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)

Ischemic colitis is a disease complex that presents as a continuum of mucosal and submucosal hemorrhage, late stricture formation and frank gangrene. The exact form depends upon the degree, site and duration of the vascular occlusion, the presence of collateral vessels and the intraluminal pressure in the colon. In a study group of 19 women and seven men, the majority of whom were in the seventh to eighth decades of life, most frequent symptoms were crampy abdominal pain and abdominal distention associated with bloody diarrhea. Ischemic colitis occurred with increased colonic intraluminal pressure, generalized decreased vascular flow and embolic phenomenon. The predominating predisposing causes were atherosclerosis, shock and congestive heart failure as well as leukemia. The results of barium enema studies showed a pathognomonic condition that included thumbprinting, mucosal ulcerations and sacculations. Arteriography, generally, was not helpful, and results of sigmoidoscopy were invariably negative, since the rectum seldom is involved in ischemic colitis. Conservative treatment should include intestinal rest, low molecular weight dextran and antibiotics. Early operative intervention is recommended when conservative therapy fails or signs of peritoneal irritation become evident.
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PMID:Ischemia of the colon. 125 13

About 15% of patients with cancer have cerebrovascular lesions, resulting from 4 kinds of disorders sometimes intermingled in advanced disseminated cancer: coagulation disorders, direct effects of the tumor, infections and therapeutic measures. Infarction, hardly less frequent than hemorrhage, mostly complicates lymphoma and carcinoma. Hypercoagulation states, such as chronic disseminated intravascular coagulation, nonbacterial thrombotic endocarditis, and nonmetastatic cerebral venous thrombosis account for about 50% of cases. Tumor emboli, as seen in intravascular malignant lymphomatosis, arteritis related to aspergillus, granulomatous angiitis with or without herpes zoster and radiation-induced atherosclerosis are rarer. Cerebral hemorrhages, excluding bleeding from the metastases of choriocarcinoma and melanoma are mainly associated with leukemia by acute disseminated intravascular coagulation as in promyelocytic leukemia, by leukostasis or by pancytopenia. Both infarction and hemorrhage rarely reveal the neoplasia. Lesions are often small and disseminated, and therefore produce a picture of diffuse acute or subacute encephalopathy rather than acute focal deficits. Finally, there may be no relationship between the cerebrovascular event and the neoplasia, and atherosclerosis or traumatic subdural hematoma may well be the causal factor.
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PMID:[Cerebrovascular complications of cancers]. 130 55

Clinical and experimental evidence suggests that shock, arthritis, osteoporosis, colitis, leukemia, diabetes, wasting and atherosclerosis are mediated, in part, by interleukin 1 (IL-1). Inhibition of this cytokine has been a strategy for studying disease and for new drug development. A naturally-occurring IL-1 inhibitor (IL-1 receptor antagonist, IL-1ra) that blocks binding of IL-1 to its receptors has been cloned and produced in recombinant organisms. IL-1ra reduces the severity of sepsis, colitis, arthritis and diabetes in animals and is presently being tested in humans with arthritis, shock and myelogenous leukemia.
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PMID:Blocking IL-1: interleukin 1 receptor antagonist in vivo and in vitro. 183 80

It is difficult to study the regulation and interactions of the connective tissue macromolecules in vivo. However, studies of genetically determined diseases of the connective tissues have yielded a large amount of new information in these areas. Specific molecular defects can then be correlated with the functional and pathological changes in the tissues. We have concentrated on this approach which takes advantage of the large number of families with genetic diseases who come to our Hospital from all parts of Australasia and also takes advantage of developments in molecular biology in our Unit which were initiated with a RACS John Mitchell Crouch Fellowship. In addition to these studies on naturally occurring mutations we are also studying specific mutations that we are able to produce in specific regions of the collagen molecule. Another approach takes advantage of a unique model culture system developed in our Unit. These studies will be supplemented by various collaborative projects such as current ones involving smooth muscle cells in atherosclerosis, bone cells metabolism and myelofibrosis in leukaemia.
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PMID:Regulation and organization of connective tissues. 307 87

