PubMed Health⌕ Search

Biomedical subjects

G B Dermer

Publications and source records attributed to G B Dermer.

At least 19 recordsLinked to original sources
PubMed1984

Unusual acidic light chains in murine SLE serum.

The sera of autoimmune and other mouse strains were analysed by high resolution two dimensional gel electrophoresis and silver staining. The most striking finding was the presence of unusually acidic immunoglobulin light chains in sera from 4-5 month old MRL/Mp-lpr/lpr mice. Similar light chains were found in lesser amounts in NZB/NZW and BXSB sera, and traces were observed in MRL/Mp-+/+, NZB, and in normal sera. The intensity of the acidic light chain spots increased with age in MRL/Mp-lpr/lpr mice, coincident with the development of autoimmunity. These acidic light chains circulated as components of complete IgG molecules, as they were no longer demonstrable in serum which had been rendered free of IgG by absorption with Cowans strain staphylococci. Because both cryoglobulins and glomerular eluates from MRL/Mp-lpr/lpr mice contained acidic immunoglobulin light chains, these molecules may be involved in immune complex formation and resultant injury.

Animals↗
PubMed1982

Origin of bronchioloalveolar carcinoma and peripheral bronchial adenocarcinoma.

The morphologic distribution of newly synthesized glycoproteins in a bronchioloalveolar carcinoma and in a peripheral bronchial adenocarcinoma with areas of bronchioloalveolar differentiation was determined and compared with bronchiolar epithelium and type II alveolar cells. Tissues were maintained in vitro, and autoradiography was used to reveal locations of glycoproteins metabolically labelled with 3H-glucosamine. Both tumors displayed glycoprotein secretory activity as most incorporated radioactivity was rapidly released from cells. Silver grains were associated with cytoplasmic granules and mucinlike secretions in the bronchioloaveolar carcinoma and granules plus unidentified secretions in the bronchial adenocarcinoma. Clara cells exhibited an association of newly synthesized glycoproteins with cytoplasmic granules similar to those found in the tumors. In bronchiolar ciliated epithelium, as in bronchial ciliated cells and central bronchogenic adenocarcinomas, glycoproteins accumulated over apical cell surfaces and were not rapidly secreted. Type II cells incorporated label into secreted contents of cytosomal inclusions and unidentified cytoplasmic material. The observations suggest that a bronchioloalveolar carcinoma and a peripheral bronchogenic adenocarcinoma are distinct from common bronchogenic adenocarcinomas and are derived from secretory cells that resemble bronchiolar Clara cells.

Adenocarcinoma↗
PubMed1982

Synthesis of alpha 1-antichymotrypsin and alpha 1-acid glycoprotein by human breast epithelial cells.

Malignant and uninvolved human breast tissues were maintained in organ culture for 3 to 6 days. Under these conditions, the three-dimensional glandular architecture is maintained with the least disruption of tissue integrity. The biosynthesis and release of glycoproteins were studied by using the incorporation of [14C]glucosamine and [14C]leucine by the breast surgical specimens. Five major families of labeled glycoproteins were identified from culture supernatants using two-dimensional gel electrophoresis. Quantitative immunoprecipitation established that 16 to 30% of the total of labeled glycoproteins were recognized as normal serum components. Two of these glycoproteins were antigenically related to normal human serum components as demonstrated with crossed immunoelectrophoresis. Evidence was obtained for the active synthesis of alpha 1-antichymotrypsin and alpha 1-acid glycoprotein by human breast epithelial cells. alpha 1-Antichymotrypsin accounted for 0.9 to 7.8% of the biosynthetically labeled glycoproteins from organ culture supernatants. This component was 11.9% of the glycoproteins released by a monolayer culture of the established breast carcinoma cell line, MCF-7. alpha 1-Acid glycoprotein made up 0.7 to 3.1% of the labeled glycoproteins. alpha 1-Antichymotrypsin is a known neutral serine proteinase inhibitor with a particularly strong affinity for cathepsin G. alpha 1-Acid glycoprotein may function primarily as a potent immunomodulator by suppressing lymphoblastogenesis. These glycoproteins may thus have regulatory roles in the proteolytic modification of breast tissue and represent the tissue's own protecting shield against invading leukocytes.

Breast↗
PubMed1982

Enhancement techniques for detecting trace and fluid-specific components in two-dimensional electrophoresis patterns.

