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Biomedical subjects

P G Murphy

Publications and source records attributed to P G Murphy.

At least 37 records · Page 2Linked to original sources
PubMed2001

CHST1 and CHST2 sulfotransferase expression by vascular endothelial cells regulates shear-resistant leukocyte rolling via L-selectin.

Sulfation is an essential component of the selectin ligands, potentially mediated by members of a new family of carbohydrate sulfotransferases. In this study, we assessed the contributions of CHST1, CHST2, CHST3, and CHST4 in producing functional L-selectin ligands. Human umbilical vein endothelial cells predominantly expressed CHST1 and CHST2 transcripts with low levels of CHST3 mRNA, while cytokine activation up-regulated CHST2 expression and induced low-level CHST4 expression. A human umbilical vein endothelial cell line, EA.hy926, displayed functional L-selectin ligands that correlated with CHST1 and CHST2 expression in the absence of CHST4 expression. Increased CHST1 or CHST2 expression by a cell line expressing low-level L-selectin ligand activity during in vitro flow chamber assays increased rolling leukocyte numbers, reduced rolling velocities, and enhanced leukocyte rolling under higher shear stresses. These results suggest that CHST1 and CHST2 contribute to the generation of optimal L-selectin ligands in vascular endothelial cells at sites of inflammation.

Animals↗
PubMed2001

Occurrence of Campylobacter spp. in water in Northern Ireland: implications for public health.

The occurrence of Campylobacter spp was examined in a variety of waters in Northern Ireland. Conventional cultural techniques were employed with 768 water specimens, including drinking waters (tap, spring, bore hole and bottled) and recreational waters (swimming pool, lough, river and sea). Positive waters included 1/11 (9.1%) drinking water from untreated well water, as well as 5/12 (41.7%) untreated surface waters from loughs and 7/8 (87.5%) untreated river waters. Overall, untreated surface waters may represent a source of contamination with Campylobacter spp. in Northern Ireland, where they have a recreational involvement or are used as a drinking source by man or agricultural livestock. Therefore waterborne campylobacteriosis should be considered in patients presenting with acute enteritis and a history of participation in water sports/activities. As faecal coliform organisms have been previously shown to be poor markers of water quality, especially for Campylobacter spp, new criteria should be established to assess the risk of this infection and to evaluate and monitor the quality of water used for recreational purposes.

Bathing Beaches↗
PubMed2000

Reciprocal actions of interleukin-6 and brain-derived neurotrophic factor on rat and mouse primary sensory neurons.

In low-density, serum-free cultures of neurons from embryonic rat dorsal root ganglia, interleukin-6 supports the survival of less than one third of the neurons yet virtually all of them bear interleukin-6 alpha-receptors. A finding that might explain this selectivity is that interleukin-6 acts on sensory neurons in culture through a mechanism requiring endogenous brain-derived neurotrophic factor. Antibodies or a trkB fusion protein that block the biological activity of brain-derived neurotrophic factor synthesized by dorsal root ganglion neurons also block the survival-promoting actions of interleukin-6 on these neurons. Two results indicate that interleukin-6 influences synthesis of brain-derived neurotrophic factor in adult dorsal root ganglion neurons. Intrathecal infusion of interleukin-6 in rats increases the concentration of brain-derived neurotrophic factor mRNA in rat lumbar dorsal root ganglia. The induction of brain-derived neurotrophic factor in dorsal root ganglion neurons that is seen after nerve injury in rats or wild-type mice is severely attenuated in mice with null mutation of the interleukin-6 gene. In brief, the ability of interleukin-6 to support the survival of embryonic sensory neurons in vitro depends upon the presence of endogenous brain-derived neurotrophic factor and the induction of brain-derived neurotrophic factor in injured adult sensory neurons depends upon the presence of endogenous interleukin-6.

