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Biomedical subjects

M O'Reilly

Publications and source records attributed to M O'Reilly.

At least 91 records · Page 5Linked to original sources

Recombinant human granulocyte colony-stimulating factor and Pseudomonas burn wound sepsis.

Multiple immune defects have been demonstrated following thermal injury, including defective granulocyte production and function. Recombinant human granulocyte colony-stimulating factor (rhGCSF) is a regulator of the myelopoietic system. The effect of rhGCSF administration on survival and on the myelopoietic system in a murine model of Pseudomonas burn wound sepsis was investigated. Male BDF1 mice that underwent a 15% total body surface area burn injury and burn wound seeding with 1 x 10(8) Pseudomonas aeruginosa organisms demonstrated an improved mean survival time with the subcutaneous administration of 100 ng of rhGCSF twice a day. Mice that underwent a similar thermal injury and burn wound seeding with 3 x 10(7) P aeruginosa organisms demonstrated an augmented myelopoietic response through the administration of rhGCSF, as represented by significantly increased white blood cell count, neutrophil count, splenic weight, femoral marrow cellularity, and femoral marrow granulocyte-macrophage colony-forming cell count. Myelopoietic augmentation through rhGCSF administration may serve to decrease the morbidity of septic events following thermal injury.

Animals↗

Recombinant granulocyte-macrophage colony-stimulating factor improves hematopoietic recovery after 5-fluorouracil.

Antitumor chemotherapy is often limited by hematopoietic toxicity. In an attempt to determine if it is possible to attenuate the myelosuppressive effects of chemotherapy, we administered recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF), a multilineage hematopoietic growth factor, to mice receiving 5-fluorouracil (5-FU). Mice receiving injection of 5-FU followed 24 hr later by a single 1-microgram injection of rmGM-CSF had significantly increased femoral bone marrow granulocyte-macrophage colony-forming cells (GM-CFC) 48 hr after 5-FU injection compared to animals receiving 5-FU alone. Animals receiving rmGM-CSF twice daily beginning 24 hr after 5-FU had significantly elevated white blood cell counts and increased granulocyte and monocyte counts at Day 7 following 5-FU injection, compared to those of 5-FU animals. The total reserve of GM-CFC was also expanded initially in the femoral marrow and later in the spleen of animals receiving rmGM-CSF following 5-FU. A means of accelerating bone marrow recovery and restoration circulating granulocytes and monocytes could allow more frequent doses of chemotherapy to be administered or shorten the time period that patients are leukopenic.

Animals↗

Molecular cloning and expression of the coagulase gene of Staphylococcus aureus 8325-4.

The gene coding for coagulase (coa) was cloned from Staphylococcus aureus 8325-4 in a lambda replacement vector in Escherichia coli. Coagulase (plasma-clotting) activity was measured in lambda coa lysates and an immunoreactive protein of 60 kDa was detected by Western immunoblotting with anti-coagulase serum. This protein comigrated with the major immunoreactive protein in supernatants of S. aureus 8325-4. The coa gene was subcloned in pUC vectors. One recombinant expressed a 60 kDa immunoreactive protein and plasma-clotting activity. A putative beta-galactosidase-coagulase fusion protein and truncated peptides were expressed by variants formed by subcloning. These results are consistent with previously published biochemical data that the prothrombin-binding domain of coagulase is located in the N-terminus of the protein. The cloned coa gene was transferred into S. aureus on a shuttle plasmid. Expression of coagulase was higher in a strain with a mutation in the agr locus, which controls the level of several exoproteins in S. aureus, suggesting that agr normally regulates coagulase expression negatively.

Chromosome Mapping↗

Independent living skills groups in a level I fieldwork experience.

Since 1985, the Tufts University-Boston School of Occupational Therapy has experimented with a service model for Level I fieldwork that uses independent living skills (ILS) groups. Under the off-site supervision of the course instructor and a Level I coordinator, students taking an Advanced Group Process course have run ILS groups in community agencies using faculty- and staff-developed group protocols. Populations served have included adolescents and adults with developmental disabilities, adults with psychosocial dysfunction, well geriatric adults, and single mothers. The response of area clinicians has been very positive--the number of settings willing to accept students for this experience has more than doubled since the ILS groups have been introduced. This approach to Level I fieldwork, which does not require as much faculty time as do other service models currently in use, could be applied to other Level I experiences and provide a structure for expanding occupational therapy into nontraditional community settings.

Activities of Daily Living↗

Regulation of exoprotein gene expression in Staphylococcus aureus by agar.

Insertion of the erythromycin-resistance transposon Tn551 into the Staphylococcus aureus chromosome at a site which maps between the purB and ilv loci has a pleiotrophic effect on the production of a number of extracellular proteins. Production of alpha, beta and delta hemolysin, toxic shock syndrome toxin (TSST-1) and staphylokinase was depressed about fifty-fold while protein A production was elevated twenty-fold. Hybridization analysis showed that the defect in expression of TSST-1 and alpha hemolysin was at the transcriptional level. Inability of the mutant strain to express either a cloned TSST-1 gene or the chromosomal gene indicates that the transposon has inactivated a trans-active positive control element. This element has been designated agr for accessory gene regulator.

Bacterial Proteins↗

Inactivation of the alpha-haemolysin gene of Staphylococcus aureus 8325-4 by site-directed mutagenesis and studies on the expression of its haemolysins.

