Search PubMed⌕ Search

Biomedical subjects

Z Argov

Publications and source records attributed to Z Argov.

At least 55 records · Page 3Linked to original sources
PubMed1996

Hereditary inclusion body myopathy maps to chromosome 9p1-q1.

Hereditary inclusion body myopathy (HIBM) is a unique disorder of unknown etiology that typically occurs in individuals of Persian Jewish descent. Distinguishing features of the disorder from other limb girdle myopathies include elderly age of onset, ethnic predisposition, and sparing of the quadriceps despite severe involvement of all other proximal leg muscles. Involved muscles demonstrate fibers with rimmed vacuoles and filamentous cytoplasmic and nuclear inclusions. Additional histological features are accumulations of beta-amyloid protein and the absence of inflammatory cells. To identify the chromosomal location of the gene responsible for HIBM, nine Persian Jewish families with HIBM were evaluated. Genomewide linkage analyses identified the recessive IBM locus on chromosome 9 band p1-q1 (maximum lod score at D9S166 = 5.32, theta = 0.0). This region contains the Friedreich's Ataxia gene, raising the possibility that HIBM may be a related neurogenic disorder.

Adult↗
PubMed1996

Inclusion body myositis: atypical clinical presentations.

Inclusion body myositis affects primarily the proximal muscles but distal limb muscles are involved too in this chronic myopathy. Characteristic histopathologic findings include "rimmed vacuoles', inflammation and typical cytoplasmic and nuclear filamentous inclusions. The patients are usually unresponsive to steroids. We present four inclusion body myositis patients with atypical clinical presentations: one with scapuloperoneal syndrome, one with post-polio-like syndrome and two with associated immune-mediated diseases (one with undefined autoimmune disorder and the second with scleroderma). Two patients responded to high-dose steroid therapy. We suggest that the clinical spectrum of inclusion body myositis is wider than previously appreciated.

Adult↗
PubMed1995

Lambert-Eaton myasthenic syndrome (LEMS) in association with lymphoproliferative disorders.

LEMS is a presynaptic neuromuscular junction disorder typically associated with small cell lung carcinoma. The characteristic electrophysiological abnormality is a low amplitude compound muscle action potential that shows a marked increment after short maximal contraction or brief tetanic nerve stimulation. Here we describe 3 patients who had LEMS in association with lymphoproliferative disorder. The first patient had Castleman's syndrome with typical clinical and electrophysiological features of LEMS, which responded partially to treatment with 3-4-diaminopyridine. The second patient was a 7-year-old boy who had an unusual acute onset of LEMS associated with relapse of his Burkitt's leukemia. The third patient was a 60-year-old woman with non-Hodgkin's lymphoma. These 3 patients (together with 6 additional patients identified in the literature) lead us to suggest that lymphoproliferative diseases are another, hitherto unrecognized, type of malignancy associated with LEMS. Thus, any patient with these malignancies and unexplained muscle weakness should have electrophysiological evaluation for LEMS.

Action Potentials↗
PubMed1995

Various classes of mutations in patients with phosphofructokinase deficiency (Tarui's disease).

Muscle phosphofructokinase (PFK-M) deficiency (glycogenosis type VII, Tarui's disease) is characterized by intolerance to vigorous exercise, often accompanied by myoglobinuria. The disease is inherited as an autosomal recessive trait. The clinical manifestations are similar to those in myophosphorylase deficiency (McArdle's disease), and the diagnosis required demonstration of the enzyme defect in muscle biopsy. In the Western hemisphere PFK deficiency appears to be prevalent among people of Ashkenazi Jewish descent. To define the molecular basis of this myopathy, we have studied 11 Ashkenazi and 2 non-Ashkenazi families with the disease. Ashkenazi patients share two common pathogenic mutations, a splicing defect and a nucleotide deletion, which account for approximately 95% of mutant alleles. The molecular diagnosis is now possible in this population by using simple PCR-based tests to screen for these mutations.

Adult↗
PubMed1995

Hereditary leukoencephalopathy and palmoplantar keratoderma: a new disorder with increased skin collagen content.

We report a new neurocutaneous syndrome of apparent autosomal recessive inheritance consisting of early-childhood-onset palmoplantar keratoderma followed in adulthood by progressive tetrapyramidal syndrome and cognitive impairment. Of the four affected siblings, two were available for evaluation. Investigation disclosed cerebral white-matter involvement on MRI and arylsulfatase A pseudodeficiency carrier state, which was also identified in clinically unaffected family members. Since skin biopsies showed dermal connective tissue abnormalities, we studied collagens I, III, and VI biosynthesis. Northern blotting of RNA extracted from cultured skin fibroblasts revealed an increased steady-state messenger RNA (mRNA) level of alpha 1(VI) collagen, whereas no differences were detected for pro alpha 1(I), pro alpha 1(III), and tropoelastin mRNAs. The skin content of collagen and total protein was higher in the patients than in controls. We suggest that an extracellular matrix abnormality may be involved in the pathogenesis of this disorder.

