1. The maximal activities ofhexokinase (HK), 6-phosphofructokinase (PFK), lactate dehydrogenase, citrate synthase (CS) and glutaminase (GLU) which provide quantitative and qualitative indices of flux through several important metabolic pathways have been examined in the wounded skin of haired immune competent Balb/c mice and hairless immune deficient Balb/c (nu/nu) mice of various ages during the first ten days of wound healing. 2. The potential for glucose utilization and for aerobic metabolism as suggested by the maximal activities of HK, PFK, CS, were raised in the skin of Balb/c mice of various ages on all post wounding days. Increases in the maximal activity of GLU was observed only in the skin of 6 and 10 weeks old Balb/c mice during wound healing. 3. There was no evidence of a contribution to the maximal activity of GLU by infiltrating cells of the immune system to the wound site in the skin of either haired or hairless mice.
1. Cells from the bone marrow and cells from the thymus of the rat were incubated in the presence of glucose and glutamine and phytohaemagglutinin, concanavalin-A or lipopolysaccharide. Cells were harvested at times up to 4 hr, extracted and maximum activities of hexokinase, lactate dehydrogenase, citrate synthase or glutaminase measured. 2. In bone marrow cells, there were little changes in enzyme activities except for an increase in the activity of citrate synthase which was prevented by concanavalin-A. This mitogen also caused a decrease in the activity of hexokinase. 3. In contrast, in thymocytes, the activities of hexokinase and glutaminase were decreased in the control condition but addition of lipopolysaccharide, a B-cell mitogen prevented these decreases in activity and concanavalin-A maintained the activity of glutaminase. Concanavalin-A caused a decrease in hexokinase activity but a marked increase in that of glutaminase. 4. It is suggested that changes in the maximum activities of hexokinase and glutaminase over this 4 hr period may represent the effect of removal of thymus-produced growth factors, whose effects can be replaced, at least in part, by two mitogens.
1. The maximal activities of hexokinase (HK), 6-phosphofructokinase (PFK), lactate dehydrogenase (LDH), citrate synthase (CS) and glutaminase (GLU) which provide a quantitative indices of flux through several important pathways have been measured in the skin of haired Balb/c and hairless Balb/c (nu/nu) mice under normal and dietary stress. 2. The skin of old haired mice exhibited higher PFK and LDH activities with lower HK, CS and GLU activities. All activities of enzymes associated with energy metabolism in the skin of old hairless mice were higher than those in the skin of haired mice. 3. HK, LDH, CS and GLU activities were maintained at normal levels in the skin of haired mice when these mice were fed diets deficient in energy or protein components (HPLE, LPNE). These enzymes however were severely suppressed when mice were fed a diet deficient in both energy and protein components (LPLE). Recovery of activities of these enzymes to the control level was observed when mice were refed with the normal diet for a week.
1. The activities of hexokinase, lactate dehydrogenase and citrate synthase were maintained in mesenteric lymph node lymphocytes during 4 hr of culture: the activity of glutaminase increased during this period of time. 2. In splenocytes, the activity of hexokinase decreased markedly during the 4 hr period, whereas those of lactate dehydrogenase and glutaminase remained constant, and that of citrate synthase increased dramatically. 3. In both mesenteric lymphocytes and splenocytes, addition of the T-cell mitogens, phytohaemagglutinin or concanavalin-A, to the culture medium caused decreases in the activities of both hexokinase and citrate synthase. 4. In contrast, these mitogens increased the activity of glutaminase in both cell types. 5. Addition of the B-cell mitogen, bacterial lipopolysaccharide, had little effect on hexokinase, lactate dehydrogenase or citrate synthase but increased markedly that of glutaminase in mesenteric lymph node lymphocytes. 6. In splenocytes this mitogen prevented much of the decrease in hexokinase activity, increased the activities of citrate synthase and glutaminase but had little effect on that of lactate dehydrogenase.
The activities of key glycolytic enzymes are, in general, similar at the three different ages of the animals used in this work (very young, adult and old). Glutaminase is present in skin of both mice and rats, but the activity was much lower in adult animals compared to the very young or the old. It is suggested that this activity is important for the provision of nitrogen for the de novo synthesis of purine and pyrimidine nucleotides during the growth of skin in the young animal and for DNA repair in the old animals; it might be important in the adult skin in response to wound healing.
