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Biomedical subjects

A F Williams

Publications and source records attributed to A F Williams.

At least 109 records · Page 6Linked to original sources
PubMed1992

Sales of alcohol to underage purchasers in three New York counties and Washington, D.C.

A study was conducted in which young males, under the legal alcohol purchase age of 21, attempted to purchase beer at grocery stores and other retail outlets. Underage purchases were attempted at a sample of stores in Washington, D.C.; Westchester County, New York: and Albany and Schenectady counties, New York. Beer was sold to the underage purchasers at 97 percent of the Washington, D.C. stores, 80 percent of the Westchester County stores, and 44 percent of the Albany and Schenectady stores, despite the fact that such sales are illegal. Beer was more likely to be sold to the underage purchasers at smaller neighborhood stores in urban areas. Sales were least likely in Albany, which experienced recent police enforcement of the alcohol purchase age laws. Vigorous enforcement of the minimum purchase age laws is needed to reverse the current national trend toward more alcohol-related highway fatalities among youth.

Adolescent↗
PubMed1992

Smoking cessation interventions by family physicians in Texas.

A survey of 1,292 family physicians in Texas indicates that most of them (99%) ask patients about their smoking behavior. Fewer physicians, however, participate in further activities recommended by the National Cancer Institute: arranging follow-up visits, providing self-help materials, prescribing nicotine gum, engaging patients in discussion, referring patients to a program for smoking cessation, and involving other office personnel in counseling. Almost 80% of the respondents cited such obstacles to their involvement in counseling/advising patients as patient attitudes or patient preferences for smoking. The survey was conducted to acquire baseline data on the involvement of family physicians in Texas in counseling their patients who smoke and the obstacles they meet in their efforts.

Adult↗
PubMed1992

The cost of cancer in Texas.

Direct and indirect costs of cancer for Texas are estimated for 1988 and are compared to costs for 1980. The distribution of these costs by age group and type of cancer is presented and discussed. Conceptual and methodological issues underlying the estimates are explained to assist the reader in interpretation. The authors conclude that future collection of more specific data at the state level would greatly assist policymakers dealing with cancer issues.

Adolescent↗
PubMed1991

Signal transduction by the CD2 antigen in T cells and natural killer cells: requirement for expression of a functional T cell receptor or binding of antibody Fc to the Fc receptor, Fc gamma RIIIA (CD16).

Crosslinking of CD2 antigen on T lymphocytes and natural killer (NK) cells leads to a rise in cytoplasmic-free Ca2+ concentration ([Ca2+]i). However, CD2 seems unlikely to interact directly with the second messenger pathways since signaling via CD2 is poor in T cells that lack the T cell receptor (TCR) and is absent in L cells or insect cells that express CD2. In contrast, NK cells that are also TCR- can be triggered via CD2, but it is unclear as to whether the CD16 Fc receptor (FcR) may facilitate this effect. The CD16 transmembrane molecule is expressed in a complex with the zeta homodimer or the zeta/gamma heterodimer and these dimers are also associated with the TCR complex. Thus, it seemed that zeta chains may provide the link between signaling on NK cells and T cells. This could be tested on TCR- cells since when CD16 is transfected into T cells it is expressed in a complex with TCR zeta homodimer or the zeta/gamma heterodimer. At first, potentiation of CD2 signaling was seen on TCR- Jurkat cells expressing CD16, but this was found to be dependent on trace levels (1%) of IgG in F(ab')2 antibody preparations. With pure F(ab')2, the effect was lost. Signaling on a rat NK cell line was also re-examined with F(ab')2 antibodies that had no IgG contamination, and again no signal transduction via CD2 was seen. We thus conclude that there is no clear evidence for potent signaling via CD2 on cells that lack a TCR complex and that TCR zeta chain expressed at the cell surface is not sufficient to potentiate signaling via CD2 as measured by an increase in [Ca2+]i.

Animals↗
PubMed1991

Structure of domain 1 of rat T lymphocyte CD2 antigen.

The CD2 antigen is largely restricted to cells of the T-lymphocyte lineage and has been established as an important adhesion molecule in interactions between human T lymphocytes and accessory cells. In the adhesion reaction, CD2 on T cells binds to LFA-3 on other cells, with binding through domain 1 of CD2. CD2 can also be a target for the delivery of mitogenic signals to T lymphocytes cultured with combinations of anti-CD2 antibodies. Two predictions that are contradictory have been made for the structure of CD2 domain 1. One suggests an immunoglobulin (Ig) fold, on the basis of sequence patterns conserved in the Ig-superfamily (IgSF), whilst the other proposes a pattern of alternating alpha-helices and beta-strands, on the basis of secondary structure predictions. Thus CD2 domain 1 is an important test case for the validity of IgSF assignments based on sequence patterns. We report here the expression of domain 1 of rat CD2 in an Escherichia coli expression system and have determined a low-resolution solution structure by NMR spectroscopy.

