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Biomedical subjects

C Hershko

Publications and source records attributed to C Hershko.

At least 145 records · Page 8Linked to original sources
PubMed1982

In vitro bioassay of erythropoietin using synchronized rabbit erythroid precursors.

Synchronized erythroid precursors obtained from the bone marrow of rabbits and plated in methyl-cellulose were used as a bioassay for the measurement of erythropoietin (Ep). Rabbits were given five daily injections of phenylhydrazine followed by a single dose of actinomycin-D. This treatment resulted in a rapid repopulation of bone marrow by synchronized erythroid precursors which can be stored at -180 degrees C for long periods. Grown in vitro for 2 days in the presence of added Ep these cells divided to form colonies (CFUE). The erythroid nature of these colonies was confirmed by 59Fe incorporation into heme. Preliminary studies indicate that this system is suitable for the measurement of Ep in human sera. It is simple, inexpensive, reproducible, and permits measurements at the physiologic range of Ep concentrations.

Animals↗
PubMed1982

Evaluation of iron-chelating agents in an in vivo system: potential usefulness of EHPG, a powerful iron-chelating drug.

Fifteen compounds with a high affinity to ferric iron have been screened for in vivo iron-chelating efficiency in a rat model. One of the most potent of these drugs was ethylenediamine-N,N'-bis(o-hydroxyphenylglycine) (EHPG). EHPG-induced iron excretion was up to 8 times higher than iron excretion induced by identical doses of desferrioxamine (DF). Studies employing selective radio-iron probes of reticuloendothelial and parenchymal iron stores showed that although EHPG is able to interact with both storage iron compartments, its effect on parenchymal iron is much more pronounced. Unlike DF which has two alternative routes of excretion, EHPG-induced iron excretion is restricted mainly to the gut. Although EHPG seems to be superior to DF in both its chelating efficiency and preferential interaction with hepatic parenchymal iron stores, information on its in vivo toxicity is at present insufficient and it cannot yet be recommended for clinical use.

Animals↗
PubMed1981

Effect of iron deficiency on transplantable murine plasmacytoma.

The effect of iron deficiency on tumour growth and on host survival was studied in BALB/c mice with transplanted Merwin Plasma Cell-II tumors. Iron deficiency was induced by maintaining the animals on an iron-free diet consisting of milk-cornflour supplemented with CuCl2 and vitamins A and D. Iron deficiency resulted in retardation of both body and tumor growth in weanling BALB/c mice. Their survival, however, was not significantly different from that of iron supplemented controls. The inhibitory effect of iron deficiency on host and tumour growth could not be reproduced in adult BALB/c mice. The survival of tumor-bearing hosts maintained on a milk-cornflour diet (whether supplemented with iron or not) was significantly longer than that of animals maintained on a purina diet.

Animals↗
PubMed1981

Diagnosis of iron deficiency anemia in a rural population of children. Relative usefulness of serum ferritin, red cell protoporphyrin, red cell indices, and transferrin saturation determinations.

The diagnostic usefulness in iron deficiency anemia of serum ferritin, red cell protoporphyrin (Epp), mean corpuscular volume, mean corpuscular hemoglobin (MCH), and transferrin saturation measurements has been studied in a population of 294 children aged 1 to 6 yr. Of the children studied 19% had hemoglobin below 11 g/dl. Iron deficiency, diagnosed by at least two abnormal independent laboratory parameters, was the cause of anemia in all except two cases. The Pearson correlation coefficient for hemoglobin was highest with MCH, followed in decreasing order of magnitude by MCV, Epp, transferrin saturation, and finally by ferritin. Sensitivity and specificity were highest for MCH and lowest for ferritin. Of anemic, iron deficient individuals 97 to 100% could be identified by low MCH, 88 to 100% by transferrin saturation, 66 to 83% by ferritin, and 61 to 74% by Epp. In contrast, only 0 to 6% of normal, nonanemic individuals had low MCH, 0 to 4% had high Epp, but 21 to 39% had low transferrin saturation and 25 to 39% had low ferritin. Although reduced serum ferritin in anemic individuals is good evidence of iron deficiency, a significant proportion of anemic iron-deficient patients is missed by this procedure rendering it less useful than other, less expensive laboratory methods.

