PubMed Health⌕ Search

Biomedical subjects

K Beiske

Publications and source records attributed to K Beiske.

At least 37 records · Page 2Linked to original sources
PubMed1992

Detection of bone marrow metastases in small cell lung cancer patients. Comparison of immunologic and morphologic methods.

An immunocytochemical method, involving four monoclonal antibodies (MAbs) previously selected for their specific binding to small cell lung cancer (SCLC) cells in human bone marrow, was used for detection of bone marrow metastases in 81 patients with diagnosed SCLC. This procedure was compared with two routine morphologic methods with regard to diagnostic efficiency and sensitivity. Bone marrow involvement was found in 26 patients (32%), one of which had limited disease according to conventional clinical criteria. Eight of the positive cases were exclusively diagnosed by immunocytochemistry, whereas the histologic and cytologic methods separately identified two patients each. Immunocytochemistry had a detection level of tumor cells in the mononuclear cell fraction of approximately 1-2%, whereas no patients with less than 10% immunocytologically detectable tumor cells were diagnosed by cytomorphologic examination of bone marrow aspirates. Evidence was obtained that the diagnostic efficiency of any method increased with the number of samples examined. Of the four MAbs used, the anti-NCAM antibody, MOC-1, labeled tumor cells in all immunologically positive patients, and in all but one of these patients all cytologically confirmed tumor cells were stained. The antibodies MOC-31, which recognize a cluster-2 antigen, and NrLu10 bound nearly all tumor cells in most cases, whereas MLuC1 only diagnosed tumor cells in a fraction of the patients. The results show that the immunocytochemical application of these antibodies is superior to morphologic techniques in detecting SCLC bone marrow metastases. Further use of the method might provide prognostically and therapeutically useful information.

Antibodies, Monoclonal↗
PubMed1992

An effective immunomagnetic method for bone marrow purging in T cell malignancies.

An immunomagnetic method was developed to purge human bone marrow of malignant T cells, for use in conjunction with autologous bone marrow transplantation in patients with acute lymphoblastic leukemia and lymphoma. Three monoclonal antibodies anti CD2 (BH1), CD5 (BB8) and CD7 (BF12) were used. In model experiments employing MOLT4 cells it was found that with 50-fold excess of immunobeads relative to antigen-positive cells, the use of each antibody alone resulted in a 3.3-3.6 log tumor cell depletion, as assessed in a sensitive and reproducible clonogenic soft agar assay. When all three antibodies were used in a mixture, a purging efficacy of 5 logs was achieved. Two treatment cycles improved these figures to about 4 logs and more than 5 logs. When MOLT4 cells were mixed 1:10 with fresh bone marrow cells the antibody mixture yielded 3.1 and more than 5 log tumor cell depletion with one and two treatment cycles, respectively. This procedure resulted in only an insignificant reduction of the number of CFU-GM and CFU-GEMM progenitor cells. In two patients autotransplanted with purged marrow, the loss of CFU-GM was 37% and 48%, and no tumor cells could be detected by immunocytochemistry after purging. Rapid and sustained engraftment was achieved and both patients remain in complete remission after more than 20 months.

Antibodies, Monoclonal↗
PubMed1991

Interleukin-7 differentiates a subgroup of acute lymphoblastic leukemias.

The bone marrow stromal cell-derived growth factor interleukin-7 (IL-7) is known to stimulate growth of normal human B-cell precursors. In the present report, we have examined the effect of IL-7 on neoplastic B-cell precursors. Leukemic cells from 20 patients with common acute lymphoblastic leukemia (ALL) were highly purified by removing contaminating T cells and monocytes by rosetting with immunomagnetic beads. IL-7 markedly reduced the DNA synthesis in leukemic cells from three patients. This inhibition of DNA synthesis was accompanied by maturation of the cells, as demonstrated by the induced expression of the differentiation antigens CD19, CD20, CDw75, and surface mu-chain, and a decreased expression of terminal deoxynucleotidyl transferase. By examining G1 parameters, such as MYC, 4F2, and transferrin-receptor levels analyzed by flow cytometry as well as RNA and the cell cycle regulated antigen Ki67, it appeared that the cells were inhibited late in G1. Leukemic cells from the majority of the cases (12 of the 20 patients) responded to IL-7 with enhanced DNA synthesis without detectable maturation, as has been reported for their normal counterparts. Low molecular weight B-cell growth factor greatly potentiated the IL-7-induced growth stimulation of these cells. Thus, we have shown that IL-7 is capable of inhibiting proliferation of leukemic cells isolated from a subgroup of ALLs, and that this growth inhibition is accompanied by maturation of the cells.

