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Biomedical subjects

R J Williams

Publications and source records attributed to R J Williams.

At least 91 records · Page 5Linked to original sources

Restrained drinking and cognitive control among adolescents.

The present study investigated restrained drinking and self-control in relation to alcohol consumption and problem drinking in a sample of adolescents. One hundred ninety-eight high school students (97 males and 101 females; mean age = 16.45 years) completed questionnaires that assessed levels of alcohol consumption, problem drinking, restrained drinking, and cognitive self-control. The findings were similar for males and females: higher levels of restrained drinking, as measured by cognitive emotional preoccupation (CEP), predicted higher levels of alcohol consumption and problem drinking. Moreover, it was high CEP in combination with a low score on a general measure of cognitive self-control that differentiated problem drinking from high levels of drinking. The results are consistent with previous research on young adults. The findings are discussed in relation to Baumeister and Heatherton's (1996) model of self-regulation failure.

Adolescent↗

Randomized controlled trial of stented and stentless aortic bioprotheses: hemodynamic performance at 3 years.

A randomized prospective trial was undertaken to compare the hemodynamic performance and left ventricular regression after aortic valve replacement with the Toronto SPV stentless bioprosthesis and the Carpentier Edwards SAV (CE) bioprosthesis. Forty patients were randomized after the annular and sinotubular diameters had been measured. Early hemodynamic measurements were made with a thermodilution cardiac output catheter, and echocardiography was used thereafter. Left ventricular mass was assessed using magnetic resonance imaging (MRI) at 1 week, 6 months, and 32 months. The mean annular size was 25.3+/-2.2 mm (CE) and 25.5+/-1.5 mm (Toronto), although it was possible to implant valves with a mean diameter 3 mm larger in the stentless group (26.0+/-1.7 mm cf. 23.0+/-1.7 mm). Hemodynamic performance in the first 24 hours showed no significant difference between the groups, but there was a trend for shorter ventilation time and shorter stays in the intensive therapy unit in the stentless group. Echocardiography showed superior transvalvular gradients in the stentless group at 1 week (mean 5.5+/-3.1 mm Hg cf. 8.9+/-2.5 mm Hg), and this difference was maintained at a mean follow-up time of 32 months (3.5+/-0.6 mm Hg cf. 6.3+/-0.6 mm Hg). Similar regression of left ventricular mass was seen in both groups at 6 months, but at 32 months, measurement in diastole showed a reduction of 38% (P<.01) in the stentless group compared with 20% (P = ns) in the stented group, and measurements in systole showed a 23% (P<.01) and 13% (P = ns) reduction, respectively. This study confirms that a larger stentless valve can be implanted into a given size of aortic annulus with superior residual aortic valve gradients. These lower gradients seem to result in improved long-term regression of left ventricular mass as measured by MRI.

Aged↗

Genes encoding multiple forms of phospholipase A2 are expressed in rat brain.

The polymerase chain reaction was utilized to determine which of six cloned phospholipase A2 (PLA2) messenger RNAs (mRNAs), encoding four distinct low molecular weight forms of secretory PLA2 (PLA2-IB, PLA2-IIA, PLA2-IIC and PLA2-V), a calcium-dependent high molecular weight PLA2 (PLA2-IV, cPLA2) and a calcium-independent high molecular weight PLA2 (PLA2-VI, iPLA2), were expressed in different regions of rat brain and in a number of peripheral tissues. Pancreatic PLA2-IB mRNA was not expressed in the brain. PLA2-IIA, PLA2-IV and PLA2-VI mRNAs appeared to be ubiquitously expressed in brain, with relatively similar levels detected in all regions. PLA2-IIC mRNA was expressed in all brain regions but not in any of the peripheral tissues studied. PLA2-V mRNA was found at low levels in most areas of the brain, but at very high levels in the hippocampus. These results indicate that mammalian brain has the potential to express multiple isoforms of PLA2 which could be important given the potential role of these enzyme activities in ischaemic damage and in the regulation of synaptic plasticity.

Animals↗

Calcium: outside/inside homeostasis and signalling.

