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Biomedical subjects

E Wiener

Publications and source records attributed to E Wiener.

At least 19 recordsLinked to original sources
PubMed1992

Mononuclear phagocyte assays, autoanalyzer quantitation and IgG subclasses of maternal anti-RhD in the prediction of the severity of haemolytic disease in the fetus before 32 weeks gestation.

In 40 cases of haemolytic disease of the fetus due to RhD immunization where the fetus required intrauterine transfusion, fetal packed cell volume was compared with the following parameters of maternal anti-D: (a) concentration, (b) IgG subclass, (c) activity in a macrophage binding assay, and (d) activity in a monocyte antibody-dependent cell mediated cytotoxicity (ADCC) assay. The anti-D concentration exceeded 4 iu/ml in all cases, correctly indicating the risk of haemolytic disease. A relationship between IgG subclass composition of the anti-D and severity of anaemia was not observed; IgG1, IgG3 and IgG1 + 3 antibodies were all detected. The ADCC assay gave the best correlation between assay results and fetal packed cell volume; high results correctly indicated fetal anaemia in 95% of cases. Macrophage binding assay results were only considered as high in 70% of cases. Overall, these results indicate that serological tests and bioassays in highly immunized mothers may not generate any information that proves more useful than ultrasonography and their previous obstetric history.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1992

In vitro effects of ethanol on the phagocytic and microbial killing activities of normal human monocytes and monocyte-derived macrophages.

Human blood monocytes were cultured within the wells of chamber slides in growth medium to which 0, 1, 2, or 3 mg ethanol per ml was added at the start of the culture. After incubation for 1 h, 1 day and 7 days, their ability to phagocytoze IgG-sensitized red cells and to phagocytoze and kill non-opsonized Candida albicans was assessed. In all alcohol-containing wells, the concentration of alcohol in the growth medium fell progressively, reaching negligible values after 3 days. When compared with control cells, monocytes incubated with 1, 2 or 3 mg ethanol/mg for 1 h showed impaired phagocytosis of IgG-sensitized RBC and non-opsonized C. albicans and those incubated with 1 or 2 mg ethanol/ml for 1 h showed impaired killing of Candida. After incubation for 7 days, the monocyte-derived macrophages in wells initially containing 1, 2 or 3 mg ethanol/ml showed increased phagocytic activity towards C. albicans but not towards sensitized RBC. In addition, in 4 of 5 experiments, the percentage of phagocytozed organisms killed was increased in wells initially containing 1 mg ethanol/ml. The results support the view that the susceptibility of chronic alcoholics to certain infections may be partly dependent on an ethanol-induced depression of the phagocytic and killing functions of macrophages. They also suggest that a few days after a brief period of exposure to ethanol there may be stimulation of certain but not all effector functions of macrophages.

Candida albicans↗
PubMed1991

Modulation of the B cell response to T-independent antigens by prostaglandins: evidence for effector system cross-talk.

The extracellular environment is a major factor in determining the responsiveness of a cell to particular stimuli. For example, E series prostaglandins suppress B cell responses to T-independent antigens, mitogen stimulation of DNA synthesis and proliferation, and the primary immune response. We investigated the effects of prostaglandins on the intracellular signals generated by receptor-coupled effector systems in B lymphocytes. Pretreating splenocytes from athymic nude mice with forskolin, PGE1, or PGE2 decreased the magnitude of anti-IgM-induced changes in cytosolic free [Ca2+]. Addition of 8-Br-cAMP, forskolin, PGE1, or PGE2 following stimulation with anti-IgM resulted in a decrease in the intracellular calcium signal measured by fluorescence-activated cell sorting using Indo-1 as a Ca2+ indicator. This decrease was not a result of an inhibition of influx across the plasma membrane. Thus activation of adenylate cyclase by prostaglandins modifies the generation of signals by phosphoinositidase C. This effector system cross-talk between adenylate cyclase and phosphoinositidase C is consistent with and may account for the inhibitory effects of prostaglandins in B cell responses.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1991

Obstructing endobronchial fibrous histiocytoma: potential for lung salvage.

