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)

Interferons (IFN) are potent antiviral, cytostatic-cytotoxic and immunomodulatory agents. Although gene technology has made available an unlimited supply of all different kinds and types of IFN, their basic modes of action have not been clarified up to now. The therapeutic effects proven differ gradually between the individual disease entities. They comprise prophylaxis, prevention of recurrences and direct therapeutic effect, either of reducing the actual disease symptoms, or of inducing a complete recovery. For the following viral diseases a positive therapeutic effect has been shown: infections by herpes-viruses (herpes simplex keratitis , herpes zoster, herpes simplex), cytomegalovirus infections, chronic-hepatitis B virus infection, acute respiratory virus infections by rhino-, corona- and influenza viruses. Especially for the group of virus-associated tumors and papillomas, IFN is considered to be therapeutically effective. IFN has been accepted to be the first line treatment for laryngeal papillomatosis. In condylomata acuminata too, IFN is a potent therapeutic agent. Moreover, IFN represents the most effective therapeutic modality for Kaposi's sarcoma in patient with AIDS. Hairy cell leukemia, malignant lymphoma, multiple myeloma, melanoma and hypernephroma are the malignancies, for which a therapeutic effect of IFN could be proven. Furthermore, IFN is considered to be the therapy of first choice for hairy cell leukemias. Although there are some signs, that IFN could be a potent agent for adjuvant therapy, this question can not be answered - not even on principle - because of lacking sufficient data so far. Up to date, the therapeutic efficacy of IFN seems to be established only for hairy cell leukemia, laryngeal papillomatosis, Kaposi's sarcoma in patients with AIDS and partly for condylomata acuminata. For all other indications, first of all, sufficient phase-II-study data will have to be evaluated, before prospectively controlled studies, comparing the IFN treatment results with placebo and standard therapy results, can be initiated for the individual disease entities. Then, it will be possible to assess the therapeutic efficacy of IFN. Already now, IFN represent a valuable enrichment of the therapeutic modalities for malignancies and viral diseases.
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PMID:[Current status of interferon therapy]. 242 97

Hybridomas producing human monoclonal antibodies (MAbs) against human cytomegalovirus (CMV) were generated by fusion of human spleen cells and mouse myeloma cells. Two of the six MAbs obtained neutralized viral infectivity even at concentrations lower than 1 microgram/ml. One MAb required complement for neutralization but the other did not. Both MAbs recognized viral proteins of Mr 130,000 and 55,000. Furthermore, these neutralizing MAbs bound to the surface membrane of CMV-infected cells. These results suggest that human MAbs may provide a new means of passive immunization against CMV infection in humans.
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PMID:Human monoclonal antibodies neutralizing human cytomegalovirus. 243 45

A pathological study was carried out in 200 autopsied cases experienced in our department from 1981 to 1988. Eight patients (4.0%) had herpes simplex virus (HSV) infections in their visceral organs. Another one patient was diagnosed as HSV hepatitis through necropsy of liver. The nine patients (five of them were male) ranged in age from 34 to 70 years (mean, 58). Four patients had non-Hodgkin's lymphoma, and the other included one with adult T-cell leukemia, one with multiple myeloma, one with idiopathic interstitial pneumonia and one with bronchial asthma, however, one did not have any underlying disease. Two patients died of HSV fulminant hepatitis and one died of HSV diffuse interstitial pneumonia. The most commonly involved organ was esophagus (7/8), followed by tongue (5/8), liver (3/9), spleen, pancreas, lymph node (2/8), and lung, adrenal, tonsil (1/8). Typical herpetic changes such as ballooning degeneration of cells, multinucleated giant cells, ground-glass nuclei and Cowdry type A intranuclear inclusions were observed at the margin of the ulcer or coagulation necrosis. Indirect immunoperoxidase stain revealed HSV-1 antigen in all of the 9 cases, HSV particles were demonstrated in 2. Seven patients had concomitant infections with one or more pathogens in addition to HSV, which included cytomegalovirus in 5, aspergillus in 4, candida in 3 and bacteria in 3.
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PMID:[A pathological study on herpes simplex virus infections in adults]. 250 85

