Biomedical subjects
Publications and source records attributed to R Hunt.
Previous work has established that whereas X/X mice carrying the sex-reversing chromosomal fragment Sxr are positive for the male-specific transplantation antigen, H-Y, X/X mice carrying the variant Sxr', although they too develop as phenotypic males, are H-Y negative. In this paper we show that X/XSxr' male mice do not express any male-specific antigen that can induce skin-graft rejection.
In a sample of 1582 deaths among South Australian patients with cancer (795 deaths in 1981 and 787 deaths in 1985), 67% of deaths occurred in a hospital, 9% of deaths in a hospice, 10% of deaths in a nursing home, and 14% of deaths in a private residence. More patients died in a hospice or nursing home in 1985 than in 1981, and fewer died in a hospital. With increasing age, fewer patients died in a hospital and more in a nursing home. Compared with men, women were less likely to die at a private residence and more likely to die in a nursing home. A greater proportion of men with a living wife died at a private residence than was so among single or widowed men. However, conjugal status was not associated with the place of death of women. Patients who lived in the more affluent metropolitan suburbs tended more to die at a private residence than did those from poorer suburbs or country areas. Patients with haematological malignancies died in major metropolitan public hospitals more frequently than did patients with other tumours. Possible explanations are given for these findings.
The calcium antagonist nimodipine blocks the effects of many vasoconstrictors of cerebrovascular smooth muscle and may reduce the incidence of delayed cerebral ischaemia following subarachnoid haemorrhage though not necessarily by inhibiting the development of angiographic cerebral vasospasm. Post-haemorrhagic CSF contains abnormally large quantities of various eicosanoids that partly reflect enhanced production by cerebral arteries. Does nimodipine affect this process? The extra-arterial and intra-arterial production of PG6 keto-F1 alpha, PGE2, PGF2 alpha and TXB2 were measured in perfused common carotid arteries taken from rabbits in which the arteries had been ensheathed by blood clot in vivo for 7 days. All rabbits were given the antifibrinolytic agent tranexamic acid to retard resolution of the clot, and half were given oral nimodipine (2 mg/kg/day) for 10 days. Nimodipine significantly reduced the extra-arterial production of TXB2 during the third and fourth hours of perfusion and, less consistently, the production of PGF2 alpha, PGE2 and PG6 keto-F1 alpha. Lutrol, the solvent for nimodipine, had no such effect.
Increments in dietary protein intake can increase glomerular filtration rate (GFR) in humans, and the glomerular hyperfiltration induced by high protein intake has been incriminated in the progression of glomerulosclerosis related to age and a number of renal diseases. GFR (as 51Cr-EDTA clearance) was measured in 18 vegans, 16 lactovegetarians and 18 omnivorous control subjects, matched for age. Omnivores ate significantly more total protein and protein of animal origin than the other two groups. Vegetable protein comprised 100% of the vegans' daily protein intake and 64% of the lactovegetarians', both significantly higher than the omnivores' (32%). Vegans and lactovegetarians also ate more carbohydrate and fibre than omnivores, although fat intake was similar. Mean GFR was significantly lower in the vegans than in the omnivores (100 +/- 13 vs. 113 +/- 16 ml/min/1.73 m2; p less than 0.04) and was intermediate in the lactovegetarians (105 +/- 16 ml/min/1.73 m2). Omnivores had significantly higher mean urinary albumin excretion rate (p less than 0.05) than vegans, and higher mean diastolic blood pressure than both vegans and lactovegetarians (p less than 0.01). The vegan diet is associated with glomerular and systemic haemodynamic changes which may be beneficial in the prevention of glomerular sclerotic changes in health and disease.
One hundred two armadillos captured from the wild were lepomin tested. Nine of them (8.8%) showed a positive Mitsuda reaction. The histopathological appearance of the reaction had a spectrum showing tuberculoid, borderline tuberculoid, borderline lepromatous, and lepromatous histology. It is possible that armadillos can develop all the different types of leprosy seen in humans. The armadillo is a good animal model to test protective vaccines against leprosy.
