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Biomedical subjects

P Biberfeld

Publications and source records attributed to P Biberfeld.

At least 163 records · Page 9Linked to original sources
PubMed1984

Phenotypic modulation of chronic lymphocytic leukemia cells by phorbol ester: induction of IgM secretion and changes in the expression of B cell-associated surface antigens.

Freshly explanted neoplastic populations from 22 cases of phenotypically well-characterized chronic type B lymphocytic leukemia were studied for their capacity to respond to the phorbol ester TPA in vitro. In all but four cases the secretion of IgM was either induced or increased, often to a high level. In contrast, the export of free immunoglobulin (Ig) light chains, an almost consistent feature of the B lymphocytic leukemias, remained relatively constant after TPA treatment. Parallel changes in leukemic cell surface phenotype were probed with both "conventional" and monoclonal antibodies, revealing some modulation of markers in every case investigated. A diminution in the level of surface Ig (preferentially IgD) and the accumulation of cytoplasmic Ig observed after phorbol ester treatment were accompanied by a corresponding reduction or loss of the B1 antigen and usually of B2 when present. The most consistent change induced by TPA was the appearance of BB-1, a marker of activated B lymphocytes, which was rarely expressed on fresh leukemic cells. Another marker of activated lymphocytes, LB-1, was also often induced or increased in its expression after exposure of the cells to TPA. The magnitude of the TPA response appeared to relate to the stage of maturation arrest of the individual leukemic clones rather than to any clinical parameter explored. The significance of the findings to normal B cell differentiation and their potential clinical utility are discussed.

Antigens, Neoplasm↗
PubMed1983

Characterization of malignant and non-neoplastic cell phenotypes in highly malignant non-Hodgkin lymphomas.

Malignant and non-neoplastic cells in 38 cases of highly malignant non-Hodgkin lymphomas: 3 centrocytic anaplastic, 18 centroblastic, 13 immunoblastic and 4 lymphoblastic (according to the Kiel classification) were immunophenotyped in cryosections and cell suspensions by means of monoclonal antibodies. Additionally, cell cycle analysis on cell suspensions was performed by DNA flow cytofluorometry. In 33 (87%) lymphomas the malignant cells expressed monoclonal surface immunoglobulin (Ig), which indicated B-cell origin of tumors. In 7 of the 19 B-cell lymphomas tested by the peroxidase-antiperoxidase method, cytoplasmic Ig was found. Four lymphomas were of T-cell and one of non-B/non-T-cell origin. In II B-cell and 2 lymphoblastic non-B-cell tumors, common acute lymphoblastic leukemia antigen (CALLA) was found. In 25 of 30 studied NHL the malignant cells expressed receptor for transferrin and in 19 of 28 cases a high percentage of cells in S-phase (greater than 10.85%) was found. Number and distribution as well as type of non-B-cells infiltrating B-cell-derived lymphomas varied considerably from case to case. Among these cells Leu 3+ (T helper/inducer) cells predominated. Leu 2+ (T suppressor/cytotoxic) and Leu 7+ (natural killer and killer) cells constituted less numerous groups. Correlation of cytodiagnostic analyses with clinical observations indicates that high content of infiltrating T cells may be a favorable prognostic feature in highly malignant B-cell lymphomas.

Adolescent↗
PubMed1983

Epstein-Barr virus-associated antibody pattern in untreated non-Hodgkin lymphoma patients. Relationship to clinical variables and lymphocyte functions.

Sera from 296 unselected and untreated patients with non-Hodgkin lymphoma (NHL) classified according to the Rappaport and the Kiel systems were analyzed for antibodies to Epstein-Barr virus (EBV). The aim of the study was to determine whether antibody spectra and titers to EBV-coded antigens correlated to clinical and immunological variables and whether the titers were of any prognostic significance. Increased antibody titers to EB viral capsid antigen (VCA) and slightly raised titers to early antigens (EA) of the diffuse (D) and restricted (R) types were noted frequently. Anti-VCA antibody titers correlated to clinical stage and age of the patients but not to histological subgroups according to the Rappaport or the Kiel classification systems. However, anti-VCA titers greater than or equal to 1:2560 were seen only in diffuse lymphomas according to the Rappaport and in non-follicle cell-derived lymphomas according to the Kiel classifications. Patients with complement-receptor-positive diffuse lymphomas had higher anti-VCA titers than complement-receptor-positive nodular cases. Anti-VCA titers also correlated positively to serum IgG levels (p less than 0.01). Total number of lymphocytes separated from peripheral blood and mitogen induced (ConA, PWM) DNA synthesis were recorded before treatment in 56 of the patients. The patients exhibited a significant lymphocytopenia as well as a significantly reduced lymphocyte response to mitogens (p less than 0.001) compared to healthy controls. Elevated anti-VCA titers and anti-EA titers correlated to a good mitogen-induced lymphocyte response (p less than 0.05). Only anti-D 1:40 at diagnosis predicted a poor prognosis.

