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Biomedical subjects

J Barker

Publications and source records attributed to J Barker.

At least 91 records · Page 5Linked to original sources
PubMed1995

Intraphagocytic growth induces an antibiotic-resistant phenotype of Legionella pneumophila.

The antimicrobial susceptibilities of Legionella pneumophila isolates grown either in U937 human monocytic cells or in Acanthamoeba polyphaga were studied after release from the host cells without further subculture. Time-survival studies showed that exposure of L. pneumophila cells, gown exclusively in vitro, to 5 micrograms of rifampin per ml resulted in at least 99% killing after 6 h and no detectable survivors at 24 h. Similar rates of killing were observed for in vitro-grown cells tested by exposure to ciprofloxacin. Conversely, time-survival studies revealed that macrophage-grown and amoeba-grown cells were ca. 1,000-fold more resistant to the activities of both drugs. Macrophage-grown cells treated with 5 micrograms of rifampin per ml showed 70 and 62% survival after 6 and 24 h, respectively. Intracellularly grown legionellae were also highly resistant to erythromycin (8 microgram/ml). After 24 h of exposure to the drug, there was 70 and 60% survival for amoeba-grown and macrophage-grown legionellae, respectively, whereas in vitro-grown cells showed a 2-log10 reduction in viable count. when intracellularly grown L. pneumophila cells were subcultured in broth for 48 h, they reverted to the phenotype characteristic of in vitro growth. Morphologically, the cells were larger than their intracellularly grown counterparts and resistance characteristics were lost. The susceptibilities of the subcultured cells to all three drugs were similar to those of Legionella cells grown exclusively in vitro. In view of these findings, the successful treatment of Legionnaires disease may be related as much to the resistance phenotype induced by intramacrophage growth as to the ability of the antibiotic to enter phagocytic cells.

Acanthamoeba↗
PubMed1995

Ethylene oxide sterilization update.

Ethylene oxide (EtO) sterilization technology faced an uncertain future a few years ago, but this situation has now changed. The factors involved and the advantages offered by the latest technically sophisticated EtO technology are reviewed in this article.

Chlorofluorocarbons↗
PubMed1995

Altered vascular endothelium integrin expression in psoriasis.

Considerable evidence indicates that microvascular changes observed in psoriasis are a result of vascular proliferation. A critical step in the sequence of events leading to neovascularization involves interactions between endothelial cells and extracellular matrix proteins mediated in part by the integrin family of adhesion molecules. A number of endothelial integrins have been shown to participate in neovascularization, including members of the beta 1, beta 3, and beta 4 subfamilies. To investigate the role of these integrins in psoriasis, specimens of lesional and nonlesional skin were taken from 10 patients with active, untreated plaque disease. Vascular endothelium was labeled with monoclonal antibodies specific for alpha 2, alpha 5, alpha 6, beta 1, av beta 3, and beta 4 integrins. The use of image analysis permitted quantification of immunoperoxidase staining and comparison of endothelial labeling in lesional and nonlesional skin. There was a significant increase in endothelial staining of av beta 3 integrin in lesional compared with nonlesional skin, both in superficial and deep vasculature. In contrast, there was a significant decrease in endothelial beta 4 staining in lesional compared with nonlesional superficial dermal vessels, alpha 2, alpha 5, alpha 6, and beta 1 staining showed no significant difference between the two groups. These results demonstrate an important role of av beta 3 and beta 4 integrins in the microvascular changes of psoriatic lesions.

Adult↗
PubMed1994

In vivo microscopy of microcirculatory injury in skeletal muscle following ischemia/reperfusion.

