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T Gordon

Publications and source records attributed to T Gordon.

At least 145 records · Page 8Linked to original sources
PubMed1989

Comparison of the effects of botulinum toxin in adult and neonatal rats: neuromuscular blockade and toxicity.

A single dose of botulinum toxin (BoTX) was injected subcutaneously to induce neuromuscular blockade in the triceps surae muscles of the hindlimbs of neonatal and adult rats. The efficacy of the toxin in producing complete neuromuscular blockade of the lower limb muscles, assessed by blockade of (a) postural and flexor reflexes and (b) muscle contraction in response to nerve stimulation, was dose dependent at all ages over a BoTX dose range of 10-60 ng/kg. However, BoTX was dramatically more toxic in adult animals resulting in a decline in body weight and lethal consequences in 25% of adult animals 1 week after administration of BoTX doses as low as 40 ng/kg. In contrast, neonatal animals, given the same dosage, continued to grow and no mortalities were observed. The differences in toxicity of BoTX in adult and neonatal rats are readily accounted for by the short duration of effect in the younger animals, which, in turn, is probably the result of more rapid generation of new and functional nerve terminals.

Aging↗
PubMed1989

Postnatal development of adrenergic responsiveness in the rabbit heart.

It is uncertain how changes in the beta-adrenoceptor population influence the contractility of developing heart. To resolve this we have examined postnatal developmental changes in the adrenergic responsiveness of the rabbit heart. The inotropic effect of isoproterenol on isolated left ventricular papillary muscles from rabbits aged 3, 21, and 90 days was compared with the relative number of beta-adrenoceptors at each age measured using [3H]dihydroalprenolol ([3H]DHA) as the specific ligand. The maximum tension developed in response to isoproterenol increases from 37 +/- 7 to 175 +/- 33% above control twitch tension between 3 and 21 days of age; this is followed by a decrease to 68 +/- 12% in the young adult. During this period of development, there is a decline in EC50 towards increased sensitivity. These differences are partially accounted for by an increase in the numbers of specific [3H]DHA binding sites from 17.3 +/- 2.3 to 56.6 +/- 9.9 fmol/mg wet tissue weight from 3 to 21 days, and a subsequent decrease to 32 +/- 4.5 fmol/mg tissue in the young adult. The proportionally larger increase in contractility compared with the number of beta-adrenoceptor binding sites during the first 3 weeks of life is discussed in terms of the developmental changes in the efficacy of coupling between receptor occupancy and contraction.

Aging↗
PubMed1989

Epithelium removal alters responsiveness of guinea pig trachea to substance P.

Removal of epithelium from mammalian tracheae has been shown to enhance responsiveness to a variety of contractile and relaxant agents. One of the most dramatic shifts reported has been for guinea pig tracheal tissue denuded of epithelium and treated with substance P. We investigated whether this shift in responsiveness was because of 1) removal of an epithelium-associated enzyme, neutral endopeptidase, which degrades substance P and 2) loss of an epithelium-derived noncyclooxygenase relaxant factor. Using a muscle bath preparation we performed concentration-response curves with substance P and acetylcholine on indomethacin-treated tissues with and without intact epithelium and with and without pretreatment with the neutral endopeptidase inhibitor, phosphoramidon. Epithelium removal potentiated the mean agonist concentration calculated to causes 30% of the maximal contractile response by 148-fold for substance P and by 7-fold for acetylcholine. Phosphoramidon potentiated the contractile response to substance P, but not to acetylcholine, by both the epithelium-intact and denuded tissues (P less than 0.05). However, the degree of enhancement by phosphoramidon was much greater in the intact tissues. With phosphoramidon treatment, therefore, the difference in responsiveness to substance P between the intact and denuded tissues was reduced from 148-fold to 18-fold. This effect of phosphoramidon suggests that the hyperresponsiveness to substance P of epithelium-denuded airway tissue is largely because of removal of neutral endopeptidase. Because all tissues were treated with indomethacin, the leftward shifts in substance P and in acetylcholine responsiveness induced by epithelium removal further suggest that an epithelium-derived noncyclooxygenase factor other than neutral endopeptidase also modulates the contractile response to substance P and to acetylcholine.