Adolescent↗
PubMed1983

Phorbol 12,13-dibutyrate (P(Bu)2)-treated human blood mononuclear cells bind to each other.

Treatment of human blood mononuclear cells with nanomolar concentrations of phorbol 12,13-dibutyrate (P(Bu)2) induced their aggregation. The phenomenon was seen within a few minutes and reached its maximum manifestation after 20 min. At this time, 20-30% of unfractionated and nylon wool-passed mononuclear leukocytes were in the aggregates. The influence of pretreatment with 2-deoxyglucose, NaN3, EDTA, cyclohexamide, or incubation at 4 degrees C on the phenomenon indicated that it is energy and temperature dependent, requires the presence of extracellular divalent cations, and is independent of protein synthesis. Nonaggregating 2-deoxyglucose-and NaN3-pretreated cells could still bind [3H]P(Bu)2 which rules out the possibility that the phorbol ester molecule acts as a bridge between the aggregated cells. Seventeen percent of the P(Bu)2-treated T-cell population bound untreated autologous and allogeneic cells. The binding property has a certain species specificity because only 4% of the cells interacted with mouse lymphocytes. At the ultrastructural level, the intercellular binding showed broad areas of surface contact (both between lymphocytes and lymphocyte-monocyte) and "trapping" by surface processes was not seen. Aggregated cells did not show cytopathogenic changes.

Animals↗
PubMed1983

Autoantibodies against the basal cell layer: an association with chronic hepatitis B.

The presence of antibodies against the basal cells of squamous epithelium (BCL-Ab) was studied by indirect immunofluorescence in Rumanian and Swedish carriers of hepatitis B surface antigen (HBsAg), in patients with acute viral hepatitis (AVH), chronic liver diseases (CLD), and various other diseases, and in apparently healthy subjects. Titers of BCL-Ab greater than or equal to 40 were found in 8% of 320 HBsAg carriers, in 20% of 292 patients with CLD associated with HBsAg, and in 2% of 816 patients with HBsAg-negative CLD. BCL-Ab were not found in 167 patients with AVH, nor in 1389 patients with various nonhepatic conditions, nor in 344 apparently healthy subjects. These data indicate an association of BCL-Ab with CLD predominantly of hepatitis B etiology. Possibly hepatitis B virus may induce a form of liver metaplasia with the expression of an antigen with a specificity in common with the regenerative layer of basal cells in the squamous epithelium.

Autoantibodies↗
PubMed1983

In vitro differentiation of chronic lymphocytic leukaemia cells with a small pre-B-like phenotype.

Neoplastic populations from three cases of chronic lymphocytic leukaemia (CLL) which had features consistent with a maturation arrest at the 'small pre-B' stage are described. The cells were small and rounded with a scanty cytoplasm and stained for mu heavy chains but not light chains intracellularly while surface immunoglobulin (SmIg) was either undetectable or expressed sparsely on a minority of cells. Other features included the weak expression of B1, a lack of B2, an absence of the common acute lymphoblastic leukaemia antigen (cALLA), the presence of Ia and a variable expression of the receptors for Fc gamma and C3. Successful induction of in vitro differentiation in all three of the cases allowed the identification of a sequence of events whereby cells initially containing isolated mu heavy chains in their cytoplasm, on commencing light chain synthesis, begin to express stable SmIgM while surplus light chain is secreted without any association with the heavy chain. Although this is followed ultimately by the secretion of intact Ig effector molecules, the export of surplus light chains is apparently maintained throughout the developmental sequence. These findings are discussed with particular emphasis on their relation to normal B-cell maturation.

Aged↗
PubMed1983

Longitudinal studies of blood lymphocyte functions in non-Hodgkin's lymphoma.

The study comprises 26 patients with non-Hodgkin's lymphoma who entered complete remission. Lymphocyte subsets and spontaneous and mitogen (ConA, PWM)-induced DNA synthesis were recorded in purified blood lymphocytes harvested before treatment, in remission and in relapse. The T and B lymphocytopenia noted in untreated patients persisted in complete remission. At diagnosis the spontaneous DNA synthesis was increased and the response to mitogen was decreased as compared to controls. Both functions became normalised during complete remission in most patients under 60 yr. The lymphocyte abnormalities reappeared during relapse. A low response to mitogen (ConA) in complete remission seemed to predict early relapse in patients younger than 60 yr. It is concluded that functional abnormalities of blood lymphocytes in non-Hodgkin's lymphoma are closely related to the presence of active disease.

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

Leu 7+ (HNK-1+) cells. I. Selective compartmentalization of Leu 7+ cells with different immunophenotypes in lymphatic tissues and blood.

