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K H Robèrt

Publications and source records attributed to K H Robèrt.

At least 37 records · Page 2Linked to original sources
PubMed1986

Activation of malignant B-lymphocytes: pathophysiologic and clinical importance.

Recent advances in clarifying the activation mechanisms of the normal immune system have provided the basis for successful experiments concerning the activation of malignant lymphocytes. Such studies with malignant cells, freshly sampled from patients with lymphoproliferative diseases, can be used for pathophysiological considerations, analysis of tumor evolution, classification of malignant subsets, and karyotyping. Of particular interest is the possibility of abrogating the maturation arrest in some clonally-restricted cells. This might lead to therapeutical implications, since the differentiation blockage plays a fundamental role in the clonal expansion and pathogenesis of tumors. Recently, it has been shown that interferon (IFN) can be a potent inducer of various degrees of transformation, differentiation and even proliferation in different subsets of normal and malignant B cells. This may be important in explaining the divergent results of IFN treatment in various malignant B-cell disorders.

B-Lymphocytes↗
PubMed1986

Chronic B-lymphocytic leukemia cells proliferate and differentiate following exposure to interferon in vitro.

The ability of interferon (IFN) to induce proliferation and differentiation in malignant B cells from 29 patients with chronic lymphocytic leukemia (CLL) and in lymphoid cells from 11 healthy donors was investigated. IFN induced transformation and plasmacytoid differentiation in B cells from 19 of 29 CLL patients. The transformed cells belonged to the malignant clone as indicated by the immunoglobulin (lg) light chain restriction. Cells exposed to IFN expressed intracellular lg to a varying degree, which was correlated to the level of plasmacytoid differentiation. IFN gave rise to proliferative responses in cells from three patients. Cytogenetic studies on lymphoid cells from one patient showed that proliferation occurred in the malignant B cells. Induction of proliferation and differentiation was observed with various alpha-IFN and gamma-IFN preparations, as well as with a completely pure beta-IFN, showing that IFN and not contaminants in the preparations were responsible for the observed effects. Maximal transformation and proliferation usually occurred after four days of incubation at an IFN concentration of 500 to 5,000 U/mL. The ability of IFN to induce differentiation in CLL cells may be of importance for the reported antitumoral effects observed in some B cell malignancies during IFN therapy.

Adult↗
PubMed1986

Induction of 2',5'-oligoadenylate synthetase and blast transformation in primary chronic lymphocytic leukemia cells following exposure to interferon in vitro.

Interferon (IFN) can induce blast transformation and differentiation of malignant cells from patients with chronic lymphocytic leukemia (CLL). In this work the capacity of IFN to induce 2',5'-oligoadenylate synthetase (2',5'-A synthetase) in lymphoid cells from patients with CLL was investigated, and the results were related to the induction of blast transformation. IFN induced enhanced levels of 2',5'-A synthetase in unseparated lymphoid cells from 18 of 24 patients with CLL. In a control group of 11 healthy donors, 2',5'-A synthetase was induced in all cases tested. There was a close correlation between induction of 2',5'-A synthetase and induction of blast transformation by IFN. Thus, transformation occurred in clones expressing enhanced levels of 2',5'-A synthetase, but not in those showing no increase in 2',5'-A synthetase. An enhancement of 2',5'-A synthetase was observed in the IFN-sensitive cells following exposure to concentrations as low as 0.5 IFN units/ml. For induction of blast transformation, 10-1000 times more IFN was required. One h of pretreatment was sufficient for induction of 2',5'-A synthetase, whereas 20 h of pretreatment were required for induction of transformation by IFN. The finding that induction of 2',5'-A synthetase parallels interferon-induced blast transformation indicates that the reason why some CLL clones do not differentiate following exposure to IFN is a resistance of these cells to the action of IFN. The resistance to IFN in some CLL clones may be due to a defect in the 2',5'-A synthetase system of the cells, but it could also be at an early stage of the interaction between IFN and the cell, for instance at the receptor level.