Monoclonal antibodies to early (2H2.4, molecular weight 72,000 daltons) and late (2F3.0, molecular weight 68,000 daltons) antigens of the AD-169 strain of cytomegalovirus (CMV) were prepared by fusing mouse spleen cells with NS-1 mouse myeloma cells. The 2H2.4 monoclonal antibody produced a dense immunofluorescence with prominent lobular staining within the nucleus of CMV-infected substrate cells, whereas the reaction of 2F3.0 was more diffuse and generally involved the entire nucleus of the cells. Both monoclonal antibodies had little or no neutralizing activity against CMV in plaque-reduction assays. No cross-reactions were observed between these monoclonal antibodies and other members of the herpesvirus group. The 2H2.4 monoclonal antibody to early CMV antigen was used in a shell vial assay with a low-speed centrifugation step for the rapid (within 16 hours after inoculation) diagnosis of CMV infections. Optimal conditions for the test included centrifugation of shell vials at 700 X g for 45 minutes at 36 degrees C. An inoculum volume of 0.2 ml provided a reasonable balance between the optimal sensitivity for detecting specific viral fluorescence and the easy discrimination of the specific immunofluorescence from the background debris. Because of the commercial availability of the monoclonal antibody and the simplicity of the procedures used in the shell vial assay and subsequent fluorescence techniques, this rapid assay can be done in any laboratory that is familiar with cell culture manipulations.
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PMID:Monoclonal antibody for rapid laboratory detection of cytomegalovirus infections: characterization and diagnostic application. 299 72

Sera from patients with adult T-cell leukemia and asymptomatic carriers of human T-cell lymphotropic virus type I (HTLV-I) from widely separated areas of the world reacted strongly in a standardized quantitative enzyme-linked immunosorbent assay procedure with HTLV-I viral antigen prepared from a strain isolated in the United States. There was a sharp differentiation of the values seen in the patients as compared with a normal population. Of the 35 acquired immune deficiency syndrome patients with Kaposi's sarcoma, only 2 were positive for HTLV-I antibodies in this test, and the distribution of the negative assay values in the other acquired immune deficiency syndrome patient sera was similar to that seen in the normal sera. Sera which contained extremely high levels of antibodies to other unrelated viruses (rubella virus, cytomegalovirus, and herpes simplex virus) all showed negative anti-HTLV-I results, in a pattern similar to the normal sera. Sera from patients with several autoimmune disease (systemic lupus erythematosus, rheumatoid arthritis, thyroiditis) as well as those with infectious mononucleosis or myeloma all also showed the normal distribution of negative results, in spite of the presence of very high levels of the autoantibodies, etc., associated with their illnesses.
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PMID:Quantitative estimation by a standardized enzyme-linked immunosorbent assay of human T-cell lymphotropic virus type I antibodies in adult T-cell leukemia and acquired immune deficiency syndrome. 300 30

In vitro stimulation of human lymphocytes were studied in connection with cell fusion. When splenic lymphocytes were stimulated with human cytomegalovirus (CMV), they produced IgG but not IgM antibody against CMV. The stimulation with 50 ng/ml of CMV antigen induced the maximum antibody response, and higher concentrations of CMV antigen decreased antibody response and increased nonspecific IgG production. Human splenic lymphocytes were stimulated for 6 days with CMV antigen (50 ng/ml) and/or B-cell growth factor (BCGF), and then fused with mouse myeloma cells. Stimulation with a combination of antigen and BCGF were able to generate CMV-specific hybridomas synergistically. Two of these hybridomas were cloned by limiting dilution. The human monoclonal antibodies produced by them, C1 and C23, bound to CMV but not to other herpesviruses. C23 neutralized virus infectivity C1 did not at all. This method for generation of hybridomas producing human monoclonal antibodies against a predefined antigen may be applicable to a variety of viral antigens.
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PMID:Generation of hybridomas producing human monoclonal antibodies against human cytomegalovirus. 301 82

