PubMed Health⌕ Search

Biomedical subjects

K Melmon

Publications and source records attributed to K Melmon.

6 recordsLinked to original sources

Structured data management--the design and implementation of a web-based video archive prototype.

In response to the lack of readily available multimedia rich medical knowledge sources to support medical education and patient care, we designed and implemented a web-based video publishing platform. In order to promote the development of high-quality, up-to-date educational content, we have devised a scalable structure that allows online submissions and continuous updating of video and accompanying textual descriptions. Our goal is to enable experts in varied medical domains to collaborate in the construction of a video library using an intuitive web-based interface. Neurologists at Stanford built a well-annotated neurology video collection that initially emphasized childhood and adult movement disorders. The collection may be accessed either as a stand-alone resource or as part of the Stanford Skolar MD, an integrated online medical knowledge provider. This manuscript discusses the design framework and implementation details of structured media content development. We present examples illustrating media data collection, content indexing using UMLS concepts, media storage, and web presentation.

Abstracting and Indexing↗

Angiotensin II binding to human mononuclear cells.

Serum angiotensin converting enzyme activity is elevated in certain human granulomatous diseases. Angiotensin II modestly suppresses thymidine incorporation and augments gamma interferon production from human blood mononuclear cells. This suggests that angiotensin II may play an immunoregulatory role in human granulomatous inflammation. For this reason, the binding of angiotensin II to human peripheral blood mixed mononuclear cells, and to the human monocyte-like cell line, U-937, was studied. Angiotensin II binding to U-937 cells reveals a low level of saturable specific binding (Kd = 3 x 10(-10) M). However, binding to human cells is not easily reversible and is poorly inhibited in a competitive manner. In addition, the molecular integrity of the radioligand is not maintained following binding. Therefore, the definition of classical receptor binding cannot be fulfilled. Since binding is decreased by low temperatures and various metabolic inhibitors, it appears likely that endocytosis occurs, perhaps along with receptor binding. Angiotensin II or its breakdown products modulate the production of monocyte cAMP in spite of the inability to demonstrate classical cell surface receptors.

Angiotensin II↗

The four stereoisomers of a high potency congener of isoproterenol. Biological activity and the relationship between the native and the chemically inserted asymmetric carbon.

The RR isomer of a para-trifluoromethyl anilide congener of isoproterenol (PTFMA) had an affinity eighty and one hundred times higher than (-)isoproterenol for the beta receptor of turkey erythrocytes and of S49 cells respectively. This affinity was also much higher than that of +/- hydroxybenzyl isoproterenol (HBI) tested in the same experiments. The chemically inserted asymmetric carbon seemed to be as important as the native asymmetric carbon of the catecholamines in determining the binding affinity. Thus the RS and SR isomers demonstrated similar affinities in the turkey erythrocyte membranes as well as in the S49 lysed cells. The RR isomer had the lowest Kact in activation of adenylate cyclase in both beta receptor systems. The three most potent PTFMA isomers showed a Kact/Kd ratio which was higher than that of (-)isoproterenol or (+/-)HBI. It is therefore possible that the large substituent on the amino group in PTFMA, which greatly increases the binding affinity, is not as efficient in receptor activation. Yet the RR isomer had a Kact considerably lower than that of (-)isoproterenol in both of the beta receptor systems. The type of beta receptor of the turkey erythrocyte could be distinguished from that of the S49 cells by comparing the relative order of affinities of the RS and SR isomers and also by comparing (+/-)HBI with (-)isoproterenol. A labeled RR isomer of PTFMA could become most useful as an agonist ligand for beta receptors because of its very high binding affinity for both beta 1 and beta 2 receptors.

Adenylyl Cyclases↗

High potency congeners of isoproterenol. Binding to beta-adrenergic receptors, activation of adenylate cyclase and stimulation of intracellular cyclic AMP synthesis.

The potency of a p-toluide derivative and a p-trifluoromethyl derivative of isoproterenol on the beta1 receptor of turkey erythrocytes and on the beta2 receptor of S49 lymphoma cells was measured in comparison with isoproterenol. Binding assays showed that the p-trifluoromethyl derivative possessed an affinity for the receptor, which was two hundred times higher than that of isoproterenol, in the case of turkey erythrocytes, and sixty times higher in the case of the S49 cells. By measuring the Kact of adenylate cyclase, the activity of the p-trifluoromethyl derivative was thirty to forty times higher than that of isoproterenol for the turkey erythrocyte membrane as well as for the S49 lysed cells. In stimulation of intracellular cyclic AMP accumulation, the Kact showed that the p-trifluoromethyl derivative was forty and twenty times more active than isoproterenol in turkey erythrocytes and in S49 cells, respectively. The p-toluide derivative gave similar results. The superior affinity of the above isoproterenol congeners for both beta 1 and beta 2 adrenergic receptors makes these compounds excellent candidates for use as labeled agonist ligands in studies of beta receptors. The possibility is discussed that the relatively large substituent on the amino group of the catecholamine congeners might perhaps bind to lipids associated with the receptor.

Adenylyl Cyclases↗

The relation of faculty academic activity to financing sources in a department of medicine.

Academic medical departments confront important changes in funding sources and consequent pressure to change faculty activities. Valid information has often been lacking concerning the existing relations of faculty activity to funding sources. We examined those relations in the Stanford Department of Medicine through a combination of randomized observations of faculty and faculty self-reports over a period of one year. For an average 62-hour workweek, there was approximate consonance between types of activities and sources of salary support. Sensitivity analyses indicated that even sizable errors in self-reports would not have changed the outcomes substantially. Over 60 per cent of the activity involved "joint products," representing two or more categories of activity. There was wide variation in activities and fund sources between divisions. Per full-time faculty equivalent, research generated far more income than the most lucrative specialty practice; thus, at least in this type of department, attempts to compensate for lost research revenue by intensifying clinical practice will probably fail and undermine present research activities. The method of analysis used here may be useful in improving prospective planning by departments and by larger medical-policy bodies, particularly in the public sector.

Academic Medical Centers↗

Long-term digitalis therapy improves left ventricular function in heart failure.

To clarify the controversy regarding the benefits of long-term oral digoxin in the treatment of heart failure, we evaluated hemodynamics at rest and during exercise in nine patients in sinus rhythm with symptomatic heart failure. Patients were studied during long-term digoxin therapy, after withdrawal of the drug, and six hours after readministration. Upon withdrawal of digoxin, pulmonary capillary-wedge pressure increased from 21 +/- 8 to 29 +/- 10 mm Hg, and cardiac index decreased from 2.4 +/- 0.7 to 2.1 +/- 0.6 liters per minute per square meter of body-surface area, suggesting a deterioration in left ventricular function. In addition, heart rate tended to increase and stroke-work index, stroke-volume index, and radioangiographic ejection fraction decreased. Acute readministration restored the hemodynamic values to those observed during long-term digoxin therapy. The improvement in hemodynamics during long-term digoxin administration was also observed during exercise. This improvement demonstrated the value of long-term oral digoxin therapy in congestive heart failure.

Administration, Oral↗