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Biomedical subjects

R J Jacobson

Publications and source records attributed to R J Jacobson.

At least 37 records · Page 2Linked to original sources
PubMed1985

Heterogeneity of B cell involvement in acute nonlymphocytic leukemia.

In order to study the pattern of B cell involvement in acute nonlymphocytic leukemia (ANLL), multiple B lymphoid cell lines were established by Epstein-Barr virus transformation of peripheral blood mononuclear cells from two patients with the disease who were heterozygous for the X chromosome-linked glucose-6-phosphate dehydrogenase (G6PD). In one patient, the progenitor cells involved by the leukemia exhibited multipotent differentiative expression, whereas in the other patient the cells showed differentiative expression restricted to the granulocytic pathway. In the patient whose abnormal clone showed multipotent expression, the ratio of B-A G6PD in B lymphoid cell lines was skewed in the direction of type B (the enzyme characteristic of the leukemia clone) and significantly different from the 1:1 ratio expected. It is, therefore, likely that the neoplastic event occurred in a stem cell common to the lymphoid series as well as to the myeloid series. In contrast, evidence for B cell involvement was not detected in the patient whose ANLL progenitor cells exhibited restricted differentiative expression. These findings underscore the heterogeneity of ANLL. Clinically and morphologically similar malignancies in these two patients originated in progenitors with different patterns of stem cell differentiative expression. This difference may reflect differences in cause and pathogenesis.

Acute Disease↗
PubMed1985

Hydroxyurea interferes negatively with triglyceride measurement by a glycerol oxidase method.

Measured triglyceride concentrations were extremely low (less than 100 mg/L) in the serum of some patients who were receiving hydroxyurea for myeloproliferative diseases. The assay being used to quantify triglycerides was a "cascaded" enzymatic method involving (a) lipase, to generate glycerol from triglycerides; (b) glycerol oxidase, to convert glycerol to glyceraldehyde, with generation of hydrogen peroxide; and (c) peroxidase, which acts on the hydrogen peroxide with subsequent coupled generation of a red-violet quinone (reagent system used in the Technicon RA-1000). Hydroxyurea added to serum samples appeared to inhibit the action of glycerol oxidase, with a stoichiometric relation to the concentration of substrate (a decrease of roughly 2.4 mmol/L in measured triglyceride per 1 mmol of hydroxyurea per liter). A different enzymatic assay for triglycerides, which involves glycerol kinase (Beckman Instruments) did not show this effect of hydroxyurea.

Autoanalysis↗
PubMed1983

Lymphoid and plasma cell malignancies: asbestos-related disorders of long latency.

We have identified 13 asbestos workers with lymphoplasmacytic neoplasms: six with chronic lymphocytic leukemia, four with IgG myeloma, two with IgA myeloma, and one with histiocytic lymphoma. The subjects' occupations were varied, but all had experienced protracted asbestos exposure (ranging from 3-37 years). Tumor latency periods were similar to other known asbestos-related malignancies and ranged from 16-41 years. Stigmata of asbestos-related pulmonary disease were evident in 12 subjects. Malignant pleural mesotheliomas co-existed with IgG myelomas in two individuals, an association which seems unlikely to be fortuitous. It has been speculated previously that asbestos may be a lymphoid system carcinogen. Our findings strongly support this view and indicate that patients presenting de novo with lymphoproliferative neoplasms should be investigated for previous occupational or environmental exposure to asbestos.

Aged↗
PubMed1981

Hodgkin's disease in South African children.

Thirty South African children with Hodgkin's disease were studied over a 7-year period (1970 - 1977). Males outnumbered females by 5:1. The most frequent histological pattern encountered was mixed cellularity (72%). Fourteen patients with stage I, II or IIIA disease were treated with radiation therapy alone, and all achieved a complete remission with a median duration of remission in excess of 48 months. Sixteen patients with stage III or IV disease received combination chemotherapy (MOPP regimen), and 13 achieved a complete remission with a median duration of remission in excess of 48 months. The overall median survival was in excess of 60 months. Seven patients died during the study period, 4 of Hodgkin's disease and 3 of other causes. There was no significant difference in treatment response or survival between Black and White children.

Adolescent↗
PubMed1981

Pernicious anemia in blacks. A study of 64 patients from Washington, D. C., and Johannesburg, South Africa.

