Search PubMed⌕ Search

Biomedical subjects

T Kameya

Publications and source records attributed to T Kameya.

At least 181 records · Page 10Linked to original sources

Production and molecular size heterogeneity of immunoreactive gastrin-releasing peptide in fetal and adult lungs and primary lung tumors.

Gastrin-releasing peptide (GRP) is known to be a bombesin-like peptide present in mammalian tissues. Using GRP radioimmunoassay specific for carboxyl-terminal portion, the immunoreactive GRP (IR-GRP) content of 5 fetal lungs, 38 adult lungs, and 131 primary lung tumors was determined. All fetal lung extracts contained IR-GRP ranging from 31 to 140 ng/g, wet weight. IR-GRP was present in 7 to 21% of normal adult lungs and lung carcinomas other than small-cell carcinoma; the amount was not very large except in two cases of adenocarcinoma, in which 110 and 140 ng/g of IR-GRP were detected. In the case of small-cell carcinoma, IR-GRP was found in 23 of the 31 cases examined (74%), and nine (29%) of these contained large amounts of IR-GRP (100 to 14,000 ng/g). As for carcinoid tumors, IR-GRP was found in five of the 12 cases examined (42%), and large amounts of IR-GRP were detected in two cases (5,100 to 130,000 ng/g). Immunohistochemically, IR-GRP was found in the neuroendocrine cells of fetal lungs and in the tumor cells of primary lung tumors. When these tissue extracts were examined by bombesin radioimmunoassay that recognizes bombesin but not GRP, they did not contain immunoreactive bombesin, suggesting that IR-GRP in these tissues is more similar to GRP than to bombesin. Sephadex G-50 gel filtration always revealed two peaks of IR-GRP in both fetal lungs and IR-GRP-producing tumors. One was eluted at the position corresponding to that of porcine GRP (Peak 1) and the other, at the position just behind that of porcine GRP (14-27) (Peak 2). In the five fetal lungs, Peak 2 comprised more than 83% of the total IR-GRP. In the 12 IR-GRP-producing tumors examined, the ratio of these two peaks differed from case to case. Our data indicate that IR-GRP, which is present in fetal lung, is often produced by primary lung tumors, especially by small-cell carcinoma and carcinoid tumor, with molecular size heterogeneity.

Amino Acid Sequence↗

[Immunomorphologic responses of regional lymph nodes and prognosis in patients with stage Ia pulmonary adenocarcinoma].

The relationship between postoperative prognosis and the immunomorphologic response of regional lymph nodes was examined in 50 patients with stage Ia peripheral bronchial adenocarcinoma and compared with 22 patients in stage Ib and II. Regarding paracortical lymphocyte hyperplasia, the prognosis of the responsive group in patients with stage Ia was significantly better than that of the non-responsive group; however, no definite relationship was found between follicular hyperplasia and prognosis. Follicular hyperplasia correlated with the size of the primary lesion or the distance from the site of the primary lesion. In stage Ib and II cases with metastasis to the pulmonary hilar lymph nodes, paracortical lymphocyte hyperplasia or follicular hyperplasia had no relation to the postoperative prognosis.

Adenocarcinoma↗

Characterization of two newly established human cell lines from patients with large-cell anaplastic lung carcinoma.

Two permanent cell lines, designated LU-65 and SK-Luci-6, were established from large-cell anaplastic lung cancers of two patients. Both cell lines grew as solid tumors in nude mice. The histologic pattern of the tumors in the nude mouse resembled that of the primary lung cancers in that the xeno-transplanted tissues showed no distinctive features indicative of cell type, a finding consistent with origin from a large-cell anaplastic lung cancer. Cells from both lines formed clones in semisolid agar. Flow cytometric analysis of SK-Luci-6 showed a hypertriploid stemline with a very high RNA-index. Line LU-65 had a hyperdiploid stemline evolving into a hypertriploid stemline with a high RNA-index. Chromosome analysis showed aneuploidy with abnormalities and marker chromosomes in both tumor cell lines. The isoenzyme pattern of LU-65 and Sk-Luci-6 indicated that they were of human origin and distinct from HeLa cells or another common contaminating line. Both cell lines released biologically active agents that could have caused the neutrophilia and hypercalcemia seen in the patients.

Adult↗

Immunohistochemical demonstration of S100 protein in malignant melanoma and pigmented nevus, and its diagnostic application.

