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Biomedical subjects

J L Gowans

Publications and source records attributed to J L Gowans.

At least 19 recordsLinked to original sources
PubMed1983

Medical research council trial of antilymphocyte globulin in renal transplantation. A multicenter randomized double-blind placebo controlled clinical investigation.

A total of 173 patients who received live donor or cadaveric primary or secondary renal transplants at five British hospitals were entered into a randomized double-blind controlled clinical trial of equine antilymphocyte globulin (ALG) administered prophylactically to prevent rejection. The ALG was prepared in the early 1970s and used cultured human lymphoblasts as antigen. Following transplantation all patients were treated with a standard immunosuppressant regimen of steroids and azathioprine and, in addition, were given either 30 mg/kg ALG or placebo daily for 10 days by intravenous infusion. In comparison with more recently produced materials, the ALG employed in this study was of moderate potency in prolonging skin graft survival in monkeys. Primary graft failure occurred in 27 patients (15/86 ALG and 12/87 placebo). At three to five years after transplantation 50 of the remaining patients had died, almost all from diseases relating to their renal condition, and 25 more had suffered complete graft failure. No significant differences were found between patients treated with ALG and placebo in the numbers with functioning grafts during the 3 years following transplantation, in the time between transplantation and the first rejection episode, or in the number of episodes during the first six months after transplantation. This applied whether live or cadaveric grafts were employed. Within the first 6 months of operation, infection was given as a major contributory cause of death in 12 patients treated with ALG and in 5 who received placebo (P greater than 0.1). Infections were also slightly more common during the two weeks following transplantation in those receiving ALG (13/86 ALG, 10/87 placebo). As expected, graft survival was significantly better in patients who received live donor grafts (P = 0.001) and in patients with the least donor-recipient histocompatibility mismatches (P = 0.008). The results of this multicenter trial show no therapeutic benefit to renal graft recipients from the administration of ALG, and suggest that the risks of fatal infection may have been aggravated. Use of such equine ALG in similar dose regimens is therefore, not, justified in renal transplantation, especially if some part of the apparent effects on fatal infections is real. It is stressed that these findings are relevant only to the equine ALG used in this study, which was raised with cultured human lymphoblasts as the antigen, and to ALG prepared in a similar way and of similar potency. It should not be inferred that these results are applicable to ALG prepared in other ways.

Adolescent↗
PubMed1981

Morton Simonsen.

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Graft vs Host Reaction↗
PubMed1980

The function and pathways of lymphocyte recirculation.

The early work on lymphocyte recirculation assumed that all recirculating lymphocytes composed a common pool and that the composition of this pool could be inferred from studies on thoracic duct lymph. These propositions are examined in the light of more recent evidence, particularly from experiments on the traffic of lymphocytes through the lamina propria of the small intestine. There has been little speculation on the functional significance of lymphocyte recirculation apart from the suggestion that it increases the efficiency of regional immune responses by allowing antigen-induced selection of precursors from pool larger than that accommodated by the regional nodes alone. In addition, the mounting of a local immunity is dependent on a peripheral recirculation through the tissues, notably in the case of the secretory immune system of the intestine.

Animals↗
PubMed1979

Summing-up.

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Cell Differentiation↗
PubMed1978

The origin and antigen-dependent distribution of IgA-containing cells in the intestine.

The aims of this paper were to establish the origin of cells producing IgA antibody to cholera toxoid in the lamina propria of the small intestine and to define the role of antigen in their distribution. The use of Thirty-Vella loops made it possible to restrict antigenic challenge to a defined segment of the intestine in rats which had been primed i.p. with toxoid in Freund's complete adjuvant. The anti-toxin-containing cells (ACC) which appeared in the draining thoracic duct lymph after challenge of a loop were almost all of IgA specificity and their numbers were proportional to the length of intestine exposed to antigen. The abolition of this cellular response which occurred when Peyer's patches (PP) were removed from a loop before challenge and the failure of mesenteric lymphadenectomy significantly to affect the response indicated that ACC originated exclusively from PP. Cell transfer studies showed that although nonrecirculating large lymphocytes gave rise to ACC in the lamina propria, some of the recirculating small lymphocytes also developed subsequently into ACC. Counts of ACC in the lamina propria of challenged loops were consistently greater than in nonchallenged loops although some ACC were always present in the latter. However, a time-course study on the appearance of ACC in the lamina propria of cannulated rats given a single dose of thoracic duct lymphocytes from immunized donors demonstrated that ACC continued to accumulate and persist in challenged loops but only appeared transiently in nonchallenged loops. These transients did not migrate from the lamina propria back into the lymph and they presumably died in situ. The increase in the number of ACC in loops which had been challenged with antigen was probably due both to cell division in the lamina propria and to the development of new ACC from recirculating lymphocytes which had been recruited into the loop. Thus, the cells which give rise to intestinal ACC can migrate into the lamina propria independently of antigen, but antigen has a profound effect on the location, magnitude, and persistence of the response.

