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Biomedical subjects

J McCarthy

Publications and source records attributed to J McCarthy.

At least 73 records · Page 4Linked to original sources

The influence of body movement on subjective presence in virtual environments.

We describe an experiment to assess the influence of body movements on presence in a virtual environment. In the experiment 20 participants were to walk through a virtual field of trees and count the trees with diseased leaves. A 2 x 2 between subjects design was used to assess the influence of two factors on presence: tree height variation and task complexity. The field with greater variation in tree height required participants to bend down and look up more than in the lower variation tree height field. In the higher complexity task participants were told to remember the distribution of diseased trees in the field as well as to count them. The results showed a significant positive association between reported presence and the amount of body movement in particular, head yaw--and the extent to which participants bent down and stood up. There was also a strong interaction effect between task complexity and gender: Women in the more-complex task reported a much lower sense of presence than in the simpler task. For applications in which presence is an important requirement, the research in this paper suggests that presence will be increased when interaction techniques are employed that permit the user to engage in whole-body movement.

Female↗

An improved direct plate method for the enumeration of stressed Escherichia coli O157:H7 from food.

The use of sorbitol MacConkey agar (SMAC) performed poorly in supporting growth of stressed Escherichia coli O157:H7 cells. Up to a 3-log difference was observed between counts on SMAC and tryptone soy agar (TSA). It is critical in the risk assessment of certain foods to be able to enumerate stressed and healthy E. coli O157:H7 in a background of potentially healthy competing bacteria. Investigations carried out to overcome the inhibitory effect of SMAC included the reduction of the selective agent concentration, inclusion of a recovery stage in broth prior to plating out, addition of recovery agents, and delayed exposure to the selective agent. The only successful approach was delayed exposure to the selective agent. This was achieved by resuscitating the stressed cells on a membrane placed on the surface of a TSA plate and, after a defined time period sufficient for full resuscitation, transferring the membrane to the surface of a SMAC plate. The choice of membrane material was critical for maintaining the positive sorbitol color change used to identify wild-type E. coli. Track-etched polycarbonate membranes allowed the typical color reactions to be visualized, whereas cellulose acetate did not. The method was validated with E. coli O157:H7 cells stressed by low pH and high salt conditions, whereby all cells that would previously be undetectable on direct inoculation of SMAC were countable.

Animals↗

Probing the presumed catalytic triad of a selenium-containing peroxidase by mutational analysis.

Glutathione peroxidases (GPx) are characterized by a catalytically active selenium which forms the center of a strictly conserved triad composed of selenocysteine, glutamine, and tryptophan. In order to check the functional relevance of this structural peculiarity, six molecular mutants of phospholipid hydroperoxide glutathione peroxidase (PHGPx) were designed, isolated, and investigated kinetically. Replacement of the selenocysteine in position 46 by cysteine decreased k + 1, i.e., the reaction rate of reduced enzyme with hydroperoxide, by three orders of magnitude. The rate of regeneration of the reduced enzyme by glutathione (k' + 2) was similarly affected. Additional substitution of Gln81 or Trp136 by acid residues resulted in a further decrease of k + 1 by three orders of magnitude, whereas histidine or neutral residues in these positions proved to be less deleterious. The data support the hypothesis that the typical triad of selenocysteine, glutamine, and tryptophan is indeed a novel catalytic center in which the reactivity of selenium is optimized by hydrogen bonding provided by the adjacent glutamine and tryptophan residues.

Animals↗

The conceptual framework of the PMM Network.

Understanding the determinants of maternal mortality is a complex task, in part because maternal deaths are influenced by many different categories of events or conditions. Biology, economics, culture, demography and the distribution and effectiveness of health services all contribute. Conceptual frameworks have made important contributions to our understanding of the determinants of other, equally complex events, such as fertility and child survival. Also referred to as 'proximate determinants frameworks', such models are useful because they identify the specific mechanisms through which social, economic and cultural factors lead to the event of interest. Our model identifies the precise sequence of events that lead to maternal death (pregnancy, complication and death) and specifies categories of intermediate factors and distant factors that directly affect one or more of these events. When the world literature on maternal mortality was analyzed in light of the causal pathways laid out in the conceptual framework, it became clear that some pathways are more amenable to intervention and change than others. Implications for strategies, programs and monitoring and evaluation are discussed.

