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Biomedical subjects

K Toyama

Publications and source records attributed to K Toyama.

At least 235 records · Page 13Linked to original sources
PubMed1994

[The clinical significance of glycosylated ferritin in iron overloads and hematopoietic malignancies].

Serum ferritin concentration had been known to represent the amount of total body iron and has been clinically used as a parameter to evaluate the iron storage pool in a whole body. Glycosylated (secreted) and non-glycosylated (non-secreted) forms of serum ferritin (sFt) have been reported by others based on the difference in their affinity to concanavalin-A binding. In this report, we assessed the amount of glycosylated serum ferritin (Glyco-sFt) and the ratio (%) of Glyco-sFt/in hematopoietic disorders including iron overloads (n = 10), leukemias (n = 36), malignant lymphomas (n = 10), multiple myelomas (n = 3) and myelodysplastic syndromes (n = 12). A high percentage of Glyco-sFt was observed in normal healthy controls (n = 18, 78.1 +/- 7.4%) and iron-overloads (61.1 +/- 17.8%) as compared with that in hematopoietic malignancies (43.8 +/- 23.4%, p < 0.001). The amount of Glyco-sFt in iron-overloads was higher than that in hematopoietic malignancies with hyperferritinemia (p < 0.005). These data demonstrated that the same part of serum ferritin in hematopoietic malignancies was the non-secreted form and appeared to be derived from tumor cell lysis. We conclude that assessment of Glyco-Ft is a useful parameter to distinguish iron-overloads from malignant hematopoietic disorders both displaying hyperferritinemia.

Concanavalin A↗
PubMed1994

[Multiple cancer].

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Combined Modality Therapy↗
PubMed1994

[Immunocompetent cells in lymph nodes of B-cell lymphomas].

In non-Hodgkin's lymphoma (NHL), the precise analysis of non-neoplastic immunocompetent cells in lymph nodes may be important to understand the pathophysiology of anti-tumor immunity. We have investigated such immunocompetent cells of 14 patients with B-cell type NHL (B-NHL) by flow cytometry, and compared them with the data obtained from 10 patients with reactive lymphadenopathy. The results on B-NHLs were as follows; CD3+ (T lymphocyte) = 45.0 +/- 19.7%, CD4+/CD3+ = 62.7 +/- 14.2%, CD4+CD45RA-/CD4+ = 82.9 +/- 8.1% (Control 62.9 +/- 14.5%, p < 0.01), CD4+CD29++/CD4+ = 29.2 +/- 7.0% (Control 42.6 +/- 12.9%, p < 0.01), CD8+/CD3+ = 36.0 +/- 11.3%, CD8++S6F1++/CD3+ = 23.2 +/- 10.6% (Control 9.1 +/- 4.3%, p < 0.01), CD8++S6F1++/CD8++ = 75.3 +/- 16.7% (Control 41.5 +/- 19.6%, p < 0.01), CD3-CD56+ cells = 1.0 +/- 0.7% (Control 2.2 +/- 1.6%, p < 0.05). These findings suggest that CD4+ T lymphocytes in lymph nodes of B-NHL may change to memory cells (CD45RA- cells), but such memory cells could only weakly express CD29 molecules which are thought to play an important role in the manifestation of helper function. This phenotypic discordance of CD4+ T lymphocytes may produce incomplete anti-tumor immunity in B-NHL.

Humans↗
PubMed1994

GATA-1, GATA-2, and stem cell leukemia gene expression in acute myeloid leukemia.

Transcription factors play an important role in the normal developmental process of hematopoietic cells. However, expression of transcription factors and its implication in various human leukemias is not well understood. We have studied GATA-1, GATA-2, and stem cell leukemia (SCL) gene expression in 30 patients with acute myeloid leukemia (AML) by the reverse transcription-polymerase chain reaction assay. In AML both GATA-1 and SCL genes were commonly expressed in M6 and M7 leukemias, and also in leukemias bearing the platelet-associated antigen. We found some AML patients with GATA-1, but not SCL expression. Most CD7+ AML and t(8;21)(q22;q22)-AML were included in this group, which often demonstrated immunoglobulin heavy chain and/or T-cell receptor gene rearrangements. Consequently, GATA-1+ SCL- AML may originate from early myeloid progenitors. Moreover, most AML patients of the M3, M4, or M5 groups were GATA-1- SCL-. Our data suggest that the expression pattern of transcription factors may help to define distinct phenotypes of AML cells.

