Phenotypic characterization and analysis of allogeneic T cell responses in ZAP-70 dominant negative transgenic mice

Antigen stimulation of T cells results in a series of biochemical events including the interaction of both SH2 domains of ZAP-70 with phosphorylated ITAMS on the T cell receptor. In order to study the physiological relevance of decreasing native ZAP-70–SH2 interaction in vivo, we generated transgenic mice expressing a T cell-specific, dominant negative form of ZAP-70 consisting of only the tandem SH2 domains (ZAP-NC). Phenotypically, these animals had a comparable distribution of lymphocyte subsets in the thymus and spleen compared with the wild-type (WT) controls. However, examination of peripheral blood revealed a slow but progressive decrease in the number of lymphocytes, particularly CD4⁺ cells, with age (17% reduction by 3 months, 58% reduction by 6 months). Allogeneic responses were then evaluated in vitro as well as in vivo using a subcutaneous sponge matrix implant. Although spleen cells cultured for 4 days in vitro with alloantigen developed normal functional responses, allogeneic responses generated in vivo within a subcutaneous sponge matrix were impaired. This was characterized by a depression in cytotoxic T lymphocyte (CTL) activity, a 82% reduction in the frequency of helper T cells, and a 78% reduction in the capacity of sponge-infiltrating lymphocytes to produce IL-2 in response to secondary antigen stimulation. These results indicate that although overt lymphocyte development and in vitro function were unremarkable, expression of a truncated ZAP-70 affected the in vivo survival of peripheral lymphocytes and altered the in vivo generation of functional activity to alloantigen.     

Detection of ambulatory ischaemia is not of practical clinical value in the routine management of patients with stable angina: A long-term follow-up study

It has been reported that medically treated patients with stableangina and positive exercise test for ischaemia have an adverse1–2 year outlook if they are shown also to have transient,and predominantly silent, ischaemic episodes detected by ambulatoryST segment monitoring during their daily activities: it hasbeen suggested that this investigation could be used to identifypatients more likely to benefit from early investigation andtreatment. We assessed the long-term (up to 65 months) prognosticsignificance of transient iscliaemic episodes during daily activitiesin 172 patients routinely attending cardiac outpatients withmedically treated stable angina who had undergone exercise testingand 48 h of ambulatory ST segment monitoring between February1988 and August 1989 for this purpose. A positive exercise testfor ischaemia was not a prerequisite for inclusion. One hundred and four patients (60.5%) had a positive exercisetest for iscliaemia and 72 (42%) had transient ischaemia duringdaily activities (63 had both tests positive). Over a median50-month follow-up period 54 patients suffered at least onecardiac event (primary event: cardiac death n=7; non-fatal myocardialinfarction n=11; unstable angina n=18; elective CABGIPTCA n=18).Two further patients suffered non-cardiac death. Cardiac events,either objective (cardiac death or non-fatal myocardial infarction)or subjective (unstable angina or revascularisation) were nomore likely to occur in those with transient ischaemia duringdaily life when compared with those without, at follow-up timesup to 65 months. The detection of transient ischaemia during daily life is oflimited practical clinical value in the management of ‘lowrisk’ medically treated patients with stable angina, anddoes not appear to help identify subgroups at increased riskof an adverse outcome at follow-up to more than 5 years.     

Catheter Ablation Without Fulguration: Design and Performance of a New System

A new system is described for catheter ablation which comprises a short time capacitive power source and a specially designed catheter. The aim of the new system is to deliver high voltages with minimal or no arcing and thus avoid the risks associated with barotrauma. The performance of the new system was compared in a saline tank with that of the conventional system. The new system allowed significant increases in delivered voltage, current and energy without arcing. This new system should allow safer catheter ablation.     

