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Biomedical subjects

R A Smith

Publications and source records attributed to R A Smith.

At least 91 records · Page 5Linked to original sources
PubMed2000

HIV prevention in the era of HAART: implications for providers.

This article reviews the medical literature regarding the association between reduced HIV viremia caused by use of HAART and the risk of HIV transmission, finding that there is a correlation but that it is not absolute. It then examines the behavioral literature, which indicates that there is evidence, though far from conclusive, that, for some, increased sexual risk taking may be related to attitudes and beliefs about combination therapy. The article also considers the message about HIV prevention being presented by public health programs and ways in which health care providers can outline changing circumstances and enable the patient to make informed choices in "gray areas."

Anti-HIV Agents↗
PubMed2000

Intoxication of sheep exposed to ozark milkweed (Asclepias viridis Walter).

Some 20 sheep died 1 at a time on a farm in Fleming County, KY, in late July of 1999 after consumption of Asclepias viridis Walter. Major histological lesions were mild multifocal nonsuppurative myocarditis. Gross pathology revealed wet and heavy lungs. Many affected animals had a hunched appearance, and marked posterior paresis was also observed.

Animals↗
PubMed2000

Rapid determination of ethylene glycol and glycolic acid in biological fluids.

Ethylene glycol poisoning of companion animals is a common occurrence and is sometimes involved in human intoxication. Ethylene glycol is of limited toxicity, but the metabolites including glycolic acid are responsible for poisoning. Conventional treatment has employed substances to prevent alcohol dehydrogenase from metabolizing the ethylene glycol, but to be effective, therapy must begin within hours of ethylene glycol consumption. We describe a rapid (10 min) analysis of biological fluids for ethylene glycol and glycolic acid using isocratic HPLC, a refractive index detector, and a Waters fast fruit juice analytical column.

Animals↗
PubMed2000

Evidence for new endothelial cell binding sites on fibrinogen.

In vitro assays were used to characterize adhesion of human aortic, microvascular and umbilical vein endothelial cells to various forms of immobilized fibrinogen. All three types of endothelial cells adhered to fibrinogen in a manner that was independent of the Aalpha-chain 572-574 RGD cell binding site. In fact, all three adhered to a fragment of the molecule which is composed of only one D domain (D1) of fibrinogen. A time course study revealed that extensive adhesion of endothelial cells on the ligand coated surface occurred between one and two hours incubation. The anti-fibrinogen gammaA-chain monoclonal antibody 4A5 as well as 4A5 Fabs, blocked adhesion of endothelial cells to fibrinogen, not vitronectin. The inhibitory effects of 4A5 seemed to be indirect because the endothelial cells adhered to the recombinant fibrinogen gamma407 (which lacks the gamma-chain AGDV sequence of the carboxyl terminal 4A5 binding site) as well as they did to normal recombinant fibrinogen. A recombinant fibrinogen lacking the gamma-chain AGDV sequence, containing RGE in place of RGD at the gamma-chain 572-574 and 95-97 positions, also supported endothelial cell adhesion. The anti-alphavbeta3 antibody, LM609, blocked adhesion of endothelial cells to fibrinogen. The peptide GRGDSP inhibited endothelial cell adhesion on fibrinogen and vitronectin. These results demonstrate that alphavbeta3 mediated adhesion (attachment and spreading) of HUVECs to fibrinogen may use a site in the D domain of fibrinogen and is not dependent on the Aalpha-chain RGD (95-97 and 572-574) sequences, as has been shown in shorter term (where cells were rounded) experiments, or the alphaA-chain 408-411 cell binding sites. Thus, the data reveal the existence of another unidentified site(s) on fibrinogen which can support the irreversible adhesion (attachment and spreading) of endothelial cells.

Binding Sites↗
PubMed2000

Soft tissue surgery in the oral and maxillofacial region.

The practice of dentistry is most often perceived as the treatment of the hard tissues of the oral region, specifically the teeth and jaws. However, there are many disorders and conditions involving surgical treatment of the soft tissues that extend to the adjacent and associated structures of the oral and maxillofacial surgery region.

Adolescent↗
PubMed1999

Structure-activity relationships within the N-terminal short consensus repeats (SCR) of human CR1 (C3b/C4b receptor, CD35): SCR 3 plays a critical role in inhibition of the classical and alternative pathways of complement activation.

