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Biomedical subjects

R Hunt

Publications and source records attributed to R Hunt.

At least 91 records · Page 5Linked to original sources

Retinyl acetate-mediated augmentation of resistance to a transplantable 3-methylcholanthrene-induced fibrosarcoma. The dose response and time course.

An otherwise conventional diet supplemented with retinyl acetate (vitamin A acetate; VAA) increased a specific antitumor resistance in vivo in mice, and this appeared to be due to the enhancement of immune functions rather than a direct antitumor activity. A range of VAA doses (up to 0.8 g VAA per kg of diet), fed for more than 6 months, did not induce any obvious signs or symptoms of hypervitaminosis A. The augmentation of resistance to transplanted tumor was linearly dependent on the dose of VAA. There was also a positive linear relationship between the resistance to transplanted tumor and the length of exposure to supplementary VAA relative to tumor inoculation time. The maximum resistance to transplanted tumor was observed in VAA-fed mice when the enrichment of the diet with VAA started three or more weeks before inoculation of tumor, whereas initiation of the VAA diet on the day of tumor administration or later had a negligible effect on the growth of tumor.

Animals↗

Arterial eicosanoid production following chronic exposure to a periarterial haematoma.

Cisternal and lumbar cerebrospinal fluid obtained some days following a subarachnoid haemorrhage contains abnormally large quantities of various prostanoids; some may be partly the result of abnormal production by the cerebral arteries. The extra-arterial and intra-arterial production of 6 oxo PGF1 alpha (prostacyclin metabolite), PGE2, PGF2 alpha and TXB2 were measured in perfused rabbit common carotid arteries taken both from normal rabbits and from rabbits in which the arteries had been ensheathed by blood clot in vivo for 7 days using two techniques. Prostaglandin production by control arteries was highest during the first hour of perfusion but declined or increased marginally (PGE2) during the succeeding three hours. Arteries exposed to a periarterial haematoma for 7 days produced prostaglandins at a high rate throughout the 4 hours of study, and there was a progressive and marked increase in PGE2 production. The disproportionate increase in the cerebral vasoconstrictor PGE2 may reflect the inflammatory response which occurred in the adventitia of the vessels. Increased prostanoid production by cerebral arteries probably does contribute to the increased levels in CSF after subarachnoid haemorrhage.

6-Ketoprostaglandin F1 alpha↗

Can fetal antigens be used for prophylactic immunization?

Even if the inoculation of fetal tissue cells were a dependable and uniformly successful method of protecting experimental animals against chemically or virally induced tumours, it would for obvious reasons still not be feasible to use fetal tissues for such a purpose in human beings. Among possible substitutes syngeneic spermatozoa were tested on the grounds that they are the only adult cells that express T-alleles, but neither they nor teratocarcinoma cells protected mice against tumours raised by 3-methylcholanthrene. Testicular and thymic cells and tissue fragments have given effective protection in a number of experiments and it is noteworthy that fetal tissues, testicular cells and thymus cells are cross-reactive in respect of anti-embryo antibodies. Testicular cells probably act like fetal cells and, like fetal cells, are very prone to give rise to 'enhancement'. Thymic cells do not 'enhance' and may act quite differently. The variability of results--a source of grave concern--is attributed to the insensitivity of the test system which is ill-adapted to show up low degrees of protection.

Animals↗

Host recognition of fetal antigens: do they induce specific antibodies?

