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Biomedical subjects

P L Brown

Publications and source records attributed to P L Brown.

At least 19 recordsLinked to original sources
PubMed1999

FG 7142- and restraint-induced alterations in the ataxic effects of alcohol and midazolam in rats are time dependent.

The purpose of this study was to examine whether acute stress exposure would alter the ataxic properties of midazolam or ethanol in rats. Rats were administered either vehicle or FG 7142 (10 mg/kg) and placed back in their home cages, or placed in restraining tubes for 90 min. Three and one-half or 24 h following injection all subjects were then administered an ataxic dose of either ethanol or midazolam and after 10 min, motoric impairment was assessed by rotarod performance. Neither FG 7142 administration nor restraint had an impact on rotarod performance 3-1/2 h later for ethanol nor 24 h later in response to midazolam. However, midazolam-induced ataxia was significantly modified 3-1/2 h following both restraint and FG 7142 exposure. Similarly, at the 24-h time point, both manipulations had a significant effect on ethanol-induced motor incoordination. Importantly, prior exposure to FG 7142 and restraint was without effect on rotarod performance in saline-treated subjects. Functional alterations in behavioral reactivity to low doses of two classes of CNS depressants by the acute stress of restraint and/or FG 7142 administration suggest the anxiogenic nature of these stressors may be the critical factor.

Animals↗
PubMed1998

Relative importance of natural and anthropogenic influences on the fresh surface water chemistry of the Hawkesbury-Nepean River, south-eastern Australia.

Fresh surface waters from the Hawkesbury-Nepean River, the major river supplying water to the Sydney region in south-eastern Australia, were sampled monthly during 1991 and analysed for major ions (Na, K, Ca, Mg, Cl, SO4 and HCO3), nutrients (NO3 and PO4), organic carbon and trace metals (Al, Fe, Cu, Zn, Pb, Cd, Ni, Co and Mn). The chemical composition of the river during 1991 was consistent with other studies of the river from 1977 to 1996. The major ion composition in the river is predominantly influenced by sea-salt aerosols in rainwater (headwaters) and connate sea-salt in groundwater (mid-lower reaches), with a cationic dominance order of Na >> Mg > Ca > K (equivalents) and an anionic order of Cl >> HCO3 > SO4. This is typical of the headwaters of other permanent coastal rivers (freshwater) in south-eastern Australia with a similar catchment lithology. These results differ markedly from the most common natural major ion assemblages established for world rivers (i.e. Ca > Mg > Na > K and HCO3 > SO4 > Cl), which tend to be predominantly influenced by chemical weathering of rocks and minerals. The mean concentrations of major ions, nutrients, organic carbon and trace metals in the freshwater reaches of the Hawkesbury-Nepean River increased by factors of 2.5-4.4, 14-18, 2.2 and 1.6-11, respectively, with increasing distance from the headwaters. Increases in major ion concentrations are attributed mainly to the increasing influence of saline groundwater inflows from regions of Wianamatta shale. Conversely, concentrations of nutrients, organic carbon and trace metals (except Fe and Al) increased as a consequence of anthropogenic inputs, particularly point discharges from sewage treatment plants (i.e. showing distinct, but variable, concentration peaks), as well as diffuse urban and/or agricultural runoff during storm events. The temporal variability of the mean concentrations of all measured parameters in this study was related to variability in water discharge. The mean concentrations of the major ions decreased by a factor of 1.5-3.0 with increasing water discharge, whereas the concentrations of nutrients, organic carbon and trace metals increased by a factor of 2.0-3.0, 1.6 and 1.3-2.0, respectively. This study provides the first survey of trace metal concentrations in the freshwater reaches of a permanent coastal river in Australia using 'clean' sampling and handling techniques. The concentrations of Cu, Zn, Pb, Cd and Ni measured in the headwaters of the Hawkesbury-Nepean River were amongst the lowest reported in the literature for riverine (freshwater) systems, and will form a benchmark for assessing the effects of increasing urbanisation in the catchment.

Australia↗
PubMed1995

Sensory acceptability of meat and dairy products and dietary fat in male collegiate swimmers.

