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Biomedical subjects

R J Clark

Publications and source records attributed to R J Clark.

At least 19 recordsLinked to original sources
PubMed2003

Mucosal co-administration of cholera toxin and influenza virus hemagglutinin-DNA in ponies generates a local IgA response.

We have previously demonstrated that equine influenza virus hemagglutinin (HA) DNA vaccination protects ponies from challenge infection, and induces protective IgGa and IgGb responses. However, this approach does not induce a nasal IgA response. The objective of this study was to examine the value of cholera toxin (CT) administration as an adjuvant for intranasal HA DNA vaccination, and to measure protection 3 months after DNA vaccination. After an immunogenic dose of CT was determined, ponies were immunized on two occasions by intranasal administration of HA DNA and cholera toxin, or HA DNA alone. Ponies in both groups received two additional HA DNA particle mediated vaccinations at skin and mucosal sites. Antibody responses, and protection from challenge infection 3 months after the last vaccination were studied and compared to an influenza virus naive control group. Ponies in both vaccination groups produced virus-specific IgG antibodies in serum following vaccination and showed clinical protection from challenge infection 3 months after the last vaccination. Co-administration of CT plus HA DNA vaccination induced a nasal IgA response. In addition, analysis of antibody titers in nasal secretions indicated local production of nasal IgGb, which was amplified by CT administration.

Administration, Intranasal↗
PubMed2001

Voluntary running improves glucose tolerance and insulin resistance in female spontaneously hypertensive rats.

We evaluated the effects of voluntary exercise training on glucose metabolism and measures of insulin sensitivity in female spontaneously hypertensive rats (SHR). Age-matched Wistar-Kyoto rats (WKY) were used as normotensive controls. Exercising SHR were housed in running wheels for 8 weeks (SHRx8) or 16 weeks (SHRx16). At 22 weeks of age, we measured systolic blood pressure, performed oral glucose tolerance tests, and determined hexokinase activity and glucose transporter (GLUT) 4 content in skeletal muscle to assess intracellular glucose metabolism. Blood pressure was lower in WKY (139+/-12 mm Hg) than untrained SHR (216+/-13 mm Hg). Exercise training caused a reduction in blood pressure (-18 mm Hg) for SHRx8. After a brief (5-h) fast, serum glucose was lower in SHR that exercised compared with sedentary SHR, whereas insulin concentrations were identical between all SHR and WKY. Corresponding free fatty acids (FFA) were twofold higher in SHR than in WKY. In response to glucose, SHR demonstrated higher glucose and FFA responses, with exercise decreasing the glucose values in a dose-dependent manner. Although the insulin response was comparable in all groups, the glucose-to-insulin ratio was higher in SHR, indicating a relative insulin resistance for both glucose disposal and suppression of free fatty acids. Hexokinase activity and GLUT4 content were elevated 1.4- and 2.8-fold, respectively, in plantaris muscle of SHRx16, suggesting an improvement in the capacity for glucose transport and phosphorylation with exercise. These results provide evidence that voluntary running in female SHR lowers blood pressure and selectively increases glucose uptake and insulin action, but not suppression of FFA.

Animals↗
PubMed2001

Library of FT-Raman spectra of pigments, minerals, pigment media and varnishes, and supplement to existing library of Raman spectra of pigments with visible excitation.

Sixty pigments, minerals and media have been analysed by Fourier-transform Raman (FT-Raman) microscopy in order to assemble a database of reference FT-Raman spectra for scientists working at the Arts-Science interface. An earlier library of Raman spectra compiled using visible excitation has been extended by the addition of 22 further reference spectra obtained with 780.0, 647.1, 632.8 and/or 514.5 nm excitation. The relative merits of 1064 nm and visible excitation are discussed.

Databases, Factual↗
PubMed2001

Antifungal alkyl amino alcohols from the tropical marine sponge Haliclona n. sp.

Three new amino alcohols presumably deriving from L-alanine were isolated from the tropical marine sponge Haliclona n. sp. and characterized by 2D NMR, while a fourth amino alcohol was characterized as an acetamide derivative. Relative stereochemistry was deduced from the NMR characteristics of oxazolidinone derivatives and absolute stereochemistry secured by preparation and analysis of an MPA ester. The amino alcohol fraction from Haliclona n. sp. acts as an antifungal agent and inhibits the development of larvae of the ascidian Herdmania curvata.

