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R Mihalik

Publications and source records attributed to R Mihalik.

At least 19 recordsLinked to original sources
PubMed1992

Down-regulation of murine B lymphocyte growth: arrest of B cells in G1 underlies immunosuppression induced by an IgM antibody.

Previous studies have demonstrated that culture supernatants of LPS-stimulated murine splenic B lymphocytes (BLPSSN) are able to inhibit the growth of freshly isolated B cells via an IgM antibody. In this work we investigated the progress of LPS-activated B lymphocytes through the cell cycle in the presence of this antibody. We found that the regulatory IgM did not affect the entry of LPS-stimulated B lymphocytes into G0*, as assessed by the increased expression of I-A antigens. Events that characterize the early G1 phase (G1A), such as cell enlargement and increased RNA synthesis, also occurred in the presence of the antibody. In contrast, events which mark the G1B phase, such as further cell enlargement and late RNA synthesis were inhibited. Moreover, a significant portion of the cells failed to incorporate [3H]thymidine and did not progress through S, G2, or M, as revealed by their DNA content. Therefore, our work points toward a well-defined stage of the early G1 phase at which the antibody inhibits the progression of B lymphocyte activation. This result shows a new insight into the mechanism of antibody-mediated down-regulation of polyclonal B cell responses.

Animals↗
PubMed1992

Autocrine regulation of murine B lymphocyte growth by an IgM antibody.

Culture supernatants of LPS-stimulated murine B lymphocytes are able to inhibit the growth of freshly isolated splenic B cells via an IgM antibody. The binding specificity of this IgM is not yet defined, but appears to be a B lymphocyte surface structure distinct from membrane immunoglobulin, MHC class II antigen, transferrin and Fc gamma receptors, and B220. The regulatory autoantibody allows the normal progression of early, but not late steps in the cycle of polyclonally-stimulated B lymphocytes and does not affect the increased antigen-presenting capacity of activated B cells. Therefore, this autoregulatory cycle is apparently ubiquitous and may be a major component of B lymphocyte homeostasis under physiological, as well as pathological conditions. Moreover, these findings bring into focus a possible regulating role of B lymphocytes in the humoral immune response.

Animals↗
PubMed1991

Correlation of the percentage of activated, CD3 + DR + lymphocytes to serum neopterin level in HIV-seropositive haemophiliacs.

The percentage of activated, CD3+ DR+ and CD8+ Leu7+ lymphocytes and the serum neopterin concentration were determined in 17 HIV-seropositive and 10 HIV-seronegative haemophiliacs and in 11 healthy control subjects. All three parameters tested were found to be significantly higher in the seropositive patients than in the seronegative controls. In the seropositive group, a significant positive correlation was found between the neopterin levels and the percentage of CD3+ DR+ cells. By contrast, no significant negative or positive correlation was observed between the neopterin levels and the percentage of the CD8+ Leu7+ subset. These data suggest that in the HIV-infected patients the activated T cells responsible for the stimulation of macrophages to produce neopterin are those that do not carry CD8.

Adolescent↗
PubMed1991

[Heterogeneity of surface antigens in chronic B-cell lymphoid leukemia].

Clinical and immunological studies of fifty patients with CLL have been performed. No correlation was found either between the clinical stage or clinical course of the disease and the distribution of cell surface makers characteristic of CLL (CD19, CD20, CD21, HLA-DR, sIg). Therapy did not influence the distribution of B lymphocyte subpopulations. On the other hand we recognized differences when examining the B-cell specific features. The CD21 antigen was present in significantly lower proportion when compared to all other B-cell markers. This suggests the presence of immature B-cell population. Correlation studies showed a strong correlation between the presence of the CD5 antigen and the antigens CD19, CD20, HLA-DR and sIg, while a similar correlation could not be proved between the CD5 antigen and CD21 marker. Thus the application of the CD5 antibody together with any of the B-cell markers seems to be sufficient for the diagnostics of CLL with the exception of the CD21 antibody that marks only a small proportion of the B-cell population in CLL, so it can be used for purposes of clinical diagnostics.

Adult↗
PubMed1991

The complement system in HIV disease.

