Gastrointestinal and cutaneous vasculitis associated with gonococcal infection in an HIV-seropositive patient.
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Adult↗
Biomedical subjects
M Johnson
Publications and source records attributed to M Johnson.
Mechanisms mediating biogenic amine deficits induced by amphetamine and its congeners.
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Amphetamines↗
Structure-activity maps for visualizing the graph variables arising in drug design.
Structure-activity problems are characterized by the topological and topographical character of the structural information determining the activity. Traditional statistical methodology requires that this predictive information be mapped to a vector space. To circumvent this vexing conversion of structural information to vector form, the edge-deletion metric is defined on the space of chemical graphs that defines the topology of the molecules. This paper proposes structure-activity maps and transformation-effect maps for directly visualizing the structure-activity relationships. The maps are illustrated using the hypotensive activities of clonidine analogs and the sweet taste of Perillartine analogs.
Clonidine↗
Aldose reductase inhibitors and galactose toxicity in neonatal and maternal rat lenses.
We reported that in utero galactose-induced cataracts could be inhibited if aldose reductase inhibitors (ARIs) were included in the galactose diet of pregnant rats. These studies involved morphological and cytochemical approaches. We undertook this investigation to evaluate the effects of ARIs in preventing the formation, accumulation and depletion of dulcitol in lenses of in utero galactose exposed neonates and in mothers during and following pregnancy. Sprague Dawley rats were fed Purina Rat Chow with 50% galactose either with or without 15mg Sorbinil or 1mg Eisai compound E-0722/day/Kg body weight during and following pregnancy. The lenses of neonates and mothers were processed to determine dulcitol concentrations. At parturition there was a significant amount of dulcitol in the lenses of pups and their mothers, which reduced rapidly in the lenses of pups regardless of the diet fed to the nursing mother. While galactose had a cross-placental but not a milk-mediated effect, the ARIs had both cross-placental and milk-mediated effects on dulcitol accumulation and depletion, respectively. The galactose feeding of mothers post-parturition maintained the high lenticular dulcitol concentration and the absence of galactose led to a reduction in lenticular dulcitol. The correlation between dulcitol accumulation and cataract development is discussed.
Aldehyde Reductase↗
Continuous formation of nail along the bed.
To resolve the problem of whether nail is formed continuously along the length of the nail bed as well as by the germinal matrix, nail thickness was measured at six anatomical points along the length of 20 normal big toe-nails removed after injury. Nail water content was constant at 9-10% along the nail length, and the nails did not shrink with dehydration. Approximately 79% of nail thickness was contributed by the nail matrix, and 21% by the nail bed. The rate of nail production was constant at 0.13 mm/mm along the lunula and 0.027 mm/mm along the whole bed from the distal lunula to the point of separation at the onychodermal band; the fractional change in linear growth and thickness showed less variation than absolute change. The continuous production of nail by the bed provides a simple biological solution to the problem of attachment of a continuously moving plate. It provides a source of entry of drugs into the distal nail plate, and a rationale for the use of much shorter courses of antifungal drugs than previously believed possible.
Adolescent↗
Investigations into factors determining the duration of action of the beta 2-adrenoceptor agonist, salmeterol.
