Butyrate treatment in beta-hemoglobinopathies.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to M Brauer.
Explore the source record for details and available documents.
Classic explanations of the "group polarization phenomenon" emphasize interpersonal processes such as informational influence and social comparison (Myers & Lamm, 1976). Based on earlier research, we hypothesized that at least part of the polarization observed during group discussion might be due to repeated attitude expression. Two studies provide support for this hypothesis. In Study 1, we manipulated how often each group member talked about an issue and how often he or she heard other group members talk about the issue. We found that repeated expression produced a reliable shift in extremity. A detailed coding of the groups' discussions showed that the effect of repeated expression on attitude polarization was enhanced in groups where the group members repeated each other's arguments and used them in their own line of reasoning. Study 2 tested for this effect experimentally. The results showed that the effect of repeated expression was augmented in groups where subjects were instructed to use each others' arguments compared to groups where instructions were given to avoid such repetitions. Taken together, these studies show that repeated expression accounts for at least part of the attitude polarization observed in the typical studies on group polarization and that this effect is augmented by social interaction, i.e., it occurs particularly in an environment where group members repeat and validate each other's ideas.
Much recent work on stereotyping has dealt with groups that are either artificially created or that do not have an extensive history of conflict. The authors attempted to overcome this limitation by examining issues of perceived variability and ethnocentrism among samples of White American and African American youth. The goals were both to examine theoretical issues in stereotyping and to describe the current state of ethnic interrelations among young people. Four studies are reported. Throughout, the samples of African Americans demonstrate interethnic judgments that are consistent with existing work on stereotyping and ethnocentrism. White American students, however, reported judgements that replicate neither the out-group homogeneity effect nor ethnocentrism. Alternative explanations for this difference are considered, and the discussion focuses on differing views concerning the role of ethnic identity and diversity in our society.
Personal exposures to ozone were measured in the summers of 1992 and 1993 in the Fraser Valley, a suburban and rural river valley bordering the metropolitan region of Vancouver, British Columbia (population approximately 1.8 million). In 1992, two groups of 25 healthy individuals were selected for 14 consecutive days of 24-hour personal monitoring, based on prior expectations of their activity patterns. The first group, composed of adult healthcare workers, was expected to spend most of the work day indoors or commuting. The second group, teenage camp counselors, was expected to spend more time outdoors. Time-activity data were collected to investigate the association between activity patterns and ozone exposures. In 1993, 15 adult farmworkers wore personal ozone samplers during their workday, which was spent entirely outdoors. Personal monitoring was conducted with a nitrite-coated filter passive ozone sampler described by Koutrakis and colleagues. Ozone collection rates were determined empirically by collocation of the passive samplers with continuous ozone analyzers at fixed sampling sites. Sampler performance was assessed by collecting several duplicate personal samples. Although ozone levels were low (< 35 ppb 24-hour average) during both summer sampling periods, the passive ozone samplers agreed well with collocated UV absorption ozone measurements. Based on replicate personal samples, we estimated that personal measurements differing by more than 35% were associated with true differences in exposure. Within the two groups with varying time activities, differences in ozone exposures were associated with the fraction of time spent outdoors. Similarly, differences in ozone exposures were observed between the three sampling populations, with higher exposures recorded in the group that spent more time outdoors.(ABSTRACT TRUNCATED AT 250 WORDS)
Nitrous acid (HONO) is formed both indirectly from the reaction of nitrogen dioxide (NO2) with water on indoor surfaces, and directly during combustion. This gaseous pollutant may be a previously unrecognized causal factor in assessments of nitrogen oxide exposure effects. The present study is the first attempt to evaluate exposure effects of HONO on the human airways and the mucous membranes of the eyes and nose. Fifteen healthy adult nonsmokers were exposed for 3.5 h in a double-blind, balanced protocol to clean air, 77, and 395 ppb HONO. Each exposure was preceded by a 1-h baseline measurement period, and exposures were separated by 1 wk. There was a 10-min exercise period during exposure. Effects measurements included assessment of bronchial reactivity, measurement of specific airway conductance, spirometry, acoustic rhinometry, nasal lavage, tear-fluid cytology, a CO2 eye-provocation test, evaluation of eye redness, and subjective sensations. Effects of HONO exposure on the eyes were found as exposure-related changes in tear-fluid cytology. In particular, the number of squamous cells increased by 20, 67, and 80% following exposure to clean air, 77, and 395 ppb HONO, respectively (p = 0.004). Possible indications of exposure effects on sensitivity to CO2 eye provocation and on specific airway conductance were also measured. For specific airway conductance there was an approximate 10% decrease in conductance following exercise in association with HONO exposure, compared with a 2% decrease with clean air (p = 0.038).
