Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 25,000 dalton protein of Mason-Pfizer monkey virus (MPMV) was isolated by gel filtration chromatography. In agreement with results from other laboratories, antisera to type-C and the non-type-C bovine leukemia and equine infectious anemia viruses did not precipitate 125I-labelled MPMV p25. In addition, these viruses did not cross-react in a competition radioimmunoassay for MPMV p25. Twenty-one human tissues (15 breast carcinomas, 2 normal breasts, 3 acute myelogenous leukemias and 1 sarcoma) were fractionated by detergent solubilization, ammonium sulfate precipitation, and DE-52 anion exchange chromatography. These methods were shown to be highly effective for purification of MPMV p25. Under assay conditions which minimized incubation damage to the 125I-MPMV p25, all tissues failed to react in the competition radioimmunoassay (RIAT). Two hundred and two human sera or plasma specimens, including those from patients with breast cancer and 33 age-matched controls, from 50 patients with hematologic malignancies, from 12 patients with amyotrophic lateral sclerosis, and from 14 patients with systemic lupus erythematosis, were examined for antibodies to MPMV p25. With the exception of two multiple myeloma plasma which produced artifactual false positive reactions based on hypergammaglobulinemia, a known complication of salt precipitation radioimmunoassays, the remainder of the specimens were negative for evidence of MPMV p25 antibodies.
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PMID:Radioimmunoassay for the major structural protein of Mason-Pfizer monkey virus: Attempts to detect the presence of antigen or antibody in humans. 40 48

Among relatives of Ashkenazi schizophrenic probands the rate of amyotrophic lateral sclerosis was 3/1,000, compared to expected population rates of approximately 2/100,000. Relative risk of bleeding disorders, including hematologic cancers, was increased more than three-fold compared to controls. Co-occurrence of motor neuron disease and blood dyscrasias, accompanied by psychosis, has long been recognized. A virally mediated autoimmune pathogenesis has been proposed. However, the familial co-occurrence of these three disease entities raises the possibility that the disease constellation be considered as a manifestation of a common underlying genetic defect. Such expansion of the spectrum of affectation might enhance the power of both candidate gene and linkage studies. Based on these findings the loci suggested as candidate regions in schizophrenia include a potential hot spot on chromosome 21q21-q22, involving the superoxide dismutase and amyloid precursor protein genes. Alternatively, genes on other chromosomes involved in the expression, transcription, or regulation of these genes, or associated with the illnesses of high frequency in these pedigrees are suggested. Candidates include the choroid plexus transport protein, transthyretin at 18q11.2-q12.1; the t(14;18)(q22;21) characterizing B-cell lymphoma-2, the most common form of hematologic cancer; and the 14q24 locus of early onset Alzheimer's disease, c-Fos, transforming growth factor beta 3, and heat shock protein A2. Expression of hematologic cancers and the suggested candidate genes are known to involve retinoid pathways, and retinoid disregulation has been proposed as a cause of schizophrenia.
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PMID:Elevated risks for amyotrophic lateral sclerosis and blood disorders in Ashkenazi schizophrenic pedigrees suggest new candidate genes in schizophrenia. 781 May 88

The human T cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that infects 10-20 million persons around the world. Initially associated with the hematological malignancy adult T cell leukemia/lymphoma (ATLL), HTLV-1 is also the cause of a chronic progressive myelopathy named "HTLV-1-associated myelopathy/tropical spastic paraparesis" (HAM/TSP). HAM/TSP arises as the tip of the iceberg of an assortment of neurological syndromes triggered by the virus such as inflammatory myopathies, polyneuropathies, amyotrophic lateral sclerosis (ALS)-like syndromes, dysautonomia, and cognitive impairment. HAM/TSP typifies a chronic progressive spastic paraparesis with neurogenic bladder and minimal sensory signs. The neuropathology of HAM/TSP is concentrated in the thoracic spinal cord and is typically biphasic. Initially, there is a perivascular lymphocytic cuffing and mild parenchymal mononuclear infiltrates. Subsequently, this is replaced by gliosis and scarring. The neuropathogenesis of HTLV-1 is still partially understood. At present, the therapy of HAM/TSP remains basically symptomatic.
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PMID:Update on Neurological Manifestations of HTLV-1 Infection. 2578 12

Alisertib (MLN8237, ALS), an Aurora kinase A (AURKA) inhibitor, exerts potent anti-tumor effects in the treatment of solid tumor and hematologic malignancies in preclinical and clinical studies. However, the fully spectrum of molecular targets of ALS and its anticancer effect in the treatment of chronic myeloid leukemia (CML) are not clear. This study aimed to examine the proteomic responses to ALS treatment and unveil the molecular interactome and possible mechanisms for its anticancer effect in K562 cells using stable-isotope labeling by amino acids in cell culture (SILAC) approach. The proteomic data identified that ALS treatment modulated the expression of 1541 protein molecules (570 up; 971 down). The pathway analysis showed that 299 signaling pathways and 459 cellular functional proteins directly responded to ALS treatment in K562 cells. These targeted molecules and signaling pathways were mainly involved in cell growth and proliferation, cell metabolism, and cell survival and death. Subsequently, the effects of ALS on cell cycle distribution, apoptosis, and autophagy were verified. The flow cytometric analysis showed that ALS significantly induced G2/M phase arrest and the Western blotting assays showed that ALS induced apoptosis via mitochondria-dependent pathway and promoted autophagy with the involvement of PI3K/Akt/mTOR, p38 MAPK, and AMPK signaling pathways in K562 cells. Collectively, this study provides a clue to quantitatively evaluate the proteomic responses to ALS and assists in globally identifying the potential molecular targets and elucidating the underlying mechanisms of ALS for CML treatment, which may help develop new efficacious and safe therapies for CML treatment.
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PMID:A SILAC-based proteomics elicits the molecular interactome of alisertib (MLN8237) in human erythroleukemia K562 cells. 2680 90