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Biomedical subjects

K Tohyama

Publications and source records attributed to K Tohyama.

At least 55 records · Page 3Linked to original sources
PubMed1997

Anti-Leukemia Chemotherapy of High-Risk Myelodysplastic Syndromes.

We evaluated the outcome of anti-leukemia chemotherapy on 42 patients with the high-risk myelodysplastic syndromes (MDS)-refractory anemia with excess of blasts (RAEB), 8 cases; RAEB in transformation (RAEB-T), 18 cases; chronic myelomonocytic leukemia (CMMOL), 6 cases; and leukemic transformation of MDS, 10 cases. The median age was 67 (range 20 to 84). As a remission-induction therapy, 35 patients received low-dose chemotherapy, such as low-dose cytarabine infusion, and seven patients received high-dose combination chemotherapy. The complete remission (CR) rates of the low-dose chemotherapy group and the high-dose combination chemotherapy group were 29% and 57%, respectively, and the overall CR rate was 33%. The median survival durations after induction chemotherapy of the CR group (14 cases), the partial remission (PR) group (11 cases), and non-remission (NR) group (17 cases) were 19 months, 8 months, and 3 months, respectively. As a post-remission consolidation chemotherapy, high-dose combination chemotherapy seemed to be superior to low-dose chemotherapy judging from the median CR duration (16 months versus 4 months), but a long-term disease-free survival is hardly expected, in contrast with results in cases of de novo acute myeloid leukemia.

Journal Article↗
PubMed1997

Intracellular pharmacodynamics of ara-C and flowcytometric analysis of cell cycle progression in leukemia chemotherapy.

To establish the most effective and reasonable mode of combining and administrering ara-C with other antileukemic agents in chemotherapy for acute leukemia, the action mechanisms of ara-C was investigated in terms of intracellular pharmacodynamics and the biochemical action mechanism of ara-C was investigated in leukemic cell. Rensonable methods of administering the agent was considered as follows. 1. A low level of ara-C in the incubation medium induced a higher concentration of ara-CTP in leukemic cells. Therefore, maintenance of even a low plasma ara-C level after ara-C therapy could enhance the antileukemic effect of the agent. 2. Ara-C activation was increased in the presence of 6MP by suppressing elevation of deaminase activity in the cell suspection medium. Therefore, administration of 6MP prior to ara-C therapy could enhance the antileukemic effect of the agent. 3. Ten micrograms/ml of ara-C, corresponding to intermediate dose ara-C therapy, induced rapid endonuclease activation, DNA ladder fragmentation and subsequent apoptosis in large numbers of leukemic cells, suggesting that intermediate dose ara-C therapy is effective in reducing residual leukemic cells after therapy. 4. Blood transfusion for patients with high grade anemia prior to bebenoyl ara-C therapy prolonged higher and longer plasma drug maintenance. 5. Flowcytometry of cell cycle progression of L1210 cells treated by ara-C and daunorubicin revealed that a combination of ara-C first and daunorubicin second was superior to the reverse sequential combination. These improvements in the mode of administering ara-C could provide better results following chemotherapy for leukemia.

Animals↗
PubMed1997

[Improvement of bleeding tendency and normalized platelet count increment following splenectomy in a patient with refractory anemia].

A 72-year-old woman with refractory anemia had severe bleeding tendency. Since 1994, platelet transfusions (10 units three times per week) were unable to maintaining her platelet count over 10 x 10(3)/ microliter. Her hemoglobin was decreased to 3.9 g/dl as a result of bleeding from early gastric cancer. At one-hour after posttransfusion corrected platelet count increment (1-hour CCI) was slightly low, as 14 x 10(3)/microliter/m2. A 24-hour posttransfusion CCI (24-hour CCI) and the (24-hour CCI)/(1-hour CCI) ratio were markedly low, as 0.5/microliter/m2 and 0.36, respectively. Anti-HLA antibody was not detected. The ineffectiveness of platelet transfusion was suspected to be highly associated with splenomegaly. Her spleen had been gradually increased in size since the first clinical examination. She underwent both subtotal gastrectomy and splenectomy, while receiving 40 units of platelet transfusion. After splenectomy, the 1-hour CCI and the (1-hour CCI)/(24-hour CCI) ratio markedly improved (76 x 10(3)/microliter/m2 and 0.79, respectively). Cutaneous bleeding halted and there have been no further episodes, despite less frequent platelet transfusions. This is the first report in which bleeding tendency and CCI were improved by splenectomy in a case of myelodysplastic syndrome.

