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Biomedical subjects

A F Williams

Publications and source records attributed to A F Williams.

At least 145 records · Page 8Linked to original sources
PubMed1988

Analysis of T cell receptor beta chains in rat thymus, and rat C alpha and C beta sequences.

In development, T cells first express their alpha beta antigen receptors in the thymus, where they may undergo selection processes leading to major histocompatibility complex (MHC) restriction and tolerance. A high proportion of thymocytes are thought to fail this selection in some way and to be destined for intrathymic death. These cells are categorized as the "cortical type" since they constitute most of the cortical cells; they express both CD4 and CD8 antigens but only very low levels of MHC class I antigens. One suggested cause of thymocyte death is a failure to produce a functional alpha beta T cell receptor (Tcr) due to errors in the rearrangements of germline DNA, resulting in V regions being absent or incorrectly spliced to the other segments of the transcribed gene. We have sequenced from the C region through to the V region of 14 rat Tcr beta chain clones isolated from thymocyte cDNA libraries. Of the 14, 13 have complete and correct rearrangements, whereas one was expressed from an unrearranged gene. Most of these clones are likely to be derived from the cortical population, for Northern blot analysis showed that these cells and total thymocytes expressed similar amounts of beta chain mRNA. Furthermore, the RNA from cortical-type cells contained a very similar ratio of full-length to truncated beta chain mRNA as did activated thymocytes and mature T lymphocytes. The data imply that defective beta chain gene rearrangement is not a major cause of failure in the selection of thymocytes. The sequences of the rat Tcr alpha and beta chain constant regions are also reported.

Amino Acid Sequence↗
PubMed1988

Squid glycoproteins with structural similarities to Thy-1 and Ly-6 antigens.

In an attempt to identify invertebrate homologs of Thy-1 antigen, the optic and central nervous tissue of squid was solubilized in deoxycholate and fractionated by lentil lectin affinity chromatography and gel filtration to yield small abundant glycoproteins. Material with biochemical similarities to Thy-1 was found and shown to consist of two glycoproteins that were ultimately purified using monoclonal antibody affinity columns. Both glycoproteins were sequenced to yield sequences of 84 residues for Sgp-1 and 92 residues for Sgp-2. The sequences were analyzed for similarities to Thy-1 and other Ig-related sequences, and Sgp-1 showed some similarities that were greater than 3 standard deviation units away from mean random scores when tested with the ALIGN program. However, the sequence patterns were not typical of Ig-related domains and the relationship of Sgp-1 to the Ig superfamily remains problematical. Sgp-2 showed no relationship to the Ig superfamily, but similarities to Ly-6 antigen sequences were noted that are in accord with an evolutionary relationship. The similarities included ten Cys residues in each sequence of which eight were matched in the best alignment given by the ALIGN program. Chemical evidence was obtained for glycophospholipid tails at the COOH-termini of Sgp-1 and Sgp-2 as is the case for Thy-1 and Ly-6 antigens.

Amino Acid Sequence↗
PubMed1988

Belt use by high-risk drivers before and after New York's seat belt use law.

Belt use among drivers traveling on limited access highways was observed before and after New York's mandatory seat belt use law. The results showed that high-speed drivers had lower belt use rates before the law and increased their belt use less in response to the law. Belt use rates before the law were 25%, 29%, and 28% for the high-, medium-, and low-speed groups as compared with 51%, 64%, and 57%, respectively, after the law. High-speed drivers also had inferior previous driving records, confirming their higher risk of motor vehicle crash involvement.

Acceleration↗
PubMed1988

Cell-surface anchoring of proteins via glycosyl-phosphatidylinositol structures.

A class of membrane molecules has been identified whose primary translation product includes a COOH-terminal protein sequence that signals attachment of a glycosyl-phosphatidylinositol anchor at a COOH-terminal residue that is newly formed by cleavage of the signaling sequence. This class includes a wide diversity of protein types from eukaryotes at many stages of evolution. The structures of the glycosyl-phosphatidylinositol anchors are being resolved, but their functions aside from membrane attachment and dynamics remain to be determined.

