Do not give paraffin to packers.
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Cocaine↗
Biomedical subjects
L Visser
Publications and source records attributed to L Visser.
Antibody-mediated targeting of CD45 isoforms: a novel immunotherapeutic strategy.
CD45 is a family of transmembrane protein tyrosine phosphatases exclusively expressed by hematopoietic cells and critically involved in the regulation of T cell activation signals. We now demonstrate that three 100-microg doses of anti-CD45RB mAb MB23G2 can induce long-term engraftment of islets into major histcompatibility complex-disparate chemically diabetic mice. Long-term graft survivors (>120 days) were tolerant to new islet allografts from the original donor strain. MB23G2 induced a temporary decrease in number circulating leukocytes but had no effect on leukocyte number in other lymphoid compartments. Histologic examination of allografts from treated and untreated recipients revealed a similar peri-islet infiltration on day 6. Eleven days after transplant, the peri-islet infiltrate in treated animals persisted, but in marked contrast to untreated control animals, there was no insulitis and islet integrity was preserved. The peri-islet infiltrate from treated animals showed a mild increase in CD4 cells, a decrease in CD8 cells, and decreased intensity of CD45RB expression. Treatment of naive animals with anti-CD45RB (MB23G2) resulted in a shift in CD45 isoform expression on T cells with a loss of higher molecular weight isoforms and increased expression of lower molecular weight (CD45R0) isoform. This shift in CD45 isoform expression from CD45RBHi to CD45RBLo was associated with an increase in the intragraft expression of transcripts for interleukin (IL) 4 and IL-10, consistent with the expected activity of this distinct immunoregulatory T cell subset. Antibody-mediated targeting of CD45 may induce tolerance through novel mechanisms and have direct applicability to clinical transplantation in humans.
Animals↗
Immune escape mechanisms in Hodgkin's disease.
BACKGROUND: The nodular sclerosis and mixed cellularity subtypes of Hodgkin's disease are histologically characterised by a small population of neoplastic cells, the so-called Reed-Sternberg cells and their mononuclear variants (RS cells) and an extensive admixture of other cell types including lymphocytes, plasma cells, eosinophils, and histiocytes. The nature of this infiltrate is largely known, but the mechanisms and functional effects are not. The small lymphocytes immediately surrounding the RS cells are mostly CD4+ T cells that express early activation markers. The absence of prominent specific cytotoxic T cell or natural killer (NK) cell populations seems to argue against a Th1-type response, whereas the sometimes prominent admixture of plasma cells and eosinophils is suggestive of a Th2-type response. Enrichment of the CD4 T-cell population may result from selective influx of CD4 T cells or from selective depletion of CD8 and NK cells. RESULTS AND DISCUSSION: The T cells surrounding RS cells have an immuno-phenotype and cytokine production capability consistent with a Th2-type response. RS cells express several members of the TNF receptor family such as the FAS ligand (CD95L) that may induce apoptosis of activated, FAS expressing, CD8+ T cells and NK cells. The RS cells also produce TGF beta and interleukin-10 that may downmodulate the Th1 response. In addition, the Reed-Sternberg cells produce the chemokine TARC that could lead to the specific attraction of a Th2 T-cell subset. CONCLUSION: RS cells have several mechanisms that may allow it to escape an effective immune response. The relative contributions of each of these and other potential mechanisms are not yet known.
CD4 Antigens↗
Therapy with antibodies against CD40L (CD154) and CD44-variant isoforms reduces experimental autoimmune encephalomyelitis induced by a proteolipid protein peptide.
Interactions between mononuclear cells are required for the formation of inflammatory infiltrates in the CNS and the activation of cellular effector functions provoking demyelination in MS. Membrane-expressed costimulatory molecules are crucial to such interactions. We therefore investigated whether two costimulatory molecules, CD40L (CD154, expressed on activated CD4-possible T cells) and selected CD44-variant isoforms (expressed on activated CD4-positive T cells), are targets for immunotherapy in MS. The model of experimental autoimmune encephalomyelitis (EAE) induced in SJL-mice by immunization with a peptide derived from the proteolipid protein (PLP139-151) was optimized to address these questions. A previous observation that anti-CD40L (CD154) monoclonal antibodies can effectively prevent EAE in this model was confirmed, and extended by demonstrating that CD40 is expressed by cells of the monocytic lineage infiltrating the spinal cord. In vivo treatment with antibody against the standard isoform of CD44 (CD44s or CD44H) did not affect disease burden. In contrast, combined treatment with antibodies against the isoforms CD44v6, v7 and v10, which are thought to be involved in inflammatory processes, reduced the disease burden considerably. In addition, CD44v10-expressing cells were detected in the spinal cord. These data support the idea that CD40-CD40L interactions form a target for immunotherapy of MS, and indicate that cells expressing CD44v6, v7 and/or v10-containing isoforms have such potential as well.
