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)

The aim of this study was to evaluate the treatment effects with recombinant human growth hormone (rhGH) in a group of patients after bone marrow transplantation for thalassemia major. At the end of treatment we divided the subjects into two groups according to the outcome of the therapy: responder and nonresponder. Responder group: after 24 months of rhGH administration, growth rate was still significantly higher in respect to start of treatment (P < 0.0001). Plasma levels of IGF-I rose significantly (P < 0.003). The serum levels of serum asparate aminotransferase (SGOT) and alanine aminotransferase (SGPT) were higher compared to normal values but improved in non-responder patients. There was no difference in the mean concentration of these parameters before and after treatment (P = NS). Non-responder group: these patients had a worsening of the growth rate during rhGH administration. There was no increase of the IGF-I levels. Single values of transaminase and ferritin levels were higher than in responder patients before and after treatment. There was a significant correlation between IGF-I, SGOT, SGPT and ferritin in all patients before and after therapy. It appears from these data that rhGH administration is worth serious consideration in patients after BMT for thalassemia major presenting impaired growth hormone secretion. This treatment can offer good results only in cases where the normal hepatic synthesis of IGF-I is conserved and where liver damage has not reached irreversible conditions, as we have seen in the responder group.
 ...
PMID:Growth after recombinant human growth hormone (rhGH) treatment in transplanted thalassemic patients. 933 58

The aim of the present prospective longitudinal study was to investigate the hormonal response in overtrained athletes at rest and during exercise consisting of a short-term exhaustive endurance test on a cycle ergometer at an intensity 10% above the individual anaerobic threshold. Over a period of 19+/-1 months, 17 male endurance athletes (cyclists and triathletes; age 23.4+/-1.6 yr; VO2max. 61.2+/-1.8 mL x min(-1) x kg(-1); means+/-SEM) were examined five times on two separate days under standardized conditions. Short-term overtraining states (OT, N=15) were primarily induced by an increase of frequency of high-intensive bouts of exercise or competitions without increase of the total amount of training. OT was compared with normal training states intraindividually (NS, N=62). During OT, the time to exhaustion of the exercise test was significantly decreased by 27% on average. At rest and during exercise, the concentrations in plasma and the nocturnal excretion in urine of free epinephrine and norepinephrine were not significantly changed during OT. At physical rest, the concentrations of (free) testosterone, cortisol, luteinizing hormone, follicle-stimulating hormone, adrenocorticotropic hormone, growth hormone, and insulin during OT were comparable with those during NS. A significantly (P < 0.025) lower maximal exercise-induced increase of the adrenocorticotropic hormone and growth hormone, as well as a trend for a decrease of cortisol (P=0.060) and insulin (P=0.036), was measured. The response of free catecholamines as well as the ergometric performance of an all-out 30-s test was unchanged. Serum urea, uric acid, ferritin, and activity of creatine kinase showed no differences between conditions. In conclusion, the results confirm the hypothesis of a hypothalamo-pituitary dysregulation during OT expressed by an impaired response of pituitary hormones to exhaustive short-endurance exercise.
 ...
PMID:Impaired pituitary hormonal response to exhaustive exercise in overtrained endurance athletes. 952 87

