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V Askanas

Publications and source records attributed to V Askanas.

At least 109 records · Page 6Linked to original sources
PubMed1985

Autosomal dominant syndrome of lipid neuromyopathy with normal carnitine: successful treatment with long-chain fatty-acid-free diet.

A family (mother and two sons) have had lifelong muscle weakness and intolerance to fatty food. Histochemistry of muscle biopsies of all three patients demonstrated increased lipids in type I muscle fibers and type II muscle fiber atrophy and paucity. Electronmicroscopy of muscle revealed increased lipids, abnormal mitochondria, and increased lipofuscin granules. Electronmicroscopy of sural nerve showed inclusions in most of the Schwann cell cytoplasm, with lipid droplets, zebra bodies, lipofuscin granules, and abnormal mitochondria. Carnitine and CPT I and II levels were normal in serum and muscle. Treatment with long-chain fatty-acid-free diet resulted in remarkable clinical improvement and in decrease of lipid droplets in the muscle. This dietary program may be useful in other forms of lipid myopathy.

Adolescent↗
PubMed1984

Abnormality of cultured muscle and Schwann's cells in familial lipid neuromyopathy. Muscle corrected by neural influence.

Muscle and Schwann's cell cultures were established from a family (mother and two sons) with non-carnitine deficient neuromyopathy. Electron microscopy of noninnervated cultured muscle showed poorly matured muscle fibers containing large "mushy" mitochondria, lipid droplets, abundant multilaminated inclusions, and dense-core dark osmiophilic bodies. Parallel innervated muscle fibers (cocultured with normal-rat motor neurons for two to three weeks) were well cross-striated, had well-developed T tubules and sarcoplasmic reticulum, and none of the abnormalities of aneural muscle cultures. Cultured Schwann's cells were normal by light microscopy, but had ultrastructurally abnormal mitochondria, lipid droplets, dark osmiophilic granular inclusions, and numerous "foamy" vacuoles. Those studies demonstrated (1) intrinsic muscle and Schwann's cell defects because of reproduction of abnormalities in culture, (2) normal muscle cell responsiveness to innervation reflected by development of contractions and longer survival in culture, and (3) beneficial influence of a neural factor(s) on the endogenous muscle cell abnormality.

Adolescent↗
PubMed1984

Adult-onset acid maltase deficiency. Electrophysiological properties of aneurally cultured muscle.

Electrophysiological studies were performed on aneurally cultured muscle cells from one patient with adult-onset acid maltase deficiency (AAMD) and from controls. The cells from the patient with AAMD had a higher mean resting membrane potential, a lower input resistance, and a higher incidence of action potentials at resting membrane potential than the control cells. Therefore, sarcolemma maturation was not adversely affected. The AAMD cells had membrane thresholds and action potential amplitudes similar to those of the control cells, and rarely produced repetitive action potentials. Therefore, the membrane instability noted in adult muscle fibers from the patient with AAMD was not present in cultured cells. This study does not support the suggestion that the biochemical and morphological abnormalities present in muscle fibers of patients with AAMD are sufficient to cause the electrical abnormalities.

Action Potentials↗
PubMed1984

Thyrotropin-releasing hormone enhances choline acetyltransferase and creatine kinase in cultured spinal ventral horn neurons.

The effect of 0.1 mM thyrotropin-releasing hormone (TRH) on ventral horn neurons was investigated in eight experimental sets of tissue cultures established from ventral and dorsal portions of spinal cords of 13-15-day rat embryos. Cultures were treated with TRH from day 1 for 2-5 weeks. TRH-treated ventral spinal cord cultures (VSCC), compared with control VSCC, had more numerous and more healthy-appearing neurons and thicker bundles of long cell processes. In TRH-treated VSCC, choline acetyltransferase (ChAT) activity was greater than 16 times (p less than 0.005) and creatine kinase greater than 3 times (p less than 0.005) that of control VSCC. Morphologic and biochemical parameters of dorsal spinal cord cultures remained unchanged by TRH treatment. Since lower motor neurons are numerous in the ventral spinal cord (and not present in the dorsal cord) and since lower motor neurons are the major ChAT-containing spinal cord cells, our data demonstrating a beneficial effect of TRH on VSCC suggest a tropic effect of TRH on lower motor neurons.