Acetylcholine↗
PubMed1989

Evaluation of syncope from head and neck cancer.

Five patients suffering from recurrent syncope in association with metastatic squamous cell carcinoma of the head and neck were examined. Two patients had exhaustive diagnostic work-up for syncope, which eventually disclosed previously undiagnosed, recurrent squamous cell carcinoma. Case reports describe glossopharyngeal neuralgia, a well recognized cause of syncope in the head and neck cancer patient, characterized by acute unilateral head or neck pain preceding each syncopal episode. The literature on the diagnosis of syncope is reviewed, and the syncopal mechanisms unique to the head and neck cancer patient are analyzed and discussed. A diagnostic approach to syncope in head and neck cancer is proposed.

Carbamazepine↗
PubMed1989

Potential bronchoconstrictor stimuli in acid fog.

Acid fog is complex and contains multiple stimuli that may be capable of inducing bronchoconstriction. These stimuli include sulfuric and niric acids, the principal inorganic acids present; sulfites, formed in the atmosphere as a reaction product of sulfur dioxide and water droplets; fog water itself, a hypoosmolar aerosol; the organic acid hydroxymethanesulfonate, the bisulfite adduct of formaldehyde; and gaseous pollutants, e.g., sulfur dioxide, oxides of nitrogen, ozone. Given this complexity, evaluation of the respiratory health effects of naturally occurring acid fog requires assessment of the bronchoconstrictor potency of each component stimulus and possible interactions among these stimuli. We summarize the results of three studies that involve characterization of the bronchoconstrictor potency of acid fog stimuli and/or their interaction in subjects with asthma. The results of the first study indicate that titratable acidity appears to be a more important stimulus to bronchoconstriction than is pH. The results of the second study demonstrate that sulfite species are capable of inducing bronchoconstriction, especially when inhaled at acid pH. The results of the third study suggest that acidity can potentiate hypoosmolar fog-induced bronchoconstriction.

Acid Rain↗
PubMed1988

Comparison of injury and development in the neuromuscular system.

Comparisons of development and regeneration have suggested that axotomized motoneurons and denervated muscles undergo dedifferentiation to an embryonic state with recovery of adult properties after reinnervation. Using electrophysiological and radioligand-binding techniques to monitor axonal size and numbers of extrajunctional acetylcholine receptors in axotomized motoneurons and denervated muscles respectively, we have demonstrated that this dedifferentiation is limited. We suggest that this limited dedifferentiation may be adaptive for survival, regeneration and reinnervation. Correlative physiological and histochemical studies of reinnervated motor units in cat and rat hindlimb muscles show that the processes of regeneration and reinnervation differ in a number of fundamental ways from developmental processes of axonal growth and muscle innervation. Enlargement of motor units after partial nerve injuries does not appear to be limited to the size of the neonatal motor unit as originally suggested but may be influenced by factors operating at the level of axonal branching. Regeneration after complete and partial nerve injuries is a random process in contrast to the specific nature of the innervation of targets during development. Regenerating axons frequently fail to make connections with their original muscles and newly reinnervated motor units contain muscle fibres which formerly belonged to several different motor units. Despite this misdirection of regenerating nerve fibres, neuromuscular plasticity restores neuromuscular properties to the extent that these are appropriate at the single motor unit level for the gradation of force by the orderly recruitment of units during movement.

Animals↗
PubMed1988

Comparison of force and stiffness in normal and dystrophic mouse muscles.

Isometric force and stiffness of fast- and slow-twitch muscles of affected and normal mice of the 129/ReJ dy/dy strain were studied at rest and during active contraction at a variety of lengths. Dystrophic muscles developed less force in response to stimulation, but the resting stiffness was not reduced as much, particularly at long muscle lengths. This is consistent with the replacement of muscle fibers by connective tissue that is considerably less elastic. When second and third stimuli are superimposed on the rising phase of a twitch in a normal muscle, a less-than-linear summation of force and stiffness generation (early depression) is followed by a more-than-linear summation (later facilitation). Dystrophic muscles showed a smaller early depression and a greater later facilitation of force and active muscle stiffness. Many of these phenomena can be predicted from a simple model of Ca2+ release and binding to troponin.

