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Biomedical subjects

A Uchida

Publications and source records attributed to A Uchida.

At least 325 records · Page 18Linked to original sources
PubMed1983

Intrapleural administration of OK432 in cancer patients: activation of NK cells and reduction of suppressor cells.

Twelve patients with carcinomatous pleural effusions were treated with single intrapleural (i.pl.) administration of OK432 on day 0 and the effects of i.pl. OK432 on natural killer (NK) cell activity were followed on day 7. Two patients showed no clinical evidence of therapeutic benefit from i.pl. OK432. In the other 10 patients, pleural effusions and/or tumor cells in the effusions had decreased or disappeared by day 7. NK cell activity was markedly low or absent in pleural effusions of untreated patients due to the presence of adherent effusion cells capable of suppressing the maintenance and interferon-induced augmentation of NK cell activity. I.pl. injection of OK432 resulted in enhancement of NK cell activity and abrogation of NK suppressor cell activity in the effusions. On the other hand, blood NK cell activity was not consistently altered by i.pl. OK432. In vitro treatment of effusion mononuclear cells from untreated patients with OK432, but not with interferon, augmented NK cell activity. In addition, adherent effusion cells of untreated patients lost their NK suppressor function following in vitro OK432 treatment. These results suggest that i.pl. administration of OK432 will result in augmentation of NK cell activity and reduction of NK suppressor cell activity in pleural effusions, which could be responsible for the antitumor activity of i.pl. OK432.

Adenocarcinoma↗
PubMed1983

Lysis of fresh human tumor cells by autologous peripheral blood lymphocytes and pleural effusion lymphocytes activated by OK432.

Lymphocytes from peripheral blood (PBL) and from pleural effusions (PEL) of cancer patients were tested for cytotoxicity against tumor cells freshly isolated from carcinomatous pleural effusion of the same patient. Significant lysis of autologous tumor cells was recorded for 4 of 28 PBL samples and for 5 of 28 PEL cases when investigated in a 4-hour 51Cr release assay. In vitro treatment of lymphocytes for 20 hours with the streptococcal preparation OK432 resulted in an induction or augmentation of cytotoxicity against autologous tumor cells in 21 of 28 PBL and PEL specimens. OK432-induced cytotoxicity required active cell metabolism, RNA and protein syntheses, but not DNA synthesis of lymphocytes. Supernatants of OK432-stimulated lymphocytes, and interferon and interleukin 2 failed to induce autologous tumor killing. Nylon wool-nonadherent lymphocytes were involved in both spontaneous and OK432-induced lysis of fresh autologous tumor cells. OK432-activated lymphocytes from normal donors and cancer patients caused lysis of fresh allogeneic tumor cells and also K562 cells.

Adenocarcinoma↗
PubMed1982

Natural killer cell activity in patients with multiple sclerosis: interferon and plasmapheresis.

Peripheral blood lymphocytes from patients with multiple sclerosis (MS) were studied for natural killer (NK) cell activity and reactivity to interferon. NK activity determined at the same time in a 4-hr chromium-51 release assay using K562 target cells was significantly lower in MS patients than in controls. In-vitro treatment of MS lymphocytes with interferon resulted in only a slight increase in NK activity, while NK activity of normal individuals was markedly augmented by interferon. Leukopheresis of MS patients gave a rapid decrease in cytotoxic activity, which returned to pretreatment levels by 24 hrs. These results are consistent with the hypothesis of an immune deficit in multiple sclerosis.

Adult↗
PubMed1982

Development of cytotoxic cells during in vitro cultures of pleural effusion lymphocytes from patients with lung cancer.

Culture-induced cytotoxic (CIC) activity developed in 7-day culture in the presence of fetal calf serum of pleural effusion lymphocytes from patients with lung cancer which initially showed markedly low or no natural killing (NK) activity against K562 cells. The development of CIC activity was proliferation-dependent. The CIC-mediating effector cells were removed by nylon-wool adherence, whereas the NK cells were enriched. Precursors for cytotoxic cells were not clarified. These results suggest that the precursors for cytotoxic cells are present in carcinomatous pleural effusions and able to develop cytotoxicity after 7-day culture in vitro.

Adult↗
PubMed1982

Autologous mixed lymphocyte reaction in the peripheral blood and pleural effusions of cancer patients.

