Persistent neutrophil activation in mild asthma.
Explore the source record for details and available documents.
Asthma↗
Biomedical subjects
R Baynes
Publications and source records attributed to R Baynes.
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.
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.
Adult↗
Transferrin iron interactions with cultured hepatocellular carcinoma cells (PLC/PRF/5).
Hepatocellular carcinoma cells of the PLC/PRF/5 cell line had 1.9 x 10(5) transferrin receptors per tumor cell with a Kd of 1.5 x 10(-8) M. At high concentrations of transferrin the binding was not saturable. Transferrin internalization by hepatoma cells was shown by time and temperature-dependent binding studies and by pronase experiments. Transferrin recycling was confirmed by the demonstration of a progressive increase in the cellular molar ratios of iron to transferrin and by chase experiments. Ammonium chloride interfered with iron unloading. The vinca alkaloid vincristine inhibited iron and transferrin uptake. The hepatocarcinoma cells appeared to lack asialoglycoprotein receptors and therefore internalized partially desialated transferrin by the regular route. Iron uptake from transferrin was markedly inhibited by the hydrophobic ferrous chelator 2,2' bipyridine but was relatively unaffected by the hydrophilic ferric chelator desferroxamine. The implication that ferrous iron was involved in postendocytic transvesicular membrane iron transport was supported by a study in which hepatoma cells were shown to take up large amounts of ferrous iron suspended in 270 mM sucrose at pH 5.5. The interaction at this pH between surface labeled hepatoma cell extracts and ferrous iron on a Sephacryl S-300 column suggested that the postendocytic transvesicular transport of iron through the membrane was in part protein mediated. The endocytosed iron in hepatoma cells was found in association with ferritin (33%), transferrin (31%) and a low molecular weight fraction (21%).
2,2'-Dipyridyl↗
Platelet aggregations, fatty acids, clotting factors and serum lipids in rural and urban blacks, and urban whites in South Africa.
Platelet fatty acids, platelet aggregations, and coagulation factors were measured in 27 rural blacks, 27 urban blacks and 39 urban whites. Platelets were significantly less aggregable to collagen and arachidonic acid in in both black groups as compared to whites (p less than 0.01), but there were no significant differences in ADP or epinephrine aggregation between these groups. Factor VIII coagulant activity was much higher in rural and urban blacks than whites (p less than 0.001), and the partial thromboplastin times were shorter (p less than 0.005). Platelet arachidonic acid showed a marked difference between the groups, being 16.4 +/- 5.4% of total platelet fatty acids in the rural blacks, 19.9 +/- 4.2% in the urban blacks and 22.6 +/- 3.3% in the whites (p less than 0.001). Whites had higher LDL and lower HDL cholesterol than blacks (p less than 0.005). These findings suggest that in addition to the well known association of raised LDL cholesterol and acute myocardial infarction, platelet aggregation patterns and platelet arachidonic acid levels may be associated risk factors in coronary thrombosis.
Adult↗
The fate of intravenously administered hepatic ferritin in normal, phenylhydrazine-treated and scorbutic guinea-pigs.
When highly purified hepatic 59Fe-ferritin was injected intravenously into normal guinea-pigs more than half of it was taken up by red cell precursors and the iron was used for haem formation. This was studied in more detail in animals in which a reticulocytosis had been induced either by phenylhydrazine or by repeated venescetions. 55% of the injected ferritin iron was found in reticulocytes at 1 h. Experiments using ferritin doubly labelled with 59Fe and 125I indicated that the whole molecule was taken up, with two-thirds of the radioactivity being associated with the membrane at 1 h and one third being already within the cell. There was a progressive loss of 125I activity over the ensuing hours, while most of the 59Fe was slowly internalized and incorporated into haem between 1 and 24 h. In contrast, 90% of the activity taken up by red cell precursors from 59Fe-transferrin was present as haem at all times. The liver and spleen were the two other major sites of 59Fe-ferritin uptake in phenylhydrazine treated animals. While there was an early uptake of 59Fe into haem in these organs, some redistribution occurred with time, since most of the 59Fe was in a non-haem fraction by 24 h. In a final experiment the distribution and fate of 59Fe-ferritin was studied in scorbutic animals treated with phenylhydrazine. The findings were similar to those in normals similarly treated, which suggests that ferritin iron was being effectively mobilized for haem formation despite the ascorbic acid depletion.
Animals↗
Transferrin receptors and transferrin iron uptake by cultured human blood monocytes.
