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Biomedical subjects

I Cohen

Publications and source records attributed to I Cohen.

At least 379 records · Page 21Linked to original sources

The steady state TTX-sensitive ("window") sodium current in cardiac Purkinje fibres.

Voltage clamp experiments on isolated sheep Purkinje fibres showed an increase of the steady state outward membrane current, over the potential range -65mV to -15 mV, in the presence of tetrodotoxin (TTX, 3.10(-5 M). This "window" current is considered to be the steady state component of the fast sodium current (INa), resulting from the crossover of the activation and inactivation curves which govern the opening of the sodium channel. TTX had no significant effect on the reversal potential, activation curve, kinetics or instantaneous I-V relationship of the pacemaker current IK2. The window found in these experiments extends to potentials well into the range of the action potential plateau. Consequently small changes of the steady state INa might have large effects on the action potential duration. The effects of TTX and local anaesthetics are discussed in this context.

Action Potentials↗

Kinetics and absolute bioavailability of atenolol.

Twelve healthy volunteers received four single doses of atenolol (25-, 50-, and 100-mg oral solutions and a 50-mg intravenous infusion), each dose separated by at least one week. Blood and urine assayed for atenolol by a high pressure liquid chromatography (HPLC) method. Kinetic analysis of the intravenous data indicates a three-compartment model with elimination from the central compartment. The mean (+/- SD) terminal elimination half-life is 6.06 +/- 2.02 hr, the mean volume of the central compartment is 0.173 L/kg, and 94.1 +/- 8.0% of the intravenous dose is excreted in the urine. The mean value of the plasma clearance is 10.7 +/- 1.27 L/hr and of the renal plasma clearance, 10.4 +/- 1.14 L/hr. The mean absolute bioavailability for the 25-, 50-, and 100-mg oral doses is 0.52 +/- 0.18, 0.54 +/- 0.12, and 0.58 +/- 0.16, respectively. The maximum plasma concentration varies as a linear function of dose. Time to mean maximum plasma concentration (3.0 hr) and the time for half of the bioavailable dose to be absorbed (2.0 hr) do not differ significantly with dose. The mean renal plasma clearance after oral doses (9.49 +/- 1.6 L/hr) is in the same range as renal clearance after intravenous doses.

Adult↗

Giant cell tumor of the ethmoid sinuses: diagnostic dilemma.

Tumors originating in the ethmoid sinuses are rare. Carcinomas of the ethmoid sinus, for example, comprise only 2-3% of all head and neck malignancies. Of this small sample, the ethmoid sinuses as the primary site varies from 5-30%. This paper presents the 14th documented case of giant cell tumor originating in the ethmoid sinuses. The pathology became the diagnostic dilemma; the case was originally diagnosed as an angiofibroma, later a reparative granuloma, and finally accepted as a giant cell tumor. The rationale for diagnosis and therapy is discussed.

Adult↗

Cycles of agglutination-disagglutination induced by ristocetin in thrombasthenic platelets.

An oscillatory pattern of platelet agglutination-disagglutination in response to Ristocetin (R) at narrow concentration ranges was observed in citrated platelet rich plasma (PRP) of 10 patients with Glanzmann's thrombasthenia. The cyclic pattern decreased in intensity over time, was reproducible, and was not pH dependent. Formalin-fixed thrombasthenic platelets agglutinated with R but did not show a cyclic pattern. Incubation with 2.5 microM ADP inhibited R oscillation response, but small increases in R dose overcame this inhibition. The addition of ATP or creatine phosphate/creatine phosphokinase to thrombasthenic platelets inhibited by ADP restored the R oscillation response. In the platelets of a single patient, intracellular levels of ADP and ATP were shown to diminish during an oscillation response to R. There was an increase in AMP levels during the same period of time. The changes in these three intracellular nucleotides were gradual over time and did not vary with phases of the oscillation. Acetyl salicylic acid (ASA), at concentrations shown to block cyclooxygenase activity in control platelets, enabled thrombasthenic platelets to respond to R with full agglutination without oscillations. Lower concentrations of ASA in the PRP gave a return of the oscillation response. Our data suggest that the disagglutination phase of the R response of thrombasthenic platelets is not a function of the known glycoprotein membrane defect, but depends on materials originating in the platelet whose release is blocked by ASA.