Acute Disease↗
PubMed1994

[An autopsy case of lymphoepithelioma-like carcinoma of the mediastinum].

A case of lymphoepithelioma-like carcinoma of the mediastinum is reported. A 67-year-old male was admitted to Tokyo Medical College Hospital, in February of 1992, for evaluation of an abnormal mediastinal shadow on chest X-ray. The mediastinal tumor was biopsied using mediastinoscopy. Histological diagnosis was undifferentiated carcinoma and radiation therapy was performed. Six months after treatment, he complained of dyspnea. Combination chemotherapy was performed. Although the tumor size decreased, he died of pneumonia. Histological findings at autopsy included nesting of large carcinoma cells with vacuolar nuclei and large nucleoli, interstitial lymphocytic infiltration similar to that of lymphoepithelioma of the epipharynx, and lymphoepithelioma-like carcinoma in the thymus. The epipharynx and thymus were, however, intact at autopsy. We found no other origins of this tumor, including the trachea and lung. This case was therefore diagnosed as lymphoepithelioma-like carcinoma of the mediastinum.

Aged↗
PubMed1994

[Diagnosis of B-cell lymphoma of lung by kappa-lambda imaging in broncho-alveolar lavage fluid lymphocytes].

We attempted to verify the clonality of proliferating cells in broncho-alveolar lavage fluid (BALF) by using a sophisticated technique known as kappa-lambda imaging. We applied this method to BALF lymphocytes from 3 cases suspected of having primary pulmonary B-cell lymphoma, by transbronchial lung biopsy, and from 2 cases with B-cell lymphoma revealing abnormal shadows. (One was diagnosed as small cell carcinoma, the other mycotic infection). B-cell monoclonality was found in the former 3 cases, but not in the latter 2 cases. We conclude that kappa-lambda imaging in BALF lymphocytes is useful for diagnosing B-cell lymphoma of the lung.

Aged↗
PubMed1994

[Molecular diagnosis and therapeutic strategy for Philadelphia chromosome-positive acute leukemia].

We focused on biological characteristics of Philadelphia chromosome-positive acute leukemia (Ph+ AL) and treated those patients with BHAC-DMPV induction chemotherapy. After obtaining complete remission, we attempted to treat with allogeneic bone marrow transplantation, while those without suitability for marrow transplantation were treated with alpha-interferon (IFN-alpha), in order to obtain prolong remission status. Chromosomal and molecular analyses, including BCR rearrangement and BCR -ABL mRNA, before and after IFN-alpha treatment demonstrated a recovery of normal hematopoiesis by the treatment of INF-alpha, however, suppressive effect for the blast cells by IFN-alpha was insufficient. To clarify the mechanism of IFN-alpha on the Ph+ leukemia cells, we studied expression of interferon stimulated genes (ISGs). However, an association between expression of ISGs and therapeutic effectiveness was not evident. Although, the exact anti-neoplastic mechanism of IFN-alpha is not established yet, our study demonstrated the possibility for utilization of IFN-alpha in some Ph+ AL patients as a maintenance therapy to obtain long survivals. Therefore, studies using a large number of patients with Ph+ AL should be performed, in order to establish induction and maintenance therapies reflecting biological characteristics of Ph+ AL.

Acute Disease↗
PubMed1994

[A case of pulmonary fibrosis associated with CMV inclusion body].

A 71-year-old woman admitted to our hospital with complaints of progressive dyspnea on exertion and weight loss. Roentgenological examination demonstrated peripheral pulmonary fibrosis and a mediastinal tumor suggesting thymoma. The pathological findings of transbronchial lung biopsy (TBLB) confirmed pulmonary fibrosis. Moreover, cytomegalic inclusion bodies in TBLB and a high titer of serum CMV IgG antibody suggested pulmonary CMV infection. It is considered that pulmonary fibrosis and CMV infection were coexistent in this patient.