T cells proliferate in response to autologous non-T cells in the autologous mixed lymphocyte reaction (AMLR). AMLR was impaired in the peripheral blood of patients with advanced lung cancer (4,159 +/- 3,878 delta cpm vs. 11,221 +/- 4,156 delta cpm for normal donors) but normal or even higher in their malignant pleural effusions (13,257 +/- 7,075 delta cpm vs. 10, 870 +/- 5,013 delta cpm for nonmalignant control effusions). Blood T cells also failed to respond to autologous effusion non-T cells, while effusion T cells strongly responded to autologous erythrocytes blood non-T cells. The presence of blood T cells did not inhibit effusion AMLR of the same patients. A subset of T cells that form rosettes with autologous erythrocytes if found to proliferate in AMLR. The number of autorosette-forming cells was lower in blood T cells of cancer patients than in blood T cells of normal donors and in effusion T cells of the patients. After enrichment of autorosette-forming cells, there was no difference in AMLR of normal blood and cancer blood and effusions. These results indicate that the loss of AMLR in the blood of cancer patients is due to a reduction of number of autoreactive T cells and not to a defect of autologous stimulator non-T cells.

Adult↗
PubMed1982

Generation of suppressor cells for natural killer activity in cancer patients after surgery.

Natural killer (NK) cell activity was examined in breast cancer patients before and after surgery, and the cells involved in the postoperative depression of cytotoxicity were characterized. NK activity against K562 target cells determined in 4-hour 51Cr release assay of blood lymphocytes from preoperative patients was comparable to that of normal donors. After surgery the patients showed a decrease in NK activity but not in number of large granular lymphocytes in the effector cell populations. When blood mononuclear cells from postoperative patients were depleted of monocytes by adherence to a serum-coated plastic dish and a Sephadex G10 column and then cultured for 24 hours, they showed an increase in NK activity. Furthermore, adherent blood cells of postoperative patients, but not of normal donors or preoperative patients, suppressed the lytic function of NK cells of normal individuals. Twenty-four-hour preculture of suppressor and effector cells was required for suppression of cytotoxicity. Neither postoperative sera nor culture supernatants of suppressor monocytes and effector cells suppressed NK activity. In contrast, the lymphoproliferative response to mitogen was not affected by surgery, and postoperative blood monocytes did not inhibit the mitogenic response of normal lymphocytes. The results suggest that the appearance of suppressor monocytes in the circulation could be one cause of depression of NK activity in postoperative cancer patients.

Adult↗
PubMed1981

Early change in mitochondrial monoamine oxidase activity of rat liver during 2-acetylaminofluorene feeding.

The activities of mitochondrial type A and B monoamine oxidase were determined in the liver of rats fed a diet containing 2-acetylaminofluorene (AAF). Three days after the initiation of AAF-feeding, there was a significant decrease of type B monoamine oxidase activity without affect on type A enzyme. The decreased activity of type B monoamine oxidase, which reached a minimum after three weeks, was sustained for as long as AAF-feeding was continued. Sex-related difference in response to AAF was seen in the rat with respect to the onset and the intensity of the decreased type B monoamine oxidase activity, male rats being more sensitive to the carcinogen than female rats. In contrast to the in vivo effect, AAF showed a potent inhibitory effect on type A monoamine oxidase, rather than on type B enzyme, when added in vitro. The pI50 values were estimated to be 7.5 against type A monoamine oxidase and 4.1 against type B enzyme, respectively. The in vitro inhibition of both types of monoamine oxidase by AAF was competitive. The Ki values for AAF were calculated to be 9.51 x 10(-9)M for type A monoamine oxidase and 1.30 x 10(-5)M for type B enzyme, respectively. In accordance with the potent inhibitory effect of AAF on type A monoamine oxidase in vitro, a single administration of the carcinogen, at a dose of 50 mg/kg, resulted in a marked and temporal decrease of the enzyme activity in the mitochondria of male rat liver. Recovery of the decreased type B monoamine oxidase activity was slow, and the enzyme activity did not return to control levels, even if rats were fed the basal diet for 2 or 4 weeks after the cessation of AAF-feeding

2-Acetylaminofluorene↗
PubMed1981

Reactivity to autologous non-T-cells and suppressor function of human autologous rosettes.

