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Biomedical subjects

A D Roses

Publications and source records attributed to A D Roses.

At least 307 records · Page 17Linked to original sources
PubMed1978

Biochemical relationships between muscle and erythrocyte membrane. Interpretations with respect to Duchenne muscular dystrophy.

Whether Duchenne muscular dystrophy (DMD) is a disease of primary myogenic, secondary neuropathic, vascular or membrane etiology is the subject of some debate. Using the erythrocyte membrane as a biopsy tissue we present biochemical data that support the possibility of a defect in myosin as the genetic defect in DMD. Peptide analysis of hydrolyzed erythrocyte spectrin supports previous data demonstrating an alteration in DMD spectrin. The biochemical and biophysical similarities between spectrin and myosin can be tested with available technology. The hypothesis that a defect in myosin may be responsible for DMD is attractive because it is testable.

Erythrocyte Membrane↗
PubMed1977

Pedigree testing in Duchenne muscular dystrophy.

Female relatives of 41 Duchenne muscular dystrophy proband cases were studied with a panel of carrier-detection tests. A total of 277 relatives were tested in order to determine which mothers had affected sons as a result of new mutation. In 39 of 41 pedigrees the data demonstrate that a mutation cannot be postulated; the 2 megative pedigrees were inadequately tested. Our data suggest that all mothers of affected sons should be considered genetic carriers (heterozygotes) until proved otherwise. Our findings also raise questions concerning what mechanisms skew the indirect statistical estimates of mutation that are in common use.

Adolescent↗
PubMed1977

Evaluation and detection of Duchenne's and Becker's muscular dystrophy carriers by manual muscle testing.

Manual muscle testing of mothers of patients with X-linked muscular dystrophy has demonstrated patterns of proximal muscle weakness. The degree of weakness usually has little effect on activities of daily living but can be detected by standardized "break" testing with manual stabilization of body parts, elimination of synergistic muscles, and mechanical advantage given to the patient. Manual muscle testing is a valuable adjunct to the clinical and biochemical tools available for detecting carriers.

Female↗
PubMed1977

Lactate dehydrogenase isoenzyme in detecting carriers of Duchenne muscular dystrophy.

Thirty mothers of patients with Duchenne muscular dystrophy were studied with serum enzyme tests, including serum glutamic-oxaloacetic transminase, creatine kinase, and lactate dehydrogenase isoenzymes. In addition, females from the mothers' pedigrees were studied. Lactate dehydrogenase isoenzyme 5 determinations were as senitive an indicator of carrier status as creatine kinase and also identified several mothers who had normal dehydrogenase isoenzyme 5 determinations, as well as extensive pedigree testing, identified 28 to 30 mothers as probable heterozygotes. These data independently support the suggestion that cases of Duchenne muscular dystrophy as a result of spontaneous mutation are more uncommon than currently accepted.

Adult↗
PubMed1976

Carrier detection in Duchenne muscular dystrophy.

We measured endogenous phosphorylation of peak II (apparent molecular weight of 220,000 daltons) of the erythrocyte membrane in 21 mothers of patients with Duchenne muscular dystrophy. The mean values of mothers with affected sons were significantly increased over those of matched controls (77.0 and 55.8 pmoles per milligram of 15-minute incubation; P less than 0.01). Detailed testing of mothers of affected sons revealed proximal muscle weakness. Seven mothers of isolated patients who had normal levels of creatine phosphokinase and no daughters with elevated levels were identified as carriers, because their mean value of peak II phosphorylation was increased (75.9 pmoles per milligram per 15 minutes) and equivalent to the level demonstrated in the 14 acknowledged carriers. Our results suggest that cases of Duchenne muscular dystrophy previously considered to be new mutations are much less common than estimated.

Adenosine Triphosphate↗
PubMed1976

Scanning electron microscopy studies in muscular dystrophy.

Scanning electron microscopy of unmanipulated erythrocytes from patients with myotonic dystrophy or Duchenne dystrophy and patients who were Duchenne carriers showed a large increase in the number of stomatocytes over the number in normal controls. No specific morhologic changes that would differentiate any of the dystrophic patients from one another were seen. Adverse conditions such as washing before fixation or extreme pH produced a greater change in erythrocytes from these patients than in those from normal controls.

