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)

We have identified by MEDLINE search the cases of gammaglobinopathy and plasma cell malignancy in HIV-positive patients reported in the English language literature. The average age at presentation among HIV-positive patients with plasma cell disorders is 33 years, far younger than the average age of presentation in the general population. Some of these patients present with transient paraproteinemias, while others have persistent paraproteins, which may or may not be associated with true plasma cell malignancies. In most cases in which it has been examined, the paraprotein contains high-titer anti-HIV activity. The presence of high-titer anti-HIV activity in the paraproteins of AIDS patients suggests that an antigen-driven process in response to HIV infection may contribute to the early development of plasma cell disorders in these patients. Recent work in plasma cell tumorigenesis has indicated that transformation at a single point in the B lymphocyte lineage can give rise to either lymphoma or myeloma, dependent upon environmental factors such as T cell function, which may be required for directing transformed lymphocytes from lymphoma and towards plasma cell differentiation. This may explain why B lineage oncogenesis in AIDS patients favors the development of lymphoma over that of myeloma.
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PMID:Paraproteinemia, plasmacytoma, myeloma and HIV infection. 944 34

Using data from a case-control study in the United States (the Selected Cancers Study), we examined the relationship between non-Hodgkin's lymphoma (NHL) and family history of different cancers. Cases were 1,511 men aged 31 to 59 years and diagnosed pathologically with non-Hodgkin's lymphoma during 1984-88. Controls were men, frequency-matched to cases by age range and cancer registry (n = 1,910). All study subjects with acquired immunodeficiency syndrome were excluded from analyses. Our results showed that the risk of NHL is associated with a history of lymphoma (odds ratio [OR] = 3.0, 95 percent confidence interval [CI] = 1.7-5.2) and hematologic cancer (OR = 2.0, CI = 1.2-3.4) in first-degree relatives after adjustment for age, ethnic background, and educational level. Further analyses were performed for the subgroups defined by age at diagnosis (younger than 45 years cf 45 years or older). The association of NHL with a family history of lymphoma and hematologic cancer was found primarily among men aged 45 and older (OR = 4.1, CI = 1.9-8.8 for lymphoma and OR = 2.3, CI = 1.3-4.0 for hematologic cancer). The association among men aged 45 and older did not vary by whether or not there were any familial patients diagnosed at the age of 45 or older. No significant associations could be found for a family history of lung cancer, breast cancer, prostate cancer, colon cancer, skin cancer, liver cancer, stomach cancer, brain cancer, thyroid cancer, or myeloma. This study suggests that the familial risk of NHL is influenced primarily by hematolymphoproliferative malignancies rather than other cancers. The familial effects of hematolymphoproliferative malignancies may be stronger for men aged 45 to 59, compared with those aged 31 to 44.
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PMID:Non-Hodgkin's lymphoma and family history of malignant tumors in a case-control study (United States). 948 66

Interleukin-6 (IL-6) is a proinflammatory cytokine whose synthesis is induced by a variety of stimuli including interleukin-1 (IL-1), substance P (SP), and histamine. Because IL-6 has been implicated in the etiopathology of different human diseases including multiple myeloma, rheumatoid arthritis, multiple sclerosis, acquired immunodeficiency syndrome dementia complex, and Alzheimer's disease, its inhibition may be of therapeutic interest. A main demand on an effective inhibitor of IL-6 expression is that it inhibits IL-6 synthesis independently of the inducing stimulus. We therefore used human astrocytoma cells to search for signal transduction cascades and transcription factors whose inhibition suppresses IL-6 synthesis after stimulation with three different inductors, IL-1beta, SP, and histamine. Whereas the antioxidant pyrrolidinedithiocarbamate was only able to inhibit IL-1beta-induced IL-6 expression, inhibition of protein kinase C prevented IL-6 expression induced by all three substances. Promoter deletion analysis revealed that IL-1beta-induced IL-6 expression required the transcription factor nuclear factor-kappaB (NF-kappaB), whereas SP- and histamine-induced IL-6 synthesis was essentially controlled by NF-IL-6. These findings suggest that inhibition of protein kinase C or a combinatory inhibition of NF-IL-6 and NF-kappaB binding are strategies to effectively suppress IL-6 synthesis. They therefore provide the basis for the development of antiinflammatory drugs used to treat disorders in which IL-6 is pathogenically involved.
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PMID:Substance P and histamine induce interleukin-6 expression in human astrocytoma cells by a mechanism involving protein kinase C and nuclear factor-IL-6. 952 75

