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K Toyama

Publications and source records attributed to K Toyama.

At least 19 recordsLinked to original sources
PubMed1992

T-cell receptor beta chain gene rearrangement in acute myeloid leukemia always occurs at the allele that contains the undermethylated J beta 1 region.

The epigenetic phenomenon could play a role in the interaction between chromatin and DNA-binding enzymes, allowing us to consider an association between the phenomenon and gene rearrangement. The correlation between methylation status and rearrangement of the T-cell receptor (TCR) beta chain gene in leukemia cells obtained from patients with acute myeloid leukemia (AML) was examined. All of the AML patients with a TCR-beta rearrangement had hypomethylated CCGG sequences within the J beta 1 region on the rearranged allele, while the germline allele had completely methylated CCmeGG sequence in this region, indicating a strong association between hypomethylation status and rearrangement of the TCR beta chain gene. In the DNA from AML patients with or without a TCR-beta rearrangement, the C beta 2 region contained completely methylated CCmeGG sequences, even though they express T-cell-associated antigens, including CD7; this pattern is quite different from that observed in T-cell neoplasias. Moreover, some AML patients showed a TCR-beta rearrangement without the presence of immunoglobulin heavy-chain gene rearrangement, suggesting that TCR beta chain gene involvement in AML is required for unknown factors other than common recombinase activity.

Adolescent↗
PubMed1992

Cytogenetic and clinical findings of myelodysplastic syndromes with a poor prognosis. An experience with 97 cases.

BACKGROUND: Clinical and cytogenetic analyses were performed in 97 patients with myelodysplastic syndromes (MDS) to evaluate risk factors for poor prognosis. METHODS/RESULTS: Among them, 22 patients survived for less than 1 year: 10 of these had complex chromosomal abnormalities (complex aberrations), but only 5 of the remaining 75 patients who survived longer than 12 months did. Leukemia did not develop in approximately half of the patients who died within 1 year. The occurrence rate of leukemic transformation appears to depend on MDS subtypes rather than cytogenetic changes. In contrast, the percentage of patients who survived for less than 1 year is related to chromosomal changes, especially to complex aberrations. Of particular interest in this study is that 7 of 11 patients with MDS who had myelofibrosis survived for less than 1 year, and 5 of 7 patients with secondary MDS were included in this group showing a poor prognosis. By hematologic analysis, significant differences were found in the hemoglobin values and platelet counts of patients who survived for less than 1 year. CONCLUSIONS: From this analysis, three major risk factors for a poor prognosis were identified: complex aberrations, a history of chemotherapy or radiation therapy (secondary MDS), and development of myelofibrosis. The survival probability in the patients with MDS having at least one of these three factors was significantly low when compared with that in patients without these factors, indicating that cytogenetic analysis in combination with observance of certain clinical manifestations is important in therapeutic management of patients with MDS.

Anemia, Refractory, with Excess of Blasts↗
PubMed1992

Clinical and prognostic significance of monoclonal small cells in the peripheral blood and bone marrow of various B-cell lymphomas.

Discordant lymphomas, in particular nodal large-cell lymphomas with marrow small-cell lymphoma, were discovered recently, and the prognosis of patients with such disease has been discussed. The small cells were reported to be small lymphocytic or small cleaved lymphoma cells. We have detected, by kappa-lambda imaging (KLI) with delta-curves, using a flow cytometer, small lymphoma cells in the peripheral blood (PB) and bone marrow (BM) of 41 untreated patients with various B-cell lymphomas expressing surface Ig (sIg+BCL), and evaluated their clinical and prognostic significance. Small cells were found in approximately 90% (37 of 41) of sIg+BCL patients when either PB or BM was analyzed and, overall, the presence of small cells correlated well with the disease activity. However, in some patients, a few cells remained in the PB (16%) or BM (27%) even when they were in remission, whereas in others, the cells were presented in the PB or BM several months before relapse. These results suggest that the detection of small cells in PB or BM by KLI may be helpful for screening and monitoring patients with sIg+BCL. When the patients were subdivided into three groups (normal, low, and high amplitude), according to the abnormal grade criteria of the delta-curves, which were based on the results of both PB-KLI and BM-KLI, the survival of the high-amplitude group tended to be shorter than that of the normal group (P = .068), which was particularly marked when the follow-up period exceeded 2 years. Moreover, as the group grading worsened (normal less than low less than high), the complete response rates deteriorated (100%, 71%, and 60%, respectively) and the respective relapse rates after complete remission increased (17%, 40%, and 67%). Thus, the determination of the proportion of small lymphoma cells in PB and BM by KLI may be useful for predicting the prognoses of patients with sIg+BCL.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

[MR imaging of amyotrophic lateral sclerosis].

