Nickel Substitution for Calcium in Excitation-Contraction Coupling of Skeletal Muscle

In 1962 Frank (22) reported that the addition of any one of a number of divalent cations, including Ni, to a Ca-free Ringer solution prevented the rapid loss of contractility seen in the absence of external Ca. To investigate further the Ni-Ca substitution, studies were made of ⁴⁵Ca and ⁶³Ni exchange during contraction and at rest using frog striated muscle. In contrast to ⁴⁵Ca, it was found that there is no increase of ⁶³Ni uptake associated with a K contracture of the sartorius muscle. The rates of loss of ⁶³Ni and ⁴⁵Ca from resting toe muscles previously bathed in the respective radioisotopes are not significantly different. Resting and action potentials, after 1 hr in a Ringer solution with Ni replacing Ca, closely resemble these potentials in normal Ca-Ringer's solution. Studies on the syneresis of isolated myofibrils indicate that Ni cannot replace Ca in activating this reaction. It is suggested that Ca is required for at least two steps in E-C coupling: one is the spread of excitation at the sarcolemma and transverse tubular system; the second is the activation of actomyosin ATPase. Conceivably Ni can substitute for Ca in the former but not in the latter.     

Enzyme-induced Formation of Spheres from Cells and Envelopes of Escherichia coli

Normal and filamentous whole cells and isolated envelopes of Escherichia coli B were exposed to various enzymatic treatments to remove surface layers and to characterize the component(s) conferring rigidity in this organism. Modification of cell rigidity was determined by sphere formation in both whole cells and isolated envelopes. Enzymes capable of converting trypsinized normal or untreated filamentous whole cells and untreated envelopes to spheres included: lysozyme plus ethylenediaminetetraacetic acid, clostridial phospholipase C, and phospholipase D from cabbage. These data suggest that there are at least two components essential for maintenance of cell rigidity in E. coli B. The first is the peptidoglycan (mucopeptide), which is susceptible to lysozyme. The second is a phospholipid which is either covalently linked to the mucopeptide or in close association with it. This phospholipase C-sensitive component is protected more completely in normal than in filamentous whole cells by a protein layer which is easily modified by trypsin treatment to allow enzymatically induced sphere formation to occur.     

Inheritance of quantitative expression of erythrocyte glucose-6-phosphate dehydrogenase activity in the Negro—a twin study

Studies have been conducted on eight sets of monozygous and nine sets of dizygous female Negro twins, both members of whom were heterozygous for G-6-PD deficiency. Twins were studied both by assay of erythrocytic G-6-PD activity and by the methemoglobin elution test (MET). The MET is a procedure which identifies histochemically cells with appreciable G-6-PD activity and permits accurate determination of the percentage of such cells in heterozygotes. Monozygous twins showed significantly less within-pair variation than dizygous twins with both the MET and G-6-PD assay.Concerning the significantly greater agreement in MET results in monozygous twins than dizygous twins, our present working hypothesis is that X-chromosomal inactivation in the Negro female is genetically controlled, rather than random. However, certain alternate hypotheses allowing for random X-inactivation have not been excluded; these include somatic cell selection after random X-inactivation, and cell exchange between identical twins in utero/it. Studies in nontwin related heterozygotes now underway should help differentiate among these various possibilities.In addition to the studies on 17 pairs of female twins heterozygous for G-6-PD deficiency, 26 pairs of nondeficient female Negro twins have been studied by G-6-PD assay. Within-pair variation in monozygous twins was significantly less than within-pair variation in dizygous twins in all cases. The genetic influences detected with the G-6-PD assay in the female twins could theoretically be due to nonrandom X-inactivation, to genetically determined quantitative differences in enzyme activity (e.g., isoalleles), or to both. By appropriate calculations, based on the MET results, we have factored out the effects of X-inactivation on overall enzyme activity in the heterozygous deficient twins. After removal of the effect of X-inactivation, monozygous twins heterozygous for enzyme deficiency continue to show significantly less within-pair variation than dizygous twins. This finding indicates significant genetic influences on quantitative G-6-PD activity other than X-inactivation and other than the deficiency allele. This conclusion has been strengthened by studies on male twins where X-inactivation is not present.Supported by USPHS research grants AM-09381, HE-17544, AM-09919, and HE-03341, by USPHS Career Development Award 1-K3-AM-7959 (Dr. Brewer) and by U.S.A.E.C. Contract (11-1)-1552.     

Severe Metabolic Acidemia in Infants: Clinical and Therapeutic Aspects

A study of 10 infants in severe metabolic acidemia (pH below 7) led to the conclusion that the clinical signs—hyperventilation, coma or lethargy, peripheral vascular collapse, a significantly palpable liver, and abdominal distension—may all be directly related to the metabolic acidemia. In five of 10 infants, an initial erroneous diagnosis of congestive heart failure or pneumonia was made. Dramatic clinical improvement followed correction of the acidemia with rapid intravenous administration of sodium bicarbonate. This rapid administration of sodium bicarbonate was safe, provided hypocalcemia was recognized and treated in its early stages. In severe metabolic acidemia the measurement of blood bicarbonate alone does not reflect adequately the magnitude of the acid-base derangement and repeated measurements of hydrogen ion concentration, Pco₂ and bicarbonates are needed to evaluate and treat such infants correctly.     

A FLORA FROM THE CHESTER SERIES (UPPER MISSISSIPPIAN) OF SOUTHERN ILLINOIS

New localities in southern Illinois have yielded a flora consisting of 9 taxa. The plant remains occur in sandstones of the Chester Series and consist of casts, molds, and flattened impressions. The most important elements in the flora are: Archaeocalamites radiatus, Lepidodendron volkmannianum, Stigmaria ficoides, Rhynchogonium fayettevillense, and an unnamed Trigonocarpus. Stems probably referable to Lepidodendron veltheimii and Dictyoxylon also occur, as do numerous casts of the Knorria and Bergeria types. The range of features found in specimens of Lepidodendron volkmannianum allows some revision to be made of several species previously described by White in the Wedington Sandstone flora of northwest Arkansas, with which the present flora is closely comparable. The difficulties in making precise correlations with Upper Mississippian floras in other parts of the world are discussed. The necessity for critical re-examination of existing described collections and of undertaking more extensive field-work in the Mississippian of N. America is emphasized.     

A Taxonomy of Continuing Medical Education Endeavour

Five basic forms of continuing educational endeavour by physicians are listed in rank order. These components constitute an indivisible unit bound together by self-learning. The scholarly habit of planned daily reading and study in a home library-sanctuary as an integral part of a physician''s workday heads the list. Day-to-day informal and formal colleague-association in patient care in the community and teaching hospital, in group practice and by consultation is the present major form of continuing educational endeavour. Emphasized is the sabbatical return every three to five years for three months at least to the teaching hospital to reinforce scholarly motivation and attitudes and to acquire new skills and knowledge. Attendance at scientific sessions of learned professional societies and short courses should be accompanied by presession and post-session guided reading to be undertaken in the physician''s home library-sanctuary.