Search PubMed⌕ Search

Biomedical subjects

W Knapp

Publications and source records attributed to W Knapp.

At least 199 records · Page 11Linked to original sources

Distinct lymphoblastic and myeloblastic populations in TdT positive acute myeloblastic leukemia: evidence by double-fluorescence staining.

Double-immunofluorescent staining for the enzyme terminal deoxynucleotidyl transferase (TdT) as a marker of primitive lymphoblasts, and for the VIM-D5 antigen as a differentiation antigen of the myeloid system gave direct evidence for distinct lymphoblastic and myeloblastic populations (mixed leukemic cell populations) in seven patients with acute leukemia. The percentage of malignant TdT positive cells contributing to a leukemic cell bulk with unequivocal signs of myeloid origin was between 10 and 80%. A defect at the level of a common progenitor cell giving rise to both the TdT and the VIM-D5 positive blast cell population is discussed.

Antibodies, Monoclonal↗

Phenotypes of human large granular lymphocytes as defined by monoclonal antibodies.

Four monoclonal antibodies VEP8, VEP9, VIM-D5, VIB-C5 against antigens expressed on human mature myeloid cells (polymorphonuclear leukocytes [PMNL] and/or monocytes) as well as on immature cells in the bone marrow were tested for reactivity with cell preparations highly enriched for large granular lymphocytes (LGL). These cells are known to be the main effector cells responsible for natural killer (NK) cell activity in human peripheral blood. Using indirect membrane immunofluorescence (IMF), none of these antibodies showed any reactivity at all. In addition, LGL-enriched cell preparations were tested with the anti-lymphocyte monoclonal antibodies OKT6, anti-Leu1, anti-Leu2a, anti-Leu3a, and anti-human Lyt3, and also with OKM1 antibody. Significant reactivity was found with anti-Leu2a (59 +/- 8%), anti-Lyt3 (55 +/- 4%) and OKM1 (81 +/- 11%) antibodies, whereas T6, Leu1, and Leu3a antigens were less pronounced or missing on LGL. As a further approach, another monoclonal antibody, VEP13, which reacts with LGL, granulocytes but not monocytes and is therefore different in its specificity from OKM1 and OKT10, was used for identification of LGL. The coexpression of antigens as defined by the above-mentioned antibodies and OKT10 on VEP13+ cells was studied. Again, phenotypes similar to those observed on LGL enriched by Percoll gradient centrifugation were found: of VEP13+ cells 84 +/- 6% reacted with OKM1, 82 +/- 5% with OKT10, 52 +/- 17% with anti-human Lyt3, and 48 +/- 14% with anti-Leu2a, whereas VEP8, VEP9, VIM-D5, VIB-C5, T6, Leu1, Leu3a antigens were not expressed on VEP13+ cells. Taken together as an overall evaluation of phenotypic characteristics, our data indicate that LGL cannot be integrated into one of the known lymphocytic or myelomonocytic lineages. LGL show an intermediate phenotype depending possibly on varying differentiation or activation stages of haemopoietic cells. However, the possibility also exists that LGL belong to a separate, yet undefined cell lineage.

Antibodies, Monoclonal↗

[Yersinia uveitis].

A 13 year-old boy was admitted with a unilateral acute fibrinous iritis accompanied by a pauciarticular arthritis which had been preceded by a febrile lower urinary tract infection. The diagnosis of a Yersinia enterocolitica infection was established by significant titers of agglutinating antibodies vs. the serotypes O-I (=0:3). The differential diagnosis of the disease included infections with salmonella, shigella, campylobacter, chlamydiae and metastatic bacterial and mycotic infections as well as rheumatic diseases. Repeated observation of Yersinia enterocolitica in our uveitis patients during the last couple of years suggests that Yersinia enterocolitica is another pathogen causing acute uveitis. The clinical significance of Yersinia enterocolitica infections in ophthalmology will have to be clarified by further specific investigations.

Acute Disease↗

In vitro effects of cyclosporin A on human B-cell responses.

