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Biomedical subjects

K Toyama

Publications and source records attributed to K Toyama.

At least 253 records · Page 14Linked to original sources

Clinical and cytogenetic significance of myelodysplastic syndromes with disease evolution.

We performed a retrospective study of 83 patients with myelodysplastic syndrome (MDS) to clarify the clinical and cytogenetic implications of disease evolution. Twenty-three patients showed disease progression; six of the 11 patients whose disease evolved within 100 days showed complex cytogenetic aberrations and most of them died within 300 days. Of the patients who survived more than 300 days, those with high bone marrow (BM) blast percentages experienced significant disease progression, but we noted no cytogenetic indicators for disease evolution at the later phase. Sixty percent of patients showing karyotypic evolution without disease evolution had deletion-type chromosome changes. The most frequent anomaly in patients with disease evolution who survived more than 300 days was an additional numerical change, whereas patients with disease evolution who survived less than 300 days showed karyotypic instability. It was difficult to predict disease progression for patients whose disease evolved more than 300 days after diagnosis, but in some patients the presence of additional numerical changes was related to disease progression. The cutoff level of early disease evolution was 100 days after diagnosis, and most patients with complex abnormalities survived less than 300 days with or without disease evolution.

Adult↗

Relationships between nodal status and cell kinetics, DNA ploidy pattern and histopathology of the deeply infiltrating sites in colorectal adenocarcinoma.

Tumor cell kinetics and DNA contents were investigated by in vitro labeling with bromodeoxyuridine (BrdU) and flow cytometry using paraffin-embedded specimens in both superficially (Sup) and deeply (Deep) infiltrating sites of 28 colorectal adenocarcinomas. Eleven were well differentiated and 17 were moderately differentiated adenocarcinomas. In moderately differentiated adenocarcinoma, histologic low grade types of Deep were frequently associated with lymph node metastasis, but the BrdU labeling indices (LI) or tumor DNA ploidy pattern did not correlate with nodal status. Among the seven aneuploid tumors of moderately differentiated adenocarcinoma, the BrdU LI and histology of Deep tended to correlate with nodal status. These findings suggest that the histology of Deep should have a greater significance than tumor cell kinetics or DNA contents. They also suggest that the tumor DNA ploidy pattern may be heterogeneous and divided into subgroups according to its cell kinetics or histology of Deep in relation to lymph node metastasis.

Adenocarcinoma↗

Primary pulmonary B-cell lymphoma diagnosed by kappa-lambda imaging of broncho-alveolar lavage fluid lymphocytes.

A 69-year-old woman was examined due to abnormal pulmonary shadows on her chest roentgenogram. Although small lymphocyte proliferation was revealed in specimens by transbronchial lung biopsy (TBLB), immunoglobulin light chain restriction could not be seen. We attempted to verify the B-cell clonality by broncho-alveolar lavage (BAL) and a new sensitive method called kappa-lambda imaging (KLI), which was available for the detection of monoclonal B cells. Therefore, B-cell monoclonality was found. Thus, the patient was diagnosed as having primary pulmonary lymphoma (PPL). PPL may be differentiated from benign lymphoproliferative disorders such as pseudolymphoma and lymphocytic interstitial pneumonia by KLI of BAL-derived lymphocytes.

Aged↗

Mesothelial splenic cyst.

A 29-year-old female was admitted because of thrombocytopenia and an abdominal mass which was palpated 5 finger breadths below the left costal margin. A computed tomographic scan of the abdomen revealed splenomegaly with a large calcified cystic lesion. The spleen was removed and the pathological examination disclosed that the cyst was monolocular and the wall was of mesothelial origin.

Adult↗

Clinical implication and prognostic significance of small lymphoma cells in the peripheral blood and bone marrow of B-cell non-Hodgkin's lymphomas.