Amino Acid Sequence↗
PubMed1991

Motor vehicle crash injury patterns and the Virginia seat belt law.

Injuries to front seat occupants in tow-away crashes in the Charlottesville, Va, area were compared for 1 year before and 1 year after Virginia's seat belt use law took effect. Vehicle and occupant data were combined to examine crash and injury patterns. Reported seat belt use in crashes increased after the law, and there were substantial decreases in injuries. Front seat occupants were less likely to receive medical treatment following a crash in the postlaw period. The reduction in the number of injuries was greater for passengers in the right front seat than for drivers and for frontal crashes than for other types of crashes. The injury reduction effects occurred primarily through reductions in the number of head and face injuries, particularly those that occur from contact with windshields and instrument panels.

Accidents, Traffic↗
PubMed1991

Autonomous roles for the cytoplasmic domains of the CD2 and CD4 T cell surface antigens.

CD2 and CD4 are single chain transmembrane T cell surface molecules that are involved in signal transduction. Chimaeric constructs from rat CD2 and CD4 antigens were expressed in the Jurkat human T cell line to examine the role of extracellular, transmembrane and cytoplasmic domains in mediating functions controlled by CD2 and CD4. The results show that the large rise in concentration of cytoplasmic free Ca2+ mediated via CD2 crosslinking is controlled by the cytoplasmic domain and does not require the CD2 transmembrane and extracellular domains. Similarly the CD4 cytoplasmic domain alone was shown to encode the specificity for binding to the p56lck tyrosine kinase and to control down-modulation of CD4 after treatment with phorbol ester. Evidence was obtained that down-modulation of CD4 occurs when p56lck dissociates from the cytoplasmic domain due to phosphorylation of Ser 405.

Amino Acid Sequence↗
PubMed1991

The dimensions of the T lymphocyte glycoprotein leukosialin and identification of linear protein epitopes that can be modified by glycosylation.

Leukosialin (CD43) is a major glycoprotein of T lymphocytes whose extracellular domain of 224 amino acids contains on average one O-linked carbohydrate unit per three amino acids. This suggests an unfolded structure for the extracellular domain which has now been established to extend to a length of 45 nm by transmission electron microscopy following low angle rotary shadowing. The antigenicity of rat leukosialin has been studied using nine monoclonal antibodies (MAbs) whose binding is differentially affected by the cell type on which leukosialin is expressed and by the removal of sialic acid. From these observations it appears that the epitopes are affected by glycosylation, yet seven of the nine MAbs reacted clearly with the extracellular domain of leukosialian expressed in an unglycosylated form in Escherichia coli. The MAbs showing this positive reaction included three of the four antibodies whose epitopes were affected by neuraminidase treatment of leukosialin. It thus appears that linear protein epitopes are recognized and that some of these can be modified in the native structure by glycosylation. The positions of the antigenic determinants have been mapped by expressing fusion proteins of different lengths and the identity of one epitope was proven by the binding of two MAbs to an octapeptide expressed as a fusion protein. For three MAbs, the location of epitopes in the native protein was confirmed by electron microscopy of shadowed leukosialin--Fab complexes. Overall it is concluded that leukosialin is a major component at the periphery of the T lymphocyte and that despite its high level of glycosylation, protein determinants are exposed that could be ligands in cell interactions.

Amino Acid Sequence↗
PubMed1991

Characteristics of belted and unbelted drivers.

Drivers who had been observed wearing or not wearing shoulder belts were compared using vehicle registration data, driver records, and telephone interviews. The observations were made on the New York Thruway during a special seat belt publicity and enforcement program, which achieved a 75% overall belt use. The results showed that those drivers who still did not wear a shoulder belt despite New York law and the special Thruway program were more likely to be male, to be driving older vehicles, to have more prior traffic convictions, to have more prior injury crash involvements, and to say they are more likely to take risks than others. Although drivers reported that assessing points against the drivers license for belt law violations could increase belt use, citations for belt use law violations were very rare, and enforcement would probably have to increase before any new penalty could be effective.

Accidents, Traffic↗
PubMed1990

High level expression in Chinese hamster ovary cells of soluble forms of CD4 T lymphocyte glycoprotein including glycosylation variants.

