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)

Exposures to extremely low-frequency electric and magnetic fields (EMF) emanating from the generation, transmission, and use of electricity are a ubiquitous part of modern life. Concern about potential adverse health effects was initially brought to prominence by an epidemiologic report two decades ago from Denver on childhood cancer. We reviewed the now voluminous epidemiologic literature on EMF and risks of chronic disease and conclude the following: a) The quality of epidemiologic studies on this topic has improved over time and several of the recent studies on childhood leukemia and on cancer associated with occupational exposure are close to the limit of what can realistically be achieved in terms of size of study and methodological rigor. b) Exposure assessment is a particular difficulty of EMF epidemiology, in several respects: i) The exposure is imperceptible, ubiquitous, has multiple sources, and can vary greatly over time and short distances. ii) The exposure period of relevance is before the date at which measurements can realistically be obtained and of unknown duration and induction period. iii) The appropriate exposure metric is not known and there are no biological data from which to impute it. c) In the absence of experimental evidence and given the methodological uncertainties in the epidemiologic literature, there is no chronic disease for which an etiological relation to EMF can be regarded as established. d) There has been a large body of high quality data for childhood cancer, and also for adult leukemia and brain tumor in relation to occupational exposure. Among all the outcomes evaluated in epidemiologic studies of EMF, childhood leukemia in relation to postnatal exposures above 0.4 microT is the one for which there is most evidence of an association. The relative risk has been estimated at 2.0 (95% confidence limit: 1.27-3.13) in a large pooled analysis. This is unlikely to be due to chance but, may be, in part, due to bias. This is difficult to interpret in the absence of a known mechanism or reproducible experimental support. In the large pooled analysis only 0.8% of all children were exposed above 0.4 microT. Further studies need to be designed to test specific hypotheses such as aspects of selection bias or exposure. On the basis of epidemiologic findings, evidence shows an association of amyotrophic lateral sclerosis with occupational EMF exposure although confounding is a potential explanation. Breast cancer, cardiovascular disease, and suicide and depression remain unresolved.
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PMID:Review of the epidemiologic literature on EMF and Health. 1174 9

It is well known that altered host defenses in general can play a significant role in the development of infection in any patient but their role becomes even more important in surgical patients where infections are the result of individual risk factors associated with the patient and other specific factors associated with the surgery itself. Thus all possible factors that can help modify the immune response should be taken into account in order to intervene, whenever possible, with therapies based on defined abnormalities to reduce the rate of post-surgical infections. Many factors associated with the patient have been clearly identified as responsible for a decreased immune response: old age, concomitant diseases (diabetes, renal and liver failure, solid and hematologic neoplasias, malnutrition, autoimmune diseases, AIDS) and concomitant therapies (corticosteroid, cytotoxic agents). Old age can affect both humoral and cell-mediated immune responses. Chronic diseases can be responsible for a reduced primary response or depression of delayed hypersensitivity reactions (renal failure, neoplasias) or changes in leukocyte function (diabetes, leukemia, lymphomas). Malnutrition frequently accompanies diseases such as cancer, chronic and acute pancreatitis, inflammatory bowel diseases. Deficiencies in important vitamins and minerals (B6, A, folate, biotin, riboflavin...) can alter significantly the leukocyte function and immune response. Finally, there appears to be innate immune-suppression following any form of injury which is correlated with its magnitude and can affect any aspect of immunity. This has been well studied both in burn and surgical trauma. Alteration of phagocytosis, opsonization and chemotaxis are typically affected in burns, whereas surgical stress can include some reduction of cell mediated immunity. The best approach today to minimizing post-surgical infections is probably, besides use of antibiotic prophylaxis, to reduce the surgical trauma which consequently reduces the stress response and immune-suppression and to optimize the immune response by maintaining homeostasis through nutritional support.
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PMID:Immune system and surgical site infection. 1193 55

The hairy cells (HCs) of hairy-cell leukemia are intrinsically activated mature clonal B cells. The aims of this study were to gain further insights into the nature of this activation and to assess its importance for the prolonged HC survival in this chronic disease. We show that HCs contain phosphorylated/activated p38 MAPK, JNK and ERK1/ERK2 (ERK1/2). PKC inhibitors increased the activation of p38 and JNK, but reduced the phosphorylation of ERK1/2. Moreover, PKC inhibition resulted in cell death; cell death was also observed when the activation of ERK1/2 in HCs was abrogated with an inhibitor of MEK1/2 activation. In addition to PKC, active Src kinase was also shown to be involved in the maintenance of Raf-independent ERK activation in HCs. During cell culture on a nonadherent surface, ERK phosphorylation was sustained, while phosphorylation of p38 and JNK decreased. This decrease was not observed in HCs cultured on vitronectin (VN), indicating that p38/JNK activation is probably a consequence of in vivo HC interaction with VN present in abundance in the red pulp of the spleen. Taken together, these results suggest that active p38/JNK make HCs susceptible to apoptosis, but the cells are effectively rescued by ERK activation involving constitutively active PKC and Src. These findings are relevant for the understanding of the prolonged cell survival of HCs and their selective sensitivity to some chemotherapeutic agents.
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PMID:Regulation of hairy-cell survival through constitutive activation of mitogen-activated protein kinase pathways. 1270 Jun 63