Iron regulatory protein-1 (IRP-1) controls the expression of several mRNAs by binding to iron-responsive elements (IREs) in their untranslated regions. In iron-replete cells, a 4Fe-4S cluster converts IRP-1 to cytoplasmic aconitase. IRE binding activity is restored by cluster loss in response to iron starvation, NO, or extracellular H2O2. Here, we study the effects of intracellular quinone-induced oxidative stress on IRP-1. Treatment of murine B6 fibroblasts with menadione sodium bisulfite (MSB), a redox cycling drug, causes a modest activation of IRP-1 to bind to IREs within 15-30 min. However, IRE binding drops to basal levels within 60 min. Surprisingly, a remarkable loss of both IRE binding and aconitase activities of IRP-1 follows treatment with MSB for 1-2 h. These effects do not result from alterations in IRP-1 half-life, can be antagonized by the antioxidant N-acetylcysteine, and regulate IRE-containing mRNAs; the capacity of iron-starved MSB-treated cells to increase transferrin receptor mRNA levels is inhibited, and MSB increases the translation of a human growth hormone indicator mRNA bearing an IRE in its 5'-untranslated region. Nonetheless, MSB inhibits ferritin synthesis. Thus, menadione-induced oxidative stress leads to post-translational inactivation of both genetic and enzymatic functions of IRP-1 by a mechanism that lies beyond the "classical" Fe-S cluster switch and exerts multiple effects on cellular iron metabolism.
 ...
PMID:Inactivation of both RNA binding and aconitase activities of iron regulatory protein-1 by quinone-induced oxidative stress. 1003 8

Growth failure is commonly described in polytransfused thalassaemia major patients (Th) with or without growth hormone (GH) releasing hormone-GH axis impairment. We have investigated the efficacy of short-term recombinant GH (rhGH) therapy (Saizen [Serono] 0.1 IU/kg/day 6 evenings/week administered s.c. for 12 months) on growth and predicted final height in 28 (19M, 9F) regularly transfused Th with growth deficiency (aged 14.8 +/- 2.0 yr) on long term desferrioxamine s.c. therapy. All Th had no evidence of congestive heart failure, hypothyroidism or impaired glucose tolerance; in all patients the GH peak (evaluated during both insulin and clonidine test) was < or = 20 mIU/l; hypergonadotropic hypogonadism was excluded in Th with delayed puberty. At the start of therapy height age (HA)/bone age (BA) ratio was 0.92 +/- 0.12. Bone age delay was positively correlated to chronological age (CA), serum ferritin levels (mean of the last three years), the age at the start of chelation therapy, growth velocity calculated for CA during the last year; a positive correlation was also found between circulating IGF-I levels and age at the start of chelation therapy. After 1 year on rhGH therapy there was a significant increase of height calculated for CA (not for BA), of growth velocity calculated for both CA and BA and of circulating IGF-I levels; the HA variation/BA variation ratio was 1.85 +/- 1.71, without any significant difference between predicted final height at the start (-1.08 +/- 1.28 SDS) and at the end of rhGH therapy (-0.88 +/- 1.13). The variation of height calculated for CA was positively correlated to both CA and growth velocity during the last year before rhGH therapy (calculated for CA) and negatively to the height at the start (calculated for CA). There were no side effects and haematological parameters did not show significant changes. In conclusion, our data, obtained in a relatively large group of Th, confirm the emerging results of short-term (12 months) rhGH therapy on growth, as shown by the increase of both growth velocity and height calculated for CA. With regard to final height, although the mean variation of HA/variation of BA ratio was 1.85, no significant increase of the predicted final height was found between the start and the end of rhGH therapy. We are evaluating the effect of long-term rhGH therapy on growth in these patients.
 ...
PMID:Short-term therapy with recombinant growth hormone in polytransfused thalassaemia major patients with growth deficiency. 1009 Nov 55