Alanine↗
PubMed2001

Raman spectroscopy as a means for the identification of plattnerite (PbO2), of lead pigments and of their degradation products.

The Raman spectra of plattnerite [lead(IV) oxide, PbO2] and of the lead pigments red lead (Pb3O4), lead monoxide [PbO, litharge (tetragonal) and massicot (orthorhombic)], lead white [basic lead carbonate, 2PbCO3.Pb(OH)2] and of their laser-induced degradation products were recorded using a range of different excitation lines, spectrometer systems and experimental conditions. The degradation of PbO2 is more extensive along the pathway PbO2-->Pb3O4-->PbO (litharge)-->PbO (massicot) the shorter the wavelength of the excitation line and the higher its power. The Raman spectrum of PbO2, which is black and of the rutile structure, is particularly difficult to obtain but three bands, at 653, 515 and 424 cm-1, were identified as arising from the b2g, a1g and e(g) modes respectively, by analogy with the corresponding modes of isostructural SnO2 (776, 634 and 475 cm-1). A further oxide was identified, PbO1.55, the Raman spectrum of which does not correspond to that of any of the laser-induced degradation products of PbO2 at any of the wavelengths used. The Raman results are critical to the future use of Raman microscopy for the identification of lead pigments on artworks.

Journal Article↗
PubMed1999

Carbon monoxide poisoning treated with hyperbaric oxygen: metabolic acidosis as a predictor of treatment requirements.

A retrospective case note analysis was made of patients who received hyperbaric oxygen for carbon monoxide poisoning and were admitted to the Royal Naval Hospital Haslar between 1991 and 1995. Males predominated (38 v 10) as did cases of deliberate self poisoning (31 v 17). The most common presenting feature was unconsciousness, which is an indication for hyperbaric oxygen and therefore reflects referral patterns. If patients had not recovered completely after one hyperbaric exposure further treatments were given. The initial hydrogen ion concentration of those requiring more than one treatment was significantly higher than those who recovered after the first treatment. The initial carboxyhaemoglobin (COHb) concentration showed only a trend to being higher in the multiple treatment group. Although metabolic acidosis is well recognised, its relationship to treatment requirements has not been shown previously. Initial COHb does not always correlate well with severity of poisoning which relates to the mechanism of toxicity of carbon monoxide: binding of carbon monoxide to the intracellular oxygen carrying proteins (for example cytochromes) rather than solely to haemoglobin. These findings are consistent with this mechanism and suggests that initial acidosis is a better predictor of treatment requirements and severity than initial COHb.

Acidosis, Respiratory↗
PubMed1999

Pressure and volume overloads are associated with ventricular hypertrophy in male rainbow trout.

We investigated whether ventricular hypertrophy in reproductively mature male trout (Oncorhynchus mykiss) is associated with elevated hemodynamic loads. We measured ventral aortic blood pressure, pulse pressure dynamics, and blood volume in cannulated, unanesthetized trout with a wide range of relative ventricle masses (RVM, 0.076-0.199% of body wt). We also investigated in vitro pressure-volume dynamics in the bulbus arteriosus taken from trout with a wide range of RVMs. RVM was positively correlated with peak systolic pressure (SBP), mean blood pressure, and pulse pressure. Diastolic pressure and the absolute duration of arterial systole were similar among all animals, but a lower heart rate and a smaller relative duration of arterial systole were correlated with increasing RVM. Blood volume was expanded up to 34% as ventricles enlarged, and clearance of Evans blue dye was greater at higher SBP. Mass, maximal volume, and the pressure-volume dynamics of the bulbus were similar among all animals, suggesting that the bulbus did not compensate for ventricular enlargement. This conclusion was supported by the elevated maximal rates of arterial pressure development (+dP/dt) and decay (-dP/dt) observed as RVM increased. We conclude that 1) mature trout are hypertensive and hypervolemic, 2) the dynamics of the bulbus may contribute to increased afterload, and 3) these changes in hemodynamic load may promote ventricular hypertrophy.

Animals↗
PubMed1998

Denaturing gradient gel electrophoresis: a rapid method for differentiating BoLA-DRB3 alleles.

