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Biomedical subjects

A G Wilson

Publications and source records attributed to A G Wilson.

At least 109 records · Page 6Linked to original sources
PubMed1984

Pulmonary arterial hypertension and emphysema.

Pulmonary artery pressures were estimated by an indirect method using echocardiography (Boyd et al. 1980), in a group of patients with chronic airflow obstruction, in order to investigate the degree of pulmonary hypertension in patients with emphysema. We found a positive correlation between the estimated pulmonary artery end diastolic pressure (PAEDP) and the radiological emphysema score (r = 0.58, P less than 0.005), and between the estimated PAEDP and the transfer constant for carbon monoxide (KCO) (r = 0.66, P less than 0.002). There was no correlation between the PAEDP and the arterial partial pressure of oxygen (PaO2) before exercise, between the PAEDP and the change in oxygen partial pressure after exercise, or between the KCO and the PaO2. It is suggested that emphysema does predispose to pulmonary arterial hypertension and that the relationship is probably secondary to vessel destruction rather than hypoxia.

Aged↗
PubMed1982

Chain length dependency of fatty acid and carbamate binding to serum albumin.

The binding interactions of bovine serum albumin (BSA) with the unbranched fatty acids (FA) pentanoate (five-carbon chain length: C5) up to nonanoate (C9), and the carbamates n-methyl carbamate (equivalent to C3) up to n-hexyl carbamate (equivalent to C8) were examined using an ultrafiltration technique. A single, high-affinity site was observed for each of the FA, with an increasing number of secondary sites with increasing chain length. From binding affinity and competition data, there appear to be distinct albumin sites for the short-chain (less than or equal to C7) and the medium-chain (greater than or equal to C8) FA. Published data suggest that the medium-chain FA site is one of the major drug-binding sites on human serum albumin (HSA) or BSA, the indole/benzodiazepine site. Competition between the FA and warfarin for BSA or HSA binding was studied by ultrafiltration and fluorescence methods and suggests that the short-chain FA site may lie in the same region as a second major drug-binding site, the large warfarin-binding area. Thermodynamic parameters of the FA-BSA interactions are suggestive of primary binding being a combination of electrostatic and hydrophobic binding and secondary binding being purely hydrophobic in nature. Carbamate interactions with BSA show several primary sites and also suggest a disparity between the binding of ligands of less than or equal to 7 and greater than or equal to 8 in total length, but there was no evidence of competition between FA and carbamates. A model is proposed to explain these observations, which includes the suggestion that several classes of hydrophobic binding areas exist, each of which is specific for ligands of a restricted range of chain lengths.

Animals↗
PubMed1982

Effect of butylated hydroxyanisole, alpha-angelica lactone, and beta-naphthoflavone on benzo(alpha)pyrene:DNA adduct formation in vivo in the forestomach, lung, and liver of mice.

The effects of alpha-angelica lactone (alpha-AL), butylated hydroxyanisole (BHA), and beta-naphthoflavone (beta-NF) on the amount of benzo(alpha)pyrene (BP) metabolite:DNA adducts formed in the forestomach, lung, and liver of ICR/Ha mice were investigated 48 hr after p.o. administration of BP. BP was administered to mice in amounts known to result in BP-induced neoplasia in certain tissues. Analysis of deoxyribonucleosides by high-pressure liquid chromatography showed that several BP metabolite:DNA adducts were formed in each tissue examined. The major identified adduct in each tissue cochromatographed with the (+/-)-7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(alpha)pyrene (BPDEI):deoxyguanosine adduct. The (+/-)-7 beta,8 alpha-dihydroxy-9 beta,10 beta-epoxy-7,8,9,10-tetrahydrobenzo(alpha)pyrene (BPDEII):deoxyguanosine adduct was detected in each of the tissues. As a percentage of total DNA-associated radioactivity, the BPDEI:DNA and BPDEII:DNA adducts accounted for 14% in the forestomach, 39% in the lung, and 3% in the liver. Another adduct, possibly derived from BP:phenol(s), was detected in lung and liver. Early eluting unidentified DNA-associated radioactivity was also present in each of the tissues and accounted for the majority of the radioactivity (88%) in forestomach, 57% in lung, 97% in liver). Although total DNA-associated radioactivity in liver was approximately 15-fold higher than in lung and 5-fold higher than in forestomach, the specific activities of the BPDEI:adducts and of the BPDEII:adducts were approximately the same in these organs. Addition of alpha-AL or BHA to the diet inhibited BPDEI:DNA adduct formation in the forestomach and liver but not in the lung. The effect of beta-NF was not tissue specific; this aryl hydrocarbon hydroxylase inducer decreased markedly (80 to 90%) BPDEI:DNA adduct formation in all three tissues. The radioactivity associated with the early eluting peaks was also reduced when associated with the early eluting peaks was also reduced when alpha-AL, BHA, or beta-NF was fed to the mice. The inhibition of BPDEI:DNA and BPDEII:DNA adduct formation by alpha-AL, BHA, and beta-NF is discussed in relation to similar studies where these compounds inhibited BP-induced neoplasia.

