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A M Vogel

Publications and source records attributed to A M Vogel.

At least 37 records · Page 2Linked to original sources
PubMed1990

Identification of a multifunctional, cell-binding peptide sequence from the a1(NC1) of type IV collagen.

We have previously identified three distinctive amino acid sequences from type IV collagen which specifically bound to heparin and also inhibited the binding of heparin to intact type IV collagen. One of these chemically synthesized domains, peptide Hep-I, has the sequence TAGSCLRKFSTM and originates from the a1(noncollagenous [NC1]) chain of type IV collagen (Koliakos, G. G., K. K. Koliakos, L. T. Furcht, L. A. Reger, and E. C. Tsilibary. 1989. J. Biol. Chem. 264:2313-2323). We describe in this report that this same peptide also bound to intact type IV collagen in solid-phase assays, in a dose-dependent and specific manner. Interactions between peptide Hep-I and type IV collagen in solution resulted in inhibition of the assembly process of this basement membrane glycoprotein. Therefore, peptide Hep-I should represent a major recognition site in type IV collagen when this protein polymerizes to form a network. In addition, solid phase-immobilized peptide Hep-I was able to promote the adhesion and spreading of bovine aortic endothelial cells. When present in solution, peptide Hep-I competed for the binding of these cells to type IV collagen- and NC1 domain-coated substrata in a dose-dependent manner. Furthermore, radiolabeled peptide Hep-I in solution also bound to endothelial cells in a dose-dependent and specific manner. The binding of radiolabeled Hep-I to endothelial cells could be inhibited by an excess of unlabeled peptide. Finally, in the presence of heparin or chondroitin/dermatan sulfate glycosaminoglycan side chains, the binding of endothelial cells to peptide Hep-I and NC1 domain-coated substrates was also inhibited. We conclude that peptide Hep-I should have a number of functions. The role of this type IV collagen-derived sequence in such diverse phenomena as self-association, heparin binding and cell binding and adhesion makes Hep-I a crucial domain involved in the determination of basement membrane ultrastructure and cellular interactions with type IV collagen-containing matrices.

Amino Acid Sequence↗
PubMed1989

The appearance, density and distribution of melanocytes in human embryonic and fetal skin revealed by the anti-melanoma monoclonal antibody, HMB-45.

The presence, densities, and patterns of distribution of melanocytes in the epidermis of human embryos and fetuses, ranging in age from 40 d to 140 d estimated gestational age (EGA), were studied using the HMB-45 monoclonal antibody that recognizes an antigen in melanoma cells and fetal melanocytes. Immunostained sections of skin and epidermal sheets revealed dendritic melanocytes within the basal or intermediate layers of 50 d EGA and older skin. Melanocytes could not be identified by immunostaining or electron microscopy in younger (40-50 d EGA) epidermis or in cultured epidermal cells from these specimens. However, skin from a 45 d EGA embryo grown in organ culture for 11 d stained positively with HMB-45, suggesting that melanocytes are present at the age either in the epidermis or dermis of the explant. Double-labeling experiments using ATPase and HMB-45 confirmed the specificity of HMB-45 for melanocytes and demonstrated that melanocytes and Langerhans cells are nonoverlapping populations. Melanocytes were present in the embryonic epidermis in relatively high numbers (mean value of approximately 1050 cells/mm2); they increased in density to approximately 2300 cells/mm2 during the late first trimester and early second trimester, then declined during later stages of development to a density of approximately 800 cells/mm2, within the range of values for the newborn child and young adult. Equivalent numbers of melanocytes were recognized by silver staining and with the HMB-45 antibody in an 87 d EGA test sample, indicating that HMB-45 reacted with the total melanocytic population. Melanocytes appeared to be distributed in epidermal sheets in a regular pattern. Statistical tests used to evaluate the randomness of a population revealed a tendency toward a non-random distribution in specimens younger than 80 d EGA, just prior to appendage formation and epidermal stratification into multiple layers, however there was variability in the degree of randomness for any given age. The results of this study have closed the gap in timing between the conclusion of neural crest formation and migration (around 6 weeks) and the appearance of melanocytes in the skin between 40-50 d EGA.