Animals↗
PubMed1984

Nature of amyloid deposits in hypernephroma. Immunocytochemical studies in 2 cases associated with amyloid polyneuropathy.

Two patients who presented with amyloid polyneuropathy were found to have an amyloid-positive hypernephroma. The amyloid extracted from the tumor of one patient was purified by gel filtration and found to immunoreact by immunodiffusion, only with antiserum against denatured lambda-type amyloid protein but not with antisera against denatured kappa amyloid, AA, or prealbumin. With the unlabeled immunoperoxidase method or immunofluorescence in combination with these specific antisera, it was shown that in both patients the amyloid deposits in the tumor, kidney, lymph node, muscle, and nerve had lambda-type amyloid antigenic fibril determinants. Some regions, amyloid-negative by congo red, immunoreacted with anti-lambda antiserum and were shown to represent amyloid fibrils electron microscopically. Several plasma cells found in the tumor and lymph node immunoreacted specifically with the anti-amyloid lambda antiserum. The findings provide the first observation that the amyloid in hypernephroma can be of immunocytic origin, even in the absence of overt signs of plasma cell dyscrasia, and suggest that amyloid polyneuropathy could be the presenting sign of hypernephroma.

Adenocarcinoma↗
PubMed1983

Electrophysiologic properties of aneurally cultured muscle from patients with myotonic muscular atrophy.

Electrophysiologic studies were performed on aneurally cultured human muscle cells from seven patients with myotonic muscular atrophy and seven controls. There was no significant difference in resting membrane potential. When the cells were hyperpolarized to -80 mV, there was no significant difference in effective membrane resistance, effective membrane capacitance, normalized membrane conductance, membrane threshold, action potential amplitude, or maximum rate of rise of the action potential. Repetitive discharges were elicited by anodal-break excitation in a few cells from each group. We found no evidence that cultured myotonic atrophy muscle cells are electrically different from control cells.

Action Potentials↗
PubMed1983

Muscle carnitine deficiency: fatty acid metabolism in cultured fibroblasts and muscle cells.

L-carnitine, as little as 25nM, greatly increased oxidation of palmitate by carnitine-depleted cultured human skin fibroblasts from normal subjects, and from two patients with muscle carnitine deficiency. Carnitine stimulated oxidation of labeled palmitate by cultured muscle cells from rat, normal humans, or patients with muscle carnitine deficiency. Carnitine reduced incorporation of palmitate into glycerides in normal fibroblasts, and it may thereby counteract cellular accumulation of glycerides in cells. Fibroblasts from patients with muscle carnitine deficiency took up labeled carnitine at a normal rate. Dexamethasone increased palmitate oxidation by normal human fibroblasts and muscle cells of rat, and normal and muscle carnitine-deficient humans. The results parallel the reported effectiveness of carnitine, glucocorticoids, or medium-chain triglycerides in treatment of these patients.

Adolescent↗
PubMed1982

Biochemical and morphological effects of 20,25-diazacholesterol on cultured muscle cells.

Effects of 20,25-diazacholesterol (DAC), a myotonia-inducing drug, were evaluated on certain biochemical and morphological properties of embryonic rat muscle cells grown in tissue culture. During DAC treatment, muscle fibers exhibited spontaneous contractions that changed from coarse twitches to finer fibrillation movements, The ultrastructural alterations produced by DAC were smeared Z-lines, disorganized myofibrils, occasional honeycomb appearance of membranes and large vacuoles connected to zipper-like structures. Biochemically, a microsomal fraction prepared from DAC-treated cells (compared to that of normal cells) showed a 30-45 per cent decrease in the isoproterenol-enhanced and the NaF-enhanced adenylate cyclase activity. however, the beta-adrenergic receptors, through which isoproterenol activates the enzyme, showed no change in density or affinity as judged by the binding of [125I]iodohydroxybenzylpindolol. That indicated that DAC treatment caused an uncoupling of beta-receptor-adenylate cyclase interaction. Guanylate cyclase and cyclic GMP-phosphodiesterase were both markedly increased in DAC-treated cells, indicating a greater turnover of cyclic GMP. Binding of [3H]concanavalin A to DAC-treated muscle membranes was decreased 20-40 per cent. The data indicate that DAC exert a direct influence on muscle fibers, affecting their functional, biochemical and morphological properties.

