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Biomedical subjects

T Gordon

Publications and source records attributed to T Gordon.

At least 163 records · Page 9Linked to original sources
PubMed1988

Acidity potentiates bronchoconstriction induced by hypoosmolar aerosols.

Naturally occurring fogs are usually hypoosmolar with respect to body fluids and can be quite acidic. Because both hypoosmolarity and acidity can cause bronchoconstriction, we studied whether there was a positive interaction between these stimuli in 12 subjects with asthma. We administered the following aerosols: hypoosmolar saline (30 mOsm) at pH 5.5, 3 hypoosmolar acids (0.005 M H2SO4, 0.01 M HNO3 and a 1:1 mixture of 0.005 M H2SO4 and 0.01 M HNO3, all 30 mOsm) at pH 2, and isoosmolar 0.005 M H2SO4 (300 mOsm) at pH 2. Each aerosol was administered on a separate day and was inhaled through a mouthpiece during tidal breathing. Specific airway resistance (SRaw) was measured before and after the subjects inhaled aerosols delivered at as much as 5 doubling nebulizer outputs. For each aerosol challenge, an output-response curve was generated, and the nebulizer output required to increase SRaw by 100% above baseline (PO100) was calculated. Mean values of PO100 were significantly lower for each of the hypoosmolar acids than for hypoosmolar saline (1.65 + 0.43 g/min [mean + SEM] for saline compared with 0.95 + 0.11, 1.05 + 0.20, and 0.90 + 0.14 for H2SO4, HNO3, and a 1:1 mixture of the two; all p values less than 0.025). Mean values of PO100 did not differ among the 3 acids studied. For 7 of 12 subjects, all 3 acids caused a leftward shift in the output-response curve from the curve generated for hypoosmolar saline aerosol. Isoosmolar H2SO4 did not increase SRaw by 100% in any subjects, even at the maximal nebulizer output that delivered a concentration of H2SO4 in excess of 40 mg/m3.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Calcium channels in normal and dystrophic hamster cardiac muscle. [3H]nitrendipine binding studies.

Progressive cardiac cell necrosis in the dystrophic hamster may be related to intracellular calcium overload, particularly as necrosis is prevented by treatment with calcium channel antagonists. Calcium overload could arise as a consequence of an imbalance in calcium influx, efflux and/or sequestration. The possibility that increased numbers of calcium channels in myopathic cells leads to excessive calcium influx has been studied by assaying the number of [3H]nitrendipine [( 3H]NTP) binding sites in cardiac muscle preparations. Crude homogenate and partially-purified ventricular muscle preparations from 60-day-old normal and genetically dystrophic hamsters were compared in this study. The results of equilibrium binding studies showed that, in both crude and partially-purified membrane preparations, the affinity and the maximum number of [3H]NTP binding sites in normal muscle were not significantly different from those measured in dystrophic muscle. For the homogenate preparation, the KD values were 0.07 +/- 0.01 and 0.08 +/- 0.01 nM for normal and dystrophic tissues, respectively, and the Bmax values were 62 +/- 6 and 73 +/- 6 fmol/mg protein for normal and dystrophic preparations respectively. These data show that a simple increase in the number of [3H]NTP binding sites is unlikely to account for calcium overload in the cardiomyopathic hamster.

Animals↗
PubMed1987

Axotomy increases the conduction velocity of C-cells in bullfrog sympathetic ganglia.

Axotomy produced an increase in the spike width and a decrease in amplitude of the afterhyperpolarization which followed the action potential in C-cells of bullfrog sympathetic ganglia. Although no change in B-cell conduction velocity was noted, C-cell conduction velocity increased significantly and approached that of B-cells. This change may reflect a process of dedifferentiation prior to the initiation of regrowth following axotomy.

Action Potentials↗
PubMed1987

The endocrinologic associations of the autoimmune rheumatic diseases.

Having seen five patients with both SLE and thyroid disease (case reports available on request) in a short period of time, we have undertaken a survey of the association between the ARD and endocrine disorders. On the basis of a literature review and our own reported study, it is apparent that an association between these major groups of disorders is well established with some individual diseases, though much more dubious in others (Table 3). The possibility of coexistent endocrine disease in a patient with a multisystem ARD should be carefully considered throughout the course of the patient's follow-up.