In the present immunohistochemical studies, Leu 7+ (HNK-1+, human natural killer and killer) cells were found to occupy preferentially germinal centres of follicles in lymph nodes and tonsils. Leu 7+ cells were also present in germinal-like zones of spleen follicles and in mantle zones of hyperplastic thymus follicles and varied in localization in lymph nodes involved in different types of follicular centre cell-derived malignant lymphomas. Most of the Leu 7+ cells in the follicles expressed the Leu 3 (helper/inducer) marker. Double staining studies of tonsil sheep erythrocyte-rosetting and peripheral blood mononuclear cell suspensions showed that two main, mutually complementary, subpopulations of Leu 7+ cells could be distinguished in both cases, namely Leu 7+/Leu 4+ (subdivided into Leu 2+ (suppressor/cytotoxic) and Leu 3+) and Leu 7+/Leu 4-, including mostly cells with OKM 1 (myelomonocytic) characteristics. Thus, in the tonsil cell suspension the cells with Leu 7+ Leu 3+/OKM 1- immunophenotype strongly predominated, whereas among peripheral blood mononuclear cells Leu 7+Leu 2+/OKM 1- and Leu 7+/OKM 1+ immunophenotypes were mostly observed.

Antibodies, Monoclonal↗
PubMed1983

Leu 7+ (HNK-1+) cells. II. Characterization of blood Leu 7+ cells with respect to immunophenotype and cell density.

In the present study, combined methods (indirect immunofluorescence with monoclonal antibodies, Percoll density fractionation, FACS analysis, and the cytotoxicity test) were used for further characterization of peripheral blood Leu 7+ cells (human NK and K cells). The Leu 7+ cell content was found to be relatively higher in the low-density cell fraction in which cells of large granular lymphocyte morphology predominated. However, Leu 7+ cells were also present in intermediate and high-density fractions. Low-density Leu 7+ cells were characterized by both Leu 2 (T suppressor/cytotoxic) and OKM1 (myelomonocytic) markers, whereas among high-density Leu 7+ cells the Leu 2 phenotype strictly predominated. Depletion of OKT3+ cells from the non-adherent cell population caused a decrease of cells with T helper and T suppressor phenotypes but did not have this effect on Leu 7+ and OKM1+ cells. After depletion of Leu 7+ cells from the OKT3- population the content of both T suppressor and OKM1+ cells decreased. Both the present results and previous reports enable us to conclude that two main Leu 7+ cell subpopulations are present in blood, namely Leu 7+Leu 2+/Leu 4+ and Leu 7+/OKM1+ cells. The presence of small and large Leu 7+ cells was also shown by FACS analysis.

Cell Separation↗
PubMed1983

Blood and lymph node T-lymphocyte subsets in non-Hodgkin lymphomas.

Blood and lymph node T-lymphocyte subpopulations have been studied in untreated non-Hodgkin lymphoma (NHL) patients and healthy controls. T-lymphocytes were determined by the E-rosette technique and by OKT3/LEU4 monoclonal antibodies; OKT4/LEU3 and OKT8/LEU2 monoclonal antibodies were used to identify T-cell subsets with helper/inducer and suppressor/cytotoxic activity, respectively. OKT4+ T-cells were low in patients, while OKT8+ T-cell numbers were normal. The OKT4+/OKT8+ blood lymphocyte ratio was below the normal range in about 50% of the patients. The ratio was higher in lymph nodes than in blood of patients and controls. The results may suggest that untreated NHL patients have a reduced pool of T-cells with phenotypic markers of OKT4/LEU3. Monoclonal blood B-lymphocytes were found in 45% of the cases. The presence of such cells in blood was frequently associated with a low OKT4+/OKT8+ ratio.

Aged↗
PubMed1983

Correlation of immunophenotype to morphology in unfavourable non-Hodgkin lymphoma.

The relationship between immunological markers and histology according to the Kiel classification was studied in 40 adult non-Hodgkin lymphoma patients of Rappaport unfavourable histology. The membrane-associated and cytoplasmic Ig as well as receptors for sheep erythrocytes, Fc gamma and C3d receptors were analyzed on cryostate sections and in suspension. In some cases, a more precise immunophenotype was achieved by the use of monoclonal antibodies detecting different T and B cell antigens. Eighty-eight per cent of the lymphomas had B-cell, five per cent T cell and 7 per cent non-B/non-T cell phenotypes. All CBCC and CC lymphomas expressed monotypic Ig, but only 66 per cent of the CB lymphomas. Thus, morphology alone did not consistently predict immunophenotype in large-cell lymphomas. A simultaneous expression of multiple heavy chains and cytoplasmic Ig was found in some lymphomas, suggesting an intratumoral differentiation. The nodular or irregular tissue distribution patterns for Ig and C3d receptors found in histologically diffuse follicle derived lymphomas also suggest intratumoral variations in the marker expression, probably related to differentiation. The results suggest that lymphoma immunophenotype is important in obtaining a definite diagnosis in large-cell lymphomas and that it may lead to a better understanding of the differentiation of lymphomas of low-grade malignancy.

