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Biomedical subjects

S M Johnson

Publications and source records attributed to S M Johnson.

At least 145 records · Page 8Linked to original sources

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

Experiments were performed in current-clamped and voltage-clamped after-hyperpolarizing (AH) neurones of the guinea-pig myenteric plexus to examine the properties of the potassium conductance (gK, Ca) underlying the slow calcium-activated after-hyperpolarization (VK, Ca). The action potential plateau lengthened by the addition of tetraethylammonium chloride (TEA) to the bathing medium was compared to VK, Ca. Results were consistent with enhanced calcium entry causing an increase of VK, Ca. 4-Aminopyridine (4-AP) directly reduced VK, Ca. Voltage-clamp data of gK, Ca were well fitted by a process with a delay (approximately equal to 60 ms) followed by exponential activation (time constant approximately equal to 300 ms) and inactivation (time constant approximately equal to 2 s). The presence of a small, much slower inactivating process was noted. Values for time constants were similar to those reported by Morita, North & Tokimasa (1982) and North & Tokimasa (1983) where gK, Ca was measured during VK, Ca subsequent to action potential stimulation. The relation between gK, Ca (or the calcium-activated potassium current IK, Ca) and estimated calcium influx resulting from short-duration calcium currents elicited at various voltages was compared. Both the integral of the calcium current and gK, Ca showed a similar dependence on the depolarizations used to elicit IK, Ca except there was a positive shift of about 4 mV for the gK, Ca curve. This shift was attributed to a requirement for calcium ions to prime the gK, Ca mechanism. An inward ion charge movement of about 8 pC was required before significant activation of gK, Ca occurred. After the 'priming' condition had been established, the sensitivity of gK, Ca to inward calcium current measured at the resting potential was about 500 pS/pC of inward charge. Large calcium entry obtained by prolonged calcium currents caused saturation of the peak amplitude of IK, Ca and initiated currents with slower time to peak amplitude and longer duration. Increasing the calcium concentration of the external solution provided proportionally larger IK, Ca currents before saturation. The saturation amplitude of IK, Ca (namely gK, Ca) was relatively unaffected.

4-Aminopyridine↗

A B-cell hybridoma product inhibiting antibody secretion via 5'-nucleotidase.

A mouse spleen cell/plasmacytoma fusion designed to generate hybridomas making monoclonal antibodies to human lymphocyte 5'-nucleotidase yielded three hybridomas secreting material which inhibited about 50% of human and mouse lymphocyte ecto 5'-nucleotidase activity. The inhibition proved not to be due to antibody but to material of molecular weight 44,000 +/- 7,000 which was not part of an immunoglobulin molecule, although it may be related to a B cell Fc gamma receptor. In a haemolytic plaque assay this material inhibited the production of IgG but not IgM antibody by spleen cells of mice immunized with dinitrophenylated keyhole limpit haemocyanin. By contrast, IgG production by pokeweed mitogen-stimulated human tonsillar lymphocytes (assessed by reverse haemolytic plaque assay) was partially inhibited only by ascitic fluid of one of the hybridomas. The factor was called BAN (B cell anti 5'-nucleotidase). The suppressive action of BAN on IgG production was blocked by antibodies against 5'-nucleotidase suggesting that the lymphocyte enzyme may be acting as a BAN receptor.

5'-Nucleotidase↗

Opioid antagonists and spinal reflexes in the anaesthetized cat.

In barbiturate-anaesthetized cats, intravenous naloxone (0.025-0.10 mg/kg) increased the amplitude of monosynaptic reflexes produced by electrical stimulation of the nerves to the biceps-semitendinosus and gastrocnemius muscles and the complex reflexes to electrical stimulation of myelinated afferents of the sural and tibial nerves and reflexes to electrical stimulation of unmyelinated primary afferents of the tibial nerve. Increases in reflexes were also produced by the (-)- but not the (+)-isomer of the opiate antagonist N- furylmethylnormetazocine (both isomers being given in the dose range 0.03-0.20 mg/kg). The doses of naloxone increasing reflexes to C primary afferents had no effect on the responses of some dorsal horn neurones with cutaneous receptive fields to the same stimuli. The results suggest that, in anaesthetized cats, inhibition involving opioid peptides at some stage is present on many motoneurones. This inhibition may have relevance to animal behaviour after injury.

Animals↗

Dependence in the absence of tolerance to morphine.

Intravenous morphine depressed the firing of cat dorsal horn neurones to impulses in unmyelinated primary afferents. Electrophoretic administration of naloxone in the substantia gelatinosa between 10 min and 6 h after morphine revealed hyper-responsiveness which was not associated with apparent tolerance to morphine. The observations suggest the changes underlying dependence occur very rapidly in the dorsal horn probably at a site different from that at which morphine acts.

