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Biomedical subjects

G Rhodes

Publications and source records attributed to G Rhodes.

At least 37 records · Page 2Linked to original sources
PubMed2000

Distribution of oxytetracycline resistance plasmids between aeromonads in hospital and aquaculture environments: implication of Tn1721 in dissemination of the tetracycline resistance determinant tet A.

Oxytetracycline-resistant (OT(r)) mesophilic aeromonads were recovered from untreated hospital effluent (72 isolates) and from fish farm hatchery tanks (91 isolates) at sites within the English Lake District, Cumbria, England. The transfer of OT(r) plasmids from these isolates was investigated. Using Escherichia coli J53-1 as a recipient, 11 isolates from the hospital site and 6 isolates from the fish farm site transferred OT(r) plasmids (designated pFBAOT1 to 17). Original isolates were identified using fatty acid methyl ester and fluorescent amplified fragment length polymorphism comparisons as either Aeromonas hydrophila HG3 (eight isolates), A. veronii b.v. sobria HG8 (six isolates), and A. caviae HGB5 (one isolate). One isolate remained unidentified, and one could not be assigned a taxonomic designation beyond the genus level. Plasmids pFBAOT1 to -17 were screened for the presence of the tetracycline resistance determinants Tet A to E and Tet G. Only determinant Tet A (10 plasmids) was detected in these plasmids, with 7 tet gene determinants remaining unclassified. In all cases, Tet A was located on a 5.5-kb EcoRI restriction fragment. Hybridization with inc-rep probes N, P, Q, W, and U showed pFBAOT3, -4, -5, -6, -7, -9, and -11, from the hospital environment, to be IncU plasmids. Further, restriction fragment length polymorphism (RFLP) analyses and DNA probing demonstrated that pFBAOT plasmids were closely related to IncU OT(r) plasmids pASOT, pASOT2, pASOT3, pRAS1 (originally isolated from A. salmonicida strains from fish farms in Scotland and Norway, respectively), and pIE420 (isolated from a German hospital E. coli strain). In addition, DNA analyses demonstrated that plasmids pRAS1 and pIE420 had identical RFLP profiles and that all fragments hybridized to each other. The presence of tetracycline resistance transposon Tn1721 in its entirety or in a truncated form in these plasmids was demonstrated. These results provided direct evidence that related tetracycline resistance-encoding plasmids have disseminated between different Aeromonas species and E. coli and between the human and aquaculture environments in distinct geographical locations. Collectively, these findings provide evidence to support the hypothesis that the aquaculture and human compartments of the environment behave as a single interactive compartment.

Aeromonas↗
PubMed2000

Sex-typicality and attractiveness: are supermale and superfemale faces super-attractive?

Many animals find extreme versions of secondary sexual characteristics attractive, and such preferences can enhance reproductive success (Andersson, 1994). We hypothesized, therefore, that extreme versions of sex-typical traits may be attractive in human faces. We created supermale and superfemale faces by exaggerating all spatial differences between an average male and an average female face. In Expt 1 the male average was preferred to a supermale (50% exaggeration of differences from the female average). There was no clear preference for the female average or the superfemale (50% exaggeration). In Expt 2, participants chose the most attractive face from sets of images containing feminized as well as masculinized images for each sex, and spanning a wider range of exaggeration levels than in Expt 1. Chinese sets were also shown, to see whether similar preferences would occur for a less familiar race (participants were Caucasian). The most attractive female image was significantly feminized for faces of both races. However, the most attractive male image for both races was also significantly feminized. These results indicate that feminization, rather than sex exaggeration per se, is attractive in human faces, and they corroborate similar findings by Perrett et al. (1998).

Adolescent↗
PubMed2000

Pharmacokinetic/pharmacodynamic modeling in drug research and development.

