Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In untreated patients with inoperable lung cancer, serum levels of alpha1-antitrypsin were found significantly increased in comparison to patients with non malignant diseases of the lung, alpha2-macroglobulin levels were unchanged in both groups of patients. There was also no difference in alpha2-macroglobulins in cancer patients reacting with DNCB and in non-reactors. Thus alpha2-macroglobulin levels do not seem to correlate with the immunestatus of cancer patients. Proteinase inhibitors are involved in a variety of biological processes including blood, clotting, digestion, and sperm capacitation. alpha1-antitrypsin, a alpha-globulin with a molecular weight of about 60,000 has been found to be decreased in patients' serum under several pathological conditions. A clear correlation exists between alpha1-antitrypsin deficiency and hereditary pulmonary emphysema (1, 2), respiratory distress syndrome (3), and juvenile cirrhoses of the liver (4). Elevated serum levels of alpha1-antitrypsin have also been found in some cancer cases. Thirty years ago a cancer test was developed on the basis of differences in the antiproteolytic activity in cancer patients' sera and in patients with other non-neoplastic diseases (5, 6). Several authors have tried to confirm these early data regarding specifity and sensitivity with respect to a screening test for cancer (7, 8). Methods of these authors were based mainly on enzyme substrate inhibition assays by addition of the patients' sera. Recently a commercially available test, based on immune-precipitation according to Mancini (9), has been developed (Behring-Werke, Partigen). By using this standardized method for determinating alpha1-antitrypsin, Harris et al. have recently demonstrated that patients with inoperable lung cancer have significantly elevated levels of this antiprotease in their sera (10), in comparison to patients with non malignant diseases of the lung. alpha2-macroglobulin is a serum protein with a molecular weight of 800,000 and with known antiprotease activity and can therefore bind trypsin, plasmin, elastase, and collagenase and it is known that alpha2-macroglobulin decreases with increasing of age. Changes of alpha-macroglobulin have also been observed in several pathological conditions (11). James et al. 4ave found decreases in serum of myeloma patients (12). An association between the development and function of lymphocytes and alpha2-macroglobulin has been suggested by several authors (13, 14). This alpha2-globulin has also been demonstrated on the surface of peripheral blood lymphocytes (15) and there is evidence that it is synthesized by lymphocytes (16). The purpose of the present study was to determine serum alpha1-antitrypsin levels in patients with inoperable lung cancer and to determine whether there is also an inverse correlation to alpha2-macroglobulin. It was further attempted to correlate alpha2-macroglobulin with general immunological parameters, as it is known that patients with lung cancer show a decreased general immune-reactivity (17).
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PMID:Serum levels of alpha1-antitrypsin and alpha2-macroglobulin in lung cancer. 6 86

Two differentiation antigens of spermatogenesis in the mouse are defined by monoclonal antibodies from hybridomas produced between the myeloma P3-X63Ag8 and spleen lymphocytes immunized with syngeneic testis cells. These antigens are on testis cells, and not liver, kidney, brain, spleen, or whole ovary. They are species but not strain specific and trypsin sensitive but collagenase insensitive. On the basis of their appearance during the onset of spermatogenesis they appear to be differentiation antigens expressed during different but overlapping time windows during spermatogenesis.
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PMID:Recognition of differentiation antigens of spermatogenesis in the mouse by using antibodies from spleen cell-myeloma hybrids after syngeneic immunization. 21

