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Biomedical subjects

S Sugihara

Publications and source records attributed to S Sugihara.

At least 145 records · Page 8Linked to original sources

[Autopsy findings in 255 cases of head and neck cancer].

Two hundred and fifty-five autopsies of patients with head and neck cancers were performed at Gunma Cancer Center between 1972 and 1986. This figure accounts for 27.8% of the total number of autopsies at the Center which was 917 cases during the period. The autopsies discussed are as follows: 1) Fifty-five cases (21.6%) were oral carcinomas, 43 cases (16.9%) maxillary carcinomas, 39 cases (15.3%) laryngeal carcinomas, 32 cases (12.5%) hypopharyngeal carcinomas and finally 22 cases (8.6%) of malignant lymphomas. 2) The incidence of visceral metastases in 200 cases of squamous cell carcinoma numbered 83, including 70 cases (84.3%) of lung metastases, the most frequently observed. 3) The causes of death in head and neck cancer were primarily of two types: Twenty five cases were due to major hemorrhage as a result of carotid rupture owing to tumor invasion and its intensive irradiation. The remaining 14 deaths resulted from interstitial pneumonitis occurring during bleomycin systemic chemotherapy. The brevity of survival from the onset of symptoms would seem to indicate that, by the time head and neck cancer manifest themselves clinically, they are already at a astage of development beyond the scope of treatment.

Autopsy↗

[Three cases of thyroid cancer, including a component of squamous cell carcinoma].

A squamous cell carcinoma of the thyroid gland is rare and its prognosis is poor. Three cases of a rare thyroid cancer are reported, the first case being an adenosquamous cell carcinoma of a 75-year-old male and the second case being a pure squamous cell carcinoma of a 64-year-old male. These two cases were pathologically diagnosed on autopsy. The overall duration of these two cases was 6 months. The third case involved a 62-year-old male. His pathological diagnosis was a mixed squamous cell carcinoma and an undifferentiated carcinoma. Postoperatively 50 Gy of irradiation was performed. This patient is still alive and has shown no evidence of recurrence for 16 months.

Adenocarcinoma↗

Autoimmune thyroiditis induced in mice depleted of particular T cell subsets. I. Requirement of Lyt-1 dull L3T4 bright normal T cells for the induction of thyroiditis.

T cell-depleted C3H/He or (C57BL/6xC3H/He)F1 (B6C3F1) mice were prepared by adult thymectomy and injection of antithymocyte serum, followed 3 wk later by lethal x-irradiation and bone marrow reconstitution. When these T cell-depleted mice were not injected or injected i.v. with normal spleen and lymph node cells treated with either anti-Thy-1, -L3T4 or -Lyt-2 antibody plus C or C alone, none of the groups of mice developed thyroiditis. In contrast, the adoptive transfer of normal cells treated with anti-Lyt-1 plus C resulted in high incidence of the production of antithyroglobulin antibody and the induction of typical thyroiditis lesion. The thyroid was the sole organ involved, because neither typical inflammatory lesion in other organs nor autoantibody such as anti-DNA antibody was detected in mice that exhibited thyroiditis. Analyses of surface phenotypes of cells required for inducing thyroiditis by the adoptive transfer revealed that an appreciable percentage of Lyt-1 dull T cells remained after the treatment of normal lymphoid cells with anti-Lyt-1 plus C. Almost all of these Lyt-1 dull T cells expressed magnitudes of L3T4 or Lyt-2 Ag comparable to those detected on Lyt-1 bright T cells. More important, the induction of thyroiditis was almost completely prevented by either in vitro or in vivo elimination of Lyt-1 dull L3T4+(bright) but not of Lyt-1 dull Lyt-2+(bright) T cells. These results indicate that Lyt-1 dull L3T4+ T cells existing in normal healthy individuals have potential to induce typical thyroiditis which is associated with the production of antithyroglobulin autoantibody, and that the activation and/or function of this T cell subset is regulated by the Lyt-1 bright T cell population coexisting in normal lymphoid cell population.

Animals↗

Type II collagen-induced murine arthritis. I. Induction and perpetuation of arthritis require synergy between humoral and cell-mediated immunity.

