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Biomedical subjects

S M Johnson

Publications and source records attributed to S M Johnson.

At least 127 records · Page 7Linked to original sources
PubMed1987

Sustained nerve-mediated contractions of guinea-pig ileum during morphine withdrawal by washout.

The effects of morphine withdrawal by washout were examined in ilea from guinea-pigs pretreated by subcutaneous implantation of two pellets, each containing 155 mg morphine. One week later preparations of the longitudinal muscle-myenteric plexus were set up in vitro in a modified Krebs solution containing morphine (1 microM). Within 5-15 min after washing in morphine-free Krebs, the preparations exhibited marked spontaneous contractions which became maximal after 20-60 min. The contractions resulting from morphine washout were greatly reduced by TTX and by hyoscine but not by hexamethonium, suggesting that excitation involved predominantly the cholinergic myenteric motor neurons, and was thus similar to that underlying the contraction induced by naloxone. In contrast to the naloxone-induced contractions, however, those resulting from morphine washout were well sustained during periods of recording up to 5 h. Morphine washout therefore provides conditions suitable for investigating the mechanisms underlying the variety of withdrawal signs observed in the ileum in vitro.

Animals↗
PubMed1987

Inhibitory effects of opioids in a circular muscle-myenteric plexus preparation of guinea-pig ileum.

The actions of opioids were examined in a strip preparation of the external muscle and myenteric plexus of the guinea-pig ileum cut parallel to the circular muscle. Contractions of the circular muscle induced by electrical stimulation of myenteric neurons were depressed in a concentration-dependent manner by the mu agonists, morphine and DAGO, and by the kappa agonist, U-50,488H. The concentrations of morphine, DAGO and U-50,488H which depressed nerve-mediated contractions by 50% (IC50) were 86 nM, 11 nM and 5.0 nM, respectively. The equilibrium dissociation constants (KD) for naloxone as an antagonist of the inhibitory effects of DAGO and of U-50,488H were 5.6 nM and 29.4 nM, respectively. In contrast to the potent inhibitory effects of mu and kappa agonists, the delta-selective agonist, D-Pen-L-Pen, produced only weak inhibition of nerve-mediated contractions. Even at a concentration of 3 microM, there was less than 50% inhibition, which was not antagonised by the delta receptor antagonist, ICI 174864. The experiments indicate that both mu and kappa opioid receptors are present on the myenteric neurons supplying the circular muscle and that delta receptors are either absent or ineffectively activated.

Animals↗
PubMed1987

Naloxone-induced depolarization and synaptic activation of myenteric neurons in morphine-dependent guinea pig ileum.

To investigate the cellular basis of opiate dependence, intracellular microelectrodes were used to record from both electrophysiologically defined classes of neurons (S and AH) in myenteric plexus longitudinal muscle preparations from morphine pretreated guinea pigs. These preparations responded to naloxone with the characteristic contraction of the longitudinal smooth muscle, indicative of morphine dependence. Depolarization in response to naloxone was observed in 42% of S neurons, but there were no consistent changes in input resistance. In some cells the depolarization was reduced or abolished after blockade of synaptic transmission, suggesting that it was due in part to the release of an excitatory transmitter producing a slow depolarization in the impaled neuron. Synaptic activation of S neurons during withdrawal was further indicated by the observation that fast postsynaptic potentials appeared after abrupt displacement of morphine from its receptors by naloxone. Morphine withdrawal, therefore, involves both the final motor neurons and interneurons. During naloxone-induced withdrawal, 25% of S neurons discharged action potentials. In contrast, no action potentials were discharged in AH neurons. Furthermore, naloxone did not alter the resting membrane potential, input resistance, soma action potential configuration, or slow hyperpolarization following a soma spike in AH neurons. The specificity of the withdrawal response for S neurons and the relatively small proportion of neurons involved suggests that morphine withdrawal occurs in quite specific neuronal circuits in the myenteric plexus.

Animals↗
PubMed1987

In vitro activity of ciprofloxacin and ofloxacin against the Mycobacterium avium-intracellulare complex.