This study was undertaken to determine whether high-level training alters food choice behavior with regard to meat and dairy products because of their high fat content. Twenty male collegiate swimmers were compared to 20 male sedentary students for dietary fat intake, nutrition knowledge, and liking of meat and dairy products. There was no significant difference between the two groups for restraint, energy intake, dietary fat intake, and energy derived from fat. Nutrition knowledge, energy derived from saturated fat, and cholesterol intake, however, were significantly higher in the athletes. The two groups did not differ in their hedonic ratings of flavor or in their overall degree of liking of the meat and dairy products, and the athletes actually liked the appearance and texture of the products significantly more than did the sedentary students. This study shows that the sensory appeal of fat-containing animal products is not affected in male swimmers by a high level of exercise.

Adult↗
PubMed1992

The cysteine residues in the carboxy terminal domain of tropoelastin form an intrachain disulfide bond that stabilizes a loop structure and positively charged pocket.

Analysis of purified bovine tropoelastin with Ellman's reagent and [14C]iodoacetamide demonstrated that the only two cysteine residues in the molecule form an intrachain disulfide bond. Molecular modeling suggests that the cysteine residues are juxtaposed as the result of a tight turn that produces an antiparallel beta structure. Protruding from the C-terminal end of the turn is the sequence Arg-Lys-Arg-Lys which forms the floor of a positively charged pocket created by the extension of the arginine and lysine side chains on opposite sides of the peptide chain perpendicular to the plane of the turn. The side chain of a conserved lysine residue in the disulfide-bonded loop forms the top of the pocket. This positively charged pocket may define a binding site for acidic microfibrillar proteins that mediate elastic fiber assembly.

Amino Acid Sequence↗
PubMed1992

Improved insulin stability through amino acid substitution.

Insulin analogs designed to decrease self-association and increase absorption rates from subcutaneous tissue were found to have altered stability. Replacement of HB10 with aspartic acid increased stability while substitutions at B28 and/or B29 were either comparable to insulin or had decreased stability. The principal chemical degradation product of accelerated storage conditions was a disulfide-linked multimer that was formed through a disulfide interchange reaction which resulted from beta-elimination of the disulfides. The maintenance of the native state of insulin was shown to be important in protecting the disulfides from reduction by dithiothreitol and implicitly from the disulfide interchange reaction that occurs during storage. To understand how these amino acid changes alter chemical stability, the intramolecular conformational equilibria of each analog was assessed by equilibrium denaturation. The Gibbs free energy of unfolding was compared with the chemical stability during storage for over 20 analogs. A significant positive correlation (R2 = 0.8 and P less than 0.0005) exists between the conformational stability and chemical stability of these analogs, indicating that the chemical stability of insulin's disulfides is under the thermodynamic control of the conformational equilibria.

Amino Acid Sequence↗
PubMed1992

An analysis of male and female Olympic swimmers in the 200-meter events.

Videotapes of the swimming events at the 1988 Seoul Olympics were analyzed to obtain the stroke rate (SR) and stroke length (SL) for each swimmer. In this paper, SR and SL data from the 200-m events were combined with anthropometric data (height and age of the swimmers) and the final time achieved by each swimmer. Statistical analyses were then carried out to determine the relationships among the different variables and their correlation with final times. Differences in performances between male and female swimmers were also investigated. Stroke lengths were found to have high correlations with the final times achieved by the competitors. A strong relationship was also found between height and final time. On an average, the men were found to have a lower stroke rate and to be faster than the women. The latter finding could be a result of the men's longer stroke length and greater height.

Adolescent↗
PubMed1991

The conformational stability and flexibility of insulin with an additional intramolecular cross-link.

The conformational stability and flexibility of insulin containing a cross-link between the alpha-amino group of the A-chain to the epsilon-amino group of Lys29 of the B-chain was examined. The cross-link varied in length from 2 to 12 carbon atoms. The conformational stability was determined by guanidine hydrochloride-induced equilibrium denaturation and flexibility was assessed by H2O/D2O amide exchange. The cross-link has substantial effects on both conformational stability and flexibility which depend on its length. In general, the addition of a cross-link enhances conformational stability and decreases flexibility. The optimal length for enhanced stability and decreased flexibility was the 6-carbon link. For the 6-carbon link the Gibbs free energy of unfolding was 8.0 kcal/mol compared to 4.5 kcal/mol for insulin, and the amide exchange rate decreased by at least 3-fold. A very short cross-link (i.e. the 2-carbon link) caused conformational strain that was detectable by a lack of stabilization in the Gibbs free energy of unfolding and enhancement in the amide exchange rate compared to insulin. The effect of the cross-link length on insulin hydrodynamic properties is discussed relative to previously obtained receptor binding results.

