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Biomedical subjects

M Takeya

Publications and source records attributed to M Takeya.

At least 109 records · Page 6Linked to original sources
PubMed1992

Development, differentiation, and proliferation of epidermal Langerhans cells in rat ontogeny studied by a novel monoclonal antibody against epidermal Langerhans cells, RED-1.

An antirat monoclonal antibody (mAb) against nonlymphoid dendritic cells, RED-1, was produced using epidermal Langerhans cells (LCs) as the immunogen. This mAb reacted mainly with the LCs and indeterminate dendritic cells (ICs), interdigitating cells in the T cell areas of lymphoid tissues, and monocyte/macrophages in various organs and tissues of adult rats. In the epidermal sheets prepared from adult rats, it specifically recognized the cell surface antigen(s) present on LCs and ICs. In the fetal rat skin, primitive or fetal macrophages migrated into the epidermis and expressed RED-1 at fetal day 17. With advance of gestation, RED-1-positive cells increased, started expressing Ia antigens at fetal day 18, and subsequently differentiated into dendritic cells. Most of them showed Ia expression by fetal day 20 and differentiated into LCs within a few days after birth. The labeling index of 5-bromo-2'-deoxyuridine in RED-1-positive cells was 18% at fetal day 17 and decreased to 5 to 6% in the postnatal period. These results imply that proliferative capacity of RED-1-positive cells is important for the formation and expansion of the IC population in the fetal stage and for the survival of LCs in the postnatal period.

Aging↗
PubMed1992

Ontogenic development of macrophage subpopulations and Ia-positive dendritic cells in fetal and neonatal rat spleen.

Development, differentiation, and distribution of macrophage subpopulations and Ia+ dendritic cells in the fetal and neonatal rat spleen were investigated by means of double immunohistochemical staining and immunoelectron microscopy. To characterize these cell populations, a panel of anti-rat macrophage monoclonal antibodies (RM-1, ED2, ED3, TRPM-3, Ki-M2R) and an anti-rat Ia antibody (OX6) were used. In the fetal rat spleen, macrophages were first detected by RM-1 at fetal day 15. ED2+ and/or Ki-M2R+ macrophages appeared at fetal day 16. TRPM-3+ and/or ED3+ macrophages appeared a day later. During the fetal and neonatal development, ED2+ and TRPM-3+ macrophages differentiated independently, maturing into red pulp macrophages and marginal metallophilic and marginal zone macrophages respectively. Intimate topographical relations were observed between ED2+ macrophages and hematopoietic cells and between TRPM-3+ macrophages and marginal zone lymphocytes. Ia+ cells were first observed around arterioles at fetal day 15. In the fetal and neonatal period, the number of Ia+ cells gradually increased, their shape became dendritic, and they matured into interdigitating cells in the inner periarteriolar lymphatic sheath. In ontogeny, Ia+ dendritic cells were not stained with ED2 or TRPM-3. These results suggest that ED2+ macrophages, TRPM-3+ macrophages, and Ia+ dendritic cells are distinct cell lines that pursue independent developmental process in spleen ontogeny.

Age Factors↗
PubMed1992

Human T-cell leukemia virus-1-positive cell line established from a patient with small cell lung cancer.

A stable cell line, KHM-3S, was established from a patient with small cell lung cancer (SCLC), who had a high serum level of soluble interleukin 2 receptors (sIL2-R) and was seropositive for human T cell leukemia virus (HTLV)-1. KHM-3S cells were positive for IL2-R (Tac) and NKH-1, but negative for other lymphocytic markers such as OKT 11, OKT 4, OKT 8, T cell receptor (WT 31), B 1, and B 4. Moreover, the KHM-3S cells were negative for leukocyte common antigen and strongly positive for neuron-specific enolase (NSE). Secretion of sIL2-R and NSE by the KHM-3S line was detected by an enzyme-linked immunosorbent assay. Rearrangement of the T cell receptor gene and monoclonal HTLV-1 integration were found by Southern blot analysis of KHM-3S DNA. However, Northern blot analysis showed no T cell receptor mRNA. KHM-3S may be useful for studies on the role of HTLV-1 in carcinogenesis and IL2-R expression in SCLC.

Antigens, Surface↗
PubMed1992

Effect of macrophages on proliferation of granulosa cells in the ovary in rats.

