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Biomedical subjects

C Clegg

Publications and source records attributed to C Clegg.

15 recordsLinked to original sources
PubMed2000

Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function.

Cytokines are important in the regulation of haematopoiesis and immune responses, and can influence lymphocyte development. Here we have identified a class I cytokine receptor that is selectively expressed in lymphoid tissues and is capable of signal transduction. The full-length receptor was expressed in BaF3 cells, which created a functional assay for ligand detection and cloning. Conditioned media from activated human CD3+ T cells supported proliferation of the assay cell line. We constructed a complementary DNA expression library from activated human CD3+ T cells, and identified a cytokine with a four-helix-bundle structure using functional cloning. This cytokine is most closely related to IL2 and IL15, and has been designated IL21 with the receptor designated IL21 R. In vitro assays suggest that IL21 has a role in the proliferation and maturation of natural killer (NK) cell populations from bone marrow, in the proliferation of mature B-cell populations co-stimulated with anti-CD40, and in the proliferation of T cells co-stimulated with anti-CD3.

Amino Acid Sequence↗
PubMed1999

Secondary syphilis in persons infected with and not infected with HIV-1: a comparative immunohistologic study.

To better understand the cutaneous immune response to Treponema pallidum, we performed an immunohistologic study of skin biopsies from a total of 11 patients with secondary syphilis; biopsies from five persons infected with HIV-1 were included in the analysis to assess at the tissue level the impact of concomitant HIV-1 infection on disease expression. In all of the biopsies, staining for HLA-DR, a marker for cellular activation, was observed among infiltrating leukocytes, dermal vascular endothelial cells, and keratinocytes. Infiltrating mononuclear cells stained positively for CD4 or CD8, with CD4+ cells always being in the majority. Surprisingly, most of the CD4+ cells had histiocytic, rather than lymphocytic, morphologic characteristics. Immunostaining for CD14 confirmed that these cells were monocytic in origin, whereas immunostaining for CD3 revealed that the lymphocytes were predominantly CD8+ cytotoxic T cells. B cells were not detected despite the presence of variable numbers of plasma cells in all specimens. By immunofluorescence, all of the specimens demonstrated perivascular deposition of immunoglobulins, complement, or fibrinogen; linear staining at the dermal-epidermal junction also was observed in most of the specimens. No differences in immunocytochemical or immunofluorescence staining patterns were observed between the specimens from patients who were HIV positive and patients who were HIV negative. In addition to providing a more precise definition of the infiltrating cells in syphilitic lesions, our results, taken as a whole, indicate that cellular immune processes are largely responsible for the development of cutaneous manifestations during syphilitic infection and that coinfection with HIV-1 has little discernible effect on the cutaneous response to T. pallidum.

Adult↗
PubMed1997

Binary transgenic mouse model for studying the trans control of globin gene switching: evidence that GATA-1 is an in vivo repressor of human epsilon gene expression.

To test whether human GATA-1 (hGATA-1) is involved in the transcriptional control of globin gene switching, we produced transgenic mice overexpressing hGATA-1, crossed them with mice carrying a human beta-globin locus yeast artificial chromosome (beta YAC), and analyzed globin gene expression in their progeny. Mice carrying both the hGATA-1 and the beta YAC transgenes had normal levels of gamma- and beta-globin mRNA and no distortion in the rate or in the timing of gamma-to-beta switch, indicating that hGATA-1 is not involved in the developmental control of gamma- and beta-globin genes. In contrast, mice carrying the hGATA-1 and the beta YAC transgenes had 5- to 6-fold lower expression of the human epsilon globin gene compared with beta YAC mice lacking the hGATA-1 transgene. These results provide direct in vivo evidence that hGATA-1 is a specific repressor of human epsilon gene expression. Our findings also suggest that binary transgenic mouse systems based on overexpression of transcriptional factors can be used to investigate the trans control of human globin gene switching. Systems as the one we describe here should be useful in the study of any developmentally controlled human gene for which transgenic mice are available.

Animals↗
PubMed1997

Changing work systems.

This paper is concerned with finding practical ways of incorporating human and organizational concerns during the development and use of new information technologies (IT). It is structured in four parts. First, we outline the work of the Institute of Work Psychology at the University of Sheffield. One major interest is with the human and organizational aspects of the new information technologies. We are especially interested in work organization and job design, the allocation of tasks between and among humans and computers, the roles of users, the roles of senior managers, the management of change, and the performance of new investments in information technology (IT). Second, we review the evidence from survey work and from detailed case studies concerning the performance of IT. This reveals that most IT investments do not meet their performance objectives, and that the reasons for this are rarely purely technical in origin. Change is too often technology-led, and too little attention is paid to human and organizational factors. Most companies fail to consider how work should be organized and how jobs should be designed to make the new technologies more effective. Usually, users have no substantial influence on system development. Senior managers are criticized for their lack of understanding and action in these areas. Third, we consider the potential in the United Kingdom for changing work systems incorporating new technology. One way forward is through the development and use of sets of theoretically derived tools that can be used by managers and others. To this end we are working with several collaborators on a portfolio of tools in the following areas: organizational design job design allocation of tasks between and among humans and computers. We then review our approach and offer views of the areas and ways in which this work could develop, including opportunities for international collaboration.

Employment↗
PubMed1996

Tools to incorporate some psychological and organizational issues during the development of computer-based systems.