Intravenous gammaglobulin is effective therapy of ITP and other autoantibody-mediated immune cytopenias. All children as well as adults unresponsive to splenectomy or with known immune deficiency are probably the best candidates for treatment with IVGG. Its major advantage, in addition to its efficacy of treatment and possible remission-inducing effect, is that it has the fewest side effects of any treatment of ITP so that it is the best maintenance therapy of patients when effective. Future uses of IVGG remain to be determined. Premature infants with a high mortality from sepsis and with hypogammaglobulinemia due to termination of pregnancy prior to transplacental antibody transfer may benefit from IVGG. A preliminary study suggested such benefit and also showed safety of IVGG treatment in that there was no impaired immune responsiveness of these prematures at 2 years of age (28). Another potential usage of IVGG involves the treatment of the hypogammaglobulinemia associated with certain types of malignancy. Patients with CLL, especially in the advanced stages, are often hypogammaglobulinemic. Multiple myeloma and Waldenstrom's macroglobulinemia are two other B-cell malignancies associated with antibody production defects which might benefit from antibody replacement therapy. Therapeutic IgG levels may be harder to obtain due to hypercatabolism of immunoglobulin. The issue of immune hyporesponsiveness during intensive chemotherapy is also unexplored. Secondary antibody responses do not seem to be impaired, but primary responses, as tested in numerous immunization studies, are decidedly impaired. Certain protocols, especially those treating high-risk acute leukemias and neuroblastoma during induction therapy are intensive with high rates of sepsis, and may warrant trials of prophylactic IVGG. Similarly, some form of humoral prophylaxis is becoming an important part of the handling of the patient undergoing bone marrow transplantation not only to prevent bacterial sepsis but also to prevent cytomegalovirus (CMV) interstitial pneumonitis. A likely additional usage is gammaglobulin replacement for patients undergoing plasmapheresis, especially if performed multiple times. Finally, the broad spectrum of antibacterial and antiviral antibodies present in the preparations (such as anti-CMV, anti-Group B strep, and antiendotoxin) and the ease and safety of delivery allow the preparations to be used in situations where a hyperimmune preparation might be desired and/or where more than one pathogen is possible. In summary, IVGG is a treatment capable of safely conferring significant benefits to selected patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Intravenous usage of gammaglobulin: humoral immunodeficiency, immune thrombocytopenic purpura, and newer indications. 404 Jul 95

Seventy-seven clones of hybridomas selected for reactivity by immunofluorescence with human cytomegalovirus (CMV)-infected cells were produced by fusing mouse myeloma cells with the spleen cells of mice immunized with CMV strain AD169. The clones were classified into seven groups on the basis of the electrophoretic properties of the polypeptides immune precipitated from extracts of CMV-infected cells. Studies on the three groups of monoclonal antibodies directed against CMV surface membrane antigens showed the following. Clones in each group were differentiated by immunoglobulin subclass, neutralizing activity, and reactivity with the antigenic domains of proteins exposed on the surface membranes of intact CMV-infected cells. Monoclonal antibodies in each group precipitated one slowly migrating protein and multiple faster migrating forms which shared antigenic determinants. The first group of monoclonal antibodies precipitated four glycosylated polypeptides with apparent molecular weights of 130,000, 110,000, 100,000, and 60,000. Monoclonal antibody CH51 of this group neutralized infectious virus but failed to react with antigenic domains on the surfaces of infected cells. The second group of monoclonal antibodies precipitated four polypeptides with apparent molecular weights of approximately 66,000, 55,000, 50,000, and 46,000. Monoclonal antibodies CH65 and CH134 in this group had neutralizing activity and reacted with antigenic domains of proteins exposed on the surface of CMV-infected cells. The third group of monoclonal antibodies precipitated four polypeptides with apparent molecular weights of 49,000, 48,000, 34,000, and 25,000. Serological analysis of 15 naturally occurring CMV strains with a panel of monoclonal antibodies to surface membrane proteins showed that the antigenic determinants reactive with the antibodies tested were conserved in all of the strains. Monoclonal antibodies to surface membrane proteins on CMV-infected cells may prove to be valuable reagents for identification of virus isolates.
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PMID:Monoclonal antibodies to human cytomegalovirus: three surface membrane proteins with unique immunological and electrophoretic properties specify cross-reactive determinants. 617 93

