Search PubMed⌕ Search

Biomedical subjects

A F Williams

Publications and source records attributed to A F Williams.

At least 73 records · Page 4Linked to original sources
PubMed1995

Sodium glycerophosphate in the treatment of neonatal hypophosphataemia.

Nineteen very low birthweight (mean (SD) gestational age 28 (3) weeks) were parenterally fed nutrition solutions containing inorganic calcium and phosphorus salts. All infants had hypophosphataemia. Plasma concentrations were maintained between 1.5 mmol/l and 2.2 mmol/l. Plasma phosphorus concentrations reached 1.5 mmol/l or greater in three patients after 12 hours, in a further nine patients after 36 hours, and in all patients by 60 hours. Changes in plasma calcium concentrations were not significant.

Calcium↗
PubMed1995

Characteristics of fatal crashes of 16-year-old drivers: implications for licensure policies.

Compared with older drivers, and even older teens, greater percentages of 16-year-old drivers in fatal crashes were involved in single-vehicle crashes, were responsible for their crashes, were cited for speeding, had high vehicle occupancy (especially other teenagers), and were female. Sixteen-year-olds were less likely than older drivers to have been drinking. In addition, their crashes occurred at different times than those of older drivers, crashes between 10:00 p.m. and 11:59 p.m. on Fridays and Saturdays being especially likely. Information about the characteristics of the crashes of 16-year-olds is important because this is the age at which most states currently allow teenagers to get an unrestricted driver's license. It is also the age at which restrictions on beginning licenses are being considered in some states. The results of this study suggest that restrictions on teenage passengers, and night-driving curfews with pre-midnight starting times--two provisions used in New Zealand's graduated licensing system--would be appropriate in attempts to reduce crashes of beginning 16-year-old drivers, who have the highest fatal crash rate of any single teen age.

Accidents, Traffic↗
PubMed1994

Driver experience with antilock brake systems.

Antilock brakes provide the capability for shorter stopping distances and the ability to steer and maintain control during hard braking, especially on wet and slippery surfaces. Owners of late model cars equipped with antilock brakes were surveyed in North Carolina and Wisconsin regarding their experiences with antilocks. The survey results indicated that more than 50% of the drivers in North Carolina and 40% in Wisconsin incorrectly indicated how to brake a car in an emergency situations on wet and slippery pavements in a way that will effectively activate the antilock feature. More drivers in Wisconsin than in North Carolina reported that their cars' antilock feature had been used, but more than 33% of the Wisconsin drivers and 62% of North Carolina drivers said they had never used the antilock feature of their cars' brakes.

Accidents, Traffic↗
PubMed1994

Homotypic adhesion of rat B cells, but not T cells, in response to cross-linking of CD48.

Rat lymphocytes were found to aggregate in response to monoclonal antibodies to the glycosyl phosphatidylinositol (GPI)-anchored surface antigen CD48. This clustering required bivalent antibodies but was not Fc mediated. It was blocked by inhibitors of cellular metabolism and cytoskeletal function but not by antibodies to leucocyte function-associated antigen-1 (LFA-1) or intracellular adhesion molecule-1 (ICAM-1). The clusters were found to be due to homotypic adhesion of B cells, with T cells showing no response despite expressing equal levels of CD48. In addition, thymocytes, which are known to cluster in response to cross-linking of Thy-1, another GPI-anchored molecule, were found not to respond to cross-linking of CD48. These results suggest that specific signalling through CD48 in B cells, but not T cells, and through Thy-1, but not CD48, in thymocytes, lead to cell adhesion events. This differential signalling is interesting as neither CD48 nor Thy-1 have transmembrane or intracellular domains. Levels of CD48-associated protein kinase activity were very low in both B and T cells, and no difference in the susceptibility to cleavage with phosphatidylinositol-specific phospholipase C was detected between B- and T-cell CD48.

Animals↗
PubMed1993

Glycosylation of CD4 and Thy-1.

The site-specific glycosylation of soluble recombinant variants of human and rat CD4 (sCD4) expressed in Chinese hamster ovary (CHO) cells has been characterized. The presence of identical oligosaccharides at the conserved glycosylation site in domain 3 of rat and human sCD4 and the greater abundance of oligomannose and hybrid type glycans at the non-conserved glycosylation site of rat sCD4 clearly indicate that the protein structure influences oligosaccharide processing. Comparisons of rat sCD4 glycopeptides with mutant molecules with only single glycosylation sites and with a truncated form containing only the two NH2-terminal domains, indicate that independent processing occurs at each glycosylation site and that domain interactions can also affect oligosaccharide processing. These and other analyses of sCD2 expressed in CHO cells and Thy-1 purified from various tissues suggest that the diversity of oligosaccharide structures on a protein is regulated by the location of the glycosylation sites and the nature of the target protein, cell and tissue. The functional significance of this control remains to be determined.

