PubMed HealthSearch

Biomedical subjects

M Tanimoto

Publications and source records attributed to M Tanimoto.

At least 19 recordsLinked to original sources

Role of the human Y box-binding protein YB-1 in cellular sensitivity to the DNA-damaging agents cisplatin, mitomycin C, and ultraviolet light.

The Y box-binding protein (YB-1) binds to DNA sequences, present in the control regions of many genes, that contain an inverted CCAAT box. The binding activity of a nuclear factor, designated MDR-NF1, to an inverted CCAAT box in the promoter of the multidrug resistance 1 (MDR1) gene has previously been shown to be increased in nuclear extracts of cells exposed to UV radiation or various anticancer agents. The MDR-NF1 cDNA has now been cloned by screening a human colon library with an active fragment of the MDR1 promoter. The amino acid sequence encoded by the cloned cDNA was identical to that of YB-1. Northern blot analysis revealed that YB-1 mRNA was present in all human tissues examined. Rabbit antibodies were generated against synthetic peptides corresponding to YB-1, and indirect immunofluorescence microscopy with these antibodies showed that the concentration of YB-1 in all cisplatin-resistant cell lines examined was higher than that in the respective drug-sensitive parental cells. Transfection of human epidermoid cancer KB cells with a YB-1 antisense construct established two cell lines with reduced concentrations of YB-1. These transfectants showed increased sensitivity to cisplatin, mitomycin C, and UV radiation but not to vincristine, doxorubicin, camptothecin, or etoposide. Thus, YB-1 may protect cells from the cytotoxic effects of agents that induce cross-linking of DNA, suggesting a novel function of this ancestor DNA-binding protein.

Amino Acid Sequence

Effect of isolated left atrial enlargement on mitral annular size and valve competence.

Effect of isolated left atrial enlargement on mitral annular size and valve competence was evaluated in 62 patients with normal left ventricular size and function and intrinsically normal mitral leaflets. Echocardiographic data showed that isolated left atrial enlargement could cause enlargement of the mitral annulus and cause mitral regurgitation.

Adult

Molecular cloning of the breakpoint of t(11;22) (q23;q11) chromosome translocation in an adult acute myelomonocytic leukaemia.

Southern blot analysis with a cDNA probe of MLL indicated that the breakpoint is in a BamHI 8.3 kb fragment which carries the exon 5-11 of MLL gene in DNA from an adult acute myelomonocytic leukaemia with a t(11;22) (q23;q11) translocation. The structural analysis of the rearranged MLL locus demonstrated that the breakpoint is localized between exon 8 and 9 of MLL locus. The normal counterpart fused to the MLL locus was proved to be derived from chromosome 22q11(AF-22) by somatic cell hybrids analysis and FISH. By FISH, AF-22 was localized to the region more centromeric to the BCR gene.

Adult

Randomized trials between behenoyl cytarabine and cytarabine in combination induction and consolidation therapy, and with or without ubenimex after maintenance/intensification therapy in adult acute myeloid leukemia. The Japan Leukemia Study Group.

PURPOSE: We analyzed complete remission (CR), disease-free survival (DFS), and event-free survival (EFS) rates in two groups of patients treated with either N4-behenoyl-1-beta-D-arabinosylcytosine (BHAC) or cytarabine, and analyzed DFS with or without ubenimex, a biologic response modifier. PATIENTS AND METHODS: Newly diagnosed patients with acute myeloid leukemia (AML) were randomized to receive either BHAC or cytarabine as remission-induction combination chemotherapy and two courses of consolidation therapy. After maintenance/intensification therapy, patients in CR were randomized to receive either ubenimex and no drug. RESULTS: Of 341 patients registered, 326 were assessable. The age of assessable patients ranged from 15 to 82 years (median, 48). The overall CR rate was 77%: 72% in the BHAC group and 81% in the cytarabine group, and there was a significant difference between the two groups (P = .035, chi 2 test). The predicted 55-month EFS rate of all patients was 30%: 23% in the BHAC group and 35% in the cytarabine group, with a significant difference between groups (P = .0253). The predicted 55-month DFS rate of all CR patients was 38% and that of CR patients less than 50 years of age was 47%. There was no significant difference in DFS between the ubenimex group and the group that did not receive ubenimex. CONCLUSION: Analyses of our clinical trial showed that the use of BHAC in remission-induction therapy and in consolidation therapy resulted in poorer CR and EFS rates in adult AML patients compared with the use of cytarabine at the doses and schedules tested. Immunotherapy with ubenimex after the end of all chemotherapy did not improve DFS.