The in vitro activity of ciprofloxacin and ofloxacin against strains of Mycobacterium avium-intracellulare complex were studied by the standard 1% proportion method. Thirty-eight of 100 strains (30%) were inhibited by ciprofloxacin at 2 micrograms/ml and 11 of 30 strains (37%) were inhibited by ofloxacin at 8 microm/ml. Patients having these more susceptible isolates may potentially benefit from therapy with these agents [corrected].

Anti-Bacterial Agents↗
PubMed1987

In vitro characterization of neurons in the ventral part of the nucleus tractus solitarius. I. Identification of neuronal types and repetitive firing properties.

1. An in vitro brain stem slice preparation from adult guinea pigs was used to determine the properties of neurons located in the ventral part of the nucleus tractus solitarius (NTS), an area associated with the dorsal respiratory group. Based upon their morphology and their repetitive firing properties, three classes of ventral NTS neurons, termed types I, II, and III, were observed. 2. Type I neurons were multipolar with pyramidal-shaped cell bodies. These neurons responded to prolonged depolarizations from a resting level of -50 mV with a discrete, high-frequency burst of spikes, which rapidly adapted to a low steady-state level. When depolarized from levels more negative than -65 mV, the initial burst was diminished. 3. Type II neurons were multipolar with fusiform-shaped cell bodies. Type II neurons responded to depolarizations from -50 mV with an initial high spike frequency, which gradually adapted to a steady-state level. When depolarized from levels more negative than -60 mV, these neurons displayed a delay between the onset of the stimulus and the first spike. This delay has been termed "delayed excitation." The expression of delayed excitation was modulated by both the size and duration of hyperpolarizing prepulses that preceded depolarization. 4. Type III neurons were multipolar with spherical shaped-cell bodies. In response to depolarizations from -50 mV, these neurons displayed high-frequency firing with little adaptation. The repetitive firing properties of type III neurons were not modulated by hyperpolarization. 5. Bulbospinal neurons in the ventral NTS were identified using retrograde transport of rhodamine-labeled latex beads injected into the region of the phrenic motor nucleus at spinal cord levels C4 through C6. Only type I and type II neurons were labeled in the ventral NTS (0.2-1.0 mm rostral to the obex). Both contralateral and ipsilateral projections were observed. Contralaterally, type I and II neurons were evenly distributed. Ipsilaterally, however, type II neurons accounted for two-thirds of the labeled neurons. 6. Type I and II neurons had similar input resistances and time constants: 97.0 +/- 17.6 M omega and 14.4 +/- 2.2 ms (n = 5) for type I and 107.0 +/- 11.2 M omega and 13.7 +/- 1.6 ms for type II (n = 5).(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1987

Effect of antacid suspension on the pharmacokinetics of ibuprofen.

The effect of antacid administration on the pharmacokinetics of ibuprofen was evaluated in a randomized, crossover study of eight healthy volunteers. Doses of 62 mL of aluminum and magnesium hydroxide suspension and single doses of ibuprofen 400 mg were used. Subjects received each of the following treatments at one-week intervals: ibuprofen alone; ibuprofen administered concurrently with one dose of antacid; antacid administered one hour after the ibuprofen dose; and antacid administered concurrently with the ibuprofen dose, plus three more antacid doses given every five hours. Blood samples were taken at various time intervals up to 24 hours after the ibuprofen dose. Serum samples were assayed for ibuprofen content using high-performance liquid chromatography. Values for AUC, Cmax, tmax, and k were not significantly different among treatment groups. The ranges of mean (+/- S.D.) values were 113.97 +/- 21.5 to 127.53 +/- 29.3 micrograms.hr/mL for AUC, 35.30 +/- 6.40 to 41.00 +/- 10.00 micrograms/mL for Cmax, 0.95 +/- 0.30 to 1.28 +/- 0.54 hr for tmax, and 0.346 +/- 0.026 to 0.388 +/- 0.040 hr-1 for k. For the doses used, concurrent administration of aluminum and magnesium hydroxide suspension and ibuprofen does not alter ibuprofen pharmacokinetics.

Adult↗
PubMed1986

Students' stereotypes of patients as barriers to clinical decision-making.

