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)

Lymph-borne immunoblasts were fixed in dilute glutaraldehyde and then treated with saponin. This treatment made most parts of the cells permeable to ferritin, so that anti-immunoglobulin (Ig) antibodies which had been conjugated to horse radish peroxidase (HRP) had no difficulty in gaining access to Ig which thus could be demonstrated at an ultrastructural level. Best results were obtained by fixing the cells in 0.1% glutaraldehyde for 7 min and then treating them with a 1% solution of saponin for 100 min at 55 degrees C before exposing them to the Ig-HRP conjugate. The method yielded reproducible results and although it causes a small amount of ultrastructural damage, it may be of value in detecting a variety of intracellular antigens.
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PMID:The use of detergents and immunoperoxidase reagents for the ultrastructural demonstration of internal immunoglobulin in lymph cells. 34 2

Best macular dystrophy (BMD), also known as vitelliform macular dystrophy (VMD2; OMIM 153700), is an autosomal dominant form of macular degeneration characterized by an abnormal accumulation of lipofuscin within and beneath the retinal pigment epithelium cells. In pursuit of the disease gene, we limited the minimum genetic region by recombination breakpoint analysis and mapped to this region a novel retina-specific gene (VMD2). Genetic mapping data, identification of five independent disease-specific mutations and expression studies provide evidence that mutations within the candidate gene are a cause of BMD. The 3' UTR of the candidate gene contains a region of antisense complementarity to the 3' UTR of the ferritin heavy-chain gene (FTH1), indicating the possibility of antisense interaction between VMD2 and FTH1 transcripts.
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PMID:Identification of the gene responsible for Best macular dystrophy. 966 95

We compared 48-hour urinary iron excretion after a twice-daily subcutaneous bolus injection of deferoxamine and after 12 hours of subcutaneous continuous infusion of the drug in 27 patients with iron overload (mean age, 55.7 years). In most patients, the iron overload was due to multiple transfusions administered during chemotherapy or as part of supportive care for a hematologic or oncologic disorder. One patient had sickle cell anemia and 1 had hereditary hemochromatosis and spherocytosis. Similar urinary iron excretion was observed with the 2 methods of administration; mean +/- SD values were 6935.3 +/- 3832.3 microg/48 hours with subcutaneous bolus injection and 6630.4 +/- 3606.9 microg/48 hours with subcutaneous continuous infusion (P =.3). Twenty-six patients (96.3%) chose to continue therapy with bolus injection. The long-term efficacy of bolus injection was evaluated by measuring the serum ferritin concentration at regular intervals for a follow-up time of 20.1 +/- 4.5 months. Ferritin concentration decreased to below 1000 microg/L in 73% of the patients and to below 500 microg/L in 42% and became normal in 26%. Best results were obtained in patients who were no longer receiving blood transfusions when chelation therapy was initiated. Three of 26 patients (11.5%) had mild, transient side effects after bolus injection. Larger prospective, randomized studies must be conducted before deferoxamine bolus injection can be routinely recommended for patients with iron overload. (Blood. 2000;95:2776-2779)
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PMID:Safety and efficacy of subcutaneous bolus injection of deferoxamine in adult patients with iron overload. 1077 20

Recombinant human erythropoietin (rhEPO), which increases red cell mass, is one of the most abused substances in sport. Abuse is currently undetectable by the only direct routine method, immunoassay, since blood and urine rhEPO are immunologically indistinguishable from endogenous EPO. Elevated EPO levels are only detectable several days after rhEPO administration. Indirect parameters have therefore been introduced, primarily the haematocrit level, but also markers of functional iron deficiency during or after rhEPO administration (hypochromic red cells and reticulocytes, serum transferrin receptors, ferritin levels) and, in the urine, fibrin degradation products. Although iron status indices have yielded promising results, athletes are currently banned solely on the basis of their haematocrit. Yet various factors can cause false positive haematocrit results with potentially fatal consequences to athletes' careers. Until new direct assays such as liquid chromatography-mass spectrometry have been evaluated and introduced, efforts must be directed at using a battery of tests to increase the sensitivity and specificity and reduce the number of false positives and false negatives.
Baillieres Best Pract Res Clin Endocrinol Metab 2000 Mar
PMID:Erythropoietin test methods. 1093 16

