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Biomedical subjects

K Toyama

Publications and source records attributed to K Toyama.

At least 271 records · Page 15Linked to original sources

[A case of Evans' syndrome in which CD4+CD45RA+ cells markedly decreased in its active phase].

A 38-year-old man was admitted to our hospital because of exertional dyspnea in February, 1990. The patient had already been diagnosed as having autoimmune hemolytic anemia (AIHA) in February, 1982 and treated with prednisolone (PSL) until January, 1988. The laboratory examination confirmed the relapse of AIHA (IgG-warm type) and additionally disclosed the marked decrease of CD4+CD45RA+/CD4+ ratio in peripheral blood lymphocytes. Thereupon, the patient was treated again with PSL and entered the remission in one month. Simultaneously, CD4+CD45RA+/CD4+ ratio also increased to the normal level. Afterwards, the remission had been maintained for about six months with a small dose of PSL. However, in September, 1990, the hemolysis relapsed with marked thrombocytopenia and decreased CD4+CD45RA+ ratio. Then the diagnosis was corrected to Evans' syndrome because PAIgG was highly elevated together with positive Coombs' test. Although danazol and azathioprine were administered in addition to PSL, the disease remained in active phase. Thus, splenectomy was carried out in March, 1992. Consequently, the patient entered the remission that has been maintained over six months. CD4+CD45RA+/CD4+ ratio was also normalized. These results suggest that CD4+CD45RA+ cells may play an important role in the pathogenesis of AIHA or Evans' syndrome.

Adult↗

[Detection of erythropoietic inhibitor factor in a case of acute non-lymphocytic leukemia after allogenic bone marrow transplantation].

A 36-year-old man was diagnosed as having acute non-lymphocytic leukemia (AML M5b) in 1985 and received allogenic bone marrow transplantation from an ABO-mismatched sibling in January 1987. Recovery of erythropoiesis in this patient was delayed, then the hemoglobin level improved in parallel with disappearance of anti-A antibody in the serum on day 260 post transplantation. However, as anemia occurred again despite no relapse of leukemia on day 350, we tried to determine the presence of erythropoietic inhibitory factor in this patients. Erythroid colony formation was decreased when bone marrow cells were co-cultured with peripheral mononuclear cells from the patient. Further, erythroid colony inhibitory activity was found in conditioned medium of PHA-stimulated T cells from the patient. Sephadex gel fractionation showed that the molecular weight of this inhibitory factor was approximately 11,000 and addition of a high concentration of EPO did not eliminate the inhibitory activity. These findings suggest that the novel inhibitor described in this manuscript, produced by T cells, was differed from previously reported inhibitors such as anti-EPO antibody, spermine and uremic toxins.

ABO Blood-Group System↗

[Advanced breast cancer with onset of multi-organ metastases successfully treated with combined loco-regional therapies: a case report].

A 56-year-old woman was referred to Shizuoka General Hospital on April 17, 1992, because of progressive jaundice and massive pleural effusion. A thorough work-up revealed the diagnosis of advanced left breast cancer complicated with direct invasion of the thoracic wall, pleural carcinomatosis, multiple liver and bone metastases and obstructive jaundice due to the hilar mass. From a prognostic point of view, we scheduled the treatment course as follows. First, we treated the chief complaints. After emergency drainage and chemo-adhesive therapy of the pleural lesion, percutaneous biliary drainage and radiotherapy were done for obstructive jaundice, followed by internal drainage with self-expandable metallic stents. For the primary cancer of the left breast, standard mastectomy was performed following 57 Gy of radiotherapy. MPA was also administered because estrogen-receptor was positive on the histological examination of the resected specimen. To complete the multi-disciplinary treatment, we implanted a vascular access percutaneously via the left femoral artery and started intermittent hepatic arterial infusion chemotherapy on an outpatient basis. The patient was discharged on the 123rd hospital day and is well and active without any symptom 9 months thereafter.

Adenocarcinoma↗

[Experience with 241 sporotrichosis cases in Chiba/Japan].

Between 1965 and 1991, 241 cases of sporotrichosis have been seen in the Department of Dermatology at Chiba University Hospital. Children under the age of 12 and patients older than 40 years had a higher rate of infection. Most affected were the upper extremities, followed by lesions of the face. One hundred twenty-four patients (51.5%) were farmers. The decrease in the number of patients observed since 1983 is attributed mainly to a drop in the percentage of the local population involved in agriculture. There was no correlation between the number of infections and the amount of precipitation, as had been suggested earlier. The patients were treated with potassium iodide and in some cases with additional thermotherapy.

