Search

Two siblings, both splenectomized at an early age for hereditary spherocytosis, had a severe hemochromatosis develop. The human leukocyte antigen (HLA) system typing showed that they were half HLA identical. All the other members of the family who did not have evidence of hereditary spherocytosis, including those who displayed identical HLA haplotypes with the two patients, did not have any increase in iron stores. These results suggest that the two siblings are heterozygous for idiopathic hemochromatosis and that the coexistence of this condition with hereditary spherocytosis can cause a severe iron overload.

Serum iron, transferrin saturation, serum ferritin and urinary iron excretion have been tested in a group of Italian subjects with beta-thalassemia trait. A number of these subjects, mostly men, had signs of increased iron load. Serum ferritin was the most sensitive index among those measured for detection of iron overload and was positively correlated with desferrioxamine-induced urinary iron excretion. Italian males with beta-thalassemia trait may be at high risk of developing iron overload even without prolonged iron or transfusional therapy.

We have characterized HLA antigens in subjects with beta-thalassaemia trait with and without iron overload. 50% of the cases with iron overload (v 18% of those without iron overload, P less than 0.01) are carriers of HLA-A3, the HLA antigen tightly linked to the IH allele. Thus, in a considerable number of these subjects, beta-thalassaemia and IH coexist. This association exerts a synergistic effect in inducing iron overload.

The Authors describe the results obtained by administering for 2-3 months a combination containing the coenzymes of vitamins B1, B6 and B12 to 16 patients with alcoholic liver disease. The patients showed a statistically significant improvement of red blood cells, haemoglobin, packed cell volume, general symptoms, together with a better utilization of iron. The Authors conclude confirming the efficacy of this product and its good tolerability.

Monoclonal antibodies (mAbs) with a high sensitivity and specificity for small cell lung cancer (SCLC) may be of potential diagnostic and therapeutic use. We selected five different mAbs generated against SCLC cell lines and tested them on paraffin-embedded SCLC and non SCLC (NSCLC) clinical samples in a retrospective study using immunohistochemical techniques. The results showed that the contemporary use of mAbs that react with different antigens allowed all the examined SCLC to be detected indicating that this panel of mAbs was extremely sensitive. Analysis of the reactivity of these mAbs with NSCLC showed that 4 of the 5 antibodies reacted also with a few NSCLC. Using higher dilutions of these mAbs their specificity improved substantially. The 5 different mAbs presented marked heterogeneity of antigenic expression within and between SCLC. This panel of antibodies may be very useful in the diagnosis of SCLC whereas their application, in vivo, in therapeutic trials, is limited by the heterogeneity of antigenic expression.

In the attempt to define the abnormalities responsible for the severe iron overload found in patients with idiopathic hemochromatosis (IH) we analyzed, in 8 patients with IH and in 7 normal subjects, by using specific cDNA probes, the genes coding for the main iron-related proteins, i.e., transferrin, transferrin receptor, as well as H and L subunits of ferritin. In all the patients tested all the probes failed to evidentiate rearranged bands with any of the restriction enzymes employed. These findings suggest the absence of gross structural alterations of the genes examined. The lack of polymorphic sites recognized by the restriction enzymes employed in this study within or around the genes examined does not allow to associate a specific gene with the disease.

Purified recombinant human ferritin composed solely of H subunit was radiolabeled and incubated with proerythroleukemic K562 human cells. A specific binding was detected, and it could be displaced only by ferritins, natural or recombinant, containing large proportion of the H subunit. The specific ferritin H-chain binding was saturable, and cells showed 17,000 to 23,000 binding sites per cell. The affinity constant measured at 37 degrees C was of 3 x 10(8) M-1. Treatment with pronase eliminated the specific binding. The binding sites were expressed in a high number during the cellular exponential phase of growth and progressively decreased to disappear when cells reached the plateau phase. Treatment of the cells with desferrioxamine increased recombinant H-ferritin binding, while iron had little effect. K562 cells induced to differentiate by hemin failed to bind ferritin H. Ferritin H-chain binding capacity is present on various cell lines such as HL60, lung cancer, and hepatoma cells. Analysis of the binding sites by western blotting showed a peptide with apparent mol wt of about 100 kd.

