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Biomedical subjects

E C Smith

Publications and source records attributed to E C Smith.

At least 55 records · Page 3Linked to original sources

Localisation of xanthine oxidase to synovial endothelium.

The presence of the xanthine oxidase enzyme system has been demonstrated in the rheumatoid synovium. This supplies a reactive oxygen species generating system to synovium that is subjected to hypoxic-reperfusion cycles (cf inflamed rheumatoid synovium). An antibody to bovine milk xanthine oxidase has been used to localise the enzyme by immunohistochemistry to synovial endothelium. This implicates the endothelial cell as playing a major part in exacerbations of synovitis, induced by radicals.

Antigens↗

A restriction fragment length polymorphism in the pigeon pro alpha 2(1) collagen gene: lack of an allelic association with an atherogenic phenotype in pigeons genetically susceptible to the development of spontaneous atherosclerosis.

A high frequency restriction fragment length polymorphism (RFLP) at the 3'-end of the pigeon pro alpha 2(1) collagen gene was detected using the restriction endonuclease EcoR1. The distribution of this allelic variant was analyzed in DNA isolated from White Carneau pigeons genetically susceptible to the development of spontaneous atherosclerosis. The atherogenic phenotype in individual pigeons was measured by the determination of total cholesterol and cholesterol ester levels in the celiac focus of the thoracic aorta of adult White Carneau pigeons. Aortic wall cholesterol levels correlated with an increase in lesion size. No correlation, however, was observed between allelic variants of the pigeon pro alpha 2(1) collagen gene and the atherogenic phenotype in White Carneau pigeons suggesting lack of linkage between this allelic marker and the genetic susceptibility to spontaneous atherogenesis. This is the first study of its kind in this animal model and serves to provide a basis for the further analysis of co-segregation of RFLPS in candidate genes to this polygenic phenotype.

Animals↗

Evaluation of environmental support in group homes for persons with mental retardation.

Types of environmental support provided to adults with mental retardation in group homes after transfer from a large state institution were compared. Substantial differences in the functioning of the group homes were found even though the service structure was held constant. Community adjustment was compared for matched groups of residents of the group homes. Differences in community adjustment occurred for residents in group homes with significantly different functional features. The findings indicate that resident outcome was generated by the interaction of several factors in combination. Both structural and functional features of facilities must be considered in any evaluation of the effectiveness of community programs.

Adult↗

5,7-Dichlorokynurenic acid, a potent and selective competitive antagonist of the glycine site on NMDA receptors.

Fourteen substituted derivatives of kynurenic acid were compared for their ability to block ionic currents evoked by N-methyl-D-aspartate (NMDA) plus glycine, or kainate, in voltage-clamped Xenopus oocytes injected with rat brain messenger RNA. Among these analogues there was an excellent correlation between the Ki for displacing [3H]glycine binding to rat brain membranes, and the ability to inhibit ionic currents evoked by glycine/NMDA in Xenopus oocytes. In the oocyte 5,7-dichlorokynurenic acid (5,7-DCK) was a competitive blocker of the glycine recognition site on NMDA receptors, and was more potent (KB 65 nM in Schild analysis) and selective (509-fold more potent vs glycine than kainate) than the prototype glycine antagonist, 7-chlorokynurenic acid, 5,7-DCK also reduced NMDA-induced neuron injury in rat cortical cell cultures.

Animals↗

Changes in vascular extracellular matrix accumulation reflect phenotypic differences between the arterial wall of pigeons resistant and susceptible to the development of spontaneous atherosclerosis.

