Biomedical subjects
M Miyazawa
Publications and source records attributed to M Miyazawa.
[Noninvasive regional cerebral blood flow measurements by 99mTc-HMPAO using only three-head SPECT system].
A special bed and a new software program were developed for noninvasive regional cerebral blood flow (rCBF) measurements by 99mTc hexamethylpropylene amine oxime (99mTc-HMPAO) using only three-head SPECT system, Siemens MULTI-SPECT3. A large field gamma camera with a minimum of 38 cm-diameter is required for simultaneous acquisition of time activity curves of brain and aortic arch in this noninvasive method. A special bed with short width was designed and inserted obliquely into the gantry of the SPECT system to acquire both time activity curves of brain and aortic arch with the use of diagonal length (51 cm) of a gamma camera with 31 x 41 cm width. Moreover a software program was developed for processing a series of the graphical analysis of time activity curves, Lassen's linearization correction of SPECT images, and drawing of a rCBF map. This noninvasive rCBF measurement using only MULTISPECT3 in a short period with high spatial resolution is quite useful for routine clinical studies.
Comparative study of cutaneous T-cell lymphoma and adult T-cell leukemia/lymphoma.
An important disease entity distinct from cutaneous T-cell lymphoma (CTCL) in Japan is adult T-cell leukemia/lymphoma (ATL), which shows almost the same phenotype as CTCL, ie, a helper/inducer T-cell phenotype (CD4-positive, CD8-negative), and usually involves the skin. This article describes differences between CTCL and ATL in terms of clinical and immunopathologic cell surface features. In patients with ATL, the predominant physical findings were lymph node, bone marrow and skin involvement, hepatosplenomegaly, leukemic manifestations, and an aggressive course. In patients with CTCL, in contrast, only skin lesions predominated at the onset of the disease and a relatively good prognosis was shown. The predominant phenotype of the neoplastic cells in the skin of patients with CTCL was CD3+, CD4+, CD29+, CD45RO+, HLA-DR+, HLA-DQ+, CD7-, L-selectin-, and CD45RA-. Some phenotypic discrepancy was found between the neoplastic cells in the peripheral blood, lymph nodes and skin of patients with ATL with respect to CD45RA and CD45RO, and CD7, CD29, CD25, and HLA-DR. That is, the predominant neoplastic cell phenotype was helper T-cell, which was CD3+, CD4+, L-selectin+, CD25+, CD45RA+, HLA-DR+, CD29-, and CD45RO- in peripheral blood, and CD3+, CD4+, L-selectin+, CD29+, CD45RO+, HLA-DR+, and CD45RA- in the skin and lymph nodes. Phenotypic heterogeneity of ATL cells and heterogeneity of CD45R isoform expression on ATL cells were evident in different organs. These findings confirm that the difference in antigen expression on the cell surface might reflect the clinical features of ATL and CTCL. CTCL cells do not share the same phenotype as ATL cells.
Interstitial nephritis in Aleutian mink disease. Possible role of cell-mediated immunity against virus-infected tubular epithelial cells.
Aleutian mink disease (AD) has been characterized by immune complex glomerulonephritis associated with persistent infection of Aleutian mink disease parvovirus (ADV). Histopathological examination of kidneys from ADV-infected mink in this study revealed that interstitial nephritis characterized by prominent damage of renal tubuli and lymphocyte infiltration was also common in AD along with glomerulonephritis. By using strand-specific in situ molecular hybridization technique, replication of ADV was observed in tubular epithelial cells, in addition to epithelial cells of Bowman's capsules and some glomerular cells of the infected mink. Analysis of tubular lesions by a combination of immunohistochemistry and in situ hybridization revealed that the renal tubuli positive for virion DNA or replicative form DNA/mRNA of ADV were also positive for an activation marker of immunocompetent cells, which is shared by B lymphocytes and thymic epithelial cells. Infiltration of a subpopulation of T lymphocytes around infected renal tubuli were observed but deposition of immune complexes in these tubular lesions was not demonstrable. ADV replication in epithelial cells of renal tubuli and cell-mediated immune responses to the infected epithelial cells may play a role in the pathogenesis of interstitial nephritis in Aleutian mink disease.
Immunoelectron microscopic localization of transforming growth factor beta 1 and latent transforming growth factor beta 1 binding protein in human gastrointestinal carcinomas: qualitative difference between cancer cells and stromal cells.
