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Biomedical subjects

M Mukai

Publications and source records attributed to M Mukai.

At least 325 records · Page 18Linked to original sources

Histogenesis of alveolar soft part sarcoma. An immunohistochemical and biochemical study.

In order to clarify the histogenesis of alveolar soft part sarcoma (ASPS), an immunohistochemical and biochemical study was performed on three cases. The immunohistochemical study indicated the presence of actin, desmin, vimentin, and Z-protein in all cases. On the other hand, intermediate filaments other than desmin and vimentin were not detected immunohistochemically. The presence of desmin and Z-protein strongly suggests the myogenic character of this tumor. As to whether ASPS shows striated muscle differentiation or smooth muscle differentiation, the immunohistochemical absence of myoglobin in the three cases suggests that the tumor does not differentiate in the direction of striated muscle. However, biochemical assay of subunits of enolase revealed significantly high amounts of beta-enolase, which is known as a marker for striated muscle, in all three cases. The determined values--735, 426, and 584 ng/mg of protein --are indicative of striated muscle differentiation. In addition, the immunohistochemical study of all cases revealed the presence of beta-enolase in tumor cells. These data definitely show the myogenic character and rhabdomyoblastic differentiation of ASPS.

Actins↗

Neurofilaments of Kultschitsky cells in human lung.

The immunohistochemical localization of three triplet proteins of neurofilaments in normal Kultschitsky cells and tumourlets of the human lung has been studied using avidin-biotin-peroxidase complex (ABC) method. Kultschitsky cells and tumourlets have been stained with antisera against 68 K, 150 K and 200 K dalton components of the neurofilaments, respectively. Ultrastructural observations of human Kultschitsky cells have revealed the presence of bundles of intermediate filaments as well as microtubules and neurosecretory-type granules. In the tumourlets, similarly sized filaments were found, but were relatively scarce. Since intermediate filaments are thought to be specific to differentiated cells and neurofilament proteins are restricted to the neuronal tissues, we conclude that Kultschitsky cells of the lung are of neuronal nature.

Cytoskeleton↗

Expression of neurofilament triplet proteins in human neural tumors. An immunohistochemical study of paraganglioma, ganglioneuroma, ganglioneuroblastoma, and neuroblastoma.

Intermediate filaments which are specific to neural cells, ie, neurofilaments, consist of three subcomponents--68, 150, and 200 kd. Thirty human neural tumors were examined for the presence of these three subcomponents by means of their monospecific antisera. All 8 paragangliomas contained cells that were positive for the 68-kd component, but only 5 of them had cells positive for the 150-kd and 200-kd components. All 4 ganglioneuromas and 11 ganglioneuroblastomas contained cells that reacted with antibodies to all three components. All 7 neuroblastomas had cells reacting with antibody to 68 kd, but only 3 of them had cells that reacted with antibodies to 150 kd and 200 kd. In each case, the number of positive cells depended on the antibody used. The largest number reacting with antibody to 68 kd and the smallest with antibody to 200 kd. Furthermore, it was possible to detect tumor cells in which the 68-kd subcomponent existed by itself, but no tumor cells in which the 150-kd or 200-kd subcomponent existed alone could be detected. These results seem to indicate that antibody to the 68-kd component is sufficiently discriminating to be applied diagnostically.

Adult↗

Interaction of rat ascites hepatoma cells with cultured mesothelial cell layers: a model for tumor invasion.