White Carneau pigeons have previously been shown to be genetically susceptible to the development of spontaneous atherogenesis. The severity of development of atheromatous lesions is considerably greater than a more resistant breed of Show Racer pigeons. Analysis of levels of total hydroxyproline and isodesmosine in the thoracic aorta and celiac bifurcation of prelesion, six-week-old White Carneau and Show Racer pigeons, revealed an increased accumulation of total collagen and cross-linked elastin in the White Carneau arterial tissue. Using dot blot hybridization, measurements of steady state levels of several mRNAs in total RNA extracted from pigeon aortic tissue were also determined. While the increased deposition of extracellular matrix proteins was paralleled by a significantly greater recovery of mRNAs coding for pro alpha 1(1) collagen and elastin, in RNA extracted from White Carneau aortal tissue, increased recovery of mRNAs coding for an intracellular protein, gamma-actin were also observed in White Carneau aortal tissue. No differences in steady state levels of mRNAs coding for pro alpha 1(1) collagen and elastin were observed in RNA extracted from pigeon liver, suggesting a tissue specific increase in the mRNAs coding for these connective tissue proteins in aorta. A markedly reduced cell population however, was responsible for this overall increase in biosynthetic activity in White Carneau pigeon aortic tissue. This was demonstrated by a reduced cell count and by the recovery of reduced levels of total DNA in the thoracic aorta and celiac bifurcation of the White Carneau pigeon. The cell population in White Carneau aortic tissue exhibits therefore a markedly different phenotype with respect to a capacity for the biosynthesis of extracellular and intracellular proteins.

Actins↗

Stereoselectivity and mode of inhibition of phosphoinositide-coupled excitatory amino acid receptors by 2-amino-3-phosphonopropionic acid.

DL-2-Amino-3-phosphonopropionic acid, a phosphonate-substituted derivative of aspartic acid, has been shown to be an inhibitor of excitatory amino acid-stimulated phosphoinositide hydrolysis in rat brain slices. In this study, the enantiomers of 2-amino-3-phosphonopropionic acid were synthesized and used to further characterize the stereoselectivity and mechanism of interaction of this compound for inhibiting phosphoinositide-coupled (metabotropic) excitatory amino acid receptors. L-2-Amino-3-phosphonopropionic acid was 3-5 times more potent than D-2-amino-3-phosphonopropionic acid as an inhibitor of ibotenate-stimulated [3H]inositol monophosphate formation in slices of the rat hippocampus or quisqualate-stimulated [3H]inositol monophosphate formation in neonatal rat cerebral cortical slices. Carbachol-stimulated phosphoinositide hydrolysis was not inhibited by L-2-amino-3-phosphonopropionic acid, and L-2-amino-3-phosphonopropionic acid had no appreciable affinity for ionotropic excitatory amino acid receptors at concentrations required to inhibit metabotropic excitatory amino acid responses. The inhibitory effects of L-2-amino-3-phosphonopropionic acid or L-2-amino-4-phosphonobutyric acid on phosphoinositide hydrolysis were not competitive, because they could not be surmounted by increasing concentrations of ibotenate or quisqualate. L-2-Amino-3-phosphonopropionic acid inhibition also could not be prevented by washing the tissue before incubation with ibotenate. Thus, L-2-amino-3-phosphonopropionic acid is a stereoselective inhibitor of metabotropic excitatory amino acid receptors with little affinity for ionotropic receptors. However, the inhibitory effects of L-2-amino-3-phosphonopropionic acid or L-2-amino-4-phosphonobutyric acid were not readily reversed, and the site at which they act to inhibit metabotropic excitatory amino acid receptors remains to be determined.

Alanine↗

Tuberculosis, tuberculin reactivity, and delayed cutaneous hypersensitivity in nursing home residents.

When all residents of a 460-bed nursing home were tuberculin tested after discovery of a fatal case of pulmonary tuberculosis, 34% reacted, including 6% who gave boosted reactions. Twenty-four of 262 (9.2%) nonreactors converted to tuberculin reactors 6 months after exposure. Six of the convertors were among the 21% of the residents who were originally considered anergic on the basis of negative Candida and Trichophyton skin tests. These results confirm the observation that aged nursing home residents have lower rates of tuberculin reactivity than earlier in their lives, and that tuberculosis is a nosocomial infection in nursing homes. However, generalized immune senescence cannot be invoked as a reason for apparent susceptibility because the very marker of infection--the development of tuberculin reaction--is evidence of some degree of immune competence. Furthermore, the presence of cutaneous anergy as clinically determined does not predict inability to develop an immune response to the tubercle bacillus.