The CD4 cell surface antigen is of interest as a marker of T lymphocytes that recognize foreign antigens in the context of MHC Class II antigen, as a receptor for the human immunodeficiency virus (HIV) and as a member of the immunoglobulin superfamily (IgSF) with four Ig-like domains present in the extracellular domain. In order to produce large amounts of soluble CD4 for x-ray crystallography and other molecular studies, a recently developed expression system based on selection via glutamine synthetase was used. Expression was attempted for rat CD4 corresponding to the full extracellular sequence (sCD4; domains 1-4), the NH2-terminal half (domains 1 and 2) and the first domain alone. Stable transfected Chinese hamster ovary cell lines were obtained that expressed sCD4 and sCD4 (half) at typical maximal levels in spent tissue culture supernatant of greater than 80 and 25 mg/liter, respectively. Domain 1 alone was not expressed and introduction of a N-linked glycosylation site did not facilitate expression. The role of glycosylation in the expression of sCD4 was investigated by mutagenesis of the constructs to remove each of the two N-linked glycosylation sites in turn and both together. All three forms were expressed at 60-120 mg/liter. The sCD4 (half) was not expressed after deletion of its N-linked site. The disulfide bonds of sCD4 were determined to be within domains 1, 2, and 4 and isolation of glycopeptides showed that both N-linked sites were glycosylated. Analysis of the hydrodynamic properties of sCD4 suggested that the molecule adopted an extended conformation in solution rather than folding to form a compact structure like an Fab. The possibility of dimerisation of CD4 was investigated but sCD4 dimers were not seen at an affinity cut-off of about 4 x 10(5) M-1.

Amino Acid Sequence↗
PubMed1990

Structure, expression, and genetic linkage of the mouse BCM1 (OX45 or Blast-1) antigen. Evidence for genetic duplication giving rise to the BCM1 region on mouse chromosome 1 and the CD2/LFA3 region on mouse chromosome 3.

The mouse BCM1 (OX45, Blast-1) antigen has been cDNA cloned and sequenced to provide data supporting the view that BCM1, LFA3, and CD2 constitute a subgroup within the Ig superfamily. Mouse BCM1 is widely expressed on leukocytes and is likely to be anchored to the cell surface by a glycosyl-phosphatidylinositol anchor, as is the case for rat and human BCM1 antigen. Genetic linkage studies by recombination and pulse field analysis showed the BCM1 locus (Bcm-1) to be on distal mouse chromosome 1 and to be linked within 1,600 kb to the locus for an ATPase alpha chain gene (Atpa-3). A similar relationship was established between the human BCM1 locus (BCM1) and ATP1A2, and other markers on chromosome 1q. Conservation of genomic organization within a segment of human chromosome 1q and mouse chromosome 1 was demonstrated. A similar situation is seen in the region of the CD2 and LFA3 genes between mouse chromosome 3 and human chromosome 1p. Furthermore, the CD2/LFA3 genes are linked within 580 kb to Atpa-1/ATP1A1 genes to provide a parallel situation to the linkage between Bcm-1/BCM1 and Atpa-3/ATP1A2 on chromosomes 1 (mouse) and 1q (human). Taken together, the data suggest duplication of a chromosome region including the precursors of the genes for BCM1, CD2, and LFA3, and the ATPase genes to give rise to the linkage groups now observed. The duplicated regions may have stayed together on chromosome 1 in the human (with the insertion of a centromere), while in the mouse, the genetic regions are proposed to have become dispersed in the formation of chromosomes 1 and 3. CD2 and LFA3 are more dissimilar in sequence than BCM1 and LFA3, and if the precursors of the CD2 and LFA3 loci formed before the proposed chromosome segment duplication, then a gene encoding a recognizer molecule for BCM1 may exist in linkage with Bcm-1/BCM1 on chromosome 1 (mouse) and 1q (human).

Amino Acid Sequence↗
PubMed1990

Crystallization of a soluble form of the rat T-cell surface glycoprotein CD4 complexed with Fab from the W3/25 monoclonal antibody.

The structure of the T-lymphocyte cell surface glycoprotein CD4 is of considerable biological and medical interest. Recombinant rat CD4 expressed in soluble form in mammalian cells and complexed with W3/25 monoclonal Fab fragments formed crystals that diffract to 3.5 A and have the orthorhombic space group P2(1)2(1)2 or P2(1)2(1)2(1). The unit cell has dimensions a = 317 A, b = 161 A and c = 41.8 A and the asymmetric unit consists of two CD4:Fab complexes. These crystals are of suitable quality for X-ray diffraction analysis.

Animals↗