Aged↗
PubMed1994

Hematopoietic supportive function of human bone marrow stromal cell lines established by a recombinant SV40-adenovirus vector.

We have previously reported the establishment of a variety of human bone marrow stromal cell lines using a recombinant SV40-adenovirus vector. Using this vector, we obtained more clonal stromal cells. Here, we have characterized these cells and analyzed their capacity to support the proliferation and differentiation of hematopoietic cells. The stromal cells were cocultured with nonadherent human bone marrow cells used as hematopoietic cells. The total numbers of hematopoietic cells and CFU-GM in culture were counted every week. Two of the six stromal cell lines, AA101 and HAS303, supported the proliferation and differentiation of hematopoietic cells and CFU-GM for more than 9 weeks. Further, granulocytes, macrophages, and megakaryocytes were detected when cocultured with these cells. When hematopoietic cells were cocultured but separated from the two stromal cell lines by a 0.45-microns millipore membrane to prevent their attachment, almost all CFU-GM disappeared within 7 weeks. The supportive stromal cells produced GM-CSF and IL-6. However, other cell lines producing these humoral factors did not support hematopoietic cell proliferation for such a long time. These findings suggest that these established human bone marrow stromal cell lines will be useful, in that analysis of their supportive function in hematopoietic cell proliferation and differentiation through cell-to-cell interaction will shed some light on this area.

Adenoviridae↗
PubMed1994

Potential molecules implicated in downstream signaling pathways of p185BCR-ABL in Ph+ ALL involve GTPase-activating protein, phospholipase C-gamma 1, and phosphatidylinositol 3'-kinase.

Constitutive activation of BCR-ABL tyrosine kinase fusion protein has been shown to be an essential step in the pathogenesis of Philadelphia chromosome (Ph)-positive leukemias. We studied the tyrosine phosphorylated proteins which might be involved in the signaling pathway p185BCR-ABL using a Ph-positive acute lymphoblastic leukemia cell line. p185BCR-ABL but not p145c-abl was constitutively phosphorylated on tyrosine in this cell line. p21ras GTPase-activating protein (GAP) was physically associated with p185BCR-ABL, but not with p145c-abl, and GAP-associated proteins p62/p190 were found to be tyrosine-phosphorylated. Furthermore, p185BCR-ABL was also physically associated with phospholipase C-gamma 1 (PLC-gamma) and phosphatidylinositol 3'-kinase (P13-kinase). Concomitantly, both PLC-gamma and p85 subunit of P13-kinase are tyrosine-phosphorylated in the cells with p185BCR-ABL. These data suggest that GAP, GAP-associated proteins, PLC-gamma, and P13-kinase may participate in downstream signaling for p185BCR-ABL tyrosine kinase.

Animals↗
PubMed1993

Two additional cases of acute myeloid leukemia with t(7;11)(p15;p15) having low neutrophil alkaline phosphatase scores.

We report two additional patients with acute myeloid leukemia (AML) and a translocation between chromosomes 7 and 11: t(7;11)(p15;p15). One patient was diagnosed as having AML-M2 and the other as AML with myelofibrosis. Both patients had low-level neutrophil alkaline phosphatase (NAP) scores. In the literature, only 15 AML patients with t(7;11)(p15;p15) have been reported; nine of them had an AML-M2 morphology, and all had a decreased NAP score. Moreover, mean survival of the reported AML patients with t(7;11)(p15;p15) was 15 months, although 85% of them obtained complete remission, indicating that this type of leukemia frequently tends to relapse. These findings indicate a strong association between the chromosome abnormality and hematologic manifestations of this disease.

Acute Disease↗
PubMed1993

[Radiation stenosis and fistula formation developed after iridium-192 high-dose-rate intracavitary radiation boost therapy for carcinoma of the esophagus].

