Biomedical subjects
Publications and source records attributed to J F Prchal.
A semisolid culture system for B-cell colony formation is described. The system includes pretreatment of B-cells by neuraminidase-galactose oxidase and help of mitomycin-treated T-cells. With this assay system, colony-forming B-cell precursors were detected in all eight patients we studied with B-cell chronic lymphocytic leukemia. These patients' own T-cell helper effect was less than that of normal T-cells.
Thirty-four patients with a probable clinical diagnosis of dysmyelopoietic syndrome (DMPS) were studied to assess the in vitro growth pattern of their hemopoietic progenitors, i.e. burst-forming unit erythroid (BFU-E) and colony-forming unit myeloid (CFU-C) progenitor cells. Twenty-one patients had DMPS confirmed by final diagnosis and were classified according to the French-American-British (FAB) recommendations. Our results indicate that the normal colony growth of hemopoietic progenitors in vitro excludes DMPS and other preleukemic conditions. In addition, within the DMPS group a low number of CFU-C (11 colonies or fewer) was a highly significant indicator for the development of acute leukemia. Analysis of the limited number of cytogenetic results in the DMPS patients did not reach statistical significance in relation to the development of acute leukemia.
This study concerns the distribution of T-cell subsets as determined by specific monoclonal antibodies in 50 individuals with complex partial seizures (31) and primary generalized tonic-clonic seizures (19), and in 30 healthy controls. The epileptic group had significantly fewer circulating T4 "helper" lymphocytes and significantly greater number of T8 "suppressor" lymphocytes than the controls. The T4/T8 ratio was consistently significantly lower in the epileptic group. There was no relation between lymphocyte subsets or T4/T8 ratio and antiepileptic medication. The results suggest a derangement of cell-mediated immunity in individuals with epilepsy.
Two families with polycythemia inherited as an autosomal dominant trait are described. Serial hemoglobin determinations in multiple family members and RBC volume measurements in selected affected subjects documented their polycythemia. Measurements of arterial p02s, p50s, and blood oxygen affinity were normal in all affected individuals from each family who were tested. Erythropoietin (EPO) levels were low in affected individuals from family 1 and normal in affected members of family 2. Stimulation of in vitro CFU-E colony growth by low levels of EPO was significantly increased in subjects from family 1, but normal in those affected from family 2. We conclude that although the inheritance pattern for the polycythemia in both of these families appeared to be the same, the biologic defect leading to the disorder in each of these unique families was different. The precise mechanism of the increased EPO sensitivity noted in affected subjects from family 1 awaits elucidation.
Serum vitamin B12 levels (as determined by radio-immunoassay) were measured in 20 subjects aged 65 years and over with Alzheimer-type dementia, 20 age-matched subjects with non-Alzheimer type dementia and 20 age-matched subjects with no dementia. Serum vitamin B12 levels were significantly lower and serum vitamin B12 deficiency was significantly more frequent in subjects with Alzheimer-type dementia and were independent of age, sex, haematological abnormality or serum folate.
Eighteen homosexual men who had had lymphadenopathy in two or more extrainguinal sites for more than 5 months but had no evidence of other illnesses or infections were studied. All had extreme malaise, and 90% had additional symptoms (fever, night sweats, weight loss or gastrointestinal dysfunction). They were compared with 10 healthy homosexual and 10 healthy heterosexual male controls. The mean numbers of circulating T8 (suppressor) lymphocytes were increased equally in the two homosexual groups, but the mean number of T4 (helper) lymphocytes was decreased only in the group with lymphadenopathy. The response to testing for recall anergy was diminished in both homosexual groups but was significantly lower in the group with lymphadenopathy. The serum immunoglobulin and complement concentrations and the numbers of circulating B lymphocytes were normal in each group. Seven of nine lymph node biopsy specimens showed characteristic hyperplasia and confluence of follicles. Thus, idiopathic persistent, generalized lymphadenopathy in homosexual men without opportunistic infections or malignant diseases appears to be a distinct syndrome; it may also be related to the acquired immune deficiency syndrome.
