Biomedical subjects

G F Gerberick

Publications and source records attributed to G F Gerberick.

58 records · Page 4Linked to original sources

PubMed1983

Toxicity of T-2 toxin, a Fusarium mycotoxin, to alveolar macrophages in vitro.

The exposure of agricultural workers to dust particulates, which may be contaminated with common fungi and/or their toxic metabolites, is an occupational health concern. To assess the cytotoxic properties of T-2 toxin, rat alveolar macrophages (AM) were exposed to T-2 in tissue culture. Determinations of cell viability, cell number, and viability index indicate that T-2, a trichothecene mycotoxin, is highly toxic to AM. The concentrations of T-2 toxin required to decrease these parameters by 50% at 20 hr were 8.93, 0.33, and 0.89 microM, respectively. The effect of T-2 toxin on AM cell volume was dose dependent, with cultures containing 0.1 microM T-2 being significantly different than controls. The data show that T-2 toxin causes significant AM shrinkage. The amount of chromium released from preloaded AM after 18 hr of incubation was significantly different in culture containing 0.01 microM or greater T-2 toxin. The percentage of chromium released was dose dependent and parallel to the amount of cell death occurring in each culture. Scanning electron microscope examination of AM treated 20 hr with 0.1 microM T-2 toxin demonstrated detachment of pseudopodia, cellular blebing, smoothing of membrane processes, and finally cell lysis. Thus, the data clearly demonstrate that T-2 toxin is cytotoxic for rat alveolar macrophages in vitro and suggest the possibility of a respiratory hazard to agricultural workers.

Animals↗

PubMed1980

In vitro susceptibility of Pseudomonas aeruginosa to carbenicillin, glycine, and ethylenediaminetetraacetic acid combinations.

Striking bacterial activity against Pseudomonas aeruginosa 9D-2 was achieved by glycine-carbenicillin, ethylenediaminetetraacetic acid-carbenicillin, and glycine-ethylenediaminetetraacetic acid combinations, whereas none of the agents used alone was capable of the same degree of bactericidal activity. Studies using a microtiter modification of the checkerboard technique were performed to evaluate the comparative activity of these antimicrobial combinations. Isobolograms showed synergistic effects with carbenicillin-glycine, carbenicillin-ethylene-diaminetetraacetic acid, and glycine-ethylenediaminetetraacetic acid combinations. Bacterial growth inhibitory curves with subinhibitory concentrations of these agents in combination confirmed these findings.

Carbenicillin↗

PubMedDate not supplied

Analysis of cytokine mRNA expression following repeated exposure of mice to chemical contact and respiratory allergens.

It has been shown previously that cytokine secretion patterns characteristic of the activation of discrete responses by functional subsets of T cells of type 1 and type 2, respectively, are elicited following topical exposure of BALB/c strain mice to chemical contact and respiratory allergens. In order to investigate if the differences in protein profiles are paralleled by changes in steady-state mRNA levels we have now investigated cultured draining lymph node cell (LNC) cytokine mRNA expression profiles by reverse transcriptase-polymerase chain reaction (RT-PCR) under conditions where divergent cytokine secretion is observed. Mice were exposed topically by repeated application of the respiratory allergen trimellitic anhydride (TMA) or of the contact allergen 2,4-dinitrochlorobenzene (DNCB). An elevation in the expression of mRNA for interleukin 4 (IL-4) and interleukin 10 (IL-10) by LNC from both TMA- and DNCB-treated animals was observed within 6 h of culture, reaching maximal levels after 72 h. Relative mRNA levels for both of these type 2 cytokines were considerably higher in cultured cells derived from TMA-exposed mice, compared with those from DNCB-treated animals. Transient low levels of the type 1 cytokine interferon y (IFN-gamma) were observed in response to treatment with TMA, whereas a substantial upregulation of IFN-gamma gene expression was seen from 24 h onwards in cultured LNC derived from DNCB-exposed mice. Changes in cytokine mRNA in allergen-activated LNC preceded protein production, although the kinetic profiles were similar. These data suggest that the divergent cytokine secretion profiles exhibited by mice treated by repeated topical exposure to contact and respiratory allergens are controlled primarily at the level of transcription. The RT-PCR methodology described herein may be more sensitive for the detection of cytokines expressed in low copy number, such as IL-4, where previously it has been found necessary to stimulate LNC with mitogen to elicit measurable levels of protein secretion. However, this technique was not found to offer major practical advantages when compared with protein detection methods (enzyme-linked immunosorbent assays) for the routine predictive characterization of chemicals as a function of cytokine 'fingerprinting'.

Allergens↗

PubMedDate not supplied

Skin sensitization thresholds: determination in predictive models.

For many years, test methods for the prospective identification of skin sensitizing chemicals have been widely available. However, although these techniques have permitted the identification of the great majority of skin sensitizers, their use in assessing the relative potency of a particular chemical as a human contact allergen has not been well described. A primary reason for this is the inherent difficulty of such an exercise. A complex phenomenon involving interactions between the vehicle, the allergen, the skin and its inflammatory responses takes place during the induction and elicitation of sensitization. All these factors can have a profound effect on the threshold values determined for a skin sensitizer. Consequently, whether the assessment is conducted in humans or in animal models, a threshold concentration is always a function of the method of measurement as much as the potency of the allergen. Although an exhaustive review has not been carried out, this paper considers the attempts that have been made to assess relative potency by the measurement of dose-response relationships and the determination of induction and elicitation thresholds in both animal models and in humans. The latter has special relevance for regulatory toxicology and this matter is given particular attention in this article. Finally, recommendations are made: (a) that threshold concentrations for skin sensitizers should be determined on a case by case basis in relation to the likely mode of skin contact; (b) where the data are used in comparisons of skin sensitization potency, then there should be standardization of the method used for the determinations.

Animals↗