Antibodies, Monoclonal↗
PubMed1991

T-cell receptor tau delta +/CD3+4-8-T- cell acute lymphoblastic leukemias: a distinct subgroup of leukemias in children. A report of five cases.

In a 10-year study of T-cell acute lymphoblastic leukemias (T-ALL) in children, we have identified five cases expressing the T-cell receptor tau delta (TCR tau delta). The incidence (26%) of TCR tau delta+T-cell leukemias in our material was high. Clinically, the TCR tau delta+ leukemias represented a distinct subgroup of T-cell leukemias. Mean age at onset of disease, 1.8 years, was remarkably low for mature T-cell leukemias. White blood cell counts were high, lymph node enlargements were discrete, and no mediastinal tumors were seen. Four of five TCR tau delta+ leukemias carried rearrangements of the C tau 2 gene, and transcribed the T-early alpha genetic element.

Antigens, CD↗
PubMed1991

Immunohistological diagnosis of "plasmacytoid T cell lymphoma" in paraffin wax sections.

An immunohistological study of paraffin wax embedded tissue from three cases of plasmacytoid monocyte neoplasms, using a panel of antibodies which react with fixation resistant leucocyte markers, is reported. This neoplasm was found to have a distinctive antigenic profile, being negative for CD3 and elastase, but positive for CD43 and CD68. This immunological phenotype, coupled with its characteristic morphological features, should facilitate the recognition of this rare neoplasm in routinely processed tissue. Furthermore, the term "plasmacytoid monocyte sarcoma" is proposed to designate it because it is inappropriate to refer to it as a lymphoma. As all cases have been associated with a myeloproliferative disorder (usually an acute or chronic myeloid leukaemia), these tumours probably represent the accumulation in lymphoid tissue of neoplastic cells which have differentiated along the plasmacytoid monocyte pathway.

Aged↗
PubMed1991

Selection of anti-SCLC antibodies for diagnosis of bone marrow metastasis.

The binding profile of 17 monoclonal antibodies (MAbs) to small lung cancer cell lines and normal bone marrow and peripheral blood cells was studied by immunocytochemistry and flow cytometry. At antibody concentrations that stained PJD tumour cells, only four MAbs (MOC1, MOC31, NrLu10, 81A6) were devoid of cross-reactivity with normal cells, whereas significant binding to subtypes of bone marrow and blood cells was seen for 13 antibodies. For the eight most promising MAbs the binding to ten SCLC cell lines was moderate to strong in 47 MAb/cell line combinations, and low or insignificantly in 33 combinations. Three cell lines lacked antigen for all MAbs studied. Flow cytometry was significantly less sensitive than immunocytochemistry in assessing MAb binding to both normal and tumour cells. The antigen expression was for several MAbs higher in exponentially growing tumour cells than in cells in stationary growth phase. Seven of the MAbs, which originally showed low to moderate cross-reactivity with normal cells, were titrated down to the lowest concentrations at which they stained H-146 tumour cells with high levels of antigen expression. At these concentrations five (MLuC1, Oat-1, SM-1, NCC-Lu-243, LAM2) of the seven Mabs showed acceptably low binding to bone marrow cells. At optimal concentrations altogether four to nine of the 17 antibodies studied may be used to detect tumour cell involvement in bone marrow of SCLC patients.

Antibodies, Monoclonal↗
PubMed1990

Immunological typing of acute leukaemias by rosetting with immunomagnetic beads: comparison with immunofluorescence staining.

Immunological phenotyping of acute leukaemias is important for a more precise diagnosis with respect to both cell lineage and maturation level. We have developed a rapid and reliable method for immunophenotyping, based on the use of magnetic monodisperse beads coated with monoclonal antibodies. After only a 10-min incubation of immunomagnetic beads (IMB) with mononuclear cells isolated from bone marrow or peripheral blood, the percentage of rosetting cells can be counted in the microscope. A panel of 16 monoclonal antibodies against haematopoietic cell-surface antigens was applied on 29 cases of acute myelogenic (AML) or lymphocytic (ALL) leukaemias, in order to compare immunological typing by immunomagnetic beads with immunofluorescence staining (IF). In all the cases tested, the two methods showed a virtually identical antigen distribution. The procedure described offers the advantages of being fast and simple to perform. Moreover, it has a high specificity and is easy to interpret in cases with low antigen expression.

Antibodies, Monoclonal↗
PubMed1989

Ki67 and 4F2 antigen expression as well as DNA synthesis predict survival at relapse/tumour progression in low-grade B-cell lymphoma.

