Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An alkaline diaminobenzidine (DAB) medium has been used to identify peroxidase activity in small granules (0.09 to 0.2 mu in diameter) present in all forms of maturing erythrocytic cells with the exception of erythrocytes. These granules, which were more frequent in proerythroblasts (from two to seven by thin section), were distinct from pleomorphic granules present in the close proximity to the Golgi apparatus. They were also distinct from ferritin molecules which were seen as aggregates in siderosomes of polychromatophilic erythroblasts. They often appeared in close association with the smooth membrane of the nuclear envelope. Optimal conditions for the visualization of these granules by incubation in alkaline DAB were obtained when the peroxidase activity of hemoglobin was reduced by addition of low concentrations of potassium cyanide. Lack of hydrogen peroxide in the incubation media completely inhibited the staining reaction of hemoglobin, while the positive reaction persisted in the granules. Aminotriazole in the incubation media prevented the staining of these organelles. These findings suggest that small granules seen in maturing erythroblasts contain catalase and that they correspond to microperoxisomes described in other tissues. The mechanism of their disappearance during reticulocyte maturation is unknown. The relationship between particulate catalase of erythroblasts and soluble erythrocytic catalase has not been elucidated.
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PMID:Fine structural and cytochemical identification of microperoxisomes in developing human erythrocytic cells. 4 50

The detailed anatomical distribution of iron in the post-mortem human brain has been studied using Perl's and Turnbull's methods with the diaminobenzidine intensification procedure for the demonstration of non-haem Fe3+ and Fe2+, respectively. Attention to methodological procedures has revealed that even brief immersion of tissue in routinely used fixatives causes a reduction of staining intensity in areas of high iron content and, often, loss of staining in areas of low iron content. Optimal staining is obtained using frozen section briefly fixed for 5 min in 4% formalin and Perl's stain (Fe3+) with diaminobenzidine intensification. Highest levels of stainable iron were found in the extrapyramidal system with the globus pallidus, substantia nigra zona reticulata, red nucleus and myelinated fibres of the putamen showing highest staining reactivity. Moderate staining intensity with Perl's technique was found in the majority of forebrain, midbrain and cerebellar structures with the striatum, thalamus, cortex and deep white matter, substantia nigra zona compacta, and cerebellar cortex showing consistent staining patterns with intensification of Perl's stain. The brain-stem and spinal cord generally only showed staining with the intensification procedure and even this was of low intensity. Microscopically the non-heam iron appears to be found predominantly in glial cells as fine cytoplasmic granules which in heavily stained areas coalesce to fill the entire cell. Iron-positive granules appear to be free in the neuropil and also around blood vessels in the globus pallidus, striatum and substantia nigra. The neuropil shows a fibrous impregnation when stained for iron which is, in part, derived from glial processes, myelinated fibres and fibre bundles. Neurones, in general, show only very low reactivity for iron, and this is difficult to discern due, often, to the higher reactivity of the surrounding neuropil. In the globus pallidus and substantia nigra zona reticulata, neurones with highly stainable iron content are found with granular cytoplasmic iron reactivity similar to that seen in the local glial cells. Our results are comparable with those of early workers, but with the use of intensification extend the distribution of non-haem iron to areas previously reported as negative. No apparent correlation of iron staining with known neurotransmitter systems is seen and the predilection for the extrapyramidal system is not easily explained, though the non-haem iron in the brain appears to be as a storage form in the iron storage protein ferritin. The localization of iron in the brain provides a foundation for the study of iron in certain neurodegenerative diseases such as Parkinson's disease, where iron has been implicated in the pathogenesis.
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PMID:Histochemical distribution of non-haem iron in the human brain. 152 78

Cutaneous pigmentation is a common complication of sclerotherapy of dilated lower limb veins. Histologic examination has shown that the pigment is due to hemosiderin deposition predominantly in the superficial dermis. Optimal technique will reduce the incidence of pigmentation but it is likely that patient factors such as total body iron storage may explain why some patients are more prone to develop pigmentation. Traditional exfoliation therapies have not given reliable reproducible results and there is need to develop an effective treatment without adverse sequelae. In this study 16 patients with refractory postsclerotherapy pigmentation were treated with the copper vapor laser. Within 3 months of treatment 11 (69%) had significant clearing of the pigmentation. Four (25%) had slight improvement and one patient had no discernible improvement. No adverse sequelae were reported or observed. The treated patients and 16 matched control patients who had not developed pigmentation were investigated with serum iron, ferritin and transferrin levels. There was a trend towards higher serum iron and ferritin levels and lower transferrin levels in the patients who developed pigmentation compared with those who did not develop this sequela. This trend was statistically significant for ferritin levels in patients 50 years of age and younger. The results indicate that serum ferritin may be a good indicator of susceptibility to postsclerotherapy pigmentation.
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PMID:Postsclerotherapy hyperpigmentation. The role of serum ferritin levels and the effectiveness of treatment with the copper vapor laser. 160 69