The molecular defect in sickle cell disease resides in the beta globin gene, with consequent defects in erythrocytes only, suggesting that the vascular occlusion and vasomotor instability which characterize this disease are the result of interactions between abnormal sickle erythrocytes and cells of the blood vessel wall. We explored whether sickle erythrocytes may have effects on vascular tone, exclusive of adhesion events. Exposure of human endothelial cells in culture to previously sickled sickle erythrocytes resulted in a four to eight-fold transcriptional induction of the gene encoding the potent vasoconstrictor endothelin-1 (ET-1). Unsickled sickle erythrocytes or normal erythrocytes exposed to "sickling" conditions had no effect on ET-1 gene induction. Contact of the sickled erythrocytes with the endothelium was not required. Elevations in the ET-1 transcript peaked at 3 h after exposure and persisted for up to 24 h. Four to sixfold increases in the amount of ET-1 peptide was released into the medium surrounding the endothelial cells after exposure to sickled sickle erythrocytes. This is the first demonstration of the regulation of gene expression in endothelial cells as a result of interaction with sickle cells, with induction of genes encoding vasoconstrictors. Furthermore, these findings suggest that sickle erythrocytes may have the capacity to affect local vasomotor tone directly.
A large number of studies have indicated associations between particulate air pollution and adverse health outcomes. Wintertime air pollution in particular has been associated with increased mortality. Identification of causal constituents of inhalable particulate matter has been elusive, although one candidate has been the acidity of the aerosol. Here we report measurements of acidic aerosol species made for approximately 1.5 years in Erfurt, Germany, and Sokolov, Czech Republic. In both locations, the burning of high-sulfur coal is the primary source of ambient air pollution. Twenty-four-hour average measurements were made for PM10, [particulate matter with an aerodynamic diameter (da) < or = 10 microns], as well as fine particle (da < 2.5 microns) H+ and SO4(2-) for the entire study. Additionally, separate day and night measurements of fine particle H+, SO4(2-), NO3-, and NH4+ and the gases, SO2, HNO3, HONO, and NH3 were collected with an annular denuder/filter pack system over a 7-month (late winter-summer) period with additional measurements during pollution episodes the following winter. At both sites, 24-hr SO2 (mean concentrations of 52 micrograms/m3, with peak levels of > 585 micrograms/m3) and PM10 (mean concentration 60 micrograms m3) concentrations were quite high. However, aerosol SO4(2-) concentrations (mean concentration of approximately 10 micrograms/m3) were not as great as expected given the high SO2 concentrations, and acidity was very low (mean concentration of < 1 microgram/m3, with peak levels of only 7 micrograms/m3). Low acidity is likely to be the result of NH3 neutralization and slow conversion of SO2 to SO4(2-).(ABSTRACT TRUNCATED AT 250 WORDS)
The bioenergetic effects of cancer cachexia on the livers of male Fischer rats inoculated with a methylcholanthrene-induced sarcoma were assessed using serial in vivo 31P magnetic resonance spectroscopy. Rats were randomized into three groups: tumor-bearing controls (n = 7); an insulin-treated group receiving 2 units/100 g body weight/day starting 21 days after implantation (n = 8); and a chronic insulin-treated group receiving insulin every day after implantation (n = 3). During the 32-day study, serial measurements of food intake, body weight, and tumor volume were taken, and 31P magnetic resonance spectroscopy analyses of the livers were conducted every 7 days after tumor implantation. Neither the short-term nor the chronic insulin treatment regimens stimulated the progress of tumor growth. However, both treatments prevented body weight loss, and the short-term insulin treatment prevented tumor-induced decrease in food intake relative to the control group. Liver bioenergetic deterioration was evaluated from the increase in the ratio of Pi to ATP obtained from the hepatic 31P magnetic resonance spectra. At day 28 postimplantation, control rats exhibited appreciable hepatic bioenergetic deterioration, i.e., a Pi/ATP ratio of 1.41 +/- 0.35 (SE), significantly higher (P < 0.05) than the Pi/ATP ratio for short-term or chronic insulin treatment groups (Pi/ATP 0.92 +/- 0.22 and 0.84 +/- 0.22, respectively) or rats before tumor implantation (Pi/ATP 0.76 +/- 0.14). This insulin-induced bioenergetic protection occurred at any given tumor burden up to at least 10%. Thus, both short-term insulin given just prior to the frank manifestations of cancer cachexia and chronic insulin treatment given throughout tumor growth ameliorated host hepatic bioenergetic deterioration without significantly stimulating tumor growth. Insulin may act by altering the host metabolism (stimulation of liver glucose uptake and utilization, decreased energy-requiring gluconeogenesis, and general protein-sparing action) at the expense of the tumor.
