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Biomedical subjects

N Tsuda

Publications and source records attributed to N Tsuda.

At least 109 records · Page 6Linked to original sources

[A clinico-statistical study of testicular tumors--a reevaluation of 90 cases at the Nagasaki University Hospital and affiliated hospitals].

We have treated 90 cases of testicular tumors at our institutes from April, 1962 to March, 1986. Of 75 which were germ cell type tumors, 35 were a seminoma, for which the 5-year survival rate was 100% for patients in stage I, and 50% for those in stage III, respectively. Forty cases were non-seminomas, and all cases determined as being in stage I survived for 5 years, whereas 47.6% cases of those in stage III survived for 4.5 years. Thirty-six percent of those with a stage I germ cell tumor were treated with a orchiectomy alone, while other cases also combined radiotherapy and/or chemotherapy. Almost all cases of an advanced tumor received combined retroperitoneal lymph node resection, radiotherapy and/or chemotherapy. Patients with an advanced nonseminomatous tumor showed better a survival rate if they were given CDDP chemotherapy.

Dysgerminoma↗

[Transplant-induced recovery from 6-OHDA lesions of the nigro-striatal dopamine neurons in mice].

Attempts to reconstruct the damaged nigrostriatal pathway in experimental models of Parkinson disease have thus far been carried out in animals with neurotoxically induced dopamine deficiency. Our study established that unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal-dopamine (DA) neurons produced a well-characterized functional asymmetry in the behavior of C57BL/6 (H-2b) mice. The intraperitoneal administration of methamphetamine induced ipsilateral rotation at 7-20 turns/min. 11 x 10(6) syngenic DA-rich cells of embryonic ventral mesencephalon were stereotaxically transplanted in the caudate-putamen. A complete recovery of methamphetamine-induced rotational response was produced around the 60-th day after the syngenic cell suspension graft. And a complete compensation of the rotational response was also brought about with the DA-rich cells from embryonic ventral mesencephalon (crown-rump length; 10-13 mm) of allogenic C 3 H/HeN (H-2k) mice. The FACS IV analysis revealed no H-2 (Kk and Iak) antigens before transplantation of these embryonic cells. Immunohistochemistry showed that the dopaminergic fibers had grown predominantly into the ipsilateral caudate-putamen. These results provide evidence of integration of syngenic and allogenic grafts and host tissue. And the immunological response in the transplanted brain are under investigation.

Animals↗

An epithelioma of the ciliary body.

A 57-year-old woman developed a ciliary body mass which compressed the anterior side of the lens with focal cataract causing the iris to protrude into the anterior chamber. The lesion was removed by a large iridocyclectomy. The mass was classified as an epithelioma of the ciliary body, which was consistent with a benign epithelioma, i.e. an adenoma of the nonpigmented ciliary epithelium. Light and electron microscopic examinations revealed that the tumor cells had characteristics of both the ciliary and iris epithelium, which originated from the neuroectoderm, including abundant cytoplasmic filaments, and pheomelanosomes, and that the gland-like lumen was the pseudoacinous lumen, i.e. invaginated stroma containing the vitreous.

Adenoma↗

In vitro investigations with selective adsorbents for IgE and IgM.

In vitro studies were carried out with IM-T. This adsorbent consists of polyvinyl alcohol joined with tryptophan side chains and was delivered by ASAHI Medical Co., Ltd., Tokyo/Japan. It was found that IM-T binds immunoglobulins G and M and also immune complexes only moderately but IgE was adsorbed in remarkable amounts. A clear dose-dependent was adsorbed in remarkable amounts. A clear dose-dependent manner of the IgE adsorption could be stated. Kinetic studies revealed that the binding was only slow and gradual.

Animals↗

[Experimental studies on the treatment of recurrent gliomas].