Magnetic resonance imaging (MR imaging) provides a sensitive method for mapping the normal and pathological distribution of iron in the brain. High field strength MR imaging (1.5 T) was used to evaluate eight patients with amyotrophic lateral sclerosis (ALS) and 49 neurological normal control patients. All eight ALS patients showed decreased signal intensity in the motor cortex on T2-weighted images, while only one of the normal control patients showed this finding. The results suggested that the decreased signal intensity in the motor cortex in ALS was caused by the deposition of iron in this area.

Adult↗
PubMed1992

Establishment of a new Hodgkin's cell line (HD-70) of B-cell origin.

A new Hodgkin's cell line, designated HD-70, was established from the peripheral blood of a 69-year-old man with Hodgkin's disease of nodular sclerosing type. The cell line grows in a single cell suspension and has a doubling time of 28 hours. The cells have a round or irregular nucleus or multiple nuclei in relatively abundant cytoplasm that is positive for acid phosphatase, alpha-naphthyl butyrate esterase, and periodic acid-Schiff stains. HD-70 cells are positive for CD30 (Ki-1/Ber-H2), CD15 (Leu-M1), and CD71 (OKT9) antigens and contain cytoplasmic immunoglobulin (Ig) (A, kappa). Southern blot analysis showed that the cells have Ig heavy and kappa light chain gene rearrangement and lack T-cell receptor gene rearrangement. Chromosome analysis disclosed that the cells have a human karyotype with complicated abnormalities, including a 14q+. Heterotransplantation of the HD-70 cell line into newborn hamsters treated with antilymphocyte serum produced massive tumors with remarkable fibrosis and collagen band formation. These tumors displayed histologic features similar to those of the nodular sclerosing type tumor of the patient. Such fibrosis production and collagen band formation in heterotransplanted tumors suggest that a certain cytokine that induces fibrosis might be produced by HD-70 cells. This cell line may be useful for understanding the biology and pathogenesis of Hodgkin's disease.

Aged↗
PubMed1992

Detecting of the minimal residual disease contaminated in peripheral blood stem cell transplantation in the B-cell malignant lymphoma patients.

For sufficient collection of hemopoietic stem cells from peripheral blood for autologous peripheral blood stem cell transplantation (PBSCT), four patients with B-cell-type non-Hodgkin lymphoma (B-NHL) were examined for the appearance of circulating hemopoietic progenitors in blood (PSC) during the hemopoietic recovery phase following marrow ablative therapy in combination with or without administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF). Each patient received only chemotherapy in the first course, and rhG-CSF (1 microgram/kg/day) was administered for 14 consecutive days from the last day of the second chemotherapy. In the second chemotherapy course with rhG-CSF administration, white blood cell (WBC) counts demonstrated two peaks, and the appearance of granulocyte-macrophage precursor cells (CFU-GM) in blood at the maximum level was coincident with the second peak of WBC elevation. Erythroid precursor cells (BFU-E) were also detectable in blood after chemotherapy but the peak level was not enhanced by the use of rhG-CSF. To determine whether the minimal residual disease (MRD) cells were contaminated in PSC corrected from blood, kappa-lambda imaging (KLI) analysis was performed to detect the malignant B-cell population (mBp) before and after chemotherapy. No mBp was found in two of four patients in blood, although three of them were involved with mBp in bone marrow. The presence of mBp was detected in two patients both before and after chemotherapy, even though these cells were hardly detected morphologically, suggesting the necessity of judging for the incidence of contamination of MRD cells when collecting PSCs.

Adult↗
PubMed1992

Trisomy of chromosome 8 in myelodysplastic syndrome. Significance of the fluctuating trisomy 8 population.

Chromosome analyses were performed in five patients with myelodysplastic syndrome (MDS) who showed trisomy of chromosome 8 during the course of their disease. Four of these patients showed trisomy 8 at the diagnosis of MDS, and the remaining one had trisomy 8 when the leukemia phase developed. The proportion of bone marrow (BM) cells with trisomy 8 in the four patients who showed trisomy 8 at MDS diagnosis fluctuated, and this fluctuation was not related to the percentage of blasts in the BM or to progression of the disease. However, in two patients, metaphase cells with trisomy 8 disappeared when their anemic state improved, although leuko-thrombocytopenia was still present, suggesting that the decrease in the number of BM cells with trisomy 8 reflects hematologic features in some MDS patients. These findings indicate that trisomy 8 in our MDS patients was possibly not the primary event in the genesis of the disease, and that there may have been competition between a normal karyotype clone and a trisomy-8-positive clone. Our results further suggest that the presence of a clone with trisomy 8 is not always a sign of disease progression or of poor prognosis in MDS patients.

