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Biomedical subjects

J Hilton

Publications and source records attributed to J Hilton.

At least 127 records · Page 7Linked to original sources
PubMed1977

DNA damage and repair in L1210 cells exposed to 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea.

The DNA of L1210 cells exposed to low concentrations of 1-(2-chloroethyl)=3-cyclohexyl-1-nitrosourea has been analyzed for the presence of single-strand breaks. DNA from 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea-treated cells both sediments more slowly than control DNA on alkaline sucrose gradients andshows a greater extent of strand separation of the DNA helix in alkali. These effects are a typical result of exposure of cellular DNA to alkylating agents or ionizing radiation. The extent of DNA damage caused by 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea has been related to the same amount of damage resulting from exposure of cells to low doses of gamma-irradiation. The rate and extent of repair of 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea-induced damage is slow and incomplete, compared with the repair of gamma-irradiation damage to DNA. It is concluded that 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea behaves as a weak alkylating agent, a property that may explain its antitumor properties.

Animals↗
PubMedDate not supplied

The mouse IgE test for the identification of potential chemical respiratory allergens: considerations of stability and controls.

The mouse IgE test is a novel approach to the predictive identification of chemicals that have the potential to cause sensitization of the respiratory tract. The method is based upon measurement of induced changes in the serum concentration of IgE in BALB/c strain mice following topical exposure to the test chemical. The investigations described here were undertaken to examine the stability of the assay, to evaluate the utility of trimellitic anhydride (TMA) and 2,4-dinitrochlorobenzene (DNCB) as, respectively, positive and negative controls for use in the test and to consider criteria for the classification of chemicals as potential respiratory allergens based upon changes induced in serum IgE concentration. On the basis of fifteen independent experiments it was found that, while there was some intra- and inter-test variability with respect to absolute concentrations of IgE measured in the sera of individual mice, the relative pattern of reactivity observed following treatment of mice with TMA, DNCB or with vehicle (4:1 acetone:olive oil) alone remained consistent. In each experiment treatment with TMA provoked a very substantial increase in serum IgE relative to vehicle controls. In no instance did exposure of mice to DNCB cause an increase in the concentration of serum IgE, and in some instances treatment with this chemical resulted in reduced IgE levels. In a parallel series of experiments it was found that serum IgE concentrations in vehicle-treated mice were comparable with those found in the serum of untreated animals. It is concluded that the differential ability of chemicals to induce changes in the concentration of serum IgE in BALB/c mice is a stable phenomenon. It is recommended that, in practice, TMA and DNCB should be incorporated in mouse IgE tests as, respectively, positive and negative controls. Finally, it is proposed that activity in the test is assessed as a function of induced changes in serum IgE levels relative to concurrent vehicle controls, rather than by reference to historical normal range values.

Allergens↗
PubMedDate not supplied

Temporal stability of local lymph node assay responses to hexyl cinnamic aldehyde.

The local lymph node assay is an alternative method for the prospective identification of chemicals that have the potential to cause skin sensitization. Activity in the assay is measured as a function of proliferative responses by draining lymph node cells induced by topical exposure of mice to the test chemical. Positive responses are defined as those where a test chemical, at one or more application concentrations, is able to induce a stimulation index of 3 or greater compared with concurrent vehicle-treated control values. Although the method has been evaluated extensively, the stability over time of responses induced in the local lymph node assay has not previously been addressed formally. It was the purpose of the investigations described here to consider this issue and, to this end, responses provoked in the local lymph node assay by hexyl cinnamic aldehyde (HCA)--a skin sensitizing chemical of moderate potency--were assessed in five separate experiments conducted in a single laboratory over a 10-month period. In each case, HCA elicited a positive response. Although some significant inter-experimental variation was recorded, this was attributable entirely to the stimulation by HCA of slightly more vigorous responses in one of the five experiments. When the results of this experiment were excluded from the data set, significant variations were lost. Finally, for each experiment an EC3 value was derived, this being the estimated concentration of test chemical required to induce a stimulation index of 3. Similar EC3 values were derived in each experiment. These data demonstrate the relative stability over time of activity in the local lymph node assay.

