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Biomedical subjects

W J Penhale

Publications and source records attributed to W J Penhale.

At least 73 records · Page 4Linked to original sources

Experimental induction of an immunohaemolytic anaemia in the chicken with Salmonella gallinarum endotoxin.

The possibility that the extreme refractoriness of the chicken to injected endotoxin would permit the buildup of sufficient free endotoxin in the circulation to immunologically modify the erythrocytes in vivo and thereby cause them to be eliminated from the circulation was investigated. It was shown that a moderately severe immunohaemolytic anaemia accompanied by a mild spenomegaly could be induced in chickens by single (large) or multiple injections of Salmonella gallinarum endotoxin (SgE). Varying degrees of reticulocytosis, with corresponding decreases in haemoglobin and haematocrit values, were observed from the tenth day after the injection of the SgE. All the injected animals also showed significant immune responses to SgE, peak haemagglutinin titres occurring coincidentally with the peaks of the haemolytic episodes. A similar injection schedule in specifically immune chickens also showed the anaemia appearing much earlier, persisting longer and being much more profound in intensity. It is considered that the in vivo erythrocyte sensitization induced by SgE injection initiates the erythrocytic changes observed and that the underlying mechanism responsible for the subsequent development of the haemolytic anaemia is immunologically mediated.

Anemia, Hemolytic↗

Thyroiditis in T cell-depleted rats: suppression of the autoallergic response by reconstitution with normal lymphoid cells.

Qualititive, quantitative and functional differences were found in lymphoid cells of female thymectomized and irradiated (Tx-X) PVG/c strain rats as compared to normal females of the same strain. Tx-X rats were lymphopenic and had reduced numbers of cells within spleen and cervical lymph nodes, depressed transformation responses of peripheral blood lymphocytes to PHA and lower percentage killing of their spleen cells by anti-T-cell serum and complement. There was an increased percentage of immunoglobulin-bearing cells in the lymph nodes. Reconstitution of Tx-X rats by the intravenous route using syngeneic lymph node cells, spleen cells or thymocytes abrogated the autoimmune responses to thyroid components generally observed in this state. Lymph node and spleen cells, but not thymocytes, also prevented thyroid changes when given intraperitoneally. In contrast, bone marrow cells appeared to give enhanced responses. Quntitative studies showed that the relative proportions of the suppressor or autoregulatory cells in various lymphoid tissues were lymph node greater than spleen greater than thymus. Complete abrogation of the autoimmune responses was possible only when cells were administered within a short time of final dose of irradiation and moderate thyroid change was again seen if transfer was delayed for 14 days post-irradiation. At 28 days reconstitution had no influence on the development of the autoimmune responses. Preliminary characterization studies using an anti-T-cell serum and fractionation of lymph node cells on a linear Ficoll gradient suggested that autoregulatory cell is a large T cell.

Animals↗

Phytohemagglutinin-induced lymphocyte transformation in newly presenting patients with primary carcinoma of the lung.

The transformation of peripheral blood lymphocytes in response to PHA was studied in 37 newly presenting patients who were subsequently proven to have carcinoma of the lung. When compared with healthy age- and sex-matched normal controls, no differences were noted in the thymidine uptake of the unstimulated lymphocytes in culture or in the response to any of the three dose levels of PHA used. Neither the extent of the spread of the carcinoma nor the type of its histology showed any correlation with the PHA response, but the PHA response was significantly depressed within 14 days of death in 7 patients. No evidence for serum inhibitory factors was found.

Adult↗

Susceptibility of inbred rat strains to experimental thyroiditis: quantitation of thyroglobulin-binding cells and assessment of T-cell function in susceptible and non-susceptible strains.