The products of the BoLA-DRB3 locus are important molecules in the bovine immune response. Several techniques have been used to study and define this locus but they are generally time consuming and limited in their ability to detect novel alleles. In this study we used denaturing gradient gel electrophoresis (DGGE), and direct sequencing, for BoLA-DRB3-typing. First, modified locus-specific primers were used in polymerase chain reaction (PCR) to amplify a 240 bp fragment of exon 2 of BoLA-DRB3 from the genomic DNA of 22 cattle and one pair of twin calves. The reverse primer included a GC-rich clamp to improve the physical separation of the BoLA-DRB3 alleles by DGGE. The denaturing gradient needed to produce separation of alleles was determined using perpendicular DGGE, and this gradient was then applied to parallel denaturing gels. The optimal time for producing allele separation was determined using a time-series analysis. The bands representing individual BoLA-DRB3 alleles were excised from the gels, reamplified, and the nucleotide sequence determined using fluorescent-based automated cycle sequencing. The nucleotide sequences of the separated bands were then compared to published BoLA-DRB3 alleles. A gradient of 10-15% acrylamide combined with a 15-50% ureaformamide gradient was successfully used to separate BoLA-DRB3 alleles in all individuals examined. Nucleotide sequencing showed that the 24 animals possessed 13 BoLA-DRB3 alleles, all of which have been previously described. The BoLA-DRB3 genotypes included 20 heterozygotes and two homozygotes. Three BoLA-DRB3 alleles were seen in each of the twin calves, possibly due to leukochimerism. The technique is reliable and rapid, and avoids cloning alleles prior to nucleotide sequencing and therefore offers distinct advantages over previous techniques for BoLA-DRB3-typing.

Alleles↗
PubMed1998

Morphometric and biochemical characteristics of ventricular hypertrophy in male rainbow trout (Oncorhynchus mykiss).

We examined the morphometric and biochemical effects of ventricular hypertrophy in male rainbow trout (Oncorhynchus mykiss) during sexual maturation. Our investigation focused on characterizing the growth of ventricular layers, on cardiomyocyte dimensions (length, cross-sectional area and cell volume) and on the activities of enzymes involved in intermediary metabolism. Relative ventricle mass (100 x ventricle mass/body mass) increased by as much as 2.4-fold during sexual maturation [as defined by an increasing gonadosomatic index (100 x gonad mass/body mass)], and this resulted in an increased proportion of epicardium relative to endocardium. Ventricular enlargement was associated with increased length (+31 %) and transverse cross-sectional area (+83 %) of cardiomyocytes, which resulted in an expansion of up to 2.2-fold in mean myocyte volume (from 1233 to 2751 micron3). These results indicate that sexual maturation induces ventricular enlargement through myocyte hypertrophy. Cell length and cross-sectional area were similar in both myocardial layers, and myocytes were elliptical rather than circular in transverse cross section. Ventricular hypertrophy did not alter transverse cell shape, perhaps reflecting the maintenance of short diffusion distances for small molecules as cells hypertrophy. Myocyte hypertrophy could not account entirely for the sevenfold range of ventricle masses from different-sized fish, indicating that myocyte hyperplasia contributes substantially to ventricular growth as trout grow. Measurements of the maximal activities of metabolic enzymes demonstrated that ventricular hypertrophy was associated with (1) higher epicardial but not endocardial activities of citrate synthase (by 23 %) and beta-hydroxyacyl-CoA dehydrogenase (by 20 %); (2) lower activities of hexokinase (by 50 %) in both layers, and (3) no change in lactate dehydrogenase or pyruvate kinase activities, which were also similar between layers. These results suggest that the energetic needs of the hypertrophied trout ventricle may be met through increased reliance on fatty acid oxidation, particularly by the endocardium, but decreased reliance on glucose as a metabolic fuel in both layers.

Animals↗
PubMed1997

Raman spectroscopic library of natural and synthetic pigments (pre- approximately 1850 AD).

To assist in the greatly increasing number of applications of Raman microscopy as a tool for non-intrusive, in situ archaeometric analysis, the Raman spectra of over 60 pigments, both natural and synthetic, known to have been in use before approximately 1850 AD, have been studied by Raman microscopy. Fifty-six pigments have yielded high quality spectra which have been arranged, by colour, into a spectroscopic library for reference purposes. The spectroscopic files may be downloaded from http:/(/)www.ucl.ac.uk/chem/resources/raman/speclib .html.

Coloring Agents↗
PubMed1995

Management of life threatening adult postpneumonectomy syndrome.

