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)

Contribution of electrostatic interactions to stability of BPTI orthorhombic, pig-insulin cubic crystals, and horse L ferritin crystals was evaluated with numerical calculation of Poisson-Boltzmann equation based on a dielectric model. The stability of a ferritin molecule (24-mer) composed of 24 subunits was also evaluated. It was found that the surface charge-charge interactions at separation distances (< 5 A) were insensitive to variations in the ionic strength, and thus stabilized assembled states of the proteins (i.e., crystalline state and oligomeric state). It was also revealed that the charge density and the packing of the protein crystals were largely responsible for the ionic strength dependence of the crystal stability. The stability of the 5PTI crystalline state with a high charge density drastically increased as the concentration of the solvent ions increased. In contrast, that of the insulin crystal with a low charge density and large solvent region was insensitive to changes in the ionic concentration. The electrostatic interaction between ferritin 24-mers was attributed to two salt bridges mediated by Cd ion. For the stability of the ferritin 24-mer, which is evolutionally designed, the electrostatic stabilization between the subunits was attributed to polar bonds such as buried salt bridges or hydrogen bonds, which occasionally yielded more than 5 kcal/mol and were numerous and very strong compared with the bonds between molecules in the 5PTI and 9INS crystals. By analyzing the atomic charge-charge interactions in detail, it was found that charge pairs separated by less than 3 A, such as hydrogen bonds, dominantly stabilize the assembled states, and that pairs 3 to 5 A apart were also important. The stability of the assembled states evaluated by the total EET was determined by the fine balance between the two competing contributions arising from the stabilizing atoms and the destabilizing atoms. Changes of the ASA and hydration free energy were also evaluated in accordance with the process of the subunit assembly. The change of hydration free energy, which was very large (i.e., approximately +100 kcal/mol/subunit) and unfavorable for the assembly, was proportional to the electrostatic hydration energy (i.e., Born energy change in the hydration process). Hydrophobic groups were likely to appear more frequently than hydrophilic groups at the interfaces. This study offers a method which can improve the stability of protein crystals by introducing polar or charged residues that are properly designed to form specific hydrogen bonds or salt bridges between neighboring protein molecules. This method is also applicable to crystallography, because it improves refinement of protein structures in crystals by taking the inter-protein interactions into account.
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PMID:Significant role of electrostatic interactions for stabilization of protein assemblies. 920 25

We evaluated endurance running performance and body mass index (BMI) in relation to biochemical cardiovascular disease (CVD) risk indicators (s-lipids, s-insulin, s-ferritin), and blood pressure in 14- and 17-year-old healthy Swedish adolescents (n = 879), also considering current dietary intake and physical activity. Endurance running performance was assessed using a 3 km running test and height, body weight, waist and hip circumference, and skinfolds were measured at clinical examination. Physical activity and dietary intake were evaluated using self-reported 7-day-records. The results showed that high endurance running performance was related to a favourable CVD risk indicator profile. Multiple regression analyses including running time, BMI, physical activity, dietary fat and iron intake, and age as independent and s-lipids, s-insulin, and s-ferritin as dependent variables revealed that, in both boys and girls, low BMI was associated to a favourable s-lipid profile and lower s-insulin values and, in boys but not in girls, also to lower s-ferritin values. There were, however, no independent associations between level of physical activity or endurance running performance on the one side and s-lipids, s-insulin, or s-ferritin values on the other. High dietary fat intake was associated to s-lipids in a non-atherogenic direction; in boys to higher HDL-C and in girls to lower TG. In conclusion the study showed that body mass seems to be the most important factor explaining the differences in s-lipid and s-insulin values between adolescents with different level of physical performance capacity. An interesting finding was, that s-ferritin, being a proposed risk factor for CVD, in the older boys related to body mass in a similar way as s-lipids and s-insulin.
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PMID:Endurance running performance in relation to cardiovascular risk indicators in adolescents. 923 49

