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Biomedical subjects

L A Brown

Publications and source records attributed to L A Brown.

At least 73 records · Page 4Linked to original sources
PubMed1996

Glutathione supplements protect preterm rabbits from oxidative lung injury.

The main objective of this study was to determine if glutathione (GSH) supplementation attenuated hyperoxic lung injury. Preterm (29 days) rabbits were delivered and exposed for 24 h to 1) room air, 2) room air and GSH, 3) 95% oxygen and GSH. GSH supplements (1 mM) were delivered in the nutritional support of 10% dextrose and saline through a peritoneal catheter. Animals assigned to oxygen had decreased lung volumes at 35 cmH2O, decreased lung compliance, increased edema, decreased cell viability, and decreased lung tissue and lavage-reduced/oxidized GSH levels, compared with control animals. Despite exposure to hyperoxia, animals supplemented with GSH were not different from room air controls with respect to lung mechanics, edema, cell viability, or tissue and lavage GSH. These studies suggest that GSH supplementation maintains normal lavage and lung tissue GSH levels in preterm animals exposed to hyperoxia and attenuates the changes in lung mechanics associated with oxygen-induced lung injury.

Animals↗
PubMed1995

Variability in glutathione-dependent detoxication in vivo and its relevance to detoxication of chemical mixtures.

Glutathione (GSH) has multiple functions in detoxication and its depletion has been associated with an increased risk of chemical toxicity. Because GSH can be depleted by different agents, combinations of compounds in chemical mixtures are likely to enhance risk over that seen with individual chemicals. Our studies have focussed on factors affecting the status of GSH in humans. In addition, we have utilized animals models and cell culture systems to understand the role of GSH in protection against chemical injury. Results of these studies show that, while large variations in sulfur amino acid content occur in the human diet, these variations are not correlated simply with GSH levels in vivo as reflected in the blood plasma pool. However, plasma levels of GSH do vary with gender, age, race and dietary habits, and these factors could affect the risk of toxicity in individuals exposed to chemical mixtures. In animal studies, we found that extracellular pools of GSH, including the blood plasma, lung-lining fluid and small intestinal lumen can be very important in protection against chemically induced injury. These pools can function to detoxify chemicals extracellularly, supply GSH and its precursors to cells and protect the extracellular surface of the plasma membrane from damage. Finally, endogenous gene-activated mechanisms of cell death which produce the characteristic morphology of apoptosis are susceptible to thiol-disulfide redox regulation. Perturbations in GSH status induced by chemical mixtures could alter this regulation and lower the threshold for chemically induced cell death by apoptosis. Thus, in vivo GSH status could be an important determinant of toxicity from chemical mixtures and may be useful as a biomarker for such risk.

Animals↗
PubMed1995

Decreased contractile responses to isoproterenol in isolated cardiac myocytes from aging guinea-pigs.

We have characterized the age-related changes of contractility and beta-adrenoceptor function in isolated cardiac myocytes from guinea-pigs. We used either adult animals from 2 to 14 weeks of age, where body weight increases linearly with age, or senescent ones aged between 53-65 weeks. There was some indication of a decrease in contractility in maximum Ca2+ with age, with significant differences between a young (< or = 4 weeks, weight < 400 g) and aged (> or = 8 weeks, weight > 600 g) group in contraction amplitude expressed as percentage shortening (but not when expressed as micron change in length) or contraction and relaxation velocities. This decline was continued into senescence, and ANOVA showed a significant difference between the three groups for contraction amplitude (percentage shortening, 12.2 +/- 0.9%, young, n = 31; 9.5 +/- 0.6%, n = 28 aged; 6.7 +/- 0.8%, n = 6, senescent; P = 0.005), and contraction or relaxation velocities (P < 0.001). There was a more pronounced decline in maximum response to isoproterenol with age. ANOVA for the maximum isoproterenol response for the three divisions showed significant differences for percentage shortening (11.8 +/- 0.7%, n = 30, young; 7.9 +/- 0.5%, n-28, aged and 5.5 +/- 1.1%, n = 6, senescent; P < 0.001), velocities of contraction (P < 0.001) and relaxation (P < 0.001), and normalized velocities of contraction (P < 0.001) and relaxation (P < 0.01) at maximum isoproterenol, as well as in ISO EC50 (P < 0.001) and isoproterenol/Ca2+ ratio (P < 0.02). A general decrease in contractility of the myocyte occurs as the animal ages, with maximum contraction amplitude being reduced and velocity of contraction and relaxation slowed. The effect was more pronounced for beta-adrenoceptor stimulation than for high Ca2+, suggesting a specific lesion in the adenylate cyclase related pathway. Much of the change occurred between the young adult (< or = 4 weeks) and the aged adult (> or = 8 weeks), although the trend was continued in senescent animals (> 52 weeks).