A subset of human peripheral blood T-cells can form rosettes with autologous erythrocytes (autologous rosettes). Fractionation of T-cells by autologous rosette centrifugation demonstrated that the autologous rosettes, but not the non-rosetting cells, have the capacity to respond with increased DNA synthesis to autologous non-T-cells in the autologous mixed lymphocyte reaction (MLR) and to suppress the mitogenic response after activation with concanavalin A (Con A). Furthermore, the autologous rosettes, autologous MLR and Con A-induced suppressor activity were particularly enriched in the nylon wool non-adherent T-cells and depleted in the nylon wool adherent T-cells. These results suggest that the same or at least largely overlapping T-cell subsets are responsible for the autologous rosettes, autologous MLR and Con A-induced suppressor function.

Animals↗
PubMed1981

In vitro augmentation of natural killing activity by OK-432.

OK-432, a streptococcal preparation, augmented the natural killing (NK) activity of peripheral blood lymphocytes of normal donors and cancer patients against both NK sensitive and resistant human target cells in vitro. The enhancement of NK activity was evident after 4 h pretreatment and maximum by 16-24 h. The manifestation of OK-432 induced augmentation required active cell metabolism, RNA and protein synthesis but no DNA synthesis of lymphocytes. The supernatants produced by OK-432 stimulated lymphocyte cultures had no enhancing substance nor interferon. Anti-interferon antibodies did not inhibit boosting activity of OK-432. Large granular lymphocytes were involved in both spontaneous and OK-432 induced cytotoxic activity. The proportion of lymphocytes conjugating to target cells was not changed by OK-432. These results suggest that OK-432 augments cytotoxic activity of large granular lymphocytes having ability to recognize target cells independent of interferon induction.

Adult↗
PubMed1981

Simulation of the initial stage of endochondral ossification: in vitro sequential culture of growth cartilage cells and bone marrow cells.

Growth cartilage cells were isolated from the ribs of young rats and cultured at high cell density in Ham's F-12 medium supplemented with 10% fetal calf serum. During 7 days, glycosaminoglycans and proteoglycans were actively synthesized and secreted, forming a metachromatic matrix. When cultured together with growth cartilage cells precultured and biosynthetically prelabeled with 35SO4(2-) in their glycosaminoglycans, bone marrow cells caused release of 35S-labeled material into the culture medium. Glycosaminoglycan was also released by addition of conditioned medium obtained from cultures of bone marrow cells or peritoneal macrophages to the growth cartilage cell cultures. Electron microscopic studies of the extracellular matrix of growth cartilage cells cocultured with bone marrow cells showed that needles of apatite mineral were deposited within and in close apposition to the surfaces of matrix vesicles. These findings suggest that enzymes released from bone marrow cells or macrophages removed glycosaminoglycan or proteoglycans, which may be inhibitors of mineral growth, and consequently mineralization was initiated. From these findings, sequential culture of growth cartilage cells and bone marrow cells is promising as an experimental system for investigating the mechanism of the initial stage of endochondral ossification.

Animals↗
PubMed1981

A preliminary study on isolation and enumeration of mycoplasmas in dental plaques: the effect of sonication on viability of oral mycoplasmas.

The effect of sonication on the viability of Mycoplasma salivarium and Mycoplasma orale was examined as a preliminary investigation on the quantitative studies on mycoplasmas in the dental plaques. Mycoplasma cell aggregations suspended in PBS or liquid medium were sonicated and the samples were removed at 5-second intervals for 20 seconds to check the viable counts. Inactivation of the mycoplasmas was almost directly proportional to the sonication time. M. orale was more sensitive to sonication than M. salivarium. Mycoplasmas were damaged more readily in PBS than in the liquid medium. Dental plaques suspended in PBS were also sonicated exactly as mentioned above. The number of mycoplasmas in the dental plaques (1 mg) ranged from 1.09 x 10(2) to 1.75 x 10(5) cfu. The desirable sonication time to prepare the homogeneous suspensions of dental plaques was concluded to be 5 seconds.

Dental Plaque↗
PubMed1981

Isolation and enumeration of mycoplasmas in dental plaques.

