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Biomedical subjects

S Saunders

Publications and source records attributed to S Saunders.

At least 37 records · Page 2Linked to original sources

Effects of noise exposure, race, and years of service on hearing in U.S. Army soldiers.

Over the last two decades the U.S. Army has instituted a comprehensive hearing conservation program (HCP) to reduce the prevalence of hearing loss in soldiers and civilian employees. As a component of this program, hearing threshold levels (HTLs) are stored in a central computerized Army-wide hearing conservation data registry. The aim of this study was to analyze the hearing threshold data to compare the hearing loss among soldiers representing different (1) race groups, (2) noise exposure groups, and (3) duration of military service. HTLs were age-corrected using data base B values from ISO 1999 (1990). As may be expected, soldiers exposed to high noise levels had significantly poorer hearing than the group of soldiers with limited noise exposure. On the average, results indicated a significant difference in HTLs among the race groups with black soldiers having the most sensitive hearing and white soldiers having the poorest. Also, subjects with greater durations of military service had the least sensitive hearing. Finally, race and years of service factors were found to interact in their effect on HTL. The findings are discussed in terms of implications of race differences, normative data, and effectiveness of the U.S. Army HCP.

Adolescent↗

Accuracy of sex determination using morphological traits of the human pelvis.

This study assesses the accuracy and reliability of 17 individual morphological traits of the pelvis frequently used to determine the sex of human skeletal remains. A sample of 49 right and left adult hip bones and sacra of documented individuals were available from an historic church cemetery dating from the 19th century. A hypothetical ranking of the accuracy of traits was drawn from the literature. Next, individual traits were evaluated for precision and accuracy of observations, and combinations of two and three traits were evaluated for their collective effectiveness as sex indicators. The effect of age on the accuracy of traits for sex determination was also examined. Precision of traits was generally good. Several combinations of three criteria produced higher levels of accuracy than the trait list as a whole. A total of six traits was judged to be most effective as sex discriminators because of low intraobserver error levels and better than 83% accuracy rats. There was no indication of an age effect on the precision or accuracy of these traits although sample sizes are small.

Adult↗

Accuracy tests of tooth formation age estimations for human skeletal remains.

Estimations of age from tooth formation standards for a large (n = 282) sample of subadult skeletal remains from a 19th century historic cemetery sample were analyzed. The standards of Moorrees et al. (1963a,b) for the permanent and deciduous teeth, and Anderson et al. (1976) for the formation of permanent dentition were employed in a variety of combinations to calculate mean dental ages. Tests of accuracy and bias were made on a small sample (n = 17) of personally identified individuals, and age of attainment scores were compared to age of prediction scores for each individual. The resulting dental age distributions for the skeletal sample were compared to documented burial records for the cemetery to determine the representativeness of the skeletal sample. These comparisons showed little difference between age of attainment versus age of prediction methodologies. The standards of Moorrees et al. (1963a,b) were observed to provide the most accurate estimates of age with a standard deviation of one-half year. The standards of Anderson et al. (1976), while easier to use and more extensive, are problematic in that the original reference sample begins at three years of age, while the sample used by Moorrees and colleagues begins at birth. The skeletal age distributions compare well to the overall chronological age distribution for the cemetery. These results affirm that tooth formation age estimates for subadult skeletal remains from archaeological or forensic samples provide accurate assessments of age at both the individual and population level.

Adolescent↗

Cardioactive neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFamide) and novel related peptides are encoded in multiple copies by a single gene in the snail Lymnaea stagnalis.

The neuropeptide Phe-Met-Arg-Phe-NH2 (FMRFamide) is a potent cardioactive neuropeptide in Lymnaea stagnalis. Isolation and sequencing of 2 cDNAs and a genomic clone shows that a single gene encodes a precursor protein which contains 9 copies of the FMRFamide peptide, 2 copies of the related peptide Phe-Leu-Arg-Phe-NH2 (FLRFamide), and single copies of the putative pentapeptides Gln-Phe-Tyr-Arg-lle-NH2 (posttranslationally modified to pQFYRlamide) and Glu-Phe-Leu-Arg-lle-NH2 (EFLRlamide). The gene is transcribed in the CNS and gives rise to a single RNA of 1.7 kb in size. The organization of the Lymnaea gene is significant with respect to the evolution of FMRFamide and related peptides in other organisms.

Animals↗

Molecular cloning of syndecan, an integral membrane proteoglycan.