Poor nutritional status in patients with cystic fibrosis (CF) is associated with increased mortality. Patients with CF often have a decreased sensation of smell secondary to recurrent sinus infections or sinus surgery; in other CF populations, a decreased sensation of smell has been associated with poor nutritional status. We hypothesized that a decreased sensation of smell would be associated with worse nutritional status in patients with CF. We studied 50 (26 F and 24 M) of 58 consecutive patients with CF (86%) aged 14-53 years (28 +/- 8; mean +/- SD) who attended the University of Washington Medical Center from June 1994 to March 1995 and who agreed to participate. Demographic information was obtained, and nutritional status was assessed by ideal body weight, arm muscle area, arm fat area, pancreatic sufficiency, insulin-requiring diabetes, vitamins A and E levels, albumin, iron, iron binding capacity, ferritin, cholesterol, and zinc levels. Objective sensation of small was examined (Sensonics, Philadelphia, PA), a sinus compacted tomogram (CT) was performed, and a questionnaire for prior sinus symptoms, sinus surgery, medications, and subjective sensation of smell was administered. Twenty-seven of 49 subjects (55%) had an objective decrease in sensation of smell, 23/50 (46%) had had prior sinus surgery. 46/50 (92%) were pancreatic insufficient, and 8/50 (16%) were insulin-requiring diabetics. Weight for height ranged from the 38th to 157th percentile (100 +/- 18; mean +/- SD). Arm muscle area ranged from the < 5th to the 75th percentile (25 +/- 23; mean +/- SD). Arm fat area ranged from the < 5th to the 95th percentile (45 +/- 39; mean +/- SD). Sinus CT scans were abnormal in all patients (100%). Patients with anosmia were more likely to have had sinus surgery, but their nutritional status was no different from that of patients with a normal sensation of smell. We conclude that decreased sensation of smell is common in patients with CF, especially those with prior sinus surgery. Subjective sensation of smell and sinus CT scans were unreliable indicators of a decreased objective sensation of smell. In this pilot study, no association was found between sensation of smell and nutritional status.
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PMID:Sensation of smell does not determine nutritional status in patients with cystic fibrosis. 926 54

Better awareness of the clinical presentation of idiopathic haemochromatosis is a key element for early diagnosis and treatment. We retrospectively analysed the medical records of 105 patients (80 males, 25 females) diagnosed with idiopathic haemochromatosis over the past two decades in the two academic hospitals of Louvain University. Age at diagnosis was 50 +/- 12 years (mean +/- SD). Median ferritin levels were 1,803 micrograms/L-1. Cirrhosis was found at histology in 51%. Ferritin levels were significantly higher in cirrhotic than non-cirrhotic subjects (P < 0.05). Impaired glucose tolerance and diabetes were found at admission in 7 and 40% of all patients. Diabetes was more frequent when cirrhosis was present (53 vs. 25% in cirrhosis-negative patients, P < 0.05). Accordingly, cirrhosis was also more frequent in diabetic than non-diabetic patients (70 vs. 40%, P < 0.05). Diabetic subjects with cirrhosis frequently presented with symptomatic hyperglycaemia at diagnosis, had higher HbA1c levels, and were more insulin-requiring than their non-cirrhotic diabetic counterparts (P < 0.05). There was also a trend towards more frequent chronic complications of diabetes in the former group. Diabetic patients with cirrhosis had slightly higher insulin levels but lower C-peptide values (P < 0.05) than diabetic subjects without cirrhosis. Chronic phlebotomy did not affect subsequent insulin requirements. Thus, diabetes is still a frequent complication of haemochromatosis in Belgium, and its presence and severity are markedly associated with that of cirrhosis at diagnosis of idiopathic haemochromatosis.
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PMID:Clinical aspects of diabetes secondary to idiopathic haemochromatosis in French-speaking Belgium. 934 44

