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Biomedical subjects

D A Johnson

Publications and source records attributed to D A Johnson.

At least 235 records · Page 13Linked to original sources
PubMed1988

Development and evaluation of an attentional test for head injured children--1. Information processing capacity in a normal sample.

The Children's Paced Auditory Serial Addition Task (CHIPASAT) was developed to assess the capacity and rate of information processing in children. This basic aspect of attention underlies many abilities, and is impaired following head injury in adults. Similar impairment may occur in children after head injury or other CNS dysfunction. A sample (N = 315) of normal school children was assessed with the CHIPASAT to establish normative data, and relationships between age, arithmetic ability, general intellectual (g) ability and information processing capacity. The results suggest that the age and, to a lesser extent, the arithmetic ability of a child have a significant influence on information processing capacity. The children's general intellectual ability (g) and sex were unrelated to CHIPASAT performance.

Adolescent↗
PubMed1988

Regulation of intraganglionic synapses among rabbit parasympathetic neurones.

1. The response of parasympathetic neurones to the removal of preganglionic innervation was studied in the ciliary ganglia of adult rabbits. After section of the preganglionic oculomotor nerve, individual ciliary neurones were characterized electrophysiologically by intracellular recording, and morphologically by intracellular injection of horseradish peroxidase. 2. Within the first 24-48 h after nerve section, only two of fifty-nine neurones responded to antidromic stimulation of the postganglionic ciliary nerve with synaptic potentials. This result indicates that synaptic connections between principal neurones are rare in normal ganglia. 3. One week after denervation, however, excitatory postsynaptic potentials were recorded in thirty-nine out of fifty-three cells examined. Thus there is a rapid and extensive formation of intraganglionic connections after denervation. Morphological analysis of these ganglion cells showed numerous fine processes arising from the cell bodies and dendrites; such neurites were not present among control neurones. Many of these newly formed processes appeared to form synapses on neighbouring cells. 4. A similar proportion of neurones (about two-thirds of the cells) showed antidromically evoked excitatory postsynaptic potentials 2 weeks after denervation. Dendrites were still longer and more complex than controls at this time. After several months the morphology and prevalence of intraganglionic connections returned to normal as the ganglion became reinnervated. 5. Thus, denervation of rabbit ciliary ganglion cells induces the rapid formation of large numbers of functional synaptic connections among ganglion cells. It is postulated that local regulatory factors govern connections between parasympathetic ganglion cells. After denervation, these trophic signals are no longer modulated by presynaptic axons and they exert a stimulus for sprouting and synapse formation among this population of cholinergic neurones.

Action Potentials↗
PubMed1988

Influence of thyroxine in the regulation of rat parotid salivary protein composition.

This study tested the role of thyroxine in the regulation of the protein composition of rat parotid saliva. Thyro-parathyroidectomy was performed on two groups of rats, one of which subsequently received thyroxine replacement; the third group was sham-operated. Parotid saliva was collected on the eighth day after surgery, with pilocarpine and isoproterenol used as a secretory stimulus. The volume of saliva collected in 30 min from the thyro-parathyroidectomized rats was 55% less than that collected from sham-operated rats. In the thyro-parathyroidectomized rats, the protein concentration as measured by absorption at 215 nm was unaltered, but that measured by the Lowry procedure was 43% higher. Spectrophotometric scans of Coomassie Blue-stained gels following sodium dodecylsulfate polyacrylamide gel electrophoresis of the secreted proteins showed an 18% reduction in the proportion of protein attributable to amylase and a 43% reduction in proportion of acidic and basic proline-rich proteins following thyro-parathyroidectomy; deoxyribonuclease and two other major secretory proteins (Fraction I and Fraction V) were increased (38%, 20%, and 46%, respectively). These changes in flow rate, protein concentration by the Lowry assay, and protein composition were prevented by treatment of thyro-parathyroidectomized rats with thyroxine replacement and are in opposition to those changes we reported earlier for hyperthyroid rats. The results indicate that the flow of saliva as well as the synthesis of the various salivary proteins are influenced by thyroxine.

Amylases↗
PubMed1988

Chronic treatment with beta adrenergic agonists and antagonists alters the composition of proteins in rat parotid saliva.