Animals↗
The prevalence of mixed-species and antifolate-resistant malaria infections in Mpumalanga.
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Drug Resistance, Multiple↗
[Breathing-related nursing care problems--a descriptive study].
Research into nursing problems related to breathing that can occur by pulmonary patients and their relationship with literature on Nursing Diagnoses (further referred to as diagnoses) on this subject has been done on two nursing wards. Interviews have been held with eleven nurses working in direct patient care. From the acquired data twelve problems with their signs and symptoms as well as the possible etiology were found, each showing one or more similarities with diagnoses from the North American Nursing Diagnosis Association (NANDA). Similarities and differences between the NANDA diagnoses and the acquired data have been analysed.
Clinical Nursing Research↗
Lessons learned from three violence prevention projects.
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Adolescent↗
CD45 (leucocyte common antigen) expression in T and B lymphocyte subsets.
CD45 is the dominant tyrosine phosphatase in haematopoietic cells and can modulate the effects of many other signaling molecules by dephosphorylation. The extracellular portion of CD45 has considerable variability due to differential splicing and glycosylation. This may allow for interactions with a variety of ligands expressed on interacting cells or on the same cell surface. Monoclonal anti CD45 antibodies that are reactive with epitopes that result from differential splicing and glycosylation can distinguish between cell populations that differ in maturation and function. These reagents can be used in the immunophenotyping of hematopoietic malignancies as well as in immunodeficiencies and autoimmune diseases. Several studies have shown that different anti CD45 reagents have different activating or inhibiting effects in vitro on a variety of T and B cell activation events. There are some indications that anti CD45 reagents can also selectively modify lymphocyte function in vivo. Such applications could potentially allow for the selective upregulation and down regulation of lymphocyte functions in a variety of immunologically mediated diseases.
B-Lymphocyte Subsets↗
A formative model for student nurse development and evaluation--Part 1--Developing the model.
Preparing student nurses for the profession is a complex task for nurse educators; especially when dealing with the development of personal and interpersonal skills, qualities and values held in high esteem by the nursing profession and the community they serve. These researchers developed a model for formative evaluation of students by using the principles of inductive and deductive reasoning. This model was implemented in clinical practice situations and evaluated for its usefulness. It seems that the model enhanced the standards of nursing care because it had a positive effect on the behavior of students and they were better motivated; the model also improved interpersonal relationships and communication between practising nurses and students. The fact that students repeatedly use the model as a norm for self evaluation ensures that they are constantly reminded of the standards required of a professional nurse.
Clinical Competence↗
In vitro system for evaluation of the immunomodulatory capacity of CD45(R) reagents.
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Antibodies↗
Acute Schistosomiasis in Travelers Returning From Mali.
Acute schistosomiasis or "Katayama syndrome" occurs in previously uninfected persons 3-6 weeks after exposure to cercaria-infested water.1,2 Many outbreaks among tourists have been reported.3-11 Such outbreaks occur because tourists are bathing or swimming in waters thought by tourist organizations to be bilharzial free. Imported schistosomiasis acquired in the Dogon country in Mali, West Africa, was first demonstrated in 1989 in three Spanish travelers;3 in 1991, an outbreak was described among Dutch travelers.7 In 1993, we investigated a similar outbreak among European and American travelers returning from the same area.
Journal Article↗
Ectopic expression of human and feline CD9 in a human B cell line confers beta 1 integrin-dependent motility on fibronectin and laminin substrates and enhanced tyrosine phosphorylation.