Transforming growth factor beta 1 (TGF-beta 1) is secreted as an inactive complex associated with latent TGF-beta 1 binding protein (LTBP). Tissue localization of these proteins has not been fully understood in human pathological conditions. We examined the immunohistochemical localization of TGF-beta 1 precursor (proTGF-beta 1) and LTBP in carcinomas and granulation tissue in the human gastrointestinal tract at the light and electron microscopic levels. In normal tissue, endothelial cells and granulocytes sporadically showed immunoreactivity for proTGF-beta 1, while epithelial cells were all negative. In cancer tissue, both cancer cells and stromal cells (fibroblasts, macrophages, and endothelial cells) were positive for proTGF-beta 1, more frequently in diffuse-type gastric carcinomas than in differentiated-type adenocarcinomas. Immunoelectron microscopy revealed that proTGF-beta 1 was localized in rough endoplasmic reticulum and perinuclear cisternae in fibroblasts, macrophages, and endothelial cells in cancer stroma and in fibrous granulation tissue. In contrast, the intracellular localization of proTGF-beta 1 in carcinoma cells was predominantly observed in the cytosol (cytoplasmic matrix). This finding suggests disarranged or blocked intracellular transportation of proTGF-beta 1 in cancer cells. The immunoreactivity for LTBP was not observed in the normal epithelial cells. It was localized in cancer stroma, not in cancer cells. Ultrastructurally, LTBP was located in the extracellular matrix around fibroblasts and smooth muscle cells. The intracellular immunoreactivity for LTBP was observed in rough endoplasmic reticulum of fibroblasts and smooth muscle cells, the same as in granulation tissue. These results suggest that gastrointestinal carcinoma cells produce no or a small amount of LTBP in vivo. Our investigation suggests that extensive fibrosis in both cancer stroma and granulation tissues may be promoted by TGF-beta 1 mainly secreted from stromal cells.
Subacute panencephalitis associated with chronic graft-versus-host disease.
A unique form of subacute panencephalitis developed in a child with aplastic anemia 8 months after an allogeneic bone marrow transplantation (BMT). It was characterized by parenchymal infiltration of CD3 lymphocytes, a marked increase in the number of microglia strongly expressing HLA-DR antigens in both the gray and white matter, and diffuse degeneration of the cerebral white matter. The onset of neurological symptoms coincided with the development of chronic systemic graft-versus-host disease (GVHD). Cellular infiltrates in the CNS lesions were exclusively CD3 lymphocytes intermingled with a small number of monocytes labeled with CD68. There was a preponderance of cells of the CD45RB phenotype. The pathological changes in visceral organs were consistent with those of chronic GVHD. In addition, scrutiny of immunohistochemistry disclosed sparse infiltration of CD3 lymphocytes and diffuse gliosis in the cerebral white matter of another child with chronic GVHD who died 9 months after allogeneic BMT. These cases are suggestive of a potential risk of CNS involvement in GVHD.
Successful treatment of adult T-cell leukemia/lymphoma with MACOP-B, M-FEPA and VEPP-B combination chemotherapy.
A 45-year-old man was referred to our department in March of 1989. Physical examination showed erythroderma, palmo-plantar hyperkeratosis, generalized lymphadenopathy, hepatosplenomegaly, and leukemic manifestation. The lymphocyte count in the peripheral blood before treatment was 1.7 x 10(4) cells/mm3. Atypical lymphocytes such as flower cells and lobulated cells were seen in the peripheral blood. A sample excised from a lymph node showed immunoblastic, pleomorphic T cells by a modified classification scheme of the Working Formulation. A high level of serum LDH was detected (2.1 times the upper normal limit). Anti HTLV-1 antibody was also detected in the serum. The atypical lymphocytes were positive for CD3, CD4, CD5, CD7 and HLA-DR, and negative for CD8. Thus, the clinical, pathologic and immunologic features were those of typical acute-type ATL. The patient was treated with VEPA-M for three months starting in March of 1989. Because of poor response, the patient was then treated with MACOP-B, M-FEPA, and VEPP-B for about one year from June of 1989 and has been free of disease up to the time of writing, March of 1993.
A case of cutaneous B-cell lymphoma with a storiform stromal reaction.
A case of cutaneous B-cell lymphoma is described. The patient was treated only by surgical excision of the skin tumors five times during a period of about two years from February of 1984 to October of 1986. After the last surgical excision, a continuous disease-free period was achieved. Biopsy samples showed dense lymphocytic infiltrations with discrete masses in the dermis and subcutis; one of them showed a storiform pattern. At the time, the infiltrating cells were composed of medium and large lymphoid cells and spindle-shaped cells. The medium and large lymphoid cells were positive for CD20, CD22 and HLA-DR and negative for CD3, CD4, CD5, CD8, CD43, and kappa and lambda light chain. The spindle-shaped cells were negative for CD20, CD43, kappa and lambda light chain, lysozyme, and S-100 protein.
