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Biomedical subjects

K Toyama

Publications and source records attributed to K Toyama.

At least 217 records · Page 12Linked to original sources
PubMed1994

Hypomethylated status, but not RAG-1, is required for T-cell receptor-beta-chain gene rearrangement in acute leukemia cells.

We studied the relation between the level of recombinase activating gene (RAG-1) and the methylation status of T-cell receptor (TCR)-beta-chain gene in TCR-beta rearrangement in acute leukemias, including 21 patients with B-precursor acute lymphoblastic leukemia (ALL) and 23 with acute myeloid leukemia (AML). The rearrangement of the TCR beta-chain gene in acute leukemia always occurs at the allele that contains hypomethylated cytosine-cytosine- guanine-guanine (CCGG) sequences within either the TCR-J beta 1 or TCR-J beta 2 regions. Moreover, all B-precursor ALL patients with TCR-beta rearrangement had hypomethylated TCR-beta with or without the presence of RAG-1 activity detectable by reverse transcript-polymerase chain reaction, whereas none of the AML patients with TCR-beta rearrangement and hypomethylated TCR-beta had detectable RAG-1 activity. Some ALL patients had hypomethylated TCR-beta and RAG-1 activity without TCR-beta rearrangement, and most of them showed t(4;11)(q21;q23) or t(9;22)(q34;q11). These results indicate a correlation between the hypomethylation status of the TCR-beta and its rearrangements, but some unknown blockage factor for this association exists in B-precursor ALL patients with specific chromosomal translocations.

Acute Disease↗
PubMed1994

Telomere shortening in leukemic cells is related to their genetic alterations but not replicative capability.

We compared telomere length in donor leukemic cells and corresponding established cell lines from three patients with chronic myeloid leukemia (CML) and three with acute lymphoblastic leukemia (ALL) to study the relation between the immortalization capacity of hematologic neoplasms and telomere length. Six of the seven established leukemia cell lines (four CML and two ALL) carried additional chromosome changes and had shorter telomere repeats than those of the donor patients' leukemic cells; the remaining ALL line showed no significant difference in telomere length between fresh leukemic cells and the corresponding cell line. Thus, most established leukemic cells lose effective telomerase activity during the process of establishment, and reduction in telomere length of established leukemic cells appeared to be associated with the presence of additional chromosome changes.

Blotting, Southern↗
PubMed1994

Cytogenetic and immunogenotypic alterations of blast crisis cells in chronic myelogenous leukemia independently linked to immunophenotypic expression.

Chronic myelogenous leukemia (CML) is a disease of the hematopoietic stem cells, which can differentiate into either B-lymphoid or myeloid cells, because most of them develop either lymphoid or myeloid blast crisis. Immunophenotypic, genotypic, and cytogenetic analyses of 22 patients (24 episodes) with Philadelphia (Ph) positive CML in blast crisis were performed to determine the genetic alterations of the blast crisis cells. In B-lymphoid blast crisis, all the five patients had immunoglobulin heavy-chain (IgH) rearrangements and most of them showed normal karyotypes. Among the five patients, T-cell receptor (TCR) genes were rearranged at the following occurrence rates: 20% in TCR-beta, 60% in TCR-gamma, and 40% in TCR-delta chain genes. A high incidence of additional chromosome changes was noted in patients with B-lymphoid/myeloid-mixed blast crisis, but about 80% of them had rearranged IgH and about 40% had TCR rearrangements. In contrast, most of the patients with non-lymphoid blast crisis showed further chromosomal abnormalities, including +8, +19, i(17q), and double Ph, and most of them had germline configurations of IgH and TCR-gamma chain genes. Notably, only one patient (dual lymphoid and myelomegakaryoblast crisis) in this group exhibited IgH rearrangement, and TCR-beta and TCR-delta rearrangements were also rarely noted. Rearrangement of the IgH gene in CML blast crisis might be linked to expression of lymphoid markers, especially CD19.

Antibodies, Monoclonal↗
PubMed1994

Clinical and biologic characteristics of CD7+ acute myeloid leukemia. Our experience and literature review.

Six patients with acute myeloid leukemia (AML) expressing CD7 antigen (CD7+ AML) were studied. They consisted of five patients with M1 and one with an M2 morphology. Two cases expressed other lymphoid-associated antigens, in addition to CD7. The complete remission rate was 50%. One patient had central nervous system recurrence. Cytogenetic analysis demonstrated normal karyotypes in all the cases. All but one had germline configurations of the T-cell receptor (TCR) genes and immunoglobulin heavy chain gene. However, all did not have detectable recombinase activating gene-1 activity by the RT-PCR technique. We performed colony formation assay in two patients, and no enhancement of colony formation by granulocyte colony-stimulating factor was noted. The results presented here, together with those reported previously, suggest that CD7+ AML may demonstrate lineage infidelity.

