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Biomedical subjects

J Canvin

Publications and source records attributed to J Canvin.

8 recordsLinked to original sources

Contact activation in shock caused by invasive group A Streptococcus pyogenes.

OBJECTIVES: The aim of this study was to characterize abnormalities of coagulation in mice with experimental, invasive group A, streptococcal shock, in an attempt to explain the prolongation of the activated partial thromboplastin time identified in patients with streptococcal toxic shock syndrome. DESIGN: A longitudinal descriptive animal model study of coagulation times and single coagulation factors in mice infected with Streptococcus pyogenes. This was followed by an experimental study to determine whether streptococci or streptococcal products could activate the human contact system in vitro. SETTING: University infectious diseases and hemostasis molecular biology laboratories. SUBJECTS: CD1 outbred mice. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Coagulation times, single factor assays, and bradykinin assays were conducted on murine plasma at different times after streptococcal infection and compared with uninfected mice. In experiments in which streptococcal products were co-incubated with human plasma, we compared coagulation times, single factor assays, and activities against a range of chromogenic substrates with control plasma. In a murine model of streptococcal necrotizing fasciitis, the activated partial thromboplastin times were significantly prolonged in infected mice compared with controls, whereas prothrombin times were normal, suggesting an isolated abnormality of the intrinsic pathway. Bleeding was not seen. Prolongation of activated partial thromboplastin time was associated with reduced factor XII and prekallikrein, whereas levels of factors VIII, IX, XI, and high molecular weight kininogen were elevated. In vitro studies suggested that streptococcal supernatants can activate prekallikrein, in addition to causing plasminogen activation through the action of streptokinase. CONCLUSIONS: Prolongation of activated partial thromboplastin time in streptococcal toxic shock syndrome is associated with activation of the contact system, possibly contributing to the profound shock associated with streptococcal toxic shock syndrome.

Animals↗

Rapid growth mutants of Escherichia coli.

If rapid growth (rap) mutants of Escherichia coli could be obtained, these might prove a valuable contribution to fields as diverse as growth rate control, biotechnology and the regulation of the bacterial cell cycle. To obtain rap mutants, a dnaQ mutator strain was grown for four and a half days continuously in batch culture. At the end of the selection period, there was no significant change in growth rate. The result means that selecting rap mutants may require an alternative strategy and a number of such alternatives are discussed.

Bacteriological Techniques↗

Identification of sodC encoding periplasmic [Cu,Zn]-superoxide dismutase in Salmonella.

sodC, encoding [Cu,Zn]-cofactored superoxide dismutase, once thought to be virtually confined to eukaryotes, has now been described in many Gram-negative pathogens that have their primary niche of colonization in the upper respiratory tract. Their role in host-parasite interactive biology is unknown. We here show that members of the major human and animal enteric pathogenic species Salmonella harbour a version of sodC most closely resembling that found in Brucella abortus. The enzyme it encodes is a novel candidate determinant of virulence in Salmonella, an intracellular pathogen potentially exposed to toxic oxygen free radicals within its intracellular niche.

Blotting, Southern↗

Synovial distribution of alpha d/CD18, a novel leukointegrin. Comparison with other integrins and their ligands.

OBJECTIVE: To define the synovial distribution of the novel leukointegrin alpha d/CD18, and compare this with other members of the beta 2-integrin family of adhesion molecules, and their counter-receptors. METHODS: Monoclonal antibodies to the CD3, CD14, CD29, CD68, beta 2-integrin, and immunoglobulin supergene families were used to immunohistologically define the distribution of these molecules in synovial tissue samples from normal subjects and osteoarthritis (OA) and rheumatoid arthritis (RA) patients. RESULTS: The normal synovial lining cell layer (SLC) expresses CD68, vascular cell adhesion molecule 1, beta 1-integrin (CD29), the beta 2-integrins CD11b/CD18 (alpha m/beta 2, Mac-1), and alpha d/CD18, whereas CD11a/CD18 (alpha L/beta 2, lymphocyte function-associated antigen 1) and CD11c/CD18 (alpha x/beta 2, gp150/95) expression is generally absent. In RA synovitis, expression of beta 2-integrins in the SLC increases in proportion to the degree of hyperplasia. The ratio of cells in the SLC which express CD11c/CD18 increases substantially, approaching that of CD11b/CD18 and alpha d/CD18, while there is minimal increase in CD11a/CD18 expression. In the sublining areas of the tissues, aggregates and diffuse infiltrates of CD3/CD11a/ICAM-3+ lymphocytes are interspersed among CD68/CD14/CD11b/alpha d+ macrophages. A number of aggregates demonstrate intense alpha d staining of the lymphocytes. The synovial endothelium variably expresses intercellular adhesion molecule-1 (ICAM-1), ICAM-2, and vascular cell adhesion molecule 1 (VCAM-1), with minimal evidence of ICAM-3 expression. CONCLUSION: The leukointegrin alpha d/CD18 is expressed constitutively by synovial macrophages and macrophage-like lining cells. In rheumatoid synovitis, the intense coexpression of this integrin and its known counter-receptor, ICAM-3, in the inflammatory infiltrates, suggests a potential role for this adhesion pathway in cellular interactions occurring the synovium.

Adult↗

Cell cycle control: prokaryotic solutions to eukaryotic problems?

Regulation of the eukaryotic cell cycle involves calcium- and lipid-stimulated kinases acting on cytoskeletal structures; there are two principal reasons for supposing that the regulation of the prokaryotic cell cycle may be fundamentally the same. First, evidence for their fundamental difference is still missing and, second, evidence for prokaryotic homologues of eukaryotic cell cycle proteins is accumulating. Such proteins include those involved in calcium regulation, such as calmodulin and calcium-dependent kinases, and those involved in lipid regulation, such as protein kinase C. Proteins identified as candidates for cytoskeletal elements now include MukB, a putative contractile protein responsible for chromosome segregation, and FtsZ, the key constituent of the "cytokinetic" ring. These similarities allow the application of powerful prokaryotic model systems to one of biology's most profound, complex and urgent problems: the nature of the regulation of the eukaryotic cell cycle.

Animals↗