S. aureus strain 8325-4 was shown to produce alpha-, beta-, delta- and gamma-haemolysins by haemolytic assays and immunoblotting. Hybridization experiments indicated that a single copy of the alpha-haemolysin gene (hla) resides in the chromosome. Site-directed mutagenesis was used to inactivate the hla gene. This gene, which had previously been cloned in E. coli, was inactivated in vitro by inserting a fragment carrying an erythromycin resistance marker. Shuttle plasmids were constructed and transformed into 8325-4 and non-haemolytic recombinants enriched by a plasmid incompatibility technique. A previously isolated Tn551 insertion defective in alpha-haemolysin was not located in hla. It had pleiotropic defects in expression of alpha-, beta- and delta-haemolysins. Expression of alpha-haemolysin from a plasmid-located hla gene was very low. In contrast, hla-erm mutants were deficient only in alpha-haemolysin and allowed high level expression of the plasmid-borne hla gene. The Tn551 insertion is probably located in a gene encoding a positive regulatory element required for expression of several exoproteins. An hla-erm mutant was less virulent than the otherwise isogenic 8325-4 hla+ strain in a mouse peritonitis model, confirming that alpha-haemolysin is an important virulence factor.

Bacterial Toxins↗

Expression of the cloned toxic shock syndrome toxin 1 gene (tst) in vivo with a rabbit uterine model.

Toxic shock syndrome (TSS) toxin 1 (TSST1) is produced by strains of Staphylococcus aureus associated with TSS. Purified TSST1 induces in rabbits a shock-like illness with many features similar to TSS in humans. These symptoms were also induced by TSST1-producing bacteria in diffusion chambers implanted in the rabbit uterus. Naturally occurring TSST1+ strains and a TSST1- strain harboring a pE194-derived plasmid carrying the cloned TSST1 determinant tst gave the same symptoms. TSST1- strains and a TSST1- strain carrying a pE194-tst plasmid with a deletion of the tst gene had no effect in rabbits. The results with the plasmid-carrying TSST1+ and TSST1- strains, which were isogenic apart from tst, show that the toxin is responsible for the illness in rabbits and suggest that it is a major factor in the pathogenesis of TSS.

Animals↗

A clinical trial of a bead bed system for the prevention of pressure sores in elderly orthopaedic patients.

This paper summarizes the results of the trial of the Beaufort Bead Bed system designed to reduce the incidence and severity of pressure sores. Elderly orthopaedic admissions were allocated alternately to the Beaufort system and to the usual trolley, table and bed surfaces, and followed from admission to hospital until separation. The incidence of pressure sores was 15.6% in the 32 'trial' patients, which was significantly less than the 48.8% in the 43 'control' patients, as was the mean maximum diameter of the pressure sores incurred: 6.4 mm for the 'trials' as against 29.5 mm for the 'controls'. In particular the trial group were free from pressure lesions to the heel, which affected 32.6% of the control group. The groups were well matched on a variety of criteria on admission, and we conclude that the Beaufort system successfully reduces the incidence and severity of pressure sores for elderly orthopaedic patients. The system--renamed recently the 'Neumark-Macclesfield Support System'--is now in regular and satisfactory use.

Aged↗

Plasmids in epidermolytic strains of Staphylococcus aureus.

Thirty-four epidermolytic toxin-producing strains of Staphylococcus aureus obtained from a variety of sources were screened for the presence of plasmid DNA. All serotype ii toxin producers harboured a large 42 kilobase pairs (kb) plasmid. Elimination of these plasmids resulted in the simultaneous loss of a bacteriocin determinant (Bac+) and type ii toxin production (Toxii+). Some strains producing serotype i toxin (Toxi+) contained similar 42 kb plasmids. Elimination of these plasmids resulted in the loss of only bacteriocin production. Strains producing both toxin serotypes readily lost Toxii+ and Bac+, which were carried on the same plasmid, but Toxi+ could not be eliminated. Thus Toxi+ was probably chromosomally determined, while Toxii+ was a plasmid-encoded marker. In some strains cadmium resistance was also linked to the 42 kb plasmid. The 42 kb plasmids from seven strains with different phenotypes were analysed with restriction endonucleases EcoRI and HindIII. The plasmids shared 19 of 22 HindIII fragments indicating that they are closely related to each other.

Bacterial Toxins↗

An experimental study of the clinical judgment of general physicians in evaluating and prescribing for depression.

Fifteen general physicians were given profiles of symptom combinations representing 80 depressed patients. They were asked to judge the severity of the disorder and to prescribe. There were two phases to the experiment, the formal structure of both being the same. In the first phase, all physicians based their judgments only on the cues of the Hamilton Depression scale; in the second, each physician defined his own cues. Multivariate regression analysis was applied to the observations. Agreement between the judges was low. Most had a more complex policy, in regard to both judgment of the severity of the depression and prescribing, when selecting their own cues than when restricted to textbook variables, but used it more consistently. The observations have important implications for training and research in psychiatry and in psychopharmacology.

Adult↗

Mural vegetations at the site of endocardial trauma in infective endocarditis complicating idiopathic hypertrophic subaortic stenosis.

In two patients infective endocarditis developed as the primary manifestation of idiopathic hypertrophic subaortic stenosis. Infected vegetations were present on the mitral and aortic valves. In addition, bacterial vegetations were observed on the septal endocardium at the site of contact between the mitral valve leaflet and the hypertrophic septum. Thus, chronic endocardial trauma, a common finding in idiopathic hypertrophic subaortic stenosis, may provide a fertile nidus for the development of bacterial vegetation.

Aged↗