Search PubMed⌕ Search

Biomedical subjects

R J Jacobson

Publications and source records attributed to R J Jacobson.

At least 55 records · Page 3Linked to original sources

Acute nonlymphocytic leukemia: expression in cells restricted to granulocytic and monocytic differentiation.

Two patients with acute nonlymphocytic leukemia who were heterozygous for the X-chromosome-linked enzyme glucose-6-phosphate dehydrogenase were studied to determine the number and type of cells in which the disease arises. Both type A and B isoenzymes were found in normal tissues, but the myeloblasts showed only one enzyme type, indicating that at the time of study, the disease had a clonal origin. The observation in one patient that erythroid cells did not arise from this clone contrasts with conclusions reached in patients previously studied with chromosomal markers. The results suggest that in this patient, the leukemic clone suppressed expression of normal granulopoiesis but did not inhibit erythroid differentiation from normal progenitors. They suggest also that the disease is heterogeneous. In some patients, the disease is expressed in cells with differentiation restricted to the granulocyte-macrophage pathway; in others, it involves stem cells that also differentiate into erythrocytes. This heterogeneity may reflect differences in causation and could have prognostic importance.

Acute Disease↗

Asbestos-associated neoplasms of B cell lineage.

Three different neoplasms of B cell lineage, chronic lymphocytic leukemia, immunoglobulin A (IgA) myeloma and immunoglobulin G (IgG) myeloma were detected in three patients who had heavy occupational exposure to asbestos dust. Two of the patients had coexistent pulmonary asbestosis, whereas the third patient had a pleural mesothelioma subsequent to his initial presentation with myeloma. Defective cell-mediated immunity and hyperactivity of B cell function have previously been noted in patients with asbestosis. We suggest the possibility that these asbestos-related immunologic derangements may predispose to the development of immunoproliferative and lymphoproliferative neoplasms, since such tumors have been observed in a variety of other settings, characterized by protracted hyperactivity of the immune system.

Aged↗

Childhood and adult acute leukaemia in Johannesburg blacks.

Thirty-four Black patients (14 children and 20 adults) suffering from acute leukaemia were assessed at the haematology clinics of Baragwanath Hospital and Johannesburg General Hospital during a recent 2-year period. It is evident that acute leukaemia in Blacks has become more prevalent in the Johannesburg area than it was 20 years ago, the increase being most striking in the younger age group. The incidence of acute myelocytic and lymphocytic leukaemia in Black children was the same. In adults acute myelocytic leukaemia predominated. The remission rate of 90% achieved in patients with acute lymphoblastic leukaemia was similar to the rates described in Europe and the USA. Results in patients with acute myelocytic leukaemia were less favourable (35% with initial complete remission). The problems of management (limited isolation facilities), complications related to prolonged hospitalization (loss of earnings, problems of visiting), and difficulties with follow-up examination are outlined. In underdeveloped and developing countries, training paramedical personnel to assist with the outpatient care of patients with neoplastic disease might alleviate some of these problems.

Acute Disease↗

Paracrystalline arrays of protein-synthesis elongation factor Tu. Comparison with polymerized actin.

Homogeneous protein synthesis elongation factor Tu from Escherichia coli forms aggregates at high concentrations of ammonium sulfate which have a filamentous appearance in the light microscope. Electron microscopy of negatively stained preparations shows that these aggregates are paracrystalline, including three different forms. On the basis of analyses by optical diffraction, this polymorphism can be explained in terms of three different tubular foldings of the same basic two-dimensional surface lattice. This can be compared with that underlying the structure of actin filaments, thus providing a crucial test of the putative relationship between the elongation factor and actin [Rosenbusch, J. P. et al. (1976) J. Supramol. Struct. 5, 391-396]. The differences between the surface lattices, in conjunction with the negative results of sensitive immunochemical tests for possible cross-reactivities between the two proteins, suggest that any such relationship is very remote.

Actins↗

Erythrocytosis in hepatocellular cancer.

A Black patient with hepatocellular cancer and an increased red cell mass (erythrocytosis) is described. Assay of the patient's serum in ex-hypoxic polycythaemic mice showed the presence of erythropoietic activity. To determine the incidence of erythrocytosis in Southern African Blacks with hepatocellular cancer, haemoglobin and haematocrit values in 117 such patients were reviewed. Four patients (3,4%) had haemoglobin levels above the upper limit of normal and 2 (1,7%) of the patients had raised haematocrit values. Fifty-eight per cent of the patients were anaemic when they were first seen.

Adult↗

Chronic myelocytic leukemia. Origin of some lymphocytes from leukemic stem cells.

