J A Marques-Magallanes

Children's Hospital Los Angeles, Los Angeles, California, United States

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Publications (8)33.77 Total impact

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    ABSTRACT: To evaluate possible alterations in the diffusing capacity of the lung for carbon monoxide (DLCO) or its components, membrane diffusing capacity of the lung for carbon monoxide (DMCO) and pulmonary capillary blood volume (Vc), in habitual smokers of "crack" cocaine (with or without tobacco) and following the short-term administration of inhaled cocaine base or IV cocaine HCl. Cross-sectional and longitudinal evaluation of DLCO and its components in smokers of cocaine alone, tobacco alone, and cocaine plus tobacco, and in nonsmokers and ex-smokers. Measurement of possible acute effects on DLCO and its components after experimental short-term administration of IV and smoked cocaine. University and Veterans Affairs hospital research laboratories. Convenience sample of habitual smokers of crack cocaine with or without tobacco and matched control nonsmokers and ex-smokers, and smokers of tobacco only. DLCO, DMCO, and Vc. Neither habitual cocaine smoking in cross-sectional or longitudinal analysis nor the short-term administration of inhaled alkaloidal cocaine significantly affected DLCO or its component parts. In contrast, a clear cross-sectional effect of regular tobacco smoking was demonstrated.
    Chest 09/2002; 122(2):629-38. · 7.13 Impact Factor
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    M D Roth, J A Marques-Magallanes, M Yuan, W Sun, D P Tashkin, O Hankinson
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    ABSTRACT: Induction of the carcinogen-metabolizing enzyme cytochrome P4501A1 (CYP1A1) is a key step in the development of tobacco-related cancers. To determine if marijuana smoke activates CYP1A1, a murine hepatoma cell line expressing an inducible CYP1A1 gene (Hepa-1) was exposed in vitro to tar extracts prepared from either tobacco, marijuana, or placebo marijuana cigarettes. Marijuana tar induced higher levels of CYP1A1 messenger RNA (mRNA) than did tobacco tar, yet resulted in much lower CYP1A1 enzyme activity. These differences between marijuana and tobacco were primarily due to Delta(9)-tetrahydrocannabinol (Delta(9)-THC), the psychoactive component of marijuana. Here we show that Delta(9)-THC acts through the aryl hydrocarbon receptor complex to activate transcription of CYP1A1. A 2-microg/ml concentration of Delta(9)-THC produced an average 2.5-fold induction of CYP1A1 mRNA, whereas a 10- microg/ml concentration of Delta(9)-THC produced a 4.3-fold induction. No induction was observed in Hepa-1 mutants lacking functional aryl-hydrocarbon receptor or aryl-hydrocarbon receptor nuclear translocator genes. At the same time, Delta(9)-THC competitively inhibited the CYP1A1 enzyme, reducing its ability to metabolize other substrates. Spiking tobacco tar with Delta(9)-THC resulted in a dose-dependent decrease in the ability to generate CYP1A1 enzyme activity as measured by the ethoxyresorufin-o-deethylase (EROD) assay. This inhibitory effect was confirmed by Michaelis-Menton kinetic analyses using recombinant human CYP1A1 enzyme expressed in insect microsomes. This complex regulation of CYP1A1 by marijuana smoke and the Delta(9)-THC that it contains has implications for the role of marijuana as a cancer risk factor.
    American Journal of Respiratory Cell and Molecular Biology 04/2001; 24(3):339-44. · 4.15 Impact Factor
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    J.A. Marques-Magallanes, T.W. Storer, C.B. Cooper
    Respiratory Medicine. 01/1999; 93(1):71–72.
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    J A Marques-Magallanes, T W Storer, C B Cooper
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    ABSTRACT: Oxygen supplementation is known to improve exercise capacity in patients with chronic obstructive pulmonary disease (COPD). Although some COPD patients use oxygen after exercise to relieve dyspnea, the effect of oxygen during recovery from exercise is not clearly understood. Exercise duration and dyspnea recovery time were studied in 18 patients with stable COPD. Patients exercised at a constant submaximal work rate on a treadmill ergometer until they no longer wished to continue. Oxygen, room air and compressed air were randomly administered in three consecutive post-exercise recovery periods. Dyspnea was scored on a 100 mm visual analog scale at 30 s intervals until return to baseline. An additional 20 minute post-recovery resting period was allowed between each test. No significant differences were found in dyspnea recovery time breathing oxygen (271 s), room air (290 s) or compressed air (311 s) When the groups were sorted by sequence of testing, there was a highly significant increase in recovery time (208 s, 307 s and 358 s for the first, second and third tests; P < 0.005) and a non-statistically significant decrease in exercise duration (89 s, 79 s and 76 s). Post-exercise oxygen supplementation had no effect on dyspnea recovery time in these COPD patients. Repeated bouts of exercise increased dyspnea recovery time and tended to decrease exercise duration. These findings suggest that, despite recovery of symptoms, physiological recovery from prior exercise is incomplete.
    Respiratory Medicine 05/1998; 92(5):735-8. · 2.59 Impact Factor
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    P Matthias, D P Tashkin, J A Marques-Magallanes, J N Wilkins, M S Simmons
