CD antigens 2001: aims and results of HLDA Workshops.
Explore the source record for details and available documents.
Antigens, CD↗
Biomedical subjects
D Mason
Publications and source records attributed to D Mason.
CD antigens 2001.
This paper reviews the Seventh Human Leucocyte Differentiation Antigen (HLDA7) workshop. Due to the limitations of "blind" antibody screening, which had been evident at the previous meeting in 1996, participants at HLDA7 adopted a more selective approach to the choice of antibodies by identifying new CD specificities. This resulted in the addition of more than 80 new CD specificities. Plans for the eighth and subsequent workshops are also previewed.
Antibodies, Monoclonal↗
The open reading frame of the Na(+)-dependent glutamate transporter GLAST-1 is expressed in bone and a splice variant of this molecule is expressed in bone and brain.
Previously we have reported expression of an mRNA with homology to the Na(+)-dependent glutamate transporter, GLAST-1, in bone. Here we demonstrate that the complete open reading frame of GLAST-1 mRNA and corresponding 69 kDa protein are expressed in rat bone in vivo. We have also discovered a novel splice variant (GLAST-1a), lacking exon 3, expressed in rat bone and brain. A 55 kDa protein detected by anti-GLAST antibody in rat cerebellum corresponds to the molecular weight of unglycosylated GLAST-1a. This has led us to propose that GLAST-1a has an opposite orientation in the cell membrane to GLAST-1.
ATP-Binding Cassette Transporters↗
CD25 is a marker for CD4+ thymocytes that prevent autoimmune diabetes in rats, but peripheral T cells with this function are found in both CD25+ and CD25- subpopulations.
Previously we have shown that autoimmune diabetes, induced in rats by a protocol of adult thymectomy and split-dose gamma irradiation, can be prevented by the transfer of a subset of CD4+ T cells with a memory phenotype (CD45RC-), as well as by CD4+CD8- thymocytes, from syngeneic donors. Further studies now reveal that in the thymus the regulatory cells are observed in the CD25+ subset of CD4+CD8- cells, whereas transfer of the corresponding CD25- thymocyte subset leads to acceleration of disease onset in prediabetic recipients. However, in the periphery, not all regulatory T cells were found to be CD25+. In thoracic duct lymph, cells that could prevent diabetes were found in both CD25- and CD25+ subsets of CD4+CD45RC- cells. Further, CD25- regulatory T cells were also present within the CD4+CD45RC- cell subset from spleen and lymph nodes, but were effective in preventing diabetes only after the removal of CD25- recent thymic emigrants. Phenotypic analysis of human thymocytes showed the presence of CD25+ cells in the same proportions as in rat thymus. The possible developmental relationship between CD25+ and CD25- regulatory T cells is discussed.
Adoptive Transfer↗
Recirculatory and sessile CD4+ T lymphocytes differ on CD45RC expression.
CD4+ T cell subsets are unequally distributed in rat secondary lymphoid organs. Those with the memory phenotype CD45RClow Thy-1- L-selectin- are present at a higher frequency in Peyer's patches (PP) than in lymph nodes and spleen, and increase in numbers with age in all three tissues, particularly in the PP. Homing experiments revealed that CD4+ T cells that recirculate through secondary lymphoid organs are mainly CD45RChigh. It was also apparent that the ability of recirculating cells to enter different lymphoid organs varies; less cells enter PP than the spleen or lymph nodes. Our results also reveal the existence of a nonrecirculating population of CD4+ T cells in secondary lymphoid organs, which are predominantly, if not exclusively, CD45RClow. Our results show that secondary lymphoid organs differ in their CD4+ T cell subset composition as a consequence of having different ratios of recirculatory:nonrecirculatory CD4+ T cells, and these cells display a different CD45RC phenotype.
Animals↗
Induction of resistance to active experimental allergic encephalomyelitis by myelin basic protein-specific Th2 cell lines generated in the presence of glucocorticoids and IL-4.