Recombinant human interstitial collagenase, an N-terminal truncated form, delta 243-450 collagenase, recombinant human stromelysin-1, and an N-terminal truncated form, delta 248-460 stromelysin, have been stably expressed in myeloma cells and purified. The truncated enzymes were similar in properties to their wild-type counterparts with respect to activation requirements and the ability to degrade casein, gelatin, and a peptide substrate, but truncated collagenase failed to cleave native collagen. Removal of the C-terminal domain from collagenase also modified its interaction with tissue inhibitor of metalloproteinases-1. Hybrid enzymes consisting of N-terminal (1-242) collagenase.C-terminal (248-460) stromelysin and N-terminal (1-233) stromelysin.C-terminal (229-450) collagenase, representing an exchange of the complete catalytic and C-terminal domains of the two enzymes, were expressed in a transient system using Chinese hamster ovary cells and purified. Both proteins showed similar activity to their N-terminal parent and neither was able to degrade collagen. Analysis of the ability of the different forms of recombinant enzyme to bind to collagen by ELISA showed that both pro and active stromelysin and N-terminal collagenase.C-terminal stromelysin bound to collagen equally well. In contrast, only the active forms of collagenase and N-terminal stromelysin.C-terminal collagenase bound well to collagen, as compared with their pro forms.
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PMID:The role of the C-terminal domain in collagenase and stromelysin specificity. 131 62

It is generally recognized that no one cell culture system can be universally applied to all cell types commonly used for biopharmaceutical manufacture. The analogous concept that no single cell type may be useful for the expression of all biopharmaceutical products may also gain credence in the biotechnology community. It may be that like specialized bioreactors, there will come to exist a variety of cell types that will be used for the production of different types of biopharmaceutical products. In addition, it may not be enough in the future just to demonstrate the stability of expression of the amino acid backbone of the protein only; the carbohydrate portion of the molecule may become the subject of real scrutiny. Questions such as how the carbohydrate side chain affects the performance of the molecule in vivo are being asked of more DNA constructs. The next question becomes, how can we control the expression of carbohydrate moieties on the molecule? Such questions are in the future of the biotech manufacturing field. Aside from those examples mentioned above dealing with the insertion of receptors, other more subtle attempts at modifying cellular metabolism are taking place. It was reported at a recent meeting that the sialyltransferase gene was inserted into a CHO line which did not normally express this enzyme (116). The transfected line was capable of expressing the transferase and, more importantly, the enzyme functioned correctly in sialylating glycoproteins. Other very complex relationships exist between the substratum and the cell that could have very direct consequences on culture maintenance. For example, researchers recently published results indicating that collagenase synthesis and secretion is stimulated in rabbit fibroblasts by autocrine factors. They determined that these autocrine proteins had sequence homology to serum amyloid-A and beta-2-microglobulin. It may be that using serum supplements in the medium in those systems that couple fibroblast and collagen substratum may not be prudent, especially for long-term culture. The traditional selection of a cell type for expressing heterologous proteins has generally been limited to the more "common" cell types such as CHO cells, C127 cells, and myeloma cells. In many cases these cell types were selected because there was a great deal of preexisting literature on the cell type (i.e., "cookbook" methods of transfection for the cell) or the cell was simply being carried in the lab at the time the effort was made to express a biopharmaceutical product.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Large-scale animal cell culture: a biological perspective. 136 73

Alpha 2-macroglobulin, a major glycoprotein component of plasma, is unique in its capacity to bind and inhibit the proteolytic activities of all classes of proteinases. Since proteinases implicated in cancer dissemination (type-IV collagenase, plasminogen activator, cathepsins B) are normal constitutents of blood, we have explored the hypothesis that elevated tissue levels of activated proteinases bound to alpha 2M might be detected in plasma of patients with cancer. To test this premise, blood was collected from 149 subjects (33 healthy controls, 31 patients with infections and non-malignant diseases, 16 with myeloproliferative disease, 10 with gastrointestinal cancer, 7 with genito-urinary cancer, 16 with lung cancer, 14 with lymphoma, 11 with miscellaneous cancers and 11 with chronic lymphocytic leukemia and myeloma). Plasma was assayed for alpha 2M-proteinase complexes using a sandwich ELISA which employs a mouse monoclonal antibody (MAb) that binds to a neo-antigenic determinant on complexed alpha 2M and a rabbit polyclonal anti-native human alpha 2M antibody. The concentration of complexed alpha 2M in healthy controls was 14.2 +/- 9.8 micrograms/ml (mean +/- standard deviation). No significant differences in complexed alpha 2M were noted between normal and cancer groups (range 7.4-14.6 micrograms/ml). On the basis of these data, we propose that, in patients with cancer, activated proteinases are bound locally to inhibitors in the tissues and are not available to form complexes with plasma alpha 2M. An alternative explanation is that proteinases are not secreted in excess by cancer cells in vivo.
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PMID:Proteinase-alpha 2 macroglobulin complexes are not increased in plasma of patients with cancer. 171 Feb 7