Aged↗

FDA's Factored Food Vocabulary for food product description.

The Food and Drug Administration's Factored Food Vocabulary (FFV) uses standardized language to describe characteristics of food products that are important for food safety and nutritional quality. Each food product is described by a set of descriptors from the following factors: product type; food source; part of plant or animal; physical state, shape, or form; degree of preparation; cooking method; treatment applied; preservation method; packing medium; container or wrapping; food contact surface; and user group. The purpose of the vocabulary is to facilitate retrieval of food composition, food consumption, food contamination, and other food-related data relative to these factors. The major advantages of this system are flexibility with specificity, enhanced searchability with economy, and ease of change and updating.

Classification↗

2-Amino- and 2-guanidino-1,2,3,4-tetrahydro-1,4-epoxynaphthalenes as conformationally defined analogues of alpha-adrenergic agents.

The exo- and endo-2-amino-5,8-dimethoxy-1,2,3,4-tetrahydro-1,4-epoxynaphthalenes++ + (3b and 4b, respectively) were prepared and evaluated as conformationally defined analogues of the alpha 1-agonist methoxamine. Only compound 3b exhibited significant alpha 1-agonist activity in the field stimulated rat vas deferens assay. Since 3b closely approximates the antiperiplanar form of (1R,2S)-(-)-erythro-methoxamine, the results suggest that methoxamine interacts with the alpha 1-adrenoceptor in the trans extended form. The exo-guanidino derivative 5 was found to be a partial alpha 1-agonist. Among the exo- and endo-2-amino-1,2,3,4-tetrahydro-1,4-epoxynaphthalenes (3a and 4a, respectively) prepared as rigid analogues of norephedrine, compound 3a possessed agonist activity at both alpha 1- and alpha 2-adrenoceptors, whereas 4a was inactive at either receptor.

Adrenergic alpha-Agonists↗

Newly treated childhood epilepsy: a prospective study of recurrences and side effects.

Eighty-two newly diagnosed children were started on anticonvulsant therapy and followed prospectively for 12 to 36 months. Compliance was excellent. However, 41% had a recurrent seizure within 6 months of starting therapy despite "adequate" serum levels. Recurrences were least frequent in those with generalized tonic-clonic seizures or those with a single seizure plus epileptiform EEG before treatment. Toxicity screening led to unnecessary drug change in two children. Seven other children had behavioral side effects requiring drug change.

Adolescent↗

Synthesis and biological activity of structural analogues of the anticancer benzophenanthridine alkaloid nitidine chloride.

The indenoisoquinoline analogue 9 of nitidine (1) has been prepared and found to possess significant anticancer activity against L1210 lymphoid leukemia, P388 lymphocytic leukemia, and B16 melanocarcinoma. Analogue 14, which lacks the B ring of nitidine (1), has also been synthesized. Compound 14 retains the in vitro toxicity associated with nitidine (1) but is devoid of antileukemic activity. The structural factors that may contribute to the difference in biological activity between the two closely related analogues 9 and 14 are discussed.

Animals↗

Comparative study using norfloxacin and amoxycillin in the treatment of complicated urinary tract infections in geriatric patients.

Norfloxacin, a new oral quinolone antimicrobial agent, was shown to have considerably greater activity than nalidixic acid and cinoxacin against sensitive and resistant strains of Enterobacteriaceae. A clinical trial was carried out comparing norfloxacin with amoxycillin in two groups of 20 geriatric patients with complicated urinary tract infection. The cure rate was 95% with norfloxacin and 75% with amoxycillin. Failures of treatment were due to increased bacterial resistance in most cases. Norfloxacin was well tolerated by all patients and no changes were noted in the toxicological assessment. Norfloxacin is a valuable addition to the oral antimicrobial agents available for the treatment of urinary tract infection.

Aged↗