Search PubMed⌕ Search

Biomedical subjects

Y Takemoto

Publications and source records attributed to Y Takemoto.

At least 91 records · Page 5Linked to original sources
PubMed1999

A cytogenetic and fluorescence in situ hybridization evaluation of interferon-alpha in the treatment of chronic myeloid leukemia.

The effect of interferon-alpha (IFN) for chronic myeloid leukemia (CML) in the chronic phase (CP) was retrospectively evaluated in comparison with that of busulfan (BU) or hydroxyurea (HU) given alone. Among 107 patients diagnosed with CML between 1982 and 1997, 72 CP cases evaluable for long-term follow-up included 13 patients treated with BU alone, 18 with HU alone, and 41 with IFN-based therapy. Complete cytogenetic response (CCR) was achieved in 4/41 IFN cases (10%), and partial or minimal cytogenetic response occurred in 18/41 IFN cases (44%). In contrast, no cytogenetic response (NCR) was achieved in any BU or HU case. IFN treatment for 6 to 60 months was needed to achieve CCR. Overall survival curves revealed that the IFN group had significantly better survival than BU and HU groups (p=0.008 and 0.04, respectively). A significant correlation was found between karyotypic findings and fluorescence in situ hybridization (FISH) analyses in IFN-treated cases (r=0.739, p=0.0001). In some cases, however, the two methods showed discrepancy; BCR/ABL-positive cells represented only 20-75% of interphase bone marrow cells in NCR cases, although all metaphases examined were positive for the Philadelphia chromosome (Ph). A discrepancy was also seen in CCR cases; up to 22% of cells assessed were BCR/ABL-positive. These findings suggest that IFN is a useful therapy for CML in CP, and may have a suppressive effect on the CML clone even in NCR cases. The results also indicate that a combination of FISH and cytogenetic analyses may provide more detailed information for evaluating the efficacy of IFN than conventional cytogenetics alone.

Adolescent↗
PubMed1999

Detection of GPI-anchored protein-deficient cells in patients with aplastic anaemia and evidence for clonal expansion during the clinical course.

The incidence of patients with aplastic anaemia (AA) who show a deficiency of glycosylphosphatidylinositol (GPI)-anchored proteins on their peripheral blood (PB) or bone marrow (BM) cells is higher than that previously reported. We analysed the expression of CD55 or CD59 on PB and BM cells and those of colonies and bursts formed in cultures with marrow cells from AA patients. 4/21 (19%) AA cases later developed paroxysmal nocturnal haemoglobinuria (PNH). 7/17 (41. 2%) AA cases showed a subpopulation without GPI-anchored proteins. The defect characteristic for PNH was observed only on the colonies/bursts but not on the PB or BM cells in three cases. We found the affected colonies/bursts in cultures using thawed marrow cells which had been cryopreserved at the diagnosis of aplasia in one patient who developed PNH 3 years later. Two different mutations of the PIG-A gene were found in the colonies/bursts at the time of AA. The nucleotide sequences were identical between the colonies/bursts at the time of AA and those after the transition to PNH. However, one of the mutations was detected only at the haemopoietic progenitor level but not in PB granulocytes. There may be latent subclones with PNH abnormalities which could expand to the level of clinical detection, or which do not progress and remain indolent for a relatively long time, implying the different extents of clonal expansion among the affected progenitors.

Adolescent↗
PubMed1999

Fluconazole versus amphotericin B for the prevention of fungal infection in neutropenic patients with hematologic malignancy.

Effective prophylaxis against fungal infection is important in neutropenic patients with hematologic malignancies, but the best method remains unclear. We investigated the effectiveness of fungal prophylaxis with amphotericin B or fluconazole. We reviewed the data on fungal isolates, plasma (1-->3)-beta-D glucan (beta-D glucan) levels, febrile periods (the number of days with an axillary temperature > 38 degrees C), and the duration of an axillary temperature > 38 degrees C when the neutrophil count was < 500/microliter. Of the 124 patients studied, 57 had acute myelogenous leukemia, 19 had acute lymphoblastic leukemia, 18 had non-Hodgkin's lymphoma, six had chronic myeloid leukemia, three had adult T-cell leukemia, and five had chronic lymphocytic leukemia. There were no significant differences in clinical characteristics between the 70 patients treated with amphotericin B and the 54 patients given fluconazole. There was a significant decrease of fungal isolates (chi 2-test, p < 0.001), the plasma beta-D glucan level (Wilcoxon test, p = 0.0001), and the febrile period (t-test, p < 0.05) in the patients given fluconazole compared with those given amphotericin B. In neutropenic patients with hematologic malignancies, prophylaxis with fluconazole significantly decreased fungal isolation and other indicators of fungal infection when compared with amphotericin B. Fluconazole may therefore be more effective for fungal prophylaxis in these patients.