Animals↗
PubMed1988

Infant weight in relation to nutritional intake and morbidity in northern Thailand.

A cross-sectional study of 58 infants (age range 2-53 weeks) was carried out in a rural area of northern Thailand. Total dietary intake (energy and protein from breastmilk and supplementary food) was measured directly during continuous observation over 48 h of randomly selected study subjects in their homes. Associations between infant weight and total energy intake, total protein intake and morbidity were analysed by multiple regression analysis. Up to 6 months of age, heavier infants had larger energy intakes, when age and birthweight were taken into account. In the 7-12 months age group, heavier infants consumed more protein and had fewer respiratory infections. Weaned infants older than 6 months were significantly heavier and consumed more protein than infants of similar age who were still receiving breastmilk. The lower protein intakes of the latter infants were due to the low protein concentration of breastmilk compared with supplementary food.

Body Weight↗
PubMed1988

Drug use by tractor-trailer drivers.

Blood or urine samples or both were obtained from 317 of 359 randomly selected tractor-trailer drivers asked to participate in a driver health survey conducted at a truck weighing station on Interstate 40 in Tennessee. Altogether, 29% of the drivers had evidence of alcohol, marijuana, cocaine, prescription or nonprescription stimulants, or some combination of these, in either blood or urine. Cannabinoids were found in 15% of the drivers' blood or urine; nonprescription stimulants such as phenylpropanolamine were found in 12%; prescription stimulants such as amphetamine were found in 5%; cocaine metabolites were found in 2%; and alcohol was found in less than 1%. These results provide the first objective information about the use of potentially abusive drugs by tractor-trailer drivers. The extent of driver impairment attributable to the observed drugs is uncertain because of the complex relationship between performance and drug concentrations.

Automobile Driving↗
PubMed1987

The sequence of rat leukosialin (W3/13 antigen) reveals a molecule with O-linked glycosylation of one third of its extracellular amino acids.

Leukosialin is one of the major glycoproteins of thymocytes and T lymphocytes and is notable for a very high content of O-linked carbohydrate structures. The full protein sequence for rat leukosialin as translated from cDNA clones is now reported. The molecule contains 371 amino acids with 224 residues outside the cell, one transmembrane sequence and 124 cytoplasmic residues. Data from the peptide sequence and carbohydrate composition suggest that one in three of the extracellular amino acids may be O-glycosylated with no N-linked glycosylation sites. The cDNA sequence contained a CpG rich region in the 3' coding sequence and a large 3' non-coding region which included tandem repeats of the sequence GGAT.

Amino Acid Sequence↗
PubMed1987

Similarities in sequences and cellular expression between rat CD2 and CD4 antigens.

The MRC OX-34 antigen of rat T lymphocytes was purified and peptide sequences were obtained. Oligonucleotide probes were synthesized and cDNA clones coding for the antigen were isolated and sequenced to yield a predicted protein sequence for the molecule that fitted the peptide data. Comparison of this sequence with that for human CD2 determined by Sewell et al. showed that OX-34 is rat CD2. The primary structure of the molecule was notable for a moderately large cytoplasmic domain of unusual sequence and also for its highly significant relationship to CD4 antigen in the membrane proximal extracellular region and the transmembrane sequence. A relationship to the Ig superfamily can be argued for the two extra cellular domains of CD2, even though neither fits the standard pattern for Ig-related domains. Within the T lymphocyte lineage, rat CD2 seemed to be present on all stages with the exception of approximately 50% of the thymic CD4-,CD8- cells. In addition, the antigen was prominent on most macrophages in the spleen but not found on peritoneal or liver macrophages. CD4 antigen is also expressed on T lymphocytes and macrophages, and thus CD2 and CD4 appear similar in their cellular expression as well as structural characteristics.

Amino Acid Sequence↗
PubMed1987

The MRC OX-44 antigen marks a functionally relevant subset among rat thymocytes.

