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PubMed1986

Trace analysis to determine heavy metal load in lung tissue. A contribution to substantiation of occupational hazards.

A routine method to determine the presence of partly environmentally relevant trace elements Al, Be, Cd, Co, Cr, Cu, Fe, Mn, Ni and Pb in lung tissue is described. The stages of process are preparation of samples conforming to the analysis material, decomposition, and subsequent trace determination by atomic absorption spectrometry. The results obtained from 125 samples show that chemical analysis is an effective aid in identifying and substantiating occupational risks.

Aluminum↗
PubMed1976

Studies of malformation syndromes of man XIB: the cerebro-hepato-renal syndrome of Zellweger: comparative pathology.

A study of 11 autopsied cases of the cerebro-hepato-renal syndrome of Zellweger (ZS) is reported. All cases had severe, persistent congenital hypotonia, hepatic lobular disarray, renal cortical cysts and pulmonary hypoplasia. Many had cardiovascular malformations, hepatomegaly, cerebral cortical gyral maldevelopment and pancreatic islet hyperplasia. Additional, less frequent findings are delineated. Results of iron content studies of hepatic and renal tissues are related to age of survival and possible development of fibrosis.

Abnormalities, Multiple↗
PubMed1989

Ferritin subunits in livers of siderotic mice.

The major ferritin species of mouse liver has been resolved by SDS-PAGE into two bands similar to the H and L subunits of rat liver ferritin with the L subunit predominating. Amino acid sequencing has confirmed the major, faster-migrating component as L chain. An additional, electrophoretically fast, minor ferritin was isolated from siderosome-containing subcellular fractions. In denaturing gels it gave a single 'F' subunit band of about 17 kDa, significantly smaller than the L and H subunits (about 20 and 21 kDa respectively). A small fragment isolated from the fast ferritin was sequenced. It corresponds to a 19-residue C-terminal peptide cleaved from L subunits in the assembled molecules. The F subunit must be derived from L subunits by loss of this peptide, and is not the expression product of a different gene. 'Fast' ferritins of siderotic mice and rats are thus analogous.

Amino Acid Sequence↗
PubMed1975

An other look at iron: role in host pathogen interaction.

Iron, as participant of many biological processes is a prerequisite for life. Uptake, internal transport and storage by organisms is handled by highly specialized chemical systems endowed with strong metal binding affinities. Apart from the homeostatic function of iron-binding compounds they appear of significance for inter-species interactions. Thus, by tight binding transferrin withholds the iron from invading microorganisms required for their optimal growth. This bacteriostatic property of the iron transport protein is however partially overcome by small molecular substances synthesized by bacteria and successfully competing for the metal. The balance of such interaction is a complex one. Yet, strong evidence points to the crucial importance of the amount of iron offered by a host to infecting agents for determining the fate of bacterial disease.

Anemia, Hypochromic↗
PubMed1982

[Serum ferritin in differential diagnosis of anemia (author's transl)].

The concentration of ferritin in the serum of normal males (n = 79) was 98 micrograms/l (geometric mean) with a 95% confidence range of 21-447 micrograms/l. In non-menstruating healthy females (n = 39), the concentration was 85 (26-279) micrograms/l. In menstruating females, serum ferritin was less than 30 micrograms/l only when the duration of menstruation was more than or equal to 4 days. Patients with uncomplicated iron-deficiency anemia had a serum ferritin level less than 20 micrograms/l. After oral or parenteral iron therapy, serum ferritin was greater than 20 micrograms/l in 7 to 17 patients. Serum ferritin was greater than 20 micrograms/l in 8 of 12 patients with a simultaneous inflammatory or malignant disease. Of patients with iron-deficiency anemia, 86% had a serum ferritin level lower than 40 micrograms/l. A serum ferritin level less than 40 micrograms/l was only observed in patients with iron-deficiency anemia and not in patients with other forms of anemia. Of patients with iron-deficiency anemia and a hemoglobin concentration lower than 100 g/l, 80% had a serum iron level less than 13 mumol/l and a total iron binding capacity higher than 70 mumol/l. Anemia of chronic disorders was diagnosed with a sensitivity of 0.93 and a specificity of 0.92 in patients with serum iron less than 13 mumol/l, total iron binding capacity less than 60 mumol/l, erythrocyte sedimentation rate greater than 25 mm in the first hour, and serum fibrinogen greater than 4 g/l. Somewhat better was the same combination except with the serum ferritin level greater than 50 micrograms/l instead of the iron binding capacity. However the predictive value using both combinations was too low.