Different aspects of the relationship between the HIV infection and the complement system were studied. 1. No significant differences were found between seronegative controls, asymptomatic, and symptomatic (ARC, AIDS) HIV-seropositive patients in the plasma levels of complement components C4, Bf, and C3. 2. Using sensitive ELISA assays, a significant increase was observed in the levels of protein-protein complexes which are formed at the activation of the classical (C1r-C1s-C1-INH) and alternative (C3b-Bb-P) pathways, indicating that both complement pathways are activated in the HIV disease. No significant differences were found, however, in the levels of these complexes between the groups of asymptomatic and symptomatic HIV-infected patients. 3. Artificial immune complexes of synthetic peptides representing some immunodominant epitopes of HIV envelope (gp120, and gp41) proteins, and human polyclonal anti-HIV IgG were found to weakly activate both the classical and alternative complement pathways. 4. An elevated percentage of the lymphocytes carrying a complement activation fragment, C3d, was detected in the blood of HIV seropositive patients as compared to the seronegative controls. No significant positive correlation was found between the percentage of these cells and that of any T cell subsets tested.

Complement Activation↗
PubMed1991

Flow cytometric analysis of DNA content in focal nodular hyperplasia and hepatocellular carcinoma.

DNA index of twenty-three surgically removed, formalin-fixed and paraffin-embedded liver specimens (10 focal nodular hyperplasias--FNH, and 13 hepatocellular carcinomas--HCC) were studied by flow cytometry. Diploid value appeared in 9/10 FNH (one was hypodiploid), while 10/13 HCC (77%) had DNA aneuploidy (one hypo- and 9 hyperdiploid). The presence of normal DNA content in 3 HCCs suggests that DNA aneuploidy only cannot indicate the malignant transformation of a benign lesion (e.g. FNH).

Adolescent↗
PubMed1991

Characterization of T lymphocyte subsets in hairy cell leukaemia: influence of splenectomy and correlations with the clinical stage of the disease.

Peripheral blood mononuclear cell surface markers were studied in a series of 26 hairy cell leukaemia patients 19 of whom were splenectomized previously. Patients with non-symptomatic and stable disease were distinguished from those with symptomatic and/or progressive disease (also termed "active" clinical stages). In all HCL patients as a group, the absolute number of CD4+ MN cells did not differ statistically from that of the controls, while the number of CD8+ MN cells was significantly increased. The reduction of the CD4/CD8 ratio in the peripheral blood of HCL patients as compared to the controls was explained by the reduction of this ratio in patients with "active disease", while the CD4/CD8 ratio of patients with non-symptomatic and stable disease did not differ statistically from that of the controls. The CD4/CD8 ratio was found to be influenced mainly by the clinical stage of the disease, and not by the effect of splenectomy.

Adult↗
PubMed1991

Peripheral blood leukocyte subpopulations a long time after posttraumatic splenectomy.

Peripheral blood leukocyte subpopulations have been determined in 50 patients a long time (2 to 20 years) after posttraumatic splenectomy. These otherwise healthy individuals had significant lymphocytosis and monocytosis, while the absolute number of granulocytes did not differ statistically from that of the controls. The absolute number of CD2+, CD3+ as well as CD4+ and CD8+ peripheral blood mononuclear cells was found to be elevated, while the number of CD21+, CD20+ and HLA-DR+ PBMN cells was significantly decreased. The absolute number of sIgM+ as well as CD16+ MN cells did not differ statistically from that of the controls. Two further patients were found to have developed B-chronic lymphocytic leukaemia 5 and 31 years following posttraumatic splenectomy, respectively.

Antigens, CD↗
PubMed1990

[Cytochemical, immunologic and gene rearrangement studies in adult acute leukemia].

Results of morphological, cytochemical and immunological studies performed in adult acute leukaemias have been compared. Thirty one cases proved to be acute myeloid leukaemia, while 25 cases were shown to be acute lymphoid leukaemia. Based on our results we conclude that immunophenotyping with monoclonal antibodies does not help in distinguishing the subtypes of AML. For purposes of clinical diagnosis cytochemical methods are valuable. On the other hand the monoclonal antibodies are essential in distinguishing the very immature myeloid and lymphoid leukaemias and this is of great importance from the clinical point of view, in determining therapy. Moreover, the diagnosis of acute lymphoid leukaemias is not possible without the specific monoclonal antibodies. Their application is first of all in haematological centers caring for leukaemia patients nowadays already obligatory. Gene rearrangement studies make the diagnosis more accurate and help in the diagnosis of leukaemias of unknown immunological origin.

Adult↗
PubMed1990

Proteoglycan-targeted antibodies as markers on non-Hodgkin lymphoma xenografts.

