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 the present study a novel Ab-avidin fusion protein has been constructed to deliver biotinylated compounds across the blood brain barrier. This fusion molecule consists of an Ab specific for the transferrin receptor genetically fused to avidin. The Ab-avidin fusion protein (anti-TfR IgG3-CH3-Av) expressed in murine myeloma cells was correctly assembled and secreted and showed both Ab- and avidin-related activities. In animal models, it showed much longer serum half-life than the chemical conjugate between OX-26 and avidin. Most importantly, this fusion protein demonstrated superior [3H]biotin uptake into brain parenchyma in comparison with the chemical conjugate. We also delivered a biotinylated 18-mer antisense peptide-nucleic acid specific for the rev gene of HIV-1 to the brain. Brain uptake of the HIV antisense drug was increased at least 15-fold when it was bound to the anti-TfR IgG3-CH3-Av, suggesting its potential use in neurologic AIDS. This novel Ab fusion protein should have general utility as a universal vehicle to effectively deliver biotinylated compounds across the blood-brain barrier for diagnosis and/or therapy of a broad range of CNS disorders such as infectious diseases, brain tumors as well as Parkinson's and Huntington's diseases.
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PMID:An antibody-avidin fusion protein specific for the transferrin receptor serves as a delivery vehicle for effective brain targeting: initial applications in anti-HIV antisense drug delivery to the brain. 1051 Mar 83

Chronic B-cell stimulation may be a predisposing event in the early pathogenesis of the acquired immunodeficiency syndrome (AIDS)-related lymphoma (ARL). ARL-derived immunoglobulin (Ig) genes are significantly diversified from germline, suggesting that antigenic stimulation via Ig receptors may occur prior to malignant transformation. We have evaluated 6 ARL-derived antibodies for binding to human immunodeficiency virus (HIV) and cell surface epitopes. Five cases expressed IgM, and 1 case expressed IgG. Expressed V genes were significantly diversified (3%-15%) from known germline V genes. A non-Ig producing mouse myeloma cell line was transfected with expression vectors containing the lymphoma-derived V genes. By enzyme-linked immunosorbent assay and Western blot assay, the lymphoma-derived Ig's showed no reactivity against HIV recombinant proteins. Also, no specific HIV reactivity was observed by flow cytometry with lymphoma-derived Ig's against the T-cell line infected with T-tropic HIV-1 or peripheral blood mononuclear cells infected with M-tropic HIV strains, indicating lack of binding to native HIV epitopes. However, 2 of the lymphoma-derived Ig's (ARL-7 and ARL-14) bound strongly to non-HIV-infected cells of various tissue origins. Thus, these findings suggest that the transformed B cells of AIDS-associated lymphomas may not arise from the pool of anti-HIV specific B cells but, rather, may develop from B cells responding to other antigens, including self-antigens. (Blood. 2000;95:1393-1399)
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PMID:Evidence that immunoglobulin specificities of AIDS-related lymphoma are not directed to HIV-related antigens. 1066 16

The human herpes virus 8 (HHV8) or Kaposi's sarcoma-associated herpes virus (KSHV) is present in all Kaposi's sarcoma, and the detection of the virus using polymerase chain reaction or in situ hybridization is a highly sensitive and specific diagnostic test for the diagnosis of this neoplasm. HHV8 is furthermore invariably present in primary effusion lymphoma (PEL) and has also been detected in patients with acquired immunodeficiency syndrome (AIDS)-associated multicentric Castleman's disease (MCD) as well as, to a lesser extent, in non-AIDS MCD. In contrast to Kaposi's sarcoma, in which the tumor cells show primarily latent HHV8 infection, a higher rate of lytically infected cells can be observed in MCD. Epidemiological surveys indicate that the seroprevalence for HHV8 parallels the risk of developing Kaposi's sarcoma--5-10% in the general population of the Western world but ranging up to 20-70% in homosexual human immunodeficiency virus (HIV)-infected patients, and the infection precedes the development of Kaposis's sarcoma. Finally, HHV8 has been reported in a number of other diseases, especially in multiple myeloma. However, the highly controversial role of HHV8 in these lesions has to be clarified. Based on the data available today, HHV8 can be assigned as a new human virus, associated with tumors.
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PMID:Human herpes virus 8: a new virus discloses its face. 1078 77