The hepatic response to a fructose challenge for control rats, and rats subjected to an acute sublethal dose of carbon tetrachloride (CCl4) or bromobenzene (BB), was compared using dynamic in vivo 31P MRS. Fructose loading conditions were used in which control rats showed only a modest increase in hepatic phosphomonoester (PME), and a small decrease in ATP, Pi, and intracellular pH after fructose administration. Both CCl4 and BB-treated rats showed a much greater fructose-induced accumulation of PME than did controls. Trolox C, a free radical scavenger, prevented most of this PME increase. BB-treated rats, given sufficient time to recover from the hepatotoxic insult, responded to the fructose load similarly to controls. Liver aldolase activities of control, toxicant-treated rats, and toxicant plus Trolox C-treated rats correlated inversely with PME accumulation after fructose loading (correlation coefficient: -0.834, P < 0.05). Perchloric acid extracts of rat livers studied by in vitro 31P MRS confirmed that the PME accumulation after fructose loading is mainly due to an increase in fructose 1-phosphate. These studies are consistent with the aldolase-catalyzed cleavage of fructose 1-phosphate being rate-limiting in hepatic fructose metabolism, and that the CCl4 and BB treatment modify and inactivate the aldolase enzyme.
OBJECTIVES: The common operation of fuel-powered resurfacing equipment in enclosed ice skating rinks has the potential for producing high concentrations of carbon monoxide and nitrogen dioxide. Exposures to these gaseous combustion products may adversely affect the health of those inside the rink. Little information is available on pollutant concentrations under normal operating conditions. METHODS: One-week average nitrogen dioxide concentrations in 70 northeastern US rinks were measured with passive samplers during normal winter season conditions. RESULTS: The median nitrogen dioxide level inside rinks was 180 ppb, more than 10 times higher than the median outdoor concentration. One-week average nitrogen dioxide concentrations above 1000 ppb were measured in 10% of the rinks. CONCLUSIONS: Considering that short-term peak concentrations were likely to have reached two to five times the measured 1-week averages, our results suggest that nitrogen dioxide levels were well above short-term air quality guidelines and constitute a public health concern of considerable magnitude.
The structure of two rhamnolipid biosurfactants produced by Pseudomonas aeruginosa UG2 was studied. Analyses by gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy showed these two rhamnolipids to be alpha-L-rhamnopyranosyl-beta-hydroxydecanyol-beta-hydroxydecanoate and 2-O-alpha-L-rhamnopyranosyl-alpha-L-rhamnopyranosyl-beta-hydroxydecan oyl-beta- hydroxydecanoate. The ability of UG2 rhamnolipid biosurfactants to enhance removal of naphthalene, anthracene, phenanthrene, fluorene, 2,2',5,5'-tetrachlorobiphenyl, and 3,3',4,4',5,5'-hexachlorobiphenyl into the aqueous phase was affected by soil type, hydrocarbon equilibration time, and biosurfactant adsorption to soil. Partially purified UG2 biosurfactants at a concentration of 5 g/L removed approximately 10% more hydrocarbon from a sandy loam soil than slit loam soil. High levels of UG2 rhamnolipids adsorbed to soil. In 18% (w/v) soil slurries 74, 49, 38, and 20% of 0.5, 1, 2, and 5 g UG2 rhamnolipids/L, respectively, were bound to the soil phase. Sodium dodecyl sulphate recovered lower levels and Witconol SN70 higher levels of phenanthrene and 2,2',5,5'-tetrachlorobiphenyl than UG2 biosurfactants.
We report the case of a patient with renal insufficiency who was admitted for the evaluation of splenomegaly. He had received a kidney allograft 6 1/2 years ago. Treatment with azathioprine and prednisolone for immunosuppression had been discontinued 1 year before admission. The underlying cause of the splenomegaly appeared to be an idiopathic portal hypertension. Until now, this disease has been described in only 13 kidney transplant patients receiving long-term immunosuppressive therapy with azathioprine. For the first time we demonstrate that azathioprine can cause this chronic liver disease even if the drug has been withdrawn some time before. Therefore, the indication for azathioprine must be considered very carefully.