Adenosine Diphosphate↗

Action of salicylate ions on the electrical properties of sheep cardiac Purkinje fibres.

1. In sheep Purkinje fibre preparations, salicylate ions produce reversible changes in resting potential and in action potential duration. In most preparations these effects resemble those produced by -ow extracellular K concentration: the resting potential first increases and then decreases, the action potential is prolonged and eventually, low potential oscillations occur in the plateau range. In a few preparations, action potential shortening occurs. 2. The threshold current for initiating action potentials by an intracellular electrode is reversibly increased by salicylate. 3. The activation curve, soo(Em), for the pace-maker K current, iK2, shifted in a hyperpolarizing direction. The magnitude of the shift is about -5 mV in 5 mM-salicylate and -30 mV in 50 mM-salicylate. 4. The apparent reversal potential for iK2 is shifted in a negative direction. The magnitude of this shift at a given salicylate concent;ation varies with the K concentration. In an extracellular K concentration of 2.7 mM an average shift of -18 mV occurs in 10 mM-salicylate; in 8 mM, the average shift is only -1 mV. 5. It is proposed that most of these effects may be produced by an increase in surface negative potential produced by the binding of salicylate to the cell membrane. This would produce the hyperpolarizing shift of activation curves for ionic current and, by increasing surface K activity, may lead to stimulation of the Na-K pump to produce an increase in the K gradient across the cell membrane.

Action Potentials↗

The interaction of ouabain and salicylate on sheep cardiac muscle.

1. The action potential duration in sheep ventricular fibres is rapidly diminished on exposure to 10(-6) M-ouabain. However, if 10--20 mM-sodium salicylate is added to the ouabain solution, glycoside-induced shortening is prevented, and a substantial increase in duration then occurs. Sodium salicylate also reverses the shortening effect of ouabain if applied after the glycoside has been allowed to act alone. 2. Sodium salicylate alone produces a much smaller prolongation than in the presence of ouabain. Alone and in the presence of ouabain it eventually increases the threshold and produces inexcitability. 3. Three other surface charge agents have been compared with salicylate: aminonaphthalene sulphonate, sodium dodecylsulphate and salicylamide, were unable to counter the actions of ouabain at the concentrations used. Since they also produced no changes in excitability it is likely that they did not bind significantly to the cell membrane. 4. In Purkinje fibres the reversal potential for the pacemaker current, iK2, is initially shifted in a negative direction in the presence of 10(-6) M-ouabain and 10 mM-salicylate instead of the positive shift expected with ouabain alone at this concentration. 5. In guinea-pig ventricle, salicylate alone reduces the duration of the action potential. This effect is rapidly reversible. Toxic levels of ouabain also reduce the action potential duration but this effect takes several hours to reverse. By contrast, the effects of salicylate and ouabain applied together are readily reversible. 6. It is suggested that the mechanism of these effects may depend on the ability of a surface negative charge agent like salicylate to increase the surface K+ concentration at the membrane and so protect the sodium-potassium pump from inhibition by large doses of ouabain.

Action Potentials↗

Stress and wound healing.