Growth retardation in children with thalassaemia major is multifactorial. We studied the growth hormone (GH) response to provocation by clonidine and glucagon, measured the circulating concentrations of insulin, insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP3), and ferritin, and evaluated the spontaneous nocturnal (12 h) GH secretion in prepubertal patients with thalassaemia and age-matched children with constitutional short stature (CSS) (height SDS < -2, but normal GH response to provocation). The anatomy of the hypothalamic pituitary area was studied in patients with abnormal GH secretion using MRI scanning. Children with thalassaemia had significantly lower peak GH response to provocation by clonidine and glucagon (8.8 +/- 2.3 micrograms/l and 8.2 +/- 3.1 micrograms/l respectively) than did controls (17.6 +/- 2.7 micrograms/l and 15.7 +/- 3.7 micrograms/l respectively). They had significantly decreased circulating concentrations of IGF-I and IGFBP3 (68.5 +/- 19 ng/ml and 1.22 +/- 0.27 mg/l respectively) compared to controls (153 +/- 42 ng/ml and 2.16 +/- 0.37 mg/l respectively). Seven of the thalassaemic children had a GH peak response of < 7 micrograms/l after provocation. Those with a normal GH response after provocation also had significantly lower IGF-I and IGFBP3 concentrations than controls. Analysis of their spontaneous nocturnal GH secretion revealed lower mean (2.9 +/- 1.77 micrograms/l) and integrated (2.53 +/- 1.6 micrograms/l) concentrations compared to controls (4.9 +/- 0.29 micrograms/l and 5.6 +/- 0.52 micrograms/l respectively). Five of them had mean nocturnal GH concentration < 2 micrograms/l and four had maximum nocturnal peak below 10 micrograms/l. These data denoted defective spontaneous GH secretion in some of these patients. MRI studies revealed complete empty sella (n = 2), marked diminution of the pituitary size (n = 4), thinning of the pituitary stalk (n = 3) with its posterior displacement (n = 2), and evidence of iron deposition in the pituitary gland and midbrain (n = 7) in those patients with defective GH secretion (n = 9). Serum ferritin concentration was correlated significantly with the circulating IGF-I (r = -0.47, p < 0.01) and IGFBP3 (r = -0.43, p < 0.01) concentrations. These data prove a high prevalence of defective GH secretion in thalassaemic children associated with structural abnormality of their pituitary gland.
 ...
PMID:Spontaneous and provoked growth hormone (GH) secretion and insulin-like growth factor I (IGF-I) concentration in patients with beta thalassaemia and delayed growth. 1066 1

Prolactin endocytosis was studied by electron microscopy with 125I-prolactin 125I-hGH (human growth hormone) and prolactin-ferritin. Endocytosis and intracellular transit of the labelled hormone proceeded identically in epithelial cells isolated from the mammary glands of pseudopregnant rabbits and in surviving fragments from mammary glands of lactating rabbits. After binding of the hormone to its receptor, the labelled material was rapidly detectable in vesicles showing an homogeneous aspect; 15 min later part of the labelled material was still localized within the same kind of vesicles, but in addition it appeared to have migrated into microvesicles of the Golgi region and into vesicles of heterogeneous aspect tentatively identified with lysosomes. Endocytosis of bovine serum albumin, labelled with ferritin followed the same intracellular pathway. Native ferritin accumulated in vesicles of various sizes, but seemed excluded from the microvesicles of the Golgi zone. In the presence of lysosomotropic agents labelled prolactin accumulated in cytoplasmic vesicles. In the presence of dansylcadaverine, endocytosis of the labelled material proceeded unimpaired. Conversely, in the presence of bacitracin, the internalisation of labelled prolactin seemed to be reduced. These observations show that the endocytosis of the hormone/receptor complex is linked to membrane movements, which eventually lead to its location within both the Golgi apparatus and the lysosomes.
 ...
PMID:[Prolactin internalisation by the epithelial mammary cell: effects of lysosomotropic agents and transglutaminase inhibitors]. 1159 98

Thirty-seven patients with thalassemina major (TM) were studied to determine the extent and rate of endocrine complications. Mean haemoglobin and ferritin concentrations were 8.8 +/- 0.6 and 3,597 +/- 1,931, respectively. Provocation tests for growth hormone secretion were applied in patients with standing heights below the third centile and/or growth velocities below the 10th centile. Sexual maturation was assessed by using the criteria of Tanner. Glucose metabolism was assessed by fasting plasma glucose and glucose tolerance test. Basal thyroid function was measured and thyrotropin-releasing hormone tolerance test was carried out. Growth retardation was found in 40 per cent of patients and growth hormone deficiency was a prominent cause of growth retardation. Gonadal dysfunction was detected in 47 per cent of patients. Hypothyroidism was observed in 16 per cent and impaired glucose metabolism in 10.8 per cent patients. The high rate of endocrine disturbances indicates the importance of regular follow-up of thalassemia major patients with regard to endocrine complications of the disease.
 ...
PMID:Endocrine complications in patients with beta-thalassemia major. 1186 38