Intracavitary irradiation using a high-dose-rate Ir-192 remote after-loading system was applied to 14 advanced or inoperable patients with esophageal carcinoma as a boost therapy. The total dose of external irradiation was 45-70 Gy/15-35 fractions and that of intracavitary irradiation was 11.6-34.0 Gy/2-4 fractions at a point 5 mm deep from the inner surface of the esophageal mucosa. The time-dose-fractionation factor (TDF) of the whole treatment was 116-186 (mean, 146). Six patients (43%) had complete response (CR), three (21%) had partial response and five (36%) had no response. Esophageal carcinoma that showed exophytic growth, was less than 5 cm ling, and showed favorable response to external irradiation was likely to be a good candidate for intracavitary radiation boost therapy. Fistula formation was produced in five patients (36%), four of whom were irradiated at more than 140 TDF. All six CR patients were free from esophageal tumors, but severe esophageal stenosis due to radiation injury developed in five (83%) of them. They were irradiated at more than 135 TDF. One- and two-year survival rates were 28.6% and 14.3%, respectively. The poor prognosis was ascribed to the frequent occurrence of fatal radiation stenosis and fistula formation. An appropriate therapeutic dose for esophageal carcinoma that does not cause severe radiation stenosis was estimated to be under 120 TDF.

Aged↗
PubMed1993

Development of neural connections between visual cortex and transplanted lateral geniculate nucleus in rats.

The development of neural connections between transplanted lateral geniculate nucleus (LGN) and host visual cortex (VC) was studied in slice preparations obtained from rat brain in which a fetal (embryonic day 15-17) rat LGN was transplanted to the white matter underlying the VC of a neonate rat (postnatal day 0-1). Placing a fluorescent dye (DiI) in the transplant of the fixed slices revealed that retrogradely labeled cortical cells projecting to the transplant were broadly distributed through layers II to VI at 1 week after transplantation. Three weeks after transplantation, these cells were virtually confined to layer VI. Likewise, anterograde labeling showed that cells in the transplant sent axons up to layer I with a few branches at 1 week after transplantation, while the axons were found to terminate at layer IV with many arborizations at 3 weeks after transplantation. These observations were supported by electrophysiological studies. Analysis of the antidromic responses of the cortical cells to stimulation of the transplant showed that the efferent cells projecting to the transplant were broadly distributed in layers II-VI at 1 week after transplantation, while they were virtually restricted to layer VI at 3 weeks after transplantation. Current source-density analysis of the field potentials and intracellular analysis of the synaptic potentials in the cortical cells demonstrated that geniculocortical connections were broadly established in layers II-VI at 1 week after transplantation, and were localized to layer IV and VI at 3 weeks after transplantation. These results suggest that the development of neural connections between transplanted LGN and host VC is characterized by an initial broad distribution of afferent and efferent connections without laminar specificity, and by later selection of appropriate connections to yield lamina-specific connections comparable to those in normal adult VC.

Action Potentials↗
PubMed1993

Hairy cells from hairy cell leukemia patients presenting with pronounced polyclonal hypergammaglobulinemia secrete a factor enhancing IgG synthesis.

We studied the immunological function of hairy cells from hairy cell leukemia (HCL) patients presenting with pronounced polyclonal hypergammaglobulinemia (PPH). Hairy cell conditioned medium (HCCM) obtained from HCL patients with PPH augmented IgG production by normal peripheral blood mononuclear cells in a dose-dependent fashion, while HCCM from patients without PPH had no effect on IgG production. HCCM from the patients with PPH failed to enhance IgG synthesis by T cell-depleted mononuclear cells. Separation of T and B cells by a 0.4-microns membrane as well as monoclonal antibodies to HLA-DR and CD3 molecules prevented HCCM-dependent IgG synthesis. No B cell growth factor activity, interleukin-1, or interleukin-6 was detected in the HCCM. On examination by fractionation of the HCCM, IgG-inducing activity was detected in the fractions of 5000 to 8000 Da. These results indicate that hairy cells from HCL patients with PPH secrete a factor inducing IgG synthesis, and that the induction of IgG synthesis by the factor requires T-B cell interactions involving T cell receptor/CD3 complex and MHC class II antigens. This factor may play an important role in the development of PPH.

B-Lymphocytes↗