Africa, Western↗

Child and family focus. Working together to develop integrated systems of care.

We've all heard the jokes about the nature of committee work: "A camel is a horse designed by committee." Or, "A committee is a group of the unwilling unprepared to do the unnecessary." In the current case, nothing could be farther from the truth. Over the past year, we were very fortunate to be able to gather a group of experts who were more than willing, and prepared, to do the very necessary. Representing all areas of children's behavioral healthcare, these respected leaders of the field worked assiduously to produce a blueprint for how child mental health and welfare workers, public purchasers, families, managed care leaders, and other stake-holders can work together to create well-managed "systems of care." The article they coauthored reflects some of the best thinking on the problems of emerging multiple managed care systems and the specific actions urgently needed to protect children and their families. We are pleased to present their recommendations to you in this month's Child and Family Focus. We feel that the hard work that went into this collaboration, and the resulting consensus, demonstrates that integration can, does, and must work to create better systems of care.

Adolescent↗

Pervanadate activation of intracellular kinases leads to tyrosine phosphorylation and shedding of syndecan-1.

Syndecan-1 is a transmembrane haparan sulphate proteoglycan that binds extracellular matrices and growth factors, making it a candidate to act between these regulatory molecules and intracellular signalling pathways. It has a highly conserved transmembrane/cytoplasmic domain that contains four conserved tyrosines. One of these is in a consensus sequence for tyrosine kinase phosphorylation. As an initial step to investigating whether or not phosphorylation of these tyrosines is part of a signal-transduction pathway, we have monitored the tyrosine phosphorylation of syndecan-1 by cytoplasmic tyrosine kinases in intact cells. Tyrosine phosphorylation of syndecan-1 is observed when NMuMG cells are treated with sodium orthovanadate or pervanadate, which have been shown to activate intracellular tyrosine kinases. Initial studies with sodium orthovanadate demonstrate a slow accumulation of phosphotyrosine on syndecan-1 over the course of several hours. Pervanadate, a more effective inhibitor of phosphatases, allows detection of phosphotyrosine on syndecan-1 within 5 min, with peak phosphorylation seen by 15 min. Concurrently, in a second process activated by pervanadate, syndecan-1 ectodomain is cleaved and released into the culture medium. Two phosphorylated fragments of syndecan-1 of apparent sizes 6 and 8 kDa remain with the cell after shedding of the ectodomain. The 8 kDa size class appears to be a highly phosphorylated form of the 6 kDa product, as it disappears if samples are dephosphorylated. These fragments contain the C-terminus of syndecan-1 and also retain at least a portion of the transmembrane domain, suggesting that they are produced by a cell surface cleavage event. Thus pervanadate treatment of cells results in two effects of syndecan-1: (i) phosphorylation of one or more of its tyrosines via the action of a cytoplasmic kinase(s) and (ii) cleavage and release of the ectodomain into the medium, producing a C-terminal fragment containing the transmembrane/cytoplasmic domain.

Animals↗

Mechanisms involved in the induction of human endothelial cell necrosis.

The effects of the inflammatory mediators lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF) and unstimulated and activated neutrophils (PMNs) on endothelial cell (EC) necrosis were studied using the cultured human EC line (ECV-304) and human PMNs in vitro. LPS and TNF alone or their combination failed to induce EC necrosis. Activated PMNs, as evidenced by augmentations in CD11b expression and respiratory burst, induced significant EC necrosis commencing at 12 hr of coculture, which was strongly dependent on the ratio of PMN:ECs and the duration of PMN:EC coculture. In contrast, unstimulated PMNs induced no significant increases in EC necrosis. To examine the mechanisms of activated PMN-mediated EC necrosis, the oxygen radical scavengers superoxide dismutase (SOD) and catalase, as well as the protease inhibitors phenylmethylsulfonyl fluoride (PMSF), alpha 1-antitrypsin (alpha 1-AT), soybean trypsin-chymotrypsin inhibitor (TCI), and aprotinin, were studied in coculture experiments. EC necrosis induced by activated PMNs could be markedly attenuated by SOD, PMSF, alpha 1-AT, TCI, aprotinin, or their combinations. Although aprotinin enhanced respiratory burst, this agent inhibited necrosis by downregulating PMN CD11b and PMN-EC adhesion. These results demonstrate that the inflammatory mediators LPS and TNF and quiescent PMNs fail to induce EC necrosis. However, PMNs activated by inflammatory mediators can induce EC necrosis through oxidative and nonoxidative mechanisms and this process is dependent on PMN-EC adhesion.