Adult↗
PubMed1994

Molecular genetic, cytogenetic, and immunophenotypic analyses in Castleman's disease of the plasma cell type.

Systemic Castleman's disease shows characteristic morphologic features in the lymph node and laboratory findings, but patients with this disease have variable clinical courses. The disease may constitute a spectrum of benign to malignant diseases. Thus, the clonal nature of the proliferating lymphoid cells was determined to obtain further insight into the malignant process of the disease. Two cases of systemic Castleman's disease were evaluated immunophenotypically, immunogenotypically, and cytogenetically. Both patients had a chronic relapsing clinical course. One patient had a clonal rearrangement of the immunoglobulin (Ig) lambda chain gene, but no restriction of the light chain expression was detected. This patient showed germ-line configurations of the Ig heavy-chain and T-cell receptor (TCR) beta chain genes; no detectable abnormal metaphases in the lymph node were noted. Another patient had predominance of lambda chain-positive plasma cells in the lymph node with a clonal chromosome change, but had germ-line Ig and TCR beta chain genes. The authors identified clonal changes in two cases of systemic Castleman's disease; one had a clonal immunogenotypic change and the other had a clonal cytogenetic change with an Ig light chain deviation. In both cases, however, a discordance of immunogenotypic and immunophenotypic changes was evident. Thus, the alteration may represent a type of lymphoproliferative disorder that lies between benign and malignant diseases.

Castleman Disease↗
PubMed1994

A case of acquired lymphangioma due to a suspected old filariasis and a review of literature.

A 65-year-old man presented in 1992 with multiple papular lesions on the scrotum and foreskin. His medical history revealed that, at the age of 25, he was diagnosed as having filariasis and treated conservatively at a hospital in Hawaii. The histologic study of the scrotal skin showed large, dilated vascular spaces in the upper dermis lined with a single layer of endothelial cells that were negative for Factor 8-related antigen. The diagnosis was acquired lymphangioma due to a suspected old filariasis infestation, although serologic tests for filarial antibodies were negative. The paper also presents a review of the literature of acquired lymphangioma in Japan with a brief discussion of etiology and nomenclature.

Adult↗
PubMed1994

A case of double cancer: a squamous cell carcinoma arising from a long pierced site on the left earlobe and a solid tubular carcinoma of the left breast.

A 43-year-old woman presented with a well differentiated squamous cell carcinoma of the left earlobe where a small hole for pierced type earrings had been made about 20 years earlier. A year after the removal of the tumor, a metastasis of a moderately differentiated squamous cell carcinoma to the left cervical lymph nodes was detected. A month later, a solid tubular carcinoma of the left breast was found. A modified radical neck dissection and a quadrantectomy with an axillary lymph node dissection were performed. A total of 5 courses of peplomycine-mitomycine combinated therapy with 26 Gy of radiotherapy was administered for the cervical lesion. A month of postoperative chemotherapy with tegafur-uracil and medroxyprogesterone acetate and a total of 56 Gy of radiotherapy to the mammary lesion were added. She has been well without recurrence for about a year after the operations. This case is not only a rare double cancer, a combination of a squamous cell carcinoma and a solid tubular carcinoma, but may also be the first case of a squamous cell carcinoma arising at a long pierced site on an earlobe for pierced type earrings.

Adenocarcinoma↗
PubMed1994

Adrenal adenomas: characteristic hyperintense rim sign on fat-saturated spin-echo MR images.

PURPOSE: To determine whether adrenal adenomas can be differentiated from metastases on fat-saturated magnetic resonance (MR) images. MATERIALS AND METHODS: Twenty-eight adrenal adenomas and 20 metastatic lesions were imaged at 1.5 T by means of fat-saturated T1- and T2-weighted and gadolinium-enhanced T1-weighted sequences. The authors evaluated visually whether structures of high signal intensity (hyperintense rim sign) could be observed in the outer margin of the adrenal masses. RESULTS: Twenty-six of 28 adrenal adenomas revealed the hyperintense rim sign on at least one kind of fat-saturated image, compared with only one of 20 metastases. The sensitivity of the hyperintense rim sign as suggestive of adrenal adenoma was 92%, specificity was 95%, and overall accuracy was 94%. CONCLUSION: The hyperintense rim sign is characteristic of adrenal adenomas. Thus, adrenal adenomas can be differentiated from metastases by means of this new imaging sign on fat-saturated MR images.

Adrenal Cortex Neoplasms↗
PubMed1994

Tau confers drug stability but not cold stability to microtubules in living cells.

