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Biomedical subjects

D Rayner

Publications and source records attributed to D Rayner.

15 recordsLinked to original sources

Amelioration of chronic and spontaneous intestinal inflammation with an antisense oligonucleotide (ISIS 9125) to intracellular adhesion molecule-1 in the HLA-B27/beta2 microglobulin transgenic rat model.

Adhesion molecules are known to be an important part of leukocyte migration and extravasation in both homeostatic and inflammatory conditions. Intracellular adhesion molecule-1 (ICAM-1 or CD54) is constitutively expressed on endothelial cells and is up-regulated during acute and chronic inflammation. We investigated the efficacy and consequences of interfering with CD54 after administration of an antisense oligonucleotide to ICAM-1 (CD54) in the transgenic HLA-B27/beta2 microglobulin rat model. One hundred percent of the HLA-B27 transgene + animals will spontaneously develop chronic inflammation (some more severely than others) in the gastric mucosa, cecum, and colon. We carried out two studies, i.p. injection and rectal administration of antisense. Following i.p. and rectal treatment, there were significant decreases in colonic mucosal wall thickness, histologic inflammation, CD54 expression in the colon and peripheral blood, and the percentage of colon weight per end body weight. Furthermore, decreased expression of CD49d, CD18, and tumor necrosis factor-alpha was observed in antisense treated rats. Therefore, the HLA-B27 transgenic model of spontaneous and chronic inflammatory bowel disease, which has increased expression of adhesion molecules, responds to both routes of administration of ICAM-1 antisense oligonucleotides. These studies support the regulatory role of adhesion molecules in chronic intestinal inflammation, the need for an understanding of how the route of drug delivery can alter the dose and area affected, and finally the role of antisense oligonucleotides as a therapeutic modality in chronic spontaneous inflammatory bowel diseases.

Administration, Rectal↗

Noncytolytic human lymphocytes injure dermal microvessels in the huPBL-SCID skin graft model.

Recent transplantation experiments using perforin-deficient mice as allograft recipients have challenged the concept that allograft rejection is mediated exclusively by CTL. We sought to determine if human noncytolytic lymphocytes could mediate rejection of allogeneic human skin grafts in the huPBL-SCID mouse model of rejection. We generated short term lines of human lymphocytes from peripheral blood mononuclear cells using PHA as a mitogen. The first group was stimulated with PHA alone, the second with PHA plus IL-4 and neutralizing antibody to IL-12, and in the third group PBL were depleted of B cells and monocytes before stimulation as in group 2. After two passages, lines were tested for cytolytic ability and IFN-gamma production. Each line was injected i.p. to mice bearing allogeneic skin grafts. The grafts were harvested between day 16 and 21 after PBL injection, then the histology was scored by a blinded observer for degree of infiltration, microvessel injury, induction of epidermal MHC class II, and perforin expression. In vitro we found that PBL in groups 2 and 3 were unable to lyse cultured endothelial cells in a lectin-directed 111In release assay. In vivo 80% of the IL-4/anti-IL-12 groups maintained the IFN-gamma-low phenotype, and no perforin was detected in these grafts. Nevertheless, human microvessel injury was similar between the two groups. This was not antibody-dependent since the B-cell-depleted group showed similar injury. Moreover adjacent murine vessels were intact. We interpret these observations to show (1) these human PBL lines maintained their phenotype following in vivo restimulation, and (2) noncytolytic graft-infiltrating lymphocytes specifically promote injury of allogeneic human microvessels.

Animals↗

Discovery of Circularly Polarized Radio Emission from SS 433.

We report the discovery of circularly polarized radio emission from the radio-jet X-ray binary SS 433 with the Australia Telescope Compact Array. The flux density spectrum of the circular polarization, clearly detected at four frequencies between 1 and 9 GHz, is of the form V~nu-0.9+/-0.1. Multiple components in the source and a lack of very high spatial resolution do not allow a unique determination of the origin of the circular polarization or of the spectrum of fractional polarization. However, we argue that the emission is likely to arise in the inner regions of the binary, possibly via propagation-induced conversion of linear to circular polarization, and the fractional circular polarization of these regions may be as high as 10%. Observations such as these have the potential to help us investigate the composition, whether pairs or baryonic, of the ejecta from X-ray binaries.

Journal Article↗

Implications in the maintenance of pregnancy: I. Presence of immunoreactive glycodelin in human umbilical cord vein endothelial cells.

