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Biomedical subjects

D Keast

Publications and source records attributed to D Keast.

At least 55 records · Page 3Linked to original sources

Effect of mitogens on the maximum activities of hexokinase, lactate dehydrogenase, citrate synthase and glutaminase in rat mesenteric lymph node lymphocytes and splenocytes during the early period of culture.

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.

Animals↗

The effect of glutamine on murine splenic leukocyte responses to T and B cell mitogens.

Murine splenic leukocytes cannot be stimulated to synthesize [3H]-DNA by various concentrations of either the T cell mitogens, Concanavalin-A (Con-A) or phytohaemagglutinin (PHA) or the B cell mitogen, lipopolysaccharide (LPS), unless glutamine is present in the culture medium. The optimum concentration of the T cell mitogens (Con-A, PHA) remained constant for all levels of glutamine while that of the B cell mitogen (LPS) increased as the concentration of glutamine in the medium increased.

Animals↗

Fine body movements and the cardiac cycle in archery.

This study examined the relationships between postural sway, aiming time, the cardiac cycle time and the placement of the first finger movement within the electrocardiac cycle, with the quality of the arrow shot. A small group of elite male and female archers who shot either the recurve or the compound bow, freestyle or bare bow was used in this study. A total of 240 arrows were shot, classified as being of good, average or bad quality and analysed in detail. The analyses were undertaken over two occasions up to 100 days apart. The area of postural sway, as measured by the movement of the centre of pressure coordinates, varied significantly (P less than 0.05-0.001) both within and between trials for all archers and for all quality of arrows shot. There was a tendency for the area of postural sway to increase as the quality of the arrow shot decreased. This increase in postural sway exceeded, for arrows of bad quality, that exhibited as normal postural sway when standing relaxed and addressing the target with the hands at the side. Aiming time was variable within the quality of arrow shot, although it was consistent for each archer. In some cases the aiming time increased as the quality of the arrow decreased, whereas in the case of bare bow archery the aiming time tended to decrease as the quality of the arrow deteriorated. The cardiac cycle time increased significantly (P less than 0.05-0.01) as the archers approached the loose of the good quality arrows but there was no significant increase in cardiac cycle time when arrows of average or bad quality were shot. The most consistent parameter related to the quality of the shot was the placement of the first finger movement within the ST phase or the mid-cycle phase of the electrocardiogram for arrows of good quality (P less than 0.0001).

Adolescent↗

Maximal activities of glutaminase, citrate synthase, hexokinase, phosphofructokinase and lactate dehydrogenase in skin of rats and mice at different ages.

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.

Aging↗

Adjuvant activity of respirable iron ore dust.

The 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.

Adjuvants, Immunologic↗

Exercise and the immune response.

A growing number of reports have become available which implicate infectious disease with reduced performance in athletes. The immune system consists of both nonspecific and specific components geared to control infections. Adaptive immunity functions through both antibody-mediated and cell-mediated compartments to establish and maintain long term immunity to infectious agents. Evidence is accumulating to support the view that physical exercise can lead to modification of the cells of the immune system. However, studies have often not been well designed to control exercise protocols when examining the effects of exercise on the immune system. Large numbers of peripheral blood lymphocytes are mobilised with exercise and in vitro tests indicate that temporarily these cells may not be capable of responding normally to mitogens. These reactions appear to be influenced by hormones to some degree and there are reports that the cells of the immune system are extremely active biochemically and may depend on products from muscles to maintain their activity. Specific populations within the circulating leucocyte pool vary significantly with exercise and there is some evidence that the T4/T8 lymphocyte ratio may become significantly reduced. This reduction in ratio may be related to the variable responses to T and B cell mitogens recorded in vitro which overall suggests that a temporary immune suppression may exist following certain training or performance schedules. It is argued that this may lead to a temporary susceptibility to infection and could result from overtraining.

Antibody Formation↗

Some biological properties of respirable iron ore dust.

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.

