Biomedical subjects

Z H Yang

Publications and source records attributed to Z H Yang.

At least 55 records · Page 3Linked to original sources

PubMed1991

Comparative effects of two acycleonucleoside derivatives on ultrastructure and replication of guinea pig cytomegalovirus in cultured cells.

Two antiviral agents, compound 164, also known as 2'-nor-cGMP, 9-[(2-hydroxy-1-3-2-dioxophosphorinan-5-yl)-oxymethyl]-guani ne P-oxide, and compound 102, 4-amino-5-bromo-7-(2-hydroxyethoxymethyl)-pyrrolo-(2-3-d)-pyrimidine, together with their parental drugs, 2-deoxyguanosine (DHPG) and acyclovir (ACV), were evaluated for their antiviral activities against guinea pig cytomegalovirus (GPCMV) infection in cultured guinea pig embryo (GPE) cells. The two compounds were demonstrated to be more potent against GPCMV replication when compared to their parental drugs DHPG and ACV. Compound 164 was the most potent of the four compounds tested, with ED50 values being approximately 20-, 80-, and 180-fold more potent than those of DHPG, compound 102, and ACV, respectively. Compounds 164 and 102 were slightly more cytotoxic to uninfected GPE cells, but their selectivity (therapeutic) indexes were higher than those of their parental drugs. Of the four antiviral agents tested, compound 164 had the highest selectivity index which was 8-, 30-, and 50-fold higher than that of DHPG, compound 102, and ACV, respectively. Ultrastructural studies suggest that compounds 164 and 102 have different mechanisms of inhibiting GPCMV replication in cultured GPE cells.

Acyclovir↗

PubMed1991

Different activation of the endothelial L-arginine and cyclooxygenase pathway in the human internal mammary artery and saphenous vein.

The endothelium releases substances controlling vascular tone and platelet function. We investigated mediators of endothelium-dependent responses in human internal mammary arteries and saphenous veins. The inhibitor of nitric oxide formation, NG-monomethyl L-arginine, enhanced the sensitivity to norepinephrine (fivefold) and evoked more pronounced endothelium-dependent contractions in internal mammary arteries (19 +/- 6% of 100 mM KCl) than in saphenous veins (2 +/- 1%; p less than 0.005). In internal mammary arteries, NG-monomethyl L-arginine, but not indomethacin, markedly reduced endothelium-dependent relaxations to acetylcholine (from 95 +/- 2% to 39 +/- 7%; p less than 0.005) and prevented those to histamine (78 +/- 6% to 4 +/- 3%; p less than 0.005). In saphenous veins, endothelium-dependent relaxations to acetylcholine were weak (24 +/- 11%), while nitric oxide caused comparable relaxations (85 +/- 3%) as in internal mammary arteries (80 +/- 5%; NS). NG-Monomethyl L-arginine prevented the relaxations to acetylcholine and unmasked endothelium-dependent contractions (30 +/- 10%). Indomethacin and the thromboxane synthetase inhibitor CGS-13080 augmented relaxations of saphenous veins to acetylcholine from 24 +/- 11% to 46 +/- 9% (p less than 0.05). Histamine-evoked contractions were converted to endothelium-dependent relaxations by indomethacin and the thromboxane A2/endoperoxide receptor antagonist SQ-30741 (38 +/- 3% and 40 +/- 6%; p less than 0.05) but not CGS-13080. Thus, 1) nitric oxide mediates endothelium-dependent relaxations in human arteries and veins; 2) internal mammary arteries release more nitric oxide than do saphenous veins, and 3) in saphenous veins, the effects of nitric oxide are reduced by endothelium-derived contracting factors originating from the cyclooxygenase pathway.

Acetylcholine↗

PubMed1990

Endothelial control of vascular tone in large and small coronary arteries.