Albumin and other serum-derived proteins were removed from several types of body fluids by affinity chromatography, to facilitate detection of trace or non-serum-derived proteins in two-dimensional electrophoresis patterns. Albumin was removed by the dye Cibacron Blue F3G-A coupled to Sepharose. Two-dimensional patterns of albumin-depleted serum lack the large albumin spot, and several families of spots become visible that ordinarily are partly or totally hidden by it. However, other proteins also bind to Cibacron Blue. Most serum proteins, including albumin, were effectively removed by anti-human serum antibodies coupled to Sepharose. Two-dimensional patterns of serum-depleted cerebrospinal fluid exhibit five clusters of probable nervous-system protein families not detected in serum. One additional family, probably antigenically related to transferrin, was removed by the affinity step. Two-dimensional patterns of serum-depleted prostatic fluid exhibit five major non-serum families, two of which may be creatine kinase B subunits and prostatic acid phosphatase. Two-dimensional patterns of serum-depleted malignant effusions exhibit one or more of three proteins that possibly are tumor products. Pattern matching suggests the presence of one non-serum-derived protein family common to cerebrospinal fluid, prostatic fluid, and malignant effusions. Prostatic fluid and malignant effusions have in common as many as three non-serum families of proteins.

Blood Proteins↗
PubMed1981

Autoradiography of cellular glycoproteins reveals histogenesis of bronchogenic adenocarcinomas.

Primary and metastatic bronchogenic adenocarcinomas, excluding bronchioloalveolar and large cell types, and normal bronchi were studied to find out if the tumors displayed a common type of glycoprotein metabolism that was also shared by one or more bronchial epithelial cell types. For comparison, the glycoprotein metabolism of a metastatic pancreatic adenocarcinoma was also investigated. Tissues were maintained in vitro, and the cellular distribution of glycoproteins, metabolically labelled with 3H-glucosamine, was determined by light and electron microscopic autoradiography. Intense reactions in the form of silver grains over luminal surfaces of primary bronchogenic adenocarcinomas and those metastatic to pleural fluids indicated that the synthesis of cell coat (glycocalyx) glycoproteins predominated. In the pancreatic adenocarcinoma, the synthesis of secretory glycoproteins predominated, reflecting a histogenesis from secretory epithelium. In bronchi, only ciliated epithelium exhibited a distribution of newly synthesized glycoproteins similar to that observed in the bronchogenic adenocarcinomas. These observations suggest that bronchogenic adenocarcinomas share a common histogenesis and most likely arise from a cell type committed to differentiation into ciliated epithelium.

Adenocarcinoma↗
PubMed1981

The synthesis of a proteinase inhibitor, alpha-1-antichymotrypsin, by human breast epithelial cells.

The synthesis and release of glycoproteins were studied in organ cultures of human breast surgical specimens and in established breast epithelial cell lines, MCF-7 and MDA-MB-231. Biosynthesis was monitored by the incorporation of 14C-glucosamine. Labeled macromolecules in the culture supernatants were analyzed by biochemical and immunological techniques. One to 8% of the labeled glycoproteins from benign breast and infiltrating ductal carcinoma specimens was precipitated by antibodies produced against human serum alpha-1-antichymotrypsin. Twelve percent of the total glycoproteins from the culture supernatants of the MCF-7 cell line was identified as alpha-1-antichymotrypsin. Both the normal serum and the human breast epithelia-derived proteinase inhibitor can be resolved into similar subclasses by two-dimensional gel electrophoresis. MDA-MD-231 and MCF-7 cells which were extensively washed with EDTA, serum-free medium, and phosphate-buffered saline retain this proteinase inhibitor on their cell surfaces. Three to 4% of the total cell-surface iodinated components was immunoprecipitated by these specific antibodies. Since alpha-1-antichymotrypsin is a potent inhibitor of neutral proteinases such as cathepsin G, the demonstration of its synthesis by benign and malignant breast epithelial cells is of considerable interest. This glycoprotein may represent the epithelia's own protective shield of cell surface components and the cell's attempt to moderate the effects of invading leukocytes. In addition, it may play a regulatory role in the maintenance of three-dimensional glandular structures.

Adenocarcinoma↗
PubMed1981

Creatine kinase BB and other markers of prostatic carcinoma.

Creatine kinase BB has been described to be elevated in the serum of patients with prostate cancer. The incidence of abnormal serum levels correlates with the degree of differentiation of the tumor; that is, the more poorly differentiated tumors are associated most frequently with elevated CK-BB levels. We have recently described two additional findings which involve CK-BB in prostate cancer: 1) the finding of abnormally migrating CK-BB bands reported to be IgG-CK-BB complexes in several Stage D patients and in 2/3 Stage B patients following 125I implants, and 2) significant differences between CK-BB purified from prostatic fluid from CK-BB of brain origin. In particular, we find two bands of prostatic CK-BB following purification as compared to a single band from brain, when the same purification protocol is used. While further characterization of these differences is proceeding, the two bands of CK-BB are being used to develop a prostate-specific antiserum for use in immunoassays to detect prostate cancer in conjunction with other traditional markers such as prostatic acid phosphatase. If serum detection of tumor markers is to be efficacious, tumor marker panels such as CK-BB and prostatic acid phosphatase may provide a significant advantage over individual markers.

