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1.
Pathol Oncol Res ; 15(2): 251-6, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19020994

ABSTRACT

Transforming growth factor beta1 (TGFbeta1) is an important immunosuppressive cytokine. Defects in its production by lymphocytes and the failure of TGFbeta1 to regulate immunological functions have been described in SLE. Expression of TGFbeta1 and the related signaling pathway was studied in the peripheral lymphocytes of SLE patients. The total plasma TGFbeta1 level in active and inactive SLE patients compared to healthy controls was also measured. TGFbeta1 and all downstream signaling elements were expressed in normal cells. However, in more than 50% of SLE patients the isolated T cell population showed no TGFbeta1 mRNA expression and at least one member of the TGFbeta1 pathway was also missing (TGFbeta-RI, Smad2 and Smad3) in more than half of the patients. Total plasma TGFbeta1 level was increased in both active and inactive SLE groups compared to normal controls (p< 0.05). These data raise questions about the availability of TGFbeta1 signaling in lymphocytes in SLE patients, however, the elevated total plasma TGFbeta1 level suggests that the failure of TGFbeta1 effects is not the consequence of low level of this cytokine in SLE.


Subject(s)
Lupus Erythematosus, Systemic/genetics , Lymphocytes/metabolism , Protein Serine-Threonine Kinases/genetics , Receptors, Transforming Growth Factor beta/genetics , Smad2 Protein/genetics , Smad3 Protein/genetics , Transforming Growth Factor beta1/genetics , Adolescent , Adult , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Lupus Erythematosus, Systemic/metabolism , Lupus Erythematosus, Systemic/pathology , Lymphocytes/pathology , Male , Middle Aged , Protein Serine-Threonine Kinases/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptor, Transforming Growth Factor-beta Type I , Receptors, Transforming Growth Factor beta/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction , Smad2 Protein/metabolism , Smad3 Protein/metabolism , Transforming Growth Factor beta1/metabolism , Young Adult
2.
Pathol Oncol Res ; 13(4): 311-9, 2007.
Article in English | MEDLINE | ID: mdl-18158566

ABSTRACT

Myelodysplastic syndromes (MDSs) are a heterogeneous group of hematological disorders characterized by ineffective hematopoiesis, enhanced bone marrow apoptosis and frequent progression to acute myeloid leukemia. Several recent studies suggested that, besides the abnormal development of stem cells, microenvironmental alterations are also present in the MDS bone marrow. In this study, we have examined the relative frequencies of stem and progenitor cell subsets of MDS and normal hematopoietic cells growing on stromal cell layers established from MDS patients and from normal donors. When hematopoietic cells from MDS patients were co-cultured with normal stromal cells, the frequency of either early or late cobblestone area-forming cells (CAFC) was significantly lower compared to the corresponding normal control values in 4 out of 8 patients. In the opposite situation, when normal hematopoietic cells were incubated on MDS stromal cells, the CAFC frequencies were decreased in 5 out of 6 patients, compared to normal stromal layer-containing control cultures. Moreover, a soluble Notch ligand (Jagged-1 protein) was an inhibitor of day-35-42 CAFC when normal hematopoietic cells were cultured with normal or MDS stromal cells, but was unable to inhibit MDS stem and early progenitor cell growth (day-35-42 CAFC) on pre-established stromal layers. These findings suggest that in early hematopoietic cells isolated from MDS patients the Notch signal transduction pathway is disrupted. Furthermore, there was a marked reduction in the plasticity of mesenchymal stem cells of MDS patients compared with those of normal marrow donors, in neurogenic and adipogenic differentiation ability and hematopoiesis supporting capacity in vitro. These results are consistent with the hypothesis that when alterations are present in the myelodysplastic stroma environment along with intrinsic changes in a hematopoietic stem/progenitor cell clone, both factors might equally contribute to the abnormal hematopoiesis in MDS.