The endothelium modulates coronary vascular tone by the release of endothelium-derived relaxing or contracting substances. The endothelium-derived relaxing factor has been identified as nitric oxide synthesized in endothelial cells from L-arginine. The endothelium can release other relaxing substances such as prostacyclin and a hyperpolarizing factor. Endothelin-1 is a potent vasoconstrictor peptide formed by endothelial cells, and is likely to be the physiologic antagonist of endothelium-derived relaxing factor. Other putative contracting factors include superoxide anions and products of arachidonic acid metabolism. Endothelium-derived relaxing factor is released spontaneously and in response to flow, platelet-derived products (that is, serotonin, thrombin and adenosine diphosphate) and certain autacoids (that is, acetylcholine, bradykinin, histamine, substance P, vasopressin, alpha-adrenergic agonists). A considerable heterogeneity of responses exists among vessels of different size from different anatomic origin and different species. Hypercholesterolemia, atherosclerosis, hypertension and myocardial ischemia or reperfusion, or both, impair endothelium-dependent relaxation. Under normal conditions, endothelium-derived relaxing factor appears to dominate the control of vascular tone of large and small coronary vessels, whereas in disease states, endothelium-derived contracting factors are released. Impairments of endothelial function may be important in the development of various forms of cardiovascular disease.

Animals↗

PubMed1990

Activity of (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC) against guinea pig cytomegalovirus infection in cultured cells and in guinea pigs.

(S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine, HPMPC, and two HPMPC-related nucleoside analogs, (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine, HPMPA, and (2-phosphonylmethoxyethyl)guanine, PMEG, were evaluated for their antiviral activities against guinea pig cytomegalovirus (GPCMV) infection in guinea pig embryo (GPE) cells and human cytomegalovirus (HCMV) infection in human diploid fibroblast (MRC-5) cells. DHPG, 9-(1,3-dihydroxy-2-propoxymethyl)guanine, was used for comparison. The antiviral activity of HPMPC against GPCMV infection in vivo and its toxicity to Hartley guinea pigs were also evaluated. The 50% antiviral effective doses (ED50) of HPMPC, HPMPA, PMEG and DHPG against GPCMV infection in GPE cells were 0.22, 1.4, 0.07 and 62 microM, respectively; and against HCMV infection in MRC-5 cells, the ED50s were 0.51, 0.72, 0.01 and 17.5 microM, respectively. Their cytotoxic doses (CyD50) in GPE replicating cells were 84, 35, 1.4 and 700 microM, respectively and in MRC-5 cells were approximately 114, 31, 0.86 and 750 microM, respectively. Based on their calculated therapeutic indexes, HPMPC was the most potent and selective of the four compounds tested. In vivo, during acute infection, the spleen indexes of all infected animals that were treated with 1.25 to 5.0 mg/kg/day of HPMPC for 5 days were significantly reduced as compared with sham-treated animals. Virus infectivity titers in blood and various tissues of infected animals treated with HPMPC, 2.5 or 1.25 mg/kg/day were not significantly lower than those of the infected, sham-treated animals; with 5 mg/kg/day, infectivity titers in the blood, spleen, and salivary gland were significantly lower in HPMPC-treated than in sham-treated animals. However, HPMPC was toxic to guinea pigs especially at doses of 5 to 10 mg/kg/day. These data showed that HPMPC was highly active and selective in cultured guinea pig cells and human fibroblast cells against CMV infection but did not effectively inhibit GPCMV infection in guinea pigs at minimum toxic concentrations.

Animals↗

PubMed1990

Impaired endothelium-dependent relaxations in hypertensive resistance arteries involve cyclooxygenase pathway.

