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Biomedical subjects

Y Shimosato

Publications and source records attributed to Y Shimosato.

At least 235 records · Page 13Linked to original sources

Large cell carcinoma of the lung associated with marked eosinophilia. A case report.

A case of large cell carcinoma of the lung which produced eosinophil colony stimulating factor and eosinophil chemotactic factor was reported. A 52-year-old Japanese man with a tumor in the left upper lobe of the lung underwent left pneumonectomy. Marked eosinophilia persisted especially after recurrence, with a maximum peripheral leukocyte count of 161,000/mm3, of which 78% consisted of eosinophils. The patient died of pulmonary insufficiency 18 months after surgery. At autopsy, metastatic tumor tissues and almost all organs were markedly infiltrated with eosinophils, especially the spleen, and there was marked proliferation of eosinophils in the bone marrow. Eosinophil colony stimulating factor production by the transplanted tumor in a nude mouse was confirmed by use of a human bone marrow culture assay system. Eosinophil chemotactic factor production by metastatic tumor tissue also was proved by a modified micro-filter technique.

Biological Assay↗

Enolase distribution in human brain tumors, retinoblastomas and pituitary adenomas.

The cellular localization of alpha-, beta- and gamma-subunits of enolase isoenzyme was studied immunohistochemically in various human brain tumors, retinoblastomas and pituitary adenomas (total, 91 cases). The alpha-subunit was found in almost all brain tumors except in medulloblastoma cases. A case of medullomyoblastoma contained beta-subunit-positive myoblastic cells, which was also positive for human myoglobin. The gamma-subunit was frequently observed in medulloblastomas, retinoblastomas and pituitary adenomas. However, gamma-subunit was also present in some non-neuronal brain tumors such as astrocytomas and oligodendrogliomas. Enzyme immunoassay technique also confirmed the presence of gamma-subunit in a medulloblastoma and two retinoblastomas.

Adenoma↗

Six cases of well-differentiated adenocarcinoma simulating fetal lung tubules in pseudoglandular stage. Comparison with pulmonary blastoma.

Six cases of well-differentiated adenocarcinoma resembling fetal lung were studied histologically, immunohistochemically, and ultrastructurally, and compared with three cases of pulmonary blastoma. The six cases had no sarcomatous features, unlike the pulmonary blastoma. Individual tumor cells characteristically possessed clear cytoplasm with plentiful glycogen and were similar to the epithelial cells of the branching tubules in the pseudoglandular stage of the fetal lung, as well as the epithelial component of pulmonary blastoma. They also showed little differentiation toward mucous cells and ciliated cells. Although cells containing endocrine-type granules were not found ultrastructurally, a few tumor cells possessed the characteristics of endocrine cells, i.e., cytoplasm was immunohistochemically reactive with anticalcitonin and antigastrin-releasing peptide. Therefore, this type of adenocarcinoma is considered to have a histogenesis similar to that of pulmonary blastoma and may be a tumor with one-sided development of pulmonary blastoma showing only an epithelial component.

Adenocarcinoma↗

Endobronchial polypoid adenocarcinoma of the lung. Histological and ultrastructural studies of five cases.

Five cases of adenocarcinomas of the lung with predominantly endobronchial polypoid growth in large bronchi were reported. The histology of these cases was well-differentiated papillary adenocarcinoma, the tumor cells of which were columnar (4/5) and cuboidal (1/5). More than 70% of the volume of each tumor grew in the bronchial lumen with neighboring intraepithelial growth. Ultrastructurally the tumor cells were characterized by numerous mitochondria (5/5), some basal bodies (5/5), poorly developed cilia (1/5), and many dilated smooth endoplasmic reticular near the cell surface (2/5); these are features characteristic of ciliated bronchial epithelial cells. There were some mucus-producing cells (3/5), which might be differentiating toward goblet cells. Membrane-bound secretory granules with an electron-dense core or fingerprint appearance were also found (2/5); these resembled Clara cell granules. The above findings suggested that polypoid adenocarcinoma in large bronchi had the ability to differentiate toward bronchial or bronchiolar surface epithelial cells with or without mucus production.

Adenocarcinoma, Papillary↗

Immunologic characterization of Reed-Sternberg cells and other cell components in lymph nodes with Hodgkin's disease.

Seven lymph nodes from patients with Hodgkin's disease were immunologically studied. Histologically these cases consisted of 3 lymphocyte predominance, 2 mixed cellularity, and 2 nodular sclerosis. Positive staining of mononuclear Hodgkin- and multinuclear Reed-Sternberg (RS) cells were obtained with anti-Ia like antigens and OKT9 (anti-transferrin receptor) monoclonal antibodies. No supportive data for discussing similarity of RS cells with ordinary histiocytes, B-lymphocytes or T-lymphocytes were obtained from the study of surface phenotype, although some analogy was present with histiocytes. Small lymphocytes around RS cells were helper/inducer T-lymphocytes, and the relationship between these T lymphocytes and RS cells was discussed.