Serum insulin, and plasma glucagon and glucose levels were measured in 56 Chinese patients with aplastic anemia (AA) and 40 normal controls. Serum insulin and plasma glucose levels in 18 newly diagnosed cases and 11 previously treated cases with prednisone were significantly higher than those in the controls. Serum insulin and plasma glucose levels in 27 cases previously treated with stanozolol were significantly higher than those in the newly diagnosed cases and the previously treated cases with prednisone. There was no significant difference in plasma glucagon levels between the patients and the controls. Serum insulin and plasma glucose levels were significantly correlated with the amount of blood transfusions and serum ferritin and cortisone concentrations in the AA patients. Our findings suggest that AA patients may have hyperinsulinemia accompanying hyperglycemia, which can be further aggravated by stanozolol and prednisone therapy and iron overload.
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PMID:Hyperinsulinemia accompanying hyperglycemia in Chinese patients with aplastic anemia. 937 26

A 37-year-old untransfused, non-drinking man with Hemoglobin H-CS disease presented with insulin-dependent diabetes mellitus, markedly elevated serum ferritin level, and marked iron deposition in hepatocytes. He did not carry either of the two common mutations of the HLA-H gene for hereditary hemochromatosis, namely, Cys282Tyr and His68Asp, nor did he have the associated HLA marker (HLA-A3, B7 nor B-14) for the disease. Patient with HbH disease should be monitored for iron overload.
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PMID:Hemosiderosis with diabetes mellitus in untransfused Hemoglobin H disease. 946 50

A total of 167 children and adolescents with insulin-dependent (Type 1) diabetes mellitus (97 males; age range 1.9-22.4 yrs) in a UK paediatric diabetic clinic were screened for coeliac disease using the IgA endomysial (EMA) test, or, in IgA deficient subjects, the IgG antigliadin (AGA) test. Antibody positive subjects were selected for small bowel biopsy, and confirmed coeliac cases started on a gluten free diet. Clinical features, height (Ht) standard deviation score (SDS), body mass index (BMI) SDS, HbA1c, insulin requirements' haemoglobin (Hb), mean red cell volume (MCV), serum folate and ferritin levels were evaluated at diagnosis and thereafter at 3-6 month intervals. A total of 156 subjects (93.4%) were antibody negative. Eleven (6.6%) were antibody positive (10 EMA/1 AGA; 6 males), of whom 9 had biopsies: 1 normal: 8 coeliac (4.8%; 5 males; 1 'classical'; 1 anaemia; 3 'atypical'; 3 asymptomatic). Seven coeliac subjects were followed during 12-24 months of dietary therapy. Pretreatment mean (range) Ht SDS = 0.08 (-1.66 to 1.88); BMI SDS = 0.32 (-0.82 to 1.29); HbA1c = 8.9 (6.2 to 11.3%); insulin dose = 0.98 (0.51 to 1.29) U kg(-1) day(-1). During treatment antibody status reverted to and remained negative, and symptoms resolved. By 24 months, there was a trend towards increased BMI SDS (mean (range) 1.31 (0.47 to 2.29), p = 0.248) and to reductions in HbA1c (8.1 (6.4-10.8), p = 0.697). Repeat small bowel biopsies were normal in 6 subjects (1 refused). No statistically significant changes occurred in any other parameters. In conclusion, serological screening is effective, although the therapeutic benefit of dietary therapy in asymptomatic cases remains uncertain.
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PMID:Coeliac disease in children and adolescents with IDDM: clinical characteristics and response to gluten-free diet. 947 62

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.
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PMID:Impaired pituitary hormonal response to exhaustive exercise in overtrained endurance athletes. 952 87

Cardiovascular risk factors were compared between 126 people with non-insulin-dependent diabetes mellitus (NIDDM) and 530 non-diabetics (controls), in a random sample of people (Chinese, Malays, and Asian Indians) aged 40-69 years from the general population of Singapore. Data were adjusted for age and ethnicity. For both genders, people with NIDDM had higher mean body mass indices, waist-hip ratios and abdominal diameters. They also had a higher prevalence of hypertension, higher mean levels of fasting serum triglyceride, slightly lower mean levels of serum high-density-lipoprotein cholesterol, and higher mean levels of plasma plasminogen activator inhibitor-1 and tissue plasminogen activator (antigen). These factors are components of syndrome X (metabolic syndrome) and increase the risk of atherosclerosis and thrombosis. In contrast, there were no important differences for cigarette smoking, serum total and low-density-lipoprotein cholesterol, serum apolipoproteins A1 and B, plasma factor VIIc and plasma prothrombin fragment 1 + 2. Females with NIDDM, but not males, had a higher mean serum fibrinogen level than non-diabetics, which could explain why NIDDM has a greater cardiovascular effect in females than males. Serum lipoprotein(a) concentrations were lower in people with NIDDM. Mean levels of serum ferritin, a pro-oxidant, were higher in people with NIDDM than controls, but there were no important differences for plasma vitamins A, C and E, and serum selenium, which are anti-oxidants.
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PMID:Cardiovascular risk factors in non-insulin-dependent diabetics compared to non-diabetic controls: a population-based survey among Asians in Singapore. 954 28

