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Biomedical subjects

A F Williams

Publications and source records attributed to A F Williams.

At least 181 records · Page 10Linked to original sources

Authentic T helper CD4 (W3/25) antigen on rat peritoneal macrophages.

The rat W3/25 antigen that appears to be equivalent to human CD4 (T4) antigen is expressed on thymocytes and T helper cells and plays a role in the response of T helper cells to antigen. The W3/25 and anti-T4 antibodies also label macrophages. In this paper we examine whether the macrophage antigen is the same as that on T cells. New monoclonal antibodies against the rat CD4 antigen, MRC OX-35 through OX-38, are described, all of which label peritoneal macrophages from normal and athymic rats. The molecular weight of W3/25 antigen on macrophages is indistinguishable from that on T cells. We conclude that macrophages express authentic CD4 (W3/25) antigen. Another new monoclonal antibody, MRC OX-34, labels an antigen of 50-54,000 mol wt that is expressed on rat T but not B cells or peritoneal macrophages. It was used to control for the presence of any T cell products in immunoprecipitation from rat macrophage extracts.

Animals↗

Molecular and antigenic heterogeneity of the rat leukocyte-common antigen from thymocytes and T and B lymphocytes.

The molecular forms and antigenic heterogeneity of the leukocyte-common antigen (L-CA) of rat lymphocytes have been analyzed. Thymocytes show one main band at 180 kDa, T cells four bands at 180, 190, 200 and 220 kDa and B cells one broad band at about 240 kDa. T helper and T cytotoxic cell subsets show the same four bands with some differences in the proportion of each. Four mouse monoclonal antibodies (MRC OX-1, 28, 29 and 30) reacted with all molecular forms of L-CA and fell into two sets that were noncompetitive in binding to L-CA (MRC OX-1, 28, 29 vs. OX-30). The antigenic determinants seen by all these antibodies were lost when L-CA was reduced and alkylated. Three antibodies (MRC OX-22, 31 and 32) reacted selectively with B cells, T cytotoxic cells and about 2/3 of T helper cells. OX-22 and OX-31 competed for binding but were noncompetitive with OX-32. All these antibodies bound to a subfraction of the 190, 200 and 220-kDa forms of T cell L-CA but not at all to the 180-kDa form of T cells or thymocytes. One antibody bound to B cells only (MRC OX-33) and precipitated a subfraction of B cell L-CA. With all the antibodies that did not label thymocytes the antigenic determinants survived reduction and alkylation. Subsequent proteolysis with trypsin then destroyed all determinants except the one reacting with MRC OX-22 antibody. In this case tryptic peptides retained full antigenic activity which was, however, destroyed by further proteolysis with pronase.

Animals↗

MRC OX-2 antigen: a lymphoid/neuronal membrane glycoprotein with a structure like a single immunoglobulin light chain.

The MRC OX-2 antigen is a rat cell surface glycoprotein of mol. wt. 41 000-47 000 found on neurones, thymocytes, B cells, follicular dendritic cells and endothelium. We now report the amino sequence for this antigen as deduced from the nucleotide sequence of cDNA clones detected by use of an oligonucleotide probe. The sequence contains 248 amino acid residues of which 202 residues are likely to be outside the cell with two domains that show homology with immunoglobulins. The N-terminal domain fits best with Ig V domains and Thy-1 antigen while the C-terminal part is like an Ig C domain. Thus the structure overall is similar to an Ig light chain or the T cell receptor beta chain. Three glycosylation sites are identified on each of the MRC OX-2 antigen domains.

Amino Acid Sequence↗

Purification, chain separation and sequence of the MRC OX-8 antigen, a marker of rat cytotoxic T lymphocytes.

The MRC OX-8 antigen is a marker of the rat cytotoxic T lymphocytes that consists of disulphide-linked chains of mol. wts. 37 and 32 kd. It is thought to be equivalent to the human T8 and mouse Lyt2,3 antigens (all now called CD8 antigens). MRC OX-8 antigen was purified from thymocytes using a monoclonal antibody column and because antigenicity was retained after reduction and alkylation the two polypeptide chains could be separated by a subsequent affinity chromatography step. Peptides were isolated from each chain and their sequences determined. A cDNA probe coding for the mouse CD8 antigen (pLY2C-1 provided by Dr L. A. Herzenberg) was used to obtain rat cDNA clones from which the sequence of the equivalent rat molecule was determined. Peptides from the 32-kd chain were identified in this translated sequence whereas peptides from the 37-kd chain were not. The 32-kd polypeptide sequence consisted of 210 amino acids and had one possible N-linked glycosylation site. The N-terminal part of the sequence was surprisingly different from both its mouse and human counterparts but, as in the other two species, it showed a clear relationship to Ig V domains.