More and more data accumulate concerning calcium dependent effects in all compartments of cells. The higher the organism in evolution the more calcium becomes involved. Inspection of the data while looking for an explanation of the involvement of calcium in metabolism, nuclear functions, control over pumps, external activities, mineralisation and so on leads one to suppose that calcium has an integrating function. The implication is that calcium flow is a large network connecting the environment, the cytoplasm, vesicles, organelles, the nucleus and in higher species, organs. There is the possibility then that calcium ion functions are being analysed, often in vitro, in a bit by bit reductionist manner while in vivo calcium is the equivalent of an electron in complicated electrical circuits. We then should look for its connections to energy, to effects where conformational switching by calcium pulses is equivalent to magnetic triggering by electron flow and where storage in vesicles is equivalent to condenser-like devices and so on. The appearance of pulsing, of time delays in parts of circuits, and other properties of electronic circuits seen in calcium triggering are then explicable as part of calcium circuit design. No other ion can operate in the same way due to the peculiarities of the calcium ion, its size, charge, ionisation potential and its availability which allow it both to flow rapidly yet to bind considerably.

Adenosine Triphosphate↗

Aqueous two-phase systems: a novel approach for the separation of proteose peptones.

Poly(ethylene glycol) and dextran aqueous two-phase systemis (ATPS) were developed to facilitate the separation of components of the proteose peptone fraction of bovine milk, which are mostly large casein derived peptides or glycoproteins. These have proved difficult to purify using conventional chromatographic procedures. ATPS exploit differences in hydrophobicity, size and ionic properties of the proteose peptones with a view to developing methods for future large scale preparations of the individual components of this whey protein fraction.

Amino Acid Sequence↗

Identification of a non peptidic RANTES antagonist.

A series of phenothiazines demonstrating inhibition of RANTES binding to THP-1 cell membranes has been identified. The lead compound RP23618 (IC50 = 3 microM) was found to inhibit specific binding of 125I-RANTES, but not 125I-MCP-1 to THP-1 cell membranes and furthermore to antagonize RANTES, but not MCP-1-induced chemotaxis of THP-1 cells.

Cell Membrane↗

Use of a cast flexible plate as a hinge substitute in a hinge-lock design removable partial denture framework.

PURPOSE: The use of a hinge for a removable partial denture with an opening labial bow was replaced by the design and construction of a flexible plate incorporated as part of a cobalt-chromium casting. METHODS: Three similar prostheses were constructed and tested in vitro on an endurance test machine. Each test piece completed 12,000 opening and closing operations without fracture, which a previous study showed is a probable life cycle of a typical removable partial denture with a hinged section. RESULTS: This plate provided sufficient flexibility to allow functional operation of the removable partial denture by a patient.

Chromium Alloys↗

Medical preparedness for a terrorist incident involving chemical or biological agents during the 1996 Atlanta Olympic Games.

During the 1996 Centennial Olympic Games in Atlanta, Georgia, unprecedented preparations were undertaken to cope with the health consequences of a terrorist incident involving chemical or biological agents. Local, state, federal, and military resources joined to establish a specialized incident assessment team and science and technology center. Critical antimicrobials and antidotes were strategically stockpiled. First-responders received specialized training, and local acute care capabilities were supplemented. Surveillance systems were augmented and strengthened. However, this extensive undertaking revealed a number of critical issues that must be resolved if our nation is to successfully cope with an attack of this nature. Emergency preparedness in this complex arena must be based on carefully conceived priorities. Improved capabilities must be developed to rapidly recognize an incident and characterize the agents involved, as well as to provide emergency decontamination and medical care. Finally, capabilities must be developed to rapidly implement emergency public health interventions and adequately protect emergency responders.

Anti-Infective Agents↗

Reduction of GABA and glutamate transporter messenger RNAs in the severe-seizure genetically epilepsy-prone rat.

