Identification of an HLA-DQ2 peptide binding motif and HLA-DPw3-bound self-peptide by pool sequencing

Molecules of the major histocompatibility complex (MHC) present antigenic peptides to T cells. Sequencing peptide pools eluted from MHC class I molecules has established allele-specific peptide binding motifs. We applied pool sequencing to analyze human MHC class II-bound peptides and found that HLA-DQ2-eluted peptides predominantly contained lysine, isoleucine, and phenylalanine at relative position i, i + 3 and i + 8, respectively. These residues putatively represent anchor residues for MHC binding. Analysis of a heterogeneous HLA-DPw3/DPw4-eluted peptide pool yielded a sequence matching an epitope from the endogeneous enzyme glyceraldehyde-3-phosphate dehydrogenase. This self-peptide and a partially identical, known allo-epitope bound specifically to DPw3 and DR13 molecules, suggesting the sharing of a binding motif. In particular, the presence of an arginine at relative position 4 appeared important for binding to these HLA class II specificities. Thus, pool sequencing is applicable for the analysis of MHC class II-eluted peptides.     

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.     

The value of MRI in diagnosing vascular abnormalities causing stridor

In a 2 year period seven patients who presented with stridor, without respiratory compromise, and three patients without obstructive symptoms were prospectively selected, and underwent MRI. In eight patients with a vascular ring and a pulmonary sling, MRI delineated the vascular abnormality and normal great vessels were found in two patients. Conclusion MRI successfully delineates the great vessels and demonstrates the presence of a vascular ring and pulmonary sling. Received: 15 May 1996 / Accepted: 17 January 1997     

Diagnostic accuracy of multislice computed tomography coronary angiography is improved at low heart rates

Purpose: Assess the effect of heart rate on diagnostic accuracy for the detection of significant coronary artery stenosis using 16-row multislice computed tomography (MSCT). Material and methods: About 120 patients (105 males; 59±11 years) with suspected coronary artery disease who underwent conventional coronary angiography (CA) and MSCT-CA were retrospectively enrolled for the study. Patients underwent a MSCT-CA (Sensation 16, Siemens, Germany), with the following protocol: collimation 16×0.75 mm, gantry rotation time 420 ms, feed/rotation 3.0 mm, kV 120, mAs 400–500. The protocol for contrast material administration was 100 ml of Iodixanol (Visipaque 320 mg l/ml, Amersham, UK) at 4 ml/s and the delay was defined with a bolus tracking technique. In all patients the mean heart rate (HR) during the scan was used as a criteria to divide the population in two groups of 60 patients each. In one group (Low HR) the 60 patients with lower heart rates, and in the other group (High HR) the patients with higher heart rates. In the two groups diagnostic accuracy (per coronary segment) for the detection of significant stenosis (≥50% lumen reduction) was evaluated in vessels ≥2 mm of diameter using quantitative CA as reference standard. The difference in diagnostic accuracy were compared with a Chi² test and a p<0.05 was considered significant. Results: There was no significant difference between the two groups regarding age, gender, weight, mean intravascular attenuation, and calcium score. Overall 1310 (652 for Low HR and 658 for High HR) segments with 219 (105 for Low HR and 114 for High HR) significant lesions were available for the analysis. The average heart rate was 52±4HU and 63±5HU for Low HR and High HR, respectively (p<0.001). The sensitivity and specificity were 92 and 96% for Low HR and 90 and 92% for High HR (p<0.05). There were 22 vs. 44 false positives, and 8 vs. 12 false negatives in the Low HR and High HR, respectively. Conclusion: Increasing HR significantly deteriorates diagnostic accuracy in MSCT-CA.     