In a collaborative study from Washington, D. C., and Johannesburg, South Africa, the clinical, laboratory, and immunologic features of 64 black patients (25 male, 39 female) who had pernicious anemia were studied. Mean age at diagnosis was 53 +/- 20 years (mean +/- SD); 29.6% of the patients were under 40 years of age, and 14% were 30 years of age or younger. This suggests that there may be an earlier age of onset of pernicious anemia amongst blacks than the reported age incidence in whites. Serum anti-intrinsic factor blocking antibodies were found in 25 of 37 patients tested (67.5%). There was a significantly higher incidence of the antibody in women (85%) than in men (50%) (P < 0.01).

Adolescent↗
PubMed1981

Functional and morphological studies of platelet reactivity with vessel wall subendothelium in chronic myeloproliferative disease.

Mechanisms of thrombus formation in myeloproliferative disease were studied using a technique which visualized platelet-vessel wall interactions under physiological conditions of blood flow. Whole blood from four patients with chronic myelogenous leukaemia and three with thrombocythaemia were pumped through perfusion chambers containing de-endothelialized artery segments. Platelet reactivity with vessel walls (thrombus formation) was measured in sections of vessels by light microscopy and quantitative morphometric analysis. Five patients produced platelet reactivity values of 130--258% of controls while two gave decreased values. The two highest platelet reactivity values occurred in samples with elevated platelet counts and normal haematocrits. In contrast, when anti-platelet drugs were administered to three patients with high platelet counts, reactivity values decreased to 11--34% of controls. Clinical correlations revealed that patients with highest platelet reactivity values (165--258%) were those subjects who also exhibited thrombotic or haemorrhagic complications. Thus absolute platelet count and haematocrit may be major determinants in predicting these complications. Qualitative evaluations of thrombus formations by light and electron microscopy provide further evidence that platelets in myeloproliferative disease also possess qualitative abnormalities.

Adult↗
PubMed1981

Evidence for a multistep pathogenesis of chronic myelogenous leukemia.

To study the relationship of the Philadelphia chromosome (Ph1) to the pathogenesis of chronic myelogenous leukemia, multiple B-lymphoid cell lines were established from a patient with Ph1-positive leukemia who was heterozygous for the X-chromosome-linked enzyme glucose-6-phosphate dehydrogenase. Both A and B types of enzyme were found in a 1:1 proportion in normal tissues, but 45 of 63 (71%) Ph1-negative B-lymphoid cells lines derived from this patient showed only the single glucose-6-phosphate dehydrogenase (type B) found in the Ph1-positive leukemic clone. Furthermore, 8 of 33 analyzable lines with B-type enzyme had chromosomal aberrations compared to 0 of 14 lines with A-type glucose-6-phosphate dehydrogenase. These results provide evidence for the suggestion that some cells of the abnormal clone do not express the Ph1 abnormality. Thus, acquisition of Ph1 may not be a sufficient cause for the disease. It is possible that at least two steps are involved in the pathogenesis of Ph1-positive chronic myelogenous leukemia, one causing abnormal proliferation of a clone of pluripotent hematopoietic stem cells and the other inducing Ph1 in descendants of these progenitors.

B-Lymphocytes↗
PubMed1981

Evidence that essential thrombocythemia is a clonal disorder with origin in a multipotent stem cell.

Essential thrombocythemia is characterized by proliferation of hematopoietic tissue predominantly involving megakaryocytes and resulting in marked thrombocytosis. The disorder has some clinical and laboratory features that resemble those seen in the clonal multipotent stem cell disorders chronic myelogenous leukemia, polycythemia vera, and agnogenic myeloid metaplasia. It has been argued that essential thrombocythemia should be classified together with those disorders as a myeloproliferative syndrome. However, without knowledge of the numbers and types of cells that are involved in essential thrombocythemia, this suggestion remains speculative. Three patients with thrombocytosis were studied. The diagnosis of essential thrombocythemia was considered to be firm in two patients and probable in the third one. The X-linked glucose-6-phosphate dehydrogenase locus was used as a cell marker. Whereas both A and B types of glucose-6-phosphate dehydrogenase were found in nonhematopoietic tissues, only a single-enzyme type was found in the granulocytes, red cells, and platelets from each patient. These data indicate that the disorders in these three patients are clonal and involve multipotent stem cells.