Interactions of rat ascites hepatoma cells with primary cultured layers of rat mesentery-derived cells were studied. The mesentery-derived cells were isolated from rat mesentery and cultured in Eagle's minimum essential medium with a 2-fold concentration of amino acids and vitamins supplemented with 10% calf serum. The primary cultured cells, consisting mainly of mesothelial cells in polygonal shape, forms a "paving stone" sheet. Upon seeding the tumor cells on the mesentery-derived cell layers, three different types of tumor cell growth were observed. Type 1 was the formation of piled-up tumor cell nests on mesothelial cell layers. Type 2 was the formation of flattened tumor cell islands underneath mesothelial cell layers. This island formation was clearly observed under a phase contrast microscope 2 days after the tumor cell seeding. Protrusion of cellular processes of the tumor cells beneath mesothelial cells was occasionally seen. Type 3 was the growth of tumor cells in suspension. These types of tumor cell growth closely resemble those in the peritoneal cavity observed after i.p. implantation of the tumor cells. When the tumor cells recovered from the blood of tumor-bearing rats were seeded, flattened tumor cell islands were formed 15 times more frequently than when the tumor cells isolated from host peritoneal cavity were seeded. Shortly after the appearance of small flattened tumor cell islands, a distinct morphological change of mesothelial cells from polygonal to spindle shape was seen preferentially at the marginal area of the cell layers (a partial retraction of cell edges). The retraction of mesothelial cells was induced not only by seeding the tumor cells but by adding the tumor ascites fluid or the medium conditioned by the tumor cell culture. The morphological change was reversed by changing the culture medium to remove the effectors. These results indicate that the system described in this study can provide a useful model to study tumor cell invasion.

Animals↗

[Application of NMR-CT in the staging of cancer of the digestive organs].

To assess the potential of NMR-CT for demonstrating cancer of the digestive organs, we examined a total of 232 patients (89 with esophageal cancer, 52 with liver cancer, 40 with colorectal cancer, 9 with pancreatic cancer, 9 with gastric cancer, and 33 with other diseases). NMR-CT has many features, but we use especially those features which it is possible to select not only in the transverse plane but also in the coronal and sagittal planes, and it has excellent soft tissue contrast resolution. Our machine is a Picker International NMR-CT using a superconducting magnet of 0.256 tesla. Diagnosis of lymph node involvement of esophageal cancer. Using only the coronal plane, each patient was scanned by the spin echo technique (TE = 40, TR = 400) from the plane of the descending aorta to the plane of the trachea 1 cm in thickness, at 1 cm intervals, continuously. All the vessels were clearly differentiated as no-signal regions, especially in coronal images, from areas of carcinomatous involvement. Lymph nodes were identified as intense grey masses in fat tissue of high intensity. Twenty cases were proved by surgery or autopsy, and it was possible to assess 160 lymph-node groups. A total of 25 patients were imaged as having positive lymph nodes, but 17 of them had metastasis-positive nodes. In other 135 nodes imaged as negative lymph nodes, only two had metastasis and 133 were negative for metastasis. Overall accuracy was 93.8%. Diagnosis of liver cancer. Intrahepatic vessels were clearly imaged without using contrast enhancement in NMR-CT, so it was easy to diagnose the segment containing the tumor and to detect tumor emboli in the portal vein. The capsule was imaged in 84% (16/19) using IR techniques, although only 37% (7/19) could be imaged by X-CT. Diagnosis of colorectal cancer. Using the sagittal plane, the sacrum, urinary bladder and other organs were imaged better parallel to their axis, so that the relationship between rectal cancer and surrounding organs could be clearly visualised with NMR-CT. With regard to lymphatic metastasis, coronal imaging was useful for picturing mesenteric and pelvic vessels, so that lymph nodes were imaged as low-intensity masses along the vessels. Lymph metastasis almost 1 cm size can be detected using coronal NMR-CT.

Digestive System Neoplasms↗

[Combined effect of the topical administration of OK-432 with radiation on the C3H mouse fibrosarcoma (NFSa)--TCD50 and the mechanism of action].

Optimal timing of topical administration of OK-432 and TCD50 were studied using weakly immunogenic and radioresistant C3H mouse fibrosarcoma (NFSa). The mechanism of action of this combined therapy was examined histologically and electron microscopically. Topical administration of OK-432 was performed from 2 days before irradiation to 7 days after irradiation and tumor volumes on the 20th day after irradiation were compared with a control group given radiation alone. Significant difference was observed only in the group which was given OK-432 just after irradiation. The TCD50 of the combined therapy of radiation with topical administration of OK-432, 4 KE which was given just after irradiation was 64.5 Gy and that of radiation alone was 83.5 Gy. Combined therapy shifted the TCD50 curve about 20Gy to the left. Histological examination of the tumor on the 6th day after combined therapy showed marked degeneration and necrosis of tumor cells with marked infiltration of lymphocytes. These lymphocytes were electron microscopically seen surrounding not only damaged cells, but also apparently active tumor cells. We postulate the latter cells had a tendency to be degenerative. This phenomenon suggests that lymphocytes recognize as foreign these tumor cells which are apparently active but some what damaged by radiation.