Adolescent↗
PubMed1999

A prospective randomized trial of KRN8602 and cytosine arabinoside vs. daunorubicin and cytosine arabinoside in adult patients with newly diagnosed acute myelogenous leukemia. The KRN8602 Leukemia Study Group.

A prospective randomized study was conducted to compare the efficacy and toxicity of two anthracyclines for the treatment of patients with acute myelogenous leukemia (AML). Fifty-eight patients were randomized and received induction therapy consisting of cytosine arabinoside (AraC) 100 mg/m2/day for 7 days combined with either KRN8602 (3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride [KRN]) 15 mg/m2/day for 5 days (KRN/AraC group) or daunorubicin (DNR) 40 mg/m2/day for 3 days (DNR/AraC group). Complete remission rate was 78.6% (22/28) in the KRN/AraC group and 73.1% (19/26) in the DNR/AraC group. There was a higher incidence of nausea/vomiting and anorexia observed in the KRN/AraC group compared to the DNR/AraC group, while the incidence of other adverse effects (stomatitis, diarrhea, and infectious complications) were similar between both groups. No electrocardiogram (ECG) abnormalities were observed after treatment in the KRN/AraC group, while in the DNR/AraC group, one patient showed ECG abnormality and three patients exhibited either arrhythmia, heart failure, or tachycardia. Mental disorder was reported in two cases in the KRN/AraC group. These findings suggest that KRN/AraC is similar in effectiveness to DNA/AraC but more toxic in central nervous system and gastrointestinal symptoms and less toxic regarding cardiac function in patients with previously untreated AML.

Adolescent↗
PubMed1999

[Fundamental and clinical study of three-dimensional compensating filters and direct dose monitoring system for total body irradiation].

We devised 3D-compensating filters to improve dose distribution during total body irradiation (TBI). This study investigated the effect of these 3D-compensating filters and related complications in patients who had undergone bone marrow transplantation (BMT) followed by TBI. The 3D-compensating filters were fabricated by CT measurement of body thickness. The effectiveness of the 3D-compensating filters in producing a homogeneous dose distribution was checked by a thermoluminescent dosimeter (TLD) and semiconductor detectors in all patients. At the pelvis, the dose was measured simultaneously with an ionization chamber. The average dose distribution to each site when the 3D-compensating filter was used was 93% to the head, 97% to the neck, 99% to the thorax, and 98% to the pelvis in TLD when the scheduled dose was taken as 100%. There was no significant difference between the TBI and non-TBI groups with regard to the frequency of lung toxicity. Clinical interstitial pneumonitis occurred in 22.7% of the patients, interstitial pneumonitis with CMV in 13.6%, and idiopathic pneumonitis in 6.1% without any virus infection. Only one patient was regarded as having radiation-induced pneumonitis. 3D-compensating filters can be conveniently produced within a short time following CT measurement, and they seem to be safe and useful for dose flattening during TBI.

Adolescent↗
PubMed1999

Clinical results of total cystectomy for 92 patients with bladder cancer.

The survival rate of 92 patients with primary bladder cancer who had undergone total cystectomy during a 13-year period from 1984 to 1996 was examined. The mean follow-up period was 1,886 days. The 5-year survival rate was 67.9% and the 10-year survival rate was 55.1%. When survival rates were compared pathohistologically, with 81 patients with transitional cell carcinoma divided into two groups, a high-stage group including T3 and T4 patients and a low-stage group with all other patients, the cancer-specific 5-year survival rate of the low-stage group was 88.9% while that of the high-stage group was 45.4%; this difference was significant (p = 0.0002). There were also significant differences in survival rate between those with and those without regional lymph node metastasis, those with and those without lymphatic infiltration, and those with and those without vascular infiltration. However, there was no significant difference in survival rate for the 34 patients with T3 or T4 disease when those with or without chemotherapy and/or radiation therapy were compared.

Adult↗
PubMed1999

[Pilot late phase II study of KRN8602 (MX2), a novel anthracycline derivative, for acute leukemia--a dose finding study in combination].

