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Biomedical subjects

C Y Hung

Publications and source records attributed to C Y Hung.

At least 37 records · Page 2Linked to original sources

Effects of soman on vascular contractility of rabbit arteries.

The effects of soman (pinacolyl methylphosphonofluoridate), an organophosphorus cholinesterase inhibitor, on vascular contractility were examined on helically cut central ear arteries (CEA) or superior mesenteric arteries (M) from New Zealand White rabbits. Concentrations of soman up to 20 microM added cumulatively to arterial strips did not alter their resting tension. Concentrations of soman up to 10 microM also did not alter the tension responses to cumulatively added norepinephrine (NE), histamine, potassium (KCl), or serotonin (5-HT). Concentration-response curves obtained to each agonist initially, or 2 h later, did not differ in artery strips from control rabbits and those from rabbits given soman at 5 micrograms/kg sc daily for 7 d. Changes in responses to NE between the two time periods did differ in arteries from soman-treated and control rabbits in both the CEA and M, and to histamine in the M. Soman at 10 microM potentiated contractions to single concentrations of agonists in most cases. Soman at 10 microM also further increased the tension of strips already contracted by the agonists. Thus, although soman did not alter the concentration-response curves of the agonists at contracting rabbit arteries, it potentiated contractions to single concentrations of agonists both when added before the agonist and when added at the peak of the agonist-induced contraction. It also altered the rate of change with time of both M and CEA in responses to NE of artery strips from rabbits given soman at 5 micrograms/kg daily for 7 d.

Animals↗

Two N-hydroxylaminopurines are highly mutagenic in the ad-3 forward-mutation test in growing cultures of heterokaryon 12 of Neurospora crassa.

3 purine analogs were tested for their mutagenic activities in the ad-3 forward-mutation test in heterokaryon 12 (H-12) of Neurospora crassa. In growing cultures of H-12, the N-hydroxylaminopurines 2-amino-6-N-hydroxylaminopurine (AHA) and 6-N-hydroxylaminopurine (HAP) are potent and strong mutagens, respectively, whereas 2-aminopurine (AP) is a weak mutagen. AHA and HAP are about equally mutagenic at low doses, but AHA is more mutagenic than HAP at high doses. Despite their potent mutagenicity in growing cultures, AHA and HAP are not mutagenic in nongrowing conidia under the conditions of our experiments. AHA is the most potent mutagen tested in the ad-3 forward-mutation test in N. crassa. At the highest dose tested (30 micrograms/ml), it gave an ad-3 mutant frequency of 0.7 X 10(-2), about a 12,000-fold increase over the average spontaneous ad-3 mutant frequency. The potent mutagenicity of AHA may make it (and possibly HAP) especially useful for obtaining specific-locus mutations in other organisms.

2-Aminopurine↗

New method for measuring myocardial blood flow by high resolution scintigraphy in the excised dog heart.

The standard method for measuring myocardial blood flow (MBF) with radioactive microspheres requires processing of selected tissue samples usually from the excised heart, and consequent loss of exact relation to myocardial morphology. A computer-based image processing method was developed by using [99mTc]microspheres (mean particle size 20 microns) for quantitative analysis of MBF in 25 dogs. A computer-controlled gamma camera was used to obtain the images of radioactive microsphere distribution in transaxial slices of the ex vivo heart. Any portion of these slice images could be quantitated by using a computer program based on modification of the formula for determining MBF by the standard microsphere method. Regional myocardial perfusion calculated by this technique correlated well with values obtained with reference microspheres (r = 0.96) over a broad range of MBF. The results show that our new method, accurately and with high resolution, delineated zones of differing MBF and confirmed the increase of MBF in surviving myocardium with healing.

Animals↗

Mutagenicity of 2-aminopurine, 6-N-hydroxylaminopurine, and 2-amino-N6-hydroxyadenine in Neurospora crassa.