Aged↗
PubMed1997

[Minute carcinoid tumor in the rectum with liver metastasis].

A 65-year-old woman was admitted to our hospital for evaluation of multiple liver tumors following endoscopic polypectomy for rectal polyp a year earlier. The polypectomy specimen was reexamined and showed inclusion of a carcinoid tumor 3 mm in diameter. The perirectal lymph node was palpated by digital examination on readmission. The patient died one mouth after readmission due to liver failure. Autopsy revealed metastatic carcinoid tumor in the liver and perirectal nodes.

Aged↗
PubMed1997

[Liver metastases from breast cancer 14 years after radical mastectomy; successful treatment with hepatic arterial infusion chemotherapy and systemic endocrine therapy--a case report].

The patient was a 73-year-old woman who was admitted to our hospital for epigastric discomfort and body weight loss. She had undergone radical right mastectomy in March 1982. Ultrasonography and computed tomography revealed multiple tumors in the liver. Three of the tumor markers (CA-125, CA 19-9, and CA 15-3) were positive. US-guided fine needle aspiration biopsy of the liver tumor showed small atypical cells with solid cell nests. Immunohistochemical tests revealed estrogen receptor was positive. We diagnosed the patient as recurrent breast cancer metastatic to liver, 14 years postoperatively. The liver tumors were successfully controlled with the combination of intra-arterial infusion chemotherapy (5-fluorouracil, epirubicin, and mitomycin C) along with systemic endocrine therapy (medroxyprogesterone acetate and fadrozole hydrochloride hydrate).

Aged↗
PubMed1997

Apoptosis as a cell biological abnormality in myelodysplasia.

Evidence is accumulating to indicate that alterations in the control of apoptosis can contribute to a variety of disorders. Among the disorders associated with abnormal regulation of apoptosis, MDS stands out unequaled in that apoptosis is related, in apparently opposite directions, to ineffective hematopoiesis and leukemic transformation of MDS; notably, excessive apoptosis in the former and deranged apoptosis or escape from apoptotic control in the latter. In this review, we want to focus on the role of apoptosis in various stages of MDS, and to discuss its possible relevance to further therapeutic interventions.

Acute Disease↗
PubMed1995

Enhancement of Ca(2+)-dependent endonuclease activity in L1210 cells during apoptosis induced by 1-beta-D-arabinofuranosylcytosine: possible involvement of activating factor(s).

Internucleosomal DNA fragmentation and morphological changes in nuclei typical of apoptosis were observed in L1210 cells incubated with 1.0 micrograms/ml of 1-beta-D-arabinofuranosylcytosine (ara-C). To investigate the mechanisms involved, we examined the activities of endogenous endonucleases in nuclei and cytoplasm. Both fractions of control cells contained Ca(2+)-dependent endonuclease which was capable of mediating internucleosomal DNA fragmentation. The assay system using two kinds of target substrates, i.e., nuclear chromatin of CCRF-CEM cells and naked DNA purified from the same cells, revealed that the activity of Ca(2+)-dependent endonuclease was enhanced in the crude nuclear extracts of cells treated with 1.0 microgram/ml of ara-C for 24 h or 48 h. The activity was extracted more easily from ara-C-treated cells than control cells without sonication of the nuclear fraction. On the other hand, in the cytoplasmic fraction of the cells, the activity towards naked DNA was unchanged, whereas that towards nuclear chromatin was clearly enhanced. These results suggest that internucleosomal DNA fragmentation induced by ara-C treatment is associated with enhancement and activation of constitutively expressed Ca(2+)-dependent endonuclease in L1210 cells.

Animals↗
PubMed1995

A novel factor-dependent human myelodysplastic cell line, MDS92, contains haemopoietic cells of several lineages.

A novel long-term cultured interleukin (IL)-3-dependent human myelodysplastic cell line, MDS92, was shown to contain several myeloid-lineage cells such as neutrophils, macrophages, eosinophils, and a small number of megakaryocyte-lineage cells. Therefore this cell line possesses at least bipotential characteristics of myeloid- and megakaryocyte-lineages. Granulocyte colony-stimulating factor clearly promoted the neutrophil alkaline phosphatase activity of MDS92 cells. To the contrary, the incidence and growth of CD41-positive cells were hardly affected by the addition of IL-6, IL-11, c-mpl ligand (thrombopoietin, TPO) or erythropoietin. TPO slightly supported the growth of CD34-positive cell fraction, but not CD41-positive cell fraction of MDS92 cells in combination with IL-3 or Steel factor. This cell line will be a useful tool for the study of MDS stem cells, but the mechanism of commitment of differentiation in MDS stem cells remains unknown.