Analysis of controlled studies performed by the Polycythemia Vera Study Group (P.V.S.G.) and the European Organization for Research in Treatment of Cancer (E.O.R.T.C.) indicate that busulphan (Myleran) (BU) is the treatment of choice for polycythemia vera (PV). BU is particularly effective as compared to aspirin and dipyridamole (Persantine) or radioactive phosphorus (32P) in preventing the thrombotic and atherosclerotic complications of PV. In contradistinction to chlorambucil (CM), BU is not associated with an unacceptable increase in the incidence of leukemia. The pharmacology of BU remains unclear, but certainly it cannot be considered a classic alkylating agent. BU suppresses the activity of the reverse transcriptase-like RNA dependent DNA polymerase in the platelets of these patients. A clearer understanding of the role of BU in the treatment of the myeloproliferative disorders will provide important insights into the etiology and pathogenesis not only of preneoplastic states, but also thrombosis and atherosclerosis.
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PMID:Busulphan: effect on platelet RNA dependent DNA polymerase--implications in the treatment of polycythemia vera, thrombosis and atherosclerosis. 618 58

The oxidative modification of low-density lipoprotein by macrophages may be an important mechanism in the pathogenesis of atherosclerosis. The human monocytic leukaemia cell line THP-1, when stimulated with phorbol ester, shares many properties with human monocyte-derived macrophages. Oxidation of LDL by these cells was characterised by depletion of alpha-tocopherol, increases in thiobarbituric acid reactive substances and increases in electrophoretic mobility. The LDL particles were also converted to a form which increased accumulation of cholesteryl esters within macrophages. The oxidative mechanism appeared to be dependent upon the presence of thiols in the cellular medium. Oxidation of LDL by THP-1 macrophages, and production of thiols by these cells, were dependent upon the presence of L-cystine in the medium. Furthermore, cellular oxidation of LDL could be partially mimicked by the addition of cysteine to Hams F10 medium. Macrophage-independent oxidation of LDL, mediated by the addition of copper ions, was inhibited by cystine and cysteine in phosphate buffered saline, but not in Hams F10 medium. The glutathione content of THP-1 macrophages was also dependent upon the presence of cysteine or cystine in the medium, but inhibition of glutathione synthesis by buthionine sulfoximine did not prevent the production of thiols or the oxidation of LDL by THP-1 macrophages.
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PMID:Human (THP-1) macrophages oxidize LDL by a thiol-dependent mechanism. 888 36

Monocyte chemoattractant protein-1 (MCP-1) mediates monocyte migration into tissues in inflammatory diseases and atherosclerosis. We have investigated structure-activity relationships for human MCP-1. Mutations were introduced based upon differences between MCP-1 and the structurally related but functionally distinct molecule interleukin-8 (IL-8). Mutant proteins produced using the baculovirus/insect cell expression system were purified and their ability to stimulate monocyte chemotaxis and elevation of intracellular calcium in THP-1 monocytic leukaemia cells was measured. Two regions in MCP-1 were identified as important for its biological activity. One region consists of the sequence Thr-Cys-Cys-Tyr (amino acids 10-13). Point mutations of Thr-10 to Arg and Tyr-13 to Ile greatly lowered MCP-1 activity. The second functionally important region is formed by Ser-34 and Lys-35. Insertion of a Pro between these two residues, or their substitution by the sequence Gly-Pro-His, caused nearly complete loss of MCP-1 activity. Competition binding experiments showed that the mutations that affected activity also lowered the ability to compete with wild-type MCP-1 for receptors on THP-1 cells. Point mutations at positions 8, 15, 30, 37, 38 and 68 had little effect on MCP-1 activity. The important regions that we have identified in MCP-1 correspond with previously identified functionally important regions of IL-8, suggesting that the two molecules bind to their respective receptors by similar contacts.
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PMID:Site-directed mutagenesis of monocyte chemoattractant protein-1 identifies two regions of the polypeptide essential for biological activity. 857 3