In the past 10 years two children, ages 3 1/2 and 7 years, have been seen with central endobronchial fibrous histiocytoma causing complete atelectasis. Each child had a 4- to 6-month history of cough, dyspnea and fever. After antibiotic failure, x-rays demonstrated complete unilateral lung collapse. Bronchoscopy in case 1 demonstrated total occlusion of the left mainstem bronchus with 80% stenosis of the right. Left pneumonectomy was ultimately performed with removal of tumor frm the right bronchus. Ten years later the patient is well. Case 2 had an extrinsic etiology ruled out by computed tomography scan. Ventilation/perfusion scan showed no ventilation and only faint perfusion of the involved lung. Pulmonary function testing showed moderate to severe restrictive changes with air trapping. Total obliteration of the left mainstem with tumor projecting into the carina was observed on bronchoscopy. Endoscopic resection was not felt to be safe. Thoracotomy showed a totally atelectatic, edematous lung filled with pus. The left main bronchus was opened, the tumor removed, and the distal bronchus lavaged and selectively ventilated. Partial lung expansion was obtained. The child is well 1 1/2 years later with a normal chest radiograph, pulmonary function tests, and bronchoscopy. Fibrous histiocytomas of the lung, if in a central endobronchial location, can cause complete lung collapse. A combination of tumor resection, lavage, and selective ventilation should be attempted as an alternative to pneumonectomy, even if the lung appears to be nonsalvageable.

Biopsy↗
PubMed1991

Natural autoantibodies may play a role in ineffective erythropoiesis during megaloblastic haemopoiesis.

Marrow aspirates from 11 patients with megaloblastic haemopoiesis and from 14 healthy individuals with normoblastic haemopoiesis were studied for antibodies associated with polychromatic/orthochromatic erythroblasts, using an 125I-labelled anti-human immunoglobulin reagent and autoradiography. In addition, the expression on these cells of receptors for FcIgG (FcR) and of the type I receptor for fragments of the third complement component (CR1) were investigated with receptor-specific monoclonal antibodies, 125I-labelled anti-mouse immunoglobulin and autoradiography. The percentages of immunoglobulin-positive erythroblasts were significantly greater in the megaloblastic than in the normoblastic marrows. Abnormally high percentages of labelled erythroblasts were present in patients without any manifestations of an autoimmune disorder. The percentage of labelled erythroblasts in the marrows of the patients correlated well with the degree of anaemia. FcR were absent on the majority of megaloblasts or normoblasts while the expression of CR1 was similar in both types of cell. The difference between the percentage labelling of megaloblasts and normoblasts was therefore unlikely to be due to greater binding of immune complexes with or without associated complement to megaloblasts than normoblasts. The megaloblast-bound immunoglobulin is, therefore, likely to have recognized abnormally expressed epitopes on the surface of megaloblasts. The results suggest that natural autoantibodies play a role in the destruction of erythroblasts during megaloblastic haemopoiesis.

Antibodies, Monoclonal↗
PubMed1990

Partial cystectomy in the management of rhabdomyosarcoma of the bladder: a report from the Intergroup Rhabdomyosarcoma Study.

Among 154 children with primary vesical rhabdomyosarcoma entered in the IRS (1972 to 1986), tumor excision constituting a partial cystectomy was performed in 33. These procedures were performed in the following situations (1) as an initial operation for localized disease (22); (2) as a secondary procedure for localized disease following chemotherapy (CT) or CT/irradiation response (6); and (3) as an initial operation in the presence of disseminated abdominal disease (5). Partial cystectomy included full-thickness resection of 15% to 80% of the bladder wall. Ureters were reimplanted or revised in two patients. The 33 patients undergoing partial cystectomy were in the following clinical groups: I, total excision (10); II, gross excision with "microscopic residual" or positive nodes (8); III, subtotal excision (10); and IV, tumor dissemination (5). Patients in clinical groups I and II received vincristine and actinomycin-D (VA) or VA + cyclophosphamide (VAC) +/- adriamycin (ADR). Patients in groups III and IV received the same agents +/- cisplatin. Irradiation (2,000 to 5,000 cGy) was administered to 18 patients (55%) in groups II to IV. Six relapses occurred among 28 patients with localized disease, and one among five patients with dissemination; all resulting in progressive disease and/or death. Estimated 3-year survival following partial cystectomy (79%) is similar to that for all patients with primary bladder tumors (78%). In contrast with the total group, in which the majority of survivors have eventually required total cystectomy; 25 of 26 survivors of partial cystectomy have functional bladders from 146 to 686 weeks (median, 356 weeks) from study entry.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Natural serum antibodies which bind to damaged erythroblasts: isotypes and light-chain composition.

