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Biomedical subjects

C Thomson

Publications and source records attributed to C Thomson.

At least 19 recordsLinked to original sources

Cognitive and psychophysiological correlates of positive, negative, and disorganized symptoms in the schizophrenia spectrum.

This study examined the cross-sectional and prospective relationships between cognitive and psychophysiological variables and positive, negative, and disorganized symptoms in 40 outpatients with diagnoses of schizophrenia or schizoaffective disorder. The results indicated that disorganized symptoms were related to deficits in auditory and visuomotor attentional processing, increased skin conductance orienting response, and lower stress reactivity. Negative symptoms were related to reduced resting heart rate, increased stress reactivity, and deficits in visuomotor processing. Prospective findings indicated that both the cognitive and heart-rate variables might be trait-related aspects of the negative symptoms, while the skin conductance, but not the cognitive, variables might be trait-related aspects of the disorganized symptoms. Positive symptoms were not related to any of the cognitive or psychophysiological variables.

Adult

Replacement of N-glycosylation sites on the MHC class II E alpha chain. Effect on thymic selection and peripheral T cell activation.

MHC class II molecules play a central role in thymic selection of developing T cells, Ag presentation to immunocompetent CD4+ T cells, and T cell activation by superantigens. We have established transgenic A.CA mice expressing either the wild-type E alpha d molecule (E alpha/E beta), or an E alpha d molecule altered at an N-glycosylation site on the E alpha chain (residue 78, 78E alpha/E beta or residue 118, 118E alpha/E beta) to identify a possible role for carbohydrates in thymic selection and peripheral T cell activation. Striking differences were found among these transgenic mice. Although V beta 10+ T cells were selected positively in all three transgenic strains, positive selection of V beta 7+ T cells was impaired in 118E alpha/E beta transgenic mice. Spleen cells from both strains with mutant E alpha chains showed selective defects in presentation of peptides to particular T cell hybridomas. In contrast, neither mutation affected presentation of the superantigen Mycoplasma arthriditis mitogen. These results demonstrate that alterations in the glycosylation of class II E alpha chains might affect both central and peripheral T cell regulation.

Amino Acid Sequence

A histochemical study of carbonic anhydrase in the plasma membranes of human oral epithelial cells.

Carbonic anhydrase (EC 4.2.1.1) was detected histochemically from the following regions in patients of various ages (14-84 yr): buccal mucosa, buccal flap, hard palate and tongue. The enzyme was principally located in the cell membranes but was also present in nuclei. There was a gradation in activity from basal (strong) to superficial cells (weak/negative). The carbonic anhydrase inhibitors ethoxyzolamide and acetazolamide abolished activity at 0.001 mM, but were ineffective, even at 1.2 mM, against a reaction associated with the granules of the stratum granulosum. No activity was detected in the absence of bicarbonate from the substrate.

Acetazolamide

Sequence identity with type VIII and association with IS176 of type IIIc dihydrofolate reductase from Shigella sonnei.

An uncommon dihydrofolate reductase (DHFR), type IIIc, was coded for by Shigella sonnei that harbors plasmid pBH700 and that was isolated in North Carolina. The trimethoprim resistance gene carried on pBH700 was subcloned and sequenced. The nucleotide sequence of the gene encoding type IIIc DHFR was identical to the gene encoding type VIII DHFR. The type IIIc amino acid sequence was approximately 50% similar to those of DHFRs commonly found in enteric bacteria. Furthermore, this gene was flanked by IS176 (IS26), an insertion sequence usually associated with those of aminoglycoside resistance genes. The gene for type IIIc DHFR was located by hybridization within a 1,993-bp PstI fragment in each of eight conjugative plasmids from geographically diverse strains of S. sonnei. Each plasmid also conferred resistance to ampicillin, streptomycin, and sulfamethoxazole and belonged to incompatibility group M. Plasmids carrying this new trimethoprim resistance gene, which is uniquely associated with IS176, have disseminated throughout the United States.

Amino Acid Sequence

A comparison of membrane enzymes of human and pig oesophagus; the pig oesophagus is a good model for studies of the gullet in man.

