Search PubMed⌕ Search

Biomedical subjects

Y Shimosato

Publications and source records attributed to Y Shimosato.

At least 217 records · Page 12Linked to original sources

S-100 protein-positive Langerhans cells in various human lung cancers, especially in peripheral adenocarcinomas.

The appearance of S-100 protein-positive Langerhans cells was studied in 90 cases of various lung cancers by an immunohistochemical method. S-100 protein-positive dendritic cells were frequently observed in many adenocarcinomas, especially in those subclassified as bronchiolar cell or type II alveolar cell type. However, no S-100 protein-positive cells were found in "goblet cell type" adenocarcinoma. In some cases of squamous cell carcinoma and large cell carcinoma, these dendritic cells were also observed though they were fewer in number. In all cases of small cell carcinoma, however, S-100 protein-positive dendritic cells were rare. Electron microscopic study of two adenocarcinomas clearly demonstrated many Birbeck granules in the cytoplasm of S-100 protein-positive dendritic cells and confirmed that S-100 protein-positive cells in lung cancer were identical with Langerhans cells.

Adenocarcinoma↗

Aromatic L-amino acid decarboxylase activities in human lung tissues: comparison between normal lung and lung carcinomas.

We measured the activity of aromatic L-amino acid decarboxylase with L-dihydroxyphenylalanine as a substrate (DOPA decarboxylase) in normal lung tissues and lung tumors obtained fresh at surgery. The activity in control human lung tissues was low and variable: 3.50 +/- 0.42 pmole/min/mg protein (n = 56, mean +/- SE, range 0.01-15), indicating the wide individual variations. Most of small cell carcinoma specimens showed very high activity, as compared with both control lung tissues and with other types of non-SCC lung cancers. Similar results were also obtained in the athymic mice heterotransplants of SCC. High activity was also observed using 5-L-hydroxytryptophan as a substrate (5-HTP decarboxylase) in nine SCC samples. Serotonin was not detected in any control lung tissues, but was detected in all the nine SCC samples, but dopamine was detected only in three out of nine SCC samples.

Animals↗

Blood group A cross-reacting epitope defined by monoclonal antibodies NCC-LU-35 and -81 expressed in cancer of blood group O or B individuals: its identification as Tn antigen.

Two monoclonal antibodies, NCC-LU-35 and NCC-LU-81, have been established after immunization of mice with membrane preparations of human lung cancer Lu65 tumor xenograft cells grown in vivo and intact cells cultured in vitro, respectively. These two antibodies react specifically with a majority of human adenocarcinomas, irrespective of the host's blood group ABO status, as well as with normal tissues and erythrocytes of blood group A individuals. The antigenicity is associated with a high molecular weight mucin-like glycoprotein separated by gel filtration of Lu65 tumor extracts. The epitope of the mucin-like glycoprotein has been identified as alpha-N-acetylgalactosaminyl residue directly linked O-glycosidically to serine or threonine residues of polypeptides. This epitope was serologically detected several years ago and given the name Tn. Our identification of the epitope is based on the following results: The antigen is sensitive to alpha-N-acetylgalactosaminidase, but not to sialidase or alpha-fucosidase. Various mono- and difucosyl A determinants, either type 1 or type 2 chain, cross-react with both antibodies. The reactivity with both antibodies can be created by treatment of glycophorin A of normal erythrocytes with sialidase followed by beta-galactosidase. N-[3H]acetylgalactosamine can be released by galactose oxidase/NaB3H4 treatment from the Lu65 mucin-like glycoprotein but not from the mucin-like glycoprotein of normal colonic mucosa upon reductive beta-elimination (alkaline borohydride treatment). The antigen may be one of the tumor-associated A cross-reacting antigens occurring in a wide variety of human adenocarcinomas of hosts belonging to all ABO blood groups.

ABO Blood-Group System↗

Diffuse malignant pericardial mesothelioma.

