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Biomedical subjects

A F Williams

Publications and source records attributed to A F Williams.

At least 127 records · Page 7Linked to original sources

Protein sequence and gene structure for mouse leukosialin (CD43), a T lymphocyte mucin without introns in the coding sequence.

A partial cDNA clone for mouse leukosialin was isolated by use of a rat leukosialin cDNA probe. The mouse cDNA was then used to isolate genomic clones that corresponded to the two mouse genes detected in Southern blots. One gene encoded an open reading frame for the homologue of rat leukosialin and this gene was notable for the absence of introns within the coding sequence. A lack of introns has previously been observed for the human leukosialin gene (Shelley, C. S., Remold-O'Donnell, E., Rosen, F. S. and Whitehead, A. S., Biochem. J., submitted). The other mouse gene was an intronless pseudogene for a leukosialin-related sequence. The presence of only one functional gene that lacked coding-region introns established that molecular heterogeneity in mouse leukosialin could not arise from multiple genes or alternative splicing of exons. The sequence of mouse leukosialin suggested an extracellular segment with a high content of O-linked carbohydrate, as is the case in the rat and human. In addition the mouse molecule had one possible N-linked glycosylation site. The cytoplasmic domain of 124 amino acids was highly conserved between rodent and human leukosialins for the functional genes but not for the pseudogene. This suggests an important functional role for the cytoplasmic domain.

Amino Acid Sequence↗

City curfew ordinances and teenage motor vehicle injury.

Several U.S. cities have curfew ordinances that limit the late night activities of minor teenagers in public places including highways. Detroit, Cleveland, and Columbus, which have curfew ordinances, were compared to Cincinnati, which does not have such an ordinance. The curfew ordinances were associated with a 23% reduction in motor vehicle related injury for 13- to 17-year-olds as passengers, drivers, pedestrians, or bicyclists during the curfew hours. It was concluded that city curfew ordinances, like the statewide driving curfews studied in other states, can reduce motor vehicle injury to teenagers during the particularly hazardous late night hours.

Accidents, Traffic↗

The Kasabach-Merritt syndrome: treatment with intermittent pneumatic compression.

A 6 week old infant presented with a giant angiomatous naevus of the leg complicated by chronic disseminated intravascular coagulation. The bleeding and laboratory abnormalities responded to intermittent pneumatic compression of the affected limb. This innocuous treatment should be considered in the Kasabach-Merritt syndrome.

Air↗

Seat belt use in cars with air bags.

Seat belt use was observed in 1,628 cars with air bags and manual belts and 34,223 cars with manual seat belts only. Sixty-six percent of drivers in cars with air bags wore seat belts compared to 63 percent of drivers in cars with manual belts only. The study found no evidence for the speculation that drivers with air bags will reduce their seat belt use because they believe an air bag alone provides sufficient protection.

Automobiles↗

Seat belt use on interstate highways.

More than 5,000 miles of limited-access highways in the eastern United States and Canada were traveled to observe seat belt use. Overall belt use was 58 percent in the United States and 79 percent in Canada. The data indicate that belt use in the United States follows a different pattern on interstate highways than on other streets and roads, with relatively high belt use rates (over 50 percent) appearing to be somewhat independent of belt use law provisions.

Adult↗

The primary structure of the human leukocyte antigen CD37, a species homologue of the rat MRC OX-44 antigen.

Comparison of NH2-terminal protein sequence from the rat OX-44 antigen with the sequence of the human CD37 antigen deduced from a cDNA clone shows that these antigens are species homologues. The CD37 sequence is 244 amino acids in length and lacks a conventional leader sequence. The molecule is likely to have an NH2-terminal cytoplasmic domain followed by three transmembrane sequences that lie within the first 110 amino acids. The rest of the molecule is hydrophillic and contains three sites for N-linked glycosylation.

Amino Acid Sequence↗

Subsets of thymopoietic rat thymocytes defined by expression of the CD2 antigen and the MRC OX-22 determinant of the leukocyte-common antigen CD45.

The MRC OX-22 monoclonal antibody recognizes a restricted determinant of the rat leukocyte-common antigen (L-CA, CD45), which is expressed on most peripheral T cells and all B cells. In contrast only 2%-3% of thymocytes are OX-22+ and these are now shown to be mostly of the immature CD4-CD8- (double-negative, DN), phenotype with very few of the mature phenotype cells being OX-22+. Analysis of immunoperoxidase sections suggests that the DN OX-22+ cells are located in the cortex. Among the DN cells about 60% are OX-22+ and a similar percentage are positive for CD2 antigen. Double staining showed that OX-22+CD2-, OX-22+CD2+, and OX-22-CD2+ populations can be defined and that these three sets account for approximately 95% of the DN cells. Measurement of the thymopoietic activity of DN subsets showed that OX-22+CD2- and OX-22+CD2+ cells have regenerative capacity whilst OX-22-CD2+ cells do not.

