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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

4-Dimethylaminoazobenzene was fed to Wistar-derived, male, albino rats after hepatic siderosis had been induced by including ferric citrate in the diet. Iron-free foci of hepatocytes developed and this characteristic enabled them to be recognized macroscopically in the brown parenchyma. Five such lesions, each 1 mm or less in diameter, were studied by light and electron microscopy. The cells in the foci were larger than those surrounding the foci and had a granular and moderately basophilic cytoplasm. Ultrastructurally, the cells closely resembled normal hepatocytes. They possessed well-developed rough endoplasmic reticulum, numerous free ribosomes, peroxisomes, bile canaliculi, and cytoplasmic junctional complexes, but only small stores of glycogen were observed. Occasional ferritin-laden lysosomes persisted in some cells. These foci were regarded as hyperplastic. Possibly, they evolved into hyperplastic nodules either of the basophilic or vacuolated type. These foci should be clearly distinguished from hyperbasophilic foci that consisted of very poorly differentiated cells.
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PMID:Hyperplastic foci in precancerous rat liver: light microscopic and electron microscopic study. 9 41

Knowledge of disturbancies of iron utilization has been considerably extended by histochemical-ultrastructural findings and the results of immunoradiometric assays for serum ferritin. -- In chronic anaemia due to infections or neoplastic diseases hyposideraemia and normal unsaturated iron binding capacity were associated with increased iron retention in macrophages and slightly to highly increased serum ferritin (500--4000 ng/ml). -- 117 patients with sideroblastic anaemia formed a heterogenous group of diverse aetiology. The iron granules of ringed sideroblasts contained nonferritin iron in mitochondria. At diagnosis, a normal iron status was found in single cases. More frequently, praelatent and latent iron overload with ferritin levels up to more than 2000 ng/ml were observed. Manifest iron overload with tissue damage was mostly the result of numerous transfusions (ferritin 4700 bis 9500 ng/ml). -- After i.v. application of colloidal iron endothelial siderosis was a regular finding. The typical uniform granules representing nonferritin-iron in lysosomes disappeared in the course of 1--3 years completely. In contrast, the colloidal iron taken up simultaneously by the macrophages was rapidly transformed into ferritin and easily used up for haemoglobin synthesis when required. The corresponding increase of serum ferritin up to maximal 4000 mg/ml was dose related. Continued blood losses lead to residual endothelial siderosis after exhaustion of macrophageal iron and recurrence of iron deficiency anaemia. The serum ferritin fell to low levels (0--12 ng/ml) as observed in untreated cases.
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PMID:[Disturbancies of iron utilization: chronic anaemia, sideroblastic anaemia, and residual endothelial siderosis (author's transl)]. 73 33

Serum ferritins from a patient with haemochromatosis and from a patient with transfusional siderosis were compared with tissue isoferritins on the basis of their iron content, isoferritin spectrum and immunological properties. Both serum ferritins had a low iron content and corresponded to only the most basic isoferritins in liver. The serum ferritins were very similar to the natural apoferritin from liver in all respects.
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PMID:Characterization of serum ferritin in iron overload: possible identity to natural apoferritin. 87 33

The disruption of lysosomes with release of their content of lytic enzymes was an early concept for the possible role of these organelles in the pathogenesis of tissue damage. Many examples are known of primary lysosomal storage diseases due to a congenital deficiency of certain acid hydrolases. It is suggested that iron overload due to either primary haemochromatosis or transfusional siderosis is a form of acquired secondary lysosomal storage disease. Subcellular fractionation experiments and electron microscopic studies have shown that liver tissue from patients with iron overload has iron-laden lysosomes. Similar results have been found in iron-overloaded rats. In patients, but not in experimental animals, enzymic analyses have shown increased activities of acid hydrolases and strikingly enhanced lysosomal fragility in liver homogenates. When it has been possible to deplete the patients of the excessive iron, these parameters have returned to normal. The possible mechanisms by which the iron compounds disrupt lysosomes, including distension with ferritin or haemosiderin or free-radical-mediated membrane damage, will be discussed.
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PMID:Lysosomal disruption in the pathogenesis of hepatic damage in primary and secondary haemochromatosis. 105 36