We previously defined two classes of microtubule polymer in the axons of cultured sympathetic neurons that differ in their sensitivity to nocodazole by roughly 35-fold (Baas and Black (1990) J. Cell Biol. 111, 495-509). Here we demonstrate that virtually all of the microtubule polymer in these axons, including the drug-labile polymer, is stable to cold. What factors account for the unique stability properties of axonal microtubules? In the present study, we have focused on the role of tau, a microtubule-associated protein that is highly enriched in the axon, in determining the stability of microtubules to nocodazole and/or cold in living cells. We used a baculovirus vector to express very high levels of tau in insect ovarian Sf9 cells. The cells respond by extending processes that contain dense bundles of microtubules (Knops et al. (1991) J. Cell Biol. 114, 725-734). Cells induced to express tau were treated with either cold or 2 micrograms/ml nocodazole for times ranging from 5 minutes to 6 hours. The results with each treatment were very different from one another. Virtually all of the polymer was depolymerized within the first 30 minutes in cold, while little or no microtubule depolymerization was detected even after 6 hours in nocodazole. Based on these results, we conclude that tau is almost certainly a factor in conferring drug stability to axonal microtubules, but that factors other than or in addition to tau are required to confer cold stability.

Animals↗
PubMed1994

Significance of VLA-4 and LFA-1 expressions in neoplastic follicle formation and its deterioration in B-cell non-Hodgkin's lymphomas.

In an attempt to determine the roles of adhesion molecules in the formation and deterioration of neoplastic follicles, we used flow cytometry to investigate how strongly neoplastic B-cells express VLA-4 alpha and LFA-1 alpha on their surfaces. Neoplastic and normal B-cells were taken from 24 patients with B-cell non-Hodgkin's lymphomas (B-NHL) and 6 with B-cell chronic lymphocytic leukemia (B-CLL). The expression intensities of the adhesion molecules were graded as follows: (-), (+), (+2) and (+3). Normal B-cells expressed those molecules with an intensity of (+2). The data for VLA-4 alpha expression were as follows: follicular B-NHL [10/11; (+2) and 1/11; (+)], partially follicular [5/5; (+)], diffuse [8/8; (+)] and B-CLL [6/6; (-)]. Those for LFA-1 alpha were as follows: follicular B-NHL [7/11; (+2), 4/11; (+)], partially follicular [3/5; (+2), 2/5; (+)], diffuse [3/8; (+2), 5/8; (+)] and B-CLL [3/6; (+), 3/6; (-)]. These results suggest that VLA-4 molecules expressed on neoplastic B-cells may be involved closely in the formation and deterioration of neoplastic follicles, although the expression of LFA-1 molecules seems to play only a minor part in such events.

Antibodies, Monoclonal↗
PubMed1994

[A case of large cell carcinoma of the lung producing granulocyte colony-stimulating factor].

A 48-year-old female was admitted complaining of cough and right chest pain. A chest X-ray showed a tumorous mass in the right lower lung field and hilar and mediastinal lymphadenopathy. The patient underwent transbronchial lung biopsy, and was diagnosed as having a malignant tumor. Because a metastatic lesion was detected in the left lung filed, we opted for chemotherapy. The white blood cell count rose to 103,700/mm3 and 190,000/mm3 in the fifth and sixth month after hospitalization, respectively. The serum granulocyte colony-stimulating factor (G-CSF) level by enzyme immunoassay exceeded 1000 pg/ml. The histological diagnosis of large cell carcinoma was made from the specimen obtained by percutaneous needle biopsy of the lung. The carcinoma cells in this specimen, showed positive staining with anti-G-CSF monoclonal antibody.

Carcinoma, Non-Small-Cell Lung↗
PubMed1994

EVI1 expression associated with a 3q26 anomaly in a leukemia cell line derived from the blast crisis of chronic myeloid leukemia.

Two leukemia cell lines, TS9;22 and YS9;22, were established from different individuals with Philadelphia chromosome (Ph)-positive chronic myeloid leukemia in blast crisis. The reverse transcript-polymerase chain reaction (RT-PCR) technique revealed that both cell lines expressed GATA-1, GATA-2, and the stem cell leukemia (SCL) gene, consistent with a megakaryocyte lineage. Chromosome analysis revealed that TS9;22 cells show the Ph translocation without abnormality of chromosome 3. In contrast, YS9;22 cells show the Ph translocation and dic(3)(q26;p12). Northern analysis revealed that YS9;22 cells express the EVI1 (ecotropic virus integration-1) gene, possibly because of the chromosomal translocation in the 3q26 region; TS9;22 cells do not express EVI1. However, no rearrangements were detected over 600 kb upstream or over 900 kb downstream of EVI1 in the YS9;22 cell line, suggesting a different mechanism of EVI1 activation from that in leukemia cells with either a t(3;3)(q21;q26) or inv(3)(q21q26). These results indicate that EVI1 expression in YS9;22 cells is linked to the 3q26 abnormality and that EVI1 activation plays an oncogenic role in the blastic transformation of chronic myeloid leukemia.