Acrolein↗
PubMedDate not supplied

Cytokine endpoints for the local lymph node assay: consideration of interferon-gamma and interleukin 12.

The murine local lymph node assay (LLNA) is a method for the prospective identification of contact allergens. Skin sensitization potential is assessed as a function of induced proliferative responses in lymph nodes draining the site of topical exposure measured in situ by incorporation of radiolabelled thymidine ([3H]thymidine). The results of previous investigations have demonstrated that the analysis of [3H]thymidine incorporation represents a robust and reliable endpoint for the LLNA for the assessment of skin sensitizing activity for strong and moderate allergens and, in addition, many weaker sensitizers. The aim of the current experiments was to explore the utility of the production of the cytokines interferon-gamma (IFN-gamma) and interleukin 12 (IL-12) by draining lymph node cells (LNC) as alternative readouts for the LLNA. Animals were exposed to a range of skin sensitizers at two application concentrations. The first of these was chosen on the basis of results from previous investigations to stimulate a strong proliferative response (tenfold or greater increase in proliferation compared with concurrent vehicle controls). The second concentration of test material in each case was the amount of chemical estimated to be necessary mathematically for elicitation of a stimulation index of 3 (EC3 value); the induction of a threefold or greater increase in proliferation is the current criterion for a positive response in the LLNA. In addition, analyses were conducted with para-aminobenzoic acid (PABA), a non-sensitizing chemical shown previously not to induce LLNA responses. Secretion of IFN-gamma and the p40 subunit of IL-12 by draining LNC was measured by cytokine-specific enzyme-linked immunosorbent assay. In parallel experiments, LNC activity was assessed as a function of [3H]thymidine incorporation in situ. All the chemical allergens tested provoked robust proliferative responses, with the stimulation indices recorded at both test concentrations reflecting only small changes in activity compared with previously recorded data. Exposure to vehicle (4:1 acetone:olive oil, AOO) alone resulted in detectable, although variable, expression of both IFN-gamma and IL-12. Treatment with chemical allergen in each case caused a marked increase in IFN-gamma secretion, with particularly vigorous production of cytokine being stimulated following exposure to oxazolone or hexyl cinnamic aldehyde. In contrast, application of chemical allergens was not generally associated with elevated IL-12 p40 secretion. Exposure of mice to PABA did not result in increased IFN-gamma or IL-12 production compared with vehicle-treated controls. In general, however, cytokine secretion did not correlate closely with the induction of LNC proliferation. These data indicate that expression by allergen-activated LNC of IFN-gamma or IL-12 does not provide a reliable or sufficiently sensitive endpoint for the LLNA compared with [3H]thymidine incorporation in situ.

Allergens↗
PubMedDate not supplied

Junctional care: the key to prevention of catheter sepsis in intravenous feeding.

Investigation of an outbreak of infection related to intravenous feeding catheters, predominantly with Staphylococcus epidermidis, suggested that the probable origin was the connections in the delivery system. Equipment and policy changes were then instituted: a catheter with integral hub was used, the connections were reduced from two to one, and improved antisepsis at the connection was devised. These actions resulted in a sustained, significant reduction in the catheter sepsis rate, supporting the hypothesis that junctional care is vital to the avoidance of catheter infection.

Catheters, Indwelling↗
PubMedDate not supplied

Chernobyl: a survivable ecological disaster?

A study of events occurring after the Chernobyl accident until 1996 was funded by the European Commission (EC). The study included work by hundreds of scientists from the EC and the former Soviet Union. An overview of these studies is given that puts the science into historical context and shows the effects of the radioactive doses on the population and on the environment. The exposed populations are considered in terms of the separate exposure subgroups (emergency workers; inhabitants of settlements near the reactor; inhabitants of settlements receiving high doses of condensation radionuclides; children in the deposition areas; the general population). The scientific understanding of the natural and anthropogenic countermeasures that reduced doses is presented, and the effects on the human population are discussed.

Adult↗