Acute Disease

Lamina propria mononuclear cells express and respond to interleukin-2 differently in Crohn's disease and ulcerative colitis.

Lymphokine-activated killer (LAK) cell activity and messenger RNA (mRNA) expression for interleukin-2 (IL-2) were analyzed using lamina propria mononuclear cells (LPMC) in inflammatory bowel disease patients. Compared with control LPMC, Crohn's disease (CD) LPMC exhibited significantly higher levels of LAK cell activity, whereas ulcerative colitis (UC) cells showed significantly lower levels of cytolytic activity with a difference in the frequency of CD3+, CD56+ and CD3+, CD56+ LAK precursor cells. After incubation with IL-2, the proportion of CD3+, CD56+ lymphocytes continued to be higher in CD cultures and substantially lower in UC cultures. Freshly isolated CD LPMC exhibited significantly higher levels of IL-2 mRNA than controls. However, no significant difference was observed between UC and control cells. The level of IL-2 expression or responsiveness to IL-2 may be responsible for different mucosal immune reactivity between CD and UC patients.

Adolescent

Analysis of 55 transplantations from unrelated volunteer donors facilitated by Tokai Marrow Donor Bank.

In October, 1989, the Tokai Marrow Donor Bank (TMDB) was established through the cooperation of patients' families, the branches of blood centers of Japanese Red Cross and the hematologists' group in Tokai Area (Aichi, Shizuoka, Gifu and Mie Prefectùres) in Japan to facilitate the procurement of suitable marrow from unrelated volunteer donors for patients lacking related donors. The number of human leukocyte antigen (HLA)-A, B typed donors totaled 3,083 and the number of patients registered for donor search totaled 1,415 by June 1992, when the activities of TMDB were transferred to the newly created Japan Marrow Donor Program (JMDP), and 55 transplanations from unrelated donors facilitated by TMDD were performed.

Adolescent

Establishment and characterization of a novel human bone marrow stromal cell line, FS-1.

We have established a human stromal cell line derived from the bone marrow of a patient with chronic myelogenous leukemia in blast crisis. This cell line, designated FS-1, exhibits a fibroblastoid morphology and does not express any hematopoietic cell marker tested. FS-1 is negative for alpha-naphthyl acetate esterase, acetylated LDL, von Willebrand factor, and shows no phagocytosis. This cell line is positive for acid phosphatase, alkaline phosphatase, collagen types I, III, IV, and fibronectin. cDNA from FS-1 cells was subjected to amplification by the polymerase chain reaction to assess the constitutive expression of several cytokine genes. Transcripts for interleukin (IL)-6, IL-7, macrophage colony-stimulating factor (M-CSF), and stem cell factor (SCF) were detected in FS-1 cells. IL-6 and SCF also were detected in the culture supernatants of FS-1 at a concentration of 95 pg/ml and 21.2 pg/ml, respectively. These data show that FS-1, established from a human bone marrow, is a stromal cell line which was not generated using transfection with SV40 T antigen. FS-1 cells may be useful in supporting human hematopoietic cells for experimental manipulation.

Antigens, CD

[The importance of serum lipid level for restenosis following initial successful percutaneous transluminal coronary angioplasty in patients with unstable angina].