A 67-year-old male case of pericardial mesothelioma is reported. The diagnosis was established by the gross appearance at autopsy and its histological findings. The tumor arising from the anterior epicardium of the right half of the heart was located within the pericardial sac, and displaced and compressed the heart to the posterior direction. Histologically, large areas of the tumor were composed of spindle-shaped malignant cells which were arranged in interlacing bundles. The other areas showed the presence of tubular structures and ill-defined solid nests. Distant metastasis was found only in a small focus of the 8th vertebral bone marrow composed of spindle-shaped cells. A meticulous search failed to find any tumor in other organs. Based on these findings, the tumor was diagnosed as diffuse malignant mesothelioma of biphasic type.

Actins↗

Large cell carcinoma of the lung--ultrastructural and immunohistochemical studies.

Twenty-seven cases of surgically resected large cell carcinoma of the lung including nine cases of giant cell carcinoma were examined ultrastructurally and immunohistochemically. Ultrastructurally, of 18 large cell carcinomas other than giant cell carcinoma eight showed characteristic differentiation toward adenocarcinoma, four toward adenosquamous carcinoma, and one each toward squamous cell carcinoma and neuroendocrine cell carcinoma, but the remaining four were undifferentiated. Six of the nine giant cell carcinomas also showed features of adenocarcinoma, two showed features of squamous cell carcinoma, and one was undifferentiated carcinoma. Immunohistochemically, secretory component (SC) was observed in seven of 14 cases with features of adenocarcinoma and two of four cases with features of adenosquamous carcinoma. Carcinomas with only squamous cell differentiation did not stain for SC. Keratin staining was positive in five of the 14 with features of adenocarcinoma, three of the four cases with features of adenosquamous carcinoma and two of the three cases with features of squamous cell carcinoma. The numbers of tumor cells positive for keratin and/or SC were small. One carcinoma with neurosecretory type granules was stained positively for calcitonin. These findings indicate that many large cell carcinomas showed differentiation toward glandular cells and/or squamous cells, and some did not show any differentiation ultrastructurally or immunohistochemically, indicating that the majority of large cell carcinomas are poorly differentiated form of either adenocarcinomas or squamous cell carcinomas.

Adenocarcinoma↗

[Immunohistochemical characterization of lymphocytes and histiocytes in bladder cancers in terms of local immune responses].

Ten resected bladder cancers were studied immunohistochemically using monoclonal antibodies to clarify the subsets of infiltrating lymphocytes and histiocytes. Leu 4+ T-lymphocytes infiltrated diffusely both in the stroma and the submucosal tissue, but Bl+ B-lymphocytes usually formed follicle-like clusters in the submucosal tissue. The number of Leu 4+, Leu 3 a+ helper/inducer T-lymphocytes was considerably more than that of Leu 4+, Leu 2 a+ suppressor/cytotoxic T-lymphocytes. Leu 7+ natural killer cells were sparsely present in the submucosal tissue, and there was no suggestion of any significant contact with cancer cells. OKT9+ OKM1+ macrophages were prominent in the inflammatory lesions, but OKT6+ T-zone histiocytes were characteristically present among the cancer cells. Patients with dense infiltration of OKT6+ T-zone histiocytes were expected to have a good prognosis.

Aged↗

Stainability of lung cancer cells with Leu-7 and OKT-9 monoclonal antibodies.

One hundred and one cases of lung cancer were immunohistochemically studied for stainability with Leu-7 (anti-myelin fiber associated glycoprotein) and OKT-9 (anti-transferrin receptor) monoclonal antibodies. All small cell carcinomas and carcinoid tumors were positively stained by Leu-7, and 22 of 41 differentiated adenocarcinomas were also positively stained, especially well-differentiated Clara cell-type adenocarcinoma, (11/14 cases). However, only one of 26 squamous cell carcinomas, one of six large cell carcinomas, one of six adenosquamous carcinomas and none of 16 poorly differentiated adenocarcinomas were stained by Leu-7. On the other hand, all squamous cell carcinomas (26/26 cases), 10 of the 16 poorly differentiated adenocarcinomas, four of the six large cell carcinomas showed positive membranous staining with OKT-9. However, only one of 41 differentiated adenocarcinomas and no small cell carcinomas nor carcinoid tumors were stained by OKT-9. The stainability of lung cancer by these antibodies is discussed.

Adenocarcinoma↗

A case of alpha-fetoprotein-producing rectal carcinoma.

