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Biomedical subjects

S R Simon

Publications and source records attributed to S R Simon.

140 records · Page 8Linked to original sources
PubMed1969

Measurement of ligand-induced conformational changes in hemoglobin by circular dichroism.

The UV circular-dichroism spectra of human and horse hemoglobins have been determined at various degrees of partial saturation with oxygen. Spectra of the two native hemoglobins were compared with spectra of the corresponding proteins modified with a reagent known to eliminate the conformational rearrangement normally associated with cooperativity. Such comparison indicates that one region, around 260 mmu, is sensitive chiefly to the state of the hemes; changes in another region, around 285 mmu, may be correlated with the conformational transformation linked to cooperative interactions. All circular-dichroism changes are strictly linear with fractional saturation with oxygen. Possible implications of these results to recently proposed mechanisms for cooperativity in proteins are discussed.

Animals↗
PubMedDate not supplied

The planning of orthopaedic reconstructive surgery using computer-aided simulation and design.

Three-dimensional reconstructions from computed tomographic (CT) images are currently being used clinically in a wide variety of orthopaedic surgical applications. The computer may be used to select the optimum standard artificial joint replacement or to design a custom artificial joint replacement for a particular patient. Where large bony defects exist, the computer may be used to design bone allografts for joint reconstruction and to manufacture models of the bones for use in planning the surgery. In cases where osteotomies are performed to improve the mechanics of the joint, each proposed osteotomy may be simulated on the computer to identify the surgical plan that will optimally normalize the diseased joint.

Adolescent↗
PubMedDate not supplied

A technique for determining femoral head containment during gait.

Kinematic gait analysis was carried out on 42 hips, including normal joints and joints affected with Legg-Calvé-Perthes disease. Data were analyzed by a computer algorithm that calculated three-dimensional femoral head contact with the acetabulum (containment). Patients were studied in and out of various abduction orthoses. The three-dimensional containment of the hip is reproducibly altered by various devices; specifically, the Atlanta brace increases posterior coverage and slightly increases lateral coverage, and Petrie casts improve lateral and anterior coverage at the expense of posterior containment. This analysis allows modeling of osteotomies and enhances clinical assessment of actual changes in containment with bracing.

Braces↗
PubMedDate not supplied

Effect of pH and nonphysiological salt concentrations on human immunodeficiency virus-1 protease dimerization.

Human immunodeficiency virus-1 (HIV-1) protease is catalytically active as a dimer of identical subunits that associate through noncovalent interactions. To investigate the forces stabilizing HIV-1 protease in its active form, we have studied the effects of pH and salts on structure and function of the enzyme. Enzymatic activity was measured by following the hydrolysis of a fluorogenic substrate. Dissociation of the dimer into its subunits was monitored by gel filtration, while conformational changes in the enzyme were probed by measurements of intrinsic tryptophan fluorescence. Mg2+ ions were capable of dissociating the dimeric enzyme with a concomitant red shift and increase in quantum yield of the tryptophan fluorescence, indicating increased accessibility of tryptophan to the aqueous environment. These structural changes also were associated with a loss of catalytic activity which was insensitive to substrate concentration, consistent with noncompetitive inhibition. Both structural and functional changes could be attributed to binding of Mg2+ ions to a site with an apparent dissociation constant of approximately 2 M. In contrast, increasing concentrations of Na ions up to 5 M were without effect. Increasing pH had similar effects on HIV-1 protease as increasing Mg2+ ions concentration, with concomitant dissociation into subunits, increase in quantum yield and red shift in tryptophan fluorescence, and loss in catalytic activity. The apparent pKa for these structural and functional transitions was 6.95 +/- 0.08. This value is consistent with that of an aspartic acid residue with an anomalously high pKa, which has been implicated in the catalytic activity of HIV-1 protease.

Amino Acid Sequence↗
PubMedDate not supplied

Elastin-derived peptide binding to a hydrophobic domain on neutrophil elastase.

To understand the contributions of binding of elastin to domains removed from the active site of neutrophil elastase, we isolated an elastin-derived peptide (EDP) fraction, which we have previously shown was tightly linked to neutrophil elastase after prolonged digestion of elastin but which can be released from the enzyme with hydroxylamine. Elastin from human aorta was incubated with human neutrophil elastase under conditions favoring proteolysis. Low molecular weight species, including free EDP, were separated from the protein fraction by a small centrifuged gel filtration column. The high molecular weight protein fraction was subjected directly to 0.5 M hydroxylamine. The reaction mixture was then fractionated on a phosphocellulose column using an ionic gradient. A fraction was collected that exhibited fluorescence with a peak at approximately 410 nm when excited at 320 nm, indicating the presence of desmosine and (or) isodesmosine. A second peak with amidolytic activity towards methoxysuccinyl-Ala-Ala-Pro-Val-p-nitroaniline (MeOSucAAPVpNa), but no fluorescence at 410 nm was also detected at the same elution volume where free elastase appeared. After removal of low molecular weight digestion products but prior to treatment with hydroxylamine, the putative elastase-EDP complex possessed no amidolytic activity towards MeOSucAAPVpNa. When the liberated EDP was added to elastase in an amidolytic assay, the EDP behaved as only a partial noncompetitive inhibitor (Vmax/Vmax approximately 90%), but bound with high affinity to neutrophil elastase (Ki congruent to 29 nM), as detected by its ability to quench elastase endogenous fluorescence.(ABSTRACT TRUNCATED AT 250 WORDS)

Aorta↗
PubMedDate not supplied

A community study of a decade of in-hospital breast-feeding: implications for breast-feeding promotion.

Information concerning a subject of interest to the health community may be gathered through simple, low-cost minisurveys. Data were gathered on postpartum breast-feeding in one community in 1974, 1979, and 1984. This community mirrored national trends and offered additional information on areas of programmatic interest; findings also confirmed the hypothesis that education and national trends over time had statistically significant relationships with the choice to breast-feed. Of special note is the finding that the level of knowledge concerning infant feeding is closely linked to the choice to breast-feed, as is the relationship between the primary influence of another woman and the choice to breast-feed. With level of education controlled for, both associated variables remained significant for women with lower levels of education, the group least likely to select breast-feeding. This would suggest the probable advantage of breast-feeding promotion based on woman-to-woman contact during preconception and antepartum periods; such a program might be particularly effective with women of lower educational levels.

Adult↗