5 years after a previous study, we followed up a group of thalassemic patients, determining DHEA-S levels in peripubertal age, with the aim of evaluating whether adrenarche maturation occurred in boys and advanced in girls. Furthermore, we evaluated the degree of bone mineral density (BMD SDS(BA)) and analyzed growth parameters calculating standard deviation score with respect to bone age (BA) of height (Ht SDS(BA)), sitting height (SH SDSBA), and subischial leg length (SLL SDSBA), body mass index (BMI) and the difference between the values of the previous and the present study (deltaBMI), thyroid function and serum markers of bone metabolism. Our results showed persistent lack of adrenarche (DHEA-S 25+/-9.5 microg/dl) in all 6 boys and the absence of pubertal signs at chronological age (CA) of 12.4+/-1.4 yr and BA of 11.1+/-1.1 yr. Only one boy, 6 months later, showed a testicular volume of 4 ml (Tanner stage G2) with an increase of DHEA-S value (181 microg/dl) at BA 12.8 yr. Body disproportion and severe degree of osteopenia (BMD SDSBA -2.41+/-0.5) were observed in all boys, even though Ht SDSBA (0.14+/-0.8) and markers of bone metabolism were within the normal range. No change in nutritional status was observed (deltaBMI 0.09+/-0.4 kg/m2). In contrast, all the thalassemic girls had DHEA-S values (172.7+/-97.7 microg/dl) within the normal range at BA 12.7 +/-0.6 yr that was similar to CA. Furthermore, the appearance of Tanner stage B2 occurred in each of them at BA, near to CA, of 10.4+/-0.9 yr, and menarche was observed in three of them at mean BA, near to CA, of 11.4+/-0.9 yr. Ht SDSBA was below normal range (-1.11+/-0.8), but SLL SDSBA and SH SDS(BA) values were reduced homogeneously, so that proportional body growth was observed. A significant change in nutritional status was observed (deltaBMI 2.69+/-0.9 kg/m2). Bone density value (BMD SDS(BA) -0.25+/-0.4) was in the normal range. There were no statistically significant differences between boys and girls for ferritin serum levels, blood consumption and desferrioxamine dosage. In conclusion, lack of change in nutritional status, measurable in the form of deltaBMI, but not BMI alone, considered an important physiological regulator of adrenarche, regardless of individual adrenal androgen secretion, could have a key role in the lack of adrenarche persisting in thalassemic boys during peripubertal age. Further follow up is necessary, in particular when boys reach puberty, because delayed adrenarche represents the most intriguing aspect in these patients.
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PMID:Persistence of delayed adrenarche in boys with thalassemia. 1132 74

The European Best Practice Guidelines for the management of anemia in patients with chronic renal failure recommend the percentage of hypochromic red blood cells (%HRCs) as the best measure of iron use by erythropoietic tissues. They suggest that "sufficient iron should be administered to attain: serum ferritin 100 ng/mL, HRCs <10%. In practice, to achieve these minimum criteria will mean aiming for optimal levels of serum ferritin 200-500 ng/mL, HRCs <2.5%." We increased prospectively the delivered dose of iron supplements to a large (n = 228) unselected hemodialysis cohort with a sustained (24-month) hemoglobin (Hb) outcome meeting the UK Renal Association minimum standard of 85%, greater than or equal to 10.0 g/dL. This was managed through a computer-aided decision support system for erythropoietin (EPO) and intravenous iron sucrose therapy. Hb outcome was maintained with medians between 11.3 and 11.8 g/dL. Median red blood cell hypochromia (%HRCs) decreased from 8% (interquartile range [IQR], 3 to 15) to 4% (IQR, 2 to 8; P < 0.001, U-Mann Whitney test). Serum ferritin level increased from a median of 188 (IQR, 115 to 256) to 480 ng/mL (IQR, 397 to 595; P < 0.001, U-Mann Whitney test). Median EPO dose decreased from 136 (IQR, 83 to 216) to 72 IU/kg/wk (IQR, 33 to 134), which strongly correlated with median %HRCs through the range less than 10% (Spearman's correlation, 0.73; P < 0.01). These data suggest that EPO responsiveness continues to improve toward the normal range for %HRCs (<2.5%) and aspiring to values much less than 10% is cost-effective. The ferritin outcome required to achieve these lower values for %HRC outcome is greater than the current recommended range, although in steady state, the mean iron treatment dose is similar to that in previous studies (ie, approximately 60 mg/wk).
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PMID:Optimizing erythropoietin therapy in hemodialysis patients. 1197 60

The invention of recombinant human erythropoietin (rHuEpo) for the treatment of renal anaemia was a hallmark in the care of patients with renal insufficiency. Recently published guidelines (European Best Practice Guidelines, NKF-DOQI) have set the target haemoglobin to be reached by treatment with rHuEpo to >11 g/dl. Normalizing haemoglobin levels may reduce morbidity and mortality and improve quality of life in haemodialysis patients. During long-term treatment, most patients will not respond adequately to therapy with rHuEpo alone. The most important confounding factor, limiting the effectiveness of rHuEpo, is absolute or functional iron deficiency, which is now recognized and treated in many dialysis units. However, there are several other adjuvant treatment options which may help to optimize the response to treatment with rHuEpo. A weekly dose of 2-3 mg of folic acid and 100-150 mg of vitamin B6 is recommended for haemodialysis patients on rHuEpo therapy. The addition of 0.25 mg/month of vitamin B12 may be necessary in selected patients. Vitamin C (1-1.5 g/week) was shown to overcome functional iron deficiency in patients with high ferritin levels. The potential increase of oxidative stress induced by intravenous iron therapy may be blunted by concomitant administration of vitamin E (1200 IU). There is clear evidence from the literature that treatment of secondary hyperparathyroidism by vitamin D improves erythropoiesis. The most recently discovered biological effects of rHuEpo include the induction of several genes in endothelial cells as well as a role for erythropoietin in the outcome of plasmodium infection. A new erythropoietin-like molecule is novel erythropoiesis stimulating protein (NESP), which is as effective and safe as rHuEpo, with the potential advantage of less frequent dosing.
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PMID:Novel aspects of erythropoietin response in renal failure patients. 1150 83