In vivo 1H magnetic resonance imaging (MRI), chemical shift selective imaging (CSI), and localized (VOSY) 1H magnetic resonance spectroscopy (MRS) were used to study fatty infiltration in the livers of rats chronically fed an ethanol-containing all-liquid DeCarli-Lieber diet. Conventional total proton MRI showed a somewhat hyperintense liver for ethanol-fed rats, compared with pair-fed controls. CSI showed a dramatic increase in the fat signal intensity for ethanol-treated rats that was fairly homogeneous throughout the liver. However, CSI also showed a substantial decrease in the water signal intensity for the ethanol-treated rats compared to pair-fed control rats. 1H VOSY MR spectra also showed a 5.5-fold increase in the methylene resonance (1.3 ppm) of fat and a 50-70% decrease in the water resonance (4.8 ppm). Relative in vivo proton T1 and T2 relaxation times for the water resonance separate from the fat resonance, determined from modified VOSY experiments, were found to tend to increase and decrease, respectively, for ethanol-treated rat livers compared with controls. The decrease in hepatic water signal intensity could be accounted for by the decrease in T2 and decrease in water density due to the presence of accumulated hepatic fat (approximately 25 mg/g wet weight of liver). When ethanol was withdrawn from the chronically treated rats, fatty infiltration was observed by both CSI and VOSY spectra to revert toward control values with a half-life of 2-4 days. By day 16, however, the signal intensity for hepatic fat was still significantly higher than control levels. In vitro 1H MRS studies of chloroform-methanol extracts confirmed the 5.5-fold increase in total hepatic fat induced by the chronic ethanol treatment, and showed further that triacylglycerols were increased 7.7-fold, cholesterol was increased fourfold, and phospholipids were increased 3.3-fold, compared with liver extracts from pair-fed control rats.
Respiratory-gated proton magnetic resonance imaging was used to study the response of the rat liver in situ to bromobenzene, a classic hepatotoxicant. A localized region of high proton signal intensity in the perihilar region of the liver was seen 24-48 hr after an intraperitoneal injection of bromobenzene. Localized proton magnetic resonance spectra from within this region indicated that the increased proton signal intensity was not due to accumulation of fat in the liver, but primarily due to a longer T2 for the proton resonance of water. This is consistent with acute edema in this localized region. In vivo 31P magnetic resonance spectroscopy studies of the same rat livers in situ were performed. Spectroscopic conditions were determined whereby localized, quantitative 31P spectra could be obtained. Using these methods, 10 mmol/kg bromobenzene was found after 24 hr to cause a number of statistically significant (p less than 0.05) effects: a decrease in adenosine 5'-triphosphate levels from 4.1 +/- 0.5 to 3.0 +/- 0.5 mM, a decrease in phosphodiester levels from 11.3 +/- 0.9 to 9.3 +/- 0.7 mM and an increase in the phosphomonoesters from 3.0 +/- 0.4 to 5.5 +/- 1.2 mM (mean +/- standard deviation). High resolution in vitro 31P spectra of perchloric acid extracts of these rat livers showed that the increased phosphomonoester resonance was due to a selective 4.3-fold increase in phosphocholine. Thus, our in vivo and in vitro 31P magnetic resonance spectra are consistent with the hypothesis that a phosphatidylcholine-specific phospholipase C (generating phosphocholine and diacylglycerol) is activated during tissue damage. Both the imaging and spectroscopy results obtained with bromobenzene closely resemble CCl4-induced liver changes previously reported, and may reflect a generalized response of the liver to any acutely acting toxic chemical.