The genetically epilepsy-prone rat is an animal model of inherited generalised tonic-clonic epilepsy that shows abnormal susceptibility to audiogenic seizures and a lowered threshold to a variety of seizure-inducing stimuli. Recent studies suggest a crucial role for glutamate and GABA transporters in epileptogenesis and seizure propagation. The present study examines the levels of expression of the messenger RNAs encoding the glial and neuronal glutamate transporters, GLT-1 and EAAC-1, and the neuronal GABA transporter, GAT-1, in paired male genetically epileptic-prone rats and Sprague Dawley control rats using the technique of in situ hybridization. In a parallel study, semiquantitative immunoblotting was used to assess GLT-1 and EAAC-1 protein levels in similarly paired animals. Animals were assessed for susceptibility to audiogenic seizures on six occasions, and killed seven days following the last audiogenic stimulus exposure. Rat brains were processed for in situ hybridization with radioactive 35S-labelled oligonucleotide probes (EAAC-1 and GAT-1), 35S-labelled riboprobes (GLT-1), and Fluorescein-labelled riboprobes (GLT-1 and GAT-1) or processed for immunoblotting using subtype-specific antibodies for GLT-1 and EAAC-1. Semiquantitative analyses were carried out on X-ray film autoradiograms in several brain regions for both in situ hybridization and immunoblotting studies. Reductions in GAT-1 messenger RNA were found in genetically epileptic-prone rats in all brain regions examined (-8 to -24% compared to control). Similar reductions in GLT-1 messenger RNA expression levels were seen in cortex, striatum, and CA1 (-8 to -12%) of genetically epileptic-prone rats; the largest reduction observed was in the inferior colliculus (-20%). There was a tendency for a reduced expression of EAAC-1 messenger RNA in most regions of the genetically epileptic-prone rat brain although this reached statistical significance only in the striatum (-12%). In contrast, no significant differences in GLT-1 and EAAC-1 protein between genetically epileptic-prone rats and control animals were observed in any region examined, although there was a tendency to follow the changes seen with the corresponding messenger RNAs. These results show differences in the messenger RNA expression levels of three crucial amino acid transporters. For the two glutamate transporters, GLT-1 and EAAC-1, differences in messenger RNA levels are not reflected or are only partially reflected in the expression of the corresponding proteins.

ATP-Binding Cassette Transporters↗

Inhibition of sCD23 and immunoglobulin E release from human B cells by a metalloproteinase inhibitor, GI 129471.

Soluble CD23 (sCD23) has been proposed to play an important role in the up-regulation of immunoglobulin E (IgE) synthesis. Production of sCD23 is dependent on the proteolytic cleavage of membrane CD23, but the protease(s) involved in this process remain unknown. Preliminary data, obtained by testing a panel of protease inhibitors, suggested that this enzyme may be a zinc-dependent metalloproteinase. Therefore, we investigated the effect of a standard hydroxamate-type Zn2+ metalloproteinase inhibitor (GI 129471) on both sCD23 and IgE release from human tonsillar B cells, stimulated with interleukin-4 (IL-4) and anti-CD40. Incubation of cells for 3 days with GI 129471 inhibited the production of sCD23 with an IC50 of 602 nm+/-3 nm (n=3), but by 14 days the activity of the compound against sCD23 had decreased by greater than threefold (IC50 2+/-0.26 microM; n=3). On the other hand, GI 129471 caused a potent inhibition of IgE production, with no apparent loss of activity over the culture period (14 days: IC50 250 nm+/-72 nm; n=3). Time-course studies showed that, despite loss of activity against sCD23, inhibition of sCD23 production early in the culture was able to cause a potent and long-lasting inhibitory effect on IgE. Furthermore, we also showed that the activity of GI 129471 is selective for IgE, as no effect was seen on immunoglobulin G1 (IgG1) or IgG4 production at test concentrations as high as 10 microM. These results support the hypothesis that metalloproteinases may be involved in the proteolytic cleavage of CD23 and subsequent regulation of IgE synthesis. Inhibition of the protease(s) responsible for such cleavage may be of value in the treatment of allergic disease.

B-Lymphocytes↗

Hydrogen peroxide enhances signal-responsive arachidonic acid release from neurons: role of mitogen-activated protein kinase.