1. This study has explored the mechanism underlying the long duration of action of the beta 2-adrenoceptor agonist, salmeterol. 2. Salmeterol, salbutamol and isoprenaline caused a concentration-related inhibition of electrically-induced contractile responses of the guinea-pig superfused trachea preparation. The effects of both isoprenaline and salbutamol were rapid in onset and rapidly reversed upon removal of the agonist. In contrast, the effects of salmeterol were slower in onset and could not be reversed by superfusion of the tissue with agonist-free Krebs solution even for periods of up to 10 h. 3. The effects of salmeterol were, however, readily reversed by a number of beta-adrenoceptor blocking drugs, as was the effect of a continuous infusion of isoprenaline. Upon removal of the antagonist, however, the effects of salmeterol and of the isoprenaline infusion were reasserted at a rate which was inversely related to the lipophilicity of a beta-adrenoceptor blocking drugs. 4. Salmeterol inhibited the binding of [125I]-(-)-iodopindolol (100 pM) to rat lung membranes (pIC50 7.1), with isoprenaline (pIC50 6.2) and salbutamol (pIC50 5.1) having lower potencies. The inhibition of binding by salmeterol was apparently non-competitive, whereas that produced by salbutamol and isoprenaline was competitive in nature. 5. Isoprenaline and salbutamol rapidly dissociated from their binding sites, whereas in marked contrast, the binding of salmeterol showed no dissociation for periods of up to 1 h. 6. These data are consistent with the mechanism in which salmeterol binds adjacent to the active site of the beta 2-adrenoceptor, such that the drug cannot be washed out of the tissue, yet can interact with and activate the receptor. This latter property is susceptible to antagonism by beta-adrenoceptor blocking drugs but is reassured when the antagonists are removed.
Adrenergic beta-Agonists↗
Comparison of the anti-inflammatory properties of formoterol, salbutamol and salmeterol in guinea-pig skin and lung.
1. We have compared some anti-inflammatory properties of formoterol, salbutamol and salmeterol in guinea-pig skin and lung. 2. Intradermal formoterol (1 x 10(-10) to 1 x 10(-8) mol/site), salbutamol (1 x 10(-8) and 1 x 10(-7) mol/site) and salmeterol (1 x 10(-8) and 1 x 10(-7) mol/site) inhibited bradykinin-induced plasma protein extravasation (PPE) in guinea-pig skin. A maximally effective dose of formoterol (1 x 10(-9) mol/site) and salbutamol (1 x 10(-8) mol/site) inhibited PPE in guinea-pig skin for 2-4 h and 1-2 h respectively, whereas salmeterol (1 x 10(-8) mol/site) was effective for > 6 h. 3. Inhaled formoterol (nebuliser concentration 0.1 to 100 micrograms ml-1 inhibited histamine-induced plasma protein extravasation (PPE) in guinea-pig lung, with significant inhibition being observed at 10 and 100 micrograms ml-1. Formoterol (100 micrograms ml-1) inhibited PPE in guinea-pig lung for 2-4 h, a duration of action intermediate between that previously obtained for salbutamol (1 h) and salmeterol (> 6 h). 4. Formoterol, like salbutamol, had no effect on neutrophil accumulation or granulocyte-dependent PPE (zymosan-induced) in guinea-pig skin. Formoterol inhibited neutrophil accumulation (lipopolysaccharide-induced) in guinea-pig lung but at doses greater than those required to inhibit granulocyte-independent PPE (histamine-induced). In contrast, salmeterol inhibited neutrophil accumulation and granulocyte-dependent PPE in guinea-pig skin and inhibited neutrophil accumulation in guinea-pig lung at doses which inhibit granulocyte-independent PPE. 5. Inhaled formoterol (nebuliser concentration 100 microg ml-1) and salmeterol (100 microg ml-1) both inhibited PAF-induced eosinophil accumulation in guinea-pig lung. However, unlike salmeterol, this effect of formoterol was observed only at suprabronchodilator doses.6. We conclude that to inhibit neutrophil accumulation, at doses which inhibit granulocyte-independent PPE, agonists acting at beta-adrenoceptors on vascular endothelium require a duration of action greater than that of salbutamol and formoterol. However, we speculate that the mechanism of inhibition of eosinophil accumulation in guinea-pig lung by beta2-adrenoceptor agonists may involve an action on beta2-adrenoceptors on a cell type other than the endothelial cell.
Adrenergic beta-Agonists↗
Effects of beta-adrenoceptor agonists in human bronchial smooth muscle.
