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Biomedical subjects

W K Engel

Publications and source records attributed to W K Engel.

At least 217 records · Page 12Linked to original sources
PubMed1977

Ultrastructural localization of calcium in normal and abnormal skeletal muscle.

Calcium was demonstrated ultrastructurally as a fine black reaction product with unbuffered 2% saturated potassium pyroantimonate, pH 9.4. In comparison with normal muscle, there was increased precipitate in degenerating skeletal muscle fibers and some degenerating-regenerating fibers occurring in pathologic human muscle, regardless of disease entity, and in experimentally injured rat muscle. The pathologically increased calcium was mainly within the sarcoplasmic reticulum and mitochondria. Both structures could be completely blackened. Nuclear calcium was also increased, the precipitates being localized as circular profiles within the nucleoli and heterochromatin as well as being associated with the nuclear envelope. Myofibrillar calcium was only modestly increased. When normal rat muscle was preincubated in 136 mM calcium-enhanced Hanks' medium, calcium accumulated in the muscle fibers--it was especially heavy in the mitochondria and sarcoplasmic reticulum and appeared identical with the pathologic human and rat muscle fibers. Preincubation of normal rat muscle in 0.1 M acetate buffer (pH 4.65) before calcium loading augmented myofibrillar staining, mainly in the H-zone of the A-bands excluding the M-zone and in broad irregular N1, N2, and "N3" lines of the I-bands. EMMA-4 electron probe microanalysis and EGTA (ethylene glycolbis (beta-aminoethyl ether)N,N'-tetraacetic acid) chelation prior to staining confirmed that the precipitate in the several loci was calcium antimonate. It is proposed that in skeletal muscle fibers injured by various pathologic processes, a breach of the plasmalemma barrier to calcium occurs as a very early abnormality. Extracellular calcium would then pour into the aqueous sarcoplasm of the muscle fiber, from which it would be withdrawn by and accumulated with the still active organelles normally having a great avidity for uptake of this ion, especially the mitochondria and sarcoplasmic reticulum. The resultant organellar calcification would impair function and damage the structure of proteins and phospholipids.

Animals↗
PubMed1977

Calcium metabolism in amyotrophic lateral sclerosis.

Calcium metabolism was studied prospectively in 12 patients with amyotrophic lateral sclerosis. Two patients showed mild hypocalcemia, malabsorption of calcium, and elevated plasma parathyroid hormone concentrations. Serum 25-hydroxyvitamin D was decreased in one and low-normal in the second. These two patients and a third showed aminoaciduria on thin layer chromatography. Calcium metabolism was apparently restored to normal by dihydrotachysterol, a vitamin D analog, but no improvement in neurologic function resulted. Bone radiographs taken in search of metabolic bone disease showed a significant increase in the incidence of congenital vertebral anomalies in the ALS patients (50% versus 8%). The relationship of the abnormalities in calcium metabolism and in vertebral structure to the etiology of motor neuron disease is not known.

Adult↗
PubMed1976

Adult-onset acid maltase deficiency. Morphologic and biochemical abnormalities reproduced in in cultured muscle.

We established muscle-tissue cultures from biopsy of a patient with adult-onset acid maltase deficiency. Morphologically and biochemically, the newly grown fibers of the cultured muscle showed the same abnormalities as those of the biopsied muscle. Light microscopy showed multiple vacuoles filled with acid-phosphatase-positive material; on ultrastructural examination there was abnormal accumulation of glycogen in membrane-bound sacs (secondary lysosomes), some of which also contained dark membranous of homogeneous material. Acid maltase (pH 4.0), a lysosomal enzyme, was undetectable in either cultured or biopsied muscle by maltose hydrolysis, whereas acid phosphatase, also a lysosomal enzyme, was increased in both sources of muscle cells. Cultured muscle fibers demonstrate the same morphologic and biochemical abnormalities characteristic of biopsied muscle, supporting the concept of a biochemically distinct primary myopathy in man.

Acid Phosphatase↗
PubMed1976

Slow saccades in spinocerebellar degeneration.

Two patients with spinocerebellar degeneration made abnormally slow horizontal refixations. One patient produced quick phases of nystagmus with identical maximum velocities, suggesting her refixations were abnormal saccades and not voluntary pursuit movements. In response to double target jumps, neither patient showed an obligatory refractory period after each saccade; they responded to every target movement after one reaction time. Their slow refixations were not preprogrammed since they could be modified in flight. To reconcile these observations with normal saccadic behavior, we hypothesized a neural network that made saccades by driving the eyes to an orbital position rather than preprogramming a distance for movement. Computer simulation of this model produced both realistically appearing normal saccades and, when appropriately "lesioned" to simulate a loss of saccadic "burst" neurons in the pontine reticular formation, slow saccades that could be modified in flight.