These data from our experiments with 3 purine analogs reveal striking differences in mutagenic potency. It seems highly likely that these analogs substitute readily for adenine and that they cause mutations in the main part, and in the case of AHA perhaps predominantly, by mispairing with cytosine. The most potent mutagens are those with the hydroxylamino group at the C6 position (AHA and HAP). Of these, the most potent is the analog with an amino group in the C2 position (AHA). The most interesting aspect of the present studies is their implications for other eukaryotic organisms. We have determined that AHA, which was shown to be a potent mutagen in bacteria [11], is an extremely potent mutagen in a eukaryotic organism. AHA is active at relatively low concentrations, and it gives rise to point mutations that appear to arise predominantly by AT----GC base-pair transitions. AHA should be an extremely useful genetic probe for studies on higher eukaryotic organisms. Its potency and specificity make it an unusual mutagen that can be expected to produce specific-locus mutants at high frequency with the genetic damage confined to the boundaries of the gene. These characteristics should make it useful not only for studies of specific-locus mutations and sex-linked recessive lethal mutations in Drosophila but also for specific-locus studies in mammalian cells in culture and in the whole animal. In these latter systems, it is extremely time consuming and sometimes impossible to distinguish between point mutations and multilocus deletions. The use of AHA as a mutagen in these systems should provide a useful new approach to genetic fine structure analysis.

2-Aminopurine↗

Molecular dosimetry of the chemical mutagen ethyl methanesulfonate. Quantitative comparison of the mutagenic potency in Neurospora crassa and Saccharomyces cerevisiae.

Extending previous work with E. coli and mammalian cells in culture, forward-mutation frequencies induced by ethyl methanesulfonate (EMS) were quantitatively compared in Neurospora crassa and Saccharomyces cerevisiae under standardized conditions. Concomitantly, the actual dose to DNA was measured by determining the amount of radioactivity bound to DNA after treatment with tritium-labeled EMS. After exposure to EMS (2.5-50 mM), alkylation levels in N. crassa and S. cerevisiae were similar to those previously determined in E. coli and cultured mammalian cells. Consistently, there was a slightly less than proportional increase of the DNA alkylation level with the exposure concentration of the mutagen. Forward mutagenesis induced in yeast and N. crassa showed exponential kinetics with exponents of 1.5 and 2.6, respectively. These results are similar to those previously reported with E. coli, which differed from the results with cultured mammalian cells, where a linear dose-effect relationship between exposure and genetic effect was observed. These differences may reflect differences in the fate of EMS-induced adducts by cellular DNA repair systems, but are not due to initial differences in DNA alkylation levels. The fate and persistence of specific DNA adducts potentially responsible for pre-mutagenic changes are under investigation.

Animals↗

Duration of interferon inhibition following single and multiple injections of morphine.

The increase in mouse serum interferon that occurs in response to poly I:C administration is markedly attenuated by injection of a narcotic preceding the polynucleotide challenge. A single injection of morphine is capable of inhibiting the mechanism(s) responsible for increasing serum interferon levels for a period of at least 9 days following the narcotic injection. Daily single injections of morphine for 5 or 10 days prior to poly I:C challenge do not amplify the extent of the decrease in serum interferon over that measured for a single injection, even though the amount of narcotic injected is increased on each successive day of the 5 or 10 day period. The implications of this relationship for the phenomenon of narcotic tolerance are evaluated and discussed as they relate to the immune processes.

Animals↗

Role of spleen in the interferon-lowering action of morphine.

1. Polyinosinie-polycytidylic acid (Poly I:C) administered intraperitioneally to mice produced an increase in the level of interferon in the tissues of the spleen, liver, lung, and kidney. The level of circulating serum interferon also was increased by the polynucleotide. 2. The highest titer of interferon, presumably resulting from the greatest response to poly I:C was measured in the splenic tissue. 3. Morphine inhibited the poly I:C induced increase in all tissues and circulating serum. The decrease in interferon titer was similar in spleen and serum. 4. These results may indicate the serum level of interferon was more closely related and dependent upon events occuring in the spleen than in the other tissues.

Animals↗

Action of naloxone on the interferon-lowering activity of morphine in the mouse.

The serum titer of interferon produced by polyinosinic:polycytidylic acid (poly I:C) was studied in mice following subcutaneous injections of either morphine alone, naloxone alone, morphine and naloxone together, morphine preceded by naloxone, naloxone preceded by morphine, or a sequence of injections of naloxone, morphine, and naloxone again. Poly I:C injected without the other drugs present served as the control. Both morphine and naloxone produced a significant decrease in the ability of the mice to increase the serum titer of interferon in response to poly I:C. Naloxone appeared to function as an antagonist to morphine when administered following the morphine injection, but not when injected before or simultaneously with the opiate. When naloxone was injected both before and following the morphine injection, results were interpreted to indicate the possibility that naloxone could function as both an agonist and antagonist under this condition.