Animals↗
PubMed1993

Mutational analysis of the CD2/CD58 interaction: the binding site for CD58 lies on one face of the first domain of human CD2.

The adhesion interaction between the immunoglobulin superfamily molecules CD2 and CD58 (lymphocyte function-associated antigen 3) plays an important role in T cell and natural killer cell interaction with various antigen-presenting and target cells. Determination of the solution structure of rat CD2 domain 1 has allowed a model of human CD2 domain 1 to be generated, and a series of mutants based on this model have been made. Residues of domain 1 of human CD2 predicted to be solvent exposed were substituted with the equivalent residues present in the rat CD2 molecule. The ability of these mutants to mediate rosetting with human and sheep erythrocytes was studied. Results show that the binding site of CD2 for both human and sheep CD58 maps to the beta sheet containing beta strands CC'C"F and G. Residues K34 and E36 in beta strand C, R48 and K49 in beta strand C', and K91 and N92 in the loop connecting beta strands F and G are shown to be critical in the interaction. The data support the proposition that the interaction between CD2 and CD58 involves the major beta sheet face of CD2.

Amino Acid Sequence↗
PubMed1993

Crystal structure of domains 3 and 4 of rat CD4: relation to the NH2-terminal domains.

The CD4 antigen is a membrane glycoprotein of T lymphocytes that interacts with major histocompatibility complex class II antigens and is also a receptor for the human immunodeficiency virus. the extracellular portion of CD4 is predicted to fold into four immunoglobulin-like domains. The crystal structure of the third and fourth domains of rat CD4 was solved at 2.8 angstrom resolution and shows that both domains have immunoglobulin folds. Domain 3, however, lacks the disulfide between the beta sheets; this results in an expansion of the domain. There is a difference of 30 degrees in the orientation between domains 3 and 4 when compared with domains 1 and 2. The two CD4 fragment structures provide a basis from which models of the overall receptor can be proposed. These models suggest an extended structure comprising two rigid portions joined by a short and possibly flexible linker region.

Amino Acid Sequence↗
PubMed1993

A rat CD4 mutant containing the gp120-binding site mediates human immunodeficiency virus type 1 infection.

CD4 is the primary receptor for the human immunodeficiency virus type 1 (HIV-1). Early mutational studies implicated a number of residues of CD4, centered in the region 41-59, in binding to gp120. However, further mutational analyses, together with studies using inhibitory antibodies or CD4-derived peptides, have suggested that other regions of CD4 are also involved in binding or postbinding events during infection. To resolve these ambiguities, we used rat CD4 mutants in which particular regions were replaced with the corresponding sequence of human CD4. We have previously shown that some of these are able to bind HIV-1 gp120, and here we test their ability to act as functional receptors. We find that the presence of human CD4 residues 33-62 is enough to confer efficient receptor function to rat CD4, and we conclude that it is unlikely that regions of CD4 outside this sequence are involved in specific interactions with HIV-1 during either infection or syncytium formation.

Animals↗
PubMed1993

Epitope mapping of anti-rat CD53 monoclonal antibodies. Implications for the membrane orientation of the Transmembrane 4 Superfamily.

CD53 is a pan-leukocyte glycoprotein which is a member of the recently described Transmembrane 4 Superfamily (TM4SF) of membrane proteins that are predicted to span the lipid bilayer four times. The major hydrophilic region of murine CD53 was expressed as a glutathione-S-transferase fusion protein, and the epitopes of four mouse anti-rat CD53 monoclonal antibodies (mAb) (OX-44, 2D1, 6E2 and 7D2) were mapped to this region using mouse/rat chimeric fusion proteins. The epitopes of OX-44, 6E2 and 7D2 are restored by the substitution of a single isoleucine residue for threonine at position 154 in the mouse protein. The 2D1 epitope is non-linear and appears to require the juxtaposition of isoleucine at position 154 with one or more of the amino acids arginine (132), methionine (133) and serine (140). All of these epitopes are shown to be sensitive to reduction, thus indicating the importance of disulfide bonding in the correct folding of the CD53 hydrophilic domain. Moreover, as these four mAb recognize CD53 at the cell surface, the data provide direct molecular evidence for the proposed membrane orientation of the TM4SF.

Amino Acid Sequence↗
PubMed1993

The NH2-terminal domain of rat CD2 binds rat CD48 with a low affinity and binding does not require glycosylation of CD2.