Dimethyl-sulphoxide-induced Friend leukaemia erythroblasts (IFLE) which had been damaged by treatment with inhibitors of protein synthesis (cycloheximide, puromycin) were incubated with normal mouse serum or with doubling dilutions of it. The erythroblasts were subsequently tested for their binding of natural antibodies of all the major immunoglobulin (Ig) isotypes and both light-chain types, using Fc- and light-chain-specific FITC-immunoconjugates, and flow cytometry. After short-term (4-h) exposure of IFLE to puromycin, some binding of IgG but not of IgM or IgA could be demonstrated. By contrast, prolonged (17-h) exposure of IFLE to cycloheximide or puromycin resulted in their reaction with antibodies of all major isotypes (IgM, IgG1, IgG2a, IgG2b, IgG3, IgA) containing kappa-light chains. Under these conditions of damage the percentage of IgM- or IgG-binding IFLE significantly exceeded that of IgA-reactive cells. Moreover, the percentage of damaged IFLE which bound IgG2a or IgG3 was greater than that of cells which bound IgG1 or IgG2b. The percentage of damaged IFLE which bound a certain Ig-isotype did not correlate with the concentration of that Ig-isotype in normal mouse serum. The results suggest that natural antibodies of all major isotypes containing kappa-light chains bind specifically to severely damaged IFLE and could facilitate their interaction with macrophages in a concerted manner.

Animals↗
PubMed1989

Activation of protein kinase C modulates the adenylate cyclase effector system of B-lymphocytes.

Antibodies to surface immunoglobulins activate inositol phospholipid hydrolysis in B-lymphocytes, but very little is known concerning their effects on cAMP levels. In other cells, products from the hydrolysis of phosphatidylinositol 4,5-bisphosphate can increase and/or potentiate cAMP accumulation. In this study we have examined whether goat anti-mouse IgM (mu-chain-specific) stimulates and/or potentiates increases in the cAMP levels of splenocytes from athymic nude mice. Goat anti-mouse IgM, by itself, stimulated a 60% increase in cAMP within 2 min. Pretreating the cell suspensions at 37 degrees C with anti-IgM produced opposite effects on the forskolin- and prostaglandin E1 (PGE1)-induced increase in cAMP. Anti-IgM (25 micrograms/ml) potentiated the rise in cAMP induced by 100 microM forskolin 76%, but it decreased the response to 50 nM PGE1 by 30%. Direct activation of protein kinase C (Ca2+/phospholipid-dependent enzyme) by 12-O-tetradecanoylphorbol 13-acetate and/or sn-1,2-dioctanoylglycerol resulted in a similar pattern of responses. A 3-min preincubation with 97 nM 12-O-tetradecanoylphorbol 13-acetate potentiated the forskolin-induced response from 1.7 +/- 0.1 to 4.3 +/- 0.6 pmol of cAMP/10(6) cells but reduced the PGE1 response from 0.98 +/- 0.06 to 0.51 +/- 0.03 pmol of cAMP/10(6) cells. Similarly, preincubating the cells for 3 min with 5 microM sn-1,2-dioctanoylglycerol increased the forskolin response from 1.7 +/- 0.1 to 5.1 +/- 0.2 pmol of cAMP/10(6) cells but reduced the response to PGE1 from 1.15 +/- 0.03 to 0.75 +/- 0.04 pmol of cAMP/10(6) cells. Thus, activation of protein kinase C by hydrolysis products of inositol phospholipids, 12-O-tetradecanoylphorbol 13-acetate, or exogenous diacylglycerols modified adenylate cyclase itself and sites upstream of adenylate cyclase such as the receptor or G proteins coupling the receptor to the cyclase. Furthermore, modification of the PGE1 response by anti-IgM provides a mechanism by which antigen can differentially regulate T- and B-cells responding to macrophage-produced prostaglandins during an immune response.

Adenylyl Cyclases↗
PubMed1989

Human monoclonal anti-D antibodies. II. The relationship between IgG subclass, Gm allotype and Fc mediated function.

