Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Tax1 protein of human T cell leukemia/lymphoma virus type I (HTLV-I) has been shown to stimulate the proliferation of human lymphocytes. Here we report that lymphocyte proliferation can be induced at extracellular Tax1 concentrations as low as 25 pM. The proliferative response induced by extracellular Tax1 is accompanied by an activation of endogenous interleukin-2 receptor alpha-chain (IL-2R alpha) expression in human lymphocytes. Functional activation of IL-2R alpha expression in peripheral blood lymphocytes treated with Tax1 was demonstrated using an [125I]IL-2-binding assay. In addition, an enzyme-linked immunosorbent assay demonstrated that soluble IL-2R alpha in the medium of IL-2- and Tax1-treated cells was over 13-fold greater than in the medium of control treated cells. Overexpression of IL-2R alpha is a common clinical feature of some patients with adult T-cell leukemia (ATL) and tropical spastic paraparesis/HTLV-I-associated myopathy (TSP/HAM). The ability of extracellular Tax1 protein to activate expression of IL-2R alpha in both infected and uninfected lymphocytes may contribute to the abnormal lymphocyte proliferation observed in both ATL and TSP/HAM.
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PMID:Activation of interleukin-2 receptor alpha expression by extracellular HTLV-I Tax1 protein: a potential role in HTLV-I pathogenesis. 150 87

Four hundred and sixty three patients with malignant diseases were studied over a period of two years; of these, 53 (11.44%) had neurological syndrome, both metastatic (32) and non metastatic (21). The lymphoma-leukaemia group accounted for 34 of the 53 cases. The maximum manifestations were seen in the 21-40 years age group, with male preponderance. The metastatic manifestations were as a result of cerebral (16), brainstem, cerebellar (12) and cord (4) deposits. These were confirmed by CT scan and myelogram. The non metastatic manifestations were peripheral neuropathies (7), leukoencephalopathy and intracranial haemorrhage (6 each), and myasthenic syndrome and myopathy (one each). These findings were confirmed by electrophysiological studies, CT scan, and histopathological examination. Autopsy studies were carried out in 12 of the 53 cases.
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PMID:Neurological manifestations of malignant diseases. 196 Jan 50

Thirty-three patients with multiple myeloma (11 untreated, 15 refractory and seven relapsed patients) have received vincristine and adriamycin infusion therapy with oral dexamethasone (VAD). The median number of course received was five. In addition 16 patients with lymphoid malignancy have received a median of four courses of VAD. Three patients who relapsed after VAD have received further VAD therapy making 52 patient treatments assessable for toxicity. Ten per cent had nausea, 4 per cent vomiting, 4 per cent total alopecia, 25 per cent constipation, 33 per cent paraesthesiae, 8 per cent proximal myopathy, 33 per cent dyspepsia, 23 per cent proven bacteraemia, and 19 per cent chest infections. Infections were not usually associated with neutropenia. Shingles was seen in four patients with myeloma, but none of the patients with lymphoid malignancy. The response rate in myeloma was 9/11, for previously untreated patients, 3/7 for relapsed, and 8/15 for refractory patients. Responses have been seen in other lymphoid malignancies-1/2 patients with relapsed acute lymphoblastic leukaemia had a complete remission. Two out of seven patients with chronic lymphocytic leukaemia achieved a partial remission, and a further three had a clinical improvement. Three out of six patients with non-Hodgkin lymphoma and one patient with macroglobulinaemia achieved a partial remission.
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PMID:VAD chemotherapy--toxicity and efficacy--in patients with multiple myeloma and other lymphoid malignancies. 311 84

A number of neurological disturbances occur during the treatment of childhood malignancies with cytotoxic drugs like vincristine, methotrexate, cytosine-arabinoside, cyclophosphamide, asparaginase and others. Neurological complications range from peripheral neuropathy, myopathy, myelopathy to encephalopathy with methotrexate induced encephalopathy leading to permanent brain damage or death in most cases. Irradiation of the brain can produce transient or permanent brain damage by a direct effect on nervous tissue and by altering the blood brain barrier or the blood circulation. The many conflicting reports concerning the quality of life of long-term survivors of childhood leukaemia do not give sufficient data for final conclusions. The experiences we have encountered over the past ten years seem to confirm the optimistic echo from others. There is, however, an urgent need for a prospective study to answer the all important question: will a child suffering from leukemia emerge physically and mentally unharmed after long and aggressive treatment?
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PMID:Therapy of acute lymphoblastic leukaemia in childhood: effects on the nervous system. 625 7