Action Potentials↗

Isocratic liquid chromatographic method for the determination of amoxapine and its metabolites.

An isocratic reverse-phase liquid chromatographic method for the determination of amoxapine and its major metabolites in human plasma utilizing UV detection is described. Plasma samples were extracted with ethyl acetate after pH adjustment. The reconstituted extracts were injected onto a cyanopropylsilane column and eluted with a mobile phase consisting of 65% acetonitrile and 35% sodium acetate buffer, 0.03 M and pH 6. The minimum detectable limit was less than 10 ng/mL of plasma. Possible interferences from other drugs which might be administered concurrently were studied. The reproducibility and precision of the method are demonstrated by the analysis of samples containing 25-600 ng/mL of plasma. The method is being applied successfully in our laboratory for the analysis of plasma from patients receiving amoxapine.

Amoxapine↗

Concomitant calcium antagonist plus isosorbide dinitrate therapy for markedly active variant angina.

The present study was performed to assess the efficacy of concomitant calcium antagonist/isosorbide dinitrate therapy in patients with frequent episodes of variant angina and to compare such combination therapy with isosorbide dinitrate alone. We enrolled nine such patients (six men and three women, aged 47 +/- 9 [mean +/- standard deviation] years) in a long-term comparison of (1) oral isosorbide dinitrate (117 +/- 63 mg per day) alone, (2) verapamil (453 +/- 75 mg per day) + isosorbide dinitrate (given in the same dose as stated above), and (3) nifedipine (71 +/- 14 mg per day) + isosorbide dinitrate (also given in the same dose as stated), each administered for 2 months. During isosorbide dinitrate therapy, these nine patients averaged 23.7 +/- 37.3 chest pains per week, consumed 24.4 +/- 47.4 sublingual nitroglycerin tablets per week, and demonstrated 46.5 +/- 43.2 episodes per week of transient ST segment deviations on calibrated two-channel Holter monitoring. During therapy with verapamil/isosorbide dinitrate and nifedipine/isosorbide dinitrate, the frequency of angina and ST segment deviations was dramatically reduced (verapamil/isosorbide dinitrate, 3.9 +/- 3.6 chest pains per week and 3.5 +/- 2.6 ST segment deviations per week, p less than 0.05; nifedipine/isosorbide dinitrate, 3.1 +/- 4.0 chest pains per week and 5.5 +/- 6.6 ST segment deviations per week, p less than 0.05). In all respects, verapamil/isosorbide dinitrate and nifedipine/isosorbide dinitrate were similar to one another.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Ga-67 uptake in the lung in sarcoidosis.

Images were obtained with Ga-67 and bronchopulmonary lavage performed in 21 patients with sarcoidosis (31 studies). The Ga-67 index, a semiquantitative criterion, was compared to a quantitative computer index based on lung:liver activity ratios; accuracy in predicting active alveolitis (defined by lavage lymphocyte counts) was assessed and differences between 24- and 48-hour studies examined. Computer activity ratios correlated well with the Ga-67 index, which had a sensitivity of 64%, specificity of 71%, and accuracy of 68% compared to 71%, 82%, and 77%, respectively, for the computer scores. Scores at 24 and 48 hours were similar. These results suggest that (a) Ga-67 scanning is useful in staging activity in pulmonary sarcoidosis, (b) quantitative computer scores are accurate in predicting disease activity, and (c) scanning can be performed 24 or 48 hours after injection.

Adult↗

Lateral reticular regions and the descending control of dorsal horn neurones of the cat: selective inhibition by electrical stimulation.

In barbiturate-anaesthetized cats, brainstem sites were electrically stimulated while studying the synaptic responses of lumbar dorsal horn neurones. The excitation of these neurones by impulses in unmyelinated primary afferents was selectively inhibited by stimulation of the ventrolateral medulla in the region of the caudal lateral reticular nucleus. The significance of this inhibition was heightened by the finding that stimulus currents producing inhibition from this area were less effective in the raphé region and not effective at intervening or dorsal sites. Bilateral lesions of the inhibition-producing ventrolateral sites reduced tonic descending inhibition of the responses of dorsal horn neurones to impulses in C fibres. The lateral reticular regions of the medulla may thus exert a considerable control over the transmission of nociceptive information in the cat spinal cord.

Animals↗

Ergonovine provocation to assess efficacy of long-term therapy with calcium antagonists in Prinzmetal's variant angina.

