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Biomedical subjects

S Sone

Publications and source records attributed to S Sone.

At least 307 records · Page 17Linked to original sources

[Intraoral ultrasound of the tongue tumor].

Transcutaneous ultrasonography scanned through the submandibular triangle has been effectively utilized for the evaluation of tongue tumors. However, because of lacking an appropriate sonic window, tumors located in the anterior portion of the tongue can not be demonstrated on the transcutaneous ultrasonogram. Intraoral ultrasonography using an echoendoscopy was effective for evaluating neoplasms of the tongue, and could clearly demonstrate tongue tumors, which failed to be shown on the transcutaneous ultrasonograms. In addition, intraoral ultrasonograms could provide more accurate anatomical informations concerning the tumor extent than the transcutaneous ultrasonograms.

Endoscopy↗

Heterogeneity in responses of human blood monocytes to granulocyte-macrophage colony-stimulating factor.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has stimulatory effects on various monocyte functions. We examined whether all or only some blood monocytes could respond to GM-CSF. Monocytes from peripheral blood of healthy donors were separated by size into five fractions by counter-flow centrifugal elutriation (CCE). The phagocytic activities of monocytes in these fractions depended on the size of the cells. On activation by bacteria-derived stimuli, these fractions showed similar responses of production of monokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF) and cytotoxicity against allogeneic tumor cells. On treatment of these fractions with optimal concentration of GM-CSF, fractions 3, 4, and 5 showed tumoricidal activity and produced cell-associated IL-1, fraction 3 producing the most, whereas release of IL-1 and TNF in the supernatant was not observed. The cell-associated IL-1 was identified as IL-1 alpha, not IL-1 beta, by neutralizing tests with antisera against IL-1 alpha and IL-1 beta. GM-CSF also induced the proliferative and colony-forming responses of medium and large monocytes. These observations suggest that adoptive therapy with macrophage progenitor cells in peripheral blood may be useful in combination with GM-CSF for treatment of monocytopenia after chemotherapy or radiation therapy.

Cell Division↗

Tumor cytotoxicity and interleukin 1 production of blood monocytes of lung cancer patients.

The effects of lung cancer on the abilities of blood monocytes to produce interleukin-1 and to mediate antitumor activity were examined. The functional integrity of blood monocytes was determined by their capacity to respond in vitro to a variety of activating agents and become tumoricidal, as assessed by a radioactive release assay and ability to produce interleukin-1 in vitro. The results show that the presence of lung cancer significantly increased the number of harvested blood monocytes and that the spontaneous tumoricidal activity of these monocytes was slightly high as compared to monocytes obtained from healthy donors. The production of interleukin-1 by monocytes of healthy donors and lung cancer patients was similar. Blood monocytes obtained from lung cancer patients were less cytotoxic against allogeneic A375 melanoma cells as compared with those of healthy donors subsequent to incubation with a soluble muramyl dipeptide analog or lipopolysaccharide, but were as tumoricidal as those from healthy donors when activated with lipophilic muramyl tripeptide (MTP-PE) entrapped in multilamellar liposomes. The finding that monocytes of patients with lung cancer can respond to MTP-PE encapsulated in liposomes, recommends the use of these liposomes in therapy of human lung cancer.

Acetylmuramyl-Alanyl-Isoglutamine↗

High resolution ultrasound of the chest wall.

To study the detailed normal ultrasonic anatomy of the pleura and chest wall, high resolution (7.5 MHz) ultrasonograms were obtained from cadaver chest wall specimens and compared with thin section computed tomograms and anatomical specimens. Ultrasonograms show three layers of the intercostal muscles (internal, external and innermost), covered by the "echogenic pleural line." The "echogenic pleural line" is caused by composite echoes from the inner parietal pleura, and the outer endothoracic fascia, with the fatty tissue covering both sides of the fascia, which are located deep to the chest wall muscles. On ultrasonograms, the subpleural fat tissue, when abundant, appeared as an apron-like structure hanging down from the inner surface of the rib (subpleural fat pad), or diffuse fat accumulation mimicking the pleural thickening.

Humans↗

Abnormally high expression of proteasomes in human leukemic cells.