Subject(s)
Hematopoietic Stem Cells/cytology , Mesenchymal Stem Cells/cytology , Myelodysplastic Syndromes/pathology , Receptors, Notch/metabolism , Aged , Aged, 80 and over , Bone Marrow Cells/cytology , Calcium-Binding Proteins/pharmacology , Cell Differentiation , Cells, Cultured , Coculture Techniques , Female , Hematopoiesis , Hematopoietic Stem Cells/drug effects , Humans , Intercellular Signaling Peptides and Proteins/pharmacology , Jagged-1 Protein , Male , Membrane Proteins/pharmacology , Middle Aged , Myelodysplastic Syndromes/metabolism , Serrate-Jagged Proteins , Stromal Cells/cytology
3.
Orv Hetil ; 148 Suppl 1: 39-42, 2007 Apr 08.
Article in Hungarian | MEDLINE | ID: mdl-17430793

ABSTRACT

Although it is clear that immunologic mechanisms play a significant role in the pathophysiology of many hematologic diseases, there are relative few situations where it is possible to gain a detailed understanding of immune damage in vivo in humans. Autoimmune hemolytic anemia, immune thrombocytopenia and immune neutropenia as antibody-mediated cell-specific disorders are of particular interest in this regard. Autoimmune hemolytic anemia represents a group of disorders in which individuals produce antibodies directed toward one or more of their own erythrocyte membrane antigens. This leads to destruction of the antibody-coated erythrocytes. The pathophysiology of the decreased erythrocyte survival has been examined with increasing sophistication for many years. This paper first discusses the underlying mechanisms responsible for autoimmune hemolytic anemias then consider immune thrombocytopenia and immune neutropenia.


Subject(s)
Anemia, Hemolytic, Autoimmune/immunology , Autoantibodies/blood , Neutropenia/immunology , Purpura, Thrombocytopenic, Idiopathic/immunology , Autoantibodies/metabolism , Humans , Immunity, Cellular
4.
Cell Biol Int ; 30(5): 401-5, 2006 May.
Article in English | MEDLINE | ID: mdl-16621624

ABSTRACT

There is an increasing body of evidence that suggests that genes involved in cell fate decisions and pattern formation during development also play a key role in the continuous cell fate decisions made by adult tissue stem cells. Here we show that prolonged in vitro culture (14 days) of murine bone marrow lineage negative cells in medium supplemented with three early acting cytokines (stem cell factor, Flk-2/Flt-3 ligand, thrombopoietin) and with immobilized Notch ligand, Jagged-1, resulted in robust expansion of serially transplantable hematopoietic stem cells with long-term repopulating ability. We found that the absolute number of marrow cells was increased approximately 8 to 14-fold in all cultures containing recombinant growth factors. However, the frequency of high quality stem cells was markedly reduced at the same time, except in cultures containing growth factors and Jagged-1-coated Sepharose-4B beads. The absolute number of hematopoietic cells with long-term repopulating ability was increased approximately 10 to 20-fold in the presence of multivalent Notch ligand. These results support a role for combinatorial effects by Notch and cytokine-induced signaling pathways in regulating hematopoietic stem cell fate and to a potential role for Notch ligand in increasing cell numbers in clinical stem cell transplantation.


Subject(s)
Calcium-Binding Proteins/pharmacology , Cell Proliferation/drug effects , Hematopoietic Stem Cells/drug effects , Membrane Proteins/pharmacology , Stem Cell Factor/pharmacology , Thrombopoietin/pharmacology , Animals , Cell Count , Cells, Cultured , Female , Hematopoietic Stem Cell Transplantation , Intercellular Signaling Peptides and Proteins , Jagged-1 Protein , Male , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Receptors, Notch/metabolism , Sepharose/pharmacology , Serrate-Jagged Proteins , Time
5.
Eur J Haematol ; 75(4): 346-51, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16146542

ABSTRACT

OBJECTIVES: Accumulating evidence suggests that non-T, non-B cell CD4+CD56+ neoplasms with lymphoblastic morphology include clinically and immunophenotypically diverse entities. Although their cells of origin or classification are still controversial several entities clearly represent a distinct type of neoplasms that are clinically aggressive. METHODS: In this work we present the immunophenotypic and genotypic features of bone marrow (BM), peripheral blood (PB), lymph node and skin lymphocytes from a patient diagnosed as plasmacytoid dendritic cell leukemia involving the skin, BM, PB, lymph nodes, liver and spleen. For determination of immunophenotypic characteristics of malignant plasmacytoid dendritic cells 73 monoclonal antibodies detecting lineage markers, chemokine receptors, cytokine receptors, activation, and co-stimulatory molecules were used. RESULTS AND CONCLUSION: The malignant cells proved to express CD4+, CD56+ lineage negative leukemia phenotype characteristically positive for CD36, CD38, CD40, CD45, CD45RA, CD68, CD123, CD184, HLA-DR, BDCA2, and granzyme-B corresponding to the preplasmacytoid dendritic cell developmental stage. The presence of CD11a/CD18, CD84, CD91, CD95, alphavbeta5, CDw197, and the absence of CD52 and CD133 in this case can be regarded as additional features of malignant cells. Completing the immunophenotypes with multidrug resistance function can provide additional information for characterizing pDC leukemia.