Animals↗
PubMed1988

Surgical unit time utilization review: resource utilization and management implications.

As health care providers seek ways to reduce the cost of health care services, hospital operating rooms (ORs) have been identified as potential areas for cost reduction efforts. Cost containment efforts which have shifted significant portions of the inpatient population to ambulatory areas have resulted in an inpatient population which is sicker and more procedure-intensive. Efficient management of operating rooms has assumed even greater importance in this environment. Inefficient or inaccurate scheduling of OR time often results in delays of surgery or cancellations of procedures, which are costly to the patient and the hospital. Approaches to efficient use of ORs include computerized scheduling, utilization monitoring, and refinement of scheduling policies and procedures. In the absence of commercially available software to meet operating room management information needs, Johns Hopkins developed its own system in 1983. This software provides detailed information for daily OR management and long-term planning. The computerized operating room scheduling and monitoring system is described in this article and an operational measure of scheduling accuracy is proposed. Suggestions are made for incorporating this measure into planning and allocation decisions.

Appointments and Schedules↗
PubMed1988

Arachidonic acid metabolites do not mediate toluene diisocyanate-induced airway hyperresponsiveness in guinea pigs.

Arachidonic acid metabolites have previously been demonstrated to mediate the airway hyperresponsiveness observed in guinea pigs and dogs after exposure to ozone. Guinea pigs were treated with indomethacin (a cyclooxygenase inhibitor), U-60,257 (piriprost, a 5-lipoxygenase inhibitor), or BW775c (a lipoxygenase and cyclooxygenase inhibitor) and exposed to air or 3 ppm TDI. Airway responsiveness to acetylcholine aerosol was examined 2 h after exposure. In control animals, the provocative concentration of acetylcholine which caused a 200% increase in pulmonary resistance over baseline (PC200) was significantly less (p less than 0.05) after exposure to TDI (8.6 +/- 2.0 mg/ml, geometric mean + geometric SE, n = 10) than after exposure to air (23.9 + 2.5 mg/ml, n = 14). The airway responsiveness to acetylcholine in animals treated with indomethacin or piriprost and exposed to TDI was not different from that of control animals exposed to TDI. Treatment with BW755c enhanced the airway hyperresponsiveness observed in animals exposed to TDI without altering the PC200 of animals exposed to air. The PC200 of animals treated with BW755c and exposed to TDI (2.3 + 0.8 mg/ml, n = 8) was significantly lower than the PC200 of control animals exposed to TDI (p less than 0.025). These results suggest that products of arachidonic acid metabolism are not responsible for TDI-induced airway hyperresponsiveness in guinea pigs. BW755c, however, appears to potentiate the TDI-induced airway hyperresponsiveness to acetylcholine by an as yet unidentified mechanism.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1988

Radioligand binding to muscle homogenates to quantify receptor and ion channel numbers.

Quantitation of the number of receptor or ion channel proteins in muscle that may be changed as a result of disease, development, or experimental manipulation can be achieved by radioligand binding assays. The problem of apparent specific binding to filters, which severely distorts these assays, is described. Results show that when techniques are applied to minimize both high nonspecific binding and spurious specific binding to filters, equilibrium and nonequilibrium binding assays can be effectively used to measure binding site densities in muscle homogenates. As no sites are lost during homogenate preparation, changes in binding site density that are not apparent when normalized per mg protein are revealed by normalizing the number of sites either per muscle or by muscle fiber diameter. Thus, the resolution of problems inherent in homogenate binding allows the use of these preparations to compare the plasticity and control of ion channels and receptors under a wide variety of experimental conditions.

Animals↗
PubMed1988

[3H]-nitrendipine binding sites in normal and cardiomyopathic hamsters: absence of a selective increase in putative calcium channels in cardiomyopathic hearts.