Anemia, Hypochromic↗
PubMed1990

Hepatic iron overload: diagnosis and quantification by noninvasive imaging.

The diagnostic efficacy of magnetic resonance (MR) and computed tomography (CT) for detection and quantification of hepatic iron was assessed in a series of patients under investigation for clinical or biochemical evidence of hepatic iron overload. Thirty patients underwent MR imaging (SE 30,60/1000 or SE 30,60/2000) at 0.5 Tesla with calculation of hepatic T2 and liver to paraspinous muscle signal intensity ratios. Twenty-nine patients also had measurement of hepatic attenuation on noncontrast CT images. Results of these imaging studies were correlated in all patients with quantitative iron determination from liver biopsy specimens. The best predictor of liver iron among parameters studied was the ratio of the signal intensities of liver and paraspinous muscle (L/M) on a SE 60/1000 sequence. Both MR using L/M ratios and CT were sensitive methods for detection of severe degrees of hepatic iron overload with 100% of patients with hepatic iron on biopsy greater than 600 micrograms/100 mg liver dry weight detected on the basis of L/M less than 0.6 or CT attenuation greater than 70 Hounsfield units (HU). The MR parameter, however, was more specific than CT (100 vs 50%) and showed a higher degree of correlation with quantitated hepatic iron from biopsy. T2 measurements showed poor correlation with hepatic iron, due to difficulty in obtaining precise T2 measurements in vivo when the signal intensity is low. None of the parameters utilized was sensitive for detecting mild or moderate degrees of hepatic iron overload. We conclude that MR and CT are sensitive techniques for noninvasive detection of severe hepatic iron overload, with MR providing greater specificity than CT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Ultrastructural observations in the carbonyl iron-fed rat, an animal model for hemochromatosis.

Rats fed a carbonyl iron-supplemented diet for 4-15 months were studied for iron content and morphologic changes in the liver, spleen, intestinal mucosa, pancreas and heart. All organs had an increased iron content measured by atomic absorption, with the highest concentrations in the liver and spleen. The periportal distribution of stored iron in the liver was similar to that in human hemochromatosis. In animals treated beyond 6 months Kupffer cells and sinusoidal lining cells also showed cytosiderosis. Electron microscopy provided information on ferritin and hemosiderin content and distribution within parenchymal and sinusoidal cells of the liver but no excessive fibrosis was found. Except for the spleen, the other organs showed less iron deposition. Iron-filled lysosomes (siderosomes) were found in macrophages in the intestinal lamina propria and pancreas, as well as in enterocytes, pancreatic acinar cells and heart muscle cells. Heavily iron-laden siderosomes had increased membrane instability which was demonstrated both morphologically and by measurements of latent lysosomal enzyme activities. Even though cirrhosis was not found, the distribution pattern of accumulated storage iron and lysosomal lability indicated that the carbonyl iron-fed rat is a suitable experimental model for human hemochromatosis.

Animals↗
PubMed2004

Ascorbic acid deficiency, iron overload and alcohol abuse underlie the severe osteoporosis in black African patients with hip fractures--a bone histomorphometric study.

