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Biomedical subjects

G C Smith

Publications and source records attributed to G C Smith.

At least 199 records · Page 11Linked to original sources

Action of angiotensin converting enzyme inhibitors in rat brain: interaction with isoproterenol assessed by Fos immunocytochemistry.

Low and high doses of angiotensin converting enzyme (ACE) inhibitors have been shown either to enhance or suppress, respectively, the water intake of rats induced by acute administration of isoproterenol. In order to assess the role and sites of action of angiotensin II (Ang II) in this dual action of ACE inhibitors, rats were administered either low or high doses of enalapril or captopril, followed by isoproterenol, and were sacrificed 1 h later for determination of Fos-like immunoreactivity (FLI) in brain. Isoproterenol induced strong FLI in the magnocellular paraventricular (PVN) and supraoptic (SON) nuclei, and moderate staining along the structures of the rostral wall of the lamina terminalis (LT). Low doses of ACE inhibitors either had no effect or slightly increased FLI along the LT following isoproterenol. Enalapril reduced FLI in some other regions, including the parvocellular PVN. In contrast, high doses of ACE inhibitors abolished FLI along the LT, and reduced FLI in the PVN and SON. Captopril, but not enalapril, induced some FLI in the LT, SON and PVN. The data are discussed in terms of access of ACE inhibitors to the brain, and interactions with structures involved in Ang-related water intake.

Angiotensin-Converting Enzyme Inhibitors↗

Assessment of retinol-binding protein excretion in normal children.

Retinol-binding protein (RBP) is a low molecular weight protein freely filtered at the glomerulus. The fractional tubular reabsorption of RBP is 99.97% and increased excretion is therefore a sensitive marker of tubular dysfunction. We obtained early-morning urine specimens from 151 well children, from newborn to 16 years of age. RBP was measured using an enzyme-linked immunosorbent assay, albumin by a radioimmunoassay and creatinine by a modified Jaffé reaction. Protein excretion was assessed by calculating the protein:creatinine ratio for early-morning urine samples. We found a fall in both RBP and albumin excretion with increasing age, particularly in the 1st year of life, with a much wider variation in values from the infants studied. The mean excretion of RBP for children aged 0-6 months [51.4 (0.6-4,719) micrograms/mmol] was significantly higher (P < 0.001) than the mean for children aged 6 months to 16-years [15.0 (3.8-60) micrograms/mmol]. It has been shown that measurement of tubular proteinuria using the RBP: creatinine ratio is useful in the assessment of children with renal disease and we propose a value two standard deviations above the geometric mean for the age of the patient as an upper limit of normal.

Adolescent↗

Lunar base CELSS design and analysis.

This paper describes the conceptual development of a hybrid biological-physical/chemical (P/C) life support system model for a lunar outpost. It presents steps that lead to loop closure and determines mass flow characteristics for an inedible biomass enzyme reactor and an activated sludge bioreactor. Computer modeling techniques were used to determine that the cellulose reactor has the design capabilities to provide significant increases in the plant harvest index. Activated sludge was found to fit design demands for a small, continuous-flow, steady-state system. Systems analysis and component sizing for these two bioreactors and information regarding supporting bioregenerative and physical/chemical components are presented.

Biomass↗

Localization of changes in immediate early genes in brain in relation to hydromineral balance: intravenous angiotensin II.

Immediate early genes, detected by Fos- and Jun-like immunoreactivity (FLI, JLI), were induced in discrete regions of the rat brain by intravenous infusion of angiotensin II (Ang II) at dipsogenic doses. The regions included subfornical organ (SFO), organum vasculosum laminae terminalis (OVLT), median preoptic nucleus (MnPO), supraoptic nucleus (SON), and the magnocellular part of the paraventricular hypothalamus (PVH). These responses were sustained for up to 6 h of infusion. In SFO, FLI was induced preferentially in the posterior part, while JLI occurred in more central regions. Cerebroventricular (ICV) injection of the Ang II type 1 receptor (AT-1) antagonist, losartan potassium, completely prevented the FLI induced by Ang II in these brain regions. ICV injection of the Ang II type 2 receptor (AT-2) antagonist, PD 123319, did not reduce Ang II-induced FLI in SFO, OVLT and MnPO, but markedly attenuated the activation in SON and PVH. To determine whether SFO is the primary site for transduction of the circulating Ang II signal, electrolytic lesions were made in or rostral to the SFO. Rats with complete lesions showed a complete absence of Ang-induced FLI in SON and PVH. The data are discussed in terms of functional mapping of the brain regions activated by circulating Ang II and neural circuitry for water intake, including the possible role of AT-2 receptors in PVH and SON.