The in vitro effects of cyclosporin A (CsA) on T-cell-dependent and T-cell-independent mitogen responses of human B cells were studied. T-cell-dependent, pokeweed mitogen (PWM)-induced B-cell proliferation and B-cell differentiation to Ig-secreting cells were significantly inhibited by CsA, when purified B cells were cultured with T-cell helper factor containing supernatants instead of T cells. This indicates that the inhibitory effect of CsA on T-cell-dependent, PWM-induced B-cell proliferation and differentiation is not exclusively due to direct effects on helper T cells. B-cell proliferations induced by anti-IgM antibodies and by Staphylococcus aureus bacteria were also found to be sensitive to CsA. Since both types of reactions are T-cell-independent, the concept that responses of human B cells can also be affected by CsA in ways that seem to be independent of the well-documented direct effects of CsA on T cells is further supported. This seems not to be a general phenomenon, however. Epstein-Barr-virus-induced activation of human B cells, as reported previously and also observed by us, is completely insensitive to CsA. It seems, therefore, that certain B-cell activation mechanisms are sensitive to CsA while others remain unaltered. The difference between these two reaction patterns cannot be exclusively explained by a T-cell dependence or T-cell independence of these responses. CsA effects on certain functional B-cell subsets or interference with accessory cell mechanisms might be responsible.

Antibody-Producing Cells↗

Treatment outcomes in a day treatment program.

A sample of 63 psychiatric patients consecutively admitted to an adult day treatment program was evaluated with the Colorado Client Assessment Record (CCAR) within 2 weeks of their admission, at regular 90-day intervals, and/or upon discharge from the program. Trained raters using the CCAR made functional assessment ratings of patients on nine behaviorally-anchored scales. A unique feature of this study was that patients' primary therapists were asked to identify the three CCAR dimensions which represented their targeted treatment goals. Purposes of this study were twofold. The first concern was to establish the validity of this instrument in monitoring the level of functioning of a young and chronically impaired sample. The second goal was to assess the clinical outcome of patients in the day treatment program. Results showed the CCAR to be a valid measure of patients' level of functioning. Further results indicated that the functional ratings on the three targeted treatment goals exhibited statistically significant improvement from admission to follow-up or discharge. Findings further suggest that patients' motivation for treatment at the time of admission may be important for achieving successful clinical outcome. This investigation, by establishing the validity and utility of the CCAR for a chronically impaired psychiatric population, lays the foundation for continued monitoring of clinical outcome and program evaluation.

Adult↗

Significance of Yersinia enterocolitica isolates and antibody titers. A prospective study in patients with enteritis and healthy controls under bacteriological, serological, epidemiological and clinical aspects.

A simple and fast isolation procedure in combination with the search for Salmonella and Shigella spp. has been applied for the screening of Yersinia enterocolitica from the faeces. The microorganisms was isolated from 31 out of 4052 patients with gastrointestinal symptoms (0.8%) and from one out of 2295 healthy individuals (0.04%). 42% of the isolates were detected from infants up to the age of 3 years. Y. enterocolitica was excreted on the average at least 22 days after the clinical onset (n = 29). In 17 out of 24 patients (71%) significant agglutinin titers were demonstrated by the first serological examination one to 13 weeks after clinical onset. Acute diarrhoea, the most prominent symptom, lasted for 15 days and was followed in one third of the cases by a protracted course of approximately eight weeks. A reliable diagnosis of "enteric yersiniosis" rests besides the uncharacteristic clinical symptoms on the isolation of the microorganism and/or the demonstration of specific antibodies in significant titers, preferable with fourfold rise or decrease.

Adolescent↗

Temperature-dependent changes in the sugar and fatty acid composition of lipopolysaccharides from Yersinia enterocolitica strains.

