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M Balls

Publications and source records attributed to M Balls.

At least 55 records · Page 3Linked to original sources
PubMed1985

The FRAME interlaboratory programme on in vitro cytotoxicology.

FRAME (the Fund for the Replacement of Animals in Medical Experiments) has established a research programme in collaboration with four research centres and a number of industrial companies, to determine whether cell cultures can reliably be used to replace live animal procedures in routine tests on the relative acute toxicities of chemicals. Following the development of the test protocol, initial trials were carried out to establish intralaboratory and interlaboratory reproducibility and the criteria for choice of cell types, end-points and metabolizing systems. A set of coded chemicals is being collected for use in blind trials and summaries of existing knowledge of the in vivo toxicity of these compounds are being produced. More recently, FRAME has established an international validation scheme for in vitro alternative methods.

Animal Testing Alternatives↗
PubMed1985

Lectin effects on thymic suppression of hemagglutinin production in vitro by spleen fragments from Xenopus laevis, the South African clawed toad.

Suppression of hemagglutinin (HA) production was studied in co-cultures of thymus and spleen fragments from the South African clawed toad, Xenopus laevis. Concanavalin (Con)A and peanut (PNA) and wheatgerm (WGA)agglutinins were tested in conjunction with, or as a substitute for antigenic induction of thymus suppression. While thymuses from animals injected with PNA or WGA and antigen expressed suppressor function, those treated with Con A and antigen did not. Spleen fragments from animals challenged with PNA or WGA and antigen were resistant to suppression by normal thymus in reciprocal co-cultures; those receiving Con A and antigen alone were equally suppressible. All three lectins can substitute for antigen in the induction of thymus suppression. However, only PNA and WGA induce suppressor function in Xenopus spleen. Since WGA can induce splenic suppression in adult thymectomized animals, it is now possible to distinguish thymic and peripheral aspects of suppression of HA in this primitive vertebrate.

Animals↗
PubMed1984

Immunologic reactivity to TNP-Ficoll during development and ageing in Xenopus laevis, the South African clawed toad.

The immunological response of Xenopus laevis to haptenated Ficoll was examined throughout development. The capacity to respond to TNP-Ficoll originated with the first appearance (at stage 48, 8 days post-fertilisation) of mature thymic lymphocytes, and preceded the ability to respond to heterologous erythrocytes. During premetamorphosis the response increased, while during prometamorphosis , particularly at stages 57-58, there was a marked reduction. The response recovered during the metamorphic climax and immature adult stages, increasing further at the onset of sexual maturity. The reduced response during prometamorphosis parallels the reported reduction in other thymus-dependent responses.

Aging↗
PubMed1984

Genetic limits of thymic immunosuppression of anti-hapten antibody production in Xenopus laevis laevis, the South African clawed toad.

Thymic immunosuppression in adult Xenopus laevis laevis, the South African clawed toad, is antigen-dependent and antigen-specific, but it is not genetically restricted. In this report, we show that combination in vitro with a thymus from an immunized Xenopus laevis laevis can suppress antibody production to a hapten from spleen fragments, if the spleen fragments are derived from a subspecies of Xenopus laevis or a species of Xenopus which shares the same diploid chromosome number (2N = 36). Some aspects of the evolution of thymic immunosuppression are considered in the light of these results.

Animals↗
PubMed1984

Lectins and substitution for helper function in anti-hapten responses in Xenopus laevis.

Substitution by lectins for the carrier-priming requirement in thymus-dependent, antigen-binding responses in Xenopus laevis has been examined. Concanavalin A (Con A) was found to substitute for carrier priming in control, early-thymectomized and adult-thymectomized animals, but not in animals given a single, high dose of N-methyl-N-nitrosourea, which has a permanent effect on certain thymus-dependent functions in this species. Lipopolysaccharide and other lectins, such as peanut agglutinin and wheat germ agglutinin, were unable to substitute for carrier priming. These effects of Con A are discussed in terms of substitution via amplifier T cells or a helper T cell subset.

Age Factors↗
PubMed1984

In vitro thymus suppression of hemagglutinin production in Xenopus laevis: location, drug and temperature sensitivity.

Suppression of splenic hemagglutinin (HA) production by allothymuses in vitro was further studied in Xenopus laevis, the South African clawed toad. Since thymic capacity to suppress splenic HA secretion into the culture medium is retained in animals previously exposed to N-methyl-N-nitrosourea (NMU), which destroys the thymus cortex in this species, suppressor function must be located in the thymus medulla. Reciprocal thymus-spleen combinations showed that normal thymus can suppress immunised spleen fragments from NMU-treated animals. Since Xenopus exposed to NMU are also devoid of helper function, thymus suppression acts directly on the antibody forming system. Cyclophosphamide removed thymic suppression and enhanced spleen fragment antibody production, while Cyclosporin A enhanced thymic suppression and blocked HA production. Therefore, antigenic stimulation of thymic suppression and antibody production are inversely related in this species. Long-term storage of Xenopus in the cold increased lymphoid cellularity of the thymus medulla, but thymuses from cold-stored animals could not suppress normal spleen fragments and their spleens were not suppressed by normal thymuses. Thus, ectotherms may retain immunological capacity when subjected to prolonged cold by a loss of thymic suppression.

Animals↗
PubMed1984

TNP-Ficoll response in Xenopus laevis: substitution and reconstitution in thymectomized animals.