The two domains in clinical pharmacology dealing with optimizing dosing recommendations are pharmacokinetics and pharmacodynamics. However, the usefulness of these disciplines is limited if viewed in isolation. Pharmacokinetic/pharmacodynamic (PK/PD) relationships and modeling builds the bridge between these two classical disciplines of clinical pharmacology. It links the concentration-time profile as assessed by pharmacokinetics to the intensity of observed response as quantified by pharmacodynamics. Thus, the resulting so-called integrated PK/PD-models allow the description of the complete time course of the desired and/or undesired effects in response to a drug therapy. PK/PD-modeling can elucidate the causative relationship between drug exposure and response and provide a better understanding of the sequence of events that result in the observed drug effect. This information can then be used to streamline the drug development process and dose optimization. This consensus paper presents an update on the current state of PK/PD-modeling from an academic, industrial and regulatory perspective.

Drug Design↗
PubMed1998

Recognition of own-race and other-race caricatures: implications for models of face recognition.

Valentine's (Valentine T. Q J Exp Psychol 1991;43A:161-204) face recognition framework supports both a norm-based coding (NBC) and an exemplar-only, absolute coding, model (ABC). According to NBC; (1) faces are represented in terms of deviations from a prototype or norm; (2) caricatures are effective because they exaggerate this norm deviation information; and (3) other-race faces are coded relative to the (only available) own-race norm. Therefore NBC predicts that, for European subjects, caricatures of Chinese faces made by distorting differences from the European norm would be more effective than caricatures made relative to the Chinese norm. According to ABC; (1) faces are encoded as absolute values on a set of shared dimensions with the norm playing no role in recognition; (2) caricatures are effective because they minimise exemplar density and (3) the dimensions of face-space are inappropriate for other-race faces leaving them relatively densely clustered. ABC predicts that all faces would be recognised more accurately when caricatured against their own-race norm. We tested European subjects' identification of European and Chinese faces, caricatured against both race norms. The ABC model's prediction was supported. European faces were also rated as more distinctive and recognised more easily than Chinese faces. However, the own-race recognition bias held even when the races were equated for distinctiveness which suggests that the ABC model may not provide a complete account of race effects in recognition.

Facies↗
PubMed1998

Coding spatial variations in faces and simple shapes: a test of two models.

Faces all have the same basic elements in the same overall arrangement, and must be discriminated using variations in this shared configuration. An efficient way to represent these variations would be to code how each configuration differs from an average face (norm-based coding model). Alternatively, configurations could be represented simply by coding their absolute values in some coordinate system (absolute coding model). The two models differ in the variables they predict will influence an image's recognizability. Absolute coding predicts that recognizability will depend on an image's distinctiveness and degree of distortion from its veridical target. Norm-based coding predicts that recognizability will also depend on the way the image differs from a norm or average face, namely its distance from the norm and/or its degree of displacement from the norm-deviation vector for the target. We determined the effects of these four critical variables on recognition of undistorted (veridical) images, caricatures, anticaricatures and 'lateral' distortions of famous faces (Experiment 1), newly learned faces (Experiment 2), and simple shapes that also share a configuration (Experiment 2). The results favored absolute coding of both faces and shapes, and indicate that caricatures derive their power from their distinctiveness.

Adult↗
PubMed1997

Facial distinctiveness and the power of caricatures.

Caricatures, which increase the distinctiveness of faces, are generally recognised at least as well as undistorted images of those faces. However, caricatures seem to facilitate recognition more for some faces than others. An investigation was made into whether the effectiveness of caricaturing depends on a face's initial distinctiveness. In experiments 1-3, subjects learned names for unfamiliar faces (photographs) that varied in distinctiveness, and were tested on recognition of caricatures, anticaricatures, and undistorted images of those faces. The test images were line drawing in experiment 1 and 2 photographic images in experiment 3. Experiments 1 and 2 were identical except that subjects had more exposure to the study photographs in experiment 1. In all three experiments, distinctive faces were recognised (named) more accurately than less-distinctive faces, and caricatures were recognised at least as accurately as undistorted images and better than anticaricatures. However, distinctiveness and caricature level did not interact. Nor did a face's initial distinctiveness correlate with the degree of recognition facilitation produced by caricaturing (experiments 1-3) or with the caricature level chosen as the best likeness (experiment 4). The effectiveness of caricatures varied across faces and experimental conditions, but these differences did not relate to differences in initial distinctiveness. These results prompted a more careful analysis of the expected relationship between initial distinctiveness and the power of caricatures, which indicated that the relationship may be curvilinear rather than linear. In addition, it was found that line-drawing caricatures functioned as superportraits (recognised better than undistorted images--experiment 1) but photographic caricatures did not (experiment 3) suggesting that the forensic potential of caricatures may be limited.