The general impact of blood donation on iron status has been studied in Danish males. Iron stores were assessed by serum (S-) ferritin and haemoglobin (Hb) in a population survey comprising 1433 males in age cohorts of 30, 40, 50, and 60 years; 389 (27%) were blood donors and 1044 (73%) non-donors. Hb levels were identical in donors and non-donors, mean 155 +/- 11 (SD) g/l (9.6 +/- 0.7 mmol/l); values less than 129 g/l (8.0 mmol/l) were observed in 1.3% of donors vs 1.9% of non-donors. Correlations between S-Ferritin and Hb were slight and without practical clinical relevance: rS = 0.13, p less than 0.01 in donors vs rS = 0.16, p less than 0.0001 in non-donors. Donors had lower S-Ferritin, median 95 micrograms/l, than non-donors, median 136 micrograms/l (p less than 0.0001). S-Ferritin values less than 15 micrograms/l (i.e. depleted iron stores) were seen in 3.3% of donors vs 0.4% of non-donors, and S-Ferritin values of 15-30 micrograms/l (i.e. small iron stores) in 9.8% of donors vs 1.4% of non-donors. Iron-deficiency anaemia (i.e. S-Ferritin less than 15 micrograms/l and Hb less than 129 g/l) was seen in 0.26% of donors vs 0.10% of non-donors; employing the 5th percentile for Hb (137 g/l (8.5 mmol/l] as discriminatory value increased the percentage of iron-deficiency anaemia to 0.51% in donors vs 0.10% in non-donors. Blood donation had a marked influence on iron status in the adult male population. The frequency of phlebotomy should be adjusted according to S-Ferritin as well as Hb levels. If Hb is used as single criterion for donation, only donors with pre-donation values greater than or equal to 135-137 g/l should be allowed phlebotomy. Optimal donation standards should include monitoring of iron status through measurement of S-Ferritin and Hb, combined with individualised postdonation iron supplementation.
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PMID:Influence of blood donation on iron stores assessed by serum ferritin and haemoglobin in a population survey of 1433 Danish males. 188 81

Isolated rat liver lysosomes were incubated with [14C]methemoglobin under various conditions. Optimal pH for the in vitro proteolysis was found to be 4-5. To evaluate whether or not degradation of added proteins could be due to enzyme leakage the integrity of the lysosomes was measured. Isolated lysosomes were found to be stable for up to 10 min of incubation at pH 5.5 and for 30 min at pH 7. The degradation of three different proteins (methemoglobin, ovalbumin, and lysozyme) was analyzed. No correlation was detected between rate of breakdown and physical properties of the proteins. Leupeptin, chloroquine, and propylamine inhibited proteolysis of added proteins by 45-65% in both neutral and acid milieu. Possible energy requirement was tested by the addition of Mg2+ and ATP to the incubation medium. A dose-dependent increase in proteolytic rate was found when ATP was added to the lysosomal suspension, a finding most likely due to acidification of the lysosomes and ensuing increased degradation. GTP and ITP were somewhat less effective. The noncleavable ATP analogue 5'-adenylylimidodiphosphate gave no stimulation. The ATP-driven proteolysis was inhibited by ethylmaleimide. Isolated lysosomes were also incubated with ferritin in order to visualize a possible uptake process of a protein in the electron microscope. Following incubation, ferritin particles were seen inside intralysosomal vesicles which appeared to be formed by invagination of the lysosomal membrane, a process designated microautophagy. The results thus support the notion that isolated lysosomes may micropinocytose and degrade exogenously added proteins and that this process is ATP dependent.
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PMID:Uptake--microautophagy--and degradation of exogenous proteins by isolated rat liver lysosomes. Effects of pH, ATP, and inhibitors of proteolysis. 396 51

Optimal molar ratios of antibody: ferritin: glutaraldehyde for the preparation of antibody-ferritin conjugates were investigated. The reaction volumes and the antibody concentration were held constant in twenty different reaction mixtures. The effect of five different antibody: glutaraldehyde ratios ranging from 1:25 to 1:400 and of four different antibody: ferritin ratios (1:1 to 1:01) on the yield of antibody-ferritin conjugates was tested in one-step reactions. The 20 different conjugates were tested by a newly developed gel precipitation technique, the inverse fused line rocket immunoelectrophoresis and by counting relative numbers of ferritin monomers and oligomers under the electron microscope. High concentrations of glutaraldehyde produced large heterogeneous precipitates as visualized in the gel technique. The relatively highest yield of ferritin-labeled antibodies without larger conjugates was produced by reacting antibodies, ferritin and glutaraldehyde at molar ratios of 1:1:100. The FRT-antibody conjugates produced at these molar ratios were partly abe to precipitate with their respective antigens.
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PMID:Ferritin-labeling of antibodies by glutaraldehyde. Comparison of conjugates prepared at different antibody: ferritin: glutaraldehyde ratios. 679 Apr 24