The autoimmune repertoire is well known from previous studies to be capable of producing catalytic antibodies directed to self-antigens. In the present study, we explored the ability of 26 monoclonal light chains (L chains) from multiple myeloma patients to cleave radiolabeled gp120, a foreign protein. One L chain with this activity was identified. 125I-gp120 and unlabeled gp120 were cleaved at several sites by the L chain, as shown by SDS-polyacrylamide gel electrophoresis, autoradiography, and immunoblotting, respectively. The apparent dissociation constant of the L chain was 130-145 nM, indicating high-affinity gp120 recognition. 125I-albumin was not cleaved by the L chain, and various proteins and peptides did not inhibit gp120 cleavage by the L chain, suggesting that the activity is not a nonspecific phenomenon. The substrate recognition determinants may be conserved in different HIV-1 strains, because gp120 isolated from strains SF2, MN, and IIIB was found to be cleaved by the L chain. Micromolar concentrations of a synthetic peptide corresponding to residues 23-30 of gp120 inhibited the cleavage of 125I-gp120, suggesting that these residues are components of the epitope recognized by the L chain. The toxic effect of gp120 in neuronal cultures was reduced by about 100-fold by pretreatment of the protein with the L chain. These observations open the possibility of utilizing gp120-cleaving antibodies in the treatment of AIDS.
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PMID:Natural catalytic immunity is not restricted to autoantigenic substrates: identification of a human immunodeficiency virus gp 120-cleaving antibody light chain. 1082 50

Hepatitis B virus (HBV) reactivation in patients with positive hepatitis B surface antibody (HBsAb) has been reported in some cases of allogenic bone marrow transplantation, acquired immunodeficiency syndrome (AIDS), and organ transplantation. However, to our knowledge, no reports have been made on the frequency and risk factors involved in HBV reactivation after autologous peripheral blood stem cell transplantation (APBSCT). Forty seven patients who underwent APBSCT were retrospectively analyzed. Three patients who were HBsAb positive before APBSCT contracted post-transplant HBV acute hepatitis. All 3 patients had multiple myeloma. HBV DNA could not be demonstrated in preserved samples of transfused blood. Therefore, we speculated that reactivation of latent HBV had occurred. The 3 patients with HBV hepatitis had relatively lower titers of pre-transplant HBsAb, and the total dose of steroids they received after APBSCT was significantly higher than for other patients who did not experience post-transplant HBV reactivation. There were no significant differences in pre-transplant hepatitis B core antibody (HBcAb) titer or total post-transplant blood transfusion volume. Our study suggested that immunocompromised states, especially those induced by high-dose steroid therapy, may allow the reactivation of HBV after APBSCT, even in patients who had HBsAb before APBSCT.
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PMID:[Reactivation of hepatitis B virus after autologous peripheral blood stem cell transplantation in patients with positive hepatitis B surface antibodies]. 1084 63

Intravenous immunoglobulin (IVIg) are therapeutic preparations of intact IgG that are obtained from a pool of more than one thousand healthy blood donors and contain antibodies directed toward a large panel of microbial agents. IVIg contain high amounts of antibodies with opsonising activity and are indicated in substitutive treatment of patients with constitutive hypogammaglobulinemia. IVIg also contain antibodies able to neutralize certain bacterial toxins exerting superantigenic activity, and by this mechanism exert both anti-infectious and immunomodulating activity. During the last fifteen years, indications of IVIg in the prophylactic treatment of infections have been well defined: a) primary antibody deficiency; b) multiple myeloma and chronic lymphocytic leukemia with hypogammaglobulinemia and recurrent bacterial infections; c) bone marrow allograft; d) childhood AIDS; e) chicken pox seroprophylaxis in immunosuppressed patients and pregnant women. Therapeutic indications of IVIg in infectious diseases are limited to chronic parvovirus B19 infection associated or not with HIV infection. Other therapeutic indications are not well defined.
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PMID:[Intravenous immunoglobulins: anti-infection indications]. 1085 66

The acquired immunodeficiency syndrome (AIDS) results in an extraordinary increase in the risk of two malignancies: Kaposi's sarcoma (KS; relative risk [RR], >10,000) and B-cell non-Hodgkin's lymphoma (NHL; RR, >100). KS appears to result from uncontrolled expression of latency genes of human herpes virus-8 (HHV-8). KS is exquisitely sensitive to immune deficiency, and its incidence has declined during the late 1990s with the advent of highly active antiretroviral therapy (HAART) against human immunodeficiency virus (HIV). The risk of NHL is highest with high-grade histologies, and the incidence has declined only slightly with HAART. The risk of KS and NHL is decreased for people with the CCRS delta32 polymorphism, and NHL risk is increased with the SDFI-3'A polymorphism. Children with AIDS have a similar pattern of risk, but also have a high risk of leiomyosarcoma (RR, approximately 10,000). AIDS-related immune deficiency also increases the risk of Hodgkin's disease (RR, 8), probably multiple myeloma (RR, 5), and possibly other tumors in adults. Although the occurrence of cervical cancer (RR, 3) and anal cancer (RR, 30) is excessive among persons with AIDS, most or all of this excess results from sexually acquired human papillomavirus (HPV) infection and not from immune deficiency. Future efforts need to focus on understanding how the immune perturbation of AIDS results in a limited spectrum of tumors and most urgently on controlling the underlying HIV epidemic.
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PMID:The epidemiology of acquired immunodeficiency syndrome malignancies. 1095 Mar 65

