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Biomedical subjects

N Shinomiya

Publications and source records attributed to N Shinomiya.

89 records · Page 5Linked to original sources
PubMed1984

T-cell subsets regulating anti-acetylcholine-receptor-antibody formation in myasthenia gravis and characterization of suppressor T-cell factors involved.

The in vitro generation of anti-acetylcholine-receptor (AChR)-antibody-forming cells from B cells of myasthenia gravis (MG) patients occurred only in the presence of OKT4+ cells. Anti-AChR-antibody formation by lymphocytes from MG patients was suppressed by normal T cells, and the requirement of both OKT4+ and OKT8+ cells was suggested for this suppression. Culture supernatant from normal T cells stimulated with excess doses of AChR antigen, but not T cells from patients, suppressed anti-AChR-antibody formation by lymphocytes from patients. The fraction of the culture supernatant with molecular weight of 45,000 to 67,000 seemed to contain an AChR-antigen-specific and antigen-binding suppressor factor with some allogeneic barrier, while the fraction with a molecular weight of 10,000 to 28,000 contained the antigen-nonspecific factor.

Antibody Formation↗
PubMed1983

Induction of suppressor T cells by anti-globoside antibodies in cancer sera.

T cells treated with cancer sera frequently suppressed immunoglobulin production by autologous lymphocytes stimulated with pokeweed mitogen. Sera from healthy individuals did not induce suppressor activity. This suppression is not caused by TG cells (T cells bearing receptors for the Fc portion of immunoglobulin G [IgG]) interacting with immune complexes, because we used T cells depleted of TG cells. The suppressor-inducing factors were separated into an IgG-containing fraction and a fraction with a smaller molecular weight. IgG fractions from all sera that were positive for anti-globoside antibody induced suppressor T cells, and elimination of the anti-globoside antibody from these IgG fractions reduced the ability to induce suppressor T cells. T cells treated with rabbit anti-globoside antiserum also activated suppressor T cells. These observations indicate that the antibodies directed to the globoside antigen on suppressor T cells stimulate the suppressor T cells, and that anti-globoside antibody in cancer sera may play a role in causing immunodeficiency in cancer patients.

Antibodies↗
PubMed1981

B and T cell involvement in anti-acetylcholine receptor antibody formation in myasthenia gravis.

The in vitro method of antibody production was applied to ascertain the contribution of B and T cells to the formation of anti-acetylcholine receptor (AChR) antibody. The anti-AChR antibody in the culture supernatant was estimated by radioimmunoassay, and the anti-AChR antibody-forming cells from cultures were detected by autoradiography of the antigen-binding cells. Thymic B cells from myasthenia gravis (MG) patients formed antibody when they were cultured with thymic T cells from MG patients and stimulated with AChR antigen. The antibody formation was more vigorous with thymic B cells, which contained more germinal centres. The antibody was also formed from the B and T cell combination of peripheral blood lymphocytes, although the amount was less than that produced by thymic lymphocytes from MG patients. The antibody produced by lymphocytes from MG patients. The antibody produced by lymphocytes from MG patients was suppressed by the addition of T cells from the culture supernatant of normal individuals, but not by autologous or allogeneic T cells from MG patients. The suppression by T cells from normal individuals was abolished when the cells were treated with mitomycin C. These observations indicated that AChR-specific B cells and helper T cells are active, while the suppressor T cells, which are usually present in normal individuals, are defective in MG patients.

Adult↗
PubMedDate not supplied

New concepts in radiation-induced apoptosis: 'premitotic apoptosis' and 'postmitotic apoptosis'.