The effect of macrophages on proliferation of granulosa cells was examined in gonadotrophin-primed immature female rats. The mouse anti-rat macrophage monoclonal antibodies TRPM-2 and TRPM-3 were used and macrophages were observed in the granulosa layer and antrum of follicles and in corpora lutea and stroma around follicles. There was no difference in distribution between TRPM-2-positive cells and TRPM-3-positive cells. Macrophages with some cytoplasmic vacuoles of various sizes were also demonstrated in growing follicles. The average ratios of macrophages to granulosa cells in preantral, antral and mature follicles were 0.008, 0.007 and 0.002, respectively. Labelling with [3H]thymidine of granulosa cells cultured with peritoneal macrophages was significantly greater and the labelling index peaked to 25.0% when the ratio of macrophages to granulosa cells was 0.01, compared with the value of 14.2% when the granulosa cells were cultured alone. This ratio of macrophages to granulosa cells was similar to that in the preantral and antral follicles in vivo. These results suggest that macrophages participate in promoting proliferation of granulosa cells as local mediators in growing follicles.

Animals↗
PubMed1992

Alpha-fetoprotein-producing pancreatic cancer--a case report and review of 28 cases.

The case of a female patient with an alpha-fetoprotein (AFP)-producing acinar cell carcinoma of the pancreas is reported, and 28 cases in the literature are reviewed. In our case, the serum AFP level declined drastically after removal of the tumor, but increased when widespread metastases appeared. AFP was detected in the cytoplasm of the cancer cells by immunohistochemical staining. Immunoelectron microscopic studies revealed AFP on the endoplasmic reticulum of the cancer cells. Of the 28 cases with AFP-producing pancreatic cancer, liver metastases were identified in 21 cases (76% overall). There was no correlation between the serum AFP level and liver metastases. Immunohistochemical studies revealed localization of AFP at the primary lesion in 6 out of eight cases tested. In cases of AFP-producing pancreatic cancer, serum AFP levels are useful for the diagnosis and as a marker for evaluating recurrent disease and therapeutic response, and for the management of gastrointestinal disease it should be remembered that some pancreatic cancers produce AFP.

Adenocarcinoma↗
PubMed1991

Production and characterization of mouse monoclonal antibodies against human monocyte chemoattractant protein-1.

We developed five different hybridoma cell lines that produced mAb against human monocyte chemoattractant protein-1 (MCP-1). The subclass of all five antibodies was IgG1. All five mAb formed complexes with metabolically labeled MCP-1 that could be demonstrated by immunoprecipitation. The antibodies were specific for MCP-1. They did not cross-react by immunoprecipitation with structurally related host defense cytokines present in metabolically labeled PHA- or LPS-stimulated mononuclear cell culture fluids, nor did they cross-react in a direct ELISA with neutrophil attractant/activation protein-1, with crude platelet lysate proteins, or with pure platelet proteins that have amino acids sequences similar to that of MCP-1. The mAb also reacted with rMCP-1 expressed in Escherichia coli, suggesting that they recognize protein structure rather than the glycosylated portion of human MCP-1. When the mAb were mixed with MCP-1, the monocyte chemotactic response to MCP-1 was inhibited. A sandwich ELISA was developed to detect MCP-1 in biologic fluids containing relatively high concentrations of other proteins. The sensitivity was 300 pg/ml, or 30 pg/ELISA well. An anti-MCP-1 mAb column was used in an improved method of MCP-1 purification. Approximately 240 micrograms of MCP-1 were purified from 5 liters of FCS-containing U-105MG cell culture supernatant. The yield was at least 60%. In addition to two forms of MCP-1 reported previously by us, two more forms of MCP-1 were found in a mixture of culture supernatants of PHA- and LPS-stimulated human PBMC.

Animals↗
PubMed1991

Molecular cloning of rat monocyte chemoattractant protein-1 (MCP-1) and its expression in rat spleen cells and tumor cell lines.

Rat monocyte chemoattractant protein-1 (MCP-1) cDNA was cloned. A cDNA library was constructed from mRNA extracted from Con A-stimulated rat spleen cells. After 2 rounds of screening with a radiolabeled oligonucleotide probe and DNA sequencing from plasmid DNAs, one clone which encoded for MCP-1 was obtained. The cDNA clone comprises 665 base pairs with an open reading frame which encodes for 148 amino acid protein. Spleen cells expressed a significant amount of MCP-1 mRNA without stimulus. But higher expression was observed when cells were stimulated with Con A. MCP-1 mRNA was also expressed in tumor cell lines, although the amount of expressed MCP-1 mRNA was different among cell lines.