Adult↗
PubMed1994

Variable effect of calcium channel blockers on the decremental response in experimental autoimmune myasthenia gravis.

We tested the effect of intravenous administration of verapamil and nimodipine on the decremental response in rabbits with experimental autoimmune myasthenia. Nimodipine produced an immediate augmentation of the decremental response to 3-Hz nerve stimulation, which lasted about 30 min. In contrast, verapamil caused marked amelioration of the decrement beginning 30 min after injection. Our findings are consistent with previous reports suggesting that verapamil has a presynaptic effect of enhanced acetylcholine release at the neuromuscular junction. Since evaluation of a drug effect in vivo in animals with experimental autoimmune myasthenia gravis may be more pertinent to its effect on patients with myasthenia gravis (MG), verapamil might prove to be safer in MG than nimodipine. However, due to the additional effects of calcium channel blockers, the safety of their use in myasthenia gravis cannot be inferred from the experimental results.

Action Potentials↗
PubMed1994

Fine specificity of T cell lines and clones that are capable of inducing autoimmune manifestations in mice.

Myasthenia gravis is a T-cell-regulated, antibody-mediated autoimmune disease. The synthetic peptides p195-212 and p259-271, which represent sequences of the human acetylcholine receptor alpha-subunit, preferentially stimulated T cells of patients with myasthenia gravis and were found to be immunodominant T cell epitopes in SJL and BALB/c mice, respectively. Therefore, we established a p195-212-specific T cell line from SJL mice and a p259-271-specific T cell line from BALB/c mice. N- and C-terminal truncated and/or extended peptides differed in their ability to stimulate proliferative responses of the lines and of their derived clones. Activated cells of the lines were inoculated into naive syngeneic mice. In both strains of mice, peptide-specific antibodies and antibodies to the murine acetylcholine receptor were detected. In addition, decremental compound muscle action potentials consistent with impairment of neuromuscular transmission were recorded from the line-inoculated mice. Thus, these T cell lines, clones, and epitopes constitute a useful model for investigating T cell pathogenicity in autoimmune manifestations related to myasthenia gravis.

Action Potentials↗
PubMed1994

Antibiotic induced meningitis.

Three patients with antibiotic induced meningitis, one following penicillin with seven episodes, are reported on--the first well documented description of penicillin induced meningitis. In this patient episodes of headache and nuchal rigidity appeared with and without CSF pleocytosis. Two patients had a total of five episodes of antibiotic induced meningitis after trimethoprim-sulphamethoxazole (co-trimoxazole) administration. The features common to all three patients were myalgia, confusion and low CSF glucose. CSF analysis was not a reliable method to differentiate antibiotic induced meningitis from partially treated bacterial meningitis.

Adolescent↗
PubMed1994

Late-onset muscular weakness in phosphofructokinase deficiency due to exon 5/intron 5 junction point mutation: a unique disorder or the natural course of this glycolytic disorder?

Late-onset muscle weakness is rare in glycolytic disorders. There are two reports in the literature of phosphofructokinase (PFK)-deficient Ashkenazi Jews with severe vacuolar myopathy manifesting in late adulthood. The genetic abnormality in these patients is unknown. We report a third patient with a similar syndrome: early-onset exercise intolerance in young childhood and progressive weakness in a limb-girdle distribution appearing at 57 years of age, leading to severe incapacity. Muscle histology showed diffuse vacuolar changes, and muscle fibers contained excess glycogen-like material. Muscle biochemistry was diagnostic for PFK deficiency. DNA analysis from the patient and his family showed that he was homozygous for a recently identified point mutation at the exon 5/intron 5 junction (a G-to-A change); two other family members were heterozygous for this mutation. It is not clear whether late-onset weakness is the natural course for all PFK-deficient patients or whether the exon 5 mutation carries increased risk for this severe myopathy.

Base Sequence↗
PubMed1994

Transient neurological events during dipyridamole stress test: an arterial steal phenomenon?

Dipyridamole-associated adverse neurological side effects have not been extensively described. We present two cases of dipyridamole-associated transient motor neurological events with no evidence of residual neurological deficits detected clinically or by head CT. The patients showed no evidence of significant extracranial (internal carotid) artery disease. We propose the presence of a regional cerebral perfusion disturbance due to an intracranial vascular steal phenomenon as the mechanism for the above side effects of dipyridamole.

Aged↗
PubMed1994

Common mutations in the phosphofructokinase-M gene in Ashkenazi Jewish patients with glycogenesis VII--and their population frequency.

