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Biomedical subjects

T M Keahey

Publications and source records attributed to T M Keahey.

9 recordsLinked to original sources
PubMed1991

Analyses of microvascular permeability in response to mediators of immediate hypersensitivity.

Mediator-induced changes in microvascular permeability were studied in rodent skin. To monitor these changes, Evan's blue dye, iodinated rat albumin and IgG, and tritiated neutral dextran molecules having different molecular radii were used. After intradermal injections of serotonin, histamine, and bradykinin, the degree of radiolabeled tracer efflux was determined by measuring the extent of blueing and the level of radioactivity in skin biopsy specimens. Although the mediators varied in potency on a molar basis (serotonin greater than bradykinin greater than histamine), the efflux resulting from each was similar. Furthermore, kinetic studies revealed that each of these vasoactive agents caused a marked but transient increase in macromolecular permeability that lasted less than 30 minutes. To determine the pore size created and the effect of charge on the transudation of macromolecules into the interstitium, fractions of neutral [3H]dextrans with a known molecular size (average radii, 12 and 4.4 nm, respectively) were infused either singly or in combination with 125I-labeled rat albumin and/or IgG before intradermal injection of serotonin, histamine, bradykinin, or compound 48/80. Regardless of the mediator used, no differences could be demonstrated in macromolecular efflux, as indicated by either the molecular size of the charge of the tracer used. Thus, all mediators of immediate hypersensitivity reactions that were studied produce venular gaps greater than 12 nm in addition to displaying similar vasopermeable characteristics.

Animals↗
PubMed1990

The effects of intravenous endotoxin on various host-effector molecules.

To understand better the pathogenesis of gram-negative infections, we administered a single intravenous injection of Escherichia coli RE-2 endotoxin (4 ng/kg) to five normal volunteers and periodically measured various host-effector molecules in blood. All subjects had a significant (p less than 0.05) increase in temperature (maximum of 1.3 +/- 0.1 degrees C at 4 hours) and white blood cell count (maximum of 7700 +/- 1800 cells per cubic millimeters at 8 hours). Thymocyte costimulatory activity in blood was markedly increased 2 hours after endotoxin administration but returned to baseline at 4 hours. Blood cortisol and beta-endorphin levels paralleled each other, peaking 4 hours after endotoxin (mean increases of 21 +/- 14 micrograms/dl and p less than 0.01; 18.6 +/- 5.9 pg/ml and p less than 0.05, respectively) and returning to baseline at 8 hours. Blood histamine levels did not significantly change at any time point after endotoxin administration. Since thymocyte costimulatory activity was the first of the measured parameters to achieve peak blood levels, we suggest that endotoxin-induced increases in various cytokines may contribute to the increases in the other measured parameters and thereby play a significant role in the pathogenesis of gram-negative infections.

Adult↗
PubMed1989

Dissociation of cutaneous vascular permeability and the development of cutaneous late-phase allergic reactions.

Cutaneous late-phase allergic reactions (LPR) are characterized by an early, immediate hypersensitivity whealing reaction followed by persistent, localized induration that peaks 6 to 8 hours later. In this study we used rodents to examine the relationship between vascular permeability (VP) and induration during LPR. Efflux of macromolecular tracers from the vasculature into skin was measured with the use of radiolabeled albumin and neutral dextran tracers having large molecular radii. To induce LPR immunologically, we used either intradermal injections of antirat IgE or passive cutaneous sensitization with IgE antidinitrophenyl followed 24 hours later by intravenous injection of albumin-dinitrophenyl. [125I]albumin and [3H]dextran tracers were injected intravenously before and at various intervals after the induction of LPR. Although a marked increase in VP occurred within the first 30 minutes after induction of mast cell degranulation, analysis of radiolabeled tracer accumulation at 2, 4, 8, and 24 hours failed to demonstrate any further increase in VP. These findings indicate that the induration observed in rodent LPR is not associated with increased VP beyond the immediate hypersensitivity stage and suggest that impairment of lymphatic drainage, cellular infiltration, and/or fibrin deposition are contributing factors.

