Search PubMed⌕ Search

Biomedical subjects

P White

Publications and source records attributed to P White.

At least 127 records · Page 7Linked to original sources
PubMed1997

Right ventricular dysfunction during coronary artery occlusion: pressure-volume analysis using conductance catheters during coronary angioplasty.

OBJECTIVE: To study the effects of coronary artery occlusion on the pressure-volume relations of the right ventricle. DESIGN: Right ventricular pressure-volume cycles were studied using conductance catheters and micromanometers in 19 subjects undergoing coronary angioplasty in a tertiary referral cardiac centre. RESULTS: Catheter occlusions of either the left anterior descending coronary artery or the right coronary artery were associated with a decline in stroke work (mean change (SD): left-13.3 (15.8)%, p = 0.008; right -13.5(16.5)%, p = 0.04). Two patterns of change were evident: an upward shift usually associated with occlusion in the left coronary artery, and a rightward shift in the right coronary artery. In the former there was an increase in maximum ventricular volume (mean change: 3.0(2.7)%, p = 0.004) and in minimum ventricular volume (mean change: 2.3(2.7)%, p = 0.01) and a fall in peak pressure (mean change: -4.8 (5.1)%, p = 0.04). In the latter there was an increase in peak pressure (mean change 9.9(16.3)%, p = 0.04) and an increase in minimum ventricular volume (mean change 3.7(5.0)%, p = 0.02) leading to a fall in stroke volume (mean change -13.3(15.8)%, p = 0.008). CONCLUSIONS: Occlusion of the left anterior descending coronary artery or the right coronary artery is associated with a decline in right ventricular work. However, different patterns of change in indices of preload and afterload lead to different effects on overall right ventricular pump function.

Angioplasty, Balloon, Coronary↗
PubMed1997

Assessment of protein permeability in normal human systemic circulation.

Vascular permeability to oncotic agents is an important determinant of transvascular fluid flux (J) and systemic fluid balance. In this study, a technique was developed to measure protein reflection coefficients (omega) for albumin (Alb), immunoglobulin (Ig) G, and IgM in the intact human systemic circulation to evaluate the role of vascular protein permeability in health and disease. A mathematical model was developed to calculate omega in the forearm circulation from changes in venous hematocrit and protein concentration that occur during edema formation. Assumptions required for the model were validated in an initial set of experiments in normal subjects when edema was induced by inflating a pneumatic cuff on the upper arm. A second series of experiments assessed omega for Alb, IgG, and IgM in men (n = 7) and in women in the follicular (n = 5) and luteal (n = 4) phases of the menstrual cycle. There was an increasing trend in omega with molecular size in aggregated subjects [omega Alb = 0.81 +/- 0.12 (SE), omega IgG = 0.88 +/- 0.12, omega IgM = 0.92 +/- 0.18; P = 0.088]. These values were consistent with those obtained with in vitro preparations. omega values were lower in women in the luteal than in the follicular phase (P = 0.047). We conclude that the assumptions required for this model can be achieved in the intact forearm circulation and that there are menstrual phase-related differences in vascular protein permeability in normal women.

Adult↗
PubMed1997

Epidemiology and control of egg-associated Salmonella enteritidis in the United States of America.

The isolation rate for Salmonella enterica serotype Enteritidis (SE) in humans in the United States of America (USA) increased from 1,207 sporadic isolates identified in 1976 (0.6 isolates/100,000 population) to 10,201 identified in 1995 (4.0/100,000 population). The proportion of reported Salmonella isolates which were SE increased from 5% to 25% during the same time period. In 1990, 1994, and 1995, SE was the most commonly reported reported Salmonella serotype in the USA. Much of this increase has been associated with the consumption of contaminated shell eggs. An examination of the results of a United States Department of Agriculture (USDA) survey of spent hens at slaughter and unpasteurised liquid egg at breaker plants (liquid egg processors) in 1991 and 1995 reveals an increase in the prevalence of SE isolates overall and in most regions of the USA. SE phage type 4 (pt 4), the predominant SE phage type in other parts of the world, has emerged in the egg industry in the western USA concurrent with a sharp increase in the number of sporadic human SE pt 4 isolates in California and Utah. Research on the molecular structure and virulence of SE pt 4 isolates from the USA as compared with isolates from other parts of the world (human and poultry) should be a priority. A comparison of DNA from pt 4 isolates from the USA and Europe may provide information about the potential threat to public health and poultry in the USA from this phage type. Some regional success in the reduction of human illness as a result of SE control efforts is apparent. The Pennsylvania Egg Quality Assurance Program has shown progress in reducing SE infection in participating flocks. At a national level, however, neither the incidence of human illness due to SE nor the prevalence of SE in flocks and unpasteurised liquid eggs have decreased significantly, despite the implementation of the USDA 'trace back' regulation from 1990 to 1995, and intensified efforts to educate food handlers and to enforce safe food handling practices. More effort is needed to control SE at every stage of the egg continuum, from production through to consumption. A risk-reduction approach, with barriers to the introduction and multiplication of the pathogen throughout the farm-to-table continuum, is the most practical method for reducing human illness from SE in shell eggs at present. An effective long-term solution will require interdisciplinary efforts involving government, industry, consumers, and academics. Interventions should be developed and evaluated in compliance with the potential for reducing the risk to human health and cost-effectiveness.