Few molecules have been shown to confer cell motility. Although the motility-arresting properties of anti-CD9 monoclonal antibody (mAb) suggest the transmembrane 4 superfamily (TM4SF) member CD9 can induce a motorgenic signal, gene transfection studies have failed to confirm this hypothesis. We report here that ectopic expression of human CD9 (CD9h) and feline CD9 (CD9f) in the CD9-negative, poorly motile, human B cell line Raji dramatically enhances migration across fibronectin- and laminin-coated polycarbonate filters. Migration of Raji/CD9h and Raji/CD9f on either substrate was inhibited by the anti-CD9 mAb 50H.19 and by the anti-beta 1 integrin mAb AP-138. Migration of Raji/CD9h on laminin was potently inhibited by the anti-VLA-6 integrin mAb GoH3 and by the anti-VLA-4 integrin mAb 44H6, whereas migration of Raji/CD9h on fibronectin was inhibited only by mAb 44H6. Since CD9h-transfected Raji cells adhered to fibronectin as effectively as mock transfectants, expression of CD9 enhanced motility, but not adhesion. CD9-enhanced migration was inhibited by the protein tyrosine kinase inhibitor herbimycin A suggesting that tyrosine phosphorylation played a role in the generation of a motorgenic signal. Raji/CD9h transfectants adherent to fibronectin expressed 6-fold higher levels of phosphotyrosine than Raji. Raji/CD9f transfectants also phosphorylated proteins on tyrosine more effectively than Raji including a protein of 110 kDa which was phosphorylated on the motility-inducing substrates laminin and fibronectin, but not on bovine serum albumin. Our results support a role for CD9 in the amplification of a motorgenic signal in B cells involving beta 1 integrins and the activation of protein tyrosine kinases.
Animals↗
Aggressive fluid resuscitation and broad spectrum antibiotics decrease mortality from typhoid ileal perforation.
One of the most severe complications of typhoid enteritis is perforation of ileal ulcerations. The typically high mortality rates from these perforations are in part due to extremely limited supportive care in hospitals in typhoid endemic areas. In the setting of a rural African hospital, this study demonstrated a decrease in overall mortality rate from 40% with one layer closure and chloramphenicol alone to 19% with two-layer closure and chloramphenicol, gentamicin and metronidazole. This was primarily due to a decrease in late (> 24 h) mortality. There was also a decrease in overall mortality rate from 43% with < 10 ml/kg of intraoperative fluid administration to 14% with > 10 ml/kg. This was primarily due to a decrease in early (< 24 h) mortality. Even within the constraints of the rural developing world, more aggressive initial fluid resuscitation can decrease early mortality, while broader spectrum antibiotics and two-layer closure can decrease late mortality from typhoid ileal perforation.
Adolescent↗
Epstein-Barr virus positivity in Hodgkin's disease does not correlate with an HLA A2-negative phenotype.
BACKGROUND: Epstein-Barr virus- (EBV) related DNA and RNA can be found in tissues involved with Hodgkin's disease, specifically in the Reed-Sternberg cells. These cells also express the membrane antigens LMP1 and LMP 2A and 2B. Studies in normal individuals indicate that cellular immunity against LMP2 was frequently mediated through human leukocyte antigen (HLA) A2, whereas responses to LMP1 appeared to be relatively infrequent. Assuming that LMP2-positive Reed-Sternberg cells would be sensitive to a CD8-positive cellular immune response, the hypothesis can be made that EBV-positive Hodgkin's disease should be more common in individuals not expressing HLA A2. To test this hypothesis, the authors have studied the frequency of HLA A2 in EBV-positive versus EBV-negative patients with Hodgkin's disease. METHODS: All 72 patients diagnosed with Hodgkin's disease in Northern and Central Alberta, Canada, during 1990 and 1991 were studied. A nonisotopic in situ hybridization method with an oligonucleotide probe specific for EBER 1 and 2 was used. In addition, sections were stained for the EBV-latent protein LMP1, HLA A2, and a monomorphic HLA class I determinant and beta 2-microglobulin. RESULTS: EBER-positive Reed-Sternberg cells were found in 26% of the patients. The percentage of positive patients was 86% in mixed cellularity, 13% in nodular sclerosis, and 0% in lymphocyte predominance. The number of those who were HLA-A2 positive was approximately 50% in the EBV-positive and -negative patients. CONCLUSIONS: Therefore, no correlation between HLA A2 expression and presence or absence of EBV in the R-S cells of Hodgkin's disease was identified.
Base Sequence↗
Physiopathology of hypernatremia following relief of urinary tract obstruction.