Purified phenolic glycolipid (PGL-1) from Mycobacterium leprae was used to detect IgG antibodies against PGL-1 in leprosy patients in an enzyme-linked immunosorbent assay (ELISA). A total of 698 sera were screened; they came from patients suffering from leprosy, autoimmune disease, myeloma, tuberculosis and sexually transmitted diseases (STDs). Cases with miscellaneous diseases and persons undergoing AIDS screening were also included. Sera from lepromatous and tuberculoid leprosy patients gave positivity rates of 60.5% and 41.7%, respectively. In non-leprosy cases, the PGL-1 ELISA showed an overall positivity rate of 6.9%; this was greatest in patients with tuberculosis (43.8%) followed by autoimmune diseases (40.9%) and miscellaneous cases including liver diseases (37.9%). This study emphasizes that PGL-1 ELISA has a low predictive value for diagnosis of active infection by Mycobacterium leprae. Positive reactions in a significant percentage of patients with autoimmune disease are intriguing and need indepth study.
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PMID:High incidence of IgG antibodies to phenolic glycolipid in non-leprosy patients in India. 960 81

Patients with defective immune systems are susceptible to Legionella infection, especially when the defect involves cell-mediated immunity. Thus, acquired immune deficiency syndrome (AIDS), corticosteroid administration, and hairy cell leukemia are risk factors for Legionellosis. Patients who have AIDS may be at risk for relapsing infections. Corticosteroid administration appears to predispose patients to simultaneous infection with multiple strains of Legionellae and development of lung abscess. Legionellosis also is found in patients who have humoral immune defects, but to a lesser extent. Thus, multiple myeloma, chronic lymphocytic leukemia, and chronic granulomatous disease have all been complicated by Legionella infection, although the risk seems to be minimal.
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PMID:Legionella and immunosuppression. 964 90

Antiphospholipid antibodies (aPL) are a heterogeneous group of antibodies that are detected in the serum of patients with a variety of conditions, including autoimmune (systemic lupus erythematosus), infectious (syphilis, AIDS) and lymphoproliferative disorders (paraproteinemia, myeloma, lymphocytic leukemias). Thrombosis, thrombocytopenia, recurrent fetal loss and other clinical complications are currently associated with a subgroup of aPL designating the antiphospholipid syndrome. In contrast, aPL from patients with infectious disorders are not associated with any clinical manifestation. These findings led to increased interest in the origin and pathogenesis of aPL. Here we present the clinical features of the antiphospholipid syndrome and review the origin of aPL, the characteristics of experimentally induced aPL and their historical background. Within this context, we discuss the most probable pathogenic mechanisms induced by these antibodies.
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PMID:Origin and pathogenesis of antiphospholipid antibodies. 969 16

Kaposi's sarcoma and non-Hodgkin's lymphoma were among the earliest recognized manifestations of the acquired immunodeficiency syndrome (AIDS) epidemic. Excluding these two tumors, the overall risk of all other cancers in human immunodeficiency virus (HIV)-infected individuals is similar to that of the general population. However, varying levels of evidence link several additional neoplasms to HIV infection. The evidence is strongest for an association with Hodgkin's disease, with lower relative and absolute risks than for non-Hodgkin's lymphoma. Anogenital intraepithelial neoplasia also appears to be HIV associated, but increases of invasive disease are still uncertain for both cervical and anal cancers. Various studies have suggested associations with testicular seminoma, multiple myeloma, oral cancer, and melanoma, but the data are inconsistent. Leiomyosarcoma and benign leiomyomas have increased in incidence in HIV-infected children but are unusual in HIV-infected adults. Conjunctival carcinoma is seen in HIV-infected individuals in sub-Saharan Africa but it is uncommon in Western countries. Most other cancers do not seem to have increased incidences in HIV infection. The etiologic mechanisms of HIV-related cancer likely differ among these diverse cancers and do not globally increase cancer risk.
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PMID:Association of non-acquired immunodeficiency syndrome-defining cancers with human immunodeficiency virus infection. 970 98

Intravenous immunoglobulins (IVIGs) are prepared from human plasma pools and further modified enzymatically or chemically. Despite careful selection of donors and inclusion of effective virus elimination steps in the production process, contamination with hepatitis C virus can still occur. IVIGs possess most of the characteristics of native immunoglobulins, such as antigen neutralisation and complement activation. The serum half-life of native immunoglobulin is about 21 days, and comparable half-lives have been reported for several IVIG preparations. IVIGs have received general approval for the treatment of primary immuno-deficiencies such as agammaglobulinaemia. Of the secondary immuno-deficiencies, only paediatric AIDS, chronic lymphocytic leukaemia and multiple myeloma, as well as allogeneic bone marrow transplantation, are accepted indications for IVIGs. Because of their immunomodulatory action, IVIGs are also recommended for the treatment of idiopathic thrombocytopenic purpura, Kawasaki disease (mucocutaneous lymph node syndrome) and, recently, Guillain Barre syndrome IVIGs have been investigated in a wide range of immunodeficient states (e.g. prematurity) and autoimmune diseases (e.g. multiple sclerosis), but conclusive results are not available. Since IVIGs are associated with a certain risk of transmission of viral infections and, secondly, because they are generally acknowledged as expensive drugs, their use requires careful consideration of risk, benefit and cost.
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PMID:Criteria for the appropriate drug utilisation of immunoglobulin. 1016 Feb 54