Subject(s)
Dendritic Cells/pathology , Leukemia/pathology , Plasmacytoma/pathology , Aged , Blood Cells/pathology , CD4 Antigens , CD56 Antigen , Cell Lineage , Flow Cytometry , Humans , Immunophenotyping , Lymph Nodes/pathology , Male , Skin/pathology
6.
Orv Hetil ; 146(7): 309-16, 2005 02 13.
Article in Hungarian | MEDLINE | ID: mdl-15782794

ABSTRACT

Notch signaling defines an evolutionarily ancient cell interaction mechanism. The signals transmitted through the Notch receptor, in combination with other cellular factors influence differentiation, proliferation and apoptotic events at all stages of development. Recent advances have elucidated both the biochemical mechanism regulating receptor activation and the molecular participants forming the intracellular signaling cascade. Authors present description of the main signaling components involved in the Notch pathway and how it can affect the growth and function of lymphocytes. Notch signaling is critical during lymphocyte development, and dysregulation of the pathway can give rise to leukemia. It is conceivable that appropriate manipulation of Notch signaling may become a useful tool in addressing a variety of human dysplastic condition and tissue regeneration.


Subject(s)
Hematopoiesis , Hematopoietic Stem Cells/metabolism , Membrane Proteins/physiology , Signal Transduction , Animals , Cell Differentiation , Cell Division , Hematopoiesis/physiology , Hematopoietic Stem Cells/physiology , Humans , Membrane Proteins/metabolism , Receptors, Notch
7.
Cancer Immunol Immunother ; 53(9): 835-9, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15052374

ABSTRACT

The aim of this study was to determine the complement functions, the serum levels of the complement components C3 and C4, and circulating immune complexes during autologous blood stem cell transplantation. Seventeen lymphoma patients receiving transplants between 1997 and 2001 were involved in this study. High-dose chemotherapy with or without total body irradiation was used for conditioning. The transplantation resulted in complete remission without complications in 14 patients. Early relapse developed in one case and two nonrelapsed patients suffered from serious toxic infection early posttransplant. Normal values of CH50, C3, C4, and immune complexes in sera of patients were detected on day -7, before the conditioning (day of transplantation was determined as day 0). After the conditioning, on day -2, the levels of the CH50, C3, and C4 decreased significantly ( p<0.05) in all patients compared with the starting values. The CH50, C3, and C4 levels exceeded the starting values in the noninfected patients from day +7. In two patients suffering from toxic infection, significantly elevated complement levels were documented early posttransplant. In the relapsed patient a significant decrease of the complement parameters was documented posttransplant accompanied by a significant elevation in the immune complex level. The results show alteration in the complement parameters during transplantation, but in the complication-free cases this remained within the normal ranges. However, an unusual elevation seemed to be the sign of infection, and the significant decrease seemed to indicate a relapse.


Subject(s)
Antigen-Antibody Complex/metabolism , Complement C3/metabolism , Complement C4/metabolism , Hodgkin Disease/metabolism , Lymphoma, Non-Hodgkin/metabolism , Stem Cell Transplantation , Adult , Complement Hemolytic Activity Assay , Female , Hodgkin Disease/immunology , Hodgkin Disease/therapy , Humans , Lymphoma, Non-Hodgkin/immunology , Lymphoma, Non-Hodgkin/therapy , Male , Middle Aged , Transplantation Conditioning , Transplantation, Autologous , Whole-Body Irradiation
8.
J Leukoc Biol ; 75(4): 714-20, 2004 Apr.
Article in English | MEDLINE | ID: mdl-14742638

