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V Ionasescu

Publications and source records attributed to V Ionasescu.

At least 55 records · Page 3Linked to original sources
PubMed1982

Twenty years-Iowa muscle clinic: reminiscences and prospects.

The activities of the last twenty years of the Iowa clinic for neuromuscular diseases are briefly reviewed. Main emphasis in this paper is on management and guidance of the patient with Duchenne muscular dystrophy (DMD) by the families, the school and the public at large. Guidance and treatment given to our patients is briefly described. It is well known that chronic debilitating disease affects not only the patient but the whole family; management of DMD should therefore include the parents and siblings of the patient. Preventability of DMD is illustrated by the experiences in our clinic. The importance of early carrier detection and genetic counseling is stressed. Possible future developments in DMD research are briefly mentioned.

Family↗
PubMed1982

Increased collagen synthesis by Duchenne myogenic clones.

Myogenic cell clones were grown in triplicates from 3 patients with Duchenne muscular dystrophy, 5 with late onset myotonic dystrophy, 2 with spinal muscular atrophy, 6 male children controls, 4 adult controls and 6 normal aborted fetuses (10-12 weeks old). The clones from patients with myotonic dystrophy and spinal muscular atrophy had normal collagen synthesis. The fetal clones showed 3.3-fold lower values than control clones for [3H] extracellular (medium) hydroxyproline, while intracellular [3H] hydroxyproline levels showed normal values. Analysis of [3H] proline incorporation demonstrated a 4-fold increase in [3H] hydroxyproline released into the medium of Duchenne myogenic cell clones while intracellular [3H] hydroxyproline levels showed normal values. The collagen turnover of Duchenne clones was normal. These results strongly suggest that the increased amount of collagen present in Duchenne dystrophic muscle is related to the primary defect of the disease and is not due to secondary replacement fibrosis.

Adult↗
PubMed1982

Gastrointestinal manifestations of the muscular dystrophies.

Skeletal and cardiac muscle involvement is a recognized feature of the muscular dystrophies. Visceral smooth muscle involvement of the gastrointestinal tract is not as well appreciated. Gastrointestinal symptoms may herald the onset of a muscular disorder and may be the predominant feature of the disorder. In some instances, smooth muscle dysfunction may be the only clinical manifestation of the disease. The gastrointestinal manifestations of the various muscular dystrophies are reviewed. Clinical, radiographic, and histologic features are discussed. Further study of the histopathology and pathophysiology of visceral smooth muscle involvement in the muscular dystrophies will have a substantial impact on treatment that, to a large extent, remains empiric.

Adolescent↗
PubMed1981

Alterations in creatine kinase in fresh muscle and cell cultures in Duchenne dystrophy.

Creatine kinase (CK) (total and isoenzymes) was measured in cultures obtained by dissociation and subsequent plating of cells from biopsied quadriceps muscle of 10 patients with Duchenne muscular dystrophy (DMD) and 20 controls. The total cellular CK and CK-MM reached highest values around 21 days in both DMD and control cultures, suggesting that DMD cultures do not show delayed myoblast fusion. There was a significant decrease of total cellular CK in DMD cultures at all stages, but the maximum differences were noted for the peak values. The CK isoenzyme pattern in DMD cultures demonstrated a higher percentage of CK-BB and CK-MB and a lower percentage of CK-MM than was observed in cultures from the controls. Addition of cytosine arabinoside after myoblast fusion to muscle cell cultures did not induce significant changes of CK isoenzyme pattern. There was no difference in the CK levels in culture medium from controls and DMD patients. The alterations of cellular CK were similar in fresh muscle and cell cultures from DMD patients.

Cells, Cultured↗
PubMed1981

Alterations in lipid incorporation in Duchenne muscular dystrophy. Studies of fresh and cultured muscle.

The incorporation of [3H] glycerol into lipids of fresh and cultured skeletal muscle obtained from patients with Duchenne muscular dystrophy (DMD), patients with myotonic dystrophy (My Dyst), controls, and aborted fetuses (10-12 weeks old) was studied. A significant increase of specific incorporation of [3H] glycerol into phosphatidylcholine (PCh), phosphatidylserine (PS), phosphatidylinositol (PI), and triglycerides (TRI) was found in DMD and fetal muscle in both fresh and cultured muscle. No significant differences, however, were noted between the values of glycerol incorporation in DMD and fetal muscle. The ratio between phospholipids and TRI changed significantly for fresh muscle in DMD (3.5) and fetal muscle (4.9) versus controls (24). The incorporation of glycerol into these lipids in My Dyst fresh and cultured muscle showed the same value as controls when expressed both as incorporation/mg protein and ratio between phospholipids and TRI.

Adolescent↗
PubMed1981

Schwartz-Jampel syndrome: a case report. Stimulatory effect of calcium and A23187 calcium ionophore for protein synthesis in muscle cell cultures.