Pediatric cancer is one of the more poignant aspects associated with the occurrence of this prominent chronic disease. Nationally, pediatric cancers occur with vastly lesser frequency than does adult disease, about 1:40 ratio. Nationally the rate is 14.6 per 100,000 population, age, 0-14 years. In Kentucky, all pediatric cancer rates are consistently lower, a statewide rate of 11.3 per 100,000. A rigorous examination was made for any evidence of unusual risk for pediatric cancer within the state; none was found. The population center of Jefferson County was examined with a bit greater detail, owing simply to the larger number. Again, no basis for public health or follow-back was identified. Among the most frequent pediatric cancers, leukemia, central nervous system, and brain were studied for implications of residential proximity to environmental hazards; no evidence of increased risk was identified. In all of the state, only Hardin County evinced any excess pediatric cancer risk, i.e., was significantly greater than the national rates. Yet this highly mobile population [owing to a large military population] may simply represent rates that are more compatible with those of the nation. For the Kentucky comprehensive disease control efforts, then, no emphasis need be placed with pediatric cancer beyond the intense personal tragedy that it poses.
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PMID:Pediatric cancer in Kentucky: good news. 1554 57

In failure time studies involving a chronic disease such as cancer, data often focus on one or more non-fatal events, in addition to survival, to describe the course of the disease. In the example of allogeneic bone marrow transplantation in leukaemic patients, acute graft-versus host disease (aGvHD), relapse and death were taken as the reported events, and we focused on testing the existence of graft-versus-leukaemia (GvL) effect, i.e. that the occurrence of aGvHD modifies the probability of relapse. One of the weaknesses of the standard competing risks models is their inability to model secondary relapses. We thus derived, from two competing risks models, two estimators of cumulative incidence functions of primary and secondary relapses, as well as statistics to test the GvL effect. The approach is illustrated by application to a data set from a cohort of 442 children with acute leukaemia who received an unrelated transplant.
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PMID:The graft-versus-leukaemia effect after allogeneic bone-marrow transplantation: assessment through competing risks approaches. 1558 Jun 2

Candidaemia due to non-albicans Candida species is increasing in frequency. We describe 272 episodes of candidaemia, define parameters associated with Candida albicans and other Candida species, and analyse predictors associated with mortality. Patients with C. albicans (55%) had the highest fatality rate and frequently received immunosuppressive therapy, while patients with Candida parapsilosis (16%) had the lowest fatality and complication rates. Candida tropicalis (16%) was associated with youth, severe neutropenia, acute leukaemia or bone marrow transplantation, Candida glabrata (10%) was associated with old age and chronic disease, and Candida krusei (2%) was associated with prior fluconazole therapy. The overall fatality rate was 36%, and predictors of death by multi-variate analysis were shock, impaired performance status, low serum albumin and congestive heart failure. Isolation of non-albicans Candida species, prior surgery and catheter removal were protective factors. When shock was excluded from analysis, antifungal therapy was shown to be protective. Unlike previous concerns, infection with Candida species other than C. albicans has not been shown to result in an increased fatality rate.
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PMID:Characteristics of candidaemia with Candida-albicans compared with non-albicans Candida species and predictors of mortality. 1600 56

Adolescent perception of physical and social impact of chronic illness was assessed to determine (1) if there is greater prejudice toward epilepsy than other chronic disease and (2) if adolescents with chronic disease have less prejudice toward similarly affected peers with all types of chronic disease or just their specific chronic disease. Cognitively normal teens aged 13 to 18 years without chronic disease (n = 41) and with epilepsy (n = 32), asthma (n = 38), diabetes (n = 21), and migraine (n = 17) were interviewed in the outpatient clinics of a tertiary care pediatric center regarding their perceptions of the physical and social impact of eight chronic diseases (epilepsy, asthma, diabetes, Down syndrome, arthritis, migraine, leukemia, human immunodeficiency virus [HIV] infection). Epilepsy was perceived to have a more adverse physical impact than all chronic illnesses except Down syndrome. The perception was that it more frequently caused mental handicap, injured the afflicted individual and bystanders, and led to death. Epilepsy was also perceived to have a more negative social impact, particularly on behavior, honesty, popularity, adeptness at sports, and fun. Significantly more adolescents expressed reluctance to befriend peers with epilepsy, both from their own and their perceived parental perspectives. Having a chronic disease did not generally alter the adolescents' perceptions of peers with chronic disease. However, cases with epilepsy ranked this disease to have less social impact than teens with other chronic diseases. In conclusion, adolescents consider epilepsy to have a greater physical and social impact than most chronic diseases. Educational efforts should focus on the "normality" of most persons with epilepsy and emphasize the low risk of injury when proper first aid is followed.
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PMID:Adolescents' perception of epilepsy compared with other chronic diseases: "through a teenager's eyes". 1690 23