A rare case of rectal carcinoma with a high serum alpha-fetoprotein (AFP) level (maximum, 6,983 ng/ml) is reported. The histology of the primary tumor was adenosquamous carcinoma, the major component being moderately to poorly differentiated adenocarcinoma. Immunohistochemically, a few AFP-positive cells were identified in the primary tumor. However, numerous AFP-positive cells were observed in metastatic tumors in the liver and lungs at autopsy, which were histologically undifferentiated carcinoma with marked pleomorphism. Furthermore, components of adenocarcinoma were present in the metastatic tumors at various sites, and components of squamous cell carcinoma were seen only in the pelvic cavity. To our knowledge, this is the first case of rectal carcinoma with verified AFP production by the tumor cells.

Autopsy↗

Carbohydrate antigen defined by a monoclonal antibody raised against a gastric cancer xenograft.

A monoclonal antibody, ST-4-39, was obtained by using a human gastric cancer xenograft, St-4, as an immunogen. Immunization was achieved by transferring immunocompetent mouse spleen cells into a nude mouse bearing St-4. Hybridomas were produced with the spleen cells of the mouse after rejection of the tumor and screened for immunohistochemical reactivity with cancers and normal tissues on formalin-fixed paraffin sections. ST-4-39 immunohistochemically reacted with various cancers including gastric, colorectal and pancreatic cancers as well as some normal tissues. ST-4-39 and NS 19-9 differed in immunohistochemical reactivity, although they reacted with some cancers and a few normal tissues in common. PBS extracts of normal and cancer tissues were examined for antigen reactive with ST-4-39 by sandwich enzyme immunoassay. Extractable antigen was detected in adenocarcinomas of colon, stomach and lung, while it was detected only in salivary gland and trachea among normal tissues examined. Gel filtration analysis of the antigen indicated a molecular weight of greater than or equal to 1 X 10(6), and the antigenic determinant was suggested to be a carbohydrate chain with terminal sialic acid by studies using periodic acid, neuraminidase and pronase treatments. Furthermore, the ST-4-39 antigen affinity-purified from two gastric cancer strains was shown to contain multiple carbohydrate determinants including sialyl-Lewisa and sialyl-Lewisx, suggesting the antigen to be a mucin.

Animals↗

Nasopharyngeal carcinoma: immunohistochemical study for keratin, secretory component and leukocyte common antigen.

Immunohistochemical studies using antisera to keratin and secretory component (SC) and monoclonal antibody against leukocyte common antigen (LCA) were performed on 92 biopsy and autopsy specimens taken from 65 patients with nasopharyngeal carcinoma. Five biopsy specimens from malignant lymphoma of the nasopharynx and tonsil, and 20 biopsy specimens of nasopharyngeal epithelium were also included in the study. Keratin was positively stained in all squamous cell carcinomas and nonkeratinizing carcinomas, and 38 of 46 undifferentiated carcinomas (82.6%), but in no malignant lymphomas. LCA was intensely stained in all malignant lymphoma, but in no nasopharyngeal carcinomas. SC was positively stained in two of the 46 undifferentiated carcinomas (4.3%). Nasopharyngeal carcinoma is a definite malignant epithelial neoplasm and can be distinguished from malignant lymphoma by immunostaining for keratin and LCA. Some undifferentiated carcinoma may show cellular differentiation toward ciliated epithelium.

Adolescent↗

Expression of carbohydrate antigen 19-9 and stage-specific embryonic antigen 1 in nontumorous and tumorous epithelia of the human colon and rectum.