ABSTRACT

Stem cells reside in customized microenvironments (niches) that contribute to their unique ability to divide asymmetrically to give rise to self and to a daughter cell with distinct properties. Notch receptors and their ligands are highly conserved and have been shown to regulate cell-fate decisions in multiple developmental systems through local cell interactions. To assess whether Notch signaling may regulate hematopoiesis to maintain cells in an immature state, we examined the functional role of the recombinant, secreted form of the Notch ligand Jagged-1 during mouse hematopoietic stem cell (HSC) and progenitor cell proliferation and maturation. We found that ligand immobilization on stromal layer or on Sepharose-4B beads is required for the induction of self-renewing divisions of days 28-35 cobblestone area-forming cell. The free, soluble Jagged-1, however, has a dominant-negative effect on self-renewal in the stem-cell compartment. In contrast, free as well as immobilized Jagged-1 promotes growth factor-induced colony formation of committed hematopoietic progenitor cells. Therefore, we propose that differences in Jagged-1 presentation and developmental stage of the Notch receptor-bearing cells influence Notch ligand-binding results toward activation or inhibition of downstream signaling. Moreover, these results suggest potential clinical use of recombinant Notch ligands for expanding human HSC populations in vitro.


Subject(s)
Cell Differentiation/physiology , Hematopoiesis/genetics , Hematopoietic Stem Cells/metabolism , Proteins/metabolism , Receptors, Cell Surface/metabolism , Transcription Factors , Animals , Calcium-Binding Proteins , Cell Differentiation/drug effects , Cell Division/drug effects , Cell Division/genetics , Cell Survival/drug effects , Cell Survival/genetics , Cells, Cultured , Female , Growth Substances/pharmacology , Hematopoiesis/drug effects , Hematopoietic Cell Growth Factors/metabolism , Hematopoietic Cell Growth Factors/pharmacology , Hematopoietic Stem Cell Transplantation/methods , Hematopoietic Stem Cells/drug effects , Intercellular Signaling Peptides and Proteins , Jagged-1 Protein , Male , Membrane Proteins , Mice , Mice, Inbred C57BL , Proteins/genetics , Proteins/pharmacology , Receptor, Notch1 , Receptors, Cell Surface/drug effects , Serrate-Jagged Proteins , Signal Transduction/drug effects , Signal Transduction/genetics
9.
Orv Hetil ; 144(36): 1755-61, 2003 Sep 07.
Article in Hungarian | MEDLINE | ID: mdl-14579672

ABSTRACT

Bone marrow transplantation is a complex medical procedure in which hematopoietic stem and progenitor cells are infused into a patient following high-dose chemotherapy with or without irradiation. Because the allogeneic transplantation is associated with life-threatening physical morbidity, lengthy convalescence, and special isolation, the potential for significant psychosocial uncertainty and psychological morbidity is high in adult patients. This work provides an overview of the medical procedures used in allogeneic transplantation and a review of psychosocial and behavioral issues relevant to transplantation. The discussion is limited to psychosocial issues pertinent to transplant recipients and donors, even though transplantation raises significant psychological issues for medical staff, families and caregivers of recipients.


Subject(s)
Adaptation, Psychological , Bone Marrow Transplantation/psychology , Stress, Psychological/etiology , Decision Making , Humans , Living Donors , Psychology, Medical , Transplantation Conditioning/psychology , Transplantation, Homologous
10.
Orv Hetil ; 144(22): 1069-76, 2003 Jun 01.
Article in Hungarian | MEDLINE | ID: mdl-12847816

ABSTRACT

INTRODUCTION: Coeliac disease (gluten sensitive enteropathy) is a very frequent disease appearing in variegated clinical form. In the last decade--concerning the immunogenetic and immunopathological aspects of the disease many of new recognition came to alight. AIM: As the disease can lay hidden in its non classical manifesting form for a very long time, authors wished to study the efficacy of screening, which may be introduced for patients attending immunological outpatient care service. PATIENTS, METHODS AND RESULTS: In the frame of nation-wide patient care, out of the 200 potential patients sent for immunological check up, various form of coeliac disease was diagnosed in 20 cases. Among these cases there are two--presented for the first time--which are connected to bone marrow transplantation. Based on the immunogenetics and autoantibody serology as well as on small intestine biopsies the following conclusions were made. CONCLUSION: 1. Coeliac disease in Hungary is very frequent. Hidden disease should be considered first of all in cases of malabsorption symptoms. 2. Demonstration of autoantibodies on wide-scale palette helps to state the diagnosis based on the systematic auto-immune disease connection. 3. Study of Human Leukocyte Antigen allotype (HLA-DQA1*0501/DQBI*02) applied as marker can considerably support the suspicion of disease. 4. Histology test of the small intestine cannot be omitted.


