The HGAR1 familial hypercholesterolemia pedigree

Data on 232 members of a single pedigree, descended from two pairs of original parents, were made available to the participants of Genetic Analysis Workshop 8 (GAW8). In addition to information concerning age and sex, measurements for 10 quantitative traits and genotypes at 22 polymorphic marker loci were also provided for a subset of 193 of these family members. © 1993 Wiley-Liss, Inc.     

Ultrastructural reversible changes in fish neuromuscular junctions after chronic exercise

Neuromuscular junctions (NJs) of fin muscles of teleostean fishes, Lebistes reticulatus, were ultrastructurally analyzed during 60 min of chronic exercise and a subsequent period of 90 min of induced recovery. NJs from 30-min-exercised fishes showed an almost complete depletion of synaptic vesicles (SVs), corresponding to 83% of SV consumption; 76% of axon terminals were branched at the end of this period. During the recovery period, it was possible to observe the reversibility of the changes induced by the exercise and the transitory events that lead to the reacquirement of the normal NJ morphology. After 15 min of rest, SV population increased to a value of 54.6 SVs/micron2 and the percentage of branched axons was 66.5%. At 60 min of recovery the number of SVs reached a value of 84.6 SVs/micron2. The SV population was fully reestablished at 80 min of rest, while the percentage of branched axons was found within normal ranges after 90 min of recovery. These results demonstrate that chronic exercise induced physiological depletion of NJ SVs and other axon terminal morphological changes, as well as that postexercise rest induces the reestablishment of the normal NJ morphology.     

Facilitated uptake of zinc into human erythrocytes. Relevance to the treatment of sickle-cell anaemia

The ability of a number of heterocyclic metal chelators to deliver zinc into red cells, to release the liganded zinc to haemoglobin and thereby cause a left shift in the oxygen dissociation curve of intact red cells has been investigated. Incubation of neutrally charged zinc-pyrone and zinc-pyridin-2-one complexes with red cells led to the rapid accumulation of zinc within cells, whereas unliganded zinc in the form of zinc acetate, zinc chloride or zinc sulphate accumulated only slowly. The rate at which zinc was delivered to red cells by pyrone and pyridin-2-one ligands increased with increasing lipid solubility of the ligands. The uptake of zinc into both normal adult and sickle red cells was associated with a dose-dependent increase in the oxygen affinity of haemoglobin. The degree of left shift in the oxygen dissociation curve following the incubation of red cells with zinc-pyrone and -pyridin-2-one complexes suggests that these complexes may find application as agents to increase the oxygen affinity of haemoglobin in sickle cell disease and thereby decrease the probability of intravascular sickling at low tissue oxygen tensions. Ethylmaltol appears to be a particularly useful agent due to its known low toxicity.     

Diets rich in n-9, n-6 and n-3 fatty acids differentially affect the generation of inositol phosphates and of thromboxane by stimulated platelets, in the rabbit

We have studied the effects of semi-synthetic diets rich in either n-9 (olive oil, OO) or n-6 (corn oil, CO), or n-3 (fish oil, FO, as MaxEPA) fatty acids on the levels of major PUFA in platelet lipids, on the generation of inositol phosphates by [3H]inositol labelled platelets after stimulation with thrombin and of thromboxane B2 (TxB2) by platelet rich plasma (PRP) after stimulation with collagen. The predicted elevations of oleic (OA), linoleic (LA) and eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids were observed in platelet lipids of each animal group, but in the MaxEPA fed group accumulation of EPA was associated with depletion of linoleic acid (LA) rather than of arachidonic acid (AA). Basal levels of inositol-tris-phosphate (IP3) in platelets were lowest in the OO group and highest in the CO group, whereas the increment after thrombin stimulation (1 unit/ml NIH) was maximal in the OO group and minimal in the FO group. Instead, when generation of TxB2 by stimulated platelets was evaluated, no appreciable difference among the various groups could be detected, in accordance with the limited modifications of platelet AA content induced by the diets. The overall data indicate that dietary fatty acids modulate the pathway of inositol phosphate generation in rabbit platelets, independently of modifications of TxB2 production.     

Multimodality evoked potentials and early prognosis in comatose patients

In 112 comatose patients somatosensory, visual and auditory evoked potentials were registered within 36 hours after the onset of coma or admission. Main causes of coma were head injury, and intracerebral and subarachnoid haemorrhage. The initial bilateral loss of any evoked potential was associated with a mortality of 98%. Normal somatosensory evoked potentials were associated with a survival rate of 74%, while normal visual and normal auditory evoked potentials had a survival rate of 60% and 66%, respectively. It is concluded that SEPs can be valuable for the prognosis of coma after primary brain lesions.     

Comparison of two analytical procedures for the determination of free urinary catecholamines under the demands of shiftwork experiments

Summary A typical shiftwork experiment was chosen to prove the validity of an automated procedure for the analysis of free noradrenaline and adrenaline in urine. The method consists of a column switching technique with an adsorption/elution clean-up and a reversed phase high performance liquid chromatography followed by chemical reaction detection based on the trihydroxyindole method. The analysis of variance was performed using a second data set obtained by a semi-automated procedure for which the accuracy had already been confirmed. The analysis of covariance showed that for field studies, as well as for laboratory experiments in which the variances contributed by the experiments themselves are greater than 10% rel., the data sets of the two methods provide the same information.Dedicated to Prof. H. Hartkamp, University of Wuppertal, on the occasion of his 60th birthday