There has been only a fragmentary knowledge concerning mycoplasmas in the dental plaques and, in particular, no quantitative studies have been made on them. For this reason, isolation and enumeration of the mycoplasmas in the dental plaques have been attempted in this present study. The incidence of mycoplasmas was significantly higher in the dental plaques accumulated on the molars (76.1%, 35/46 specimens) than on the incisors (37.2%, 16/43); on the healthy enamel surface (hereafter called normal plaques; 61.0%, 61/100) than on the superficially decayed enamel surface (hereafter called caries plaques; 14.8%, 4/27) and on the healthy cervical enamel surface but in contact with the inflamed gingival marginal area (hereafter called gingivitis plaque ; 30.3%, 10/33). The number of organisms (cfu) in the dental plaques (mg) was greater in the normal plaques (range 0-1.57 x 10(6): mean, 6.31 x 10(4)) than in the caries (0-4.62 x 10(2): 2.28 x 10(2)) and in the gingivitis (0-4.14 x 10(4): 6.55 x 10(3)). There was a significant difference only between the normal and caries plaques. In addition, the number of organisms in the 1-day and 3-day-old dental plaques suggested that the mycoplasmas were not one of the microorganisms which appeared at the early stages of dental plaque formation. M. salivarium (311 strains) and M. orale (13) were isolated from 67 samples of dental plaques, but U. urealyticum was not. Of the 67 samples, 60 (89.5%) and 6 (9.0%) samples were positive for M. salivarium, M. orale and both of these two species, respectively.

Adolescent↗
PubMed1980

Reduction of suppressor cells in cancer patients treated with OK-432 immunotherapy.

OK-432, a streptococcal preparation, was intradermally injected daily into patients with advanced cancer of the stomach or lung for 4 weeks and the effects of OK-432 on the mitogenic responses of cancer patients were followed. The cells involved in the depression of the response of untreated cancer patients were characterized. The cells responsible for impaired responses were nylon wool non-adherent and suppressed the mitogen responses of autologous and allogeneic lymphocytes. These cells lost their suppressive activity during 7 days' culture in vitro. Following OK-432 immunotherapy, mononuclear cells from cancer patients showed increased responses to PHA and Con A, and nylon wool non-adherent cells did not inhibit the mitogen responses. These results suggest that the cells suppressing non-specific mitogen responses are sensitive to in vitro culture, belong to nylon wool non-adherent cells and are lost during 4 weeks of OK-432 therapy.

Adult↗
PubMed1980

Clinical studies on cell-mediated immunity in patients with malignant disease. I. Effect of immunotherapy with OK-432 on lymphocyte subpopulation and phytomitogen responsiveness in vitro.

Immunotherapy with daily intradermal injections of OK-432, penicillin- and heat-treated lyophilized powder of Su-strain of streptococcus pyogens A3, for over a period of four weeks resulted in quantitative and qualitative effectiveness on impaired cell-mediated immunity even in many patients with far advanced cancer of the stomach or lung. In vitro lymphocyte studies following immunotherapy with OK-432 demonstrated restoration of circulating lymphocyte counts to more than 1,500/microliters, a level associated with normalized subpopulation constitution and increases of phytomitogen blastogenesis. Furthermore, a delayed hypersensitivity skin reaction to PPD was boosted or converted into a positive reaction in some cases. There was, however, no detectable, definite effect on humoral immunity after the therapy. Survival rates at three and six months after the initiation of immunochemotherapy using OK-432 and another chemotherapeutic agent, 5-fluorouracil, in 40 patients with cancer were significantly longer than those of matched control patients given chemotherapy alone.

Adult↗
PubMed1980

Controlled clinical evaluation of a 10% strontium chloride dentifrice in treatment of dentin hypersensitivity following periodontal surgery.

Sixty adult patients were examined for dentin hypersensitivity prior to periodontal surgery. Stimuli used included mechanical, cold water and compressed air blasts. A subjective assessment of the degree of hypersensitivity for each stimulus was recorded. This presurgical examination revealed 249 hypersensitive areas among 60 subjects. Following surgery there was over a 100% increase in the pain (hypersensitivity) score. Desensitization with a 10% strontium chloride hexahydrate dentifrice was begun 1 week after surgical treatment. After 7 weeks of dentifrice use the pain score was reduced 75.5% in the test group. This was a reduction to a point below the preoperative level. The placebo group showed a reduction of 34.2% which was still above the preoperative level. These results agree with other clinical studies that have demonstrated a desensitizing effect of strontium chloride.

Adult↗