This report describes a 3-year-old male patient with dwarfism, generalized muscular hypertrophy, stiffness, myotonia, multiple skeletal deformities and normal intelligence. Serum creatine kinase was twice elevated. EMG showed 'dive bomber' discharges and muscle biopsy revealed mild to moderate myopathic changes with variability in fiber size and 'moth-eaten' fibers. Multiple muscle cell cultures showed significantly lower values of total protein synthesis as determined by (3H)-leucine incorporation. The addition of calcium and/or A23187 calcium ionophore to cultures significantly stimulated total protein synthesis in contrast to the lack of effect of these drugs in control cultures. These findings suggest a dysfunction of muscle sarcolemma in Schwartz-Jampel syndrome.

Abnormalities, Multiple↗
PubMed1981

Muscle ribosome detachment factor. Does it have a role in the pathogenesis of Duchenne muscular dystrophy?

A protein that detaches ribosomes from rough microsomal membranes ("detachment factor") (DF) was isolated from the cytosol fraction of rat and human muscle. The procedure of isolation included differential centrifugation, precipitation with ammonium sulfate and column chromatography with Sephadex G-100. The protein which is not completely homogenous, has a molecular weight of 50,000-60,000 daltons, is heat labile and has an optimum pH at 7.4-7.6. The DF activity of the protein is inhibited by soybean trypsin inhibitor (73%), pepstatin (67%), and leupeptin (42%), although no proteolysis could be measured. The DF activity was tested on muscle samples (rough microsomal membranes) obtained from Duchenne muscular dystrophy (DMD) patients (7 cases) and normal controls (16 cases). The yield of membrane bound ribosomes (MBR) obtained from muscle samples of DMD patients by extraction with DF is 5-fold higher than from muscle samples of normal controls. The difference in MBR yield is not related to the type of DF. Similar values for MBR were obtained with rat and human (normal and dystrophic) DF. Ribosomal protein synthesis (RPS) with ribosomes extracted by DF showed values similar to the RPS of detergent extracted ribosomes. Our findings suggest the observed increase in membrane bound ribosomes in DMD probably results from increased levels of mRNAs coding for membrane and secretory proteins such as collagen.

Amino Acids↗
PubMed1980

Discriminant analysis of ribosomal protein synthesis findings in carrier detection of Duchenne muscular dystrophy.

Previous studies have shown that in vitro muscle ribosomal protein synthesis (RPS) by monomeric ribosomes (MR) and total polyribosomes (TPR) and collagen synthesis (CS) are significantly increased (P less than 0.01) in 47 known carriers of Duchenne muscular dystrophy as compared to 60 age-matched controls. However, there was considerable overlap of the distribution of controls and carriers, particularly for monomeric ribosomal protein synthesis and collagen synthesis. To improve detection of carriers we used discriminant analysis utilizing logs of each measurement as superior to a univariate or bivariate scheme. This study considered four groups: proven carriers (30) (group 1), presumptive carriers (female relatives of Duchenne patients with high serum creatine kinase (CK) levels) (32) (group 2), controls greater than or equal to 20 years old (42) (group 3) and controls less than 20 years (36) (group 4). Comparison of groups, Misclassification (%), (see chart). These results suggest that discriminant analysis reduces the misclassification rates as compared with univariate or bivariate analysis and confirm the superiority of RPS measurements as a carrier test for Duchenne muscular dystrophy.

Adult↗
PubMed1980

Frequency of new mutants among boys with Duchenne muscular dystrophy.

Haldane's rule states that one-third of the cases of an X-linked recessive lethal should represent new mutations. This rule is derived under the assumptions that there is equilibrium between mutation and selection, that mutation rates in ova and sperm are equal, and that heterozygous and homozygous normal women have the same fitness. To test this rule for Duchenne muscular dystrophy (DMD), we have examined the mothers of 55 boys with DMD (16 familial and 39 isolated cases) and classified them as carriers or noncarriers on the basis of measures of ribosomal protein synthesis (RPS). Of the 55 mothers, only nine (16.4%) are classified as noncarriers, a figure significantly different from the expected one-third. When the analysis is limited to the 39 mothers of isolated cases, 23.1% (9/39) are classified as noncarriers, still significantly different than expected under Haldane's rule. Violation of any of the assumptions under which Haldane's rule is derived could lead to deviations from the expected one-third new mutants. We find the most likely explantation to be a higher male than female mutation rate. This is supported also by the finding that maternal grandfathers in whom a mutation occurred had higher mean age at birth of the carrier daughter (33.7 +/- 1.6) than did the general population or intrapedigree controls (29.5 +/- 1.3).

Female↗
PubMed1980

Altered protein synthesis and creatine kinase in breast muscle cell cultures from dystrophic chick embryos.