Adolescent↗
PubMed1976

Extrajunctional acetylcholine receptors. Alterations in human and experimental neuromuscular diseases.

Diffuse extrajunctional acethycholine receptors (AChR) of skeletal muscle fibers were readily visualized by light and electron microscopy in muscle biopsy specimens of experimental denervation and human denervating diseases by use of an alpha-bungarotoxin immunoperoxidase technique. In peripheral neuropathies and various motor neuron diseases, a significant number of muscle fibers appearing denervated by histochemical criteria have diffuse extrajunctional AChR like those experimentally denervated by cutting the motor nerve supply. In portions of muscle fibers experimentally deprived of neuronal influence by direct injury, diffuse extrajunctional AChR developed, demonstrating that a denervation-like diffuse appearance of extrajunctional AChR can develop other than with neuronal damage, ie, it can be myogenous. Similar extrajunctional AChR was seen in some regenerating fibers of human myopathies, especially inflammatory myopathies.

Amyotrophic Lateral Sclerosis↗
PubMed1976

Ocular motor abnormalities in hereditary cerebellar ataxia.

Twelve members of a family with hereditary cerebellar ataxia of late onset were examined and, in 5, quantitative recording of eye movements were obtained. The initial and most severe symptom in all patients was ataxia of gait, followed by dysarthria and later by dysmetria of the limbs. Clinical examination did not reveal involvement of structures other than the cerebellum. Ocular motor examination showed: (1) inability to hold eccentric gaze resulting in gaze-paretic nystagmus; (2) downward beating nystagmus, accentuated on lateral gaze; (3) defective smooth pursuit, with relative preservation of optokinetic nystagmus induced by full-field stimulation; (4) rebound nystagmus; (5) enhanced gain (eye velocity/head velocity) of the vestibulo-ocular reflex during rotation in darkness; (6) decreased ability to suppress the vestibulo-ocular reflex during fixation of an object rotating with the patient; (7) saccadic dysmetria, especially downward overshoot; and (8) square wave-jerks. Although each of these signs can probably occur with lesions elsewhere in the brain, in combination they are highly suggestive of cerebellar involvement. With the reservation that we do not yet have pathological confirmation of the location of our patients' lesions, our results support the suggestion that the cerebellum specifically: (1) helps maintain eccentric gaze; (2) produces smooth pursuit eye movements; and (3) modulates the amplitude of saccadic eye movements. Many of the characteristics of the altered vestibulo-ocular responses and rebound nystagmus could be explained by the underlying anomaly in the smooth pursuit system.

Adult↗
PubMed1976

Light-cored dense particles in mitochondria of a patient with skeletal muscle and myocardial disease.

A 15-year-old boy with skeletal muscle and myocardial disease was found to have large numbers of abnormal muscle mitochondria, the distinguishing feature of which was the presence of many light-cored dense particles. These particles bore a marked resemblance to those seen in situations where mitochondria accumulate calcium. If that is what they were, it remains to be determined whether such an accumulation of calcium, or other mitochondrial abnormality, played a role in the patient's muscle weakness. Alternatively, the granules might have represented evidence of virus involvement of the mitochondria, but this seems less likely.

Adolescent↗
PubMed1976

Immunoperoxidase localization of alpha bungarotoxin: a new approach to myasthenia gravis.

The IPBT method has made it possible to precisely visualize the AChR. Normal distribution of AChR is at the peaks of the postjunctional folds of the muscle sarcolemmal membrane with a small amount present on the axonal tip as well. Denervated muscle fibers have extrajunctional AChR. In MG, there are also denervated-appearing fibers but these do not have extrajuctional AChR with the IPBT stain. To explain this, we have been able to demonstrate a serum factor capable of blocking the binding of alpha-BuTx to the AChR and have shown for the first time that this factor is capable of acting at the neuromuscular junction itself. This blocking factor may play a major role in causing the weakness of MG.

Acetylcholine↗
PubMed1976

Antibodies to nucleic acids in myasthenia gravis.

An increased frequency of antibodies to native DNA, thymocytes, and striated muscle was found in patients with myasthenia gravis (MG). The prevalence of such antibodies lends considerable support to the concept of MG as an autoimmune disorder and militates in favor of major abnormalities in the thymic dependent immune system. There was no correlation between serum-blocking activity to acetylcholine receptor protein and antibodies to thymocytes.

Acetylcholine↗