The ability to formulate quick, accurate clinical judgments is stressed in medical training. Speed is usually an asset when a physician sorts through his biomedical knowledge, but it is often a liability when the physician assesses the sociocultural context of a clinical encounter. At the Michigan State University College of Osteopathic Medicine, a study was designed which graphically illustrated to beginning students that unconscious sociocultural stereotypes may influence clinical decision-making. Three entering classes of students were shown a videotape depicting five simulated patients (attractive black woman, attractive white woman, professional man, middle-aged housewife, and elderly man), each presenting with the same physical complaint. Elements of positive and negative stereotypes were incorporated into each of the portrayals, and the students rated these patients on positive and negative characteristics. The results suggested that the students attributed both positive and negative characteristics to patients on the basis of irrelevant characteristics, such as attractiveness, and with little further justification for their attributions. Such stereotypic generalizations held by students may become barriers to the students' objective clinical decision-making.

Clinical Competence↗
PubMed1986

Morphine withdrawal in guinea-pig ileum is confined to one electrophysiologically defined class of myenteric neurone.

Intracellular microelectrodes were used to record changes in myenteric neurones underlying morphine dependence in the guinea-pig ileum. Of the two electrophysiologically defined classes of neurones (S and AH), only a proportion of S-neurones were involved in the naloxone-induced withdrawal responses. Withdrawal caused direct depolarization and discharge of action potentials in S-neurones and also resulted in synaptic activation of neurones of this class. Both fast and slow synaptically mediated depolarizations were evoked by naloxone. The experiments suggest that morphine withdrawal is expressed in quite specific neuronal circuits in the myenteric plexus.

Animals↗
PubMed1985

Processing and transport of insulin by vascular endothelial cells. Effects of sulfonylureas on insulin receptors.

Polypeptide hormones such as insulin must cross the vascular barrier to mediate their biologic actions. A substantial vascular barrier may be encountered in muscle and fat tissues, which are supplied by continuous capillaries lined with tightly joined endothelial cells. Endothelial cells have previously been shown to bind and release insulin with minimal degradation. Because 125I-labeled insulin transport was demonstrated to be receptor-mediated, factors regulating insulin-receptor binding may also affect the insulin transport rate across the vascular barrier. Since sulfonylureas may have a glucose-lowering action by altering insulin receptors, the effects of tolazamide and glyburide on vascular endothelial cell insulin receptors were evaluated. Exposure of aortic endothelial cells in culture to insulin at 37 degrees C resulted in a 75 percent loss of receptors. Five to seven days of tolazamide exposure led to a 35 percent time-dependent increase in insulin binding. More strikingly, tolazamide altered the dose-receptor to insulin-induced down-regulation. Cells down-regulated with insulin (10 ng/ml) showed a 100 percent increase in binding in the presence of tolazamide; a dose-dependent effect occurred at the 75 to 200 micrograms/ml dosage level. Scatchard analysis indicated that the increase in 125I-labeled insulin binding was due to an increase in receptor number. When insulin receptors were identified with 125I-labeled insulin, tolazamide-treated cells clearly showed an increase of a band at Mr = 145 K, the alpha subunit of the receptor. Tolazamide may thus help normalize glucose in diabetes by preventing receptor down-regulation in endothelial cells.

Blood Vessels↗
PubMed1985

Receptor-mediated transport of insulin across endothelial cells.

Hormones such as insulin are transported from the interior to the exterior of blood vessels. Whether endothelial cells, which line the inner walls of blood vessels have a role in this transport of hormones is not clear, but it is known that endothelial cells can internalize and release insulin rapidly with little degradation. The transport of iodine-125-labeled insulin was measured directly through the use of dual chambers separated by a horizontal monolayer of cultured bovine aortic endothelial cells. In this setting, endothelial cells took up and released the labeled insulin, thereby transporting it across the cells. The transport of insulin across the endothelial cells was temperature sensitive and was inhibited by unlabeled insulin and by antibody to insulin receptor in proportion to the ability of these substances to inhibit insulin binding to its receptor. More than 80 percent of the transported insulin was intact. These data suggest that insulin is rapidly transported across endothelial cells by a receptor-mediated process.

Animals↗
PubMed1985

Ventricular ectopic activity with spontaneous variant angina: frequency and relation to transient ST segment deviation.