Adult↗
PubMed1992

Restoration of cytogenetically normal marrow cells after remission of lymphoblastic crisis in a case of Ph positive CML treated with alpha-interferon.

A patient with Philadelphia (Ph) chromosome-positive chronic myelogenous leukemia (CML) who was treated with alpha-interferon (alpha-IFN) is reported. After the treatment, the number of Ph+ bone marrow (BM) cells decreased gradually and the intensity of the rearranged major breakpoint cluster region (M-BCR) gene became faint; however, a lymphoblastic crisis developed about 1 year later. At the time of the blast crisis, the rearranged M-BCR band was detected, indicating that the blast crisis clone was derived from CML cells. The patient was treated with a combination of vincristine, prednisolone, daunorubicin, and L-asparaginase, and a hematologic remission was obtained. During the remission status, no rearranged M-BCR fragment was detected by conventional Southern analysis. Thus, the hematologic and genetic alteration in this case appeared to be identical to Ph+ acute leukemia with M-BCR rearrangement. The current case therefore indicates that alpha-IFN can reduce the proportion of Ph+ cells, but is unable to prevent blast crisis. Furthermore, the quantitative reduction of the cell population with a Ph chromosome may have some effects in modifying the genetic manifestations and clinical features of Ph+ CML, e.g., the delay in the appearance of the blast crisis.

Antigens, CD↗
PubMed1992

Double 20q- anomaly in myelodysplastic syndrome.

Two patients with myelodysplastic syndrome (MDS) whose bone marrow (BM) cells contained duplicate 20q- chromosomes are reported. No particular differences between the hematologic findings of four patients with single 20q- and the two patients with double 20q- chromosomes were noted. No differences in breakpoints on the 20q- chromosome were noted in these six patients, and the breakpoint was identified as 20q11. The presence of double 20q- chromosomes in MDS patients suggests, however, that the deleted chromosome has oncogenic activity.

Aged↗
PubMed1992

Laminar specificity of extrinsic cortical connections studied in coculture preparations.

The formation of specific neural connections in the cerebral cortex was studied using organotypic coculture preparations composed of subcortical and cortical regions. Morphological and electrophysiological analysis indicated that several cortical efferent and afferent connections, such as the corticothalamic, thalamocortical, corticocortical, and corticotectal connections, were established in the cocultures with essentially the same laminar specificity as that found in the adult cerebral cortex, but without specificity of sensory modality. This suggests the existence of a cell-cell recognition system between cortical or subcortical neurons and their final targets. This interaction produces lamina-specific connections, but is probably insufficient for the formation of the modality-specific connections.

Afferent Pathways↗
PubMed1992

Hlf, a novel hepatic bZIP protein, shows altered DNA-binding properties following fusion to E2A in t(17;19) acute lymphoblastic leukemia.

Oncogenic conversion of transcription factors by chromosomal translocations is implicated in leukemogenesis. We report that the t(17;19) in acute lymphoblastic leukemia produces a chimeric transcription factor consisting of the amino-terminal portion of HLH proteins E12/E47 (products of the E2A gene) fused to the basic DNA-binding and leucine zipper dimerization motifs of a novel hepatic protein called hepatic leukemia factor (Hlf). Hlf, which is not normally transcribed in lymphoid cells, belongs to the recently described PAR subfamily of basic leucine zipper (bZIP) proteins, which also includes Dbp and Tef/Vbp. Wild-type Hlf is able to bind DNA specifically as a homodimer or as a heterodimer with other PAR factors. Structural alterations of the E2a-Hlf fusion protein markedly impair its ability to bind DNA as a homodimer compared with wild-type Hlf. However, E2a-Hlf can bind DNA as a heterodimer with other PAR proteins, suggesting a novel mechanism for leukemogenic conversion of a bZIP transcription factor.

Amino Acid Sequence↗
PubMed1992

Hilar and mediastinal lymphadenopathy with hypersensitivity pneumonitis induced by penicillin.

A 54-year-old Japanese man demonstrated a sultamicillin-induced hilar and mediastinal lymphadenopathy with hypersensitivity pneumonitis. A positive lymphocyte stimulation test for sultamicillin and a decreased CD4/CD8 ratio of lymphocytes in BAL fluid suggested that an alteration in cell-mediated mechanisms was responsible for the patient's symptoms.

Alveolitis, Extrinsic Allergic↗
PubMed1992

Leukemic phase of intermediate non-Hodgkin's lymphoma with cells showing different matured stages in invaded various organs.

