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Biomedical subjects

R O'Connor

Publications and source records attributed to R O'Connor.

At least 91 records · Page 5Linked to original sources
PubMed1990

Human monoclonal antibody against a tissue polypeptide antigen-related protein from a patient with a signet-ring cell carcinoma of the stomach.

For a comparative study of the humoral immunity of patients with gastric signet-ring cell carcinoma, lymphocytes from spleen and lymph nodes were fused with the heteromyeloma SPM4-0. Immunoglobulin-producing clones were primarily tested in binding assays on autologous and allogeneic tumor cells and tissues. One of the resulting human monoclonal antibodies, designated 56/16 (IgM, lambda), was found to be suitable for a detailed biochemical characterization. Immunoblotting and comparative two-dimensional gel electrophoresis on cell and tissue extracts as well as on preparations of the cytoskeleton revealed that the main epitope is not an integral membrane molecule but a degradation product of cytokeratin 8, which is a main component of the tumor marker, tissue polypeptide antigen. The Mr 38,000/45,000 antigen could be identified in tumor and normal tissues, with highest expression in secretory cells and organs. Thus, the human monoclonal antibody 56/16 might represent an immune response in the patient against breakdown products of cytokeratin 8, which are released from the tumor cells during cell division, secretion, or cell death. A possible association of the antibody with the secretory activity of signet-ring carcinoma cells is discussed.

Adenocarcinoma, Mucinous↗
PubMed1990

Synergistic and antagonistic effects of IL-1 alpha and IL-4, respectively, on the IL-2-dependent growth of a T cell receptor-gamma delta+ human T leukemia cell line.

The TALL-103/2 cell line was derived from an immature acute T lymphocytic leukemia with T-myeloid differentiating capacity. The leukemic cells were first expanded in recombinant human IL-3 in which they acquired a myeloid phenotype, and subsequently were adapted to grow in human rIL-2 in which they became lymphoid committed. The TALL-103/2 cell line expresses only T cell-specific differentiation Ag (CD2, CD3, CD7, and CD8) but has retained the CD33 myeloid Ag originally present on the IL-3 expanded population. By using mAb directed at the TCR-alpha beta or specific for framework determinants on human TCR-gamma and -delta chains, the TALL-103/2 cells were shown to be WT31-, TCR delta 1+, TCS-1+, and Ti gamma A-, thus representing a T cell subset expressing the nondisulfide-linked form of the TCR-gamma delta. The TALL-103/2 cells have been maintained for more than 1 y in the presence of human rIL-2 on which they are strictly dependent. Chemical cross-linking and immunofluorescence studies indicate the presence of both high and intermediate affinity IL-2R on the TALL-103/2 cells. Whereas mAb antiTac and H-31 with reactivity to the IL-2R alpha-chain (p55) compete only partially for the IL-2-induced proliferation of these cells, mAb TU27, specific to the IL-2R beta-subunit (p75), inhibits such growth completely even at high concentrations of IL-2. The interactions of the two T cell-stimulating factors IL-1 and IL-4 on the IL-2-dependent growth of TALL-103/2 cells were investigated. IL-1 alpha synergizes with IL-2 in supporting the short and long term growth of this cell line, whereas IL-4 abrogates its growth. These effects are, at least in part, due to the modulation of IL-2R expression induced by the two lymphokines. Functionally, the TALL-103/2 cells display MHC-nonrestricted cytotoxic activity that is significantly enhanced by addition of either IL-4, IL-6, or IFN-gamma. Because of its properties and its stable requirement for IL-2 for continuous growth, this T lymphocytic leukemia-derived cell line represents an interesting model to analyze ontogeny and function of leukemic T cells.

Antigens, CD↗
PubMed1990

Characterization of a protein with an acetylcholine receptor epitope from myasthenia gravis-associated thymomas.

Immunohistochemical studies have shown that almost all thymomas of myasthenia gravis patients contain at least one protein sharing an antigenic determinant with the nicotinic acetylcholine receptor (AchR) of human muscle. We describe the characterization of this protein (p153) which has a molecular weight of 153 and an isoelectric point of 5.0. By treatment of p153 with endoglycosidases, no significant glycosylation has been detected. Immunologically, p153 crossreacts with monoclonal antibodies against the amino acid sequence 371-378 of the alpha-chain of the AchR. No cross-reactivity to the main immunogenic region of the AchR nor an alpha-bungarotoxin binding site are found. By Western blotting, p153 was generally neither detectable in normal tissues nor extrathymic tumors with the exception of paraganglioma and neuroblastoma. In conclusion, the structure of p153 is apparently unrelated to the AchR from muscle or the alpha-bungarotoxin binding proteins from thymoma. Since there is no evidence for an AchR expression in thymoma, the antigenic homology of p153 with the nicotinic AchR might be relevant for triggering an intrathymomatous autosensitization of maturing T cells and could be responsible for the high association of thymomas with myasthenia gravis.

Antibodies, Monoclonal↗
PubMed1989

SC-1, a functional human monoclonal antibody against autologous stomach carcinoma cells.