Amino Acid Sequence↗
PubMed1991

A new monoclonal antibody, PM-2K, specifically recognizes tissue macrophages but not blood monocytes.

A new monoclonal antibody, PM-2K, was raised against 24-h cultured human peritoneal macrophages. Immunohistochemically, PM-2K recognized most tissue macrophages in lymphoreticular organs such as the thymus, spleen, lymph node, and tonsil. Kupffer cells of the liver, alveolar macrophages, and macrophages in the interstitial tissue of the kidney, pancreas, and many other organs were also positively labelled. On the other hand, PM-2K failed to recognize blood monocytes, freshly isolated peritoneal macrophages, microglial cells, osteoclasts, and dendritic cells such as Langerhans cells, interdigitating cells, and follicular dendritic cells. In various pathological conditions, PM-2K labelled a wide variety of proliferating macrophages. Reaction products of PM-2K were observed by immunoelectron microscopy on the cytoplasmic membrane of cultured peritoneal macrophages. The molecular weight of the antigen recognized by PM-2K was determined to be 150 kD by Western blotting. As no cells other than macrophages were reactive with PM-2K, this antibody is considered to be very useful not only in the investigation of macrophage differentiation and maturation, but also in the diagnosis of various proliferative disorders of macrophages.

Animals↗
PubMed1991

Production of monocyte chemoattractant protein-1 by malignant fibrous histiocytoma: relation to the origin of histiocyte-like cells.

Human malignant fibrous histiocytoma (MFH) comprise both fibroblast-like cells and histiocyte-like cells. We previously showed that the latter are not neoplastic cells, but are infiltrating macrophages. Since migration of blood monocytes into the tumor might be a response to a locally elaborated monocyte chemoattractant, we designed experiments to determine if the fibroblast-like tumor cells produced a chemoattractant for human monocytes. Malignant fibrous histiocytoma from three patients was put into culture. Cells of all three lines had a spindle shape, and showed no reactivity with antibodies against macrophages (MAC387), HLA-DR (LN3), or leukocyte common antigen. Immunohistochemically, they stained with antibody against human monocyte chemoattractant protein-1 (MCP-1). Culture supernatants of the three cell lines had chemotactic activity for monocytes. This activity was due to MCP-1, since it was absorbed by an anti-MCP-1 column. The production of MCP-1 by MFH tumor lines was confirmed by immunoprecipitation of metabolically labeled MCP-1. These results suggest that the histiocyte-like cells are the infiltrated macrophages that originate from blood monocytes attracted by tumor-derived MCP-1.

Chemokine CCL2↗
PubMed1991

Immunohistochemical characterization of multinucleated giant cells in the brain of a Japanese AIDS patient.

In an autopsy case of a 35-year-old Japanese hemophiliac with acquired immune deficiency syndrome (AIDS), many multinucleated giant cells (MGCs) were observed throughout the central nervous system. Immunohistochemically, MGCs possessed surface and cytoplasmic macrophage antigens expressed in the late stage of differentiation indicating them to be macrophages in the terminal stage of differentiation. Fine nuclear extensions connecting one nucleus (or lobe) to another were often observed in the MGCs. This feature was interpreted as multilobulation and considered to be a morphological characteristic of MGCs in AIDS encephalopathy. Similarity between MGCs in AIDS encephalopathy and highly lobulated lymphocytes in adult T cell leukemia is discussed.

AIDS Dementia Complex↗
PubMed1991

Histopathologic pulmonary changes from mechanical ventilation at high peak airway pressures.