4-Butyrolactone↗
PubMed1981

Inhibition in vivo of the formation of adducts between metabolites of benzo(a)pyrene and DNA by aryl hydrocarbon hydroxylase inducers.

The lungs of A/HeJ mice are susceptible to benzo(a)pyrene (BP)-induced neoplasia whereas the livers are resistant. Following p.o. administration of a carcinogenic dose of [3H]BP, radioactivity was associated with the DNA of both lung and liver. Analysis of the deoxyribonucleosides by high-pressure liquid chromatography showed that the major adduct in both tissues chromatographed as the (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDEI)-deoxyguanosine adduct. The (+/-)-7 beta, 8 alpha-dihydroxy-9 beta, 10 beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDEII)-deoxyguanosine adduct was 9 to 15% of the BPDEI adduct in both lung and liver. Although total DNA-associated radioactivity was approximately 12-fold higher in liver than in lung, the specific activities of the BP diol-epoxide adducts were approximately the same in these organs. Treatment of animals with beta-naphthoflavone (beta NF), an inhibitor of pulmonary adenoma formation, markedly decreased the amount of the BDPEI and BPDEII adducts in the lung and the liver. The decrease in the amount of these adducts in the lung correlates with the inhibition of tumorigenesis by beta NF. The inhibition of total DNA-associated radioactivity was significantly less than the BP diol-epoxide adducts. Thus, beta NF appears to inhibit BP-induced pulmonary neoplasia by reducing the amount of the BPDEI-deoxyguanosine adduct. Other inducers of aryl hydrocarbon hydroxylase were also tested for their effect on the formation of BP-deoxyribonucleoside adducts. Both 2,3,7,8-tetrachlorodibenzo-p-dioxin and Aroclor 1254 significantly reduced the amount of the BPDEI adduct in both lung and liver. These data would suggest that both 2,3,7,8-tetrachlorodibenzo-p-dioxin and Aroclor 1254, like beta NF, should protect against BP-induced pulmonary neoplasia. The effects of aryl hydrocarbon hydroxylase inducers on the binding of BP to DNA in vivo markedly contrast with their effect in vitro. Treatment of animals with aryl hydrocarbon hydroxylase inducers stimulates the formation of BP diol-epoxide adducts in vitro. The reason for the differences between our in vivo results and those predicted from in vitro studies is unclear.

Animals↗
PubMed1981

Inhibition in vivo of the formation of adducts between metabolites of benzo(a)pyrene and DNA by butylated hydroxyanisole.

Antioxidants have been shown to inhibit the carcinogenic effects of a variety of chemical carcinogens. For example, the phenolic antioxidant butylated hydroxyanisole (BHA) has been shown to be a potent inhibitor of benzo(a)pyrene (BP)-induced neoplasia in mouse lung and forestomach. The objective of the present study was to determine whether or nt BHA, under conditions known to result in inhibition of BP-induced neoplasia, affects the formation of BP metabolite:DNA adducts. Following p.o. administration of a carcinogenic dose of [3H]BP to A/HeJ mice, radioactivity was detected in the DNA of both lung and liver. Analysis of the deoxyribonucleosides by high-pressure liquid chromatography showed that the major adduct in both tissues cochromatographed with the (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDEI):deoxyguanosine adduct. The 7 beta, 8 alpha-dihydroxy-9 beta, 10 beta-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene (BPDEII):deoxyguanosine adduct was 10 to 15% of the BPDEI adduct in both lung and liver. Another adduct, possibly derived from BP phenol(s), was also detected in lung and was 10 to 20% of the BPDEI adduct. Treatment of animals with BHA decreased the amount of the BPDEI adduct in the lung and the liver approximately 55 and 75%, respectively. The decrease in the amount of this adduct in the lung appears to correlate with the inhibition of pulmonary adenoma formation (L. W. Wattenberg, J. Natl. Cancer Inst., 50: 1541-1544, 1973; J. L. Speier, L. K. Lam, and L. W. Wattenberg, J. Natl. Cancer Inst., 60: 605-609, 1978). Thus, BHA appears to inhibit BP-induced pulmonary adenoma formation by inhibiting the amount of the BPDE:DNA adducts formed in lung. Possible mechanisms by which BHA treatment inhibits the formation of BPDE:DNA adducts are discussed.

Animals↗
PubMed1980

Comments on Alonso's "theory of movement".

"The equation system which constitutes Alonso's 'theory of movement' [see 44: Title 2104] is compared with that of a standard family of spatial interaction models. It is argued that they are essentially equivalent."

Demography↗
PubMed1980

Influence of bronchomotor tone on airway dimensions and resistance in excised dog lungs.