A case of cutaneous B-cell lymphoma treated successfully with MACOP-B.
A case of cutaneous B-cell lymphoma successfully treated by MACOP-B therapy is described. The patient was a 43-year-old man with reddish tumors measuring 3 to 7 cm in diameter on the right cheek and the post-auricles. Histopathologically, massive infiltrations of medium-sized atypical lymphoid cells were found in the reticular dermis and subcutis. A clear zone beneath the epidermis was also detected. The atypical lymphoid cells were positive for CD19, CD20, CD22 and HLA-DR but negative for CD3, CD4, CD5, CD10, CD43, CD45RO and CDw75. The patient was treated successfully with the MACOP-B protocol from March of 1990 to May of 1990. Since April of 1990, he has been free of disease.
Cutaneous B-cell lymphoma--a clinical, pathological and immunohistochemical study.
Eleven cases of cutaneous B-cell lymphoma (CBCL) were studied. The ages at presentation ranged from 34 to 79 years (mean = 59.9 years). Six patients were female and five male. Five of the 11 patients had a solitary tumour and the other six had multiple tumours at initial presentation. According to Burg's classification, six cases were at stage I, two stage II, two stage III and one was at stage IV at initial presentation. Abnormalities in laboratory data were rare, except for serum lactic dehydrogenase values. Epidermotropism was not detected, and the area mainly affected by neoplastic cells was the reticular dermis (seven cases) and subcutis (four cases). Biopsy specimens from the patients analysed by immunohistochemical techniques on paraffin or cryostat sections showed CD20 and/or CD22 positivity. Biopsy specimens from two patients which showed CD10 positivity were diffuse large cell types by the working formulation and presented as pre-B-cell lymphoma. At least two groups of CBCL were demonstrable on the basis of prognosis. One was a benign low-grade lymphoma presenting with solitary tumours, mature B-cell markers and intermediate-grade pathology, and the other was a high-grade lymphoma with multiple tumours, pre-B-cell or mature B-cell markers and a poor prognosis.
Cutaneous B-cell lymphoma consisting of large cleaved cells with multilobated nuclei.
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A macrophage differentiating factor derived from human T cell line HUT102 acting on a mouse myeloid cell line M1.
Human T cell leukemia virus type I-transformed T cell line HUT102 constitutively secreted soluble factors which induced differentiation of a murine myeloid leukemic cell line, M1, to increase the immune complex-binding and/or phagocytizing capacity. This macrophage differentiating factor(s) (MDF) was purified from the culture supernatants of HUT102 cells by using several steps of column chromatography and novel immune-adherence and/or immune-phagocytic assays. The finally purified MDF activity was detected in the fraction that consisted of 40,000- and 45,000- molecular weight molecules. Antibodies specific for human interleukin-6 or for human granulocyte-colony stimulating factor, both of which have differentiation-inducing activity on M1 cells when used as a single factor, could not neutralize the MDF activity. These findings suggest that the 40,000- and/or 45,000- molecular weight molecules in the HUT102 cell products may be possible novel differentiation-inducing factors acting on a murine macrophage lineage across the species barrier.
Oxygen transport capacity and hemodynamic effect of newly developed artificial blood "Neo Red Cells (NRC)".
The purpose of this study was to evaluate liposome-encapsulated hemoglobin, named Neo Red Cells (NRC), on hemodynamics and oxygen-transport capacity in a blood exchange experiment. The experiment was carried out in nine mongrel dogs. Depending on the percentage of blood exchange with NRC, the animals were divided into two groups; Group I (4 animals with an exchange rate less than 88%), and Group II (5 animals with an exchange rate over 88%). After blood exchange, total peripheral vascular resistance index (TPRI) decreased and cardiac index (CI) increased. These changes were more marked in Group II than in Group I, thus showing that NRC relieved the burden on the heart, probably due to the fact that the viscosity of NRC is 2 cp which is less than 1/3 that of whole blood. The oxygen binding capacity per 1g hemoglobin in NRC was 2-4 times as much as red blood cells. Thus, NRC was superior to natural red blood cells in terms of oxygen transport capacity and its effects on the circulatory system.
Spontaneous recovery from Friend retrovirus-induced leukemia. Mapping of the Rfv-2 gene in the Q/TL region of mouse MHC.
