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Biomedical subjects
Publications and source records attributed to A Willis.
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The monoclonal antibodies HML-1, B-ly7 and Ber-ACT8 recognize intramucosal gut T lymphocytes, activated cells, and hairy cell leukemia. The antigen on hairy cells consists of three glycoproteins (160 kappa D, 130 kappa D and 105 kappa D unreduced; 145 kappa D and 120 kappa D reduced). These peptides have biochemical features reminiscent of integrins but we have shown by immunoprecipitation that they are not known integrin subunits. We have used a newly produced antibody (BP6) to purify this molecule and shown by N-terminal sequence analysis that the smallest subunit is the product of integrin beta 7 cDNA. This molecule is thus a new member of the integrin family of leucocyte adhesion proteins. Immunoprecipitation experiments indicate that the two larger subunits are recognized by HML-1, B-ly7 and Ber-ACT8.
The differentiation of embryonic stem (ES) cells is controlled by the regulatory factor differentiation inhibiting activity/leukemia inhibitory factor (DIA/LIF). Examination of feeder cell-mediated suppression of ES cell differentiation revealed that DIA/LIF is produced both as a diffusible protein and in an immobilized form associated with the extracellular matrix. This alternative localization arises from the expression of alternate transcripts that diverge throughout exon 1. The effect of alternate first exon usage is to change the amino terminus of the primary translation product and to direct incorporation of mature, biologically active DIA/LIF into the extracellular matrix. The production of a potent regulatory factor in both diffusible and immobilized forms may be an important element of developmental control mechanisms.
The rapid accumulation of sequence data has provided insight into the evolution of proteins and led to the identification of 'mosaic proteins'. These proteins have evolved by duplication, insertion and deletion of a common pool of structural units or modules, yet their biological functions are diverse. They are involved in cell adhesion and migration, embryogenesis and the pathways of blood clotting, fibrinolysis and complement. The modular units are defined by 'consensus sequences' which often include conserved disulphide bonds. Despite the available sequence information, little is known of the tertiary structure of mosaic proteins. If, however, the 'consensus structure' of the modules were known, valuable structural information could be inferred about a wide variety of proteins and biological systems. An important mosaic protein is fibronectin, an extracellular matrix protein that consists of three types of module (see refs 3, 7 for reviews). Here we describe the structure of the fibronectin type 1 module which appears twelve times in fibronectin and is also found in factor XII and tissue plasminogen activator. The module was produced using a yeast expression system and the structure was determined in solution using 1H NMR. This methodology promises to be extremely powerful in the investigation of modules from a wide range of mosaic proteins.
It has been suggested that epidermal growth factor-like (EGF-like) domains, containing conserved carboxylate residues, are responsible for the high-affinity calcium binding exhibited by a number of vitamin K-dependent plasma proteins involved in the control of the blood coagulation cascade. These include the procoagulant factors IX and X, and the anticoagulants protein C and protein S. To test this hypothesis we have expressed the first EGF-like domain from human factor IX (residues 46-84) using a yeast secretion system, and examined calcium binding to the domain. Using 1H-NMR to measure a calcium-dependent shift assigned to Tyr69 we have detected a high-affinity calcium binding site (Kd = 200-300 microM). We suggest that other EGF-like domains of this type may have similar calcium binding properties. In addition, we have completely assigned the aromatic region of the NMR spectrum by NOESY and COSY analysis, and have used these data to discuss the effect of calcium and pH on the conformation of the domain with reference to a model based on the structure of human EGF.
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The Library Association Medical, Health and Welfare Libraries Group was asked by the Library and Information Services Council (LISC) for England to submit a paper on health information services for the lay person and this presented a timely opportunity to consider the situation thus far and possibilities for the future. A working group was set up from amongst those active in the field to pool ideas and experience, and it was fortunate also in being able to include consideration of Elaine Kempson's recently published study Informing health consumers. It was felt particularly that whilst a number of worthwhile services were developing there was no guarantee of adequate local provision and that in the absence of any sort of framework there was considerable danger of duplication of effort and isolation on the part of the practitioners. The paper was considered by LISC in October 1988 and in the intervening period our recommendation that public library development incentive funding might be used to enable a public library to co-operate with other local statutory and voluntary agencies in the setting up of a pilot local health information centre, perhaps capitalizing on existing expertise by buying-in a database such as that of Help for Health, has been fulfilled by the establishment of the Dorset Health Information Service whose progress will be watched with interest. Nevertheless there is still much to be achieved in this field and it is hoped that this paper will prove a useful basis for continued discussion.
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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.
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The professions of law and medicine exert a profound influence on sexual attitudes and behaviour in our society. Previous reported studies of legal and medical students found no differences in sexual knowledge for entering first-year students. However, in this study, a sample of 160 medical and seventy-nine law students revealed significant differences in knowledge and attitudes about sexuality. The data indicate that a gender-linked double standard of acceptable behaviour is not present. Results further reinforce the necessity of medical sex education.
This report summarizes data gathered thus far from an ongoing study. Two groups (total N = 12) of Vietnam War veterans diagnosed with Posttraumatic Stress Disorder (PTSD) received a single session of exposure or Eye Movement Desensitization and Reprocessing (EMDR) focusing on the veterans' most distressing war experience. Group assignment was random, treatment providers were blind to assessment data, and the pre- and posttreatment assessor was blind to treatment assignment. Both groups showed improvement on the Impact of Event Scale. EMDR treatment resulted in greater positive changes in within-session Subjective Units of Discomfort levels and on self-monitored severity of intrusive recollection. A trend toward decreased heart rate reactivity was observed in both groups. Results must be considered carefully due to the small number of subjects used in the study.