Formerly, the mechanisms responsible for the killing of cells by ionizing radiation were regarded as being divided into two distinct forms, interphase death and reproductive death. Since they were defined based on the classical radiobiological concepts using a clonogenic cell survival assay, biochemical and molecular biological mechanisms involved in the induction of radiation-induced cell death were not fully understood in relation to the modes of cell death. Recent multidisciplinary approaches to cell death mechanism have revealed that radiation-induced cell death is divided into several distinct pathways by the time course and cell-cycle position, and that apoptotic cell death plays a key role in almost every mode of cell death. This review discusses the mechanisms of radiation-induced apoptosis in relation to cell-cycle progression and highlights a new concept of the mode of cell death: 'premitotic apoptosis' and 'postmitotic apoptosis'. The former is a rapid apoptotic cell death associated with a prompt activation of caspase-3, a key enzyme of intracellular signaling of apoptosis. A rapid execution of cell killing in premitotic apoptosis is presumably due to the prompt activation of a set of pre-existed molecules following DNA damages. In contrast, the latter is a delayed apoptotic cell death after cell division, and unlike premitotic apoptosis, it neither requires a rapid activation of caspase-3 nor is inhibited by a specific inhibitor, Ac-DEVD-CHO. A downregulation of anti-apoptotic genes such as MAPK and Bcl-2 may play a key role in this mode of cell death. Characterization of these two types of apoptotic cell death regarding the cell cycle regulation and intracellular signaling will greatly help to understand the mechanisms of radiation-induced apoptosis.

Apoptosis↗
PubMedDate not supplied

Correlation between telomerase activity and DNA ploidy in gastric cancer.

Telomerase has been reported to be activated in most immortal cells and human cancers. In the present study, we assessed the correlation between telomerase activity and cellular DNA ploidy level in gastric cancer. Telomerase activity was determined semiquantitatively using the telomeric repeat amplification protocol assay, a polymerase-chain-reaction-based assay, in surgical specimens of primary tumors obtained from 36 patients with gastric cancer. No correlation was observed between telomerase activity and the proliferating cell nuclear antigen labeling index. In contrast, a positive linear correlation was observed between telomerase activity and the DNA index (r = 0.59; p < 0.01). Tumor cells with aneuploid patterns showed higher telomerase activity than those with diploid patterns (27.6+/-5.8 vs. 5.8+/-1.1%; p < 0.01). Telomerase activity of tumors with liver metastases was significantly higher than activity of those without metastases (34.5+/-16.6 vs. 11.8+/-2.4; p < 0.05). There was a trend toward a lower survival rate in 9 patients with a telomerase activity of 20% or higher compared to 27 patients with telomerase activity lower than 20%. These results suggest that the telomerase activity of gastric cancer tissue may reflect the malignant potential of the tumor.

Adult↗
PubMedDate not supplied

Effects of cisplatin on cell cycle kinetics, morphological change, and cleavage pattern of DNA in two human ovarian carcinoma cell lines.

We evaluated the effects of cisplatin on the cell kinetics, cytomorphological changes, and cleavage patterns of DNA in two lines of human ovarian carcinoma cells. KF-1 cells displayed a cell cycle arrest in the G2M phase, while HMG cells displayed a transient cell accumulation in the S phase, without obvious G2M arrest. Morphological changes characterized by condensation and fragmentation of chromatin, and DNA cleavage by oligonucleosome-sized DNA fragments were observed in the HMG cells but not in the KF-1 cells. The pattern of cell death in HMG cells was considered to be apoptosis, but that of KF-1 cells necrosis. These findings showed the different mechanisms of anti-tumor effect of cisplatin on human ovarian carcinoma cell lines, including cell kinetics and pattern of cell death.

Carcinoma↗
PubMedDate not supplied

Induction of apoptosis by JTE-522, a specific cyclooxygenase-2 inhibitor, in human gastric cancer cell lines.