1. We have investigated the potency and duration of action of isoprenaline and a range of beta-adrenoceptor agonists as relaxants of inherent tone in human superfused, isolated bronchial smooth muscle, a tissue reported to contain a homogeneous population of beta 2-adrenoceptors. 2. All of the beta-adrenoceptor agonists caused concentration-related inhibition of inherent tone, with isoprenaline having an EC50 of 27 nM. The rank order of agonist potency was: formoterol > or = -salmeterol > or = clenbuterol > fenoterol = isoprenaline > terbutaline > or = salbutamol > quinprenaline. 3. Relaxant responses to salmeterol were fully reversed by the selective beta 2-adrenoceptor blocking drug, ICI 118551, demonstrating the involvement of beta 2-adrenoceptors. 4. Rt50, i.e. the time taken for 50% recovery from the effects of an EC50 concentration of agonist, differed considerably between the different beta 2-adrenoceptor agonists. Most agonists were short-acting, having Rt50 values less than 13 min. Quinprenaline was of moderate duration, with an Rt50 value of > or = 20 min. In contrast, salmeterol was extremely long-acting, with no sign of recovery within 4 h. 5. Estimates of relative potency and duration of action were similar to those previously determined for these agonists in the guinea-pig isolated trachea. These results suggest, therefore, that guinea-pig trachea is a suitable alternative to human bronchus for the evaluation of the actions of beta-adrenoceptor agonists on airways smooth muscle.
Adrenergic beta-Agonists↗
Preferences for decision-making autonomy.
Nurses' lack of autonomy has been identified as a leading cause of job dissatisfaction, but attempts to increase satisfaction by increasing autonomy have not always been successful. This survey of 356 randomly selected staff nurses and 130 head nurses from 16 hospitals extends previous work by identifying the preferred level of involvement in 21 patient care and 21 unit operation decisions. Staff nurses agreed on 60 percent of the decisions and, in general, preferred independent decision-making for patient care decisions and shared decision-making for unit operation. Head nurses indicated that staff nurses should have a higher level of autonomy than the staff nurses indicated for themselves.
Adult↗
California's Proposition 99 on tobacco, and its impact.
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Adolescent↗
Role of pulmonary surfactant in airway closure: a computational study.
A numerical model that simulates airway closure by liquid bridging during expiration has been developed. The effects of both surfactant and time-varying geometry have been included; the model determines the liquid layer flow resulting from a surface tension (Rayleigh) instability, and the computation traces the film's development to closure, yielding pressure, velocity, surface shape, and surfactant concentration distributions. It is found that surfactant is effective in retarding or eliminating liquid bridging through the reduction of the mean surface tension and the action of surface tension gradients. The former effect is also critical in minimizing the magnitude of the negative pressure in the liquid layer and thus presumably in reducing the tendency for airway compliant collapse.
Animals↗
Hippocampal p75 nerve growth factor receptor immunoreactivity in development, normal aging and senescence.
Using the monoclonal antibody ME 20.4, p75 nerve growth factor (NGF) receptor immunoreactivity has been studied in the hippocampus and adjacent cortex in a series of 57 cases ranging in age from 24 weeks gestation to 95 years of age. The activity of the neurotransmitter-synthesizing enzyme choline acetyltransferase (ChAT), the activity of which is regulated by NGF, has also been determined in parallel experiments. p75 NGF receptor immunoreactivity was detected in the fetal neocortex as nerve terminal staining, potentially derived from basal forebrain neurons which were positive for NGF receptor, and was also localized in nerve cells of the cerebral cortex. Cortical reactivity for NGF receptor increased with age up to the 4th decade thereafter remaining constant. NGF receptor reactivity localized to neocortical neuronal cell bodies was not present in the postnatal or adult brain. Hippocampal reactivity for the NGF receptor was not present before birth appearing first in the postnatal period and thereafter showing an identical development pattern to the neocortex. ChAT activity in the entorhinal cortex and hippocampus partially paralleled NGF receptor development being present in the neocortex in the fetus but not in the fetal hippocampal formation and increasing postnatally to reach maximum levels in the 4th decade. Whilst entorhinal cortex ChAT values remain relatively constant with ageing, hippocampal ChAT declined with age after the 4th decade. The results may have implications for the aetiology of age-related cholinergic deficits in the hippocampus.