A family of mono- and polyclonal antibodies raised against proteoglycans or their "subcomponents" served as novel markers to characterize the phenotypes of three non-Hodgkin lymphoma xenograft lines (HT 58 lymphoblastic, HT 117 centroblastic, HT 130 centrocytic) together with normal, human peripheral blood B lymphocytes. These xenografted NHL lines, maintained by serial transplantations on artificially immunosuppressed mice, expressed very similar B-cell-related antigens and differences on the cell surface (HT 58 greater than HT 117 greater than HT 130 greater than B cells) when they were exposed to monoclonal antibodies (mAb) to cartilage proteoglycans. Anti-proteoglycan antibodies used in this study recognize complex epitopes of core protein segment associated with carbohydrate, shared by human cartilage proteoglycans and certain lymphoma cells. The binding of these antibodies was independent of cell-cycle phase. The results suggest that the anti-proteoglycan mAbs could be used as new phenotypic markers to individualize non-Hodgkin lymphomas.

Animals↗
PubMed1990

Age dependency of the progression of HIV disease in haemophiliacs; predictive value of T cell subset and neopterin measurements.

Sixteen HIV-seropositive haemophiliacs were followed up for 42 months and 9 other patients for 24 months. All patients were infected in 1983 or 1984. T cell subsets and serum neopterin levels were measured twice a year. The patients were divided into three groups according to their age in 1989: group A (children) less than 14 years old (n = 6); group B (adolescents) 14-20 years old (n = 8); group C (adults) greater than 20 years old (n = 11). At the last measurement performed in November, 1989, patients of group A had significantly higher absolute number and percentage of CD4+ lymphocytes and significantly lower serum neopterin levels than patients of group B and C. In addition, the percentage of the activated, CD3+ DR+ lymphocytes was also significantly higher in the adult-adolescent group than in the children group. Until the end of December, 1989, AIDS developed in 0, 1 and 2 patients and ARC was diagnosed in 0, 5, and 2 patients of groups A, B, and C, respectively. The progression of the HIV disease towards AIDS in these patients was predicted by the T cell subset and neopterin measurements performed in 1987. Only those 3 patients who progressed to AIDS had CD4+ cells less than 350/microliters and a neopterin value of more than 20 nmol/l. These findings confirm previous observations indicating that in patients with haemophilia the progression of HIV disease is influenced by age: a relatively slow progression can be expected in prepuberty children.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Differences in non-MHC restricted cytotoxic activities of human peripheral blood lymphocytes after transfusion with allogeneic leukocytes or platelets possessing class I and/or class II MHC molecules.

MHC-unrestricted cytotoxic activity of peripheral blood lymphocytes (PBL) from 4-6 healthy donors was investigated before and after transfusion with allogeneic leukocytes or platelets. Natural killer and lectin-dependent cellular cytotoxicity (LDCC) of PBL was tested against K562 and Raji target cells in a 4-h and 16-h 51Cr-release assay, respectively. After allotransfusion with leukocytes, we found increased cytotoxic activity of each donor's PBL against all the three targets on day 3 or 7. The highest non-specific cytotoxic activity was detected against the relatively NK resistant Raji target cells. The increase of cytotoxic activity was lowest against the LDCC target (PHA-treated Raji) cells. On the contrary, no changes in cytotoxic activity against any targets were observed after allotransfusion with platelets (possessing class I HLA antigens but no HLA class II molecules). Our results suggest that HLA class II molecules, presumably by inducing immune responses, are essential for activation/generation of non-specific killing of tumor targets after leukocyte transfusion. Thrombocytes, known to be less immunogenic than leukocytes, are not effective in in vivo enhancing of non-specific cytotoxicity. Cellular activation of PBL following leukocyte allotransfusion was confirmed by detection of elevated serum neopterin and beta-2-microglobulin levels on day 3. This was not the case after platelet allotransfusion. In addition, the expression of ICAM-1 antigen (as a molecule involved directly in MHC-unrestricted cytotoxicity) was also found to be increased in two donors' PBL on day 3 after leukocyte transfusion in contrast to transfusion with platelets.

Biopterins↗
PubMed1990

Activation of lymphocytes after platelet allotransfusion possessing only class I MHC product.

After platelet allotransfusion, we found a characteristic increase in the expression of interleukin-2 receptor, dipeptydilpeptidase IV (CD26), activation-inducer molecule (AIM, CD69) and transferrin receptors (CD71) on day 3 indicating that important functional molecules expressed on the activation of lymphocytes by allogeneic platelets. At the same time, no consistent increase of other activation molecules such as Ki-l (CD30), intercellular adhesion molecule (ICAM-1, CD54) and Ki-24 (CDw70) antigen expression was detected, probably as a result of the selective activation of some lymphocyte subsets. In order to obtain further evidence for the in vivo activation triggered by allogeneic platelets, subsequent step of T cell activation towards differentiation was investigated with monoclonal antibodies to leucocyte common antigens. A sharp expression of the UCHL1, coupled with a decrease of the CD45R molecule was detected on day 7 or 14, suggesting a T cell priming.