Age Factors↗
PubMed1981

Ferritin synthesis in inflammation. II. Mechanism of increased ferritin synthesis.

The mechanism of increased ferritin synthesis in inflammation was studied in rat livers 0-48 h after turpentine injection. A subcellular protein synthesizing system was employed in which the respective roles of cell sap factors and polysomes from normal and treated animals could be studied. Two waves of increased ferritin synthesis were found, an early wave with peak activity at 6 h of inflammation, and a second wave starting at about 24 h. The early wave of enhanced ferritin synthesis was associated with increased activity of cell sap factors. In contrast, the late enhancement of ferritin synthesis was characterized by increased polysomal activity as well as increased cell sap activity. These observations suggest a post-transcriptional control mechanism for the early phase of enhanced ferritin synthesis in inflammation, and a transcriptional as well as post-transcriptional control for the late phase of enhanced ferritin synthesis.

Albumins↗
PubMed1981

Mechanism of in vivo iron chelation by pyridoxal isonicotinoyl hydrazone and other imino derivatives of pyridoxal.

The source of iron chelated in vivo by the new iron-chelating agent PIH and its mechanism of excretion have been studied in normal and hypertransfused rats. PIH is able to chelate iron from both parenchymal and RE iron stores. Unlike DF, which promotes both urinary and fecal iron excretion, in this model PIH-induced iron excretion is limited almost entirely to the gut. Response to PIH is directly related to dosage, and oral doses ranging from 125 to 500 mg/kg/day are well tolerated. Six additional imino derivatives of pyridoxal have been studied, but none of these new compounds was as effective as PIH. Our study indicates that oral PIH is comparable in efficiency with parenteral DF and is of potential usefulness in the management of iron overload.

Animals↗
PubMed1981

Veno-occlusive disease and primary hepatic vein thrombosis in Israeli Arabs.

In a survey of nine major Israeli hospitals, 29 patients diagnosed between 1955 and 1975 as suffering from hepatic vein thrombosis were identified. Fifteen of the patients were Jews and 14 were Arabs. In contrast to the Jewish patients, all of whom were adults, the majority of the Arab patients were children below 10 years of age. Primary hepatic vein occlusion was 2.4 times more common among Arab than among Jewish patients. Of the 11 Arab patients with primary hepatic vein occlusion, three had histological changes typical of veno-occlusive disease; whereas in five others, thrombotic occlusion of large hepatic veins or of the vena cava was documented. Although no plant alkaloids could be directly implicated in any of the Arab patients, circumstantial evidence strongly supports such an etiology. All of our Arab patients originated from small agricultural communities where ancient methods of winnowing, which expose the home-ground wheat to a high risk of contamination by grains containing pyrrolizidine alkaloids, are still in use. This report confirms the world-wide distribution of veno-occlusive disease, and under-lines the need for a systematic search for possible sources of poisoning by pyrrolizidine alkaloids.

Adolescent↗
PubMed1980

Serum ferritin in hematologic malignancies.

Serum ferritin was measured in a variety of hematologic malignancies at presentation, in remission following therapy, and in relapse. Ferritin was strikingly increased in all acute leukemias at presentation and in relapse, in the blastic crisis of CML, and in smouldering leukemia. Remission in both ALL and ANLL was associated with a reduction of serum ferritin, and this normalization was a function of remission duration. In the malignant lymphomas serum ferritin was related to tumor histology. Highest levels were found in Hodgkin disease and histiocytic lymphoma, normal levels in lymphocytic lymphoma, and intermediate levels in mixed histiocytic-lymphocytic lymphoma. In all cases, remission was associated with normalization of serum ferritin. These correlations suggest that serum ferritin measurements may be of clinical usefulness in the initial evaluation and in the assessment of response to therapy in patients with acute leukemia and malignant lymphoma.

Acute Disease↗
PubMed1980

ABH antigens and bone marrow transplantation.