Amino Acid Sequence↗

Visualisation by low-angle shadowing of the leucocyte-common antigen. A major cell surface glycoprotein of lymphocytes.

The leucocyte-common antigen (L-CA) from rat thymocytes is a cell surface glycoprotein of 180 000 apparent mol. wt. with an 80-kd cytoplasmic domain. This paper reports the molecular dimensions of the molecule visualised by electron microscopy after low-angle shadowing. The L-CA monomer consists of a globular head region of approximately 12 nm diameter and a short tail approximately 18 nm long. In deoxycholate both monomers and multimers are seen with aggregation occurring at the head groups. When the detergent is removed, larger clusters are formed with tails extending from a central aggregate. A 100-kd tryptic fragment of L-CA that is known to include the extracellular parts of the molecule also exists in monomer and multimer forms and is seen to have a rod-like structure of length 28 nm without evidence of the head group. Altogether the data indicate that the rod-like structure is found outside the cell and that the extra sequence that forms the head is inside. The tryptic fragment is likely to be derived by cleavage after the transmembrane sequence.

Animals↗

Nighttime driving and fatal crash involvement of teenagers.

Data from the 1977 National Personal Transportation Survey and from the Fatal Accident Reporting System were used to compute mileage-based fatal crash involvement rates of drivers, by age, sex, and time of day. Teenagers drive less than older drivers but do more of their driving at night. They have much higher numbers of drivers in fatal crashes based on miles driven than do older drivers; their nighttime rates are particularly high. Sixteen year olds, especially males, have by far the highest fatal crash rates per mile, both nighttime and daytime. More widespread adoption of driving curfew laws would very likely produce substantial reductions in fatalities involving 16 yr old drivers.

Accidents, Traffic↗

Teenage driver licensing in relation to state laws.

Previous studies have shown that delaying licensure reduces motor vehicle injuries. This study examined the relationship between licensing laws and the timing of obtaining drivers licenses. The states studied have various laws, including minimum licensing ages of 15, 16 and 17; minimum learners permit ages of 15 and 16; and teenage night driving curfews. A questionnaire survey of 52,304 students was conducted in 75 high schools during the spring of 1983. The schools were selected from Orange County, California; rural Colorado; and most or all of Louisiana, Michigan, Mississippi, New Jersey and New York. The results indicated that the minimum age of licensure has obvious strong effects in delaying licensure. Setting the learners permit age later also apparently delays licensure. The night driving curfew in New York State (9 p.m.-5 a.m.) is seen by students as a factor in their decisions to delay obtaining licenses; Louisiana's 11 p.m.-5 a.m. curfew has a much smaller effect, if any.

Accidents, Traffic↗

A review of the literature evaluating the Defensive Driving Course.

The Defensive Driving Course (DDC), like other post-licensure driver training programs, is intended to reduce the rate of motor vehicle crashes among those who take the course. A review of the literature revealed 14 controlled studies of the effects of DDC. About a third of these studies provided methodologically strong tests of DDC, but the remainder had design flaws that made their findings questionable or inadequate as tests of DDC. Only among the flawed tests were there large, positive effects of DDC. In the methodologically strong tests, DDC had no consistent effect on crashes but did decrease the frequency of traffic violations by about 10%. The failure of violation reductions to be translated into crash reductions may indicate that the violation reduction is an artifact of traffic record procedures or that the changes in driver behavior, if real, were insufficient to modify individual crash likelihoods. In either event, the best available evidence does not support the hypothesis that DDC decreases the likelihood of motor vehicle crashes.

Accidents, Traffic↗

Night driving curfews in New York and Louisiana: results of a questionnaire survey.

New York and Louisiana, two states having night driving curfews, were included in a questionnaire survey of high school students conducted in 1983. Most students in these states knew about their curfew law. In both states the majority of licensed drivers said they had violated the curfew, but the majority claimed to have violated the curfew no more than twice. Students do not believe that the police enforce curfew restrictions vigorously, but many parents require their children to obey the law. New York students were more knowledgeable than Louisiana students about the restrictions, and there was more evidence in New York than Louisiana of reduced driving resulting from the curfew. These findings are consistent with results of an earlier study that found curfews in both of these states reduced crashes but estimated crash reductions during curfew hours were greater in New York than in Louisiana.

