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

To determine the frequency of HLA histocompatibility antigens in persons with idiopathic hemochromatosis and their usefulness as genetic markers of the disease, HLA typing for the A, B and C loci was carried out. HLA-A3 was found in 61% of 18 unrelated individuals with idiopathic hemochromatosis compared with 25% of 253 randomly chosen control subjects (P less than 0.001), and HLA-B7 was found in 50% and 22% respectively (P less than 0.025). Eighty-six members of seven families with idiopathic hemochromatosis were screened for abnormalities in iron metabolism with tests for serum iron concentration, transferrin saturation, serum ferritin concentration and iron content of the hepatocytes. Of the 14 persons selected for liver biopsy because of abnormalities detected by these tests, 8 had increased amounts of stainable iron in the hepatocytes. Body iron overload was subsequently demonstrated in six of the seven, who had undergone repeated phlebotomy. In sibships having one member with hemochromatosis, only 1 of 22 members had two haplotypes in common with the proband, whereas in sibships having more than 1 member with the disease 4 of 5 affected members had two haplotypes in common. HLA typing in families with hemochromatosis may provide a means of identifying persons at risk of acquiring the disease.
 ...
PMID:Histocompatibility antigens as markers of abnormal iron metabolism in idiopathic hemochromatosis. 8 5

A study of 18 unrelated families with idiopathic haemochromatosis (I.H.C.) was undertaken to define the relative values of HLA typing and serum-ferritin estimation in the early detection of the disease. Sharing of both HLA haplotypes with the proband indicated a high risk of I.H.C. in siblings; but HLA typing was of limited value in detecting affected offspring. Non-identical HLA indicated a low risk of I.H.C. in both siblings and offspring. The presence of HLA A3 was not clinically useful as a marker for I.H.C., since this antigen was also present in 40% of unaffected relatives. In contrast, the serum-ferritin concentration was elevated in 96% of patients with I.H.C. and in only 5% of unaffected relatives. HLA typing provides some indication of the risk of I.H.C. in first-degree relatives, but the combination of serum-ferritin, serum-iron, and transferrin saturation remains the most reliable screening regimen for early diagnosis of I.H.C.
 ...
PMID:Early detection of idiopathic haemochromatosis: relative value of serum-ferritin and HLA typing. 8 15

Structural similarity between antigens and self molecules could be responsible for low antibody responses in different immunogenetic (IR-gene) systems. B10.M and B10.D2 strains are high responders, whilst A. Thy-1-1 mice are low responders, following primary immunization with ferritin in saline. Cross-reactivity between mouse-self antigens and ferritin was tested by antigen excess and radioimmunoassay techniques, using cells obtained from normal, unimmunized high- and low-responder mice, to compete for specific antibody. Low-responder A.Thy-1-1 mouse cells consistently displaced more anti-ferritin antibodies than did high-responder B10.M and B10.D2 mouse cells at varying antibody and cell concentrations and these differences were statistically significant (P less than 0.001). It is suggested that the responder status of different strains of mice, following primary immunization with ferritin in saline, could be explained by the degree of cross-activity between self determinants and antigen, such that low responders cross-react to a greater degree with the test antigen than do high-responder mice. A similar mechanism of cross-reactivity could operate in the pathogenesis of HLA-linked diseases.
 ...
PMID:Cross-reactivity with mouse antigens in the ferritin immunogenetic (IR-gene) system. 10 71

Over the last few years the study of idiopathic haemochromatosis has not brought to light any basic change in the overall pattern of organic and metabolic damage produced by the disease and comprising altered skin pigmentation, liver disease, diabete mellitus, heart disease, endocrine dysfunction, bone and joint disease. Nevertheless, certain facets of the clinical picture have been described and progress has been made in understanding the signs of the disease. Although the desferrioxamine test is no without merit, especially if performed after vitamin C administration, for measuring the extent of iron overload, two methods seem better equipped: serum ferritin radioimmunoassay and measurement of iron concentration in a liver biopsy specimen. The HLA antigen A3 and, more especially, haplotype A3, B14, are markers for the genetic basis of the disease. Repeated phlebotomy therapy generally brings about symptomatic improvement and a significant increase in survival.
 ...
PMID:[Idiopathic haemochromatosis. I. Clinical, biological and therapeutic aspects (author's transl)]. 37 16