Administration, Topical↗

Infantile digital fibromatosis. An electron microscopic and immunohistochemical study.

Three cases of infantile digital fibromatosis were studied by electron microscopy and immunohistochemistry. The tumor was made up equally of myofibroblasts containing long narrow bundles of microfilaments with dense bodies. Another striking feature was the intracytoplasmic electron-dense inclusion. The inclusions were constituted of packed fibrils similar to those of the long bundles. At the periphery of these inclusions were seen prominent felt-like filamentous structures; the diameter varied from 5-12 nm. The 10 nm filaments were seen most abundantly in the cytoplasm surrounding the inclusions, but sometimes they were also found within the inclusions themselves, mainly at their periphery. These findings suggest that the inclusions may represent an abnormal accumulation of cytoskeletal proteins. On the other hand, various kinds of immunohistochemical study showed that actin, actomyosin, myosin, and vimentin were distinctly observed in cytoplasms of tumor cells. They were located fringing the intracytoplasmic inclusions, but the inclusion themselves showed negative findings, thus indicating a hollow-like staining pattern. These data can be synthesized as follows. The inclusion results from an accumulation of cytoskeletal proteins (actin-myosin complex and vimentin, at least), and antigenicity seems to be lost by for a certain mechanism or in the degenerative process.

Child, Preschool↗

[Combination therapy of local administration of OK-432 and radiation on a murine fibrosarcoma (NFSa)--combination effect and histological examination].

The combined effect of radiation with local administration of OK-432 was studied using natural fibrosarcoma (NFSa) of C3H mice that are less immunogenic and resistant to radiation (TCD 50, 83, 15 Gy). When 2KE of OK-432 was administered together with 1 X 10(6) tumor cells, tumor survival was inhibited in 7/8 (87.5%) of mice. Single local administration of OK-432 (2KE, 4KE, 8KE) showed hardly any effect on tumor survival. Combined treatment of 2KE of OK-432 and 4-Gy radiation, however, not only controlled tumor growth but also eradicated 1/5 (20%) of them, compared with single application of 45-Gy radiation. OK-432 worked most effectively when administered just before or after the application of X-rays. The optimum dose of OK-432 was studied by administering 2KE, 4KE and 8KE of the agent together with the application of 55-Gy radiation. 8KE groups showed the best eradication rate but 4KE groups showed the best cure rate. Therefore, the optimum dose was considered to be between 4KE and 8KE. With regard to histological effects, both the single radiation treatment and its combined treatment with OK-432 were most effective on the 6th day. The degree of degeneration and necrosis of tumor cells together with lymphocyte exudation were much higher in the combined treatment than in single radiation application.

Animals↗

[A multi-center trial of MY-1, a new biological response modifier, on the immunological parameters of postoperative gastric cancer patients].

A multi-center study was performed to clarify the immunological effects of MY-1, a new biological response modifier, on postoperative gastric cancer patients. A total of 90 patients were randomly allocated either to an MY-1 treated or an untreated group. MY-1 was given 3 times a week from the 4th postoperative day for a period of 3 weeks. Immunological parameters of the patients, such as lymphocyte subsets measured with flow cytometry using various monoclonal antibodies, blast transformation responses against PHA, ConA, and PPD, natural killer activity of peripheral lymphocytes, and skin test for MY-1 and PPD, were evaluated preoperatively, before and after MY-1 treatment. The results of the two color staining method with flow cytometry showed that the population of lymphocytes positive for both OKT8 and Leu15 antigens (suppressor cells) was statistically less, and that the population of lymphocytes positive for OKT8 and negative for Leu15 antigens (killer cells) was statistically increased in patients treated with MY-1 compared with the control group.

Adult↗

Histopathologic and immunohistochemical study of malignant tumors of peripheral nerve sheath (malignant schwannoma).

