Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Free radicals, intermediates in the tissue damage caused by radiation, are formed, inter alia, in interactions catalyzed by iron, which synergizes with radiation and some cytostatics (anthracyclins) in causing cell damage. Conversely, iron chelators can counteract cell damage. Similarly, antioxidants can slow atherogenesis, caused in part by oxidative stress and free radicals. Cell damage is also prevented by physiological defense systems like superoxide dismutase, against endogenous free radicals formed by granulocytes, monocytes, etc. Iron can thus induce free radicals which cause DNA double strand breaks and oncogene activation. This is suggested by four epidemiological studies suggesting a higher cancer risk in patients with larger iron stores than in those with small iron stores. In addition to its effect on carcinogenesis, iron can also maintain the growth of malignant cells as well as growth of pathogens. Breast cancer cells, for instance, display 5-15 times more transferrin receptors than normal breast tissue. Iron-carrying transferrin is in fact a growth factor. Hyposideremia in patients with cancer or infection is not a paraphenomenon but a functioning defense mechanism ('nutritional immunity'). If this immunity is broken by iron administration, relapses of diseases like tuberculosis, brucellosis, and malaria have been described. While iron-deficiency anemia should of course be diagnosed, treated and if possible prevented, there are good reasons to avoid over-utilization of medicamental iron.
 ...
PMID:Iron, free radicals and cancer. 182 Apr 88

There are differences between young and adult organisms regarding toxokinetic aspects and clinical manifestations of heavy metal intoxications. Chronically, toxic Cd intake causes a microcytotic hypochromic anemia in young rats at lower exposure levels and after shorter exposure periods than in adult animals. Cd absorption is increased by co-administration of milk and in conjunction with iron deficiency. After long exposure periods toxic Cd concentrations accumulate in the kidney cortex; this process starts very early in life. In 3-year-old children Cd concentrations in the kidney can reach up to one-third of those found in adults. Hg++ and methyl-Hg can cause Hg encephalopathia, and frequently cause mental retardation in adults. Correspondingly, Hg++ accumulation in the brains of suckling rats is approx. 10 times higher than in grown animals. Milk increases the bioavailability of Hg++. In suckling rats Hg is bound to a greater extent to ligands in the erythrocytes. Methyl-Hg concentrations in breast milk reach 5% of those in maternal plasma and that is a severe hazard for breastfed children of exposed mothers. Toxic Pb concentrations can lead to Pb encephalopathia. A high percentage of surviving children have seizures and show signs of mental retardation. Anemia and reduced intelligence scores were recently observed in children after exposure to very low levels of Pb. Pb absorption is increased in children and after co-administration of milk. There are no definite proofs for carcinogenesis or mutagenesis after oral exposure to Cd, Hg, and Pb in man. Heavy metal concentrations were found in the same order of magnitude in commercial infant formulas and in breast milk. When infant formulas are reconstituted with contaminated tap water, however, Pb and Cd concentrations can be much higher. The average heavy metal uptake from such diets exceeds the provisional tolerable weekly intake levels set by the WHO for adults, calculated on the basis of an average food intake and a downscaled body weight. These considerations do not even provide for differences in absorption and distribution or for the increased sensitivity of children to heavy metal exposure. However, dilution effects for essential heavy metals were observed in fast-growing young children; this effect might be extrapolated to toxic metals. These theoretical considerations are compared with epidemiological evidence. A health statistic from Baltimore shows a decline of Pb intoxications in infants. This observation correlates with a simultaneous decline in exposure to Pb which was due, for example, to decreased use of lead dyes in house paints and the abolition of tin cans for infant food.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[The toxicological estimation of the heavy metal content (Cd, Hg, Pb) in food for infants and small children]. 218

Although the toxicity of lead was recognized centuries ago, concern was restricted to overt symptoms: colic, encephalopathy, anemia, or renal disease. Two major reasons for lack of progress in restricting toxicity were that interest was limited to occupational exposures and there was lack of awareness of specific biochemical or metabolic effects. Identification of subclinical effects has been possible the last 15 or 20 years because of the development of sensitive measures to detect cognitive and behavioral changes that are not apparent clinically and because of methods to measure the reduced activity of heme enzymes. This progress was driven by basic and clinical research that resulted in a better understanding of cellular toxicology. The new awareness prompted the lowering of acceptable occupational exposures, as measured by blood lead from 80 to 40 to 60 micrograms/dL range, and the establishment of maximum recommended exposures in children to a blood lead level of 25 micrograms/dL. Lowering the lead content in gasoline has been accomplished by a nearly 50% decrease in average blood levels of persons in the United States (NHANES II data). Current research implicates lead as a contributing etiologic factor in a number of common diseases affecting large portions of the population such as subtle cognitive and neurological deficits, hypertension, congenital malformations, immunotoxicity, and deficits in growth and development. For each of these disorders there may be multiple etiologic factors; the scientific challenge is to develop sensitive methodology to detect the specific role of lead. Other potential subtle health effects include the influence of small amounts of lead on cell proliferation and lead as a cofactor in carcinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Lead toxicity: from overt to subclinical to subtle health effects. 220 87