Serum lipids were investigated as a risk factor for restenosis following initial percutaneous transluminal coronary angioplasty (PTCA) for unstable angina (Braunwald III-B2). Follow-up angiography was used to classify 41 patients who received successful emergency PTCA into two groups: 21 patients with and 20 without restenosis. The clinical factors (age, sex), lesion characteristics and extent of coronary narrowing before and after PTCA were similar in the two groups. In the group without restenosis, the serum cholesterol level was significantly reduced from 225 +/- 48 (before PTCA) to 188 +/- 34 mg/dl (at the follow-up PTCA; p < 0.01), but in the group with restenosis serum cholesterol level showed no difference between before PTCA (211 +/- 42) and at the follow-up (201 +/- 32 mg/dl). The levels of triglycerides and high-density lipoprotein (HDL) cholesterol were not significantly different between before PTCA and at the follow-up in both groups. The restenosis rate in patients with serum cholesterol level reduced by 30 mg/dl or more at the follow-up after PTCA was significantly lower (three of 15 patients, 20%) compared with the restenosis rate in patients with serum cholesterol level lowered by less than 30 mg/dl (18 of 26 patients, 69%; p < 0.01). Moreover, the restenosis rate in patients with serum cholesterol level below 180 mg/dl at the follow-up angiography was significantly lower (six of 19 patients, 32%) compared with patients with serum cholesterol levels above 180 mg/dl (15 of 22 patients, 68%; p < 0.05). A high level of serum cholesterol may be a predictor of restenosis following PTCA in patients with unstable angina.

Angina, Unstable

Mechanisms of hypotension during dobutamine stress echocardiography in patients with coronary artery disease.

Fifty-nine consecutive patients with angiographically documented coronary artery disease were prospectively studied during dobutamine stress echocardiography. Twelve patients (20%) developed hypotension, defined as a decrease in systolic blood pressure of > or = 20 mm Hg compared with baseline. The transmitral flow velocities, isovolumic relaxation time (IVRT), and flow in the left ventricular (LV) outflow tract were measured at baseline, at maximal dobutamine dose, or during a hypotensive episode; stroke volume, cardiac output, and systemic vascular resistance (SVR) were computed. Correlates of hypotensive response to dobutamine stress echocardiography included therapy with angiotensin-converting enzyme inhibitors (p = 0.032), a longer IVRT at baseline (121 +/- 25 vs 103 +/- 28 ms, p = 0.047), a greater decrease in LV end-diastolic (-6.0 +/- 3.1 vs -2.2 +/- 2.1 mm, p < 0.0001) and end-systolic (-8.3 +/- 7.0 vs -5.1 +/- 3.7 mm, p = 0.037) dimensions, and a greater decrease in stroke volume (-10 +/- 10 vs -2 +/- 11 ml, p = 0.023) compared with those with a normal response. The groups did not differ significantly with regard to baseline stroke volume, cardiac output, SVR, and LV ejection fraction or LV mass.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

All-trans retinoic acid for the treatment of newly diagnosed acute promyelocytic leukemia. Japan Adult Leukemia Study Group.

We conducted a multicenter trial of treatment with all-trans retinoic acid (ATRA) for newly diagnosed acute promyelocytic leukemia (APL) in the AML-92 study and compared it with our previous study with standard intensive chemotherapy, the AML-89 study, in the view of complete remission (CR) rate, incidence of early death, and event-free survival (EFS). Patients were scheduled to receive oral ATRA 45 mg/m2 daily until CR. If patients had leukocyte counts above 3 x 10(9)/L at the start of therapy, they received daunorubicine (DNR) 40 mg/m2 for 3 days and behenoyl cytosine arabinoside (BHAC) 200 mg/m2 for 5 days in addition to ATRA. During the ATRA therapy, if patients showed myeloblast plus promyelocyte counts higher than 1 x 10(9)/L in the peripheral blood, they received additional DNR and BHAC in the same schedule, as well. A total of 110 patients were entered into the study. Median age was 43 years (range, 16 to 74). Twenty-eight (26%) of 109 patients (one died before the start of therapy) received ATRA alone. Ninety-seven patients (89%) achieved CR; 48 of 49 (98%) aged less than 40 years, 44 of 52 (84%) aged between 40 and 69, and 5 of 8 (63%) aged above 70 achieved CR, respectively; 25 of 28 (89%) with ATRA alone, 46 of 51 (90%) with ATRA plus initial chemotherapy and 26 of 30 (87%) with ATRA plus later chemotherapy attained CR, respectively. Nine (8%) patients died within 28 days after the start of therapy. In contrast, 44 of 62 patients (71%) attained CR, and 13 (21%) died within 28 days in the AML-89 study with the combination of DNR, BHAC, 6-mercaptopurine and prednisolone. Seven developed retinoic acid syndrome and one died of it in the present study. Other toxicities associated with this drug included cheilitis, desquamation, muscle pain, and hypertriglyceridemia. Predicted 23 months EFS for all ATRA-treated patients and disease-free survival (DFS) in the CR cases were 75% and 81%, respectively, in a median follow-up period of 21 months. Compared to the AML-89 study, there was a highly significant difference in remission rate (P = .004), EFS (P = .0007), and also early mortality rate (P = .02). Present results demonstrated that ATRA with or without chemotherapy gives a statistical improvement in CR rate and early mortality rate, as well as superior survival in newly diagnosed APL.

