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Biomedical subjects

A D Roses

Publications and source records attributed to A D Roses.

At least 289 records · Page 16Linked to original sources
PubMed1981

Patients with myotonic dystrophy, a possible segmental progeroid syndrome, and Duchenne muscular dystrophy have fibroblasts with normal limits for in vitro lifespan and growth characteristics.

Myotonic dystrophy (MyD) has been suggested to be a segmental progeroid syndrome in man, as this syndrome has some clinical manifestations of premature aging. Fibroblasts from patients with other progeroid syndromes have been shown to have diminished in vitro lifespans or growth characteristics; therefore, it was of interest to study cellular senescence in fibroblasts from patients with MyD. Fibroblast cultures from patients with Duchenne muscular dystrophy (DMD) were used as additional controls, as premature aging is not associated with this genetic disorder. Primary skin fibroblast cultures obtained from patients with MyD or DMD and from age-sex matched controls were grown in DMEM plus 10% FBS. The in vitro lifespan was determined by either a 1:4 split ratio or with a constant initial inoculum of 1 times 10(4) cells/cm2, followed by determination of the final density at weekly intervals. Our results demonstrate that there is no difference in the limits of the in vitro lifespan for either the MyD or DMD fibroblast strains compared to the controls. Likewise, no difference could be detected in the growth characteristics of these cells. The only observable difference was that the pooled age-matched controls and MyD cultures had a shorter in vitro lifespan than the DMD group and their pooled controls, a finding expected because of the age of the patients in each group. Unlike the other progeroid syndromes, MyD fibroblasts have normal limits for in vitro lifespan. MyD is probably not closely related to the other premature aging syndromes, although there is an increasing phenotypic expression as a function of age.

Adolescent↗
PubMed1981

The pathogenesis of myasthenia gravis--a hypothesis.

We have suggested that a thymic factor plays a critical role in the pathogenesis of myasthenia gravis. The presence of specific ACh R antibodies in more than 90% of patients with myasthenia gravis has provided us with a marker for this disorder and has greatly increased our understanding of the pathophysiology. These antibodies can induce physiological parameters similar to those seen in myasthenia gravis following passive transfer to experimental animals and can accelerate degradation of ACh R in myotube culture. However, clinical studies suggest that additional factors of thymic origin are necessary for the development of the clinical features of myasthenia gravis. While the nature of the thymic factor(s) is speculative, this hypothesis has a significant clinical implication as it argues for an early, total thymectomy as the treatment of choice for myasthenia gravis.

Antibodies↗
PubMed1981

The effect of plasmapheresis on post-thymectomy ocular dysfunction.

Five myasthenia patients with post-thymectomy residual ocular signs were treated with plasmapheresis. Despite a significant reduction in AChR antibody titer, there was no clinical improvement. Subsequently, there was a dramatic response to prednisone. The AChR antibody titer did not correlate with the clinical state of the individual patient. It is suggested that plasmapheresis may operate by removing a thymic factor and that prednisone acts by a different mechanism.

Adult↗
PubMed1981

No direct correlation between serum antiacetylcholine receptor antibody levels and clinical state of individual patients with myasthenia gravis.

Serum acetylcholine receptor antibodies were measured serially in myasthenia gravis patients before and after early extended thymectomy; they received no medication postoperatively. Clinical improvement occurred with little or no change in antibody level. After plasmapheresis without immunosuppressive drug therapy, we also found clinical improvement without decrease in serum antibody level.

Acetylcholine↗
PubMed1981

Identification of abnormally [32P]-phosphorylated cyanogen bromide cleavage product of erythrocyte membrane spectrin in Duchenne muscular dystrophy.

We measured [32P]-phosphorylation of erythrocyte membrane spectrin band 2 peptides from patients with Duchenne muscular dystrophy. Erythrocyte ghosts were prepared and subjected to [32P]-phosphorylation by endogenous protein kinase incubations. Purified spectrin was then cleaved by cyanogen bromide, and the resulting peptides were analyzed by electrophoresis on 5%/15% SDS polyacrylamide stacking slab and tube gel systems. More than 50% of the incorporated [32P] was associated with a single band, CN-A, with an apparent molecular weight of 23 kilodaltons. The Coomassie blue-stained peptides were identical in patients and controls. Band CN-A represented approximately 2% of the total peptide protein but was more [32P]-phosphorylated in patients than in controls.