SummaryThe influence of the respirable fraction of an iron ore dust on immunity has been studied. The iron ore dust enhanced the specific immune responses to both sheep erythrocytes and a bacterial lipopolysaccharide. The IgG class of antibody was enhanced significantly and its pattern of enhancement suggested that the iron ore dust was functioning as an adjuvant. In studies to test this possibility further, the pattern of antibody development over both the primary and the secondary immune response to sheep erythrocytes closely matched that of Freund's incomplete adjuvant and low levels of silica. The splenocytes, from animals that had received iron ore dust for various lengths of time, exhibited enhanced polyclonal mitogenic activity for phytohaemagglutinin, in vitro. These properties were seen when the dust had been inhaled or injected into the pleural cavity and persisted for over 1 year following the injection or inhalation of the dust. Attempts to show the induction of interleukin‐1 by the macrophages from mice implanted intraperitoneally with the iron ore dust were unsuccessful.
The respirable fraction of an ore dust from the North-West of Western Australia was tested for biological properties by inhalation and intrapleural implantation trials using rats and mice. Pulmonary histology indicated significant levels of interstitial pneumonia occasionally associated with bronchopneumonia, bronchiectasis, emphysema, and lung collapse over that found in age-matched control animals. While there was a significant increase of the incidence of tumors in general in WAG inbred rats up to 2 years following dust exposure, this did not persist into old age. No mesotheliomas were induced by any treatments associated with iron ore dust, although the rats were shown to be susceptible to crocidolite asbestos-induced mesothelioma. In the mouse models, tumors which are normally seen only in aged animals were induced with a significant number of bronchial adenomas being recorded following intrapleural implantation of dust into inbred BALB/c mice. Leukemia/lymphoma associated with murine leukemia virus was increased following dust inhalation by inbred C57BL mice.
Daily exposure of the high leukemic AKR strain of mice to low levels of fresh tobacco smoke (TS) produces significantly different mortality profiles associated with both the sex of the animals and the age at which TS exposure commences. Females tend to be susceptible and die sooner than males, where a significant proportion of animals survives longer than age-matched controls. This prolongation of life appears to be due to a failure of the leukemic state to be mobilized in the TS-exposed males. Exposure of both the females and the males to the TS does not induce significant detectable immunological reactivity against the leukemic cells for several parameters tested, possibly due to a significant enhancement of suppressor activity in the serum of the chronically exposed animals over and above that which also occurs in age-matched control animals.
Multiple exposures to broadband ultraviolet (uv) radiation resulted in alterations in the ability of BALB/c mice to produce antibodies to the T-dependent antigens ovalbumin and sheep erythrocytes following intraperitoneal, intradermal, and intravenous inoculation. A number of differences were observed in the influence of uv radiation on the specific cells producing antibody, as opposed to pure serological analyses. While both enhancement and reduction of the humoral response occurred, the experiments have suggested that the alterations in antibody responses following uv irradiation appear to be dependent on the nature of the antigen, the route of antigen administration, and the sometimes transient nature of the responses. The intradermal route of antigen inoculation was under the greatest influence of uv radiation.
A statistical technique has been employed to study the effects of various environmental factors in altering the actinomycete populations of soils located in the western part of Australia. Over 12,000 actinomycetes obtained at 28 different locations were included in the evaluation. Among factors that had a significant influence were the geographic area at which the sample was taken, the nature of plant rhizosphere, and a rainstorm. Seasonal changes in population did occur, but there was considerable stability of population with time. Although marked differences occurred in types of actinomycetes present among different geographic locations, multiple samples taken within a location at distances of 30 cm or greater showed marked similarity in populations. There were varied degrees of diversity among the populations studied. The population that developed after a rainstorm was low in diversity, whereas the populations of root rhizospheres were as diverse as those of plant-free soil-litter areas. In assessing the ecology of soil actinomycetes, it is important to consider the degree of change in population induced by an environmental factor and also its effect on diversity, since the effects may be complementary or may be opposite in nature.
Mice were exposed to high-tar (HT) (16 mg tar/cigarette) filtered cigarettes for up to 32 weeks. Intraperitoneal caseinate induction of polymorphonuclear (PMN) cells in both tobacco smoke (TS)-exposed and age-matched control mice provided the source of cells which enabled an assessment to be made in vitro of both their phagocytic and degradative properties. Radioactive Staphylococcus aureus were opsonized with either immune serum or heat-inactivated (complement deficient) immune serum for the tests. Two strains of mice were used in all trials. The PMN cells from BALBc strain mice were less affected by TS exposure than those of C57 Black mice in both phagocytic and degradative capacities when the S. aureus were opsonized with immune serum. However, heat inactivation of complement within the serum reduced the differences between TS-exposed animals and age-matched controls in both strains of mice. The treatment effects were seen at all times tested from 3 days to 32 weeks of TS exposure. The results suggest that fc-receptor site activity of PMN cells is not significantly affected by TS exposure but that complement interactions within the phagocytic process are significantly suppressed. Whether this is due directly to complement receptors or metabolic associations of phagocytosis of the complement/opsonin/antigen complex is unclear.