Animals↗
PubMed1982

Myosin isoenzymes in cultured human muscle.

Cultured human muscle grown aneurally and innervated by the ventral part of fetal rat spinal cord was examined using antimyosin antibodies specific for isomyosins from fast and slow mammalian skeletal muscle. Cultured muscle displayed multiple reactivity with antibodies against both types of myosins, with no evident compartmentalization of different forms of myosin into different muscle cells, such as seen in adult muscle. Innervation of cultured muscle resulted in better growth and longer survival of cultured muscle and its more advanced maturation, with a larger number of cross-striated muscle fibers. The pattern of immunofluorescence reaction, however, was the same in both innervated and noninnervated cultured muscle.

Antibodies↗
PubMed1982

Demonstration of 2',3'-cyclic nucleotide 3'-phosphohydrolase in cultured human Schwann cells.

Schwann cell cultures were established from adult human sural nerve biopsies. 2'3'-Cyclic nucleotide 3'-phosphohydrolase (CNPase) activity was estimated in the homogenates of those cells by a sensitive isotope assay using [3H]2',3'-cyclic AMP as substrate. A high level of CNPase activity was observed in cultured Schwann cells, whereas cultured human muscle and skin fibroblasts contained negligible levels of CNPase activity. CNPase of human Schwann cells followed typical enzyme-substrate kinetics, with an apparent Km of 1.6 mM for 2',3'-cyclic AMP, and the enzyme was stimulated by detergents such as Triton X-100 and deoxycholate. It was inhibited by p-chloromercuricbenzoate and 2'-AMP. These properties are typical of CNPase isolated from adult brain and spinal cord. CNPase can serve as a new biochemical marker of normal cultured human Schwann cells and can be useful in analyzing the properties of cultured Schwann cells from patients with dysschwannian neuropathies.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1982

Single cholinergic receptor channel currents in cultured human muscle.

Single cholinergic channel currents were recorded in adult human muscle tissue culture. The agonists suberyldicholine and carbamylcholine produce channels with the same conductance as channels produced by acetylcholine but with different closing kinetics. The antagonist tubocurarine, alone or mixed with suberyldicholine, activates channels which close very rapidly. For agonist-activated channels, the distribution of open state lifetimes shows deviations from the usual single exponential form. An excess of short duration openings indicates the presence of an additional faster kinetic process. The lifetime distribution data can be interpreted in terms of varying proportions of slow and fast components which are present in a ratio determined by curve-fitting the appropriate two-exponential function to observed open time distributions. This ratio shows great variability in muscle from older cultures, but the fast and slow time constants are relatively constant. The observation of double exponential open time distributions indicates that the mechanism of channel closing is more complicated than earlier evidence indicated.

Acetylcholine↗
PubMed1981

Lysosomal abnormalities in cultured schwann cells from a patient with peripheral neuropathy and continuous muscle fiber activity.

Schwann cell cultures were established from a sural nerve containing large membrane-bound vacuoles in its Schwann cells, obtained from a patient with neuropathy and continuous muscle fiber activity. Cultured Schwann cells contained many large membrane-bound vacuoles, presumably lysosomes, resembling those present in the biopsied nerve. The acid phosphatase reaction was excessive in the patient's cultured Schwann cells but practically negative in normal cultured Schwann cells. This study indicates that the patient's neuropathy is primary dysschwannian with abnormal lysosomes as a major abnormality.

Acid Phosphatase↗
PubMed1981

Ultrastructural and cytochemical characteristics of cultured rat Schwann cells.