2',5'-Oligoadenylate Synthetase↗
PubMed1986

Haematological remission of leukaemic polymorphic immunocytoma following splenectomy. Case report with longitudinal immunological and cytogenetic studies.

A 56-year old man with a Rai stage IV B-cell chronic lymphocytic leukaemia (polymorphic immunocytoma according to the Kiel classification) of mu kappa-phenotype with a clonal chromosomal abnormality in cells from peripheral blood, bone marrow, and spleen is reported on. Following splenectomy (without further therapy) the blood lymphocytosis gradually decreased to normal and the patient entered a remission, assigned 42 months after splenectomy by immunological and cytogenetic studies that revealed no cells of clonal origin in blood or bone marrow. Utilizing cellular markers of clonality, we thus confirm that haematological remissions may follow splenectomy. A subsequently developed orbital lymphoma (without leukaemia) consisted of tumor cells derived from the initial leukaemia cell clone as indicated by their immune and cytogenetic phenotype. The case report is discussed in relation to previous reports on "spontaneous" remissions of lymphoid leukaemias.

Antigens, Neoplasm↗
PubMed1985

Del(3)(p13) in B-prolymphocytic leukemia--a new nonrandom chromosomal aberration possibly related to the c-ras oncogene.

Cytogenetic analysis was performed on the leukemic cells from two patients with B-prolymphocytic leukemia. Both patients had del(3)(p13) chromosomal abnormality, as well as other clonal aberrations. Del(3p) was previously reported in one case of B-cell prolymphocytic leukemia, and is known to be a specific aberration in small-cell carcinoma of the lung. In B-cell prolymphocytic leukemia, as in other B-lymphocytic leukemias/lymphomas, the karyotype often involves chromosomes #3, #6, #11, and #12. All of these chromosomes are suggested sites for the c-ras oncogene family.

Aged↗
PubMed1985

Immune phenotype and prognosis in chronic B-lymphocytic leukaemia and leukaemic immunocytoma.

Fifty-nine patients with a leukaemic B-lymphocytic malignancy ("CLL") were studied. According to the Kiel classification, 29 patients had chronic lymphocytic leukaemia (CLL) and 30 had immunocytoma (IC). Cell surface immunoglobulin staining showed mu heavy chain phenotype in 14 patients, mu in 35, gamma in 7; in cells from 3 patients the staining was too weak to permit identification. The light chain phenotype was kappa in 39 patients, lambda in 17, and unidentified in 3. The immunoglobulin isotypes differed between the diagnoses. The gamma chain phenotype was found only in IC patients (p less than 0.02), and more CLL than IC patients showed a lambda chain phenotype (p less than 0.04). Blood lymphocytes from IC patients contained more T cells than CLL cell samples (p less than 0.002). No prognostic difference was found between the CLL and IC group. Compared to the lambda phenotype, the kappa phenotype was associated with a poorer prognosis in the IC group, but with a better prognosis in the CLL group. IC patients with mu phenotype had a poorer prognosis than those with gamma phenotype. Low relative T cell numbers were associated with a poor survival (p less than 0.01).

Aged↗
PubMed1985

Prognostic value of B-cell mitogen-induced and spontaneous thymidine uptake in vitro in chronic B-lymphocytic leukaemia cells.