Reducing Ventral Tegmental Dopamine D2 Receptor Expression Selectively Boosts Incentive Motivation

Altered mesolimbic dopamine signaling has been widely implicated in addictive behavior. For the most part, this work has focused on dopamine within the striatum, but there is emerging evidence for a role of the auto-inhibitory, somatodendritic dopamine D2 receptor (D2R) in the ventral tegmental area (VTA) in addiction. Thus, decreased midbrain D2R expression has been implicated in addiction in humans. Moreover, knockout of the gene encoding the D2R receptor (Drd2) in dopamine neurons has been shown to enhance the locomotor response to cocaine in mice. Therefore, we here tested the hypothesis that decreasing D2R expression in the VTA of adult rats, using shRNA knockdown, promotes addiction-like behavior in rats responding for cocaine or palatable food. Rats with decreased VTA D2R expression showed markedly increased motivation for both sucrose and cocaine under a progressive ratio schedule of reinforcement, but the acquisition or maintenance of cocaine self-administration were not affected. They also displayed enhanced cocaine-induced locomotor activity, but no change in basal locomotion. This robust increase in incentive motivation was behaviorally specific, as we did not observe any differences in fixed ratio responding, extinction responding, reinstatement or conditioned suppression of cocaine, and sucrose seeking. We conclude that VTA D2R knockdown results in increased incentive motivation, but does not directly promote other aspects of addiction-like behavior.     

Une cause de cardiomyopathie dilatée chez l’enfant : le déficit primaire en carnitine

Aim

The aim of this case report was to show the importance to research metabolic etiology, especially a carnitine deficiency in dilated cardiomyopathy of children.

Case report

A three years old Togolese child presented muscular hypotonia, dyspnea. Examination showed left galop murmur and systolic murmur 2/6. Chest X-ray showed cardiomegaly (CTI: 0.66), electrocardiogram, a sinusal rythm, left ventricle hypertrophy and T wave abnormalities. Echocardiogram showed a markedly dilated left ventricle with reduced systolic function (EF: 0.43; reference range 0.55–0.80) and moderate mitral regurgitation. The inflammatory signs where negatives. Magnetic resonance imaging don’t show signs of ischemic or myocarditis. The levels of free and total plasmatic carnitine decreased: 3 μmol/L (N: 18–48 μmol/L) and 5 μmol/l (N: 29–70 μmol/L) respectively. Mutation analysis of the gene SLC22A5 confirms the diagnosis of primary systemic carnitine deficiency. Treatment with oral carnitine was started at 200 mg/kg per day. Within three weeks of treatment, we observed the decrease of all symptoms and the left ventricular size and function normalized (EF: 0.62). He has now been on oral carnitine for live.

Conclusion

Primary carnitine deficiency is a cause of dilated cardiomyopathy in child. It must systematically be suspected when a child presents a primitive cardiomyopathy. The treatment with oral carnitine for live is simple, with excellent prognosis.     

Alcohol-related effects on automaticity due to experimentally manipulated conditioning

Background: The use of alcohol is associated with various forms of automatic processing, such as approach tendencies and attentional biases, which may play a role in addictive behavior. The development of such automaticity has generally occurred well before subjects perform tasks designed to detect them. Although it seems plausible that this development involves some form of alcohol‐related conditioning, this process is not usually included in the experimental procedure. Methods: The development of automaticity involving alcoholic or nonalcoholic stimuli was experimentally manipulated via a conditioning task. Subjects were presented with pairs of stimuli from a set of 4 stimuli: 2 pictures of alcoholic beverages, and 2 pictures of nonalcoholic beverages. One of the alcoholic and 1 of the nonalcoholic beverages was associated with reward, the other stimuli with punishment. Subjects had to learn to select the rewarded stimuli from pairs of 1 rewarded and 1 punished stimulus. The task, thus experimentally established reward versus punishment stimulus–response–outcome associations, for alcoholic and for nonalcoholic stimuli. Subsequently, a cued reversal task was used to test automaticity involving alcoholic versus nonalcoholic, and rewarded versus punished stimuli. Results: An association was found between heavier drinking and an alcohol‐related conditioning bias: heavier drinkers had more difficulty overcoming a conditioned response when it involved selecting a previously punished nonalcoholic stimulus over a previously rewarded alcoholic stimulus. Conclusions: The study provided novel information on secondary reinforcement involving alcoholic stimuli: heavier drinkers may more easily develop automaticity related to alcohol‐reward contingencies. This may have implications for interventions and the interpretation of findings concerning alcohol‐related automatic processing.