In order to determine the clinically optimal dose of KRN8602, a new anthracycline derivative, in combination therapy for acute leukemia, we performed a pilot late phase II study in combination with cytarabine (Ara-C) for acute myelogenous leukemia (AML), and with vincristine (VCR) and prednisolone (PSL) for acute lymphocytic leukemia (ALL). KRN8602 was given at a dose of 12 or 15 mg/m2 for 5 consecutive days, Ara-C at a dose of 100 mg/m2 for 7 consecutive days, VCR 1.4 mg/m2 (max. 2.0 mg/body) weekly for 4 weeks, and PSL 40 mg/m2 for principally 28 consecutive days. Of 14 patients with relapsed or refractory leukemia entered in the study, thirteen patients were evaluable for safety and 12 were evaluable for response. In AML, there was 1 partial response (PR) in 4 patients at a dose of 12 mg/m2. Against 1 complete response (CR) and 3 PRs in 4 patients at a dose of 15 mg/m2. In ALL, there was 1 PR in 1 case at a dose of 12 mg/m2, and 1 CR and 2 PR in 3 at a dose of 15 mg/m2. Major toxicities were nausea/vomiting and anorexia, but incidences and grades of toxicities were not dose-dependent, and all toxicities were tolerable and manageable. From these results it is concluded that the optimal dose of KRN8602 is 15 mg/m2 for 5 consecutive days in combination with Ara-C for AML, and with VCR and PSL for ALL.

Adult↗
PubMed1998

Growth factor receptor-bound protein 2 (Grb2) association with hemopoietic specific protein 1: linkage between Lck and Grb2.

To analyze the growth factor receptor-bound protein 2 (Grb2) signaling pathway in lymphoid cells, we used expression cloning to isolate the genes encoding proteins that associate with Grb2. We find that the Src homology 3 domains of Grb2 directly associate, in vitro and in vivo, with murine hemopoietic specific protein 1 (HS1), a protein identical to Lck-binding protein 1. Because HS1 associates with the p56(lck) and p59(lyn) tyrosine kinases in vitro and in vivo, and becomes tyrosine phosphorylated upon various receptor stimulations, our present data suggest that HS1 mediates linkage between Lck or Lyn and Grb2 in lymphoid lineage cells.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Identification and characterization of a novel SH3-domain binding protein, Sab, which preferentially associates with Bruton's tyrosine kinase (BtK).

Protein interaction cloning method was used to identify a novel molecule, Sab, which binds to the SH3 domain of Bruton's tyrosine kinase (Btk), the deficient cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia and murine X-linked immunodeficiency. Immunoprecipitation using the anti-Sab antibody identified the protein product of the gene as a 70 kDa molecule. While Sab does not have a proline-rich sequence, it was shown to bind to Btk through the commonly conserved structure among SH3 domains. Remarkably, Sab exhibited a high preference for binding to Btk rather than to other cytoplasmic tyrosine kinases, which suggests a unique role of Sab in the Btk signal transduction pathway.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Cloning and mapping of Np95 gene which encodes a novel nuclear protein associated with cell proliferation.

We previously obtained a monoclonal antibody (Th-10a mAb) that recognizes a single 95-kDa mouse nuclear protein (NP95). Immunostaining analyses revealed that the NP95 was specifically stained in the S phase of normal mouse thymocytes. In contrast, mouse T cell lymphoma cells exhibited a constantly high level of NP95 accumulation irrespective of cell stages during the cell cycle. In the present study, we isolated the cDNA encoding the NP95 from a lambdagt-11 cDNA expression library, using the Th-10a mAb. Sequencing of the whole 3.5-kb cDNA revealed that NP95 is a novel nuclear protein with an open reading frame (ORF) consisting of 782 amino acids. The ORF contains a zinc finger motif, a potential ATP/GTP binding site, a putative cyclin A/E-cdk2 phosphorylation site, and the retinoblastoma protein (RB)-binding motif "IXCXE". The chromosomal location of Np95 gene was determined by fluorescence in situ hybridization. Np95 gene locates on mouse Chromosome (Chr) 17DE1.1. and rat Chr 9q11.2-q12.1. Np95 was strongly expressed in the testis, spleen, thymus, and lung tissues, but not in the brain, liver, or skeletal muscles. These results collectively implicate this novel nuclear protein in cell cycle progression and/or DNA replication.

Amino Acid Sequence↗
PubMed1998

Long acting calcium antagonist amlodipine prevents left ventricular remodeling after myocardial infarction in rats.

