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)

Amyloidosis is the name given to a group of clinically protean diseases whose common feature is the tissue accumulation of amyloid fibrils which have specific optical and staining properties, and are both insoluble in physiological solvents and resistant to proteolytic enzymes. Fibril deposition and progressive extracellular infiltration eventually result in atrophy due to compression. The structure of these fibrils embraces a wide range: immunoglobulin light chain or their fragments, acute phase proteins, hormones, protease inhibitors, beta 2-microglobulin, natriuretic peptides, and proteins whose function is still unknown. Despite this heterogeneity, however, they share a common crystallographic beta-pleated sheet structure. The clinical spectrum includes apparently primary forms, amyloidosis of myeloma, forms secondary to familial Mediterranean fever, Alzheimer's disease, forms associated with type 2 diabetes or medullary carcinoma of the thyroid, inherited-familial amyloidosis, and other less common conditions. Two pathogenetic phases are involved: enhanced production of precursor proteins and their abnormal enzyme cleavage, resulting in the formation of intermediate products corresponding to the amyloid fibrils. The results of treatment are still disappointing: alkylating agents and/or cortico-steroids are used in primary forms and for amyloidosis of myeloma; colchicine in familial Mediterranean fever; DMSO in renal amyloidosis; plasmapheresis in inherited-familial forms, together with the supportive management obviously dictated by clinical manifestations.
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PMID:Amyloidosis: clinical picture, immunological and biomolecular features, treatment prospects. 174 46

Amyloid is a beta-pleated fibrillar protein principally constituted of light chains of immunoglobulins (kappa or lambda) in primary or myeloma-associated amyloidosis, of AA proteins in secondary amyloidosis and familial. Mediterranean fever, and of variants of prealbumin - now called transthyretin - in senile amyloidosis and in familial polyneuropathies. Other identified amyloidogenic proteins involve APUD protein derivatives (calcitonin), beta 2 microglobulin in chronic hemodialysis-related amyloidosis and beta protein in Alzheimer disease. After a short review of experimental findings and theories concerning the pathogenesis of amyloid deposition, the clinical aspects of amyloidosis are discussed stressing their great diversity. The diagnostic approach is also examined, with particular emphasis on rectal and kidney biopsy and subcutaneous adipose tissue aspirates. Finally, some comments on the treatment of amyloidosis (role of colchicine and DMSO) are made.
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PMID:Amyloid proteins and amyloidoses: complexity updated. 266 33

A 40-year-old man who developed acute myelomonoblastic leukemia (M4) after 7 years of treatment for multiple myeloma with the alkylating agent melphalan and steroids is presented. Leukemia was treated with courses of adriblastin, cytosine arabinoside, and thioguanin (DAT protocol), with a 8 months' survival.
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PMID:Acute myelomonoblastic leukemia in a patient with multiple myeloma. 271 63

Degenerative central nervous system diseases such as Alzheimer's disease and lymphoreticular malignancies such as multiple myeloma occur with increased frequency with advancing age. Relatives of early-onset Alzheimer's disease patients may have an increased risk of lymphoreticular malignancies. This led us to evaluate the family history of central nervous system diseases in a case-control study of multiple myeloma. Thirteen of 439 multiple myeloma cases had one or more first-degree relatives with degenerative or demyelinating central nervous system disease. In comparison, there were nine "positive" family histories in 1,317 matched hospital controls (relative risk = 4.4, 95% confidence interval = 1.9-10.3). Relative risks for the component categories of Parkinson's disease, multiple sclerosis, and miscellaneous degenerative central nervous system diseases were 3.0, 4.0 and 11.9, respectively. Our findings suggest that the degenerative and demyelinating central nervous system diseases and the lymphoreticular malignancies may comprise an etiologically related group of "protean diseases." These diseases may have a shared genetic susceptibility, possibly an immunologic abnormality. The varied disease manifestation in family members suggests a second necessary etiologic step of a variable and possibly environmental nature.
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PMID:Familial aggregation of multiple myeloma and central nervous system diseases. 292 51

