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Biomedical subjects

W J Fraser

Publications and source records attributed to W J Fraser.

4 recordsLinked to original sources
PubMed1997

Rheumatic Aschoff nodules revisited. II: Cytokine expression corroborates recently proposed sequential stages.

AIMS: A recent immunohistochemical analysis of the Aschoff lesions in rheumatic fever, combining immunohistochemical analysis with comparative morphology, permitted the division of the Aschoff nodules into three stages: (1) Aschoff nodule without admixed lymphocytes, (2) Aschoff nodules with a few T lymphocytes, and (3) Aschoff nodules containing many admixed lymphocytes of both B- and T-cell phenotype. It was postulated that the order of progression was from stage 1 with macrophages only, to accumulation of first T lymphocytes (stage 2) and then B lymphocytes (stage 3). This study was undertaken to determine the role and distribution of interleukin 1 (IL-1), interleukin 2 (IL-2) and tumour necrosis factor alpha (TNF alpha) in the various stages of the rheumatic Aschoff nodule to investigate our hypothesis on the progression of these nodules. METHODS AND RESULTS: Sixteen fresh valve specimens from patients with acute rheumatic fever undergoing valve surgery were obtained. Tissue sections from 14 specimens identified as containing Aschoff nodules were subjected to immunohistochemistry for (1) T and B lymphocytes, to stage the lesions according to our previously proposed criteria; (2) IL-1, IL-2 and TNF alpha; and (3) CD4 and CD8 to phenotype the T lymphocytes. The stage 1 and 2 lesions expressed IL-1 and TNF alpha in the macrophages. The stage 3 lesions showed more variable expression of all three cytokines including IL-2 within T lymphocytes. CONCLUSION: TNF alpha and IL-1 secretion in macrophages is required for T and B lymphocytes activation and aggregation; suggesting that macrophages arrive at the scene of rheumatic injury prior to the lymphocytes. IL-2 is usually expressed later in the inflammatory process and was found only in the lymphoid aggregates. This study therefore produces corroborative evidence for our previously proposed developmental stages of the Aschoff nodule.

Acute Disease↗
PubMed1996

Performance-based exposure control limits for pharmaceutical active ingredients.

For many years pharmaceutical companies have established employee exposure limits for the active ingredients used in their products. Historically these limits were derived using traditional risk assessment methods. Because the trend in the pharmaceutical industry is to identify and develop more selective drugs of increasing potency, and because of the difficulty in identifying no-effect levels for certain drugs, a new performance-based approach for setting limits was developed. This method involves assigning materials into one of five hazard categories according to their inherent toxicological and pharmacological properties. The criteria used to assign compounds into performance-based exposure control limit (PB-ECL) categories focus on the degree to which exposure impacts human health. These assignments dictate the level of containment required to assure employee safety that is achieved through the use of engineering controls and safe handling practices. Several matrices were developed to specify general design concepts and controls for unit operations in laboratory and manufacturing operations. Containment options range from conventional handling practices for low potency (PB-ECL Category 1) materials, to technologically advanced systems that result in essentially no open handling for potent or toxic (PB-ECL Category 3) materials, to state-of-the-art facilities employing closed processes and use of robotics for extremely potent (PB-ECL Category 5) materials.

Containment of Biohazards↗
PubMed1995

Rheumatic Aschoff nodules revisited: an immunohistological reappraisal of the cellular component.

Rheumatic fever is still the leading cause of acquired heart disease in children and young adults in developing countries. Recent reports have documented a rising incidence of rheumatic fever in both the USA and Europe. The disease is characterized by specific lesions in the heart muscle and valves called Aschoff nodules. The Aschoff nodule has been neglected in the last few decades as most of the studies were conducted in the 1960s on autopsy tissues. This study examines Aschoff nodules using heart valve material obtained at valve surgery with updated commercially available immunohistochemical antibodies to determine the phenotypic characteristics of the cells involved in the formation of these lesions. Fifteen cases of rheumatic valvulitis, as indicated by the presence of Aschoff nodules, were examined. The Anitschkow and Aschoff cells stained prominently with macrophage markers. Three stages of nodules with Aschoff and Anitschkow cells were identified: stage 1, central fibrinoid necrosis without lymphocytes, stage 2 with occasional T lymphocytes (< 10) and stage 3 with lymphoid aggregates containing both T- and B-lymphocytes (with occasional admixed macrophages). We propose that the stage 1 lesion is the earliest granulomatous stage with the lymphoid aggregates being a later stage in the development of Aschoff nodules. The Aschoff and Anitschkow cells demonstrated mitotic activity and stained with antibodies to the proliferation cell nuclear antigen (PCNA) suggesting that the multinucleated giant cells may be formed, at least partially, by nuclear division rather than fusion.

Biomarkers↗