Antibodies, Monoclonal↗
PubMed1989

Differential diagnosis of genitourinary tumors using monoclonal antibodies to intermediate filament proteins.

Definitive diagnosis of poorly differentiated and metastatic neoplasms may be impossible using conventional histologic criteria. Recent developments in cell biology and immunology now enable us to answer such difficult diagnostic problems. Several varieties of structural proteins can be identified in malignant cells using monoclonal antibodies. The composition of these proteins can yield information regarding the origin of a neoplasm. Intermediate filaments are one such family of structural proteins. By characterization of these proteins, using a panel of monoclonal antibodies, poorly differentiated tumors may be definitively classified as carcinomas, sarcomas, lymphomas, or neural tumors. This approach to tumor diagnosis is now applicable to difficult problems in clinical urology.

Adenocarcinoma↗
PubMed1988

Heparin type IV collagen interactions: equilibrium binding and inhibition of type IV collagen self-assembly.

Interactions between type IV collagen and heparin were examined under equilibrium conditions with rotary shadowing, solid-phase binding assays, and affinity chromatography. With the technique of rotary shadowing and electron microscopy, heparin appeared as thin, short strands and bound to the following three sites: the NC1 domain, and in the helix, at 100 and 300 nm from the NC1 domain. By solid-phase binding assays the binding of [3H]heparin in solution to type IV collagen immobilized on a solid surface was found to be specific, since it was saturable and could be displaced by an excess of unlabeled heparin. Scatchard analysis indicated three classes of binding sites for heparin-type IV collagen interactions with dissociation constants of 3, 30, and 100 nM, respectively. Furthermore, by the solid-phase binding assays, the binding of tritiated heparin could be competed almost to the same extent by unlabeled heparin and chondroitin sulfate side chains. This finding indicates that chondroitin sulfate should also bind to type IV collagen. By affinity chromatography, [3H]heparin bound to a type IV collagen affinity column and was eluted with a linear salt gradient, with a profile exhibiting three distinct peaks at 0.18, 0.22, and 0.24 M KCl, respectively. This suggested that heparin-type IV collagen binding was of an electrostatic nature. Finally, the effect of the binding of heparin to type IV collagen on the process of self-assembly of this basement membrane glycoprotein was studied by turbidimetry and rotary shadowing. In turbidity experiments, the presence of heparin, even in small concentrations, drastically reduced maximal aggregation of type IV collagen which was prewarmed to 37 degrees C. By using the morphological approach of rotary shadowing, lateral associations and network formation by prewarmed type IV collagen were inhibited in the presence of heparin. Thus, the binding of heparin resulted in hindrance of assembly of type IV collagen, a process previously described for interactions between various glycosaminoglycans and interstitial collagens. Such regulation may influence the assembly of basement membranes and possibly modify functions. Furthermore, qualitative and quantitative changes of proteoglycans which occur in certain pathological conditions, such as diabetes mellitus, may alter molecular assembly and possibly permeability functions of several basement membranes.

Animals↗
PubMed1988

Association of increased platelet-derived growth factor secretion and retroviral expression in transformed mouse and human cells.

The activation of platelet-derived growth factor (PDGF) production by transformed cells is often observed but not well understood. We have examined cell lines that showed "spontaneous" increases in PDGF secretion, i.e., in which the increase was not in response to intentional intervention. In one case the increase was associated with an obvious change in morphology and mitogen requirements accompanying spontaneous transformation of Swiss 3T3 cells. In the other case the increase occurred during growth of a human tumor cell in a nude mouse and was not associated with an alteration in the morphology or growth properties of the cells. Rates of PDGF secretion did not correlate with specific changes in the pattern of expression of PDGF mRNA. In the human tumor system PDGF A- and B-chain transcripts were present at similar levels before and after transplantation in the nude mouse. In the 3T3 cell system, B-chain transcripts were detected only after transformation, and there was no change in the low basal expression of A-chain. A change which did consistently correlate with the increased secretion of PDGF was that both the spontaneously transformed murine cells and the transplanted human cells expressed murine leukemia virus transcripts and synthesized retroviral envelope glycoproteins, while their original counterparts did not.

Animals↗
PubMed1988

Identification of a secreted Mr 95,000 glycoprotein in human melanocytes and melanomas by a melanocyte specific monoclonal antibody.

