Immunological IgE Cross-Reactions of Bovine and Human α-Lactalbumins in Cow's Milk Allergic Patients

Despite great homology with the equivalent human protein, bovine α-lactalbumin (B α-La), a major component of whey, has been identified as a major milk allergen. The aim of this study was to investigate the relationship between structure and IgE binding capacity in α-Las: (1) the importance of three-dimensional structure using native vs disulfide bridgereduced B α-La; and (2) the incidence of amino acid sequence divergence on specific IgE cross-reactivity to human vs bovine α-La. Purified native, reduced and S-carboxymethylated B α-La and human α-La (H alpha-LA) were prepared. Specific IgE of 20 sera from patients with clinically recognized cow's milk protein allergy and positive RAST tests to B α-La were measured in original direct and competitive ELISA inhibition tests. All sera containing specific anti-native B α-La IgE also reacted with denatured protein, but the IgE levels were generally lower, showing that three-dimensional structure is an important feature in B α-La allergenicity but that sequential epitopes are also exposed after protein denaturation. Despite lower IgE levels, all sera also gave significant IgE responses to H α-La. Competitive ELISA inhibition confirmed results obtained by direct ELISA. The demonstrated IgE cross-reactivity between B α-LA and H α-La could be related to the high degree of sequence homology between the two proteins but did not prove to have a clinical significance. However, it is of great interest for a study of the relationship between structure, IgE binding capacity and allergenicity in alpha-Las.     

Malignant Ventricular Tachycardia During Propafenone Treatment in a Child with Junctional Automatic Tachycardia: Effectiveness of Intravenous Molar Sodium Lactate

Propafenone may aggravate the preexisting arrhythmia or induce another one. Usually, such proarrhythmic effects occur in patients with spontaneous ventricular arrhythmias and/or coronary heart disease with poor left ventricular function. We report the case of a 5-year-old girl with Junctional automatic tachycardia and no structural heart disease, in whom malignant ventricular tachycardia occurring during propafenone treatment could be terminated by molar sodium lactate (MSL) infusion. The serum propafenone level obtained before MSL infusion was within the therapeutic range. Two hypothesis could explain the beneficial effects of MSL in our patient: (1) alkalinization facilitates the cell membrane hyperpolarization and thus can decrease the voltage-dependent effect of Class Ic drugs, (2) alkalinization could displace propafenone from its tissue receptor sites by an increase in the nonionized fraction.     

Characterization of a new family of toxin-like peptides from the venom of the scorpion Leiurus quinquestriatus hebraeus-NMR structure of leiuropeptide II

To extend our knowledge about the structural features of short scorpion toxins, the ion-exchange fractions obtained from Leiurus quinquestriatus hebraeus venom were investigated by plasma desorption mass spectrometry in order to select low molecular mass polypeptides. Three toxin-like peptides with molecular mass close to 3 kDa, named leiuropeptides I, II and III, were purified and found devoid of any significant toxicity against mammals and insects. Their amino acid sequences revealed a cysteine pattern analogous to that of short-chain scorpion toxins. The solution structure of leiuropeptide II was determined by 2D H-NMR spectroscopy and indicated the presence of a helix accomodating a proline, connected to a two-stranded β-sheet by three disulfide bonds. The overall fold of leiuropeptide II is found to be similar to that of leiurotoxin I, a 31-residue toxin present in the same scorpion venom which acts on K⁺ channels. In order to rationalize the absence of toxicity, the electrostatic potential of leiuropeptide II was compared to that of leiurotoxin I. The peptide is characterized by a large negative zone around Glu4, Asp5 and Asp8 residues, beginning in the neighbourhood of the β-turn and extending along the helix. In the same area, leiurotoxin I exhibits a positive surface, around Arg6 and Argl3 basic residues, which are essential for its receptor affinity. © Munksgaard 1997.     

Analytical Review: Multiple Differentiation in Megakaryocytes and Platelets

The properties of the megakaryocyte and the platelet may be briefly summarized as follows: a polyploid cell secretes, by an apocrine type mechanism, an anucleate element, endowed with strong autolytic and endocytic properties, and capable of performing contractile work. The latter element, specialized in this way, is prepared to play a major role in hemostatic reactions.

The relationships between the five properties considered for these elements are still largely unknown. A certain degree of polyploidy may conceivably be necessary for the megakaryocyte to secrete platelets, but the importance of polyploidy in its cytoplasmic maturation has recently been questioned.⁶ The influence of the absence of a nucleus on platelet metabolism, as well as on the endocytic properties of cells, is still a matter of controversy.^97,98 Finally, there remains to be established the possible role of contraction in the release of platelet material,⁸⁴ and molecular material degraded by lysosome action.