The purpose of this study was to ascertain whether the protection afforded to adult mice against the induction and growth of 3-methylcholanthrene-induced tumours by prior exposure to syngeneic fetal cells has an immunological basis. Adult CBA mice were inoculated with fetal cells according to a variety of protocols and the sera were tested for their ability to bind to fetal and adult tissue cells, using a staphylococcal protein A binding assay. All 10 sera tested showed some degree of binding though this varied from strong to weak, and there was some cross-reactivity with adult thymic cells but relatively little with adult spleen cells. Absorption studies were carried out with one of these sera and with two others raised against testicular and thymic cells, respectively. The absorption patterns obtained so far suggest that fetal cells possess at least three, and possibly up to five, distinct antigens. Although none of the anti-fetal sera were produced with a sensitizing protocol identical with that used in in vivo protection, some of them were so close as to suggest that protection is associated with, and perhaps causally related to, these IgG antibodies. The in vitro evidence presented here, together with the in vivo data of P. B. Medawar & R. Hunt, shows that antigens are shared between fetal cells and adult thymic and testicular cells. It therefore lends support to the notion that the production of a vaccine against anaplastic neoplasms, using immunogens derived from adult tissues, is within the realms of possibility.

Animals↗

Enhancement of specific antitumor immunity in mice fed a diet enriched in vitamin A acetate.

Age-matched male CBA mice on a conventional or a vitamin A acetate (VAOAc)-rich diet were immunized with irradiated cloned 3-methylcholanthrene- or Harvey sarcoma virus-induced (McSa-1 or HT3-2.1) sarcoma cells and then challenged with viable corresponding or unrelated (non-crossreacting) syngeneic sarcoma cells. The survival of the specifically immunized mice on the VAOAc diet was significantly prolonged in comparison with all control groups of mice as assessed by using logrank tests. Moreover, the specific immunization markedly decreased the incidence of tumors after the McSa-1 (but not HT3-2.1) challenge in a group of mice on the VAOAc diet (5% tumor incidence) compared with the equivalent group on the control diet (50% tumor incidence). Neither the VAOAc diet nor in vivo immunization alone or combined influenced natural killer cell activity. Specific T-cell-mediated cytotoxicity after in vivo priming and in vitro boosting with sarcoma cells was increased in VAOAc-fed mice. However, the marginal increase in cytotoxicity does not in itself explain the strikingly increased resistance to tumor transplants in preimmunized mice on the VAOAc diet in comparison with preimmunized mice on the control diet. The results indicate that a diet enriched in VAOAc can modify the ability of the immune system of a mouse to respond effectively to tumor antigens and can influence whether a tumor grows or regresses.

Animals↗

Wound infection rates after gastric surgery in a Melbourne hospital.

In four groups of 25 patients in whom perioperative prophylactic antibiotics were not used, the wound infection rates after partial gastrectomy were 40% in gastric cancer, 44% in chronic gastric ulcer, 24% in chronic duodenal ulcer and after trunkal vagotomy and pyloroplasty, the wound infection rate was 12%. In gastric cancer and chronic gastric ulcer, most wound infections were caused by enterobacteria, while in chronic duodenal ulcer almost all infections were caused by Staphylococcus aureus. Appropriate short-term perioperative prophylactic antibiotic use is likely to decrease wound sepsis rate in patients who have a gastric resection in the presence of gastric cancer or gastric ulcer.

Adult↗

Differences in putative minor histocompatibility but not IgH genes can prevent T-cell priming and T--B co-operation in the response of mice to sheep erythrocytes.

A positive association has been observed in Igh allotype "congenic' mice between skin graft rejection and a block to effective T--B co-operation in the development of both IgM and IgG responses to sheep erythrocytes. Mismatch of Igh alone is insufficient for such a block to become apparent since pairs of Igh-allotype congenic strains of mice which reciprocally accept skin grafts for at least 5 weeks, show successful positive co-operation (help) between T and B cells. The observed block is manifest both during the education (priming) of T cells in irradiated (first stage) recipients and during co-operation between primed T cells and unprimed B cells in second stage irradiated "syngeneic' recipients.

Animals↗

Anti-cancer action of retinoids.

The anti-cancer action of retinyl acetate (Vitamin-A acetate, VAA), chosen as a representative retinoid substance, is attributed to its power to exercise immunopotentiation, though other possibilities are considered. The reasons for forming this opinion were: (1) chronic administration of VAA brought about enlargement of the thymus and peripheral lymph nodes; (2) the administration of VAA curtailed the life of skin allografts though (3) its action could be reversed by the concomitant administration of immunosuppressive agents.