A monoclonal antibody called MRC OX-44 is described that labels all myeloid cells and peripheral lymphoid cells but only 12% of thymocytes. The OX-44+ thymic cells include most if not all cells found in the medulla but only a small fraction of the cortical cells. Together with CD4 and CD8 antigens, seven subsets of thymic cell were defined and it was notable that most CD4- CD8- cells were OX-44+ whereas almost all CD4+ CD8+ cells were OX-44-. In functional tests, the OX-44+ cells accounted for all proliferation by thymocytes when stimulated by allogeneic spleen cells or concanavalin A plus growth factors and OX-44- cells were completely negative in these assays. Also, in tests for thymopoiesis after intra-thymic injection of cells, all activity was OX-44+. It seems possible that the OX-44+ set may include all functionally relevant cells in the rat thymus.

Animals↗
PubMed1987

Tissue-specific N-glycosylation, site-specific oligosaccharide patterns and lentil lectin recognition of rat Thy-1.

To examine the extent to which protein structure and tissue-type influence glycosylation, we have determined the oligosaccharide structures at each of the three glycosylation sites (Asn-23, 74 and 98) of the cell surface glycoprotein Thy-1 isolated from rat brain and thymus. The results show that there is tissue-specificity of glycosylation and that superimposed on this is a significant degree of site-specificity. On the basis of the site distribution of oligosaccharides, we find that no Thy-1 molecules are in common between the two tissues despite the amino acid sequences being identical. We suggest, therefore, that by controlling N-glycosylation a tissue creates an unique set of glycoforms (same polypeptide but with oligosaccharides that differ either in sequence or disposition). The structures at each of the three sites were also determined for the thymocyte Thy-1 that binds to lentil lectin (Thy-1 L+) and for that which does not (Thy-1 L-). Segregation of intact thymus Thy-1 into two distinct sets of glycoforms by lentil lectin was found to be due to the structures at site 74. Analysis of oligosaccharide structures at the 'passenger' sites (23 and 98) suggests that either Thy-1 L+ and Thy-1 L- molecules are made in different cell-types or that the biosynthesis of oligosaccharides at one site is influenced by the glycosylation at other sites.

Animals↗
PubMed1987

Lymphocyte specific heterogeneity in the rat leucocyte common antigen (T200) is due to differences in polypeptide sequences near the NH2-terminus.

The leucocyte-common antigen (L-CA, T200 or CD45) consists of a family of heavily glycosylated glycoproteins of apparent Mr 180,000-240,000 which are restricted to lymphoid and myeloid cells. Forms of L-CA which differ in their apparent Mr, antigenicity and glycosylation are expressed on different lymphocyte types. One specific antigenic determinant called MRC OX-22 is of particular interest because it distinguishes two sets of T helper cells that have different functions. From the sequence of different L-CA cDNA clones we now conclude that there is sequence heterogeneity such that at least four forms of L-CA exist with sequences in the range 1118-1250 amino acids. All the sequence variation occurs at a point starting 6 residues from the NH2-terminus and the last 1112 residues of all forms are identical. Two of the variants can be directly related to the antigenic variation because they include sequence that was determined for a peptide that carries the MRC OX-22 determinant. Analysis of glycopeptides from thymocyte L-CA identified only one non-glycosylated position out of 14 possible N-glycosylation sites and established that all O-glycosylation was within the first 32 amino acids. The extra protein sequence in the longer forms was also suggestive of extensive O-glycosylation.

Amino Acid Sequence↗
PubMed1987

Preliminary estimates of the effects of mandatory seat belt use laws.

Analyses of motor vehicle fatality counts in New York and several comparison states for the years 1980 through 1985 indicate that New York's seat belt use law reduced fatalities by about nine percent during the first nine months of the law. This estimate is preliminary, and the estimated long-term effect of the law could change as more sophisticated analyses are applied to the data and as belt use changes (it had declined to less than 50 percent over most of the state by the end of the first year of the law). In addition, New York's law is one of the strongest in terms of enforceability, and the effect may be smaller in states with weaker laws. However, the estimated effect in New York is consistent with the experience of other countries with seat belt use laws.

Accidents, Traffic↗