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Biomedical subjects

A F Williams

Publications and source records attributed to A F Williams.

At least 199 records · Page 11Linked to original sources

MRC OX-22, a monoclonal antibody that labels a new subset of T lymphocytes and reacts with the high molecular weight form of the leukocyte-common antigen.

A mouse monoclonal antibody (MRC OX-22) is described that labels rat T cells which mediate graft-versus-host reactions and those responsible for the suppression of antibody synthesis in hosts undergoing these reactions. In contrast, most of the T cells that provide help for B cells are MRC OX-22 negative. These results, taken together with those published previously, demonstrate that the rat contains at least three phenotypically and functionally distinct subsets of T cells. The MRC OX-22 antibody also labels all B cells, 50% of bone marrow cells, but only 2% of thymocytes. Of these latter cells about half are found at the edge of the medulla and the remainder are randomly distributed throughout the cortex and medulla. These findings lend support to the view that mature thymocytes leave the thymus at the cortico-medullary junction, and also suggest that both cortex and medulla may be sites where thymocytes mature. Biochemical studies showed that the MRC OX-22 antibody reacts with the high molecular weight form of the leukocyte-common antigen (L-CA). Comparison with data on human L-CA suggests that the molecular and antigenic heterogeneity of this set of glycoproteins has been conserved between rat and man.

Absorption↗

Variations in minimum licensing age and fatal motor vehicle crashes.

The effect of differences in the legal minimum licensing age on fatal motor vehicle crashes was studied in New Jersey (age 17), Massachusetts (age 16 1/2), and Connecticut (age 16). New Jersey's 17-year-old licensing law was associated with greatly reduced fatal crash involvement. It is estimated that 65 to 85 per cent reductions in 16 year-old-driver fatal crash involvement can be expected if the licensing age is increased from 16 to 17 without increasing fatal crash rates at older ages.

Accidents, Traffic↗

Passenger car size and driver seat belt use.

The National Highway Traffic Safety Administration (NHTSA) claims, on the basis of survey results, that seat belt use in small cars is twice as high as in large cars. The agency interprets this as being due in part to perceptions of higher risk by small car occupants. In fact, little is known about the factors motivating belt use, including whether risk perception is important. A reanalysis of the NHTSA data indicates that most of the differences in belt use by car size can be explained by higher use in imported cars, and by geographical differences in belt use in domestic cars.

Automobiles↗

Neuronal cell Thy-1 glycoprotein: homology with immunoglobulin.

The amino acid sequences of mouse brain Thy-1 glycoproteins are shown to be homologous to those of variable-region immunoglobulin domains. There is also good homology with constant domains and beta 2-microglobulin; overall the results suggest that Thy-1 may be like the primordial immunoglobulin domain. Preliminary evidence for an invertebrate Thy-1 homolog supports this possibility.

Amino Acid Sequence↗

Mouse monoclonal antibodies against rat major histocompatibility antigens. Two Ia antigens and expression of Ia and class I antigens in rat thymus.

A rat Ia (RT-1B) antigen (called Ia-A) equivalent to the mouse I-A product has been defined with mouse monoclonal antibodies (W. R. McMaster and A. F. Williams, Eur. J. Immunol. 1979. 9: 426). To identify other Ia antigens mouse monoclonal antibodies were raised against rat spleen glycoproteins depleted of the Ia-A antigen. An IgG antibody (called MRC OX17) was obtained and used to purify a molecule which had a similar structure to the Ia-A antigen and reacted with anti-Ia alloantibodies. There was no cross-reaction between the two Ia glycoproteins in assays with mouse monoclonal antibodies, alloantibodies or rabbit antibodies. In one alloantiserum almost all the detectable anti-Ia antibodies reacted with a mixture of the two Ia glycoproteins. The MRC OX17 antibody did not bind to mouse cells, but rabbit antibodies to the pure rat glycoprotein cross-reacted and recognized determinants mapping to the mouse I-E region. In the thymus the rat Ia-E antigen was on cortical epithelial and medullary reticular cells. An IgG monoclonal antibody (MRC OX18) to isotypic determinants of rat histocompatibility RT-1A antigens was also produced and used to analyze these antigens on thymus cells. The heavily labeled thymocytes were those with characteristics of mature T lymphocytes. Cortical epithelial cells and medullary dendritic-like cells were also RT-1A positive.

Animals↗

The predominant surface glycoproteins of thymocytes and lymphocytes.

The surfaces of thymocytes and T and B lymphocytes differ markedly in their predominant glycoprotein constituents. Amino acid sequence studies show that a surprising number of the cell surface molecules have homologies with immunoglobulins. Analysis of carbohydrate shows major differences between glycoproteins on the same cell and between the same (or closely related) glycoproteins on the different cell types.

Amino Acid Sequence↗

Lymphocyte cell surface glycoproteins which bind to soybean and peanut lectins.

In cellular immunology, peanut (Arachis hypogaea) lectin has been used to selectively agglutinate immature lymphoid cells and soybean (Glycine max-lectin to agglutinate B lymphocytes. We have used affinity chromatography to study the surface glycoproteins of rat and mouse lymphoid cells which bind to these lectins. Thymocyte and T and B lymphocyte glycoproteins were analysed either without modification (native) or after the removal of sialic acid with neuraminidase (asialo). The only native glycoprotein which was seen to bind to peanut lectin was the 95,000 mol. wt sialoglycoprotein from thymocytes. The equivalent molecules from T lymphocytes bound to peanut lectin only after neuraminidase digestion. Thus the selective agglutination of thymocytes by peanut lectin would seem to be due to a partial lack of sialic acid residues on the O-glycosidically-linked oligosaccharides of the thymocyte sialoglycoprotein. The B lymphocyte form of the leucocyte-common antigen was the only prominent native glycoprotein which was seen to bind to soybean lectin and this probably accounts for the specific binding of this lectin to B cells. The leucocyte-common antigens, in their asialo forms, from thymocytes and B and T lymphocytes differed in their binding to the lectins and this establishes that these glycoproteins which share antigenic determinants differ in their carbohydrate structures.

