[Evaluation of the routes of administration of a streptococcal preparation, OK-432--with special reference to augmentation of the natural killer cell activity].
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Biomedical subjects
Publications and source records attributed to M Miyata.
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Plasma levels of glucose and insulin were measured during the oral glucose tolerance test (2.0 g/kg, for 180 min) in six children who had undergone caudal pancreatectomy for pancreatic trauma or non-functioning tumors. Fasting plasma levels of glucose and insulin were the same in these patients and in ten children with an intact pancreas. After glucose ingestion, hyperglycemia was apparent throughout the test in patients in whom one third of the entire pancreas had been left intact, but not in patients in whom over a half of the whole pancreas had been preserved. Plasma levels of insulin in these patients, however, were not significantly different from those of the controls. It is suggested that factors other than the response of plasma radioimmunoassayable insulin contribute to the production of glucose intolerance in cases of extensive pediatric pancreatectomy.
Effect of a streptococcal preparation OK-432 and its derivatives on the augmentation of human natural killer cell activity in vitro was examined. The strong augmentation was found by the OK-432 stimulation. Cell separation procedures revealed that cytotoxic activity augmented by the stimulant was considered to be mediated mainly by nonadherent, nonphagocytic, IgG-Fc receptor positive, non-T cells, i.e. NK cells. In addition, supernates cultured with OK-432 augmented NK activity, suggesting some kinds of soluble factors released in the supernates may be participating on the augmentation of human NK activity by OK-432.
Inasmuch as human natural killer (NK) cell activity was markedly augmented by a streptococcal immunopotentiator, OK-432, both in vivo and in vitro, the mechanism in which OK-432 augmented human NK cell activity was analyzed. Culture supernatants of nonadherent lymphocytes stimulated with OK-432 significantly augmented NK cell activity. Significant activity of both interferon (IFN) (both alpha- and gamma-types) and interleukin-2 (IL-2) was detected in the culture supernatants from nonadherent lymphocytes. Concomitant treatment of supernatants with anti-IFN-alpha antiserum and pH-2 glycine-HCI buffer or the absorption of supernatants with an IL-2-dependent cell line completely abrogated the NK-augmenting activity, whereas the treatment with either one of these resulted in only partial elimination of the activity. These results indicate that OK-432 stimulates human nonadherent lymphocytes to produce IFN and IL-2 and that both factors are primarily responsible for the NK augmentation by OK-432.
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Mice were immunized with 1 X 10(3) viable Listeria monocytogenes, and the mechanism of the acquired resistance against challenge infection with 5 X 10(4) L. monocytogenes was studied by the use of the peritoneal cavity of mice as the site of challenge. An enhanced elimination of bacteria from the peritoneal cavity became detectable on day 5 after immunization, and lasted thereafter. Before day 10 postimmunization, a marked accumulation of macrophages was observed after the challenge but the in vitro listericidal activity of macrophages was not so enhanced. After day 15 postimmunization, peritoneal macrophages did not increase in number after the challenge but the in vitro listericidal activity of macrophages was the stronger. Accumulation of non-activated macrophages seemed to contribute mainly to the expression of acquired resistance against challenge in the early stage of immunization. So-called activated macrophages appeared to be generated only in the later stage of immunization. Thus it was suggested that there may be at least two steps in the expression of acquired listerial resistance.
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Recently, a streptococcal preparation, OK-432 has been used successfully as an immunopotentiator for immunotherapy in patients with malignant tumors in Japan. In this paper, we report that the administration of OK-432 augments the cytotoxic activity of peripheral blood lymphoid cells against a natural killer (NK) cell-sensitive erythroleukemic cell line, K562, in tumor patients. In patients before or after surgery, sufficient amounts of OK-432 strongly augmented the cytotoxic activity within 3 days after the initial administration of OK-432. Thereafter the levels of cytotoxicity declined rapidly. The administration of a lower dose of OK-432 gave a lower increase in cytotoxicity. Enhanced cytotoxicity occurred with the reintroduction of OK-432 but remained at lower levels of activity. Characterization and fractionation of OK-432-induced effector cells revealed that the augmented cytotoxicity seemed to be carried mainly by NK cells. A low titer of interferon was detected in 3 of 10 patients within 72 hr after the first inoculation of the agent. Furthermore, we discuss the potency of OK-432 for the induction of interferon in detail.
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A case with ruptured aneurysm of the sinus of Valsalva into the right atrium directly visualized by cross-sectional echocardiography was reported. A 31-year-old male was referred to our hospital for evaluation of recently developed cardiac murmur. A systolic ejection murmur and diastolic blowing murmur were audible maximally at 3-4L and the latter one was also well audible at the right lower sternal border. Cardiac catheterization data revealed a large left-to-right shunt at the atrial level. The cross-sectional echocardiogram, obtained with a transducer at 5R towards the upwards and the medial direction, revealed a mass echo showing a pendulous motion through cardiac cycle in the right atrial cavity. Ruptured aneurysm of the sinus of Valsalva originated from the non-coronary sinus was demonstrated by aortography, and it showed the same motion as in echocardiography. From this angiographic finding and its disappearance after operation, the mass visualized by echocardiography was considered to be ruptured aneurysm itself. Thus, direct visualization of ruptured aneurysm of the sinus of Valsalva into the right atrium, as well as other types, was possible by cross-sectional echocardiography. In addition, multiple coronary A-V fistulae with a small shunt were demonstrated by coronary angiography in this case. Clinical significance of the complication has not been clarified.
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Cells of Schizosaccharomyces pombe grown in the presence of aculeacin A, a peptide antibiotic, were lysed resulting the death of cells. Under high osmolarity, the cellular lysis induced by aculeacin A was considerably reduced. The use of synchronous-culture systems distinguished cell elongation from cell division revealed that the sites of aculeacin A-induced lysis on the fission yeast were the end(s) and the cell plate region, corresponded to the regions of the cell wall synthesis. Aculeacin A-resistant survivors exhibited morphological alterations which were swollen at one or both ends of the cell and appeared drumstick or dumbbel like; the wall of the bulge region was observed to be stained with a fluorescent brightner, as well as that of the cell plate region. These effects of aculeacin A are discussed as compared with effects of 2-deoxy-D-glucose.