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Biomedical subjects

C Hershko

Publications and source records attributed to C Hershko.

At least 163 records · Page 9Linked to original sources
PubMed1979

Suppressive effect of ferritin on in vitro lymphocyte function.

This study describes the effect of ferritin on lymphocyte function in vitro. Peripheral blood lymphocytes isolated from normal donors were incubated with purified human splenic ferritin, and the mitogenic effect of phytohaemagglutinin (PHA), concanavalin A (Con A), pokeweed mitogen (PWM) and mixed lymphocyte reaction (MLR) were assessed by the uptake of 3H-thymidine (3H-TdR). Ferritin (0.25--5.0 micrograms/ml culture) caused a marked suppression of PHA nad Con A blastogenesis but had no suppressive effect on PWM-induced transformation. Maximal suppression was obtained at a ferritin concentration of 1 microgram/ml and this was not enhanced by increasing ferritin concentrations. Ferritin also reduced the Con A capping phenomenon in normal lymphocytes from 22% to 6%, suppressed the MLR reaction but had no effect on the ability of normal lymphocytes to form E, EA and EAC rosettes or on in vitro lymphocyte cytoxicity against the K-562 cell line. Visual proof of the suppressive effect of ferritin on mitogen induced blastogenesis was provided by scanning electron microscopy, and direct evidence for the ability of lymphocytes to bind ferritin was obtained from studies with radioiodine labelled ferritin. The above findings indicate that ferritin suppresses certain parameters of T-lymphocyte function in vitro. The relation of the present findings to recognized abnormalities of T-cell function encountered in certain neoplastic disorders associated with high serum ferritin levels is at present unknown.

Cytotoxicity, Immunologic↗
PubMed1979

Serum ferritin and mean corpuscular volume measurement in the diagnosis of beta-thalassaemia minor and iron deficiency.

The value of serum ferritin and mean corpuscular volume (MCV) measurement in distinguishing between iron deficient, beta-thalassaemia trait and normal subjects has been studied. Normal subjects had normal ferritin and MCV, iron-deficient ones had low ferritin and low or normal MCV, and thalassaemics had normal ferritin and low MCV. By the combined use of these two measurements it was possible to identify individuals belonging to one of the three categories with an accuracy of over 95%. Although definitive diagnosis of beta-thalassaemia trait requires the demonstration of abnormal haemoglobin A2 levels or reduced beta-chain synthesis, serum ferritin and MCV measurements are useful screening procedures for the initial diagnosis of beta-thalassaemia trait and iron deficiency. Because of the very small amounts of blood required for both of these measurements, they are particularly suitable for surveying large numbers of subjects in populations with a high prevalence of hypochromic-microcytic anaemias.

Adult↗
PubMed1979

Prevalence and causes of anemia in elderly hospitalized patients.

The prevalence and causes of anemia have been studied in 104 patients over 60 years of age admitted to a general medical ward in Jerusalem. In males and females, mean hemoglobin levels were about 1 g less than in the corresponding groups of healthy younger controls. A primary nutritional anemia could not be implicated in any of the 15 patients with hemoglobins below 11 g/dl. The most important causes of anemia were chronic renal failure, metastatic carcinoma, gastrointestinal bleeding, and infection. Conversely, in diseases with no adverse effect on erythropoiesis such as chronic ischemic heart disease, hypertension and diabetes, hemoglobin levels were equal to those of the younger controls. These findings indicate that although diminished serum iron and RBC folate levels may occasionally be found in elderly subjects, nutritional deficiency is seldom responsible for anemia in this age group in Israel- and anemia when present is often the manifestation of a chronic underlying disease.

Adult↗
PubMed1979

Autologous bone marrow transplantation in patients with cancer.

Ten patients with non-leukemic neoplasms received intensive, marrow-lethal doses of drugs and radiation followed by rescue with autologous cryopreserved bone marrow (nine) or marrow from an identical twin as part of a phase 1-2 study. Nine patients had extensive disease that was unresponsive to conventional therapy. Marrow engraftment was documented in all evaluable cases and most patients had a substantial anti-tumor response. Three patients are alive from 4 to 10 months following transplantation without evidence of disease.

Bone Marrow Transplantation↗
PubMed1978

Non-specific serum iron in thalassaemia: an abnormal serum iron fraction of potential toxicity.