Adult↗
PubMed1996

Chemical approaches to improve the oral bioavailability of peptidergic molecules.

This review discusses both tools and strategies that may be employed as approaches towards the pursuit of orally active compounds from peptidergic molecules. Besides providing a review of these subjects, this paper provides an example of how these were utilized in a research programme at SmithKline Beecham involving the development of orally active GPIIb/IIIa antagonists. The tools for studying oral drug absorption in-vitro include variants of the Ussing chamber which utilize either intestinal tissues or cultured epithelial cells that permit the measurement of intestinal permeability. Example absorption studies that are described are mannitol, cephalexin, the growth hormone-releasing peptide SK&F 110679 and two GPIIb/IIIa antagonist peptides SK&F 106760 and SK&F 107260. With the exception of cephalexin, these compounds cross the intestine by passive paracellular diffusion. Cephalexin, on the other hand, crosses the intestine via the oligopeptide transporter. Structure-transport studies are reviewed for this transporter. The tools for studying oral drug absorption in-vivo involve animals bearing in-dwelling intestinal or portal vein catheters. A study of the segmental absorption of SK&F 106760 is provided. The review concludes with two chemical strategies that may be taken towards the enhancement of oral bioavailability of peptidergic molecules. The first strategy involves the chemical modification of peptides which enhance intestinal permeability, specifically the modification of amide bonds. The second strategy involves the design of compounds bearing nonpeptide templates, which are more amenable to the discovery of compounds with oral activity, from peptide pharmacophore models. An example is given regarding the discovery of SB 208651, a potent orally active GPIIb/IIIa antagonist, designed from the peptides SK&F 106760 and SK&F 107260.

Absorption↗
PubMed1994

Self-replicating Semliki Forest virus RNA as recombinant vaccine.

Recombinant RNA based on the Semliki Forest virus (SFV) replicon was used to express the nucleoprotein of influenza virus in mice. Two strategies were employed to deliver the RNA. In the first, recombinant RNA was packaged into infectious suicide SFV particles which were used directly for immunization. The second approach involved injection of in vitro-synthesized RNA directly into the quadriceps muscle. Both approaches resulted in the generation of humoral responses with high antibody titres. Immunization with suicide particles showed that a strong, class I-restricted cytotoxic T-cell response can be obtained using only 100 infectious units. We conclude that the self-replicative recombinant SFV RNA may be quite useful as a nucleic acid vaccine.

Animals↗
PubMed1994

Determination of BRL 46470 in human plasma by high performance liquid chromatography with ultraviolet absorbance detection followed by post-column photochemical reaction and fluorescence detection.

A very sensitive and specific quantitative assay for BRL 46470, a selective 5-HT3 receptor antagonist, in human plasma was developed. The method uses HPLC with serial UV absorbance detection followed by post-column photochemical reaction and fluorescence detection to provide an ultra-sensitive and specific method with a wide quantitative range. The post-column photochemical reaction enhances the very weak native fluorescence of BRL 46470 by a factor of approximately 150. The quantification ranges were determined to be 0.1-1.5 ng ml-1 (fluorescence detection) and 1.5-200 ng ml-1 (UV absorbance detection) for BRL 46470. Results from a 3 d validation at nominal BRL 46470 concentrations of 0.1, 0.4, 1.0 and 1.5 ng ml-1, using post-column photochemical reaction and fluorescence detection, demonstrated precision ranges of 3.4-5.8% (average within-day) and 1.6-5.6% (between-day). The average accuracy ranged from 93.4 to 114.5%. Results from a 3 d validation at nominal BRL 46470 concentrations of 1.5, 4.0, 25 and 200 ng ml-1, using UV absorbance detection, demonstrated precision ranges of 2.0-8.2% (average within-day) and 1.0-3.4% (between-day). The average accuracy ranged from 86.3 to 103.7%. The recovery of BRL 46470 from human plasma was approximately 64%. Assay specificity was confirmed by HPLC-MS.