The total protein synthesis (TPS), myosin synthesis (MS) and creatine kinase (CK) levels in muscle cell cultures obtained from 400 normal (strain 454) and 400 dystrophic chick embryos (strain 455) were investigated. The cultures were obtained from breast muscles of 12 day chick embryos by dissociation in 0.25% trypsin, preplating and plating of 5 x 10(5) floating cells on gelatin coated dishes in Minimal Essential Medium, 10% horse serum and 2% chick embryo extract. After 6 days, when electron-microscopic studies demonstrated good muscle differentiation, cell cultures were labeled with [3H]leucine. TPS and MS, respectively, showed 85% and 65% increases in breast muscle cell cultures from dystrophic chick embryos. The half-life times for total protein and myosin from dystrophics were 19 and 32 hr, respectively as compared with 36 and 48 hr from controls. Noncollagen protein content (NCP) showed 27% decrease in postfusion stage (12 days) of cell cultures from dystrophics. The CK level showed 30% lower values in the cells from dystrophics but 50% higher values in their culture medium. The addition of leupeptin plus pepstatin (50 microgram/ml) to these cultures resotred NCP content, total protein and myosin turnover to normal values and significantly increased TPS and MS. The addition of diphenylhydantoin (DPH) (20 microgram/ml) to cell cultures from dystrophics did not change the NCP content nor the turnover for total protein and myosin but significantly increased TPS, MS and CK while medium CK significantly decreased. The addition of leupeptin plus pepstatin or DPH to muscle cell cultures from normal chick embryos also significantly stimulated TPS and MS.

Animals↗
PubMed1980

Combined partial deficiency of muscle carnitine palmitoyltransferase and carnitine with autosomal dominant inheritance.

The authors studied a 53 year old woman and her 22 year old son with episodes of paroxysmal muscle cramps and dark urines lasting several hours related to high fat diet and strenuous physical exercise beginning on both at age 14 years. The father, paternal uncle, paternal grandfather and another son of the mother also had paroxysmal muscle cramps. The two studied cases showed normal findings for physical evaluation, blood lactate after ischemic exercise, and muscle histology (light and electron microscopy). The serum creatine kinase was elevated in the son and normal in the mother. However, 72 hour fasting significantly raised the serum creatine kinase level in both cases. Plasma concentration of ketone bodies and acid soluble acyl-carnitine increased normally with prolonged fasting. The biochemical evaluation of the muscle tissue revealed intact anaerobic glycolysis and normal glycogen content but combined partial deficiency of muscle carnitine palmitoyltransferase and carnitine in both cases.

Acyltransferases↗
PubMed1980

Sporadic Duchenne muscular dystrophy in females; genetic counseling of women with pelvifemoral muscular dystrophy.

The first two cases of sporadic Duchenne muscular dystrophy (DMD) in females without a family history of DMD are reported. Both females had normal chromosomes and were identified as DMD by in vitro studies of protein synthesis by muscle ribosomes and by carrier studies of the mother of the proband. These observations are important for the genetic counselor. The possible diagnosis X-linked DMD has to be considered for every female with sporadic pelvifemoral MD, and carrier studies have to be requested for the proband's mother and possibly other maternal female relatives.

Adult↗
PubMed1979

Stimulatory effects of drugs for protein synthesis on muscle cell cultures in Duchenne dystrophy.

The influence of the membrane-stabilizing agents diphenylhydantoin (DPH) and orgotein (a drug with superoxide dismutase activity) on protein synthesis was studied in cultured human muscle cells obtained from 7 patients with Duchenne muscular dystrophy (DMD) and 14 controls. The cultures were obtained by dissociation and subsequent plating of cells from biopsied quadriceps muscle. These cultures were then labeled with tritiated leucine in the presence and absence of the membrane-stabilizing drugs. Total protein synthesis (cpm/mg noncollagen protein) in first-passage muscle cell cultures from DMD patients showed a 35% decrease, but myosin synthesis revealed normal values. DPH and orgotein increased total protein synthesis by 35 and 50%, respectively, in dystrophic cultured cells, but only by 7 and 8%, respectively, in control cultured cells.

Cells, Cultured↗
PubMed1977

Fibroblast cultures in Duchenne muscular dystrophy. Alterations in synthesis and secretion of collagen and noncollagen proteins.

Primary skin fibroblast cultures were grown from forearm pinch skin biopsies obtained from 24 patients with Duchenne muscular dystrophy (DMD) and ten normal controls matched for sex and age. The first subcultures were grown for 7 days and incubated with L-(3H)-proline for 24 hours. Intracellular collagen incorporation was significantly decreased (2.2 X) and extracellular collagen incorporation significantly increased (1.8 X) in fibroblast cultures from patients with DMD by both collagenase assay and polyacrylamide gel electrophoresis. The synthesis of noncollagen proteins showed low values from the DMD fibroblast cultures. The alterations in synthesis and secretion of collagen and noncollagen proteins were characteristic only for the log phase of DMD fibroblasts.

Cells, Cultured↗
PubMed1977

Protein synthesis in muscle cultures from patients with myotonic dystrophy. Influence of A23187 ionophore and calcium: preliminary investigation.

Muscle samples for cultures were obtained from the tibialis anterior by open biopsy under local anesthesia in 12 patients with myotonic dystrophy and 15 controls. Total protein synthesis in muscle cultures from patients with myotonic dystrophy showed a nonsignificant increase in (3H)-leucine incorporation. Addition of A23187 ionophore significantly stimulated the protein synthesis in muscle cultures from patients with myotonic dystrophy, but had an inhibitory effect in the cultures from controls. Myosin heavy chain synthesis was measured and found normal in all patients with myotonic dystrophy.

Anti-Bacterial Agents↗