We describe cDNA clones for a cell surface proteoglycan that bears both heparan sulfate and chondroitin sulfate and that links the cytoskeleton to the interstitial matrix. The cDNA encodes a unique core protein of 32,868 D that contains several structural features consistent with its role as a glycosamino-glycan-containing matrix anchor. The sequence shows discrete cytoplasmic, transmembrane, and NH2-terminal extracellular domains, indicating that the molecule is a type I integral membrane protein. The cytoplasmic domain is small and similar in size but not in sequence to that of the beta-chain of various integrins. The extracellular domain contains a single dibasic sequence adjacent to the extracellular face of the transmembrane domain, potentially serving as the protease-susceptible site involved in release of this domain from the cell surface. The extracellular domain contains two distinct types of putative glycosaminoglycan attachment sites; one type shows sequence characteristics of the sites previously described for chondroitin sulfate attachment (Bourdon, M. A., T. Krusius, S. Campbell, N. B. Schwartz, and E. Ruoslahti. 1987. Proc. Natl. Acad. Sci. USA. 84:3194-3198), but the other type has newly identified sequence characteristics that potentially correspond to heparan sulfate attachment sites. The single N-linked sugar recognition sequence is within the putative chondroitin sulfate attachment sequence, suggesting asparagine glycosylation as a mechanism for regulating chondroitin sulfate chain addition. Both 5' and 3' regions of this cDNA have sequences substantially identical to analogous regions of the human insulin receptor cDNA: a 99-bp region spanning the 5' untranslated and initial coding sequences is 67% identical and a 35-bp region in the 3' untranslated region is 81% identical in sequence. mRNA expression is tissue specific; various epithelial tissues show the same two sizes of mRNA (2.6 and 3.4 kb); in the same relative abundance (3:1), the cerebrum shows a single 4.5-kb mRNA. This core protein cDNA describes a new class of molecule, an integral membrane proteoglycan, that we propose to name syndecan (from the Greek syndein, to bind together).

Amino Acid Sequence↗

Cell surface proteoglycan binds mouse mammary epithelial cells to fibronectin and behaves as a receptor for interstitial matrix.

The proteoglycan (PG) on the surface of NMuMG mouse mammary epithelial cells consists of at least two functional domains, a membrane-intercalated domain which anchors the PG to the plasma membrane, and a trypsin-releasable ectodomain which bears both heparan and chondroitin sulfate chains. The ectodomain binds cells to collagen types I, III, and V, but not IV, and has been proposed to be a matrix receptor. Because heparin binds to the adhesive glycoproteins fibronectin, an interstitial matrix component, and laminin, a basal lamina component, we asked whether the cell surface PG also binds these molecules. Cells harvested with either trypsin or EDTA bound to fibronectin; binding of trypsin-released cells was inhibited by the peptide GRGDS but not by heparin, whereas binding of EDTA-released cells was inhibited only by a combination of GRDS and heparin, suggesting two distinct cell binding mechanisms. In the presence of GRGDS, the EDTA-released cells bound to fibronectin via the cell surface PG. Binding via the cell surface PG was to the COOH-terminal heparin binding domain of fibronectin. In contrast with the binding to fibronectin, EDTA-released cells did not bind to laminin under identical assay conditions. Liposomes containing the isolated intact cell surface PG mimic the binding of whole cells. These results indicate that the mammary epithelial cells have at least two distinct cell surface receptors for fibronectin: a trypsin-resistant molecule that binds cells to the sequence RGD and a trypsin-labile, heparan sulfate-rich PG that binds cells to the COOH-terminal heparin binding domain. Because the cell surface PG binds cells to the interstitial collagens (types I, III, and V) and to fibronectin, but not to basal lamina collagen (type IV) or laminin, we conclude that the cell surface PG is a receptor on epithelial cells specific for interstitial matrix components.

Animals↗

Cell surface proteoglycan of mouse mammary epithelial cells is shed by cleavage of its matrix-binding ectodomain from its membrane-associated domain.

The cell surface proteoglycan on normal murine mammary gland (NMuMG) epithelial cells consists of a lipophilic domain, presumably intercalated into the plasma membrane, and an ectodomain that binds via its glycosaminoglycan chains to matrix components, is released intact by proteases and is detected by monoclonal antibody 281-2. The antibody 281-2 also detects a proteoglycan in the culture medium conditioned by NMuMG cells. This immunoactive proteoglycan was purified to homogeneity using DEAE-cellulose chromatography, isopycnic centrifugation, and 281-2 affinity chromatography. Comparison of the immunoreactive medium proteoglycan with the trypsin-released ectodomain revealed that these proteoglycans are indistinguishable by several criteria as both: (a) contain heparan sulfate and chondroitin sulfate chains; and (b) are similar in hydrodynamic size and buoyant density; (c) have the same size core protein (Mr approximately 53 kD); (d) are nonlipophilic as studied by liposomal intercalation and transfer to silicone-treated paper. Kinetic studies of the release of proteoglycan from the surface of suspended NMuMG cells are interpreted to indicate that the immunoreactive medium proteoglycan is derived directly from the cell surface proteoglycan. Suspension of the cells both augments the release and inhibits the replacement of cell surface proteoglycan. These results indicate that the cell surface proteoglycan of NMuMG cells can be shed by cleavage of its matrix-binding ectodomain from its membrane-associated domain, providing a mechanism by which the epithelial cells can loosen their proteoglycan-mediated attachment to the matrix.