A sensitive, specific and precise immunoradiometric assay for ferritin has been developed. Ferritin was measured in the serum of 160 hospital controls, 101 females (118 +/- 9 mug/l) and 59 males (189 +/- 16 mug/l). This difference was statistically significant. In 28 patients with untreated iron deficiency anaemia, serum ferritin concentration (6.1 +/- 0.7 mug/l) was significantly lower than in the controls, but it was within the normal range in 14 cases of polycythaemia vera treated by repeated phlebotomy. In 4 patients with primary haemachromatosis (2884 +/- 56 mug/l), 25 with secondary iron overload states (5702 +/- 1235 mug/l) and 8 with haemolytic anaemia (1612 +/- 605 mug/l), serum ferritin levels were markedly elevated. In 14 cases of transfusional siderosis there was a highly significant correlation between serum ferritin concentration and units of blood transfused. A circadian rhythm in serum ferritin concentration was observed in 7 healthy subjects.
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PMID:Immunoradiometric assay for ferritin in human serum. 121 36

1 hour after i. v. infusion of colloidal iron in iron deficient subjects uniform phagosomal iron granules were observed in macrophages and endothelial cells of several organs. 7 to 10 days later transformation into ferritin coould be visualized in macrophages only. Now, these cells showed diffuse iron staining of the cytoplasm due to dispersed ferritin molecules. Polymorphous lysosomes contained densely packed particles from still unchanged ferric hydroxide to paracristalline ferritin. The macrophageal iron was mobilizable in few days to several weeks. The univorm lysosomal iron granules of endothelial cells disappeared after 1 to 2 years. Endothelial iron siderosis without previous i. v. iron application was a frequent finding in pernicious anaemia and iron overload of diverse origin.
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PMID:Iron storage in macrophages and endothelial cells. Histochemistry, ultrastructure, and clinical significance. 126 Jan 44

The relationship of pretreatment serum ferritin and hepatic iron concentration to body iron removed by venesections was evaluated in 33 patients with genetic hemochromatosis. The median values of the three variables considered were 1,950 micrograms/L (range = 255 to 10,000), 1,175 micrograms/100 mg dry weight (range = 270 to 4,310) and 10 gm (range = 2 to 41), respectively. At basal liver biopsy 18 patients had cirrhosis, 6 patients had fibrosis and 9 patients had a normal pattern; siderosis was degree 3 in 6 patients and degree 4 in 27 patients. The results of fitting a polynomial regression of second degree showed that the curve of serum ferritin on iron removed was a straight line (R2 = 0.79, with a significant coefficient of linearity, p less than 0.01, and a nonsignificant coefficient of curvature), whereas that of hepatic iron concentration on iron removed showed a curvature (R2 = 0.62, with significant coefficient of linearity and curvature, p less than 0.01) and reached a plateau. The sigmoid model fit the curve of hepatic iron concentration on iron removed (R2 = 0.61), which suggested a saturation of hepatic iron storage capability; the asymptote corresponded to a hepatic iron concentration of about 2,000 micrograms/100 mg. In alcoholic patients (17 cases) the location of the sigmoid was greater than in nonalcoholic patients. Our results suggest that iron deposition occurs in the liver before other organs are involved and that with massive iron overload hepatic deposits reach saturation, after which hepatic iron concentration does not always reflect the amount of total stores. Alcohol consumption could slow the saturation of hepatic iron deposits.
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PMID:Saturability of hepatic iron deposits in genetic hemochromatosis. 139 2