The number of putative calcium channels in cardiac muscle from young adult hamsters (60 days old) was compared in normal (F1B) hamsters and two different mutant strains (CHF 146 and Bio 14.6) which express cardiomyopathy and muscular dystrophy. Equilibrium binding assays of high affinity sites for [3H]-nitrendipine in ventricular homogenate preparations showed that the maximum number of [3H]-nitrendipine binding sites (Bmax), which corresponds to the number of putative calcium channels, was not significantly different in normal and cardiomyopathic hearts: 79(SEM 9), 64(14) and 69(10) fmol.mg-1 protein in 4-6 hearts from F1B, Bio 14.6 and CHF 146 hamster strains, respectively. Similar results were obtained with binding data after partial purification of the preparation. These data are in agreement with earlier studies comparing two normal strains (CHF 148 and random bred Syrian hamsters) with cardiomyopathic (CHF 146) hamsters, and conflict with other studies comparing normal and cardiomyopathic hamsters. Comparisons with the conflicting data suggest (a) that change in the number of high affinity [3H]-nitrendipine binding sites is not responsible for calcium overload and cell necrosis in cardiomyopathy, and (b) that increased numbers of low affinity [3H]-nitrendipine binding sites may emerge in cardiomyopathic hearts.

Animals↗
PubMed1988

Weight and mortality in men: the Albany Study.

In the Albany Study cohort of 1910 men, first examined between 1953 and 1955, 27-year mortality was least at relative weights between 100 and 109% of those considered desirable according to the 1959 Build and Blood Pressure Study. Mortality was greater at lower and higher weights. This association of weight and mortality was substantially stronger during the first 15 years after characterization than in the remaining 12 years. In contrast to the Albany Study, the 1979 insurance study and a study by the American Cancer Society reported minimum mortality for men at average weight by height, which is 15-20 pounds above the 1959 insurance standards. Other studies have reported minimum mortality at above-average weights. Perhaps the concept of an unvarying 'desirable' weight should be abandoned.

Adult↗
PubMed1988

Neural regulation of [3H]saxitoxin binding site numbers in rat neonatal muscle.

1. Neural regulation of the density of sodium (Na+) channels in rat muscle was studied by measuring specific binding of tritiated saxitoxin ([3H]STX) to muscles from rat hindlimbs during normal development and in rats in which neuromuscular function was interrupted by sciatic nerve section or neuromuscular blockade with botulinum toxin (BoTX). 2. The normal developmental increase in [3H]STX binding site numbers followed a simple exponential with a time constant of 12 days. The most rapid incorporation of channels coincided with the onset of accelerated muscle growth and increased neuromuscular activity at 2 weeks of age. 3. Elimination of neuromuscular activity retarded muscle growth and inhibited the normal incorporation of Na+ channels into neonatal muscle. Muscles denervation was more effective than BoTX paralysis: denervation at 2 weeks of age prevented the normal 3-fold increase in the binding site density between 2 and 3 weeks of age while age-matched BoTX-treated muscles incorporated an average of 66% of the normal Na+ channel incorporation. 4. Denervation and BoTX treatment were equally effective in reducing the numbers of [3H]STX binding sites in adult muscle. A reduction of 30% in binding sites brought the numbers to levels which corresponded with levels normally seen in muscles at 3 weeks of neonatal development. 5. It was concluded that the neural influence on incorporation of Na+ channels into membranes of neonatal muscle is, at least in part, mediated by neuromuscular activity.

Animals↗
PubMed1988

Pharmacological elevation of cyclic AMP and transmitter release at the mouse neuromuscular junction.

Intracellular recordings of spontaneous and evoked end-plate potentials have been made at the neuromuscular junction of mouse hemidiaphragms to determine a possible role of cyclic AMP (cAMP) in the release of acetylcholine from presynaptic terminals. Spontaneous release, as determined from the frequency of miniature end-plate potentials, was increased by drugs that inhibit phosphodiesterase: isobutylmethylxanthine (IBMX), SQ 20,009, theophylline, and caffeine; drugs that stimulate adenylate cyclase: forskolin, fluoride, and cholera toxin, and the stable analogue of cAMP: 8-bromo-cAMP but not dibutyryl cAMP. Release increased with time during maintained exposure to the drugs and generally followed a simple exponential time course with time constants ranging from 8 to 17 min at 20 degrees C, except for SQ 20,009 and cholera toxin which required longer exposure times for effect. The order of potency of the phosphodiesterase inhibitors was IBMX = SQ 20,009 greater than theophylline = caffeine. This is consistent with an effect mediated by an increase in cAMP concentrations within the nerve terminal. Evoked release, determined from the quantal content of the end-plate potential, was increased to a lesser extent than spontaneous release. The results are discussed with reference to the possible involvement of second messengers in the release of vesicles from nerve terminals in vertebrate synapses.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Tumor necrosis factor inhibits a polymorphonuclear leukocyte-dependent airway edema in guinea pigs.