The expression of carbohydrate antigen 19-9 (CA 19-9) and stage-specific embryonic antigen 1 (SSEA-1) in various human colorectal epithelia was examined by an immunohistochemical method. In mucosa remote from the carcinoma, CA 19-9 was not expressed, whereas SSEA-1 was only faintly expressed in lower crypts in all cases. In mucosa adjacent to the carcinoma, CA 19-9 was weakly expressed in upper crypts in 20% of the cases, whereas SSEA-1 was expressed not only in lower crypts in all cases but also in upper crypts in 93.3% of the cases. In adenoma, CA 19-9 was expressed in 80.6% of the cases, and SSEA-1 was expressed in all cases. The expression of both antigens was to some extent related to the degree of cellular atypia. In focal carcinoma in adenoma, CA 19-9 was strongly and diffusely expressed in 50% of the cases, and SSEA-1 was strongly and diffusely expressed in all cases. In advanced carcinoma, CA 19-9 was homogeneously or heterogeneously expressed in 82.2% of the cases, and SSEA-1 was homogeneously or heterogeneously expressed in all cases, but lower intensity of SSEA-1 staining was associated with a decrease in the degree of carcinoma differentiation. These results show that the expression of both CA 19-9 and SSEA-1 changes along with neoplastic transformation and progression in the colon and rectum. Immunohistochemical studies of SSEA-1 in flat colorectal mucosa might be a useful approach for detecting foci with preneoplastic change in the general population, whereas those of SSEA-1 and CA 19-9 could be a useful method for detecting focal carcinoma in adenoma.

Adenoma↗

Papillomavirus infection among Japanese: an immunohistochemical study for papillomavirus genus-specific antigen in human surface epithelial lesions.

In order to clarify the relationship between human papillomavirus (HPV) and a variety of surface epithelial lesions, the presence of papillomavirus genus-specific common structural antigen (pgs-antigen) was immunohistochemically investigated in 256 cases of various tumors and tumorous lesions. The pgs-antigen was demonstrated in cases of verruca vulgaris (11/23 cases), condyloma acuminatum (13/26), adult laryngeal papilloma (3/12) and bowenoid papulosis (2/2). No pgs-antigen was observed in ordinary Bowen's disease and other hyperkeratotic skin lesions, such as keratoacanthoma and seborrheic keratosis. In uterine cervical lesions, about 15% of cervical dysplasia, most of which later developed into carcinoma in situ, contained pgs-antigen-positive koilocytotic cells. These results suggest that HPV infection is frequently present in human hyperplastic and atypical surface epithelial lesions of Japanese patients and might indicate possible association with neoplastic transformation, especially in the cervix and skin.

Animals↗

Giant cell carcinomas of the lung producing colony-stimulating factor in vitro and in vivo.

Two culture cell lines (C-Lu65, C-Lu99) were established from human giant cell carcinomas of the lung transplanted in athymic nude mice (BALB/c, nu/nu). During early passage in tissue culture, C-Lu65 grew as a loosely adherent monolayer with some piling-up and with floating cells. After 30 successive subcultures, C-Lu65 began to grow in suspended cell clusters, showing a faster growth rate. C-Lu65 was characterized by multinucleated giant cells with large abnormal nuclei and prominent nucleoli. C-Lu99 grew as adherent cells, and fewer multinucleated giant cells were observed. C-Lu65 and C-Lu99 showed some ultrastructural differences in cell surface and cytoplasmic features. Chromosomal analysis revealed numerical and structural abnormalities in both cell lines. Cell-free supernatants from both cell lines stimulated the colony formation of mouse bone marrow cells in vitro. In addition, mice bearing tumors induced by transplanting C-Lu65 and C-Lu99 showed remarkable leukocytosis without evidence of infection. These results suggest that these two cell lines release colony-stimulating factor both in vitro and in vivo.

Animals↗

Second primary cancers in patients with gastrointestinal cancers.

The occurrence of multiple primary malignant neoplasms in 9,191 consecutive cases of primary gastrointestinal (GI) tract cancer from 1962 to 1981 at the National Cancer Center was analyzed. The person-years of the cases totaled 28,399.4: 185 second cancers were diagnosed clinically and 85 were first diagnosed at autopsy. The overall frequency was 2.01% for clinically recognizable cancers and 2.94% including those discovered at autopsy. The overall observed/expected ratio was 0.96 for clinical cancers and 1.33 including autopsy cases. However, a significant association between the first and second cancers was present in the oro-pharynx and esophagus; esophagus, stomach and colon; stomach and all other parts of the GI tract; and the colon and rectum. The mode of appearance was also analyzed to clarify the organ relationship.

Age Factors↗

Recurrence of thymoma with appearance of myasthenia gravis 18 years after surgery: a case report.