To determine whether a correlation exists between the biochemical expression of hemochromatosis and the HLA genotype, we studied 174 family members of 32 persons with the disease. Persons who shared both HLA haplotypes with the proband (and presumably having two hemochromatosis alleles) differed significantly from those who shared only one haplotype (and presumably having one hemochromatosis allele) in terms of serum iron (P less than 0.001 for both sexes), unsaturated iron-binding capacity (P less than 0.01 for female and P less than 0.0001 for male subjects) and serum ferritin (P less than 0.0001 for female and P less than 0.00001 for male subjects). The only significant difference between relatives having one hemochromatosis allele and age and sex-matched controls was related to serum ferritin values in male subjects (P less than 0.05, despite considerable overlap). In our hands, serum ferritin was the best indicator of disordered iron metabolism and was elevated among most homozygous but among few heterozygous family members.
 ...
PMID:Serum ferritin as a possible marker of the hemochromatosis allele. 44 73

The crosstolerance hypothesis suggests that animals sharing antigens with some microorganisms will produce low antibody levels in the early part and high levels in the latter part of an infection. Antibody responses have been measured in high responder B10.M and B10.D2 mice and low responder C3H and A.Thy-1.1, as well as F1 hybrids (B10.M X A.Thy-1.1) and (B10.M X C3H/He), after repeated immunisation with the antigen ferritin, involving altogether 483 mice. An inversion in the immune response was found to occur and similar delayed high antibody responses have been described in rheumatic fever. It is suggested a mechanism of immune inversion may operate in the pathogenesis of HLA and blood group-linked diseases.
 ...
PMID:Immune response inversion after hyperimmunisation. Possible mechanism in the pathogenesis of HLA-linked diseases. 64 66

Five subjects undertook 10 days of twice daily interval training sessions on a treadmill followed by 5 days of active recovery. On days 1, 6, 11, and 16 the subjects were required to undertake a test of submaximal and maximal work capacity on a treadmill combined with a performance test consisting of a run to exhaustion with the treadmill set at 18 km.h-1 and 1% gradient. Also on these days a pre-exercise blood sample was collected and analysed for a range of haematological, biochemical and immunological parameters. The subjects experienced a significant fall in performance on day 11 which had returned to pretraining levels on day 16. Serum ferritin concentrations were depressed significantly from pretraining concentrations at the conclusion of the recovery period while the expression of lymphocyte activation antigens (CD25+ and HLA-DR+) was increased both after the training phase and the recovery phase. The number of CD56+ cells in the peripheral circulation was depressed at the conclusion of the recovery period. Several parameters previously reported to change in association with overload training failing to reflect the decrease in performance experienced by subjects in this study, suggesting that overtraining may best be diagnosed through a multifactorial approach to the recognition of symptoms. The most important factor to consider may be a decrease in the level of performance following a regeneration period. The magnitude of this decreased performance necessary for the diagnosis of overtraining and the nature of an "appropriate" regeneration period are, however, difficult to define and may vary depending upon the training background of the subjects and the nature of the preceding training. It may or may not be associated with biochemical, haematological, physiological and immunological indicators. Individual cases may present a different range of symptoms and diagnosis of overtraining should not be excluded based on the failure of blood parameters to demonstrate variation. However, blood parameters may be useful to identify possible aetiology in each separate case report of over-training. An outstanding factor to emerge from this study was the difficulty associated with an objective diagnosis of overtraining and this is a possible reason why there have been new accounts of overtraining research in the literature.
 ...
PMID:Biological responses to overload training in endurance sports. 159 59

