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J T Kemshead

Publications and source records attributed to J T Kemshead.

At least 127 records · Page 7Linked to original sources
PubMed1985

Altered expression of cell surface membrane antigens in a common acute lymphoblastic leukemia-associated antigen-expressing neuroblastoma cell line (SJ-N-CG) with morphological differentiation.

The expression of common acute lymphoblastic leukemia antigen (CALLA) on a human neuroblastoma cell line, SJ-N-CG, was demonstrated by indirect membrane immunofluorescence, complement-dependent cytotoxicity, and quantitative absorption, using two monoclonal antibodies (J-5 and BA-3) directed against CALLA. Immunoprecipitation of solubilized 125I-labeled membrane proteins from SJ-N-CG cells with J-5 antibody revealed a protein with a molecular weight of 100,000 as determined on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Morphological differentiation of SJ-N-CG cells could be induced in the presence of 2.0 mM dibutyryl adenosine 3'-5'-cyclic monophosphoric acid for 10 days of culture. Changes in cell surface membrane antigens associated with morphological differentiation were studied by indirect immunofluorescence and complement-dependent cytotoxicity using a panel of seven monoclonal antibodies. Increases in the antigens recognized by BA-2 (detecting leukemia-associated antigen), anti-Thy-1, and antibody 390 (Thy-1 antigen) were found in "differentiated cells," while those detected by BA-1 (B-cell-associated antigen) and J-5 (CALLA) were unchanged. In contrast, the antitransferrin receptor defined by B3/25 was inhibited, and expression of B7/21-defined la-like antigen was not induced. Kinetic studies on antigenic alterations showed that the expression of BA-2-defined antigen rose on Day 2 and remained at the same level until Day 10. The expression of CALLA was not changed from Days 2 to 10. The augmentation of Thy-1 antigen was noted on Day 4 and reached the maximum on Day 10. These results show that dibutyryl adenosine 3'-5'-cyclic monophosphoric acid is capable of inducing phenotypic changes in SJ-N-CG cells. The changes of expression of some antigens on exposure of cells to dibutyryl adenosine 3'-5'-cyclic monophosphoric acid may enable us to have a greater understanding of the differentiation of neuroblastoma to a more mature ganglioneuroblastoma phenotype.

Antibodies, Monoclonal↗
PubMed1985

Possible differential diagnosis of neuroblastoma from rhabdomyosarcoma and Ewing's sarcoma by using a panel of monoclonal antibodies.

The accurate diagnosis of malignant tumor type is essential to enable the correct therapeutic regimen to be followed and to predict a patient's prognosis. However, the differential diagnosis of "small-round-cell" tumors, represented by neuroblastoma, rhabdomyosarcoma, lymphoma/leukemia and Ewing's sarcoma, can occasionally be difficult by conventional morphological and biochemical methods. If tumor membrane markers were available, these could provide rapid and accurate diagnostic aids. In the present work, a panel of 9 monoclonal antibodies raised against hematopoietic cells (BA-1, BA-2, J-5 and B7/21), brain cells (UJ-13A, UJ-127-11 and anti-Thy-1), and neuroblastoma cells (HSAN1.2 and PI153/3) was used to analyze the membrane phenotypes of 12 neuroblastoma, 4 rhabdomyosarcoma and 3 Ewing's sarcoma cell lines and cells of 3 fresh bone marrow tumors. BA-1, UJ-127-11 and PI153/3 antibodies may be useful for the differential diagnosis of neuroblastoma from rhabdomyosarcoma and Ewing's sarcoma.

Antibodies, Monoclonal↗
PubMed1984

Use of monoclonal antibody panel to identify malignant cells in cerebrospinal fluid.