Rabbit uterine collagenase was purified from the medium of involuting uterus (1-2 days postpartum) in culture using ammonium sulfate fractionation, DEAE-cellulose, heparin-affinity, and high performance liquid chromatography. The enzyme was purified more than 1600 fold. Hybridoma cell-lines producing monoclonal antibodies were prepared by fusing the spleen cells of mice immunized with the purified enzyme with mouse myeloma cells (Sp2/O-Ag14). The hybridoma cells were selected with HAT medium, cloned, and screened by ELISA. Antibody-producing ascites were prepared by injecting hybridoma cell-lines into the peritoneal cavities of mice. Western-blot analysis indicated that the antibodies recognized a polypeptide having a molecular weight of 52,000. The IgG isolated from the ascites inhibited the enzyme. Indirect immunofluorescent staining demonstrated that polymorphonuclear leukocytes (PMNs) in the superficial layer of alkali-burned corneas contained collagenase, whereas stromal cells and PMNs within the stroma were not stained by the antibodies. Our results suggest that collagenases produced by rabbit PMNs are different from those produced by fibroblasts from cornea. We hypothesize that PMNs in alkali-burned corneas secrete all or most of their collagenases by degranulation at the anterior surface of the cornea, and then continue to migrate into the deeper portion of the stroma.
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PMID:Development of monoclonal antibodies recognizing collagenase from rabbit PMN; the presence of this enzyme in ulcerating corneas. 243 Jul 58

In vitro perfused kidneys of ovalbumin-sensitized guinea-pigs consistently released relatively large quantities of histamine when challenged with the specific antigen (mean +/- SEM in twelve experiments was 37.7 +/- 6.0% of total kidney histamine, maximum 70.6%, compared with a basal release of 0.5 +/- 0.46% over a comparable period) but not with non-cross-reacting antigens. There was also no release from non-sensitized kidney. Rabbit antisera to guinea pig IgG1 and IgG2 immunoglobulins (but not normal rabbit serum) also consistently released histamine from perfused kidneys of sensitized guinea-pigs, but the release was smaller than with antigen, and could also be obtained from kidneys of non-sensitized guinea-pigs (maximum release 62.4% with the most potent antiserum). Guinea-pig kidney cell suspensions prepared by collagenase dispersion in vitro responded similarly, but the release with antigen was small (less than 10% net release, minus the spontaneous release 9.46% on average) as compared to anti-IgG1 (net release up to 38%) or anti-IgG2 (up to 44%). Rat kidney cells prepared by a similar procedure, and passively sensitized in vitro by incubation with rat immunoglobulin E (IgE) myeloma protein also responded to the addition of antiserum to rat IgE by releasing substantial amounts of histamine (up to 44% net release). In addition, heparin-containing cells (presumably mast cells or equivalent) in the enzyme-dispersed kidney cell preparations in both species were identified and counted by an adaptation of the Technicon H 6000 system used for counting blood basophils, and shown to represent 1 in 10,000 or less of the total cell population, which was not different from the count of similar cells in lung and heart tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal histamine: release by immune stimuli. 243 15

