Biomedical subjects
Publications and source records attributed to J Demeter.
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The determination of clinical stage in hairy cell leukemia is hampered by the lack of common criteria. Furthermore, clinical stages in which the disease should be treated have not yet been defined. In this paper we propose common criteria for the clinical staging of all hairy cell leukemia patients (treated or untreated), as well as for the assessment of responses to therapy. These criteria are absence or presence of disease-related symptoms and disease progression. Based on these criteria we propose that hairy cell leukemia patients in the most favorable stage of the functional system, non-symptomatic Stable Disease (nsSD), do not require treatment. Only in patients with disease-related symptoms and/or signs of disease progression is treatment justified and necessary. No symmetry was observed between the functional stages and Jansen's stages. For evaluation of responses to treatment, our stages were more sensitive than the Leeds criteria. Experimental evidence enables the differentiation of patients with non-symptomatic stable disease from those with symptomatic and/or progressive disease.
Serum immunoglobulin and natural antibody concentrations to environmental antigens have been determined in 26 hairy cell leukaemia (HCL) patients. The serum IgG, IgA and IgM levels as well as the concentration of antibodies to the majority of intestinal bacteria were found to be normal in both groups of HCL patients. In contrast to the data on the impaired humoral immunity of chronic lymphocytic leukaemia (CLL) patients, our results show that in HCL the studied aspects of humoral immunity are normal. Serum IgE levels were found to be significantly decreased in HCL when all patients were taken as a group. The difference was due to the decreased serum IgE concentration of splenectomized HCL patients, while IgE levels of untreated HCL patients did not differ statistically from that of the healthy controls.
Peripheral blood mononuclear cell surface markers were studied in a series of 26 hairy cell leukaemia patients 19 of whom were splenectomized previously. Patients with non-symptomatic and stable disease were distinguished from those with symptomatic and/or progressive disease (also termed "active" clinical stages). In all HCL patients as a group, the absolute number of CD4+ MN cells did not differ statistically from that of the controls, while the number of CD8+ MN cells was significantly increased. The reduction of the CD4/CD8 ratio in the peripheral blood of HCL patients as compared to the controls was explained by the reduction of this ratio in patients with "active disease", while the CD4/CD8 ratio of patients with non-symptomatic and stable disease did not differ statistically from that of the controls. The CD4/CD8 ratio was found to be influenced mainly by the clinical stage of the disease, and not by the effect of splenectomy.
Peripheral blood leukocyte subpopulations have been determined in 50 patients a long time (2 to 20 years) after posttraumatic splenectomy. These otherwise healthy individuals had significant lymphocytosis and monocytosis, while the absolute number of granulocytes did not differ statistically from that of the controls. The absolute number of CD2+, CD3+ as well as CD4+ and CD8+ peripheral blood mononuclear cells was found to be elevated, while the number of CD21+, CD20+ and HLA-DR+ PBMN cells was significantly decreased. The absolute number of sIgM+ as well as CD16+ MN cells did not differ statistically from that of the controls. Two further patients were found to have developed B-chronic lymphocytic leukaemia 5 and 31 years following posttraumatic splenectomy, respectively.
Human cultured monocyte-like tumour cells of the U937 histiocyte derived line were stimulated with phorbol myristate acetate, and generated and released an 18,000 MW polypeptide fibroblast-activating factor (FAF). Based on recognition by an antiserum to a synthetic peptide representing the 17 amino-terminal amino acids of FAF, two proteins of 32,000 and 35,000 MW were identified in extracts of U937 cells. Purification of the intracellular FAF-related proteins to homogeneity allowed the generation and amino acid sequencing of nine tryptic fragments of 4-11 amino acids. Neither of the intracellular FAF-related proteins exhibited the fibroblast proliferation-stimulating activity of FAF, suggesting that they are biosynthetic precursors analogous to the inactive propeptides of interleukin-1 beta and tumour necrosis factor-alpha.
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In the course of a post-splenectomy follow-up study, 2 out of 102 patients who had been splenectomized after an abdominal trauma were found to have developed chronic lymphocytic leukaemia 5 and 31 years after splenectomy, respectively. The possible association between splenectomy and secondary leukaemia is discussed.
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Natural killer (NK) cell activity and antibody-dependent cellular cytotoxicity of 48 posttraumatic splenectomy patients was found to be normal despite the increase in the proportion and the absolute number of large granular lymphocytes (LGLs). The NK cell activity of 2 further posttraumatic splenectomy cases was severely decreased, despite elevated number of LGLs and normal number of CD16+ peripheral blood mononuclear cells. Besides increased susceptibility to upper respiratory tract infections, 1 of these patients developed herpes genitalis recidivans. Two posttraumatic splenectomy patients were found to have developed chronic lymphocytic leukemia 5 and 31 years following splenectomy, respectively.
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Serum immunoglobulin and antibacterial antibody concentrations have been determined in 50 patients 2 to 20 years after posttraumatic splenectomy. The serum levels of IgG, IgA and IgM were found to be significantly greater in the group of posttraumatic splenectomy patients than in that of the healthy controls. The serum IgE concentrations did not differ statistically from that of the controls. The serum level of natural antibodies against intestinal bacteria were found to be elevated (Shigella 1b, 2a, 3 and Salmonella typhi 02 strains) or normal (Salmonella typhi 0901 as well as E Coli 026 and 055 strains). Our results show that the studied functional aspects of humoral immunity in this group of otherwise healthy splenectomized individuals were not impaired.
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Follow-up studies of natural killer (NK) cells, NK activity and antibody dependent cellular cytotoxicity (ADCC) in the course of hairy cell leukaemia (HCL) were carried out in a series of patients affected by the disease. NK activity against K562 targets was found to be high in all the patients with non-symptomatic stable disease. On the other hand, absent or extremely low NK activity was found only in patients with symptomatic progressive disease. NK activity determined in the transitional stages showed values between these two extremes. Antibody dependent cellular cytotoxicity (ADCC) was less closely correlated with the clinical stage than NK activity. Our findings suggest that investigation of in vitro NK cell cytotoxicity might serve as a useful adjunct in determining clinical stage in HCL.