Immunization of DBA/1 mice with type II collagen resulted in typical and progressive arthritis, which is associated with the production of high titer of anti-collagen antibody and the induction of cell-mediated immunity as exemplified by delayed type hypersensitivity response as well as lymphokine production. In contrast, administration of heat-denatured collagen into DBA/1 mice failed to induce the arthritis. These mice produced only marginal antibody, whereas they developed comparable cell-mediated immunity to that induced by immunization with native collagen, and therefore the inoculation of heat-denatured collagen provided the regimen capable of inducing preferentially cell-mediated immunity without the generation of high level of antibody. Inasmuch as administration of antibody induced only marginal and transient joint swelling not associated with typical histologic lesion, the synergistic effect of humoral and cell-mediated immunities was investigated using antibody preparation and the regimen to induce selectively cell-mediated immunity. The results demonstrate that administration of antibody into DBA/1 mice pre-sensitized with heat-denatured collagen resulted in potent and progressive arthritis. Such synergy was further confirmed by the induction of arthritis in T cell-depleted DBA/1 mice that had been adoptively transferred with antibody and lymphoid cells from heat-denatured collagen-sensitized mice. Moreover, it was revealed that the nature of cells capable of transferring cell-mediated immunity was of Thy-1+ and L3T4+ Lyt-2-. These results indicate that anti-collagen antibody and L3T4+ T cell-mediated cellular immunity are crucially required for the perpetuated development of type II collagen-induced arthritis.

Animals↗

Establishment and characterization of a new human renal cell carcinoma cell line (KRC/Y).

A new renal cell carcinoma (RCC) cell line (KRC/Y) has been established from a surgical specimen of a 41-yr-old Japanese female patient with RCC composed of both clear cells and granular cells. This cell line has been maintained for more than 15 mo. through 45 passages with a stable growth. KRC/Y cells have clear or eosinophilic polygonal cytoplasm and round to oval nuclei with one or two nucleoli, and proliferate in a pavementlike cell arrangement with a lack of contact inhibition. By electron microscopy, these cells contain abundant fat droplets and glycogen granules or well-developed organelles or both, which were also observed in the original tumor. The doubling time of these cells at the 15th passage was 73 h. The chromosome number was from 37 to 45 with a hypodiploid modal number of 42. Tumorigenicity was identified by tumor formation after subcutaneous injections of KRC/Y cells in nude mice, which showed close resemblance to the original tumor by light and electron microscope observations.

Adult↗

Heterotransplantation of an alpha-fetoprotein-producing human gallbladder carcinoma into nude mice.

An alpha-fetoprotein (AFP)-producing human gallbladder carcinoma showing direct invasion into the liver was transplanted into BALB/c-nu/nu nude mice. Although patient serum levels of AFP and carcinoembryonic antigen (CEA) were within normal limits, they were elevated to 1,040 ng/ml and 22.1 ng/ml, respectively, after cholecystectomy. Prominent liver metastasis was demonstrated by diagnostic imaging techniques shortly after the operation. Pathologically, the resected tumor consisted of papillotubular adenocarcinoma and the part which had invaded the liver showed a solid growth pattern with no papillo-tubular structure. The transplanted tumor showed both papillo-tubular and solid growth patterns, in which positive reactions for AFP, CEA, ferritin (FER), carbohydrate antigen 19-9 (CA 19-9), albumin (ALB) and fibrinogen (FIB) were confirmed by the avidin-biotin-peroxidase complex method. Serum levels of AFP, CEA, CA 19-9, beta 2-microglobulin (BMG) and FER were elevated in the nude mice bearing tumor transplants. Twenty-five percent of the serum AFP from nude mice with tumor transplants bound with concanavalin A (Con A), suggesting that the tumor was of gastrointestinal rather than hepatic origin.

Adenocarcinoma↗

A new human pleomorphic hepatocellular carcinoma cell line, KYN-2.

A new human hepatocellular carcinoma (HCC) cell line, KYN-2, has been established from a surgical specimen obtained from a 52-year-old Japanese male HCC patient. The originally resected HCC was classified as pleomorphic HCC corresponding to Edmondson-Steiner's grade III with a thick trabecular to solid arrangement. The cell line has been maintained for 17 months through 35 passages. Morphologically, the KYN-2 cells have retained the characteristics of the original HCC, being pleomorphic and composed of various types such as cells with relatively small, polygonal, eosinophilic cytoplasm and oval-shaped nuclei with a marked tendency to pile up, flat cells with abundant clear cytoplasm and oval-shaped nuclei, and many multinucleated giant cells, proliferating in a pavement-like cell arrangement. Some junctional complexes and a number of microvilli are evident between the cells by electron microscopy. Functionally, these cells were found to secrete albumin, alpha 1-acid glycoprotein, alpha 1-antitrypsin, ceruloplasmin, transferrin, complement C, fibrinogen, fibronectin, prothrombin, retinol-binding protein (serum type), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), ferritin and beta 2-microglobulin in chemically defined medium (CDM). The secretion of AFP and CEA is apparently dependent upon culture medium and passage. The doubling time of cells growing in serum-containing medium at the 14th passage was 84 h, and those of cells in serum-containing medium, HB101 (serum-free medium) and CDM at late passage were 28, 68, and 42 h, respectively. Chromosome analysis revealed that the chromosome number ranged from 56 to 69 without a mode, and the presence of marker chromosomes. HB virus DNA sequence was not detected by hybridization analysis. The tumorigenicity of KYN-2 cells was identified by development of tumors in nude mice after subcutaneous injection of the cells; the tumors showed an appearance basically similar to that of the original HCC. Thus, these findings suggest that the KYN-2 cell line is available as a new human HCC cell line and should be useful for various studies on HCC.