Alkaline Phosphatase↗
PubMed1995

Enlargement of multiple cavernous hemangioma of the liver in association with pregnancy.

Four cavernous hemangiomas were found in a 34-year-old woman after the first delivery. All four hemangiomas became enlarged after the second delivery. Due to complaints of symptoms of compression, and to rule out malignancy, surgical intervention was employed. Histologically, the tumors were typical cavernous hemangiomas. Although a relationship between enlargement of hemangiomas and estrogen was suggested, estrogen receptors were not detected in the tumors.

Adult↗
PubMed1994

Neuronal differentiation of PC12 cells as a result of prevention of cell death by bcl-2.

Rat pheochromocytoma PC12 cells die when cultured in serum-free medium. Neurotrophic factors can rescue PC12 cells from cell death, and induce neuronal differentiation. To further investigate the relationship among cell death, survival, and differentiation, the bcl-2 cDNA, which is known to prevent apoptosis in various types of cells, was transfected into PC12 cells. Six monoclonal bcl-2-transfected cell lines were isolated and confirmed to express mRNA and protein product of bcl-2. The wild-type and bcl-2-transfected PC12 cells were kept to adhere to collagen-coated dishes at the initiation of serum-free experiments to avoid cellular damage due to detachment of the cells by trituration. Even under the conditions, the control PC12 cells mostly died within 24 h, when cultured in serum-free medium, whereas those expressing Bcl-2 survived even for 7 days in serum-free medium. Moreover, outgrowth of long processes in the bcl-2-transfected cells was only observed under the condition to keep the cells attached to the dishes in serum-free medium without any additive neurotrophic or growth factors. Neurofilament medium protein, which is a neuron-specific cytoskeletal component, was also expressed in the differentiated cells, suggesting that the long processes in bcl-2-transfected PC12 cells are neurites. However, neuronal differentiation of PC12 cells expressing Bcl-2 was not observed when cultured in serum-containing medium. Accordingly, survival of PC12 cells expressing Bcl-2 under the condition which cells usually die may be accompanied with neuronal differentiation.

Animals↗
PubMed1994

Establishment and characterization of a novel myeloid cell line from the bone marrow of a patient with the myelodysplastic syndrome.

A novel long-term cultured myeloid cell line was established from the bone marrow of a patient with myelodysplastic syndrome (MDS). This cell line, designated MDS92, proliferated in the presence of interleukin-3 or granulocyte-macrophage colony-stimulating factor and transiently in the presence of Steel factor, with a tendency for gradual maturation, and formed myeloid colonies in the semi-solid culture condition. In addition, the MDS92 cell line represented rather complicated karyotypic abnormalities including the deletion of fifth and seventh chromosomes and a point mutation at codon 12 of the N-ras oncogene. These characteristics of the MDS92 cell line are exclusively compatible with the property of preleukaemia.

Anemia, Sideroblastic↗
PubMed1994

Altered responses of purified blast cells from the myelodysplastic syndromes to colony-stimulating factors in vitro: comparison with normal blast cells.

To evaluate the effects of colony-stimulating factors (CSFs) on pathological cells from myelodysplastic syndromes (MDS), the blast cells from 19 MDS patients (eight low-risk MDS, six high-risk MDS, and five leukemic transformation of MDS [LT-MDS]) and four normal volunteers were successfully enriched by separating CD34-positive cells by the use of immunomagnetic beads, and their responsiveness to granulocyte or granulocyte-macrophage CSF (G-CSF or GM-CSF) was examined in short-term liquid suspension culture. The proliferation of MDS blast cells was clearly promoted by these CSFs in all cases examined, but considerable percentages of them often remained immature compared with the favorable maturation of normal blast cells, especially in the more advanced disease groups (LT-MDS and high-risk MDS) that included two prominent cases with a remarkable blast cell growth without maturation induction by CSFs. The expression of esterase activities was rather sluggish in the MDS cases, in contrast to normal expression. These data showed that MDS blast cells proliferate in response to CSFs but that maturation is less than that observed with normal blast cells in vitro. Much care should be taken with in vivo application of CSFs to high-risk MDS patients.

Adult↗
PubMed1993

Analysis of polyols in uremic serum by liquid chromatography combined with atmospheric pressure chemical ionization mass spectrometry.