This study was performed (1) to assess the frequency of ventricular ectopic activity (ventricular bigeminy, couplets, or ventricular tachycardia) during spontaneous variant angina; (2) to assess the relation between ventricular ectopy and the severity and duration of ischemia; and (3) to evaluate the precise temporal relation between episodes of ischemia and ventricular ectopy. Fifteen ambulatory patients with variant angina (12 men, 3 women, aged 50 +/- 8 [mean +/- SD] years) had Holter monitoring for 24 hours/week for 10 months (total, 10,238 hours of monitoring), from which the following were measured during each episode of ST deviation (elevation or depression): duration of ST deviation (minutes), maximal ST deviation (millivolts), presence of ventricular ectopic activity, and timing of ventricular ectopy in relation to ST deviation. Of 645 episodes of ST deviation, 79 (12.2%) had associated ectopy, almost all of which occurred in three patients. The 79 episodes of ST deviation with ectopy lasted 4.6 +/- 3.3 minutes and averaged 0.16 +/- 0.12 mV, whereas the 566 episodes of ST deviation without ectopy lasted 4.7 +/- 6.1 minutes and averaged 0.17 +/- 0.11 mV (NS in comparison to the 79 episodes with ectopy). Of 489 episodes of ST elevation, 72 (14.7%) were accompanied by ventricular ectopy; of 156 episodes of ST depression, only seven (4.5%) had ectopy (chi 2 = 11.531, p less than 0.001). Of the 79 episodes of ventricular ectopy, almost all appeared during a period of increasing or maximal ST deviation, whereas only two appeared as ST deviation was resolving.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1985

Teaching medical students the effects of values and stereotyping on the doctor/patient relationship.

As part of an introductory course on the doctor/patient relationship, a teaching unit was designed which emphasized to students that values, biases and prejudices may affect their behaviors when interacting with patients. The unit included lectures on values, specific readings and a survey component which challenged students' value systems and provided them with the opportunity for exploration of hidden biases and prejudices. The survey component involved a series of trigger vignettes depicting five patients interacting with the same (actor) physician. On a rating instrument, students were asked to rate each patient on ten positive and ten negative characteristics, identify the characteristic which best described each patient and select the patient they would most like to treat. The survey was administered to an incoming class of medical students at the orientation session to a course on the doctor/patient relationship. Students were asked to keep a copy of their ratings and bring it to the small group discussion session on physician values. The data were collected, and a class composite developed and submitted to the course instructors prior to the discussion and processing sessions on values. Specific instructions on how to utilize the materials were provided. The class composite, which revealed that students have biases, served as a focus for discussion and facilitated students awareness that unconscious stereotypes exist in their value systems. This teaching approach provided students with a beginning insight that biases and prejudices affect the doctor/patient relationship and the quality of care patients receive.

Adult↗
PubMed1985

The calcium current in a myenteric neurone of the guinea-pig ileum.

The active and passive electrical properties of the after-hyperpolarizing (AH) cell of the guinea-pig myenteric plexus were analysed using a single-electrode voltage or current clamp. Action potentials were compared under normal conditions, in the presence of tetrodotoxin (TTX) and in the presence of both TTX and tetraethylammonium chloride (TEA). Calcium action potentials were studied by examining their calcium dependence, the actions of manganese and the effect of substituting barium for calcium. The maximum rate of rise of the action potential did not increase in calcium concentrations above 10 mM. The half-saturation concentration was 2 mM-calcium. AH cells exhibited five predominant currents consisting of an inward sodium current, an inward calcium current and three outward currents. There was a transient outward current which was inactivated at holding potentials more positive than -65 mV and was suppressed by 4-aminopyridine and barium but not by external TEA. A second outward current observed in the presence of 10 mM-external TEA had properties consistent with that of the delayed rectifier (Hodgkin & Huxley, 1952). A third outward current was the calcium-dependent slow after-hyperpolarizing current (Hirst, Johnson & van Helden, 1985). The voltage dependence, the action of calcium antagonists, the effect of barium substitution and the temporal characteristics of calcium currents were studied. The peak calcium current density was in excess of 100 microA/cm2 in 2.5 mM-calcium solution at 35 degrees C for depolarizations to -10 mV. Calcium currents showed at least two phases of inactivation. Both calcium and barium currents showed early inactivation with decay occurring over the first 10-40 ms. The calcium-activated current precluded direct measurement of slow inactivation of the calcium current. Barium currents studied over the first 100-150 ms had a very slow inactivating component.

Action Potentials↗