A panel of monoclonal antibodies was systematically applied to cerebrospinal fluid from 17 patients with suspected neoplastic meningitis and the results were compared with those obtained from routine cytological preparations. The antibody panel consisted of markers for neuroectodermal tissue ( UJ13A ), epithelial cytokeratin ( LE61 ), leucocytes ( 2D1 ), and neoplastic neuroblasts ( UJ181 .4). Additional antibodies were used to refine diagnosis when indicated. Cerebrospinal fluid samples from 12 patients with non-neoplastic conditions were used as controls. The use of monoclonal antibodies gave a positive diagnosis in 16/17 cases and the cells were accurately categorised as carcinoma (5/6 cases), neuroectodermal tumour (8/8 cases), and lymphoma (3/3 cases). In the 14 cases examined by routine cytology, malignant cells were reported in 10 cases and accurately categorised in only 3/14 cases. Immunocytological testing of cerebrospinal fluid with an antibody panel has greatly increased the accuracy with which malignant cells can be identified and categorised.

Aged↗
PubMed1984

Removal of neuroblastoma cells from bone marrow with monoclonal antibodies conjugated to magnetic microspheres.

Monoclonal antibodies bound to polystyrene microspheres containing magnetite have been used to remove tumour cells from bone marrow destined for autologous transplantation. The small magnetic beads can be targeted to the surface of tumour cells to render these magnetic. A flow system using permanent samarium cobalt magnets effects the rapid and efficient removal of "magnetic" tumour cells from bone marrow. The system is designed to be used with any type of tumour cell, so that by changing panels of monoclonal antibody it can be used for "cleaning" the bone marrow in many different malignancies.

Abdominal Neoplasms↗
PubMed1984

Properties of monoclonal antibodies to nicotinic acetylcholine receptor from chick muscle.

Four stable, hybrid-cell lines secreting monoclonal antibodies to distinct determinants on the nicotinic acetylcholine receptor from chick muscle have been established. These were characterised by the following criteria: immunoglobulin isotype, ability to produce experimental autoimmune myasthenia gravis in mice and reactivity towards homologous and heterologous acetylcholine receptor proteins. Two monoclonal antibodies were found to inhibit the reaction of alpha-bungarotoxin with homologous acetylcholine receptor; in addition one of these, on binding to receptor-toxin, induced a rapid dissociation of the complex (t1/2 = 0.5 h at 23 degrees C). Three of the antibody preparations recognised epitopes on this receptor from muscle of other species and two of these caused experimental autoimmune myasthenia gravis in BALB/c mice following passive transfer. The latter two recognised to significant extents the alpha-bungarotoxin binding component purified from chick optic lobe and brain cortex. Sedimentation analysis demonstrated that two of the monoclonal antibodies form a distinct size (s20, w = 12S) of complex with the receptor of chick muscle which most probably corresponds to a 1:1 attachment of antibody and receptor; this may involve cross-linking of two determinants within the same oligomer. A similar observation was made with the alpha-bungarotoxin binding component from optic lobe using one of the cross-reacting antibodies. Another monoclonal antibody was found to be capable of forming much heavier complexes with the receptor from chick muscle, these are thought to involve inter-molecular cross-linking of oligomers. The observed properties of these antibodies are discussed in relation to their myasthenogenicity and with reference to the extent of structural similarities between the peripheral nicotinic acetylcholine receptor and the alpha-bungarotoxin binding protein from brain.

Animals↗
PubMed1984

A monoclonal antibody binding to human medulloblastoma cells and to the platelet glycoprotein IIB-IIIA complex.

A monoclonal antibody, designated M148, produced by the hybridoma technique from spleen cells of mice immunized with human medulloblastoma, was found by indirect immunofluorescence to bind to normal human platelets (both PlA1 positive and PlA1 negative) and megakaryocytes, as well as to some medulloblastoma and neuroblastoma cells and cell lines and certain other solid tumours. No binding was observed to other marrow constituents, nor to any other normal tissue examined. The antibody bound to platelets from a patient with the Bernard-Soulier syndrome but not to thrombasthenic platelets. It immunoprecipitated glycoproteins IIb and IIIa from 125I-labelled normal platelet membranes, and completely inhibited ADP-induced fibrinogen binding and aggregation of platelets. Aggregation was also inhibited in response to adrenaline, collagen, thrombin, sodium arachidonate and the ionophore A23187; clot retraction was partially inhibited. The antibody was without effect on thromboxane formation or 5-hydroxytryptamine (5HT) secretion in response to thrombin, but inhibited 5HT secretion in response to arachidonate. It did not inhibit factor VIII binding or agglutination in response to ristocetin, but completely inhibited factor VIII binding in response to thrombin. These findings suggest that the epitopes are close to the fibrinogen and factor VIII binding sites on glycoproteins IIb/IIIa, and that the lack of these glycoproteins is sufficient explanation for the pattern of dysfunction observed in thrombasthenic platelets, without invoking any other membrane abnormality.