Previous work has shown that parameters of cell activation studied on lymphoma biopsies can be used to discriminate between low-grade and high-grade non-Hodgkin's lymphomas and to predict prognosis in the low-grade malignancy group alone. We have now examined expression of several activation antigens and indicators of DNA synthesis in 29 patients with low-grade malignant B-cell lymphomas at the time of primary diagnosis and later at relapse and/or tumour progression. At both times, the level of 4F2 antigen expression examined by flow cytometry on cells in suspension as well as the number of Ki67 antigen-positive cells examined by immunohistochemistry were predictive of patient survival. DNA synthesis estimated by (3H-TdR) thymidine incorporation was of prognostic value at the second biopsy only. These parameters were more sensitive than histological demonstration of morphological transformation in secondary high-grade lymphomas in identifying high-risk patients at repeated biopsy. We propose that Ki67 or 4F2 expression or a marker of DNA synthesis (such as 3H-TdR incorporation or labelling index) should be evaluated when repeated biopsies are performed, in order to select patients for whom aggressive chemotherapy may be considered.

Antigens, Surface↗
PubMed1989

[Giant cell anaplastic anemia].

The Ki-1-antibody was raised against a cell-line of Hodgkin-cells, and reacts with most Hodgkin- and Reed-Sternberg-cells. By use of this antibody a new entity of non-Hodgkin's lymphomas has been identified; the anaplastic large cell lymphoma. We report our experience from studying 16 such tumours diagnosed during the period October 1986 to February 1988. In three cases the anaplastic large cell lymphoma appeared in patients who presented Hodgkin's disease as well. Of 15 cases studied using frozen section immunohistochemistry, ten showed T-, one B-, and one monocyte/macrophagephenotype, whereas three cases presented a mixed T-, B- and monocyte/macrophagephenotype. All cases showed a high proliferative activity as evaluated by presence of activation antigens. In paraffin sections six of 16 cases expressed epithelial membrane antigen (EMA). In 13 cases EMA, leucocyte common antigen (LCA) and Ber-H2 (a Ki-1-antibody) reactivity was compared in paraffin and frozen sections. The EMA reactivity was of nearly equal intensity in paraffin and frozen sections, while the reactivity of LCA and Ber-H2 was significantly reduced in paraffin sections, implying only partial preservation of the antigens. Clinically, most cases were in an advanced (III and IV) stage by the time of diagnosis. Of 14 actively treated patients, nine went into complete and two into partial remission, while three patients did not respond. Six patients are dead, five after less than one year. The coexistence of anaplastic large cell lymphoma and Hodgkin's disease and the common Ki-1 (CD30) antigen expression in these tumours suggest a possible histogenetic relationship.

Adolescent↗
PubMed1989

Intracellular events associated with inhibition of B cell activation by monoclonal antibodies to HLA class II antigens.

We have investigated several aspects of the inhibitory effects of monoclonal antibodies (mAb) directed against MHC class II antigens in B cell activation/proliferation, using a panel of mAb specifically reactive with antigens encoded by HLA class II loci (DP, DQ, DR). All mAb except the anti-DP mAb inhibited significantly anti-mu plus B cell growth factor-induced DNA synthesis. Only one mAb, however, which was reactive with gene products of all three class II loci (DP, DQ, DR) inhibited anti-mu-induced DNA synthesis as well as c-myc mRNA expression. In addition, the same mAb inhibited the early events induced by anti-mu stimulation alone, including phosphatidylinositol turnover and elevation of [Ca2+]i. In contrast to previous findings in the murine system, none of the anti-MHC class II mAb used in this study increased the cAMP levels.

Antibodies, Monoclonal↗
PubMed1989

Low-grade intestinal lymphoma of intraepithelial T lymphocytes with concomitant enteropathy-associated T cell lymphoma: case report suggesting a possible histogenetic relationship.

In a low-grade small cell intestinal lymphoma found in a 41-year-old woman with celiac disease, the neoplastic intraepithelial lymphocytes (IELs) showed cytoplasmic granules, expressed the alpha/beta T cell antigen receptor (TCR), and stained positively for the IEL antibody, HML-1. The tumor cells carried the CD3 and CD7 T cell antigens, but were double negative for CD4 and CD8 and also lacked other T cell antigens (CD1, CD2, and CD5). Tumor cell monoclonality was proven by the demonstration of a rearranged TCR-beta chain gene. The special marker profile of the lymphoma may be explained by partial antigenic deletion of the phenotype which characterizes the majority of normal IELs (TCR alpha/beta+, CD3+, CD8+, or CD4+). Alternately, the tumorous cell clone might originate from an as yet unrecognized TCR alpha/beta+, CD3+, CD7+, CD4-, CD8- normal subset of IEL. In the presented case, a concomitant high-grade large cell lymphoma supports the assumption that enteropathy-associated T cell lymphomas (EATCLs) derive from the intestinal IEL population and suggests that EATCLs may be preceded by a low-grade IEL lymphoma.

