Reticuloendothelial phagocytic function in human liver diseases.
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Hepatitis↗
Biomedical subjects
J W Halliday
Publications and source records attributed to J W Halliday.
Renal damage after subtotal nephrectomy.
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Adrenalectomy↗
HLA typing in idiopathic hemochromatosis: distinction between homozygotes and heterozygotes with biochemical expression.
In a study of 20 families with idiopathic hemochromatosis, relatives of probands were classified as either homozygous, heterozygous, or normal according to their HLA phenotype. An abnormality in the serum iron concentration, total iron-binding capacity, or serum ferritin concentration was present in all homozygotes and in 25% of heterozygotes. In heterozygotes, the mean total iron-binding capacity was significantly decreased, and the mean hepatic iron concentration was significantly increased compared to normals. However, in contrast to homozygotes, clinical evidence of iron overload was not observed in heterozygotes, and there was no biochemical or histological evidence of liver disease resulting from excessive iron stores. Progressive iron overload did not develop in 44 heterozygotes who were studied for up to 16 yr.
Adolescent↗
Value of hepatic iron measurements in early hemochromatosis and determination of the critical iron level associated with fibrosis.
The role of the measurement of hepatic iron in the diagnosis of genetic hemochromatosis was studied, with particular reference to the differentiation of early hemochromatosis from alcoholic siderosis and the critical hepatic iron concentration associated with fibrosis in hemochromatosis. Hepatic iron was measured in 30 homozygous relatives of 17 hemochromatosis probands, 8 heterozygous relatives, 51 patients with alcoholic liver disease and 40 control subjects. Hepatic iron concentrations were greatly increased in the majority of homozygous hemochromatosis subjects, and there was little overlap with the other groups. In the absence of alcoholism, fibrosis or cirrhosis in hemochromatosis was present only with hepatic iron concentrations above a threshold of approximately 400 mumoles per gm (22.3 mg per gm) dry weight. In some heterozygous hemochromatosis subjects and in some alcoholic patients, hepatic iron concentrations were in the range seen in young homozygous subjects. However, an age-related rise in hepatic iron was seen only in hemochromatosis homozygotes, and calculation of an hepatic iron index (hepatic iron/age) resulted in a clear distinction between homozygotes and the other three groups. It is concluded: that chemical measurement of hepatic iron concentration, when corrected for the age of the subject, reliably distinguishes early hemochromatosis from alcoholic siderosis, and, that there appears to be a threshold level of hepatic iron above which there is a high risk of fibrosis.
Adolescent↗
The prognosis of chronic active hepatitis without cirrhosis in relation to bridging necrosis.
Sixty-nine patients with chronic active hepatitis without cirrhosis were studied to define the prognostic implications of bridging necrosis of various types. There were 19 patients without bridging necrosis compared with 50 patients with bridging necrosis. The two groups did not differ significantly at presentation in age, sex, clinical or laboratory features. In the group without bridging necrosis, no patient died from the disease and none of 13 having a later biopsy developed cirrhosis. In the group with bridging necrosis, one patient died from hepatic failure and 7 of 36 developed cirrhosis (19%). When analyzed statistically, a significant (p less than 0.05) relationship is seen between increasing severity of initial lesion and the subsequent development of cirrhosis. It is concluded that patients with piecemeal necrosis without bridging should not be grouped together with patients with bridging necrosis or cirrhosis when considering management decisions.
Adolescent↗
Transferrin receptors in hemochromatosis.
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Cells, Cultured↗
Isolation of a human hepatic ferritin receptor.
A human hepatic ferritin receptor has been isolated from human liver and has been purified using affinity chromatography. An affinity constant of 6.0 x 10(8) moles-1 liter was determined for the ferritin receptor. The molecular weight was estimated to be approximately 53,000 by gel electrophoresis. Binding of ferritin to the receptor coupled to a microparticulate support was specific for human liver ferritin with no binding of rat or porcine ferritin. Binding was unaffected by a 100-fold excess of human transferrin, human asialoorosomucoid and bovine albumin. After treatment of the receptor protein with trypsin, binding was not detected. The human hepatic ferritin receptor may play an important role in the uptake of iron into the hepatocyte in physiological and pathological conditions.