Adult↗

Heterogeneity of histiocytes in primary lung cancer stained with anti-S100 protein, lysozyme and OKT 6 antibodies.

The heterogeneity of histiocytes in primary lung cancer was investigated by immunohistochemical methods using anti-S100 protein and anti-lysozyme antibodies on paraffin sections and OKT-6 monoclonal antibody on frozen sections. T-zone histiocytes (Langerhans cells and their precursors stained by anti-S100 protein and/or OKT-6 monoclonal antibodies) heavily infiltrated tumor tissues and regional lymph nodes in cases of moderately or well-differentiated adenocarcinoma, especially in areas of papillary growth or bronchiolo-alveolar pattern. These cells were interspersed amongst tumor cells showing dendritic figures and were occasionally present in squamous cell carcinoma. However, they were seldom found in other histological types, particularly in small cell carcinoma and carcinoid tumor. The distribution of these cells was different from that of lysozyme-positive macrophages. In this connection, T-zone histiocytes were thought to have a different immunological function from that of the monocyte-macrophage series against lung cancer. The closely similar reactivity of T-zone histiocytes with anti-S100 protein and OKT-6 monoclonal antibodies indicated that these two markers can be employed for paraffin and frozen sections, respectively.

Adenocarcinoma↗

Interconversion of biological characteristics of small cell lung cancer depending on culture conditions.

Two distinct cell lines were obtained from a single heterotransplanted tumor which had originated from a primary focus of small cell carcinoma of the lung (SCCL). They were maintained separately from the beginning in culture media with and without fetal calf serum supplementation. Cells in the serum-free medium grew mostly floating in loose aggregates and showed poor cell cohesiveness, scanty cytoplasm and a few intracytoplasmic small dense-cored granules; all of these features are characteristics of oat cell type SCCL. On the other hand, cells in the serum-supplemented medium grew mostly floating in flatter and more closely associated clumps, were larger, and showed increased cell cohesiveness, occasional tubular structures, better developed organelles including dense-cored granules, and an increased number of cell attachments; these features are characteristics of intermediate cell type SCCL. The modal number of chromosomes differed from each other. Neuron-specific enolase (gamma enolase) and aromatic L-amino acid decarboxylase (ADC) activities in cell pellets were significantly higher in both lines than in control non-small cell lung cancer cell lines. The alpha/gamma type enolase ratio was lower, as was the ADC activity, in serum-free cultures than in serum-supplemented cultures. Interchange of the culture medium induced changes of the growth pattern and cell type from "oat cell type" to "intermediate cell type" and vice versa. The chromosomal number also partially changed. These findings suggest that cultured cells of SCCL alter their growth pattern and cell type depending on the culture conditions and that the selective growth of one cell type might then take place.

Animals↗

Distribution of blood group antigens A, B, H, and I(Ma) in mucus-producing adenocarcinoma of human lung.

The distribution of blood group antigens A, B, and H and their precursor antigen I(Ma) in the mucus of lung cancer patients was studied histochemically. Antigens A, B, and H compatible with the ABO status of the patients were expressed in the mucus of bronchial gland mucous cells and bronchial goblet cells except in a few patients presumed to be nonsecretors , while antigen I(Ma) was not expressed at all in these cells. In contrast, compatible antigens A, B, and H were decreased or not present in cancer cells but antigen I(Ma) accumulated. Accumulation of antigen I(Ma), which resulted from incomplete synthesis of antigens A, B, and H, was a tumor-associated phenomenon in the mucus of the lung and was found in all patients examined. However, the degree of this accumulation varied from patient to patient, and tumor cells showed marked heterogeneity even in an individual case. In addition, accumulation of antigen associated with loss of antigens A and B was demonstrated in cancer cell mucus of patients with a blood group status other than O. Expression of incompatible blood group antigen reactive with anti-A serum (A-like antigen) also was detected in cancer cell mucus of blood group B patients.

ABO Blood-Group System↗

Monoclonal antibody reactive with the sialyl-sugar residue of a high molecular weight glycoprotein in sera of cancer patients.

