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Biomedical subjects

L T Smith

Publications and source records attributed to L T Smith.

At least 109 records · Page 6Linked to original sources

Marfan syndrome: abnormal alpha 2 chain in type I collagen.

Cells in culture from a woman with a variety of the Marfan syndrome produce two species of the alpha 2 chains of type I collagen. One alpha 2 chain appears normal; the abnormal chain has a higher apparent molecular weight than normal and migrates more slowly during electrophoresis in sodium dodecyl sulfate/polyacrylamide gels. A similar change in electrophoretic behavior is seen in the prepro alpha 2 chain and the pN alpha 2 chain (which contains the amino-terminal extension). Asymmetric cleavage of the pepsin-treated procollagens with a fibroblast collagenase locates the abnormal segment amino terminal to the cleavage site, and analysis of cyanogen bromide peptides of collagenase cleavage peptides and of whole collagens indicates that the abnormal segment is in either the alpha 2CB3 peptide or the short segment of alpha 2CB5 amino terminal to the collagenase site of the altered alpha 2 chain. The higher apparent molecular weight is consistent with the insertion of a small peptide fragment of approximately 20 amino acids. This alteration in chain size has marked effects on crosslinking because collagen from the patient's skin was 5-10 times more extractable in nondenaturing solvents than that from control skins. Although the abnormal chain was not found in several other individuals with the Marfan syndrome, these findings suggest that the phenotype may be the expression of a variety of primary structure alterations in the chains of type I collagen that interfere with normal crosslink formation.

Adult↗

Altered secretion of type III procollagen in a form of type IV Ehlers-Danlos syndrome. Biochemical studies in cultured fibroblasts.

Cultured dermal fibroblasts from a woman with one variety of type IV Ehlers-Danlos syndrome synthesized type III procollagen but fail to secrete the bulk of the protein. Although total collagen production is similar to that of controls, the affected cells retain almost twice as much collagen as controls. The additional retained protein is a disulfide-boned collagenous trimer that remains disulfide-linked after limited proteolysis with pepsin and, after pepsin treatment, migrates with type III collagen on polyacrylamide gel electrophoresis. Affected cells have markedly increased staining with antibodies directed against type III procollagen. These studies indicate that decreased secretion of type III procollagen that is synthesized can result in the clinical syndrome of type IV Ehlers-Danlos syndrome.

Adult↗

Assessing readability of patient information materials.

Four readability tests that can be used for evaluating the level of difficulty of patient drug information are described, and instructions for their use are given. Assessment of readability procedures are based on either word and sentence lengths (method 1) or word elimination from a standard list (method 2). The Flesch and Fog formulas (method 1) are suitable for determining readability levels from fifth or fourth grade, respectively, to college. The Fry readability graph (method 1) allows a quick estimation of readability levels between grade 1 and college. The Spache system (method 2), used for children's material, determines readability levels between grades 1 and 3. Using the Flesh formula, the readability levels of 111 patient-oriented brochures and pamphlets were assessed. Only 50% were written at or below the accepted standard of eighth-grade level. To fulfill its function, patient drug information should not exceed the reading level of the intended readers. The described tests provide relatively simple methods for assessing readability levels.

Evaluation Studies as Topic↗

A common uptake system for serotonin and dopamine in human platelets.

Kinetic and pharmacologic properties of uptake of serotonin and dopamine by normal human platelets have been investigated to test whether platelets can be employed as a model system for the reuptake of serotonin and dopamine in brain. Uptake of serotonin into platelets closely resembles reuptake of serotonin into serotonergic neurons. In contrast, uptake of dopamine into platelets appears to be mediated inefficiently via the specific serotonin uptake mechanism, based upon several lines of evidence. Serotonin and dopamine compete with each other, Antidepressant drugs, which are competitive inhibitors of uptake of both of these neurotransmitters, act at the same concentration of drug despite large differences in the Km values. Serotonin antagonists inhibit both serotonin and dopamine uptake. Finally, a serotonin-specific uptake inhibitor (fluoxetine) blocks dopamine, as well as serotonin, uptake.

Antidepressive Agents, Tricyclic↗