Adult↗
PubMed1980

Involvement of the B-lymphoid system in chronic myelogenous leukaemia.

Studies with glucose-6-phosphate dehydrogenase (G6PD) isoenzymes have demonstrated that chronic myelogenous leukaemia (CML) is a clonal disorder of pluripotent haematopoietic stem cells which are capable of differentiation to myeloid cells, monocytes, erthrocytes and platelets. It has been observed recently in G6PD heterozygous patients with chronic phase CML that the non-E-rosetting lymphocytes were restricted to a single enzyme type, indicating that some lymphoid cells must also arise from the leukaemic clone. Surface or cytoplasmic immunoglobulin could be detected in up to 46% of the cells of these isolated non-T-lymphocyte populations, which suggested that cells from the CML clone were capable of differentiating into B lymphocytes. To investigate this further, we established Epstein-Barr virus (EBV)-transformed B-lymphoblastoid cell lines derived from patients with CML and studied chromosomes and G6PD to determine whether progenitor B lymphocytes for any of the cell lines had originated from the CML clone. We report here direct evidence that immunoglobulin-synthesizing B lymphocytes can arise from the CML stem cell clone.

B-Lymphocytes↗
PubMed1980

Malignant histiocytosis simulating granulomatous disease.

In its clinical presentation, malignant histiocytosis may mimic infections or hematologic neoplasms, and pathologically it may be mistaken for Hodgkin's disease, histiocytic lymphoma, or viral lymphadenitis. The case histories of three patients in whom malignant histiocytosis clinically and pathologically simulated granulomatous diseases are reported. Erythrophagocytosis was not present in the initial bone marrow aspirates from two of the patients. One patient was considered to hve sarcoidosis or Wegener's granulomatosis; the second patient, Weber-Christian disease, and the third patient, a granulomatous disease of infectious origin. Granulomas have been found in tissues of patients who have Hodgkin's disease, but have been found only rarely in association with malignant histocytosis. An explanation for the presence of granulomas in association with malignant histiocytosis is offered: they may represent a phase in the evolution of the disease.

Adolescent↗
PubMed1980

Immunocytoma in black and white South Africans.

The clinical and immunochemical presentations of immunocytomata in black and white South African patients are described. Age distribution in white patients is similar to previously published series. However, black patients with multiple myelomatosis and Waldenstrom's macroglobulinaemia on average presented clinically ten and twenty years respectively earlier than white patients. No significnat differences in the various immunochemical classes of multiple myelomatosis was shown despite greater serum immunoglobulin concentrations (especially IgA) in the black population. Age adjusted incidence rates for multiple myelomatosis in South African blacks were as high as those in the United States and Jamaica. This finding contrasts with low rates previously reported in Africa. Furthermore, age adjusted incidence rates for multiple myelomatosis in South African whites were higher than those in whites reported in the United States. There was a higher incidence in blacks of fractures of the thoracolumbar spine with collapse and consequent paraplegia and urinary tract infection. While there was a greater frequency of solitary myeloma in black patients, cases of benign paraproteinaemia were seen only in white patients.

Adult↗
PubMed1980

Philadelphia chromosome (Ph1)-negative chronic myelogenous leukemia (CML): a clonal disease with origin in a multipotent stem cell.

It has been shown with glucose 6-phosphate dehydrogenase (G-6-PD) mosaicism that Ph1-positive chronic myelogenous leukemia (CML) is a clonal disease that involves multipotent hematopoietic stem cells. We now report G-6-PD studies of a 79-yr-old woman with Ph1-negative CML. Equal amounts of B and A-type activities were found in nonhematopoietic tissues, indicating that the patient was heterozygous for G-6-PD. In contrast, only A-type G-6-PD was found in marrow cells, blood erythrocytes, leukocytes, and platelets and in granulocyte-monocyte and eosinophil colonies grown from blood mononuclear cells. Unlike most cases of PH1-positive CML, colony growth in this patient increased during blastic transformation and the colonies contained only immature monocytic cells. The data indicate that in this patient, Ph1-negative CML is similar to the Ph1-positive form of the disease in involvement of multipotent stem cells and probable clonal origin, but the two disorders differ in the rapidity with which they enter blastic transformation and in the pattern of granulocyte-monocyte colony growth at that time.

Aged↗