Transferrin receptors have been previously found on human macrophages and it has also been shown that transferrin iron is taken up by these cells. It has therefore been inferred that the uptake is receptor mediated and involves an endocytic pathway. The subject was addressed directly in the present study in which the transferrin-iron-receptor interaction was characterized in cultured human blood monocytes. Specific, saturable diferric transferrin binding was demonstrated, with a kDa of 3.6 X 10(-8) M and a calculated receptor density of 1.25-2.5 X 10(5) receptors per cell. Incubation at 4 degrees C markedly reduced transferrin binding and completely inhibited iron uptake. Chase experiments confirmed progressive cellular loading of iron, with concomitant loss of transferrin. Inhibitors of endocytic vesicle acidification (ammonium chloride and 2,4-dinitrophenol) inhibited iron unloading from endocytosed diferric transferrin, while microtubular inhibitors (colchicine and vindesine) and a microfilament inhibitor (cytochalasin B) reduced diferric transferrin uptake but had little effect on the iron unloading pathway. A similar effect was noted with a calcium ion antagonist (verapamil) and with 2 calmodulin antagonists (chlorpromazine and imipramine). These latter findings suggest the importance of cytoskeleton-membrane interactions via a calcium, calmodulin and protein kinase C mediated system. Endocytosed iron accumulated progressively as ferritin within the cultured monocytes.
Ammonium Chloride↗
The non-immune inflammatory response: serial changes in plasma iron, iron-binding capacity, lactoferrin, ferritin and C-reactive protein.
The interrelationships between various components of the non-immune inflammatory response (white cell count, plasma lactoferrin, C-reactive protein, ferritin, iron and iron-binding capacity), were studied serially in a variety of inflammatory conditions including acute lobar pneumonia, active pulmonary tuberculosis, rheumatoid arthritis on gold therapy and sepsis in the face of marrow hypoplasia induced by chemotherapy. Lactoferrin concentrations paralleled the white count in all groups. They were highest in pneumonia and tuberculosis, mildly elevated in rheumatoid arthritis and markedly decreased in neutropenic sepsis. Very high initial lactoferrin concentrations were associated with a poor prognosis in acute pneumonia. C-reactive protein and ferritin concentrations remained elevated through the period of study in acute pneumonia and neutropenic sepsis, while they gradually normalised over weeks in subjects with tuberculosis or rheumatoid arthritis on therapy. In pneumonia and tuberculosis moderate hypoferraemia and a reduced iron-binding capacity were evident. In contrast, a raised percentage saturation was present in neutropenic sepsis, probably related to erythroid marrow suppression. Comparisons between ferritin, lactoferrin and C-reactive protein in the various groups supported the concept that ferritin behaves in part as an acute phase reactant and that hypoferraemia in inflammation is due to deviation of iron into ferritin stores. The suggestion that lactoferrin is responsible for the hypoferraemia and hyperferritinaemia was not supported by the present data. Iron deficiency appeared to limit the hyperferritinaemic response in rheumatoid arthritis, while erythropoietic inhibition by chemotherapy dampened the hypoferraemic response in neutropenic sepsis.
Arthritis, Rheumatoid↗
Severe deficiency of alpha 1-antitrypsin associated with cutaneous vasculitis, rapidly progressive glomerulonephritis, and colitis.
The association of vasculitis with severe deficiency of alpha 1-antitrypsin is rare. This report describes a 44-year-old man with severe deficiency of alpha 1-antitrypsin associated with diffuse vasculitis involving skin, kidney (rapidly progressive glomerulonephritis), and colon (colitis). Colitis has not previously been reported in association with deficiency of alpha 1-antitrypsin. Other reported cases are reviewed and the possible immunologic mechanisms underlying the association are discussed.
Adult↗
Does plasma transferrin regulate iron absorption?
It has been suggested that transferrin that has recently donated its iron to receptor sites is 'activated' to take up iron more avidly from donor tissues. The hypothesis was tested in vitro in a system in which use was made of the different electrophoretic mobilities of normal and desialated transferrin. Recently desaturated transferrin and native apotransferrin were added in equal amounts to a solution of radioactive ferric citrate to produce various end saturations. The resultant mixture was electrophoresed on 5.4% polyacrilamide gel, which was then sliced and counted for 59Fe counts. The size of the 2 radioactive peaks was then compared and expressed as a ratio. Using this in vitro system no supporting evidence could be found for the hypothesis that diferric transferrin which has just donated its iron is able to bind available iron more avidly than native apotransferrin.
Apoferritins↗
Serum ferritin and Hodgkin's disease.
The haemoglobin, serum iron, transferrin saturation, serum ferritin, erythrocyte sedimentation rate (ESR), splenic weight and non-haem iron concentration in the marrow, liver and spleen were measured prior to treatment in 35 patients with Hodgkin's disease who underwent staging laparatomy. The Hb, serum iron and transferrin saturation showed a significant decrease with increasing stage of the disease. In contrast, there was a significant increase in the serum ferritin, ESR, splenic weight and in all the tissue non-haem iron concentrations. The calculated total iron content of the body remained relatively constant throughout at about 2 g but with increasing stage there was an internal redistribution of iron, with a progressive drop in Hb iron and a reciprocal rise in storage iron, especially in the liver. Serum ferritin concentrations, which rose with progression of the disease, were inappropriately high in relation to the size of body stores at all stages but especially in patients with 4B disease and hepatic involvement. It was concluded that the serum ferritin concentrations are raised for several reasons in Hodgkin's disease. They reflect an increase in body iron stores, ferritin's role as an 'acute phase' protein in the inflammatory response and hepatic damage in patients with advanced disease.
Blood Sedimentation↗