Peptide specificity and HLA restriction do not dictate lymphokine production by allergen-specific T-lymphocyte clones.

Human and murine CD4+ T lymphocytes can be subdivided into distinct subsets [T-helper type 0 (Th0), Th1 or Th2], based on their lymphokine production profiles. Not much is known about the factors that determine these restricted lymphokine secretion profiles. Peptide specificity and human leucocyte antigen (HLA) restriction may be such factors. As it is well established that allergen-specific T lymphocytes from atopic individuals and non-atopic controls differ in their lymphokine secretion profile, we studied two allergen-specific T-lymphocyte clones (TLC) with identical peptide specificity and HLA restriction that were generated from the peripheral blood of an atopic donor and a non-atopic control donor. The two CD4+ TLC recognize the same epitope (20-33) of the house dust mite Dermatophagoides pteronyssinus major allergen Der p II. Both TLC recognize the epitope in an HLA-DQB1*0602-restricted manner. However, the lymphokine production profiles of these TLC show clear differences after allergen-specific or polyclonal activation. As expected, TLC JBD4 from the atopic donor produced high levels of interleukin-4 (IL-4) without detectable interferon-gamma (IFN-gamma), whereas TLC PBA1 from the non-atopic donor produced both IFN-gamma and IL-4 upon allergen-specific or polyclonal activation. Inasmuch as both TLC recognized the same epitope of Der p II in association with the same HLA-DQ molecule, these data suggest that peptide specificity and HLA restriction of human allergen-specific TLC do not dictate their lymphokine secretion profile.     

Suppression of spontaneous breathing during high-frequency jet ventilation

Conditions which suppress spontaneous breathing activity during high-frequency jet ventilation (HFJV) were analysed in Yorkshire piglets under pentobarbital anesthesia. The highest P_aCO₂ at which the animals did not breathe against the ventilator (apnea point) was established during different patterns of ventilation, either by changing the minute volume or by adding CO₂ to the inspiratory gas. Arterial oxygen tension was maintained throughout the study above 80 mm Hg. An elevation of ventilatory rate increased the apnea point, suggesting a progressive suppression of spontaneous breathing. This suppression did not depend on the amount of lung stretch during insufflation, because at higher rates lower tidal volumes were used. Suppression also appeared to be independent of insufflatory flow, i.e. the velocity of lung stretch. At higher frequencies end-expiratory airway pressure (P_EE) increased and there appeared to be a positive relationship between the apnea point and P_EE. In a separate series this positive relationship between the apnea point and P_EE was confirmed. A hysteresis effect in this relationship, however, suggests that other than jet frequency, lung volume rather than positive end-expiratory pressure (PEEP) is a major determinant of suppression of spontaneous breathing activity during HFJV.     

Donor genetic variants as risk factors for thrombosis after liver transplantation: A genome-wide association study

Thrombosis after liver transplantation substantially impairs graft- and patient survival. Inevitably, heritable disorders of coagulation originating in the donor liver are transmitted by transplantation. We hypothesized that genetic variants in donor thrombophilia genes are associated with increased risk of posttransplant thrombosis. We genotyped 775 donors for adult recipients and 310 donors for pediatric recipients transplanted between 1993 and 2018. We determined the association between known donor thrombophilia gene variants and recipient posttransplant thrombosis. In addition, we performed a genome-wide association study (GWAS) and meta-analyzed 1085 liver transplantations. In our donor cohort, known thrombosis risk loci were not associated with posttransplant thrombosis, suggesting that it is unnecessary to exclude liver donors based on thrombosis-susceptible polymorphisms. By performing a meta-GWAS from children and adults, we identified 280 variants in 55 loci at suggestive genetic significance threshold. Downstream prioritization strategies identified biologically plausible candidate genes, among which were AK4 (rs11208611-T, p = 4.22 × 10⁻⁰⁵) which encodes a protein that regulates cellular ATP levels and concurrent activation of AMPK and mTOR, and RGS5 (rs10917696-C, p = 2.62 × 10⁻⁰⁵) which is involved in vascular development. We provide evidence that common genetic variants in the donor, but not previously known thrombophilia-related variants, are associated with increased risk of thrombosis after liver transplantation.     

Allergy to pine nuts in a bird fancier

A patient is described with the bird-egg syndrome who experienced an anaphylactic reaction after eating some of her parrot's food (pine nuts: Pinus pinea ). Specific IgE against this nut and another pine nut ( P cembra ) was demonstrated by RAST. Cross-reactivity between these botanically related seeds was shown by RAST inhibition. Besides avian antigens, bird food antigens should be taken into consideration when symptoms of allergy occur on exposure to birds.     

Bacterial adhesion to medical polymers--use of radiation techniques for the prevention of materials-associated infections

The basic principles of the adhesion of bacteria to polymer surfaces are discussed, as the first important step in the pathogenesis of foreign-body infections. Strategies for the prevention of foreign-body infections by polymer modification with ionizing radiation are presented. These include the modification of polymer surfaces by radiation or glow discharge techniques to obtain antiadhesive or antimicrobial surfaces, as well as the fixation or incorporation of antibiotic drugs to or into the polymer.     

