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)

Leukotrienes have been proposed as important chemical mediators of allergic inflammation, and there is evidence that azelastine (Astelin) can affect leukotriene-mediated allergic responses. One of the enzymes required for the synthesis of leukotrienes from arachidonic acid is 5-lipoxygenase (5-LO). Azelastine, which is preferentially taken up by the lung and alveolar macrophages, inhibits leukotriene generation in the airways. This property of azelastine may contribute to its therapeutic efficacy in the long-term treatment and management of rhinitis and asthma. Azelastine does not directly inhibit 5-LO in disrupted murine peritoneal cells and rat basophilic leukemia cells (IC50 > 100 microM), but does have moderate 5-LO inhibitory activity in intact murine peritoneal cells (IC50 = 10 microM, 5 min) and in chopped guinea pig liver (IC50 = 14 microM, 2 hr). The generation and release of leukotrienes in human neutrophils and eosinophils is also inhibited by azelastine (IC50 = 0.9-1.1 microM). Furthermore, azelastine is a potent and specific inhibitor of allergen-induced generation of leukotrienes in the nose of the guinea pig (ID50 < 100 micrograms/kg, im, 20 min) as well as in patients with rhinitis (2 mg, po, 4 hr; ID50 < 30 micrograms/kg). Azelastine also inhibits allergen-induced, leukotriene-mediated, pyrilamine-resistant bronchoconstriction (oral ID50 = 60 micrograms/kg, 2 hr and 120 micrograms/kg, 24 hr). This profile suggests that azelastine may be a novel inhibitor of Ca(2+)-dependent translocation of 5-lipoxygenase from cytosol to the nuclear envelope or a FLAP inhibitor rather than a direct 5-LO inhibitor.
J Asthma 1995
PMID:Azelastine--a novel in vivo inhibitor of leukotriene biosynthesis: a possible mechanism of action: a mini review. 775 63

Chronic urticaria is a common clinical disorder that is idiopathic in over 75% of cases. Less commonly, urticaria may be the presenting manifestation of an allergic or infectious disease, endocrinopathy, inherited syndrome, or autoimmune disorder. Rarely, urticaria may be a sign of underlying malignancy, including leukemia. C.C. is a 48-year-old white female who was referred for evaluation of recurrent urticaria for 3 years. The pruritic, erythematous wheals were pinpoint, and appeared to be precipitated by heat, stress, and effort. Prick tests were negative except to D. pteronyssinus. CBCs over the past 5 years revealed WBCs of 2,300-5,000 cells/mm3. Skin biopsy revealed interstitial edema with infiltration of eosinophils and mast cells consistent with urticaria. The impression was probable cholinergic urticaria, for which hydroxyzine was prescribed with fair symptomatic control. One year later, she presented with bright red blood per rectum. Repeat physical examination revealed lymphadenopathy and splenomegaly. Subsequent laboratory studies showed pancytopenia. Endoscopy was normal except for small, nonbleeding hemorrhoids. Bone marrow biopsy revealed histologic evidence of hair, cell leukemia that was treated with 2-chlorodeoxyadenosine. Upon initiation of chemotherapy her pruritus and urticaria subsided. Recent CBC revealed Hgb 9.2 g/dL, platelets 290,000 cells/mm3, and WBC 4,100 cells/mm3. Peripheral blood smear showed no hairy cells.
Allergy Asthma Proc
PMID:Chronic urticaria as a presenting sign of hairy cell leukemia. 1007 10

Asthma is a complex condition in which exposure to environmental antigens induces inflammatory reactions in the airway characterized by activation of mast cells and eosinophils. Mast cells are known to be the main effector cells in eliciting IgE-mediated allergic response. These cells secrete various substances that perpetuate inflammation and provoke airway smooth muscle (ASM) contraction. A newly recognized addition to the repertoire of FcepsilonRI-mediated signaling events is the activation of sphingosine kinase leading to the generation of the potent sphingolipid mediator, sphingosine-1-phosphate (S1P) from sphingosine. S1P secretion by the lung significantly increases after challenge with an allergen, adding this sphingolipid metabolite to the variety of mediators that are released during an allergic reaction [FASEB J. 15 (2001) 1212]. Indeed, similar to previous reports, we found that FcepsilonRI cross-linking not only increased cellular levels of S1P, it also markedly enhanced its secretion from rat basophilic leukemia RBL-2H3 cells. Moreover, S1P induced degranulation of RBL and bone marrow derived mast cells (BMMCs) cells as determined by hexosaminidase release. Treatment of BMMCs with the sphingosine kinase inhibitors, DL-threo-dihydrosphingosine and dimethylsphingosine, reduced IgE/Ag stimulated histamine release. RT-PCR analysis demonstrated that these mast cells express S1P receptors EDG-1 and EDG-5 but not EDG-3, EDG-6 or EDG-8 transcripts. Further studies are needed to determine whether IgE triggering results in transactivation of EDG-1 or EDG-5 present on mast cells and whether this is a critical event for mast cell activation.
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PMID:The roles of sphingosine-1-phosphate in asthma. 1221 90