Animals↗
PubMed1984

Determination of cell surface membrane antigens common to both human neuroblastoma and leukemia-lymphoma cell lines by a panel of 38 monoclonal antibodies.

The surface membrane antigens of 7 neuroblastoma and 91 leukemia-lymphoma cell lines were studied with the use of a total of 36 murine monoclonal antibodies (MoAb) primarily developed against hematopoietic cells and 2 MoAb developed against human fetal brain. Five of the MoAb against hematopoietic cells (BA-1, BA-2, DU-ALL-1, J-5, and BA-3) consistently bound to common acute lymphoblastic leukemia cell lines, and 2 others (MCS-2 and OKM-1) reacted uniformly with acute myeloblastic-acute monoblastic leukemia cell lines. However, these 7 MoAb also reacted with 1-7 neuroblastoma cell lines. All the human neuroblastoma cell lines bound MoAb BA-2 and DU-ALL-1. Six of the 7 lines reacted with BA-1. Only 1 neuroblastoma cell line (SJ-N-CG) gave positive staining with J-5 and BA-3, and another line (SK-N-AS) bound MoAb MCS-2 and OKM-1. Anti-fetal brain MoAb (UJ-13A and UJ-127-11) were highly positive for all the neuroblastoma cell lines. By contrast, 4 of 43 leukemia-lymphoma cell lines tested bound these anti-fetal brain antibodies. Both B3/25 and OKT-9, anti-transferrin receptor antibodies, reacted with all of the hematopoietic and neuroblastoma cell lines. These results demonstrate that neuroblastoma and hematopoietic cell lines possess common antigenic determinants despite their different embryologic origins. The neuroblastoma cell lines may be classified into subgroups on the basis of phenotype profiles determined by the MoAb. MoAb may be useful in characterization and classification of neuroblastoma cells, as has already proved to be the case for cells of the hematopoietic lineages.

Antibodies, Monoclonal↗
PubMed1983

Biological characterization and clinical applications of a monoclonal antibody recognizing an antigen restricted to neuroectodermal tissues.

The monoclonal antibody UJ13A was raised following immunization of mice with human foetal brain and subsequent somatic cell hyridization of spleen cells with the mouse myeloma cell line P3-X63-AG8-653. The antibody is of the IgG1 subclass and has been shown by indirect immunofluorescence studies on normal foetal, paediatric and adult tissues to selectively bind to most tissues of neuroectodermal origin. Many tumours of neural origin also express the UJ13A antigen and the reagent can be used to distinguish primary intracranial neural tumours from secondary carcinomas and lymphomas. UJ13A is also useful as one of a panel of reagents employed for the identification of metastatic spread of neuroblastoma cells to bone marrow and cerebrospinal fluid. Knowledge of the full spectrum of normal and malignant tissues binding UJ13A suggests that the antibody may have a role in the radioimmunolocalization of neuronal tumours such as neuroblastoma.

Animals↗
PubMed1983

Monoclonal antibody UJ 127:11 detects a 220,000-240,000 kdal. glycoprotein present on a sub-set of neuroectodermally derived cells.