The causes of growth retardation of children with thalassaemia major are multifactorial. We studied the GH response to provocation by clonidine and glucagon, measured the circulating concentrations of insulin, IGF-I, IGF-binding protein-3 (IGFBP-3) and ferritin, and evaluated IGF-I generation after a single dose of GH (0.1 mg/kg per dose) in 15 prepubertal patients with thalassaemia, 15 age-matched children with constitutional short stature (CSS) (height standard deviation score less than -2, with normal GH response to provocation) and 11 children with isolated GH deficiency (GHD). Children with thalassaemia had significantly lower peak GH response to provocation by clonidine and glucagon (6.2 +/- 2.3 and 6.8 +/- 2.1 microg/l respectively) than the CSS group (18.6 +/- 2.7 and 16.7 +/- 3.7 microg/l respectively). They had significantly decreased circulating concentrations of IGF-I and IGFBP-3 (47.5 +/- 19 ng/ml and 1.2 +/- 0.27 mg/l respectively) compared with those with CSS (153 +/- 42 ng/ml and 2.06 +/- 0.37 mg/l respectively), but the IGF-I and IGFBP-3 concentrations were not different from those with GHD (56 +/- 25 ng/ml and 1.1 +/- 0.32 mg/l respectively). These data demonstrate that the GH-IGF-I-IGFBP-3 axis in thalassaemic children is defective. Serum ferritin concentration correlated significantly with GH peak response to provocation (r = -0.36, P < 0.05) and circulating IGF-I (r = -0.47, P < 0.01) and IGFBP-3 (r = -0.42, P < 0.01) concentrations. In the IGF-I generation test, after GH injection, the thalassaemic children had significantly lower IGF-I and IGFBP-3 levels 86.7 +/- 11.2 ng/ml and 2.05 +/- 0.51 mg/l respectively) than those in the CSS group (226 +/- 45.4 ng/ml and 2.8 +/- 0.43 mg/l respectively). The IGF-I response was significantly higher in children with GHD (158 +/- 50 ng/ml) than in thalassaemic children. Six short (height standard deviation score less than -2) thalassaemic children who had defective GH response to provocation (< 10 microg/l), all the children with GHD and eight short normal children (CSS) were treated for 1 year with human GH (18 units/m2 per week divided into daily s.c. doses). After 1 year of GH therapy there was a marked acceleration of growth velocity in both thalassaemic children (from 3.8 +/- 0.6 cm/year to 7.2 +/- 0.8 cm/year) and controls. However, the linear acceleration of growth velocity on GH therapy was significantly slower in thalassaemic children (3.3 +/- 0.3 cm/year increment) compared with those with CSS (5.3 +/- 0.4 cm/year increment) and GHD (6.9 +/- 1.2 cm/year increment) (P < 0.05). Their circulating IGF-I concentration (105 +/- 36 ng/ml) was significantly lower than those for CSS (246 +/- 58 ng/ml) and GHD (189 +/- 52 ng/ml) after 1 year of GH therapy. These data prove that some children with beta-thalassaemia major have a defective GH-IGF-I-IGFBP-3 axis and suggest the presence of partial resistance to GH.
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PMID:GH response to provocation and circulating IGF-I and IGF-binding protein-3 concentrations, the IGF-I generation test and clinical response to GH therapy in children with beta-thalassaemia. 957 6


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