We have produced T cell lines with a Th2 phenotype in the presence of IL-4 and the glucocorticoid dexamethasone (DEX). IL-4 and DEX together were more effective in inducing a Th2 response than IL-4 alone. Myelin basic protein (MBP)-specific Th2 lines were obtained and their ability to induce experimental allergic encephalomyelitis (EAE) was studied. Lines treated with IL-4 and DEX did not transfer passive EAE and did not induce cellular infiltration into the central nervous system as opposed to the encephalitogenic Th1 lines. Lines treated with IL-4 and DEX did not protect animals from the effect of encephalitogenic Th1 lines when the two were injected together. However, a high proportion of animals injected with IL-4 + DEX-treated lines became refractory to the development of EAE after immunization with MBP; that is, it was possible to induce resistance to active EAE without prior episodes of disease. Interestingly, animals injected with T cell lines had accelerated antibody responses against MBP and the predominant isotype was dependent on the cytokines synthesized by the T cell line injected. There was not evidence that the resistance to active EAE was due to anergy of MBP-reactive cells or the action of CD8+ cells. Our data suggest that MBP-specific T cell lines prevent the induction of disease by deviating the reactivity to MBP from a cell-mediated to a humoral one and not merely from a Th1 to a Th2 response.
Adoptive Transfer↗
The third function of the thymus.
Nonresponsiveness of mammalian T cells to self-antigens is not totally accounted for in terms of clonal deletion, T-cell anergy and T-cell ignorance: studies have shown that the T-cell repertoire of healthy individuals contains cells with the potential to cause autoimmune disease. This article describes a T-cell-mediated mechanism that prevents the realization of this potential and indicates how its failure can lead to the development of autoimmunity.
Animals↗
Phenotypic analysis of peripheral CD4+ CD8+ T cells in the rat.
Among peripheral T cells, the expression of CD4 and CD8 is almost mutually exclusive. However, here we show, using flow cytometric analysis, that ex vivo approximately 6% of rat T cells stained for both CD4 and CD8. These double positive cells were also detected by confocal microscopy. Only around 50% of double positive cells expressed the CD8beta chain, the remaining cells expressed the CD8alpha chain alone. Double positive cells were blast-like with a phenotype, distinct from that of either CD4 or CD8 single positive cells, suggestive of an activated state. Previous reports of double positive T cells have also suggested that coexpression of CD4 and CD8 is linked to the activation state of the cell. There was an indication that priming animals with a hapten-carrier complex increased the ratio of CD8alphaalpha : alphabeta expressing double positive T cells, although we did not detect an increase in the frequency of double positive T cells following priming. We also show that the frequency of double positive cells was reduced following thymectomy and with age. In conclusion, these studies show that peripheral T cells expressing both CD4 and CD8 can be detected in the rat and that they are phenotypically distinct from CD4 and CD8 single positive T cells.
Aging↗
Modified sector-integration method for predicting the output factors of electron beams including extended source to surface distance.
A modified sector-integration method is presented that can predict the output factors of irregular shaped electron fields even in the case of extended source to surface distance (SSD). The model takes as input measured output factors for circular inserts of various radii. These circular fields were measured at SSDs of 100, 105 and 110 cm to determine the effective source distance as a function of radius (ESD(r)). For an arbitrary electron field at any SSD, the shape is divided into small sectors, and the contribution calculated from the radius and ESD(r). The calculated output factors were verified by direct measurements of various types of electron fields mainly based on clinical use. The energies modelled were 8, 10 and 12 MeV for applicator sizes of 10 cm x 10 cm and 14 cm x 14 cm (defined at 95 cm). The calculated values agreed with the measured data within 1% for the various rectangular cutouts including extended source to surface distance. We retrospectively modelled 97 patient inserts of irregular shape, and found agreement within 2% of measured values.
Algorithms↗
Nurses and models of practice...then & now.
Explore the source record for details and available documents.
History of Nursing↗
Nurses. Then and now. Oncology nursing.
Explore the source record for details and available documents.
History, 20th Century↗
'Hallmark' cells in nodal cytotoxic lymphomas.
Explore the source record for details and available documents.
Anaplastic Lymphoma Kinase↗
Absorption characteristics of sustained-release 4-aminopyridine (fampridine SR) in patients with chronic spinal cord injury.
