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S H Appel

Publications and source records attributed to S H Appel.

250 records · Page 14Linked to original sources
PubMed1968

Effect of diphenylhydantoin on synaptosome sodium-potassium-ATPase.

Previous studies have demonstrated that electrically induced seizures in rat result in an increased brain intracellular sodium which can be decreased by treatment with sodium diphenylhydantoin (DPH). The correlation of cation transport with membrane-oriented sodium-potassium-adenosine triphosphatase (Na-K-ATPase) prompted an investigation of the effect of DPH upon ATPase enzyme activity.Rat cerebral cortical synaptosomes isolated in Ficoll gradients were employed as the source for Na-K-ATPase. With 50 mM Na, 10 mM K, 7.5 mM Mg, and 1.8 mM ATP, the specific activity of the preparation was 70 mumoles P(i) released/mg synaptosomal protein per 30 min. The ionic and substrate concentrations yielding one-half maximal velocity were 0.5 mM K, 5 mM Na, and 8.5 x 10(-5) M ATP, respectively. At 50 mM Na and 0.2 mM K, DPH produced an average of 92% stimulation of P(i) release above control. The ratio of Na:K rather than the absolute levels of the ions was critical in determining the effect of DPH. DPH produced significant stimulation of enzyme activity under conditions of a high Na:K ratio (25-50:1). At ratios of 5-10:1, DPH produced little or no effect, and at low Na:K ratios (less than 5:1), DPH was inhibitory. Under all ionic conditions examined, DPH produced no apparent change in enzyme affinity for ATP. Assuming the proposed association of Na-K-ATPase with cation transport in brain, the data suggest the possibility that DPH may control seizures by its stimulation of Na-K-ATPase activity.

Adenosine Triphosphatases↗
PubMedDate not supplied

Red blood cell alterations in muscular dystrophy: the role of lipids.

Biochemical, morphologic, and biophysical studies support the concept that the red blood cell (RBC) membrane is altered in both myotonic muscular dystrophy (MyD) and Duchenne muscular dystrophy (DMD). These studies have not identified a primary metabolic defect that would explain the various alterations of membrane properties. Since the lipid milieu of the membrane affects most membrane properties, it has been extensively investigated in MyD and DMD. Although some studies have suggested specific lipid abnormalities, no reproducible alterations have been reported in the major lipid constituents of the RBC membrane in these disorders. These findings suggest that major alterations of the predominant membrane lipids are not involved in these diseases. Furthermore, studies of the RBC membrane do not provide definitive statements as to the inborn error of metabolism, whether proteins or lipid constituents are primarily affected, or even whether the described alterations are intrinsic to the membrane or are secondary to some circulating factors. Nevertheless, RBCs have proved useful in demonstrating the involvement of the plasma membrane in muscle disorders and should be important in defining how such membrane perturbations affect transport mechanisms.

Adenylyl Cyclases↗
PubMedDate not supplied

Will neurotrophic agents be harmful in Alzheimer's disease?

The thesis that neurotrophic therapy in Alzheimer's disease may exacerbate the pathological state merits careful experimental verification. We are concerned about prematurely dismissing an important avenue of potential therapy which would provide a trophic stimulus to compensate for enhanced proteolysis and the deposition of A4 amyloid peptide.

Alzheimer Disease↗
PubMedDate not supplied

Neurotoxicity of A beta amyloid protein in vitro is not altered by calcium channel blockade.

In cortical cultures, A beta protein destabilizes calcium homeostasis, but direct neurotoxicity of A beta is not observed. In hippocampal cultures, we and others find treatment with A beta protein decreases neuronal survival, but the mechanism of neurotoxicity is unknown. We have used low-density, serum-free cultures of hippocampal neurons to determine whether the neurotoxicity of A beta protein in vitro can be altered by voltage- or ligand-gated calcium channel antagonists or cyclic nucleotides. In these cultures, neither omega-conotoxin, nifedipine, verapamil, APV, nor MK-801 altered the survival of neurons exposed to synthetic A beta 1-40. The N-channel antagonist diltiazem decreased A beta 1-40 toxicity repeatedly, but slightly, perhaps by indirectly contributing to increased neuronal viability. Treatment of cultures with dibutyryl cAMP, 8-bromo cAMP, dibutyryl cGMP, and 8-bromo cGMP also failed to alter A beta toxicity. Thus, the toxicity of beta protein in low-density hippocampal cultures was not directly altered either by calcium channel blockers or by the addition of cyclic nucleotides.

Amyloid beta-Peptides↗
PubMedDate not supplied

Magnetic resonance imaging in multiple sclerosis: results in 32 cases.

A prospective clinical study was performed in 32 patients with multiple sclerosis (MS) to evaluate the sensitivity of lesion detection and accuracy of lesion localization by neurologic examination, delayed enhanced computed tomography (CT) with a double dose of contrast material, and proton magnetic resonance (MR) imaging. After neurologic examination patients were classified by probability of MS (possible, four patients; probable, three patients; and definite, 25 patients) and by disease activity (acute, chronic with acute exacerbation, or chronic progressive). Subsequently they underwent delayed enhanced CT scanning and MR imaging with more than one spin-echo technique. In five of seven patients with possible or probable MS, both MR imaging and delayed enhanced CT were negative. In 25 cases of definite MS, MR imaging detected pathology in 19 (76%) cases, while CT detected lesions in 15 (60%) of 25 cases. In acute lesions (acute or chronic with acute exacerbation), the two techniques were of similar sensitivity (delayed CT was positive in 65% and MR imaging in 60%), while in chronic progressive MS, MR imaging was superior in lesion detection (MR imaging positive in 75%; delayed CT in 25%). While most lesions (55%) were seen in corresponding locations in both studies, neither MR nor delayed CT correlated well with lesion localization by neurologic examination because a large number of asymptomatic lesions were imaged and many symptomatic lesions were undetected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Increased intracellular calcium triggered by immune mechanisms in amyotrophic lateral sclerosis.

Although the causes of motor neuron degeneration and death in amyotrophic lateral sclerosis (ALS) is unknown, recent evidence suggests a prominent role for increased intracellular calcium, possibly triggered by autoimmune mechanisms. The presence in ALS patients of paraproteinemias, lymphomas, lymphoid cells in the central nervous system (CNS) and the availability of animal models of immune-mediated motor neuron disease provide circumstantial evidence for autoimmunity. Direct evidence derives from the demonstration that ALS IgGs bind to voltage-gated calcium channels in 75% of sporadic cases, but not in familial ALS cases, and that ALS IgGs increase N-type and P-type calcium currents in neuronal cells and in lipid bilayers. These same ALS IgGs are cytotoxic for a motor neuron cell line (VSC 4.1) in vitro. In addition, following passive transfer to mice in vivo, ALS IgGs produce ultrastructural and calcium changes in synaptic vesicles and mitochondria of motor axon terminals, as well as in rough endoplasmic reticulum and Golgi complex of motor neuron perikarya, but not in sensory neurons or Purkinje cells. The reason for the selective vulnerability of motor neurons is not clearly defined, but a prominent possibility is the physiological absence in motor neurons of the calcium-binding proteins calbindin-D28k and parvalbumin. These studies emphasize the central role of increased intracellular calcium in motor neuron cell death in sporadic ALS, and the role of autoimmunity in triggering such increases.

Amyotrophic Lateral Sclerosis↗