Age Factors↗
PubMed1999

L-selectin ligands expressed by human leukocytes are HECA-452 antibody-defined carbohydrate epitopes preferentially displayed by P-selectin glycoprotein ligand-1.

Leukocytes express L-selectin ligands critical for leukocyte-leukocyte interactions at sites of inflammation. The predominant leukocyte L-selectin ligand is P-selectin glycoprotein ligand-1 (PSGL-1), which displays appropriate sialyl Lewis x (sLex)-like carbohydrate determinants for L-selectin recognition. Among the sLex-like determinants expressed by human leukocytes is a unique carbohydrate epitope defined by the HECA-452 mAb. The HECA-452 Ag is a critical component of L-selectin ligands expressed by vascular endothelial cells. However, HECA-452 Ag expression on human leukocyte L-selectin ligands has not been assessed. In this study, the HECA-452 mAb blocked 88-99% of neutrophil rolling on, or attachment to, adherent cells expressing L-selectin in multiple experimental systems. A function-blocking anti-PSGL-1 mAb also inhibited L-selectin binding to neutrophils by 89-98%. In addition, the HECA-452 and anti-PSGL-1 mAbs blocked the majority of P-selectin binding to neutrophils. Western blot analysis revealed that PSGL-1 immunoprecipitated from neutrophils displayed HECA-452 mAb-reactive determinants and that PSGL-1 was the predominant scaffold for HECA-452 Ag display. Leukocyte L-selectin ligands also contained sulfated determinants since culturing ligand-bearing cells with NaClO3 abrogated L-selectin binding. Consistent with this, human neutrophils expressed mRNA encoding five different sulfotransferases associated with the generation of selectin ligands: CHST1, CHST2, CHST3, TPST1, and HEC-GlcNAc6ST. Therefore, the HECA-452-defined carbohydrate determinant displayed on PSGL-1 represented the predominant L-selectin and P-selectin ligand expressed by neutrophils.

Animals↗
PubMed1999

Nature of the retrograde signal from injured nerves that induces interleukin-6 mRNA in neurons.

In previous studies, interleukin-6 was shown to be synthesized in approximately one-third of lumbar dorsal root ganglion neurons during the first week after nerve transection. In present studies, interleukin-6 mRNA was found to be induced also in axotomized facial motor neurons and sympathetic neurons. The nature of the signal that induces interleukin-6 mRNA in neurons after nerve injury was analyzed. Blocking of retrograde axonal transport by injection of colchicine into an otherwise normal nerve did not induce interleukin-6 mRNA in primary sensory neurons, but injection of colchicine into the nerve stump prevented induction of interleukin-6 mRNA by nerve transection. Therefore, it was concluded that interleukin-6 is induced by an injury factor arising from the nerve stump rather than by interruption of normal retrograde trophic support from target tissues or distal nerve segments. Next, injection into the nerve of a mast cell degranulating agent was shown to stimulate interleukin-6 mRNA in sensory neurons and systemic administration of mast cell stabilizing agents to mitigate the induction of interleukin-6 mRNA in sensory neurons after nerve injury. These data implicate mast cells as one possible source of the factors that lead to induction of interleukin-6 mRNA after nerve injury. In search of a possible function of inducible interelukin-6, neuronal death after nerve transection was assessed in mice with null deletion of the interleukin-6 gene. Retrograde death of neurons in the fifth lumbar dorsal root ganglion was 45% greater in knockout than in wild-type mice. Thus, endogenous interleukin-6 contributes to the survival of axotomized neurons.

Animals↗
PubMed1999

Pseudoaneurysm of the profunda femoris artery due to intertrochanteric fracture of the hip.

Arterial injury caused by hip fracture is a rare event. We report a case of pseudoaneurysm of the profunda femoris artery that presented 4 weeks after correction of an intertrochanteric hip fracture with a dynamic hip screw. The diagnosis was confirmed by Duplex ultrasound scanning, and it was treated by ligation of the profunda femoris artery at the level of the pseudoaneurysm.