Blood lymphocytes from 50 patients with chronic B-lymphocytic leukaemia (B-CLL) were cultured in vitro with and without the polyclonal B-cell activators (PBA) dextran sulphate (DxS), lipopolysaccharide from E. coli (LPS), and Epstein Barr virus (EBV). Patients with blood lymphocytes that showed a high spontaneous or PBA-induced 3H-thymidine uptake in 4 d cultures had a significantly shorter therapy-free survival than patients whose lymphocytes showed a low thymidine uptake. The DxS-induced cellular thymidine uptake was the most powerful predictor of prognosis. Eighteen patients with leukaemic cells responding to DxS stimulation had a median therapy-free survival of 17 months and a probability of 5 year therapy-free survival of less than 0.1, whereas for 30 patients with DxS unresponsive cells the corresponding figures were greater than 120 months and greater than 0.7, respectively (log rank, P less than 0.0001). A multivariate Cox's regression analysis revealed that the DxS-induced leukaemic cell response was of greater prognostic importance than clinical features such as blood counts and staging according to Rai and Binet. Therefore PBA-induced leukaemic cell thymidine uptake seems valuable in the prediction of prognosis in B-CLL.

Adult↗
PubMed1985

Prognostic information from cytogenetic analysis in chronic B-lymphocytic leukemia and leukemic immunocytoma.

Fifty-five patients with a clonal expansion of B lymphocytes in the peripheral blood were studied. According to the Kiel classification, 22 patients had chronic lymphocytic leukemia (CLL), 29 had immunocytoma (IC), two had prolymphocytic leukemia, and one had centrocytic lymphoma; one was not subclassified. Cytogenetic studies after B cell mitogen stimulation showed that six patients had an extra chromosome 12 as the sole abnormality. Another ten patients had an extra chromosome 12 together with other abnormalities. One patient had dup(12). Fifteen patients showed clonal aberrations without +12. Eleven patients showed only normal metaphases, and 12 patients were not evaluated cytogenetically. The cytogenetic subgroup pattern did not distinguish between CLL and IC patients. There was no significant difference between the CLL and IC groups as regards clinical findings and prognosis. However, the cytogenetic typing proved to be of prognostic significance. Increasing numbers of chromosomal aberrations within the cell clone were significantly associated with a poorer prognosis, ie, with impairment of survival (P = .04) and therapy-free survival (P less than 10(-4]. Patients with complex karyotypes (at least clonal aberrations) showed the poorest survival (P = .007). Patients with +12 required treatment earlier than patients with a normal karyotype (P = .01) and patients with karyotypic changes other than +12 (P = .006). These latter differences were even more pronounced when only IC patients were considered (P = .005 and P = .002, respectively). A multivariate analysis revealed that +12 was as strong an indicator of poor survival as advanced Rai or Binet stages and a stronger predictor of therapy-demanding disease.

Adult↗
PubMed1983

Mitogen-induced switching of immunoglobulin heavy-chain class secretion in chronic B-lymphocytic leukaemia and immunocytoma cell populations.

Lymphocytes from peripheral blood, bone marrow, and lymph nodes from six patients with chronic B-lymphoproliferative disease were studied. Two of the patients had a polymorphic immunocytoma with surface membrane immunoglobulin phenotype mu kappa. Four patients had chronic B-lymphocytic leukaemia (CLL) with the phenotypes mu kappa, mu delta kappa, mu lambda, and mu delta lambda, respectively. In no case did the monoclonal cell populations express gamma chains on the surface, and none produced monoclonal immunoglobulin in vivo. The malignant B lymphocytes were cultured in the presence of polyclonal B-cell activators. Immunoglobulin secretion was detected with the protein A plaque assay and with a modification of the reversed haemolysis-in-agar plaque assay. Immunoglobulin secretion was induced in four of the cell populations. In both the immunocytomas and in one of the CLL cell clones the heat-inactivated Staphylococcus aureus strain Cowan I induced secretion of IgG, as well as IgM, associated only with the same light chain as was expressed on the surface of the unstimulated cells. Thus, mitogens can induce immunoglobulin secretion in vitro in malignant B lymphocytes, and Cowan I bacteria also have the ability to induce a switch of immunoglobulin production from IgM to IgG in a fraction of the leukaemic cell populations.

Adult↗
PubMed1983

Chronic lymphocytic leukaemia cells activated in vitro reveal cellular changes that characterize B-prolymphocytic leukaemia and immunocytoma.