We investigated the histopathologic pulmonary changes induced by mechanical pulmonary ventilation (MV) with a high peak airway pressure and a large tidal volume in healthy baby pigs. Eleven animals were mechanically ventilated at a peak inspiratory pressure (PIP) of 40 cm H2O, a respiratory rate (RR) of 20 min-1, a positive end-expiratory pressure (PEEP) of 3 to 5 cm H2O, and an FIO2 of 0.4. High airway pressure MV was terminated in 22 +/- 11 h because of severe hypoxemia in the animals. Five of the baby pigs were killed for gross and light microscope studies. The pulmonary changes consisted of alveolar hemorrhage, alveolar neutrophil infiltration, alveolar macrophage and type II pneumocyte proliferation, interstitial congestion and thickening, interstitial lymphocyte infiltration, emphysematous change, and hyaline membrane formation. Those lesions were similar to that seen in the early stage of the adult respiratory distress syndrome (ARDS). The remaining six animals were treated for 3 to 6 days with conventional respiratory care with appropriate ventilator settings. Prominent organized alveolar exudate in addition to lesions was also found in the five animals. These findings were indistinguishable from the clinical late stage of ARDS. Six control animals were mechanically ventilated at a PIP of less than 18 cm H2O, a RR of 20 min-1, a PEEP of 3 to 5 cm H2O, and an FIO2 of 0.4 for 48 h. They showed no notable changes in lung functions and histopathologic findings. Aggressive MV with a high PIP is often applied to patients with respiratory distress to attain adequate pulmonary gas exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Differentiation and maturation of macrophages into interdigitating cells and their multicellular complex formation in the fetal and postnatal rat thymus.

Three mouse anti-rat macrophage monoclonal antibodies, TRPM-1, TRPM-2, and TRPM-3, as well as anti-rat Ia monoclonal antibody, were used to study the emergence, differentiation, and maturation of macrophages in the fetal and postnatal rat thymus immunohistochemically and immunoelectron microscopically. At 14 days of gestation, primitive/fetal macrophages entered the thymic primordium and showed Ia expression, where afterwards the epithelial cells also expressed Ia antigens prominently at 15 days of gestation. After 16 days of gestation, differentiation of a subpopulation of primitive/fetal macrophages into interdigitating cells (IDCs) is suggested. From 19 days of gestation, TRPM-1-positive dendritic cells including IDCs started forming multicellular complexes with thymocytes and the epithelial cells also formed similar complexes with thymocytes. One day after birth, TRPM-1 positive IDC-thymocyte complexes distributed throughout the thymic medulla. The number of TRPM-1- and Ia-positive IDCs increased by day, and Langerhans cells (LCs) appeared in the thymic medulla within a few days after birth. By two weeks after birth, the distribution pattern of Ia- and TRPM-1-positive cells became similar to that of adult rats. In ontogeny, intimate cell membrane appositions were frequently observed between thymocytes and Ia-positive epithelial cells or IDCs in the thymic multicellular complexes. These complexes were discriminated into two types; epithelial cell-thymocyte complexes and IDC- or LC-thymocyte ones. In vitro, two types of the thymic nurse cells (TNCs) were identified: epithelial cells and IDCs or LCs. Besides epithelial cells, IDCs or macrophages formed rosettes with thymocytes. These TNCs and rosettes in vitro seem to correspond to the thymic multicellular complexes in vivo.

Animals↗
PubMed1991

[Non-secretory primary plasma cell leukemia with hyperammonemia].

A 78-year-old man was admitted because of lumbago and chest pain. A diagnosis of non-secretory primary plasma cell leukemia was made based on the laboratory findings and his history. However, the plaque-forming cells assay of bone marrow cells revealed secretion of monoclonal immunoglobulin from the myeloma cells. Hyperammonemia was detected in the serum. Although the patient was treated with 4 courses of combination chemotherapy (vincristine, adriamycin, cyclophosphamide, methylprednisolone), he died of respiratory failure five months after diagnosis. Autopsy showed widespread multiple myeloma and prominent infiltration of myeloma cell in the sinusoid of the liver. Recently, there have been a few reports which increased the plasma ammonia concentration with multiple myeloma. This report strongly suggested that liver infiltration of myeloma cell caused hyperammonemia.

Aged↗
PubMed1990

Ontogenetic development of synovial A cells in fetal and neonatal rat knee joints.

Ontogenetic development of the synovial A cells in fetal rat knee joints was investigated by immunohistochemistry, immuno-electron microscopy, cultivation, and autoradiography. At day 17 of gestation, immature macrophages were first seen in the articular interzone, and thereafter they differentiated into macrophages (synovial A cells), which were found in the synovial intima. The degree of reactivity of macrophages with five monoclonal antibodies increased in the developing synovial membranes of fetal rats as shown by immunohistochemistry. Similar findings were obtained in organ cultures of fetal knee joints. A marked difference of proliferative potential was found between A and B cells during ontogeny. A cells after birth did not incorporate 3H-thymidine in contrast to B cells. Before birth, B cells had a labelling index which was at least five times larger than that of A cells. The results of this study indicate that the synovial A cells are derived from both monocytes and fetal macrophages circulating in peripheral blood and that they differ from the synovial B cells in morphology, differentiation, and proliferative potential.