Schwann cell cultures were established from sciatic nerve of 3 day-old rats. Described are the ultrastructural, histochemical and ultracytochemical properties of amyelic cultured rat Schwann cells. Ultrastructural characteristics of the cultured Schwann cells are compared to the Schwann cells of 3 day-old and adult rat sciatic nerve. These findings serve as a basis for comparison when studying experimentally induced alterations in the cultured Schwann cells as well as changes due to myelination in vitro.

Animals↗
PubMed1981

Immunocytochemical localization of thymosin-alpha 1 in thymic epithelial cells of normal and myasthenia gravis patients and in thymic cultures.

Thymosin alpha 1 (alpha 1) is a potent thymic polypeptide hormone. With antibodies against synthetic thymosin alpha 1, indirect immunofluorescence was applied to human normal thymus and to hyperplastic, thymomatous or "involuted" thymus of myasthenia gravis (MG) patients. Alpha 1 was localized only in the epithelial cells, lying singly, grouped, in Hassall's corpuscles or proliferated in thymomas. In contrast to normal thymus, which had fewer and more weakly stained cells, MG hyperplastic thymus had many strongly positive epithelial cells: this was markedly evident in thymomas. "Involuted" MG thymus had a few but brightly stained cells lying within the fatty tissue. In tissue cultures of human thymus, anti-alpha 1 stained the epithelial cells, but not fibroblasts. These findings: (a) demonstrate the origin of the thymic hormone alpha 1 to be the thymic epithelial cell; (b) raise the possibility that excess alpha 1 may act pathologically to facilitate and perpetuate the dysimmune mechanism in MG; (c) may partially explain the beneficial effect of thymectomy in MG patients of any age; and (d) suggest that epithelial cells may be autonomous for the production of alpha 1 as evidenced by their positivity in tissue culture.

Adolescent↗
PubMed1981

Systemic manifestations of gyrate atrophy of the choroid and retina.

In ten patients with gyrate atrophy (GA) and hyperornithinemia, the head hair was fine, straight, and sparse. On microscopic examination, both scalp and pubic hair contained intermittent dark cores within the medullary zone, which was not a deposit, but appeared to be due to the unusual refractive properties of loosely formed macrofilaments amidst wide spaces containing a structureless electron lucent but compact substance, which was insoluble in both water and solvents. Seven of the ten patients had abnormal wave forms on electroencephalography. Three of the five patients who underwent muscle biopsy had tubular aggregates. Of particular interest was the toxicity of exogenous ornithine added to muscle cell culture from GA patients as compared with the lack of toxicity in muscle from control patients. What specific role the hyperornithinemia and absence of OAT is playing in the histopathology of hair and muscle and the EEG changes awaits further biochemical investigation.

Adolescent↗
PubMed1981

Identification of human thymic epithelial cells with antibodies to thymosin alpha 1 in myasthenia gravis.

Thymosin-alpha 1 (alpha 1) is a potent thymic polypeptide hormone. Using anti-alpha 1 antibodies, we applied indirect immunofluorescence to human normal thymus of different ages and to hyperplastic, thymomatous, and "involuted" thymus of myasthenia gravis (MG) patients. Alpha 1 was localized only in the epithelial cells, lying singly, grouped, in Hassell's corpuscles, and proliferated in thymomas. Whereas normal thymuses and fewer and weakly stained cells, MG thymuses had many strongly positive epithelial cells; this was more evident in thymomas. Germinal centers were unstained. "Involuted" MG thymuses had small islands of brightly stained cells lying among the fatty tissue. In cultured thymuses from three MG patients, epithelial cells but not fibroblasts were brightly stained for alpha 1. Our findings (a) demonstrate the location, and presumably the origin, of alpha 1 to be the thymic epithelial cell; (b) suggest the possibility that excess alpha 1, because of its known effect on T-lymphocyte maturation and transformation of precursors to helper T-cells, may act pathologically to facilitate and perpetuate the dysimmune mechanism in MG; (c) may partially explain the beneficial effect of thymectomy in MG patients of any age; and (d) indicate that epithelial cells may be autonomous for the production of alpha 1 as evidenced by their alpha 1 positivity in culture.

Adolescent↗