Hydrogen peroxide (H2O2) is a potent stimulator of signal-responsive phospholipase A2 (PLA2) in vascular smooth muscle and cultured endothelial cells. We investigated whether H2O2 plays a similar regulatory role in neurons. H2O2 did not stimulate a release of arachidonic acid from cultured neurons when applied alone but strongly enhanced the liberation of arachidonic acid evoked by maximally effective concentrations of either glutamate, the glutamate receptor agonist N-methyl-D-aspartate (NMDA), the muscarinic receptor agonist carbachol, the Na+-channel opener veratridine, or the Ca2+-ionophore ionomycin. The potentiating effects of H2O2 were strongly inhibited in the presence of the PLA2 inhibitor mepacrine, suggesting that the site of action was within the signal responsive arachidonic acid cascade. The enhancing effect of H2O2 was not reversed by protein kinase C inhibitors (chelerythrine chloride or GF 109203X) nor was it mimicked by phorbol ester treatment. H2O2 alone strongly enhanced the levels of immunodetectable activated mitogen-activated protein kinase (activated MAP kinases ERK1 and ERK2) in a Ca2+-dependent manner and this effect was additive with increases in the levels of activated MAP kinase evoked by glutamate. The enhanced release of arachidonic acid, however, was not clearly reversed by the MAP kinase kinase (MEK) inhibitor PD 98059, although this treatment effectively abolished H2O2 activation of MAP kinase. Thus, MAP kinase activation and Ca2+-dependent arachidonic acid release are regulated by oxidative stress in cultured striatal neurons.

Animals↗

Relation of drinking and eating to masculinity and femininity.

The relationship between desirable and undesirable aspects of masculinity and femininity and drinking and eating was investigated. A sample of 144 university women in Australia completed questionnaires that assessed masculinity and femininity, reported drinking, alcohol dependence, eating restraint, frequency of dieting, and overeating. Evidence of a common underlying dimension linking aspects of problem drinking and overeating to undesirable masculine characteristics was found. The results are consistent with the view that women engage in excessive consummatory behaviors such as binging to deal with their gender-role conflict.

Adult↗

Experimental simian varicella virus infection of St. Kitts vervet monkeys.

Experimental simian varicella virus (SVV) infection of St. Kitts vervet monkeys was evaluated as an animal model to investigate human varicella-zoster virus (VZV) infections. During the incubation period, viremia disseminated infectious virus throughout the body via infected peripheral blood lymphocytes (PBLs). A vesicular skin rash in the inguinal area, and on the abdomen, extremities, and face appeared on day 7-10 postinfection. Necrosis and hemorrhage in lung and liver tissues from acutely infected monkeys were evident upon histologic analysis. Recovery from simian varicella was accompanied by a rise in the serum neutralizing antibody response to the virus. SVV latency was established in trigeminal ganglia of monkeys which resolved the acute infection. This study indicates that experimental SVV infection of St. Kitts vervets is a useful animal model to investigate SVV and VZV pathogenesis and to evaluate potential antiviral agents and vaccines.

Animals↗

Human vascular smooth muscle cells express receptors for CC chemokines.

Arteriosclerotic lesions are characterized by the accumulation of T lymphocytes and monocytes and the proliferation of intimal smooth muscle cells. Expression of the chemokine monocyte chemoattractant protein-1 (MCP- 1) has been observed in arteriosclerotic plaques and has been proposed to mediate the transendothelial migration of mononuclear cells. More recently, MCP-1 has been proposed to affect the proliferation and migration of vascular smooth muscle cells (VSMCs). We have used reverse transcription-polymerase chain reaction (RT-PCR) to investigate chemokine mRNA expression in human arteriosclerotic lesions obtained from surgical biopsy of diseased vascular tissue and show, in addition to MCP-1, expression of the chemokine macrophage inflammatory protein-1alpha (MIP-1alpha) at higher levels than in "normal" aortic tissue. We have also used RT-PCR to characterize the expression of known chemokine receptors by primary human VSMCs. Messenger RNA for the MIP-1alpha/RANTES receptor, CCR-1, and the MCP-1/MCP-3 receptor, CCR-2, was expressed by unstimulated VSMCs grown under serum-free culture conditions for 24 hours. The receptors CCR-3, CCR-4, CCR-5, CXCR-1, and CXCR-2 were not expressed by VSMCs. The presence of functionally coupled receptors for MIP-1alpha on VSMCs was demonstrated by specific binding of biotinylated MIP-1alpha and increases in intracellular Ca2+ levels after exposure to this chemokine. Taken together, these results suggest that chemokines are likely to be involved in arteriosclerosis and may play a role in modulating the function of VSMCs in vivo.

Adult↗