Animals↗

Induction of insulitis by adoptive transfer with L3T4+Lyt2- T-lymphocytes in T-lymphocyte-depleted NOD mice.

To clarify the pathogenesis of insulitis in the nonobese diabetic (NOD) mouse, an animal model for human insulin-dependent diabetes mellitus, T-lymphocyte-depleted NOD mice (B mice) were adoptively transferred with spleen and lymph node cells from cyclophosphamide-treated NOD mice after separating the cells with monoclonal antibodies against various T-lymphocyte surface antigens plus complement. Light-microscopic and immunohistochemical studies were also performed to investigate the lymphocytic infiltrations. The incidence of insulitis detected in B mice was much lower when compared with that of the lesion naturally occurring in the NOD mouse. However, higher incidence of insulitis was inducible in B mice by transferring unfractionated lymphoid cells from NOD mice. When the Thy1+ cell-depleted fraction was transferred into the B mice, no increase in the incidence of insulitis was observed. The Lyt1+ or L3T4+ cell-eliminated fraction was also unable to transfer insulitis. Conversely, donor cells depleted of Lyt2+ components successfully induced insulitis in the recipient B mice. These data were consistent with the immunohistochemical study, which showed that the main phenotype of the cells infiltrating the islets was L3T4+. These results suggest the importance of L3T4+Lyt2- T-lymphocytes in the pathogenesis of insulitis in NOD mice.

Animals↗

[An adenoid tumor of the epididymis--electron microscopy and immunohistochemistry].

A case of an adenomatoid tumor of the epididymis is reported. The patient, a 41-year-old male, had a total right orchiectomy of his testicular mass. The tumor was located in the inferior portion of the right epididymis and was a well-circumscribed solitary mass, measuring 3 X 3 X 3 cm. Microscopically, the tumor contained plump acidophilic cells arrange in cords and trabecula with fibrous connective tissue. Immunohistochemical studies for keratin and vimentin in the tumor cells were positive. Electron microscopical findings of the tumor were similar to those of a benign mesothelioma. These findings suggest that adenomatoid tumors are of mesothelial origin.

Adult↗

[A case of primary carcinoid tumor of the testis].

A case of a primary carcinoid tumor of the testis which occurred in a 57-year-old man is reported. The patient was treated by orchiectomy, and no clinical features of a carcinoid syndrome had been noted. The tumor measured 4.0 X 3.2 X 2.0 cm in size and was yellowish in color. Histochemically, the tumor cells were composed in part of argentaffin and in part of argyrophil. Immunohistochemically, the argentaffin tumor cells were positive for neuron-specific-enolase. No tumor cells were positive, however, for neurofilaments, vimentin, keratin, desmin, GFAP, S-100 protein, ACTH, and somatostatin. Electronmicroscopy revealed numerous neurosecretory granules. Tumorous tissue presented a histomorphology of a pure carcinoid tumor composed of parts of argentaffin and argyrophil.

Carcinoid Tumor↗

Studies on macrophage-activating factor (MAF) in antitumor immune responses. II. Molecular characterization of MAF produced by the tumor-immune Lyt-1+2- T cell subset.