Animal Husbandry↗
PubMed1996

Uncoupling cadherin-based adhesion from wingless signalling in Drosophila.

The Wnt genes encode secreted glycoproteins used in intercellular communication at multiple steps during development. Signalling by Wingless, the Drosophila Wnt-1 homologue, requires the activity of Armadillo, the homologue of vertebrate beta-catenin, which is a component of the cadherin/catenin complex at adherens junctions. The genetic link between wingless and armadillo suggests that cell fate specification and cell-cell adhesion might be controlled concurrently. For instance, in one extreme view, Wingless could specify cell fate entirely by modulating cell adhesion. Alternatively, it might signal independently of adherens junctions. To distinguish between these alternatives, we have expressed two polypeptides that have opposite effects on cadherin-dependent adhesion: full-length Drosophila E-cadherin and a dominant-negative truncated form. We found that overexpression of either construct mimics wingless phenotypes, thereby uncoupling changes in adhesion from signalling effects. We demonstrate that both constructs titrate Armadillo from a 'signalling' pool which is functionally distinct from the junctional pool.

Animals↗
PubMed1996

Interaction of cytochrome c with flavocytochrome b2.

Flavocytochrome b2 from Saccharomyces cerevisiae couples L-lactate dehydrogenation to cytochrome c reduction. At 25 degrees C, 0.10 M ionic strength, and saturating L-lactate concentration, the turnover rate is 207 s-1 [per cytochrome c reduced; Miles, C. S., Rouviere, N., Lederer, F., Mathews, F. S., Reid, G. A., Black, M. T., & Chapman, S. K. (1992) Biochem. J. 285, 187-192]. The second-order rate constant for cytochrome c reduction in the pre-steady-state has been determined by stopped-flow spectrophotometry to be 34.8 (+/- 0.9) muM-1 s-1 in the presence of 10 mM L-lactate. This rate constant has been found to be dependent entirely on the rate of complex formation, the electron-transfer rate in the pre-formed complex being in excess of 1000 s-1. Inhibition of the pre-steady-state reduction of cytochrome c by either zinc-substituted cytochrome c or ferrocytochrome c has led to the estimation of a Kd for the catalytically competent complex of 8 microM, and from this the dissociation rate constant of 280 s-1, a value much less than the actual electron-transfer rate. The inhibition observed is only partial which indicates that electron transfer from the 1:1 complex to another cytochrome c can occur and that alternative electron transfer sites exist. The cytochrome c binding site proposed by Tegoni et al. [Tegoni, M., White, S. A., Roussel, A., Mathews, F. S. & Cambillau, C. (1993) Proteins 16, 408-422] has been tested using site-directed mutagenesis. Mutations designed to affect the complex stability and putative electron-transfer pathway had little effect, suggesting that the primary cytochrome c binding site on flavocytochrome b2 lies elsewhere. The combination of tight binding and multiple electron-transfer sites gives flavocytochrome b2 a low K(m) and a high kcat, maximizing its catalytic efficiency. In the steady-state, the turnover rate is therefore largely limited by other steps in the catalytic cycle, a conclusion which is discussed in the preceding paper in this issue [Daff, S., Ingledew, W. J., Reid, G. A., & Chapman, S. K. (1996) Biochemistry 35, 6345-6350].

