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)

CT examinations of the cranium were carried out among 15 children who had previously received cranial radiation and i.th. methotrexate during leukemia management. Surprisingly, 10 of 15 patients had abnormal CT findings. Only 2 of the 10 "CT-positive" children were clinically-neurologically conspicuous. The visible CT alterations of brain structure seemed especially marked and frequent the more time had elapsed since CNS-treatment. The most striking CT pathologica were found among children up to 5 years of age, who were also conspicuous through convulsions and delayed development.
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PMID:[Unusual CT skull findings after preventive CNS treatment of acute leukemia in children]. 11 13

The H-2, thymus-leukemia (TL), and Qa-2 antigens of mice are encoded by closely linked genes on murine chromosome 17, and have structural similiarity in that each antigen is borne on a approximately 44,000 dalton molecule associated with beta2 microglobulin (beta2mu). The extensive homology of major histocompatibility complex (MHC) products that exists for the mouse and guinea pig suggested that a similar homology might exist for products of genetic regions closely linked to the MHC. By taking advantage of the selective association of beta2mu with H-2, Qa-2, and TL antigens, and by using the technique of sequential immunoprecipitation, we demonstrated two previously undescribed guinea pig molecules reactive with anti-guinea pig beta2mu. The first molecule was composed of a 36,000 dalton glycoprotein associated with beta2mu and was found on guinea pig thymocytes, but not lymphocytes. The second molecule was composed of a 40,000 dalton glycoprotein associated with beta2mu, and was found on both guinea pig thymocytes and lymphocytes. By structure, chemical composition, association with beta2mu, and tissue distribution, the first molecule is an attractive candidate for the guinea pig homologue of TL antigen, whereas the second fits the criteria for the guinea pig homologue of Qa-2 antigen.
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PMID:Guinea pig homologues of TL and QA-2 antigens. 35 57

Two hundred and thirty-four cerebrospinal fluid (CSF) specimens from 183 different children were analysed for total lactate dehydrogenase (LD) activity and LD isoenzyme distribution. The LD activities were elevated in the CSF of patients with meningitis, especially with bacterial infections, and with central nervous system (CNS) leukaemia. The CSF LD isoenzyme patterns of both groups generally reflected the number and distribution of lymphocytes and granulocytes in the CSF. Increases in CSF LD levels also occurred in patients with other neurological disorders, such as hydrocephalus, raised intracranial pressure, and epileptic seizures. However, no significant increases in CSF LD activity nor abnormality of the isoenzyme distribution were noted in children who had had a non-specific febrile convulsion.
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PMID:Diagnostic significance and source of lactate dehydrogenase and its isoenzymes in cerebrospinal fluid of children with a variety of neurological disorders. 121 17

An exhaustive computer-assisted analysis of the Moloney murine leukemia virus nucleotide sequence shows numerous deviations in the oligomeric distribution, suggesting three overlapping levels of a stepwise duplicative evolution. (1) The sequence fits the universal rule of TG/CT excess which has been proposed as the construction principle of all sequences, and maintains some degree of symmetry between the two complementary strands. (2) Oligomeric repeating units share a core consensus regularly scattered throughout the sequence. This consensus is not merely predictable from the doublet frequencies and codon usage, but could correspond to an intermediary stage in a so-called periodic-to-chaotic transition. (3) Probable stepwise local duplications could be accounted for by slippagelike mechanisms. Comparison with the human spumaretrovirus (HSRV) shows similar segments in the overrepresented oligomers of the two sequences. The intermediary stage of transition oligomeric repeating units is not so clearly suggested in HSRV, perhaps because of numerous stepwise local duplications. In any case, a common evolutionary origin for the two viruses is not ruled out.
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PMID:Mo-MuLV nucleotide sequence exhibits three levels of oligomeric repetitions, suggesting a stepwise molecular evolution. 133