Haemochromatosis may be inherited or acquired. The commonest inherited form is HFE-related genetic haemochromatosis (GH). This is associated with homozygosity for the C282Y mutation in the HFE gene. Individuals with GH present in several ways depending upon the severity of iron overload. However, only a small proportion of genetically susceptible individuals develop disease. Diagnosis of GH is based on measurement of transferrin saturation, serum ferritin levels and mutation analysis of HFE. Liver biopsy is not necessary for diagnosis. It is used to establish the severity of liver disease in selected patients. Other complications of iron overload are identified by specific tests. Initial management of GH is by weekly venesection until borderline iron deficiency is achieved. The serum ferritin is then maintained at 50 microg/l by 3-6 monthly venesection. Specific organ damage is managed appropriately. Early diagnosis and treatment before irreversible damage has occurred gives a normal life expectancy. Non-HFE related inherited iron overload may be due to mutations in other iron related genes. Management is along the same lines as for GH, although if venesection is not tolerated, other approaches may be necessary.
Best Pract Res Clin Haematol 2002 Jun
PMID:Diagnosis and management of genetic haemochromatosis. 1240 8

Iron overload in body tissues can cause complications such as cirrhosis, cardiomyopathy, diabetes, hypogonadism and arthritis. In populations of northern European descent, most iron overload is due to hereditary haemochromatosis (HHC), a genetic condition that causes increased iron absorption. HHC can be treated or prevented by regular phlebotomy treatments. Some experts have called for population screening for HHC, so that early phlebotomy treatment can be initiated. Two screening tests are available: measurement of the serum iron transferrin saturation (Tf%) and genetic testing for HFE mutations. However, both methods have low positive predictive values. Current data suggest that most people at risk are unlikely to develop clinical symptoms and that the population prevalence of clinical complications of HHC is low, arguing against population screening. Two other prevention strategies are available. (1) Health provider education, to heighten awareness of HHC as an explanation for symptoms and signs seen in early iron overload including unexplained fatigue, joint pain, palpitations, abdominal pain, elevated liver function tests, hepatomegaly and elevated serum ferritin. (2) Family-based testing after a diagnosis of HHC, to ensure that relatives are evaluated for evidence of iron overload. More research is also needed to identify the factors that increase risk for disease in persons with excess iron uptake, to determine whether moderate iron overload is a health risk and to evaluate the causes of iron overload other than HHC.
Best Pract Res Clin Haematol 2002 Jun
PMID:Hereditary haemochromatosis: a realistic approach to prevention of iron overload disease in the population. 1240 10

Effective management of iron overload in thalassaemia requires monitoring both for iron toxicity and the effects of excessive chelation. Careful monitoring together with adherence to established regimens using desferrioxamine (DFO) results in a 78% survival rate at 40 years of age at UCLH, with steadily improving survival as progressive cohorts receive chelation earlier in life. By contrast, survival is considerably below this in non-specialist centres. The prognostic significance of the measures being used in monitoring should be known so that decisions about chelation management are evidence-based. Serum ferritin measurement, although easy to perform frequently, is subject to variability and falsely high or falsely low values in relation to body iron are frequently obtained. However, there is evidence that persistently high ferritin values above 2500 microg/l have poor prognostic significance in patients treated with DFO. Liver iron predicts total body iron in a more predictable way than serum ferritin in thalassaemia. Liver iron concentrations of 15 mg/g dry weight appear to predict those patients who develop heart failure in subjects treated with DFO. The prognostic significance of this measurement or indeed other measurements of iron overload in patients treated with other chelation regimens is not known. Recent advances with MRI imaging have aroused interest in its use for monitoring patients with thalassaemia. A recent publication suggests a relationship between left ventricular ejection fraction and cardiac T2*, the value of which shortens with increasing iron concentrations in the liver and hence by inference in the heart. The prognostic value of this technique has not yet been demonstrated in prospective studies and hence changes in therapy based on this measurement alone should be considered with caution at this time. The value of monitoring to decrease morbidity from iron overload is also discussed, particularly with reference to the estimation of iron deposition in the pituitary.
Best Pract Res Clin Haematol 2002 Jun
PMID:Monitoring chelation therapy to achieve optimal outcome in the treatment of thalassaemia. 1240 11


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