Modification of the radiation sensitivity of human tumour cells by a bis-benzimidazole derivative

A comparison was made of the ability of either X-radiation or a DNA-specific ligand (the vital bis-benzimidazole dye; Hoechst 33342) to induce: cell killing, inhibition of de novo DNA synthesis, DNA strand breakage and the delay of cell division in human colon adenocarcinoma cells in vitro. Unlike radiation-induced cell killing, ligand-induced cytotoxicity appeared to be positively correlated with the extent of inhibition of de novo DNA synthesis--a feature consistent with the persistent binding of ligand molecules to nuclear DNA. Ligand-induced DNA strand-breaks disappeared slowly although ligand-treated cells retained apparently normal capacities to repair discrete radiogenic DNA strand-breaks. Pre-treatment of cells with Hoechst 33342 resulted in a dose-modifying enhancement of radiation resistance not associated with altered dosimetry for strand-break induction. However, radioresistance was accompanied by the protracted retention of cells in the G2 phase of the cell cycle. We suggest that the results provide direct evidence that the retention of cells in G2 phase is a sparing phenomenon and is triggered by the responses of chromatin domains to the presence of DNA damage. Our results have implications for the use of DNA-interactive agents in combined modalities for tumour therapy, and indicate a possible basis for the sparing of some tumour cells in dividing populations.     

Congenital entropion in a litter of rabbits

Conjunctivitis and blepharospasm were observed in a litter of four, 2-week-old New Zealand white rabbits. Corneal opacity and neovascularization of the cornea and entropion of the upper eyelids were observed when the rabbits were examined 10 weeks later. Conjunctival cultures of these rabbits yielded normal bacterial flora. Treatment with a steroid-antibiotic ophthalmic ointment did not alter the ocular abnormalities. Surgical correction of the entropion resulted in a complete regression of all clinical signs.     

An Euler contribution to stable theory from Süssmilch's göttliche Ordnung

In a paper published in 1760, the great Swiss mathematician Leonard Euler developed relationships between age structure and vital rates that would hold for stable populations, but without attention to the process by which stabilization comes about. He had not overlooked the latter problem. We introduce in this paper an earlier brief communication of his to Johann Peter Süssmilch in which he postulates that stability must ultimately result if fertility and mortality regimes are fixed. The mathematical treatment of this concept had not been thought to predate Alfred Lotka's work in the early part of the present century.     

An immune response profile model for immunogenicity quantitation

We propose an analytical model, which can simultaneously depict many fundamental characteristics of the immunogenicity of various vaccines. This model, the Immune Response (IR) profile, conveniently expresses the mathematical relation between pre- and post-vaccination titers. A vaccine's IR profile is antigen-specific, dose-dependent and post-vaccination interval-dependent. The maximal capability for serological response to a vaccine can be determined using this model irrespective of the dose administered, the post-vaccination assay interval, or the live or killed state of the vaccine. The IR profile obtained from analysis of booster vaccine responses in a limited number of seropositive study subjects can be used to predict maximal antibody titers which are expected after vaccination and can predict the geometric mean post-vaccination antibody titer of a cohort of subjects undergoing primary immunization. Using this model, it is anticipated that the immunoregulation implied by the IR profile may also prove to be correlated with cellular subpopulations and idiotypic antibody functions. Although derived from influenza vaccines analyses, the model successfully describes immune response characteristics following natural infection with malaria and following diphtheria and rubella vaccine administration.     

The effect of water-soluble aromatic hydrocarbons on some haematological parameters of rainbow trout, Salmo gairdneri Richardson, during acute exposure

Rainbow trout were exposed to a model mixture of water-soluble aromatic hydrocarbons (AH) at concentrations of 0.3–15.2 ppm for periods of 1–72 h. None of the parameters monitored except RBC changed at 0.3 ppm AH, while all constituents, except blood glucose, changed at 7.2 ppm AH. At 15.2 ppm, all fish died within 1 h. Haematological changes included increased haematocrit, haemoglobin concentration, erythrocyte counts, and blood clotting (prothrombin) times. Plasma Cl⁻ concentration decreased significantly. Changes resembled a stress response except for the increased clotting times, which typically decrease, and lack of increase in blood glucose.