Yersinia enterocolitica S and R strains change the pattern and the amount of their lipopolysaccharide-linked fatty acids with the respective growth temperature. As described also for other enterobacterial strains, saturated fatty acids are decreased, especially the amount of C14:0, when growth was done at 10 degrees C and unsaturated fatty acids, notably C16:1 (palmitoleic acid), appear, which are present in trace amounts only when bacteria are grown at 40 degrees C. In addition to these changes in the fatty acids, also the amount of O-specific sugars is temperature-dependent. 6-Deoxy-L-altrose which is the only main O-specific sugar in the LPS investigated, amounts to 30-40% (based on LPS dry weight) when grown at 10 degrees C, but only to 13-20% when growth was done at 40 degrees C. The decrease in O-specific material at 40 degrees C can at least partly be explained by the finding of a high number of unsubstituted R core stubs in polyacryl gel-electrophoresis.

Carbohydrate Metabolism↗

Surface antigens defined by monoclonal antibodies as tumor markers in human leukemia.

The detection of surface-linked antigenic determinants by heteroantisera has greatly contributed to a better understanding of the heterogeneity of benign and malignant hematopoietic cells. The difficulties encountered in rendering these heteroantisera specific for a unique cell surface component have been a major drawback to a more rapid development of immunologic cell typing. With the introduction of hybridoma technology, it became possible to obtain monoclonal antibodies and markedly improve immunologic cell typing. We have, therefore, used this new technology for the production of monoclonal antibodies against human leukocyte surface antigens. This paper describes four cell type-specific monoclonal antibodies, which turned out to be very useful reagents in leukemia diagnosis. One of these antibodies, VIM-D5, is directed against a myeloid cell surface antigen. VIL-A1 is specific for the common acute leukemia associated antigen. VIB-C5 recognizes B-cell differentiation antigen and VIE-G4 is specific for glycophorin A, and thus detects erythroid precursor cells.

Antibodies, Monoclonal↗

Comparison of currently available monoclonal antibodies with conventional markers for phenotyping of one hundred acute leukemias.

One hundred acute leukemia cell samples (89 ALL, 11 AMML) derived from children's bone marrow at diagnosis were typed for the reaction with 15 monoclonal antibodies (mAbs). Subdivision in ALL-subgroups was performed according to conventional markers. Only some mAbs like VIL-Al which is directed against the cALL-antigen, can substitute polyclonal rabbit antisera. Additional subclassifications became evident by the use of mAbs for T-cell differentiated ALL forms. However, unexpected negative reactions must be taken into account as observed for all T-directed mAbs with individual T-cell ALL samples.

Acute Disease↗

VIL-A1, a monoclonal antibody reactive with common acute lymphatic leukemia cells.

The VIL-A1 monoclonal antibody raised against Reh cells reacts with common acute lymphatic leukemia (CALL) cells but not with normal or malignant B or T lymphocytes. It also shows no binding to normal or malignant myeloid, monocytic or erythroid cells, nor does it react with thrombocytes. The antibody is of IgM class and lyses CALL cells very efficiently in the presence of rabbit but not human complement. Immunoprecipitation experiments followed by SDS-polyacrylamide gel electrophoresis under reducing conditions revealed that VIL-A1 defines a 95,000 mol. wt membrane protein. Approximately 40% of it binds to lens culinaris lectin. Capping experiments showed that the membrane component defined by VIL-A1 co-caps with the one recognized by another recently described monoclonal antibody to CALL cells (J5).

Antibodies, Monoclonal↗

Anatomical distribution of call antigen expressing cells in normal lymphatic tissue and in lymphomas.

Anatomical distribution of common acute lymphoblastic leukemia antigen (CALLA) was studied in lymphomas as well as in normal lymphatic organs using the monoclonal antibody VIL-A1. Twelve lymphomas were labelled by VIL-A1. Three of the 12 tumours also had T-cell marker, six lymphomas also showed immunoglobulin staining and only three tumours were pure CALLA lymphomas. Tonsils showed a distinct CALLA labelling of many germinal centre cells and of singular cells in interfollicular T-cell regions. Children's thymuses showed rare distinctly labelled cells in the cortex and medulla and slightly more cortical cells stained faintly by VIL-A1. Foetal thymuses of about the twelfth week of gestation contained many heavily labelled cells. The findings are discussed as evidence for the presence of CALLA on immature B as well as T lymphocytes. They favour the idea of CALLA as a common lymphocyte differentiation antigen although other possibilities of interpretation are also discussed.