This investigation was undertaken to determine the role of beta-adrenergic receptors in the regulation of the protein composition of rat parotid saliva. Chronic treatment of rats with dobutamine, a beta 1-adrenergic agonist, resulted in changes in parotid saliva volume, protein concentration, and composition which were essentially the same as those changes which occurred following chronic treatment with isoproterenol, a non-specific beta-adrenergic agonist. Chronic treatment with the beta 2-adrenergic agonist, terbutaline, had no effect on parotid saliva volume, protein concentration, or composition. Chronic treatment of rats with a beta 1-adrenergic antagonist, metoprolol, had different effects on saliva dependent on the manner by which the drug was delivered. Twice-daily injections of metoprolol led to a decrease in flow rate, but protein concentration and composition were unaltered. When metoprolol was delivered by surgically implanted osmotic minipumps, neither the flow of parotid saliva nor its concentration of protein was altered; however, there was a reduction in the proportion of proline-rich proteins in saliva. Comparable changes in parotid saliva protein composition occurred when the minipumps delivered propranolol, a non-specific beta-adrenergic antagonist. Chronic treatment of rats with an alpha 2-adrenergic agonist (clonidine) or antagonist (yohimbine) was without effect on parotid saliva flow rate, protein concentration, or composition. These findings suggest that the synthesis of proline-rich proteins is regulated, in part, by beta-adrenergic receptor stimulation, and primarily by the beta 1-receptor subtype.

Adrenergic beta-Agonists↗
PubMed1988

The significance of depression in the prediction of relapse in chronic schizophrenia.

The prospective monitoring of two separate groups of chronically schizophrenic patients on regular depot maintenance therapy suggests that depression developing after an interval of 1 year from recovery from an acute relapse indicates a significant increase in the risk of a further relapse within 2 years, compared with depression within the first year, or no depression. Patients with such depression were more prone to relapses than other patients, despite regular medication within normal dose ranges. The results suggest that the aetiology of depression occurring in patients after 1 year in a stable mental state is different from that of depression within the first year, and in many patients, the former represents underlying schizophrenic activity prior to an early relapse.

Adult↗
PubMed1988

Bronchial leukocyte proteinase inhibitor levels in bronchial washings in asthma patients.

To evaluate whether epithelial damage of airways in asthma could be related to diminished levels of the low molecular weight bronchial leukocyte proteinase inhibitor (BLPI) in airways, we determined BLPI in bronchial washings of 13 asthma patients and 13 healthy subjects, using a sensitive enzyme-linked immunoassay. The patients had asthma due to western red cedar and had bronchial washings done 24 to 48 hours after a mild to moderate asthmatic reaction induced by inhalation challenge. We did not find significant differences in BLPI concentrations in lavage fluid of asthma patients and healthy control subjects. The ratios of BLPI to albumin levels in bronchial washings appeared to be lower among asthmatic patients, but this difference was mainly due to an increase in albumin levels in lavage fluid in asthma. In addition, there were no significant differences in BLPI levels in washings obtained from main and segmental bronchi in both control subjects and asthma patients.

Adult↗
PubMed1987

Rapid isolation of human kininogens.

A rapid, two-step procedure is described for the isolation of both "high molecular weight" (H-) and "low molecular weight" (L-) plasma kininogens from a single sample of plasma. Affinity chromatography on carboxymethyl-papain-Sepharose is used, together with high-resolution anion exchange chromatography.

Blood Coagulation↗
PubMed1987

Decidium. A novel fluorescent probe of the agonist/antagonist and noncompetitive inhibitor sites on the nicotinic acetylcholine receptor.