Adrenergic beta-Agonists↗
PubMed1995

Pulmonary alveolar proteinosis in SCID mice.

Pulmonary alveolar proteinosis (PAP) is an uncommon disorder of unknown origin in which the alveoli are filled with lipoproteinaceous material, including surfactant. We have characterized a spontaneously occurring lesion in the lungs of CB.17 scid/scid mice which resembles PAP in humans. Lungs from 45 severe combined immunodeficient (SCID) mice were evaluated by light and electron microscopy and immunohistochemistry. Lung lavage fluid was evaluated biochemically and for the presence of surfactant protein A (SP-A) and B (SP-B) by enzyme-linked immunosorbent assay and Western blot. Light microscopy showed varying amounts of a homogeneous to granular proteinaceous material in alveolar spaces. This material was eosinophilic by hematoxylin and eosin stain and was periodic acid-Schiff (PAS) positive. Ultrastructurally, the material was predominantly homogeneous with areas of a lamellated pattern that resembled surfactant. Biochemical analysis revealed 2.7- and 3.6-fold increases in the surfactant-associated phospholipids phosphatidylcholine and disaturated phosphatidylcholine respectively, when affected SCID mice were compared with control mice. Immunohistochemical staining of lung tissue and Western blot and enzyme-linked immunosorbent assay of lavage fluid showed marked increases in SP-A and SP-B in comparison with controls. These results suggest that SCID mice have a defect in surfactant homeostasis that resembles PAP in humans and may serve as an animal model in further elucidating the pathogenesis of this disease.

Animals↗
PubMed1995

The uprooting of people, migration, and labor force experiences: Ecuador 1982 and 1990.

"Moving beyond traditional theories of migration, this paper considers how actual economic, socio-political, and natural events impacted uprooting of people in Ecuador since the 1950s. Major eras of economic growth and economic devolution are represented by Census data for 1982 and 1990. Through these, individual labor force experiences of migrants and stayers, and gender differentials within each group, are considered. Uprooting of people persists forty to fifty years after events initiating its occurrence, and differentially impacts each population group. Gender differentials are noticeably significant among occupational sectors of employment, less so for economic sectors. Predominance and continual growth of informal activities also is apparent, a trend which impacts women more strongly." (SUMMARY IN GER)

Americas↗
PubMed1995

Selective increase in endothelin-1 and endothelin A receptor subtype in the hypertrophied myocardium of the aorto-venacaval fistula rat.

OBJECTIVE: At present little is known about the factors that regulate the expression of the endothelins and their receptors in cardiac tissue in vivo. The aim of this study was to investigate changes in expression of the endothelins (ET-1, ET-2, and ET-3) and their receptors (ETAR and ETBR) in the hypertrophied heart of the aortovenocaval (AV) fistula rat. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify cardiac mRNA expression of the endothelins and their receptors during the development of cardiac hypertrophy, while radioligand binding was employed to quantify the amount of [125I]-ET-1 binding to cardiac membranes. Tissue and plasma concentrations of ET-1 were measured by radioimmunoassay. RESULTS: In control sham operated animals, ET-1 mRNA was approximately fivefold greater in atria than in ventricles (P < 0.05), but there were no atrioventricular differences in ET-2 or ET-3 mRNA. In the AV fistula rats there was a prompt three- to fourfold increase in ET-1 mRNA in atria and a progressive five- to sevenfold rise in ventricles during cardiac hypertrophy. There were no changes in ET-2 or ET-3 transcript prevalences, except for a late rise (35 d) in ET-2 mRNA levels in left ventricle. Consistent with ET-1 mRNA measurements, immunoreactive endothelin levels were increased by 7 d in atria, but not in ventricles. In control rat hearts, ETAR mRNA levels were similar in atria and ventricles, but the prevalence of ETBR was approximately sevenfold greater in the former. ETAR mRNA prevalence increased with hypertrophy in all chambers, while ETBR transcript levels were raised only in the right ventricle. There was no significant difference in [125I]-ET-1 binding between atrial samples from 35 d control and 35 d AV fistula rats, suggesting rapid turnover of endothelin receptors balanced by increased transcription from the ETAR gene. CONCLUSIONS: During cardiac hypertrophy in AV fistula rats there is increased activity of the endothelin system mediated principally by ET-1 and the ETAR subtype.