Fampridine SR (4-aminopyridine) is a potassium channel-blocking drug currently being investigated for its therapeutic efficacy in ameliorating central conduction deficits due to demyelination in patients with spinal cord injury (SCI). The present open-label pharmacokinetic trial examined the absorption characteristics of a sustained-release form of the drug in 25 SCI subjects with chronic incomplete injuries. The overall group mean Cmax of 27.7 +/- 6.2 ng/mL occurred at a tmax of 3.4 +/- 1.4 hours. AUC0-12 was 210.5 +/- 49.5 ng/mL.h. For paraplegics, AUCtmax was 76.02 +/- 33.28 and for tetraplegics was significantly less at 51.25 +/- 20.36 (p = 0.037). A statistically significant difference in the initial rate and extent of absorption, but not in total 4-AP bioavailability over the 12-hour study period, was evident between tetraplegic patients, 0.60 +/- 0.23, and paraplegic patients, 0.39 +/- 0.14 (p = 0.02). There was a linear correlation (p < 0.05) between the neurological level of injury and Cmax/AUCtmax. These results confirm and extend previous observations of different rates of drug absorption among SCI patients with lesions above and below the sympathetic outflow (T6) and provide evidence of the absorption characteristics of this sustained-release form of 4-aminopyridine, which is helpful for optimal dosing.
4-Aminopyridine↗
Peripheral autoantigen induces regulatory T cells that prevent autoimmunity.
Previous studies have shown that autoimmune thyroiditis can be induced in normal laboratory rats after thymectomy and split dose gamma-irradiation. Development of disease can be prevented by reconstitution of PVG rats shortly after their final irradiation with either peripheral CD4(+)CD45RC- T cells or CD4(+)CD8(-) thymocytes from syngeneic donors. Although the activity of both populations is known to depend on the activities of endogenously produced interleukin 4 and transforming growth factor beta, implying a common mechanism, the issue of antigen specificity of the cells involved has not yet been addressed. In this study, we show that the regulatory T cells that prevent autoimmune thyroiditis are generated in vivo only when the relevant autoantigen is also present. Peripheral CD4(+) T cells, from rats whose thyroids were ablated in utero by treatment with 131I, were unable to prevent disease development upon adoptive transfer into thymectomized and irradiated recipients. This regulatory deficit is specific for thyroid autoimmunity, since CD4(+) T cells from 131I-treated PVG.RT1(u) rats were as effective as those from normal donors at preventing diabetes in thymectomized and irradiated PVG.RT1(u) rats. Significantly, in contrast to the peripheral CD4(+) T cells, CD4(+)CD8(-) thymocytes from 131I-treated PVG donors were still able to prevent thyroiditis upon adoptive transfer. Taken together, these data indicate that it is the peripheral autoantigen itself that stimulates the generation of the appropriate regulatory cells from thymic emigrant precursors.
Animals↗
Regulatory T cells in the control of autoimmunity: the essential role of transforming growth factor beta and interleukin 4 in the prevention of autoimmune thyroiditis in rats by peripheral CD4(+)CD45RC- cells and CD4(+)CD8(-) thymocytes.
Previous studies have shown that induction of autoimmune diabetes by adult thymectomy and split dose irradiation of PVG.RT1(u) rats can be prevented by their reconstitution with peripheral CD4(+)CD45RC-TCR-alpha/beta+RT6(+) cells and CD4(+)CD8(-) thymocytes from normal syngeneic donors. These data provide evidence for the role of regulatory T cells in the prevention of a tissue-specific autoimmune disease but the mode of action of these cells has not been reported previously. In this study, autoimmune thyroiditis was induced in PVG.RT1(c) rats using a similar protocol of thymectomy and irradiation. Although a cell-mediated mechanism has been implicated in the pathogenesis of diabetes in PVG.RT1(u) rats, development of thyroiditis is independent of CD8(+) T cells and is characterized by high titers of immunoglobulin (Ig)G1 antithyroglobulin antibodies, indicating a major humoral component in the pathogenesis of disease. As with autoimmune diabetes in PVG. RT1(u) rats, development of thyroiditis was prevented by the transfer of CD4(+)CD45RC- and CD4(+)CD8(-) thymocytes from normal donors but not by CD4(+)CD45RC+ peripheral T cells. We now show that transforming growth factor (TGF)-beta and interleukin (IL)-4 both play essential roles in the mechanism of this protection since administration of monoclonal antibodies that block the biological activity of either of these cytokines abrogates the protective effect of the donor cells in the recipient rats. The prevention of both diabetes and thyroiditis by CD4(+)CD45RC- peripheral cells and CD4(+)CD8(-) thymocytes therefore does not support the view that the mechanism of regulation involves a switch from a T helper cell type 1 (Th1) to a Th2-like response, but rather relies upon a specific suppression of the autoimmune responses involving TGF-beta and IL-4. The observation that the same two cytokines were implicated in the protective mechanism, whether thymocytes or peripheral cells were used to prevent autoimmunity, strongly suggests that the regulatory cells from both sources act in the same way and that the thymocytes are programmed in the periphery for their protective role. The implications of this result with respect to immunological homeostasis are discussed.