The monoclonal antibody UJ 127-11 was raised following immunization of mice with human foetal brain and subsequent somatic cell hybridization of spleen cells with the mouse myeloma cell line P3-X63-Ag8-653. Studies on normal foetal and adult tissues show that, by indirect immunofluorescence, the antigen recognized by UJ 127:11 is restricted in its expression to cells of neural rather than glial origin. Neural tumours such as neuroblastoma, medulloblastoma and ganglioglioma (neural component) bind the monoclonal antibody whereas malignancies originating from glial cells do not bind UJ 127:11. Biochemically the monoclonal antibody has been shown to bind to a glycoprotein of 220,000-240,000 mol. wt. under reducing and non-reducing conditions. Despite similarities in the molecular weight between human fibronectin and the antigen recognized by UJ 127:11, they have different serological and biochemical characteristics, suggesting that the monoclonal antibody is not binding to either cell or plasma fibronectin.

Animals↗
PubMed1983

Use of panels of monoclonal antibodies in the differential diagnosis of neuroblastoma and lymphoblastic disorders.

Panels of monoclonal antibodies offer a rapid and accurate adjunct to conventional techniques in the diagnosis of neuroblastoma, leukaemia, and lymphoblastic lymphoma. Heterogeneity of antigen expression is observed within a tumour type, and therefore a panel of reagents should be used for each malignancy investigated. Eight monoclonal antibodies which bind to neuroblastoma but not to normal bone marrow and five which bind to leukaemic and lymphoma cells but not to neuroblastoma have been selected for indirect-immunofluorescence testing of bone-marrow aspirates, frozen sections of tumours, and cells from malignant effusions. With this technique a confident diagnosis can be made within 2 h. Profiles of antibodies binding to tumour cells have been used to establish a definitive diagnosis in cases where conventional techniques have proved inadequate.

Adrenal Gland Neoplasms↗
PubMed1983

Identification of cell-surface antigens present exclusively on a sub-population of astrocytes in human foetal brain cultures.

We have examined two monoclonal antibodies (McAbs; coded MI/N1 and 308) raised to human neuroblastoma cells for cell-type-specific reactivity in cultures of human neural tissues and in frozen sections of intact primate spinal cord. In dual-label immunofluorescence assays using established cell-type antigenic markers as positive controls, the reactivity patterns obtained with both McAbs MI/N1 and 308 were consistent with the detection of astrocyte-specific cell-surface antigens. No reactivity of the antibodies with other human neural cell-types, or with human muscle cells was detected. In cultures of human foetal brain a sub-population of astrocytic cells remained unlabeled by antibodies MI/N1 and 308. The significance of the latter observation has not yet been defined but may represent a developmental or functional division within the astrocytic cell lineage.

Antibodies, Monoclonal↗
PubMed1982

Human Thy-1: expression on the cell surface of neuronal and glial cells.

The Thy-1 antigen is a cell surface glycoprotein found in neural tissue of all mammalian species so far studied. The distribution and amount of this antigen has been measured on 4 human neuronal and 2 neuroglial cell lines and on fresh tumour cells of neuronal origin. In 3 out of 4 neuronal lines (LAN-1, TR14, CHP 212) more than 90% of cells were Thy-1+, however, LAN-1 cells showed only weak immunofluorescence and bore on average 2.4 times fewer molecules of Thy-1 per cell than those of either TR14 or CHP 212. The mean number of Thy-1 molecules per TR14 cell was shown to be approximately 2.25 x 10(5). In contrast, only 66% of cells in the fourth neuronal line (CHP 100) were Thy-1+, although these showed strong immunofluorescence. Both glial cell lines, UCH-203 and H314/123, showed strong Thy-1 immunofluorescence on more than 90% of cells. Similarly, with fresh neuronal tumour cells, although approximately 80% of tumours were Thy-1+ (essentially 100% of cells in these being positive) there were considerable differences in the intensity of labelling by immunofluorescence between different tumours. Such heterogeneity in cell lines and malignancy may reflect normal in vivo variation. Different phenotypes might therefore represent separate neural cell lineages, or simply differences in maturational status within a lineage. The very low frequency of Thy-1+ cells in normal bone marrow (less than 0.1% of nucleated cells) indicates that anti-Thy-1 antibodies may be valuable in both the diagnosis and subsequent treatment of neuroblastoma.

Antigens, Neoplasm↗