The tissue sites of monomeric IgA (mIgA) catabolism were determined in a BALB/c mouse model. Mouse mIgA myeloma proteins were labeled either by direct iodination or by coupling the residualizing label, dilactitol-125I-tyramine (125I-DLT) to the proteins; catabolites from protein labeled with 125I-DLT accumulate at the site of protein degradation, allowing identification of the tissue and cellular sites involved in catabolism of the protein. The circulating half-lives of 125I- and 125I-DLT-mIgA were the same. The distribution of radioactivity in tissues was measured at 1, 3, 24, and 96 h after iv. injection of 125I-DLT-labeled mIgA, dimeric IgA (dIgA), IgG, or mouse serum albumin. The greatest uptake of 125I-DLT-mIgA was attributable to the liver. This organ accounted for more internal catabolism of mIgA than all other tissues combined. In contrast, 125I-DLT-IgG was catabolized equally in skin, muscle, and liver. These data indicate that, in mice, the liver is the major site of mIgA catabolism. To determine the cell types involved, collagenase digestion was used to isolate parenchymal and non-parenchymal cells from perfused liver of animals injected with 125-DLT-mIgA. Most of the radioactivity was associated with the hepatocyte fraction, even though both cell types showed uptake of 125I-DLT-mIgA. Inhibition studies, with asialofetuin and mouse IgA demonstrated that the uptake of mIgA by liver cells was mediated primarily by the asialoglycoprotein receptor.
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PMID:The sites of catabolism of murine monomeric IgA. 245 58

We previously have shown [Takahashi & Kobayashi (1982) Hepatology 2, 249-254] that the administration of concanavalin A to mice with schistosomiasis caused liver collagen content to be reduced by 50%. Here we report the effects of concanavalin A and aggregated mouse myeloma IgG on liver lysyl oxidase activity and present further evidence concerning the possible mechanism by which the liver collagen content was decreased in infected-treated mice. The lysyl oxidase activity at 8 weeks after infection in both treated mice and untreated infected controls was about 28-fold greater than in the age-matched uninfected controls. The specific radioactivity of intracellular free [14C]proline, the rate of collagen synthesis, the ratio of collagenase-sensitive, protein-bound, hydroxyproline to proline of collagen and the intracellular degradation of newly synthesized collagen were similar in treated animals and in untreated infected controls. In contrast, the extracellular degradation of newly secreted collagen and the specific radioactivity of protein-bound [14C]hydroxyproline in the agent-treated groups were about 2-fold greater than those in the untreated infected controls. These results suggest that the observed 50% decrease in content of liver collagen of mice treated with the agents apparently was due to the increased extracellular degradation of newly secreted collagen.
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PMID:Collagen metabolism in fibrotic liver. Effects of concanavalin A and aggregated myeloma immunoglobin G. 288 49

Antigen expression is studied corresponding to a monoclonal autoantibody (IC2) derived from a hybridoma of rat myeloma Y3 cells and splenocytes of the diabetic BB rat. The selective reactivity of IC2 with islet cells has earlier been proven. We studied the possible specificity for beta islet cells, and the possible variation in autoantigen expression. Islet cells were isolated by cautious collagenase and dispase treatment. The cells were labelled with IC2 alone or together with anti-insulin immunoglobulin in double-labelling experiments. Extensive series of cells were examined by immunofluorescence microscopy, and some samples also by flow cytometry. In double-labelling examinations we found that only anti-insulin positive cells could bind the IC2 antibody, thus showing beta-cell selectivity. On the other hand, not all anti-insulin positive cells were IC2-positive. Since insulin treatment has been shown to decrease the incidence of diabetes in the BB rat, islet cells were examined after reduced beta-cell strain. Islet cells from Lewis and Wistar Furth rats display 21.4 +/- 1.4% IC2-positive cells, while islet cells from 24-hour fasting animals showed 7.0 +/- 1.4% (p less than 0.0001). Similar results were seen for BALB/c mice (25.0 +/- 1.8% vs. 13.7 +/- 2.3%, p less than 0.002). Also, after a week of insulin treatment, autoantigen expression was significantly decreased. Thus, the IC2 antibody is beta-cell-specific, and expression of the corresponding cell surface antigen depends on the functional state of the beta-cells.
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PMID:Antigen expression of the pancreatic beta-cells is dependent on their functional state, as shown by a specific, BB rat monoclonal autoantibody IC2. 328 66


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