Bridged Bicyclo Compounds↗
PubMed1993

Configural coding, expertise, and the right hemisphere advantage for face recognition.

Expertise in recognizing faces is associated with configural coding and configural coding is associated with a right hemisphere advantage for face recognition. Therefore one would expect the orientation-specific LVF (left visual field) advantage for face recognition to be moderated by expertise. The present experiments examined the effect of expertise with face ethnicity on the LVF advantage. In Experiment 1 subjects showed expertise-related use of configural coding, but no orientation-specific LVF advantage. In Experiment 2 subjects with high hemispheric arousal asymmetry showed an orientation-specific LVF advantage, but no expertise-related use of configural coding. Low arousal asymmetry subjects showed the opposite pattern. These results suggest that different kinds of configural coding may underlie ethnicity-related expertise effects and laterality effects in face recognition.

Adult↗
PubMed1993

What's lost in inverted faces?

Disproportionate inversion decrements for recognizing faces and other homogeneous stimuli are often interpreted as evidence that experts use relational features to recognize stimuli that share a configuration. However, it has never directly been shown that inversion disrupts the coding of relational features more than isolated features. Here we report three studies that compare inversion decrements for detecting changes that span the isolated-relational features continuum. Relatively large inversion decrements occurred for relational features (Thatcher illusion changes, internal feature spacing), with smaller decrements for isolated features (presence/absence of facial hair or glasses). The one discrepancy was a relatively large inversion decrement for detecting changes to the eyes and mouth, which we had classified as an isolated feature change. However, this decrement disappeared when the features were presented out of the face context (Experiments 2 and 3), suggesting that it occurs because subjects spontaneously code relations between the features and the rest of the face. Although the results support the interpretation of disproportionate inversion effects as evidence of relational coding, the difficulty of classifying changes as isolated or relational highlights an undesirable ambiguity in the isolated-relational feature distinction. We therefore consider alternative construals of the configural coding notion.

Facial Expression↗
PubMed1993

Survival of nonculturable Aeromonas salmonicida in lake water.

The survival of Aeromonas salmonicida subsp. salmonicida was investigated in sterile and untreated lake water. In sterile lake water (filtered and autoclaved), it was found that cells of A. salmonicida entered a nonculturable but viable condition. Viability was determined by flow cytometry with the dye rhodamine 123, which is taken up and maintained within cells with a membrane potential. For survival studies in untreated lake water, A. salmonicida was marked with the xylE gene by using the plasmid pLV1013. Marked cells were detected by growth on tryptone soy agar and tryptone soy agar supplemented with kanamycin. Cells were also detected by polymerase chain reaction DNA amplification of the xylE gene and a chromosomal DNA fragment specific for A. salmonicida (pLV1013). The results indicated that A. salmonicida entered a nonculturable condition in untreated lake water over a 21-day study. The viability of nonculturable cells could not be determined in mixed samples; however, the presence of nonculturable cells containing both chromosomal and plasmid DNA was confirmed.

Aeromonas↗
PubMed1992

Determination of the enantiomers of fenoldopam in human plasma by reversed-phase high-performance liquid chromatography after chiral derivatization.