Of the many varieties of drug interactions, which occur when the disposition or actions of one drug are changed by another, only a few are serious or potentially fatal. A representative outline of some of these illustrates the problem. Precipitant drugs are those which produce the interaction, and object drugs are those whose effects are changed. The interactions which are usually significant are those which alter the metabolism, involve renal excretion, or change the effects of the object drug, especially when the object drug has a low therapeutic index (cardiovascular drugs, anticoagulants, drugs acting on the brain, hypoglycemic drugs, hormones, and cytotoxic drugs). Warfarin toxicity, for example, is produced by aspirin, phenylbutazone, and azapropazone. The dosage requirements of warfarin are reduced by chloramphenicol, ciprofloxacin and other quinolones, erythromycin and some of the other macrolides, metronidazole and other imidazoles, tetracyclines, amiodarone, cimetidine (but not ranitidine), and fibrates. Potassium-depleting drugs can potentiate the action of digoxin, and the elimination of digoxin can be reduced by amiodarone, propafenone, quinidine, and verapamil. Combined oral contraceptives can lose effectiveness through the interaction of carbamazepine, griseofulvin, phenytoin, or rifampicin, which increase estrogen metabolism. In addition, broad-spectrum antibiotics such as ampicillin or tetracyclines also reduce contraceptive effectiveness by altering gut absorption. Even a single drink of an alcoholic beverage may be dangerous to people taking antidepressants, antihistamines, antipsychotic drugs, benzodiazepines, or lithium. Antihistamines suffer inhibited metabolism in the liver if taken in conjunction with the antifungal imidazoles and some of the macrolide antibiotics. Cardiotoxicity of antihistamines is also enhanced by drugs with similar cardiotoxic effects. Lithium potentiation is enhanced by the new serotonin-reuptake inhibitors, and lithium excretion can be reduced by diuretics or fluoxetine. When drugs such as antifungal imidazoles, azapropazone, or phenylbutazone are permitted to inhibit the metabolism of sulphonylureas, hypoglycemic effects are enhanced and, if unnoticed, may cause brain damage. Fibrates should not be combined with HMG-CoA reductase inhibitors because of the increased risk of myopathy. Patients taking non-selective monoamine oxidase inhibitors should avoid amine-containing foods and drugs such as matured cheeses, meat, yeast extracts, some wines, unfresh protein, and cold-curing medications. The metabolism of azathioprine is inhibited by allopurinol, and this combination requires a reduced dosage of azathioprine. Mercaptopurine, used in the treatment of leukemia, is also a metabolite of azathioprine. Sources of comprehensive information on drug interactions are 1) the "British National Formulary," appendix 1; 2) Chapter 10 of "The Oxford Textbook of Clinical Pharmacology and Drug Therapy"; and 3) a monograph by Stockley entitled "Drug Interactions."
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PMID:Serious drug interactions. 790 48

To investigate the mechanism of polymyositis in human T-cell leukemia virus type I (HTLV-I) infection, we studied 6 HTLV-I-positive patients, 3 with polymyositis and 3 with adult T-cell leukemia but without clinical signs of muscle disease, by (a) quantitative single or double immunocytochemistry on serial 4-microns-thick muscle biopsy sections using antibodies to lymphocyte subsets, major histocompatibility complex (MHC) antigens, and HTLV-I proteins; (b) polymerase chain reaction using HTLV-I primers in the RNA and DNA extracted from 50 micrograms of muscle tissue or from serial 5-microns-thick fresh-frozen tissue sections; and (c) cocultures of the patients' HTLV-I-positive peripheral blood lymphocytes with their homologous muscles searching for replication of HTLV-I within the myotubes. In the muscle of patients with HTLV-I-associated myopathy, the predominant endomysial cells surrounding healthy muscle fibers were CD8+ cells followed by CD4+ cells and macrophages. MHC-I antigens were ubiquitous in the muscles of all 6 patients, even in those without endomysial inflammation. HTLV-I sequences were amplified from the whole muscle biopsy specimens but the cells harboring viral antigens were rare endomysial macrophages and not muscle fibers. Although HTLV-I sequences were amplified from all the patients' peripheral blood lymphocytes, these cells did not exert myotoxicity or resulted in viral replication in cocultures with their homologous myotubes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Polymyositis in patients infected with human T-cell leukemia virus type I: the role of the virus in the cause of the disease. 794 97