Animals↗
PubMed1990

Equilibrium denaturation of insulin and proinsulin.

The guanidine hydrochloride induced equilibrium denaturation of insulin and proinsulin was studied by using near- and far-ultraviolet (UV) circular dichroism (CD). The denaturation transition of insulin is reversible, cooperative, symmetrical, and the same whether detected by near- or far-UV CD. These results are consistent with a two-state denaturation process without any appreciable equilibrium intermediates. Analysis of the insulin denaturation data yields a Gibbs free energy of unfolding of 4.5 +/- 0.5 kcal/mol. Denaturation of proinsulin detected by near-UV CD appears to be the same as for insulin, but if detected by far-UV CD appears different. The far-UV CD results demonstrate a multiphasic transition with the connecting peptide portion unfolding at lower concentrations of denaturant. Similar studies with the isolated C-peptide show that its conformation and susceptibility to denaturation are independent of the rest of the proinsulin molecule. After the proinsulin denaturation results were adjusted for the connecting peptide contribution, a denaturation transition identical with that of insulin was obtained. These results show that for proinsulin, the connecting peptide segment is not a random coil; it is an autonomous folding unit, and the portion corresponding to insulin is identical with insulin in terms of conformational stability.

Circular Dichroism↗
PubMed1990

Equilibrium denaturation of human growth hormone and its cysteine-modified forms.

The equilibrium denaturation of human growth hormone (hGH) derived from heterologous gene expression in Escherichia coli was studied. Denaturation was measured by ultraviolet absorbance, intrinsic fluorescence, far ultraviolet circular dichroism, and size exclusion chromatography. The denaturation transitions obtained from each method of detection were coincident, indicating a two-state denaturation mechanism. The denaturation transitions were independent of the concentration of protein. The Gibbs free energy of unfolding is 14.5 +/- 1 kcal/mol. Human growth hormone contains two disulfide bridges between residues 53-165 (large loop) and 182-189 (small loop). The small loop was selectively reduced and cysteines alkylated with iodoacetic acid or iodoacetamide. The tetra-S-carbamidomethylated and tetra-S-carboxymethylated derivatives were also prepared. All S-alkylated hGH forms were indistinguishable from the native conformations in the absence of denaturant by far ultraviolet circular dichroism. The circular dichroism-detected equilibrium denaturation of each derivative was determined and the Gibbs free energy of unfolding of the tetra-S-modified forms was 5.3 +/- 0.5 kcal/mol and of the di-S-alkylated derivatives was 11.2 +/- 0.8 kcal/mol. These results for hGH are different than previously obtained results for bovine, ovine, and rat growth hormones. Stable equilibrium intermediates have been identified for these non-human species of growth hormone. The stable intermediates observed in the denaturation of reduced, alkylated hGH or nonhunam growth hormones are similar and characterized as compact, helical, lacking native-like tertiary structure, and having a tendency to aggregate. The apparent absence of intermediates in the folding of oxidized hGH is due to the relative instability of intermediates compared with their native structures. The hGH conformation is at least 5 kcal/mol more stable than the growth hormones from other species. Reduction and alkylation of the disulfide bridges of hGH diminish the stability differences between the native and intermediate states, such that the denaturation behavior is similar to the nonhuman growth hormones with well-populated intermediates. Most proteins do not demonstrate equilibrium folding intermediates presumably because intermediates are only marginally stable in conditions that disrupt the native state. The folding results with hGH and alkylated hGH substantiate this.

Alkylation↗
PubMed1987

Injuries caused by personal violence.

