Biomedical subjects
Publications and source records attributed to A Jacobs.
Eight cases of tenosynovitis of the foot and ankle are reviewed with special attention to the value of tenography as a diagnostic and prognostic tool. Stenosing tenosynovitis of the posterior tibial and peroneal tendons may be a cause of chronic pain and disability. Surgical treatment is often required and the tenogram can be an important adjunct in decision-making.
The anemia of malignancy is characterized by a reduced output of erythroid cells but with a normal red cell survival. In this study, clonal assays of normal human marrows in the presence of serum from 13 patients with bronchial cancer gave significantly reduced yields of erythroid colonies compared with control cultures with normal serum. More than half the cultures showed no growth of either CFU-E or BFU-E. Four sera producing marked depression of erythroid colony growth had no effect on CFU-GM. The evidence suggests the presence of a circulating inhibitor that may be found in either anemic or nonanemic patients.
It has been suggested that the iron storage protein ferritin has a number of physiological functions not directly related to iron metabolism and a number of these relate to lymphocyte and macrophage activity. The present study demonstrates a selective distribution of ferritin on lymphocyte and macrophage surface membranes which may be relevant to these hypotheses. Flow cytometry using specific antibodies shows 66% of human peripheral blood monocytes, 75% of B cells but only 6% of T cells to have significant amounts of surface ferritin. No difference was found between OKT4 and OKT8 subsets. Ferritin was also found on the surface of the pathological lymphocytes of B cell chronic lymphatic leukaemia (CLL) but not T cell CLL.
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Monocytes, lymphocytes and polymorphs were separated from the peripheral blood of normal human subjects. Ferritin concentrations were determined with antibodies to both human spleen and heart ferritins. The heart type ferritin concentration in monocytes was 38.4 +/- 21.6 fg/cell (mean +/- SD), in lymphocytes 8.6 +/- 6.6 fg/cell and in polymorphs 3.2 +/- 2.4 fg/cell. Spleen type ferritin concentrations (fg/cell) were 15.6 +/- 7.0 in monocytes, 6.6 +/- 5.7 in lymphocytes and 7.0 +/- 4.6 in polymorphs. The mean heart/spleen ferritin ratios were 2.8/1 for monocytes, 2.0/1 for lymphocytes and 0.6/1 for polymorphs. The cell extracts were also subjected to anion exchange chromatography. Heart type ferritin eluted at a higher chloride ion concentration than spleen type ferritin. Both H and L subunits were synthesized by mononuclear cells when incubated with 3H-leucine. Human leucocytes contain a wide range of isoferritins and ferritin concentrations may be considerably underestimated in conventional assays for serum ferritin which employ antibodies to liver or spleen ferritin.
Human spleen ferritin was labelled with 131I and injected into two normal men. The labelled ferritin left the plasma rapidly. The experimental clearance curve could be fitted with accuracy into two single exponential functions. The first component, T 1/2 = 9 min, accounted for the clearance of about 90% of the labelled ferritin. Surface counting showed uptake of 131I by the liver but not by the spleen. Such a rapid plasma turnover is similar to that found after injection of tissue ferritins into experimental animals but contrasts with the slow turnover previously found for 131I-labelled human plasma ferritin. Differential clearance of isoferritins from the plasma is an important factor explaining the biochemical and immunological differences between tissue and plasma ferritins.
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Globin synthesis ratios were measured on reticulocytes from nine patients with primary acquired sideroblastic anaemia (SA), four patients with hereditary or congenital SA, two patients with secondary acquired SA and three patients with iron deficiency (ID). Ten of the samples from patients with SA and all the samples from patients with ID had normal ratios. Samples from three patients had significantly abnormal ratios, one from a patient with SA and acquired Hb H disease (alpha/beta 0 X 26), one from a patient with secondary acquired SA (alpha/beta 0 X 88), and one from a patient who went on to develop acute myeloblastic leukaemia (alpha/beta 1 X 36). Globin synthesis was stimulated by 100 microM haem similarly in normal, SA and ID reticulocytes. Any limitation of globin synthesis in SA and ID is therefore not easily reversible by adding haem. Inhibition of haem synthesis in nonsideroblastic reticulocytes using 4 mM isonicotinic acid hydrazide for 1 h incubation affected neither total globin synthesis nor the alpha/beta ratio. These results contradict the view that decreased haem synthesis decreases globin chain synthesis and decreases the alpha/beta globin chain synthesis ratios in human reticulocytes. Previously reported findings that haem could reverse globin chain synthesis inhibition in SA were good evidence for a primary deficiency of haem synthesis in the erythroblasts of these patients. Our inability to substantiate these findings emphasizes the need for a re-evaluation of the aetiology of sideroblastic anaemia.