OBJECTIVE: The purpose of this study was to examine the effect of amlodipine, a long-acting calcium antagonist, on the left ventricular remodeling, including systolic and diastolic dysfunction, the change of cardiac gene expression in the myocardial infarcted rats (MI). METHODS: On the first day after myocardial infarction, the animals were randomly assigned to amlodipine treatment (n = 8) or untreated groups (MI; n = 9). We then performed Doppler-echocardiographic examinations and measured the hemodynamics at four weeks after myocardial infarction. Following these measurements, their cardiac mRNA was analyzed. RESULTS: Left ventricular end-diastolic pressure (LVEDP) and central venous pressure (CVP) increased to 22 +/- 1 mmHg and 5 +/- 1 mmHg. Amlodipine reduced LVEDP and CVP to 15 +/- 1 mmHg (P < 0.01) and 3 +/- 0 mmHg (P < 0.01). The weight of right ventricle in MI was significantly larger than in the control rats (Control; 0.48 +/- 0.01 g/kg, MI; 0.79 +/- 0.04 g/kg, P < 0.01). Left ventricular end-diastolic dimension (LVDd) in MI increased to 10.3 +/- 0.3 mm (P < 0.01) (Control; 6.2 +/- 0.3 mm). Amlodipine prevented an increase of the weight of right ventricle (0.62 +/- 0.03 g/kg, P < 0.01) and LVDd (7.9 +/- 0.2 mm, P < 0.01 to MI). The rats in MI showed systolic dysfunction shown by the decreased fractional shortening (Control; 31 +/- 2% versus MI; 15 +/- 1%, P < 0.01), and diastolic dysfunction shown by E wave deceleration rate (Control; 18.1 +/- 2.0 m/s2, MI; 32.6 +/- 2.1 m/s2, P < 0.01). Amlodipine significantly prevented systolic and diastolic dysfunction. The increases in beta-MHC, alpha-skeletal actin, and ANP mRNAs in the non-infarcted left ventricle and right ventricle at four weeks after the myocardial infarction were all significantly suppressed by the treatment with amlodipine. On the other hand, depressed alpha-MHC was restored to normal levels by amlodipine in both regions. CONCLUSIONS: Amlodipine prevents the left ventricular remodeling process accompanied by systolic and diastolic dysfunction, and inhibits abnormal cardiac gene expression after myocardial infarction.

Actins↗
PubMed1998

Recombinant human erythropoietin for late-onset anemia after allogeneic bone marrow transplantation.

Recombinant human erythropoietin (rHu EPO) has been reported to accelerate early erythroid reconstitution after bone marrow transplantation (BMT). We conducted a pilot study on rHu EPO for late-onset anemia in 9 patients after allogeneic BMT. The patients achieved initial erythropoietic recovery (hemoglobin (Hb) range 9.1-13.4, mean 10.8 g/dl), but then developed transplant-related anemia (Hb range 6.3-9.7, mean 8.2 g/dl) more than 50 days after BMT. This type of anemia was related to graft-versus-host disease (GVHD), cytomegalovirus infection, and/or impaired EPO secretion. The patients received 3,000 or 12,000 U of rHu EPO subcutaneously three or seven times weekly. Hb levels increased by more than 2 g/dl in 6 of the 9 patients, but were unchanged in the 3 patients with severe GVHD. These findings suggest that in some cases rHu EPO is effective for the treatment of late-onset anemia after BMT.

Adult↗
PubMed1998

Myelodysplastic syndrome with B cell clonality in a patient five years after renal transplantation.

A female patient received a renal transplantation from an unrelated cadaver donor, and five years later developed myelodysplastic syndrome (MDS) with immunological abnormalities. Chromosomal analysis showed trisomy 8 in bone marrow cells. FISH analysis indicated that trisomy 8 was present in 4% of CD19 + cells, suggesting that the MDS clone involved B lymphocytes. Polymerase chain reaction of the human androgen receptor gene indicated B cell clonality (54%) and granulocyte clonality (63%). There have been no previous reports of secondary MDS following renal transplantation in which the MDS clone involved the B cell lineage. The abnormal MDS B cell clone may have caused the immunological abnormalities.

B-Lymphocytes↗
PubMed1998

Serum carcinoembryonic antigen as a prognostic factor in resectable gastric cancer.

