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Biomedical subjects

W Knapp

Publications and source records attributed to W Knapp.

At least 181 records · Page 10Linked to original sources
PubMed1985

Differences in the fine specificities of monoclonal (Class A) antibodies to human myeloid cells.

Among 13 monoclonal antibodies to human myelomonocytic cells, six could be assigned to a group designated Class A with the following properties: (a) they react almost exclusively with granulocytes among cells of the peripheral blood, (b) they resemble the previously described anti-granulocyte antibodies, VEP8 and VEP9, and the anti-mouse embryo, anti-SSEA-1, in their strong reactions with human meconium glycoproteins and ovarian cyst mucins of non-secretor type and (c) they recognize the carbohydrate antigen 3-fucosyl-N-acetyllactosamine (alpha 1----3fucosylated Type 2 blood group chains). The binding of these anti-myeloid antibodies is more strongly inhibited by lacto-N-fucopentaose III than by the trisaccharide-fucosyl-N-acetyllactosamine, in contrast to anti-SSEA-1 which is more strongly inhibited by the trisaccharide. These observations suggest that the myeloid Class A antibodies recognize additional determinants on the neolacto (Gal beta 1----4GlcNAc beta 1----3Gal beta 1----4) backbone of the pentasaccharide which occurs on the glycoproteins and glycolipids of myeloid cells. However, no two of the anti-myeloid antibodies were identical in their inhibition patterns with the glycoproteins and the two oligosaccharides. They also differed in their cellular reactivities, for example, the proportion of cells in the K-562 cell line reacting with each antibody ranged from 15-57%.

Antibodies, Monoclonal↗
PubMed1985

Analysis of T cell activation with a non-mitogenic anti CD3 antibody and the phorbol ester TPA.

We used a non mitogenic anti CD3 antibody, termed VIT3, to study the signals required for the activation of normal resting T lymphocytes. Besides being not mitogenic, this antibody completely inhibits mitogen induced proliferative responses. In the presence of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), however, VIT3 induces DNA replication and cell proliferation comparable to PHA responses. In addition, T cells cultured with VIT3 plus TPA but not with VIT3 or TPA alone express high levels of interleukin 2 (IL-2) receptors and transferrin receptors. This co-stimulation appears to be accessory cell independent. Purified T cells respond equally well to VIT3 plus TPA as do unseparated mononuclear cells and addition of non-T cells has no enhancing effect. We conclude that the IgM antibody VIT3, although non-mitogenic by itself, still delivers a first and for the activation essential signal. In resting T cells this signal does not induce demonstrable anti-Tac antibody binding nor does it lead to a fully developed proliferative response in the presence of recombinant IL-2. Together with a second signal provided by TPA it serves, however, as a potent inducer of T cell growth.

Animals↗
PubMed1985

Lymphocytes of haemophilia patients treated with clotting factor concentrates display activation-linked cell-surface antigens.

Peripheral blood lymphocytes from 30 patients with haemophilia A were investigated for the expression of six activation-linked cell surface antigens as well as with regard to the relative proportions and total numbers of Leu-3a and Leu-2a positive cells. Twenty-nine of the haemophilia patients showed no clinical symptoms of immunodeficiency or infection whereas one patient presented the typical symptomatology of the acquired immunodeficiency syndrome (AIDS). The proportions and total numbers of circulating lymphocytes displaying Ia antigens, the p45 protein and/or the two recently defined surface antigens VIP-4 and VIP-5 were significantly increased in haemophilia patients when compared to healthy individuals of the same age group. No such increases could be observed for transferrin receptor and IL-2 receptor expression. After the observation of depressed helper/suppressor T-cell ratios in many haemophiliacs, the expression of activation linked surface antigens represents a further lymphocyte abnormality which resembles the findings in AIDS and its prodromal stages and can also be found in certain viral and parasitic diseases.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Studies on differentiation of committed hemopoietic progenitor cells with monoclonal antibodies directed against myeloid differentiation antigens.