Adolescent

Dobutamine stress echocardiography for the diagnosis and management of coronary artery disease.

Infusion of dobutamine in low and high doses in combination with echocardiography can be used for the assessment of myocardial viability and functional significance of coronary artery disease. Improvement of contractile function of hypokinetic or akinetic ventricular wall segment with low-dose dobutamine has a high predictive value for the detection of hibernating and stunned myocardium. High-dose dobutamine stress is of value for noninvasive diagnosis of coronary disease, assessment of its clinical significance, risk stratification of patients after myocardial infarction, preoperative evaluation of patients undergoing major noncardiac surgery, and assessment of the efficacy of coronary revascularization. It has an excellent safety record even in the immediate postmyocardial infarction period.

Analysis of Variance

Elevation of interleukin-6 in inflammatory bowel disease is macrophage- and epithelial cell-dependent.

Local interleukin-6 (IL-6) activity was studied using colonic mucosal tissues in inflammatory bowel disease (IBD) and inflammatory control patients. Active IBD specimens exhibited significantly higher IL-6 activity than control specimens in both cultures of isolated lamina propria mononuclear cells (LPMC) and mucosal tissues with an increased number of IL-6-producing cells. However, the activity in inactive IBD or inflammatory controls did not differ from controls. Northern blot analysis demonstrated IL-6 messenger RNA in LPMC and colonic epithelial cells isolated from active IBD specimens but not in control cells. Furthermore, immunofluorescent microscopic study of active IBD specimens showed more conspicuous staining of IL-6 in infiltrating LPMC (mostly CD68+ cells) and colonic epithelial cells. These results suggest that elevation of local IL-6 activity may be a characteristic feature of active IBD and both macrophages and colonic epithelial cells are the major cell types responsible for this phenomenon.

Adenocarcinoma

Acute myeloblastic leukemia (M2) with translocation (7;11) followed by marked eosinophilia and additional abnormalities of chromosome 5.

We present an 18-year-old woman who was diagnosed with acute myeloblastic leukemia (AML M2), and in whom chromosome analysis of bone marrow cells revealed t(7;11), an abnormality rarely found in leukemias with a differentiation potency. She relapsed 1 year after complete remission was achieved by chemotherapy. Bone marrow examination then revealed a t(7;11) abnormality in 48 of 50 metaphases examined, even when there were less than 7.5% leukemic blasts in the marrow, indicating that the morphologically normal cells were derived from leukemic blasts. The number of leukemia clones with the additional abnormalities in chromosome 5 increased, with concurrent development of eosinophilia, fever, asthma-like symptoms, erythema, itching, and hepatosplenomegaly. Elevation of interleukin 5 (IL-5) in serum and an enhanced expression of IL-5 mRNA were also detected. The increase in IL-5 may have been produced by an abnormality on chromosome 5.

Adolescent

Inhibition of mitogen-induced proliferative responses of lymphocytes by bovine kappa-caseinoglycopeptides having different carbohydrate chains.