It seems possible that small lymphoma cells (SLC) may have a role even in aggressive B-cell non-Hodgkin's lymphoma (B-NHL) such as large-cell lymphoma. However, SLC are often difficult to distinguish morphologically from normal or reactive small lymphocytes. In this study, we used a flowcytometric technique (kappa-lambda imaging; KLI) for detection of SLC. Peripheral blood (PB) and bone marrow (BM) samples taken from 41 patients with surface immunoglobulin positive (sIg+) B-NHL were analysed. SLC were detected in about 90% (37/41) of the untreated patients when either PB or BM was analysed by KLI. The presence of SLC correlated well with disease activity. However, a few SLC were present even in the PB (16%) or BM (27%) of the 31 patients who achieved complete remission, indicating that minimal residual disease (MRD) was present. In some cases, the reappearance of SLC in the PB or BM preceded clinical relapse. Furthermore, the initial volume of SLC, particularly in the BM, tended to be related to the prognosis (P = .068). These results suggest that the detection of SLC by KLI may be helpful not only for the screening and clinical staging of sIg+ B-NHL, but also for monitoring disease activity and detecting MRD. Moreover, the volume of SLC in the BM may be a useful predictor of prognosis.

Bone Marrow↗

Therapy for Philadelphia chromosome-positive acute lymphoblastic leukemia: possible use of interferon on the basis of some novel concepts.

Current understanding of molecular genetics enables the establishment of new categories based on pathogenesis. Philadelphia (Ph) chromosome-positive leukemia has been reclassified into two molecularly distinct subsets, and the leukemogenesis at the cell level might be linked to the molecular changes. Therefore, treatment for leukemia patients with Ph chromosome could be based on the molecular characteristics. In this review, we discuss the strategy of treating patients with Ph-positive acute lymphoblastic leukemia and the benefit of the combined modality of interferon and chemotherapy.

Adult↗

Acute myeloid leukemia with concomitant expression of T-/B-lymphoid antigens and immunogenotypic alterations exhibiting t(7;12)(q32;q24).

We report here a patient with acute myeloid leukemia (AML) expressing both T- and B-lymphoid-associated antigens. The leukemia cells in this case had rearrangements of not only immunoglobulin heavy-chain but also T-cell-receptor beta- and delta-chain genes. Although a relatively large number of AML patients with lymphoid markers have been reported, only about a dozen AML patients expressing both T- and B-lymphoid markers have been reported so far.

Antigens, CD↗

[Enhanced sensitivity to cytosine arabinoside by combined stimulation of steel factor and GM-CSF in a factor-dependent leukemic cell line, MO7e--in terms of a possible clinical application to AML treatment].

In normal hematopoiesis, granulocyte macrophage-colony stimulating factor (GM-CSF) is known to stimulate the proliferation and differentiation of myelo-monocytoid lineage, while Steel factor (SLF) has been supposed to support the proliferation of more primitive hematopoietic progenitors including stem cells. We investigated the stimulatory effect of SLF and GM-CSF in twelve cases of acute myeloid leukemia (AML) cells in vitro by MTT assay. In 10 out of 12 cases, SLF or GM-CSF stimulated the proliferation of leukemic cells in short term liquid culture. In 7 out of these 10 cases, the leukemic cells responded to both cytokines. To investigate the possibility of the clinical application of these cytokines by combination with cell cycle-specific anti-tumor reagents, we assessed the effects of SLF and GM-CSF on the modulation of the cell cycle and sensitivity against cytosine arabinoside (ara-C) in a human factor-dependent leukemic cell line, MO7e. Flow cytometric analysis revealed the effect of cell recruitment into the cell cycle in the quiescent MO7e cells by exposure to these cytokines. The drug-sensitivity test using the MTT assay system demonstrated that pre-treatment with each cytokine enhanced sensitivity of ara-C. Furthermore, by combination of SLF and GM-CSF, the ara-C sensitivity was significantly wore graty enhanced than by each cytokine alone. These data suggest that combined pre-treatment with SLF and GM-CSF may provide new benefits for cure-oriented chemotherapy of AML followed by bone marrow transplantation or peripheral blood stem cell transplantation.

Adult↗

Comparison between immunogenotypic findings in de novo AML and AML post MDS.

We compared immunogenotypic findings in 73 patients with de novo acute myeloid leukemia (AML) and 30 patients with AML developed in myelodysplastic syndrome (AML post MDS) to determine the biological difference between these hematopoietic neoplasias. Lymphoid-associated antigens were detected in 13 patients with de novo AML, four of whom exhibited rearrangement of the immunoglobulin heavy-chain (IgH) gene. T-cell receptor (TCR) gene rearrangements were detected in 10 patients with de novo AML who did not have lymphoid-associated antigens, none of whom carried rearranged IgH. This group included two AML patients with trilineage dysplasia. Neither lymphoid markers nor IgH rearrangement was detected in any of the 30 patients with AML post-MDS; TCR rearrangements were detected in eight out of 30 patients, TCR-beta rearrangements in six out of 30, and TCR-delta rearrangements in five out of 30. The TCR rearrangement without rearranged IgH in some AML post MDS patients might not be due to a common recombinase activity, and this alteration may link to genomic instability. Some patients with de novo AML also showed this pattern, suggesting a close biologic association between AML post MDS and some patients with de novo AML.