Human monoclonal antibodies were isolated from stomach carcinoma patients by the fusion of spleen and lymph node lymphocytes with the heteromyeloma line SPM4-0. Initial screening was carried out on autologous primary tumor cell cultures in an adhesion assay in order to select surface-reactive functional antibodies. This was followed by live cell immunoperoxidase staining assays. The human monoclonal antibody SC-1 was found to selectively react with cultured cells isolated from autologous and allogeneic stomach carcinoma patients, and with cryostat sections of the primary tumors. More extensive screening revealed that the antibody showed no reactivity with a wide range of tumor tissues and normal cells. Some reactivity was present on fetal tissues. SC-1 inhibits movement of the autologous tumor cells and identifies a protein with a molecular weight of 50,000. This study demonstrates that, with the use of selective screening assays on primary tumor material, it is possible to isolate antibodies which not only result from an immune response in the patient but also interfere with intercellular processes of tumor cells.

Antibodies, Monoclonal↗
PubMed1989

Tubal pregnancy after total vaginal hysterectomy.

We report the case of a 26-year-old woman who presented to our emergency department for evaluation of abdominal pain 24 days after a vaginal hysterectomy. The patient's serum pregnancy test was positive. An ectopic pregnancy of the right adnexa was diagnosed by ultrasound and confirmed by laparotomy. The patient recovered uneventfully. Ectopic pregnancy after a total hysterectomy can occur if the fertilized ovum is in the fallopian tube at the time of the hysterectomy or if a fistulous tract exists between the vagina and the ovaries, enabling fertilization to occur. The diagnosis of ectopic pregnancy after a total hysterectomy is unusual yet must be considered in the presence of intact ovaries to avoid a delay in treatment.

Adult↗
PubMed1989

Mucin-negative biopsy in extra-mammary Paget's disease. A diagnostic problem.

A case of extra-mammary Paget's disease with a mucin-negative small biopsy is reported. Study of a small series of vulvar Paget's disease demonstrated that areas devoid of mucin in the mm range are frequently found, creating the conditions for diagnostic problems in small biopsies. In this situation, positive immunoreactions for carcinoembryonic antigen and low molecular weight cytokeratins and a negative reaction for S-100 protein serves to differentiate Paget's disease from other pagetoid lesions.

Aged↗
PubMed1989

Proteins with epitopes of the acetylcholine receptor in epithelial cell cultures of thymomas in myasthenia gravis.

Thymomas from 12 patients with myasthenia gravis (MG) were investigated for the presence of epitopes of the alpha-subunit of the nicotinic acetylcholine receptor (AchR) using monoclonal antibodies (MAb) reacting against the AchR. In all but two of the tumors epitopes corresponding to antigenic determinants located on the cytoplasmic side of the AchR were identified. From eight thymomas cell lines were established that have been kept in culture for up to 6 months. The cultured cells expressed the same AchR-epitopes as did the primary tumors. During early passages the percentage of epithelial cells positive for the AchR epitopes approximately mirrored the percentage of positive cells in the original tumors. With passaging the relative number of positive cells usually declined but in some cultures an increase was observed. Three cell lines that showed extensive staining with an MAb against the AchR were radiolabeled to characterize the antigen. From protein extracts of these three cell lines proteins of 45 kd and 156 kd molecular weight (MW) were precipitated. These proteins are different from other proteins described in the context of both thymomas and MG. The negative reactivity with MAb against other epitopes of the alpha-subunit, especially against the main immunogenic region (MIR), speaks in favor of membrane-associated proteins of only limited crossreactivity to the AchR. A previous study found an almost exclusive occurrence of these AchR-epitopes in thymomas associated with MG, but not in other thymomas of similar histologic type. The expression of the proteins described here could therefore play a role in the triggering of the autoimmune process against the AchR of the motor, endplate in MG patients.

Adult↗
PubMed1989

Acetylcholine receptor epitope in proteins of myasthenia gravis-associated thymomas and non-thymic tissues.

Immunohistochemical studies have shown that almost all thymomas of myasthenia gravis (MG) patients contain proteins which share antigenic determinants with the nicotinic acetylcholine receptor (AChR) of human muscle. Here we describe one of the proteins (p153) which (1) is not part of a compound structure, (2) has a MW of 153 kd, (3) has an isoelectric point of 5.0, and (4) is probably free of sugar residues. The protein does not bind mAb to the main immunogenic region of the AChR and has no alpha-bungarotoxin (alpha-btx) binding site. p153 was not found in both normal tissues and a variety of tumours. However, the epitope defined by mAb155 also occurs in at least two other proteins (from muscle and TE671 cells) which have MW different from 153 kd and which are unrelated to AChR. Experiments presented elsewhere [Geuder et al., this volume] show that there are no proteins in thymomas which share an extensive molecular homology with the AChR. All these findings suggest that p153 is unrelated to the AChR. As p153 is the only protein demonstrated in thymomas which is significantly correlated with MG and which shares an antigenic determinant with AChR, p153 is a candidate protein determining the AChR-specificity of the autoimmune process in MG.

Antibodies, Monoclonal↗
PubMed1989

Identification of a leukocyte alloantigen with a high-frequency expression in leukemia patients.