Bovine kappa-caseinoglycopeptides (i.e. residues 106-169, CGP) were prepared from kappa-casein digested with rennin and a commercial whey protein concentrate. CGP from whey protein concentrate was further divided into seven CGP fractions having different carbohydrate compositions using FPLC. Unfractionated CGP inhibited lipopolysaccharide (LPS)- and phytohaemagglutinin (PHA)-induced proliferative responses of mouse spleen cells and rabbit Peyer's patch cells. The unfractionated CGP also inhibited antibody responses to sheep red blood cells in mouse spleen cell cultures. However, seven CGP fractions having zero to five N-acetylneuraminic acid (NANA) residues had different inhibitory effects on both LPS- and PHA-induced proliferative responses of mouse spleen cells. The inhibitory effect on PHA-induced proliferative responses increased with increasing numbers of NANA residues, whereas that on LPS-induced proliferation was highest with the CGP fraction having two NANA residues. Both inhibitory effects decreased significantly after neuraminidase or chymotrypsin digestion. These findings indicate that both the carbohydrate (particularly the NANA residues) and the polypeptide portions are essential for inhibitory effects on LPS- and PHA-induced proliferative responses of mouse spleen cells.

Animals

Ethylene is a positive regulator of root hair development in Arabidopsis thaliana.

Evidence is provided that ethylene is a positive regulator of hair cell development in the root epidermis of Arabidopsis thaliana. Treatment of seedlings with increasing concentrations of the ethylene precursor, 1-aminocyclopropane-1-carboxylic acid (ACC) results in progressively more root hair cells developing in positions normally occupied by non-hair cells. Consistent with these findings are observations that treatments that block either ethylene synthesis or its perception reduce the number of root hairs. A model is proposed in which either ethylene or ACC is a signal involved in specifying the pattern of cell differentiation in the Arabidopsis root epidermis.

Arabidopsis

[Indication of allogeneic bone marrow transplantation (BMT) from HLA identical sibling in adult acute myeloblastic leukemia--comparative study of BMT and chemotherapy in patients with the first remission state. Nagoya BMT Group. Japan Adult Leukemia Study Group].

The indication of allogeneic bone marrow transplantation (BMT) from HLA identical siblings during the first remission of acute myeloblastic leukemia was discussed according to the results of BMT and chemotherapy study groups. The comparison of disease free survival between both groups was done, after selection biases such as risk factors and time of BMT were adjusted by multivariate analysis or matched-pair analysis. In conclusion, patients with more than one high risk factors for leukemia relapse, that is, high peripheral white blood cell count (PBC) (> 20,000/cmm) at diagnosis or more than two remission induction courses should be considered for BMT, and the indication of treatments for patients with no high risk factors should be determined depending on situations of the disease and patient's intention.

Adult

Low incidence of acute GVHD in patients transplanted with marrow from HLA-A,B,DR-compatible unrelated donors among Japanese.

To prevent GVHD in BMT from unrelated donors, the matching of HLA between patient and donor is crucial. The appearance of acute GVHD was studied in 51 patients with hematological malignancies who were transplanted with non-T cell purged marrow from HLA-A,B and DR compatible unrelated donors with the assistance of the Tokai Marrow Donor Bank of Nagoya, Japan. Probability of grade II-IV acute GVHD was 32.0% and of grade III-IV acute GVHD was 17.0%. HLA-class II antigen compatibility showed a good correlation with the occurrence of acute GVHD. When the percentage relative response (RR) of MLC between patient and donor (GVHD vector) was < or = 5, grade II-IV acute GVHD was found in only 7.7% of patients (n = 16) and no severe grade III-IV GVHD occurred. Among patients with 6-10% RR (n = 10), 25.9% showed grade II-IV GVHD and 14.3% grade III-IV GVHD. Among patients with > or = 11% RR (n = 20), however, the incidence of grade II-IV acute GVHD reached 51.8% and that of grade III-IV acute GVHD 36.2%. These reactivities of MLC reflected the compatibility of HLA-DRB1 and DPB1. The fact that the incidence of acute GVHD in BMTs from HLA-A,B,DR compatible Japanese pairs was found to be lower than in the USA may be due to less diversity of the genetic background in Japan.

Adolescent