Adult↗
PubMed1983

A clinico-pathological and immunological study of unfavourable non-Hodgkin lymphomas. Comparison of the Rappaport and Kiel classifications.

To evaluate the prognostic information of the Kiel classification a homogeneous material of 63 non-Hodgkin lymphomas of unfavourable Rappaport histology were re-evaluated according to the definitions of the Kiel classification. The patients were selected from a prospective lymphoma study including 775 patients. Only ambiguous histological diagnoses analysed independently by two hematopathologists were accepted. Immunological markers of the tumours studied both in suspensions and on cryostate sections were in addition analysed in 40 of the patients. Forty-one per cent (26/63) were of high grade malignancy according to the Kiel classification, 59% (36/63) were of low-grade malignancy. The DLPD group was most heterogeneous while a better concordance was found between DM and CB/CC and between DH and CB cases. However, prognostic subgroups of the two classifications were only partly equivalent. A good correlation was found between the Kiel high-grade malignant group and patients of Rappaport poorest prognosis (DU, DH). Eighty-eight per cent of the lymphomas were of B cell, 5% of T cell and 7% of non-B-non-T phenotypes. Both the Kiel and Rappaport morphologic classifications predicted survival in this selected material. Patients with B phenotypes survived longer than patients with lymphomas of non-B type. Among patients with diffuse lymphomas, those with a nodular and irregular distribution of immunoglobulin and C3d receptors tended to respond better and survived longer. No prognostic information was obtained from immunoglobulin isotypes, C3d or Fc-gamma receptors. It is concluded that the Kiel classification is equally reliable for clinical judgement as the Rappaport system and that immunological marker studies may add prognostic information.

Adult↗
PubMed1983

Phenotypes in chronic B-lymphocytic leukemia probed by monoclonal antibodies and immunoglobulin secretion studies: identification of stages of maturation arrest and the relation to clinical findings.

Neoplastic populations from 25 cases of B-lymphocytic leukemia (B-LL) were investigated in an attempt to define the stages of maturation arrest represented in this disease and the relationship, if any, to various clinical parameters. Intrinsic to this study was the expression of a number of B-cell antigens defined by monoclonal antibodies. These included antibodies to B1 and B2, both expressed exclusively on B lymphocytes, but with the latter probably restricted to a narrow window of differentiation, BB-1 and LB-1, both markers of activated lymphocytes, and 38.13, a monoclonal antibody raised against and recognizing an epitope expressed on Burkitt lymphoma cells. While the patterns of reactivities were complex, the cases could be classified into various groups on the basis of the phenotypes revealed. These were termed "pre-B," "early-B," "intermediate-B," "mature-B," and "secretory-B" from their patterns of immunoglobulin (Ig) isotype expression and their capacity to secrete Ig in short-term culture. Although B1 was detected on neoplastic cells from all but one case, its intensity of expression varied markedly, being strongest on the "mature-B" and "secretory-B" cases and weakest on the "pre-B" type. The expression of B2 was essentially restricted to the "intermediate-B," "mature-B," and "secretory-B" cases and was usually, but not invariably, accompanied by the coexpression of surface IgM and IgD. While expression of BB-1 was restricted to a few cases with mature features, LB-1 was more frequently detected and found predominantly on "intermediate-B" and "mature-B" cases. The 38.13 antibody was found to react weakly with a number of the populations coexpressing IgM and IgD. The export of large amounts of whole Ig was restricted to three "secretory-B" cases all of which were associated with a serum M-component corresponding to the Ig isotype secreted in vitro. In contrast, the secretion of free Ig light chains was a consistent feature of all B-LL, and the amounts detected did not vary considerably between the different types. No correlation between immunologic cell-type and the stage of the disease was apparent. Classification of the cases into "true" B-chronic lymphocytic leukemia and immunocytoma similarly revealed no strict association of these histopathologic entities with any particular phenotypic group, although those cases with the more mature features tended to be immunocytomas. The findings are discussed within the context of normal B-cell differentiation pathways.

Antibodies, Monoclonal↗
PubMed1982

Myocardial rupture with cardiac tamponade as a lethal early manifestation of acute myeloblastic leukemia.

A 73-year-old woman presented with a two-week history of increasing lassitude and fever. The hemoglobin level was 152 g/l and the total leucocyte count was 348 X 10(9)/l with 97% blasts. Before the diagnosis of acute leukemia could be confirmed by bone marrow examination, the patient developed shock and died within a few minutes. At autopsy a myocardial rupture of the left lateral wall apparently due to a massive leukemic infiltration was found.

Aged↗