Variation of pressure with cycle length and duration of systole in the two-chambered cardiovascular model

Variation in the heart rate and the duration of systole modifies the pressures in the two-chambered model of the cardiovascular system by several mechanisms. The theoretical results indicate that prediction of chamber pressures would require moment-to-moment knowledge of the resistances peripheral to each chamber in addition to the cardiac output per cycle, cycle length, and duration of systole. Lengthening of systole with increase in cycle length—a physiologically observed relationship—theoretically stabilizes the end-diastolic pressure in the ascending aorta and may be a homeostatic mechanism to steady blood flow through the coronary arteries.     

A note concerning quantum mechanics and medicine

The rapid growth of quantum mechanics in the twentieth century has in no small part been due to the advanced state of classical mechanics. The introduction of new mathematical concepts to biology and medicine, on the other hand, is difficult because of the absence of a strong mathematical foundation. As a result, in many instances, new theoretical approaches to biological material have depended upon the use of mechanical and electrical analogues. As this paper shows, from a solution to a mechanical problem by means of quantum mechanics comes a potentially useful approach to a common medical problem.     

The use of amphipathic maleimides to study membrane-associated proteins

A series of amphiphilic polymethylenecarboxymaleimides has been synthesized for use as sulfhydryl reagents applicable to membrane proteins. Physical properties of the compounds which are relevant to their proposed mode of action have been determined. By comparing rates of reaction in aqueous and aprotic solvents, the compounds have been shown to react exclusively with the thiolate ion. The effects of the reagents on three membrane-associated proteins are reported, and in two cases a comparative study has been made of the effects on the proteins in the absence of membranes. A mechanism is proposed whereby the reagents are anchored at the lipid/water interface by the negatively charged carboxyl group, thus siting the reactive maleimide in a plane whose depth is defined by the length of the reagent. Supporting evidence for this model is provided by the inability of the reagents to traverse membranes, and variation of their inhibitory potency with chain length when the proteins are embedded in the membrane, but not when extracted into solution. As examples of general use of the reagents to probe sulfhydryl groups in membrane proteins, the reagents have been used to (a) determine the depths in the membrane at which two populations of sulfhydryl groups occur in the mitochondrial phosphate transporter; (b) locate a single sulfhydryl associated with the active site ofD--hydroxybutyrate dehydrogenase in the inner mitochondrial membrane; (c) examine sulfhydryl groups in theD-3-glyceraldehyde phosphate dehydrogenase associated with the human red blood cell membrane.     

Phosphorylation of cardiac junctional and free sarcoplasmic reticulum by PKCα, PKCβ, PKA and the Ca2+/calmodulin-dependent protein kinase

Phosphorylation of cardiac junctional and free sarcoplasmic reticulum (SR) by protein kinase C (PKC) isoforms and was investigated. Both SR and PKC were isolated from canine heart. Junctional and free SR vesicles were prepared by calcium-phosphate-loading. The substrate specificities of PKC and PKC were found to be similar in both SR fractions. A high molecular weight junctionally-associated protein was phosphorylated by PKA, PKC and an endogenous Ca²⁺/calmodulin-dependent protein kinase activity: the highest levels of phosphate incorporation being catalysed by the latter kinase. In addition to this high molecular weight junctionally-associated protein, PKC induced phosphorylation of 45, 96 kDa and several proteins of greater than 200 kDa in junctional SR. A protein of 96 kDa was phosphorylated by both isoforms in junctional and free SR. The major substrate for PKA, PKC, PKC and the Ca²⁺/calmodulin-dependent protein kinase, in both junctional and free SR, was phospholamban. Although the phosphorylation of phospholamban by PKC was activated by Ca²⁺, a component of this activity appeared to be independent of Ca²⁺. PKC-mediated phosphorylation of phospholamban was fully activated by 1 M Ca²⁺ whereas the Ca²⁺/calmodulin dependent kinase required concentrations in excess of 5 M Ca²⁺. In the in vitro system employed in these studies, the concentrations of either PKC or the catalytic subunit of PKA required to phosphorylate phospholamban were found to be similar. In addition, in the presence of a 15 kDa sarcolemmal-associated protein, which becomes phosphorylated upon activation of PKC in vivo, phosphorylation of phospholamban by PKC was unaffected. These results demonstrate that, although substrates for both subtypes are found in both junctional and free SR, PKC and PKC do not show differences in selectivity towards these substrates.Abbreviations Ca²⁺ free calcium - CaM kinase Ca²⁺/calmodulin-dependent protein kinase - DTT dithiothreitol - EDTA ethylenediaminetetraacetic acid - EGTA ethylene glycol bis(b-aminoethylether)-N,N,N,N-tetraacetic acid - FSR free sarcoplasmic reticulum - JSR junctional sarcoplasmic reticulum - PKC protein kinase C - PS phosphatidylserine - SDS sodium dodecyl sulfate - SAG 1-stearoyl-2-arachidonylglycerol - TPCK L-1-tosylamido-2-phenylethyl chloromethyl ketone - Tris/HCI tris(hydroxymethyl)aminomethane hydrochloride This work was supported by a grant (to S.K.) from the Heart and Stroke Foundation of B.C. and Yukon. The costs of publication of this article were defrayed in part by the payment of page charges This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.Recipient of a Studentship form the Heart and Stroke Foundation of Canada.     

A review of selected triassic to Early Cretaceous ferns

After becoming nearly extinct during the Permian, the ferns began a slow recovery during the Triassic as the climate of the earth moderated. As a result, a considerable number and variety were present and widely distributed during the Jurassic and Early Cretaceous. However, with the rapid expansion of the angiosperms during the Late Cretaceous, the ferns once again became reduced in variety and greatly restricted in distribution. Some of the Mesozoic ferns are rather primitive and obviously are closely related descendants of Paleozoic taxa. Such ferns are assigned mostly to the Marattiaceae, Guaireaceae, Osmundaceae, and Gleicheniaceae. The majority of the Mesozoic ferns, however, are distinctive and appear to have originated during that era. These fossil ferns generally fit into modern orders and families such as the Matoniaceae or the Dipteridaceae. In some cases, it is difficult to clearly distinguish some of the Mesozoic ferns from living genera. A portion was presented as an invited paper to the symposium: Evolution of pteridophytes and gymnosperms at the XV International Botanical Congress, Yokohama, Japan (1993).