The capacity to respond to haptenated Ficoll, though thymus-independent in mammals, is lost in Xenopus laevis following thymectomy at any stage of development. This capacity can be restored to thymectomized Xenopus by whole allogeneic thymus implants, by thymus implants from animals treated with N-methyl-N-nitrosourea (which have an active thymus medulla but no cortex, and which lack certain thymus-dependent immunological functions), and Concanavalin A. These results are discussed in terms of the cell populations and/or factors which may be involved.

Animals↗
PubMed1983

Differentiated cell and organ culture in toxicity testing.

The safety evaluation of new chemicals involves a range of investigations, including acute and sub-acute toxicity testing, long-term toxicity testing, studies on mutagenicity, carcinogenicity, and reproductive toxicity, and special investigations involving the interaction of the chemical under test with particular parts of the body, such as the skin or the nervous system. We shall consider the potential role of differentiated cell and organ culture in toxicity testing, and the criteria available for assessing cell viability, damage, and death, with a view to establishing whether such methods could be used for determining the relative acute toxicities of chemicals. We shall also consider methods for studying the effects of chemicals on general and specific aspects of cell structure and function, including liver cell and organ cultures both as primary targets themselves susceptible to damage and as providers of metabolically activated compounds able to affect other cells and tissues.

Animals↗
PubMed1982

Amphibian organ culture in experimental toxicology: the effects of paracetamol and phenacetin on cultured tissues from urodele and anuran amphibians.

Organ cultures of various tissues from urodele amphibians deacetylate paracetamol to p-aminophenol, which polymerises to form a brown precipitate. Paracetamol addition results in a loss of glycogen and lactate dehydrogenase (LDH) from urodele liver cultures and an increase in glucose release, and in LDH loss from kidney cultures. Organ cultures from anuran amphibians are unable to metabolise paracetamol and are not affected by its presence in the culture medium. The addition of unpolymerised p-aminophenol resulted in a loss of LDH from urodele and anuran organ cultures, whilst the addition of polymerised p-aminophenol had no such effects. This suggests that the toxic effects which follow the addition of paracetamol to urodele organ cultures are caused by unpolymerised p-aminophenol, a known toxicant in mammals. Cultures from both urodele and anuran amphibians are able to deacetylate phenacetin to p-phenetidine, but p-phenetidine was found to be much less toxic to amphibian tissues than p-aminophenol, causing LDH loss from kidney cultures only at very high dose levels.

Acetaminophen↗
PubMed1982

Co-existence of thyrotrophin releasing hormone and 5-hydroxytryptamine in the skin of Xenopus laevis.

1. The location, release and re-synthesis of thyrotrophin releasing hormone (TRH) and 5-hydroxytryptamine (5-HT) in the skin of Xenopus laevis (the South African clawed toad) have been determined using both morphological and analytical procedures. 2. High levels of TRH and 5-HT are located specifically within the dermal granular glands of X. laevis and discharged from these glands following alpha-adrenergic stimulation. 4. The common occurrence and separate production of high levels of TRH and 5-HT in amphibian skin may provide a model for studying the mechanisms of biosynthesis, interaction and release of these substances in mammalian tissues such as ventral spinal cord, where TRH and 5-HT are found in the same neurones.

Animals↗
PubMed1982

Effects of N-methyl-N-nitrosourea on carrier-primed anti-hapten responses in Xenopus laevis.

Young adult Xenopus laevis were treated with N-methyl-N-nitrosourea at doses which temporarily or permanently remove the thymic cortex and suppress allograft immune competence. Their ability to mount a carrier-primed, helper T cell-mediated, hapten-specific response was tested in terms of numbers of antigen binding cells in the spleen. Animals which had retained skin allografts for more than 300 days lacked helper activity, while those which had eventually rejected their allografts were able to mount an anti-hapten response. All groups of Xenopus exposed to the carcinogen rejected skin xenografts after the same time as untreated control animals.

Animals↗
PubMed1981

Location and release of TRH and 5-HT from amphibian skin.

The occurrence and release of thyrotrophin-releasing hormone (TRH) and 5-hydroxytryptamine (5-HT) from amphibian skin have been described by previous investigators. In the present study, the precise location and site of release of TRH and 5-HT from the skin of Rana pipiens and Xenopus laevis have been examined using a combination of procedures including immunohistochemistry, HPLC, and radioimmunoassay. The results indicate that TRH is located specifically within the dermal glands of these species, and that both TRH and 5-HT are discharged from these glands following adrenergic stimulation. The origin and functional significance of these substances in amphibian skin granular glands are discussed.

Animals↗
PubMed1981

A comparative study of the deacetylation of paracetamol by urodele and anuran amphibian organ cultures.

1. p-Aminophenol is the major metabolite produced by urodele amphibian tissues in vitro. The deacetylation enzyme system involved is located in the liver microsomal fraction of Amphiuma means. 2. Paracetamol was deacetylated to p-aminophenol by organ cultures of liver, kidney, pancreas and stomach epithelium from adult A. means, by liver, stomach epithelium, bladder and lung cultures from neotenic larval Ambystoma tigrinum, and by adult Triturus cristatus carnifex in vivo. 3. Liver cultures from all seven urodele amphibian species metabolized paracetamol and produced p-aminophenol, but no evidence was found of paracetamol metabolism by liver cultures from any of five anuran amphibian species. 4. The significance of p-aminophenol production from paracetamol and of this difference within the Amphibia are discussed.

Acetaminophen↗