The Rfv-2 gene that influences the rate of spontaneous recovery from erythroleukemia induced by a low dose of Friend retrovirus complex was mapped to the Q/TL region of mouse MHC. Rfv-2 was physically and functionally distinct from the I-A-linked Ir gene that has been shown to control the responsiveness of Th cells to the envelope glycoprotein of Friend murine leukemia helper virus. The negative effect of the Rfv-2s allele was overcome by the B10.D2-H-2dm1 mutation of the D-L genes of H-2, suggesting functional similarities between the D-L and Q/TL genes in influencing resistance against Friend murine leukemia retrovirus complex infection or possible modification of Q/TL expression by genes in the D-L region.
Influence of MHC genes on spontaneous recovery from Friend retrovirus-induced leukemia.
Genes influencing the rate of spontaneous recovery from erythroleukemia induced by a low dose of Friend virus complex were located in the right and left portions of the mouse MHC. The right side gene was most likely the previously described Rfv-1 in the H-2D region. Using the B6.C-H-2bm12 mutant mice, the left side gene was mapped to the A beta class II locus. The A beta b was a resistant allele and A beta k and A beta bm12 were susceptible alleles. Genes at this class II locus controlled the responsiveness of Th cells to envelope glycoprotein of Friend murine leukemia helper virus and affected the class switching of virus-neutralizing antibodies from IgM to IgG in FV-infected mice.
Use of low toxicity adjuvants and killed virus to induce protective immunity against the Friend murine leukaemia retrovirus-induced disease.
Low toxic and synthetic adjuvants were investigated in the induction of protective immunity against Friend murine retrovirus-induced erythroleukaemia by immunization with inactivated Friend murine leukaemia helper virus (F-MuLV). 6-O-(2-tetradecyl-hexadecanoyl)-N-acetylmuramyl-L-alanyl-D-isoglutamine (B30-MDP) showed a significant enhancement of the protective immunity against Friend virus-induced erythroleukaemia not only in H-2a/b mice known to make good immune responses to F-MuLV envelope, but also in H-2a/a mice which are usually unable to respond to F-MuLV envelope protein. Another analogue of N-acetylmuramyl-D-isoglutamine (MDP), N alpha-acetylmuramyl-L-alanyl-D-isoglutaminyl-N epsilon-stearoyl-L-lysine [MDP-Lys(L18)], which has been shown to enhance non-specific protective activity against bacterial and viral infections, however, showed no adjuvant activity in the present system. A combined adjuvant of the synthesized mycobacterial cord factor, trehalose dimycolate (TDM) and detoxified bacterial endotoxin, monophosphoryl lipid A from Salmonella minnesota, gave good protection which was comparable to complete Freund's adjuvant in both H-2a/b and H-2a/a mice.
Adult T-cell leukemia/lymphoma (ATL)--clinical, histopathological, immunological and immunohistochemical characteristics.
Twenty-one patients with ATL were assessed. The predominant physical findings were lymph node and bone marrow involvement, skin involvement, hepatosplenomegaly and leukemic manifestations. The predominant histopathological findings in both skin and lymph node specimens were the diffuse medium-sized cell type and the diffuse mixed cell type. Some phenotypic discrepancy was found between the neoplastic cells in the peripheral blood, lymph nodes and skin of patients with ATL with respect to CD45RA and CD45RO, and CD7, CD29, CD25 and HLA-DR. That is, the predominant neoplastic cell phenotype was the helper T-cell, which was CD3+, CD4+, CD7+, CD25+, CD45RA+ and HLA-DR+, and CD29- and CD45RO- in peripheral blood and lymph nodes, and CD3+, CD4+, CD7+, CD29+, CD45RO+ and HLA-DR+, and CD45RA- in the skin. In other words, we have described the phenotypic heterogeneity of ATL cells and demonstrated the heterogeneity of CD45R isoform expression on ATL cells in different organs--the skin, peripheral blood and lymph nodes--of the same patient.
Detailed mapping of the Rfv-1 gene that influences spontaneous recovery from Friend retrovirus-induced leukaemia.
Using H-2 recombinant and mutant mice, the Rfv-1 gene influencing spontaneous recovery from Friend retrovirus (FV)-induced leukaemia was mapped in the D locus. Two Db alleles were required for full recovery, and a single Dd transgene did not convey increased susceptibility to FV in the presence of homozygous Db/b genotype. The results suggest that an increase in the expression of Db may lead to more effective stimulation of FV-specific CTL.