Genes coding for between one and four short consensus repeats (SCR) of the N-terminal region of human complement receptor 1 (CR1) were synthesized from oligonucleotides and those encoding SCR(1-2), SCR(1-3), SCR(1-4), SCR3 and SCR(3-4) were expressed as inclusion bodies in Escherichia coli. Following solubilization in urea, the proteins were partially purified and refolded and the activity of each protein was assessed in both classical and alternative pathway complement assays. All fragments showed a varying degree of activity with the general order being SCR(1-3) = SCR(1-4) > SCR(1-2). Addition of SCR3 to SCR(1-2) significantly improved potency, whereas the addition of SCR4 conferred no additional benefit. This observation, coupled with the ability of the single-domain SCR3 to inhibit classical pathway mediated lysis with an IH50% (inhibition of hemolysis by 50%) of 4.8 microM, demonstrates that SCR3 provides key binding interactions with activated complement components. SCR(1-3) was able to inhibit both classical and alternative pathways of complement activation, showing that the N-terminal SCR of CR1 retain the ability to interact with C3b. Assays for CR1-like cofactor activity for factor I using C4b-like C4 or C3b-like C3 as substrates showed that SCR(1-3) possessed such cofactor activity and that C4b-like C4 was a better substrate. When compared to full-length (30 SCR) soluble CR1 (sCR1), SCR(1-3) was significantly less potent in accord with a model involving multi-valent binding of C3b/C4b to CR1.

Animals↗
PubMed1999

Role of CD8+ and WC-1+ gamma/delta T cells in resistance to Mycobacterium bovis infection in the SCID-bo mouse.

The role of various effector T cell populations in the bovine immune response to Mycobacterium bovis infection is poorly understood. This is largely due to the difficulties associated with performing in vivo challenge studies in the natural host species. In this report, we utilized a fetal bovine-severe combined immunodeficient (SCID-bo) xenochimeric mouse model to study the protective role of two putative effector cell types, CD8+ T cells and a subpopulation of gamma/delta T cells that express WC-1, a member of the cysteine-rich scavenger receptor superfamily (CRSR). We demonstrate that CD8+ T cells play a key role in protection and contribute substantially to bovine IFN-gamma mRNA levels at 30 days post-infection. The role of WC-1 bearing cells to protection was less definitive but our results suggest that this population may play a pivotal role early in infection. Granuloma architecture was altered in anti-WC-1 (ILA29) but not anti-CD8 (ILA51) -treated animals, suggesting that this population may be involved in recruitment of various cell types to sites of infection.

Animals↗
PubMed1999

Early diagnosis of septicaemia in preterm infants from examination of peripheral blood films.

Clinically significant staphylococcal septicaemia associated with the presence of bacteria in neutrophils in a routine peripheral blood film is described in four preterm infants. In all cases this allowed the diagnosis of infection prior to the result of microbiological cultures. It is likely that this finding is relatively common in this subgroup of patients resulting from a combination of severe infection associated with indwelling catheters and defective neutrophil bacteriacidal mechanisms. The findings in these cases suggest that careful blood film inspection in selected premature neonates may allow the early identification of sepsis.

Female↗
PubMed1999

Selective targeting of an antioxidant to mitochondria.

Mitochondrial oxidative damage contributes significantly to a range of human disorders, including neurodegenerative diseases, ischaemia-reperfusion injury and ageing-associated dysfunction. To prevent this damage we have delivered a molecule containing the active antioxidant moiety of vitamin E to mitochondria. This was carried out by covalently coupling the antioxidant moiety to a lipophilic triphenylphosphonium cation. This mitochondrially targeted antioxidant, 2-[2-(triphenylphosphonio)ethyl]-3,4-dihydro-2, 5,7,8-tetramethyl-2H-1-benzopyran-6-ol bromide (TPPB), accumulated several-hundred fold within the mitochondrial matrix, driven by the organelle's large membrane potential. When cells were incubated with micromolar concentrations of TPPB, they accumulated millimolar concentrations within their mitochondria. The amount of TPPB taken up by mitochondria was approximately 80-fold greater than endogenous levels of vitamin E. Consequently the targeted derivative of vitamin E protected mitochondrial function from oxidative damage far more effectively than vitamin E itself. The mitochondrially targeted antioxidant TPPB has potential as an antioxidant therapy for disorders involving mitochondrial oxidative damage. It also suggests a new family of mitochondrially targeted antioxidants, redox-active and pharmacologically active molecules designed to prevent damage or manipulate mitochondrial function.

Animals↗
PubMed1999

Attitudes and exercise adherence: test of the Theories of Reasoned Action and Planned Behaviour.