Accidents, Traffic↗

Evidence from cDNA clones that the rat leukocyte-common antigen (T200) spans the lipid bilayer and contains a cytoplasmic domain of 80,000 Mr.

The leukocyte-common antigen (L-CA or T200) includes a family of lymphoid and myeloid cell surface glycoproteins with apparent molecular weights from 180,000 to 240,000. We report a partial protein sequence for thymocyte L-CA containing 1073 amino acids predicted from cDNA clones isolated using an oligonucleotide probe. Only one segment (residues 347-368) is likely to cross the membrane, and peptide data suggest that sequences N-terminal to this are outside the cell, with residues 369-1073 inside. The cytoplasmic domain includes possible phosphorylation sites and an internal homology between residues 385-671 and 676-986. Analysis of B lymphocyte cDNA clones suggests that B cell and thymocyte mRNAs are identical in 3' sequences, but size differences in Northern blots suggest 5' sequences may differ.

Amino Acid Sequence↗

Skills performance at low blood alcohol levels.

The effect of low blood alcohol levels (BALs) on driving skills performance was examined experimentally. Ten moderate drinkers were tested on divided-attention and information processing tasks at BALs of zero, 15, 30, 45 and 60 mg/dl. All response measures showed evidence of impairment beginning at 15 mg/dl and increasing impairment with increasing BALs. Thus there is no evidence that low or very low BALs improve performance on driving-related skills, as has sometimes been suggested.

Adolescent↗

Driver licensing age and lifestyles of 16 year olds.

The relationship of driver licensure rate differences to 16 year old lifestyles was assessed by surveying 15 and 16 year olds in New York, Michigan, and New Jersey. Michigan 16 year olds reported the highest rates of licensure (56 per cent), whereas New York (14 per cent licensed) and New Jersey (2 per cent licensed) had much lower rates. Teenagers in Michigan reported greater decreases in use of bicycles and reliance on parents and relatives for transportation but, for the most part, the differences in 16 year old licensure and mobility were not reflected in lifestyle differences.

Adolescent↗

Analysis of lymphopoietic stem cells with a monoclonal antibody to the rat transferrin receptor.

A mouse monoclonal IgG2a antibody, designated MRC OX-26, is shown to be specific for the rat transferrin receptor, but does not block transferrin binding. The antibody labelled a myeloma, three leukaemia cell lines and normal dividing cells of various types, but also bound to a number of nondividing normal tissues. No labelling of lymphopoietic stem cells could be detected, even though approximately 25% of bone marrow and over 95% of fetal liver cells were clearly labelled.

Animals↗

A comparison of two methods of milk sampling for calculating the fat intake of breast-fed babies.

Fat intake at a breast feed was estimated by either sampling milk intermittently during the feed using a thin latex nipple shield ('shield method') or by expressing samples before and after the feed ('expression method'). These sampling techniques were compared within 30 mother/infant pairs using a randomized cross-over design. Mean fat intake estimated by the expression method was significantly greater than that estimated by the shield method (first breast P less than 0.0001, second breast P less than 0.002). This finding was partly explained by a significantly lower mean milk intake when the nipple shield was used, but the higher fat content of expressed milk samples compared to samples obtained during suckling also played a part. Use of the nipple shield confirmed that breast-milk fat content does not change in a predictable way during a feed. Nevertheless, for practical purposes, the advantages of studying changes in milk composition during the feed have to be set against the potential restrictive effect of the nipple shield system when it is used to sample intermittently during the feed.

Breast Feeding↗

Evaluating breast-milk intake by test weighing: a portable electronic balance suitable for community and field studies.

A K-Tron Digital Scale (Model DS-1) was used to weigh a group of 52 new born babies. The regression of the weights on true weights obtained with a Sartorius electronic balance 3806MP was 0.9911, with an estimated residual variance of 5.25. With the same babies weighed on a Marsden Weighmaster, the estimated residual variance was 68.93. Data from published studies on other balances are presented for comparison. The K-Tron is a reliable, portable, battery operated balance suitable for measuring milk intake by test weighing in homes or in the field.

Biometry↗