for the coming transplantation medicine.

Base Sequence↗
PubMed1999

Recent progress in P-glycoprotein research.

P-glycoprotein can extrude a variety of structurally diverse, toxic xenobiotic compounds from cells. It is believed to be one of key molecules which can cause multidrug resistance in cancer. This paper deals with recent progress in P-glycoprotein research, especially in its structure, mechanisms for substrate recognition and transport. The review also discusses specific modulators of multidrug resistance in cancer and gene therapy using the MDR1 gene.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Treatment of infant acute lymphoblastic leukemia in Japan. Childhood Leukemia Study Group of the Ministry of Health and Welfare (Kouseisho).

Although current chemotherapeutic regimens cure as many as 70% of children with acute lymphoblastic leukemia (ALL), infants continue to show a poor outcome. In this paper, we describe the outcome in 37 ALL infants treated between 1989 and 1995 in Japan. Patients had characteristic findings of infant ALL, including hyperleukocytosis > 100 x 10(9)/l (15/37, 41%), blast cells with a CD10-negative phenotype (30/37, 81%), and 11q23/MLL involvement (21/37, 57%). Seven were treated according to Aggressive Treatment Research Group protocol, 15 according to the Ministry of Health and Welfare protocol, and 15 according to protocols of other institutions. The 3-year overall event-free survival (EFS) was 33%. The EFS was 13% for infants aged < 26 weeks at diagnosis and 43% for infants aged > 26 weeks. Infants who had blast cells with CD10 negative phenotype with 11q23/MLL involvement were also associated with poor prognosis. However, infants with CD10 positive blasts without 11q23/MLL involvement had a better outcome (EFS 75%). These results suggest that intensive chemotherapy is effective for patients with good prognostic factors, but for infants with poor prognostic factors a more aggressive approach such as stem cell transplantation might be necessary.

Female↗
PubMed1999

Instability of chromosome 7 in colony forming cells of patients with aplastic anemia.

Monosomy 7 in isolated bone marrow mononuclear cells and colony forming cells from patients with aplastic anemia who later developed myelodysplastic syndrome/leukemia with monosomy 7 were examined by fluorescence in situ hybridization. Colonies derived from bone marrow mononuclear cells of the aplastic anemia patients consisted of a mixture of cells of normal karyotype and monosomy 7, ranging from 0 to 97.2%. This result suggests that colony forming cells initially had a normal karyotype but then lost chromosome 7 during growth in the semisolid culture. This finding suggests the genetically unstable condition of chromosome 7 in colony forming cells in aplastic anemia patients. This chromosome instability of colony forming cells may lead to malignant transformation.

Anemia, Aplastic↗
PubMed1999

Induction of apoptosis in T98G glioblastoma cells by transfection of GML, a p53 target gene.

Expression of the glycosyl-phosphatidylinositol-anchored molecule-like protein (GML) gene, a p53 target, correlates with the sensitivity of some cancer cell lines to anticancer drugs and ionizing radiation. To investigate the function of GML further, we introduced the GML cDNA into various cancer cell lines under control of the tetracycline-regulated system. When we introduced GML into human glioblastoma cell line T98G, which lacks wild-type p53 and expresses no endogenous GML, we observed significant growth suppression accompanied by G2/M arrest in two independent, stable cell lines. We confirmed induction of apoptosis by fluorescence-activated cell sorting (FACS) analysis and nuclear staining. Our results indicated that GML could induce apoptosis of T98G without functional p53, and implied that GML plays a crucial role in the apoptotic pathway in some cancer cells.

Apoptosis↗
PubMed1999

[A case of common variable immunodeficiency that responded to long-term erythromycin chemotherapy].

A 32-year-old woman with common variable immunodeficiency (CVID) accompanied by sinopulmonary infection was evaluated for purulent sputum, cough, and nasal obstruction that did not respond to regular intravenous immunoglobin (IVIG) infusion. Chest X-ray films revealed bronchiectasis affecting both lung bases, and a bacteriological examination of sputum was positive for Pseudomonas aeruginosa. Long-term chemotherapy with erythromycin (EM) was started, and the patient's respiratory symptoms gradually subsided. Sinopulmonary infection is the dominant clinical complication in patients with CVID. This case suggested that long-term EM chemotherapy is useful for the treatment of IVIG-refractory sinopulmonary infection associated with CVID.

Adult↗
PubMed1999

Active efflux of CPT-11 and its metabolites in human KB-derived cell lines.