Animals↗
PubMed1990

Chemically induced transplantable malignant fibrous histiocytoma of the rat. Analyses with immunohistochemistry, immunoelectron microscopy and [3H]thymidine autoradiography.

Malignant fibrous histiocytoma was produced in rats by injection of 9,10-dimethyl-1,2-benzanthracene into their knee joints. The original tumors consisted mainly of fibroblast-like cells and histiocyte-like cells, often intermixed with bizarre giant cells, and they frequently showed the storiform-pleomorphic pattern. By immunohistochemistry, anti-rat macrophage monoclonal antibodies, TRPM-3, RM-1, and Ki-M2R, and anti-rat leukocyte common antigen reacted to the histiocyte-like cells but not to the fibroblast-like cells. By the single cell cloning method, we established six tumor cell lines, none of which reacted with the anti-rat macrophage monoclonal antibodies, possessed any Fc receptors, or conducted immune phagocytosis and Latex particle phagocytosis. The ultrastructure of the cloned tumor cells resembled that of long-term cultured dermal fibroblasts. Collagen production by the tumor cells was demonstrated immunohistochemically with a monoclonal antibody for type I collagen. Inoculation of the cloned tumor cells into rats produced tumors with the histology of malignant fibrous histiocytoma and induced prominent macrophage infiltration. In the rat tumors produced by the inoculation of [3H]thymidine labeled cells, no reactivity of tumor cells with the anti-rat macrophage monoclonal antibodies was observed. Transplantation of the cultured rat tumor cells into nude mice produced tumors similar in histology to the original rat malignant fibrous histiocytoma. Tumor cells in nude mice induced marked macrophage infiltration as detected by immunohistochemistry with the anti-mouse macrophage monoclonal antibody F4/80. No differentiation of tumor cells into macrophages was detected, since no cells were stained with biotinylated anti-rat macrophage monoclonal antibody TRPM-3. By the flash labeling method with [3H]thymidine, infiltrating macrophages in the nude mouse tumors were proved to derive from the bone marrow of the host animals. These results indicate a possible experimental reproduction of malignant fibrous histiocytoma by proliferation of malignant fibroblasts or their related cells in combination with macrophage infiltration.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1990

A monoclonal antibody, RbM2, specific for a lysosomal membrane antigen of rabbit monocyte/macrophages.

An anti-macrophage monoclonal antibody (mAb), RbM2, was produced using thioglycolate-elicited rabbit peritoneal macrophages as immunogen. The immunohistochemical approach revealed an intense reactivity of this mAb to macrophages, particularly those engaged in phagocytosis, in different organs and tissues, and to peripheral blood monocytes. Immunoelectron microscopy demonstrated reaction products of RbM2 in the lysosomes of macrophages and monocytes. This selective reactivity with the mAb was further confirmed in various experiments by endocytosis of Latex particles with different diameters or IgG-coated sheep erythrocytes. The results indicate that RbM2 recognizes a lysosomal membrane antigen of 50,000 molecular weight (MW). In contrast, dendritic cells, such as follicular dendritic cells (FDC) of lymphoid follicles, interdigitating cells (IDC) of lymphoid T zones, or epidermal Langerhans' cells, were not reactive with the antibody. Thus, RbM2 is useful not only in differentiating the phagocytic macrophages from the immunologically accessory dendritic cell populations but also in identifying lysosomes and their related structures in macrophages.

Animals↗
PubMed1989

Amylase-producing multiple myeloma. Cytochemical, immunohistochemical and immunoelectron microscopic studies.

The first autopsy case of amylase-producing IgA-lambda-type multiple myeloma is described. Immunohistochemically, amylase and alpha and lambda chains of immunoglobulin were demonstrated in the cytoplasm of the myeloma cells. Secretion of amylase by cultured myeloma cells obtained from the patient's pleural effusion was clearly demonstrated by the starch film method. Immunoelectron microscopically, positive reaction products for amylase and the alpha chain of immunoglobulin were observed in the well developed endoplasmic reticulum. Since no secretory granules were observed, we postulated that the secretory process of amylase was not via the zymogen granules but via a mechanism similar to that for immunoglobulin.

Amylases↗