Angiotensin II↗

Interactions between indomethacin, noradrenaline and vasodilators in the fetal rabbit ductus arteriosus.

1. Interactions between indomethacin, noradrenaline and vasodilators were studied in rings of ductus arteriosus isolated from fetal rabbits. The effect of incubation with prostaglandin E2 (PGE2) on the noradrenaline concentration-contraction response curve was studied in the presence and absence of indomethacin. Also, the ductus was pre-contracted with 10 microM noradrenaline and concentration-relaxation response curves (CRRC) to PGE2, cicaprost, cromakalim and forskolin were obtained in the presence and absence of indomethacin. 2. In the absence of indomethacin, PGE2 (from 1 nM to 100 nM) decreased the pEC50 to noradrenaline to a maximum of 0.4 to 0.5 log units (i.e. an approximately three fold increase in EC50 [M]). In the presence of 1 microM indomethacin, PGE2 (0.1 nM to 100 nM) decreased the pEC50 to noradrenaline by 2.39 log units (i.e. a 245 fold increase in EC50). By comparing the control pEC50 to noradrenaline with the relationship between the pEC50 to noradrenaline and [PGE2] in 1 microM indomethacin, the effect of endogenous PGE2 synthesized in the vessel wall was estimated as being equivalent to a bath concentration of approximately 1 nM exogenous PGE2. 3. When the vessel was pre-contracted with 10 microM noradrenaline, indomethacin had no effect on the CRRC to PGE2 but did alter the CRRC to other vasodilators. The sensitivity of the vessel to cicaprost, cromakalim and forskolin was decreased in 1 microM indomethacin compared with control. Forskolin caused complete relaxation in the presence and absence of indomethacin. Indomethacin decreased the maximum response to cromakalim but increased the maximum response to cicaprost. PGE2, 0.3 nm, partially reversed the effect of indomethacin on the sensitivity of the vessel to forskolin.4. We conclude that under varying experimental conditions, indomethacin increased the sensitivity of the ductus to the effects of PGE2 but decreased its sensitivity to other vasodilators. Both effects can be explained by elimination of endogenous PGE2. However, indomethacin increased the maximum response to cicaprost, which cannot be explained by elimination of endogenous PGE2 but may be due to elimination of endogenous prostacyclin.

Animals↗

Comparison of fos-like immunoreactivity induced in rat brain by central injection of angiotensin II and carbachol.

Rats were given intracerebroventricular injections of either angiotensin II (ANG II) or the cholinomimetic carbachol. Some rats received cotreatment with ANG II antagonists selective for either angiotensin receptor AT1 (losartan) or AT2 (PD-123319, CGP-42112A). One hour later, the rats were killed and the brains processed for immunocytochemical detection of Fos-like immunoreactivity (FLI). ANG II treatment induced strong FLI in the anterior subfornical organ (SFO), median preoptic nucleus (MnPO), organum vasculosum laminae terminalis (OVLT), and supraoptic and paraventricular hypothalamic nuclei (SON, PVH). The AT1 antagonist abolished FLI in all regions normally stimulated by ANG II. The AT2 antagonist PD-123319 reduced FLI in SON and PVH, but CGP-42112A was less effective. Carbachol induced strong FLI in SON, PVH, and MnPO and only moderate FLI in SFO and OVLT. The AT1 antagonist prevented carbachol-induced FLI in the MnPO only. The distributions of FLI are compared between these central dipsogens and with that previously reported after peripheral infusion of ANG II, and their implications for mapping central thirst pathways are discussed.

Angiotensin II↗

Incidence of injection-site blemishes in beef top sirloin butts.

The occurrence of damaged muscle tissue resulting from intramuscular injections of animal-health products represents a "quality control" problem and an economic loss to the beef industry. Five individual and sequential national audits of injection-site blemishes in beef top sirloin butts have been conducted at the steak-cutter level. During the most recent audit (March 1993), the incidence of injection-site blemishes in top sirloin butts was determined to be 10.87 +/- 2.99%, with an average weight per blemish of 123.39 +/- 5.48 g. A 5-point classification system used to partition the blemishes into chronological stages of the healing process suggested that the majority of the blemishes originated at the cow-calf or stocker levels, or early in the finishing period. Evaluation of blemish data by geographic location of plant-of-origin suggests that the problem occurs throughout the beef production sector.