Human Herpesvirus 8 (HHV-8) is clearly associated with Kaposi's sarcoma (KS), body cavity-based lymphomas (BCBL), and certain forms of multifocal Castleman's disease (MCD). It appears to be the sexually transmissible agent involved in the development of AIDS-associated KS. HHV-8 genomes are invariably present in BCBL-derived cell lines where lytic replication of the virus can be induced by phorbol esters (PE). First-generation HHV-8 serological assays were based on these cell lines. More recently, several genes encoding HHV-8 antigens have been identified. One of the most reactive antigens is encoded by HHV-8 open reading frame K8.1. Although K8.1 does not exhibit overt sequence homology to any other known gene, it is likely to be analogous to gp220/350 of Epstein-Barr or gp150 of murine herpesvirus-68, virion-envelope glycoproteins involved in target cell recognition. Mice were immunized with purified GST-K8.1 fusion protein expressed in E. coli. After fusion of murine plasma cells with the myeloma cell line P3-X63-Ag8. monoclonal antibodies (MAbs) were generated, which are specifically directed against K8.1 protein. The binding site for each MAb was identified by deletion mutant analysis using recombinant GST-K8.1 mutants and K8.1-specific peptides. Without exception, the epitopes recognized by these MAbs were located within the N-terminal part of the protein [amino acids (aa) 29 to 80], thus identifying a highly immunogenic region. These antibodies will not only be useful tools for HHV-8 diagnostics, but will also facilitate the analysis of K8.1 function.
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PMID:Generation of monoclonal antibodies directed against the immunogenic glycoprotein K8.1 of human herpesvirus 8. 1100 1

Despite the high prevalence of infection by the Human Immunodeficiency Virus (HIV) in South Africa, information on its association with cancer is sparse. Our study was carried out to examine the relationship between HIV and a number of cancer types or sites that are common in South Africa. A total of 4,883 subjects, presenting with a cancer or cardiovascular disease at the 3 tertiary referral hospitals in Johannesburg, were interviewed and had blood tested for HIV. Odds ratios associated with HIV infection were calculated by using unconditional logistic regression models for 16 major cancer types where data was available for 50 or more patients. In the comparison group, the prevalence of HIV infection was 8.3% in males and 9.1% in females. Significant excess risks associated with HIV infection were found for Kaposi's sarcoma (OR=21.9, 95% CI=12.5-38.6), non-Hodgkin lymphoma (OR=5.0, 95%CI=2.7-9.5), vulval cancer (OR=4.8, 95%CI= 1.9-12.2) and cervical cancer (OR= 1.6, 95%CI= 1.1-2.3) but not for any of the other major cancer types examined, including Hodgkin disease, multiple myeloma and lung cancer. In Johannesburg, South Africa, HIV infection was associated with significantly increased risks of Kaposi's sarcoma, non-Hodgkin lymphoma and cancers of the cervix and the vulva. The relative risks for Kaposi's sarcoma and non-Hodgkin lymphoma associated with HIV infection were substantially lower than those found in the West.
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PMID:The spectrum of HIV-1 related cancers in South Africa. 1105 82

Post-transplant lymphoproliferative disorders (PTLDs) comprise a histologic spectrum, ranging from hyperplastic-appearing lesions to frank non-Hodgkin's lymphoma or multiple myeloma histology. Multiple clones may coexist, each representing a discrete lymphomagenic event, a situation that is unique to immunodeficiency states. The incidence varies from 1% in renal recipients to 5% in heart recipients, but can be markedly increased by the use of anti-T-cell therapies or by T-cell depletion in bone marrow transplantation. PTLD continues to arise, even many years after transplantation, and late T-cell lymphomas have recently been recognized. Pretransplant Epstein-Barr virus (EBV) seronegativity increases risk to as high as 30%-50%. PTLD has a highly variable clinical picture; certain patterns are, however, seen. Reversibility of PTLD with reduction in immunosuppressives has long been recognized. Predicting reversibility has been difficult. The presence or absence of bcl-6 mutations has recently been identified as being of predictive value. Surgical resection can be curative. Cytotoxics, although problematic, can also be curative. Long-term remission has been achieved with anti CD21 and CD24 antibodies; efficacy has been reported for interferon alfa and for rituximab. In vitro expanded EBV-specific T cells have been effective as treatment and as prophylaxis in the setting of bone marrow transplantation. EBV viral load measured in blood appears to associate with the emergence of PTLD and may facilitate prophylactic studies. PTLD is a model of immunodeficiency-related EBV lymphomagenesis. Pathogenetic, therapeutic, and prophylactic insights gained from the study of PTLD are likely to be applicable to the acquired immunodeficiency syndrome setting.
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PMID:Post-transplant lymphoproliferative disorders: implications for acquired immunodeficiency syndrome-associated malignancies. 1115 5


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