Autoimmune Diseases↗
PubMed1987

A 90-day inhalation toxicity study of raw shale oil in Fischer 344 rats.

The potential health effects of a raw shale oil were evaluated in a 90-day inhalation study in Fischer 344 rats. Groups of 15 male and 15 female rats were exposed 6 hr/day, 5 days/week for 13 weeks to aerosol concentrations of 0, 56, 120, or 492 mg/m3. In the high-dose group, 10 males and 7 females died prior to the termination of the study, most within the first 5 weeks of the experiment. A dose-dependent suppression in weight gain was seen in all of the shale oil-exposed groups. The failure to gain weight was associated with a variety of clinicopathologic abnormalities, including a dose-related decrease in red and white blood cells, with lowered plasma protein levels and increased serum alkaline phosphatase, and with total bilirubin levels in males. The exposure of the test animals to aerosolized raw shale oil was also associated with inflammatory and hyperplastic lesions in the lungs and upper respiratory tract, atrophy of the thymus and thymic-dependent portions of the peripheral lymphoid system, and bone marrow. These changes demonstrate that inhalation of raw shale oil aerosol can produce major organ toxicity similar to that found after exposure to other unrefined oil products.

Administration, Inhalation↗
PubMed1987

Drinking and mortality. The Albany Study.

The relation of alcohol consumption to mortality was examined in a cohort of 1,910 employed men aged 38-55 years, enrolled in the Albany Study, a prospective investigation of factors related to cardiovascular disease. Two follow-up periods were examined, one between 1953-1954 and 1971-1972 and the other after 1971-1972. In both periods, there was a positive relation between the rate of alcohol consumption and noncoronary heart disease death, not assignable to any specific cause. Coronary heart disease death was not associated with drinking during the initial follow-up but was negatively associated with drinking in the later follow-up. All-cause mortality was positively associated with alcohol consumption in the earlier follow-up, because of the greater cigarette use among drinkers, but not in the later follow-up. There was a significant positive relation of drinking to deaths from liver cirrhosis and diabetes but not to deaths from motor vehicle accidents.

Adult↗
PubMed1987

Acetylcholine receptors and sodium channels in denervated and botulinum-toxin-treated adult rat muscle.

1. The number of acetylcholine (ACh) receptors and Na channels was measured in adult rat hind-limb muscles after denervation or injection of botulinum toxin type A (BoTX), using specific binding of radiolabelled neurotoxins. 2. Denervation by sciatic nerve section increased the number of [125I]iodo-alpha-bungarotoxin ([125I]BTX) binding sites from low, unmeasurable levels to 39 +/- 3 fmol of toxin bound per milligram muscle protein at 21 days. 3. Subcutaneous injection of BoTX produced complete neuromuscular blockade for 11-14 days over which time the number of [125I]BTX binding sites increased with the same time course and to the same extent as following denervation. 4. Neither denervation nor BoTX treatment significantly altered the number of tritiated saxitoxin ([3H]STX) binding sites from normal values of 7.8 fmol/mg muscle weight or 57 +/- 3 fmol/mg homogenate protein. This may, however, correspond to a lower density of [3H]STX sites in the muscle membrane. 5. It was concluded that neuromuscular blockade with BoTX is equivalent to denervation in its effects on synthesis of ACh receptors. Numbers of Na channels are more stable than ACh receptors but may also be modulated by neuromuscular activity.

Animals↗
PubMed1987

The effects of axotomy on bullfrog sympathetic neurones.