Animals↗

Staffing and funding of consultation-liaison psychiatry services in Australia and New Zealand.

The aim of the study was to establish the current and desired levels of staffing and funding of the 52 consultation-liaison (C-L) psychiatry training units in Australian and New Zealand general hospitals. Administration of a questionnaire and follow-up verification provided data on referral rates, existing and preferred staffing levels, and staff workloads. The referral rates and staffing levels in most cases fall below those quoted for Europe and the USA, and those considered optimal by the respondents. This, together with the large variation in referral rates and workload, has implications for the type of clinical activity conducted and quality of the training experience in different units.

Australia↗

Method and effect of adjustment for heterogeneous variance of Holstein conformation traits.

Type classification records of Canadian Holsteins were investigated for evidence of heterogeneous variance across herds. Data consisted of records for 1,139,104 cows from 20,226 herds with classifications on 26 conformation traits collected from 1982 through 1992 and 338,046 cows from 9600 herds with classifications on 2 additional traits from 1990 through 1992. Phenotypic standard deviations of herd-round-classifier were fitted to a mixed model that included round, classifier, and region as fixed effects, herd size as a covariant, and herd as a random effect. Estimates of the variance components, solutions of fixed effects, and BLUP estimates for herd were obtained by maximum likelihood procedures. Repeatability of within-herd standard deviation across rounds ranged from 1.4 to 10.3% for the 28 traits. Type classification data were subsequently standardized for phenotypic standard deviations of herd-round-classifier that were derived from estimates of the fixed effects and the BLUP estimate of the herd effect. Genetic evaluations for cows and bulls were produced from adjusted and unadjusted data. Correlations between 3754 sire and 1,142,782 cow estimated transmitting abilities obtained from unadjusted and adjusted data were essentially unity. Although some evidence of heterogeneous variance existed across herds for 28 conformation traits, standardization of the classification records had only a minor effect on genetic evaluations.

Animals↗

Identification of damaged adult female specimens of Aedes albopictus and Aedes aegypti in the New World.

Two introduced species of Aedes (Stegomyia), Aedes albopictus and Aedes aegypti, occur in the New World. Three characters, easily and simultaneously observed from an anteroventral view, allow for rapid and reliable specific identification of most specimens that lack the characteristic scutal scale patterns. These 3 characters are the presence or absence of pale scales on the clypeus; the presence or absence of a narrow, median line of pale scales on the anterior face of the midfemora; and the pattern of pale and dark scales on abdominal sterna III-V.

Aedes↗

Vector competence of Aedes albopictus from Pine Bluff, Arkansas, for a St. Louis encephalitis virus strain isolated during the 1991 epidemic.

The vector competence of Aedes albopictus from Pine Bluff, AR, was assessed for a St. Louis encephalitis (SLE) virus strain isolated during the 1991 epidemic. Aedes albopictus were fed on hamsters with viremia levels of 10(4.6)-10(4.9) Vero cell plaque-forming units (PFU)/ml. At 7 and 15 days postbloodfeeding, transmission trials were conducted using individual suckling mice. Three of 313 Ae. albopictus were determined to be infected with SLE virus with titers of 10(6.3)-10(7.0) PFU/mosquito. At 15 days postbloodfeeding, one of 209 Ae. albopictus that refed transmitted virus resulting in a 15-day population transmission rate of 0.5%. The infection threshold (i.e., the amount of virus required to infect from 1 to 5% of mosquitoes) was determined to be approximately 10(2.3) PFU/mosquito. Virus inoculated intracoelomically into Ae. albopictus replicated and reached mean titers above 10(6.0) PFU/mosquito on day 6. The combination of low susceptibility to infection and a mammalophilic bloodfeeding pattern suggests that Ae. albopictus is unlikely to play a significant role in SLE transmission.

Aedes↗

Characterization of dilator prostanoid receptors in the fetal rabbit ductus arteriosus.

