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P M Murphy

Publications and source records attributed to P M Murphy.

144 records · Page 8Linked to original sources

The formyl peptide chemoattractant receptor is encoded by a 2 kilobase messenger RNA. Expression in Xenopus oocytes.

Activation of the formyl peptide chemoattractant receptor (FPCR) of phagocytic cells mobilizes intracellular calcium stores and affects the plasma membrane potential. Affinity crosslinking of FPCR has demonstrated a 60-80 kDa glycoprotein, with core peptide of 32 kDa. It is not known whether functional FPCR is this single peptide or requires multiple subunits. We used Xenopus oocyte expression system to determine the size of mRNA required for synthesis of functional FPCR. Injection of oocytes with poly(A)+ RNA from HL60 cells differentiated to the granulocyte phenotype resulted in acquisition of formyl peptide-specific responses (inward transmembrane current with a reversal potential consistent with a chloride conductance, and calcium efflux). FPCR activity expressed in oocytes had a ligand concentration dependence, ligand structure dependence and pertussis toxin sensitivity similar to those reported in phagocytic cells. When RNA was size fractionated, a single peak of FPCR activity at 2 kilobases was observed after injection of mRNA into oocytes. Our data strongly suggest that FPCR is composed of a single-sized polypeptide.

Amino Acid Sequence↗

Marked disparity in incidence of bacterial infections in patients with the acquired immunodeficiency syndrome receiving interleukin-2 or interferon-gamma.

STUDY OBJECTIVE: To compare the infectious complications that occurred during trials of immunomodulatory agents in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A survey of two cohorts of patients with AIDS who participated in nonrandomized, unblinded, non-placebo-controlled investigations of the toxicity and efficacy of interleukin-2 and interferon-gamma. SETTING: Clinical research unit in a tertiary care center. PATIENTS: Consecutive samples of 52 patients given interleukin-2 and 22 patients given interferon-gamma. Selection criteria for referred patients included a diagnosis of AIDS, hemoglobin level of greater than 100 g/L (2.0 mg/dL), creatinine level of less than 176.8 mumol/L, bilirubin level of less than 25.65 mumol/L (1.5 mg/dL), the absence of active infection, and the absence of other drug therapy for 2 weeks before entry. Four patients given interleukin-2 failed to complete the study. INTERVENTIONS: Intravenous infusion of natural-product or recombinant human interleukin-2, 250 to 10,000,000 U/day for 23.4 +/- 1.5 (SE) days, or recombinant human interferon-gamma, 0.001 to 1.0 mg/m2.d for 17.7 +/- 4.8 days. MEASUREMENTS AND MAIN RESULTS: Twenty nonopportunistic bacterial infections occurred in 17 of 52 patients given interleukin-2, whereas non occurred in 22 patients given interferon-gamma (P less than 0.05). Bacteremia accounted for 12 of the infections. Staphylococcus aureus and gram-negative bacilli accounted for 16 of the isolates. Opportunistic infections occurred in 6 patients during interleukin-2 infusion and in 1 patient during interferon-gamma infusion (P greater than 0.5). Clinical and immunologic variables and methods of management of intravenous catheters were similar in the two groups. CONCLUSIONS: A marked disparity in infection with nonopportunistic bacteria, but not with opportunistic organisms, occurred in patients with AIDS who were treated with interleukin-2 as compared with those who were treated with interferon-gamma. A high incidence of bacteremia and localized bacterial infection should be anticipated in patients with AIDS who receive interleukin-2.

Acquired Immunodeficiency Syndrome↗

Detection of multiple forms of Gi alpha in HL60 cells.

Comparison of cDNA sequences from multiple sources predicts a genus of highly homologous but structurally distinct G protein alpha-subunits, designated as Gi alpha, that may include the alpha-subunit of the functionally defined adenylate cyclase inhibitory G protein. Using specific oligonucleotide probes on Northern blots, we show that Gi alpha-2 and Gi alpha-3, but not Gi alpha-1, are expressed in HL60 cells. Antisera raised against synthetic peptides from regions predicted to be conserved (AS6) and divergent (LE3) among Gi alpha subtypes bind to a 40 kDa protein in Western blots of HL60 membranes. AS6 identifies an additional protein at 41 kDa. Thus, Northern blot and immunoblot results show that at least two Gi alpha subtypes, a 40 kDa protein likely to correspond to Gi alpha-2 and a 41 kDa protein possibly representing Gi alpha-3, may be expressed in a single cell type.