1. The effects of axotomy on the electrical properties of B cells in paravertebral sympathetic ganglia were studied using standard intracellular recording techniques. The effects were apparent after 1 week and persisted throughout the 47 days of study. 2. Action potential duration (spike width) and amplitude (spike height) were significantly increased in axotomized neurones. 3. The duration of the after-hyperpolarization which followed the action potential showed considerable scatter in control neurones (mean +/- S.E. of mean, 159.0 +/- 5.8 ms for 100 cells). Following axotomy, the duration was significantly reduced (50.9 +/- 2.3 ms for 97 cells). The amplitude of the after-hyperpolarization was also significantly smaller in axotomized neurones. 4. Changes in the characteristics of the action potential and the after-hyperpolarization in axotomized neurones were not due to alteration in resting membrane potential or input resistance which were unchanged after axotomy. Rheobase current was significantly increased. 5. There was neither a significant depression of the rate of rise or the amplitude of orthodromically evoked nicotinic e.p.s.p.s nor any obvious ultrastructural alteration following axotomy. 6. Despite the decrease in the duration of the after-hyperpolarization, the rate of discharge in response to constant current injection was little changed in axotomized neurones. 7. Although axotomy produces significant changes in several measurable electrophysiological parameters in bullfrog sympathetic ganglion cells, the present results imply that mature neurones are able to maintain relatively normal electrical activity despite injury.

Action Potentials↗
PubMed1987

Patterns of reinnervation and motor unit recruitment in human hand muscles after complete ulnar and median nerve section and resuture.

Following complete ulnar or above-elbow median nerve sections, there was no significant correlation between motor unit size (twitch amplitude) and recruitment threshold, as assessed by spike triggered averaging. This absence of orderly recruitment was attributed to misdirection of motor axons during regeneration. Following median nerve section at wrist level, where the reinnervated muscles have more synergistic actions, orderly recruitment by size appeared to be re-established. Thus, the size principle of motor unit recruitment can be re-established after nerve section in humans, if motor axons innervate their original muscles or ones with closely synergistic functions.

Action Potentials↗
PubMed1987

The effects of pH on force and stiffness development in mouse muscles.

Changes in force and stiffness during contractions of mouse extensor digitorum longus and soleus muscles were measured over a range of extracellular pH from 6.4 to 7.4. Muscle stiffness was measured using small amplitude (less than 0.1% of muscle length), high frequency (1.5 kHz) oscillations in length. Twitch force was not significantly affected by changes in pH, but the peak force during repetitive stimulation (2, 3, and 20 pulses) was decreased significantly as the pH was reduced. Changes in muscle stiffness with pH were in the same direction, but smaller in extent. If the number of attached cross-bridges in the muscle can be determined from the measurement of small amplitude, high frequency muscle stiffness, then these findings suggest that (a) the number of cross-bridges between thick and thin filaments declines in low pH and (b) the average force per cross-bridge also declines in low pH. The decline in force per cross-bridge could arise from a reduction in the ability of cross-bridges to generate force during their state of active force production and (or) in an increased percentage of bonds in a low force, "rigor" state.

Animals↗
PubMed1987

Motor units and histochemistry in rat lateral gastrocnemius and soleus muscles: evidence for dissociation of physiological and histochemical properties after reinnervation.

A reexamination of the question of specificity of reinnervation of fast and slow muscle was undertaken using the original "self" nerve supply to the fast lateral gastrocnemius (LG) and slow soleus muscles in the rat hindlimb. This paradigm takes advantage of the unusual situation of a common nerve branch, which supplies both a fast and slow muscle, and of the opportunity to keep the reinnervating nerve in its normal position. In addition it provides a test of the effects of cross-reinnervation among muscles of the same functional group. The properties of soleus and LG muscles and of individual muscle units were characterized in normal rats and in rats 4-14 mo after cutting the lateral gastrocnemius-soleus (LGS) nerve and suture of the proximal stump to the dorsal surface of the LG muscle. Individual muscle units were functionally isolated by stimulation of single motor axons to LG or soleus muscle contained in teased filaments in the L4 and L5 ventral roots. Motor units were classified as fast contracting fatiguable (FF), fast contracting fatigue resistant (FR), and slow (S) on the basis of criteria described in the cat by Burke et al. and applied to rat muscle units by Gillespie et al. Muscle fibers were classified as fast glycolytic (FG), fast oxidative glycolytic (FOG), and slow oxidative (SO) on the basis of histochemical staining for myosin ATPase, nicotinamide-adenine dinucleotide diaphorase (NADH-D), and alpha-glycerophosphate (alpha-GPD). Reinnervated muscles developed less force and weighed less in accordance with having fewer than normal motor units and having lost denervated muscle fibers. Normal LG contained a small proportion of S-type motor units (9%), whereas the majority (80%) of control soleus units were S type. After reinnervation, each muscle contained similar proportions of fast and slow motor units with S-type units constituting 30% of units in both muscles. When compared with the normal motor-unit sample, there was no significant change in average twitch and tetanic force in reinnervated muscles for each type of motor unit. However, the range within each type was greater, and there was considerable overlap between types. Twitch contraction time was inversely correlated with force in normal and reinnervated muscles as shown previously in self- and cross-reinnervated LGS in the cat. Changes in proportions of motor units in reinnervated LG were accompanied by corresponding changes in histochemical muscle types. This contrasted with reinnervated soleus in which the proportion of muscle fiber types was not significantly changed from normal despite significant change in motor-unit proportions.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphatases↗
PubMed1987