In the patient with Prinzmetal's variant angina, the response to therapy with calcium antagonists may be assessed symptomatically, electrocardiographically (that is, by ambulatory electrocardiographic monitoring), or by response to ergonovine provocation. Although some studies have suggested a good relation between anginal frequency and ergonovine responsiveness in these patients, none has compared ambulatory electrocardiographic activity with the results of ergonovine provocation during the long-term administration of calcium antagonists. Therefore, the present study was performed to compare ergonovine responsiveness with both clinical and ambulatory electrocardiographic activity in patients with Prinzmetal's variant angina during long-term therapy with placebo, verapamil, and nifedipine. Accordingly, 27 patients with variant angina (19 men and 8 women, mean age 52 years) received placebo and verapamil for 2 months each, after which 23 of the 27 also received nifedipine for 2 months. All patients kept a diary of chest pains, and all had weekly 24-hour 2-channel ambulatory electrocardiographic (Holter) monitoring, from which episodes of transient S-T segment deviation were quantitated. During the final week of therapy with each agent, ergonovine was administered, beginning at 0.025 mg and incrementally increasing to 0.20 mg. It was discontinued when the patient had chest pain with S-T segment elevation greater than or equal to 0.1 mV or received a total dose of 0.50 mg. Of the 74 tests, 59 were negative; 6 of the negative tests occurred during a treatment period in which the patient had greater than 10 chest pains/week and greater than 25 episodes of S-T segment deviation/week. Of the 15 positive tests, 8 became positive during administration of less than 0.20 mg ergonovine; 5 of the positive tests occurred during a treatment period in which the patient had no chest pain or S-T segment deviation. Thus, in patients with variant angina, disease activity cannot be monitored reliably by ergonovine provocation because some patients have negative ergonovine tests at a time of marked clinical and electrocardiographic activity, whereas others have positive tests at a time of little (or no) disease activity.

Adult↗

Parental characteristics and interactional dysfunction in families with child behavior problems: a preliminary investigation.

Thirty-six families with a preteenage behavior problem child were assessed on measures of marital discord, parental psychopathology, and three parental cognitive factors: knowledge of behavioral principles, tolerance for child deviancy, and expectations regarding their child's behavior. Nine nonproblem families with demographic characteristics similar to the problem families were also assessed. Correlational analyses across all families revealed a strong association between marital discord and the parental index of child behavior problems. While a number of significant associations were discovered between the various measures of marital discord, parental psychopathology, and parental cognitive factors, no other measure besides marital discord was associated with parental perception of child behavior problems. The nonproblem families and 15 of the problem families also participated in home observations obtained through random audio recordings during high interaction periods. These observational data indicated a significant relationship between parental perception of child behavior problems and parental negative behavior toward the child, but no significant relationship between parental perception of child behavior problems and child behavior, even when child behavior was weighted by parents' reactions to that behavior. Through sequential analysis, several contingent relations between parent and child behavior were discovered. Findings are discussed in relation to family systems theory.

Aggression↗

Histopathological study of the attrition of challenge cercariae of Schistosoma mansoni in the skin of mice immunized by chronic infection and by use of highly X-irradiated cercariae.

To find direct evidence for the sites of death of newly transformed schistosomula of Schistosoma mansoni in the skin of challenged immunized hosts, a histopathological study of the skin of chronically infected mice and of highly X-irradiated cercaria-immunized mice was made at different post-challenge times. Attrition of infecting organisms in naive mice was used as a control. In general, three main kinds of schistosomular attrition were observed: (1) in the granulocytic exudates in the epidermis, (2) in the granulocytic aggregates in the subcutaneous tissue, and (3) in the granuloma-like foci in the subcutaneous tissue. Schistosomula killed by the epidermal granulocytic exudates and by the subcutaneous granuloma-like foci occurred in all three groups of mice, but the schistosomula killed by the subcutaneous granulocytic aggregates were found only in the highly X-irradiated cercaria-immunized animals. Schistosomula killed by the epidermal granulocytic exudates were encountered occasionally in the challenged naive mice but more frequently in both the challenged chronically infected mice and the challenged highly X-irradiated cercaria-immunized mice. The number of subcutaneous granuloma-like foci was greater in the challenged mice immunized with highly X-irradiated cercariae than in the challenged naive mice or the challenged chronically infected mice. Another differentiating character among the three groups of mice was that in the highly X-irradiated cercaria-immunized group, the subcutaneous granuloma-like foci appeared on day 3 after the challenge, but on day 5 in the naive and chronically infected groups. The results clearly indicate that skin is an important site for the attrition of the challenged cercariae in the highly X-irradiated cercaria-immunized mice, and that immunity in the chronically infected and X-irradiated cercaria-immunized mice occurs by different mechanisms.

Animals↗

Verapamil for unstable angina at rest: a short-term randomized, double-blind study.