The pathogenesis of superficial siderosis of the central nervous system (CNS) may be examined by the repeated intracisternal injection of washed autologous red blood cells (RBC). In rabbits, the injections cause the accumulation of iron in the cytoplasm of microglial cells and astrocytes of cerebellar and cerebral cortices. Immunocytochemistry for ferritin reveals enhanced reaction product mainly in microglia but hemosiderin occurs only after extending the injections to 6 months. In an effort to determine the biochemical correlates of these morphological changes, iron, ferritin, ferritin subunits and the ferritin repressor protein (FRP) were quantitated. There was no increase of total iron or ferritin in the exposed cortical areas. However, the injections of RBC caused dramatic shifts of the relative contributions by heavy (H-) and light (L-) ferritin subunits. The initial response was a prompt increase of the H/L ratio to over 4.0 from the normal ratio near 1.0. Extended injections caused the ratio to drop to below unity, and the predominance of L-ferritin at 6 months coincided with the appearance of granular hemosiderin. This investigation also confirmed the presence of FRP in rabbit brain cytosols but the induction of experimental superficial siderosis did not change its levels or in vitro affinity for the iron-responsive element in ferritin messenger ribonucleic acid. It is proposed that the incrustation by hemosiderin which characterizes superficial siderosis of the CNS in humans occurs when prolonged exposure to hemoglobin produces persistent shifts of the H/L-ratios by accumulation of L-ferritin.
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PMID:Experimental superficial siderosis of the central nervous system: biochemical correlates. 146 38

Excessive hemosiderin-laden perivascular macrophages have been described in the brains of patients with the acquired immunodeficiency syndrome (AIDS) who underwent autopsy; its meaning remains unclear. In the brains of 53 patients with AIDS who consecutively underwent autopsy, we quantified the abnormality, elucidated its relationship to the pathologic features of AIDS, and asked if there was some relationship to endogenous iron storage and transport proteins in brain macrophages and microglia. The number of perivascular siderotic macrophages was significantly increased in patients with AIDS compared with age-matched control subjects. Macrophage siderosis was strongly correlated with the presence of disseminated mycobacterial infection and vacuolar myelopathy at autopsy; a generalized wasting (cachexia) also was related significantly. Many other pathologic abnormalities were not related, including putative human immunodeficiency virus-specific neuropathologic changes such as multinucleated cells and myelin pallor. Activated macrophages and microglial cells in the central nervous system had dense intracytoplasmic accumulation of ferritin (iron storage protein) in AIDS and non-AIDS patients. These results suggest that siderosis of cerebral macrophages is related to an ill-defined nonspecific systemic imbalance associated with the breakdown of abundant stores of endogenous intracellular ferritin. Understanding chronic "secondary" effects of human immunodeficiency virus type 1 infection will become increasingly important as improved survival in patients with AIDS is realized.
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PMID:Siderotic cerebral macrophages in the acquired immunodeficiency syndrome. 158 Jul 55

Alcohol abuse is associated with disturbances to iron metabolism in man, ranging from anemia to siderosis. Also seen in these patients are increased serum ferritin levels. Since the liver not only stores iron in cytosolic ferritin, but has also been shown to take up this molecule from the plasma by an active transport mechanism, it has been suggested that the iron in this circulating ferritin may contribute to the increased incidence of siderosis seen in alcoholics. As part of an ongoing study of these disturbances, using a rat model, we have examined the uptake of ferritin by freshly isolated hepatocyte suspension to test the hypothesis that increased hepatocyte uptake of ferritin iron contributes to the siderosis seen in some alcoholics. Incubation of hepatocytes in the presence of ethanol resulted in a progressive reduction in uptake with increasing alcohol concentration, from 1.23 +/- 0.05 ng of ferritin/10(6) cells/min to 0.65 +/- 0.02 ng/10(6) cells/min (mean +/- SD) at an ethanol concentration of 100 mM. 4-Methylpyrazole (0.1 mM) restored 70% of this activity, but higher concentrations also decreased ferritin uptake in the absence of ethanol. The addition of 5 microM cyanamide decreased ferritin uptake slightly in the presence of ethanol (0.82 +/- 0.04 ng of ferritin/10(6) hepatocytes/min vs. 0.86 +/- 0.03 ng/10(6) cells/min for ethanol alone), while having no effect in the absence of ethanol (1.01 +/- 0.04 vs. 1.12 +/- 0.05 ng/10(6) cells/min). Preincubation of the hepatocytes with acetaldehyde resulted in a dose-dependent reduction to a maximum reduction of approximately 25% at 300 microM acetaldehyde.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of ethanol metabolism on ferritin uptake by freshly isolated rat hepatocytes: is acetaldehyde responsible for this alteration? 159 May 51


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