We surveyed cognitively normal teens with and without chronic illness regarding the perceived physical and social impact of various chronic diseases including asthma. The overall physical impact of asthma was perceived equivalently to diabetes and arthritis, but less than epilepsy, Down's syndrome, leukemia, and human immunodeficiency virus infection. However, asthma was rated to more commonly cause physical disability (p < 0.001) and restrict activities (p < 0.0005). The social impact of asthma was perceived equivalently to diabetes, but more favorably than the other chronic diseases surveyed. Specifically, teens with asthma were perceived as having fewer behavior problems, being more honest, popular, and fun to be around, but less adept at sports. Only 6 of 149 (4%) teens surveyed expressed any degree of reluctance to befriend peers with asthma.
J Asthma 2006 Mar
PMID:How do teens view the physical and social impact of asthma compared to other chronic diseases? 1651 33

Multi drug resistance(MDR) is a major problem in the treatment ofcancer and hematological malignancies. This resistance is multi factorial and is the result of decreased intra cellular drug accumulation. This is partly due to the presence of a 170KD intra membranous protein termed P-glycoprotein(P-gp) that is an energy- dependent efflux pump which has increased expression on drug-resistance cells. In this study we identified the presence of P-gp by staining with Fluorescent Iso Thio Cyanate (FITC) conjugated anti P-gp in acute leukemia patients and flow cytometry in addition to performing immunophenotype analysis and French, American British (FAB) classification. Results revealed that one fifth of leukemic patients expressed P-gp and this phenotype was more prevalent in Acute Undifferentiated Leukemia(AUL) and Acute Myelogenous Leukemia (AML) than in Acute Lymphoblastic Leukemia(ALL). Other findings showed a logical relationship between this phenotype and age groups. There was not any association between P-gp+ phenotype and FAB and Immunophenotyping sub classification, but there was a linear relationship between CD34 and CD7 expression and P-gp+ phenotype. The accumulation of P-gp molecule that was stated as Mean Fluorescence Intensity (MFI) on the blasts' membrane of AUL and AML patients showed marked increase in comparison to ALL. Furthermore MFI in P-gp+ relapsed patients was much more than P-gp+ pretreatment patients. Kepvords: Leukemia, Drug resistance, P-glycoprotein, Flowcytometry, FAB classification, Immunophenotyping, Mean Fluorescence Intensity.
Iran J Allergy Asthma Immunol 2003 Jun
PMID:P-glycoprotein quantitation in acute leukemia. 1730 57

Apoptosis, or active cell death, is a specific mode of cell death, which is characterized by morphological changes such as chromatin condensation, fragmentation of the nucleus, cytoplasmic retraction and appearance of apoptotic bodies' containing apparently intact organelles. Apoptosis occurs in physiological conditions as a regulatory mechanism of tissue growth, where cell proliferation is balanced. The aim of this research was to study the ability of Fas to initiate apoptosis in vitro before and after treatment with Cytarabin on tissue culture and to correlate the response. The human leukemia and normal cells were treated with cytarabin in tissue culture, and apoptotic treated cells were estimated by flow cytometry and phosphatidylserines kit. The results were analyzed by statistical tests (post hoc). From these data, it was found that Fas antigen was expressed in all cases, but the expression level varied widely. Apoptosis and also Fas antigen expression in short term cell culture were higher in media containing drug than in media without drug; but there had been no reasonable correlation between percentage of Fas antigen and apoptosis responses before culture.Expression of Fas antigen was low in most of the leukemic cells and the preliminary results showed that increase in Fas antigen expression (above 20%) after treatment, was a favorable prognostic outcome. It is associated with increase relapse, free and total survival. In addition, using this antigen as a chemotherapic and immunotherapic target, would initiate a new strategy for treatment of leukemia (chemotherapy and immunotherapy).
Iran J Allergy Asthma Immunol 2005 Dec
PMID:In vitro Evaluation of Cytarabin Induced Apoptosis in Leukemic Blasts. 1730 42

