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Biomedical subjects

B Atkinson

Publications and source records attributed to B Atkinson.

At least 55 records · Page 3Linked to original sources
PubMed1986

Differential diagnosis between mesotheliomas and metastatic adenocarcinomas using monoclonal antibodies against gastrointestinal carcinoma antigen and stage-specific embryonic antigen.

Monoclonal antibodies made against gastrointestinal carcinoma antigen (GICA) and stage specific embryonic antigen (SSEA) were evaluated for their ability to distinguish normal mesothelial cells present in pleural and peritoneal fluids from adenocarcinoma cells in tissue and cytology specimens. The presence of GICA was documented in a high percentage of adenocarcinomas from the gastrointestinal tract (75/98) and in 52% of pulmonary (15/29) and 29% of ovarian (6/21) adenocarcinomas. GICA was found infrequently in breast carcinoma (1/18) and not in mesotheliomas (0/16). A similar pattern of GICA expression was seen in malignant effusions from adenocarcinomas (18/47) and mesotheliomas (0/6). SSEA was found in a high percentage of adenocarcinomas derived from the gastrointestinal tract (47/56) and the lung (26/29). SSEA was detected in breast carcinoma (8/15) more often than GICA. SSEA was detected rarely in mesotheliomas (1/16). Reactivities for epithelial membrane antigen, keratin, carcinoembryonic antigen, GICA and SSEA in adenocarcinoma and mesotheliomas were compared.

Adenocarcinoma↗
PubMed1986

Expression of melanoma-associated antigens by normal and neurofibroma Schwann cells.

The cell surface antigen distribution on traumatic neuroma Schwann cells and neurofibroma Schwann-like cells was characterized using monoclonal antibodies that define melanoma-associated antigens. Immunofluorescence staining of cultured cells, immunoprecipitation of radioiodinated antigens from cells placed in short-term cultures, and immunoperoxidase staining of frozen tissue sections revealed most of the melanoma-associated antigens tested on traumatic neuroma and neurofibroma Schwann cells and on fetal and adult femoral nerve. The cross-reactivity of the antibodies with neural cells may reflect the common neural crest embryological origin of Schwann cells and melanocytes. Cell sorter analysis of neurofibroma cells using a monoclonal antibody directed against the melanoma nerve growth factor receptor resulted in cell cultures highly enriched for Schwann-like cells which may bear the genetic defect responsible for neurofibromatosis. The antigen detected by this monoclonal antibody is the neurofibroma nerve growth factor receptor and the antibody was a potent inhibitor of nerve growth factor binding to neurofibroma cells.

Antibodies, Monoclonal↗
PubMed1986

Human cutaneous nevi transplanted onto nude mice: a model for the study of the lesional steps in tumor progression.

Normal human cutaneous nevi were transplanted to the skin of nude mice and some of the grafts were treated topically with 7,12-dimethylbenz[a]anthracene (DMBA, 1.6 mumol weekly). Histologically proven human skin was present in 22 grafts. In the 9 untreated control grafts, the tendency of nevic cells to form nests and the number of nevomelanocytes decreased with time; the melanocytic cells showed no signs of hypertrophy or atypia. In most of the 14 specimens treated with DMBA, the nevomelanocytes showed distinct signs of hypertrophy. The cells were enlarged and often dendritic and were filled with melanin granules for which the transfer to keratinocytes appeared to be blocked. The nevomelanocytes of 4 of the 9 specimens treated with DMBA for greater than or equal to 82 days (9-16 DMBA applications), showed atypical enlarged nuclei with mitotic figures. Since atypia is one criterion for identifying precursors of transformed cells, the model of human nevi grafted onto nude mouse skin may be useful for studying the various steps involved in the progression of benign melanocytic nevi to malignant melanoma.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1985

Isolation and amino terminal sequencing of a novel melanoma-associated antigen.