Brain↗
PubMed1980

Incidence of a split alpha 2-glycoprotein band in the electrophoretic pattern for serum of adenocarcinoma patients.

We electrophoresed serum samples on Mylar-backed cellulose acetate membranes and stained for glycoproteins with the periodic acid--Schiff reagent. The samples were from untreated adenocarcinoma patients, adenocarcinoma patients receiving chemotherapy, and patients with other malignancies, and also from patients with benign proliferative diseases, inflammatory diseases, and other non-malignant conditions. Forty-five per cent of the sera from untreated adenocarcinoma patients and 80% of those from adenocarcinoma patients with progressive systemic disease exhibited a splitting of the alpha 2-glycoproteins into a fast and slow band. Such a pattern was seen in only 4% of the non-adenocarcinoma cancer patients and 4% of the control group. Serial studies indicated that electrophoretic patterns of alpha 2-glycoproteins change with clinical status. Non-cancer patients with high concentrations of acute-phase proteins in their serum did not exhibit two alpha 2-glycoprotein bands. Further characterization of serum proteins from the fast alpha 2 region suggest that alpha 1-acid glycoprotein and haptoglobin beta chains are the principal components staining with periodic acid--Schiff reagent. These components are markedly less apparent in, or are absent from, the fast alpha 2 region of normal sera.

Adenoma↗
PubMed1979

Creatine kinase BB: a new tumor-associated marker.

Creatine kinase isoenzyme BB (CK-BB) is found in the serum of patients with various types of cancer. Using both radioimmunoassay and agarose electrophoresis, we found abnormal amounts of this isoenzyme in the serum of 15 of 17 patients with untreated prostatic carcinoma. Among patients with other types of adenocarcinomas and metastatic disease, serum CK-BB was increased in most of those who were unresponsive to therapy. In benign or malignant prostate tissue and in malignant pleural effusions, cytoplasmic CK-BB as determined by immunoperoxidase staining was found in epithelial cells. Prostatic fluid had high concentrations of CK-BB, as did malignant, but not benign, pleural fluid supernates. We conclude that glandular epithelial cells contain CK-BB, which is released in benign and malignant states and may appear in higher concentrations in the circulation in malignant states. These conclusions are consistent with predictions we have made from a model experimental system concerning characteristics of possible tumor markers. The observations indicate a role for CK-BB as a tumor marker, particularly for adenocarcinoma of the prostate.

Adenocarcinoma↗
PubMed1978

Basal cell proliferation in benign prostatic hyperplasia.

Two cell types are found within glandular acini of the human prostate. These basal and secretory cells can be distinguished in the light microscope by their different affinity for toluidine blue. Toluidine blue exhibits a strong affinity for basal cells while secretory cells are poorly stained. In benign prostatic hyperplasia, toluidine blue stained basal cells commonly form a single layer which rests on the basement membrane of glands. Also present are areas where cell layers located nearer gland lumina, thought to be composed of secretory cells, are occupied by cells with a basal like morphology and which exhibit a strong affinity for toluidine blue. The ultrastructure of these cells resembles that of basal cells. Autoradiographic analysis of 3H-thymidine incorporations by hyperplastic prostatic expants in organ culture shows that within glands only basal cells are active in DNA synthesis. The data suggest that basal cells are capable of proliferating and may be a source of secretory cells.

Cell Division↗
PubMed1978

In vitro synthesis and secretion of glycoprotein by human mammary tissue.

Organ cultures of human surgical specimens can be used to investigate glycoprotein production in vitro under conditions in which three-dimensional tissue structures and cell-cell interactions resemble those present in vivo. In this report, an organ-culture system is used to investigate the synthesis, transport and release of glycoprotein by normal and benign hyperplastic human mammary epithelium. Autoradiography of explants pulse-labeled with individual glycoprotein precursors ([3H]glucosamine, [3H]fucose, [3H]acetylmannosamine) and maintained in organ culture for intervals up to 72 hr revealed that glycoprotein is synthesized and then secreted by mammary epithelium. Incorporation of each isotope took place in the Golgi apparatus. Most of the newly synthesized glycoprotein, labeled with each of the three precursors, then was transported to apical cell surfaces and secreted into gland lumina. Observations were indistinguishable in normal and benign hyperplastic glands. Thus nonlactating human mammary epithelium exhibits a glycoprotein secretory activity. Analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of [3H]glucosamine-labeled macromolecules released into the medium showed a group of glycoproteins with a molecular weight of 48,000 +/- 6,000 daltons plus high-molecular-weight glycosylated components at the top of gels. The nature of gp48 is not known, but similar molecular-weight glycoproteins also are released by surgical specimens of human mammary cancer maintained in organ culture.

