Lessons learned from three violence prevention projects.
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Adolescent↗
Biomedical subjects
L Visser
Publications and source records attributed to L Visser.
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↗
In vitro system for evaluation of the immunomodulatory capacity of CD45(R) reagents.
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Antibodies↗
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↗
Patterns of leucocyte common antigen expression in peripheral blood T cell populations.
The restricted forms of CD45 are differentially expressed on lymphocyte subsets in different maturation stages and with different functional activities. The best-known examples are the expression of CD45RA on naive and CD45RO on memory T cells. Multicolor flow cytometry allows for the analysis of lymphocyte subsets with respect to the expression of the various CD45R isoforms (RA, RB, RO). Here we report on the distribution of these isoforms in normal peripheral blood T cells, including the CD4, CD8, and CD56 subsets. The results indicate the presence of a number of consistent patterns within these subsets, which can be linked to populations with well-defined functional activities, and also identify several transitional stages and hitherto undefined subsets.
Antigens, CD↗
Characterization of the alkaline phosphatase expressed on the surface of a Hodgkin's lymphoma cell line.
Alkaline phosphatase solubilized from a human Hodgkin's lymphoma cell line (L428) was compared with purified amphiphilic and hydrophilic forms of the enzyme from human liver, and with the enzyme solubilized from a cultured osteosarcoma cell line (Saos-2). Purified hydrophilic alkaline phosphatases from human placenta and intestine were also compared in some experiments. Alkaline phosphatase was released from the plasma membrane of intact lymphocytes by phosphatidylinositol phospholipase C and thus is anchored to the outside of the plasma membrane by covalently attached phosphatidylinositol. Enzyme released in this way was hydrophilic and that solubilized with Triton X-100 was amphiphilic, as assessed by adsorption to octyl-Sepharose. Lymphocyte alkaline phosphatase, when released from the membrane by phosphatidylinositol phospholipase C or solubilized by Triton X-100, had apparent M(r) values on gradient gel electrophoresis of 227 and 494 kDa, respectively. These values were consistently higher than equivalent ones obtained with enzymes purified from human liver, but were similar to those of cultured osteosarcoma cells. Isoenzyme-specific inhibitors of alkaline phosphatase showed similar patterns of inhibition between the enzyme from L428 cells and the tissue-nonspecific (liver/kidney/bone) isoenzyme from human liver. Heat stabilities were similar for the enzymes from L428 and Saos-2 (bone isoform) cell lines, but differed significantly from those of liver, intestine and placenta. We conclude that the alkaline phosphatase expressed in this lymphoma cell line (L428) has properties that most closely resemble those of the tissue-nonspecific isoenzyme found normally in osteoblasts of bone (bone isoform).
Alkaline Phosphatase↗
Spontaneous hybridoma formation induced by immunization with Haemophilus paragallinarum: evidence for a lipopolysaccharide fusion inducer.
The phenomenon of spontaneous fusion between myeloma cells and splenocytes from mice immunized with formalin-inactivated Haemophilus paragallinarum cells, has been reported on recently (1). The identity and properties of the bacterial inducer of fusogenicity of splenocytes have been further investigated with the aid of a monoclonal antibody VF3 against H. paragallinarum (2), which has a bacterial strain specificity correlating with the ability of the strains to induce spontaneous fusion between splenocytes of immunized mice and myeloma cells. It was shown that the lipopolysaccharide fraction of the bacteria was required for the induction of fusogenicity. LPS involvement was clearly indicated by the parallel effects on VF3 antigenicity and fusogenic inductivity of various treatments such as proteolytic digestion, periodate oxidation and sensitivity towards alkali, acid or freezing.
Animals↗
Biology of Hodgkin's disease.
The biology of Hodgkin's disease is one of the most intriguing subjects in lymphoma research. The presence of only a small proportion of neoplastic cells and a vast majority of reactive cells reflects the presence of complex interactions between these cell types. In this paper we discuss findings indicating that Reed-Sternberg cells may be virally transformed cells that have evaded a cytotoxic immune response and induce an ineffective delayed type hypersensitivity reaction.
Cell Transformation, Viral↗
Neoplastic changes involving follicles: morphological, immunophenotypic and genetic diversity of lymphoproliferations derived from germinal center and mantle zone.
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Antigens, CD↗
Reactivity of monoclonal antibody B-ly7 with a subset of activated T cells and T-cell lymphomas.
Antibody B-ly7 is reactive with hairy cell leukemia and a small subpopulation of normal lymphocytes. The B-ly7 antigen can also be induced on normal peripheral blood lymphocytes by phorbol ester stimulation. Recently it has been found that the reactivity pattern of B-ly7 is similar to that of HML-1, an antibody reactive with mucosal T lymphocytes and so called enteropathy associated T-cell lymphomas. Reactivity of B-ly7 with 6/61 peripheral T-cell lymphomas, including two intestinal and four extraintestinal cases, is described. The intestinal cases were CD8 and CD7 positive, whereas the extraintestinal cases were CD4 positive and CD7 negative. Activation of purified peripheral blood T cells resulted in approximately 20% B-ly7+ T cells at Day 3. Approximately 75% of the B-ly7+ cells were CD8+, whereas the remainder were CD4+. The results indicate that B-ly7 as well as HML-1 recognize an activation-associated antigen that is expressed on small normal T-cell and B-cell populations and can be induced on a relatively high proportion of T and B cells in vitro.
Adult↗
Antibody MT3 is reactive with a novel exon B-associated 190-kDa sialic acid-dependent epitope of the leukocyte common antigen complex.
MT3 is a new antibody reactive with a restricted isoform of the leukocyte common Ag (CD45) family. The Ag is mainly expressed on T lymphocytes and thymocytes. It is differentially expressed on B cell subpopulations, with no staining of the majority of small follicular mantle zone B cells but positive staining of the majority of marginal zone B cells of spleen. Like most CD45 antibodies, reactivity can be demonstrated in fresh frozen as well as in formalin-fixed, paraffin-embedded tissues. This reactivity clearly differs from all other published anti-CD45 antibodies. In immunoprecipitation and Western blot procedures, the antibody reacts with a major band with a molecular mass of 190 kDa and weak bands with molecular masses of 205 and 220 kDa. Compared to antibody PD7 that reacts with exon B-encoded sequences, the reactivity with the 205 and 220 bands is much weaker. This is reflected in MT3 reactivity with leukocyte common Ag transfectants that include exon B-encoded sequences, such as AB and B, but not with those that also include C-encoded sequences, such as ABC or BC. It can be concluded that MT3 recognizes additional heterogeneity in the leukocyte common Ag complex, that is based on the differential expression of sialic acid-dependent determinants associated with exon B-encoded sequences.
Antibodies, Monoclonal↗
Vaginal delivery after previous cesarean section in a rural West African hospital.
Two hundred twenty women with prior cesarean section were delivered at our institution between January 1987 and February 1990. Vaginal delivery was achieved in 111 (66%) of 169 patients given a trial of labor (TOL). Success of TOL correlated positively with the number of prior vaginal deliveries (P less than 0.05) and inversely with the number of prior cesarean sections (P less than 0.005). Maternal and fetal outcome were not significantly different between the TOL and non-TOL groups.
Female↗