Leukaemic blood lymphocytes from a patient in the terminal stage of chronic lymphocytic leukaemia (CLL) according to the Kiel classification were stimulated by lipopolysaccharide from Escherichia coli. During progression to blast transformation, stimulated cells lost receptors for mouse erythrocytes (MRBC), accumulated intracellular Ig (cIg), and expressed more surface membrane immunoglobulin (SmIg). In addition, transforming cells expressed receptors for the monoclonal antibody FMC7, known to distinguish between CLL cells and prolymphocytic leukaemia (B-PLL) cells. Thus, activation of the patient's CLL cells induced changes in the cellular phenotype so as to resemble B-PLL. Some clonal cells progressed further to a secretory stage of differentiation. Thus, in vitro stimulation induced cellular changes reminiscent of not only B-PLL but also immunocytoma. Further studies of this kind may elucidate the relationship between these lymphocytic malignancies.

Aged↗
PubMed1983

Purpura provoked by cold exposure in a skier.

Case of a previously healthy young skier who developed purpura on his lower legs after cold exposure; the patient was not taking any medicine. No disease or disturbance except the physical trauma of cold could be found to explain his purpura.

Adolescent↗
PubMed1981

Conditions for cytomegalovirus stimulation of lymphocytes.

Lymphocytes from healthy donors or from patients with chronic lymphocytic leukaemia were subjected to live or inactivated cytomegalovirus (CMV) or the mitogen phytohaemagglutinin. No early or late CMV antigens could be demonstrated in the lymphocytes, indicating that neither abortive nor replicative CMV infection takes place. Only cells from CMV antibody-positive leukaemic and non-leukaemic donors were stimulated by CMV to DNA synthesis, with a maximum on day 5. Cells from all individuals responded to phytohaemagglutinin stimulation, the peak of activity occurring on day 3. The stimulation with CMV occurred in T cells and was independent of early CMV antigen production, viral DNA synthesis, or viral replication. CMV is thus not an in vitro lymphocyte mitogen like Epstein-Barr virus but is a very potent antigen for memory T cells.

Antibodies, Viral↗
PubMed1980

Clinical significance of mitogen-induced responses in lymphocytes from patients with chronic lymphocytic leukemia.

The mitogenic response patterns as well as surface membrane receptors of peripheral blood lymphocytes were investigated repeatedly during progression of the disease in 27 patients with chronic lymphocytic leukemia. Each patient was characterized by a reproducible mitogenic response pattern. Eleven patients, who required treatment within 0-24 months after diagnosis, had significantly higher cellular responses to dextran sulphate (DxS) and lipopolysaccharide (LPS) than 10 patients who have not required treatment within an observation time of 10-40 months from diagnosis. The high LPS and DxS responses, which may indicate leukemias composed of more immature cells, appear to predict a poor prognosis.

Cells, Cultured↗
PubMed1980

Nonrandom chromosomal aberrations in chronic lymphocytic leukemia revealed by polyclonal B-cell-mitogen stimulation.

Peripheral blood lymphocytes from 11 patients with chronic lymphocytic leukemia were stimulated by Epstein-Barr virus (EBV), lipopolysaccharide from Escherichia (LPS), and phytohemagglutinin (PHA). Chromosome analysis with the Q-banding technique after 5 days incubation revealed an extra chromosome 12 in 5 of the patients and a translocation between chromosome 11 and chromosome 14 in 1. Two patients had a deletion of chromosome 6, and only 3 patients had a normal karyotype. In most patients, the abnormalities were found in the majority of metaphases after stimulation with EBV, LPS, or both mitogens, while PHA revealed a normal karyotype, with the exception of a total of 4 metaphases in 3 patients. An extra chromosome 12 appears to be specifically associated with chronic lymphocytic leukemia. The frequency of chromosomal abnormalities in this disease appears to be much higher than has previously been thought.

B-Lymphocytes↗