Adult↗

Clinical and cytogenetic findings of myelodysplastic syndromes showing hypocellular bone marrow or minimal dysplasia, in comparison with typical myelodysplastic syndromes.

Hematologic and cytogenetic data were collected on 401 myelodysplastic syndromes (MDS) patients in Japan and their clinical relevance was analyzed. More than 50% of the MDS patients with hypocellular bone marrow had > 5% marrow blasts at the time of MDS diagnosis and frequently had complex aberrations (chromosome changes at three or more regions). They showed peripheral blood findings resembling those of aplastic anemia, but progression into leukemic phase and the prognosis tended to mimic typical MDS. In MDS patients with minimal dysplasia, hematologic parameters were different from those of aplastic anemia. However, the low incidence of leukemic transformation and the favorable prognosis was similar to that of aplastic anemia. More than 90% of the patients in this group had refractory anemia and had normal karyotypes. Thus differential diagnosis from a low grade aplastic anemia is important, since this type of MDS might have a clonal nature as well. In conclusion, although some hematologic and clinical deviations are noticed in MDS with hypocellular marrow or minimal dysplasia, these MDS subtypes might constitute marginal forms of MDS.

Adult↗

[Early detection of chronic obstructive pulmonary disease by following individual annual changes in lung function].

The possibility of early detection of chronic obstructive pulmonary disease (COPD) was investigated among subjects whose lung function could be followed for more than ten years. Ten subjects aged 60 or more were selected from among about 1500 cases using the following diagnostic criteria; (1) subjects had complained of exertional dyspnea (2) chest X-ray abnormalities were suggestive of COPD (3) FEV1.0% was under 55%. Data on FVC/height, FEV1.0/height and FEV1.0% of these subjects were available for the previous ten years. Individual linear regression equations were estimated. Average annual changes of cases of obstruction were compared with those of normal cases, and individual deviations from the normal standard range were observed. Declines of the regression lines were as follows; FEV1.0/height: normal case--0.016 +/- 0.017, obstruction cases--0.038 +/- 0.018 (L/m/yr), FEV1.0%: normal cases 0.164 +/- 0.627, obstruction cases--1.522 +/- 0.638 (%/yr). Significant differences were observed between the normal and the obstruction cases (p < 0.01). FEV1.0% of all obstruction cases was under--2 SD of that of normal subjects. All individual FEV1.0% regression lines of the obstruction cases were outside +/- 2 RSD of the normal standard range more than 5 years before the onset of symptoms. Following individual annual changes in lung function was considered to be useful for the early detection of COPD.

Adult↗

[Molecular implication of Ph positive leukemias: treatment with alpha-interferon in Ph positive acute leukemia].

Patients with Philadelphia chromosome-positive acute leukemia (Ph + AL) were treated with natural interferon-alpha (IFN-alpha) after entering complete remission. In this study, subsequent cytogenetic analysis during complete remission in Ph + AL patients with major-BCR rearrangement revealed that the percentage of bone marrow cells with the Ph chromosome increased, while the bone marrow maintained a remission status. This cytogenetic-hematologic discrepancy led us to consider that the Ph + metaphases might be derived from cells with a non-lymphoid lineage rather than residual leukemic lymphoblasts. After administration of IFN-alpha, the percentage of bone marrow cells with a Ph chromosome decreased. Although this study is on going and we do not yet have the final results, treatment of IFN-alpha should be attempted on more patients with such a genetic abnormality.

Acute Disease↗

[A two-dimensional analysis of B-lymphoma cells by flow cytometry--a comparative study with pathological classification].