The effect of two α2-adrenoreceptor agonists and an antagonist on gastric emptying and mouth to caecum transit time in humans

Experiments were performed to investigate the effect of two alpha 2-adrenoreceptor agonists, clonidine and lidamidine, and a specific alpha 2-adrenoreceptor antagonist, idazoxan, on gastric emptying and mouth to caecum transit time (MCTT) of a radiolabelled meal in 27 healthy male subjects. Lidamidine (20 mg p.o.) and clonidine (0.3 mg p.o.), given alone had no significant effect on gastric emptying or MCTT suggesting that the anti-diarrhoeal action of clonidine and lidamidine are unlikely to be explained by a slowing of small intestinal transit. Idazoxan (20 mg p.o.) reversed the effect of clonidine in 10 subjects, who showed a delay in MCTT after taking clonidine, but did not alter MCTT under basal conditions. These results suggest that although the sympathetic nervous system can influence upper gastrointestinal motility by an action on alpha 2-adrenoreceptors, this action does not exert a tonic influence on upper gastrointestinal motility under basal conditions.     

Aspects of early social smiling by infants with Down''s syndrome

Smiling by five Down's syndrome and seven nonhandicapped infants was recorded longitudinally during face-to-face interactions with their mothers over the first 6 months of the infants' lives. Two conditions, 'mobile' (mothers were asked to talk to the baby as naturally as possible) and 'immobile' (silent and maintain an impassive face), were contrasted. Between-group comparisons confirmed previous findings of significantly delayed emergence and less frequent smiling by the infants with Down's syndrome. Their smiles were also found to be shorter, and less discriminative between the two face-to-face conditions. The non-handicapped infants showed significantly more cry/distress vocalizations in the immobile than in the mobile condition, while the reverse was found for the Down's syndrome infants. A close temporal association between smiling and eye contact with mothers was found for both groups of infants. In a free interaction condition, mothers of the Down's syndrome babies showed a stronger tendency to use kinaesthetic and tactile stimulation than mothers of the non-handicapped infants.     

ANTERIOR MEDIASTINAL FIBROSIS WITH SUPERIOR VENA CAVAL OBSTRUCTION COMPLICATING THE SYNOVITIS--ACNE--PUSTULOSIS--HYPEROSTOSIS--OSTEOMYELITIS SYNDROME

A syndrome of predominantly palmo-plantar pustular psoriasisassociated with anterior chest wall (sternoclavicular, manubriosternal)inflammation has previously been described. In this case, afurther patient is reported where chest wall involvement iscomplicated by anterior mediastinal fibrosis and superior venacaval obstruction. KEY WORDS: Mediastinal fibrosis, superior vena caval obstruction, Synovitis-acne-pustulosis-hyperostosis-osteomyelitis syndrome     

Early neutrophil but not eosinophil or platelet recruitment to the lungs of allergic horses following antigen exposure

Previous studies have shown that bronchoalveolar lavage fluid from horses with allergic respiratory disease and showing clinical symptoms contains increased numbers of neutrophils. In some cases, the eosinophil count is also increased. In this study the time course of changes in lung function and the accumulation of radiolabelled leucocytes and platelets in the lungs of allergic and normal horses has been examined during a 7 hr allergen exposure. Antigen challenge had no effect on pleural pressure or the distribution of radiolabelled neutrophils, eosinophils or platelets in normal horses. In contrast, in 6/8 allergic horses, there was an increase in pleural pressure and neutrophil accumulation in the lungs, both of which were evident after 4-5 hr. However, during the 7 hr challenge period radiolabelled eosinophils were detected in the lungs of only 1/6 horses exhibiting an increase in pleural pressure and in 1/7 horses that failed to show a change in airway function despite a clinical history of allergic respiratory disease. Antigen challenge did not alter the distribution of radiolabelled platelets in the five allergic horses tested. These results demonstrate that increased pleural pressure is not accompanied by eosinophil or platelet accumulation in the lungs of horses with allergic respiratory disease following exposure to antigen. However, changes in airway function can be associated with neutrophil accumulation but can also take place in the absence of this cell recruitment. This raises the possibility that the presence of neutrophils in the lung is not a prerequisite for changes in lung function.     

Inflammation of solar keratoses following systemic 5-fluorouracil

Several cutaneous reactions have been reported following systemic 5-fluorouracil (5-FU) for the treatment of malignancies. We report three patients with marked inflammation of the solar keratoses following continuous infusion of 5-FU for solid tumours. This side-effect with 5-FU. only previously reported in three other cases, was beneficial as most solar keratoses cleared following the inflammatory reaction. The reasons why 5-FU should be selectively taken up by solar keratoses are discussed.