In the present study we investigated some of the physicochemical properties of macrophage-activating factor(s) (MAF) produced by the tumor-immune Lyt-1+2- T cell subset. Supernatant from mixed culture of spleen and lymph node cells, obtained from C3H/HeN mice immunized with syngeneic MH134 hepatoma or MCH-1-A1 fibrosarcoma, with the corresponding tumor cells exhibited the capability of activating peritoneal exudate macrophages to exert their cytostatic and cytolytic activities on tumor cells. Such MAF production was abolished by treatment of tumor-immune spleen and lymph node cells with anti-Thy-1.2 or anti-Lyt-1.1 antibody plus complement (C) before culturing. Anti-Lyt-2.1 and/or anti-asialo GM1 plus C treatment, however, had only marginal effect on the generation of MAF by these cells, despite the complete disappearance of natural killer (NK) cell activity of spleen and lymph node cells after the treatment with anti-asialo GM1 plus C. Thus, the tumor-specific Lyt-1+2- T cell subset could fulfill a crucial role in generating MAF without the support of NK cells. The MAF activity was heat, acid, and trypsin sensitive. On Sephacryl S-300 column, MAF activity was eluated in a broad single peak around a molecular weight (m.w.) of 70,000 daltons. Antiviral activity was detected in the concentrated pool of MAF-containing fractions from Sephacryl S-300. Gel permeation analysis using HPLC also showed a coincident peak of MAF and antiviral activities at a m.w. of approximately 70,000 daltons. In addition, MAF activity was almost completely neutralized by incubation with rabbit antiserum against recombinant murine gamma-interferon (IFN gamma). Taken together, these results indicate that MAF generated by tumor-immune Lyt-1+2- T cell subset is closely related to IFN gamma.

Animals↗

The generation of tumor-specific in vivo protective immunity in the tumor mass from mice rendered tolerant to tumor antigens.

C3H/He mice were inoculated i.v. with 10(6) heavily X-irradiated syngeneic X5563 plasmacytoma cells 3 times at 4 day intervals. When these mice received an appropriate immunization procedure consisting of i.d. inoculation of viable tumor cells plus the surgical resection of the tumor which enables i.v. nonpresensitized mice to produce anti-X5563 immunity, they failed to develop tumor-specific immunity. This was demonstrated by the abrogation in potential of spleen and lymph node cells to generate in vivo protective immunity. In contrast, the tumor mass from X5563 tumor-bearing mice which had received the i.v. presensitization contained comparable anti-X5563 tumor neutralizing activity to that obtained from the tumor mass from nonpresensitized, X5563 tumor-bearing mice. Such an in vivo protective immunity was revealed to be mediated by tumor-specific T cells. These results demonstrate the differential generation and antitumor capability of tumor infiltrating T cells and T cells in lymphoid organs from mice which are in the tumor-specific tolerant state. The results are discussed in the context of potential utilization of tumor infiltrating in vivo protective T cells to enhance the local tumor-specific immunity in tumor-specific tolerant mice.

Animals↗

Relationship of histologic grade of hepatocellular carcinoma (HCC) to tumor size, and demonstration of tumor cells of multiple different grades in single small HCC.

The histologic features of 65 surgically resected cases of hepatocellular carcinoma (HCC) were studied, and the cellular differentiation was graded from I to IV according to Edmondson-Steiner's classification. HCC cells of 2 or more grades were seen in 31 (47.7%) of the 65 cases. There was no significant difference in the proportion of HCC composed of tumor cells of more than one histologic grade between HCCs with association with liver cirrhosis and without cirrhosis. Among these 31 cases, extremely well-differentiated HCC, corresponding to Edmondson-Steiner's grade I carcinoma, was found in 9 of 11 tumors smaller than 3 cm in diameter, but it was not seen in 20 tumors larger than 3 cm in diameter. In the 34 HCCs with a uniform histologic pattern, all of two minute tumors smaller than 1 cm in diameter consisted of extremely well-differentiated HCC, but there were no cases consisting of extremely well-differentiated HCC in tumors larger than 2 cm in diameter. Taken together, these findings suggest that HCCs originate as relatively well-differentiated tumors, which may be difficult to distinguish from adenomatous regenerative nodules, and become progressively less differentiated at a later stage of their development.

Aged↗

[Tritium and carbon-14 concentrations around an incinerator for radioactive liquid scintillator waste].

Activity measurements of 3H and 14C in several environmental samples around the incinerator for radioactive liquid scintillator waste at the Radioisotope Center, Kyushu University were carried out to estimate their levels. It was indicated that 3H and 14C concentrations in the atmosphere at 1 m from the outlet were about 0.2% of those estimated at the outlet, respectively. At 6 m away from the outlet, 3H concentration decreased to about one twentieth of that at 1 m and 14C concentration to background level. For soils and plants, 14C concentrations showed negligibly low values. The existence of these nuclides in particle form was not confirmed. It is considered that the result of the higher 3H concentrations as compared to 14C concentrations reflects not only the difference of the waste amounts of their nuclides, but also the discharge of 3H as moisture as well as water vapor.

Carbon Radioisotopes↗