The presence of nervous tissue specific S100 protein was studied immunohistochemically in 47 cases of malignant melanoma and 25 pigmented nevi of various types of peroxidase-antiperoxidase immunoenzyme method on routine paraffin sections of the surgical specimens. Of 47 cases of malignant melanoma, 44 were positively stained for S100 protein. The intensity of S100 protein immunostaining was suggested to be inversely proportional to the amount of melanin pigment. In ten cases of 12 amelanotic melanomas, the immunoreaction for S100 protein in tumor cells was stronger than that of normal Bergmann glial cell in human cerebellum. Intradermal nevi and juvenile melanomas were strongly positive for S100 protein, but blue nevi contained little or no S100 protein. Our results suggest that S100 protein is widely distributed among melanotic tumors and is also a very useful diagnostic indicator for malignant melanoma, especially of the amelanotic type.

Histocytochemistry↗

Induction of supermelanin synthesis and morphological changes in interspecific reconstituted cells and its reversal by tumor promoter.

Chloramphenicol-resistant (CAPr) reconstituted cells and cybrids were isolated by fusion of karyoplasts (or intact cells) of mouse amelanotic melanoma B16 cells with cytoplasts of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) -deficient, CAPr rat myoblastic cells, L6TG.CAPr, and double selection in HAT medium containing CAP. Reconstituted cells or cybrids exhibited unique cellular arrangement, and about one third of the isolated clones expressed high tyrosinase activity and marked melanin synthesis, although the parental mouse cells expressed low tyrosinase activity and the parental rat cells did not express tyrosinase activity. These phenotypic changes have been stable for more than a year. The phenotypic reversions of these clonal cells were induced by treatment with a tumor promoter. There were changes in the morphology of the treated cells to that of the mouse B16 cells and extinction of tyrosinase activity and melanin synthesis in pigmented clonal cells. These phenotypic changes and reversions induced by a promoter were repeatedly reversible.

Animals↗

An immunoperoxidase study of S-100 protein distribution in normal and neoplastic tissues.

The presence of S-100 protein was immunohistochemically studied in many types of formalin-fixed and paraffin-embedded tumors (260 cases). Peripheral nerve tumors, i.e., schwannomas, neurofibromas, granular cell tumors, and neurogenic sarcomas were demonstrated to contain variable amounts of S-100 protein in the tumor cell cytoplasm and nuclei. In ganglioneuromas and ganglioneuroblastomas, neoplastic Schwann cells or satellite cells were positive for S-100 protein. About one-half of the cases of carcinoid tumors stained weakly for S-100 protein. In addition to these nervous tissue and carcinoid tumors, chondrosarcoma, chordomas, pleomorphic adenomas of the salivary gland, and Langerhans cell granulomatosis were also shown to produce S-100 protein. In many types of breast tumors and other lesions, S-100 protein positive cells were likely to correspond to the distribution of myoepithelial cells. These results indicate that S-100 protein is not strictly specific to nervous tissue and its tumors; however, the immunohistochemical demonstration of S-100 protein can be a useful diagnostic tool in tumor diagnosis.

Breast Diseases↗

A case of pituitary adenoma with possible simultaneous secretion of thyrotropin and follicle-stimulating hormone.

A TSH- and FSH-screening pituitary adenoma was demonstrated in a 23-yr-old man who presented with bitemporal hemianopsia, but without clinical or laboratory evidences of hyper- or hypothyroidism or hypogonadism. Basal TSH (29-45 microunits/ml) and FSH (44-63 mIU/ml) were moderately elevated. GH and ACTH secretion were impaired, and basal PRL and testosterone were normal. TRH and LRH elicited a significant increase in TSH and FSH, respectively. The plasma glycoprotein alpha-subunit concentration was normal, and its response to simultaneous administration of TRH and LRH was low. Plasma TSH was not suppressed completely by exogenous T3. After operation and radiotherapy, elevated TSH and FSH as well as failure of T3 to suppress TSH were corrected. No significant changes in thyroid hormone concentration in the blood were detected in spite of the reduction of TSH. TSH and FSH concentrations in the tumor extract were lower than those in normal pituitaries. Histologically, the tumor was very vascular and consisted mostly of a single type of cell. The tumor cells were positively stained for FSH beta-subunit by immunohistochemical study, but for none of other pituitary hormones or subunits examined. Electron microscopic examination revealed relatively abundant single type secretory granules of high electron density. It is possible that the tumor simultaneously secreted TSH and FSH, the former possibly being immunologically active, but biologically inactive.

Adenoma↗

Ultrastructural characterization of human corticotrophs (ACTH cells).