Iron binding in the sera of 35 patients with beta thalassaemia major and intermedia was studied. In patients receiving regular blood transfusions since infancy transferrin was completely saturated and about 2.7--7.1 mumol/l of the serum iron could be removed by dialysis or ultrafiltration in the presence of a chelating agent or by filtration on DEAE-Sephadex-catecholdisulphonic acid columns. In contrast, less than 1.0 mumol/l of transferrin bound iron was removed when subjected to the same procedures. The non-specific iron of thalassaemic sera could no longer be demonstrated after incubation with normal serum. These findings indicate that non-specific iron is a chelatable with normal serum. These findings indicate that non-specific iron is a chelatable compound which is readily available for transferrin binding. In view of the known toxicity of unbound iron, its identification in thalassaemic sera might be of relevance to the pathogenesis of tissue damage and the protective effect of iron chelating therapy in this disease.

Adolescent↗
PubMed1978

Granulocyte transfusion therapy: a clinical trial in patients with acute leukemia and sepsis.

The effect of granulocyte transfusions on the course of infection in patients under treatment for acute leukemia was evaluated by comparing 19 febrile episodes in 15 patients receiving antibiotics alone with 18 febrile episodes in 13 patients receiving antibiotics in combination with granulocyte transfusions from ABO-matched donors. Both groups had a similar age, sex distribution and duration of disease prior to the febrile episode. About two-thirds of the patients in both groups had acute myeloblastic leukemia. 94% of the patients in the transfused group and 74% of the control group survived the febrile episode. In patients with positive blood cultures all transfused patients survived as compared to only 57% in the control group (p=0.05). In patients with persistent bone marrow failure 92% of the transfused patients survived as compared to 73% in the control group. Granulocyte transfusions had no effect on the outcome of febrile episodes in patients with negative blood cultures or early recovery of marrow function. These data appear to support the contention that granulocyte transfusions are beneficial in patients with blood culture-proved sepsis with persistent neutropenia.

Adult↗
PubMed1978

Determinants of fecal and urinary iron excretion in desferrioxamine-treated rats.

Radioiron excretion in the urine and feces after continuous subcutaneous infusion of desferrioxamine (DF) was studied in normal and hypertransfused rats in whom reticuloendothelial and parenchymal iron stores had been labeled by selective 59Fe probes. The existence of two alternative pathways for the chelation of iron in vivo by DF was indicated by the results. The first pathway was intracellular chelation in hepatocytes with chelated iron excreted through the bile only. The second pathway, which was extracellular, could only be activated after saturation of the transferrin iron binding capacity, with the chelated iron excreted by the kidneys. The last mechanism was probably identical with the mode of action of diethylenetriaminepentaacetic acid (DTPA). Further studies will be required in order to establish whether the enhancement in iron chelation obtained by the continuous infusion of DF in patients with complete saturation of circulating transferrin may or may not be related to the extracellular mechanism of iron chelation in hypertransfused rats.

Animals↗
PubMed1978

Mechanism of iron chelation in the hypertransfused rat: definition of two alternative pathways of iron mobilization.

The mechanism of action of two recently identified iron-chelating drugs, RA and CHA, was compared with that of two well-known chelating agents, DF and DTPA, in hypertransfused rats labeled with selective parenchymal and RE cell radioiron probes. The existence of two alternative pathways for the in vivo chelation of iron has been indicated by the present findings. The first of these pathways involves the extracellular chelation of RE cell iron and its subsequent excretion in the urine. The second pathway is concerned with the intracellular binding of hepatic parenchymal cell iron and its subsequent excretion in the bile. Iron chelation by DTPA is restricted to the first pathway, whereas iron chelation by CHA is confined to the second pathway. DF and RA have a dual effect and are able to enhance the urinary excretion of RE cell iron as well as the biliary excretion of hepatic parenchymal iron. Hypertransfused rats are a simple and useful experimental model for the study of iron mobilization by chelating agents of potential clinical usefulness. However, further studies are required to show whether the pathways of iron chelation identified in rats may represent the mechanism of iron chelation in patients with transfusional iron overload.

Animals↗
PubMed1978

Surface morphology and ultrastructure of isolated hepatic Kupffer and endothelial cells.