Proteasomes are eukaryotic ring-shaped or cylindrical particles with multicatalytic protease activities. To clarify the involvement of proteasomes in tumorigenesis of human blood cells, we compared their expression in human hematopoietic malignant tumor cells with that in normal peripheral blood mononuclear cells. Immunohistochemical staining showed considerably increased concentrations of proteasomes in leukemic cells from the bone marrow of patients with various types of leukemia and the predominant localization of these proteasomes in the nuclei. Moreover, enzyme immunoassay and Northern blot analysis indicated that the concentrations of proteasomes and their mRNA levels were consistently much higher in a variety of malignant human hematopoietic cell lines than in resting peripheral lymphocytes and monocytes from healthy adults. Proteasome expression was also greatly increased in normal blood mononuclear cells during blastogenic transformation induced by phytohemagglutinin; their expression increased in parallel with induction of DNA synthesis and returned to the basal level with progress of the cell cycle. Thus, abnormally high expression of proteasomes may play an important role in transformation and proliferation of blood cells and in specific functions of hematopoietic tumor cells.

Antibodies, Monoclonal↗

Monoclonal anti-P-glycoprotein antibody-dependent killing of multidrug-resistant tumor cells by human mononuclear cells.

Mouse monoclonal antibodies (MRK16 and MRK17) against human multidrug-resistant cancer cell lines were tested for antibody-dependent cytotoxicity mediated by human blood mononuclear cells, using a 4-h 51Cr release assay. MRK16 (IgG2a isotype) was shown to be more effective than MRK17 (IgG1 isotype). Moreover, when four pairs of drug-resistant and their parent sensitive human cancer cells were tested for antibody-dependent cell-mediated cytolysis (ADCC) using MRK16, only the drug-resistant cell lines were susceptible to ADCC reaction. When highly purified lymphocytes (greater than 99%) and monocytes (greater than 97%) were isolated from blood mononuclear cells by centrifugal elutriation and adherence, MRK16 promoted both lymphocyte- and monocyte-mediated tumor cell killing, whereas MRK17 induced only a lymphocyte-mediated ADCC reaction. These results suggest that MRK16 of IgG2a subtype may be a useful therapeutic agent in eradication of drug-resistant cancer cells expressing P-glycoprotein through ADCC reaction.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Production of tumor necrosis factor-alpha by alveolar macrophages of lung cancer patients.

The abilities of human alveolar macrophages (AM) obtained from healthy donors and patients with lung cancer to produce tumor necrosis factor (TNF) were compared with those of their blood monocytes after activation with lipopolysaccharide (LPS). TNF activity was assayed by measuring cytotoxicity against actinomycin D-treated L929 cells and TNF was determined quantitatively by sandwich enzyme-linked immunosorbent assay (ELISA) with polyclonal and monoclonal antibodies against TNF-alpha. Unstimulated AM from healthy donors released variable amounts of TNF spontaneously, whereas blood monocytes did not. When treated with LPS for 24 h, AM and monocytes produced TNF dose-dependently, but TNF production by AM was significantly more than that by blood monocytes. This TNF activity was inhibited completely by monoclonal anti-TNF-alpha antibody. Macrophages generated by in vitro maturation of monocytes induced by granulocyte-macrophage colony-stimulating factor (GM-CSF) produced more TNF than freshly isolated monocytes. No difference was found in the abilities of AM from healthy donors and patients with lung cancer to produce TNF after activation stimuli. These observations suggest that human AM may be important in in vivo antitumor defense of the lung through TNF-alpha production.

Adult↗

Suppression by interleukin 4 of activation of human blood monocytes to the tumoricidal state.

The effect of interleukin 4 (IL-4) on expression of antitumor activity of blood monocytes purified by counter-flow centrifugal elutriation from healthy donors was examined. The blood monocytes were incubated for 24 h in medium with lipopolysaccharide, interferon gamma (IFN-gamma) or desmethyl muramyl dipeptide (norMDP) or with IFN-gamma and norMDP in the presence of IL-4, and then their tumoricidal activity was assayed by measuring 125IUdR release from human melanoma (A375) cells. Irrespective of activation stimulus, addition of IL-4 to cultures of monocytes and activators resulted in dose-dependent suppression of the tumoricidal activity of monocytes against parent A375 melanoma cells and the variant cells, A375-R resistant to IL-1 and tumor necrosis factor alpha. IL-4 suppressed the early induction phase of monocyte activation. Rabbit anti-IL-4 antisera completely blocked the IL-4-mediated suppression of monocyte activation to the tumoricidal state. These findings suggest that IL-4 is important in vivo in down-regulation of anti-tumor expression of monocytes.

Cells, Cultured↗

Role of phosphatidylserine in membrane actions of tumor necrosis factor and interferons alpha and gamma.