For the purpose to study reasonable treatment for recurrent gliomas, in vitro immunochemosensitivity tests were performed by using human malignant glioma cell line (ONS-12) and its ACNU-resistant cell line (ONS-12/ACNU), which were established in our laboratory. ONS-12/ACNU cells showed a cross-resistance to Ara-C, but not for cisplatin and methotrexate. The lymphokine-activated killer (LAK) cells induced in vitro from the peripheral blood lymphocytes (PBL) of healthy subjects, showed stronger cytotoxicity to ONS-12/ACNU than ONS-12 cells. From these data, selection of appropriate anti-tumor agents on the in vitro sensitivity tests was a most useful method for the treatment of recurrent gliomas, and the adoptive immunotherapy with LAK cells may be useful for ACNU-resistant gliomas.

Antineoplastic Agents↗

[Effects of phenytoin on cell-mediated immunity].

Phenytoin is a highly effective anticonvulsant agent that is widely administrated to prevent some kinds of patients with brain tumor. But it has been said that phenytoin may have some immunosuppresive potential for hosts. In this study, we evaluated the effects of phenytoin upon cellular immunity such as NK, CTL and LAK activity in murine models. Fresh splenocytes were taken out from mice (CBA/J, C 3 H/HeN, C 57 BL/6) into which phenytoin had been injected intraperitoneally at a daily dose of 1,000 micrograms for 28 days. The serum concentration of phenytoin in the experimental models was 10-20 micrograms/ml. The cytotoxic activities were estimated by a 4-hr 51Cr release assay. The mitogen-stimulated lymphocyte function was evaluated by 3H-thymidine incorporation into DNA. The NK activity was estimated by cytotoxicity of splenocytes of CBA/J mice against NK-sensitive YAC-1 cells. The cytotoxic T-lymphocyte (CTL) activity was estimated by cytotoxicity of splenocytes of C 57 BL/6 mice which were stimulated in vitro for 5 days by splenocytes of C 3H/HeN treated with mitomycin C, against RSV-M glioma cells. Lymphokine-activated killer (LAK) activity was estimated by cytotoxicity of LAK cells, which were induced from splenocytes of C 3 H/HeN mice by human recombinant interleukin-2 (rIL-2), against syngeneic RSV glioma and allogeneic 203 glioma cells. 3H-thymidine incorporation of splenocytes of C 57 BL/6 mice was reduced significantly (p less than 0.01) in phenytoin-treated mice. The cytotoxicity of splenocytes of non-treated CBA/J mice against YAC-1 cells was 75%, but that of phenytoin-treated CBL/J mice was a few %.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Immunohistological observation of blood group-related antigens in lung adenocarcinomas using monoclonal antibodies].

The immunohistological distribution of blood group (BG)-related antigens including A, B, H type 2, and sialylated Lex in lung adenocarcinomas was examined using monoclonal antibodies. BG-A, B, and H type 2 compatible with the ABO status in tumor cells were expressed in 60% of the cases. Accumulation of H type 2, associated with loss of BG-A and B, was observed in tumor cells of patients with BG status other than 0. Tumor-associated antigens, Lex and sialylated Lex were detected in 36.0% and 72.0%, respectively. Modification of carbohydrate antigens in cancer may be associated with incomplete synthesis; accumulation of precursor antigen; and activated sialylation.

ABO Blood-Group System↗

[Antitumor efficacy of recombinant interferon-beta on human glioma].