Genetic haemochromatosis is characterised by an inappropriately high rate of iron absorption by the small intestine. The disease is transmitted as an autosomal recessive condition. The gene frequency in the Caucasian population is approximately 1 in 20 and the disease frequency is 1 in 400. Excessive iron deposition occurs in the liver, pancreas, heart, pituitary and joints and hepatic iron concentrations above approximately 400 mumol/g dry weight are always associated with fibrosis and usually with cirrhosis and progressive liver failure. Accurate diagnosis depends upon the demonstration of elevated hepatic iron stores. An hepatic iron index [hepatic iron concentration (in mumol/g dry weight) divided by patient age] of greater than 2.0 distinguishes homozygous subjects from the other conditions in which slight increases in hepatic iron concentration may occur, e.g. in a subject heterozygous for haemochromatosis or alcoholic liver disease. If cirrhosis is present, patients are at a high risk of developing hepatocellular carcinoma. Therefore, they should undergo regular abdominal ultrasound and alpha-fetoprotein estimation. In the absence of cirrhosis, phlebotomy restores life expectancy to normal. Venesection should be continued until all excess iron stores are removed as judged by failure of a rise in haemoglobin concentration on cessation of phlebotomy. Screening of first degree relatives should commence from a young age (e.g. 10 years). If serum ferritin or transferrin saturation are abnormal, liver biopsy should be undertaken. HLA typing of the family allows for the identification of those siblings who are most likely to develop the disease. Secondary iron overload is often multifactorial in origin. Iron chelation therapy with subcutaneous deferoxamine (desferrioxamine) should only commence after careful consideration of the potential benefits in each individual patient.
 ...
PMID:Current concepts in rational therapy for haemochromatosis. 171 64

What then are the lessons to be learned about prevention and treatment of hemochromatosis? Early diagnosis is essential. The best indicator would be testing of serum iron and total saturation followed by a serum ferritin if elevated. Once these indices are abnormally high, MRI and or a liver biopsy should confirm the stage of the iron over-loaded state. If indeed the patient is not iron-overloaded (normal liver biopsy in the face of high saturation and ferritin level) phlebotomies should be performed until these indices are normal and then maintained at a normal level. This should entail four to six phlebotomies a year. Family members should also be screened and managed in a like manner. HLA typing may be a partially helpful screening device. The abnormal gene is closely linked on chromosome 6 with HLA histocompatibility loci. Now, by means of HLA typing, we can identify heterozygote carriers and homozygous (abnormal) among first degree relatives of patients with hemochromatosis. Unfortunately, HLA typing can only be used within a given family and cannot be used to screen the general population. It is estimated that 70% of hemochromatoics have the antigen HLA-A3; however, so does 28% of the (well) general population. Patients with unexplained cirrhosis, arthritis, liver disease, diabetes, impotency, cardiomyopathy and neurological symptoms should be screened in a like manner. Routine health practice profile chemistries must include a serum iron and iron saturation, and if high followed by a serum ferritin. Once diagnosed, therapy must be maintained with phlebotomy for the life time of the patient.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Hemochromatosis: diagnosis and treatment. 179 61

The frequency of the HLA linked iron-loading gene was assessed in 1783 Afrikaner men over the age of 40 years living in the South Western Cape. Measurements, made on three occasions over a 4.5 year period, included the serum ferritin concentration, a screening test for reduced unsaturated iron-binding capacity and the percentage transferrin saturation. The serum gamma-glutamyl transferase concentration was used as a marker of alcohol abuse. The diagnosis of homozygosity was based on a serum ferritin concentration that was persistently greater than 400 micrograms l-1 and a percentage transferrin saturation greater than 55%. Using these criteria, 17 subjects were diagnosed as homozygous, corresponding to a disease frequency of 0.0095, a gene frequency of 0.0976 and a heterozygote frequency of 0.176 (95% confidence limits: 0.135-0.213). None of the subjects had overt clinical haemochromatosis. Typing for the HLA-A, -B, -C and -DR loci showed that the HLA-A3 allele (frequency 0.6471 and relative risk 4.4) was the only independent marker for the iron-loading gene in this asymptomatic population. Using the present approach it was not possible to distinguish between heterozygotes, alcohol abusers and normal subjects with serum ferritin concentrations at the upper end of the normal range.
 ...
PMID:Phenotypic expression of the HLA linked iron-loading gene in males over the age of 40 years: a population study using serial serum ferritin estimations. 197 75


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