In three patients with chronic myelocytic leukemia who were heterozygous at the X-linked glucose-6-phospháte dehydrogenase locus, lymphocytes were studied to determine if they had the same stem cell origin as the leukemic myeloid cells. Normal tissues such as skin had both B and A glucose-6-phosphate dehydrogenase isoenzymes, but the leukemic myelogenous cells displayed only one isoenzyme type, consistent with their clonal origin. A population of cells with undoubted thymus-derived (T)-lymphocyte characteristics had both isoenzymes. Presumably, then, these T cells did not arise from the leukemic stem cell, either because they antedated the development of leukemia in that stem cell or, more likely, because they arose from progenitors not involved by the disease. In contrast, another population of lymphocytes showed only one isoenzyme type, suggesting that it arose from the chronic myelocytic leukemia stem cell. However, although this population contained many cells with the characteristics of bone marrow-derived (B) lymphocytes, it is not certain that the single enzyme produced by the cells over all can be attributed to B lymphocytes rather than to contaminating non-B-lymphoid cells.

Adult↗

Waldenström's macroglobulinaemia in South African Negroes.

Waldenström's or primary macroglobulinaemia has rarely been documented in Black Africans. Six South African Negro patients with Waldenströms macroglobulinaemia were assessed and followed during a 10-year period from 1966 to 1976. The hyperviscosity syndrome was the presenting feature in four patients and one patient each presented with the nephrotic syndrome and a lacrimal mass respectively. On initial evaluation of the six patients, the serum IgM varied from 1.3 to 4.8 g% and in two patients cryoglobulinaemia was found. The patients received supportive treatment, chemotherapy, and when necessary, plasmaphoresis. One patient was lost to follow-up, one patient died 7 years after the onset of his illness, but the remaining four patients are alive 18 months to 5 years after presenting with their disease. Although the disease occurred in a younger age group (mean age 43 years) than in Caucasians it did not differ in clinical features or response to treatment from other parts of the world.

Adult↗

Probable clonal origin of acute myeloblastic leukemia following radiation and chemotherapy of colon cancer.

A 64-yr-old female developed acute myeloblastic leukemia following radiation and drug therapy for colon carcinoma. The patient was heterozygous for glucose-6-phosphate dehydrogenase (G-6-PD) and displayed types A and B isoenzymes in nonhematopoietic tissue. In contrast, only type B G-6-PD was observed in peripheral blood white cells. In addition, a karyotypic abnormality was found in peripheral blood and marrow cells but not in skin fibroblasts. The data are consistent with a clonal origin of this leukemia.

Chromosomes↗

Agnogenic myeloid metaplasia: a clonal proliferation of hematopoietic stem cells with secondary myelofibrosis.

The glucose-6-phosphate dehydrogenase (G-6-PD) types and chromosomes of hematopoietic and other tissues were determined in a woman with agnogenic myeloid metaplasia. The patient was heterozygous at the X-linked G-6-PD locus so that both B and A isoenzymes were found in nonhematopoietic cells. In contrast, only one G-6-PD type was found in granulocytes, red cells, and platelets. She also had a distinctive chromosome abnormality in blood cells but not in other tissues. These results indicate that agnogenic myeloid metaplasia is a disorder of a pluripotent stem cell and provide strong evidence that it is of clonal origin. In contrast to blood cells, the patient's cultured marrow "fibroblasts" had normal chromosomes and both B and A G-6-PD types, suggesting that the marrow fibrosis is a secondary abnormality. Thus, at least in this case of agnogenic myeloid metaplasia, the hematopoietic cell proliferation appears to be clonal, and, by inference, possibly neoplastic, whereas the marrow fibrosis is probably not clonal, and therefore appears to be secondary.

Aged↗

Partial exchange transfusion as treatment for hemoglobin SC disease in pregnancy.

Serious infarctions and embolic events can complicate the course of pregnant patients with hemoglobin SC disease. In two cases, partial exchange transfusion preceded recovery in severely ill pregnant women with hemoglobin SC disease. There seem to be pathophysiological correlations for the observed clinical findings, and there are potential beneficial effects of partial exchange transfusion. Based on our experience, partial exchange transfusion should be considered as a means of reversing the often fatal complications attending hemoglobin SC disease and pregnancy. The exchange should be of sufficient volume to ensure a postexchange level of hemoglobin A of at least 30%.

Adult↗

Leukaemic involvement of the pleura. A case report.