Animals↗

An influence of diet on transplantation immunity.

It was discovered by chance that mice raised under otherwise entirely conventional conditions of husbandry but fed upon autoclaved diet (diet A) had stronger cell-mediated immune reactions than those of mice raised under the same conditions but with an unmodified diet (diet B) : skin allografts were rejected more quickly, transplantation tolerance was more difficult to procure and fibrosarcomas induced by the injection of methylcholanthrene (MCA) arose more slowly and less often. Analysis showed that these findings could be explained at least in part by the discovery of Mertin & Hunt (1976, p. 928) that a partial deprivation of polyinsaturated fatty acids led to an intensification of cell-mediated immunity; on the other hand, experiments with dietary mixtures made it seem unlikely that this was the whole explanation and pointed towards some positive immunopotentiation by an ingredient of autoclaved diet. This, it was proposed, might be a compound of unknown composition resulting from the interaction of vitamin A with other dietary constituents. This interpretation was not supported by direct evidence but by confirming that retinol derivatives, especially retinyl acetate, could exercise an immunopotentiation of the kind and degree under investigation: retinyl acetate could counteract the immunosuppressive action of linoleic acid, though retinyl methyl ether was ineffective. Although retinyl derivatives may protect against MCA tumours by impeding its metabolic conversion to an oncogenic form, the effects of an autoclaved diet upon skin allograft survival, the induction of tolerance and the formation of tumours is probably mediated through an immunological mechanism.

Animals↗

Prolonged apnea of an oral surgery patient after administration of succinylcholine.

To properly diagnose the presence of a genetic pseudocholinesterase variation, the family history is important. Furthermore, the DN and pseudocholinesterase tests are most useful, but if facilities for these are not available, one should be wary of patients with abnormal liver function tests. Certainly medical history, family medical history, laboratory evaluation, and knowledge of the disease processes should avoid unnecessary complications.

Adolescent↗

Reduction by linoleic acid of the severity of experimental allergic encephalomyelitis in the guinea pig.

This paper reports the effects of supplementation of the diet with linoleic acid on the severity of experimental allergic encephalomyelitis (EAE) in guinea pigs. Clinical signs of disease (e.g. paresis, paraplegia, urinary incontinence), weight loss, frequency of perivascular lesions in the central nervous system and ability of isolated lymph node cells to respond to myelin basic protein in vitro were all reduced by linoleic acid supplementation. Linoleic acid was effective when fed at a dose of 0.5 ml/day from 7 to 21 days after sensitization of the animals with basic protein, i.e., before and during the time in which clinical signs normally appeared. The same daily dose fed from 7 days before to 7 days after sensitization, i.e., ceasing about 7 days before the normal time of appearance of clinical signs, produced no significant effect. Feeding linoleic acid to normal guinea pigs significantly altered the fatty acid composition of their serum and lymph nodes, but not of their brain. Of several possible explantations for the protective effect of lineolic acid in EAE, we considered action by this essential fatty acid on the immune system most likely.

Animals↗

Cardiopulmonary manifestations of systemic lupus erythematosus.

Nine of 17 patients (52%) with systemic lupus erythematosus participating in a controlled prospective study were found to have maximal mid-expiratory flow rates suggestive of obstructive or obstructive and restrictive pulmonary disease. Cigarette smokers with systemic lupus erythematosus had significantly lower (P less than .05) maximal mid-expiratory flow rates than either non-smokers with systemic lupus erythematosus or smokers with degenerative joint disease. By echocardiography, pericardial thickening was seen in six of 17 patients (41%) and mitral valvular abnormalities were noted in four of 17 (24%) patients with systemic lupus erythematosus. Echocardiography was found to be an effective means of detecting pericardial disease in patients with systemic lupus erythematosus.

Adolescent↗