Cell Count↗
PubMed1976

Substrate heterogeneity of component a of the human erythrocyte membrane.

Component a of the erythrocyte membrane is a specific substrate for endogenous protein kinase activity and its phosphorylation is significantly decreased under assay conditions in myotonic muscular dystrophy (Roses, A.D., and Appel, S.H.J. Membr. Biol 20:51-58 (1975)). We have demonstrated substrate heterogeneity of two fractions of component a separated by concanavalin A (Con-A) sepharose chromatography. The fraction of component a that is retarded by Con A and eluted with alpha-methyl-D-glucoside does not accept the transfer of phosphate from [gamma-32 P] ATP as a substrate for endogenous protein kinase activity. The nonretarded fraction contains greater than 90% of the radioactive label. These experiments also confirm the carbohydrate heterogeneity of component a (Findley, J.B.C., J. Biol. Chem. 249:4398 (1974).

Cell Membrane↗
PubMed1976

Erythrocyte spectrin peak II phosphorylation in Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a rapidly progressive crippling disease of young boys that is inherited as an X-linked recessive trait. Previous studies have demonstrated the usefulness of erythrocyte studies in exploring membrane abnormalities in inheritied muscular dystrophy. Erythrocyte spectrin peak II protein (m.w. equivalent to 220,000) was more highly phosphorylated under initial rate conditions in DMD than in controls. The extent of peak II phosphorylation was greater in DMD erythrocytes and a Na+ stimulated peak II phosphorylation effect (Avruch and Fairbanks 1974) was not found to account for the differences between DMD and controls. The phosphorylated state of spectrin proteins in the membrane was evaluated and no differences in DMD could be measured. The maximal transfer of phosphate from differences in DMD could be measured. The maximal transfer of phosphate from [gamma-32P]ATP to spectrin peak II accounts for approximately 5-10% of the total phosphate content of spectrin.

Adenosine Triphosphate↗
PubMed1976

Increased phosphorylated components of erythrocyte membrane spectrin band II with reference to Duchenne muscular dystrophy.

Increased erythrocyte band II phosphorylation has been demonstrated in patients with Duchenne muscular dystrophy (DMD). Band II has been purified by preparative sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. Isoelectric focusing of purified band II from which SDS has been removed reveals heterogeneity. Band II migrates as multiple bands on isoelectric focusing gels and as a single band on SDS-polyacrylamide gels. The increased phosphorylation in DMD does not occur uniformly in all components of band II. Highly phosphorylated components of band II are present in DMD in which only minimal phosphorylation occurs in controls. These results suggest the presence of an abnormal band II substrate in erythrocyte membranes from DMD patients.

Adult↗
PubMed1976

Stoichiometry of sodium and potassium transport in erythrocytes from patients with myotonic muscular dystrophy.

1. 22Na and 42K radioisotopes were used to measure Na efflux and K influx in identical suspensions of fresh erythrocytes from myotonic dystrophy patients and matched controls under the same conditions and in the same time interval. K was present in concentration 10 mM in the suspending medium to prevent Na-for-Na exchange. Each flux was measured in the presence and absence of ouabain. The mean ouabain-sensitive Na efflux rate in controls (2-33+/-0-13, S.E. of mean, m-equiv/1. cells.hr) was significantly greater (P less than 0-001) than the corresponding rate in myotonic dystrophy (1-64+/-0-09). 2. No significant differences between myotonic dystrophy and controls in mean ouabain-insensitive Na efflux, mean ouabain-sensitive K influx, or mean ouabain-insensitive K influx were found. 3. The stoichiometric ratio (ouabain-sensitive Na efflux)/(ouabain-sensitive K influx) was determined for each flux experiment. The mean stoichiometric ratio determined in controls (1-46+/-0-08) reconfirms extensive previous evidence favouring a 3Na-for-2K active exchange in controls. 4. The mean stoichiometric ratio determined in myotonic dystrophy (1-01+/-0-06) is statistically significantly different (P less than 0-001) from that in controls. These findings are interpreted as indication of 2Na-for-2K exchange in erythrocytes from patients with myotonic dystrophy.

Adenosine Triphosphatases↗