Basic ferritin (liver-type) was measured in erythrocytes of subjects with alpha- and beta-thalassemia trait, thalassemia intermedia and Cooley's disease, and compared with normals and patients with abnormal iron metabolism without erythrocyte metabolic defect (iron deficiency anemia and idiopathic hemochromatosis). In all the thalassemic syndromes considered, erythrocyte ferritin was significantly higher than in normals (p less than 0.001) and increased progressively with the increasing 'severity' of the thalassemic disorder. In both thalassemic and non-thalassemic subjects, erythrocyte ferritin levels were related to body iron status, but in the thalassemic group, the increased erythrocyte ferritin values seemed also to be closely related to the intracellular metabolic abnormality. The severity of the defect in globin chain synthesis seemed to play an important role in determining ferritin accumulation in red cells of thalassemic subjects.

Thirty two unrelated Italian subjects with idiopathic haemochromatosis were studied. HLA-A3 was present in 26 of them (81% v 22% in controls; p less than 0.001) and HLA B7 in eight (28% v 9%; p less than 0.01). There was no important association between idiopathic haemochromatosis and HLA B14. Subdividing the patients on the basis of their regional origin a noticeably higher prevalence of HLA Bw35 in patients with idiopathic haemochromatosis from north eastern Italy was found than in those from Lombardy, or in the controls; there were no differences in the incidence of HLA A3 and B7 between patients with idiopathic haemochromatosis from different areas. A high prevalence of A3, Bw35, and A3, B7 haplotypes was found in our patients with idiopathic haemochromatosis. A3, Bw35 could be the haplotype most commonly linked to the idiopathic haemochromatosis gene in north eastern Italy.

Many agents have been reported to cause hemolytic anemia in glucose-6-phosphate dehydrogenase (G6PD) deficient subjects. We investigated whether cimetropium bromide, a new antispasmodic drug, can be safely given to these patients. In the first study, ten healthy volunteers were given 50 mg, p.o. 3 times per day, before meals for 1 week. Blood samples were drawn before and after treatment and stimulation of the hexose monophosphate shunt (HMS) was evaluated. No significant stimulation of HMS was observed. In a second study, 12 G6PD-deficient patients with spastic colon were given cimetropium bromide and placebo according to a double blind, cross-over design. None of the patients showed any significant abnormalities in any of the several hematologic parameters tested.

Patients with idiopathic hemochromatosis exhibit an unexplained increase in intestinal iron absorption. The aim of this work was to study immunohistochemical H- and L-ferritin distribution in duodenal mucosal cells of patients with idiopathic hemochromatosis, and of subjects with various degrees of iron loading. Biopsy sections of gastrointestinal mucosa from 24 patients with idiopathic hemochromatosis, 10 patients with secondary iron overload, 6 normal subjects, and 13 iron-deficient subjects were analyzed with monoclonal antibodies for the presence of immunohistochemical H and L ferritin types, and with Perls' stain for hemosiderin. Ferritin content of duodenal homogenates was evaluated in 5 cases. The absorptive duodenal cells were found to contain ferritin, mostly of the L type, in apical granules; these ferritin granules were present in all normal, iron-deficient, and iron-over-loaded subjects, but were absent in 21 (87%) of the patients with established idiopathic hemochromatosis. In cells other than those of the duodenal epithelium, such as lamina propria or antral mucosa, ferritin and hemosiderin contents were related to iron loading and no difference was evident between primary and secondary iron overload. These findings indicate that (a) idiopathic hemochromatosis is associated with an altered ferritin expression in the duodenal absorptive epithelial cells, (b) this alteration cannot be detected by analysis of duodenal homogenates, (c) idiopathic hemochromatosis does not affect ferritin accumulation in the other cell types analyzed, and (d) ferritin in absorptive duodenal cells may have a regulatory role in iron absorption.