The antitumor efficacy of recombinant interferon-beta (rIFN-beta) on human glioblastomas was investigated in vitro and in meningeal gliomatosis(MG) models. A total of 1.5 X 10(5) human glioma (ONS-12 and ONS-20) cells were suspended in 2 ml of RPMI-1640 with 10% fetal calf serum and placed in plastic dishes (Falcon #3001). rIFN-beta 10(2)-10(5) units were then added to each culture dish on days 3, 5 and 7. Both ONS-12 and ONS-20 human glioma cells were suppressed with a low dose of rIFN-beta. As MG models, 5 X 10(7) ONS-12 glioma cells were suspended in saline and transcutaneously inoculated into the cisterna magna of BALB/c nu/nu mice using a 27-gauge needle. The median survival times (MST) of MG models which were treated by intrathecal administration of 10(3) U of rIFN-beta and intraperitoneal injection of 10(4) U of rIFN-beta were 11.0 and 8.0 days, compared with an MST of 7 days for control mice. The rIFN-beta was not effective by intraperitoneal administration but was effective by intrathecal administration in the MG models. The MSTs of MG models which were treated by administration of 10(5) U, 10(3) U of rIFN-beta and 0.1 ml saline were 15.0, 19.0 and 9.0 days, respectively. The therapeutic efficacy in MG models depended on the administration route of rIFN-beta, and as far as could be determined from the MG models, high-dose administration of rIFN-beta was not always useful.

Animals↗

Glioblastoma with sarcomatous component associated with myxoid change. A histochemical, immunohistochemical and electron microscopic study.

The case of a 22-year-old female suffering from glioblastoma with sarcomatous component (WHO; gliosarcoma) is presented. The tumor consisted of glioblastomatous and sarcomatouos components, and in part of the pleomorphic astrocytomatous region of the glioblastoma there was a prominent production of myxoid matrix. On the basis of its histochemical and immunohistochemical characteristics, the present case strongly suggested that glial cells of neuroectodermal origin assume part of the responsibility for production of myxoid material.

Adult↗

An immunoperoxidase investigation of S-100 protein in the epithelial component of Warthin's tumor.

Using the peroxidase-antiperoxidase (PAP) immunohistochemical method, we studied the epithelial component of Warthin's tumor of the human salivary gland with respect to the presence of S-100-protein-positive cells. The tumor epithelium consisted of two layers of oxyphilic cells (an apical layer of tall columnar cells and a basal layer of small cuboidal cells) and irregularly shaped, dendritic cells scattering throughout the neoplastic epithelial cells. Two types of the oxyphilic cells were devoid of the immunoreaction products for S-100 protein. However, in the epithelial layer of Warthin's tumor, S-100-protein-positive material was observed in the cytoplasm and nuclei of dendritic cells. They were more abundant in the lymphoid tissue than in the neoplastic epithelium. The morphologic appearance of these cells was identical to that of Langerhans' cells, which were absent from the normal human salivary glands. The presence of these cells, which have a special function of antigen presentation in immune responses, indicates that delayed hypersensitivity may be the main pathogenic factor in the development of Warthin's tumor.

Adenolymphoma↗

Immunohistochemical localization of carcinoembryonic antigen in carcinoma in pleomorphic adenoma of salivary gland: use in the diagnosis of benign and malignant lesions.

The localization of carcinoembryonic antigen (CEA) and lysozyme (LZM) was immunohistochemically studied in 34 carcinomas arising in benign pleomorphic adenomas and 25 normal salivary glands in order to assess its potential diagnostic value. CEA in the normal salivary gland was located in luminal cell membranes of intercalated duct cells and serous acinar cells. Strongly positive cell surface and intraluminal staining of CEA appeared in the areas of gland-forming pattern in pleomorphic adenoma. CEA activity was detected in 7/9 cases (78%) of adenocarcinoma, 10/11 cases (91%) of epidermoid carcinoma, 3/8 cases (38%) of anaplastic carcinoma, 5/5 cases (100%) of mucoepidermoid carcinoma, and 1/1 case (100%) of adenoid cystic carcinoma. CEA was always present in the cytoplasm of epithelial cells and luminal contents of neoplastic glands. CEA in epidermoid carcinoma may occasionally react strongly in the cytoplasm. Lysozyme-immunoreactivity was detected in the cytoplasm of intercalated duct cells and serous acinar cells of the normal salivary gland but little or no LZM was observed in any of the tumors. These results suggest that the presence of CEA could be a useful marker that provides valuable information for the differential diagnosis between benign and malignant areas of carcinoma in pleomorphic adenoma of the salivary gland. Moreover, LZM could be of valuable use for discriminating neoplastic from non-neoplastic tissue of salivary glands.