Adolescent↗

Myelodysplastic syndrome evolving into a myeloproliferative disorder: one disease or two?

We report two patients who had been initially diagnosed as having a myelodysplastic syndrome but subsequently progressed into a leukothrombocytosis state which mimicked a chronic myeloproliferative disorder. Both patients had anemia and mild neutropenia without thrombocytopenia at the time of their diagnosis of myelodysplastic syndrome, and dyshematopoietic features were present in the bone marrow. After treatment with vitamin D3 for 7 and 18 months, respectively, they developed leukothrombocytosis which responded to hydroxyurea. We speculate that these and other similar patients with this unusual course might constitute an entity distinct from the typical myelodysplastic syndromes or chronic myeloproliferative disorders.

Aged↗

Clinical implications of chromosomal abnormalities in 401 patients with myelodysplastic syndromes: a multicentric study in Japan.

It is well known that cytogenetic analysis in patients with myelodysplastic syndrome (MDS) provides information useful in determining their prognosis. Based on the chromosomal results obtained from 401 MDS patients by a multicentric study in Japan, we studied correlations between chromosomal findings and prognosis or leukemic transformation in MDS patients. Patients with complex aberrations (cytogenetic abnormalities at more than three chromosomes), of any subtype, had a poor prognosis; for example, > 60% of patients with refractory anemia (RA) showing complex aberrations died within one year, but only 11% of them developed leukemia. In patients with RA with ringed sideroblasts (RARS), > 70% of those with complex aberrations evolved into the leukemic phase and survived for less than one year, suggesting a biologic heterogeneity in RARS patients. By contrast, about 5% of patients with RA or RARS exhibiting chromosomal findings other than -7/7q-, +8, two aberrations, and complex aberrations, developed leukemia and had a favorable prognosis. Therefore, the presence of chromosome abnormalities alone in patients with RA or RARS is not a factor in predicting leukemic transformation or poor prognosis. In patients with refractory anemia with an excess of blasts (RAEB), the presence of chromosome aberrations at MDS diagnosis affected the occurrence of leukemic transformation (24% versus 43%), however, no particular difference was noted in patients with RAEB in transformation with regard to whether they had chromosome changes or not, and about 60% of them evolved into leukemia. The poor prognosis related to complex aberrations was consistently noted in all MDS subtypes or age-matched groups, indicating that this cytogenetic anomaly is an independent risk factor for a poor prognosis in MDS patients. The duration between MDS diagnosis and development of the leukemic phase and that between the latter and death were significantly shorter in patients with complex aberrations than those without this change. Although the clinical significance of certain chromosomal abnormalities differs among subtypes of MDS, a new scoring system for predicting prognosis by cytogenetic changes, in combination with hematologic parameters, was proposed.

Adolescent↗

[Clinical implications of chromosome analysis in myelodysplastic syndrome].

We attempted to identify the cytogenetic significance in predicting the prognosis of patients with myelodysplastic syndrome (MDS). From the results, we established scoring system (Bournemouth scoring+cytogenetic scoring: 3 for > or = 3 chromosomal abnormalities; 1 for -7/7q-, +8, 2 abnormalities); patients with score of > or = 5 had significant worse prognosis than that with score 0-2. Moreover, RARS with complex abnormalities consists of specific subtype showing a high leukemic rate with a high mortality rate. MDS with hypocellular marrow showed prognosis similar to those with typical MDS, while those with minimal dysplasia had prognosis similar to those with aplastic anemia. Patients with MDS were categorized into 3 subtypes, i.e., early disease-evolution, late disease-evolution, and no disease-evolution group. About 50% of patients with complex abnormalities showed early disease-evolution, while the remaining died before disease-evolution. In patients showing late disease-evolution, no cytogenetic factor are informative to predict the timing of disease-evolution, except percentage of marrow blasts at the diagnosis.

Cell Transformation, Neoplastic↗

[Acute megakaryoblastic leukemia associated with Sweet's syndrome, including review of the literature].