Animals↗
PubMed1976

Nature of cells binding anti-IgE in rats immunized with Nippostrongylus brasiliensis: IgE synthesis in regional nodes and concentration in mucosal mast cells.

The possibility that IgE is a secretory immunoglobulin has been examined by studying the tissue and cellular localization of IgE in rats infested with the enteric parasite, Nippostrongylus brasiliensis. The lamina propria of the small intestine and the colonic and pulmonary mucosal surfaces contained numerous anti-IgE-binding cells, but these were shown to be mast cells and not plasma cells. The major site of IgE synthesis was the regional lymph node of the small intestine, the mesenteric node, which contained large numbers of IgE-secreting plasma cells. Smaller numbers of IgE-secreting plasma cells were also found in the axillary node, which drained the site of larvae injection. Peyer's patches, the intrapulmonary bronchial lymphoid tissue and the spleen contained few, if any, IgE-secreting plasma cells. The significance of the IgE which was readily demonstrated in germinal centers of the mesenteric lymph nodes, the Peyer's patches and the axillary lymph nodes, is not known. In contrast to the infested animals, the lymphoid organs of normal rats rarely contained any IgE-CONTAINING CELLS; An unexpected observation was that mast cells in mucosal organs appear to contain intracellular IgE, differing in this respect from connective tissue mast cells. Mast cells lying between epithelial cells, the "globule leukocytes", also appear to contain intracellular IgE, and it is suggested that such cells may be responsible for the presence of IgE in exocrine secretions. This study does not support the suggestion that IgE is a secretory immunoglobulin with a physiology analogous to that of IgA.

Animals↗
PubMed1975

Cellular kinetics of the intestinal immune response to cholera toxoid in rats.

The aims of this study were (a) to find a regime of immunization with cholera toxoid in rats which would establish a high density of antitoxin containing cells (ACC) in the lamina propria of the intestine and (b) to determine the origin of the ACC. The best cellular response was achieved by a single i.p. dose of toxoid in FCA followed by an intraintestinal boost 2 wk later. ACC appeared in the thoracic duct lymph 2 days after boosting, reaching a peak of about 200,000 ACC/h at 3--4 days. This was followed by the appearance of large numbers of ACC in the intestine. The i.p. dose of toxoid by itself gave rise to very few ACC in the gut or thoracic duct lymph, but it had clearly primed the gut immune system for a secondary response. Priming was also achieved by the prolonged oral intake of toxoid. The importance of the intestinal route for boosting was shown by the failure of i.p. challenge to give an ACC response in the intestine after i.p. priming and the small response it provoked after oral priming. ACC among thoracic duct lymphocytes (TDL) and in the lamina propria contained predominantly IgA. Two observations indicated that the major source of the lamina propria ACC was from cells that emerged in the thoracic duct lymph after intraintestinal challenge. Firstly, the establishment of a thoracic duct fistula immediately before challenge prevented the appearance of ACC in the intestine. Secondly, many ACC appeared in the intestine of normal rats after the injection of TDL rich in ACC. Although homing of ACC precursors to the gut was not antigen-dependent, the distribution of ACC in the lamina propria was considerably influenced by the site of the intestinal challenge, the density of ACC being greatest at or distal to the site of injection of toxoid into the lumen of the gut.

Animals↗
PubMed1975

The presence of IgA on the surface of rat thoractic duct lymphocytes which contain internal IgA.

The presence of lymphocytes with internal IgA among cells from rat thoracic duct lymph wdy. The number of cells detected was greater in animals kept in a convential animal house compared with those maintained under specific pathogen-free conditions. Thoracic duct lymph from B rats and adult thymectomized rats also contained cell with internal IgA. The surface Ig of the IgA-containing cells was studied using a double-labeling technique with (126I) anti-Ig to detect surface Ig, and fluorescein-conjugated anti-IgA in large amounts, but very little IgM and no surface IgG2. The surface IgA was not acquired passively.

Animals↗
PubMed1975

Lymphocytes.

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Humans↗
PubMed1974

Alternatives to animal experiments in medical research.

In laboratory work which involves the large-scale routine assay of biologically-active substances the sponsors of "alternative" (in vitro) methods and the scientists have a common aim: a reduction in the use of living animals. In vitro methods are usually more accurate, easier to perform, and cheaper. Animals are no longer required for the production of certain antiviral vaccines.Those engaged in medical research where new knowledge is being sought also need no incentive to develop in vitro methods because they make refined analysis possible. Nevertheless, such in vitro methods are usually not alternatives in the sense that they substitute for animals; they complement experiments on animals. A legal requirement "that no experiment on a living animal may be performed if the purpose of the experiment can be achieved by alternative means not involving an experiment on a living animal" would be unenforceable.

Animals↗