Breast↗
PubMed1977

Glycoprotein synthesis as a function of epithelial cell arrangement: biosynthesis and release of glycoproteins by human breast and prostate cells in organ culture.

We demonstrate that a technique is available to investigate glycoprotein synthesis in organ cultures of human breast and prostate surgical specimens where the 3-dimensional epithelial cell arrangement remains intact. Malignant breast and prostate epithelium maintained their capacity to synthesize glycoproteins for at least 3 days as followed by the incorporation of [3H]glucosamine into macromolecules. Over 70% of incorporation was by malignant cells as judged by autoradiography. Labeled glycoproteins were released into glandular lumina and consequently into the culture fluid. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed predominantly one group of macrmolecules released with an apparent molecular weight of 48,000 +/- 6,000 daltons. This glycoprotein was found in all of the breast specimens studied, which included 1 medullary, 1 infiltrating lobular, and 8 infiltrating duct carcinomas. The pattern was independent of the availability of estrogen receptors. A similar glycoprotein was also observed in the culture media from a Grade I and a Grade II well-differentiated infiltrating prostate carcinoma. Incorporation was below the level of detection in 4 of 6 cases of benign prostatic hyperplasia. A more complex pattern of labeled glycoproteins was found in the media of a Grade II and a Grade III poorly-differentiated prostate carcinoma. The established human mammary carcinoma cell line MCF-7 synthesized and released a similar 48,000 molecular weight glycoprotein but additional components with larger molecular weights were also released. An intriguing interpretation that 3-dimensional tissue integrity restricts some glycoprotein synthesis is discussed. Cells grown in 2-dimensional monolayers could escape from such a topographic restriction and express additional families of glycoproteins.

Adenocarcinoma↗
PubMed1977

Electrophoretic patterns for serum glycoproteins reflect the presence of human breast cancer.

We describe a group of glycoproteins that are synthesized and released by human breast tumors maintained in organ culture and similar glycoproteins released by a human breast carcinoma cell line (BT-20). The electrophoretic mobility of these glycoproteins on cellulose acetate is consistent with increased glycoprotein-staining material present in the alpha2- to beta-globulin region of serum glycoprotein electropherograms from patients with breast cancer. Moreover, after mastectomy, this glycoprotein material in serum decreases to concentrations seen in a control population of patients with benign breast lesions. Patients with proven metastatic breast cancer have patterns reflecting their clinical status: those who respond to treatment have glycoprotein electropherograms similar to the group of patients with benign breast lesions, while those who do not have increased amounts of alpha2- beta-glycoprotein. We believe serum glycoprotein measurements in breast-cancer patients reflect the presence of glycoproteins that are released by the malignant cells and enter the circulation.

Breast Neoplasms↗
PubMed1975

Autoradiographic localization of glycoprotein in human breast cancer cells maintained in organ culture after incubation with (3H)fucose or (3H)glucosamine.

Explants of nine infiltrating duct carcinomas of the human female breast, maintained in organ culture, were exposed to the glycoprotein precursors, L-[3H]furcose and [3H]glucosamine, in order to determine the cellular distribution of newly synthesized glycoprotein as revealed by autoradiography with the light and electron microscopes. Explants were incubated with a single isotope for 2 hr, at which time some of the labeled explants were removed for autoradiographic analysis while the rest were transferred to nonradioactive medium for an additional 24 hr. After exposure to label for 24 hr, autoradiography with each isotope was similar and showed strong reactions over most tumor cells. The reactions were due to clumps of silver grains over intracytoplasmic lumina within single tumor cells and silver grains over Golgi saccules, cytoplasmic vesicles, lysosome-like bodies, lateral and basal plasma membranes, and microvilli. Extracellular ductular structures were also heavily labeled. At the later sampling time, Golgi saccules often showed a reduced reaction while the reactions over other organelles and intracellular and extracellular ductular structures remained strong. The observations suggest that in our in vitro system the tumor cells are metabolically active and complete the synthesis of the carbohydrate side chains of glycoproteins within the Golgi apparatus. From there, some of the newly synthesized glycoprotein appears to migrate to plasma membranes and lysosome-like bodies. Furthermore, our data support the notion that many duct carcinomas of the breast exhibit secretory activity by showing that some newly synthesized glycoprotein also appears to become products that are secreted into intracellular and extracellular ductular structures.

Autoradiography↗