To understand the role of the proinflammatory cytokine interleukin-1 (IL-1) in disease, investigators have studied how production of the different members of the IL-1 family is controlled, the various biologic activities of IL-1, the distinct and various functions of the IL-1 receptor (IL-1R) family, and the complexity of intracellular signaling. Mice deficient in IL-1Beta, IL-1Beta converting enzyme, and IL-1R type I have also been studied. Humans have been injected with IL-1 (either IL-1alpha or IL-1beta) for enhancing bone marrow recovery and for cancer treatment. The IL-1-specific receptor antagonist (IL-1Ra) has also been tested in clinical trials. The topics discussed in this review include production and activities of IL-1 and IL-1Ra molecules, the effects of IL-1 on gene expression, functions of cell-bound and soluble IL-1 receptors, the importance of the IL-1R accessory protein, newly discovered signal transduction pathways, naturally occurring cytokines limiting IL-1 production or activity, the effects of blocking cyclooxygenase and nitric oxide, and the outcomes of IL-1 and IL-1 Ra in human trials. Special attention is paid to IL-1beta converting enzyme and programmed cell death. The roles of IL-1 in hematopoiesis, leukemia, atherosclerosis, and growth of solid tumors are also discussed. This is a lengthy review, with 586 citations chosen to illustrate specific areas of interest rather than a compendium of references. At the end of each section, a short commentary summarizes what the author considers established or controversial topics linking the biology of IL-1 to mechanisms of disease.
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PMID:Biologic basis for interleukin-1 in disease. 863 Mar 72

The regulation of macrophage lipoprotein lipase (LPL) by cytokines is of potentially crucial importance in the pathogenesis of atherosclerosis and in the responses to endotoxin challenge. However, the precise mechanisms by which different cytokines modulate the expression of macrophage LPL activity are poorly understood. The action of six cytokines and bacterial lipopolysaccharide (LPS) on LPL function using the murine J774.2 cell line as a model system has, therefore, been studied. Although exposure to LPS, interleukin 11 (IL-11), tumour necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma) and IL-1, over the physiological range of concentrations, resulted in a decrease in the heparin-releasable LPL activity, LPL-mRNA levels and LPL-protein content of the cells, stimulation with IL-6 and leukaemia inhibitory factor (LIF) had no effect. The maximum suppression of LPL activity and mRNA levels in the cells by IFN-gamma (60%) was lower than that produced by LPS, IL-11, TNF-alpha and IL-1 (78-97%). Each cytokine displayed a characteristic dose-dependent pattern for the suppression of LPL activity and mRNA levels with IL-11/TNF-alpha being more potent than IFN-gamma/IL-1. More than 80% of the decrease in the LPL activity, at all doses of IL-11, TNF-alpha, IFN-gamma and IL-1, was due to a corresponding reduction in the mRNA levels. The time course of responses to LPS, IL-11, TNF-alpha, IFN-gamma and IL-1 were similar, with the time required to achieve half maximal suppression of LPL activity being between 7 and 9.5 h in each case. These results indicate that LPL in J774.2 macrophages is regulated differentially by various cytokines and that the major control responsible for the reduction of LPL activity by IL-11, TNF-alpha, IFN-gamma and IL-1 is exerted at the level of mRNA metabolism (decreased transcription or RNA stability). The responses identified also displayed several differences to those described previously for adipocytes (e.g. 3T3-L1 cell line), thereby suggesting the existence of potential cell-specific mechanisms for the regulation of LPL by cytokines.
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PMID:Differential regulation of lipoprotein lipase in the macrophage J774.2 cell line by cytokines. 889 33

The oxysterols, 7beta-hydroxycholesterol and 7-ketocholesterol, are involved in the cytotoxicity of oxidized LDL. To elucidate their molecular mechanisms, the human promonocytic leukemia cells U937 and U4 were used. U4 cells overexpressing Bcl-2 were obtained by transfection of U937 cells. 7Beta-hydroxycholesterol and 7-ketocholesterol induced nuclear condensation and/or fragmentation, internucleosomal DNA fragmentation, and IL-1beta secretion, which were partially inhibited by Bcl-2 overexpression. These findings underline that these oxysterols could constitute major risk factors in atherosclerosis by their cytotoxicity and their ability to induce IL-1beta release which might favor the recruitment of immunocompetent cells in the atherosclerotic plaque.
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PMID:Induction of apoptosis and of interleukin-1beta secretion by 7beta-hydroxycholesterol and 7-ketocholesterol: partial inhibition by Bcl-2 overexpression. 942 50


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