Animals↗
Functional roles of the ferritin receptors of human liver, hepatoma, lymphoid and erythroid cells.
Ferritin receptors are present on the membranes of many normal and malignant cells. The binding specificity of these receptors for H and L subunits was examined using recombinant human ferritin homopolymers. At least two different types of ferritin receptors were found, one derived from normal rat, pig, and human liver which shows similar binding of H- and L-ferritin. The second receptor type, specific for the H-chain ferritin, has been identified on membranes of hepatic and other transformed cells, and of normal lymphoblasts and erythroid precursors. These two receptor types may have different metabolic functions: the hepatic receptor acting as a scavenger for circulating ferritin and possibly for iron exchange between hepatocytes and macrophages; the H-ferritin receptor having a regulatory role which is not directly related to iron metabolism. The expression of the H-ferritin receptor is closely related to the activation and proliferation state of the cells. Addition of H-ferritin to the culture medium of cells expressing the H-ferritin receptor resulted in inhibition of cell proliferation and of colony formation.
Animals↗
Differential regulation of ferritin H and L subunit mRNA during inflammation and long-term iron overload.
Iron overload, such as occurs in the genetic disease haemochromatosis, leads to synthesis of ferritin containing an increased proportion of L subunits. Inflammation also leads to clinically important increases in ferritin synthesis but the predominant subunit involved is unclear. Elevation of serum ferritin concentration during the acute phase response confounds its use as an indicator of body iron stores and identification of the major subunit involved may allow distinction of the ferritin associated with inflammation from the synthesized during iron overload. The present study examined H and L ferritin subunit mRNA levels in rats with: (i) longstanding iron overload, both parenteral and oral, in which changes should be maximal and stable; and (ii) inflammation of 24 and 48 h duration. A two-fold increase in L mRNA level was found in both groups of iron loaded animals while H mRNA level was unchanged. This finding would account for the observed preponderance of L subunits in ferritin during iron overload. During the course of inflammation there was a progressive decrease in L mRNA level in the liver but not the spleen. H mRNA relative to total RNA level was unchanged in both liver and spleen. It is concluded that the differential regulation of the two ferritin subunits in response to different stimuli and in different tissues occurs at the level of alteration in mRNA concentration.
Acute-Phase Reaction↗
Carbohydrate-deficient transferrin in alcoholics with liver disease.
To assess the relationship between carbohydrate-deficient transferrin (CDT) and alcoholic liver disease, we measured the ratio of carbohydrate-deficient transferrin to total transferrin (rCDT) in 32 male alcoholics with liver disease (Child-Pugh class A, 8; B, 11; C, 13) and 14 male alcoholics without clinically evident liver disease. Twenty of 32 with liver disease and six of 14 without clinically apparent liver disease had recent abstinence. The 32 patients with liver disease were assessed, in addition to the Child-Pugh class, using a linear prognostic score, the Combined Clinical and Laboratory Index (CCLI). Transferrin and CDT were measured by isocratic anion exchange chromatography and a radio-immunoassay. When the total group (n = 46) was divided into those with recent abstinence (n = 26) and those without (n = 20), the rCDT was lower in the abstainers than non-abstainers (0.7 +/- 0.6 vs 2.9 +/- 2.4, P < 0.005). Similarly, abstainers with liver disease (n = 20) had a significantly lower rCDT than non-abstainers (n = 12) with liver disease (0.7 +/- 0.7 vs 3.5 +/- 2.8, P < 0.005). The rCDT in the 20 abstaining patients with liver disease did not differ significantly between Child-Pugh classes. Furthermore, there was no correlation between the CCLI and rCDT (r = 0.05). We conclude that the relationship between rCDT and alcohol abuse is not appreciably altered by the presence of clinically severe liver disease in male alcoholics.
Alcoholism↗