The biochemical characteristics are described for a melanoma-associated glycoprotein antigen, whose expression depends on stage of tumor progression and melanocytic differentiation. This antigen, identified using a monoclonal antibody which specifically stains melanoma cells in immunoperoxidase assay of fixed tissue sections, is synthesized as a 30,000-Da precursor and then processed to a 30,000- to 60,000-Da sialylated glycoprotein. Two-dimensional gel electrophoresis of the antigen resolved more than 20 forms, heterogeneous in both charge and molecular weight. The kinetics of post-translational processing, the sensitivity of processing to tunicamycin, and the molecular weight of the oligosaccharide chains indicate that the oligosaccharides are N-linked. Amino acid sequencing of the antigen purified by immunoaffinity chromatography and by high-pressure liquid chromatography or polyacrylamide gel electrophoresis allowed the assignment of the first 20 acids.

Amino Acid Sequence↗
PubMed1985

Metastatic uveal melanoma. Hepatic metastasis identified by hybridoma-secreted monoclonal antibody MAb8-1H.

Monoclonal antibody MAb8-1H, which defines an ocular melanoma-associated antigen retained in fixed tissue, was used to demonstrate metastatic melanoma cells in liver biopsy specimens from five patients with primary choroidal melanoma. In all cases, the monoclonal antibody bound to tumor cells and not to normal hepatocytes. In one case, a well-delineated focus of tumor cells bound to MAb8-1H; in two cases, MAb8-1H appeared to delineate individual tumor cells that were difficult to categorize by conventional staining techniques. The liver biopsy specimens were almost completely replaced by tumor cells in the remaining two cases. This monoclonal antibody may be applicable to the diagnosis of metastatic uveal melanoma and to delineate micrometastasis.

Antibodies, Monoclonal↗
PubMed1985

Monoclonal antibody to a highly glycosylated protein reacts in fixed tissue with melanoma and other tumors.

A highly glycosylated protein with a molecular weight of 30,000 to 60,000 and a protein core of 20,000 daltons has been identified by antimelanoma monoclonal antibodies. The antigenicity of this melanoma-associated glycoprotein (MAG) was not destroyed in fixed paraffin-embedded melanoma tissue, and was present in malignant cells of cutaneous superficial spreading melanomas in skin (31/33) and in half of all metastatic melanomas examined (5/10). The antigen was not expressed by normal melanocytes. The strong reactivity of dysplastic nevi with the anti-MAG antibodies was comparable to that seen in radial growth phase melanoma. Antigen expression was much weaker in compound nevi where reactivity ranged from moderate in the junctional component and the upper dermis to absent at the base of the nevus.

Antibodies, Monoclonal↗
PubMed1985

Circulating tumor markers and assessment of response to intrahepatic chemotherapy of colon carcinoma.

To assess the change in concentrations of circulating gastrointestinal cancer-associated antigens in response to therapy, we analyzed the sera of patients with hepatic metastasis from colorectal carcinoma who were treated with intrahepatic arterial chemotherapy. Serial serum samples were assessed for the tumor-associated antigens, carcinoembryonic antigen (CEA) and the gastrointestinal cancer antigen CA 19-9. Computed axial tomographic (CAT) scans were made to assess the size of the hepatic metastasis. In 9/10 of these patients the CEA predicted tumor response within 2-6 weeks after initiation of treatment, and in 7/10 the information was supported or more dramatically demonstrated by the CA 19-9. Combining data from both tumor markers may provide a more accurate assessment of the clinical response than one antigen alone. Recurrence of hepatic metastatic growth or extrahepatic tumor also was identified by elevation of one or both circulating tumor-associated antigens prior to other laboratory or clinical evidence of tumor growth.

Adult↗
PubMed1985

Tissue distribution and biochemical properties of an ocular melanoma-associated antigen.