Base Sequence↗
PubMed1996

Perception and recognition of normal and negative faces: the role of shape from shading and pigmentation cues.

A face is surprisingly difficult to recognise when presented in photographic negative, and negation has also been shown to affect simple perceptual judgments about a face. Two possible explanations for this effect are examined. In the shape-from-shading explanation it is argued that negating an image results in an impossible pattern of shading, and that this disrupts the formation of a three-dimensional representation of the surface geometry of the face. In an alternative account for this effect it is suggested that identification errors occur as a consequence of changes to the apparent pigmentation of the face caused by negating the image. Three experiments are reported which are designed to test these explanations by using novel colour-image transformations in which the hue and luminance components of images are independently manipulated. The results of these studies suggest that although changes to the apparent pigmentation of a face might result in identification errors in some situations, the loss of shape-from-shading cues is a more important cause of the negation effect. The role of these two sources of information in the recognition of normal faces is also discussed.

Face↗
PubMed1996

Effects of streptozotocin-induced diabetes on vascular reactivity in genetically hyperinsulinaemic obese Zucker rats.

Although the fa/fa Zucker rat shows many of the features of type II diabetes, the absence of consistent cardiovascular complications in this model may be due to the absence of significant hyperglycaemia. We studied the consequences of streptozotocin (STZ)-induced insulin deficiency and hyperglycaemia on vascular reactivity in the fa/fa Zucker rat. Hyperinsulinaemic obese Zucker rats were rendered diabetic by injection of STZ (50-60 mg/kg intraperitoneally, i.p.), and vascular tissue was removed for study 10-12 weeks later. In isolated aorta, there was no difference in the phenylephrine (PE) concentration-response relation between lean and obese control animals, but the concentration-response curve was shifted to the left in diabetic animals, (pD2 7.56 +/- 0.04 in STZ diabetic animals, n = 8; 7.4 +/- 0.04 in obese control, n = 9, p < 0.05). The maximum response was also enhanced in both aorta and perfused mesentery of STZ-treated animals. In contrast, the potency of serotonin (5-HT) in inducing contractions of isolated aorta were enhanced in tissues from obese as compared with lean animals (pD2 6.63 +/- 0.06, n = 9; 6.17 +/- 0.07, n = 7 respectively; p < 0.01) and was attenuated in animals with STZ-induced diabetes (pD2 6.31 +/- 0.09, n = 8, p = 0.05). The differential effects of hyperglycaemia on PE-and 5-HT-induced vasoconstriction suggest that the long-lasting modulation of vasoconstrictor responses induced by increases in blood glucose level may be specific for some agonists.

Acetylcholine↗
PubMed1996

Bacterially induced bone destruction: mechanisms and misconceptions.

Normal bone remodelling requires the coordinated regulation of the genesis and activity of osteoblast and osteoclast lineages. Any interference with these integrated cellular systems can result in dysregulation of remodelling with the consequent loss of bone matrix. Bacteria are important causes of bone pathology in common conditions such as periodontitis, dental cysts, bacterial arthritis, and osteomyelitis. It is now established that many of the bacteria implicated in bone diseases contain or produce molecules with potent effects on bone cells. Some of these molecules, such as components of the gram-positive cell walls (lipoteichoic acids), are weak stimulators of bone resorption in vitro, while others (PMT, cpn60) are as active as the most active mammalian osteolytic factors such as cytokines like IL-1 and TNF. The complexity of the integration of bone cell lineage development means that there are still question marks over the mechanism of action of many well-known bone-modulatory molecules such as parathyroid hormone. The key questions which must be asked of the now-recognized bacterial bone-modulatory molecules are as follows: (i) what cell population do they bind to, (ii) what is the nature of the receptor and postreceptor events, and (iii) is their action direct or dependent on the induction of secondary extracellular bone-modulating factors such as cytokines, eicosanoids, etc. In the case of LPS, this ubiquitous gram-negative polymer probably binds to osteoblasts or other cells in bone through the CD14 receptor and stimulates them to release cytokines and eicosanoids which then induce the recruitment and activation of osteoclasts. This explains the inhibitor effects of nonsteroidal and anticytokine agents on LPS-induced bone resorption. However, other bacterial factors such as the potent toxin PMT may act by blocking the normal maturation pathway of the osteoblast lineage, thus inducing dysregulation in the tightly regulated process of resorption and replacement of bone matrix. At the present time, it is not possible to define a general mechanism by which bacteria promote loss of bone matrix. Many bacteria are capable of stimulating bone matrix loss, and the information available would suggest that each organism possesses different factors which interact with bone in different ways. With the rapid increase in antibiotic resistance, particularly with Staphylococcus aureus and M. tuberculosis, organisms responsible for much bone pathology in developed countries only two generations ago, we would urge that much greater attention should be focused on the problem of bacterially induced bone remodelling in order to define pathogenetic mechanisms which could be therapeutic targets for the development of new treatment modalities.