Aged↗
PubMed1999

Urease-positive thermophilic strains of Campylobacter isolated from seagulls (Larus spp.).

Three strains of urease-positive thermophilic Campylobacter (UPTC), designated A1, A2 and A3, were identified by biochemical characterization after isolation from faeces of seagulls in Northern Ireland in 1996. The biochemical characteristics of the strains were identical to those of strains described previously. Analysis by pulsed-field gel electrophoresis (PFGE) after separate digestion with ApaI and SmaI demonstrated that the respective PFGE profiles were indistinguishable. The PFGE analysis also suggested that the genomes were approximately 1810 kb in length. This is the first example of the isolation of UPTC from flying homoiothermal animals, i.e. from seagulls (Larus spp.).

Animals↗
PubMed1999

Endogenous interleukin-6 contributes to hypersensitivity to cutaneous stimuli and changes in neuropeptides associated with chronic nerve constriction in mice.

Partial nerve injury is a potential cause of distressing chronic pain for which conventional analgesic treatment with opiates or anti-inflammatory agents is not very effective. Constriction nerve injury, widely used to study neuropathic pain, was shown here to induce interleukin-6 (IL-6) mRNA in a subset of rat primary sensory neurons. When we inflicted chronic nerve constriction on mice with null mutation of the IL-6 gene, the hypersensitivity to cutaneous heat and pressure that is induced in wild-type mice was not evident, the loss of substance P in sensory neurons was excessive and the induction of galanin in central sensory projections was reduced. In additional experiments, intrathecal infusion of IL-6 in rats was shown to stimulate synthesis of galanin in approximately one-third of lumbar dorsal root ganglion neurons. The results of these experiments indicate that endogenous IL-6 mediates some of the hypersensitive responses that characterize peripheral neuropathic pain, and influences two neuropeptides that have been implicated in pain transmission.

Animals↗
PubMed1998

Galanin expression in neuropathic pain: friend or foe?

We investigated a possible link between galanin expression and evoked pain accompanying painful partial sciatic nerve lesions. Increased galanin immunoreactivity (IR) in the dorsal horn, in gracile nucleus, and in sensory neurons following chronic constriction injury (CCI) compared to complete sciatic transection suggested a facilitatory role in thermal and mechanical hypersensitivity (allodynia). We therefore investigated the effects of endogenous interleukin-6 (IL-6) and nerve growth factor (NGF) on allodynia and neuropeptide expression. IL-6 knockout mice showed decreased allodynia and galanin-IR compared to wild-type mice, but also decreased substance P (SP)-IR in the dorsal horn. Anti-NGF-treated rats with CCI also showed decreased allodynia and SP-IR, but increased galanin-IR in the dorsal horn. These results suggest that evoked pain is more tightly linked to SP than to galanin expression. If galanin's effects are inhibitory as the bulk of the literature suggests, its effects are subordinate to those of SP and to other changes following CCI.

Animals↗
PubMed1998

Correction of soft tissue contractures of the wrist using the Ilizarov technique.

The Ilizarov technique can allow new histiogenesis of soft tissue as well as bone. Three cases of wrist contracture successfully treated by this method are described. One patient had transient superficial pin site infections. There were no other complications. At 2 years follow-up there was no recurrence of contractures.

Adolescent↗
PubMed1998

Antimicrobial susceptibility of bacteria isolated from orthopedic implants following revision hip surgery.

The susceptibilities of 49 isolates recovered from orthopedic implants to seven antimicrobial agents were evaluated by the broth microdilution method. Ciprofloxacin and vancomycin were more active than gentamicin, representing aminoglycosides which are routinely incorporated into bone cement, and also more active than the peroperative antimicrobial agents cefamandole and erythromycin. The use of ciprofloxacin and vancomycin in vivo, therefore, warrants further evaluation.

Anti-Bacterial Agents↗