Amino Acid Sequence↗

The relationship between curative factors perceived by patients in their psychotherapy and treatment outcome: an exploratory study.

Researchers are becoming increasingly interested in those aspects of the curative process that are not specific to any treatment approach. Two hypotheses were tested in this study: (1) that patients would, among those factors they suggest as helpful in their treatment, develop a list of consistently suggested curative factors; (2) that some of the consistently suggested factors will have a direct positive relationship to outcome. Twenty-four out-patients were interviewed. Both hypotheses were supported. Two factors emerged as having a significant influence on outcome: they were advice and the understanding of the therapist.

Humans↗

Cure of bacille Calmette-Guérin vaccination abscesses with erythromycin.

Postvaccination subcutaneous abscess due to bacille Calmette-Guérin (BCG) is an uncommon complication and is especially rare in the United States, where the general population is not vaccinated with BCG. This type of abscess is usually chronic, and optimal therapy has not been defined. Two Americans, a husband and wife, underwent primary BCG vaccination abroad and developed chronic subcutaneous abscesses at the primary inoculation site. Four months after vaccination, Mycobacterium bovis strain BCG was cultured from material aspirated from both lesions. Direct susceptibility studies revealed a minimal inhibitory concentration of less than 3.0 micrograms of erythromycin/mL for both isolates. Erythromycin was given orally to the husband and wife for 3 and 4 weeks, respectively, during which time complete healing occurred in both cases.

Abscess↗

A new sterile bicarbonate dialysis solution for use during cardiopulmonary bypass.

Adding a dialysis filter to the perfusion circuit at the end of cardiopulmonary bypass (CPB) has become an accepted means of reducing potassium rapidly and safely. Rapid removal of solute requires a dialysate for diffusion, and peritoneal dialysis solutions have been the standard because of availability, although occasionally normal saline or bicarb/ saline mixtures are used. Cardioplegia solution is high in glucose as well as potassium and, with many diabetic patients undergoing CPB, it is desirable to minimize glucose loads. In this prospective cohort study, six patients received a commercially available sterile bicarbonate dialysate prepared in a point of care fashion. From the cardiovascular data base, four control patients (receiving lactate based dialysis solution during CPB) were matched for age, surgery type, body surface area (BSA), and pump duration for each of the six patients receiving bicarbonate dialysate. All of the control patients were dialysed against lactate buffered peritoneal dialysis solution. Plasma levels of potassium, glucose, and bicarb were measured before and after dialysis for each dialysate. Plasma potassium, glucose, and bicarb were not significantly different at start of dialysis. The lactate dialysate (LD) group received a mean of 17.4+/-7.7 L of lactate containing dialysate versus 14.6+/-4.7 L of bicarbonate dialysate (BD) (p = 0.41). After dialysis, potassium had been reduced to a similar degree in both groups, but plasma glucose levels had increased during LD while they fell during BD, and bicarbonate levels fell during LD while they rose during BD. Use of a commercially available sterile bicarbonate dialysate can safely help to lower plasma potassium during CPB and preserve more physiologic levels of glucose and bicarbonate.

Acidosis↗

Molecular piracy of chemokine receptors by herpesviruses.

To succeed as a biological entity, viruses must exploit normal cellular functions and elude the host immune system; they often do so by molecular mimicry. One way that mimicry may occur is when viruses copy and modify host genes. The best studied examples of this are the oncogenes of RNA retroviruses, but a growing number of examples are also known for DNA viruses. So far they all come from just two groups of DNA viruses, the herpesviruses and poxviruses, and the majority of examples are for genes whose products regulate immune responses, such as cytokines, cytokine receptors, and complement control proteins. This review will focus on human and herpesvirus receptors for chemokines, a family of leukocyte chemoattractant and activating factors that are thought to be important mediators of inflammation. Although the biological roles of the viral chemokine receptor homologues are currently unknown, their connection to specific sets of chemokines has suggested a number of possible functions.

Amino Acid Sequence↗

Regional anaesthesia for cataract surgery.

Growing waiting lists and pressure on inpatient resources promote the need for cataract surgery to be undertaken on a day surgery basis. Retrobulbar and peribulbar anaesthesia are well suited for cataract surgery and are easily performed by both anaesthesists and ophthalmologists. This article reviews the methods, efficacy and safety of these techniques.

Ambulatory Surgical Procedures↗