We have examined the interaction of the nicotinic acetylcholine receptor with decidium diiodide, a bisquaternary analogue of ethidium containing 10 methylene groups between the endocyclic and trimethylamino quaternary nitrogens. Decidium inhibits mono-[125I]iodo-alpha-toxin binding, inhibits agonist-elicited 22Na+ influx in intact cells, augments agonist competition with mono-[125I]iodo-alpha-toxin binding, and enhances [3H]phencyclidine (PCP) binding to a noncompetitive inhibitor site. These effects occur over similar concentration ranges (half-maximum effects between 0.1 and 0.4 microM). Thus, decidium binds to the agonist site and converts the receptor to a desensitized state exhibiting increased affinity for agonist and heterotropic inhibitors. These properties are similar to metaphilic antagonists characterized in classical pharmacology. At higher concentrations decidium associates directly with the noncompetitive inhibitor site identified by [3H]phencyclidine binding. Dissociation constants of decidium at this site in the resting and desensitized states are determined to be 29 and 1.2 microM, respectively. Analysis of fluorescence excitation and emission maxima reveal that binding to both the agonist and noncompetitive inhibitor sites is associated with approximately 2-fold enhancement of fluorescence. The excitation maximum for decidium bound at the agonist site appears at 490 nm while that for decidium bound at the noncompetitive inhibitor site appears at 530 compared to 480 nm in buffer. These results suggest that decidium experiences a more hydrophobic environment upon binding to the nicotinic acetylcholine receptor sites, particularly to the noncompetitive inhibitor site. Fluorescence energy transfer between N'-fluorescein isothiocyanate-lysine-23 alpha-toxin (FITC-toxin), and decidium is not detected when each is bound to one of the two agonist sites on the receptor. This allows a minimal distance to be estimated between fluorophores. In contrast, energy transfer is observed between decidium nonspecifically associated with the membrane or with nonspecific sites and the FITC-toxin at the agonist sites.

Animals↗
PubMed1987

The isolation of high-molecular-weight DNA from plants.

A procedure to isolate high-molecular-weight DNA from plant materials has been devised. With this procedure, high-molecular-weight DNA suitable for Southern transfer experiments has been isolated from over 30 plant species including angiosperms (both dicots and monocots), a gymnosperm, members of other divisions, and two microorganisms.

Buffers↗
PubMed1987

Antitumor xenograft activity with a conjugate of a Vinca derivative and the squamous carcinoma-reactive monoclonal antibody PF1/D.

The human squamous carcinoma-reactive murine monoclonal antibody PF1/D was used to derive a conjugate with the Vinca derivative 4-desacetylvinblastine-3-carboxyhydrazide (PF1/D-DAVLBHYD). This immunoconjugate was shown to be largely aggregate free and there was no loss of immunoreactivity postconjugation. When tested in vivo in a 3-day-established human squamous carcinoma nude mouse xenograft model, the PF1/D-DAVLBHYD conjugate eliminated tumor growth with three injections (days 3, 6, and 9) at 2 mg/kg Vinca content. Significant tumor suppression was also observed with 0.5 mg/kg conjugate doses. In contrast, free PF1/D antibody had minimal antitumor activity and no activity was seen with identical doses of a control non-tumor-binding IgG-DAVLBHYD conjugate. Together, these data demonstrate the specificity of the PF1/D-DAVLBHYD antitumor effects.

Animals↗
PubMed1987

Interaction of noncompetitive inhibitors with the acetylcholine receptor. The site specificity and spectroscopic properties of ethidium binding.

The spectroscopic properties and specificity of binding of a fluorescent quaternary amine, ethidium, with acetylcholine receptor-enriched membranes from Torpedo californica have been examined. Competition binding with [3H]phencyclidine in the presence of carbamylcholine showed that ethidium binds with high affinity to a noncompetitive inhibitor site (KD = 3.6 X 10(-7) M). However, in the presence of alpha-toxin, ethidium's affinity is substantially lower (KD approximately 1 X 10(-3) M). Ethidium was also found to enhance [3H]acetylcholine binding with a KD characteristic of ethidium binding to a high-affinity noncompetitive inhibitor site. These findings indicate that ethidium binds to an allosteric site which is regulated by agonist binding and can convert the agonist sites from low to high affinity. Fluorescence titrations of ethidium in the presence of carbamylcholine yielded a similar KD (2.5 X 10(-7) M) and showed an ethidium stoichiometry of one site/acetylcholine receptor monomer. Ethidium was completely displaced by noncompetitive inhibitors such as phencyclidine, histrionicotoxin, and dibucaine. The enhanced fluorescence lifetime of the bound species showed that the increased fluorescence intensity reflects a 13-fold increase in quantum yield for the complex compared to ethidium in buffer. Fractional dissociation of ethidium with phencyclidine produced a double-exponential fluorescence decay rate with lifetime components characteristic of ethidium free in solution and bound to the receptor. These data argue that the alterations in ethidium fluorescence elicited by other ligands is due to a change in the fraction of specifically bound ethidium rather than a change in quantum yield of a pre-existing ethidium-acetylcholine receptor complex. The extent of polarization indicates that bound ethidium is strongly immobilized. The magnitude of the quantum yield enhancement and the shifts of excitation and emission maxima of bound ethidium suggest that its binding site is within a hydrophobic domain with limited accessibility to the aqueous phase.