Proton magnetic resonance imaging (MRI) and 31P magnetic resonance spectroscopy (MRS) have been used to study the response of the rat liver in situ to bromobenzene, a classic hepatotoxicant. A localized region of high proton signal intensity was seen in the perihilar region of the liver 24 hr after injection of a sublethal dose of bromobenzene. The signal intensity of the entire liver was increased at 48 hr with a gradual return approaching control values by 120 hr. These results are consistent with acute hepatic edema followed by repair of the damaged tissue. In vivo 31P MRS studies of the same rat livers were performed under conditions whereby localized, quantitative spectra could be obtained without surgical intervention. Initial concentrations of the major endogenous phosphorus-containing metabolites within the livers of control rats were 2.97 +/- 0.43 mM for the phosphomonoesters (PME), 2.92 +/- 0.56 mM for inorganic phosphate, 11.3 +/- 1.0 mM for phosphodiesters (PDE), 4.09 +/- 0.54 mM for ATP, and 0.56 +/- 0.50 mM for ADP and the intracellular pH was 7.39 +/- 0.14 (mean +/- SD, n = 10). Bromobenzene was found to cause statistically significant (p less than 0.05) changes in several of these metabolites: a decrease in hepatic ATP levels (20% at 24 hr; 27% at 48 hr), a decrease in PDE levels (15% at 24 hr; 18% at 48 hr), and an increase in the PME (63% at 24 hr; 84% at 48 hr). Both the proton MRI and the 31P MRS changes have an onset of 15-20 hr and maximum effect at 25-60 hr, but the MRS changes returned to normal well before the MRI changes. The decreased ATP levels indicate deleterious effects of bromobenzene on the bioenergetic status of the liver in situ, while the increase in PME, due to a selective increase in phosphocholine, suggests the activation of a phosphatidylcholine-specific phospholipase C in response to tissue damage. Trolox C, a potent inhibitor of lipid peroxidation, prevented the bromobenzene-induced hepatic edema (i.e., the increase in proton MRI signal intensity) and the bioenergetic deterioration (i.e., the decrease in ATP levels). However, the bromobenzene-induced increase in PME levels was not prevented by Trolox C. These results indicate that the process of lipid peroxidation plays a significant role in the hepatotoxicity of bromobenzene within the intact animal.
In vivo 31P nuclear magnetic resonance (NMR) spectroscopy provides unique opportunities to study the biochemistry of an organ within the intact animal in a totally non-invasive way. We have used in vivo and in vitro 31P NMR spectroscopy to study steady state changes in the major phosphorus-containing metabolites of the rat liver in control and chronically ethanol-treated rats. Chronic (4 month) ethanol treatment caused a statistically significant increase in the inorganic phosphate and phosphodiester resonances of rat liver in in vivo 31P NMR spectra relative to pair-fed control rats. Phosphomonoester and adenosine 5'-triphosphate resonances, as well as intracellular pH, were not appreciably altered. The effects of chronic ethanol treatment were particularly apparent in the response of the liver to a metabolic challenge of glycerol. Glycerol is phosphorylated almost exclusively in the liver and metabolized predominately via glycolysis and gluconeogenesis. Our in vivo 31P NMR results after administration of glycerol showed a significant increase in the phosphomonoester resonance in the liver of chronic ethanol-treated rats but not for their pair-fed controls. In vitro 31P NMR studies of perchloric acid extracts of liver showed that the increase was due to an accumulation of sn-glycerol 3-phosphate. This effect is due to the NAD(+)-dependent glycerol 3-phosphate dehydrogenase step being inhibited in the chronic ethanol-treated rats. This glycerol test may be useful in assessing the ability of the liver to rapidly regenerate NAD+ in situ and may be a more sensitive indicator of redox imbalance than steady state ratios of redox pairs (e.g., lactate/pyruvate).
This analysis of private health insurance plans offered in 100 four-year colleges and universities in 1988 indicates a tremendous diversity in plan options, benefits covered, cost-sharing requirements, and catastrophic protections. Consistent with relatively low premium prices, most student health insurance plans offer limited benefits and expose students to significant out-of-pocket medical cost liabilities. Only a minority of schools use financial incentives, such as preferred provider arrangements, to integrate their health insurance plans with their university health service system. We conclude that universities should carefully reexamine the adequacy of their health insurance plans and their relationship to student health centers. As more students rely on student health insurance as their only source of coverage, the quality of these plans assumes an even greater importance.
Annular denuder-filter pack sampling systems were used to make indoor and outdoor measurements of aerosol strong H+, SO4(2-), NH4+, NO3- and NO2-, and the gaseous pollutants SO2, HNO3, HONO and NH3 during summer and winter periods in Boston, Massachusetts. Outdoor levels of SO2, HNO3, H+ and SO4(2-) exceeded their indoor concentrations during both seasons. Winter indoor/outdoor ratios were lower than during the summer, probably due to lower air exchange rates during the winter period. During both monitoring periods, indoor/outdoor ratios of aerosol strong H+ were 40-50 percent of the indoor/outdoor SO4(2-) ratio. Since aerosol strong acidity is typically associated with SO4(2-), this finding is indicative of neutralization of the acidic aerosol by the higher indoor NH3 levels. Geometric mean indoor/outdoor NH3 ratios of 3.5 and 23 respectively were measured for the summer and winter sampling periods. For HONO, NH3, NH4+ and NO2-, indoor concentrations were significantly higher than ambient levels. Indoor levels of NO3- were slightly less than outdoor concentrations.