This study examines the effects of in-vivo immune regulation by vitamin A acetate (VAA) and 13-cis-retinoic acid (13-CRA) on in-vitro accessory cell function. Mice were fed a control diet, or diet containing VAA or 13-CRA, and monitored by body weight gains and diet consumptions at weekly intervals. At 4, 7 and 12 weeks mice were killed, differential blood counts performed and accessory cells isolated from lymphomedullary tissues. Histology confirmed that the chief feature of the lymphomedullary organs of the VAA-fed animals was an expansion of the splenic marginal zone and the paracortical region of the lymph nodes. There was an increase in the number of accessory cells present, and this included both dendritic cells and macrophages. The accessory cell function of these cells was also increased, as evidenced by both alloproliferative and allocytotoxic responses in vitro. In 13-CRA-fed animals the effects were similar to those seen with VAA, but were less pronounced. We suggest that the primary effects of these compounds on in-vivo immunoregulation could be due to their promotion of accessory cell function.
Substance P, thyrotropin-releasing hormone (TRH) and serotonin are putative neurotransmitters which have been proposed to co-exist in some brain neurons. Our previous immunocytochemical and biochemical studies have demonstrated that 85-100% of all serotonin neurons are destroyed following neonatal 5,7-dihydroxtryptamine (5,7-DHT) treatment. In this study, we have determined the effect of neonatal 5,7-DHT and desipramine (DMI) treatment on the biochemical content and immunocytochemical localization of substance P and TRH throughout the brain. Interestingly, we have observed that virtually all substance P- and TRH-immunoreactive cells in the ventral pons-medulla are destroyed by the neurotoxin. However, peptide-containing neurons in other regions were not affected. Additionally, we measured the peptide content and found that TRH is significantly decreased in the spinal cord (-50%) and pons-medulla (-20%), but not in other brain regions. Substance P content was not significantly altered in any region, even after a greater than 90% reduction of serotonin. These data indicate that the co-localized substance P and TRH forms a small proportion of the total peptide in brain.
Highly purified human recombinant interleukin 2 (IL-2) markedly accelerated lethal GVHD in the H-2-identical B10.BR----CBA combination, but had no effect when the donor cells were depleted of mature (Thy-1.2-positive) T lymphocytes, indicating a strong immunopotentiating effect of IL-2 on mature T cells causing GVHD. In the same donor-host combination, IL-2 did not influence the recovery from the post-transplantation bone marrow aplasia. The results suggest that IL-2 could be considered for adjuvant hormonal therapy to enhance immune recovery in recipients of T-cell-depleted allogeneic marrow.
Explore the source record for details and available documents.
Sex reversed X/X male mice carrying Sxr or the variant Sxr' were typed for expression of the male specific histocompatibility antigen H-Y, by skin grafting and by in vitro cytotoxic and proliferative tests. The X/XSxr males, like X/Y males, were H-Y positive by in vitro testing, and failed to reject semi-syngeneic male skin grafts. In contrast X/XSxr' males, like X/X females, were H-Y negative and rejected semi-syngeneic, male skin. Spleen cells from X/Y males sensitized C57BL/10 female recipients to reject syngeneic male skin rapidly, whilst immunization with X/X female or X/XSxr' male cells failed to stimulate such second-set responses. These data suggest that the H-Y antigen detected by cytotoxic T cells is the same as that detected by graft rejection responses, that the Sxr' variant is not a tissue-specific regulatory mutation, and that X/XSxr' individuals do not express H-Y antigen but nevertheless develop as phenotypic males.
The intraperitoneal (i.p.) administration of autologous spleen cells treated with recombinant interleukin-2 (IL-2) in vitro resulted in the rejection of C57BL/10ScSn (B10) skin grafts that had survived for 18 months on CBA/Ca mice tolerant to B10 alloantigens. Cytotoxic lymphocytes specific for the graft alloantigens, assayed by limiting dilution analysis, appeared after the breaking of this immunological tolerance, whereas they were not detectable in tolerant mice. In these mice the frequencies of precursor cytotoxic cells specific for third-party alloantigens were unaffected by the IL-2 treatment.