Endothelial cells modulate vascular tone by releasing endothelium-derived relaxing (EDRF) and contracting factors. An imbalance of these factors in hypertension could contribute to increased peripheral vascular resistance. Mesenteric resistance arteries of Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) were suspended in a myograph filled with physiological salt solution (37 degrees C; 95% O2-5% CO2). In WKY rings contracted with norepinephrine, acetylcholine (10(-9)-10(-4) M) evoked endothelium-dependent relaxations (88 +/- 2%, IC50 7.3 +/- 0.1; n = 31). Hemoglobin (10(-5) M) but not meclofenamate (10(-5) M) reversed the relaxations delineating EDRF as the mediator. Nitric oxide (3 X 10(-9)-10(-5) M) induced comparable relaxations as acetylcholine. In SHRSP, relaxations to acetylcholine but not those to nitric oxide were impaired (61 +/- 5%, IC50 greater than 6.6 +/- 0.4; n = 24; P less than 0.005). In SHRSP, meclofenamate but not the thromboxane synthetase inhibitor CGS 13080 normalized endothelium-dependent relaxations. Relaxations to sodium nitroprusside were enhanced in SHRSP both in rings with and without endothelium. Thus our results are compatible with the concept that endothelium-dependent relaxations in resistance arteries are mediated by nitric oxide. In SHRSP, endothelium-dependent relaxations are impaired because of a cyclooxygenase-dependent substance interfering with the release and/or action of EDRF.

Animals↗

PubMed1990

Threshold concentrations of endothelin-1 potentiate contractions to norepinephrine and serotonin in human arteries. A new mechanism of vasospasm?

Endothelin-1 is an endothelium-derived vasoconstrictor peptide. Its circulating levels are below those known to evoke direct vascular effects. To study whether low concentrations of endothelin-1 potentiate the effects of other vasoconstrictor hormones, we suspended isolated human internal mammary and left anterior descending coronary artery rings in organ chambers for isometric tension recording. In mammary artery rings, the contractions to norepinephrine (3 x 10(-8) M) were potentiated by threshold (3 x 10(-10) M) and low concentrations (10(-9) M) of endothelin-1 (96 +/- 35% and 149 +/- 58% increase from control; p less than 0.01 and 0.001; n = 6). The inhibitor of endothelial nitric oxide formation L-NG-monomethyl arginine did not affect the potentiating effects of the peptide. The calcium antagonist darodipine (10(-7) M) prevented the potentiation of the response to norepinephrine evoked by endothelin-1. Similarly, contractions to serotonin (10(-7) or 3 x 10(-8) M) were amplified by endothelin-1 (3 x 10(-10) M) in the mammary (30 +/- 9%) and in the coronary arteries (59 +/- 25%). Endothelin-1 (10(-9) M) further potentiated the response (57 +/- 23% in mammary and 87 +/- 26% in coronary arteries; p less than 0.05; n = 7 and 3). The sensitivity of mammary arteries to calcium chloride was markedly enhanced in the presence of endothelin-1 (3 x 10(-10) M; concentration shift, eightfold; p less than 0.01; n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗

PubMed1990

[Spatial association of nucleotide substitutions during the evolution of DNA sequences].

Evolutionary models for estimating the number of nucleotide substitutions between DNA sequences are evaluated with data from histone gene sequences of 7 remote species. It is found that the nucleotide compositions at the third codon position of H2A genes vary greatly among species and are highly correlated with the compositions at the first position of H2A genes, with those at the first and third position of H4 genes and with those in the up- and downstream sequences of H2A genes. This implies the existence of regional constraints over DNA sequences during the evolutionary process, which is different over species. Possible causes for the variations are increment of G + C content in higher eukarotypes, and chromosomal recombination, which brought the histone genes onto different isochores and thus under different selective or mutational pressures. Substitutions at different positions in a codon have been found not to be independent, probably due to multiple substitutions, i.e., single substitution events involving multiple sites. The implication of these results to phylogeny inferring is discussed.

Base Composition↗

PubMed1989

Pre- and postoperative sequential study on the immunosuppressive activity of serum and cell-free skin bleb fluid of patients with lung cancer and esophageal cancer.