Azobenzene (AZB) is non-carcinogenic in mice, but a potent rat carcinogen, inducing tumours in the spleen and other abdominal organs. The present paper shows that AZB clearly induces micronuclei in the bone marrow of rats at a dose of 375 mg/kg and above. In mice, however, only a marginally positive response was seen at much higher doses, thus reflecting the species-specific carcinogenic effect of the compound. The clastogenic effect of a single dose of AZB was not detectable in the rat 24 h after dosing, but at the 48 h sampling time and later. However, when a multiple-dosing regimen was used, an accumulation of micronucleated polychromatic erythrocytes (PEs) was seen and the effect was detected 24 h after the last dose. Micronucleus induction in rats was paralleled by increased methaemoglobin levels followed by anaemia. This resulted in accelerated erythropoiesis, as indicated by both the increased percentage of PEs in bone marrow and the increased reticulocyte count in peripheral blood. In mice, anaemia and methaemoglobaemia were seen. However, there was no compensatory increase in the percentage of PEs or any consistent change in the reticulocyte count. Stimulation of erythropoiesis could therefore be a contributory factor in the micronucleus induction by AZB seen in rats. One of the major metabolites of AZB, aniline, was also found to cause micronucleus induction in rats. Aniline is also a rat-specific carcinogen. It may therefore be speculated that AZB acts as a carcinogen via the formation of aniline, which might then be metabolized in different ways in rats and mice.
Carcinogenesis 1990 Sep
PMID:Effects of azobenzene and aniline in the rodent bone marrow micronucleus test. 240 Oct 44

The activity of the DNA excision repair enzyme uracil-DNA glycosylase was measured in peripheral blood mononuclear cells and in bone marrow aspiration samples obtained from patients with pernicious anemia (PA) or other types of megaloblastic anemia (one case of tapeworm anemia and three cases of myelodysplastic syndromes). In addition, the expression of uracil-DNA glycosylase was investigated in biopsies from the antrum and body of the stomach obtained from nine PA patients, from five patients having atrophic gastritis (AG) not associated with PA, and from six control patients having transient upper abdominal complaints without AG. Our results revealed that there was a considerable interindividual variation in gastric uracil-DNA glycosylase activity. No clear correlation between the enzyme level and the level of gastric atrophy was noted, although AG is generally regarded as a risk factor of gastric cancer. Furthermore, uracil-DNA glycosylase activities in peripheral blood mononuclear cells and in bone marrow cells in PA and in myelodysplastic syndromes were similar to the activities observed previously in non-hematological patients and healthy persons. Transient uracil incorporation into DNA may have a role in the cellular abnormalities associated with megaloblastic hematopoiesis. The present findings demonstrated that the enzymatic activity required for rapid removal of uracil from DNA is also expressed in the megaloblastic state.
Carcinogenesis 1987 Feb
PMID:Hematopoietic and gastric uracil-DNA glycosylase activity in megaloblastic anemia and in atrophic gastritis with special reference to pernicious anemia. 380 19

1-Amino-2,4-dibromoanthraquinone (ADBAQ), an intermediate in the production of commercial dyes for wool, silk, and synthetic fibers, was selected for toxicology and carcinogenesis studies in two rodent species. In advance of the 2-year studies, 13-week studies were conducted in male and female F344/N rats and B6C3F1 mice which were fed a diet containing ADBAQ at concentrations of 0, 0.25, 0.50, 1.00, 2.50, and 5.00%. ADBAQ stained the skin and fur red at all doses in rats and at 1.00% and higher concentrations in mice. Lethargy and emaciation were noted at the 2.50% and higher doses in rats of both sexes. In general, the absolute weight of the liver and the liver/organ weight ratios increased in both sexes and species at all doses. Treated rats developed a chronic toxic hepatitis characterized by hepatocytomegaly, centrilobular vacuolar degeneration and necrosis, regenerative nodules, acute necrotizing cholangitis, bile duct hyperplasia, chronic active inflammation in periportal areas, and focal pigmentation. The hepatopathy occurred at all doses in males and at 0.50% and higher in females and correlated with elevations of serum glutamic-pyruvic and glutamic-oxaloacetic transaminases, leukocytosis, and neutrophilia. Hyaline droplet degeneration in the proximal convoluted tubules of the kidneys occurred in male rats, and uterine atrophy was observed in female rats at 1.00% and higher. Anemia occurred in both sexes of rats at all doses and thymic atrophy was observed in both sexes of high-dose rats. In male mice minimal dose-related lesions in the liver included centrilobular glycogen depletion at 1.00% and higher and pigmentation at all doses. At comparable doses, ADBAQ was considered to be markedly toxic in rats and of minimal nonlife-threatening toxicity in mice.
 ...
PMID:Thirteen-week toxicology studies of 1-amino-2,4-dibromoanthraquinone in Fischer 344/N rats and B6C3F1 mice. 395 25