Animals↗
PubMed1994

Which cervical sampler? A comparison of four methods.

Four cytology sampling methods were compared in 1063 patients referred for colposcopy with a recent abnormal smear. A dyskaryotic smear of any grade was considered a positive result, though comparisons were limited to cases with a subsequent biopsy confirming CINII or III. There were no differences between the abilities of any of the four methods to detect higher grades of CIN (chi (2)3 = 4.603, P > 0.20). The presence or absence of endocervical cells in a smear was not significantly associated with any variation in success rate (chi (2)1 = 0.959, P > 0.30). The joint analysis of the four methods and the presence/absence of endocervical cells also showed no significant effects (chi (2)7 = 12.768, 0.1 > P > 0.05). In the latter analysis the trend towards a conventional level of significance was accounted for by the Aylesbury spatula giving a relatively high success rate when endocervical cells were present. The suggestion of advantage for the Aylesbury spatula merits further investigation.

Cervix Uteri↗
PubMed1994

Frontier migration as a multi-stage phenomenon reflecting the interplay of macroforces and local conditions: the Ecuador Amazon.

"This paper considers frontier migration to the Ecuador Amazon as a multistage phenomenon, examining the entire migration stream from its origins in highland and coastal locales of Ecuador, to intermediate stops outside and within the Amazon, to final Amazon destinations. The approach is one where models pertaining to regional development, migration, and pioneer activity are treated as complementary to one another and meshed with a qualitative knowledge of place. It is shown that frontier settlement patterns reflect the composite of these models, a maturing space-economy, and the interaction of local characteristics with exogenous circumstances representing national and international contexts."

Americas↗
PubMed1994

Glutathione protects signal transduction in type II cells under oxidant stress.

Brief exposure of type II cells to 100 microM t-butyl hydroperoxide (tBOOH) inhibits agonist-induced surfactant secretion and second messenger generation presumably through the oxidation of membrane lipids. Since glutathione (GSH) reduces lipid peroxides and protects type II cells from oxidant injury as determined by crude indicators, then GSH should also protect signal transduction. In the current study, tBOOH inhibited ATP-induced adenosine 3',5'-cyclic monophosphate and inositol trisphosphate generation and surfactant secretion. Stimulation of surfactant secretion by forskolin or phorbol acetate was also inhibited by tBOOH. Pretreatment with GSH (1 mM) blocked the tBOOH inhibition. This protection occurred in the presence of gamma-glutamyl transferase and gamma-glutamylcysteine synthetase inhibitors and suggested GSH was transported as an intact molecule. GSH protection was blocked by gamma-L-glutamyl-L-glutamate, an agent that blocks GSH transport. Protection of surfactant secretion and signal transduction was also provided by the constitutive amino acids but not if GSH synthesis was blocked. In the cultured type II cell model, GSH transport and synthesis protected signal transduction and, subsequently, surfactant secretion against oxidant injury.

1-Methyl-3-isobutylxanthine↗
PubMed1994

Glutathione transport by type II cells in perfused rat lung.

Glutathione (GSH) is an antioxidant that protects the lung against oxidative-injury. Most cells rely on synthesis of GSH to maintain intracellular supply and only a few cell types take up intact GSH. Although isolated type II cells from rat have a Na(+)-dependent uptake system that transports GSH into the cells against a concentration gradient, it is not known whether this occurs from the vasculature in the intact lung or whether other cell types in the lung also transport GSH. Based on the knowledge that gamma-glutamyl analogues of GSH are also transported by the Na(+)-GSH transporter, a method was developed and used to study the cell specificity of GSH uptake in perfused lung. A stable, fluorescent GSH S-conjugate (GSH-I14) was synthesized and separated from the original dye as analyzed by high-performance liquid chromatography. Studies with isolated alveolar type II cells showed that uptake of GSH-I14 was Na+ dependent and inhibited by GSH. In addition, uptake of GSH by the type II cells was inhibited by GSH-I14. After perfusion of the isolated rat lung with GSH-I14, the conjugate accumulated primarily in the alveolar type II cell as observed by fluorescence microscopy. This was confirmed by isolation of type II cells and measurement of GSH-I14 content. Thus these results show that specificity of GSH transport can be studied with the fluorescent derivative, GSH-I14, and that in the isolated perfused lung type II cells can transport and concentrate GSH-I14 from the perfusate. Quantitative fluorescence microscopy will be required to further determine relative transport activities by other cell types.