The Armitage-Doll model of carcinogenesis is fitted to Japanese bomb survivors with the DS86 dosimetry and to three other radiation-exposed cohorts. The model is found to provide an adequate description of solid cancer incidence and also, to a lesser extent, of that of leukemia as a function of radiation dose when up to two radiation-affected stages are assumed. For non-leukemias the optimal model is one in which there are two radiation-affected stages separated by two additional stages. In the case of leukemia one radiation-affected stage or two adjacent stages provide suitable fits. There appear to be significant differences between the optimal models fitted to each cohort, although there is no heterogeneity within the Japanese data set by sex, by cancer type, or by age at exposure. Low-dose and low-dose-rate population risks for a population having the cancer and overall mortality rates of the current UK population are calculated on the basis of the optimal models fitted to the Japanese data to be about 8.3 x 10(-2) excess cancer deaths person-1 Sv-1, 10.1 x 10(-2) radiation-induced cancer deaths person-1 Sv-1, or 1.40 years of life lost person-1 Sv-1. Risks for a population having the mortality rates of the current Japanese population are about 6.5 x 10(-2) excess cancer deaths person-1 Sv-1, 7.8 x 10(-2) radiation-induced cancer deaths person-1 Sv-1, or 0.89 years of life lost person-1 Sv-1. It is a feature of the Armitage-Doll model, and other multistage models of carcinogenesis, that if radiation acts at more than one stage then (inverse) dose-rate effects may arise as a result of interactions between the effects of a protracted dose at the various radiation-affected stages. However, it is shown in this paper that these three measures of cancer risk in general display fairly slight dependence on administered dose in the range 0.001 to 1.0 Sv and on the length of the time over which the dose is administered in the range 1 to 100 years. Dose-rate effects resulting from the protraction of a radiation exposure over many years acting on (the same) cells at various stages of a multistep process of carcinogenesis are therefore expected to be slight. Dose-rate effects which have been observed in epidemiological studies and cellular radiobiology may thus find their explanation in other phenomena such as short-term intracellular repair.
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PMID:Fitting the Armitage-Doll model to radiation-exposed cohorts and implications for population cancer risks. 826 82

Today about 70% of children with leukemia are cured by intensive chemotherapy. Therefore how to deal with the children and their families before, during, and after the treatment has become a major concern for caregivers. And it is a fact that there are still a few patients who relapse and are destined to die. We are now taking care of two groups of patients. One group is truly cured and one group is dying. We have been trying to establish a good total care system that fits our society. We have formed medical teams which consist of doctors, nurses, and care workers. From our experience, we think the most important principle for the caregivers is frankness. Sometimes this is very difficult. Other important points of total care, especially from psychosocial aspects, are mentioned.
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PMID:Principles of total care for children with leukemia--psychosocial interventions. 179 19

Hundreds of murine dilute mutations have been identified and analysed, making dilute one of the best genetically characterized of all mammalian loci. The recessive dilute (d) coat colour mutation carried by many inbred strains of mice produces a lightening of coat colour, caused by an abnormal adendritic melanocyte morphology that results in an uneven release of pigment granules into the developing hair shaft. Most dilute alleles (dilute-lethal) also produce a neurological defect, characterized by convulsions and opisthotonus, apparent at 8-10 days of age and continuing until the death of the animal at 2-3 weeks of age. The discovery that the original dilute allele (now termed dilute-viral or dV) is the result of the integration of an ecotropic murine leukaemia provirus has allowed the cloning of genomic DNA and in this study complementary DNA, from the dilute locus. The predicted dilute amino-acid sequence indicates that dilute encodes a novel type of myosin heavy chain, with a tail, or C-terminal, region that has elements of both type II (alpha-helical coiled-coil) and type I (non-coiled-coil) myosin heavy chains. Dilute transcripts are differentially expressed in both embryonic and adult tissues and are very abundant in neurons of the central nervous system, cephalic ganglia, and spinal ganglia. These results suggest an important role for the dilute gene product in the elaboration, maintenance, or function of cellular processes of melanocytes and neurons.
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PMID:Novel myosin heavy chain encoded by murine dilute coat colour locus. 199 38