In order to investigate the size variation of neoplastic cells from lymph nodes of 19 patients with B-cell non-Hodgkin's lymphomas (B-NHL), we have carried out the two-dimensional analysis by flow cytometry using the parameters of the forward light scatter (FLS) and the fluorescence intensity of surface immunoglobulin light chain (sIgL). Neoplastic B cells were identified as having the homogeneous characters of both FLS and sIgL (kappa or lambda) in comparison of normal B cells with the heterogeneity of counterpart sIgL (lambda or kappa). Then the size variation of neoplastic B cells was analyzed by regarding CD3+ T cells to a control scale. Consequently, the present procedures disclosed that B-NHL cases could be divided into five patterns from the view-point of the cell size and distribution. These results almost coincided with the cell types determined by the pathological diagnosis. Furthermore, it was also found that our data made it possible to classify small cleaved cell or large cell lymphomas into subtypes. The two-dimensional analysis by using the parameters of FLS and sIgL would be clinically useful for the rapid diagnosis of B-NHL and its malignant grade in addition to supporting pathological findings.

Flow Cytometry↗

[Effects of inhibitors of intracellular signal transduction on lipopolysaccharide-induced increase in permeability of cultured pulmonary endothelial cell monolayers].

To investigate the mechanism of lipopolysaccharide (LPS)-induced endothelial response, we measured the permeability to albumin of cultured pulmonary endothelial cell monolayers. PMA and SC-9, used as activators for protein kinase C (PCK), failed to cause an increase in permeability to albumin. H-7, a potent PKC inhibitor, did not prevent the LPS-induced increase in permeability to albumin. In contrast, H-8, which strongly inhibits cyclic nucleotide-dependent protein kinases, and a calmodulin antagonist prevented the LPS-induced increase in permeability to albumin. These results suggest that calmodulin and protein kinases other than PCK are implicated in the mechanism of LPS-induced increase in permeability to albumin.

Albumins↗

[Determination of pulmonary blood flow by acetylene rebreathing method in patients with chronic respiratory disease].

Non-invasive measurement of pulmonary blood flow by acetylene rebreathing was performed in patients with pulmonary diseases. Cardiac output measurement by thermodilution method was also used simultaneously. A fast computation system was coupled with the measurement. Fourteen emphysema patients and 7 pulmonary fibrosis patients were the subjects. Ten patients with normal lung function were normal controls. After the measurement of cardiac output, the subjects rebreathed mixed gas containing acetylene and argon from the end tidal level. The inspiratory and expiratory gas was measured by mass-spectrometer. A lung model made of two compartments connected in series, a compartment of the rebreathing bag and a compartment of the lung were used for the analysis, while taking account of 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 was reached. Values in 9 emphysema cases and 6 fibrosis cases were within or near the 90% confidence limits of control. Five emphysema cases were obviously out of the range, and their pulmonary blood flow was less than the cardiac output and their mean arterial PCO2 was higher than that of the other emphysema cases. These cases were considered to have blood flow to the sites with low alveolar ventilation per unit volume.

Acetylcholine↗

[Usefulness of (1-->3)-beta-D-glucan measurement for diagnosis of deep mycosis].

The number of deep mycosis has been increasing because of increases in immunocompromised hosts and in fungal colonization associated with increasing use of broad-spectrum antibacterial antibiotics. Based on these phenomenon, a simple test method for an early diagnosis of deep mycosis is urgently desired. We therefore investigated the usefulness of assaying a fungal cell component, (1-->3)-beta-D-glucan (beta-glucan). The amount of beta-glucan was obtained from the difference between the amounts determined using Toxicolor and Endospecy, and the serum levels of more than 10 pg/ml were considered positive signs for beta-glucan. The following results were obtained: We found that beta-glucan was positive in 75% of the patients who had been definitely diagnosed to have mycosis, and in 58.3% of the patients strongly suspected of mycosis. The numbers of beta-glucan positive patients' in these 2 groups of patients were significantly different from that in those without mycosis (14.7%, P < 0.05). Thus a usefulness of beta-glucan measurement for the diagnosis of mycosis was demonstrated. However, beta-glucan was sometimes negative even in patients with fungemia at an early phase of the disease and turned positive several days later. Even in a patient with definite lung mycosis, who had a latent circumscribed lesion (afebrile and CRP-negative), beta-glucan was also negative. From these findings, one should be aware that the beta-glucan test produces false negatives even in patients with definite mycosis and that the test should be repeated during the course of the disease.

Aged↗