A screening method is described to select monoclonal antibodies (Mabs) that bind to ocular melanoma-associated antigens (MAAs) retained in formalin-fixed, paraffin-embedded tissue sections. Small sections of epithelioid or spindle-cell-type uveal melanomas were cut into 2 mm cubes and reembedded in one block. Microslides were cut from this block and used to screen hybridoma supernatant fluid. Using this screening method, three MAbs were selected from two separate fusions of mouse myeloma cells with spleen cells of mice immunized previously with either ocular melanoma cells obtained fresh at enucleation or cells of a cutaneous melanoma cell line. Although all three MAbs showed similar specificities, MAb8-1H showed the strongest immunohistochemical reaction and was studied further in detail. MAb8-1H bound to 91% (71/79) of the choroidal or ciliochoroidal melanomas tested, indicating a high prevalence of this antigen in uveal melanomas. The antigen defined by MAb8-1H was isolated, purified, and partially characterized as a 40,000-50,000 dalton, highly glycosylated protein rich in glycine, serine, and glutamic acid, as is typical of a mucin-type glycoprotein.

Antibodies, Monoclonal↗
PubMed1984

Efficient selection of human tumor growth-inhibiting monoclonal antibodies.

A method is described for selection early after fusion for hybridomas that secrete IgG2a monoclonal antibodies (MAbs) with binding specificity for antigens on the human tumor cells used to immunize mice. By combining this preselection method with antibody-dependent macrophage-mediated cytotoxicity assays, it was possible to select those MAbs mediating a tumoricidal effect against tumor cells in culture and inhibiting the growth of tumor xenografts in nude mice. Two such MAbs, GA733 and CO441, inhibited the growth of colorectal carcinoma cells, and one of them (GA733) was effective even when administered 6 days after implantation of tumor cells. These results suggest the potential usefulness of the 2 MAbs in immunodiagnosis and immunotherapy of human tumors.

Animals↗
PubMed1984

Binding of murine immunoglobulin to human tissues after immunotherapy with anticolorectal carcinoma monoclonal antibody.

An anticolorectal carcinoma antibody, 17-IA, that is of gamma 2a isotype and has been used in previous immunotherapy trials, binds to an antigen on most human colon tumors. This antigen is destroyed by the fixative and embedding procedures employed for routine histologic evaluation of tissues. It can be demonstrated by the avidin/biotin-labelled peroxidase complex (ABC) immunoperoxidase technique on briefly fixed, frozen sections of fresh human tissues. With this assay technique, the antibody is found to bind in vitro to both human colonic carcinoma and normal gastrointestinal epithelia. Tissues removed from patients having received the 17-IA antibody intravenously in an immunotherapy trial show bound antibody 1-2 after administration. This is no longer evident 3 weeks later though the antigen is present on the cell surface and is still capable of binding antibody in vitro.

Animals↗
PubMed1984

Characterization of nerve growth factor receptor in neural crest tumors using monoclonal antibodies.

The nerve growth factor (NGF) receptor was characterized by using a new series of anti-receptor monoclonal antibodies (MAbs). These MAbs (i) showed significantly greater reactivity with a melanoma cell line expressing higher levels of NGF receptor, (ii) inhibited the binding of 125I-labeled NGF to its receptor, and (iii) immunoprecipitated both metabolically labeled and 125I-labeled NGF affinity-labeled receptor. These experiments defined the receptor as a 75-kDa cell-surface protein. The NGF receptor was visualized by immunoperoxidase staining in tissue sections of human nevi, melanomas, neurofibromas, a pheochromocytoma, and peripheral nerves. Uniform staining of the cytoplasm suggests that, in addition to cell-surface NGF receptors, there is a population of intracellular receptors.

Affinity Labels↗
PubMed1984

Bactericidal effect of polymorphonuclear neutrophils on antibiotic-induced filaments of gram-negative bacilli.

Exposure of strains of Escherichia coli to ampicillin and mezlocillin and of strains of Pseudomonas aeruginosa to azlocillin and cefsulodin caused the bacilli to elongate into filaments. The bacilli and their filaments were incubated with fresh human polymorphonuclear neutrophils (PMNs), and the phagocytic process was recorded by means of phase-contrast microscopy. The bactericidal effect of PMNs on both filaments and bacilli was quantitated by counts of colony-forming units. A single PMN phagocytized one or more filaments, some of which were as long as 90 micron and contained as many as 20 genomes. Two predominant patterns of phagocytosis of filaments were observed. When the ratio of bacteria to PMNs was low (0.2-1.8), the rate of killing was 62%-81%. When the ratio was higher (5-12), the rate of killing of both filaments and bacilli was lower. As an alternative to colony-forming units, cell mass was used as a gauge of phagocytic activity. The relative mass of killed filaments was considerably greater than that of killed bacilli; this finding indicated that filaments were much more susceptible than were bacilli to the bactericidal activity of PMNs.