Acetylcholine↗
PubMed1987

Ozone effects on inhibitors of human neutrophil proteinases.

The effects of ozone on human alpha 1-proteinase inhibitor (A-1-PI), alpha 1-antichymotrypsin (A-1-Achy), bronchial leukocyte proteinase inhibitor (BLPI), and Eglin C were studied using in vitro exposures in phosphate-buffered solutions. Following ozone exposure, inhibitory activities against human neutrophil elastase (HNE) and/or cathepsin G (Cat G) were measured. Exposure of A-1-PI to 50 mol O3/mol protein resulted in a complete loss of HNE inhibitory activity, whereas A-1-Achy lost only 50% of its Cat G inhibitory activity and remained half active even after exposure to 250 mol of O3. At 40 mol O3/mol protein, BLPI lost 79% of its activity against HNE and 87% of its Cat G inhibitory activity. Eglin C, a leech-derived inhibitor, lost 81% of its HNE inhibitory activity and 92% of its ability to inhibit Cat G when exposed to 40 mol O3/mol. Amino acid analyses of ozone-exposed inhibitors showed destruction of Trp, Met, Tyr, and His with as little as 10 mol O3/mol protein, and higher levels of O3 resulted in more extensive oxidation of susceptible residues. The variable ozone susceptibility of the different amino acid residues in the four proteins indicated that oxidation was a function of protein structure, as well as the inherent susceptibility of particular amino acids. Exposure of A-1-PI and BLPI in the presence of the antioxidants, Trolox C (water soluble vitamin E) and ascorbic acid (vitamin C), showed that antioxidant vitamins may protect proteins from oxidative inactivation by ozone. Methionine-specific modification of BLPI reduced its HNE and Cat G inhibitory activities. Two moles of N-chlorosuccinimide per mole of BLPI methionine caused an 80% reduction in activity against Cat G, but only a 40% reduction in HNE inhibitory activity.

Amino Acids↗
PubMed1987

Psychiatric morbidity among spouses of patients with stroke.

The medium term psychiatric morbidity of spouses of patients with stroke was evaluated one to three years after the event. Compared with a control group the spouses were more likely to be depressed (p less than 0.005) and had more physical symptoms (p less than 0.01). Depression increased with the severity of the stroke in the spouse (p less than 0.05) and with time during the three years. Regular contact with friends and neighbours protected spouses (p less than 0.005). Depressed spouses were more likely to be taking tranquillisers than non-depressed spouses (p less than 0.0001) but no more likely to be taking antidepressants. Social rehabilitation after stroke was less successful when the spouse was depressed. Proper attention paid to spouses of patients with stroke might improve the prospects of these patients.

Attitude to Health↗
PubMed1987

Human pituitary tryptase: molecular forms, NH2-terminal sequence, immunocytochemical localization, and specificity with prohormone and fluorogenic substrates.