Phosphofructokinase (PFK) catalyzes the rate-limiting step of glycolysis. Deficiency of the muscle enzyme is manifested by exercise intolerance and a compensated hemolytic anemia. Case reports of this autosomal recessive disease suggest a predominance in Ashkenazi Jews in the United States. We have explored the genetic basis for this illness in nine affected families and surveyed the normal Ashkenazi population for the mutations we have found. Genomic DNA was amplified using PCR, and denaturing gradient-gel electrophoresis was used to localize exons with possible mutations. The polymorphic exons were sequenced or digested with restriction enzymes. A previously described splicing mutation, delta 5, accounted for 11 (61%) of 18 abnormal alleles in the nine families. A single base deletion leading to a frameshift mutation in exon 22 (delta C-22) was found in six of seven alleles. A third mutation, resulting in a nonconservative amino acid substitution in exon 4, accounted for the remaining allele. Thus, three mutations could account for all illness in this group, and two mutations could account for 17 of 18 alleles. In screening 250 normal Ashkenazi individuals for all three mutations, we found only one delta 5 allele. Clinical data revealed no correlation between the particular mutations and symptoms, but male patients were more symptomatic than females, and only males had frank hemolysis and hyperuricemia. Because PFK deficiency in Ashkenazi Jews is caused by a limited number of mutations, screening genomic DNA from peripheral blood for the described mutations in this population should enable rapid diagnosis without muscle biopsy.

Adult↗
PubMed1992

Multifocal motor nerve conduction abnormalities in amyotrophic lateral sclerosis.

Motor nerve conduction in motor neuron disease is considered normal until the terminal stages of the disease, a notable exception being lower motor neuron syndrome associated with anti-glycolipid antibodies. We reviewed the electrophysiological findings in all our patients who were diagnosed as having amyotrophic lateral sclerosis (ALS) during the last 6 years. Six patients, clinically indistinguishable from "classical" ALS patients, out of 31 (19%) displayed motor nerve conduction abnormalities. The most consistent finding, occurring in all 6, was prolonged distal latency or reduced conduction velocity in the distal segment of the median nerve, with normal sensory conduction, suggesting possible pressure proneness of motor nerve fibers in ALS. Additional abnormalities included multifocal motor conduction slowing (3 patients), and conduction blocks (4 patients). None of the patients had paraproteinemia and anti-GM1 and anti-GD1a antibodies were not detected. Thus, a subgroup of clinically indistinguishable ALS patients may have multifocal motor nerve conduction abnormalities, indicating motor nerve fiber involvement. The etiology and pathogenesis of the peripheral nerve involvement are presently unknown.

Adult↗
PubMed1992

Substrate regulation of mitochondrial oxidative phosphorylation in hypercapnic rabbit muscle.

Endurance muscle performance is highly dependent on ATP production from mitochondrial oxidative phosphorylation. To study the role of the mitochondrial oxidative enzymes in muscle fatigue, we analyzed the relationship between the concentrations of substrates associated with ATP synthesis and the muscle performance of electrically stimulated rabbit muscle under CO2-induced acidosis. Two different conditions of pacing-induced muscle performance were produced in the gastrocnemius and soleus muscle groups in anesthetized rabbits by stimulating the sciatic nerve submaximally at two frequencies. Phosphorus nuclear magnetic resonance was used to measure ATP, phosphocreatine, and Pi and to provide data for a calculation of intracellular pH and free ADP. To induce acidosis, the animal was ventilated with 20% CO2. The administration of CO2 effectively reduced the intracellular pH from 6.9 to 6.7 and reduced the isometric tension-time integral (TTI) to below half the value measured in normocapnia at the low pacing frequency. A twofold increase in the pacing frequency resulted in a doubling of the TTI in normocapnia and a tripling of TTI in hypercapnia. The increases in TTI corresponded with increases in free ADP and Pi concentrations. Under the various conditions, all free ADP values were near the in vitro Michaelis-Menten constant (Km) of ADP. The Michaelis-Menten relationship of the oxidative phosphorylative enzymes was applied to the change in substrate concentrations with respect to TTI. From this relationship we observed that the in vivo Km of free ADP was 26 microM, which is close to the in nitro Km, and that Km and maximal reaction velocity did not change under hypercapnia and increased pacing frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis↗
PubMed1991

Phosphorus magnetic resonance spectroscopy (31P MRS) in neuromuscular disorders.