We studied the role of ABH antigens in determining graft outcome in 104 patients who received HLA-identical bone marrow transplants for aplastic anaemia and acute leukaemia. ABH compatibility had no significant effect on incidence of graft rejection or graft-versus-host disease. Fifteen recipients ahd pre-transplant antibodies against donor ABH antigens. In 14, large volume plasma exchange and transfusion of donor-type erythrocytes was successful in reducing the antibody titre to low or undetectable levels. In one patient, plasma exchange was unsuccessful and red cells were removed from the marrow inoculum by unit gravity sedimentation. This approach prevented transfusion reaction, and permitted engraftment of all haematopoietic cell lines despite persistently elevated antibody titres. Parallel in vitro studies revealed that antibodies to ABH antigens failed to inhibit the growth of progenitor cells committed to both granulocyte-macrophage (CFU-C) and erythroid (BFU-E) development. These findings indicate that ABH-antigens are not clinically important transplantation antigens and suggest that ABH antigens are not operationally present on hematopoietic stem cells.

ABO Blood-Group System↗
PubMed1980

Anemia among Druze children in the Golan Heights.

The prevalence and causes of anemia were studied in 294 Druze children aged 10 months to six years. The hemoglobin level was less than 11.0 g/dl in 19%; none of these anemic children had folate deficiency. Iron deficiency, diagnosed on the basis of abnormal values for at least two independent laboratory parameters, was the cause of anemia in all but two cases. The Pearson correlation coefficient for hemoglobin was highest with mean corpuscular volume, erythrocyte protoporphyrin, serum iron, transferrin saturation, total-iron-binding capacity, and serum ferritin. Mean corpuscular hemoglobin and transferrin saturation were abnormal in greater than 90% of anemic children, whereas serum ferritin and total-iron-binding capacity were abnormal in only 70%. In view of its limited sensitivity, serum ferritin appears to be a less useful diagnostic aid in iron-deficiency anemia than other, less expensive laboratory methods.

Anemia, Hypochromic↗
PubMed1979

Cure of aplastic anaemia in paroxysmal nocturnal haemoglobinuria by marrow transfusion from identical twin: Failure of peripheral-leucocyte transfusion to correct marrow aplasia.

The ability of syngeneic peripheral leucocytes to cure marrow aplasia was tested in a patient with paroxysmal nocturnal haemoglobinuria (P.N.H.). Transfusion of 7.1X10(10) white cells obtained by leucopheresis from an identical-twin donor, providing 3.4X10(4) myeloid progenitors (C.F.U.-C)/kg, failed to improve marrow function within two months. In contrast, transfusion of 1.3X10(10) nucleated bone-marrow cells, representing 6.4X10(4) C.F.U.-C/kg, from the same donor resulted in prompt bone-marrow recovery. These observations support the hypothesis that aplastic anaemia in P.N.H. is a stem-cell defect that may be corrected by the simple infusion of relatively small numbers of normal bone-marrow cells. They also seem to indicate a distinct advantage of marrow cells over peripheral-blood mononuclear cells in their ability to correct marrow aplasia.

Adult↗
PubMed1979

Systemic leishmaniasis mimicking malignant histiocytosis.

A 22-year-old man with fever, hepato-splenomegaly and severe pancytopenia is described in whom the histologic features of the spleen, liver and lymph nodes were consistent with malignant histiocytosis. Characteristic Leishman-Donovan bodies were demonstrated on a bone marrow aspirate, and the diagnosis of visceral leishmaniasis was confirmed by culturing the flagellated forms of the pathogen, and by an excellent response to sodium stibogluconate. In view of the similarity in clinical and histologic appearance, visceral leishmaniasis must be considered in the differential diagnosis of malignant histiocytosis in geographic areas where leishmaniasis is still endemic.

Adult↗
PubMed1979

Serum ferritin in an elderly population.

Serum ferritin was assayed by an immunoradiometric method in 82 people above 60 years of age. For comparison purposes, the same assay was performed in 71 younger normal adults. The serum ferritin distribution in the elderly had a larger variance than in the younger adults and in addition, there was a clear shift to higher values in the elderly. The latter was more notable in females than in males but there was still a statistically lower mean in elderly females than in elderly males. Ten out of 55 elderly subjects with evidence of iron deficiency (response to oral iron therapy) had a normal or high serum ferritin which suggests that variables unrelated to iron status may operate in determining serum ferritin levels in the elderly. The shift to higher values appears to occur upon reaching grossly 70 years of age. Whether the shift is a physiologically normal event is at present an open question.

Aged↗