Recent progress in molecular biology has shown that cancer cells acquire common phenotypes such as self-sufficiency of growth signals, resistance to anti-proliferative and apoptotic signals through the accumulation of genetic and epigenetic changes. Recently developed anticancer drugs target these molecular mechanisms and good results have been reported for various cancer types. In lung cancer, tyrosine kinase inhibitors specific for the epidermal growth factor receptor such as gefitinib and erlotinib have changed clinical practice dramatically. About half of the Japanese patients with lung cancers harbor an activating mutation of the epidermal growth factor receptor gene and they are very sensitive to epidermal growth factor receptor tyrosine kinase inhibitors. Progression-free survival of such patients is approximately 10 months when treated with gefitinib, whereas the survival for those treated with platinum doublet therapy is approximately 6 months. Target therapies against echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion protein or a mutated ERBB2 (v-ERB-B avian erythroblastic leukemia viral oncogene homologue 2) present in approximately 5% and approximately 3% of the Japanese patients with adenocarcinomas, respectively, are currently under development. Addition of an anti-epidermal growth factor receptor antibody, cetuximab, or anti-vascular endothelial growth factor antibody, bevacizumab, to platinum doublet therapy significantly but modestly prolonged the survival in recent clinical trials. However, clinical development of small molecule multi-kinase inhibitors including those targeting vascular endothelial growth factor receptors, such as vandetanib, sunitinib and sorafenib, has not been very successful. Through these collaborations among clinicians, basic researchers and pharmaceutical companies, it should be possible to individualize lung cancer treatment to turn this fatal disease into a chronic disorder and, eventually, to cure it.
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PMID:Advances in target therapy for lung cancer. 2003 62

Inactivation of p15INK4b, an inhibitor of cyclin-dependent kinases, through DNA methylation is one of the most common epigenetic abnormalities in myeloid leukemia. Although this suggests a key role for this protein in myeloid disease suppression, experimental evidence to support this has not been reported. To address whether this event is critical for premalignant myeloid disorders and leukemia development, mice were generated that have loss of p15Ink4b specifically in myeloid cells. The p15Ink4b(fl/fl)-LysMcre mice develop nonreactive monocytosis in the peripheral blood accompanied by increased numbers of myeloid and monocytic cells in the bone marrow resembling the myeloproliferative form of chronic myelomonocytic leukemia. Spontaneous progression from chronic disease to acute leukemia was not observed. Nevertheless, MOL4070LTR retrovirus integrations provided cooperative genetic mutations resulting in a high frequency of myeloid leukemia in knockout mice. Two common retrovirus insertion sites near c-myb and Sox4 genes were identified, and their transcript up-regulated in leukemia, suggesting a collaborative role of their protein products with p15Ink4b-deficiency in promoting malignant disease. This new animal model demonstrates experimentally that p15Ink4b is a tumor suppressor for myeloid leukemia, and its loss may play an active role in the establishment of preleukemic conditions.
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PMID:Myeloid-specific inactivation of p15Ink4b results in monocytosis and predisposition to myeloid leukemia. 2045 73

Human T-cell lymphotropic virus type 1 is vertically transmitted in neonatal life and is causatively associated with adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in adults. Persistence of HTLV-1 in host T cells, clonal expansion of the HTLV-1 carrying T cells, and emergence of malignantly transformed T cells are in accord with the multistep model of human cancer and roles for continuous interaction between host genes and environmental factors. This article reviews two lines of HTLV-1 investigation, one regarding worldwide surveillance of HTLV-1 infection foci by serological testing and molecular analysis of HTLV-1 isolates, and the other focusing on genetics of the human leukocyte antigen (HLA) that determines the ethnic background of HTLV-1 permissiveness and susceptibility to ATL or HAM/TSP. The serological surveillance revealed transcontinental dispersal of HTLV-1 in the prehistoric era that started out of Africa, spread to Austro-Melanesia and the Asian continent, then moved to North America and through to the southern edge of South America. This was highlighted by an Andean mummy study that proved ancient migration of paleo-mongoloid HTLV-1 from Asia to South America. Phylogenetic analysis of HLA alleles provided a basis for ethnic susceptibility to HTLV-1 infection and associated diseases, both ATL and HAM/TSP. Ethnicity-based sampling of peripheral blood lymphocytes has great potential for genome-wide association studies to illuminate ethnically defined host factors for viral oncogenesis with reference to HTLV-1 and other pathogenic elements causatively associated with chronic disease and malignancies.
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PMID:Ethnoepidemiology of HTLV-1 related diseases: ethnic determinants of HTLV-1 susceptibility and its worldwide dispersal. 2120 73


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