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Biomedical subjects

R Bayer

Publications and source records attributed to R Bayer.

At least 91 records · Page 5Linked to original sources

Filterability of human erythrocytes--drug induced prevention of aging in vitro.

Using a computer assisted filtration system, 6 drugs (bencyclane, moxaverine, naftidrofuryl, pentoxyfylline, vincamine, vinpocetine) were tested (versus placebo) to improve filterability of in vitro aged red blood cells (RBC). Up to a concentration of 1 x 10(-7) mol/l all drugs significantly inhibit in vitro aging, indicating an improved of action is still present in RBC incubated with 10 x 10(-8) mol/l naftidrofuryl and pentoxifylline but, comparison in between the compounds reveals no significant difference of action. The data presented confirm the results on the beneficial action of these drugs presented by others. However, direct comparison shows only minor differences in drug potency.

Adult↗

Demonstration that lysine-501 of the alpha polypeptide of native sodium and potassium ion activated adenosinetriphosphatase is located on its cytoplasmic surface.

Evidence that the peptide HLLVMKGAPER, which can be released from intact sodium and potassium ion activated adenosinetriphosphatase by tryptic digestion, is located on the cytoplasmic surface of the native enzyme has been obtained. An immunoadsorbent directed against the carboxy-terminal sequence of this tryptic peptide has been constructed. The peptide KGAPER was synthesized by solid-phase techniques. Antibodies against the sequence -GAPER were purified by immunoadsorption, using the synthetic peptide attached to agarose beads. These antibodies, in turn, were coupled to agarose beads to produce an immunoadsorbent. Sealed, right-side-out vesicles, prepared from canine kidneys, were labeled with pyridoxal phosphate and sodium [3H]borohydride in the absence or presence of saponin, respectively. A tryptic digest of these labeled vesicles was passed over the immunoadsorbent. Large increases in the incorporation of radioactivity into the peptides bound by the immunoadsorbent were observed in the digests obtained from the vesicles exposed to saponin. From the results of several control experiments examining the labeling reaction as applied to these vesicles, it could be concluded that this increase in incorporation resulted only from the access that the reagents gained to the inside of the vesicles in the presence of saponin and that the increase in the extent of modification was due to the cytoplasmic disposition of this segment in the native enzyme.

Amino Acid Sequence↗

Fendiline: a review of its basic pharmacological and clinical properties.

Fendiline is an anti-anginal agent for the treatment of coronary heart disease. Together with other diphenylalkylamines it is sub-classified in the group of lipophilic calcium antagonists. It binds to the calcium channel and to calmodulin with rather similar affinities. Pharmaco-dynamically, it exerts the typical calcium as well as calmodulin antagonistic actions: inhibition of the transmembrane calcium current, smooth muscle relaxation, negative inotropism, cardioprotection, inhibition of calmodulin-activated myosin light-chain kinase and phosphodiesterase. Pharmacokinetics reveal slow onset of action and a long half-life. The anti-anginal and anti-ischaemic efficacy of fendiline has been proven in several placebo-controlled, double-blind trials. It does not interfere with digoxin therapy. Direct comparison with other calcium antagonists by means of controlled studies revealed that its potency is at least equal to that of nifedipine but, in contrast to nifedipine, verapamil, and diltiazem, its anti-anginal action increases during chronic therapy, reaching a steady state of action after 2 to 3 weeks. In addition, the anti-ischaemic and anti-anginal potency is about equal to that of isosorbide dinitrate but fendiline has the advantage of lacking tolerance development. Nevertheless, the data presented indicate that a combination of fendiline with low doses of ISDN may be beneficial. Adverse cardiac and haemodynamic actions, such as increase or decrease in heart rate, disturbance of AV nodal conduction, impairment of cardiac contractile performance or considerable decrease in arterial pressure in hypotensives and normotensives, are lacking.

Fendiline↗

Comparative QSAR studies on vasodilatory and negative inotropic properties of ring-varied verapamil congeners.

In the present study quantitative structure-activity relationships (QSAR) for the vasodilator properties of verapamil have been derived: Potency of ring-varied verapamil congeners on the phasic and tonic component of K+-contractures has been measured in aortic rings of the cat. Potency of verapamil derivatives on the phasic component significantly correlates with lipophilic properties of the compounds. Inhibition of the tonic component best correlates with a parameter combination of steric and electronic properties (MV, sigma). These results contrast with investigations with dihydropyridine derivatives where identical SAR have been found for both response components. Furthermore, SAR analyses yield disparate results in comparison to investigations in heart muscle where primarily electronic and secondarily steric parameters best explain the potency of verapamil derivatives. The postulate of chemically differing binding sites for verapamil congeners in heart and smooth muscle is substantiated by calculating binding energies to the hypothetical binding site arginine. While negative inotropic potency of verapamil derivatives significantly correlates with binding energy to the model binding site arginine, this correlation fails in case of aortic ring. These results obtained for verapamil congeners contrast with observations with dihydropyridine derivatives where the chemistry of binding sites in heart and smooth muscle seems to be identical.