Two proviral HIV transgenic mouse models, one bearing wild-type HIV proviral DNA and the other a modified provirus in which the viral LTRs contained the core enhancer of the Moloney murine leukemia virus (MLV), were compared. The MLV/HIV chimeric LTR, in which the MLV enhancer replaced the NF-kappa B-binding motifs, was transcriptionally active in human and murine cells in vitro and virus containing the chimeric LTR was replication competent in human cell cultures. Transgenic mice derived from microinjections of chimeric MLV/HIV proviral DNA transcribed HIV genes at a greater frequency and at higher levels than wild-type HIV proviral transgenic mice. MLV/HIV mice were also more apt to develop disease; wasting, periocular infections, and a degenerative myopathy characterized the most predominant phenotype. The tissue specificities of the wild-type and chimeric LTRs in transgenic mice were remarkably similar, but a significant difference was apparent in lymphoid cells. Basal level and LPS-inducible HIV gene expression occurred in peritoneal and bone marrow-derived macrophages from wild-type HIV transgenic mice. In contrast, HIV gene expression in macrophages from MLV/HIV mice was undetectable, even following LPS induction. However, cultured splenocytes from MLV/HIV mice supported HIV proviral gene transcription better than splenocytes from HIV mice, particularly after induction with LPS or anti-IgD antibody but not with concanavalin A. These data suggest that in transgenic mice, the HIV and MLV/HIV LTRs display a differential tropism for macrophages and B cells, respectively. HIV and MLV/HIV transgenic mice represent alternative models amenable to in vivo studies of HIV gene regulation in lymphoid cells, the induction of HIV-related disease and the evaluation of anti-HIV therapies.
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PMID:Models of HIV type 1 proviral gene expression in wild-type HIV and MLV/HIV transgenic mice. 884 15

In an effort to augment human immunodeficiency virus type 1 (HIV-1) gene expression in transgenic mice, an infectious proviral DNA clone was modified by deleting the two NF kappa B binding sites and some adjacent upstream LTR sequences and replacing them with the core enhancer of Moloney murine leukemia virus (MLV). Two independent lines of MLV/HIV transgenic mice were established that expressed HIV-1-specific RNA in lymphoid tissue, striated skeletal muscle, and the eye lens. Heterozygous animals from each transgenic line spontaneously developed an inflammatory disease of the eye associated with the production of copious amounts of purulent lacrimal secretions beginning at 2 weeks of age. Periorbital abscess formation became grossly apparent by 2 months of age and Pasteurella pneumotropica was cultured from the harderian glands and conjunctival surfaces of many of the MLV/HIV animals but not their nontransgenic, cohabiting littermates. This gram-negative commensal bacterium has been previously associated with a similar disease phenotype in immunocompromised (e.g., nude mice) rodent colonies. MLV/HIV mice developed normally until 15 weeks of age, when weight loss and wasting occurred, culminating in premature death (as earlier as 6 months of age). The cachexia was associated with an initially focal and subsequently progressive myopathy, coinciding with age-related increases of HIV gene expression in muscle.
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PMID:Myopathy and spontaneous Pasteurella pneumotropica-induced abscess formation in an HIV-1 transgenic mouse model. 886 75

Sporadic inclusion body myositis (IBM) is the most common inflammatory myopathy affecting patients over the age of 50 years. Dysimmune and degenerative aetiologies have been postulated, but viral infections have not been associated with the disease. Two HIV-I (human immunodeficiency virus type 1) infected men and one woman infected with HTLV-1 (human T cell leukaemia virus type 1) developed progressive proximal muscle weakness unrelated to antiretroviral therapy. Their muscle biopsies were studied by light and electron microscopy, by immunocytochemistry to determine the expression of major histocompatibility complex (MHC) molecules and identify the type of infiltrating cells and T cell receptor (TCR) subunits, and by reverse transcription-polymerase chain reaction (RT-PCR) and single or double immunocytochemistry to search for retrovirally infected endomysial cells. The clinical features were consistent with sporadic IBM. The muscle biopsies showed primary endomysial inflammation, red-rimmed vacuoles, amyloid deposits, eosinophilic inclusions, and small round fibres in groups, all diagnostic of IBM. The muscle fibres expressed MHC class-1 antigens and were invaded primarily by CD8+ T-lymphocytes preferentially bearing TCR V beta 5.1 and V beta 13 chains. The HIV-1 or HTLV-1 antigens were detected only on endomysial macrophages on or around muscle fibres, but not within the muscle fibres. We conclude that IBM occurs in HIV-1 and HTLV-1 infected individuals and has a clinical, histological and immunological pattern identical to sporadic IBM in the non-retrovirally infected patients. Retroviruses do not directly infect the muscle, but persistent retroviral infections may provide superantigenic stimulation and trigger an endomysial inflammatory response identical to that occurring in sporadic IBM.
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PMID:Inclusion body myositis in HIV-1 and HTLV-1 infected patients. 900 95

Several infectious agents can cause chronic or acute myopathy. Most current investigations into possible infectious causes of the idiopathic inflammatory myopathies have focused on retroviruses, including HIV and human T-cell leukemia-lymphoma virus type I. In both cases, viruses likely do not directly infect muscle fibers but instead induce an immunologically mediated myositis. Other interest has focused on enteroviruses as potential etiologic agents of idiopathic inflammatory myopathy, but their relationship to human myositis is less clear. In addition to chronic muscle disease, several infectious agents can cause acute myositis, including pyomyositis, which is being recognized in temperate climates with increasing frequency, and rhabdomyolysis.
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PMID:Infectious agents associated with myopathies. 901 53


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