Eight monoclonal antibodies (mabs) to the Rh antigen D produced by Epstein-Barr virus transformed B-lymphoblastoid cell lines from two individuals have been compared for their behaviour in in vitro cell-mediated assays. Three IgG1 Glm(1,17) and two IgG3 G3m(21) mabs from one donor and three IgG1 Glm(3) mabs from another were used. IgG3 anti-D mabs induced greater adherence and phagocytosis of sensitized red cells by U937 monocytes than IgG1 anti-D mabs or the polyclonal anti-D. Minimum sensitization levels for rosetting and phagocytosis by U937 monocytes were 2,000 molecules IgG/cell for IgG3 and 5,000 molecules/cell for IgG1 mabs; maximum rosetting mediated by both IgG1 and IgG3 mabs was obtained at 15,000-20,000 molecules/cell. The IgG3 anti-D mabs were comparable to polyclonal anti-D in mediating binding of sensitized red cells to gamma-interferon stimulated monocyte-derived cultured macrophages and were markedly more effective than the IgG1 anti-D mabs. However, in lymphocyte ADCC assays, only anti-D mabs which were IgG1 Glm(3) were effective in mediating high levels of lysis of sensitized red cells, unlike the IgG1 Glm (1,17) or IgG3 G3m(21) mabs. Minimum sensitization levels required for this lymphocyte-mediated red cell lysis were found to be approximately 5,000 molecules/cell with one IgG1 Glm(3) mab; maximum lysis with this mab was obtained at 10,000 molecules/cell. Polyclonal anti-D containing both IgG1 and IgG3 was effective in all three assays. These observations suggest that different isotypes and allotypes of anti-D antibodies mediate red cell removed or destruction by monocyte or lymphocyte effector cell through functionally dissimilar Fc receptor interactions.

Antibodies, Monoclonal↗
PubMed1988

Differences between the activities of human monoclonal IgG1 and IgG3 anti-D antibodies of the Rh blood group system in their abilities to mediate effector functions of monocytes.

Seven IgG1 and seven IgG3 human monoclonal antibodies derived from heterohybridoma or Epstein-Barr virus-transformed lymphocytes and specific for the D antigen of the human Rh blood group system were tested for their ability to bring about red cell attachment to and phagocytosis by monocytes. The antibodies produced by the heterohybridomas were also investigated for their potency to mediate antibody-dependent cellular cytotoxicity (ADCC) by monocytes. When red cells were sensitized with any of the IgG1 anti-D antibodies, most of them were ingested by the phagocytes. By contrast, many of the red cells coated with any of the IgG3 antibodies remained attached to the monocyte surface while only few underwent phagocytosis. Some of the attached red cells remained on the phagocyte exterior for a considerable length of time. The ADCC activities of the IgG3 anti-D antibodies was greater than that of the IgG1 anti-D antibodies. The results mean that in vitro IgG1 anti-D mediates red cell destruction mainly by phagocytosis, while IgG3 anti-D causes their destruction predominantly by prolonged cytolysis. These differences between the effector functions of human monoclonal IgG1 and IgG3 anti-D antibodies might have important implications for their use in the prophylaxis of haemolytic disease of the new-born.

Antibodies, Monoclonal↗
PubMed1987

Initiation of DNA synthesis in murine B cells is independent of early changes in the cytosolic free calcium.

The relationship between changes in the intracellular free Ca2+ concentration, [Ca2+]i, and the initiation of proliferation of murine B cells after the addition of mitogens and activators was studied. The effects of lipopolysaccharide (LPS), 12-O-tetradecanoyl phorbol-13-acetate (TPA), rabbit IgG antimouse Fab (IgG RAM Fab), and its F(ab')2 fragment (F(ab')2 anti-Fab) on the [Ca2+]i were measured using the fluorescent calcium indicator Fura-2. In parallel experiments, DNA and/or RNA synthesis were measured by assaying [3H]thymidine and/or [3H]uridine uptake. LPS stimulated a 20-120 X increase in the [3H]thymidine uptake, and a 3-7 X increase in [3H]uridine uptake without inducing any change in the [Ca2+]i. TPA induced a marginal increase in [3H]thymidine and [3H]uridine uptake, without effecting any change in the [Ca2+]i. In contrast, low doses of IgG RAM Fab produced a triphasic change in the [Ca2+]i, but had no effect on the [3H]thymidine or [3H]uridine uptake, even at much higher concentrations. Similarly, low doses of the F(ab')2 fragment induced sizable increases in the [Ca2+]i without affecting the [3H]nucleoside uptake. However, higher concentrations of F(ab')2 anti Fab increased the [3H]thymidine uptake and [3H]uridine uptake, while also increasing the [Ca2+]i. Significantly, pretreating the cells with TPA for 3 min virtually abolished the [Ca2+]i increase induced by IgG RAM Fab while simultaneously potentiating an increase in the IgG RAM Fab-induced [3H]thymidine uptake 85-fold. In the presence of TPA, IgG RAM Fab also induced a 2- to 30-fold increase in [3H]uridine uptake. Similarly, TPA virtually abolished the [Ca2+]i increase induced by the F(ab')2 anti-Fab fragment, yet it stimulated a F(ab')2 anti-Fab-induced uptake of [3H]thymidine and [3H]uridine by 120 and 10 times, respectively.