Adult↗
PubMed1988

Successful clinical use of an anti-HLA-DR monoclonal antibody for autologous bone marrow transplantation.

It has been widely assumed that anti-HLA-DR antibodies react with pluripotent stem cells and cannot be used in bone marrow purging. We report a case of non-Hodgkin's lymphoma in which an anti-HLA-DR antibody (AB4) was used for immunomagnetic purging and the subsequent autologous bone marrow transplantation resulted in rapid marrow engraftment with no serious complications. The results indicate that the AB4 antibody, which binds to an antigen encoded by the B3 gene of the DR region, can be safely used in the clinic in the purging of bone marrow from patients with AB4-positive tumors (non-T-cell acute lymphocytic leukemia, non-Hodgkin's lymphoma, and some cases of acute myelogenous leukemia.

Adult↗
PubMed1988

Triggering of neoplastic B cells via surface IgM and the cell surface antigens CD20 and CDw40. Responses differ from normal blood B cells and are restricted to certain morphologic subsets.

By raising monoclonal antibodies (MAbs) against B cells, a number of cell surface molecules have recently been identified which after binding by their specific antibody can trigger B cells, either alone or in co-operation with antibodies to surface immunoglobulin (sIg). The anti-CD20 (Bp35) MAb IF5 can deliver a strong activation signal to resting normal B cells, and the anti-CDw40 (Bp50) MAb G28-5 can promote activated G1 B cells to enter S phase. These antibodies were tested for their functional effects in vitro on suspended cells from 17 follicle-center-cell (FCC) lymphomas, 5 cases of chronic lymphatic B-cell leukemia (B-CLL) and 8 cases of various histological types. Changes in cellular volume, RNA and DNA synthesis were compared with the results obtained with a polyclonal anti-mu [F(ab')2] antiserum, a MAb to surface IgM (AF6), 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and B-cell growth factor (low-molecular-weight BCGF). Our data reveal differences in the requirements for triggering of various B-cell subsets: cells from CLL responded strongly to TPA but not to anti-mu, which is a potent stimulator not only of normal B cells but also of cells from individual cases of FCC lymphomas. Our observations suggest that the differentiation stage of B-CLL cells is distinct from that of small resting B cells from peripheral blood. Centrocytic lymphomas could not be activated by any of the reagents. CD20-mediated triggering was seen in neoplastic B cells from only 4 of 30 cases, indicating that most B-cell neoplasias were not responsive to this activation pathway. In contrast, the anti-CDw40 MAb consistently stimulated DNA synthesis together with anti-mu or TPA in cells from FCC lymphomas, but not from CLL. Together, these results suggest that activation in different neoplastic B-cell subsets depends on distinct signal transduction mechanisms.

Antigens, CD20↗
PubMed1988

Immunological typing of acute leukemias: immunoenzymatic staining of fixed cells compared with immunofluorescence staining of unfixed cells in suspension.

A panel of 14 monoclonal antibodies (McAb) against hematopoietic cell surface antigens was applied on mononuclear blood or bone marrow cells from 40 cases of acute leukemia in order to compare immunoenzymatic staining (IE) (alkaline phosphatase) of fixed cells with immunofluorescence staining (IF) of unfixed suspended cells. According to the immunological results, 25 cases were phenotyped as ALL and 15 cases as AML. Cases with blast crisis secondary to chronic myelogenous leukemia (CML-BC) were not represented in this series. In all ALL cases the two methods gave an identical antigenic distribution. In 20 our of 21 cases of non-T-cell ALL, a B-cell progenitor origin was demonstrated by a positive staining reaction with the anti-CD19 McAb AB1 or HD37, and in 10 cases additionally with the anti-CD20 McAb B1 or 1F5. In contrast to the results obtained with IF, IE revealed a poor preservation of the AB1 epitope on CD19, whereas the HD37 epitope was equally well demonstrated by both methods. In 15 cases of AML the distribution of positive versus negative cells with IE or IF was identical for all McAb except J5 (anti-CALLA) (CD10) and B1 (CD20). Thus, 10/15 AML cases expressed CALLA with IE compared to 2/15 with IF. The corresponding figures for B1 were 5/15 and 0/15, respectively. Accordingly, normal myeloid precursor cells were CALLA-positive with IE but negative with IF. The discrepancy probably reflects the fact that, whereas both intracytoplasmatic and membrane-bound antigens are exposed in IE, only the latter are in IF. If the alteration of antigenic accessibility after fixation is considered, IE can safely be used for immunophenotyping of acute leukemia.

