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T Foster

Publications and source records attributed to T Foster.

At least 37 records · Page 2Linked to original sources

The psychological autopsy approach to studying suicide: a review of methodological issues.

The psychological autopsy approach to studying suicide is becoming an increasingly used research method. It presents considerable methodological problems. In order to assist future researchers in this field and to help readers assess reports of psychological autopsy studies the authors have reviewed these issues on the basis of their own experience and those of other workers. The areas covered include research design, identification of subjects, sources of information and the particular issues concerned with approaching relatives and other informants, choice and recruitment of controls, the difficulties of conducting psychological autopsy interviews with relatives, problems for interviewers, the selection of appropriate measures to obtain information, and achieving valid and reasonably reliable conclusions from diverse information sources.

Autopsy↗

Role of Staphylococcus aureus surface-associated proteins in the attachment to cultured HaCaT keratinocytes in a new adhesion assay.

Colonization of human skin with Staphylococcus aureus is a common feature in a variety of dermatologic diseases. In order to reproducibly investigate the adherence of Staphylococcus aureus to human epidermal cells, an in vitro assay was established using the biotin/streptavidine labeling system and the HaCaT cell line. This assay was used to define the role of several Staphylococcus aureus surface proteins with regard to their function in the staphylococcal adhesion process. Our studies included the standard laboratory strain Newman as well as its genetically constructed mutants DU5873, DU5852, DU5854, and DU5886 generated by allele replacement or transposon mutagenesis, which are deficient in the elaboration of staphylococcal protein A (spa), clumping factor (clfA), coagulase (coa), and the fibronectin-binding proteins A and B (fnbA/B), respectively. In comparison with strain Newman all mutants showed remarkably reduced adherence to the HaCaT keratinocyte cell line in our assay, yielding only between 43% and 60% of the adherence capacity of strain Newman after 60 min. Bacterial adherence could be re-established by introducing the cloned wild-type genes for the surface proteins on shuttle plasmids into the chromosomally defective mutants, thus suggesting a pathogenetic role of these proteins in the attachment of Staphylococcus aureus to human keratinocytes. Bacterial adherence was additionally enhanced by alkaline pH-values that are characteristic for skin conditions with epidermal barrier dysfunction. The use of Staphylococcus aureus mutant strains, deficient in the elaboration of defined proteins, allows specific investigation of colonization and virulence factors of this dermatologic relevant microorganism.

Bacterial Adhesion↗

Characterization of the interaction between the Staphylococcus aureus clumping factor (ClfA) and fibrinogen.

The ability of Staphylococcus aureus to adhere to adsorbed fibrinogen and fibrin is believed to be an important step in the initiation of biomaterial and wound-associated infections. In this study, we show that the binding site in fibrinogen for the recently identified S. aureus fibrinogen-binding protein clumping factor (ClfA) is within the C-terminus of the fibrinogen gamma chain. S. aureus Newman cells expressing ClfA adhered to microtitre wells coated with recombinant fibrinogen purified from BHK cells, but did not adhere to wells coated with a purified recombinant fibrinogen variant where the 4 C-terminal residues of the gamma chain were replaced by 20 unrelated residues. In addition, a synthetic peptide corresponding to the 17 C-terminal amino acids of the fibrinogen gamma chain effectively inhibited adherence of ClfA-expressing cells to fibrinogen. In western ligand blots, a recombinant truncated ClfA protein called Clf33 (residues 221-550) recognized intact recombinant fibrinogen gamma chains, but failed to recognize recombinant fibrinogen gamma chains where the 4 C-terminal amino acids were altered by deletion or substitution. Previous studies have shown that the C-terminal domain of fibrinogen gamma chains contains a binding site for the integrin alphaIIb beta3 (glycoprotein gpIIb/IIIa) receptor on platelets [Kloczewiak, M., Timmons, S., Bednarek, M. A., Sakon, M. & Hawiger, J. (1989) Biochemistry 28, 2915-1919; Farrell, D. H., Thiagarajan, P., Chung, D. W. & Davie, E. W. (1992) Proc. Natl. Acad. Sci. USA 89, 10729-10732; Hettasch, J. M., Bolyard, M. G. & Lord, S. T. (1992) Thromb. Haemostasis 68, 701-706]. We now show that Clf33 inhibits ADP-induced, fibrinogen-dependent platelet aggregation in a concentration-dependent manner and inhibits adhesion of platelets to immobilized fibrinogen under fluid shear stress, indicating that the binding sites for the platelet integrin and the staphylococcal adhesin overlap. The interaction between Clf33 and fibrinogen was further characterized using the BIAcore biosensor. When soluble Clf33 was allowed to bind to immobilized fibrinogen, a Kd of 0.51 +/- 0.19 microM was experimentally determined using equilibrium binding data. It was also shown that the synthetic C-terminal gamma-chain peptide effectively inhibited this interaction.