The treatment of anemia in patients with renal failure has been dramatically changed with the development of recombinant human erythropoietin (r-HuEPO). This review discusses the pathogenesis of the anemia renal failure and the biology of erythropoietin. Causes of poor response to r-HuEPO therapy are outlined, and the importance of adequate available iron is highlighted. Parameters used to measure iron adequacy include serum iron levels, transferrin saturation, and ferritin levels. Other nutritional deficiencies, such as folic acid and vitamin B-12, can also impair r-HuEPO response. Clearly, the advent of r-HuEPO treatment for patients with renal failure and anemia has brought another dimension to the care of these patients. Optimal nutrition management is critical for the success of this new agent.
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PMID:Nutritional implications of recombinant human erythropoietin therapy in renal disease. 807 84

To investigate the possibility of targeting chelators into the lysosomal iron pool, nine bidentate 3-hydroxypyridin-4-ones with basic chains have been synthesized. As the turnover of ferritin iron is centred in the lysosome, such strategy is predicted to increase chelator efficacy of bidentate ligands. The pKa values of the ligands together with their distribution coefficients between 1-octanol and 4-morpholinepropane sulphonic acid (MOPS) buffer pH 7.4 have been determined. The in-vivo iron mobilization efficacy of these basic 3-hydroxypyridin-4-ones has been investigated in a 59Fe-ferritin-loaded rat model. No obvious correlation was observed between efficacy and the pKa value of the side chain, although those with pKa > 7.0 tended to be more efficient than those with pKa < 7.0. The imidazole-containing molecules are much less effective than the tertiary amine derivatives. A dose-response study suggested that basic pyridinones are relatively more effective at lower doses when compared with N-alkyl hydroxypyridinones. Optimal effects were observed with the piperidine derivatives 4h and 4i. The derivative 4i at a dose of 150 micromol kg(-1) was more effective than 450 micromol kg(-1) deferiprone, the widely adopted clinical dose.
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PMID:Design, synthesis and evaluation of N-basic substituted 3-hydroxypyridin-4-ones: orally active iron chelators with lysosomotrophic potential. 1075 13

Early diagnosis and treatment of hemochromatosis is essential to prevent organ damage. Screening strategies to detect early hemochromatosis include testing for iron overload and/or genetic testing. Voluntary blood donors numbering 5,211 were screened with unbound iron-binding capacity (UIBC), transferrin saturation (TS), and genetic testing for the C282Y mutation of the HFE gene. The study found 16 C282Y homozygotes (1 in 327), 69 compound heterozygotes, 371 simple heterozygotes, and 4,755 normals. There were 5 men and 11 women homozygotes with a mean age of 42, range 28 to 57. Mean UIBC (24 +/- 7 microL) and TS (48% +/- 17%) in homozygotes were significantly different from compound heterozygotes, simple heterozygotes, and normals (ANOVA). Only 3 homozygotes had an elevated serum ferritin. Family studies found an additional 4 iron-loaded homozygotes. Optimal thresholds were < or =28 micromol/L for UIBC and > or =46% for TS. Receiver operating characteristic (ROC) curve analysis showed an area under the curve for UIBC of 0.93 (0. 85-1.0, 95% confidence interval), and for TS of 0.83 (0.7-0.95). Screening with UIBC to preselect those for genotyping is a cost-efficient strategy for population screening for hemochromatosis.
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PMID:Population screening for hemochromatosis: a comparison of unbound iron-binding capacity, transferrin saturation, and C282Y genotyping in 5,211 voluntary blood donors. 1079 97

Studies employing mRNA transfection are currently limited by a lack of transcription vectors for generating a long poly(A) tail-containing mRNA and published methods for efficient mRNA transfection. We have constructed a transcription vector containing firefly luciferase gene (pBS-FLuc-A100) to generate luciferase mRNA with A100 tail followed by no heterologous sequence. The pBS-FLuc-A100 was propagated in XL1-Blue, in which the plasmid was more stable than in other bacterial strains. Optimal mRNA transfection conditions were determined using TransMessenger Transfection Reagent (Qiagen) and yeast tRNA as a carrier. Firefly luciferase expression, which peaked at about 12 h post-transfection, was detected with as little as 5 ng mRNA and was linear with mRNA amount up to 100 ng. When cells were transfected with luciferase mRNA containing different lengths of poly(A) tail, luciferase expression increased proportionally with poly(A) tail length up to 60A residues and then declined. Cell lines from monkey, mouse, and rat were transfected efficiently by this method. Like cellular ferritin heavy chain mRNA, which contains an iron response element in its 5'UTR, translation of transfected luciferase mRNA containing the 5'UTR of ferritin mRNA was iron-dependent. Our results demonstrate that the poly(A) vector and the transcription method described will be useful to study the regulation of gene expression at the mRNA level by UTRs.
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PMID:Optimized transfection of mRNA transcribed from a d(A/T)100 tail-containing vector. 1580 89


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