Serial changes of immunosuppressive activity of serum and cell-free skin bleb fluid that can suppress the activity of acid a-naphthyl acetate esterase (ANAE) of lymphocytes and phagocytosis of macrophages were detected by immunoregulatory tests in vitro in 50 lung cancer and 42 esophageal cancer patients. In comparing these tests with those of 53 cases of noncancerous thoracic lesion and 69 normal adults, the immunosuppressive activity of serum and skin bleb fluid from cancer patients is significantly higher than that of noncancerous thoracic lesions and normal individuals (P less than .01). The activity is related to the stages of cancer, the size of primary tumor, the presence of lymph node metastasis, and tumor resect-ability, but not to histological classification, sex, and age. The immunosuppressive activity of serum and skin bleb fluid decreased gradually after the removal of the tumor and was eliminated on the 30th postoperative day. These results suggest that serum and skin bleb fluid from cancer patients may contain immunosuppressive factors that can suppress the immune responsive functions of lymphocytes and macrophages in vitro in a manner similar to that seen in vivo. Therefore, complete surgical removal of cancer is likely the most effective immunotherapy.

Adult↗

PubMed1989

Different effects of endothelin-1 on cAMP- and cGMP-mediated vascular relaxation in human arteries and veins: comparison with norepinephrine.

Endothelin-1 (ET-1) is a new cardiovascular hormone produced by endothelial cells. The vascular effects of the peptide and its interaction with cAMP- and cGMP-dependent relaxation were investigated in human arteries and veins. Internal mammary arteries and veins and saphenous veins were obtained intraoperatively and suspended in organ chambers; isometric tension was recorded. The blood vessels were contracted with ET-1 or norepinephrine and relaxations to prostacyclin or sodium nitroprusside were studied. Mammary veins exhibited an enhanced sensitivity to ET-1 (10(-11) to 3 X 10(-7) M) as compared to the artery and saphenous vein (log shift at ED50: 32- and 79-fold, respectively; p less than 0.005). In saphenous veins maximally contracted with ET-1, relaxations to prostacyclin were blunted as compared to the artery (p less than 0.005; n = 5). Similarly, ET-1 inhibited relaxations to sodium nitroprusside in the vein, but not in the artery. In contrast, venous rings contracted with norepinephrine were more sensitive to sodium nitroprusside than the artery. Thus, the human mammary vein, but not the saphenous vein, is more sensitive to the vasoconstrictor effects of ET-1 when compared to the mammary artery. In veins, ET-1 but not norepinephrine inhibits the vascular effects of prostacyclin and sodium nitroprusside, suggesting a specific interaction of the peptide with cAMP- and cGMP-dependent relaxation.

Arteries↗

PubMed1989

Effect of 2'-nor-cyclic GMP against guinea pig cytomegalovirus infection.

Cyclic phosphate derivative of DHPG, 2'-nor-cGMP [9-[(2-hydroxy-1,3,2-dioxaphosphorinan-5-yl)oxymethyl]-guani ne phosphate-oxide] was evaluated for activity against guinea pig cytomegalovirus (GPCMV) infection in cultured guinea pig embryo cells and in guinea pigs. By virus yield reduction and plaque reduction assays, 2'-nor-cGMP was demonstrated to be 15- to 20-fold more potent against GPCMV infection than its parental drug DHPG. The selectivity index of 2-nor-cGMP was 110, which was 10-fold higher than that of DHPG. In cultured cells, 2'-nor-cGMP attained maximal antiviral activity when added to the cells within 12 h postinfection. In the studies on GPCMV infection in guinea pigs, 2'-nor-cGMP administered subcutaneously once daily (5 mg/kg per day) for 8 days, starting 24 after virus inoculation, significantly suppressed GPCMV infectivity titers in the blood, spleen, lung, and salivary gland during acute infection (10 days postinfection) as compared with sham-treated infected animals. A greater reduction of GPCMV infectivity titers in the salivary gland was noted during chronic infection (i.e., 24 days postinfection). Clinically, splenomegaly and peripheral lymphocytosis were significantly modified as compared with the sham-treated animals (P less than 0.05). The drug, administered at this dosage, was reasonably tolerated by the guinea pigs and showed clinical benefit.

Animals↗

PubMed1989

Endothelium-derived relaxing factor and protection against contractions induced by histamine and serotonin in the human internal mammary artery and in the saphenous vein.