Adenosine Diphosphate↗

Role of Staphylococcus aureus surface adhesins in orthopaedic device infections: are results model-dependent?

Bacterial colonisation of prosthetic material can lead to clinical infection or implant failure, or both, often requiring removal of the device. Adherence of Staphylococcus aureus to bioprosthetic materials is mediated by adhesins belonging to the MSCRAMM (microbial surface components recognising adhesive matrix molecules) family of microbial cell surface proteins. The objective of this study was to compare the virulence of a mutant strain of S. aureus Newman that possesses all three fibrinogen-, fibronectin- and collagen-binding MSCRAMMs (MSCRAMM-positive strain) with that of a mutant strain that lacks all three types of MSCRAMMs (MSCRAMM-negative strain) in a rabbit model of orthopaedic device-related infection. After a hole was drilled into the knee joint of each animal, a group of 10 rabbits was inoculated with the MSCRAMM-positive strain and another group of 10 rabbits received the MSCRAMM-negative strain. A stainless steel screw was then placed into the drilled hole. Two weeks later, the rabbits were killed and serum samples, bone tissue and implants were harvested for bacteriological and histopathological evaluation. No significant difference in infection rates was demonstrated between the two groups. The ability to delineate the role of S. aureus surface adhesins in causing orthopaedic device-related infection could be model-dependent.

Adhesins, Bacterial↗

Mental disorders and suicide in Northern Ireland.

BACKGROUND: The aim of this part of the Northern Ireland Suicide Study was to investigate the prevalence of DSM-III-R axis I (clinical syndrome) and axis II (personality) disorders among suicides (14 years and older) in Northern Ireland during a one-year period. METHOD: A psychological autopsy study based on a variety of documentary sources and interviews with bereaved informants and health care professionals. RESULTS: Ninety per cent of suicides (106/118) had a current axis I and/or an axis II mental disorder. At least one current axis I disorder was diagnosed in 86% of suicides (102/118), and at least one axis II disorder was diagnosed in 44% (52/118). Suicides under 30 years (92% male) were less likely to have a current axis I disorder (68%; 26/38) than those 30 years and older (95%; 76/80). Psychiatric comorbidity was present in 55% of suicides (65/118). The time between the last contact with a health care professional and death was greater among suicides under 30 years and male suicides. CONCLUSIONS: Notwithstanding the aetiological complexity of suicide, the prevention, recognition and treatment of mental disorder will continue to play key roles in suicide prevention.

Adolescent↗

Going public.

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Hospitals, Pediatric↗

Selective killing of human monocytes and cytokine release provoked by sphingomyelinase (beta-toxin) of Staphylococcus aureus.

The best-known activity of Staphylococcus aureus sphingomyelinase C, alias beta-toxin, is as a hemolysin that provokes hot-cold lysis of erythrocytes which contain substantial amounts of sphingomyelin in the plasma membrane. Sheep erythrocytes are most susceptible, and we found that one hemolytic unit, representing the toxin concentration that elicits 50% hemolysis of 2.5 X 10(8) erythrocytes per ml, corresponds to 0.05 enzyme units or to approximately 0.25 microg of sphingomyelinase per ml. The cytotoxic action of beta-toxin on nucleated cells has not been described in any detail before, and the present investigation was undertaken to fill this information gap. We now identify beta-toxin as a remarkably potent monocytocidal agent. At a concentration of 0.001 U/ml, corresponding to approximately 5 ng/ml, beta-toxin killed over 50% of human monocytes (10(6) cells per ml) within 60 min. By contrast, 1 to 5 microg of beta-toxin per ml had no cytocidal effects on human granulocytes, fibroblasts, lymphocytes, or erythrocytes. A selective monocytocidal action was also observed with sphingomyelinase C from Bacillus cereus and a Streptomyces sp., whereas phospholipase A2 and phospholipase D at 100 U/ml were without effect. Monocytes succumbing to the action of beta-toxin processed and released interleukin-1beta, soluble interleukin-6 receptor, and soluble CD14 into the supernatant. Thus, monocyte killing by beta-toxin is associated with cytokine-related events that are important for the initiation and progression of infectious disease. These findings uncover a potentially important role for sphingomyelinase as a determinant of microbial pathogenicity.

Antigens, CD↗

Treatment of high-energy proximal tibial fractures using the Monticelli-Spinelli external fixator: a preliminary report.

