Ischemia-associated intraventricular conduction disturbances during exercise testing as a predictor of proximal left anterior descending coronary artery disease

To determine the incidence and significance of transient intraventricular conduction abnormalities occurring in association with myocardial ischemia during exercise testing, the recordings of 2,200 consecutive exercise tests were reviewed. Ten patients (0.45%) were identified as having both ischemia and intraventricular conduction abnormalities that developed transiently during the exercise test. In all 10 patients both typical angina and electrocardiographic evidence of ischemia developed during exercise. Among the 10 patients, left anterior hemiblock developed in 4, left posterior hemiblock in 2, right bundle branch block (RBBB) in 2, RBBB with left axis deviation in 1, and left anterior hemiblock progressing to complete left bundle branch block (LBBB) in 1. All 10 patients had cardiac catheterization showing significant obstruction of the left anterior descending (LAD) coronary artery at or before the origin of the first septal branch. Eight patients were treated surgically and 2 medically, all with relief of ischemic symptoms. Nine of the 10 had repeat exercise stress testing without angina or electrocardiographic evidence of ischemia and without recurrence of the transient intraventricular conduction disturbance. It is concluded that the development of transient intraventricular conduction abnormalities associated with myocardial ischemia during exercise testing is an uncommon occurrence (0.45%). When such conduction disturbances do develop, the existence of significant disease in the proximal portion of the LAD coronary artery is strongly suggested. With control of myocardial ischemia, the transient conduction disturbances during exercise are ameliorated.     

Morphological observations on motor end-plates in rabbits with experimental myasthenia

The morphology of motor end-plates in rabbits immunized with Torpedo nicotinic acetylcholine receptor (nAChR) has been studied by light and electron microscopy. Rabbits were studied either after one period of paralysis, some in parallel with electrophysiological recordings of MEPPs and EPPs and of Naja naja alpha-neurotoxin binding properties or after recovery followed by a second paralysis. Changes in the sub-neural apparatus were noted after cholinesterase staining only in the latter group. Ultrastructurally, however, most end-plates in both groups contained a wide range of abnormalities. Many were similar in appearance to those observed in human myasthenia gravis (MG). This further supports the theory that immunized rabbits can be used as a model for myasthenia gravis. In the rabbits with 1 period of paralysis an acute stage of influence on the neuromuscular junction seemed to be present while simplified motor end-plates typical for human MG were mostly found in rabbits with 2 periods of paralysis. Short post-synaptic folds in conjugation with thickeneed membrane-bound vesicles at their tops, inside the basement membrane, were frequently observed. These were interpreted as if the crests of the folds containing nAChR had degenerated and had been budded off. If so, a large number of receptor sites had been lost which would be one possible explanation for the lowered capacity of the muscles to bind Naja naja alpha-neurotoxin. Membrane thickenings with projections and striations were interpreted as reflecting ACh receptors and were observed in the post-junctional membrane without proximity to the nerve terminal. The degeneration of the top of the post-synaptic folds and the occurrence of receptors at other locations within the motor end-plate will result in a widened distance between the nerve terminal and the receptors, which can explain previous interpretations of a presynaptic defect in MG.     

Assessment of the arachidonic acid content in foods commonly consumed in the American diet

Arachidonic acid (AA) is an extremely important fatty acid involved in cell regulation. When provided in the diet, it is cogently incorporated in membrane phospholipids and enhances eicosanoid biosynthesis in vivo and in vitro; however, controversy exists as to the levels of AA in food and in the diet. This study determined the amount of AA in cooked and raw portions of beef (rib eye), chicken (breast and thigh), eggs, pork (loin), turkey (breast), and tuna; it compared these results to values published in Agriculture Handbook No. 8 (HB-8). The cooked portions were prepared as described in HB-8. With the exception of chicken thigh and tuna, the levels of AA (w/w) in the selected foods analyzed were significantly higher, in general, than those values published in HB-8. The greatest differences were observed in beef (raw and cooked), turkey breast (raw and cooked), and pork (cooked) where AA levels were twice that of the values in HB-8. In contrast, the AA and n-3 fatty acid contents in tuna were almost half the HB-8 values. The present data indicate that HB-8 tends to underreport the amounts of AA in a number of foods commonly consumed in the American diet, and new initiatives should be considered to validate and update the current database for fatty acid composition of foods.     

Intracochlear factors contributing to psychophysical percepts following cochlear implantation

Glycosyl-phosphatidylinositol (GPI) lipids have a structural role as protein anchors to the cell surface. In addition, they are implicated in hormone, growth factor and cytokine signal transduction. Their phosphodiesteric hydrolysis mediated by an activated phospholipase results in the generation of water soluble oligosaccharide species termed the inositol phosphoglycan (IPG). This product has been demonstrated to possess biological properties when added exogenously to cells mimicking the biological effects of a variety of extracellular ligands. This may be accomplished since IPG is generic for a family of closely related species which are released in a tissue-specific manner and additionally have cell-specific targets. Micro-organic synthesis has recently been able to shed new light on this topic by the introduction of defined oligosaccharide analogues of IPG for the assessment of their biological activity. These have complemented the findings observed with purified IPG from biological sources thus strengthening the belief that the GPI/IPG signalling system represents a truly novel aspect of transmembrane signalling.     

Racial differences in the distribution of a low density lipoprotein receptor-related protein (LRP) polymorphism and its association with serum lipoprotein, lipid and apolipoprotein levels

We recently demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) is an autocrine growth factor for human osteoblastic (hOB) cells. Since GM-CSF is a member of the heparin-binding factor family, we examined the interactions between GM-CSF and glycosaminoglycans (GAGs) present in the osteoblast microenvironment. Using a bioassay in which the mitogenic activity of recombinant human (rh) GM-CSF was measured after incubation in the presence of an hOB cell layer or extracellular matrix (ECM) produced by these cells, we showed that rhGM-CSF binds to GAG components present in the ECM and that the bound rhGM-CSF retains its ability to stimulate hOB cell proliferation. Heparan sulfate compounds on the hOB cell surface were also found to sequester GM-CSF. Moreover, treatment with sodium chlorate, an inhibitor of GAG sulfation, suppressed the mitogenic activity of rhGM-CSF on hOB cells. This inhibitory effect was rescued by a low dose of heparin. Heparin was also found to promote the effect of rhGM-CSF on hOB cell proliferation, allowing nonmitogenic high doses of rhGM-CSF to stimulate hOB cell growth. Western blot analysis showed that undersulfation of cellular GAGs by chlorate inhibited the increased tyrosine phosphorylation of proteins involved in GM-CSF signaling in cloned immortalized hOB cells. The data demonstrate that GM-CSF binds to proteoglycans on the hOB cell surface and in ECM produced by these cells and that the bound GM-CSF is biologically active. Furthermore, this study shows that cellular proteoglycans play an essential role in GM-CSF signaling and biological activity in hOBs.