Animals↗

Seat belt education program--a model for public health settings.

A cohort of 268 low-income mothers participating in the Women, Infants, and Children (WIC) Supplemental Food Program was enrolled in a seat belt education and motivation program. The goal of the study was to determine whether seat belt use could be increased by incorporating a brief educational intervention into an existing public health program. Seat belt use was monitored by an unobtrusive observer prior to and one month following the intervention. Seat belt use increased from a baseline of 4.9 to 12.6% one month following education (p less than .01).

Adult↗

Electrostatic modification of protein surfaces: effect on hemoglobin ligation and solubility.

Protein amino groups can be carboxymethylated under mild conditions by the combined use of glyoxylate ion and cyanoborohydride. The amino group is converted to a zwitterionic residue where the pK of the secondary amine is only slightly altered and a carboxyl group has been added some 3 A from the nitrogen atom in the amine. Modification of hemoglobin to low levels of carboxymethylation yields derivatives specifically modified at the terminal alpha-amino groups. These modified hemoglobins are models for the interactions between the protein and small anions. When the extent of modification is increased by treating the protein with a higher concentration of the modifying agents, lysine residues become converted to N epsilon-(carboxymethyl)lysine. In excess of 90% of lysine residues in hemoglobin and myoglobin can be modified by this technique. The increased negative charge can be adjusted to any intermediate level of modification. The change in electrostatic free energy that results from the altered distribution of charge on the protein surface can be correlated with functional properties. Thus, the increased repulsion between the hemoglobin dimers leads to dimerlike oxygen binding properties at a high degree of modification. Similarly, changes in protein solubility secondary to modification reflect altered tetramer-tetramer interactions in the solid state. This method for achieving an altered distribution of charge on the protein surface, a method which can be carried out in a specific or nonspecific fashion to achieve varying degrees of modification, represents a powerful tool for the study of electrostatic interactions in protein chemistry.

Amino Acid Sequence↗

Promoting the use of car safety devices for infants: an intensive health education approach.

Efforts to promote the use of infant car seats through health education techniques have been disappointing when strict criteria for evaluation are used. Low-income families were targeted and were provided with educational sessions in the prenatal, postdelivery , and infant follow-up periods. Free car seats were given to 179 clients. Base-line and follow-up observations were performed at 4 months after delivery. The proportion of correctly restrained infants increased from 9% to 38%. The number of infants who were lap held decreased from 38% to 18%. The proportion of clients who had an approved car seat but who were using it incorrectly increased from 11% to 23%.

Accident Prevention↗

Stereoselectivity of chloroperoxidase-dependent halogenation.

The stereoselectivity of chloroperoxidase halogenation of four substrates has been examined. Chloroperoxidase catalyzes the bromination, but not chlorination, of racemic 2-exo-methylbicyclo[2.2.1]hept-5-ene-2-endo-carboxylic acid (to the delta-lactone) and racemic bicyclo-[3.2.0]hept-2-en-6-one (to the 2-exo-bromo-3-endo-hydroxy-bromohydrin). These products are obtained in near quantitative yield and are racemic. The circumstances of the bromination strongly suggest that halogenation does not occur at the active site but rather by chloroperoxidase-catalyzed formation of Br2 and its release into solution. The inability of chloroperoxidase to halogenate these two alkenes at its active site most probably derives from a steric exclusion from the active site. The stereoselectivity of two additional substrates that undergo active site chlorination was determined. Methionine is quantitatively converted to a 50:50 ratio of the two methionine sulfoxide diastereomers. 2-Methyl-4-propylcyclopentane-1,3-dione is quantitatively chlorinated to 2-chloro-2-methyl-4-propylcyclopentane-1,3-dione. On the basis of optical rotation and proton nuclear magnetic resonance, this product is present as a 40:60 ratio of the racemic diastereomers. It is concluded that active site chlorination by chloroperoxidase proceeds without appreciable stereoselectivity.

Bromine↗

Improvement in antiepileptic drug levels following reduction of intervals between clinic visits.

Antiepileptic drug levels (AEDLs) may reflect how well patients adhere to prescribed medical regimens. Of 30 patients on stable drug regimens AEDLs were increased in 33% by decreasing clinic visit intervals from a mean of 3.4 months to 1.1 months. The testing situation was applied to patients who had AEDLs in the "therapeutic range" (n = 15) as well as those with one or more AEDLs below "therapeutic range" (n = 15). In the latter group 73% of patients showed improvement in AEDLs. Although a less reliable parameter, verbally reported seizure frequencies were also improved. Overall, the reduction in clinic visit interval could be expected to yield improvement in 46 to 80% (confidence interval = 95%). These patients responded equally well to physician and non-physician practitioners. This technique may be useful as an intervening measure for those patients who are noncompliant.

Adolescent↗