Cloned human T lymphocytes reactive with Dermatophagoides farinae (house dust mite): a comparison of T- and B-cell antigen recognition.

In this report, T-cell and B-cell recognition of the house dust mite Dermatophagoides farinae (D. far.) is compared. Nitrocellulose immunoblots of polyacrylamide gel electrophoresis (SDS-PAGE)-fractionated D. far. were added to proliferation assays to map the antigen specificity of cloned human helper T cells and a long-term line induced with D. far. T-cell recognition was of a polypeptide of molecular weight 9000-13,000, that migrates with the serologically defined allergen Der fII (12,500 MW). Since the cloned T cells, unlike the polyclonal response, failed to respond to Dermatophagoides pteronyssinus (D. pter.), this suggests that they recognize a species-specific epitope. In contrast, analysis of the B-cell response using Western blotting demonstrated that, in addition to Der fII, antibodies reactive with the major allergens Der fI (26,000 MW) and Der fIII (29,000 MW) were present in the serum. Similar specificities were seen in the antibody response to D. pter., and while it has been reported that the B-cell response to D. far. and D. pter. are predominantly cross-reactive, our observations suggest that species-specific CD4-positive T cells are present in the overall cellular response to D. far.     

Restorative treatment need assessment by dentally and nondentally trained subjects

A study was carried out which compared how two groups of people, one with clinical dental experience and one without, assessed restorative dental treatment need. Using a visual analogue scale, a group of final year dental students ( n = 50) and nonclinical university students ( n = 50) assessed the extent to which they considered common dental imperfections, viz. spacing of the upper anterior teeth and discolouration of upper anterior teeth, warranted restorative correction. The group of dental students judged the necessity for treatment of discolouration to be more urgent than correction of spacing. The nondental group did not differentiate between the degrees of need. Data were non‐normal in distribution but the use of appropriate statistical tests showed the differences in mean assessments to be significant.     

Augmentation strategies in geriatric depression

Approximately 30–40% of elderly patients with major depression have inadequate response to an initial therapeutic trial of antidepressant medication. In these cases augmentation of the antidepressant has been recommended as one way of improving the rate of response. This article reviews the literature on augmentation strategies in treatment-resistant geriatric depression. Successful augmentation with lithium, triiodothyronine, stimulants, carbamazepine, valproate and a tricyclic–serotonin reuptake inhibitor combination have been described. However, there have been no controlled trials and, with the exception of two open prospective studies of lithium potentiation, the literature consists entirely of case reports and retrospective case series. As a result, it is difficult to draw conclusions about the efficacy of these strategies in late life, especially since treatment failures seldom get reported. Side-effects may limit the usefulness of some augmentation regimens in old age—up to 25% of patients treated with lithium or carbamazepine discontinued these medications because of adverse events. There is a need for controlled studies to better determine the clinical utility of augmentation strategies in physically well depressed elderly, as well as those with depression complicating medical illness, dementia and other neurological disorders.     

Effects of the PKA inhibitor H-89 on excitation–contraction coupling in skinned and intact skeletal muscle fibres

This study investigated the effects of the protein kinase A (PKA) inhibitor, H-89, in mechanically-skinned muscle fibres and intact muscle fibres, in order to determine whether PKA phosphorylation is essential for normal excitation–contraction (E–C) coupling. In skinned EDL fibres of the rat, force responses to depolarization (by ion substitution) were inhibited only slightly by 10M H-89, a concentration more than sufficient to fully inhibit PKA. Staurosporine (1 M), a potent non-specific kinase inhibitor, also had little if any effect on depolarization-induced responses. At 1–2 M, H-89 significantly slowed the repriming rate in rat skinned fibres, most likely due to it deleteriously affecting the T-system potential. With 100 M H-89, the force response to depolarization by ion substitution was completely abolished. This inhibitory effect was reversed by washout of H-89 and was not due to block of the Ca²⁺ release channel in the sarcoplasmic reticulum (SR). In intact single fibres of the flexor digitorum longus (FDB) muscle of the mouse, 1–3 M H-89 had no noticeable effect on action-potential-mediated Ca²⁺ transients. Higher concentrations (4–10 M) caused Ca²⁺ transient failure in fibres stimulated at 20 Hz in a manner indicative of action-potential failure. At 10–100 M, H-89 also inhibited net Ca²⁺ uptake by the SR and affected the Ca²⁺-sensitivity of the contractile apparatus in rat skinned fibres. All such effects were proportionately greater in toad muscle fibres. These results do not support the hypothesis that phosphorylation is essential for the Ca²⁺ release channel to open in response to voltage-sensor activation in skeletal muscle fibres.     

Requirements for the development of IL-4-producing T cells during intestinal nematode infections: what it takes to make a Th2 cell in vivo

Summary: Components of the type 2 immune response may mediate host protection against both helminthic parasites and harmful allergic responses. A central player in this response is the T‐helper 2 (Th2) effector cell, which produces interleukin (IL)‐4, IL‐5, IL‐13, and other Th2 cytokines during the primary and memory response. Specific aspects of the parasite that trigger Th2‐cell differentiation are not yet defined. Furthermore, the cell types and cell surface and secreted molecules that provide the immune milieu required for the development of Th2 effector cells and also Th2 memory cells are not well understood. They will probably vary with the particular helminth or other antigen inducing the Th2 response. We have used third stage larvae of intestinal nematode parasites as adjuvants to promote naïve nonparasite antigen‐specific T cells to differentiate into Th2 cells. This model system avoids possible parasite antigen‐specific T‐cell clones or cross‐reactive memory T cells that may preferentially differentiate into Th2 effector cells during the course of infection and confound the stereotypical components of parasite‐induced Th2 cell differentiation. We have found that these parasites have a potent adjuvant effect and have used our model system to begin to investigate the events that lead to the development of polarized Th2 cells in vivo.     

An in vitro and in vivo study of the effect of incorporation of chlorhexidine into autopolymerizing acrylic resin plates upon the growth of Candida albicans

Chlorhexidine acetate was incorporated into autopolymerizing acrylic resin and, after studying its ability to diffuse out in vitro, an investigation was made into the potential of the mixture to treat palatal candidosis in the rat. Chlorhexidine was found to diffuse out of acrylic in fungicidal concentrations for up to three weeks when mixed with the acrylic powder in the proportion of 7.5% (w/w). At this concentration it was found that palatal candidosis as produced by the technique of Shakir et al. was cured or prevented. However, rats fitted with chlorhexidine supplemented plates were found not to take sufficient food during the experimental period to maintain their body weight.