In chronic myelocytic leukaemia (CML), the pleura is a most uncommon site of extramedullary involvement. A 34-year-old man with CML presented with a massive pleural effusion. His peripheral blood contained few blast cells and the leucocyte alkaline phosphatase level was low. Cytological examination of the pleural fluid revealed cells with the morphological features of myeloblasts and monoblasts. The patient was treated with systemic chemotherapy, with no effect on the leukaemic pleural effusion.

Adult↗

Chronic myelocytic leukemia: clonal origin in a stem cell common to the granulocyte, erythrocyte, platelet and monocyte/macrophage.

Glucose-6-phosphate dehydrogenase (G-6-PD) isoenzymes types of granulocytes were determined in eight women with chronic myelocytic leukemia (CML). The patients were heterozygous at the X-linked G-6-PD locus for the common gene, GdB, and a variant, such as GdA, so that both B and A enzyme types were found in skin cells. In contrast to these normal cells, only one G-6-PD type was found in CML granulocytes. The fact that such single-enzyme phenotypes are found in CML granulocytes, but not in nonleukemic granulocytes, provides strong evidence that the disease has a clonal origin. Single-enzyme phenotypes were also found in erythrocytes, platelets and cultured blood macrophages indicating that these cells have a common stem cell which is the site of the abnormality in CML. In the one studied patient, no evidence was found for involvement of cultured marrow fibroblasts. Clonal origin of CML virtually excludes cell recruitment as a sole pathogenetic mechanism. Either the leukemia arises as a consequence of a rare initial event in a single cell, or a series of events occurs in a clone such that it evolves into CML, or both.

Adolescent↗

Angio-immunoblastic lymphadenopathy. A report of 3 cases.

Angio-immunoblastic lymphadenopathy (AILD) was diagnosed in 3 Black patients, AILD is a non-malignant disorder which resembles a malignant lymphoma clinically and morphologically. It is thought to represent an abnormal response of B lymphocytes to antigenic stimuli which are often therapeutic agents. The disorder usually affects adults of the older age group and the clinical course can be rapidly fatal, particularly if vigorous chemotherapy is given. Of the 3 patients with AILD, 2 died from complicating infections within 6 months after the initial diagnosis. The third patient was completely cured after short courses of prednisone and vincristine. It appears that in some patients the disorder may be completely reversible but whether these patients are at a greater risk of eventually developing a lymphoma is uncertain at the present time, and remains to be ascertained by their long-term follow-up.

Adult↗

Choriocarcinoma presenting as Jacksonian epilepsy.

Cerebral deposits of choriocarcinoma tend to be multiple and usually result in a rapidly fatal course. Two patients presented with Jacksonian epilepsy due to metastatic choriocarcinoma in the brain. In the first patient, the diagnosis of metastatic choriocarcinoma was unsuspected, since curetted uterine material was normal, the haemagglutination inhibition test for pregnancy was negative and a chest radiograph was unremarkable. A diagnosis of choriocarcinoma was made by brain biopsy 2 days before death. The second patient had been previously treated with systemic chemotherapy (methotrexate and actinomycin D) for uterine and pulmonary choriocarcinoma associated with hyperthyroidism. Human chorionic gonadotrophin could not be detected in the urine when the patient presented with Jacksonian epilepsy. A brain scan showed multiple areas of increased uptake consistent with metastatic choriocarcinoma. She was treated with both systemic chemotherapy and intrathecal methotrexate and cranial irradiation. A complete remission was obtained. Intrathecal methotrexate and cranial irradiation appear to offer a hopeful new approach to the problem of metastatic cerebral choriocarcinoma.

Adult↗

Choriocarcinoma as a cause of thyrotoxicosis.

Three patients with choriocarcinoma had clinical and biochemical evidence of hyperthyroidism. Diminution in the thyrotoxicosis closely paralleled the fall in human chorionic gonadotrophin (hCG) levels. Three patients originally presented to internal medicine units as a problem of hemoptysis. Thyroid-stimulating hormone bioassay activity was demonstrated in the serum of all three patients prior to therapy. Recently evidence has been presented that hCG has intrinsic thyrotropic activity and that in conditions, such as hydatidiform mole, in which serum hCG levels are grossly elevated this thyrotropic activity can be sufficient to produce hyperthyroidism. Two of our cases supported the concept that hCG was also the substance with thyroid-stimulating activity in patients with choriocarcinoma. The third case left open the possibility that, in addition to the thyroid-stimulating activity of hCG, there may also be the production of a true ectopic thyroid-stimulating hormone (TSH). It is considered that the development of biochemical and clinical thyrotoxicosis in patients with choriocarcinoma depends upon the duration of the choriocarcinoma and the level of hCG.

Adult↗