Adenoma, Pleomorphic↗

[The anti-tumor efficacy of lymphokine-activated killer (LAK) cells induced in vitro from peripheral blood lymphocytes of patients with malignant glioma].

We studied whether lymphokine-activated killer (LAK) cells were capable of being induced in vitro from peripheral blood lymphocytes (PBL) of patients with malignant glioma, by using recombinant IL-2 (rIL-2). We then investigated whether they possessed anti-tumor efficacy against malignant gliomas (ONS-12, -20, -44). Human LAK cells were generated by placing 5 X 10(6) PBL into each well of 24-well plates (Corning) containing 2 ml of complete medium (CM) with 10 units of rIL-2 (TGP-3, provided by TAKEDA Chemical Industries, Ltd.). The CM consisted of RPMI 1640 with 0.1 mM nonessential amino acids, 1 microM sodium pyruvate, 5 X 10(-5) M 2-mercaptoethanol, 50 micrograms/ml gentamicin sulfate, 0.03% glutamine and 1% heat-inactivated human AB serum. The plates were incubated horizontally at 37 degrees C in a 5% CO2 atmosphere for 72-96 hours. The LAK cells were then harvested, washed three times with Hanks balanced solution, and resuspended in RPMI 1640 with 1% heat-inactivated human AB serum for the in vitro cytotoxicity assays. The anti-tumor cytotoxic activity of LAK cells was estimated in triplicate by 4-hr 51Cr release assays. The cytotoxic activity of the LAK cells against autogeneic ONS-44 glioma cells and PHA blasts was approximately 30% and a few %, respectively. The Natural Killer (NK) activity of the patient with ONS-44 glioma cells was equivalent to that of healthy subject.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Neoplasms↗

Protection of mumps in children with various underlying diseases: application of a live attenuated mumps and trivalent measles-rubella-mumps (MRM) vaccines in these children.

A live attenuated mumps and trivalent measles-rubella-mumps (MRM) vaccines have been applied to 887 and 148 children with various underlying diseases at the vaccine clinic of Osaka University Hospital between 1975 and 1985, respectively. Clinical reactions after mumps vaccination occurred in only 7 children (0.8%) and those after MRM vaccination in 28 children (19%), but their underlying diseases were not deteriorated by either vaccination. Clinical follow up study revealed that 2 of the 430 children immunized with mumps vaccine had contracted the disease during 7 year period and 2 of the 123 children immunized with MRM vaccine had contracted clinical mumps or rubella during 3 year period. The seroconversion rates after mumps vaccination were 70% and 61% by the hemagglutination inhibition (HI) test and neutralization (NT) test, respectively, while 94% by the fluorescent antibody to membrane antigen (FAMA) test. Those after MRM vaccination were 87% for measles, 96% for rubella by the HI test and 89% for mumps by the FAMA test. Serological follow up study revealed that antibodies elicited by mumps vaccination were sustained without substantial decline for at least 7 years. These results suggest that a live attenuated mumps and MRM vaccines are safe and effective in children with various underlying diseases.

Antibodies, Viral↗

[The in vitro antitumor effectiveness of murine lymphokine-activated killer (LAK) cells induced by recombinant IL-2].