Animals↗
PubMed1988

A case study on the induction of clinical tolerance in cold urticaria.

The mechanism(s) by which repeated cold challenge in a patient with idiopathic acquired cold urticaria resulted in the induction of clinical tolerance to cold stimuli was studied. Plasma histamine levels, mast cell ultrastructure, and the cutaneous response to intradermal injections of morphine, histamine, and substance P were examined before and after the induction of tolerance. Plasma histamine levels draining cold-challenged, clinically tolerant skin were markedly diminished compared to histamine levels obtained during cold-induced angioedema. Furthermore, electronmicroscopy of skin samples taken from tolerant skin after cold challenge revealed intact, largely normal appearing mast cells. Intradermal injection of mast cell secretagogues and vasoactive agonists into normal and tolerant skin sites resulted in similar whealing responses. Thus, these studies suggest that the state of clinical tolerance to cold stimuli is due neither to mast cell-mediator depletion or tachyphylaxis of the cutaneous vasculature to vasoactive agonists. It appears likely that tolerance may be due to the induction of a specific state of unresponsiveness of mast cells to cold stimuli or possibly to depletion of a cold-induced cutaneous antigen capable of triggering mast cell degranulation.

Adaptation, Physiological↗
PubMed1987

Delayed vibratory angioedema: insights into pathophysiologic mechanisms.

Plasma histamine levels and the histologic, electronmicroscopic, and immunofluorescent analysis of skin biopsy specimens were examined during the development of vibration-induced angioedema in two patients. The reactions to vibration in these patients were characterized by (1) clinical angioedema peaking 4 to 6 hours after challenge, (2) evidence of mast cell degranulation as indicated biochemically by an early and late increase in plasma histamine and histologically by exocytosis of mast cell granules, (3) a progressive infiltration of inflammatory cells, coinciding with the peak clinical reaction, and (4) an absence of the immunoreactants IgG, IgM, IgA, C3, and fibrinogen. The reactions in both patients were morphologically and biochemically similar to the cutaneous late-phase allergic reactions that occur after IgE-mediated, antigen-provoked mast cell degranulation. These studies suggest that vibratory angioedema is a manifestation of mast cell-induced cutaneous late-phase reactions.

Adult↗
PubMed1986

Exercise-induced anaphylactic syndromes. Insights into diagnostic and pathophysiologic features.

To differentiate the diagnoses of exercise-induced anaphylaxis and cholinergic urticaria/anaphylaxis, we developed reproducible diagnostic provocative challenges. The data derived from the study of two representative patients, one with cholinergic urticaria and the other with exercise-induced anaphylaxis, suggest approaches to distinguishing these diagnoses. After specific exercise challenges, both patients developed symptoms consistent with anaphylaxis and had associated increases in plasma histamine levels. After passive heat challenges inducing increases in core body temperature more than 0.7 degrees C, only the patient with cholinergic urticaria developed anaphylactic symptoms and had a rise in the plasma histamine level. Neither patient developed symptoms of anaphylaxis when core body temperatures were increased after administration of intravenous endotoxin. Thus, passive heat challenges are extremely valuable in differentiating these two exercise-related syndromes. Although not important in exercise-induced anaphylaxis, specific thermoregulatory mechanisms appear to play an intricate part in the pathophysiology of cholinergic urticaria/anaphylaxis.

Adult↗
PubMed1985

The pathogenesis of urticaria.

The pathogenesis of urticaria cannot be entirely ascribed to any one mechanism although many "etiologic" or initiating factors have been defined over the years. The author presents a general overview of major effector pathways that may lead to urticarial reactions. Emphasis is placed on the role of the mast cell and the various mediators of inflammation as they apply to the pathobiologic events defining the urticarial tissue reaction.

Arachidonic Acid↗