Biomedical subjects

L O Simpson

Publications and source records attributed to L O Simpson.

123 records · Page 7Linked to original sources

PubMed1979

Experimental granulomatous inflammation: I. Gross and light microscopical observations in freund adjuvant-sensitized Cavies following the injection of killed tubercle bacilli.

The tuberculous granuloma, induced by injection of microgram doses of killed mycobacteria into guinea pigs sensitized by injection of Freund adjuvant is immunologically mediated. Formation of the granuloma is preceded by development within 24 h of a lymphocyte-dominated mononuclear cell response typical of a delayed hypersensitivity (type IV immune response) reaction. About the sixth day, following a marked decrease in intensity of the cellular reaction, a nodule containing monocytes and macrophages develops at the injection site. With increasing numbers of monocytes and macrophages the nodule forms a non-caseating granuloma with giant cells but dominated by epithelioid cells and reaching a maximum size about 3 wk after injection. Thereafter the granuloma undergoes gradual demolition being replaced and surrounded by fibroblasts and collagen deposition. The very delayed nature of this immune response as well as its histological character appear clearly to separate it from classical cell-mediated and humoral immune responses. These facts justify the hypothesis of a third type of (usually protective) immune response characterized histologically by the development of an epithelioid cell granuloma and determined by the nature of the antigenic material and the reactivity of the host. The initial polymorphonuclear leucocyte reaction to injection of mycobacteria, being similar in sensitized and control animals, does not appear to be under immunological control.

Animals↗

PubMed1979

Experimental granulomatous inflammation: II. Effect of injection of intact and disrupted killed tubercle bacilli into Freund adjuvant-sensitized Cavies.

The reaction of Freund adjuvant-immunized cavies to subsequent injection of Mycobacterium tuberculosis H37Ra is confirmed as an immunologically mediated phenomenon. Ultrasonic disruption of mycobacteria to be injected as "challenge" markedly increases the intensity of the consequent 24-48 h reaction and subsequent fibrosis in Freund adjuvant-sensitized cavies and has an apparently inhibiting effect on the extent of subsequent granuloma formation with marked reduction of the density of epithelioid cells. From this study, the 24-48 h reaction to injection of M. tuberculosis into sensitized animals appears clearly to be separable from subsequent granuloma formation depending upon the integrity or otherwise of the injected myocobacteria used as the challenge injection material.

Animals↗

PubMed1979

Thiamphenicol and lupus nephritis. The effects of long-term therapy on kidney function and pathology: a pilot study.

NZB x OUW F1 hybrid mice were treated with thiamphenicol at 25, 50 and 250 mg/kg/day from the time of their first positive antinuclear antibody test until their death. Untreated mice fed the same diet served as controls with body weight, mortality and renal disease patterns conforming to published reports of the biology of the BW mice. Regular testing of urine and bloodm and detailed postmortem examinations showed (a) that with increasing drug dose levels heavy proteinuria was almost eliminated and blood urea concentrations significantly lowered; (b) that in treated and untreated mice moderate to severe anaemia developed, apparently unrelated to the degree of uraemia; (c) that changes in renal function did not correlate with antinuclear antibody activity, nor did the drop in packed cell volume correlate with fixed or free circulating antierythrocyte autoantibody positivity; (d) that histological analysis of renal changes showed that at the highest dose level glomerular lesions were minimal. Thus the prolonged treatment with thiamphenicol reduced the severity of the spontaneous renal disease and resulted in a significant extension of lifespan.

Animals↗

PubMed1979

Thiamphenicol and lupus nephritis. II. The effects of giving the drug from weaning to NZBxOUW F1 hybrid female mice.

Thiamphenicol at the rate of 50 mg/kg/day given to female NZBxOUW F1 hybrid mice from weaning and continuing throughout life resulted in a considerable extension of lifespan, although this was less than in mice given the same drug dosage from first antinuclear antibody (ANA) positivity (Simpson, Aarons and Howie, 1979). Assessment of the changes in renal dysfunction and renal histology shows that thiamphenicol treatment did not prevent the development of immune complex glomerulonephritis although the rate of progression of the disease was slower than in untreated controls. Thiamphenicol failed to influence greatly the progressive anaemia which develops in these mice or to alter the pattern of ANA production. Although azotaemia developed in treated mice it was a terminal event. It was concluded that the action of thiamphenicol was to depress but not prevent immune complex formation possibly by impairing immunoglobulin formation although why immunofluorescent ANA formation remained unaffected is not understood.

Animals↗

PubMed1976

An NZB virus or NZB mice with viral infections?

Evidence for and against the possibility that the autoimmune disease of NZB mice has a viral aetiology is presented. It is considered that the case for a viral aetiology is unproven, although the possibility exists that virus may be present in incomplete form. Widely varying experimental results can be expected in experiments involving NZB mice until acceptable standards of mouse strain definition are laid down. Thus the comparison of results obtained from studies of NZB mice of diverse origin may invite misleading conclusions.

AKR murine leukemia virus↗

PubMed1975

Localisation and pathology of Mortierella wolfii toxin in mice.

Using 125I labelled M. wolfii toxin the site of action in mice was shown to be the kidney. Autoradiographic studies revealed the label to be localised in the proximal convoluted tubules of the kidney, where there was a marked necrosis and degeneration of the epithelium causing the tubules to become considerably distended. Although the distal and collecting tubules maintained their integrity, many contained amorphous casts. An injected dose of 1 toxic unit (10 mug protein) was sufficient to produce damage to the kidney with subsequent anaemia, azotemia and albuminuria. Other organs appeared to be essentially normal and renal failure was the probable cause of death of mice.

Animals↗

PubMed1975

Spleen and liver weight changes in NZB mice with haemolytic anaemia.

Spleen and liver weights from 998 NZB mice were subjected to computerised multivariate analysis. 3-dimensional graphs relating predicted spleen and liver weights to age and bodyweight were prepared and the relationship of the fitted surface to the histology and pathological autoantibody is discussed. On the basis of spleen weight increase, red-cell destruction throughout the greater part of life seems to be mainly intrasplenic, while intrahepatic destruction does not become important until later, when it is probably a dominant feature in the terminal period of the disease. Only limited organ weight increases occur in breeding females, and it is suggested that pregnancy lessens the effect of the haemolytic disease, the 'protective' effect extending long after the cessation of breeding.

Anemia, Hemolytic, Autoimmune↗

PubMed1975

The origins of some hitherto undescribed inbred mouse strains.

The origins of 7 inbred mouse strains (OUBW, OUCW, OUGW, OUYW, OUBCr, OUF and OUW) are reported. 6 of these strains have been in existence for a number of years, and 4 of them have not been mentioned in the literature. 2 of the strains have been referred to in published work, but because of incorrect designation may have caused some confusion. The remaining strain (OUBCr), which has considerable research potential, has been developed from a mutation in an NZB subline.

Animals↗

PubMed1974