An increased expression of cyclooxygenase (COX)-2 has been observed in various cancers including gastric cancer. Although specific COX-2 inhibitors have a chemopreventive effect on colon cancer, their molecular mechanisms remain unclear. To clarify these mechanisms, we investigated the effects of JTE-522, a newly developed COX-2-specific inhibitor, on gastric cancer cell lines (MKN28 and MKN45). The baseline levels of COX-2 expression were higher in MKN45 than in MKN28. JTE-522 obviously suppressed the levels of COX-2 mRNA, COX-2 protein and PGE2 at a dose of 250 microM in both cancer cells. Apoptosis was induced at 24 hours after treatment with JTE-522 (250 microM) in both cancer cells. To determine the mechanisms of apoptosis induction by JTE-522, the time course of the cell cycle and the apoptosis-related protein levels were examined. An increase in the G1 phase and a decrease in the S phase were observed prior to apoptosis. Moreover, an increase of c-myc protein and a decrease of bcl-2 protein were observed in both cells treated with JTE-522. These findings suggested that JTE-522 could induce apoptosis by blocking the cell cycle, enhancing c-myc expression and diminishing bcl-2 expression. JTE-522 also suppressed proliferation activity in both cell lines. These effects of JTE-522 were more dramatic in MKN45 than in MKN28. Since JTE-522 strongly suppresses cell growth by inducing apoptosis in gastric cancer cell lines, it may therefore serve as a chemopreventive agent.

Anticarcinogenic Agents↗
PubMedDate not supplied

Functional changes of alveolar macrophages in carragheenan-induced aspiration pneumonia model mice.

Alveolar macrophages (AMs) are cells with unique characteristics because of their localization in the aerobic environment and are receiving stimuli by inhalation. To estimate the functional changes of AMs induced by inflammation, a murine model of aspiration pneumonia was made by an intratracheal injection with carragheenan, whose mortality rate was approximately 25%. The cell component which increased predominantly in the inflammatory site was polymorphonuclear leukocytes, and the number of AMs did not show a remarkable increment. Control group showed a high level of intracellular oxidation of 2'7'-dichlorofluorescin (DCFH) by AMs, while that in carragheenan-treated mice decreased significantly (p < 0.05). There were two populations in AMs classified according to the oxidative activity of DCFH; the population showing high oxidative activity of DCFH was asialo GM1 positive, in contrast, that with lower oxidative activity was asialo GM1 negative. Decrease in DCFH-oxidative activity of AMs in control group was observed after a treatment with KCN or deferoxamine. But in the carragheenan-treated group, this decrease was not observed after treatment with KCN. These results show that both oxygen-derived radical produced in mitochondria, which is inhibited by KCN, and cytoplasmic OH radical, which is selectively inhibited by deferoxamine, are concerned with intracellular oxidation of DCFH by AMs, and that a decrease in DCFH-oxidative activity in the carragheenan-treated group was attributed to the depression of mitochondrial respiration. Nevertheless, increased expressions of Ia and F4/80 in AMs of the carragheenan-treated group were observed and phagocytic activity was well preserved at the control level. These results suggest that AMs may play a crucial role, as well as differentiated phagocytes possessing antigen-presenting ability and/or digestive activity against various types of foreign bodies despite showing an obvious decrement in oxidative activity. These results imply that AMs have a strong oxidative activity and deal with various types of antigens in normal states, but in case of acute inflammation they will change into mature type macrophages with high expression of class II molecules which correlates with an antigen-presenting capacity.

Amino Acid Oxidoreductases↗
PubMedDate not supplied

Effects of macrophage colony-stimulating factor on the activities of murine monocytes and peritoneal macrophages in vivo.

The ability of peripheral blood monocytes, granulocytes and resident peritoneal macrophages to generate hydrogen peroxide in response to concanavalin A was enhanced by a single intravenous injection of macrophage colony-stimulating factor (M-CSF) of recombinant human type in AKR mice. In response to phorbol myristate acetate, only granulocytes and resident peritoneal macrophages showed the enhanced ability. Phagocytosis by those cells was not stimulated by M-CSF. Surface marker analysis showed an increased expression of F4/80 and Mac1 on monocytes, Mac1 expression on granulocytes and LFA-1 expression on resident peritoneal macrophages. Ia antigen on resident peritoneal macrophages was suppressed by M-CSF. M-CSF can induce monocytes, granulocytes and resident peritoneal macrophages to generate hydrogen peroxide and enhances their maturation in vivo.

Animals↗