Animals↗
Target controlled infusion of ketamine as analgesia for TIVA with propofol.
PURPOSE: To determine the accuracy of a target controlled infusion system for ketamine and to assess its suitability for the provision of analgesia when used in conjunction with a propofol infusion in spontaneously breathing patients. METHODS: Nineteen, adult, ASA I-III patients scheduled for elective surgery were studied. After premedication with 20 mg temazepam an appropriate plasma concentration of ketamine was selected and, when the target controlled infusion (TCI) system indicated that this had been achieved, anesthesia was induced and maintained using a propofol infusion. The plasma ketamine concentration was measured at predetermined intervals and cardiovascular and respiratory parameters recorded at 10 min intervals. Patients were reviewed in recovery and 24 hr postoperatively to assess the adequacy of their recovery and the presence of any undesirable side effects. RESULTS: The TCI system had a median performance error against predicted plasma concentrations of 18.9% (SE 2.5%) and a median absolute performance error of 23.3% (SE 2.3%). Divergence was 20.3% (SE 30.1%) and wobble was 12.9% (SE 2.1%). There was a mean decrease in arterial pressure of 6.4% (SD 19.7%) and a mean increase in heart rate of 4.3% (SD 17.4%). Little respiratory depression occurred and all patients made a rapid postoperative recovery with none describing unpleasant dreams or hallucinations. CONCLUSION: The TCI system provided a clinically acceptable degree of control of the plasma ketamine concentration although some further improvement should be possible by amending the pharmacokinetic model. Clinically the combination with a propofol infusion proved to be a satisfactory anesthetic technique.
Adolescent↗
Heparin after percutaneous intervention (HAPI): a prospective multicenter randomized trial of three heparin regimens after successful coronary intervention.
OBJECTIVES: The purpose of this study was to determine the incidence of bleeding, vascular, and ischemic complications using three different heparin regimens after successful intervention. BACKGROUND: The ideal dose and duration of heparin infusion after successful coronary intervention is unknown. METHODS: Patients were randomized to one of three heparin strategies after coronary intervention: Group 1 (n = 157 patients) received prolonged (12 to 24 h) heparin infusion followed by sheath removal; Group 2 (n = 120 patients) underwent early removal of sheaths, followed by reinstitution of heparin infusion for 12 to 18 h; Group 3 (n = 137 patients) did not receive any further heparin after intervention with early sheath removal. The primary end point of the study was the combined incidence of in-hospital bleeding and vascular events. Secondary end points included in-hospital ischemic events, length of stay, cost and one-month outcome. RESULTS: After successful coronary intervention, 414 patients were randomized. Unstable angina or postinfarction angina was present in 83% of patients before intervention. The combined incidence of bleeding and vascular events was 21% in Group 1, 14% in Group 2 and 8% in Group 3 (p = 0.01). The overall incidence of in-hospital ischemic complications was 2.2%; there were no differences between groups. Length of hospital stay was shorter (p = 0.033) and adjusted hospital cost was lower (p < 0.001) for Group 3. At 30 days, the incidence of delayed cardiac and vascular events was similar for all three groups. CONCLUSIONS: Heparin infusion after successful coronary intervention is associated with more minor bleeding and vascular injury, prolonged length of stay and increased cost. In-hospital and one-month ischemic events rarely occur after successful intervention, irrespective of heparin use. Routine postprocedure heparin is not recommended, even in patients who present with unstable ischemic syndromes.
Angioplasty, Balloon, Coronary↗
Transobturator vascular graft biopsy at cystoscopy.
Explore the source record for details and available documents.
Aged↗