The distribution and relative catalytic activities of five plasma membrane enzymes (alkaline phosphatase, dipeptidyl peptidase IV, gamma-glutamyl transpeptidase, microsomal alanyl aminopeptidase and glutamyl aminopeptidase) were examined in human and pig oesophagus. In both species, alkaline phosphatase activity occurred in basal and suprabasal cells of the epithelium and in capillaries. Stromal cells in the human submucosa were particularly reactive. Dipeptidyl peptidase IV was present in blood vessels and capillaries in man and pig and in submucous glands in the pig. The enzyme was also present in both species in the lamina propria cells immediately adjacent to the epithelial basal lamina. In the human, gamma-glutamyl transpeptidase occurred in the epithelial basal cells and in isolated basal and lower prickle cells in the pig. Stromal cells in the human submucosa were strongly reactive and capillaries in the muscularis propria in both species moderately active. Microsomal alanyl aminopeptidase was detected in lamina propria cells adjacent to the epithelial basal cell layer in man and pig and at the apices of mucous cells in pig submucous glands. Weak glutamyl aminopeptidase activity was confined to capillaries in both species. The findings of this study, along with the ready availability of pig oesophagus, suggest that the pig may be a suitable model for studies of the gullet in man.

Animals

Thoracic spinal calcinosis circumscripta causing cord compression in two German shepherd dog littermates.

Two young German shepherd dog littermates had progressive, painless, hindlimb ataxia. In both dogs plain radiography of the vertebral column revealed a solitary mineralised lesion on the dorsal laminae between the dorsal spines of the second and third thoracic vertebrae, and myelography with iopamidol demonstrated cord compression at the level of the lesions. The first dog died 18 hours after the myelography. A dorsal laminectomy performed in the second dog resulted in neurological improvement. A histopathological examination confirmed that both lesions were calcinosis circumscripta. The cause of the death of the first dog was meningitis.

Animals

Sumatriptan and cerebral perfusion in healthy volunteers.

1. The effect of sumatriptan on regional cerebral perfusion was studied in healthy volunteers. 2. Intravenous sumatriptan (2 mg) had no detectable effect on regional cerebral perfusion as measured using a SPECT system with 99technetiumm labelled hexemethylpropyleneamineoxime. 3. Sumatriptan had no effect on pulse, blood pressure or ECG indices. 4. All six volunteers experienced minor adverse effects during the intravenous infusion.

Adult

Structural requirements for inhibitors of poly(ADP-ribose) polymerase.

The purpose of this study was to examine the structure/activity relationships of a series of substituted benzamides as poly(ADP-ribose) polymerase inhibitors. The experimental approach has involved the use of in vitro and in vivo assays in order to gather information either on the intrinsic activity of the benzamides or on the effect of various pharmacodynamic parameters on the activity in vivo. Although some discrepancies between the data obtained in vivo and in vitro were found in this study, results seem to indicate that most powerful inhibitors were characterized by acylation of the -NH2 function in the 3 position or by substitution in this same position with hydroxy or methoxy groups. The best inhibitors were not cytotoxic under these experimental conditions. Computed calculations of molecular electrostatic potential of these molecules were also performed and a good correlation was found between the similarity index and the experimental inhibitory activity.

Benzamides

The molecular structures of 11-methyl and 1,12-dimethylbenz[a]anthracene: purely theoretical semi-empirical AM1 calculations are able to predict accurate structures of these polycyclic hydrocarbons.

Semi-empirical self consistent field calculations are reported on 11-methyl and 1,12-dimethylbenz[a]anthracene using the AM1 method. Comparison of the results of complete geometry optimizations with experimental X-ray structures shows that it is now possible to compute the structure of these large molecules with errors in bond lengths of less than 0.02 A and in bond angles of less than 1.5 degrees.

Benz(a)Anthracenes

The conformations and electrostatic potential maps of phorbol esters, teleocidins and ingenols.

Phorbol esters and the structurally dissimilar teleocidins and ingenols bind to and activate protein kinase C (PKC) during the course of tumour promotion. These compounds are referred to as TPA-like tumour promoters (from 12-O-tetradencanoyl phorbol-13-acetate, the most active of the class) and are amongst the most potent tumour promoters known. Despite their structural dissimilarity, all three groups of molecules have been shown to bind to the diacylglycerol site of PKC with high affinity. It is thought that this binding to and consequent activation of PKC is the crucial step in tumour promotion by these compounds. The aim of this work was to provide a description of the binding site by comparing structural features (in particular the electrostatic potential) with the activity of numerous derivatives of the three classes. Initially the description was obtained by consideration of the phorbol derivatives, and then refined using the teleocidins and ingenols. The activity data were collected from a variety of sources and the structures calculated using the semi-empirical MNDO approximation embodied in the MOPAC program. Where possible, the crystal structure was obtained from the Cambridge Crystallographic Database, and used as a starting point for the calculation. In other cases, a preliminary calculation was carried out using the molecular mechanics program AMBER. Electrostatic potentials were calculated and displayed using an in-house program 3D2, while superpositions of molecules were carried out using CHEM-X.

Diterpenes