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    ABSTRACT: To determine whether smoking more, compared to less, potent marijuana (MJ) cigarettes to a desired level of intoxication ("high") reduces pulmonary exposure to noxious smoke components, in 10 habitual smokers of MJ, we measured respiratory delivery and deposition of tar and delta9-tetrahydrocannabinol (THC), carboxyhemoglobin (COHb) boost, smoking topography, including cumulative puff volume (CPV) and breathholding time, change in heart rate (deltaHR) and "high" during ad lib smoking of 0, 1.77, and 3.95% MJ cigarettes on 3 separate days. At each session, subjects had access to only a single MJ cigarette. On average, smoking topography and COHb boost did not differ across the different strengths of MJ, while THC delivery, as well as HR, were significantly greater (p < 0.01) and tar deposition significantly less (p < 0.03) for 3.95% than 1.77% MJ. Although individual adaptations in smoking topography for 3.95% compared to 1.77% MJ were highly variable, three subjects with the lowest 3.95% MJ:1.77% MJ ratios for CPV also displayed the lowest 3.95% MJ:1.77% MJ ratios for tar deposition. In vitro studies using a standardized smoking technique revealed a mean 25% lower tar yield from 3.95% than 1.77% MJ (p < 0.05), but no difference between 1.77% and 0% marijuana. Under the conditions of this study, we conclude that tar delivery is reduced relative to THC content in a minority of subjects, and this reduction appears to be due to a reduced intake of smoke (decreased CPV) and/or a reduced tar yield from the stronger MJ preparation.
    Pharmacology Biochemistry and Behavior 12/1997; 58(4):1145-50. · 2.82 Impact Factor
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    J A Marques-Magallanes, S N Koyal, C B Cooper, E C Kleerup, D P Tashkin
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    ABSTRACT: Habitual smoking of alkaloidal cocaine (crack) has been reported to be associated with a number of cardiopulmonary complications that may not be clinically obvious but could potentially interfere with normal physiologic responses to exercise and thus impair maximum exercise performance. To evaluate the impact of regular use of cocaine on maximum exercise. Observational study in crack users and age- and gender-matched control subjects. Thirty-five habitual cocaine smokers (21 male and 14 female) and 29 age-matched sedentary control nonsmokers of cocaine (15 male and 14 female), all of whom were in good general health. In these subjects, we compared physiologic responses to symptom-limited, incremental maximal exercise performed on a cycle ergometer using a ramp protocol. Comparisons were made for men and women separately. For both men and women, long-term cocaine smokers had a reduced aerobic capacity (maximum oxygen consumption) compared with control nonsmokers but did not show evidence of ventilatory limitation, reduced gas exchange threshold, increased physiologic dead space, or gas exchange abnormality at maximum exercise compared with the healthy control subjects. Although cocaine smokers had reduced maximum heart rates compared with control subjects, the relationship between submaximal heart rate and oxygen uptake was normal, indicating a normal cardiovascular response pattern. However, effort perception was similar between the two groups despite the difference in heart rate at maximum exercise, suggesting the possibility of perceptual dysfunction for effort. Differences in aerobic capacity between the crack users and nonusers could not be explained by differences in physical fitness or altered perception of dyspnea. In the subjects we studied, long-term cocaine smoking was associated with reduced maximum exercise performance, probably due to poor motivation or altered effort perception. No other identifiable physiologic abnormality appeared to limit exercise in the habitual crack users.
    Chest 11/1997; 112(4):1008-16. · 7.13 Impact Factor
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    E C Kleerup, M Wong, J A Marques-Magallanes, M D Goldman, D P Tashkin
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    ABSTRACT: Some habitual crack cocaine smokers who deny IV drug abuse show decreased pulmonary transfer of carbon monoxide (DCO). We speculated that repeated elevations in pulmonary artery pressure (PAP) might cause pulmonary capillary damage and result in a lowered DCO, or that the reduction could be due to anoxic lung injury secondary to repeated episodes of cocaine-induced pulmonary vascular constriction. Compare the acute effects of i.v. cocaine HCl and placebo on PAP, cardiac stroke volume, and cardiac output estimated indirectly by continuous Doppler echocardiography. A single-blind crossover study in which placebo always preceded the active drug. Ten current crack-smoking subjects, 32 to 47 years of age, with a history of limited previous i.v. cocaine use. PAP, cardiac stroke volume, heart rate, and BP were measured continuously after injection of placebo followed by cocaine HCl (0.5 mg/kg). i.v. cocaine resulted in no significant change in PAP (-0.14 +/- 3.3[SD] mm Hg, 95% confidence interval [CI] for difference -2.48, +2.21). Stroke volume index showed no significant change after cocaine (-0.1 +/- 2.0 mL; 95% CI, -1.5, +1.3). Heart rate showed a significant increase (10.0 +/- 7.2 min-1; p = 0.0017, 95% CI, +4.9, +15.1). Cardiac index showed a significant increase (0.48 +/- 0.32 L/min; p = 0.0012, 95% CI, +0.25, +0.71). Pulmonary vascular resistance showed no significant change (-44 +/- 101 dyne.s.cm-5/m2, 95% CI, -116, +29). i.v. cocaine HCl does not cause short-term increases in PAP or stroke volume index, but causes an increase in cardiac index due to its chronotropic effect.
    Chest 02/1997; 111(1):30-5. · 7.13 Impact Factor
  • P. Matthias, D.P. Tashkin, J.A. Marques-Magallanes, J.N. Wilkins, M.S. Simmons
    Pharmacology Biochemistry and Behavior 01/1997; 58(4). · 2.82 Impact Factor