Ultrastructural characterization of human corticotrophs (ACTH cells) was performed by 'superimposition technique', which enabled detailed ultrastructural observation of immunoreactive ACTH cells in adjacent semi-thin light microscopic immunoperoxidase and routine electron microscopic sections. The human corticotrophs were large and round or polygonal and were not stellate. They had scanty rough endoplasmic membranes and were packed with numerous large secretory granules measuring from 250 to 500 nm in diameter. The sizes of secretory granules in 6 human pituitaries were 448 +/- 128, 344 +/- 86, 448 +/- 117, 244 +/- 65, 316 +/- 76, and 340 +/- 93 nm, respectively. The granules were not seen in a single row along the plasma membrane as is the case in the rat. They possessed somewhat irregular outlines with a rarely discernible halo. Different densities of granule matrices were occasionally found. The cells often contained a few large heterogeneous vacuoles. From these findings, the human ACTH cells were recognized to be remarkably different in cell shape and size, properties of secretory granules and cytoplamic inclusions from those of the rat pituitary gland. In respect to secretory granule properties, the human ACTH cells are similar to those of some other mammals (fox, young pig, and lerot). More data is required to elucidate the relationship between human ACTH cell morphology and functional state.

Adenoma↗

Production of alpha-fetoprotein, normal serum proteins, and human chorionic gonadotropin in stomach cancer: histologic and immunohistochemical analyses of 35 cases.

By immunoperoxidase histochemical staining of formalin-fixed paraffin-embedded sections, the production of alpha-fetoprotein(AFP), albumin(ALB), transferrin(TF), alpha-1-antitrypsin(AAT), and human chorionic gonadotropin(HCG) was examined in 35 operatively resected stomach cancers with elevated serum AFP levels (higher than 20 ng/ml as determined by radioimmunoassay). Cells positive for AFP were found in 19 cases (54%). In 29 cases (83%), some tumor cells contained normal serum proteins (ALB, TF, or AAT). All 19 tumors with AFP-positive cells also stained positively for two or three kinds of normal serum proteins. In some cases, AFP and normal serum proteins were localized in the same cells. There were two cases in which metastatic tumors produced AFP, whereas the primary sites did not. In nine cases (26%), HCG was present in tumor cells and HCG- and AFP-positive cells were coexistent in six tumors. Histologic examination of AFP-producing stomach tumors revealed medullary or papillotubular arrangements with marked nuclear atypia and eosinophilic granular or clear cytoplasms containing no glycogen or mucin. Some tumors with medullary patterns resembled liver cell carcinomas. Concordant phenotypic expression of AFP and normal serum protein production appears to be a general feature of AFP-producing tumors such as liver cell carcinoma, yolk sac tumor, and stomach cancer.

Blood Proteins↗

Arylsulfatases of human-lung tumors transplanted into athymic mice. Cancer-associated modification of arylsulfatase B variant.

The activities and properties of arylsulfatase A and B from human lung carcinoma transplanted into athymic mice were demonstrated. The activities of arylsulfatase A and B from transplanted carcinomas with four histological types were more than twofold higher as compared to those from surgical tumors, except for arylsulfatase A activity in blastoma. Arylsulfatase B in transplanted tumors was almost completely replaced, except for blastoma, by an anionic B variant (B1) which was a minor component of arylsulfatase B in surgical lung tumor and absent in normal human lung. The properties of arylsulfatases A and B from transplanted tumors were essentially identical, respectively, with those from normal lung or surgical tumors in respect of molecular weight, heat stability, pH optimum, isoelectric point (pI), Km, time course profile and substrate specificity. Arylsulfatase B1 showed the properties similar to B enzyme except for net charge. The cause of the negative charge of tumor B1 enzyme was investigated. By the action of phosphatase, which was added exogenously or had been persistently included in the partially purified enzyme preparation, B1 enzyme (pI 7.5) shifted to about pI 8.2. Treatment of B1 enzyme with neuraminidase, concomitant with the endogenous phosphatase, resulted in marked increase (pI 9.5) of the isoelectric point, identical to that of arylsulfatase B. Thus, it is most probable that tumor B1 enzyme is modified by additional sialic acid and phosphate bound to arylsulfate B.

Animals↗

Characterization of amylases produced by tumors.

