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Biomedical subjects

J W Halliday

Publications and source records attributed to J W Halliday.

At least 145 records · Page 8Linked to original sources

Duodenal ferritin content and structure: relationship with body iron stores in man.

The relationship between serum ferritin and duodenal ferritin was examined in normal subjects and in patients with iron deficiency, secondary iron overload, or idiopathic hemochromatosis (IHC). A positive correlation between serum ferritin and duodenal ferritin concentrations was found in all groups. In the iron-overload conditions, duodenal ferritin concentration was lower at all levels of serum ferritin in comparison with normal and iron-deficient subjects. Patients with secondary iron overload did not differ from those with IHC, which indicates that any decrease in duodenal ferritin concentration was secondary to the excess body iron stores. Purified duodenal ferritin from normal subjects and patients with iron-overload conditions showed the same two distinct isoferritins by isoelectric focusing. After the oral administration of iron, two additional isoferritins were detected. These resembled the major isoferritins of liver.

Administration, Oral↗

Serum-ferritin in diagnosis of haemochromatosis. A study of 43 families.

242 members of 43 families with idiopathic haemochromatosis were investigated for increased body-iron stores in order to assess the value of serum-ferritin determination as a screening-test to detect preclinical disease. The serum-iron concentration was elevated in only 76% of relatives with increased iron stores, and it was also elevated in 10% of relatives with normal iron stores. The percentage saturation of transferrin was elevated in all relatives with increased iron stores but also in 33% of relatives with normal iron stores. Serum-ferritin was raised in 98% of relatives with increased iron stores and in only 3 (1.8%) of those with normal iron stores. These 3 subjects consumed alcohol in excess of 100 g ethanol per day, and their serum-ferritin levels fluctuated widely. Increased iron stores were reflected in increased serum-ferritin concentrations in subjects as young as 14 years in whom the liver-iron concentration was twice the normal upper limit and before there was any evidence of architectural damage to the liver. The serum-ferritin concentration is a useful non-invasive screening test for precirrhotic haemochromatosis.

Adolescent↗

Serum ferritin in haemochromatosis: changes in the isoferritin composition during venesection therapy.

The isoferritin composition of serum ferritin in 13 patients with untreated idiopathic haemochromatosis (IHC) has been shown to differ from normal in exhibiting an increase in isoferritins in the pH range 5.54-5.62. A similar change was observed in four patients with gross iron overload secondary to haemolytic anaemia. During the course of venesection therapy there was a progressive rise in isoferritins of pI 5.02-5.06 relative to the more basic isoferritins. These observations are consistent with previous studies showing alterations in tissue isoferritins in untreated IHC before and after venesection therapy and they are compatible with the hypothesis that the more basic isoferritins correspond to a 'storage' ferritin and the more acidic to a 'secretory' ferritin. The studies also provide further evidence for a possible biological role of the individual isoferritins.

Adult↗

Immunological detection of isoferritins in normal human serum and tissue.

A method is described which permits the detection of isoferritins in normal human serum and tissues. The technique makes use of 125I-labelled monospecific anti-human-liver-ferritin antibody to demonstrate the isoferritins after isoelectric focussing of the purified ferritin in polyacrylamide gels. The organ-specific variation in tissue isoferritin profile previously reported in normal subjects has been confirmed by this technique using only 50 ng of each ferritin sample. Serum ferritin from normal healthy subjects was also shown to exhibit a microheterogeneity on isoelectric focussing; six clearly defined isoferritin peaks were detected in the pH range of 5.04 to 5.62. This isoferritin profile of normal serum contained isoferritins over the whole range of the various tissue isoferritins suggesting that a number of organs may contribute to the normal serum ferritin pool.

Chemical Phenomena↗

Normal serum ferritin concentrations in precirrhotic hemochromatosis.

We investigated 33 of 58 members of two families with latent or precirrhotic hemochromatosis to determine its pattern of inheritance and to evaluate the serum ferritin levels as an index of iron stores. In both families, the pattern of inheritance was as an autosomal dominant trait with incomplete expressivity. Mean serum ferritin values in the affected family members were 88.5 ng per milliliter (range, 28.0 to 201.9) for males and 65.2 ng per milliter (range 23.7 to 97.0) for females, which were no different from controls (P is less than 0.5). Furthermore, the serum ferritin values did not correlate with or reflect mobilizable iron stores, and there were no relations between the serum iron, iron-binding capacity and transferrin saturation (P is less than 0.2). Thus, serum ferritin concentrations in precirrhotic familial hemochromatosis appear to underestimate iron stores. Serum ferritin levels do not help to identify such patients with increased iron stores for therapeutic phlebotomy.

Adult↗

Iron absorption in the rat: the search for possible intestinal mucosal carriers.

The biological relevance of four iron-containing fractions previously detected in rat intestinal mucosal cells has been studied. The distribution of iron in these fractions obtained by chromatography on Sepharose 6B has been examined after in vivo and in vitro incubation of mucosal cells with 59Ce. In addition, the effects of phenobarbitone, cycloheximide, iron-deficiency and iron-loading on the uptake and distrubution of iron within the four mucosal cell fractions was studied. The iron in fraction I was mostly bound to intracellular membrane particles. Fraction II was shown to be ferritin. Fraction III contained some transferrin and also a protein of molecular weight similar to transferrin but which was not precipitable by antitransferrin antiserum. Quantited with the results of 'chaser' experiments suggested that, in addition to ferritin, at least two of the fractions (I and III) were involved in the process of iron absorption by the mucosal cell.

Animals↗

Haemolysis in liver disease: relationship to erythrocyte membrane function, serum bilirubin concentration and plasma electrolyte disturbances.