The purpose of this study was to determine which receptors mediate the dilator effects of prostaglandins (PGs) on the ductus arteriosus of the fetal rabbit. Isolated rings of the vessel from fetal New Zealand White rabbits were precontracted with indomethacin (1 microM) and potassium (25 mM) in 100 to 110 mmHg oxygen, and the dilator effects of a range of synthetic prostanoids were quantified by cumulative relaxant concentration-effect curves. The potencies of agonists were quantified with reference to PGE2 by the equieffective molar ratio (EMR): EC50 test agonist/EC50 PGE2. The effects on these responses of available antagonists were also studied. None of a range of synthetic prostanoids with selective agonism of EP1, EP2 or EP3 receptors was as potent as PGE2. The rank order of potency was as follows: PGE2 (EC50 = 0.36 nM [95% confidence intervals [CI] = 0.32-0.41, n = 44], EMR = unity) >> misoprostol (EMR 145, 95% CI 73-217) > [1R-[1 alpha (Z),2 beta (R*),3 alpha]]-4-(benzoyl-amino)phenyl 7-[3 hydroxy-2(2-hydroxy-3-phenoxypropoxy)-5- oxocyclopentyl]-4-heptenoate, single enantiomer (GR 63799K) (EMR 685, 95% CI 427-944) >> ((+/-)-trans-2-[4[(1-hydroxphenyl) phenyl]-5-oxocylopentaneheptanoic acid (AH13205) (EMR > 100,000) > or = sulprostone (EMR > 10,000) > or = 0. The EP1 antagonists, 6-isopropoxy-9-oxoxanthine-2-carboxylic acid (AH6809) (10 microM) and 8-clorodi-benz[b,f][1,4]oxazepine-10 (11H)-carboxylic acid, 2-acetylhydrazide (SC19220) (30 microM), had no significant effect on the sensitivity of the ductus to PGE2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Involvement of phenyl radicals in iodonium inhibition of flavoenzymes.

Iodonium inhibition of the flavoenzymes neutrophil NADPH oxidase and cytochrome P450 reductase has been suggested to require reductive metabolism of the inhibitor to a phenyl radical. Inhibition would ultimately result from covalent attachment of phenyl radicals to either the flavin cofactor or adjacent amino acid side chains important in catalysis. In this paper we provide evidence, using EPR techniques, that phenyl radicals are formed during reaction of iodonium diphenyl with reduced free flavin (FMN) and protein-bound (cytochrome P450 reductase or xanthine oxidase) flavin. Kinetic analysis indicated iodonium diphenyl to be an uncompetitive inhibitor of xanthine oxidase, suggesting the need for reduced enzyme for inhibition. A study of the catalytic and structural properties of different flavoenzymes suggested that only enzymes containing flavins that function in one-electron transfer are targets for iodonium inhibition.

Animals↗

Autoantibodies to hepatic microsomal carboxylesterase in halothane hepatitis.

Halothane hepatitis can be life-threatening, and this severe adverse reaction may arise via an immune process. We have detected autoantibodies to purified human liver microsomal carboxylesterase in sera of 17 out of 20 patients with halothane hepatitis (85%) but not in 9 halothane-exposed controls and in only 2 (at low levels) of 33 patients with liver disease due to other causes. Immunohistochemical studies localised the carboxylesterase predominantly to the centrilobular region of liver sections, which is consistent with the area affected by halothane hepatitis. Human hepatic microsomal carboxylesterase is a target antigen in halothane hepatitis, and an immune response to this protein may be involved in the liver damage observed.

Adult↗

Establishing a consultation-liaison psychiatry clinical database in an Australian general hospital.

This paper describes the institution of a clinical database in the consultation-liaison psychiatry service of an Australian general hospital psychiatry unit. One of the problems faced was that many researchers and clinicians in Australia use the ICD-9 rather than the DSM-III-R classification system. Nevertheless, it was possible to use the DSM-III-R-based MICRO-CARES clinical database management system in this project. The data obtained during the first 12 months of its use are presented. Despite differences in the patient demographic characteristics, the data obtained are within the ranges described for North American and European sites. The local benefits of such a clinical database are described, and it is argued that such a database is also necessary for interhospital and international collaborative studies and comparisons.

Adult↗

Consultation-liaison psychiatry in Australia.

Consultation-liaison (C-L) psychiatry as a service entity has developed slowly and to a variable extent in Australia despite the presence of factors conducive to its development. These include a compulsory national health insurance system and a favorable disposition to the biopsychosocial model and to psychoanalytic ideas. C-L psychiatry, however, does enjoy a high profile in many undergraduate medical and postgraduate psychiatry teaching programs. Research on C-L psychiatry is emerging, complementing a strong history of research in psychosomatic medicine. An Australian and New Zealand C-L psychiatry interest group is being formed. Collaboration with the MICRO-CARES Consortium and the European Consultation-Liaison Workgroup is proving to be a great stimulus.

Australia↗