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P Hayes

Publications and source records attributed to P Hayes.

At least 73 records · Page 4Linked to original sources
PubMed1994

A novel initiator/promoter element within the CD45 upstream region.

Transcripts of the murine hematopoietic cell surface antigen CD45 (also known as Ly-5, LCA, T200 and B220) initiate at three distinct sites--P1a, P1b and P2--within the upstream region, though P1b is the major site of initiation in lymphoid cells. In our studies of the CD45 upstream region, we identified a cluster of nucleotides comprising the P2 start site, called the TC box, that acts as a minimal promoter for transcription from the P2 site. Thus, the TC box is functionally analogous to elements called initiators that direct RNA polymerases to begin transcription at specific positions. However, in contrast with other initiators, the CD45 TC box directs activated tissue specific expression. The TC initiator, therefore, may provide an effective means to achieve broad expression of exogenously introduced genes in immunologically relevant cells.

Animals↗
PubMed1994

Acetylcysteine as a cytoprotective antioxidant in patients with severe sepsis: potential new use for an old drug.

OBJECTIVE: To stimulate debate regarding a potential new use for acetylcysteine as a cellular antioxidant in severely septic patients with systemic inflammatory response syndrome (SIRS). DATA SOURCES: A MEDLINE review of published animal, human, and laboratory studies relating to the cytopathogenic effects of active radicals in SIRS and the protective effects of acetylcysteine and glutathione. STUDY SELECTION: Few studies were available so all studies pertinent to the objective were reviewed. DATA EXTRACTION: Clinical and basic science data from the available trials of the effects of acetylcysteine on active radical production or active radical cell injury were extrapolated to predict the effect of acetylcysteine on human sepsis. DATA SYNTHESIS: Severe sepsis is a major cause of SIRS. Much of the cellular injury associated with SIRS is mediated by active radicals produced by inflammatory cells that overwhelm endogenous antioxidants. Reduced glutathione is a crucial intracellular antioxidant that becomes depleted during SIRS. Regeneration of glutathione can be achieved by acetylcysteine, which unlike glutathione itself penetrates cells. In animal models of sepsis and lung injury, acetylcysteine mitigates the cytopathologic effects of SIRS. In humans, clinical benefit has been demonstrated in the SIRS of established fulminant hepatic failure. CONCLUSIONS: The data do not as yet lead to any firm conclusions regarding the value of acetylcysteine in the management of SIRS in severe sepsis. The animal and human studies are, however, sufficiently encouraging to warrant formal trials to test the hypothesis that acetylcysteine therapy has a cytoprotective effect in sepsis.

Acetylcysteine↗
PubMed1994

Gene therapy for cystic fibrosis in humans by liposome-mediated DNA transfer: the production of resources and the regulatory process.

The number of clinical trials using gene transfer technology, either active or under discussion, is increasing rapidly. However, little information is available describing the regulatory procedures or safety specifications that must be considered before initiation of such trials in Europe. We describe the procedure used by our group to produce resources for the first stage of a phase I trial of liposome-mediated gene therapy for cystic fibrosis. The current lack of written and co-ordinated guidance from the numerous interested regulatory agencies within the UK and Europe makes determination of the appropriate safety specifications and procedures for these novel trials difficult, as does the fact that some new agencies (such as the Genetic Therapy Advisory Committee in the UK) and some which are unfamiliar with clinical trials (such as the Department of the Environment) are involved as well as the Medicines Control Agency. In addition, we estimate that the realistic cost of these trials, which in many cases will have to be covered from research budgets provided by government agencies or medical charities, could lead to delays in the clinical application of this important new therapeutic strategy.

Base Sequence↗
PubMed1994

My license is not on the line: the art of delegation.

Teaching staff and charge nurses how to skillfully delegate responsibility to assistive personnel can alleviate fears and mistrust. A workshop defining the art of delegation leaves nurses feeling more in control and less victimized. As a result, they begin to see delegation as a viable solution.

Humans↗
PubMed1993

Prevention and treatment of Staphylococcus aureus infections with recombinant cytokines.