Antibodies, Monoclonal↗
PubMed1990

Ultrastructure and antigenicity of the unique cell wall pimple of the Candida opaque phenotype.

Cells of Candida albicans WO-1 switch frequently and reversibly between two colony-forming phenotypes, white and opaque. In the white form, budding cells appear similar to those of most other strains of C. albicans, but in the opaque form, budding cells are larger, are bean shaped, and possess pimples on the wall. These pimples exhibit a unique and complex morphology. With scanning electron microscopy, a central pit can be discerned, and in many cases, a bleb can be observed emerging from the pimple center. With transmission electron microscopy, channels are evident in some pimples and vesicles are apparent under the pimple in the cytoplasm, in the actual wall of the pimple, or emerging from the tip of the pimple. A large vacuole predominates in the opaque-cell cytoplasm. This vacuole is usually filled with spaghettilike membranous material and in a minority of cases is filled with vesicles, many of which exhibit a relatively uniform size. An antiserum to opaque cells recognizes three opaque-cell-specific antigens with molecular masses of approximately 14.5, 21, and 31 kilodaltons (kDa). Absorption with nonpermeabilized opaque cells demonstrated that only the 14.5-kDa antigen is on the cell surface; indirect immunogold labeling demonstrated that it is localized in or on the pimple. The possibility is suggested that the vacuole of opaque cells is the origin of membrane-bound vesicles which traverse the wall through specialized pimple structures and emerge from the pimple with an intact outer double membrane, a unique phenomenon in yeast cells. The opaque-cell-specific 14.5-kDa antigen either is in the pimple channel or is a component of the emerging vesicle. The functions of the unique opaque-cell pimple and emerging vesicle are not known.

Antigens, Fungal↗
PubMed1990

Bigenotypic and biphenotypic appearance of immunoglobulin light chains in 1 of 3 non-Hodgkin's lymphoma xenografts.

Chromosomal analysis of three human non-Hodgkin's lymphoma (NHL) xenografts revealed common extra 14q+ segment and other individual clonal markers without involvement of immunoglobulin light-chain regions. Two NHL xenografts (HT 58 and HT 130) showed restricted lambda light chain expression and deleted kappa and rearranged lambda genes. However, in HT 117 both kappa and lambda chains were present on the cell surface, and both light chain genes showed rearranged alleles. This unique phenomenon could have resulted from either disturbed regulation of isotype exclusion or from the malignant transformation of light chain 'uncommitted' B cells.

Animals↗
PubMed1990

Pheno- and genotypic characteristics of human non-Hodgkin lymphoma xenografts.

The three human non-Hodgkin lymphoma xenografts with different morphological appearance (lymphoblastic, centroblastic, centrocytic) had many common pheno- and genotypic features positivity of B-cell markers, 14q+ chromosomal abnormality, etc.). Furthermore, two lines (HT 58 and 130) expressed lambda light chain monoclonally. The third line (HT 117) showed bigenotypic rearrangement of light genes. A set of new anti-proteoglycan markers, especially anti-chondroitin sulfate mAbs made possible to individualize the xenografts.

Animals↗
PubMed1990

Clinical value of cytomorphologic, immunologic and cytogenetic investigations of acute leukaemias.

The valuability of immunophenotyping of acute myeloid and lymphoid leukaemias in comparison to morphological and cytochemical classification were approached in 56 cases. In the case of acute myeloid leukaemias the immunophenotyping by monoclonal antibodies CD14, CD13, CD33 was less informative concerning the subtypes of the disease. The clinical diagnosis can be achieved on the basis of cytochemical investigation alone. In contrast, the diagnosis of lymphoid leukaemias requires all information obtained by immunophenotyping by a series of monoclonal antibodies CD3, CD2, CD4, CD8, CD1, CD19, CD20, CD21 and CD10. On the other hand, the monoclonal antibodies are essential in differentiation of the very immature myeloid and lymphoid leukaemias. This is of great importance from the clinical point of view for determining the therapy. Molecular genetic studies based on the characterisation of the state of gene rearrangement of immunoglobulin and T-cell receptor beta chains have basic importance in the confirmation of the result of immunophenotyping and in the determination of leukaemias of unknown origin.

Acute Disease↗