Amylases were purified and characterized from three amylase-producing human tumors. The relative molecular mass of the amylases was estimated to be 54 000 on sodium dodecyl sulfate/polyacrylamide gel electrophoresis, different from human salivary amylase (61 000 and 64 000) and human pancreatic amylase (60 000). The tumor amylases had completely identical antigenicities with human salivary and pancreatic amylases against antibody to human salivary amylase, while the intensity of the tumor amylases was less than 20% of that of human salivary and pancreatic amylases on single radial immunodiffusion. On isoelectric focusing, two of the three tumor amylases showed a major peak at pH 6.4, which corresponded to a major peak of human salivary amylase, the other showed a major peak at pH 6.4, which corresponded to a minor peak of human salivary amylase. The three tumor amylases showed similar amino acid composition, different from those of human salivary and pancreatic amylases. These findings suggest that tumor amylases have a tertiary structure similar to that of normal human amylases, but differ from them in amino acid composition.

Adenocarcinoma↗

Elevation of glycoprotein galactosyltransferase activity in human lung cancer related to histological types.

Uridine diphosphogalactose:glycoprotein galactosyltransferases were examined in human lung adenocarcinoma and squamous cell carcinoma. The galactosyltransferase activities in tissue homogenates from both carcinomas were higher than in adjacent normal control with asialoagalactofetuin as a substrate. This activity in adenocarcinoma (27 cases) was two times higher than that in squamous cell carcinoma (19 cases) with statistical significance (p less than 0.001). Using Triton-solubilized enzymes from a particulate fraction, similar differences in the activity were observed with ovalbumin, asialoagalactofetuin, and its beta-eliminated derivative as acceptors but not with bovine submaxillary mucin. These observations mean that the higher activity of galactosyltransferase(s) in lung carcinomas (especially in adenocarcinoma) is mainly responsible for galactosylation of carbohydrate chains in N-glycoside-type but not O-glycoside-type glycoproteins.

Adenocarcinoma↗

Pulmonary blastoma. An ultrastructural study of a case and its transplanted tumor in athymic nude mice.

A pulmonary blastoma in a 52-year-old Japanese man was serially transplanted into athymic nude mice. This report emphasizes the characteristics of the neoplasm seen on light and electron microscopic examination. The original tumor consisted of branching tubular structures and primitive mesenchymal components with a few smooth-muscle cell bundles, and resembled fetal lung tissue. Electron microscopic examination revealed that the immature stromal cells resembled epithelial cells. After serial passages in nude mice, the stromal element of the tumor disappeared, and the epithelial element showed squamous metaplasia and occasional mucus production. Endocrine-type granules were observed in a few tumor cells. Histogenetic considerations, including a suggestion that the tumor was derived from entodermal cells, are presented.

Animals↗

Neuroendocrine carcinoma of the paranasal sinus: a morphological and endocrinological study.

Four cases of small cell carcinoma of the paranasal sinuses were studied histologically, ultrastructurally, and endocrinologically. All tumors showed features of undifferentiated carcinoma with alveolar patterns but without acinar or squamous differentiation and contained cells possessing endocrine-type small secretory granules, which were indistinguishable from non-neoplastic neurosecretory granules. The three cases also possessed a small number of microtubules, and in one of these fine cytoplasmic filaments were observed. One case showed elevated plasma levels of cortisol and adrenocorticotropic hormone associated with adrenocortical hyperplasia and Crooke's changes of the pituitary gland. Another case showed hypercalcemia with bone metastasis, hypercalcitonemia with a high content of calcitonin in the tumor tissue, calcitonin-positive tumor cells, and C-cell hyperplasia of the thyroid. It was concluded that all four cases should be called neuroendocrine carcinoma, which might be related to neoplasms derived from amine precursor uptake and decarboxylation cell series rarely encountered in the paranasal sinuses.

Adrenocorticotropic Hormone↗

Ultrastructure, immunohistochemistry and hormone release of pituitary adenomas in relation to prolactin production.

Fifteen cases of pituitary adenoma, 14 of which were associated with hyperprolactinemia, were studied by observation and granule morphometry of electron micrographs, immunohistochemistry and sequential observation of in vitro release with regard to hormone production, storage and secretion. Adenoma cells of 6 cases with marked elevation of plasma prolactin were sparsely granulated, showed characteristic ultrastructures including the presence of small secretory granules, well developed Golgi and rough membranes, misplaced exocytosis, and positive or negative immunostaining for prolactin. These adenomas also showed vigorous release of the hormone into the circulation and/or culture medium. In vitro studies showed that negative immunostaining of adenoma cells did not preclude the production and secretion of the hormone. One densely granulated adenoma containing cells with numerous lactotroph type granules showed moderate release of prolactin into the circulation. In an acromegalic case associated with both high plasma growth hormone and prolactin, some cells were shown by immunohistochemistry to store both hormones There were 4 adenomas which could not be shown to produce, store and secrete prolactin by any method available.

Adenoma↗