Animals↗

Rat brain Thy-1 glycoprotein. The amino acid sequence, disulphide bonds and an unusual hydrophobic region.

The full sequence of the Thy-1 membrane glycoprotein of rat brain is reported. The sequence was determined from tryptic and V-8 proteinase peptides and consisted of 111 amino acids. The amino terminus was blocked and consisted of a pyroglutamic acid residue. The molecule contained two disulphide bonds, namely Cys-9--Cys-111 and Cys-19--Cys-85. Three N-linked amino sugars were located at Asn-23, Asn-74 and Asn-98. In each case the sequence on the C-terminal side of the attachment point was Asn-Xaa-Thr as would be expected for N-linkage. The C-terminal peptides were unusual, in that they were either obtained in a highly aggregated form, or could only be purified after binding to Brij 96 micelles. Thus they appeared to have hydrophobic properties, yet did not contain any extended sequence of hydrophobic amino acids. Other unusual features of the C-terminal peptides were the presence of unidentified ninhydrin-positive material and of glucosamine and galactosamine. The C-terminal residue has not been directly identified but Cys-111 is the last conventional amino acid. It is suggested that the hydrophobic properties of the C-terminal peptides may be due to the linkage of lipid. The sequence of the Thy-1 glycoprotein showed homologies with immunoglobulin domains. This relationship is examined in detail in the paper following [Cohen et al. (1981) Biochem. J. 193, 000--000].

Amino Acid Sequence↗

Analysis of structural similarities between brain Thy-1 antigen and immunoglobulin domains. Evidence for an evolutionary relationship and a hypothesis for its functional significance.

The Thy-1 membrane glycoprotein from rat brain is shown to have structural and sequence homologies with immunoglobulin (Ig) domains on the basis of the following evidence. 1. The two disulphide bonds of Thy-1 are both consistent with the Ig-fold. 2. The molecule contains extensive beta-structure as shown by the c.d. spectrum. 3. Secondary structure prediction locates beta-strands along the sequence in a manner consistent with the Ig-fold. 4. On the basis of rules derived from known beta-sheet structures, a three-dimensional structure with the Ig-fold is predicted as favourable for Thy-1. 5. Sequences in the proposed beta-strands of Thy-1 and known beta-strands of Ig domains show significant sequence homology. This homology is statistically more significant than for the comparison of proposed beta-strand sequences of beta 2-microglobulin with Ig domains. An hypothesis is presented for the possible functional significance of an evolutionary relationship between Thy-1 and Ig. It is suggested that both Thy-1 and Ig evolved from primitive molecules, with an Ig fold, which mediated cell--cell interactions. The present-day role of Thy-1 may be similar to that of the primitive domain.

Amino Acid Sequence↗

Identification of a glycophorin-like molecule at the cell surface of rat thymocytes.

There are three predominant glycoproteins in the rat thymocyte plasma membrane. Two of these have carbohydrate compositions that are characteristic of structures N-glycosidically linked to protein. The other glycoprotein is very different, having about 20 O-glycosidically linked carbohydrate units per 100 amino acids. It has similarities to the major sialoglycoprotein of human erythrocytes.

Amino Acids↗

The Tennessee child restraint law in its third year.

Observations of child travel were made in Knoxville and Nashville, Tennessee, and Lexington and Louisville, Kentucky about two and one-half years after the Tennessee child restraint law went into force. Use of child restraints anchored by seat belts increased in Tennessee from 8 per cent prior to the law to 29 per cent, compared to a change from 11 to 14 per cent in Kentucky, which does not have a child restraint law. Travel in arms, a hazardous practice permitted by the law, was at the same level in Tennessee and Kentucky as prior to passage of the law.

Automobiles↗

Fatal falls and jumps from motor vehicles.

In 1978, 345 persons were killed in the United States in jumps and falls from non-crashing motor vehicles: 64 per cent fell; 15 per cent jumped; and it was not known whether the other 21 per cent jumped or fell. Two hundred and one people had been traveling on the exterior of vehicles, especially truck beds, and almost all of these people fell from their vehicles. The other 144 fatalities involved people in passenger compartments. Many of the falls from compartments occurred when occupants opened doors, or when vehicles changed direction. Seventy-seven per cent of those who fell from passenger compartments were males, and 44 per cent were less than five years old. Among those who jumped from vehicle compartments, 62 per cent were women and all were older than 14 years. Fatal falls and jumps from vehicles could be reduced in a variety of ways. These include legislation to prohibit travel on vehicle exteriors, designing vehicles so that doors cannot be opened when in motion, improving door designs, installing signals that provide warning if doors are not closed completely, and using occupant restraints.

Accidents↗

Evaluation of the Rhode Island child restraint law.

In Rhode Island, a law went into force July 1, 1980, requiring drivers to transport children who are in the front seats of vehicles in properly used child restraints. In the fourth month of the law, restraint use and travel in rear seats had increased moderately; the net result was an increase in proper restraint use in rear seats (11 to 23 per cent) and a decrease in unrestrained, front seat travel (41 to 26 per cent). (Am J Public Health 1981;71:742-743.)

Child↗