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Sequential lysis of human bone marrow cells with a monoclonal antibody directed against myeloid cells (TG1) and a rabbit antiserum raised against peripheral blood mononuclear cells gave preparations in which 78-97% of the nucleated cells were erythroid, with a 24-77% recovery. Viability was high, morphology was good and the cells were able to divide and differentiate in culture. No metabolic experiments were carried out but the ferritin content of the erythroblasts was measured in four experiments and found to be about 200-2000 times higher than that found in normal erythrocytes. The H/S ratio was high in both erythroblasts and erythrocytes. Fractionation on the basis of density of two erythroblast preparations, one from a patient with sideroblastic anaemia and one from a patient with megaloblastic anaemia, showed that the most immature erythroblasts contained the highest content of ferritin and that this fell with maturation. The H/S ratio stayed the same or fell with maturation. It was concluded that this method would be valuable for the study of the role of erythroblast ferritin in normal and pathological situations.
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A study was carried out to assess the effect of total body irradiation on pancreatic and parotid isoenzymes of amylase in patients about to undergo bone-marrow transplantation who had received high-dose cyclophosphamide. Twelve patients were studied, enzyme activity being measured before and at various times after total body irradiation. Serum total amylase activity rose rapidly within 12 hours of irradiation to a maximum at 36 hours, returning to normal by six days; most of the increase was derived from salivary damage, with a much smaller pancreatic component. These results confirm that radiation produces acute changes in amylase activity, which may be of use in assessing radiation-induced damage.
Equilibrium centrifugation of either peripheral blood mononuclear cells or of pure lymphocytes (obtained by carbonyl iron or glass bead adherence removal of monocytes) on a continuous density gradient of Percoll yielded lymphocyte fractions containing between 92 and 99% T lymphocytes as shown by sheep red blood cell rosetting. B lymphocytes with surface immunoglobulin were found in the regions of low density (1.03-1.065 g/ml) and T lymphocytes in the regions of higher density (1.06-1.08 g/ml). TM lymphocytes with their characteristic positive 'dot' pattern of staining for non-specific esterase were also found mainly in regions of high density. It was concluded that Percoll continuous equilibrium density gradient centrifugation can be used to obtain T lymphocytes in high yield, with high viability and without metabolic changes which may occur after contact with sheep red blood cells. The esterase staining suggested that there was also some separation of T lymphocyte subsets.
Twenty-four untreated patients with myelomatosis were studied in order to characterize their anaemia, using standard haematological and ferrokinetic techniques, together with measurements of circulating erythropoietin, erythropoietin sensitivity of marrow cultures and in vitro measurements of haem synthesis. There is a reduction in total erythroid output by the marrow, together with a minor degree of plasma expansion. In patients with normal renal function there is an appropriate increase in erythropoietin in response to anaemia, but in a few cases there may be reduced response of CFU-E to the hormone in vitro. No abnormality of iron status or haem synthesis was found. One case of folate deficiency was discovered.
1. The ferritin content of iron-overloaded tissues was higher than that of normal tissues. There was also an increased iron content of ferritin extracted from these tissues. 2. In the limited number of tissues that we examined haemosiderin deposition appeared to be greater in the iron-overloaded livers than in the iron-overloaded spleens. 3. Ferritins extracted from iron-overloaded liver, spleen and kidney had similar properties to those extracted from the corresponding normal tissues. 4. Ferritin from iron-overloaded heart had a greater proportion of more basic isoferritins than had ferritin from normal heart. 5. Immunoreactivity to heart and spleen ferritin antibodies, subunit composition, iron content and rate of iron uptake of both unfractionated ferritin and isoferritin fractions separated by ion exchange chromatography were related to the isoelectric point.
The uptake of iron by bone marrow erythroblasts and its intracellular distribution have been studied in 23 patients with primary sideroblastic anaemia (SA), five patients with secondary SA and one patient with only non-ringed sideroblasts. EM of erythroblasts from 18 cases showed both mitochondrial iron deposits and cytoplasmic ferritin aggregates in all cases except the patient with only non-ringed sideroblasts. Iron uptake by erythroblasts in whole bone marrow was normal but there was a decreased incorporation into haem and an increased incorporation into cell stroma. Age matching of erythroblasts using Percoll density gradient centrifugation indicated that stromal iron incorporation was high at all stages of erythroblast development even before haem synthesis had become a major metabolic activity and in intermediate and late erythroblasts a real decrease in haem synthesis appeared less certain. These observations, together with the inability to correct the abnormality in vitro with either pyridoxal phosphate or delta amino-laevulinic acid suggest that the primary defect in SA may be an abnormality of mitochondrial iron metabolism rather than an abnormality of haem synthesis.