An experiment was performed to compare the effects of stressors--cold, heat and noise--on primary wound activity (i.e., wound closure in the first 24 h after wound infliction) and on rate of healing in mice. A significant correlation was found between reduced primary wound activity and a faster rate of healing. Conversely, a correlation was found between relatively greater primary wound activity and a slower rate of healing. A possible explanation of this correlation is a compensatory mechanism inherent to the skin healing process. This mechanism is visualized as (1) stress exposure affecting the skin by (a) causing it to become thinner and tauter and (b) causing it to have less elastic recoil; therefore, (2) when a square wound is produced in stressed skin, (a) the wound does not recoil readily or gapes soon after cutting and (b) a longer wound perimeter results. Because there is evidence that rate of healing is governed by cells on the wound perimeter, the greater the perimeter, the greater the number of cells that will undergo rapid mitosis and the faster will be the rate of healing. Therefore, stressed skin will heal at a faster rate, compensating for the loss of elasticity and cellular depletion caused by stress. This study is of interest to anthropology because it deals with dynamic adaptation, trying to grasp the meaning of the elusive endocrine interface between environmental stimulation and a measurable physical entity like healing. This work may have revealed a functional complex that is common to the healing of all mammalian skin, whereby retarding effects of stress on the healing process are obviated.

Adaptation, Physiological↗

Role of endothelial injury and platelets in atherogenesis.

Endothelial cell injury is usually followed by the adherence and activation of platelets to exposed subendothelial surfaces. This is then followed by intimal smooth muscle cell proliferation and formation of connective tissue matrix by the smooth muscle cells through synthesis and secretion of collagen, elastic fiber proteins, and proteoglycans, and intracellular and extracellular lipid accumulation. Platelet activation is associated with morphological transformations which lead eventually to the "release reaction". A mitogenic factor has been recently recognized among the substances released from platelets and it may play a crucial role in promoting the intimal proliferation of smooth muscle cells which characterize atherosclerotic plaques.

Animals↗

The contractile system of blood platelets and its function.

The various manifestations of platelet activation are derived from a reorganization of components of the contractile and microtubular systems. The controversial initial stages of excitation-contraction coupling in platelets lead to the release of calcium from the dense tubular system, the morphological counterpart of the muscle sarcotubular closed vesicles. Calcium triggers the actin-myosin interaction and the developing force, possibly together with a local increase of the cation concentration, may cause the collapse of the microtubular ring and its reappearance in the forming long pseudopodia. Actin-myosin interaction is modulated by several factors among which tropomyosin-troponin, responsible for the calcium-sensitivity of contractile processes, and phosphorylation of one of the myosin light chains. Platelet actin is anchored to the membrane and its sliding towards the short myosin filaments may form the basis for platelet shape change. Platelet alpha-actinin and actin-binding protein are able to aggregate actin into an impressive gel. Therefore, the contractile proteins seem to have a double role in controlling the consistency of the cytoplasmic gel on the one hand, and the contractile manifestations related to motility on the other hand. One of the most important features of the 'contracted' platelet is the rigidity of the pseudopodia brought about by the 'gelification' of actin filaments and the presence of microtubules. A new model for clot contraction is proposed, based on the rigidity of the long spiky pseudopodia and on the motile properties of platelets. While migrating towards each other, the interlocking pseudopodia from different platelets adhere to the polymerizing fibrin, compressing the fibrin nets in their pathway. Since the anchoring of contractile fibers to membranes is crucial for the platelet contractile manifestations, the integrity of the membrane structure should be considered in the study of pathological aspects of platelet function.

Actins↗

[Larsen's syndrome].

Explore the source record for details and available documents.

Abnormalities, Multiple↗

Changes in serum electrolyte levels during marathon running.

Serum electrolytes were measured in 18 well-trained, experienced long-distance runners before and after a standard marathon run (42 km), during which they ingested no electrolytes. Their sweat losses and water deficits after completion of the marathon were also measured. In 12 of the subjects, the percentage change in plasma volume and in total circulating plasma electrolytes was determined. There was a highly significant fall in serum magnesium concentration, with an increase in both potassium and sodium levels. Changes in total circulating plasma sodium and chloride were closely correlated with alterations in plasma volume. On the basis of these observations, it is recommended that athletes drink an augmented volume of fluid during marathon running, irrespective of the prevailing weather conditions. Supplementation of potassium and magnesium is contraindicated during long-distance running. Salt intake is unnecessary during races over the standard marathon distance. Subjective evidence for glucose supplementation is presented.

Adult↗