Animals↗

Effect of ascorbic acid, sodium salicylate, and caffeine on the serum interferon level in response to viral infection.

The ability of ascorbic acid, sodium salicylate, and caffeine to alter the circulating serum level of interferon was investigated in mice. The animals were singly injected subcutaneously with one of the compounds, 4-8 h later again singly injected intraperitoneally with poly I:C, and bled 6-8 h afterward. The sera from the mice were assayed for interferon titer by the use of the plaque inhibition method utilizing vesicular stomatitis virus. Ascorbic acid, sodium salicylate, and caffeine increased the serum level of interferon; however, the increase produced by sodium salicylate was dose-dependent, i.e. low doses increased interferon titers, high doses decreased the titers. Caffeine produced minimal increases in the interferon titer. These observations suggest that a potential prophylactic result may occur in virus infections from administration of the three compounds either singly or in combination at the proper concentration.

Animals↗

Effect of morphine, hydromorphone, methadone, mescaline, trypan blue, vitamin A, sodium salicylate, and caffeine on the serum interferon level in response to viral infection.

The ability of morphine, hydromorphone, methadone, mescaline, trypan blue, vitamin A, sodium salicylate and caffeine to alter the circulating serum level of interferon was investigated in mice. Sodium salicylate, and caffeine increased the serum level of interferon; however, the interferon increase produced by sodium salicylate was dose-dependent, i.e. low doses increased interferon titers, high doses decreased the titers. All other compounds decreased the circulating level of interferon. These results suggest that compounds of varied structure and biological activity, and possessing teratogenic potential, are capable of depressing the circulating level of interferon. Some of these "anti-interferon" compounds, i.e. morphine, hydromorphone, methadone, depressed interferon levels at all doses whereas sodium salicylate decreased the interferon level only at relatively high dose levels.

Animals↗

Effect of the homokaryotic or heterokaryotic state of the uvs-2 allele in Neurospora crassa on mitomycin C-induced killing and ad-3 mutation.

Mitomycin C (MC) was tested for its killing and mutagenic activities in the ad-3 forward-mutation test in Neurospora crassa. The test was conducted in 4 dikaryons of N. crassa in order to determine the effect of the uvs-2 allele, which causes a defect in nucleotide excision repair, on MC-induced killing and ad-3 mutation. These dikaryons were homokaryotic for uvs-2+ (H-12), homokaryotic for uvs-2 (H-59), and heterokaryotic for uvs-2/uvs-2+ (H-70 and H-71). MC induced killing and ad-3 mutation in H-12, but the presence of uvs-2 in the homokaryotic state (H-59) resulted in a great increase in the killing and mutagenic activities of MC. This increased sensitivity to MC-induced killing and mutation conferred by uvs-2 in the homokaryotic state (H-59 vs. H-12) is a different effect than that noted by others for a defect in nucleotide excision-repair in Escherichia coli and Salmonella typhimurium or in human cells. The dikaryons heterokaryotic for uvs-2/uvs-2+ had the same sensitivity to MC as H-12, indicating that for MC-induced killing and ad-3 mutation uvs-2 is recessive to uvs-2+.

Adenine↗

Age-related refractoriness of PHA-induced lymphocyte transformation. I. Comparable sensitivity of spleen cells from young and old mice to culture conditions.

The decline in phytohemagglutinin (PHA) responsiveness of spleen cells from aged mice was studied in an effort to determine the nature of the depressed PHA reactivity. The reduced response of DNA synthesis (thymidine incorporation) to PHA stimulation could not be attributed to a decreased viability of spleen lymphocytes from old mice in in vitro culture conditions, to different PHA dose requirements, or to longer periods of culture time for old mouse spleen cells to reach maximal activity. Culture of cells for 24-48 h prior to addition of PHA gave patterns of thymidine incorporation similar to those of freshly prepared spleen cells. The elimination of red blood cells by a brief hypotonic shock significantly increased thymidine incorporation in spleen lymphocytes from both yound and old mice.

Age Factors↗