Primary effusion lymphoma (PEL) is a new lymphoma entity occurring predominantly, but not exclusively in HIV+ patients with acquired immunodeficiency syndrome (AIDS). PEL grows exclusively in body cavities as serous lymphomatous effusion without evidence of mass disease or dissemination. The cells are infected with the newly discovered human herpesvirus-8 (HHV-8), often accompanied by co-infection with Epstein-Barr virus (EBV). Several lymphoma cell lines have been established from patients with AIDS- and non-AIDS-associated PEL. Given their phenotypical relationship to plasma cells, several cytokines may be important for growth and survival of PEL cells. We investigated the spectrum of cytokines produced by nine HHV-8+ PEL cell lines, in comparison with five Burkitt lymphoma, seven other B non-Hodgkin's lymphoma (B-NHL) and seven multiple myeloma-derived cell lines. In addition, we tested the response of the PEL cells to selected cytokines and the effects of neutralizing anti-cytokine and anti-cytokine receptor antibodies. Using specific ELISAs, PEL cell lines were found to produce large amounts of interleukin-6 (IL-6; 10-5000 pg/ml), IL-6 soluble receptor (IL-6sR; 30-600 pg/ml), IL-10 (600-80,000 pg/ml) and oncostatin M (OSM; 50-80 pg/ml) which in most cases were significantly higher than the levels produced by the Burkitt, B-NHL or myeloma cell lines; on the contrary, PEL cell lines did not elaborate significant levels of macrophage inhibitory protein (MIP-1alpha) and leukemia inhibitory factor (LIF). However, the levels of MIP-1alpha were increased 10- to 100-fold by treatment with phorbol ester TPA. PEL cell lines did not respond proliferatively to IL-6, IL-10, IL-11, LIF, MIP-1alpha, or OSM. Incubation with IL-6sR and IL-6 inhibited cell growth. Anti-IL6 neutralizing antibodies had no effect on PEL cell line proliferation; conversely, whereas anti-IL6R alone inhibited only weakly, anti-gp130 and anti-gp130 plus anti-IL6R showed strong inhibitory effects (>20% inhibition in 5/9 lines and >60% inhibition in 3/9 lines). In summary, PEL cell lines produce high amounts of cytokines (IL-6, IL-10, OSM); proliferation could be inhibited by blocking the receptors of the IL-6 signaling pathway.
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PMID:Constitutive cytokine production by primary effusion (body cavity-based) lymphoma-derived cell lines. 1021 73

The most important link between the immune network theory and clinically useful therapies so far is the use of human intravenous immunoglobulin (IVIg) in the treatment of autoimmune diseases. Although still controversial, one of the main mechanisms that has been postulated for the in vivo effects of IVIg, is the selection of immune repertoires through idiotypic interactions. We describe here anti-idiotype IgG monoclonal antibodies (MAbs), which were obtained by immunization of syngeneic mice (Balb/c) with an anti-ganglioside antibody. These anti-idiotype MAbs show multiple idiotypic connections and share some of the properties of the IVIg pool. The antiidiotype (Ab2) MAbs B7 and 34B7 showed heterogeneous binding with the idiotypes of several anti-ganglioside antibodies, MAbs obtained from splenocytes of nonimmunized newborn mice, F(ab')2 fragments of IgG human myeloma proteins, and nonimmunoglobulin antigens. The recognition pattern of the B7 MAb to the idiotypes of human immunoglobulins was also studied using a phage display library obtained from the variable region genes of an asymptomatic AIDS patient and also F(ab')2 fragments obtained from an IVIg pool of healthy human donors. We also demonstrated that these MAbs produced some of the in vitro effects reported for the human IVIg pool, such as the inhibition of cell proliferation of human B and T cell lines and of normal human lymphocytes activated with different mitogens. Another striking property of the MAb B7 was its ability to induce a dose-dependent specific antibody T-cell response in vivo in syngeneic mice. Both anti-idiotype MAbs showed anti-metastatic effect in vivo when injected intravenously to mice inoculated with MB16-F10 melanoma cells. The antimetastatic effect of the antiidiotype MAbs was not observed in athymic mice inoculated with the same tumor. This kind of antibody can become an interesting tool for further exploration of the role of idiotypic network connections in the regulation of the immune system and to study the effects of interventions on network connectivity in experimental autoimmune disease, using a reagent better chemically defined than the IVIg pool.
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PMID:Novel cross-reactive anti-idiotype antibodies with properties close to the human intravenous immunoglobulin (IVIg). 1047 41


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