Submitted on May 2, 1966 Accepted on October 14, 1966     

Mobility of the Intimal Flap and Thrombus Formation in Aortic Dissection: A Transesophageal Echocardiographic Study

The mechanisms of the motion of the intimal flap and of thrombus formation in acute or chronic aortic dissection are not definitively elucidated. Transesophageal echocardiography seems to be a technique of choice to analyze the flow in the true and false lumina. Twenty-one consecutive patients were studied in order to define the mobility of the intimal flap, the color Doppler flow patterns, the presence of spontaneous echocardiographic contrast, and thrombus formation at different levels of the aorta. The results suggest that clotted false lumen is more often seen in chronic aortic dissection at the level of the descending thoracic aorta. However, thrombosed false lumen in the aortic arch is suggestive of a retrograde aortic dissection. In cases of complete obliteration of the false lumen, the differentiation between aortic dissection and aortic ectasia with mural thrombus may be extremely difficult.     

Directional Variability of Stimulation Threshold Measurements in Isolated Guinea Pig Cardiomyocytes: Relationship with Orthogonal Sequential Defibrillating Pulses

BARDOU A.L., ET AL.: Directional Variability of Stimulation Threshold Measurements in Isolated Guinea Pig Cardiomyocytes: Relationship with Orthogonal Sequential Defibrillating Pulses. Reports on delivery of separated orthogonal pulses markedly improving cardiac defibrillation have suggested that the stimulation threshold of heart fibers varies in accordance with their orientation within the electric field. The present work was aimed at investigating the directional variability of stimulation thresholds in isolated guinea pig cardiomyocytes. This variability was measured in 48 single myocytes by rotating each one through a theta (θ) angle between two-fixed parallel electrodes 1.1 cm apart, thus making θ vary between the electric field and the myocyte axis. For θ= 0°, the mean longitudinal current stimulation threshold was 16.92 ± 4.20 mA (n = 48). When θ was increased by increments of 10° up to 90°, the stimulation threshold increased in an exponential way. For θ= 90°, the mean transverse stimulation threshold was 63.23 ± 13.30 mA. These results clearly demonstrate the dependence of isolated cardiomyocyte stimulation thresholds on their orientation within the electric field and may account for the improved efficacy of defibrillation previously observed after delivery of orthogonal pulses.     

A new c-kit mutation in a case of aggressive mast cell disease

Systemic mast cell disease (SMCD) is a disorder characterized by a mast cell proliferation in various tissues. Mast cells express the c -kit proto-oncogene. A few cases of c -kit mutations have been described in SMCD. We report an aggressive SMCD in a patient who presented with a bone marrow infiltration by abnormal mast cells. Molecular studies of mast cell DNA and RNA revealed a new c- kit heterozygous mutation (Asp820Gly). This mutation leads to a drastic amino-acid change and is located close to the highly oncogenic Asp816Val. These findings suggest that the Asp820Gly has a potential role in c- kit activation.     

DNA Metabolism and Development of Organelles in Guinea-Pig Megakaryocytes: A Combined Ultrastructural, Autoradiographic and Cytophotometric Study

The thick and thin section technique was used to study guinea-pig megakaryocytes by electron microscopy, combined with either autoradiography orcytophotometric determination of DNA. Megakaryocytes engaged in polyploidization already showed granule formation, which began in the Golgi apparatuspartially encircled by the nucleus. The ploidization phase stopped at the 8N,16N or 32N level, after an average of 3 ± 0.5 (1 S.D.) genome duplications.Microtubules, myofibrils and demarcation membranes were also present in theimmature megakaryocytes but organelles were formed in increasing amountsin non DNA-synthesizing cells. Platelet liberation, possible at the 8N, 16N or32N stage, occurred in non DNA-synthesizing cells, principally at the 16N level.

Submitted on May 23, 1969 Accepted on August 14, 1969     

High Accuracy of Automatic Detection of Atrial Fibrillation Using Wavelet Transform of Heart Rate Intervals

DUVERNEY, D., et al. : High Accuracy of Automatic Detection of Atrial Fibrillation Using Wavelet Transform of Heart Rate Intervals. Permanent and paroxysmal AF is a risk factor for the occurrence and the recurrence of stroke, which can occur as its first manifestation. However, its automatic identification is still unsatisfactory. In this study, a new mathematical approach was evaluated to automate AF identification. A derivation set of 30 24-hour Holter recordings, 15 with chronic AF (CAF) and 15 with sinus rhythm (SR), allowed the authors to establish specific RR variability characteristics using wavelet and fractal analysis. Then, a validation set of 50 subjects was studied using these criteria, 19 with CAF, 16 with SR, and 15 with paroxysmal AF (PAF); and each QRS was classified as true or false sinus or AF beat. In the SR group, specificity reached 99.9%; in the CAF group, sensitivity reached 99.2%; in the PAF group, sensitivity reached 96.1%, and specificity 92.6%. However, classification on a patient basis provided a sensitivity of 100%. This new approach showed a high sensitivity and a high specificity for automatic AF detection, and could be used in screening for AF in large populations at risk.