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A family in which two male siblings were affected with Wiskott-Aldrich syndrome (WAS) was studied using G-6-PD isoenzymes as an X-linked marker in order to investigate the nature of cellular abnormalities. Isolated peripheral blood cell types from the doubly heterozygous mother of the affected males seemingly failed to express the G-6-PD allele in cis position with the WAS allele while her cultured skin fibroblasts expressed both G-6-PD alleles. Additionally, a histogram analysis of platelet size revealed a single population of abnormally small platelets in the affected propositus, whereas the heterozygous mother had no appreciable small platelet subpopulation. In vitro culture of hemopoietic progenitor cells of the heterozygous mother showed that the majority of progenitor cells did not express the WAS allele. However, a small number of cells expressing the G-6-PD type linked with the WAS allele were detected. The proportion of the latter progenitors was significantly higher among more primitive progenitors (those giving rise to later appearing colonies). This observation suggests that selection against cells expressing the Wiskott-Aldrich defect takes place in the hemopoietic system of the heterozygous female and offers a possible means of carrier detection in some women. Linkage studies in this family revealed one example of probable recombination between the loci for WAS and G-6-PD among three informative subjects, suggesting that these two loci may not be closely linked on the X-chromosome.
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Bone marrow cells from two glucose-6-phosphate dehydrogenase (G-6-PD) heterozygotes with polycythemia vera were cultured to determine whether progenitors which wre not of the polycythemia vera clone were present, and, if present, which cell lines contributed to the increase in erythroid colonies observed in response to added erythropoietin (ESF). To accomplish this, the G-6-PD isoenzyme activity of individual erythroid colonies was determined. All of the erythroid colonies analyzed in cultures without added ESF, contained the G-6-PD isoenzyme type characteristic of the abnormal clone. With higher ESF concentrations in the culture, however, there was an increase in the colonies that were not of the polycythemia vera clone. Analysis of the ratio of the various types of colonies indicated that normal and polycythemia vera cells are capable of responding to ESF in vitro. In selected patients, this technique permits analysis of the ratios of normal to abnormal cells during the course of the disease, in response to therapy and during late complications, such as myelofibrosis or leukemic transformation.
Two women with polycythemia vera and heterozygosity (GdB/GdA) at the X-chromosome-linked locus for glucose-6-phosphate dehydrogenase were studied to determine the nature of the cellular origin of their polycythemia. In contrast to unaffected tissue, such as skin fibroblasts, which consisted of both B and A types, the glucose-6-phosphate dehydrogenase of the patients' erythrocytes, granulocytes and platelets was only of Type A. These results provide direct evidence for the stem-cell nature of polycythemia vera and strongly imply a clonal origin for this disease. The fact that no descendants of the presumed normal stem cells were found in circulation suggests that bone-marrow proliferation in this disorder is influenced by local (intramarrow) regulatory factors.
Human marrow cells, suspended in methylcellulose medium containing erythropoietin, give rise to discrete colonies of hemoglobin synthesizing cells. The presumption that such colonies originate from single progenitor cells has been tested directly in females with X-chromosome inactivation mosaicism using glucose-6-phosphate dehydrogenase (G-6-PD) as a marker. When individual colonies were grown from marrow cells obtained from two black females heterozygous for G-6-PD, only one or the other isoenzyme type was observed, but not both. These results are most consistent with the interpretation that human erythroid colonies arise from single cells.
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Nine patients with rheumatoid arthritis were treated with low dose oral weekly methotrexate for 6 months. Successful therapy was not associated with changes in concentrations of total circulating lymphocytes nor with alterations of T lymphocytes in the helper-inducer, OKT4, or cytotoxic-suppressor, OKT8, subpopulations. Concentrations of methotrexate in circulating erythrocytes stabilized by 1 month of therapy and this measurement did not correlate with clinical efficacy or methotrexate toxicity in the long-term patient assessments.