Liquid chromatography with atmospheric pressure chemical ionization mass spectrometry in the negative-ion mode was used to analyse polyols in uremic serum obtained from haemodialysis patients. With post-column addition of 1% chloroform-methanol as an ionization accelerating solvent, the chloride addition ions, [M+Cl]-, were detected as base peaks, and the molecular masses of the polyols were easily determined by comparing [M+Cl]- and [M - H]- ions. Concentrations of erythritol, myoinositol, mannitol and sorbitol were markedly increased, and that of 1,5-anhydroglucitol was markedly decreased in the uremic serum compared with normal serum. After haemodialysis, the serum concentration of these polyols decreased significantly. This method was found to be useful in analysing the profile of polyols.

Atmospheric Pressure↗
PubMed1993

Spinal xanthogranuloma in a child: case report.

A case of a patient with a xanthogranuloma in the thoracic spine is presented. Magnetic resonance imaging revealed an intradural extramedullary tumor between T6 and T9 as a low-intensity mass on both T1- and T2-weighted images. Total removal of this tumor was achieved through a laminoplastic laminectomy. Differentiation of this disease from other xanthogranulomas in the central nervous system is discussed.

Diagnosis, Differential↗
PubMed1993

Enhancement of cytosine arabinoside cytotoxicity by granulocyte/macrophage colony-stimulating factor and granulocyte colony-stimulating factor in a human myeloblastic leukemia cell line.

Enhancement of the cytotoxicity of cytosine arabinoside (ara-C) by granulocyte/macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), and the mechanisms involved, were studied in the AML-193 human leukemia cell line. AML-193 cells require GM-CSF and G-CSF(CSFs) for optimum growth, and 24 h deprivation of CSFs decreased DNA synthesis measured in terms of 3H-thymidine incorporation. The DNA synthesis gradually recovered upon addition of CSFs. To examine the sensitivity to ara-C under different growth conditions, two groups of cell suspensions, one pretreated with CSFs after 24 h deprivation (CSFs(+) cells), and the other held continuously under CSFs-free conditions (CSFs(-) cells), were exposed to 1.0 microgram/ml of ara-C for 16 h. In clonogenic assays, CSFs(+) cells showed higher sensitivity to ara-C than CSFs(-) cells. These cell groups showed no significant difference in ara-C triphosphate accumulation or retention, though the amount of ara-C incorporated into the acid-insoluble fraction was two times greater in CSFs(+) cells than CSFs(-) cells, and that difference became even clearer in the retention pools. These data suggest that the enhancement of cytotoxicity by CSFs was due to the promotion of ara-C incorporation into DNA as a result of an increase of the cell fraction in the S phase.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

[Treatment of myelodysplastic syndromes with cytokines].

To evaluate the effects of colony-stimulating factors (CSFs) on pathological cells from myelodysplastic syndromes (MDS), CD34-positive cell fractions (mainly blast cells) from nineteen MDS patients and four normal volunteers were successfully enriched by the use of immunomagnetic beads, and their responsiveness to CSFs was examined in short-term liquid suspension cultures. Considerable parts of blast cells from MDS patients remained immature as compared with the favorable maturation of normal blast cells, especially in high-risk MDS group that included two prominent cases with a remarkable blast cell growth without maturation induction by CSFs. Short-term clinical administrations of G-CSF often brought about hematological improvements on MDS patients. Other cytokines are also reported to be of use on some patients. However, a few cases progressed to overt leukemia in relation to G-CSF treatment. Much care should be taken with in vivo application of CSFs to high-risk MDS patients, although there may be no effective clue to foresee the risk of leukemic transformation yet.

Adult↗
PubMed1992

Effects of nefiracetam, DM-9384 on amnesia and decrease in choline acetyltransferase activity induced by cycloheximide.

The effects of nefiracetam, [N-(2,6-dimethyl-phenyl)-2-(2-oxo-pyrrolidinyl)acetamide, DM-9384], a cyclic derivative of GABA, were investigated in the cycloheximide (CXM)-induced amnesia animal model using the passive avoidance task. Pre-training administration of DM-9384 attenuated the CXM-induced amnesia as indicated by prolongation of step-down latency. It protected against CXM-induced inhibition of choline acetyltransferase activity in the cerebral cortex. These results suggest that DM-9384 attenuates CXM-induced amnesia by interacting with AChergic neuronal system and enhancing protein synthesis in the brain.

Amnesia↗