Age Factors↗

Observed use of automatic seat belts in 1987 cars.

Usage of the automatic belt systems supplied by six large-volume automobile manufacturers to meet the federal requirements for automatic restraints were observed in suburban Washington, D.C., Chicago, Los Angeles, and Philadelphia. The different belt systems studied were: Ford and Toyota (motorized, nondetachable automatic shoulder belt), Nissan (motorized, detachable shoulder belt), VW and Chrysler (nonmotorized, detachable shoulder belt), and GM (nonmotorized detachable lap and shoulder belt). Use of automatic belts was significantly greater than manual belt use in otherwise comparable late-model cars for all manufacturers except Chrysler; in Chrysler cars, automatic belt use was significantly lower than manual belt use. The automatic shoulder belts provided by Ford, Nissan, Toyota, and VW increased use rates to about 90%. Because use rates were lower in Ford cars with manual belts, their increase was greater. GM cars had the smallest increase in use rates; however, lap belt use was highest in GM cars. The other manufacturers supply knee bolsters to supplement shoulder belt protection; all--except VW--also provide manual lap belts, which were used by about half of those who used the automatic shoulder belt. The results indicate that some manufacturers have been more successful than others in providing automatic belt systems that result in high use that, in turn, will mean fewer deaths and injuries in those cars.

Accident Prevention↗

Comparative effects of driver improvement programs on crashes and violations.

Recent reviewers of well-controlled driver improvement program evaluations have suggested that some programs result in measurable reductions in violations but not crashes. A comprehensive review of 65 studies evaluating driver improvement activities was conducted to determine the generality of these findings and to explore possible explanations of the lack of correspondence between violation and crash effects. Nineteen studies evaluating 59 driver improvement activities were found to be methodologically adequate. The major findings of the review are: (1) that driver improvement activities generally do result in reductions in violations; (2) there is an unpredictable and sometimes undesirable effect on crashes even in the presence of desirable violation effects; and (3) the lack of correspondence between violation and crash effects is not explained by lack of statistical power or by the types of violations affected. Further examination of driver improvement interventions revealed no strong evidence for different effects related to characteristics such as direct vs. indirect participant contact and group vs. individual contact.

Accident Prevention↗

Activation of T lymphocytes via monoclonal antibodies against rat cell surface antigens with particular reference to CD2 antigen.

In the rat, monoclonal antibodies (mAbs) against the T-lymphocyte receptor (TCR), CD3 antigen and CD2 antigen are mitogenic for T lymphocytes. Antibodies against CD43 (leukosialin) and CD5 are not, but can enhance the effects of other stimuli. Activation of a T-lymphocyte cell line in terms of triggering an increase in free cytoplasmic Ca2+ [( Ca2+]i) was mediated by mAbs against Class 1 MHC and CD4 in addition to the mitogenic mAbs. In the presence of non-activating levels of anti-TCR mAb a strong synergistic signal was seen with anti-CD4, but incubation with anti-CD4 prior to activation with anti-CD3 inhibited the CD3 signal. Stimulation of DNA synthesis in resting T cells via anti-CD2 mAbs required a combination of two non-competitive antibodies and addition of a third anti-CD2 mAb inhibited the activation. The anti-CD2 mAbs were active on all types of mature T cells from peripheral lymphoid organs and the thymus, but cells in the thymus that lacked a TCR could not be activated via CD2. Rat CD2 was transfected into Jurkat cells and cross-linking with anti-rat CD2 mAbs gave an increase in [Ca2+]i similar to that seen with an anti-human CD3 mAb. All three types of anti-rat CD2 mAbs gave a signal including the mAb that inhibited mitogenesis. Signal transduction via CD2 was not seen in L cells and was only weakly observed in TCR-ve Jurkat cells that had been transfected with rat CD2. The cytoplasmic domain of transfected CD2 was shown to be important for the signal transduction since no increase in [Ca2+]i could be triggered in cells expressing mutant CD2 that lacked the cytoplasmic domain. Mutant forms with increasing lengths of cytoplasmic domain showed functions that progressively approached that of the native function.

Amino Acid Sequence↗

Driver age and crash involvement.

The youngest and oldest drivers have the highest crash risk, but the problem lies predominantly in the youngest age groups because elderly drivers have low exposure. The elderly driver problem will increase gradually as their share of the population increases but will remain relatively small. The bulk of the problem will continue to reside among drivers younger than age 65, particularly the youngest drivers.