OBJECTIVE: We previously reported an antipeptide antibody to human glycodelin that recognizes glycodelin in amniotic fluid and epithelial glands of the endometrium. The objective of this study was to determine the presence of glycodelin in human umbilical cord. DESIGN: Controlled clinical study. SETTING: Healthy women undergoing normal delivery at Grady Memorial Hospital, Atlanta, Georgia. PATIENT(S): Healthy women undergoing normal delivery. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Umbilical cord vein was isolated from the cord and used for immunohistochemical studies. Human umbilical cords and placentae were collected after full-term delivery. Cords were washed and fixed with formal sucrose. Decidua tissues and blood vessels from placentae were dissected out and fixed. Cryostat sections were immunostained with anti-glycodelin peptide antibody and anti-von Willebrand factor antibody. RESULT(S): Endothelial cells of human umbilical cord vein and artery were strongly immunostained with antiglycodelin antibody. Endothelial cells of the vein were more strongly stained than those of the artery. These cells were confirmed as endothelial cells by positive immunostaining with anti-von Willebrand factor. The epithelial cells outlining the cord were stained with antiglycodelin antibody but not with anti-von Willebrand factor antibody. CONCLUSION(S): This is the first study showing that immunoreactive glycodelin is present in endothelial cells of the umbilical cord. Glycodelin in the umbilical cord may have immunosuppressive or other, unknown functions affecting the physiology or pathophysiology of pregnancy. Whether umbilical vein endothelial cells synthesize glycodelin or serve as reservoir for glycodelin is currently under investigation.

Case-Control Studies↗

Kidney allograft with a lymphocytic infiltrate: acute rejection, posttransplantation lymphoproliferative disorder, neither, or both entities?

The two cases presented illustrate the diagnostic difficulties and recommend an approach to use in patients in whom features of acute renal allograft rejection and posttransplant lymphoproliferative disorder (PTLD) appear simultaneously in allograft biopsies. Both patients developed acute allograft rejection episodes in the early post-transplant period followed by severe immunosuppression (OKT-3) and active Epstein-Barr virus infection. In addition to early recognition of light microscopic features of PTLD, immunohistology and in situ hybridization for EBV complement the diagnostic work-up and provide clues to the prompt diagnosis of rapidly developing PTLD affecting the allograft even in the face of persisting rejection.

Adult↗

Gutta percha removal utilizing GPX instrumentation.

Two studies were performed in order to test the efficiency of GPX rotary instrumentation in removing gutta percha from endodontically-treated extracted teeth. A pilot project compared GPX to gates glidden instrumentation, and then a GPX technique was performed on 60 obturated mesial canals of mandibular molars. Assessment of the technique included radiographic and microscopic analysis of remaining debris. Results indicated that the GPX is a useful adjunct in these retreatment procedures. The clinical technique and time involved in the use of the GPX are discussed.

Dental Cavity Preparation↗

Identification and partial purification of ABGP205, an integral membrane glycoprotein from brain that binds ankyrin.

1. A procedure was devised that allows the membrane-skeletal proteins brain spectrin and ankyrin to be extracted selectively from a membrane-skeletal preparation, together with some actin, an Mr-103,000 protein and a population of glycoproteins. 2. Ankyrin-binding activities of the glycoproteins were investigated by affinity chromatography. We detected only one, Mr 205,000, that binds ankyrin and is prevented from binding by the cytoplasmic domain of Band 3, the established erythrocyte-membrane-binding site for ankyrin. The Mr-205,000 glycoprotein, designated ABGP205, may be a candidate for a membrane-binding site for ankyrin.

Animals↗

An investigation of the nature of induced suppression to experimental autoimmune thyroiditis.

When mice are pretreated with soluble mouse thyroglobulin (MTg), subsequent induction of autoantibodies in experimental allergic thyroiditis (EAT) is suppressed. This suppression can be reproducibly transferred to low-level irradiated syngeneic recipients and is specific for MTg. Injection of normal cells does not reverse this tolerance, also indicative of an active suppression. Neither can the induced unresponsiveness be overcome by immunization with cross-reactive xenogeneic Tg; although antibodies are formed which will bind to MTg, these are not to epitopes to which antibodies are normally formed on immunization or towards which tolerance is induced. This implies that tolerance might be induced at least at the B-cell level, a view supported by the inability of DNP to provide a new carrier to break tolerance when conjugated to MTg. The poorer response to DNP in these animals also suggests anergy of the MTg-specific T helpers.

Animals↗

Reducing the spread of tuberculosis in the homeless population.

Tuberculosis (TB) is an old infectious disease that has re-emerged in recent years and is responsible for many deaths throughout the world. Homeless people residing in shelters and hostels within inner city areas of the UK and the USA are at risk from this serious disease. Interventions to control the spread of TB are described in the literature researched; these include the introduction of inducements to encourage participation in screening programmes and the recommendation of directly observed therapy. The literature reflects the partial success of these programmes in the UK and USA. Targeting homeless persons most at risk is challenging as is gaining accurate information on those who are affected by TB. Effective coordination of care by healthcare providers in hospital and the community is imperative. It appears that healthcare professionals are becoming more prescriptive in their approach which is relinquishing the homeless population from taking responsibility for their own health care.

Attitude to Health↗