A case of life threatening airway obstruction secondary to bronchial compression following right pneumonectomy is reported. The aetiology of postpneumonectomy syndrome and the anaesthetic dilemmas faced are discussed with reference to the adaptation and use of a chest drain tube as an improvised airway to bypass the bronchial obstruction.

Adult↗
PubMed1994

Pulmonary barotrauma in submarine escape training.

A 25 year old submariner sustained pulmonary barotrauma during simulated submarine escape. The unusual features of the distribution of pleural and extrapleural air are described and explained.

Accidents, Occupational↗
PubMed1994

In vivo measurement of neutrophil activity in experimental lung inflammation.

Positron emission tomography (PET) was used to quantify 18fluorodeoxyglucose (18FDG) uptake in rabbits with experimental pneumonitis localized to the right upper lobe. In Streptococcus pneumoniae-induced pneumonia, which causes a profound inflammatory response lasting several days before it resolves, 18FDG uptake was pronounced at 15 h after the onset of inflammation, but by 48 h there was little uptake. In bleomycin injury, which progresses from an acute inflammatory stage to chronic inflammation and scarring, 18FDG uptake detectable by PET persisted for up to 21 d. Autoradiography of histologic sections after intravenous administration of [3H]deoxyglucose 15 h after streptococcal instillation and 2 wk after bleomycin instillation showed that, in both models, deoxyglucose uptake was localized to neutrophils. In the streptococcal model there was little 18FGD signal at 6 h, when major neutrophil migration occurs. At 15 h, [3H]deoxyglucose-labeled neutrophils were present in the airspaces but not in the alveolar septa, suggesting that the deoxyglucose signal reflected a postmigratory neutrophil event, probably the respiratory burst. Thus, PET of 18FDG uptake may provide a novel and readily repeatable, noninvasive approach to the in vivo study of neutrophil activity at otherwise inaccessible sites.

Acute Disease↗
PubMed1993

Ventricular CSF shunt infections associated with Corynebacterium jeikeium: report of three cases and review.

Ventricular CSF shunt infections due to Corynebacterium jeikeium are rare. Such infections may become manifest weeks to months after surgery. They are difficult to eradicate and often recur. We report three cases of C. jeikeium ventricular CSF shunt infections, all of which occurred in patients who received long-term prophylactic therapy with antibiotics and had protracted hospitalizations. Two patients had multiple recurrences, and all patients required shunt revision. Additional therapy with intrathecal vancomycin for 6-10 days after surgery was effective for this unusual cause of ventricular CSF shunt infection. On the basis of our experience and a review of six previously published case reports, we recommend CSF sterilization with intravenous and intrathecal vancomycin, followed by replacement of shunt hardware.

Adult↗
PubMed1993

Cost-effective diagnosis of HIV-1 and HIV-2 by recombinant-expressed env peptide (566/996) dot-blot analysis.

OBJECTIVE: To characterize the recombinant env peptides, 566 (HIV-1) and 996 (HIV-2), for their ability to serodiagnose HIV-1 and HIV-2 infection. To develop a cost-effective dot-blot format for these peptides, and to evaluate its performance in a developing country laboratory. DESIGN: The recombinant env peptides were evaluated using a select panel of sera (n = 327) with known serostatus from geographically diverse areas. A dot-blot assay was developed and tested on a second set of immunoblotted sera (n = 331) and further evaluated in the field on a third set of sera (n = 2718) from study populations. METHODS: All sera were evaluated by immunoblot with both HIV-1 and HIV-2 viral lysates. The recombinant env peptides were characterized in immunoblot assay before development of the dot-blot assay. RESULTS: The 566 (HIV-1) peptide showed 100% sensitivity and specificity. The 996 (HIV-2) peptide performed similarly, but showed the presence of HIV-1 cross-reactive epitopes. When the two env peptides were used together, there was high specificity and sensitivity for detecting HIV-positive sera in both immunoblot and dot-blot formats. The dot-blot assay performed in the field showed slightly lower specificity and sensitivity for HIV diagnosis. The relative cost of this assay combined with non-commercial immunoblot confirmation was 10-fold lower than conventional commercial assays. CONCLUSIONS: The 566 and 996 env peptides are appropriate antigens for HIV serotype diagnosis. A dot-blot assay using these peptides may be a useful cost-effective method for HIV diagnosis applicable in developing country laboratories.

AIDS Serodiagnosis↗