Osteoporosis and femoral neck fractures (FNF) are uncommon in black Africans although osteoporosis accompanying iron overload (from traditional beer brewed in iron containers) associated with ascorbic acid deficiency (oxidative catabolism by iron) has been described from sub-Saharan Africa. This study describes histomorphometric findings of iliac crest bone biopsies and serum biochemical markers of iron overload and of alcohol abuse and ascorbic acid levels in 50 black patients with FNFs (29 M, 21 F), age 62 years (40-95) years (median [min-max]), and in age- and gender-matched black controls. We found evidence of iron overload in 88% of patients and elevated markers of alcohol abuse in 72%. Significant correlations between markers of iron overload and of alcohol abuse reflect a close association between the two toxins. Patients had higher levels of iron markers, i.e., siderin deposits in bone marrow (P < 0.0001), chemical non-heme bone iron (P = 0.012), and serum ferritin (P = 0.017) than controls did. Leukocyte ascorbic acid levels were lower (P = 0.0008) than in controls. The alcohol marker mean red blood cell volume was elevated (P = 0.002) but not liver enzymes or uric acid. Bone volume, trabecular thickness, and trabecular number were lower, and trabecular separation was greater in patients than in controls, all at P < 0.0005; volume, surface, and thickness of osteoid were lower and eroded surface was greater, all at P < 0.0001. There was no osteomalacia. Ascorbic acid deficiency accounted significantly for decrease in bone volume and trabecular number, and increase in trabecular separation, osteoid surface, and eroded surface; iron overload accounted for a reduction in mineral apposition rate. Alcohol markers correlated negatively with osteoblast surface and positively with eroded surface. Relative to reported data in white FNF patients, the osteoporosis was more severe, showed lower osteoid variables and greater eroded surface; FNFs occurred 12 years earlier and were more common among men. We conclude that the osteoporosis underlying FNFs in black Africans is severe, with marked uncoupling of resorption and formation in favor of resorption. All three factors--ascorbic acid deficiency, iron overload, and alcohol abuse--contributed to the osteoporosis, in that order.

Adult↗
PubMed1994

[Systemic karyomegaly with chronic interstitial nephritis. Discussion of the disease picture based on an autopsy case].

Systemic karyomegaly associated with interstitial nephritis was first described in 1978 by Mihatsch. Seven cases have been reported to date. We give an account of an autopsy case of systemic karyomegaly in a 30-year-old Italian man. Bizarre enlargement of nuclei was found in renal tubular epithelial cells, Schwann cells and in smooth muscle cells of vessels and bowel and, less obviously, in endothelial and adventitial cells of vessels, in alveolar epithelial cells and in astrocytes of the brain. These findings were associated with chronic interstitial nephritis, nonspecific hepatopathy, adenocarcinoma of the rectum and multiple sclerosis. The clinical course was marked by chronic renal failure, chronic haemodialysis and renal transplantation. The patient died 8 years after diagnosis in septic-toxic shock. The aetiology and pathogenesis of the disease are discussed.

Adenocarcinoma↗
PubMed2000

[Sideroelastosis of pulmonary vessels after welder dust exposure].

Sideroelastosis pulmonum was first described by Ceelen (1931) and Gellerstedt (1939), mentioning an idiopathic type, but also vascular alterations in chronic pulmonary congestion. We analysed the question wether secondary sideroelastosis can be demonstrated also in lungs after previous welder dust exposure. Lung samples of 43 patients and deceased with various exposure periods to welder dust were investigated. On each sample, light microscopical, scan electron microscopical and energy dispersive x-ray micro analyses (EDX) were performed. In six samples (14%) vascular alterations in the area of denaturated elastic fibres with siderophilic "impregnation" were seen, corresponding to the features described by von Ceelen and Gellerstedt. Giant cell or granulomatous reactions, however, were present only in exceptional cases. This phenomenon was seen mostly in cases of marked local siderin deposits and reactive fibrosis. Using EDX, a number of metals characteristic for welder dust (Al, Ti, Cr, Ni) as well as iron were found in siderophages. No other metal than iron was detected in siderophilic elastic fibres using EDX. Causal pathogenetically, a correlation between increased iron uptake connected with welding particles and sideroelastosis of the vessel walls has to be established. However, in formal pathogenesis, other factors such as local perfusion disturbances due to fibrotic processes after exposure to harmful substances must be taken into consideration.

Dust↗
PubMed1984

Functional efficiency of mitochondrial membrane of rats with hepatic chronic iron overload.

The effect of in vivo hepatic iron overload, induced by two different amounts of iron, on the energy-transducing efficiency of the mitochondrial membrane has been examined. It has been found that when the epatic iron concentration is up to a threshold value mitochondria present an anomalous membrane potential. Addition of oligomycin fully restitutes it. A low content of intramitochondrial K+ is connected with this pathological condition. A relative lack of antioxidant capability is parallely exhibited by these mitochondria. A possible involvement of lipid peroxidation process in vivo in causing the membrane potential drop and the net efflux of intramitochondrial K+ is suggested.

Animals↗