A monoclonal antibody, ST-4-39, was obtained by means of a unique immunization procedure using a gastric cancer xenograft as an immunogen. ST-4-39 reacted immunohistochemically with various cancers and a limited number of normal tissues. The antigen reactive with ST-4-39 was detected in sera of cancer patients, and possessed a molecular weight of greater than or equal to 1 X 10(6). The antigenic determinant was a sialyl-sugar residue different from sialyl-Lewis a recognized by NS 19-9.

Antibodies, Monoclonal↗

Histochemically demonstrable changes in cell surface carbohydrates of human germ cell tumors.

Cell surface carbohydrate chains of human germ cell tumors were investigated histochemically using peanut agglutinin (PNA), Dolichos biflorus agglutinin (DBA), Ulex europaeus agglutinin I (UEA-1), and anti-I-(Ma) antibody. Of 16 cases of embryonal carcinoma in adult testis, peanut agglutinin, a lectin specific for terminal beta-galactosyl residues, bound to the surface of tumor cells in 11 cases, D. biflorus agglutinin, a lectin specific for terminal alpha-N-acetyl galactosamine residues, in 10, and U. europaeus agglutinin, a lectin specific for terminal alpha-L-fucosyl residues in 7. I-(Ma) antigen, a branched carbohydrate chain composed of three N-acetyl lactosamine units, was found in 12 cases as well. The cell surface of tubular or organoid architecture tended to be positive for some of these four reagents, whereas that of a papillary pattern tended to be negative. All yolk sac tumors (three in adult testis, 10 in infantile testis, and four in ovary) were positive for peanut and U. europaeus agglutinins and anti-I-(Ma) antibody but were negative for D. biflorus agglutinin. Seventeen of 18 seminomas (in adult testis) and one dysgerminoma (in ovary) did not react with these four reagents. Four choriocarcinomas (three in testis and one in ovary) were not positive for any of them either. In 10 cases of immature teratoma, the appearance of the binding sites to these lectins and antibody depended on the direction of differentiation and the degree of maturity. These findings suggest that carbohydrate chains of human germ cell tumors change greatly in the process of differentiation from embryonal carcinoma cells to somatic cell (teratoid) component or yolk sac carcinoma component, and that histochemical detection of the binding sites described may assist in the classification of germ cell tumors, in spite of the lack of precise knowledge about the biologic role of cell surface carbohydrates.

Adult↗

[Progress and prospect in basic and clinical lung cancer researches].

After looking back upon the progress in both basic and clinical lung cancer researches in the past twenty-some years, what is to come in the future was anticipated. In the diagnostic field, interpretation of chest X-ray films became more accurate, scraping cytology for peripheral carcinoma was developed, and then fiberoptic bronchoscope was devised, all of which contributed to more accurate diagnosis of lung cancer. In lung cancer therapy, extended surgery and bronchoplasty were introduced, resulting in an increase in the 5 year survival rate. Chemotherapy for small cell carcinoma was much improved. Pathologically, adenocarcinoma and squamous cell carcinoma of the peripheral type appear to have increased in incidence. In the field of basic research, both K-ras and myc-oncogenes were found to be amplified in a case of giant cell carcinoma. Several human monoclonal antibodies were produced, each of which has some interesting characteristics. In the future, the results of basic researches will be applied to prevention, diagnosis and therapy, hopefully reducing the morbidity and mortality of lung cancer.

Adenocarcinoma↗

Distribution of blood group antigens and CA 19-9 in gastric cancers and non-neoplastic gastric mucosa.

The distribution of blood group ABH antigens, their precursor I(Ma) antigen, Lewis a antigen and monoclonal antibody-defined tumor-associated antigen CA 19-9 in gastric cancers and their surrounding non-neoplastic mucosa was studied by using immunohistochemical methods. ABH antigens were localized in the foveolar epithelium except for a few cases presumed to be non-secretors, but ABH antigens were lost focally from metaplastic mucosa. In contrast, Lewis a and I(Ma) antigens were present in the foveolar epithelium of non-secretors and metaplastic mucosa where ABH antigens were not detected. Gastric cancers also showed focal loss of ABH antigens and gain of Lewis a and I(Ma) antigens, and the cancer cells showed marked heterogeneity in antigen expression compared with non-neoplastic mucosa. Expression of incompatible blood group antigen (A-like antigen) reactive with monoclonal anti-A antibody was also detected in cancer cells of blood group O and B cases. CA 19-9 (sialylated-Lewis a) was detected in 62% of gastric cancers and in the restricted areas of gastric mucosa where Lewis a was positive.

ABO Blood-Group System↗

Amplification of the c-myc oncogene in human stomach cancers.