To investigate the possible involvement of P-glycoprotein (P-gp), multidrug resistance-associated protein (MRP), and/or other glutathione S-conjugate export pump (GS-X pump) family members on the active efflux of irinotecan [(7-ethyl-10-[4-(1-piperidino)-1-pipertidino)-1-piperidino]carb onylox y camptothecin (CPT-11)] and its metabolites, as well as their contribution to the acquisition of resistance, we studied the uptake of CPT-11, its active metabolite SN-38, and glucuronide conjugate (SN38-Glu) using membrane vesicles from human epidermoid KB-3-1-derived cell lines. These lines included KB-C2, C-A500, and KCP-4, which overexpress P-gp, MRP, and the unidentified GS-X pump, respectively. The carboxylate form of SN-38 exhibited significant ATP-dependent transport, with a Michaelis constant of 17 microM, into membrane vesicles from C-A500 but not from other cell lines. Among these KB-derived cells, significant ATP-dependent uptake of the carboxylate form of CPT-11 was only observed in KB-C2 vesicles. In addition, the uptake of the lactone and carboxylate forms of SN38-Glu into membrane vesicles from C-A500 and KB-C2, but not KCP-4, was ATP dependent, although the transport activity in C-A500 was much higher than that in KB-C2. The 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay revealed that the resistance of KB-C2 to CPT-11 and SN-38, compared with that of KB-3-1, was 6.3- and 6.8-fold, respectively; the corresponding figures for C-A500 were 12- and 27-fold, respectively, whereas those for KCP-4 were 2.3- and 20-fold, respectively. These results suggest that MRP and P-gp are involved in the active efflux of SN-38 and CPT-11, respectively, from human KB-derived cells. In addition, a difference in substrate specificity among GS-X pump members was demonstrated.

Antineoplastic Agents, Phytogenic↗
PubMed1998

Degenerative terminals of the perforant pathway are human alpha-synuclein-immunoreactive in the hippocampus of patients with diffuse Lewy body disease.

We investigated the hippocampal pathology in diffuse Lewy body disease (DLBD) using alpha-synuclein immunohistochemistry. Ubiquitin-positive intrahippocampal structures caused by the degeneration of terminal axons of the perforant pathway were observed to be alpha-synuclein immunoreactive. These alpha-synuclein-positive degenerative terminals contained granulo-filamentous or vesiculo-tubular components similar to those of Lewy bodies (LB) immunoelectron microscopically, suggesting that alpha-synuclein may abnormally aggregate into filamentous or membranous cytoskeletal components including neurofilaments and synaptic vesicles in DLBD. A 'dying back' degenerating process due to a blockage of axonal transport may explain why the degenerative terminals and LB share similar alpha-synuclein-positive components, but the origin cells of the perforant pathway contain only a few LB.

Aged↗
PubMed1998

Long-term efficacy of low-density lipoprotein apheresis on coronary heart disease in familial hypercholesterolemia. Hokuriku-FH-LDL-Apheresis Study Group.

Familial hypercholesterolemia (FH) is characterized by severe hypercholesterolemia and premature coronary heart disease (CHD). The lower the plasma cholesterol level, the more likely it is that CHD can be prevented or retarded; aggressive cholesterol-lowering therapies may be indicated for FH patients with CHD. This study describes the long-term (6 years) safety and efficacy of intensive cholesterol-lowering therapies with low-density lipoprotein (LDL) apheresis in heterozygous FH patients with CHD. One hundred thirty heterozygous FH patients with CHD documented by coronary angiography had been treated by cholesterol-lowering drug therapy alone (n=87) or LDL apheresis combined with cholesterol-lowering drugs (n=43). Serum lipid levels and outcomes in each treatment group were compared after approximately 6 years. Both treatment groups had significant reductions in serum cholesterol, LDL cholesterol, and high density lipoprotein cholesterol levels. LDL apheresis significantly reduced LDL cholesterol levels from 7.42+/-1.73 to 3.13+/-0.80 mmol/L (58%) compared with group taking drug therapy, from 6.03+/-1.32 to 4.32+/-1.53 mmol/L (28%). With Kaplan-Meier analyses of the coronary events including nonfatal myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, and death from CHD, the rate of total coronary events was 72% lower in the LDL-apheresis group (10%) than in drug therapy group (36%) (p=0.0088). It is concluded that LDL-apheresis is effective as treatment of CHD in FH heterozygotes, and may become the therapy of choice in severe types of FH.

Aged↗
PubMed1998

Biliary excretion mechanism of CPT-11 and its metabolites in humans: involvement of primary active transporters.