A 56-year-old male was admitted to our hospital with lymphocytosis (16.4 x 10(9)/l; 79% lymphocytes including 50% small lymphocytes), generalized lymphadenopathy, massive splenomegaly, and heavily infiltrated bone marrow. Immunophenotype analysis of the neoplastic cells in the bone marrow revealed that they were B cells (CD20 + CD19 + Ia1 + sIgM+) positive for CD10. By contrast, the cells in the lymph node were CD20 + CD19 + Ia1 + sIgM+ but negative for CD10. The patient was tentatively diagnosed as having lymphosarcoma cell lymphoma, however, the final diagnosis was leukemic phase of intermediate lymphocytic lymphoma. We concluded that CD10+ neoplastic cells in the bone marrow and peripheral blood had differentiated to CD10- cells.

Antigens, Differentiation↗
PubMed1992

[Thrombotic thrombocytopenic purpura achieving complete remission by slow infusion of vincristine].

A case of thrombotic thrombocytopenic purpura (TTP) which was successfully treated by slow infusion of vincristine (VCR) is reported. A 40-year-old female was admitted to our hospital because of sudden onset of genital bleeding. Her blood cell count showed severe anemia and thrombocytopenia. Biochemistry disclosed high titers of serum LDH. Based upon these findings, the patient was initially diagnosed as having Evans syndrome and was treated with steroid-pulse therapy and high-dose immunoglobulin. However, no response was obtained. A diagnosis of TTP was established when mental disturbance and renal dysfunction developed later. Aspirin and plasmapheresis relieved the mental disturbance and decreased serum LDH level, but anemia and thrombocytopenia were not corrected. Slow infusion therapy of 1 to 2 mg VCR was performed for 4 to 8 hours once a week, which dramatically improved the hematological abnormalities and controlled the disease. In conclusion, slow infusion of VCR may indicated, if initial standard therapies such as PE would fail.

Adult↗
PubMed1992

[Clinical evaluation of sulbactam/cefoperazone for severe infections associated with hematological disorders].

The combination therapy of sulbactam/cefoperazone (SBT/CPZ) and piperacillin (PIPC) was evaluated in 49 patients with severe infections associated with hematological disorders. Clinical responses in 43 evaluable patients out of the 49 patients were excellent in 12, good in 18, thus, overall efficacy rate was 69.8% (excellent plus good). Efficacy rates of this combination therapy were 60% (3/5) for sepsis, 75% (21/28) for suspected sepsis, and 50% (4/8) for pneumonia. The efficacy rate was 71.4% (10/14) in patients with neutrophil counts less than 200/microliters; this combination therapy was highly effective even in the neutropenic patients. Transient increases in hepatic function test values were observed in 2 patients, but no other side effects were observed during the combination therapy. From these observations it appears that the combination therapy of SBT/CPZ and PIPC is a very useful empiric therapy for severe infections associated with hematological diseases.

Adolescent↗
PubMed1992

[Pulmonary blood flow measurement by acetylene rebreathing method in subjects without respiratory function disturbance].

Simultaneous measurement of pulmonary blood flow by the acetylene rebreathing method and cardiac output by the thermodilution method was performed in subjects without respiratory function disturbance during right heart catheterization. After the measurement of cardiac output, the subjects rebreathing a gas mixture containing acetylene and argon from the end tidal level. The inspiratory and expiratory gases were measured by a mass-spectrometer. Results were analyzed by a lung model consisting of two compartments (rebreathing bag compartment and lung compartment), while taking into account the volume reduction due to O2 and CO2 exchange and the fluctuation of end tidal gas concentration until equilibrium between the bag and the lung. The correlation coefficient between these two methods was 0.944, which was statistically significant. The regression line was near the line of identity. The measurement of pulmonary blood flow by the acetylene rebreathing method was applicable in cases without lung function disturbance.

Acetylene↗
PubMed1992

[Immunogenotypes and surface marker analysis in Ph1 positive chronic myelogenous leukemia in the blastic crisis].

Immunophenotypic and immunogenotypic changes in 23 patients with Ph positive chronic myelogenous leukemia in blast crisis were determined using a panel of monoclonal antibodies and gene probes. According to the immunophenotypes, 9 patients were considered to be in lymphoid blast crisis, including 7 patients with lymphoblastic crisis and 2 patients with lymphoid/myeloid mixed blast crisis. Leukemia cells from the remaining 14 patients showed myeloid phenotypes and 10 of these had platelet-associated antigens. Rearrangement of the immunoglobulin (Ig) gene was observed in all the 9 patients with lymphoid blast crisis, and Ig gene rearrangement was associated with the expression of CD19 antigen. Two patients with myeloid blast crisis showed rearrangements of T-cell-receptor gene, but, dissociation between phenotypes and genotypes was not frequently observed in patients with blast crisis.

Antigens, CD↗