Nine hybrid cell lines producing antibodies specific for cytomegalovirus (CMV) antigen were obtained after fusion of P3/X63-Ag8 myeloma cells with spleen cells from BALB/c mice immunized with CMV complement-fixing antigen. By the immunoblot technique, five of nine antibodies (4D11, 7B4, 7D2, 8E3, and 8E10) were identified as being reactive to a CMV glycosylated polypeptide with molecular weight of 66,000 (GP66). Four other antibodies (1B8, 8E9, 4D2, and 7E2) appeared to be reactive with CMV antigen(s) only if the antigen was not denatured by sodium dodecyl sulfate. These remain unassigned until further studies are done. With the enzyme-linked immunosorbent assay (ELISA), competitive bindings were performed with a constant amount of horseradish peroxidase-conjugated antibody and various concentrations of unconjugated homologous and heterologous antibodies on CMV antigen-coated ELISA wells, and the antigenic determinant specific for each antibody was determined. The nine antibodies could be classified into six different groups, each group reacting with a different epitope or a different region with two or more antigenic determinants which are so close to each other that they cause binding inhibition. They are groups A (4D11), B (7B4, 8E10), C (7D2), D (4D2, 7E2, 8E9), E (8E3), and F (1B8). The extent of competition among antibodies within each group was the same. By using the two antibodies that reacted with different epitopes on GP66, a double-antibody sandwich ELISA method was developed. The method was sensitive enough to detect as little as 50% of the antigen present in one infected cell or 0.000245 U of CMV complement-fixing antigen per test well. Other strains of CMV (David, Kerr, Espilat, C-87, and five clinical isolates) gave positive results, whereas herpes simplex virus types 1 and 2, varicella-zoster virus and Epstein-Barr virus nuclear antigen preparations did not. By the indirect immunofluorescence assay, antibodies 4D11 and 8E3 were able to detect GP66 in the nucleus of CMV-infected F-5000 human embryonic fibroblasts as early as 2 h postinfection and were superior in this respect to the remaining seven antibodies tested. By the double-antibody sandwich ELISA, the presence of GP66 in CMV-infected cells was detected as early as 2 h postinfection.
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PMID:Production and characterization of monoclonal antibodies specific for a glycosylated polypeptide of human cytomegalovirus. 619 74

Six colonies producing antibodies were obtained by fusing mouse myeloma SP2-O cells with spleen cells from mice immunized with cytomegalovirus Davis strain. Among 88 surviving clones, 29 produced antibodies detectable by immunofluorescence on infected MRC5 cells and 2 others produced neutralizing antibodies against a homologous virus. Supernatants from these 31 positive clones and 4 others which were negative in immunofluorescence or neutralization were tested for their capacity to bind polypeptides from labelled Davis-infected cell extracts. Only 8 were found to be positive: five clones (A8, E3, F2, F8 and F20) precipitated 76 K, 60 K and 54 K bands; three others (A4, B9 and C24) precipitated 76 K and 54 K only. Surprisingly, these 8 monoclonal antibodies recognized a unique polypeptide 67 K of Towne-infected MRC5 cells. No correlation was found between (1) the pattern of fluorescence on MRC5 cells infected with Davis strain, (2) the neutralizing activity, and (3) the polypeptides recognized by the monoclonal antibodies.
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PMID:Identification of shared antigenic determinants of different polypeptides from Davis and Towne cytomegalovirus strains with monoclonal antibodies. 619 10


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