Between 1990 to 1993, 21 patients with tibial plateau or proximal tibial fractures resulting from high-energy trauma were treated with the Monticelli-Spinelli external fixator. There were 13 men and 8 women (mean age, 45.2 years; range, 26 to 78). There were a total of 5 type A, 2 type B, and 14 type C fractures, using the Arbeitsgemeinschaft Fur Osteosynthesefragen (AO) classification system. Immediate postoperative reductions were good or excellent, according to strict radiographic criteria, in 16 of 21 patients. All patients obtained at least 90 degrees of knee flexion, and only one patient lost more than 5 degrees of full extension. Complications included seven superficial pin-tract infections and one deep vein thrombosis with resultant pulmonary embolism. Nineteen patients were available for follow-up (mean, 14 months). Clinically, 13 patients had satisfactory results where good or excellent radiographic reductions were maintained, knee extension was within 5 degrees of full, flexion was > or = 90 degrees, with < or = 5 degrees valgus/varus angulation. Six patients had unsatisfactory results, not meeting the above criteria. The Monticelli-Spinelli external fixator is a much-needed tool in the treatment of high-energy tibial plateau fractures that are not amenable to more extensive surgical procedures because of the associated soft-tissue injuries.

Adult↗

Effects of serum separation tubes on serum benzodiazepine and phenobarbital concentrations in clinically normal and epileptic dogs.

OBJECTIVE: To characterize the effects of serum separation tubes (SST) on serum drug concentrations. SAMPLE POPULATION: Clinically normal dogs (clorazepate, n = 7) or dogs with epilepsy (phenobarbital, n = 7) were studied in experiment 1, and samples submitted for therapeutic drug monitoring (n = 87) were studied in experiment 2. PROCEDURE: In experiment 1, blood containing either drug was placed in 2 types of 4-ml SST (SST-A and SST-B) and in nonserum separation tubes (non-SST [control]). Samples were processed, then stored at 20 to 22 C (both drugs) or 10 C (phenobarbital only). Aliquots were collected for 96 hours. The rate constant of disappearance and the percentage decrease of each drug over time were determined for each tube. For experiment 2, paired samples were collected in non-SST and SST and submitted by mail for therapeutic drug monitoring. The SST samples were either decanted from SST prior to shipment (group 1; n = 30) or mailed in SST with serum in contact with the silica gel (group 2; n = 57). Drug concentrations and drug elimination half-life were compared between groups. For both experiments, drugs were detected in samples, using polarized immunofluorescence. RESULTS: For experiment 1, the rate constant of drug disappearance for both drugs was greater in the 4-ml SST-A (P < 0.0001). This SST also caused the greatest percentage decrease (20% for phenobarbital and 35% for benzodiazepines) at 96 hours. Refrigeration reduced the mean decrease in phenobarbital at 96 hours to 11%. For experiment 2, phenobarbital concentration was lower for both SST, compared with non-SST (P < 0.0005). Phenobabital had decreased a mean 6.4 +/- 0.5% in group-1 and a mean 30.5 +/- 11.1% in group-2 (P < 0.0005) samples. CONCLUSION: The SST should be avoided when collecting serum for monitoring of either phenobarbital or benzodiazepines. CLINICAL RELEVANCE: The SST can falsely decrease serum drug concentrations and should be avoided when collecting blood for therapeutic drug monitoring.

Animals↗

Homeobox genes in the functioning of plant meristems.

The maize homebox gene knotted1 (kn1) is expressed in vegetative and floral meristems and is down-regulated at the site of primordia formation. kn1-related genes from maize and other species also show meristem-specific expression and offer additional tools for studying the activities of shoot meristems. Members of this gene family are expressed early in embryogenesis, providing molecular markers for meristem initiation. Ectopic expression of either kn1 or a related Arabidopsis gene, KNAT1, causes dramatic alterations in Arabidopsis and tobacco leaf morphology. Most significantly, meristems form on the leaf, producing small shoots. We discuss whether the phenotypes can be interpreted as changes in positional information or timing of determination.

Gene Expression Regulation, Plant↗

The application of high-definition video systems in medicine.

High-definition television is now available in two quite separate systems, with advantages over existing broadcast television formats which would benefit the medical user. The 1125 line, 60 Hz system is described, and the technical jargon explained. Production and broadcast techniques are discussed. Some recent applications of high-definition television for the demonstration of medical procedures are described, and possible future developments for medical users are outlined. A glossary of technical terms is included for those not familiar with video technology.

Teaching Materials↗

Conservation of the regulatory subunit for the Clp ATP-dependent protease in prokaryotes and eukaryotes.

Bacteria, tomatoes, and trypanosomes all contain genes for a large protein with extensive homology to the regulatory subunit, ClpA, of the ATP-dependent protease of Escherichia coli, Clp. All members of the family have between 756 and 926 amino acids and contain two large regions, of 233 and 192 amino acids, each containing consensus sequences for nucleotide binding. Within these regions there is at least 85% similarity between the most distant members of the family. The high degree of similarity among the ClpA-like proteins suggests that Clp-like proteases are likely to be important participants in energy-dependent proteolysis in prokaryotic and eukaryotic cells.

ATP-Dependent Proteases↗