Histologic and immunochemical analyses were performed on 38 cases and 33 cases of malignant tumors of the peripheral nerve sheath, respectively. The histologic features consisted of either closely packed or loosely arranged interlacing fascicles of slender spindle cells that showed a wavy pattern. Although no characteristic findings indicative of neurogenic differentiation could be confirmed with anti-S-100-protein, a fair number of positive cells were seen in the area where the tumor cells were loosely arranged and displayed a wavy pattern. When anti-neuron-specific enolase (NSE) and anti-neurofilament antibody (68K, 200K) were applied, they were found to be positive in cells differentiating to ganglion cells and in epithelial cells. Since S-100-protein-positive cells indicate a differentiation to Schwann cells and NSE-positive cells and neurofilament-positive cells to nerve cells, it was concluded that immunohistochemistry can serve as an effective supplementary method for the diagnosis of malignant tumors of the peripheral nerve sheath.

Adolescent↗

Establishment and characterization of a new clonal strain derived from human benign gastric teratoma.

Various kinds of cell-types such as squamous epithelial cells, columnar epithelial cells, sarcomatous cells and fibroblast-like cells proliferated in vitro during the initial period of the primary culture from the human benign gastric tridermal teratoma. The fibroblast-like cells designated HOGT clonal strain were established from a single cell of primary cultures. The HOGT clonal strain grew well and 70 serial passages were successively carried out within 17 months. Although the HOGT cells are karyologically normal, when transplanted into the subcutis of nude mice they produced a benign tridermal teratoma. The results obtained from cell culture and heterotransplantation of teratoma strain enabled us to hypothesize that the graft (tridermal teratoma) in mice may arise from a pluripotent stem cell.

Animals↗

[Production and characterization of monoclonal antibody to uterine cervical cancer cell line SKG-IIIa].

By means of an immunization procedure using intact living cells, the established uterine cervical epidermoid cancer cell line SKG-IIIa, a monoclonal antibody (Mab) which reacts with uterine cervical epidermoid cancer cells was obtained. The Mab was of IgG2a subclass. Immunohistochemically the Mab reacted with uterine cervical epidermoid cancer cells (17 out of 25). At the same time, it reacted with a basal layer of normal squamous epithelium, surface mucus secreting cells and parietal cells in stomach and kidney uriniferous tubules. The Mab reacted with the cell surface epitope on HeLa cells to the same extent as on SKG-IIIa cells, but on CCD18-Lu cells (normal diploid) to about one-half as much. The results of an inhibition test using a competitive reaction between Mab and conventional polyclonal antibody indicated that the Mab didn't react with 39 kinds of human serum proteins such as albumin, transferrin, IgG, fibrinogen, lysozyme and some tumor markers. Immunohistochemical staining also revealed that the Mab didn't recognize human blood group substances (A,B,H type, Lewis's a,b type). Treatment of SKG-IIIa cells with a mixture of glycosidases neuraminidase or periodate didn't change the reactivity to the Mab, suggesting that the epitope didn't reside in sugar chains.

Antibodies, Monoclonal↗

Cellular differentiation of epithelioid sarcoma. An electron-microscopic, enzyme-histochemical, and immunohistochemical study.

For the purpose of clarifying cellular differentiation of epithelioid sarcoma, studies based on various methods were performed. Enzyme histochemical studies showed that epithelioid sarcoma tumor cells have characteristics intermediate between epithelial cells and the large plump cells of synovial sarcoma-incomplete epithelial differentiation. For alkaline phosphatase and adenosine triphosphatase particularly, positive cells and negative cells coexisted, as in the large plump cells of synovial sarcoma. Immunohistochemical studies for alpha 1-antitrypsin, alpha 1-antichymotrypsin, vimentin, and keratin also showed that epithelioid sarcoma tumor cells are very similar to the large plump cells of synovial sarcoma and have incomplete epithelial differentiation. For example, the examinations of serial sections and double staining methods revealed that keratin-positive cells are always vimentin-positive in epithelioid sarcoma and in the monophasic area of synovial sarcoma. Electron-microscopically, bundles of intermediate filaments and filopodia toward the intercellular lumen were observed, as in the monophasic area of synovial sarcoma. The results of enzyme-histochemical and immunohistochemical studies of non-neoplastic synovial lining cells, performed here for the first time, are also discussed.

Adenosine Triphosphatases↗