Alveolar Bone Loss↗
PubMed1996

Resistance of herpes simplex virus type 1 to peptidomimetic ribonucleotide reductase inhibitors: selection and characterization of mutant isolates.

Herpes simplex virus (HSV) encodes its own ribonucleotide reductase (RR), which provides the high levels of deoxynucleoside triphosphates required for viral DNA replication in infected cells. HSV RR is composed of two distinct subunits, R1 and R2, whose association is required for enzymatic activity. Peptidomimetic inhibitors that mimic the C-terminal amino acids of R2 inhibit HSV RR by preventing the association of R1 and R2. These compounds are candidate antiviral therapeutic agents. Here we describe the in vitro selection of HSV type 1 KOS variants with three- to ninefold-decreased sensitivity to the RR inhibitor BILD 733. The resistant isolates have growth properties in vitro similar to those of wild-type KOS but are more sensitive to acyclovir, possibly as a consequence of functional impairment of their RRs. A single amino acid substitution in R1 (Ala-1091 to Ser) was associated with threefold resistance to BILD 733, whereas an additional substitution (Pro-1090 to Leu) was required for higher levels of resistance. These mutations were reintroduced into HSV type 1 KOS and shown to be sufficient to confer the resistance phenotype. Studies in vitro with RRs isolated from cells infected with these mutant viruses demonstrated that these RRs bind BILD 733 more weakly than the wild-type enzyme and are also functionally impaired, exhibiting an elevated dissociation constant (Kd) for R1-R2 subunit association and/or reduced activity (kcat). This work provides evidence that the C-terminal end of HSV R1 (residues 1090 and 1091) is involved in R2 binding interactions and demonstrates that resistance to subunit association inhibitors may be associated with compromised activity of the target enzyme.

Amino Acid Sequence↗
PubMed1996

Identification of randomised clinical trials in the Australian and New Zealand Journal of Psychiatry for the Cochrane Collaboration.

Biased and otherwise unsystematic reviews of the literature may result in factual errors in the conclusions reached by reviewers. The Cochrane Collaboration is an attempt to address some of these concerns. Randomised clinical trials published in the Australian and New Zealand Journal of Psychiatry are now available for inclusion in the Cochrane Collaboration reviews.

Australia↗
PubMed1996

A comparison of computerized tomographic staging systems in chronic sinusitis.

A number of different systems exist for staging computerized tomography (CT) scans in rhinosinusitis. The aim of this study was to determine which of four selected staging systems, currently in common use facilitated the highest level of agreement. The systems studied were those by Jorgensen (1991), May and Levine (1991), Lund and Mackay (1993) and Newman (1994). Ten observers independently assessed 10 representative films. In our assessment, the Lund and Mackay system facilitated the highest level of both inter-observer and intra-observer agreement of the four systems tested. We recommend it be adopted as the standard method of measuring the extent of disease, as depicted by CT scanning for chronic. rhinosinusitis.

Chronic Disease↗
PubMed1996

Orbital floor fracture following nose blowing.

A 70-year-old woman with an upper respiratory infection sustained an orbital floor fracture after vigorous nose blowing. The injury was complicated by orbital emphysema and cellulitis. CT scanning confirmed orbital floor fracture and associated orbital soft tissue herniation into the maxillary antrum. A follow-up sinus endoscopy three months later showed a healed periosteum and mucosa, but continued orbital herniation. As the patient's symptoms had largely resolved, repair was averted. Follow-up after nine months showed no recurrence of orbital swelling. The case presented illustrates a rare complication of vigorous nose blowing, coupled with thinning of the sinus walls seen in aging.

Aged↗