Previous studies demonstrated significant differences in a number of HLA allele frequencies in leukemia patients and normal subjects. In this study, we have analyzed HLA class II alleles and haplotypes in 110 leukemia patients (60 acute myelogenous leukemia "AML", 50 chronic myelogenous leukemia"CML") and 180 unrelated normal subjects. Blood samples were collected from all of the patients and control subjects. DNA was extracted by salting out method and HLA typing was performed using PCR-SSP method. Significant positive association with AML was obtained for HLA-DRB1*11allele (35% vs. 24.7%, P=0.033). Two alleles including HLA-DRB4 and -DQB1*0303 were significantly less frequent in AML patients than in controls. HLA-DQB1*0303 allele was never observed in CML patients compared with allele frequency in controls (4.2%). According to haplotype analysis, HLA-DRB1*0101/DQA1*0104/-DQB1*0501 frequencies were significantly higher and -DRB1*16/-DQA1*01021/-DQB1*0501 frequencies were significantly lower in CML patients than in controls. In conclusion it is suggested that HLA-DRB1*16 allele and HLA-DRB1*15/-DQA1*0103/-DQB1*06011 and -DRB1*16/-DQA1*01021/-DQB1*0501 haplotypes predispose individuals to AML and HLA-DRB4 allele predispose to CML. Future studies are needed to confirm these results and establish the role of these associations in AML and CML.
Iran J Allergy Asthma Immunol 2007 Sep
PMID:HLA class II allele and haplotype frequencies in Iranian patients with leukemia. 1789 34

Xenotropic murine leukemia virus-related virus (XMRV) is a gamma retrovirus that has been associated with chronic fatigue syndrome (CFS) and prostate cancer. The search for viral causes of these syndromes was reignited by the finding that RNase L activity was low in hereditary prostate cancer and some CFS patients. The six strains of XMRV that have been sequenced have greater than 99% identity, indicating a new human infection rather than laboratory contamination. DNA, RNA, and proteins from XMRV have been detected in 50% to 67% of CFS patients and in about 3.7% of healthy controls. XMRV infections could be transmitted to permissive cell lines from CFS plasma, suggesting the potential for communicable and blood-borne spread of the virus and potentially CFS. This troubling concept is currently under intense evaluation. The most important steps now are to independently confirm the initial findings; develop reliable assays of biomarkers; and to move on to investigations of XMRV pathophysiology and treatment in CFS, prostate cancer, and potentially other virus-related syndromes, if they exist.
Curr Allergy Asthma Rep 2010 May
PMID:Xenotropic murine leukemia virus-related virus in chronic fatigue syndrome and prostate cancer. 2042 7

New information about the pathophysiology of idiopathic nonallergic rhinopathy indicates a high prevalence in chronic fatigue syndrome (CFS). This article shows the relevance of CFS and allied disorders to allergy practice. CFS has significant overlap with systemic hyperalgesia (fibromyalgia), autonomic dysfunction (irritable bowel syndrome and migraine headaches), sensory hypersensitivity (dyspnea; congestion; rhinorrhea; and appreciation of visceral nociception in the esophagus, gastrointestinal tract, bladder, and other organs), and central nervous system maladaptations (central sensitization) recorded by functional magnetic resonance imaging (fMRI). Neurological dysfunction may account for the overlap of CFS with idiopathic nonallergic rhinopathy. Scientific advances are in fMRI, nociceptive sensor expression, and, potentially, infection with xenotropic murine leukemia-related virus provide additional insights to novel pathophysiological mechanisms of the "functional" complaints of these patients that are mistakenly interpreted as allergic syndromes. As allergists, we must accept the clinical challenges posed by these complex patients and provide proper diagnoses, assurance, and optimum care even though current treatment algorithms are lacking.
Allergy Asthma Proc
PMID:Relationships among rhinitis, fibromyalgia, and chronic fatigue. 2061 18

The inclusion of children's samples in biobanks brings forward specific ethical issues. Guidelines indicate that children should be involved in the consent procedure. It is, however, unclear how to allocate an appropriate role for children. Knowledge of current practice will be helpful in addressing this issue. Therefore, we conducted an international multiple-case study on the child's role in consent procedures in pediatric biobanks. Four biobanks were included: (1) LifeLines, (2) Prevention and Incidence of Asthma and Mite Allergy (PIAMA), (3) Young-HUNT3 and (4) the Oxford Radcliffe Biobank contribution to the Children's Cancer and Leukaemia Group tissue bank (ORB/CCLG). Four themes linked to the child's role in the consent procedure emerged from the multiple-case study: (1) motives to involve the child, (2) informing the child, (3) the role of dissent, assent and consent and (4) voluntariness of children to participate. We conclude that biobank characteristics influence the biobank's motives to include children in the consent procedure. Moreover, the motives to include children influence how the children are involved in the consent procedure, and the extent to which children are able to make voluntary decisions as part of the consent procedure. This insight is valuable when designing pediatric biobank governance.
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PMID:Consent procedures in pediatric biobanks. 2553 61


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