We have isolated a monoclonal antibody, designated HMB-50, that is highly specific for melanomas and melanocyte derived lesions. The antibody recognizes melanomas, neonatal melanocytes, and junctional nevi but does not react with adult melanocytes, dermal nevi, or a variety of non-melanocyte derived neoplasms. In tissue culture, the antibody reacts with five of seven human melanoma lines and neonatal foreskin melanocytes but fails to recognize fibroblasts and a number of different carcinomas. HMB-50 identifies a Mr 95,000 glycoprotein that is released into the growth medium by melanoma cells and neonatal melanocytes in vitro. This molecule is unrelated to antigens recognized by a variety of antimelanoma monoclonal antibodies isolated in other laboratories. The Mr 95,000 glycoprotein has been purified by antibody affinity chromatography and a polyclonal rabbit antiserum raised that exhibits identical specificity to the monoclonal antibody. The Mr 95,000 glycoprotein is rapidly released by melanoma cells (within 60 min) and one line produces relatively large quantities of the molecule (1 microgram/10(6) cells/24 h). The molecule in normal melanocytes differs slightly in electrophoretic mobility compared to its counterpart in melanomas and this difference appears to result from posttranslational modification.

Animals↗
PubMed1988

A novel synthetic peptide from the B1 chain of laminin with heparin-binding and cell adhesion-promoting activities.

Recent studies using solid-phase-binding assays and electron microscopy suggested the presence of a heparin-binding domain between the inner globule of a lateral short arm and the cross region of laminin. Using the information from the amino acid sequence of the B1 chain of laminin, several peptides were synthesized from areas with a low hydropathy index and a high density of lysines and/or arginines. One of these, peptide F-9 (RYVVLPRPVCFEKGMNYTVR), which is derived from the inner globular domain of the lateral short arm, demonstrated specific binding to heparin. This was tested in direct solid-phase binding assays by coating the peptide either on nitrocellulose or on polystyrene and in indirect competition assays where the peptide was in solution and either laminin or heparin was immobilized on a solid support. The binding of [3H]heparin to peptide F-9 was dramatically reduced when heparin but not other glycosaminoglycans other than heparin (dextran sulfate, dermatan sulfate) were used in competition assays. Modification of the free amino groups of peptide F-9 by acetylation abolished its ability to inhibit the binding of [3H]heparin to laminin on polystyrene surfaces. Peptide F-9 promoted the adhesion of various cell lines (melanoma, fibrosarcoma, glioma, pheochromocytoma) and of aortic endothelial cells. Furthermore, when peptide F-9 was present in solution, it inhibited the adhesion of melanoma cells to laminin-coated substrates. These findings suggest that peptide F-9 defines a novel heparin-binding and cell adhesion-promoting site on laminin.

Amino Acid Sequence↗
PubMed1988

Neoplasms in NIH type II athymic (nude) mice.

Necropsy and histopathology were performed over an 18-month period on 173 NIH type II athymic (nude) mice and 53 NIH type II mice heterozygous at the nu locus. A total of 149 mice were used in studies of tumor transplantation while 77 mice were screened as part of the quality assurance program for the colony. Twenty-nine neoplasms were found in 173 nu/nu mice. Only one neoplasm, an ovarian granulosa cell tumor, was found in 53 nu/+ mice. In nu/nu mice, there were nineteen lymphosarcomas, nine ovarian granulosa cell tumors, and one transitional cell carcinoma of the urinary bladder. A greater number of lymphosarcomas occurred in mice greater than 6 months old. A greater number of tumors, particularly lymphosarcomas, were found in nu/nu mice than in nu/+ mice.

Animals↗
PubMed1987

Production of platelet-derived growth factor by cultured Wilms' tumor cells and fetal kidney cells.

We have cultured human Wilms' tumors (nephroblastomas) in vitro and examined their growth properties, tumorigenicity in nude mice, karyotypes, and production of a platelet-derived growth factor (PDGF)-like activity (PDGFc). The cultured Wilms' tumor cells do not exhibit transformed growth properties, senesce after 15-25 passages, and are not tumorigenic in nude mice. Two of the three Wilms' tumors examined had karyotypic abnormalities but none contained a deleted 11p region. The Wilms' tumor cells and control human fetal kidney cells produce significant amounts of PDGFc and express few PDGF receptors on the cell surface. Analysis of Wilms' tumor cell RNA using probes specific for PDGF A-chain and B-chain (c-sis) detects A-chain but not B-chain transcripts in the tumor cells.