Three studies of exercise adherence and attitudes are reported that tested the Theory of Reasoned Action and the Theory of Planned Behaviour. In a prospective study of adherence to a private fitness club, structural equation modelling path analysis showed that attitudinal and social normative components of the Theory of Reasoned Action accounted for 13.1% of the variance in adherence 4 months later, although only social norm significantly predicted intention. In a second study, the Theory of Planned Behaviour was used to predict both physical activity and sedentary behaviour. Path analyses showed that attitude and perceived control, but not social norm, predicted total physical activity. Physical activity was predicted from intentions and control over sedentary behaviour. Finally, an intervention study with previously sedentary adults showed that intentions to be active measured at the start and end of a 10-week intervention were associated with the planned behaviour variables. A multivariate analysis of variance revealed no significant multivariate effects for time on the planned behaviour variables measured before and after intervention. Qualitative data provided evidence that participants had a positive experience on the intervention programme and supported the role of social normative factors in the adherence process.

Adult↗
PubMed1999

An ultrastructural study of age-related changes in mouse olfactory epithelium.

Transmission and scanning electron microscopic examinations were undertaken to detail changes in the olfactory epithelium (OE) resulting from the ageing process. Samples were prepared from 3% glutaraldehyde/1% formaldehyde perfused mice aged 6 months and 29-30 months. Compared to OE from young adults, a number of striking changes were apparent in tissue from older animals. The most obvious of these were extensive local accumulations of large inclusion bodies, totally disrupting the normal morphology of such affected areas of olfactory epithelium. Even in areas where these deposits were absent, other significant signs of ageing were noted in the seemingly unaffected OE of all older mice studied. Quantitative analysis of semi-thin resin sections revealed that the OE of aged mice was significantly reduced in thickness, and with significantly fewer olfactory sensory neurons, irrespective of whether or not inclusions were present. In addition, pale cells, which have been suggested to be a form of degenerating cells, were more abundant in aged OE. The straight, sharp boundary between respiratory and olfactory epithelia which is seen in young adults became irregular and disrupted with age due to an intermingling of the respiratory and olfactory cells. Such structural alterations may parallel olfactory dysfunction reputed to occur in older mammals.

Aging↗
PubMed1999

Ultrastructural studies demonstrate that epithelial polarity is established in cultured mouse pre-Sertoli cells by extracellular matrix components.

The effect of three different substrates, laminin, fibronectin and reconstituted basement membrane, on isolated mouse pre-Sertoli cells maintained in vitro has been investigated. Cultures were monitored on a daily basis by phase contrast microscopy, and processed for light and electron microscopy at the end of the culture period. Extra-cellular matrix components have been found to influence Sertoli cell differentiation: both fibronectin and laminin promoted cell adhesion and differentiation, though laminin cultures showed poor viability. Pre-Sertoli cells cultured on reconstituted basement membrane showed the highest degree of differentiation, developing a polarized epithelial phenotype and forming cord-like aggregates; such cultures provide a model system for the investigation of factors involved with gonadal differentiation.

Animals↗
PubMed1999

Cardiopulmonary resuscitation: effect of CPAP on gas exchange during chest compressions.

BACKGROUND: Conventional cardiopulmonary resuscitation (CPR) includes 80-100/min precordial compressions with intermittent positive pressure ventilation (IPPV) after every fifth compression. To prevent gastric insufflation, chest compressions are held during IPPV if the patient is not intubated. Elimination of IPPV would simplify CPR and might offer physiologic advantages, but compression-induced ventilation without IPPV has been shown to result in hypercapnia. The authors hypothesized that application of continuous positive airway pressure (CPAP) might increase CO2 elimination during chest compressions. METHODS: After appropriate instrumentation and measurement of baseline data, ventricular fibrillation was induced in 18 pigs. Conventional CPR was performed as a control (CPR(C)) for 5 min. Pauses were then discontinued, and animals were assigned randomly to receive alternate trials of uninterrupted chest compressions at a rate of 80/min without IPPV, either at atmospheric airway pressure (CPR(ATM)) or with CPAP (CPR(CPAP)). CPAP was adjusted to produce a minute ventilation of 75% of the animal's baseline ventilation. Data were summarized as mean +/- SD and compared with Student t test for paired observations. RESULTS: During CPR without IPPV, CPAP decreased PaCO2 (55+/-28 vs. 100+/-16 mmHg) and increased SaO2 (0.86+/-0.19 vs. 0.50+/-0.18%; P < 0.001). CPAP also increased arteriovenous oxygen content difference (10.7+/-3.1 vs. 5.5+/-2.3 ml/dl blood) and CO2 elimination (120+/-20 vs. 12+/-20 ml/min; P < 0.01). Differences between CPR(CPAP) and CPR(ATM) in aortic blood pressure, cardiac output, and stroke volume were not significant. CONCLUSIONS: Mechanical ventilation may not be necessary during CPR as long as CPAP is applied. Discontinuation of IPPV will simplify CPR and may offer physiologic advantage.

Animals↗