We investigated the release of endothelium-derived relaxing factor (EDRF) in response to serotonin and histamine in the human internal mammary artery and saphenous vein. The arteries and veins were obtained intraoperatively and were suspended in organ chambers to record isometric tension. In mammary arteries, histamine (10(-8) to 3 X 10(-6) M) induced relaxations in rings with (70 +/- 5%, IC50, 6.5 +/- 0.2) but not without endothelium (p less than 0.005 for rings with compared with those without endothelium, n = 7-10). The response was inhibited by methylene blue or hemoglobin, but not meclofenamate, and, therefore, EDRF was delineated as the mediator. Because chlorpheniramine but not cimetidine inhibited the response, EDRF was released by the H1-histaminergic receptor (n = 5-8). In contrast, in saphenous veins, histamine caused only weak or absent endothelium-dependent relaxations, but contractions were enhanced in rings with endothelium (p less than 0.05, n = 6). Serotonin did not induce endothelium-dependent relaxations, but contractions were markedly greater in veins compared with arteries (p less than 0.005, n = 6). The endothelium inhibited the maximal contraction to serotonin in arteries (p less than 0.034) but not in veins. Thus, EDRF protects against contractions induced by histamine and serotonin in the mammary artery but not in the saphenous vein. This may be important for improved graft function and patency of the artery compared with that of the vein.

Endothelium, Vascular↗

PubMed1989

Endothelium-derived vasoactive substances: potential role in hypertension, atherosclerosis, and vascular occlusion.

The endothelium can profoundly affect vascular tone by releasing endothelium-derived relaxing and contracting factor. Nitric oxide (EDRF) is the most important relaxing factor that is released from L-arginine and evokes relaxation by increasing intracellular cyclic GMP in vascular smooth muscle. Endothelin and other endothelium-derived contracting factors (i.e., a cyclooxygenase product and a substance released during hypoxia) may be released as well. In hypertension and atherosclerosis, endothelium-dependent relaxations are impaired and endothelium-dependent contractions may occur, at least in some blood vessels. These changes in endothelium function may promote vasospasm and vascular occlusion and contribute to increased vascular resistance in hypertension. The more effective release of EDRF in arterial coronary bypass grafts-which have a better patency than venous grafts-is in line with the concept that EDRF may play a role in the prevention of vascular occlusion.

Arterial Occlusive Diseases↗

PubMed1989

Interaction between endothelium-derived nitric oxide and SIN-1 in human and porcine blood vessels.

Nitric oxide (NO) is a potent vasodilator and inhibitor of platelet function that is produced from L-arginine in endothelial cells. The mechanism of action of nitrovasodilators such as SIN-1 has striking similarities with endothelium-derived nitric oxide. We studied the effects and interactions of endothelium-derived relaxing factor with SIN-1 in isolated human internal mammary arteries, saphenous veins, and porcine coronary arteries. In human arteries, SIN-1 induced potent relaxations (IC50 value of 6.6 +/- 0.1; maximal response of 100%) that were comparable to that induced by acetylcholine and were augmented by removal of the endothelium (concentration shift of 3.2-fold; n = 8 and 6, respectively, p less than 0.05). The relaxation to SIN-1 was also enhanced in saphenous veins as compared to mammary arteries (concentration shift of 6.3-fold; n = 7 and 6, respectively, p less than 0.005). In human and porcine arteries, incubation with the false precursor substance of endothelium-derived NO, L-NG-monomethylarginine (10(-5) and 10(-4) M), enhanced the relaxation induced by SIN-1 (concentration shift of 3.2- and 2.5-fold, respectively; n = 4 to 6; p less than 0.05). Thus, SIN-1 is a potent vasodilator of human and porcine blood vessels. Its effects are attenuated by spontaneously released endothelium-derived NO.

Analysis of Variance↗

PubMed1989

[The effects of longterm selection on the genetic structure of populations--a simulation study. II. The effects of selection on genetic variances].