Amplified c-myc oncogene was found in the DNAs of 2 of 11 human stomach cancers transplanted into nude mice; the amplification was 8- to 10-fold in one tumor and 13- to 15-fold in the other. Both tumors in which the c-myc oncogene was amplified were poorly differentiated adenocarcinomas, but there was no clear-cut correlation between the histological types or growth rates of the tumors and amplification of the c-myc oncogene. No amplification of the c-myc gene was detected in DNAs from 4 cultured stomach cancer cell lines, 19 primary stomach cancers or 11 metastases to lymph nodes from human stomach cancers.

Adenocarcinoma↗

Multiple primary cancers in 5,456 autopsy cases in the National Cancer Center of Japan.

Multiple primary malignant neoplasms in 5,456 consecutive autopsy cases from 1962 to 1981 in the National Cancer Center were analyzed. There were 285 (5.2%) double primary cancers, 58 (1.1%) triple or more, and 65 (1.2%) minute cancers of the thyroid or prostate gland. Higher incidence of second cancer is observed in cancers of the oropharynx, intestine, larynx, uterus, bladder, and thyroid. Organ association between the two cancers was present in certain organs; for example, there was a tendency for upper gastrointestinal tract cancers to be associated with lower gastrointestinal tract cancers. Influence of histologic subtypes in multiple cancer cases is discussed for lung cancer.

Adult↗

Malignant histiocytosis and Letterer-Siwe disease. Neoplasms of T-zone histiocyte with S100 protein.

Eight cases with malignant histiocytosis (MH), two cases with systemic Letterer-Siwe disease, and one case with sarcomatous variant of MH were studied clinicopathologically. Characterization of neoplastic histiocytes was performed by immunohistochemical staining for S100 protein, lysozyme, and nonspecific cross reacting antigen with carcinoembryonic antigen (NCA). The immunohistochemical characteristics of histiocytes were S100+lys-NCA- in eight MH and two Letterer-Siwe disease cases and S100-lys+NCA+ in the sarcomatous variant of MH. MH and Letterer-Siwe disease were considered to have derived from a specific S100+ histiocytic cell lineage (T-zone histiocyte with S100 protein) independent of the monocyte--macrophage system, from which a sarcomatous variant was derived. Leukemic change of MH was discussed with special reference to the maturation and differentiation of T-zone histiocytes.

Adult↗

Peptide hormone production by adenocarcinomas of the lung; its morphologic basis and histogenetic considerations.

The cell source of peptide hormone production and the morphological differentiation were investigated in 18 adenocarcinomas of the lung by immunohistochemistry and/or by electron microscopy. These tumors were found by radioimmunoassay of tumor extracts to contain either one or more of 7 peptide hormones, i.e. adrenocorticotropin (ACTH), beta- and gamma-melanocyte stimulating hormones (MSH), somatostatin (SS), vasoactive intestinal polypeptide (VIP), gastrin releasing peptide (GRP) and calcitonin (CT). In a combined adeno- and small cell carcinoma, a considerable number of small tumor cells were positively stained for ACTH, beta- and gamma-MSHs and GRP. In a poorly differentiated adenocarcinoma with mucin and CT production, these products were localized in some single cells. Electron microscopy revealed secretory granules indistinguishable from exocrine or endocrine types. In another mucin-positive adenocarcinoma with high SS and CT contents, some tumor cells were stained for SS and/or CT. Two distinct exocrine and endocrine type secretory granules were found in the same cells. In tumors with 100 ng or less of the peptides/g tissue, most tumor cells were not stained for the peptides but a small number showed morphological endocrine differentiation. In conclusion, a considerable proportion of the adenocarcinomas of the lung may show heterogeneous differentiation in both endocrine and exocrine directions.

Adenocarcinoma↗

Production of gastrin releasing peptide by medullary carcinoma of the thyroid. An immunohistochemical study.

Forty medullary carcinomas of the thyroid (MCT) with documented calcitonin (CT) production were studied immunohistochemically for the production of gastrin releasing peptide (GRP), a mammalian counterpart of amphibian bombesin. GRP-positive cells, revealed by an unlabelled peroxidase-antiperoxidase immunoenzyme histochemistry were found in 81% (34/40) of the MCTs. Variable numbers of tumor cells in positive MCTs were immunostained for GRP. In 3 cases with Sipple's syndrome, cells in scattered microscopic MCT nodules and hyperplastic intrafollicular C cells of the thyroid were frequently positive for GRP as well as for CT. Non-neoplastic C cells (or CT-positive cells) of the human thyroids were also positive for GRP. In the neoplastic and non-neoplastic C cell system, some cells were confirmed to be immunoreactive with both anti-GRP and anti-CT. All these findings indicate that GRP and CT are closely associated peptide hormones produced by the C cell system.

Calcitonin↗