After administration of CTP-11, a camptothecin derivative exhibiting a wide spectrum of antitumor activity, dose-limiting gastrointestinal toxicity with great interpatient variability is observed. Because the biliary excretion is a major elimination pathway for CPT-11 and its metabolites [an active metabolite, 7-ethyl-10-hydroxy-camptothecin (SN-38), and its glucuronide, SN38-Glu], several hypotheses for the toxicity involve biliary excretion. Here, we investigated whether primary active transport is involved in the biliary excretion of anionic forms of CPT-11 and its metabolites in humans using bile canalicular membrane vesicles (cMVs). Uptake of the carboxylate form of CPT-11 and the carboxylate and lactone forms of SN38-Glu by cMVs prepared from five human liver samples was ATP dependent. The concentration dependence of the ATP-dependent uptake of the carboxylate form of CPT-11 and SN38-Glu suggests the involvement of at least two saturable transport components, both with lower affinity and higher capacity than in rats. The ATP-dependent uptake of the carboxylate form of SN-38 showed a single saturable component but was detectable only in one human cMV sample. Both carboxylate and lactone forms of SN38-Glu uptake also showed a large intersample variability, although the variability was less than that observed for the carboxylate form of SN-38. On the other hand, the carboxylate form of CPT-11 exhibited much less variability. The carboxylate forms of SN38-Glu and SN-38 almost completely inhibited the ATP-dependent uptake of leukotriene C4, a well-known substrate of canalicular multispecific organic anion transporter, whereas the inhibition by the carboxylate form of CPT-11 was not as marked. Thus, multiple primary active transport systems are responsible for the biliary excretion of CPT-11 and its metabolites, and the major transport system for CPT-11 differs from that for the other two compounds. A greater degree of inter-cMV variability in the uptake of SN-38 and SN38-Glu may imply that interindividual variability in biliary excretion of these metabolites might contribute to interpatient variability in the toxicity caused by CPT-11.

Adenosine Triphosphate↗
PubMed1998

Methylmalonic aciduria (cblF): case report and response to therapy.

Methylmalonic acidemia can be secondary to a deficiency of methylmalonyl CoA mutase or to a defect of cobalamin metabolism that is classified by complementation group. We report on a new patient with cblF complementation group that is associated with an elevation of both methylmalonic acid and homocysteine, and her outcome in response to routine therapy and a dietary restriction.

Adolescent↗
PubMed1998

In vivo phosphorylation of poly(ADP-ribose) polymerase is independent of its activation.

Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme, which is activated by DNA strand breaks. Although PARP is known to be cleaved by the cysteine protease, caspase-3/CPP32, during apoptosis, signal cascade which regulates the PARP activity has not been fully understood. In this study, we investigated post-translational modification of PARP. We found that PARP was phosphorylated by a serine kinase in vivo. PARP was activated temporarily and extensive auto-modification occurred on PARP, possibly by the fragmented DNA during apoptosis induced by etoposide in Jurkat cells. However, the phosphorylation level was not changed for up to 6 h, after PARP cleavage began in apoptosis by the treatment with etoposide. Furthermore, we showed the presence of a PARP-associated kinase in nuclear extracts of the HTLV-I infected T-cell lines but not in uninfected T-cell lines, whereas this kinase did not inhibit the PARP activity even in the presence of ATP. Taken together, in vivo phosphorylation of PARP might be independent of the activation or cleavage of PARP.

Cell Line↗
PubMed1998

Reversed-phase high-performance liquid chromatographic assay method for quantitating 6-mercaptopurine and its methylated and non-methylated metabolites in a single sample.

Methods of assaying 6-mercaptopurine (6MP) and its methylated and non-methylated metabolites are essential for the therapeutic dose in treating patients with acute lymphoblastic leukemia. However, previous methods are technically complicated and unsuitable for clinical use. Thus, we have now developed a method utilizing reversed-phase high-performance liquid chromatography (HPLC) in order to quantify these compounds in human red blood cells (RBCs) in a single sample to serve as an index of cytotoxic activity. The agents 6MP, 6-thioguanine (6TG) and 6-methylmercaptopurine (6MMP) were well separated by this assay. Linear relationships were observed between the peak areas and the RBC concentrations of 6MP, 6TG and 6MMP over the range of 20-2000, 18-1800 and 18-1800 pmol per 25 mg hemoglobin (Hb), respectively. The limit of quantitation of the assay is 20, 18 and 18 pmol per 25 mg Hb, respectively. This assay system is suitable for routine clinical use.

Antimetabolites, Antineoplastic↗