In 10 excised dog lobes we measured total lobar resistance (Rlo) by forced oscillation at various transpulmonary pressures (Ptp) before and after bronchodilators and obtained simultaneous tantalum bronchograms in 5. Mean airway diameter increased up to a Ptp of 30 cmH2O, although the increase was greater between 0 and 10 cmH2O. In contrast, Rlo decreased between 0 and 10 cmH2O but increased again between 10 and 30 cmH2O. At a Ptp of 30 cmH2O, the mean diameter of small airways (< 2 mm) increased 31%, that of large airways (> 7 mm) 2% after aerosolized bronchodilators. At a Ptp of 1 cmH2O, increases were 44 and 15%, respectively. Values of Rlo were reduced at all Ptp after bronchodilator, but minimum Rlo occurred at lower Ptp than before, and the absolute increase in Rlo at greater Ptp was preserved. In four additional lobes, we partitioned Rlo using a retrograde catheter. All of the increase in Rlo at large Ptp was peripheral to the retrograde catheter. We conclude that excised lungs have bronchomotor tone that narrows airways even at high Ptp and that loss of tone magnifies the relative increase in Rlo at high Ptp, supporting suggestions that the increase is due to tissue resistance and hysteresis.

Airway Resistance↗
PubMed1979

Studies on the covalent binding of an intermediate(s) in prostaglandin biosynthesis to tissue macromolecules.

We investigated the covalent binding of intermediates in prostaglandin biosynthesis to tissue macromolecules. Following incubation of [1-14C]arachidonic acid with the microsomal fraction from guinea pig lung, ram or bovine seminal vesicle, human platelets, rabbit kidney, or rat stomach fundus, the amount of covalent binding of arachidonic acid metabolites expressed as percentage of total arachidonic acid metabolized varied from tissue to tissue ranging from 3% in human platelets to 18.2% in ram seminal vesicles. In general, the thromboxane synthesizing tissues had less covalently bound metabolites than the other tissues. The amount of covalently bound metabolites was increased in the guinea pig lung microsomes when the thromboxane synthetase inhibitor, N-0164, was added to the incubation mixture. The covalent binding of arachidonic acid metabolite(s) was greatly reduced by the addition of glutathione to the incubation mixture. In addition to the covalently bound metabolites, water-soluble metabolites derived from arachidonic acid metabolism were also observed. The amount of water-soluble metabolites was small in each tissue except for the rat stomach fundus. In the rat stomach fundus the water-soluble metabolites accounted for over 50% of the total metabolites. Conditions which would tend to increase or decrease the levels of free prostaglandin endoperoxides during the incubation of arachidonic acid with the microsomes gave increased or decreased levels of covalent binding. Our data suggest that the prostaglandin endoperoxides are responsible for the covalent binding observed during prostaglandin biosynthesis. This covalent binding to tissue macromolecules may be of physiological and pathological significance.

Animals↗
PubMed1978

Interaction between serotonin and efferent vagus nerves in dog lungs.

We anesthetized, paralyzed, and ventilated 32 dogs. In 16 dogs we measured total pulmonary resistance (RL) during inhalation of acetylcholine (ACh), serotonin (5-HT), and histamine (Hist) aerosols. Cooling both cervical vagi reduced the bronchoconstriction caused by 5-HT 64% (P = 0.001), reduced Hist-induced bronchoconstriction 17% (P = 0.003), and did not significantly reduce bronchoconstriction due to ACh. In seven dogs, we ventilated both lungs separately through a double-lumen catheter. Application of 5-HT to one lung increased the transpulmonary pressure amplitude in the homolateral but not in the contralateral lung. Cooling the homolateral vagus reduced this response 32% (P = 0.02). In nine dogs, we stimulated the peripheral ends of both cut cervical vagi before and during aerosol application of ACh, 5-HT, and Hist. ACh and Hist increased baseline RL 97 and 134%, respectively, without increasing the effect of vagal stimulation. 5-HT increased baseline RL only 27% but greatly augmented the effect of vagal stimulation (mean increase, 271%, P = 0.001). We conclude that 5-HT acts to potentiate vagal effects on airway smooth muscle via the efferent vagal pathway.

Acetylcholine↗
PubMed1977

Uptake and metabolism of prostaglandins by isolated perfused lung: species comparisons and the role of plasma protein binding.

We have investigated the uptake and subsequent metabolism of the prostaglandins (PGs) PGE1, PGA1, and PGB1 by rat, guinea pig and rabbit isolated perfused lungs (IPL). Significant species differences were not observed in the uptake or metabolism of any PG on passage through the IPL. However, differences in the uptake of PGA1 and PGB1 and in the metabolism of PGA1 were observed with a given species when the composition of the perfusion medium was varied. The IPL removed minimal amounts (less than 20% of the supply rate) of PGA1, and PGB1 from the circulation when the perfusate contained 4.5% bovine serum albumin (BSA). In the absence of BSA, however, both PGA1 and PGB1 were substantially removed from circulation (approximately 53% of the supply rate) and PGA1 was also metabolized. The composition of the perfusate had no effect on the uptake and metabolism of PGE1 which was always taken up and metabolized to a greater extent than was PGA1 and PGB1. Thus, the apparent species differences previously reported for the pulmonary biotransformation of PGA can result from differences in the perfusion medium used. Our data suggest that both plasma protein binding and a transport system play important roles in determining the selectively of the uptake of PGs by the lung.

Animals↗