Animals↗
PubMed1994

Prostate-specific antigen screening for prostate cancer: no reduction in Gleason scores.

Skepticism regarding prostate-specific antigen (PSA) screening arises from the possibility that screening procedures increase the yield of diagnosed prostate cancers occurring in an indolent form that does not require treatment. If PSA screening serves only to increase the yield of clinically trivial prostate cancer, one would expect a drop in the average Gleason score of prostate cancers detected with PSA screening compared with prostate cancers detected before the advent of PSA screening. In a 3-yr study of newly diagnosed prostate cancer, there was almost a 7-fold increase in PSA screening tests ordered between 1989 and 1992 and a greater than 2-fold increase in the number of newly diagnosed prostate cancers. In the same time period, the average Gleason scores of newly diagnosed prostate cancer increased slightly (from 6.2 to 6.5). In this study there was no prognostic difference (as predicted by Gleason score) between prostate cancers in populations whose cancers were diagnosed before and after the increased use of PSA as a screening tool.

Biopsy, Needle↗
PubMed1994

The incompetent defendant: support systems help avoid future legal problems.

Reducing crime and improving efficiency of our criminal justice system should be facilitated by identifying how to treat and manage mental health patients who are prone to committing criminal acts more effectively. A total of 142 competency evaluations were reviewed from cases evaluated by the Galveston County Forensic Psychiatrist from 1984 to 1990. Examination of data from these defendants allowed us to address the psychiatric needs of these defendants in terms of contact with the mental health system, particularly those who had more than one criminal justice system contact. The latter defendants lacked social support systems and consistent mental health system follow-up to provide stabilization of their condition. It was felt that this was a factor in their more frequent contact with the criminal justice system.

Adolescent↗
PubMed1993

On the involvement of a cyclosporin A sensitive mitochondrial pore in myocardial reperfusion injury.

Mammalian cardiomyocytes may withstand prolonged periods of ischaemia, only to die on reperfusion. We review data that implicate mitochondrial dysfunction as a basis for reperfusion induced cell injury, and present some new evidence that suggests that such a mechanism operates in intact cardiomyocytes. The mitochondrial dysfunction is the consequence of the opening of high conductance pores in the inner mitochondrial membrane, which uncouple mitochondrial oxidative phosphorylation, promoting ATP hydrolysis. The conditions required to open the pores correlate closely to conditions that prevail upon reperfusion of the ischaemic heart: a high [Ca2+]i and Pi, low [ATP], and oxidative stress. Pore opening is suppressed by physiological concentrations of ATP. Pore opening may be prevented by cyclosporin A. Studies in isolated myocytes show that mitochondria become uncoupled after reoxygenation, and that this is associated with the hypercontracture that signals cell death. Cyclosporin A reduces the proportion of hypercontracted myocytes in populations of cells rendered anoxic.

Adenosine Triphosphate↗
PubMed1993

Differential regulation of natriuretic peptide receptor messenger RNAs during the development of cardiac hypertrophy in the rat.

The heart expresses the three natriuretic peptide receptors (NPR), namely NPR-A, NPR-B, and NPR-C. We have examined the temporal relationship between the expression of mRNA transcripts for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and their receptors in the heart during the development of cardiac hypertrophy in the aortovenocaval fistula rat. Messenger RNAs were measured by cDNA amplification. Progressive cardiac hypertrophy was accompanied by increased ANP mRNA prevalence throughout the heart and increased BNP mRNA in the left atrium. The most striking observation was the gradual disappearance of NPR-C transcripts (the putative "clearance" receptor) in all chambers; this was in marked contrast to the increase in mRNA levels for NPR-A and NPR-B (the guanylyl cyclase-linked receptors). Our observations have important therapeutic implications if the transcript changes are mirrored at the receptor protein level because (a) the apparent down-regulation of NPR-C may enhance the local action of natriuretic peptides on the heart, and (b) the loss of NPR-C, particularly if it is widespread, may reduce the rate of elimination of the natriuretic peptides, restricting the therapeutic potential of specific NPR-C ligands designed to reduce peptide clearance.

Animals↗