We have studied the in vitro antitumor effectiveness of murine lymphokine-activated killer (LAK) cells induced by recombinant IL-2 (rIL-2). LAK cells were generated by placing 5 X 10(7) fresh C 57 BL/6 splenocytes (erythrocytes were lysed osmotically) in 10-cm (diameter) dishes (Falcon) containing 10 ml of complete medium (CM). The CM consisted of RPMI 1640 with 0.1 mM non-essential amino acids, 1 microM sodium pyruvate, 5 X 10(-5)M 2-mercaptoethanol, 50 micrograms/ml gentamicin sulfate, 0.03% glutamine, 10% heat-inactivated fetal calf serum (FCS) and 10 units/ml of rIL-2 (TGP-3, provided by TAKEDA Chemical Industries, Ltd). The dishes were incubated horizontally at 37 degrees C in a 5% CO2 atmosphere for 72-96 hr. The LAK cells were then harvested, washed three times, and resuspended in RPMI 1640 with 5% heat-inactivated FCS for the in vitro cytotoxicity assay. The antitumor cytotoxic activity of LAK cells was estimated in triplicate by 4 hr 51Cr release assays. The cytotoxic activity of LAK cells against syngeneic 203 glioma and normal syngeneic glioblasts was approximately 50% and a few %, respectively. The in vitro cytotoxicity of LAK cells against syngeneic EL-4 thymoma, allogeneic YAC-1 lymphoma and P-815 mastocytoma was 72%, 87% and 43%, respectively. Thus LAK cells have apparent tumor specificity in vitro and are easily generated. Fresh splenocytes of CBA/J mice were markedly lytic for natural killer (NK)-sensitive YAC-1 cells, but not for 203-glioma cells or NK-resistant P-815 cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Antitumor efficacy of activated macrophages against murine glioma cells].

A crucial manifestation of malignant gliomas is the regrowth of already-invaded neoplastic cells after surgical intervention. One possible approach for inhibiting such tumor growth is to utilize the tumoricidal potential of macrophages. In order to investigate the clinical application of this concept, peritoneal exudate cells (PEC) activated in vitro and in vivo by immunomodulating agents were tested for cytotoxic activity against murine glioma (203-glioma) cells. As immunomodulating agents, heat-killed Propionibacterium acnes (P. acnes), OK-432 and Concanavilin A supernatant (Con A sup) were used in these experiments. P. acnes was provided by Kowa Pharmaceutical Co., Tokyo, and OK-432 by Chugai Pharmaceutical Co., Ltd., Tokyo. Klinische Einheit (KE) units were used to express the strength of the preparation, with 1 KE equal to 0.1 mg of dried streptococci. Con A sup was produced by Con A pulsing of BALB/c splenocytes resuspended in complete medium. PEC harvested from mice to which 5% glycogen in saline had been inoculated intraperitoneally 6 d previously were activated in vitro by P. acnes (P. acnes-PEC), OK-432 (OK-432-PEC) and Con A sup (Con A-PEC). The cytotoxic activities of P. acnes-PEC, OK-432-PEC and Con A-PEC were approximately 25%, 65% and 60%, respectively. PEC were then collected from mice into which either 100 micrograms of P. acnes or 1 KE of OK-432 had been injected intraperitoneally several times. The antitumor effects of P. acnes-PEC and OK-432-PEC were about 35% and 50%, respectively. These activated PEC demonstrated cytotoxic activity against murine glioma in the tumor neutralization assay (Winn assay). Also, the antitumor efficacy of OK-432-PEC belonged mainly to adherent cells. Meningeal gliomatosis (MG) models were prepared for clinical studies. Viable 203-glioma cells (5 X 10(6) were injected percutaneously into the cisterna magna of C57BL/6 mice. The median survival time (MST) of the untreated group was 8.5 days. The MST of the groups treated by intraperitoneal and intracisternal administration of P. acnes were 26 and 33 days. This therapy significantly prolonged the survival time of these models, particularly by the intracisternal treatment. The differential cell count by Giemsa staining and latexphagocytic cell findings revealed that macrophages accounted for more than 90% of the P. acnes-PEC. These results may indicate that activated (PEC) macrophages were induced intracisternally by P. acnes and that activated macrophages induced intraperitoneally exerted antitumor effects in MG models.

Animals↗