While the sequence of biochemical and cellular events in the pathogenesis of ischemia/reperfusion injury is increasingly well understood, the way that these processes interact at the level of microcirculation to promote a distinctive reperfusion injury is less well defined. It is becoming clear, however, that these processes are initiated at the level of microcirculation, and that microcirculatory damage may precede actual tissue injury. Such damage causes microvascular no-reflow, which in turn effectively prolongs the time of tissue ischemia and extends tissue injury. Recently, microcirculatory models have been adapted for study of the microvascular effects of ischemia/reperfusion. We have used a new in vivo mouse cremaster muscle model to study, by direct and quantitative measurement, the acute microvascular changes involved in ischemia/reperfusion. Previously described changes in capillary perfusion and venular leukocyte adhesion were observed in this model following reperfusion after prolonged ischemia (4-6 hours). We have further characterized an intense reactive vasoconstriction or vasospasm that occurs after prolonged ischemia; this vessel reaction may represent an important overlooked cause of no-reflow following ischemia/reperfusion. This article summarizes our work in the context of other available methods that have been used to define the microvascular changes of ischemia/reperfusion.

Animals↗
PubMed1994

Tracheal mucosal edema in hydrostatic pulmonary edema.

Airway edema has been described in heart failure, and, in animal experiments, airway narrowing was observed with elevated left atrial pressure (Pla). On the basis of double-indicator-dilution principles using helium and dimethylether, we were able to measure a water compartment of the tracheal mucosa (VH2O) in dogs. Hypervolemia with an attendant increase in Pla caused by infusion of 2 liters of dextran increased VH2O from 368 +/- 71 (SE) to 794 +/- 177 microliters (P < 0.01). Pulmonary arterial wedge and central venous pressures (Pcv) rose concomitantly. Increases in pulmonary arterial wedge and Pcv by a left atrial balloon catheter produced similar increases in VH2O, whereas increases in Pcv alone by a right atrial balloon did not increase VH2O. Increasing VH2O by dextran infusion was associated with an increase in pulmonary resistance from 1.16 +/- 0.19 to 2.15 +/- 0.24 cmH2O.l-1.s (P < 0.01). These observations show that fluid accumulation in the lung during pulmonary congestion also involves extraparenchymal airways and is related to Pla rather than right atrial pressure. This indicates that sufficient collateral drainage exists during right-sided but not left-sided pressure elevations.

Anesthesia↗
PubMed1993

Effect of silicon on gastrointestinal absorption of aluminium.

The reported geographical association between Alzheimer's disease and levels of aluminium (Al) in water supplies may reflect the inverse relation between Al and silicon (Si) concentrations in water, and the potential for Si to reduce the bioavailability of the metal. We tested this hypothesis using isotopic 26Al tracer administered orally to five healthy volunteers in the presence and absence of Si. Dissolved Si, at a concentration found in some water supplies (100 mumol/L), reduced the peak plasma 26Al concentration to 15% of the value obtained in the absence of Si. The results indicate that dissolved Si is an important factor in limiting the absorption of dietary Al.

Administration, Oral↗
PubMed1993

Many spinal cord cells transiently express low molecular weight forms of glutamic acid decarboxylase during embryonic development.

At early developmental stages in the rat spinal cord (embryonic day 13), when neuronal progenitors are still proliferating, most differentiating neurons express truncated forms of glutamic acid decarboxylase (GAD) (approximately 25 kDa) which are the products of alternative splicing of the GAD67 gene. These truncated proteins do not appear to synthesize gamma-aminobutyric acid (GABA). The amino acid is detected in cells only after alternative splicing of the GAD67 gene generates a full-length, 67 kDa enzymatically active form of GAD. Both the 67 kDa GAD and GABA colocalize and appear diffusely distributed in the cytoplasm of embryonic neurons. GABA does not appear associated with synaptic vesicles until after birth, when its intracellular distribution becomes punctate and it colocalizes with synaptophysin. At this time, it also colocalizes with an immunologically distinct 65 kDa GAD protein encoded by a second GAD gene (GAD65). Expression of different GAD-related proteins with distinct intracellular distributions during development suggests that GABA, the product of these enzymes, may have trophic or metabolic roles during spinal cord differentiation.

Animals↗
PubMed1993

Influence of intra-amoebic and other growth conditions on the surface properties of Legionella pneumophila.