For elucidation of the role of phosphatidylserine (PS) in the membrane actions of human recombinant tumor necrosis factor (TNF) and interferons (IFNs) alpha and gamma, the actions of these cytokines on liposome membranes containing PS were compared with those on liposome membranes containing two other anionic phospholipids, phosphatidylglycerol (PG) and phosphatidic acid (PA). At pH 4.0 or 4.5, where these three cytokines were bound almost completely to the liposome membranes, (1) the ratios of the rates of membrane action of TNF and IFN-alpha on PS-containing liposomes to those on PG- or PA-containing liposomes were similar, but always greater than the ratio of the former to the latter rates of IFN-gamma, and (2) progressive replacement of either PG or PA in membranes by PS at a constant anionic phospholipid concentration decreased or increased the rates of membrane action of TNF and IFN-alpha but only decreased that of IFN-gamma, suggesting that membrane PS modulates the membrane actions of these three cytokines. The possible role of PS in the cytotoxic actions of these cytokines on tumor cells is discussed.

Humans↗

Decrease of lymphokine (interleukin-2)-activated killer activity in peripheral blood after administration of natural interferon-gamma.

Interferon-gamma (IFN-gamma) acts on a large array of different types of cell and has potent immunomodulatory activities besides cytotoxic effects on tumors. In a phase I study, some immunologic parameters of blood mononuclear cells from healthy volunteers who received intramuscular injections of natural human IFN-gamma were analyzed. The percentage of Leu-11a positive cells, natural killer (NK) activity, lymphokine (interleukin-2)-activated killer (LAK) activity and monokine production were measured either in blood mononuclear cells or in purified samples of lymphocytes or monocytes of the donors before and 24 h after IFN-gamma injection. After IFN-gamma injection, the percentage of Leu-11a positive cells and the LAK activity in the blood were significantly reduced, but NK activity and monokine production remained unchanged. These findings suggest that in vivo IFN-gamma acts directly or indirectly on Leu-11a positive cells and reduces LAK activity by changing the recruitment of LAK precursors in the blood.

Burkitt Lymphoma↗

[Vestibular function in severely retarded children in relation to their motor disabilities].

We examined vestibular functions of thirty-one severely retarded children with caloric test and rotation nystagmus test, in combination with auditory brainstem response (ABR) recordings and measurement of brainstem width on cranial CT scans. The laterality of vestibular response was over 20% in most of the bedridden cases and was under 20% who could move. Abnormal findings in ABR had no relationship with the degree of motor disabilities, but decreased width of brainstem on CT scan showed some relationship with the degree of motor disabilities. We conclude that vestibular function tests are useful to predict future motor development in severely retarded children.

Adolescent↗

[Eosinophil colony stimulating activity induced by administration of interleukin-2 into the pleural cavity of patients with malignant pleurisy].

Systemic administration of interleukin-2 (IL-2) in patients with malignant diseases induces peripheral eosinophilia. In the present study, to clarify the mechanisms of eosinophilia induced by IL-2, we examined the changes in the number of eosinophils and in eosinophil colony stimulating activity (Eo-CSA) in the pleural fluid of six patients with malignant pleurisy caused by lung cancer or malignant mesothelioma, during and after intrapleural administration of IL-2. Results showed that intrapleural administration of IL-2 induced marked eosinophilia in the pleural fluid and mild eosinophilia in the peripheral blood, and that during IL-2 administration, marked Eo-CSA appeared in the pleural fluid before increase in the number of eosinophils. The Eo-CSA seemed to be a polypeptide or protein because it was trypsin-sensitive and had a molecular weight of 40-60 kDa.

Aged↗

[N-isopropyl I-123 p-iodoamphetamine single photon emission computed tomography of herpes simplex encephalitis].

Two patients with herpes simplex encephalitis were studied with N-Isopropyl I-123 p-Iodoamphetamine (IMP) single photon emission computed tomography (IMP-SPECT) and X-ray computed tomography (CT). In both cases the affected temporal lobes showed an increased IMP uptake. In case 1, the initial increased IMP uptake decreased as symptoms and CT findings improved. In case 2, the increased IMP uptake was shown at the time of symptoms progressed, while CT had no abnormal findings. IMP uptake is sensitive for its demonstration of inflammatory processes of herpes simplex encephalitis.

Aged↗

Up-regulation by granulocyte-macrophage colony-stimulating factor (GM-CSF) of induction of lymphokine (IL-2)-activated killer (LAK) cells by human blood monocytes.