Animals↗
PubMed1986

Unique proteins defined by monoclonal antibodies specific for human melanoma. Some potential clinical applications.

A panel of monoclonal antibodies, designated HMB 18, 45, and 50, have been isolated that are highly specific for malignant melanoma. When tested on fixed, paraffin-embedded tissue sections, they reacted with 97 percent of melanomas tested (58 of 60), including pigmented, unpigmented, primary, and metastatic melanoma. The specificity in differentiating melanomas from other malignant tumors, including 112 carcinomas, 35 lymphomas, and 39 sarcomas, was 100 percent. Normal melanocytes were unreactive, although some benign melanocytic lesions were recognized. Using immunoprecipitation and SDS-PAGE analysis of 35S-methionine-labeled melanoma cells in tissue culture, a previously undescribed protein of approximately 10 kd was recognized by all three antibodies. HMB 50 also precipitated two high molecular weight proteins of 97 kd and 110 kd from the conditioned medium of melanoma cells. These monoclonal antibodies are the most sensitive and specific antibodies generated against human melanoma to date. Their clinical application in diagnostic surgical pathology and potential use in immunotherapy are discussed.

Antibodies, Monoclonal↗
PubMed1986

Monoclonal antibodies specific for melanocytic tumors distinguish subpopulations of melanocytes.

The authors have generated monoclonal antibodies to an extract of melanoma. When tested on a variety of fixed, embedded sections of malignant tumors, one antibody (HMB-45) reacted with 60 of 62 melanomas and none of 168 nonmelanomas (carcinomas, lymphomas, and sarcomas). The antibody reacts with junctional nevus cells but not intradermal nevi, and recognizes fetal and neonatal melanocytes but not normal adult melanocytes. This antibody thus demonstrates absolute specificity for melanocytic tumors and thus has great utility for the surgical pathologist in distinguishing among poorly differentiated tumors of uncertain origin. It also identifies differences among populations of melanocytes which may be useful in understanding the biology of and interrelationships between these cells.

Animals↗
PubMed1985

A smooth muscle-specific monoclonal antibody recognizes smooth muscle actin isozymes.

Injection of chicken gizzard actin into BALB/c mice resulted in the isolation of a smooth muscle-specific monoclonal antibody designated CGA7. When assayed on methanol-Carnoy's fixed, paraffin-embedded tissue, it bound to smooth muscle cells and myoepithelial cells, but failed to decorate striated muscle, endothelium, connective tissue, epithelium, or nerve. CGA7 recognized microfilament bundles in early passage cultures of rat aortic smooth muscle cells and human leiomyosarcoma cells but did not react with human fibroblasts. In Western blot experiments, CGA7 detected actin from chicken gizzard and monkey ileum, but not skeletal muscle or fibroblast actin. Immunoblots performed on two-dimensional gels demonstrated that CGA7 recognizes gamma-actin from chicken gizzard and alpha- and gamma-actin from rat colon muscularis. This antibody was an excellent tissue-specific smooth muscle marker.

Actins↗
PubMed1985

Monoclonal antibodies to human intermediate filament proteins. III. Analysis of tumors.

A panel of monoclonal antibodies to human intermediate filament proteins was tested on an unselected series of 246 neoplasms. The antibody panel includes two different anti-cytokeratin antibodies, an anti-vimentin antibody, and an anti-neurofilament antibody (Gown and Vogel, Am J Pathol 114:309, 1984). The studies were done on Carnoy's or methacarn-fixed, paraffin-embedded tissue. When used as a panel, they can unequivocally distinguish carcinomas, melanomas, and lymphomas. All carcinomas react with at least one of the anti-cytokeratin antibodies, and carcinomas can be subtyped based upon the pattern of reactivity with the two anti-cytokeratin antibodies. Melanomas react only with the anti-vimentin antibody, and lymphomas react with none of the antibodies. Neural and neuroendocrine tumors can be identified with the anti-neurofilament antibody. A minority of neoplasms, including lymphomas, seminomas, and some sarcomas, do not react with any of the antibodies. These antibodies are reliable diagnostic reagents that are useful in distinguishing different categories of human tumors.