Injury is the leading cause of death for Americans from infancy to middle age. Thirty-seven per cent of injuries admitted to this faculty are the result of personal violence. A prospective pilot study sought to elucidate the circumstances of such injuries. Medical records of all admissions for gunshot wounds, stab wounds or assault during a 30-day period were reviewed (N = 105). A subset (N = 32) were interviewed and given psychometric tests. Distribution by mode of injury was assault, 46 per cent; stabbing, 42 per cent; shooting, 12 per cent. Single, black males aged 18-44 dominated the sample. Injuries tended to occur in or near bars (82 per cent), between 1800 and 0600 hours (79 per cent) and were accompanied by alcoholic intoxication (63 per cent). Un- or underemployment was prevalent (56 per cent). Thirty-eight per cent of incomes were below the official poverty level. Some victims were illiterate. Histories of previous violent encounters (mean number = 22) during the year before the injury and hospital treatment for previous injury were common (56 per cent). Those interviewed reported high frequencies of recent and developmental stresses. The yearly cost of the acute care of patients with injuries caused by violence and treated at this hospital is estimated to be $8,000,000. Of this 80 per cent is paid for with public funds. Personal violence is a serious but neglected part of public health.

Adolescent↗
PubMed1987

Interlibrary cooperation in the Kingdom of Saudi Arabia: the holder-of-record system.

The Saudi Arabian Ministry of Defense and Aviation, which contracts for management of military hospitals, responded to the libraries' needs for more complete and extensive journal holdings. Better journal coverage was achieved through improved communication and cooperation among neighbor libraries, and through systematic implementation of a holder-of-record system. Interlibrary loan activity was more evenly distributed, and 70% of requisitions which previously had to be handled by foreign libraries can now be filled in Saudi Arabia.

Hospitals, Military↗
PubMed1979

Effects of sodium loading and depletion in normotensive first-degree relatives of essential hypertensives.

To examine potential mechanisms responsible for the greater prevalence of hypertension among relatives of hypertensives than among relatives of normotensives, we subjected 43 normotensive first-degree relatives of known essential hypertensives and 43 age-, race-, and sex-matched normal subjects with no family history of hypertension to sodium loading and depletion. The data show that the relatives had higher blood pressures than did controls. They also had higher PRA values before and after a 2 L intravenous saline infusion over 4 hr. In addition, the relatives excreted less (p less than 0.05) sodium on the day of the infusion than did the controls. PA values and UNe excretion in the two groups did not differ. In the relatives, age correlated with systolic and diastolic blood pressure. Age correlated inversely with the 24 h urine sodium excretion on the sodium loading day. These correlations were not observed in controls. Normotensive first-degree relatives of hypertensives differ from relatives of nonhypertensives in that they have higher PRA values and a blunted natriuretic response to a saline load. These features may predispose them to the development of hypertension.

Adult↗
PubMed1978

Evaluation of an automated immunoassay procedure for apo-LDL for phenotyping type II hyperlipoproteinemia.

Apo-low density lipoproteins were determined by an automated immunoassay procedure on serum samples from 88 normolipidemic individuals and 84 hyperlipoproteinemic subjects, to establish whether this method was useful in the routine detection of type II hyperlipoproteinemia. The results obtained were compared with the cholesterol levels of the same specimens. In subjects with type II hyperlipoproteinemia, the apo low density lipoprotein levels, as well as the ratio of low density lipoprotein cholesterol/apo-low density lipoprotein were higher, as expected, than in normals or in subjects with other types of hyperlipoproteinemia. However, there was considerable overlap in individual values of both these parameters, between patients with type II hyperlipoproteinemia and normals or subjects with other types of hyperlipoproteinemia, suggesting that apo low density lipoprotein levels alone were not sufficiently discriminatory for the laboratory determination of type II hyperlipoproteinemia.

Adult↗
PubMed1975

Liver glutathione and glutathione reductase response of endotoxin-treated mice.

The decrease in the level of liver glutathione (GSH) in endotoxin-treated mice was in part due to formation of glutathione disulfide (GSSG). An electron-generating system (EGS) had no effect when incubated with soluble liver extracts from normal controls but resulted in recovery of GSH amounting to 25% in endotoxin-treated animals. Incubation in the absence of the EGS caused a decline of 16% in the GSH in extracts from normal animals compared with a 50% decrease in endotoxin-treated animals. Exclusion of nicotinamide adenine dinucleotide phosphate (NADP) from the EGS resulted in a slight decline in the GSH of the extract from the normal controls but 25% for the endotoxin-treated animals. Reduction of exogenous GSSG by the liver extracts required that exogenous NADP be added to ghe incubation mixtures.

Animals↗