BACKGROUND: Carcinoembryonic antigen (CEA) has been widely accepted as a tumor marker useful in the diagnosis and management of colorectal cancer. When CEA levels are positive in gastric cancer patients, they could be useful prognostic indicators. However, the value of CEA as a tumor marker for gastric cancer remains a matter of controversy. STUDY DESIGN: We measured preoperative serum CEA levels in 196 patients with resectable gastric cancer between May 1986 and April 1996 and then evaluated the correlation between serum CEA levels, clinicopathologic features, and prognostic information. RESULTS: Serum levels of CEA were above the normal range in 29 of 196 (14.8%) surgically resected patients (range, 5.2-570 ng/mL). Among 100 early gastric cancers confined to the submucosal layer, only 7 patients (7.0%) had positive CEA levels, but among 96 advanced cancers, 22 patients (22.9%) had high CEA levels. The CEA positive patients had more macroscopically infiltrative tumors, a more prominent serosal invasion, more frequent lymph nodes involvement, and a more advanced stage than did the CEA negative patients. The 3- and 5-year cumulative disease-specific survival rates of patients positive for serum CEA were 39.6% and 31.7%, respectively; these rates for patients negative for CEA were 83.0% and 77.3%, respectively (p < 0.0001 for comparison of survival curves). In various clinicopathologic parameters, nine parameters (tumor size, macroscopic type, type and time of operation, Laurén classification, depth of invasion, lymph node involvement, CEA, alpha-fetoprotein [AFP], and carbohydrate antigen [CA] 19-9) showed statistically significant differences in the cumulative survival rates. Of these nine parameters, independent prognostic factors by multivariate analysis were depth of invasion (T1, 2 versus T3, 4, p < 0.0001), serum CEA levels (negative versus positive, p = 0.0003), and lymph node metastasis (negative versus positive, p = 0.0005). CONCLUSIONS: Preoperative serum CEA levels provide a predictive value in determining tumor stage and prognostic information for patients with potentially resectable gastric cancer during the preoperative period.

Adenocarcinoma↗
PubMed1998

Effect of cilazapril on ventricular remodeling assessed by Doppler-echocardiographic assessment and cardiac gene expression.

The purpose of this study is to determine whether the administration of the ACE inhibitor cilazapril can lessen the adverse effects of ventricular remodeling, including systolic and diastolic dysfunction, modulation of fetal gene expression, increase of collagen genes, and depression of the sarcoplasmic reticulum (SR) Ca2+ ATPase gene in a myocardial infarcted (MI) rat model. At 1 day after MI, the animals were randomly assigned to cilazapril treatment or no treatment. We performed Doppler-echocardiographic examinations and measured cardiac mRNA in rats at 1 month and 3 months after MI (each group n = 8). The weights of the right (RV) and left ventricles (LV) in 1- and 3-month MI rats were significantly larger than those of the control rats. Cilazapril significantly prevented the increase. The MI rats showed systolic dysfunction, as evidenced by decreased fractional shortening (control, 34 +/- 3% vs. MI, 17 +/- 3%; P < 0.01) and ejection fraction measured by the modified Simpson's method (control, 61 +/- 2% vs. MI, 36 +/- 3%; P < 0.01) in rats at 1 month after operation. MI rats showed diastolic dysfunction, defined as increased peak early filling velocity, increased deceleration rate of the early filling wave, decreased late filling velocity, and an increase in the ratio of early filling to late filling velocity. Cilazapril significantly prevented systolic and diastolic dysfunction in rats after MI. The increases in beta-MHC, alpha-skeletal actin, ANP, and collagen I and III mRNAs in the nonischemic LV and RV were significantly suppressed by treatment with cilazapril. Depressed SR Ca(2+)-ATPase mRNA (nonischemic LV, 0.7-fold, P < 0.05 vs. control; RV, 0.5-fold, P < 0.05 vs. control) at 3 months after MI was significantly restored to normal levels by cilazapril. Cilazapril improved the adverse remodeling process by attenuating the progression of systolic and diastolic dysfunction, and prevented abnormal cardiac gene expression following MI.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Tauroursodeoxycholic acid protects cholestasis in rat reperfused livers: its roles in hepatic calcium mobilization.

Tauroursodeoxycholic acid (TUDCA) is of potential benefit in cholestatic disorders. However, the effect of TUDCA on hepatic ischemia-reperfusion injury is unknown. We studied this subject with particular regard to its roles in hepatic calcium mobilization. Three doses of TUDCA were used with continuous intravenous infusion (1.0, 0.1, and 0.01 micromol/kg body weight/min). At 3 hr after 1 hr of ischemia and reperfusion in 70% rat liver, high-dose TUDCA reduced hepatic reperfused injury according to biochemical and histological findings and significantly increased bile flow after reperfusion. It significantly increased tissue calcium content and serum calcium concentration after reperfusion. Furthermore, it also enhanced biliary calcium concentration and total output during reperfusion. In conclusion, TUDCA has a salutary effect on ischemia-reperfusion injury of the liver. However, it is still unclear how the calcium mobilization induced by TUDCA is associated with the hepatoprotection against ischemia-reperfusion injury.

Animals↗