The role of recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) in monocyte-mediated up-regulation of lymphokine-activated killer (LAK) cell induction by IL-2 was examined. Treatment of blood mononuclear cells (MNC) of healthy donors with GM-CSF for 4 days in the presence of IL-2 resulted in a significant increase in LAK activity against natural killer (NK)-resistant Daudi cells, as assessed by the 4 hr 51Cr-release assay. For determination of the role of GM-CSF in LAK induction, highly purified lymphocytes (greater than 99%) and monocytes (greater than 90%) were isolated from MNC by counter-flow centrifugal elutriation (CCE). Pre-treatment of monocytes for 4 days with GM-CSF before addition of lymphocytes plus IL-2 resulted in a significant dose-dependent increase in monocyte-mediated up-regulation of LAK induction, but in the absence of monocytes GM-CSF had no effect on LAK cell induction. Similarly, GM-CSF augmented the proliferative response of lymphocytes to IL-2 in the presence of monocytes as assessed by 3H-TdR uptake. Treatment with anti-GM-CSF antibody completely abolished up-regulation of LAK induction by GM-CSF-treated monocytes. When blood monocytes were separated into 5 fractions by CCE, GM-CSF-responding monocytes were found to be responsible for up-regulation of LAK induction. These results suggest that GM-CSF may be important in monocyte-mediated up-regulation of LAK cell induction in vivo.

Colony-Stimulating Factors↗

A case of bronchogenic cyst with high production of antigen CA 19-9.

A 35-year-old man was hospitalized with complaints of retrosternal pain and high fever. A chest radiograph showed a large round mass in the mediastinum. Of the several tumor markers in the serum tested, only CA 19-9 was elevated. Thoracotomy revealed a cystic mass with purulent hemorrhagic materials. Histologically the cyst was lined by bronchial epithelium with no evidence of malignancy. The high level of CA 19-9 in the cystic fluid, and positive immunohistochemical staining of the bronchial glands in the cyst wall for CA 19-9 indicated that the elevated serum level of CA 19-9 originated from the bronchogenic cyst after its infection.

Adult↗

Membrane-associated interleukin 1 alpha as a mediator of tumor cell killing by human blood monocytes fixed with paraformaldehyde.

Human blood monocytes isolated by centrifugal elutriation from healthy donors were tested for ability to produce membrane-associated antitumor monokine(s) in response to activation stimuli such as various types of interferon (IFN) and/or synthetic desmethyl muramyl dipeptide (norMDP). IFNs (alpha, beta, and gamma) and norMDP rendered blood monocytes cytotoxic to allogeneic A375 melanoma cells, as assayed by measuring release of [125I]iododeoxyuridine in 72 h. When monocytes were treated with any type of IFN for 16 h, and then fixed with paraformaldehyde, they did not show cytotoxicity to A375 cells, but when they were fixed after treatment with norMDP or lipopolysaccharide they showed significant cytotoxicity to A375 melanoma cells. This membrane-associated antitumor monokine induced by the synergistic actions of suboptimal concentrations of IFN-gamma and norMDP, was cytotoxic to HT-29 colon cancer cells as well as A375 melanoma cells, but not to actinomycin D-treated L-929 cells. The fixed monocyte-mediated cytotoxicity against A375 melanoma cells was completely inhibited by a specific anti-interleukin 1 alpha antiserum, but not by a specific anti-interleukin 1 beta antiserum or monoclonal anti-TNF antibody. These results suggest that membrane-associated interleukin 1 alpha is involved through cell-to-cell contact in the host defense mechanism against cancer.

Acetylmuramyl-Alanyl-Isoglutamine↗

Synergistic induction of lymphokine (IL-2)-activated killer activity by IL-2 and the polysaccharide lentinan, and therapy of spontaneous pulmonary metastases.

Spleen cells of C57BL/6N mice bearing lung metastases were induced to the cytotoxic state by subcutaneous injection of recombinant human interleukin-2 (IL-2) at a minimum dose of 5 x 10(4) U/mouse three times a day for 3 consecutive days. A single intraperitoneal injection of lentinan alone at concentrations of up to 10 mg/kg body weight did not render spleen cells cytotoxic to P-29 cells, but a combination of subthreshold doses of these agents (5 x 10(4) U/ml IL-2 and 5 mg/kg lentinan) induced significant in vivo lymphokine-activated killer activity in spleen cells of tumor-bearing mice. Similarly, spleen cells from mice treated i.p. with lentinan became cytotoxic on in vitro treatment with IL-2. The in vitro responsiveness of spleen cells to IL-2 was maximal 3 days after i.p. injection of lentinan. Synergism between IL-2 and lentinan was also observed in mice bearing spontaneous lung micrometastases: neither IL-2 (less than 5 x 10(4) U/mouse) nor lentinan (less than 2.5 mg/kg) alone had a therapeutic effect, but multiple injections of IL-2 with a single injection of lentinan resulted in significant inhibition of spontaneous pulmonary metastases. From these results we conclude that IL-2 and lentinan in combination are more effective than either one alone for inducing destruction of pulmonary metastases.

Adjuvants, Immunologic↗