Antibodies, Monoclonal↗
PubMed1985

Laryngeal injury in a dog model of prolonged endotracheal intubation.

Using a dog model of prolonged translaryngeal intubation, the authors studied laryngeal injury. Segments of 10.7 mm diameter endotracheal tube were sutured in place in the larynges of anesthetized animals, and the animals were allowed to awaken and the tubes left in place for periods of 24 h to 84 days in a total of 13 dogs. Each animal's larynx was studied endoscopically at weekly intervals and at the time of death. Both endoscopic and postmortem examination revealed erythematous laryngeal mucosa at 24 h and severe mucosal ulceration by 1 week. Microscopic examination revealed mucosal inflammation at 24 h with loss of mucosal architecture by 1 week. In several animals intubated 1 week or longer, inflammatory infiltrates were present in the arytenoid cartilage. While damage was generally severe by 1 week, it did not tend to become more severe after that time. Between week 1 and week 12, there was no significant correlation of the severity of laryngeal injury with the duration of endotracheal intubation. The results suggest that duration alone may not be a factor in laryngeal injury after the first week of intubation.

Animals↗
PubMed1985

Intermediate filaments in the developing type II cell of fetal monkey lung.

Anticytokeratin monoclonal antibody was used to study epithelial cell development in fetal monkey lungs taken from animals of different ages. It is well established that the overall maturity of fetal lung depends greatly on the maturation of type II epithelial cells in the alveolus. In this study, we have correlated the cytokeratin phenotype of mammalian epithelial cells with pneumocyte maturation. We show that differentiation and maturation of the type II cell is related to intermediate filament expression. Twenty-four fetal monkeys (Macaca nemestrina) were delivered by cesarean section at a gestational age of 135-140 days (term = 168 days) and divided into two groups. One group of animals was sacrificed during the first 3 hr of life, and the other group was maintained in incubators for 92-120 hr. Anticytokeratin monoclonal antibody recognizes only alveolar type I and type II epithelial cells. In the first 3 hr of life, the cytokeratin was localized only at the alveolar surface and at the cytoplasmic periphery of the type II cells of these premature animals. However, at the age of 92-120 hr, the epithelia in the lungs reacted more intensely than they did during the first 3 hr. Electron microscopy revealed and confirmed that the type II cells were matured and abundant intermediate filaments appeared in the cytoplasm. The filaments appeared to form either aggregates or parallel filament bundles and few were closely associated with the lamellar bodies. In the immature type II cells at 0-3 hr of life, few intermediate filaments could be localized in the cytoplasm, and no parallel filament bundle was observed, though many appeared in the 92-120 hr lungs. This suggests that the intermediate filaments have a functional significance in the development and maturation of the type II cell. The location and stability of keratin filaments in type II cells may confer the structural strength necessary for cells covering a free surface in the alveoli during lung maturation.

Animals↗
PubMed1985

Coexpression of intermediate filaments in human epithelial neoplasms.

A wide variety of human neoplasms were examined by immunocytochemical and ultrastructural techniques. In most, one intermediate filament (IF) type was expressed reflecting the tissue of origin. However, multiple classes of intermediate filaments were regularly found in a subgroup of these tumors. We chose to subdivide them into those with a complex or mixed growth pattern, and those which showed a more "monomorphic" histologic growth pattern. This latter group is the subject of this paper. Regular coexpression of cytokeratin and vimentin was observed in tumors of endometrial, thyroid, ovarian and renal origin, and coexpression of cytokeratin and neurofilament was observed in a subgroup of neuroendocrine tumors. Immunocytochemical/ultrastructural correlation demonstrated few, if any, observable intermediate filaments in tumors expressing only low molecular weight cytokeratin, whereas vimentin and neural filament characteristically were randomly dispersed or formed whorled bundles of cytoplasmic filaments. The potential diagnostic usefulness of these observations in surgical pathology is discussed.

Carcinoid Tumor↗