MR contribution in surgery of epilepsy

The contribution of MR imaging in patients with drug-resistant epilepsy considered for surgical therapy is discussed. In this review we focus on: (a) focal abnormalities (mesial temporal sclerosis, focal migration disorders, hamartomatous lesions and low-grade tumours, phakomatosis and vascular malformations) associated with therapy-resistant partial epilepsy, requiring resective surgery; (b) abnormalities leading to generalized seizures that require more drastic surgical procedures, such as callosotomy and functional hemispherectomy; and (c) localisation of implanted depth-electrodes. Received: 6 April 1998; Revision received: 2 June 1998; Accepted: 3 June 1998     

55Cobalt (Co) as a PET-tracer in stroke, compared with blood flow, oxygen metabolism, blood volume and gadolinium-MRI

Axonal degeneration plays an important role in the accumulation of disability in patients with multiple sclerosis (MS). Pathological studies have demonstrated axonal damage, particularly in areas of acute inflammation and demyelination, and in chronic lesions. Axonal loss and its progression, which is associated with neurological disability, has also been demonstrated by magnetic resonance imaging (MRI) studies. The mechanisms of axonal loss are uncertain, but may involve axonal degeneration secondary to demyelination, or damage to the axonal cytoskeleton. Inflammatory mediators, including cytokines and proteolytic enzymes may contribute to axonal damage, as may nitric oxide. Axonal destruction may also be due to immune attack directed at axonal components. The realisation that axonal degeneration is a fundamental component of MS that may occur early in the disease course should alter the approach to management and open avenues to a more targeted immunotherapy aimed at reducing the progression of disability.     

An experimental test of the relationship between self-esteem and concern about body shape and weight in restrained eaters

OBJECTIVE: Although self-esteem and overconcern with body shape and weight are considered to be closely connected in bulimia nervosa, little empirical research has been done to investigate the alleged link. METHOD: In this study, we examined experimentally whether overconcern with body shape and weight was connected with self-esteem in an analogue sample of high restrained eaters by means of a subliminal lexical decision task. RESULTS: It could indeed be demonstrated that low self-esteem and overconcern with body shape and weight are associated in high restrained eaters: after priming low self-esteem, the accessibility of subliminally presented body shape and weight stimuli was increased. The effect was not found with a supraliminal lexical decision task. DISCUSSION: Apparently, the automatic, nonconscious processing of body shape and weight words was influenced in high restrained eaters with a low state self-esteem, whereas the strategic, conscious processing was not. As soon as the body shape and weight stimuli were processed consciously, the initial increased accessibility was countered and the effect disappeared.     

Adjuvant immunotherapy with BCG in squamous-cell bronchial carcinoma. Immune-reactivity in relation to immunostimulation (preliminary results in a controlled trial).

Jansen, H M, The, T H, de Gast, G C, Esselink, M T, van der Wal, A M, and Orie, N G M (1978).Thorax, 33, 429-438. Adjuvant immunotherapy with BCG in squamous-cell bronchial carcinoma. Immune-reactivity in relation to immunostimulation (preliminary results in a controlled trial). Twenty-nine patients with, at operation, evidence of locally advanced primary squamous-cell bronchial carcinoma (stage II, UICC, Geneva, 1974) had lung resection to remove all the visible tumour. Postoperatively a randomly chosen group of 16 patients received adjuvant BCG immunostimulation by scarifications, while the control group received no adjuvant treatment. Follow-up studies were done from three to 23 months. Immune-reactivity in vivo with PPD and DNCB skin tests, and in vitro with E-rosetting tests and lymphocyte transformation tests with PHA, Con A, diphtheria toxoid, and PPD was monitored in 10 treated and in seven untreated patients. Recurrence rates decreased appreciably in the BCG-stimulated group after a six to 23 months'' follow-up (p<0·005). A pronounced increase in both in-vivo and in-vitro immune-reactivity went in parallel with a more favourable clinical outcome in the BCG-treated group. In these cases there was a significant increase in skin reactivity to PPD three months after surgery (p<0·025) and a statistically significant rise in lymphocyte reactivity to Con A (p<0·05), diphtheria toxoid (p<0·01), and PPD (p<0·05) but not to PHA 12 months after surgery. DNCB skin reactivity increased as well in the BCG-treated group, but the number of individuals was too small for statistical evaluation. Increase in immune responsiveness did not occur in the control group and appeared to be independent of the initial immune state of the patients. No differences were found in the numbers of E-rosetting lymphocytes in relation to immunotherapy. It is concluded that adjuvant BCG immunotherapy used in patients with minimal residual bronchial carcinoma improves the prognosis and a favourable clinical outcome is mirrored by an increase in cellular immune reactivity.     

Chronic infusion of clonidine does not alleviate spontaneous morphine withdrawal symptoms in rats

Opiate withdrawal is associated with behavioural symptoms and a sympathetic hyperactivity, the latter being sensitive to clonidine. The central question is whether behavioural symptoms would be also sensitive to clonidine. A rat model was used in which the locomotor activity was measured 24 h a day during the morphine withdrawal phase. Spontaneous withdrawal of morphine reduced strongly the high nocturnal locomotor activity, concomitently decreasing food intake and body weight. Chronic infusion of clonidine (30–120 µg/kg/day) using osmotic minipumps had no effect on the withdrawal symptoms. Higher dosages (250–1000 µg/kg/day) potentiated rather than alleviated the withdrawal symptoms, suggesting an ₁-adrenergic effect of clonidine rather than an ₂-action. Therefore, we studied the action of a more specific ₂-agonist UK-14.304. UK-14.304 was less potent than clonidine in naive animals. It slightly alleviates the decrease of nocturnal activity during spontaneous morphine withdrawal. Furthermore, we have tested whether the effects of high dosages of clonidine could be altered by a specific ₁-antagonist doxazosine. Doxazosine reduced only slightly the potentiation in the decrease in food intake by clonidine during morphine withdrawal. For the other symptoms no interaction between doxazosine and clonidine was found. The data suggest that the use of clonidine in the detoxification of opiate dependent people is based on the suppression of the sympathetic hyperactivity rather than on symptoms with a more behavioural character.