Animals↗

The effect of ultraviolet radiation on humoral immune responses to T-dependent antigens.

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.

Animals↗

The effect of ultraviolet radiation on the generation of plaque-forming cells and on T-suppressor cell activity to sheep erythrocytes.

Following the development of a sun simulator it has been shown that, in a murine model, photo-augmentation of sub-erythemal doses of UVB radiation by UVA significantly influences the histological changes that develop in the epidermal layers of the skin. In this model the polyclonal mitogenic responses to phytohemagglutinin (PHA-P), concanavalin A (Con A) and bacterial lipopoly-saccharide (LPS) are largely unchanged following UV-radiation under sun simulator conditions. However, the specific adaptive plaque-forming cell immune response for both IgM and IgG to the T-dependent antigen SRBC (sheep erythrocytes), given intradermally, is suppressed. This suppression can be abrogated in adoptive immune transfer experiments by treating the cells from the inguinal lymph nodes with monoclonal anti Thy-1.2 antibody.

Animals↗

Effects of chronic daily exposure to tobacco smoke on the high leukemic AKR strain of 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.

Age Factors↗

Use of a computer to group actinomycetes for studies on the ecology of soil microorganisms.

A computer program has been prepared for grouping soil actinomycetes into cluster groups based on the presence or absence of aerial mycelium, the color of soluble pigment, and the shade of color of surface and reverse mycelium. The program automatically condenses cultures with wide ranges of characteristics into a limited number of groups and provides a permanent record so that comparisons can be made among experiments performed over a span of time. The program permits the grouping of large numbers of cultures with minimal laboratory effort and has proven useful in defining some of the ecological factors that lead to changed actinomycete populations in soils.

Actinomycetales↗

The effects of chronic tobacco smoke exposure from high-tar cigarettes on the phagocytic and killing capacity of polymorphonuclear cells of mice.

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 BALB/c 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.

Animals↗

The location of antigenic sites on the surface of the nematode parasite Strongyloides ratti reactive to antibody-directed cellular cytotoxicity from both macrophages and eosinophils from the natural host.

Heat-treated and untreated sera from rats immune to Strongyloides ratti are capable of arming both immune and non-immune macrophages and eosinophils in vitro. These cells are capable of killing larvae of the parasite. Electron microscopy has indicated multi-point attachment of the cells to the epicuticular transverse grooves of the larvae within 4 and 24 h of incubation at 37 degrees.

Animals↗

The influence of methimazole on thyroglobulin-induced autoimmune thyroiditis in the rat.

Experimental autoimmune thyroid disease was induced in August rats by immunization with rat thyroglobulin in complete Freund's adjuvant. Disease severity, assessed by thyroid histology and circulating levels of anti-TG antibody measured by an enzyme immunoassay, was maximal between 30 and 60 days after the initial immunization and thereafter waned. Thyroid function through the duration of the disease, assessed by measurement of serum TSH levels by RIA, remained normal. Once the natural history of the disease was established, groups of rats received methimazole (MMI) with or without T4 in their drinking water, either before or after disease induction. The animals were bled at regular intervals and killed on day 49 for histological grading of their thyroids. MMI alone (group 3) or with T4 (group 4) before disease induction significantly reduced the severity of the disease, although the effect on circulating antibody levels was less marked in the animals in group 4. In animals given MMI alone (group 5) or with T4 (group 6) after establishment of the disease, MMI again significantly reduced the severity of the established disease, although this effect was less marked in the T4 supplemented animals. MMI significantly impaired the induction and reduced the severity of experimental autoimmune thyroid disease in August rats. The ability of MMI to influence the autoimmune process may have important implications for the use of this and other agents that act on the immune system in the management of human autoimmune disease.

Animals↗

Effects of tobacco smoke exposure on splenic architecture and weight, during the primary immune response of BALB/c mice.

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 are 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.

Animals↗

A survey of pathological changes associated with long-term high tar tobacco smoke exposure in a murine model.

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.

Animals↗