Ten inbred strains of rats were immunized with crude homologous thyroglobulin emulsified in Freund's complete adjuvant in order to investigate strain susceptibility to the induction of both thyroiditis and antibody to thyroglobulin. Two strains (LH and AUG) were found to be extremely susceptible and had 100% incidence of thyroid lesions which in general varied from moderate to very severe (mean index of pathology+/-SE, 2-5+/-0-2 and 2-1+/-0-4 respectively). One other strain (HL) also had 100% incidence of lesions but there were consistently mild in character (1-1+/-0-1). Two strains (DA and SD) were variable, with thyroid change varying from negative to severe. Three strains (LEW, WAG and PVG/c) had occasional lesions and the remaining two strains (AS and CAM) showed no thyroid change. Four strains (LH, AUG, HL and DA) consistently produced good antibody responses to thyroglobulin (mean titres+/-SE 7-3+/-0-3, 9-5+/-0-4, 6-9+/-0-3 and 6-6+/-0-5 respectively). In contrast WAG and CAM rats failed to develop autoantibody and the responses of AS, PVG/c and SD strain rats were quite variable. Although the autoantibody response generally correlated well with the presence of thyroiditis in a particular strain, LEW, AS and PVG/c rats often had good antibody levels with minimal thyroid lesions. Females of the most susceptible strains (LH and AUG) were found to have significantly more severe thyroid lesions and higher antibody titres to thyroglobulin than males. The most susceptible strains were all found to be of the Ag-B5 major histocompatibility genotype whilst the least susceptible were of the Ag-B2 genotype. However, wide interstrain variability was noted within the Ag-B5 genotype particularly with respect to the induction and extent of thyroid lesions. It was not found possible to relate the divergence in susceptibility between rat strains of Ag-B5 and Ag-B2 genotypes to differences in respective numbers of thyroglobulin-binding cells within the circulation of the non-immunized animal. Similarly, there were no differences in response between a susceptible (LH) and non-susceptible (CAM) strain to the phytomitogens PHA and Con A.

Animals↗

Thyroiditis in T cell-depleted rats. Influence of strain, radiation dose, adjuvants and antilymphocyte serum.

Strain differences in susceptibility to the development of thyroiditis following adult thymectomy and repeated sublethal X-irradiation (4 X 200 rad) were investigated in the rat. Marked strain variation was noted, with AUG and PVG/c rats having the highest incidence and severity of lesion (100 and 80% respectively) whilst CAM rats had a low incidence (9%). WAG and LIS rats occupied an intermediate position. The incidence of autoantibodies to thyroglobulin correlated closely with the strain incidence of thyroiditis (r = 0-87). Fractionation of the sera from thymectomized and irradiated rats by gel filtration chromatography indicated that the bulk of the antibodies to thyroglobulin were of the IgG class. Freund's complete adjuvant, but not lipopolysaccharide, enhanced the rate of development of thyroiditis in thymectomized rats given a shortened series of irradiations. It was not found possible to induce thyroiditis in thymectomized rats by substituting antilymphocyte serum for irradiation as a T cell-depleting agent, despite the fact that the treated rats had markedly reduced responses to phytohaemagglutinin. A combination of thymectomy, three doses of 200 rad, and a development period of 8 weeks were found to be the optimum conditions for induction of severe thyroiditis together with high antibody titres to thyroglobulin. These findings add support for the role of thymus-derived cells in the regulation of autoimmune responses and further suggest that thymectomy, combined with a series of sublethal irradiations, causes a selective depletion of those T cells specifically involved in the suppression of autoimmune reactivity to thyroid components, whilst leaving autoreactive helper T cells unimpaired.

Animals↗

Observations on the antibody-dependent cytotoxic cell by scanning electron microscopy.

The cytotoxic effect of human peripheral blood leucocytes on antibody-coated sheep erythrocyte monolayers has been investigated using scanning electron microscopy. Only a small proportion of leucocytes were found to adhere to the monolayers. A progressive destruction was observed beginning as small plaque-like areas of erythrocyte clearing which later became confluent. Three distinct cell types were found to be associated with the areas of lysis. No destruction was observed in control monolayers incubated for a similar period in the absence of either antibody of leucocytes. Surface changes in the erthrocytes adjacent to the leucocytes suggest that mechanical factors may be involved in erythrocyte lysis in this system. It is concluded that more than one leucocyte type may damage antibody-coated erythrocytes, possibly by a mechanism involving attachment to and mechanical disruption of the red cell membrane.

Animals↗

Evidence for circulating immune complexes in thyroid disease.

Anti-complementary activity was detected in the sera of 23 (59%) out of 39 patients with Hashimoto thyroiditis; in 10 (29%) out of 34 patients with primary hypothyroidism; in six (17%) out of 36 patients with thyrotoxicosis; and in only six (8%) out of 78 control subjects. Fractionation of Hashimoto sera by Sephadex G-200 chromatography showed that the anti-complementary activity was founding fractions of larger molecular size than monomeric IgG, being localized predominantly in the ascending limb of the second elution peak, suggesting that it was in the form of small immune complexes.

Animals↗