Adult↗

A polymerase chain reaction assay for detection of the parasite Wuchereria bancrofti in human blood samples.

To identify Wuchereria bancrofti DNA sequences that could be used as the basis for a simple and rapid parasite detection assay, a genomic library of W. bancrofti was constructed and screened for highly repeated DNA. The repeat found with the highest copy number was 195 basepairs (bps) long, 77% AT, and 300 copies per haploid genome. This sequence was designated the Ssp I repeat because it has a unique recognition site for that restriction endonuclease in all or most of the repeat copies. The Ssp I repeat DNA family is dispersed, genus-specific, and exists in all of the different geographic isolates of W. bancrofti tested. Based on DNA sequence analysis of this repeat, we have developed an assay to detect very small quantities of W. bancrofti DNA using the polymerase chain reaction (PCR). With this PCR assay, the Ssp I repeat was detected in as little as 1 pg of w. bancrofti genomic DNA (about 1% of the DNA in one microfilaria) added to 100 microliters of human blood. The PCR assay also amplified Ssp I repeat DNA from geographic isolates of W. bancrofti from around the world but not from other species of filariae or from human or mosquito DNA. Microfilaria-positive human blood samples collected in Mauke, Cook Islands were shown to be Ssp I PCR-positive, while microfilaria-negative samples were PCR-negative. The specificity and sensitivity of the Ssp I PCR assay indicates that this approach has significant potential for improved screening of large human populations for active W. bancrofti infection.

Animals↗

Exposure of the peritoneal cavity to air regulates early inflammatory responses to surgery in a murine model.

Factors in circulating air may play a role in immune responses after surgery through induction of gut-derived lipopolysaccharide (LPS) translocation across the gut. CD-1 mice were randomized to one of four treatment groups: controls, laparoscopy with carbon dioxide inflation, laparoscopy with air inflation and laparotomy. The peritoneal and systemic immune response was assessed by evaluating peritoneal macrophage, blood monocyte and neutrophil activity. In a second study, the effect of each of the treatments on fluorescein isothiocyanate (FITC)-LPS translocation across the gut was assessed. There were significant (P < 0.05) increases in peritoneal tissue macrophage release of superoxide and tumour necrosis factor after laparoscopy with air and laparotomy compared with control procedures and carbon dioxide laparoscopy. However, peritoneal macrophage FITC-Candida albicans ingestion was significantly decreased after air laparoscopy and laparotomy compared with controls and carbon dioxide laparoscopy (P < 0.05). These findings correlated with a significant (P < 0.05) decrease in CD11b expression. Significant translocation into the peritoneal cavity and systemic circulation occurred after air laparoscopy and laparotomy only. Factors in circulating air can induce LPS translocation and subsequent stimulation of postoperative immune responses. The beneficial effects of laparoscopic surgery may be explained by the minimal air contamination of the peritoneal cavity.

Abdomen↗

Four-year review of cigarette ingestions in children.

The objective of our study was to assess the demographics, incidence, types of symptoms, and outcomes of cigarette product ingestions in children. The study was a retrospective database review. Seven hundred children under six years of age ingesting cigarettes or cigarette butts reported to a Poison Control Center between 1988 and 1991. Among 143 patients (20.4%) with symptoms, vomiting was the only symptom in 138 (98.6%) and occurred in less than 20 minutes in 104 (74.3%). The five remaining patients (two with vomiting, three without) developed transient lethargy or irritability that completely resolved. Forty-four of 700 patients ingested potentially toxic amounts and were referred to the emergency department; three were lost to follow-up. Initially asymptomatic patients never developed symptoms. Symptomatic patients improved without sequelae. No patient developed seizures. We concluded that significant toxicity from the ingestion of cigarette products in children is rare. Vomiting within 20 minutes is the most common symptom. Its absence predicts a favorable outcome, even when large amounts are suspected to have been ingested.

Decision Trees↗