In the present study we evaluated the reactivity of monoclonal cytotoxic antibodies directed against myeloid differentiation antigens with hemopoietic precursor cells. VIM-D5 and VIM-2 inhibit the proliferation of clusters and colony formation after seven days of incubation. Day-14 CFU-GM are not affected by these antibodies. After complement-mediated cytolysis with VIM-2, the number of BFU-e was significantly reduced; however, this effect was largely abrogated by addition of leukocyte-conditioned medium to the cultures as an exogenous source of burst-promoting activity. Furthermore, the maturation of myeloid progenitor cells has been examined by delayed treatment with VIM-D5 and complement during the in vitro culture period. In these experiments a different maturation behavior of day-7 and day-14 CFU-GM was demonstrated. To study whether a cryptic carbohydrate structure is present on more immature CFU-GM, the effect of neuraminidase treatment of myeloid progenitor cells on reactivity with VIM-D5 was tested.

Antibodies, Monoclonal↗
PubMed1984

Immunopathology of non-Hodgkin lymphomas.

The immunopathological features of lymphocytic non-Hodgkin lymphomas (NHL), follicular centre cell tumours and "large-cell" NHL are described with particular emphasis on in situ evaluation of cryostat sections using monoclonal antibodies. The immunological phenotypes of tumour cells and the pattern of "reactive" cellular infiltrates with characteristic differences for the various subtypes are summarized. Immunological membrane features of the following lymphocytic NHL of B lymphocyte origin are discussed in detail: B-CLL (most common phenotype of the lymphoma cells: VIB-C5, To-15, Ia, Leu-1), lymphoplasmocytoid NHL (To-15, Ia), B-prolymphocytic leukaemia (VIB-C5, To15, Ia, Leu (+/-), FMC-7(+/-] and hairy-cell leukaemia (HCL: To-15, Ia, FMC-7). NHL of T-lymphocytes detailed in respect of mycosis fungoides and Sézary syndrome (OKT-3, OKT-4, OKT-11), to subtypes of T-CLL with particular emphasis on the "azurophilic" type, to T-zone NHL, and to adult T-cell leukaemia/lymphoma (OKT-3, OKT-4, OKT-11, anti-tac), all of them with the usual immunological phenotype of T-helper (TH) lymphocytes. NHL with a predominance of T-suppressor (TS) lymphocytes include the immunoblastic lymphadenopathy like T-cell lymphoma (OKT-3, OKT-8, OKT-11) and some lymphoepitheloid (Lennert) lymphomas. Immunological features of follicular centre cell tumours are discussed with emphasis on similarities and differences with the normal germinal centre. Tumour cells usually show the following membrane phenotype: centroblastic/centrocytic (cb/cc: To-15, VIL-Al, Ia; meshwork of non-neoplastic R4/23+, To-5 + DRC), centrocytic (VIB-C5, To-15, Leu-1, Ia; R4/23 and To-5 meshwork), centroblastic (cb, To-5, To-15, Ia, VIL-Al +/-). "Large-cell" NHL include the last entity (cb), immunoblastic (B-ib, T-ib) and lymphoblastic (lb) NHL and are discussed in respect to B-ib (Ia, To-15 +/-, VIL-Al +/-), T-lb (WT-1, OKT-6 +/-, OKT-11 +/-), pre-B-lb (VIB-C5, Ia, TdT, VIL-Al +/-) and Burkitt-type NHL (VIB-C5, VIL-Al, Ia, sIg). "Reactive" cellular infiltrates may account for a large fraction of the cellular content of NHL (e.g. the mean TH and TS content amount to about 40% of that seen in normal lymph nodes). In comparison to other NHL B-CLL and cb/cc showed the highest, HCL the lowest number of TH X TS exhibited less typical alterations.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1984

Interferon induction in human mixed leukocyte-tumor-cell reactions: evidence for restriction to a certain lineage expressing glycophorin A.