Tachykinins mediate the acute increase in airway responsiveness caused by toluene diisocyanate in guinea pigs.

Exposing guinea pigs to toluene diisocyanate (TDI) causes an acute increase in airway responsiveness to inhaled acetylcholine. The mechanism of this increase in airway responsiveness is unknown. Capsaicin-sensitive afferent nerves and the tachykinins they release upon activation are important in controlling bronchomotor tone in guinea pigs. To determine whether tachykinins are important in TDI-induced airway hyperresponsiveness, we studied the effects of tachykinin depletion, using capsaicin, and competitive tachykinin antagonism, using (D-Arg1, D-Pro2, D-Trp7.9, Leu11) substance P, on TDI-induced airway hyperresponsiveness. In 9 of 9 untreated animals, TDI exposure caused a large and significant increase in airway responsiveness to acetylcholine. The mean concentration of acetylcholine required to decrease specific airway conductance by 50% below baseline (the PD50) was 1.51% before TDI exposure and 0.17% after TDI exposure (p less than 0.0005). Capsaicin treatment had no effect on the PD50 but prevented the TDI-induced increase in airway responsiveness in 10 of 12 animals. (The PD50 was 1.03% before TDI and 1.27% after TDI exposure.) Treatment with the tachykinin antagonist (D-Arg1, D-Pro2, D-Trp7.9, Leu11) substance P also abolished the TDI-induced increase in airway responsiveness in all 5 animals treated. Although TDI exposure also causes airway edema, the effect of capsaicin treatment on TDI-induced airway hyperresponsiveness did not result from prevention of airway edema. TDI exposure caused a marked increase in tracheal extravasation of intravenously administered Evans blue dye that was not prevented by capsaicin treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1987

The roles of pH and ionic species in sulfur dioxide- and sulfite-induced bronchoconstriction.

Sulfur dioxide (SO2) and sulfites are well-described causes of bronchoconstriction in persons with asthma that are chemically related and, therefore, may share a common mechanism of action. When either sulfur species dissolves in aqueous solutions, a pH-dependent equilibrium is established predominantly among bisulfite ion (HSO3-), sulfite ion (SO3=), and SO2. In addition, hydrogen ions may be released. To assess the relative bronchoconstricting potencies of these chemical forms and the role of acidity caused by the release of hydrogen ions in SO2- and sulfite-induced bronchoconstriction, we administered to 10 asthmatic subjects nebulized sodium sulfite (Na2SO3) solutions at pH 9 containing 95% sulfite, at pH 6.6 containing 80% bisulfite, and at pH 4 containing 99% bisulfite but greater than an order of magnitude more SO2 than the pH 6.6 solutions. Subjects inhaled increasing concentrations of aerosolized Na2SO3 at each pH during 1 min of tidal breathing. Subjects also breathed buffered acetic acid aerosols with the same acidity of the pH 4 Na2SO3 solutions to control for the airway effects of acid aerosols. To assess sensitivity to SO2 gas, subjects inhaled increasing concentrations of SO2 during eucapneic hyperpnea. Bronchoconstrictor response was assessed by measuring specific airway resistance (SRaw) before and after each challenge. Nine of the 10 subjects developed bronchoconstriction after inhaling the Na2SO3 aerosols at all 3 levels of pH and the SO2 gas. The mean concentration of Na2SO3 solution calculated to increase SRaw by 100% above baseline was significantly different (p less than 0.01) at the various levels of pH: pH 4 (0.17 mg/ml) less than pH 6.6 (0.49 mg/ml) less than pH 9 (2.10 mg/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1987

The role of titratable acidity in acid aerosol-induced bronchoconstriction.