Accidents, Traffic↗

Coverage gaps in seat belt use laws.

Some seat belt use laws exempt occupants in certain seating positions and in certain types of vehicles, or both. A state-by-state analysis was conducted of the extent to which passenger vehicle occupants killed before the laws went into effect would have been covered by the laws subsequently passed. Only five states had laws that covered all passenger vehicle occupants; the majority excluded 4 to 8 per cent and six states excluded 14 per cent or more. More inclusive laws can reduce injuries and save lives.

Accidents, Traffic↗

A role in transmembrane signaling for the cytoplasmic domain of the CD2 T lymphocyte surface antigen.

The CD2 antigen can mediate mitogenesis of T lymphocytes after binding combinations of monoclonal antibodies. To examine the importance of the cytoplasmic domain in signaling, rat CD2 cDNA has been transfected into the human Jurkat cell line and triggering of an increase in cytoplasmic free Ca2+ concentration [( Ca2+]i) has been assayed. In cells expressing full-length CD2, a clear signal was triggered with anti-CD2 monoclonal antibodies. In contrast, a barely detectable increase in [Ca2+]i occurred with mutant rat CD2 molecules that included only 6 or 40 amino acids of the full-length cytoplasmic domain of 116 residues. It thus appears that the CD2 cytoplasmic domain plays a role in the signaling event.

Amino Acid Sequence↗

Activation of rat T lymphocytes by anti-CD2 monoclonal antibodies.

Rat T cells and thymocytes were induced to proliferate by a pair of mAbs, MRC OX-54 and MRC OX-55, directed against rat CD2. Accessory cells were required but their role was not simply for crosslinking of the two mAbs, as neither MRC OX-54 nor MRC OX-55 alone, in the presence of a crosslinking second antibody, caused T cell mitogenesis. Nor could the phorbol ester PMA replace either antibody. The two mAbs recognized distinct epitopes on rat CD2; however, MRC OX-54 could partially block MRC OX-55 binding whereas the reverse situation was not seen. A further CD2 epitope was recognized by two mutually competitive mAbs, MRC OX-34 and MRC OX-53, which were not mitogenic. Neither MRC OX-34 nor MRC OX-53 affected the binding of MRC OX-54 or MRC OX-55, yet they prevented the mitogenic effect induced by these mAbs. The presence of mAbs against CD4 and the IL-2-R also abrogated this mitogenesis, whereas an anti-CD5 mAb augmented the CD2-induced proliferation.

Animals↗

Complete structure of the glycosyl phosphatidylinositol membrane anchor of rat brain Thy-1 glycoprotein.

Glycosyl-phosphatidylinositol (GPI) anchors have recently been identified as alternatives to hydrophobic amino acid sequences for the attachment of a variety of eukaryotic cell surface molecules to the lipid bilayer. In single cell eukaryotes the GPI group appears to be the predominant form of membrane attachment, and in vertebrates a substantial minority of molecules have this anchor including cell surface hydrolytic enzymes, antigens and cell adhesion molecules. Analysis of different GPI anchors suggests they share common structural features including linkage to the COOH group of the terminal amino acid via ethanolamine phosphate, the presence of phosphatidylinositol lipid and a glycan between the bridging ethanolamine phosphate and the lipid. In the case of the Trypanosoma brucie variant surface glycoprotein (VSG) the full structure of the GPI anchor has been determined and this provides a prototype for comparison with other molecules. We now report the structure of the GPI anchor of rat brain Thy-1 glycoprotein. It has an identical backbone to the VSG anchor but shows significant differences in side chain moieties.

Animals↗

The MRC OX-45 antigen of rat leukocytes and endothelium is in a subset of the immunoglobulin superfamily with CD2, LFA-3 and carcinoembryonic antigens.

The MRC OX-45 cell surface antigen is a glycoprotein of 45,000 apparent mol. wt of rat leukocytes and endothelium. Antibodies against the antigen inhibit T lymphocyte responses by stimulation of suppression by accessory cells. We now report the immunochemical characterization of this antigen and its cDNA sequence. The predicted protein sequence contains 240 amino acids including a leader sequence of 22 residues and a carboxy-terminal sequence of 23 residues that is replaced in the processed molecule by a glycosyl-phosphatidylinositol anchor attached at serine 195. Two Ig-related domains are predicted to account for all of the processed sequence and the circular dichroism spectrum shows pure beta-structure. The amino-terminal domain is V-like, but without a disulphide bond, while the second domain is C-like (C2-SET) with two disulphide bonds. The sequence matches particularly well with the extracellular parts of LFA-3 and CD2 antigens and the first two domains of carcinoembryonic antigen and non-specific, cross-reacting antigen.

Animals↗