We report a case of postobstructive hypernatremia, and illustrate its pathogenesis and treatment. Physicians should be aware of this condition, given its high mortality rate (up to 70%), the high prevalence of potentially obstructive prostatic disease in elderly people and the peculiar sensitivity of this age group to disorders of osmotic regulation. Knowledge of the processes involved in osmoregulation has provided insights into the pathogenesis of this condition, which includes at least three factors: (i) decreased efficacy of the thirst mechanism in elderly patients, (ii) water loss in excess of effective solutes, resulting from osmotic diuresis from urea and transient renal tubular unresponsiveness to antidiuretic hormone, and (iii) inadequate fluid administration and failure to induce a positive fluid balance. These insights led to the development of specific strategies aimed at adequate correction of hypernatremia. Initial therapy should be rapid infusion of normal saline (or half-normal saline) coupled to administration of free water to restore euvolemia and correct hypernatremia, relying on repeated calculations of the free water deficit and taking into account ongoing urinary and insensible losses.
Adenocarcinoma↗
Postnatal changes of CD45 expression in peripheral blood T and B cells.
One known postnatal change of CD45 expression is the decline of the CD45RAhigh CD45ROlow T subsets and the reciprocal increase of the CD45RAlow CD45ROhigh T subsets in the peripheral blood. Using a panel of monoclonal antibodies reactive with either protein or carbohydrate epitopes on the variable regions of CD45, we were able to detect more postnatal changes of CD45 expression. These changes are largely caused by modulation of the CD45 glycosylation, including: (1) lesser sialylation of the CD45RA region on T cells, and (2) differential sialylation of the CD45RB region leading to the distinction of CD45RBhigh and CD45RBlow T and B subsets. In addition, the existence of the CD45RAdim CD45ROdim labelled as transitional T cells is only found during the postnatal life. These changes may reflect the maturation of the immune system.
Adolescent↗
Clinical significance of bcl-2-MBR gene rearrangement and protein expression in diffuse large-cell non-Hodgkin's lymphoma: an analysis of 83 cases.
PURPOSE: The goal of this study was to assess the prognostic significance of a rearrangement of the major breakpoint region of the bcl-2 gene and/or expression of bcl-2 protein in diffuse large-cell lymphomas of B-cell origin. PATIENTS AND METHODS: All 83 patients diagnosed at the Cross Cancer Institute between 1987 and 1992 with malignant lymphoma (ML), diffuse large-cell ML non-cleaved-cell ML or cleaved-cell ML, or with diffuse large-cell immunoblastic ML were studied. bcl-2 rearrangement was identified by a polymerase chain reaction technique. This technique detects the approximately 60% of rearrangements involving the major breakpoint region bcl-2 gene (bcl-2-MBR). bcl-2 protein expression was studied by immunohistochemistry. RESULTS: More than 66% of the cases expressed bcl-2 protein, whereas 18% had a detectable bcl-2-MBR gene rearrangement. Overall, cases with bcl-2-MBR rearrangement had shorter disease-free periods. Cases with nodal and extranodal presentation had a similar frequencies of bcl-2-MBR rearrangement; however, the disease-free period of patients with extranodal presentation and bcl-2-MBR rearrangement was significantly shorter than that of those without rearrangement. CONCLUSION: bcl-2 protein is frequently expressed in diffuse large-cell lymphomas, but does not influence prognosis. The bcl-2-MBR gene rearrangement may possibly be associated with a shorter disease-free period, particularly in the specific setting of a lymphoma with extranodal presentation.
Adolescent↗
Absence of HLA class I expression by Reed-Sternberg cells.
The reactive cell population in Hodgkin's disease consists of predominantly CD4+ helper T cells and lacks CD8+ cytotoxic T cells and natural killer cells. This lack of a CD8+ response is surprising in view of the expression of the latent Epstein-Barr viral protein LMP by Reed-Sternberg cells in many cases of Hodgkin's disease, Deficient HLA class I expression would be one possible mechanism to avoid a CD8+ cytotoxic immune response. To test this possibility we studied the expression of HLA class I and II determinants on Reed-Sternberg cells in tissue sections and cell suspensions of Hodgkin's disease. Frozen tissue sections of 40 cases and cytocentrifuge preparations from cell suspensions of 10 lymph nodes involved by Hodgkin's disease were studied with monoclonal antibodies reactive with HLA determinants. As a control frozen tissue sections of two cases of infectious mononucleosis were studied. Careful examination of the tissue sections and subsequently of cytospins of cell suspensions showed that the Reed-Sternberg cells frequently lacked HLA class I but showed strong staining for HLA class II. Absence of HLA class I expression on Reed-Sternberg cells and their variants provides an explanation for the lack of a CD8+ cytotoxic immune response against antigens expressed on Reed-Sternberg cells.
Epitopes↗