Intravenously administered endotoxin inhibits the polymorphonuclear leukocyte (PMN)-dependent airway edema produced in guinea pigs exposed to toluene diisocyanate (TDI). Tumor necrosis factor (TNF) is produced in vivo by peripheral blood monocytes and tissue macrophages stimulated with endotoxin and has been shown to activate PMN's and vascular endothelial cells. To determine whether the inhibition of airway edema is mediated by TNF, guinea pigs were treated with intravenous saline or 75,000 U/kg recombinant human TNF 1.5 h before exposure to air or 3 ppm TDI for 1 h. Animals were then injected intravenously with 50 mg/kg Evans blue dye as a marker of protein extravasation. Saline-treated animals exposed to TDI had a significant increase in tracheal Evans blue dye extravasation (85 +/- 6.5 micrograms dye/g trachea, mean +/- SE) compared with saline-treated animals exposed to air (31.3 +/- 2.5, P less than 0.001). The tracheal extravasation of Evans blue dye was significantly inhibited (P less than 0.05) in TDI-exposed animals treated with TNF (64.7 +/- 7.5). Neither heat-inactivated TNF (104.9 +/- 9.5) nor TNF neutralized with a monoclonal antibody against TNF (99.7 +/- 17.9) inhibited TDI-induced airway edema. In addition, treatment with 15,000 U/kg (99.9 +/- 21.3) or 150,000 U/kg (103.2 +/- 17.6) interleukin 1, a monokine also produced in response to endotoxin, did not prevent airway edema. These results suggest that TNF released in response to endotoxin mediates endotoxin's inhibition of a PMN-dependent airway edema.

Animals↗
PubMed1988

Comparison of physiological and histochemical properties of motor units after cross-reinnervation of antagonistic muscles in the cat hindlimb.

1. Physiological and histochemical properties of the cat ankle extensor muscles, the lateral and medial gastrocnemius, and the soleus were studied after cross-reinnervation by flexor motoneurons. 2. Tibial and common peroneal nerves were cut and cross-united in the popliteal fossa of 2- to 6-mo-old cats. Eighteen to 24 mo later, single motor units were isolated by dissection and stimulation of ventral root filaments and classified into four types: fast-twitch, fatigable (FF), fast-twitch with intermediate fatigue resistance (FI), fast-twitch, fatigue-resistant (FR), and slow, fatigue-resistant (S). Muscle fibers were classified as fast glycolytic (FG), fast, oxidative glycolytic (FOG), and slow oxidative (SO) on the basis of histochemical staining. 3. Although motor-unit force was normally well correlated with the size of the innervating motor axon in the cross-reinnervated muscles, the force of different unit types overlapped considerably. The reinnervated motor units also showed a higher than normal degree of fatigability. 4. The range of muscle unit forces in cross-reinnervated triceps surae muscles was the same as in the normally innervated triceps surae muscles. This range is 2-3 times greater than the flexor muscles, which the common peroneal nerve normally supplies. The range of contraction speed of units in the cross-reinnervated extensor muscles was comparable to that in the flexor muscles, consistent with a motoneuron-specific determination of muscle speed (28). 5. SO and FOG muscle fibers were found in all reinnervated triceps surae muscles, but FG fibers were only found in reinnervated medial gastrocnemius (MG) and lateral gastrocnemius (LG) muscles, consistent with previous findings of the resistance of soleus muscles to complete conversion (10, 16, 20, 21). Type grouping of muscle fibers was characteristic of the reinnervated muscles. 6. Reinnervated SO muscle fibers were larger than the corresponding fibers in normally innervated muscles as were the estimated number of muscle fibers innervated by slow motor axons. Nonetheless, the force generated by the S motor units remained relatively smaller than FR and FF units. The relative contributions of the number, cross-sectional area and specific tension to the force generation of reinnervated motor units are discussed.

Adenosine Triphosphatases↗