A human pituitary-derived serine protease, immunologically identical to human lung tryptase (Smith, T. J., Hougland, M.W., and Johnson, D.A. (1984) J. Biol. Chem. 259, 11046-11051), was found immunohistochemically to be associated with mast cells present in pituitary connective tissue. Western blotting combined with sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated the presence of multiple forms: a major Mr 36,300 form and three minor forms with Mr 32,400, 33,400, and 34,600. Two major forms with Mr 35,600 and 34,100 were detected by affinity labeling with 125I-D-Tyr-Glu-Phe-Lys-Arg-CH2Cl. Treatment of the pituitary tryptase preparation with N-glycosidase F indicated that some of the molecular weight heterogeneity results from N-linked glycosylation. The multiple molecular weight forms appear to have the same NH2-terminal sequence: Ile-Val-Gly-Gly-Gln-Glu-Ala-Pro. Pituitary tryptase has an apparent Mr = 110,000 by gel filtration on Sephadex G-200 in the presence of 0.3 M NaCl, indicating that the enzyme may be a tetramer of Mr = 32,400-36,300 subunits. However, this quaternary structure was not stable to gradient polyacrylamide gel electrophoresis. Human pituitary tryptase was so reactive toward synthetic tripeptide coumarin-containing substrates containing a pair of basic amino acids at the site of cleavage such as benzyloxylcarbonyl-L-Ala-L-Lys-L-Arg-4-methylcoumarin-7-amide (k cat/Km = 2.38 X 10(8) M-1 s-1) that Briggs-Haldane kinetics may apply. The reversible inhibitor NaCl at a concentration of 1 M decreased the k cat/Km for benzyloxylcarbonyl-L-Ala-L-Lys-L-Arg-4-methylcoumarin-7-amide to 6.53 X 10(6) M-1 s-1, which reflected a 100-fold increase in apparent Km. Based on active site titration with fluorescein mono-p-guanidinobenzoate hydrochloride, NaCl had no effect on the number of accessible active sites. Substrate specificity studies with prohormones indicated that pituitary tryptase has a preference for cleaving COOH-terminal to arginine or lysine residues which are preceded by a proline residue 4 or 6 residues NH2-terminal to the site of cleavage.

Amino Acid Sequence↗
PubMed1987

Serum angiotensin converting enzyme activity in evaluation of patients with liver disease.

This study was undertaken to evaluate angiotensin converting enzyme activity in patients with liver disease, and to explore its relationship to thyroid function in patients with liver disease. Serum angiotensin converting enzyme activity and thyroid hormone levels, determined in 79 patients with intrahepatic-type liver disease and 18 patients with extrahepatic biliary obstruction, were compared with values in 129 euthyroid controls. Serum angiotensin converting enzyme activity was higher in intrahepatic disease than in extrahepatic obstruction, but statistically significant only for acute intrahepatic disease. In the patients studied, high serum angiotensin converting enzyme activity (22 units/ml or more) virtually excluded extrahepatic biliary obstruction, with a negative predictive value of 94 percent. Low serum angiotensin converting enzyme activity had a positive predictive value for extrahepatic obstruction of only 67 percent. Increased angiotensin converting enzyme activity could not be explained as a function of enhanced thyroid activity. Serum angiotensin converting enzyme activity may be useful in separating patients with intrahepatic liver disease from those with extrahepatic obstruction.

Cholestasis, Extrahepatic↗
PubMed1987

Scintigraphic evaluation of duodenogastric reflux. Problems, pitfalls, and technical review.

Bile reflux has been implicated in the pathogenesis of gastritis, gastric ulcer, and esophagitis. Radionuclide techniques provide the only non-invasive method to detect duodenogastric reflux. To analyze the problems that occur with attempts at quantitation, 55 patients were prospectively evaluated (45 patients with reflux esophagitis or Barrett's esophagus and ten patients with clinical symptoms of bile reflux, four of whom had Bilroth II surgery) with Tc-99m DISIDA, using a fasting technique with gallbladder stimulation by sincalide. Visual duodenogastric reflux occurred in 16 of 55 patients. Overlap of small bowel with the stomach is the major problem for accurate quantitation and occurred in 20 of 55 patients (36%). Overlap of left lobe of the liver occurred in 40 of 55 patients (73%), but its contribution to gastric activity was slight and could be easily subtracted. Reflux was intermittent in six of the 16 positive studies (38%), and continuous computer acquisition is needed to detect its maximum value. Primarily because of the problem of small bowel overlap, scintigraphic evaluation of duodenogastric reflux is only, at best, semi-quantitative. A review of the technical variables used in this examination, as well as potential problems that can occur, is provided.

Adult↗