CD2, CD48 and CD58 are structurally similar cell adhesion-molecules forming a subset of the immunoglobulin superfamily (IgSF). In humans CD58 is a ligand for CD2 while in mice CD2 binds CD48. We constructed a soluble chimeric molecule comprising the extracellular portion of rat CD48 and domains 3 and 4 of rat CD4 (sCD48-CD4) and used it to examine whether CD2 is a ligand for CD48 in rats. sCD48-CD4-coated polystyrene Dynabeads formed rosettes on rat CD2-transfected COS-7 cells, and this rosetting was blocked by anti-CD2 (OX34) and anti-CD48 (OX45) monoclonal antibodies. We used sucrose-gradient ultracentrifugation to show that sCD48-CD4 binds, in solution, to soluble forms of rat CD2 including the single NH2-terminal IgSF domain of rat CD2 expressed in bacteria. The upper limit of the affinity of the rat CD48-CD2 interaction is 4 x 10(5) M-1, lower than the published affinity of human CD2 for CD58. These results show that rat CD48 binds CD2 on its NH2-terminal IgSF domain with a low affinity and that binding is independent of glycosylation.

Animals↗
PubMed1993

The effect of city curfew ordinances on teenage motor vehicle fatalities.

Of 149 large cities surveyed, 72 were found to have nighttime curfew ordinances applying to teenagers of various ages. The typical city curfew identified starts at midnight, ends at 5 A.M., and affects all activity of teenagers ages 13-17 in a public place and unaccompanied by a parent. In comparisons of 47 cities with curfews covering 13- to 17-year-olds and 77 cities without curfews, curfews were associated with a 23% reduction in fatal injury for 13- to 17-year-olds for the 9 P.M.-5:59 A.M. time period. This is identical to the 23% reduction estimated for both fatal and nonfatal motor vehicle injuries for 13- to 17-year-olds in an earlier, more limited study of curfews in Detroit, Cleveland, and Columbus, Ohio.

Accidents, Traffic↗
PubMed1993

Comparative analysis of the N-glycans of rat, mouse and human Thy-1. Site-specific oligosaccharide patterns of neural Thy-1, a member of the immunoglobulin superfamily.

Protein structure and tissue type are known to influence glycosylation of proteins. We have previously investigated the N-glycans at each of the three glycosylation sites of the cell surface glycoprotein Thy-1 when isolated from rat brain and thymocytes. Here we report a comparative analysis of the site-specific N-glycosylation patterns from rat (Asn 23, 74, 98), mouse (Asn 23, 75, 99) and human (Asn 23, 60, 100) neural Thy-1. Despite considerable differences in amino acid sequence, the results show a remarkable conservation of the pattern of N-glycans at corresponding sites between the three species, as judged by chromatographic comparisons and glycosidase susceptibility. This is particularly marked for sites at Asn 74/75 in rat/mouse and the equivalent site at 60 in human Thy-1, as well as for sites at Asn 98/99 and 100, respectively. The sites at Asn 23 in rat/mouse also contained almost identical glycosylation patterns, but at this site human Thy-1 showed significantly different glycosylation patterns. These site glycosylation patterns are discussed in relation to the likely accessibility of the oligosaccharides for processing. It is known that within a species, the glycosylation of Thy-1 is tissue specific; therefore, this degree of conservation of glycosylation of Thy-1 expressed in the same tissue in different species is all the more striking, given the known variation between species in the amino acid sequence of Thy-1. It is therefore proposed that neural cells have a particular requirement for specific surface carbohydrates and that the Thy-1 polypeptide serves as an appropriate carrier for these structures.

Amino Acid Sequence↗
PubMed1993

Gene structure, chromosomal localization, and protein sequence of mouse CD53 (Cd53): evidence that the transmembrane 4 superfamily arose by gene duplication.

CD53 is a pan-leukocyte surface glycoprotein which spans the plasma membrane four times and is a member of the transmembrane 4 superfamily (TM4SF). The protein sequence and gene structure of mouse CD53 (Cd53) were determined by isolation of both genomic and cDNA clones. CD53 is highly conserved in evolution, as mouse Cd53 was 91% identical to rat CD53 and 82% identical to human CD53. The mouse Cd53 gene spanned approximately 9.0 kb of DNA and encoded the 219 amino acid residues of CD53 over seven exons. The Cd53 gene produced a 1.8 kb transcript which was dramatically upregulated after cell activation. The mouse Cd53 gene was mapped to chromosome 3, whereas the locus of another TM4SF member, CD37 (Cd37), was mapped to mouse chromosome 7. Three lines of evidence suggest that the TM4SF arose divergently from an ancestral gene. First, the gene structure of CD53 was strikingly similar to two other members of the TM4SF, CD63 and TAPA-1; second, Cd37 mapped to the same chromosome as Tapa-1; and, third, Cd37 mapped to a segment of chromosome 7 that contains a number of genes that are structurally or functionally related to genes closely linked to Cd53 on chromosome 3.

Amino Acid Sequence↗