Antigens, Neoplasm↗

Regulation of pokeweed mitogen-induced human B-cell differentiation: effects of hydrocortisone.

Hydrocortisone (HC), when added in pharmacologically attainable concentrations (10(-6)M) to pokeweed mitogen (PWM) cultures of unseparated human mononuclear cells (MNC) caused a marked enhancement of the in vitro secretion of all three major immunoglobulin (Ig) classes and of two out of three antibody specificities tested x (Ig) M anti-IgG antibodies and anti ss-DNA antibodies, but not anti-tetanus toxoid antibodies). Such an effect was not observed when HC was added to cocultures of isolated B cells with mitomycin C-treated autologous T cells. This result suggests, that HC effects on T-mediated suppressor mechanisms--rather than direct stimulatory effects--on B cells are involved in the observed enhancement of PWM induced in vitro B cell differentiation. One possible explanation for this phenomenon might be that HC, by inhibiting interleukin 2 release, inhibits also suppressor T-cell acitivation. This hypothesis would also fit the observation that HC significantly inhibits concanavalin A-mediated suppression of PWM-induced B cell differentiation, but that it has no effect on in vivo preactivated suppressor T cells from human cord blood.

Antibody-Producing Cells↗

In vitro effects of cyclosporin A (CSA) on human hemopoietic cell lines.

The sensitivity of 18 permanent hemopoietic cell lines to Cyclosporin A (CsA) was tested in a 3H-thymidine incorporation rate assay. Two human T cell lines (Molt4 and CEM) were significantly inhibited by a CsA concentration of 0.5 microgram/ml. Not affected at all or only inhibited by 10 to 20 times higher CsA concentrations were: three human B cell lines (4413a, Daudi, Raji), a monkey B cell line (B95-8), a mouse plasmocytoma line (X63-Ag8/653), a human non-B T cell line (Reh), four human myeloid lines (HL-60, ML-1, ML-2, ML-3), a human myelomonocytic line (Karpas 230), four human monoblastic lines (U 937, SU-DHL-1, THP-1, Karpas 241) and a human erythroid line (K 562). It therefore seems that among permanently growing hemopoietic cells a cell type specificity for T cells also exists.

Animals↗

Monoclonal antibodies to the structural glycoprotein of tick-borne encephalitis virus.

Hybridomas secreting antibodies to the structural glycoprotein of tick-borne encephalitis (TBE) virus were prepared by fusion of X63-Ag8/653 mouse myeloma cells with spleen cells from mice immunized with purified glycoprotein complexes of TBE virus. These antibodies were tested against 10 different TBE virus strains isolated in different European countries over a period of 26 years from different hosts. Quantitative evaluation of enzyme immunoassay results did not reveal any differences in reactivity among these strains, pointing further to the homogeneity of European TBE virus isolates, which has previously been inferred from results obtained by peptide mapping and competitive radioimmunoassay. Hybridomas defining three different antibody-combining sites (epitopes) on the glycoprotein of TBE virus were selected on the basis of cross-reactivity with another flavivirus. West Nile virus, as well as the ability to inhibit hemagglutination. Two epitopes were type specific, and the third was indistinguishably also present on West Nile virus. Hemagglutination was inhibited by monoclonal antibodies reacting with one of the type-specific epitopes as well as the cross-reactive determinant, which is apparently responsible for the broad cross-reactivity among different flaviviruses observed in hemagglutination inhibition tests with polyvalent immune sera.

Animals↗

Expression of a myeloid marker on TdT-positive acute lymphocytic leukemic cells: evidence by double-fluorescence staining.

The expression of a myeloid-specific antigen was detected on TdT-positive blast cell populations in two cases of childhood acute lymphocytic leukemia. Double-fluorescence staining by using the monoclonal antibody, VIM-D5, which is specific for cells of myeloid origin, in combination with TdT antiserum revealed that a distinct portion of the blast cells carried both markers. The finding represents the first direct demonstration of this specific biphenotype in leukemic cells and was interpreted as the abnormal expression of a myeloid antigen on lymphoid blast cells.

Animals↗