Isolated non-parenchymal cells from the rat liver were separated by centrifugal elutriation into two fractions containing structurally intact Kupffer and endothelial cells with purities of over 90% in both fractions. These two cell types were then examined by transmission and scanning electron microscopy. It is concluded that Kupffer and endothelial cells are readily distinguished under the scanning electron microscope on the basis of their different surface features. Kupffer cells show ridges and ruffles while endothelial cells have microvilli and blebs and lack ruffles. As in earlier studies, transmission electron micrographs show that Kupffer cells are larger, have a smaller nucleus--cytoplasm ratio and contain lysosomes while endothelial cells are smaller, have a higher nucleus-cytoplasm ratio and show extensive sieve-plates and fenestrations.

Animals↗
PubMed1978

Surface features and ultrastructure of isolated Kupffer cells as seen by scanning and transmission electron microscopy.

The present report describes ultrastructural and surface features of hepatic Kupffer cells, with particular emphasis on the characteristics of these cells in suspension, as seen under the scanning electron microscopy (SEM), after their successful isolation by pronase digestion of liver tissue. Kupffer cells were readily recognized in sections of the liver examined by transmission electron microscopy, particularly after tagging by carbon, heat-damaged erythrocytes, and latex spheres. Their ultrastructural features in suspension and in liver sections were similar to those described for peritoneal macrophages. In the present study, a high yield of well-preserved Kupffer cells was obtained after selective enzymatic digestion of intact rat liver. Kupffer cells were readily distinguished from lymphocytes and hepatocytes on the basis of their surface architecture, and showed transverse ridge-like profiles and ruffled folds which became more prominent during phagocytosis. The sequence of events during the various stages of latex bead phagocytosis was well visualized with the SEM. Kupffer cells in suspension, during spreading and attachment to glass and during phagocytosis, resembled peritoneal macrophages isolated from rats, providing further evidence that these cell types are closely related.

Animals↗
PubMed1978

Iron chelation in thalassemia: mechanism of desferrioxamine action.

The mechanism of iron chelation was studied in 16 patients with homozygous beta-thalassemia. Following the i.v. infusion of desferrioxamine, chelated iron accumulated in the plasma and its maximal level at 2 h was closely correlated with the 24-h excretion of iron in the urine. The high specific activity of chelated urinary iron indicated that the chelatable pool was much smaller than the total storage iron pool and was probably derived from nonviable red blood cells in the reticuloendothelial system. This postulate was confirmed by the direct measurement of specific activities in the spleen and liver, revealing identical values of chelated urinary iron and of iron in reticuloendothelial tissues. These findings support the concept of an easily chelatable iron pool that is derived from the catabolism of hemoglobin.

Adolescent↗
PubMed1978

Serum ferritin in beta-thalassemia trait.

The diagnostic value of serum ferritin measurements in discriminating iron-deficiency anemia from thalassemia trait has been studied. In contrast to serum iron, percent transferrin saturation and total iron-binding capacity, where a high degree of overlap existed between the two groups, a clear-cut difference in serum ferritin levels was found between iron deficiency and thalassemia trait. The best separation of iron deficiency, thalassemia and normal controls was given by the combination of mean corpuscular volume and serum ferritin. Although definitive diagnosis of beta-thalassemia trait requires the demonstration of abnormal Hb A2 levels or beta-chain synthesis, serum ferritin is a useful screening test for the initial diagnosis of thalassemia trait. Because of the very small amounts of serum required for the measurement of ferritin, it is particularly suitable for surveying populations with a high prevalence of hypochromic-microcytic anemias.

Anemia, Hypochromic↗
PubMed1977

Renal salvage of haemoglobin iron.

Recycling of radioiron by renal tubular cells was studied in rats labelled by the i.v. injection of free 59Fe-Hb. Within 24 h, most of the renal radioactivity has been transferred from Hb to cellular ferritin and haemosiderin. Between day 1 and 14 of the study, urinary loss of radioactivity was less than 1% and most of the reduction in renal radioactivity represented transfer of renal iron into the circulation. An unexpected flexibility in the ability of rat kidney to recycle iron into the body has been found ranging from 13% in hypertransfused rats to 70% in bled animals. The high rate of renal iron transfer in bled animals was maintained under experimental conditions simulating chronic haemoglobinuria when most of the Hb removed by bleeding has been reinjected in the form of soluble Hb. Thus, epithelial cells in rat kidney as well as in the gut, appear to be able to transport iron with a much greater efficiency than in man, thereby contributing to the supply of iron for the rapid rates of growth and reproduction characteristic of this animal species.

Animals↗