We evaluated the importance of pH, titratable acidity, and specific chemical composition in acid aerosol-induced bronchoconstriction in 8 asthmatic subjects. We administered aerosols of HCl and H2SO4 at pH 2.0 in an unbuffered state and buffered with glycine. The buffered acids were given in order of increasing titratable acidity (defined as the number of ml of 1 N NaOH required to neutralize 100 ml of acid solution to pH 7.0). Each set of buffered or unbuffered acid aerosols was given on a separate day and each aerosol was inhaled through a mouthpiece during 3 min of tidal breathing. Bronchoconstriction was assessed by measurement of specific airway resistance (SRaw) before and after inhalation of each aerosol. SRaw increased by more than 50% above baseline in 1 of 8 subjects after inhalation of unbuffered HCl and in no subjects after inhalation of unbuffered H2SO4, even at pH 2.0. In contrast, SRaw increased by greater than 50% in all 8 subjects after inhalation of HCl and glycine at pH 2.0 and 7 of 8 subjects after inhalation of H2SO4 and glycine at pH 2.0. The mean titratable acidity required to increase SRaw by 50% above baseline was calculated for each challenge by linear interpolation; these values for H2SO4 and glycine (5.1 ml of 1 N NaOH) and HCl and glycine (2.2 ml of 1 N NaOH) were slightly, but significantly, different (p = 0.01) and were considerably higher than the titratable acidity of the unbuffered acids at pH 2 (1.0 ml of 1 N NaOH).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Apparent effect of catalase on airway edema in guinea pigs. Role of endotoxin contamination.

The airway edema that develops in guinea pigs after exposure to toluene diisocyanate (TDI) requires the presence of polymorphonuclear leukocytes (PMN). To determine whether this airway edema is mediated by the release of hydrogen peroxide from PMN, we treated animals intravenously with catalase bound to polyethylene glycol and examined the extravasation of Evans blue dye into the tracheal wall after exposure to air or 3 ppm TDI for 1 h. Catalase (25,000, 100,000, and 300,000 IU/kg) caused a dose-dependent inhibition of the TDI-induced increase in dye extravasation. However, treatment with catalase, inactivated at the peroxide binding site with 3-aminotriazole, inhibited dye extravasation after exposure to TDI as effectively as the equimolar 100,000 IU/kg dose of active catalase. Injection of polyethylene glycol alone was without effect. Dose-dependent decreases in extravascular migration of PMN and in circulating PMN also were noted after catalase treatment. These results suggest that the catalase preparations used in these studies inhibited the PMN-dependent airway edema by an effect other than hydrogen peroxide scavenging. Examination of this and other commercially available catalase preparations revealed trace concentrations of endotoxin at levels that could be responsible for the observed effects on PMN function. Treatment of animals with doses of Escherichia coli endotoxin similar to those inadvertantly administered to the catalase-treated groups (0.1 ng/kg to 100 ng/kg, intravenously) inhibited TDI-induced extravasation of Evans blue dye in a dose-dependent manner. These results suggest that contaminating endotoxin may contribute to some of the protective effects of preparations of catalase observed in previous studies of vascular permeability.

Animals↗
PubMed1986

Axotomy affects calcium-sensitive potassium conductance in sympathetic neurones.

Following peripheral nerve section, the cell body and proximal axon undergo various physiological and morphological changes which may be associated with regrowth. We found that axotomy reduced the amplitude and duration of the afterhyperpolarization (AHP) of the action potential (AP) of bullfrog sympathetic neurones. In addition, the repolarization of the AP was slowed. The Ca2+-channel blocker, Cd2+ (200 microM) produced similar effects in normal cells by blocking the Ca2+-sensitive K+ conductances (gK, Ca) which contribute to the AHP and to AP repolarization. Although Ca2+-channel function was preserved after axotomy, Cd2+ did not affect axotomized neurones. This suggests that axotomy promotes a functional loss of gK, Ca which could reflect a regenerative response of the cell to injury.

Action Potentials↗