In this report we describe the production and characterization of a monoclonal antibody to the human promyelocytic leukemia cell line HL-60. The antibody, NC-2, is of the IgG1 subclass and precipitates a 50-Kd protein from 125I-labeled HL-60 cells. The antigen is insensitive to treatment with trypsin, papain, or neuraminidase. NC-2 did not react with a number of established human cell lines, including Daudi, Molt-4, K562, U937, KG-1, CEM, Raji, and Gash-P. Neutrophils and monocytelike cells derived from HL-60 cells that were induced to differentiate continued to express the antigen. NC-2 reacted with all peripheral-blood cells except erythrocytes from eight (5%) of 150 normal individuals tested. Bone marrow samples from patients with myelogenous leukemias were more frequently reactive with NC-2 than were those from normal individuals (12/33 v 1/10). Family studies indicated that the antigen was inherited in an autosomal-dominant manner. These findings suggest that the expression of the above alloantigen is associated with an increased incidence of leukemia.

Animals↗
PubMed1987

Production and characterization of a monoclonal antibody to a myeloid specific differentiation antigen.

A monoclonal antibody termed NC-1 was produced which binds to an antigen present on the human promyelocytic leukemia cell line HL-60 and peripheral blood neutrophils. The antibody bound to the majority of promyelocytes in the HL-60 culture, but not to myeloblasts. No antibody reactivity was detected to a range of other cell lines or to a limited number of normal human tissues. Peripheral blood lymphocytes, monocytes, basophils, eosinophils, erythrocytes and platelets did not react with the antibody. Bone marrow smears exhibited binding of NC-1 to myeloid cells at the promyelocyte and later stages of differentiation along the granulocyte lineage. The KG-1 myeloblastoid and U937 myelomonocytic lines could be induced to express the antigen, when exposed to neuraminidase which removes terminal sialic acid from carbohydrate residues. Similarly myeloblasts in bone marrow samples bound NC-1 when they were treated with neuraminidase. HL-60 cells induced to differentiate to granulocytes by treatment with retinoic acid continued to express the antigen. A similar result was observed when HL-60 cells were induced to differentiate to monocytes, even though blood monocytes failed to bind the antibody. These data indicate that the antibody NC-1 reacts with an antigen expressed on myeloid cells beyond the promyelocyte stage of differentiation.

Antibodies, Monoclonal↗
PubMed1987

An epidemic of pseudomembranous colitis: importance of person to person spread.

Twenty three cases of pseudomembranous colitis (PMC) occurred in three hospitals in 10 months. Retrospective analysis shows that they represented a single epidemic with a readily traceable chain of person-to-person contact within and between hospitals. Most patients had severe pre-existing illness and all had broad spectrum antibiotics, including either ampicillin/amoxycillin, a broad spectrum cephalosporin (particularly cefotaxime), or both. All patients had severe diarrhoea and all responded to vancomycin, but relapse occurred in five. Ten patients eventually died, principally because of underlying disease rather than from PMC. Failure to find fibrin thrombi in blood vessels in biopsies and the scanty distribution of non-invasive bacteria supports the concept of mucosal damage by bacterial toxin, rather than by direct infection, or ischaemia. Although environmental colonisation cannot be excluded, the observed pattern of spread suggests a major role for direct person-to-person crossinfection in the spread of disease in this outbreak.

Aged↗
PubMed1986

Effectiveness of dietary manipulation in the prevention of food allergy in infants.

The desire to alter the natural incidence of atopic illness has piqued physicians' imaginations for decades. Specifically, the phenotypic expression of IgE-mediated disorders, which appears regulated by multiple genetic factors and modulated by environmental experiences (allergen exposure, infection, and smoking), has been a target for preventive medicine since the 1920s when dietary intervention was espoused in infancy. To be successful, such intervention must overcome many patient factors that in concert markedly increase the risk for development of atopic disease (Table XII). During the past 60 years, much controversy has emerged from multiple clinical studies designed to evaluate the effect of dietary and other environmental exclusions on the subsequent manifestation of atopy. One may conservatively conclude, from critical evaluation of these conflicting studies, that sole breast feeding for about 6 months combined with delayed introduction of solid foods for at least 6 months may reduce atopic dermatitis and food allergy in early infancy. A randomized, prospective study of allergy prophylaxis during infancy is mandatory to determine definitely the benefits and feasibility of such a regimen and its long-term effects on the development of atopy. From our recent findings, which demonstrate the development of atopy in infants entered in a strict prophylactic protocol, it becomes apparent that monumental obstacles confront preventive efforts to overcome the strength of the allergic constitution. In the very near future, results from our prospective study of prenatally randomized allergy prophylaxis should be available for critical scrutiny of the effectiveness and feasibility of allergy prevention during infancy.

Breast Feeding↗
PubMed1986

Bronchial asthma.

Bronchial asthma is a very common disease afflicting 2 to 3 per cent of the general population. Attacks may be mild or life-threatening. Modern guidelines for diagnosis, therapy, and prognosis are presented in this article.

Acute Disease↗