This study reports the induction of interferon (IFN) in human mononuclear cells (MNC) by hematopoietic tumor cells. Only 3 out of 15 cell lines were capable of inducing IFN in the mixed leukocyte/tumor-cell reaction (MLTR). K562, a pluripotent stem cell line and DUTKO-I, a hybrid between K562 and Daudi (Burkitt lymphoma) induced high levels of antiviral activity (ranging from 50-440 units IFN/ml). PUTKO-I, a hybrid between K562 and P3HR-I (Burkitt lymphoma) induced very low levels of IFN (10 units/ml). This antiviral activity was produced by HLA-DR + adherent cells as revealed by different cell separation techniques, and shared well-known properties of IFN gamma (isoelectric point, inactivation by anti-human IFN gamma antibodies; species-restricted protection). MLTR-induced IFN induction could be blocked by enzyme treatment of tumor cells, but was still present when glutaraldehyde-fixed cells were used for induction. Analysis of the cells by flow cytometry for expression of glycophorin A (GpA) revealed that expression of GpA correlated with the ability to induce antiviral activity in MLTR. Furthermore, isolated GpA could be used as a stimulant as well and the response to either K562 cells or soluble GpA was enhanced up to ten-fold by the addition of a GpA-specific monoclonal antibody.

Cell Communication↗
PubMed1984

Evidence of HLA-DR antigen biosynthesis by human keratinocytes in disease.

As opposed to normal human skin where HLA-DR expression is restricted to the Langerhans cell (LC) population, HLA-DR, but not HLA-DS antigens can be readily detected on keratinocytes (KC) in certain disease states, i.e., cutaneous T cell lymphoma (CTCL), graft-vs-host disease (GVHD), and lichen planus (LP). To clarify the cellular origin of KC-bound HLA-DR antigens, we used a monoclonal antibody directed against determinants solely expressed on the cytoplasmic HLA-DR gamma chain (VIC-Y1) and observed that, by immunofluorescence, KC displaying HLA-DR alpha/beta complexes on their surface uniformly displayed cytoplasmic VIC-Y1 reactivity. In view of the crucial role of the gamma chain for HLA-DR biosynthesis, we conclude that HLA-DR antigens on KC are actively synthesized by these cells.

Epidermis↗
PubMed1984

M2, a novel myelomonocytic cell surface antigen and its distribution on leukemic cells.

The selectivity of a novel myelomonocytic cell surface antigen, designated M2, has been assessed in a series of 208 leukemias. The M2 antigen is defined by a monoclonal antibody (VIM-2) of the IgM class. Its expression within the normal hemopoietic system is restricted to myelomonocytic cells. Lymphocytes, erythrocytes, thrombocytes and their morphologically recognizable precursors are negative. Sixty of the 66 acute myeloblastic leukemias (= 91%) and 28 of the 30 myeloid blast crises of CML patients (= 93%) were M2-positive. As expected from our findings with normal myeloid cells, the myeloid cells found in stable phase of CML were also in all instances, M2-positive. Quite in contrast, lymphoid cells from patients with B-CLL, T-CLL, prolymphocytic leukemia, hairy-cell leukemia, lymphoblastic lymphoma, Sézary syndrome, from CML patients in lymphoid blast crisis and from the majority of patients with ALL, were completely M2-negative. Also negative were the blast cells of patients with acute megakaryoblastic leukemia and acute erythroleukemia. A direct comparison of M2 expression with the display of the 3-fucosyl-N-acetyllactosamine determinant, the structure recognized by most of the anti-myeloid monoclonal antibodies reported so far, shows that more AMLs are M2-positive and the proportion of M2-positive blast cells in individual AML samples is higher.

Antibodies, Monoclonal↗
PubMed1984

[High-dosage oral gestagen therapy as a failure-regime in metastatic breast cancer].

High-dosage medroxyprogesterone (Farlutal, 1 g/d orally) was administered to 42 female patients with progressive disseminated carcinomas of the breast after conventional cytostatic and hormonal treatment had failed. Besides evaluation of success of treatment the pharmacokinetics of medroxyprogesterone were investigated. A remission rate of 37% (total and partial remissions) indicated that high-dosage oral treatment with gestagens can be used as "failure-regime" in patients at the end of conventional treatment. The plasma level of the gestagen approached values corresponding to high-dosage intramuscular application.