Ampicillin↗
PubMed1984

Production and characterization of monoclonal antibodies to peripheral and central nervous system myelin.

Monoclonal antibodies against P0, myelin basic protein, or myelin-associated glycoprotein were generated by fusing mouse myeloma cells with spleen cells from BALB/c mice immunized with central and peripheral nervous system myelin proteins. The antibodies secreted were either IgG, IgM, or IgA. Clone C6B5 (iso-type IgM) secreted antibody(ies) that bound to both myelin basic protein and myelin-associated glycoprotein, although binding of antibody to myelin basic protein as detected by the immunoblot technique appeared to be much less than to the myelin-associated glycoprotein. Antibodies were characterized in solid-phase radioimmunoassay for their species cross-reaction, and histologically for the specificity of binding to myelin in central and peripheral nervous system tissues. These monoclonal reagents should prove valuable in studying CSF and myelin-producing cells, since in both cases the concentration of myelin proteins is low.

Animals↗
PubMed1984

Monoclonal antibody localization of Lewis antigens in fixed tissue.

Monoclonal antibodies that bind specifically with Lewisa (Lea) and Lewisb (Leb) antigens were used in an immunoperoxidase assay to characterize Lewis (Le) antigenic profile of a variety of fixed tissues. Representative sections of normal and malignant tissue from the stomach, colon, pancreas, and kidney were examined and compared. Lea antigen was expressed more often in gastric adenocarcinomas (80%) than normal gastric mucosa (40%). In gastric tumors with concomitant expression of Le antigens, larger areas within an individual tumor expressed Lea antigen rather than Leb antigen. Expression of Leb antigen in normal colonic tissue was seen only in the proximal colon and not distal colon; colon carcinomas, on the other hand, expressed Leb antigen (64%) regardless of where the primary arose. Leb antigen was expressed in large pancreatic ducts (three of three) more often than Lea antigen (one of three); exclusive expression of Lea antigen was demonstrated in the proximal convoluted tubules of normal kidney (three of three) and in renal cell carcinomas (six of eight).

Animals↗
PubMed1984

Immunoassay for melanoma-associated proteoglycan in the sera of patients using monoclonal and polyclonal antibodies.

A melanoma-associated proteoglycan antigen is expressed by primary cutaneous and ocular melanomas, metastatic melanomas, nevus cells, some astrocytomas, and fetal fibroblasts, and it is shed into culture supernatant by both melanoma and nevus cells. The antigen is also expressed by tumor cells in vivo. Melanoma and nevus cells, but not normal melanocytes, were specifically stained by the immunoperoxidase procedure. The proteoglycan antigen, purified by immunoaffinity chromatography using a monoclonal antibody that specifically detects this antigen, was used to immunize rabbits. The resulting serum was tested by sequential immunoprecipitation and found to react with the same population of molecules detected by the anti-proteoglycan monoclonal antibodies. Furthermore, the reactivity patterns of the rabbit serum and of the monoclonal antibodies with a variety of tumor and normal cells were the same. Based on the these data, we conclude that the entire proteoglycan molecule is a melanoma-associated antigen. The monoclonal antibodies and immunoglobulin from the rabbit serum were tested in a double determinant immunoassay for the detection of antigen in a total of 339 sera from patients with various diseases. Elevated levels of circulating proteoglycan antigen were found in 76% of patients with a high metastatic melanoma tumor burden compared to 2% of healthy donors. A fraction (22%) of patients with light tumor burden or nonmelanoma neoplastic disease also had elevated levels of circulating proteoglycan antigen. The source of the antigen for the latter patients may be collagenous connective tissue which, as judged by immunoperoxidase staining, expresses the antigen in both normal and transformed tissues.

Antibodies↗