The pathogenesis of the mild to moderate haemolysis that is almost universal in patients with liver disease was investigated to determine if it was related to dysfunction of the red blood cell (RBC) membrane resulting from abnormalities in plasma electrolyte, urea or bilirubin concentrations. Thirty-nine patients with various forms of liver disease were investigated as well as six with miscellaneous diseases associated with plasma electrolyte disturbance. RBC membrane permeability was measured by the rate of 22Na influx. The results showed that the shortened RBC survival in liver disease is not related to morphological changes in the RBC or altered membrane integrity as measured by osmotic fragility, mechanical fragility, autohaemolysis, membrane ATP and membrane permeability.

Anemia, Hemolytic↗

Isoferritin composition of tissues and serum in human cancers.

A highly sensitive technique for isoferritin detection using 125I-labeled monospecific anti-human liver ferritin antibody for the identification of isoferritins after the analysis of small quantities of ferritin by isoelectric focusing in polyacryl-amide gels was applied to the study of renal, pancreatic, and colonic carcinomas. In all tumors studied, the isoferritin composition differed from that of the corresponding normal tissue; major isoferritins with pl more basic than those of the normal tissues were consistently detected. Composition of purified ferritin from metastases closely resembled the isoferritin composition of the primary tumors. Examination of the serum isoferritin profiles of four patients with cancers did not reveal the presence of any tumor-specific changes in isoferritins. It is suggested that the abnormality in tissue ferritins in the three human cancers studied is the synthesis of major isoferritins in the more basic range, rather than the appearance of tumor-specific isoferritins in the more acidic range.

Colonic Neoplasms↗

Hepatitis B-antigen subtypes in Australia as detected by radioimmunoassay.

The distribution of the major subtypes of hepatitis B surface antigen (HBsAg) was examined in asymptomatic white Australian blood donors and patients with liver disease to attempt ot assess the biological significance of these subtypes in this relatively homogeneous Caucasian population. Since previous studies have shown a very low prevalence of HBsAg in white Australians, a highly sensitive solid phase radioimmunoassay (RIA) was developed and used to subtype the antigen. A total of 46 samples of hepatitis B-antigen positive sera, obtained from 21 asymptomatic volunteer blood donors and 25 patients with liver disease, were tested. Sixteen of these 21 asymptomatic carriers were shown to have subtype "ad" whereas only seven of the patients with liver disease had this subtype. This difference was significant (P less than 0.005) and supports the view that subtype "ad" is associated with a carrier state and subtype "ay" with liver disease in Australia.

Acute Disease↗

Solid phase radioimmunossay for serum ferritin.

A solid-phase "direct" radio immunoassay which is highly sensitive (detecting less than 0.5 ng/ml) and reproducible is described for the assay of ferritin in human serum. The method makes use of specific anti-ferritin antibody prepared using human liver ferritin; It has the advantage that tubes coated with specific antiserum may be stored for later use and lends itself readily to an automated washing procedure. The concentration of ferritin present in the serum of normal males in the population was 56,9 ng/ml (geometric mean) with a 95 percent confidence range of 18 to 180 ng/ml. In normal females the concentration was 34.0 ng/ml (geometric mean) with a 95 percent condidence range of 10 to 143 ng/ml.

Animals↗

The relationship of red cell membrane lipid content to red cell morphology and survival in patients with liver disease.

The relationship of red blood cell (RBC) membrane lipid content to RBC morphology and survival was studied in patients with liver diseases. An increase in RBC cholesterol and phospholipid was detected in most patients with hepatocellular disease or cholestatic jaundice but the alteration in RBC lipid content did not correlate with RBC survival. The main abnormality of RBC morphology observed was the presence of macrocytes and target cells. In a small proportion of patients (approximately 3%) with severe hepatocellular disease, significant numbers of severely deformed ("spur") cells were seen. In these patients haemolysis was moderately severe and the RBC lipid profile showed increased membrane cholesterol without a concomitant increase in phospholipids. It is concluded that only in patients with "spur" cell anaemia do the morphological alterations lead to premature removal of cells from the circulation. The cause of the shortened RBC survival in jaundiced patients without "spur" cells remains to be determined.

Adolescent↗

Alterations in tissue ferritins in iron storage disorders.

Purified tissue ferritins isolated from Bantu subjects with gross haemosiderosis, from a patient with idiopathic haemochromatosis (HC) treated by phlebotomy, and from rats with experimental iron overload were studied in order to determine the significance of the abnormality previously demonstrated in tissue isoferritins in patients with IHC. The isoferrin profile of the tissues from the Bantu subjects and the iron-loaded rats showed a similar abnormality to that previously found in patients with untreated IHC--that is, an abnormally uniform distribution of iron-containing isoferritins with an increase in the more basic isoferritins and an apparent absence of the more acidic ones. In contrast, tissues from the patient with treated IHC, who was iron depleted at the time of death, showed the normal organ-specific isoferritin distribution. These findings strongly suggest that the abnormal distribution of tissue isoferritins in IHC is an acquired phenomenon and unlikely to be related to an underlying genetic defect in ferritin or iron metabolism.

Animals↗

Specific immunodiagnosis of hepatocellular carcinoma by leucocyte adherence inhibition.

The leucocyte adherence inhibition test provides a rapid, reliable, and specific technique for the immunodiagnosis of primary hepatocellular carcinoma (malignant hepatoma). The patient's blood leucocytes are tested in vitro for cell-mediated immunity against tumour-associated antigens and the serum is tested for blocking factor which interferes with the immunological reaction. Specific reactivity of both leucocytes and serum was consistently detected in patients with malignant hepatoma, and negative reactions were obtained in other liver diseases including secondary tumours of the liver. The test has provided positive evidence for the presence of hepatoma when more conventional methods gave doubtful or negative results. A positive result preceded the clinical appearance of tumour by up to three years in two patients.

Adult↗