The surface properties of Legionella pneumophila were examined by analyzing outer membrane (OM) proteins, lipopolysaccharides (LPS), and cellular fatty acids after growth within Acanthamoeba polyphaga and in vitro under various nutrient-depleted conditions. Intra-amoeba-grown legionellae were found to differ in several respects from cells grown in vitro; most notably, they contained a 15-kDa OM protein and a monounsaturated straight-chain fatty acid (18:1(9)). These compounds were also found in abundant quantities in the host amoeba. Immunoblot analysis of intra-amoeba-grown legionellae with antiacanthamoebic serum revealed that both the bacterial whole cells and Sarkosyl-extracted OMs contained amoebic antigens. The findings suggest that the 15-kDa OM protein is likely to be of amoebic origin and associates with the OM of the bacterium. It is proposed that disruption of amoebic membranes, as a result of intra-amoebic infection, may liberate macromolecules, including a 15-kDa polypeptide, a major constituent of the amoebic membrane, which adhere to the surface of the legionellae. Growth under specific nutrient depletions also had a significant effect on the surface composition of L. pneumophila. Cells grown under phosphate depletion were markedly sensitive to protease K digestion and contained lower levels of LPS, as observed by silver staining of the digests on polyacrylamide gels. Intra-amoeba-grown cells contained more bands than the in vitro-grown organisms, reflecting further differences in the nature of the LPS. The whole-cell fatty acids of the phosphate-depleted cells were appreciably different from those of cells grown under other nutritional conditions. We found no evidence for expression of iron-regulated OM proteins under iron depletion.

Acanthamoeba↗
PubMed1993

An audit of distribution and use of guidelines for management of head injury.

Ensuring effective distribution of guidelines is an important step towards their implementation. To examine the effectiveness of dissemination of a guidelines card on management of head injury and determine its usefulness to senior house officers (SHOs), a questionnaire survey was performed in May 1990, after distribution of the cards in induction packs for new doctors and at postgraduate lectures and displaying the guidelines in accident and emergency departments and wards. A further survey, in March 1992, assessed the impact of modifying the distribution. All (175) SHOs working in general surgery, accident and emergency medicine, orthopaedics, and neurosciences on 1 February 1990 in 19 hospitals including two neurosurgical units in Northern region were sent self completion questionnaires about awareness, receipt, use, and perceived usefulness of the guidelines. 131 of 163(80%) SHOs in post responded (median response from hospitals 83% (range 50%-100%)). Over three quarters (103, 79%) of SHOs were aware of the guidelines and 82(63%) had ever possessed a guidelines card. Only 36(44%) acquired the card in the induction pack. 92%(98/107) found them useful and 81% (89/110) referred to them to some extent. Owning and carrying the card and referring to guidelines were associated with departmental encouragement to use the guidelines. Increasing the displays of guidelines in wards and departments and the supply of cards to consultants in accident and emergency medicine as a result of this survey did not increase the number of SHOs who received cards (52/83, 63%), but more (71/83, 86%) were aware of the guidelines. The guidelines were welcomed by SHOs and used in treating patients with head injury, but their distribution requires improvement. Increased use of the guidelines may be achieved by introducing other distribution methods and as a result of encouragement by senior staff.

Craniocerebral Trauma↗
PubMed1992

Novel responses of human skin to intradermal recombinant granulocyte/macrophage-colony-stimulating factor: Langerhans cell recruitment, keratinocyte growth, and enhanced wound healing.