The organization, findings and outcomes of a joint industrial/academic project are described. The principal goal of the project was to develop and test some tools through which people involved in system development can incorporate explicit consideration of certain key psychological and organizational issues. Five tools developed for this purpose are outlined. These are concerned with the design of work organization, job design, the allocation of tasks between humans and computers, usability and task analysis. The use of the tools is described in a 'live' system development project in a large company. The authors briefly review the extent to which these tools meet a set of pre-specified requirements, compare their approach with those of Mumford (1986) and Lim et al. (1992), and make explicit what claims they are making of these tools.

Computer Systems↗
PubMed1994

Presence of multiple genetic subtypes of human immunodeficiency virus type 1 proviruses in Uganda.

DNA sequences encoding the C2-V3 regions or the C2-V5 regions of the surface glycoprotein gp120 of the human immunodeficiency virus type 1 (HIV-1) were amplified by the polymerase chain reaction (PCR) from peripheral blood mononuclear cells obtained in 1990/1992 from 20 infected Ugandans. The PCR-amplified DNA was cloned into a phagemid vector and between 1 and 12 clones from each provirus were sequenced. The Ugandan proviruses were aligned into four subtypes (A, B, C, and D) by phylogenetic analysis of consensus nucleotide sequences for the C2-V3 regions. Analysis of the deduced amino acid sequences of the C2-V3 regions by a maximum parsimony program gave a similar phylogenetic relationship. The data indicated that phylogenetic analysis of nucleotide and/or amino acid sequences from the C2-V3 regions is a reliable method of subtype determination. The consensus amino acid sequence of the subtype A and D proviruses were almost identical to those of the Albert et al. group B and group A proviruses, respectively. The deduced amino acid sequences of the C2-V5 regions of six of these proviruses showed considerable diversity both between patients and within patients. The region varied in length between 234 and 243 amino acids and included deletions and repetitions, particularly in the V4 region.

Adult↗
PubMed1993

Sequence analysis of the gp120 region of the env gene of Ugandan human immunodeficiency proviruses from a single individual.

DNA sequences encoding the surface glycoprotein gp120 of the human immunodeficiency virus type 1 (HIV-1) were amplified by the polymerase chain reaction (PCR) from peripheral blood mononuclear cells obtained from a Ugandan AIDS patient. The PCR-amplified DNA was cloned into a phagemid vector and nine clones sequenced. The gp120 sequences of the proviruses were similar to that of the Zairian isolate HIV-JY1 and unlike that of another Ugandan provirus, U455. Six of the clones were closely related to each other (maximum nucleotide sequence divergence 1.9%), and had a V3 amino acid sequence similar to that frequently seen in recent isolates from Uganda. Two others formed a second group that diverged from the first by an average of 6.0% at the nucleotide level, resulting in a 12.5% divergence of amino acid sequence. These divergent clones had extensive amino acid sequence changes not only in the V3 region, which was highly atypical, but also in V1 and V4, and to a lesser extent in V2 and V5. A further proviral clone had a sequence intermediate between those of the other two groups of clones.

Acquired Immunodeficiency Syndrome↗
PubMed1980

The isolation and characterization of a clonally related series of murine retrovirus-infected mouse cells.

Starting with cloned NIH 3T3 mouse cells we have isolated a series of related lines infected with the Kirsten murine sarcoma/leukaemia (MSV/MLV) virus complex. These lines exhibit all three possible infected cell phenotopes: (i) transformed MSV/MLV producers; (ii) non-transformed MLV producers; (iii) transformed non-producers. We have also selected non-transformed revertants from one of the non-producer clones. This series of lines allows the study of the expression of the virus genome against a constant background of cellular gene expression. We have further characterized the lines with regard to anchorage dependence of growth, tumorigenicity and the presence of a rescuable sarcoma genome. The non-producer clones are uniform in their transformed properties. The revertants contain rescuable sarcoma virus, biologically indistinguishable from the original transforming virus, implying that the reversion is due to a change in cellular rather than viurs genetic information.

Animals↗
PubMedDate not supplied

Recovery of atrazine, bromacil, chlorpyrifos, and metolachlor from water samples after concentration on solid-phase extraction disks: interlaboratory study.

An interlaboratory comparison was conducted in 1997 and 1998 to examine the feasibility of using C18 solid-phase extraction disks (Empore) to simultaneously determine the herbicides atrazine, bromacil, and metolachlor and the insecticide chlorpyrifos in water samples. A common fortification source and sample processing procedure were used to minimize variation in initial concentrations and operator inconsistencies. The protocol consisted of paired laboratories in different locations coordinating their activities and shipping fortified water samples (deionized or local surface water) or Empore disks on which the pesticides had been retained and then quantitating the analytes by a variety of gas chromatographic methods. Average recoveries from all laboratories were >80% for atrazine, bromacil, and metolachlor, and >70% for chlorpyrifos. Detection of bromacil was unachievable at some locations because of chromatographic problems. Shipping samples between cooperating laboratories did not affect the recovery of atrazine, chlorpyrifos, or metolachlor in either matrix. Recoveries tended to be higher from disks shipped to cooperating laboratories compared with those from fortified water. Shipping disks eliminated many problems associated with the shipment of water samples, such as bottle breakage, higher shipping cost, and possible pesticide degradation. Recoveries of bromacil and metolachlor were lower from fortified surface water samples than from fortified deionized water samples. This collaborative research demonstrated that pesticides in water samples can be concentrated on solid-phase extraction disks at one location and quantitated under diverse analytical conditions at another location. The extraction efficiencies of the disks were comparable with or better than the recoveries obtained from the shipped water samples, and the problems associated with shipping water samples were eliminated by using the disks.

Acetamides↗