Animals↗
PubMed1987

Heterogeneity of IgG1 monoclonal anti-Rh(D): an investigation using ADCC and macrophage binding assays.

Three monoclonal IgG1 anti-Rh(D), UCH D4, ARC 7D5 and UKTS FC3, produced by Epstein-Barr virus transformed cells from Rh(D)-sensitized individuals, were compared with polyclonal single donor anti-D sera and therapeutic immunoglobulin preparations in antibody dependent cellular cytotoxicity (ADCC) and macrophage binding tests. When assayed at equal anti-D concentrations monoclonal antibodies varied considerably in their ADCC and macrophage binding activities: only UKTS FC3 showed significant activity in both assays, but these were substantially lower than those of the polyclonal anti-D sera and immunoglobulins. When examined in different combinations the monoclonal antibodies showed little synergism in mediating red cell destruction by the effector cells. Factors which might contribute to the diverse ADCC and macrophage binding activities of the monoclonal anti-Ds of the same IgG subclass are discussed.

Antibodies, Monoclonal↗
PubMed1987

The use of macrophages stimulated by immune interferon as indicator cells in the mononuclear phagocyte assay.

Macrophages obtained from human monocytes by monolayer culture were stimulated with recombinant immune interferon. They were compared with unstimulated macrophages and monocytes as indicator cells in the mononuclear phagocyte assay, using both IgG anti-Rh(D)-coated complement-coated red cells. The presence of the interferon in the culture medium improved the adherence of macrophages in monolayers. The interferon markedly augmented the number of IgG-coated red cells which became attached to the macrophages and reduced the amount of antibody needed for red cell-macrophage interaction. This stimulatory effect occurred regardless of the IgG subclass composition of the anti-Rh(D) antibody. The activity of the stimulated macrophages to interact with IgG- or complement-coated red cells was considerably greater than that of monocytes. The results imply that macrophages treated with recombinant immune interferon are more sensitive than monocytes as indicator cells in the mononuclear phagocyte assay.

Cell Adhesion↗
PubMed1987

Differences between the activities of human monoclonal IgG1 and IgG3 subclasses of anti-D(Rh) antibody in their ability to mediate red cell-binding to macrophages.

Four IgG1 and three IgG3 human monoclonal antibodies specific for the blood group D(Rh) antigen were tested for their ability to mediate red cell-binding to macrophages in vitro. The IgG3 monoclonals were found to opsonize at a density of approximately 100 molecules per red cell, whereas the IgG1 antibodies were only active at a level of 10,000 molecules per cell. There was no substantial difference between the two IgG subclasses in their ability to bind to Fc receptors on macrophages and it is suggested that the more potent opsonic activity of IgG3 is the result of the relatively long hinge, leading to greater accessibility to the Fc receptor binding site on the Fc piece.

Antibodies, Monoclonal↗
PubMed1987

Biochemically damaged erythroblasts bind natural serum antibodies and activate complement.

Friend leukaemia erythroblasts which had been damaged biochemically by treatment with inhibitors of cellular metabolism (sodium fluoride, sodium azide) or of protein synthesis (cycloheximide, puromycin) were incubated with heat-inactivated or fresh mouse serum and tested for surface-bound IgG and C3c, respectively, by reaction with FITC-immunoconjugates followed by flow-cytofluorometry. Erythroblasts exposed to sodium azide, cycloheximide or puromycin showed specific binding of IgG; the extent of binding was related to the concentration of the drugs and duration of treatment. Moreover, prolonged exposure of the cells to the inhibitors of protein synthesis lead to a dose-dependent activation of complement. The results suggest that the opsonization of biochemically-damaged Friend leukaemia erythroblasts with IgG and C3 may facilitate their interaction with macrophages.

Antibodies, Anti-Idiotypic↗