A 59-year-old woman was admitted to the hospital because of recurrence of thymoma with appearance of myasthenia gravis 18 years after excision of an invasive thymoma. Recurrence was observed in the anterior mediastinum, right pleura, pericardium and left supraclavicular lymph node. Hashimoto's thyroiditis, vitiligo vulgaris and leukopenia were also seen. After creation of a pericardial window for pericardial effusion, she received vincristine, then carbazilquinone intravenously as single chemotherapeutic agents based on the chemosensitivity by clonogenic assay of the supraclavicular tumor, but response was not achieved. At one and a half years after radiotherapy to the mediastinum, she is now doing well without symptoms and is receiving a fairly low dose of anticholinesterase medication.

Female↗

Morphometry of bladder cancer cells in tissue sections according to histological grade of malignancy.

Morphometrical analysis was performed on cells of bladder carcinomas taken from patients who had undergone surgery at the National Cancer Center Hospital. Ten cases each of the following groups were compared as to the nuclear area, standard deviation of nuclear areas, cytoplasmic area, and nuclear/cytoplasmic ratio: normal mucosa and grade I transitional cell carcinoma obtained by transurethral resection (TUR), and normal mucosa, grade II, III and in situ transitional cell carcinomas obtained by total cystectomy. There were significant differences in both nuclear area and nuclear/cytoplasmic ratio between normal epithelium obtained by TUR and grade I carcinoma. There were also significant differences in nuclear area and nuclear/cytoplasmic ratio among the four total cystectomy groups. In this cytomorphometrical analysis, cells of carcinoma in situ had the characteristics of grade II or grade III carcinoma cells. The morphometrical features of the two advanced cases of grade II carcinoma revealed that the nuclear area, the standard deviation of the nuclear area and the cytoplasmic area were rather small, whereas the nuclear/cytoplasmic ratio was almost average for the grade II group. The results of this analysis, especially those for the nuclear/cytoplasmic ratio, corresponded well with the histological grading of bladder carcinoma.

Carcinoma in Situ↗

A case of large "thymic granuloma". Neoplasm of T-zone histiocyte.

An unusual case of classic thymic granuloma is reported. A 16-year-old boy presented with a huge mediastinal mass and the superior vena caval syndrome. Irradiation and combination chemotherapy induced complete remission, despite several episodes of lymph node recurrence. Examination of the first biopsy specimen was considered to indicate a histiocytic tumor or malignant form of eosinophilic granuloma, because of the diffuse proliferation of histiocytes and marked infiltration of eosinophils. Late involvement in the lymph node appeared to have the same histologic characteristics as the mediastinal tumor. Immunohistochemically, the proliferating histiocytes were stained with anti-S100 protein IgG but not with anti-lysozyme or anti-NCA (nonspecific cross-reacting antigen with carcinoembryonic antigen) antibody. These characteristics were similar to those of interdigitating cells in the lymph nodes, thymus, and other lymphoid tissues. The relationship of this case to mediastinal Hodgkin's disease or proliferative disorders of histiocytes is discussed.

Adolescent↗

A novel combination of K-ras and myc amplification accompanied by point mutational activation of K-ras in a human lung cancer.

Amplifications of two oncogenes, c-K-ras-2 and c-myc, were found in a human lung giant cell carcinoma (LGCC) Lu-65, which is maintained in nude mice. The extent of c-K-ras-2 and myc amplifications were estimated to be 10- and 8-fold, respectively, by means of the Southern hybridization procedure. In addition, NIH3T3 cells were transformed by transfection of Lu-65 DNA and the transforming gene was identified as c-K-ras-2. c-K-ras-2 genes were cloned from a gene library of Lu-65 and a single point mutation causing a substitution of cysteine for glycine in codon 12 was found by DNA sequencing. It was concluded that the amplification of the c-myc and c-K-ras-2 genes are accompanied by point mutational activation of c-K-ras-2 in the human LGCC Lu-65. This is the first report of multiple gene amplification accompanied by a point mutation of oncogenes in human cancer cells, providing further support for the idea that co-operation of at least two activated cellular oncogenes is required for carcinogenesis.

Amino Acid Sequence↗