We have established a monoclonal antibody (MoAb) AM34 (IgG1) which was prepared by a hybridoma constructed from fusion between murine myeloma cells and murine splenocytes. Crude amyloid proteins which were used as immunogen, were extracted from the kidney of a patient with rheumatoid arthritis by the distilled water method. This antibody strongly reacted with all 8 cases of secondary amyloidosis, but did not react or very weakly reacted with 17 tissue sections of primary or myeloma-associated amyloidosis. Other amyloid tissues did not give any positive reaction. Interestingly, 6 brain tissues of Alzheimer's disease clearly showed positive staining with this antibody, whereas two apparently normal brain tissues exhibited negative staining. Senile plaque cores, neurofibrillary tangles (weakly stained) and cerebrovascular amyloid in Alzheimer's disease were stained. Absorption of the MoAb AM34 with the crude amyloid proteins abolished the immunoreactivity of the MoAb AM34 not only with the kidney tissue section of the secondary amyloidosis, but also with the above mentioned portions of the brain in the case of Alzheimer's disease. Therefore, these immunohistological data suggest that the MoAb AM34 recognizes common epitope which exists in amyloid deposits of both secondary amyloidosis and Alzheimer's disease. An inhibition test on the kidney section showed that the reactivity of MoAb AM34 was not at all inhibited by the pretreatment of the section with 10 times higher concentration of anti-human amyloid A (AA) MoAb KM268 which was prepared against synthetic peptides of AA protein, suggesting that MoAb AM34 might react with amyloid-related protein other than AA protein. In addition, MoAb KM268 did not react with any lesions in Alzheimer's disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of novel proteins associated with secondary amyloidosis and Alzheimer's disease by monoclonal antibody. 320 35

A 48-year-old woman with multiple myeloma, developed progressive neurological disturbances one year after the bone marrow remission. There was neither intrathecal chemotherapy nor brain irradiation. She received cyclophosphamide, phenylalanine mustard, urethane, and prednisolone intravenously or orally. At postmortem examination the cerebral hemispheres had a conspicuous destruction of white matter, consistent with a necrotizing leukoencephalopathy with focal and diffuse demyelination. No myeloma cells were found in the nervous system. Alzheimer type II glias and abnormal glias closely resembling Alzheimer type I glia were numerous in the affected white matter. No oligodendroglias with intranuclear inclusions were found. No virus particles were detected by electron microscope. The neuropathological changes had features similar to those seen in leukoencephalopathy with intrathecal administration of methotrexate. The glial abnormality, the most striking feature in the present case, strongly suggests toxic and metabolic disturbances. It appears that the leukoencephalopathy of the present case developed on the more complicated etiopathogenesis. However, it would be emphasized that the side-effects of the drugs could be considered as one of the etiologica factors causing the glial abnormality.
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PMID:Necrotizing leukoencephalopathy and treated multiple myeloma. An autopsy case without intrathecal chemotherapy or irradiation of the brain. 646 55

Interleukin-6 (IL-6) is a pro-inflammatory cytokine with a wide range of functions. Perhaps the most important physiologically is its role as a mediator of the acute phase inflammatory response. Normally, there is little measurable IL-6 in the circulation, but levels increase abruptly to nanogram amounts during an inflammatory process. During aging, it has been proposed that the tight regulation of IL-6 gene expression becomes less effective and levels are measurable even when there is no evidence for inflammation. Several investigators have identified this cytokine as being involved in the pathogenesis of various disease processes and we have suggested that certain age-associated diseases are directly related. Among these are late-life lymphoma and myeloma, osteoporosis and possibly Alzheimer's disease.
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PMID:The role of interleukin-6 in certain age-related diseases. 783 89

Epidemiologic studies document that work in the agricultural sector is associated with many occupational health hazards. Exposure to organic dusts and airborne microorganisms and their toxins may lead to respiratory disorders. The burden of exposure-related chronic bronchitis, asthma, hypersensitivity pneumonitis, organic-dust toxic syndrome, and chronic airflow limitation can be diminished by appropriate preventive measures. The contribution of exposures to agricultural chemicals to cancers and neurodegenerative disorders is being investigated. Some studies document that farmers and those in related industries are at higher risk for the development of cancer of the stomach, soft tissue sarcoma, non-Hodgkin's lymphoma, and multiple myeloma. Chronic encephalopathy and Parkinson's and Alzheimer's diseases are being studied in relation to agricultural chemicals. The possible carcinogenicity and neurotoxicity of pesticides emphasize the need to promote the safe use of chemicals. Another area for health promotion programs is disabling injuries and traumatic deaths. Farm accidents are important because of their frequent occurrence among young people and disturbing fatality rates. Other health issues of concern in these industries include skin diseases, hearing loss, and stress.
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PMID:Epidemiology of health and safety risks in agriculture and related industries. Practical applications for rural physicians. 847 Mar 86

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

Amyloidosis is a heterogenous group of diseases, all characterized by extracellular deposition of amyloid either systemically or localized. Of wellknown diseases are Alzheimer's dementia, AL-amyloidosis (e.g. in multiple myeloma) and AA-amyloidosis (e.g. in rheumatoid arthritis). Amyloid is composed of three components of which the fibrillary component is the basis of amyloid classification. Many types of amyloid have a systemic distribution and give rise to varying symptoms. The diagnosis is based on biopsy, preferably of abdominal subcutis. The prognosis is poor, however, recent investigations on the three-dimensional structure of the P-component provide hope for future therapy.
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PMID:[Amyloidosis. A review]. 1037 50


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