To assess the efficacy of verapamil in individuals with unstable angina at rest, 11 patients (five men and six women, average age 55 years) with recurrent chest pain at rest and transient ST segment deviation (elevation or depression greater than or equal to 0.1 mV) on continuous ECG monitoring were enrolled in a 3-day double-blind, randomized study. The day before randomization (day 1), all received single-blind placebo. On day 2 they were randomized to placebo (n = 6) or verapamil, 320 mg per day (n = 5). On placebo, the number of chest pains (day 1, 2.8 +/- 2.1; day 2, 2.2 +/- 2.5; NS), nitroglycerin used (day 1, 2.7 +/- 4.4 tablets; day 2, 2.2 +/- 3.5 tablets; NS), and ST segment deviations (day 1, 8.5 +/- 5.9; day 2, 5.3 +/- 7.1; NS) did not change. On verapamil, the number of chest pains (day 1, 5.4 +/- 2.2; day 2, 1.6 +/- 2.1; p less than 0.01), nitroglycerin used (day 1, 5.0 +/- 4.5 tablets; day 2, 1.6 +/- 2.6 tablets; p = 0.057), and ST segment deviations (day 1, 12.6 +/- 4.7; day 2, 6.2 +/- 6.2; p less than 0.05) fell. Since five of six placebo patients had frequent chest pain and ST segment deviations on day 2, they were changed blindly to verapamil, 320 mg per day. Of the five verapamil patients, three had no chest pain or ST segment deviations on day 2, but two had continued chest pain and ST segment deviations and were increased blindly to 480 mg verapamil per day. Of the eight patients given verapamil (320 mg per day) on day 3, five had chest pain or ST segment deviations and were increased blindly to 480 mg verapamil per day on day 4. Of the seven who received 480 mg verapamil per day on day 4, three had chest pain and ST segment deviations similar in frequency to that occurring on day 1. Thus in patients with unstable angina at rest, verapamil exerts an initial beneficial effect, but in some individuals this salutary influence is not sustained.

Adult↗

The location of brainstem neurones tonically inhibiting dorsal horn neurones of the cat.

In an investigation of the origin of tonic descending inhibition of dorsal horn neurones by impulses in unmyelinated primary afferents, brainstem regions were electrolytically lesioned. With each neurone studied, tonic descending inhibition was measured before and after brainstem lesions by cooling a segment of spinal cord cephalic to the recording site. Such inhibition was not reduced by lesions of areas which, when stimulated, produce analgesia. These included the periaqueductal grey and the raphé areas of the midbrain and pons-medulla. Tonic descending inhibition was reduced by bilateral lesions of the ventrolateral caudal medulla in the region of the lateral reticular nuclei. Lateral reticular areas may have a functional role in the control of pain.

Afferent Pathways↗

Selective uptake of lucifer yellow by retinal cells.

When turtle retinae were incubated with the fluorescent dye, lucifer yellow, in the absence of Ca2+, the dye was selectively accumulated by cell bodies located in the inner nuclear layer (INL). The morphological features of the labeled cells suggested that they were bipolar cells. Other fluorescent dyes, Procion yellow and Primulin, were also taken up by somata in the INL, in the absence of external Ca2+, although the identity of the labeled cells was uncertain. As with turtle retina, lucifer yellow was accumulated predominantly by cell bodies in the INL of goldfish, frog, and rat retinae. Lucifer yellow uptake appeared to be independent of synaptic activity since dark-adaptation or aspartate treatment of retinae did not alter the dye uptake. Further, retinae from dystrophic (RCS) rats showed uptake similar to that seen in normal rat retinae. After uptake, most of the dye was found intracellularly as patches or vacuoles in the somata of the labeled cells. Dye uptake was not inhibited by removal of Na+ from the incubation medium. Further, prior treatment with metabolic inhibitors, cyanide and iodoacetate, or cytochalasin B, did not block the dye uptake.

Animals↗

Isocratic high-performance liquid chromatographic method for the determination of tricyclic antidepressants and metabolites in plasma.

An isocratic high-performance liquid chromatographic method for the determination of six tricyclic antidepressants and their major metabolites is presented. Hexane containing 0.5% diethylamine was used as an extraction solvent to minimize adsorption onto glass. A reversed-phase cyanopropylsilane column was used with a mobile phase consisting of 70% acetonitrile and 30% 0.03 M acetate buffer, pH 7.0. Good identification and quantitation were obtained by the use of both UV detection at 245 nm and spectrofluorometric detection with an excitation wavelength of 276 nm and an emission filter with a 370-nm cutoff. A minimum detectable limit of less than 5 ng/ml of plasma is possible with this system. The reproducibility and precision of the method are shown from the analysis of samples containing 20-400 ng/ml in plasma.

Adsorption↗