The long-term effects of N-ethylretinamide (NER) on the haematology of the rat, and the dose-related effects of retinoids on lymphoid organs of the mouse and rat were investigated. Retinoid-induced long-bone changes were used to develop a method for quantifying skeletal effects. This technique was used to investigate the activity of five retinamides in inducing long-bone changes in the rat. The ability of non-steroidal anti-inflammatory compounds (NSAICs) to prevent retinoid-induced skeletal effects was examined, and preliminary investigations made into the mechanisms of retinoid-induced long-bone remodelling. NER-fed rats had reduced red blood cell counts and fibrinogen values. Retinoids caused dose-related proliferation of the spleen and lymph nodes in the mouse and to a lesser extent in the rat. They induced dose-related reductions in femoral diaphysis and medullary cavity diameters in both rats and mice. Aspirin prevented NER-induced changes of rat long bones, but subsequent studies indicated this effect may be closely dependent on the dose level of both the retinoid and NSAIC administered. Retinoids induce rapid long-bone remodelling in the rat which tends to revert on feeding a control diet, but remodelling processes are different in the young growing rat and the mature animal.
Twenty-four hours after skin painting nude mice with picryl chloride, there was an increase in the number of dendritic cells (DC) isolated from the draining lymph nodes. This increased inflow or retention of DC in lymph nodes following skin painting is therefore unlikely to depend on interaction of DC with T cells. The DC obtained initiated primary proliferative responses in vitro in lymph node cells from congenic euthymic mice. Contact sensitivity developed in congenic mice when they received footpad injections of 60,000 DC from the lymph nodes of nude mice skin sensitized 1 day previously with picryl chloride or oxazolone. The initiation of delayed hypersensitivity was therefore independent of T-cell contamination within the donor DC.
Dendritic cells (DC) exposed to antigen are potent initiators of immune responses, and the numbers of DC and the dose of antigen control the level of response. The influence of these variables was tested on the growth of mouse sarcoma cells in vivo. When normal syngeneic DC (100,000) were given to mice with palpable tumors, tumor regression or delay in tumor growth was obtained. DC exposed to increasing doses of tumor extract in vitro before administration had progressively less effect. DC exposed to antigen delayed tumor growth significantly only when given on the same day as 500 tumor cells. The studies suggested that low doses of antigen on DC elicit immune responses and that high doses block them. The numbers of antigen-presenting cells and the dose of antigen modulate the degree of immunity to mouse sarcoma in vivo.
The susceptibility of newborn mice to the inception of tolerance after exposure to antigen is associated with their deficiency in the production of endogenous interleukin 2 (IL-2). As further evidence of the complicity of IL-2 in the inception and maintenance of tolerance, it is shown here that a solid and long-lasting state of tolerance induced by the intravenous injection into newborn CBA mice of lymphoid cells from (CBA X C57BL/10ScSn)F1 hybrids can be brought to an end by the administration of exogenous IL-2 or by supplementing an otherwise normal diet with vitamin A acetate, the effect of which is to increase the proportion of the moiety of the T-cell population that produces IL-2. These results indicate that certain nonspecific stimuli can influence whether immunological tolerance is maintained.
A conventional diet enriched in retinyl acetate (vitamin A acetate; VAA) or in vivo administration of exogenous interleukin-2 (IL-2) can effectively annul the otherwise tolerogenic stimulus represented by (CBA X C57BL/10ScSn) F1 cells injected intraperitoneally into newborn CBA mice. On the basis of these data and results of others, we postulate that an antigenic stimulus associated with a relative lack of IL-2 (or generally the lack of a 'secondary stimulus') can be tolerogenic rather than immunogenic. However, the tolerogenicity of the antigenic stimulus can be substantially reduced or even converted to sensitization (R. P. Cleveland & H. N. Claman, J. Immun. 124, 474-480, 1980), when the antigenic signal is appropriately associated with a concomitant or additional stimulus possibly mediated through IL-2.
The subcellular distribution of Zn, Cd, Cu and Hg in liver and kidney from a narwhal was determined by ultracentrifugation and gel filtration. Most of the total mercury in the liver and kidney was bound by the cellular pellet (88 and 73%, respectively). Of the total mercury, 7 and 11% was in the form of methylmercury in the liver and kidney, respectively. More than half (74%) of the total Zn and Cu in the kidney was in the cytosol and somewhat less than this was in the cytosol of the liver. Almost all of the cadmium in liver and kidney (88 and 92%, respectively) was in cytosol. Cytosolic fractions from liver and kidney were evaluated for the presence of metallothionein by analysing for Zn, Cd, Hg, Cu, Fe and--SH groups, by molecular weight estimation and by u.v. absorption spectra. Metallothionein was found in these organs in estimated concentrations similar to those present in terrestrial and other marine mammals.
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.