Antibodies, Monoclonal↗
PubMed1987

Activation of human B cells: alternate options for initial triggering and effects of nonmitogenic concentrations of anti-IgM antibodies on resting and activated cells.

The monoclonal antibody 1F5, which is reactive with the CD20 (Bp 35) pan-B cell antigen, was shown to activate resting human peripheral blood B cells into the middle to late G1 phase of the cell cycle. However, in contrast to F(ab')2 fragments of polyclonal anti-mu, 1F5 synergized only weakly with B cell growth factor (BCGF) for DNA synthesis in these cells. We provide evidence that the CD20 molecule and surface immunoglobulin represent two alternative activation pathways in resting B cells. We also show that anti-immunoglobulins, during co-stimulation with BCGF, may play an important role in G1 as well as for the initial cell triggering. Thus, anti-mu in nonmitogenic concentrations was shown to provoke distinct effects on 1F5-pretreated G1 cells, as monitored by increases in cellular volumes as well as in cytoplasmic Ca2+ levels. Moreover, anti-mu could increase c-myc mRNA levels in 1F5-primed cells, implying that c-myc expression can be regulated in G1 as well as during the initial G0 to G1 transition. Partially purified human BCGF neither induced G1 entry in resting peripheral blood cells nor primed the cells for DNA synthesis. The finding that BCGF did not influence c-myc mRNA levels in resting or in activated B cells suggests that its mitogenic action does not involve the c-myc function.

Antibodies, Anti-Idiotypic↗
PubMed1987

Cyclic AMP-mediated suppression of normal and neoplastic B cell proliferation is associated with regulation of myc and Ha-ras protooncogenes.

Cyclic AMP functions as a negative regulator of cell proliferation in a variety of cell systems. We show here that the proliferation of normal and neoplastic B cells can be inhibited by high intracellular levels of cAMP. Thus forskolin treatment of the neoplastic B precursor cell line Reh induced a rapid increase in the cAMP level, which was followed by an accumulation of cells in the G0/G1 phase of the cell cycle over a period of 2-3 days. Similar inhibition of Reh cell proliferation after 3 days was observed whether forskolin was present continuously or only during the first 5 hr. Both c-myc and c-Ha-ras protein levels were transiently down-regulated at 4 hr of forskolin treatment, suggesting that these protooncogenes play a role in the process leading to cAMP-mediated growth cessation. Northern-blot analysis showed that the steady-state levels of c-myc RNA rapidly declined in all phases of the cell cycle, to return to control levels within a time period of 24 hr. In contrast, the c-Ha-ras mRNA level was steadily maintained. Thus the expression of c-myc and c-Ha-ras protein was regulated at different metabolic levels. The reduced proliferative capacity of the B precursor cell line in the presence of forskolin was not linked to induced differentiation. This was judged from the lack of appearance of three different B cell differentiation markers; cytoplasmic immunoglobulin heavy chain and two antigens recognized by the monoclonal antibodies B1 (CD20) and HH1 (CD37). We also showed that forskolin partially inhibited the proliferation of normal B lymphocytes stimulated by anti-immunoglobulins (anti-mu) and B cell growth factor (BCGF). The burst of c-myc mRNA during activation of normal B cells was also reduced by forskolin.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

Regulation of c-myc transcription and protein expression during activation of normal human B cells.

The close link between an actively expressed c-myc gene locus and cellular proliferation has been established in a variety of cell types. By using normal human peripheral blood B cells as a model for in vivo quiescence, we have assessed the expression pattern of the c-myc gene in terms of transcriptional activation and concurrent production of c-myc protein, following induction by antibodies directed against antigens on the cell membrane. Both the 1F5 monoclonal antibody, which reacts with the pan B cell antigen CD20, and the anti-mu could promote transcriptional activation of the c-myc gene roughly corresponding to the increased levels of cytoplasmic c-myc mRNAs. In addition, more than 80% of the B cells could be induced to express c-myc protein by either stimulus. Since treatment only with polyclonal anti-mu renders the B cells competent to proliferate in the presence of BCGF, c-myc protein expression is not per se sufficient for cell cycle progression into S phase.

B-Lymphocytes↗