Autoradiography↗
PubMed1980

Altered erythrocyte spectrin extractability in Duchenne muscular dystrophy.

Spectrin extractability was measured in the erythrocyte membranes obtained from patients with Duchenne muscular dystrophy (DMD) and normal matched controls. After the extraction of spectrin by adding deionized water, an aliquot of the pellet was applied to 6% SDS-polyacrylamide gels. Spectrin-Band 3 ratio on the gels was used as an indicator of spectrin extractability. Our data disclosed that spectrin extractability is significantly reduced in DMD patients when compared with that of controls and these results suggest that spectrin from DMD patients is more tightly bound to the membranes. Our data may also be applicable to the discussion of the relationship of spectrin to other membrane properties as well as to previously described membrane abnormalities in DMD erythrocytes.

Electrophoresis, Polyacrylamide Gel↗
PubMed1980

Comparison of antigenic sources for acetylcholine receptor antibody assays in myasthenia gravis.

Antibody titers to the acetylcholine receptor (AChR) from patients with myasthenia gravis, in identical serum samples, were directly compared using denervated rat, human, and baboon muscle as the source of AChR antigen for radioimmunoassay (RIA). Calculations were standardized by using binding isotherms for each antigen source and calculating the percentage of AChR sites labeled with [125I]alpha-bungarotoxin at the concentration used in the RIA. In patients with high AChR antibody titers, the antibody concentration when human muscle was used as the antigen source measured up to tenfold higher than that with denervated rat muscle. In patients who had low antibody titers with human muscle antigen, assays using rat denervated muscle AChR frequently failed to demonstrate diagnostically abnormal titers. The data explain difference among several reported series in the percentages of patients with myasthenia gravis who had elevated serum antibody concentrations. AChR antibody concentrations with baboon muscle as the antigen source were comparable to those in which human muscle was used.

Acetylcholine↗
PubMed1980

Myotonic muscular dystrophy: defective phospholipid metabolism in the erythrocyte plasma membrane.

Myotonic muscular dystrophy (MyD) is a systemic genetic disorder that is thought to result from a generalized cellular membrane defect although the exact nature of this defect is unknown. This study examines two calcium-dependent membrane processes that have been observed in erythrocytes from healthy individuals: calcium-stimulated phosphatidic acid accumulation and calcium-induced potassium leak. We find that erythrocytes from MyD patients, in contrast to controls, have markedly impaired phosphatidic acid accumulations while maintaining normal potassium leaks. The calcium uptakes and ATP contents of MyD erythrocytes are not different from controls. We conclude that phospholipid metabolism is altered in MyD erythrocytes. The specificity of this abnormality and its relationship to altered muscular function are not known.

Biological Transport, Active↗
PubMed1980

Electrocardiographic abnormalities in carriers of Duchenne muscular dystrophy.

Electrocardiographic (ECG) abnormalities characteristic of Duchenne muscular dystrophy (tall R waves in the right precordial leads and deep Q waves in the lateral chest leads) are rarely observed in carriers, but Emery (1969) found that the (R-S) amplitude sum in lead V1 was significantly greater in carriers than in age-matched controls. In a prospective single-blind study, we analyzed coded records from 11 carriers and 12 age-matched normal women for (R-S) amplitude sums and R/S ratios in leads V1 and V2. Values in carriers were significantly greater for all these characteristics, discrimination being most marked for R/S in V2 (p less than 0.01). This was confirmed in a further retrospective study, comparing records from 18 carriers with 100 normal ECGs from women of the same age range. Density functions for (R-S) in V1 and the R/S ratio in V2 derived from carrier and normal population can be incorporated into probability calculations to determine risk of carrier status.

Adult↗
PubMed1979

Erythrocyte membrane autophosphorylation in Duchenne muscular dystrophy: effect of two methods of erythrocyte ghost preparation on results.