Monte Carlo simulation has been done to study the effects of longterm artificial selection on genetic variances under additive, dominant, and over-dominant models. The effects of population size, linkage, and heritability have been considered. Just as under the additive model, the additive variance under the dominant and over-dominant models has also been decomposed into three components which represent changes in gene frequencies (VT), departure from Hardy-Weinberg equilibrium (VHW) and from linkage equilibrium (VLD) respectively. These present a resonable approach to study the association among multiple genes. In small populations, genetic variance fluctuates wildly over generations and replicates due to the establishment of linkage disequilibrium. Rapid decrease of VT observed. Intense linkage retained a greater additive variance in the small populations while slowing down responses, which makes it difficult to predict responses during longterm selection.

Animals↗

PubMed1989

[Studies on Epstein-Barr virus strain differences with monoclonal antibodies].

In order to differentiate a new EBV strain, H18, from other EBV strains, we prepared and screened by indirect immunofluorescence (IF) viable cells and fixed cells of a series hybridoma lines that produce monoclonal antibodies against H18 EBV membrane antigen (MA). T1-11 clone was used for further study: T14-11 antibody neutralizes EBV in vitro and recognizes polypeptides P220, P175 and P140 from purified H18 EBV particles, as shown by the Western Blot technique. The presence of the three polypeptides on the plasma membrane and in the cytoplasm may be detected by IF using T14-11 antibody. Treatment with puromycin completely abolished the expression of the antigen recognized by T14-11, and this Ab was shown to be specific for an early membrane antigen of EBV.

Animals↗

PubMed1989

Effect of fluorocarbon blood substitute on neutrophil phagocytic function.

Neutrophils were incubated at 37 degrees C for 2 h with fluorocarbon blood substitute or its main components in vitro. Neutrophil phagocytosis was determined by the method of chemiluminescence (CL) and the concentration of intracellular cAMP and cGMP were assessed. The results showed that the CL was inhibited while the level of cAMP was elevated. The alteration of cAMP seemed to be correlated with the inhibition of CL. Only did the emulsifier Poloxamer F-68 (F-68) of fluorocarbon blood substitute have the same effects. It is suggested that fluorocarbon blood substitute can inhibit neutrophil phagocytic function and the emulsifier F-68 may be responsible for it. The mechanism may be associated with the elevation of intracellular cAMP concentration.

Blood Substitutes↗

PubMed1989

[Surgical treatment of primary pulmonary cryptococcal granuloma--report of 4 cases].

Primary pulmonary cryptococcal granuloma is not common in Sichuan. The diagnosis of this disease is difficult to make because the patient has no characteristic symptoms and the chest X-ray findings of the mass are not easily differentiated from carcinoma of the lung. The incidence of this disease is apparently increasing. Pulmonary cryptococcosis may be disseminated hematogenously to the meninges and cryptococcal meningitis is very difficult to treat. If the pulmonary lesion is localized, the patient's general condition is good with no evidence of systemic lupus erythematosis, diabetes, leukemia or lymphoma, partial resection of the lung is indicated. But, if the patient has a history of recent cryptococcal meningitis, surgery must be deferred. Four cases of primary pulmonary cryptococcal granuloma have been treated surgically supplemented with medical therapy in the First Affiliated Hospital from 1986 to 1987. Follow-up of more than one year showed good results in each case.

Adult↗

PubMed1989

[Effects of longterm selection on the genetic structure of populations--a simulation study. I. Simulation models and selection responses].

Monte Carlo method has been utilized to investigate responses to longterm selection. The simulation involves 3 gene effect models (additive, dominant, and over-dominant), two population sizes, three linkage intensities, and three heritability levels, thus making 54 combinations. For each combination, 5 replicate populations are selected over 49 consecutive non-overlapping generations. The results demonstrate that under all the gene effect models, linkage is important only in the case of small populations and intense linkage, when it reduces responses significantly due to hampering the fixation of favourable alleles and accelerating their loss. Linkage has no apparent effect if it is not very tight or if the population is large. Much greater responses are achieved in the large populations than in the small ones, especially for traits with low heritability. Among those discussed are problems of crossing selected lines to obtain extra responses, and discrepancy of some theoretic results on selection limits.

Computer Simulation↗