Adolescent↗
Psychiatric comorbidity in patients with generalized anxiety disorder.
OBJECTIVE: The goal of this study was to test the validity of generalized anxiety disorder as an independent diagnostic entity and to evaluate the prevalence and type of other psychiatric disorders coexisting with generalized anxiety disorder. Although a few published studies have addressed the subject, this study presents data from a larger group of subjects and excludes concurrent major depression as a potential confound. METHOD: The authors studied patients with a primary diagnosis of generalized anxiety disorder assigned after evaluation with the Structured Clinical Interview for DSM-III-R. Patients with a concurrent major depressive episode were excluded. All diagnoses for which the patient met criteria were determined, including lifetime occurrence of major depressive episode and substance use. RESULTS: One hundred nine patients with generalized anxiety disorder were included in the analysis. Twenty-eight (26%) of these patients were not given any other lifetime psychiatric diagnosis. The most prevalent comorbid diagnoses were social phobia (25 [23%] of the patients) and simple phobia (23 [21%] of the patients). Forty-six (42%) of the patients with generalized anxiety disorder had experienced at least one major depressive episode during their lifetime. CONCLUSIONS: These results support previous findings of high rates of psychiatric comorbidity in generalized anxiety disorder and validate the usefulness of generalized anxiety disorder as a separate diagnostic entity.
Adult↗
Beta 2-agonists as anti-inflammatory therapies in the lung.
The new generation of long-acting beta 2-agonists, represented by salmeterol and formoterol, inhibit a number of the processes involved in acute inflammation in the lung: inflammatory mediator release, vascular permeability and inflammatory cell accumulation. These effects arise from prolonged activation of beta 2-adrenoceptors in a range of target cells. Salmeterol and formoterol therefore have the potential to be used as additional anti-inflammatory therapy in the treatment of respiratory disease.
Acute Disease↗
Serum proteins and aqueous outflow resistance in bovine eyes.
PURPOSE: Recent evidence shows that much of the protein in the anterior chamber aqueous humor enters diffusively through the root of the iris. The proximity of the protein entry point to the trabecular meshwork suggests that the protein content of the aqueous humor in the trabecular meshwork might be much higher than previously suggested. The authors were interested in investigating the possible hydrodynamic implications of these proteins. METHODS: Bovine eyes were perfused with concentrations of bovine serum in buffer ranging from 0% to 15% to determine the effect on outflow resistance. Immunohistochemical methods were used on these eyes and unperfused eyes to determine the distribution of albumin in the anterior segment. RESULTS: Preliminary perfusion studies suggested that increasing the concentration of serum in buffer from 0% to 15% decreased the rate of "wash-out" in bovine eyes, with a 15% solution essentially eliminating the wash-out phenomenon. Perfusion of a series of bovine eyes with a total of 5 ml of 15% serum in buffer showed a "wash-out" rate of 0.0498 +/- 0.0428 ([microliters/min/mm Hg]/[ml perfusate]), whereas control eyes perfused with buffer washed-out at a rate of 0.1677 +/- 0.0271 (P < 0.05); a second series of eyes perfused with a total of 10 ml of 15% serum washed-out at a rate of 0.0533 +/- 0.0294, whereas control eyes had a rate of 0.1813 +/- 0.0342 (P < 0.02). Immunohistochemical investigations showed significant quantities of albumin in the outflow pathway of unperfused eyes, whereas perfusion with buffer eliminated this protein; perfusion with 10% to 15% serum in buffer maintained the level of albumin in the outflow pathway similar to that found in unperfused eyes. Use of cuprolinic blue in a critical electrolyte concentration confirmed previous findings that sulfated proteoglycans are not eliminated from the trabecular meshwork during wash-out. CONCLUSIONS: Wash-out in nonhuman species may result from progressive depletion of an anterior segment depot of plasma-derived proteins entering the trabecular meshwork. Modeling studies confirm that plasma-derived proteins in the aqueous humor of the trabecular meshwork can generate a significant fraction of aqueous outflow resistance. The lack of wash-out in human eyes suggests that this system may maintain flow resistance in a fashion fundamentally different from other species.
