The nucleic acid fraction from cells of 6 species of bacterium and 2 kinds of vertebrate, calf and salmon, was extracted and purified by the same procedures as described previously. When the spleen cells from BALB/c mice were incubated with the nucleic acid fraction from either of the bacteria, natural killer (NK) activity of the cells was remarkably elevated and the cells produced factors to activate macrophages and to inhibit viral growth. It was shown that the factor to activate macrophages was interferon (IFN)-gamma and that to inhibit viral growth was IFNalpha/beta. On the other hand, the nucleic acid fraction from either of the vertebrate cells did not show such activities. Pretreatment of the bacterial nucleic acid fraction with DNase, but not with RNase, abrogated completely the biological activities. The activities of the bacterial nucleic acid were not influenced by the presence of polymyxin B, an inhibitor of lipopolysaccharide (LPS), and the spleen cells from not only BALB/c mice but also LPS-insensitive C3H/HeJ mice were activated, indicating that the activities of the fraction were not ascribed to LPS contaminated possibly into the fraction, but to DNA itself. Intralesional injection with the bacterial DNA fraction caused regression of mouse IMC tumors, but the injection with the vertebrate DNA fraction did not. These findings prompted us to examine the biological activities of DNA samples from a variety of animals and plants, which were provided from other laboratories or purchased from manufacturers. All of the DNA samples from cells of 5 kinds of bacterium, 2 of virus and. 4 of invertebrate augmented NK activity and induced IFN, more or less, in mouse spleen calls, while the DNA from 10 kinds of vertebrate, including 3 of fish and 5 of mammal, showed no such activities. The DNA from 2 species of plants, were also inactive. Possible mechanisms to explain the different biological activities of DNA from different cell sources were discussed based on our previous finding that the particular palindromic sequences with a G-C motif (s) are required for induction of IFNs and activation of NK cells with synthetic 30-mer oligonucleotides.We have demonstrated that a DNA-rich fraction, extracted fromMycobacterium bovis BCG and designated MY-1 (22), exhibited strong antitumor activities against 98 3
Seventy-five cirrhotic patients with hyperammonemia in ing number of patients with compensated or noncompenthe past or at the time of the study were randomly divided sated cirrhosis are managed in outpatient clinics over a long into two groups (treated with lactulose or nontreated) in 14 period. In these patients, prevention of the above complicahospitals in Japan. Thirty-six cirrhotic patients were diag-tions is necessary in long-term home care to improve the nosed as having subclinical hepatic encephalopathy (SHE), quality of life (QOL). and 39 were diagnosed as non-SHE. SHE was diagnosedIn hepatic encephalopathy, psychoneurological symptoms when the results of all three of the quantitative psychometric are clinically absent before the onset and during the interval tests used (number connection test, and symbol digit and period of encephalopathic episodes. However, subclinical heblock design tests of the Wechsler adult intelligence scale patic encephalopathy (SHE), in which behavior abnormali-[revised]) were abnormal as compared with age-matched ties and impairment in cognitive functions can be shown by normal values. The mean number of abnormal psychometric quantitative psychometric (neuropsychologic) tests, has been test results and the prevalence of SHE were used for a quanti-reported recently in cirrhotic patients who have no history tative evaluation of the efficacy of the lactulose treatment. of encephalopathy, and clinically appear to be free of encephTwenty-two of the SHE patients were treated with lactulose alopathy.1,2 Moreover, recent imaging analysis of the brain (45 mL/d) for 8 weeks, and the other 14 SHE patients did in cirrhotic patients with and without encephalopathy has not receive lactulose. In the SHE patients administered lactu-shown brain atrophy on computed tomography, 3 abnormal lose, the results of the quantitative psychometric evaluation regional cerebral blood flow on single photon emission comwere significantly improved at 4 and 8 weeks after the begin-puted tomography, 4 and high signals in the basal ganglia on ning of the lactulose administration. The SHE had disap-T1-weighted magnetic resonance imaging. Therefore, it is important for the long-term management it persisted in 11 (85%) of the untreated 13 patients. We of cirrhotic patients to understand the presence of these morconcluded that lactulose treatment in cirrhotic patients with phological changes and functional impairments of the brain, SHE is effective with respect to psychometric tests. (HEPA-and to pay attention to changes in daily behavior and sleep. TOLOGY 1997;26:1410-1414.)This approach would be useful for maintaining the compensated stage of cirrhosis over a long period and for reversing Because the treatment for complications of cirrhosis such as hepatic encephalopathy, jaundice, ascites, and gastrointes-the noncompensated cirrhosis to compensated cirrhosis. tinal bleeding has improved, the survival period of cirrhotic Lactulose has been used worldwide for the treatment of patients has been markedly prolonged. Th...
A nucleic acid‐rich fraction extracted and purified from BCG (MY‐1) augmented natural killer (NK) cell activity of mouse spleen cells in vitro, and produced factor(s) which showed anti‐viral activity and rendered normal macrophages cytotoxic towards tumor cells. These cellular responses were induced by the MY‐1 digested preliminarily with RNase, but not by the MY‐1 digested with DNase, indicating that DNA contained in MY‐1 was essential for the responses. The function of the factor to activate macrophages was destroyed by treatment with a small amount of anti‐interferon (IFN)‐γ antiserum or under acidic conditions (pH 2), but not by treatment with anti‐IFN‐α/β antiserum, while the anti‐viral activity was destroyed almost completely by treatment with anti‐IFN‐α/β antiserum. It appears that DNA from BCG stimulated mouse spleen cells in vitro, resulting in augmentation of NK activity and production of IFN‐α/β and ‐γ.
The relationships between plasma drug concentration and antihypertensive effect of eight calcium channel antagonists (nicardipine, nifedipine, nilvadipine, benidipine, manidipine, barnidipine, nitrendipine and efonidipine) in Japanese essential hypertensive patients were analyzed. Based on the effect compartment model, we could explain the long duration of the pharmacological effect, and there was significant correlation (r = 0.876, p < 0.05) between estimated EC50 values and the dissociation constants (Kd) obtained from in vitro binding studies. We also developed the ion-channel binding model to understand the pharmacodynamics of long acting calcium antagonists. The model was also well fitted to antihypertensive effect data. A significant correlation between the apparent in vivo dissociation constants and in vitro Kd values was observed with a slope of 1.45 (r = 0.913), suggesting that the mechanism of long-lasting antihypertensive effect of newer developed calcium antagonists is due to their high binding affinity at ion-channel sites.
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