Adult↗
PubMed1994

Percentages of bone marrow blasts and chromosomal changes in patients with refractory anemia help to determine prognoses.

We statistically analyzed the hematologic findings of patients with refractory anemia (RA) to identify parameters associated with a poor prognosis. We first separated the RA patients into two groups: one group with disease progression and one without. The patients with disease progression were predominantly male and had a significantly higher percentage of bone marrow (BM) blasts at the time of diagnosis (3.06 +/- 1.29% vs. 1.44 +/- 1.38%, P < 0.005). This finding was confirmed when the patients were separated into the two groups; those who survived and those who expired (BM blasts: 2.68 +/- 1.59% vs. 1.37 +/- 1.27%, P < 0.005). The survival probabilities were calculated depending on whether or not the RA patients had > or = 3% BM blasts. The RA patients with > or = 3% BM blasts had a significantly worse prognosis (P < 0.01) than the patients with < 3% BM blasts. Notably, the RA patients with > or = 3% BM blasts did not show any significant differences in the incidence of disease progression, mortality rate, or survival probability, when compared with the patients with RA with an excess of blasts (RAEB). The present findings indicate that RA patients are heterogeneous with regard to prognosis, and the RA patients with > or = 3% BM blasts might have a poorer prognosis than those with fewer BM blasts. Thus we propose a general approach in predicting the prognosis of RA patients: those with complex chromosomal changes will expire shortly. Secondly, when the patients do not have any complex changes, the prognosis might be linked to the percentage of BM-blasts at the MDS diagnosis.

Anemia, Refractory↗
PubMed1994

Establishment of a human thymic stromal cell line (R-3-4) and its adhesive capacity with T cells in vitro.

T cells are considered to be activated in the thymus, and it has been emphasized recently that the thymic stromal cells play an important role in the process of T-cell maturation. To clarify how the stromal cells interact with T cells a cloned stromal cell line from human thymus was established and its adhesive capacity with T cells was studied. A recombinant plasmid, pSV3gpt containing SV40 large T antigen was introduced to human thymic stroma by the calcium phosphate co-precipitation method, and the thymic stromal cell line R-3-4 was obtained. Immunohistochemical examination showed that R-3-4 possessed with HLA-class 1 antigen, laminin, fibronectin, and keratin. To determine if the R-3-4 interacts with T cells, the binding activity of R-3-4 with T cells examined by using rosette formation technique. The R-3-4 formed rosette only with the T cells, but both B cells and myeloid cells did not bind to the R-3-4. This rosette formation between R-3-4 and T cells was inhibited when T cells were pretreated with anti-CD2 antibodies, suggesting that some mechanism involving CD2 participates in this binding. Our novel established thymic stromal cell line might be useful for studying the interactions between thymic stroma and T cells in vitro.

Antibodies, Monoclonal↗
PubMed1994

Evaluation of the order entry system by end users--a step to the new hospital information system.

Nagoya University Hospital has developed a new, comprehensive computerized hospital administration system since April 1992. In the present study, a user's evaluation questionnaire survey on the order entry system revealed that the improvements at the human interface level were appreciated by some respondents, but not all users felt the human interface provided, adequately meets their needs. Another presumed advantage of the micro-mainframe-link architecture is fast response, but in our study respondents considered the response time too long. Most users felt that transmission of orders was fast, accurate and clear, and that fast retrieval of the results of laboratory tests was good. Our system with this kind of architecture has thus proved satisfactory except for the slow response time. This study will be useful to reengineer our hospital information system in the next phase.

Evaluation Studies as Topic↗
PubMed1994

[Immunoregulatory cells in patients with monoclonal gammopathies].

The authors detected immunoregulatory cells by two-color cytometric analysis in the peripheral blood of 21 patients with multiple myeloma (MM) and 10 patients with monoclonal gammopathy of undetermined significance (MGUS). CD3-CD56+ cells increased in both MGUS and IgG, IgA type MM in clinical stage (CS) I & II, whereas CD3+ cells decreased. On the other hand, the CD4/8 ratio, the proportions of CD45RA+ cells and CD29++ cells in CD4+ cells, and S6F1++ cells in CD8++ cells remained normal. In CS III MM of IgG and IgA type, CD3-CD56+ cells did not increase, although CD3+ cells decreased. Additionally, both CD4/8 and CD4+ CD45RA+/CD4+ ratios were low, while the proportions of CD29++ cells in CD4 cells and S6F1++ cells in CD8++ cells were high. However, this type of change in the T-cell subset balance was not observed in CS III MM of the Bence-Jones type, which showed no significant elevation of serum M-protein. These findings suggest that serum monoclonal idiotypes could affect immunoregulatory cells, especially T cells.

Flow Cytometry↗