A case of Sweet syndrome (SS) associated with acute megakaryoblastic leukemia (AMKL) is reported. A 66-year-old male was admitted to Ashikaga Red Cross Hospital because of skin eruption and sore throat. His eruption was tender and erythema-like nature. He developed a spiking fever after admission. CBC revealed pancytopenia, and a bone marrow specimen showed increased megakaryoblasts and fibrosis. These blasts were shown to be CD41-positive by flow cytometric analysis. A diagnosis of AMKL was then made. Skin biopsy revealed infiltration of neutrophils without vasculitis, compatible with SS. Oral administration of prednisolone was begun which improved his skin lesions considerably. He was then treated with low dose Ara-C, which was however ineffective. The blasts increased in the peripheral blood and he died on the 72nd hospital day. There are 37 reported cases of SS associated with acute nonlymphocytic leukemia, and this is the first case report of SS associated with AMKL.

Aged↗

[Pulmonary disease as the chief manifestation of chronic graft-versus-host disease after allogeneic bone marrow transplantation].

A 17-year-old man diagnosed as acute myelogenous leukemia (M5a) underwent allogeneic bone marrow transplantation from his HLA-identical, MLC non-reactive sister on the occasion of the second complete remission. On day 14 engraftment was confirmed by karyotypic expression. The patient had no evidence of acute graft-versus-host disease (GVHD), therefore cyclosporine A was discontinued on day 62. Having complained of cough and dyspnea by day 100, the patient was diagnosed as interstitial pneumonitis (IP) based on chest X-ray findings. However, no other typical signs of chronic GVHD were present except for modest abnormality of liver function. Since there was no evidence of infection on bronchofiberoscopic examination and prednisolone was very effective, it was considered that the IP might be pulmonary disease of chronic GVHD. It has been reported that HLA-DR which is not normally found, is expressed on epithelial tissues of the patient with GVHD. In this case alveolar epithelial cells were positive for LN-3 (anti-HLA-DR). In conclusion, pulmonary disease in this case may represent a possible manifestation of chronic GVHD, thus suggesting that the current case could provide information to ascertain the mechanism of chronic GVHD.

Adolescent↗

The methylation status of the major breakpoint cluster region in human leukemia cells, including Philadelphia chromosome-positive cells, is linked to the lineage of hematopoietic cells.

The Philadelphia (Ph) translocation [t(9;22)(q34;q11)] is the most common genetic abnormality in human leukemia; a transposition of the ABL gene to the major-breakpoint cluster region (M-BCR) is associated with the pathogenesis in Ph+ chronic myelogenous leukemia (Ph+ CML) and in some cases of Ph+ acute leukemia (Ph+ AL). Our current understanding of the methylation of human genomes allows us to consider the association between the epigenetic phenomenon and the control of differentiation and proliferation in mammalian cells. In order to determine whether the methylation status of the M-BCR is associated with breakpoint-localization in this region and with the lineage of hematopoietic cells, we have examined 28 patients with Ph+ leukemias, including nine with Ph+ AL, six patients with acute myeloblastic leukemia without Ph (Ph- AML), and five patients with Ph- acute lymphoblastic leukemia (Ph- ALL); using the restriction endonuclease isochizomers, MspI and HpaII. In CML patients in the chronic phase, the hypomethylated status within the normal M-BCR allele is heterogeneous. In contrast, patients with Ph+ CML in the lymphoid blast crisis phase exhibited a 2.5/2.7 kb band with a complete disappearance of the germline M-BCR fragment (type L). This pattern is consistently noted in Ph- ALL cells, and the pattern is quite different from that found in myeloid blast crisis or Ph- AML (type M). In patients with M-BCR-nonrearranged Ph+ ALL, it is suggested that the M-BCR methylation patterns are cell-lineage specific but some Ph+ ALL cells had a hypomethylation pattern that was identical to that observed in Ph- AML, suggesting a distinction of genetic diversity of leukemia cells with the Ph chromosome, especially Ph+ AL.

5-Methylcytosine↗

[A case of vivax malaria with thrombocytopenia suggesting immunological mechanisms].

Recently, it has been shown that the thrombocytopenia that complicates some malarial infections is caused by immune mechanisms. We report a case of malaria associated with thrombocytopenia and increased platelet-associated IgG (PAIgG). In this case, anti-malarial therapy reduced the level of PAIgG to normal levels in association with normalization of the platelet count. This case suggests the immunological mechanisms of thrombocytopenia in malaria.

Adult↗

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↗

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↗

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↗

[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↗

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↗

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↗