We have compared the effects of two slightly different methods of erythrocyte ghost preparation on membrane autophosphorylation in Duchenne muscular dystrophy. Addition of 1 mmol/l EDTA to two of the washing steps altered the differences between patients and controls. These data support the known sensitive interrelationship of Ca2+ and erythrocyte membrane autophosphorylation, underline the importance of strict adherence to methodology when comparing data, and have suggested a new direction of investigation.

Calcium↗
PubMed1979

Isolation of an abnormally phosphorylated erythrocyte membrane band 3 glycoprotein from patients with myotonic muscular dystrophy.

A fraction of erythrocyte Band 3 (Mr, 93,000) glycoprotein that demonstrates decreased autophosphorylation in membranes from myotonic muscular dystrophy patients is demonstrated. Sequential affinity chromatography of Triton X-100 solubilized erythrocyte membrane proteins separated three specifically retained glycoprotein fractions on a Ricin Communis I-Sepharose 4B column. One fraction contains a portion of the major sialoglycoprotein (apparent Mr, 78,000) and is specifically eluted from the column by 10 mM NaCl and 100 mM D-galactose (10/100). The two other glycoprotein fractions are eluted by 100 mM NaCl, 10 mM D-galactose (100/10) and 100 mM NaCl, 100 mM D-galactose (100/100). The composition of both fractions contains greater than 95% Band 3 (apparent Mr, 93,000 glycoprotein. The quantities of glycoprotein in each fraction obtained from erythrocytes of myotonic dystrophy patients did not differ from the quantities obtained from control erythrocytes. Following endogenous protein kinase incubations of ghosts with [gamma-32P]ATP, the specific [32P] phosphorylation of the 10/100 and 100/10 fractions are identical. The 100/100 fraction, which makes up approximately 3% of the total erythrocyte membrane protein, demonstrates a different pattern for myotonic dystrophy patients; specific phosphorylation was reduced by 50% relative to activity in control experiments. These findings are consistent with previous experiments that demonstrated decreased autophosphorylation of the glycoprotein portion of Band 3 (Roses & Appel, 1975, J. Membrane Biol 20:51) and are consistent with the autosomal dominant mode of inheritance in this disease.

Chromatography, Affinity↗
PubMed1979

Debrancher deficiency: neuromuscular disorder in 5 adults.

Five patients, 4 men and 1 woman, had adult-onset and slowly progressive weakness. There was distal wasting in 2, hepatomegaly in 3, and congestive heart failure in 2. Electromyography showed a mixed pattern with abundant fibrillations. Serum creatine phosphokinase was increased 5- to 45-fold. Blood glucose failed to respond to epinephrine or glucagon, and venous lactate did not rise after ischemic exercise. Muscle biopsy showed vacuolar myopathy affecting both fiber types. By electron microscopy the vacuoles corresponded to large pools of glycogen not limited by a membrane. Glycogen concentration was 3 to 5 times normal in muscle and 7 to 21 times normal in erythrocytes. In the presence of iodine, muscle glycogen showed a spectrum characteristic of phosphorylase-limit-dextrin. Debrancher activity was measured by a spectrophotometric assay and by a radioactive reverse reaction. The activity was lacking in muscle and erythrocytes of 4 patients according to both assays; in 1 patient the reverse reaction was not impaired. Though previously reported in only 5 patients, debrancher deficiency myopathy may not be rare and should be considered in the differential diagnosis of adult-onset hereditary myopathies.

Adolescent↗
PubMed1979

The natural history of conduction system disease in myotonic muscular dystrophy as determined by serial electrophysiologic studies.

To evaluate the progression of conduction system disease in myotonic muscular dystrophy, nine patients underwent serial electrophysiologic studies at a mean of 35 months apart. At the initial study, seven patients had first-degree atrioventricular block and three of these seven had disease in the His-Purkinje system (HV greater than 55 msec). At the second study, seven patients had prolonged HV intervals, and during the almost 3-year period, HV intervals increased by at least 5 msec in all seven patients. No electrophysiologic or electrocardiographic measures could be found that correlated with progression of conduction disease in these patients. Because of the failure of electrophysiologic measures to predict progression of conduction disease in these patients, electrophysiologic studies are recommended only for symptomatic patients. If significant disease is found in either impulse formation or conduction, permanent pacemaker therapy is warranted.

Adult↗