Recombinant granulocyte/macrophage-colony-stimulating factor (rGM-CSF), prepared from Chinese hamster ovary (CHO) cells and Escherichia coli, was administered to 35 patients with the borderline and polar lepromatous forms of leprosy by the intradermal and subcutaneous routes at doses of 7.5-45.0 micrograms/d for 10 d. With each of these doses and routes, increases in the number of circulating eosinophils were noted. After the intradermal injection, the local skin sites demonstrated zones of roughening and micronodularity that appeared within 24-48 h and persisted for more than 6 d. Reinjection of sites led to enhanced areas of epidermal reaction. GM-CSF prepared from CHO cells was a more potent inducer of this effect. GM-CSF given by the subcutaneous route, at higher doses, failed to initiate these changes. At the microscopic level, the epidermis became thickened (+75%) with increased numbers and layers of enlarged keratinocytes. These contained increased numbers of ribosomes and prominent nucleoli, and were imbedded in a looser meshwork of the zona Pellucida. The modified keratinocytes remained MHC class II antigen negative throughout the course of the response. A major change in the dermis was the progressive accumulation of CD1+, Birbeck granule-positive cells. These Langerhans were recognizable at 48 h after intradermal injection and reached maximum numbers by 4 d. During this period the number of epidermal Langerhans cells remained relatively constant. No increment in dermal Langerhans cells occurred when GLM-CSF was injected by the subcutaneous route. No appreciable increase in the numbers of T cells and monocytes was noted, and granulocytes and eosinophils were largely present within the dermal microvasculature. 4-mm punch biopsies taken from injected sites and adjacent controls were compared in terms of the rapidity of wound healing. 22 of 26 sites demonstrated more rapid filling and hemostasis, whereas four were equivalent to controls. We conclude that rGM-CSF, when introduced into the skin, leads to enhanced keratinocyte growth, the selective recruitment of Langerhans cells into the dermis, and enhanced wound healing of the prepared site. There was no evidence of an enhanced cell-mediated response to Mycobacterium leprae, and bacillary numbers remained unchanged.

Adolescent↗
PubMed1992

Continuous culture of neuronal cells from adult human olfactory epithelium.

Cells from the olfactory epithelium of adult human cadavers have been propagated in primary culture and subsequently cloned. These cells exhibit neuronal properties including: neuron-specific enolase, olfactory marker protein, neurofilaments, and growth-associated protein 43. Simultaneously, the cells exhibit nonneuronal properties such as glial fibrillary acidic protein and keratin, the latter suggesting properties of neuroblasts or stem cells. These clonal cultures contain 5-10% of cells sufficiently differentiated to show odorant-dependent cyclic adenosine 3',5'-monophosphate (cAMP) or calcium-release responses when challenged with submicromolar concentrations of odorants. The potential of culturing neuronal cells from patients with neuropsychiatric disorders, such as Alzheimer's disease or schizophrenia, could enable the study of the pathophysiology of these neurons in the culture dish and allow new approaches to the study of mental illness.

Adult↗
PubMed1992

Relationship between Legionella pneumophila and Acanthamoeba polyphaga: physiological status and susceptibility to chemical inactivation.

Survival studies were conducted on Legionella pneumophila cells that had been grown intracellularly in Acanthamoeba polyphaga and then exposed to polyhexamethylene biguanide (PHMB), benzisothiazolone (BIT), and 5-chloro-N-methylisothiazolone (CMIT). Susceptibilities were also determined for L. pneumophila grown under iron-sufficient and iron-depleted conditions. BIT was relatively ineffective against cells grown under iron depletion; in contrast, iron-depleted conditions increased the susceptibilities of cells to PHMB and CMIT. The activities of all three biocides were greatly reduced against L. pneumophila grown in amoebae. PHMB (1 x MIC) gave 99.99% reductions in viability for cultures grown in broth within 6 h and no detectable survivors at 24 h but only 90 and 99.9% killing at 6 h and 24 h, respectively, for cells grown in amoebae. The antimicrobial properties of the three biocides against A. polyphaga were also determined. The majority of amoebae recovered from BIT treatment, but few, if any, survived CMIT treatment or exposure to PHMB. This study not only shows the profound effect that intra-amoebal growth has on the physiological status and antimicrobial susceptibility of L. pneumophila but also reveals PHMB to be a potential biocide for effective water treatment. In this respect, PHMB has significant activity, below its recommended use concentrations, against both the host amoeba and L. pneumophila.

Acanthamoeba↗
PubMed1992

Rotavirus diarrhoea in children in the highlands of Papua New Guinea.

Children from the highlands of Papua New Guinea, hospitalized for severe diarrhoea, were examined for clinical signs and the presence of rotaviruses. Rotavirus was detected in faecal samples from 68% (23/38) of patients examined. In contrast to other studies, an excess of respiratory symptoms was not observed and the infection rate of disease due to rotavirus was relatively high in children under 6 months of age. In an environment where pigs and humans share close contact a rotavirus strain infecting piglets was also demonstrated.

Animals↗