Fenoldopam, a selective agonist at peripheral dopaminergic (DA-1) receptors, is administered as a racemic mixture and, consequently, an indirect stereospecific high-performance liquid chromatographic assay was developed to study the disposition of the individual enantiomers in human subjects. Fenoldopam enantiomers were extracted from alkalinized plasma into ethyl acetate prior to precolumn derivatization with the chiral reagent 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate (GITC). The resulting diastereomers were separated on a reversed-phase butylsilica column and determined using triple-electrode coulometric detection. The limits of determination and detection for the S- and R-enantiomers of fenoldopam were 0.5 and 0.25 ng/ml, respectively. A linear response was observed for (S)- and (R)-fenoldopam concentrations ranging from 0.5 to 50 ng/ml in plasma. The intra-day relative standard deviations (R.S.D.s) for the plasma assay at nominal concentrations of 0.5, 5 and 50 ng/ml were 17.4, 5.2 and 6.9%, respectively, for (S)-fenoldopam and 9.9, 6.2 and 7.4%, respectively, for (R)-fenoldopam. The inter-day R.S.D.s of the method at these concentrations were 9.3, 7.7 and 7.4%, respectively, for (S)-fenoldopam and 9.5, 1.9 and 7.3%, respectively, for (R)-fenoldopam. The mean accuracy of the method at concentrations of 0.5, 5 and 50 ng/ml in plasma was found to be 106.4, 111.8 and 108.9%, respectively, for (S)-fenoldopam and 116.2, 104.2 and 111.2%, respectively, for (R)-fenoldopam. The assay developed was sufficiently sensitive, accurate and precise to support pharmacokinetic studies in human subjects.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Non-culturable Aeromonas salmonicida in lake water.

The survival of Aeromonas salmonicida subsp. salmonicida was investigated in lake water. During a 21-day study A. salmonicida became non-culturable in sterile lake water held at 10 degrees C. The incubation of replicate samples between 5 degrees C and 25 degrees C produced similar results. The recovery of colony-forming units of A. salmonicida from different lake water systems indicated that they survived longer in water that was naturally enriched (eutrophic) or enriched with tryptone soya broth. Flow cytometry, fluorescence light microscopy, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) indicated that non-culturable cells were present. These cells could not be revived in dilutions of tryptone soya broth, whole dead fish or dissected fish tissue. Although viability could not be proven, it was shown that the morphological integrity found in viable cells was also maintained in non-culturable cells.

Aeromonas↗
PubMed1992

The effect of microcosm design on the survival of recombinant Pseudomonas putida in lake water.

The survival of Pseudomonas putida marked with the xylE gene was monitored in lake-water microcosms. Various designs of microcosms were compared. These ranged from 250-ml conical flasks containing 100 ml surface lake water to 12-1 glass containers with lake water overlying sediment, continuous aeration and a supply of fresh surface lake water. The presence of a low flow-through rate was shown to have little effect on the survival of P. putida. An increase in the size of microcosm, presence of sediment and aeration had a significant effect on survival in lake water and increased the rate of decline of released cells. The implication of these results in predicting the survival of P. putida in lake water using microcosms is discussed.

Genes, Bacterial↗
PubMed1991

Infection of human thymocytes by Epstein-Barr virus.

The Epstein-Barr Virus (EBV) causes infectious mononucleosis, and has been strongly associated with certain human cancers. The virus is thought to exclusively bind to B lymphocytes and epithelial cells via receptors (CR2/CD21) that also interact with fragments of the third component of complement (C3). Recent evidence, however, has challenged this belief. We have used two-color immunofluorescence analysis using biotin-conjugated EBV and streptavidin-phycoerythrin along with fluorescein-conjugated anti-T cell antibodies and demonstrated that CD1-positive, CD3-dull (immature) human thymocytes express functional EBV receptors. In four replicate experiments, the binding of EBV to thymocytes ranged between 8 and 18%. This interaction is specific as evidenced by inhibition with nonconjugated virus, anti-CR2 antibodies, aggregated C3, and an antibody to the gp350 viral glycoprotein that the virus uses to bind to CR2. EBV can infect the thymocytes as evaluated by the presence of episomal EBV-DNA in thymocytes that had been incubated with the virus as short as 12 days or as long as 6 weeks. Episomal DNA analysis was performed by Southern blotting with a EBV-DNA probe that hybridizes to the first internal reiteration of the viral DNA. The presence of the EBV genome is also supported by the detection of EBV nuclear antigen 1 in infected thymocytes, assessed by Western blotting with EBV-immune sera. The EBV infection is specific as determined by blocking experiments using anti-CR2 and anti-gp350 antibodies. Finally, virus infection of thymocytes can act synergistically along with interleukin 2 and induce a lymphokine-dependent cellular proliferation. In view of previously reported cases of EBV-positive human T cell lymphomas, the possibility is raised that EBV may be involved in cancers of T lymphocytes that have not been previously appreciated.

Antigens, CD19↗