Administration, Oral↗
PubMed1984

Hemophilia and thrombocytopenia in a patient with impaired cellular immunity. A case report.

ITP in hemophiliacs may produce severe bleeding complications. We here report on an eight-year-old boy suffering from severe hemophilia A, who developed ITP and an acquired impaired immune function similar to AIDS. Steroid therapy reverted the thrombocyte count to normal, however it had to be discontinued because of a severe Cushing syndrome. The thrombocytopenia also responded to IgG-therapy and the patient is treated with a long term schedule according to Imbach. It is of interest that the impaired T-helper/T-suppressor cell ratio (0.45) improved to a value of 1.0 after initiation of this therapeutic regimen. We conclude from our observation that i.v. immunoglobulin therapy is of particular value for the treatment of ITP in patients with impaired cellular immunity.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Monoclonal antibodies to human myelomonocyte differentiation antigens in the diagnosis of acute myeloid leukemia.

The immunological definition of malignant lymphatic cells has already been routinely applied by many laboratories over a number of years. Today it is clear and undisputed that the phenotypic data obtained in that way are often very useful and supporting. The immunological definition of non-lymphoid leukemias is not yet as far advanced. Additional surface markers for the recognition of poorly differentiated non-lymphoid cells are clearly needed. In this paper ten monoclonal antibodies to myeloid surface antigens are described. It is hoped that they are a useful addition to the presently available relatively small panel of well studied myeloid surface markers which are displayed by immature malignant blast cells.

Antibodies, Monoclonal↗
PubMed1984

Diagnostic specificity of the monoclonal anti-CALLA antibody VIL-A1 in leukemia and malignant lymphoma.

VIL-A1 is an anti-CALLA antibody which binds efficiently and exclusively to CALLA positive cells. When the cell type specificity of VIL-A1 is studied in acute leukemias and lymphomas, results show that in those leukemias which could be characterized by cytochemical and morphological methods, VIL-A1 reactivity was specific for cells of lymphoid origin. It can therefore be assumed that VIL-A1 positive AUL cells (in this case 4 out of 9 patients) are also lymphoid in origin. In no case were AML blasts found to be positive with this antibody. Seventy-four per cent of the 88 ALL patients were positive (L1 + L2) whereas none in the L3 subgroup were positive, and 48% of CML patients in blastic crisis were positive. Of the low grade non-Hodgkin malignancies, only CB/CC was positive, distinguishing it from the CC type which was negative. Of the high grade lymphomas IB was found to be negative, while the others showed a heterogeneous picture which was not related to other immunological parameters.

Acute Disease↗
PubMed1984

A human Ia cytoplasmic determinant located on multiple forms of invariant chain (gamma, gamma 2, gamma 3).

An antigenic determinant present in the cytoplasm, but not on the surface membrane of human Ia+ cells, is defined by a monoclonal antibody (VIC-Y1) and is shown by immunoprecipitation and by NEPHGE to be expressed by Ia oligomers. Immunoprecipitations of cellfree translates and of purified Ia subunits indicate that the VIC-Y1 determinant is located on the Ia gamma-(invariant) chain, as well as on two other related molecules, provisionally termed gamma 2 and gamma 3. Within our experimental conditions, the three forms of gamma-chains co-precipitate exclusively with Ia oligomers. As detected by VIC-Y1 and in the limits of our assays, gamma-chains could not be found at the cell surface; their tissue distribution, determined by cytoplasmic indirect immunofluorescence with VIC-Y1, closely resembles that of Ia antigens, with the possible exception of acute lymphatic leukemia cells (Ia+, gamma-chain-).

Animals↗
PubMed1984

Exposure by desialylation of myeloid antigens on acute lymphoblastic leukemia cells.