Reduced serum insulin-like growth factor-1 (IGF-1) and hypogonadotrophic hypogonadism are common features of adult beta-thalassemia, and warrant evaluation of the growth hormone (GH)-IGF-1 axis. The aim of this study was to determine GH reserve in beta-thalassemia patients (9 females, 7 males, 15 major, 1 intermedia), age 29.3 +/- 6.9 years, BMI 21.3 +/- 1.9 kg/m2, and in 20 age, sex and BMI-matched healthy controls, using the GH-releasing hormone (GHRH)-arginine test. The associations between peak GH response and hormonal and biochemical indices were evaluated. Using BMI-related cut-off limits for peak GH response in the GHRH-arginine test, 4/16 beta-thalassemia patients had peak GH lower than 11.5 microg/l, the cut-off limit suggested for lean subjects, and were diagnosed as GH deficient (GHD). Using 9 microg/l as the cut-off limit 2/16 patients were GHD. Reduced serum IGF-1 and IGFBP-3 were present in 69% and 19% of the patients, respectively. Peak GH did not correlate with serum IGF-1, TSH, and fT4 levels or gonadal status. Neither peak GH nor IGF-1 correlated with serum ferritin. Our findings suggest that GHD is present in up to a quarter of adult beta-thalassemia patients. The clinical benefits of GH therapy need to be determined. GHD alone does not account for the high prevalence of reduced IGF-1 in adult beta-thalassemia.
 ...
PMID:Growth hormone reserve in adult beta thalassemia patients. 1770 95

This study assessed levels of growth hormone, albumin and ferritin in human fascioliasis and schistosomiasis. Forty three patients and ten healthy parasite free subjects were included as controls. All were subjected to clinical, parasitological, and haematological examinations. Serum growth hormone (GH) levels were measured by an immunoenzymometric assay. Statistical analysis revealed significant elevation in GH levels in acute and chronic fascioliasis patients compared to controls. Serum albumin was significantly low in schistosomiasis patients compared to controls. Non-significant changes in serum ferritin were in all patients. The results were critically discussed on the light of the work done before.
 ...
PMID:Levels of growth hormone, albumin and ferritin in human fascioliasis and schistosomiasis. 1798 97

We performed a study of magnetic resonance imaging (MRI) assessment of hemosiderosis in the heart (T2/T2*), liver (T2*), pancreas (T2*), and pituitary gland (T2/T2*/SIR) in 20 hemopoietic stem cell transplant (HSCT) recipients (median peak ferritin levels 7615 pmol/L, range 3411 to 33000 pmol/L). MRI reading was abnormal in the heart (5%), liver (85%), pancreas (40%), and pituitary gland (55%). The heart T2 correlated with peak ferritin levels (P=.024), while the liver T2* correlated with current ferritin (P=.038) values only. Pancreatic T2* values correlated with pituitary T2 and signal intensity ratio values. The ejection fraction was abnormal in 10% of cases and did not correlate with ferritin level or heart T2. The peak liver enzymes correlated with peak ferritin (P=.025), but the current liver enzymes were mostly normal. Pancreatic assessments (fasting glucose, insulin, beta cell function, insulin reserve, and C-peptide) and pituitary growth hormone axis assessments (growth hormone, insulin growth factor-1, and insulin growth factor binding protein-3) were abnormal in 40% to 70% of cases. They were unrelated to pancreas or pituitary MRI values. Interestingly, endocrine assessments correlated with heart T2 values and peak (but not current) ferritin levels. We concluded that iron overload may contribute to organ damage after HSCT, and MRI assessment may be useful in its detection and treatment monitoring.
 ...
PMID:A magnetic resonance imaging study of iron overload in hemopoietic stem cell transplant recipients with increased ferritin levels. 1808 87


<< Previous 1 2 3 4 Next >>