Animals↗
Management of community-acquired pneumonia.
Pneumonia is one of the most common infectious illnesses treated by primary physicians. Accurate diagnosis requires a thorough history and physical examination, supplemented by a chest x-ray to confirm the presence of pneumonia and an adequate sputum sample to establish the etiologic agent. Empiric treatment is guided by a knowledge of the most likely organisms and their sensitivities in a particular community.
Aged↗
Comparison of intranasal versus intravenous verapamil bioavailability.
Intranasal verapamil administration may limit intrasubject variability encountered due to the metabolism differences of the d and l-isomers. We simultaneously measured verapamil/norverapamil concentrations, PR interval, heart rate (HR), and mean arterial pressure (MAP) in six healthy volunteers receiving verapamil 5 mg intranasally and intravenously on two separate occasions. Two subjects achieved measurable verapamil concentrations after intranasal administration with a mean bioavailability of 16.1%. Intranasal bioavailability was limited secondary to instillation volume. No relationship between HR, MAP and verapamil concentration was noted. A relationship between mean intravenous verapamil concentration and mean PR interval was observed; however, extensive interpatient variability existed: two subjects demonstrated enough counterclockwise hysteresis to skew mean data. Mean data may falsely represent the verapamil concentration-effect relationship. Intranasal verapamil administration is limited by instillation volume. Development of a concentrated dosage form is necessary to assess bioavailability. Concentration-effect relationships are more accurately described using individual, rather than mean data.
Administration, Intranasal↗
Short-term effects of 2,4,5-trihydroxyamphetamine, 2,4,5-trihydroxymethamphetamine and 3,4-dihydroxymethamphetamine on central tryptophan hydroxylase activity.
In previous studies, we have reported the long-term effects of several metabolites of 3,4-methylenedioxymethamphetamine (MDMA) on tryptophan hydroxylase (TPH) activity. In this study, the short-term effects of three metabolites of MDMA. 2,4,5-trihydroxyamphetamine (THA), 2,4,5-trihydroxymethamphetamine (THM) and 3,4-dihydroxymethamphetamine, and the in vitro effect of THA on TPH activity are reported. After short-term treatment, hippocampal TPH activity was decreased to 8 and 54% of control in response to THA and THM, respectively, but was unaltered after 3,4-dihydroxymethamphetamine. Incubating TPH from THM-treated rats with dithiothreitol under nitrogen failed to reverse the decrease in enzyme activity induced by THM treatment. THA also decreased tyrosine hydroxylase activity to 75% of control, whereas the enzyme activity remained unaltered by THM. The structural analog of THA, 6-hydroxydopamine, failed to reproduce the effect of THA on TPH activity; however, 5,6-dihydroxytryptamine decreased hippocampal TPH activity to 18% of control. In the in vitro study, the hippocampus and the striatum were incubated in varying concentrations of THA. After a 1-h incubation at 37 degrees C, hippocampal TPH activity was decreased to 83, 71, 68, 47 and 3% of control after exposure to 0.001, 0.01, 0.1, 0.5 or 5.0 mM THA, respectively; striatal TPH activity was reduced to 98, 95, 70, 54 and 17% of control, respectively. Incubating the enzyme under reducing conditions failed to restore the enzyme activity to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)
5,6-Dihydroxytryptamine↗