The 3-fucosyl-N-acetyllactosamine structure, a sugar sequence contained in the human milk oligosaccharide lacto-N-fucopentaose III, is recognized by most of the granulocyte-specific monoclonal antibodies (MoAb) reported in the literature, including the six MoAb from our laboratory. Blast cells from patients with acute myeloblastic leukemia (AML) displayed a heterogeneous reaction pattern when they were exposed to MoAb against this moiety, and the proportion of reactive cells in individual cell samples was highly variable. The intensity of the reaction was strongly enhanced by neuraminidase treatment of AML blasts, and reactive structures were exposed on previously negative AML blast cells. Surprisingly, this granulocyte-associated antigen was exposed by desialylation not only on malignant myeloid precursor cells but also on common acute lymphoblastic leukemia cells. No such effect was seen when normal peripheral blood lymphocytes, lymphocytes from patients with chronic lymphatic leukemia, or blast cells from patients with B-cell acute lymphoblastic leukemia, acute erythroid leukemia, and acute megakaryoblastic leukemia were treated with neuraminidase.

Animals↗
PubMed1984

Inhibition of phagocytosis by monoclonal antibodies to human myeloid differentiation antigens.

The influence of eight antimyeloid monoclonal antibodies on human leukocyte phagocytosis was investigated using flow cytometry. A granulocyte-specific monoclonal antibody, VIM-D5, inhibited the phagocytosis of both zymosan particles and Staphylococcus aureus in a dose-dependent fashion. In the presence of 5 micrograms/ml, the numbers of phagocyte-associated zymosan particles and bacteria were reduced by about 35% and 40%, respectively. Another monoclonal antibody, VIM-12, reacting with granulocytes, monocytes, and null lymphocytes, inhibited both granulocyte and monocyte phagocytosis of S. aureus. The inhibition was dose dependent, and in the presence of 10 micrograms/ml, the number of phagocyte-associated bacteria was reduced by about 40%. VIM-12 did not influence the phagocytosis of zymosan particles. Both VIM-D5 and VIM-12 inhibited the internalization phase of phagocytosis, whereas the attachment to the phagocyte surface was unaltered. The combined effect of VIM-D5 and VIM-12 was additive, amounting to about 70% reduction of phagocytosis of bacteria. The remaining six antimyeloid antibodies had no effect on leukocyte phagocytosis. The combined use of antimyeloid monoclonal antibodies and flow cytometry appears to be a promising tool for the study of phagocyte functions.

Antibodies, Monoclonal↗
PubMed1983

[Transfer factor as adjuvant immunotherapy in invasive cervix cancer. Report of a double-blind study].

From 1977 to 1982 a prospective randomized double-blind study comparing transfer-factor (TF) versus placebo was conducted in invasive cervical cancer patients after radical surgery and irradiation. The husbands of the cancer patients were selected as leukocyte donors for TF preparations. 60 patients entered the study; 28 patients received placebo and 32 patients received TF. The comparability of both collectives was excellent concerning age and tumor stage. One patient treated with TF died intercurrently. The rate of recurrence of cancer was 5 in the 31 TF-treated patients and 11 in the 28 patients receiving placebo, which was significantly different (p less than 0,05). This difference was even greater when only patients treated for at least 3 months were compared (3 recurrences in the TF-group and 11 recurrences in the placebo-group). Further aspects of this clear clinical results are discussed.

Adult↗
PubMed1983

Glycophorin A expression in malignant hematopoiesis.

Two hundred twenty-nine patients with hematopoietic malignancies were tested for reactivity with a monoclonal anti-human glycophorin A antibody. One hundred twenty-three of these cases were classified as acute leukemias of either the myeloid, lymphoid, erythroid, or undifferentiated type. The monoclonal antibody we used (VIE-G4) was obtained after immunization with a human thymocyte suspension. It selectively reacts with glycophorin A (GpA) and strongly binds to 40% of K-562 cells and all morphologically recognizable erythroid precursor cells. Apart from two cases with acute erythroid leukemia, this antibody reacted with none of the malignant cells in the 229 tested hematopoietic malignancies, including the 121 nonerythroid acute leukemias. This finding seems to contradict the earlier observations by L. Andersson and colleagues that a considerable proportion of acute leukemias express GpA on their surface. One reason for this discrepancy might be the fact that VIE-G4 detects only complete glycosylated GpA. If this is the sole explanation, this would mean that the poorly differentiated cells in these cases express incompletely glycosylated GpA.

Acute Disease↗