This report has two aims: (1) to describe and analyze the age/time patterns of excess cancer risk in the atomic bomb survivor cohort followed up by the Radiation Effects Research Foundation (RERF), and (2) to describe statistical methods which are used in RERF's analyses of data on mortality and morbidity in the cohort. In contrast to previous analyses of the cohort cancer mortality data, substantial use is made of Japanese national cancer rates for the purpose of investigation of the age/time variations in excess risk. This analysis considers mortality from all cancers except leukemia as a group. Primary attention is given to description in terms of the age-specific excess relative risk, but the importance of appropriate descriptions of the absolute excess risk is also emphasized. When models for the excess risk allow variation with age and time, both constant relative and absolute excess risk models provide similar fits to the data. Previous reports have indicated that for a given age at exposure and sex, the excess age-specific relative risk is remarkably constant throughout the current follow-up period. Statistical analysis here indicates that for those less than about 35 years of age at exposure there is no departure from this pattern, beyond ordinary sampling variation. For those over about 35 years of age at exposure, there is modest evidence of an increasing trend in the excess relative risk, which could plausibly be attributed to effects related to minimal latent period. Some brief consideration is given to modeling the absolute excess risk as the product of an age-at-exposure and time-since-exposure effect. Interpretation of these results, particularly in regard to projections beyond the current follow-up, is discussed.
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PMID:Analysis of time and age patterns in cancer risk for A-bomb survivors. 202 88

The Japanese atomic bomb survivors and three other cohorts of children exposed to radiation are analyzed, and evidence is found for a reduction in the radiation-induced relative risk of cancers other than leukemia with time following exposure. Multiplicative adjustments to the excess risk either of the form exp[-delta.(time since exposure)] or of the form [time since exposure] gamma give equivalent goodness of fit. Using the former type of adjustment an annual overall reduction of 6.9-8.6% in excess relative risk is indicated (depending on the year after which this reduction might take effect). Using the second type of multiplier an adjustment to the excess relative risk varying between [time after exposure]-2.0 and [time after exposure]-3.2 fits best overall. All these reductions are statistically significant at the 5% level. There is no significant variation by cohort, by sex, by cancer type, or by age at exposure group in the degree of annual reduction in excess relative risk. Although time-adjusted relative and absolute risk models give equivalently good fits within each cohort, there is significant variation between cohorts in the degree of increase of risk with time in the absolute risk formulation, in contrast to the lack of such heterogeneity for the relative risk formulation. It is shown that if the range of observed reductions in relative risk is assumed to operate 40 or more years after exposure in the youngest age groups, the calculated UK population risks would be reduced by 30-45% compared to those based on a constant relative risk model.
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PMID:Time variations in the risk of cancer following irradiation in childhood. 203 88

Serial cranial computed tomograms were carried out in 136 children with acute lymphoblastic leukaemia who were receiving 24 Gy or 18 Gy of cranial irradiation and continuing treatment with doses of methotrexate given weekly orally or intramuscularly. The findings were correlated with treatment variables, the development of fits, and the intelligence quotient (IQ). Reversible brain shrinkage, attributed to treatment with steroids, was found on 87 of 114 initial scans (76%); 14 showed changes in white matter during treatment (10%), and calcification was found in 13 either during or after treatment (10%). Eight children (6%) had fits, and in six of the eight there were changes in white matter or calcification on the scans. Comparison of the two radiotherapy dosages showed no difference in the incidence of abnormalities seen on computed tomography, fits, or serial IQ measurements, but children receiving intramuscular methotrexate had a higher incidence of calcification and a lower mean IQ at one year than those who received the drug orally, although this difference was not apparent later. Younger children were more likely to develop changes on computed tomograms and fits, and to have low IQs on completion of treatment, with changes most apparent in those less than 2 years of age. There were highly significant correlations between abnormalities on computed tomography, fits, and IQ. These findings confirm the neurological vulnerability of younger children with acute lymphoblastic leukaemia, show an association between abnormalities on computed tomography and intellectual deficit, and suggest that methotrexate is more toxic when given intramuscularly than orally. They provide no evidence that 18 Gy of cranial irradiation is less toxic than 24 Gy, and indicate the need for alternative treatment regimens.
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PMID:Neurotoxicity in lymphoblastic leukaemia: comparison of oral and intramuscular methotrexate and two doses of radiation. 234 34


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