Animals↗

HIV antibody screening. An ethical framework for evaluating proposed programs.

We believe that the greatest hope for stopping the spread of HIV infection lies in the voluntary cooperation of those at higher risk--their willingness to undergo testing and to alter their personal behavior and goals in the interests of the community. But we can expect this voluntary cooperation--in some cases, sacrifice--only if the legitimate interests of these groups and individuals in being protected from discrimination are heeded by legislators, professionals, and the public. Yet voluntary testing is not enough. We must proceed with vigorous research and educational efforts to eliminate both the scourge of AIDS and the social havoc that has accompanied it.

Acquired Immunodeficiency Syndrome↗

Biological monitoring in the workplace: ethical issues.

This paper addresses the following questions concerning medical surveillance and the worker's relationship to management: Do workers have a moral obligation to participate in workplace screening and monitoring when undertaken to enhance the interests of occupational health? What conditions would be necessary to establish the existence of such a moral obligation? If such an obligation were to be established, ought it be satisfied solely on the basis of voluntary collaboration? Is compulsory participation in monitoring and screening ever morally justified? Should the principle of informed voluntary consent that obtains in medical research apply to workplace investigations that involve potentially invasive procedures and risks to privacy?

Civil Rights↗

Reconstitution of M13 bacteriophage coat protein. A new strategy to analyze configuration of the protein in the membrane.

The configuration of M13 bacteriophage coat protein in a model membrane was analyzed using protease digestion followed by gel permeation chromatography on Fractogel TSK in formic acid/ethanol. Important information is contained in the chromatographic patterns of the membrane-bound fragments, as well as of the fragments released by the digestion. A new reconstitution was thereby developed which involves adding a small volume of a concentrated solution of cholate-solubilized coat protein to preformed vesicles (with the amount of detergent added being less than that required to solubilize the vesicles), freezing in liquid nitrogen, thawing, followed by dialysis to remove excess detergent. The coat protein is incorporated with high efficiency (95 percent) making subsequent fractionation unnecessary. In addition, the incorporated protein is not aggregated, and is incorporated with most molecules spanning the membrane, oriented in the same manner as in vivo (N-terminus outwards). Two previously described reconstitutions, using sonication or cholate dialysis, are analyzed and found to be less satisfactory.

Amino Acid Sequence↗

Neurosis, psychodynamics, and DSM-III. A history of the controversy.

The adoption of DSM-III by the American Psychiatric Association has been viewed as representing a major advance for psychiatry and as an indication of the emergence of a broad professional consensus on diagnostic issues. The process of drafting the new manual was not, however, free of conflict. This article presents a narrative account of the controversies over the role of psychodynamic formulations in DSM-III and the more focused, though sharply contested, symbolic dispute over the inclusion of neurosis in the nomenclature. It traces the evolution of these disputes and focuses on the interplay of scientific and political considerations as psychiatrists committed to differing professional and therapeutic paradigms confronted each other for more than two years as the profession sought to develop a new manual that would improve the level of reliability of psychiatric diagnosis.

Attitude of Health Personnel↗

Medicare reform: social and ethical perspectives.

Despite Medicare's success as a social program, its future is in question because of the program's enormous costs. Because the issue of Medicare reform has been forced upon us at this juncture by a crisis of finance rather than by the long-standing inequities in the present system of paying for the health care of the elderly, questions about how best to secure its fiscal integrity have seized the attention of the public. Yet, such questions are hard to contain; they force an examination of broader and more fundamental issues. In this article, we examine the validity of the ultimate moral and social rationales for continuing Medicare in something approximating its present form; the legitimacy of a social entitlement program that is age- rather than means-based; the implications for the future of health care reform if significant changes were to be made in the Medicare program and its underlying rationale; and the possibility that changes in that program may jeopardize the chances for a more rational, just, and systematic approach to the provision of health care to all Americans.

Aged↗

The limits of the ledger in public health promotion.

Recent efforts to support state regulation of risky behavior like cigarette smoking, alcohol consumption, driving without seatbelts and riding motorcycles without helmets have focused on economic justifications--the costs to society of the consequences of these activities. However, opponents have successfully argued that the economic burdens of regulation outweigh the social benefits. To reduce the toll on society of these behaviors, we need justification for regulation that asserts the moral primacy of health and the well-being of the community.

Accident Prevention↗

The importance of drug ionization for the action of calcium-antagonists and related compounds.

pK-Values of Ca-antagonists and related cardiodepressive drugs have been measured by means of potentiometric microtitration. The presumable active species for all compounds investigated is the protonated molecule except nifedipine. This drug must exert its action via the uncharged form. From these results it could be concluded that protonization of ionizable nitrogen is one molecular prerequisite for voltage- or frequency dependence of action. Drug ionization does not correlate with the negative inotropic potency of the compounds investigated.

Calcium Channel Blockers↗