Phosphorus magnetic resonance spectroscopy monitors muscle energy metabolism by recording the ratio of phosphocreatine to inorganic phosphate at rest, during exercise, and during recovery from exercise. In mitochondrial diseases, abnormalities may appear during some or all these phases. Low phosphocreatine-inorganic phosphate ratios at rest are not disease-specific, but can be increased by drug therapy in several myopathies. Phosphorus magnetic resonance spectroscopy can also record intracellular pH and thus identify disorders of glycogen metabolism in which the production of lactic acid is blocked during ischemic exercise. The measurements of accumulated sugar phosphate intermediates further delineate glycolytic muscle defects. Myophosphorylase deficiency responds to intravenous glucose administration with improved exercise bioenergetics, but no such response is seen in phosphofructokinase deficiency. The muscular dystrophies show no specific bioenergetic abnormality; however, elevation of phospholipids metabolites and phosphodiesters was detected in some cases. While phosphorus magnetic resonance spectroscopy remains primarily a research tool in metabolic myopathies, it will be clinically useful in identifying new therapies and monitoring their effects in a variety of neuromuscular disorders.

Energy Metabolism↗
PubMed1991

Hereditary branching enzyme dysfunction in adult polyglucosan body disease: a possible metabolic cause in two patients.

We describe 2 unrelated patients with adult polyglucosan body disease (APBD) diagnosed by sural nerve biopsy. Both patients were offspring of consanguineous marriages. They presented clinically with late onset pyramidal tetraparesis, micturition difficulties, peripheral neuropathy, and mild cognitive impairment. Magnetic resonance imaging of the brain revealed extensive white matter abnormalities in both. In search of a possible metabolic defect, we evaluated glycogen metabolism in these patients and their clinically unaffected children. Branching enzyme activity in the patients' polymorphonuclear leukocytes was about 15% of control values, whereas their children displayed values of 50 to 60%, suggesting a possible autosomal recessive mode of transmission. This is the first report of an inherited metabolic defect in patients with adult polyglucosan body disease. We suggest that branching enzyme dysfunction may be implicated in the pathogenesis of some patients with adult polyglucosan body disease.

1,4-alpha-Glucan Branching Enzyme↗
PubMed1991

Canine X-linked muscular dystrophy studied with in vivo phosphorus magnetic resonance spectroscopy.

Duchenne muscular dystrophy (DMD) is an X-linked disease characterized by progressive muscle weakness and degeneration. Dystrophin is the product of the missing gene in this disorder. However, the cause of the dystrophic process is not understood. Transient muscle injury is normally seen after muscle exercise, and may be a necessary process in muscle growth and preservation. We, therefore, chose to evaluate the role of exercise in Duchenne dystrophy by studying the canine X-linked animal model (CXMD). These dogs also lack dystrophin and have clinical signs similar to humans. Exercise was initiated by electrical stimulation, and muscle metabolism was monitored with phosphorus magnetic resonance spectroscopy (P-MRS). Dogs with CXMD had abnormal muscle pathology and markedly elevated serum CK. The inorganic phosphate (Pi) to phosphocreatine (PCr) ratio was increased in CXMD dogs at rest compared with normal dogs (Pi/(Pi + PCr) = 0.166 +/- 0.054 for CXMD and 0.073 +/- 0.017 for normals, mean +/- SE). No changes in resting ATP, pH, phosphomonoesters (PME), and phosphodiesters (PDE) were seen. The mean Pi/(Pi + PCr) and pH values during stimulation were normal in the CXMD dogs. Two to three days after electrical stimulation, resting Pi/(Pi + PCr) ratios were significantly increased in the CXMD dogs (0.127 +/- 0.029 compared with 0.172 +/- 0.054, mean +/- SD). Normal dogs showed no increase in Pi/(Pi + PCr) following stimulation. There was a 50-fold greater increase in serum CK in CXMD compared with normal dogs following exercise. These results indicate greater muscle injury in CXMD muscle, and suggest that in the absence of dystrophin, exercise-induced muscle injury may play a role in the dystrophic process.

Adenosine Triphosphate↗
PubMed1991

Apparent absence of glycogen branching enzyme activity in phosphofructokinase deficiency.

A 30-year-old woman with clinical features and biochemical findings of muscle phosphofructokinase deficiency was found to have a very low level of alpha-1,4-glucan:alpha-1,4-glucan-6-transglucosylase (branching enzyme, EC 2.4.1.18) activity in muscle. In contrast, branching enzyme activity in the leukocytes was in the range of control values. After sedimentation of the glycogen from muscle homogenates by centrifugation at 105,000 g, branching enzyme activity in muscle of the patient was similar to that of control subjects. This patient illustrates the possibility of falsely diagnosing branching enzyme deficiency when muscle glycogen content is elevated. It is likely that such an artefact may also cause a false positive diagnosis of branching enzyme deficiency in other metabolic diseases associated with glycogen accumulation.

1,4-alpha-Glucan Branching Enzyme↗