Antibiotic therapy is only moderately efficacious for bovine Staphylococcus aureus mastitis. We have used recombinant bovine cytokines to activate the natural host defenses, to prevent and treat bovine mastitis. Uninfected mammary glands infused with GM-CSF or IL-2 increased the percentage of phagocytic cells in the milk by 2-3 fold. IL-1 increased the number of polymorphonuclear cells in the milk, enhanced their inducible oxygen radical formation, and had no effect on phagocytosis. Treatment with IL-2 increased the number of polymorphonuclear cells in the milk, enhanced their inducible oxygen radical formation, and enhanced their phagocytosis. GM-CSF had no effect on the number polymorphonuclear cells in the milk but enhanced their inducible oxygen radical formation, and enhanced their phagocytosis. All cytokines were effective in preventing S. aureus infections (20-100%). 52% of all chronically infected mammary gland quarters treated with three doses of IL-2 responded to therapy and 32% of the treated quarters remained cured. 75% of all mammary glands treated with three doses of IL-1 beta responded to therapy by clearing the infection and 22% of the treated glands remained cured. These studies demonstrate that recombinant bovine cytokines can be used effectively to prevent infections as well as treat established chronic infection.

Animals↗
PubMed1993

Who are clinicians?

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Clinical Nursing Research↗
PubMed1993

Replicative studies.

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Clinical Nursing Research↗
PubMed1992

A cDNA clone for a novel nuclear protein with DNA binding activity.

In an effort to identify trans-acting factors regulating specific genes, we cloned a novel human gene, DBP-5. The cDNA clone contains a predicted open reading frame coding for a potential 1,179 amino acid protein. The mRNA corresponding to DBP-5 is ubiquitously distributed, and the gene is phylogenetically conserved. Immunofluorescence analyses with several cell lines indicate that the protein is localized to the nucleus. Sequence analysis revealed unusual features of the predicted protein structure, including four completely conserved repeats. The phylogenetic conservation of DBP-5, the ubiquity of its expression, its nuclear localization, and its ability to bind DNA sequences, raise the possibility that DBP-5 may play a role in the organization of interphase chromatin and/or in transcriptional regulation.

Amino Acid Sequence↗
PubMed1992

Sensitive detection of trypanosomes in tsetse flies by DNA amplification.

African trypanosome species were identified using the Polymerase Chain Reaction (PCR) by targeting repetitive DNA for amplification. Using oligonucleotide primers designed to anneal specifically to the satellite DNA monomer of each species/subgroup, we were able to accurately identify Trypanosoma simiae, three subgroups of T. congolense, T. brucei and T. vivax. The assay was sensitive and specific, detecting one trypanosome unequivocally and showing no reaction with non-target trypanosome DNA or a huge excess of host DNA. The assay was used to identify developmental stage trypanosomes in the tsetse fly. The use of radioisotopes was not necessary and mixed infections could be detected easily by incorporating more than one set of primers in a single reaction. The use of crude preparations of template made the process very rapid. The methodology should be suitable for large-scale epidemiological studies.

Animals↗
PubMed1992

Physiologic effects of administration of interleukin 1 beta in cows.

The immunomodulating polypeptide interleukin 1 beta (IL-1 beta) has been shown to be homologous to osteoclast-activating factor and is capable of stimulating increased osteoclastic bone resorption. This effect prompted an investigation into the potential use of IL-1 beta for prevention of parturient paresis, a disease of dairy cows characterized by hypocalcemia and poor osteoclastic resorption of bone. Six nonpregnant cows were treated with a high dosage of IL-1 beta (166 ng/kg of body weight) every 8 hours for 4 days. The IL-1 beta treatment significantly (P < 0.05) increased urinary hydroxyproline excretion, an index of osteoclast activity, indicating that bone calcium resorption might be stimulated by IL-1 beta treatment of cows. However, IL-1 beta treatment also caused transient fever, inappetence, increased pulse and respiratory rate, and diuresis. The acute, but transient, effect of IL-1 beta treatment was to cause a decrease in plasma calcium and phosphorus concentrations. The pleiotropic effects of IL-1 beta administration negated the positive effects on osteoclastic bone resorption, and indicates that this cytokine may be of minimal benefit for prevention of parturient paresis.

Animals↗