Renal hemangioendothelioma (HE) is an extremely rare malignant tumor. The sixth case is presented and all six analysed. The tumor affects middle-aged persons of either sex with past history of chronic renal disease and very recent onset of renal pain and hematuria. Anemia is common and a renal mass or tenderness is present. Pyelography shows poor function hydronephrosis, filling defect or collecting system distortion. A radical nephrectomy and radiotherapy is indicated and histology establishes the diagnosis. Renal HE appears to take a hurricane course and local recurrence and widespread vascular metastases occur in a matter of days or weeks after traditional cancer therapy. Industrial carcinogenesis is likely while chronic renal disease may predispose.
 ...
PMID:Renal hemangioendothelioma. 716 Oct 1

Fanconi anaemia (FA) is a hereditary tumour-prone disorder. FA cells exposed to DNA crosslinking agents show an increased frequency of chromosome aberrations and of deletion type mutations. The molecular basis of FA presumably is a deficiency in cellular repair of DNA adducts. In this work a shuttle vector plasmid was treated with 8-methoxypsoralen + a split dose of UVA (leading to crosslink induction), and transfected into FA lymphoblasts. The supF gene of the vector showed a mutation frequency similar to that of normal cells; however, the number of base substitutions was relatively low, whereas a high level (50%) of deletions was seen. With both normal and FA cells these deletions varied greatly in size and were randomly distributed within the supF gene. DNA cross-links were also induced using a triple helix forming 22-mer oligonucleotide linked to a psoralen molecule and being complementary to part of supF, leading to a > 30-fold increase of mutations, which were mainly position 167 single-base substitutions and showed a pattern identical to that of the normal cells. This normal response of FA cells to the site-specific DNA cross-links may reflect that not all gene sequences of FA cells are subjected to abnormal DNA repair. Alternatively, it may reflect a lower than normal genome-overall activity of a DNA cross-link repair complex, fully capable of efficiently repairing only molecules carrying relatively few adducts.
Carcinogenesis 1995 Mar
PMID:Mutational response of Fanconi anaemia cells to shuttle vector site-specific psoralen cross-links. 769 13

Research on contraceptive implants began when it was learned that steroids could be released from Silastic rubber capsules. The six-capsule Silastic drug delivery system, which would eventually be called Norplant, was by 1974 perfected and prepared for clinical trials. By 1978, data had accumulated to indicate a failure rate for Norplant after two years of only 0.6%, so Leiras Pharmaceuticals of Turku, Finland, was licensed in 1983 to manufacture Norplant, and Finland became the first country to give regulatory approval for distribution of the new contraceptive. The World Health Organization, after a 1984 evaluation, concluded that the Norplant system is an effective, reversible, long-term method of fertility regulation which is particularly appropriate for women in need of long-term contraceptive protection. Wyeth-Ayerst Laboratories began to distribute the device in the US after it met US Food and Drug Administration approval. 24 countries have now approved Norplant for distribution and use among women. This paper describes the Norplant contraceptive system, its mechanism of action, insertion and removal, effectiveness, contraindications, and adverse effects with regard to menstrual problems, medical problems, infection or pain, drug interactions, ectopic pregnancy, foreign body carcinogenesis, and other adverse reactions. It also notes use benefits in terms of contraceptive action, convenience, the reduction of adverse reactions for former oral contraception users, and the prevention of anemia, and lists categories of potential acceptors and women who may not wish to use Norplant.
 ...
PMID:Implantable contraception. 770 29

Four disease genes (NBCCS, ESS1, XPAC, FACC) map to 9q22.3-q31. A fine map of this region was produced by linkage and haplotype analysis using 12 DNA markers. The gene for nevoid basal cell carcinoma syndrome (NBCCS, Gorlin) has an important role in congenital malformations and carcinogenesis. Phase-known recombinants in a study of 133 meioses place NBCCS between (D9S12/D9S151) and D9S176. Haplotype analysis in a two-generation family suggests that NBCCS lies in a smaller interval of 2.6 cM centromeric to D9S287. These flanking markers will be useful clinically for gene tracking. Recombinants also map FACC (Fanconi anemia, group C) to the same region, between (D9S196/D9S197) and D9S287. The recombination rate between (D9S12/D9S151) and D9S53 in males is 8.3% and 13.2% in females, giving a sex-specific male:female ratio of 1:1.6 and a sex-averaged map distance of 10.4 cM. No double recombinants were detected, in agreement with the apparently complete level of interference predicted from the male chiasmata map.
 ...
PMID:Analysis of 133 meioses places the genes for nevoid basal cell carcinoma (Gorlin) syndrome and Fanconi anemia group C in a 2.6-cM interval and contributes to the fine map of 9q22.3. 783 1


1 2 3 4 5 6 7 8 9 10 Next >>