Tri-iodothyronine has been shown to affect murine lymphocyte responses to phytohaemagglutinin in vitro. These results coupled with previously obtained results on the effect of thyroid hormone on humoral responses suggest a possible novel approach to immunization.
Balb/c mice were exposed to fresh smoke, equivalent to 30 high-tar filtered cigarettes/day, for 83 wk or less. After groups of mice were subjected to 56, 64, 72, and 80 wk of tobacco smoke (TS) exposure, serum antibody responses to both T-dependent and T-independent antigens, numbers of plaque-forming cells, spleen cell and lymph node PHA responses, and systemic clearance of normal and opsonised antigen were investigated. Aged TS-exposed mice showed some deterioration of immune responsiveness with age, but results varied; in extreme old age the immunological responsiveness of TS-exposed mice was similar to that of age-matched controls. In addition, groups of mice inoculated with fibrosarcoma cells after 78 wk TS-exposure did not show significantly greater susceptibility to the early development of pulmonary metastases.
Mice exposed to tobacco smoke (TS) for 3 days or 18 or 28 weeks, prior to SRBC inoculation, subsequently displayed less pronounced and/or “shorter‐lived” splenomegaly than age matched controls. In addition mice exposed to TS for three days or 18 weeks displayed a reduction in both the magnitude and duration of the primary immune response as evidenced by the pattern of expansion of splenic white pulp and “RNA‐rich” white pulp volumes. In contrast mice exposed to TS for 28 weeks, prior to inoculation, displayed white pulp and “RNA‐rich” white pulp volumes similar to those of control mice.
Balb/c mice were exposed to the fresh smoke of a daily equivalent of thirty high tar filtered cigarettes for periods of up to 95 weeks. Detailed surveys of the gross and histopathological data are presented which indicates that there is the induction or production of significant numbers of malignant tumours of several types in the animals exposed to tobacco smoke. There are also significant histopathological changes which consist mainly of interstitial pneumonia and focal low grade emphysema. These features contribute significantly to the reduction in life span of the test animals in which the main causes of death are malignancies and inflammatory diseases of the lungs.
It has been previously shown that the thyroid gland and its associated hormones are able to influence mammalian immune responses. The purpose of this study was to determine whether humoral immune responses are under similar control in avian systems. We report that during the primary response to sheep erythrocytes (SRBC), serum antibody titres and depression of serum T3 levels are significantly correlated. We also show that chemical modification of thyroid function inhibits the production of serum antibody titres, following both primary and secondary challenge with SRBC. However, serum antibody titres were found to rise dramatically within 48 h of cessation of treatment. These results indicate that T3 may play an important role as a regulator of avian humoral immune responses.
Mice were exposed to high-tar (HT) (16 mg tar/cigarette) or low-tar (LT) (5 mg tar/cigarette) filtered cigarettes for 8 min per day for up to 30 weeks. Phagocytic and degradative properties of the liver and spleen were assessed using unopsonized and opsonized radioactive sheep erythrocytes (SRBC) inoculated intravenously into naive or immune animals. Initially phagocytosis of unopsonized SRBC was shown to be compromised in HT-tobacco smoke-exposed animals of both the Balbc and C57Black strains of mice but not for LT-exposed animals of the BALBc strain of mice. Later phagocytosis was also affected in some instances with opsonized SRBC. Degradation of phagocytosed material did not appear to be compromised until after 18 weeks of chronic exposure. There was clear evidence of the C57Black strain of mice being more generally affected by tobacco smoke exposure than the BALBc strain of mice.
Ruthenium-103-labelled tris-(1,10 phenanthroline)ruthenium (II) chloride is shown to be an acceptable non-specific marker for the rate of passage of food through the gut of wild birds maintained under aviary conditions. The radiotracer is shown to attach itself equally well to sodium sulphate precipitable material in the gastrointestinal tract as to solids. There is no evidence of its being absorbed from the gut and returned to the faeces via urine deposition.
Chlamydospores of Phytophthora cinnamomi Rands have been shown to survive in the intestinal tracts of termites (Nasutitermes exitiosus) and two species of forest birds indigenous to West Australian jarrah forests. Viable chlamydospores were recovered from bird feces within the normal rate of passage time for food through the gut. The above factors would allow these creatures to function as vectors for the spores.