Subject(s)
Ambulatory Care , Autoantibodies/blood , Celiac Disease/diagnosis , Celiac Disease/immunology , Intestine, Small/pathology , Mass Screening/methods , Adolescent , Adult , Age of Onset , Aged , Biopsy , Celiac Disease/genetics , Female , HLA-DQ Antigens/genetics , Humans , Immunoglobulins/blood , Male , Middle Aged
11.
Pathol Oncol Res ; 9(2): 131-3, 2003.
Article in English | MEDLINE | ID: mdl-12858220

ABSTRACT

Relapse is the main cause of treatment failure following hematopoietic stem cell transplantation for blastic phase chronic myeloid leukemia. Treatment options including donor lymphocyte infusion, second transplantation, interferon- and re-induction chemotherapy are often unsuccessful. We report a patient with blastic phase chronic myeloid leukemia relapsing after allogeneic stem cell transplantation. The post-transplant leukemia was characterized with B-lymphoid markers and multiple genetic abnormalities including double Ph-chromosomes. The disease was treated with three courses of salvage chemotherapy combined with donor lymphocyte infusion and bcr-abl tyrosine kinase inhibitor. The leukemia proved to be non-responsive both to immune therapy and STI 571. The presented case demonstrates the need for combination approaches in post-transplant relapsed leukemia and discusses the possible contributing mechanisms of STI-571 resistance.


Subject(s)
Blast Crisis/therapy , Bone Marrow Transplantation , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Leukocyte Transfusion , Piperazines/therapeutic use , Pyrimidines/therapeutic use , Antineoplastic Agents/therapeutic use , B-Lymphocytes/pathology , Benzamides , Drug Resistance, Neoplasm , Enzyme Inhibitors/therapeutic use , Fusion Proteins, bcr-abl/antagonists & inhibitors , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/therapy , Protein-Tyrosine Kinases/antagonists & inhibitors , Remission Induction , Salvage Therapy , Tissue Donors , Transplantation, Homologous , Treatment Outcome
12.
Orv Hetil ; 144(19): 907-16, 2003 May 11.
Article in Hungarian | MEDLINE | ID: mdl-12809067

ABSTRACT

The authors survey the clinical, immunophenotypic, cytogenetic, molecular genetic spectrum and pathogenetic mechanisms of donor cell derived acute leukemias after allogeneic bone marrow transplantation. The main aspects for detection of donor cell origin and the available therapeutic approaches are discussed through demonstration of one documented patient and data of the literature. Several hypotheses are summarized which try to explain how donor cell leukemia might arise including occult leukemia in the donor cells, transfer of oncogene from host to donor cells and the role of impaired immune surveillance. Investigation of donor cell leukemia cases might bring closer to understand the pathogenesis of leukemia serving as a model for studying the leukemiagenesis in vivo.


Subject(s)
Bone Marrow Transplantation/adverse effects , Leukemia/etiology , Leukemia/therapy , Neoplasms, Second Primary/etiology , Neoplasms, Second Primary/therapy , Acute Disease , Bone Marrow Transplantation/methods , Humans , Immunophenotyping , Incidence , Leukemia/immunology , Leukemia/pathology , Neoplasms, Second Primary/immunology , Neoplasms, Second Primary/pathology , Risk Factors , Transplantation, Homologous
13.
Acta Microbiol Immunol Hung ; 50(1): 55-65, 2003.
Article in English | MEDLINE | ID: mdl-12793201

ABSTRACT

Reaction patterns of the 7th Human Leukocyte Differentiation Antigen Workshop blind panel adhesion molecules were studied on CD3/CD4, CD3/CD8, CD3/TCR gamma delta double positive T cells from peripheral blood of patients with chronic graft versus host disease (n = 8) and healthy controls (n = 4). Reactivity of 14 adhesion antibodies was tested by three-colour immunophenotyping. The mean proportion of CD3+ T cells (69 +/- 19%). CD3/CD8++ (31 +/- 13%) and CD3/TCR gamma delta++ (4 +/- 2%) T sub-populations of patients were comparable with the healthy controls. However, the mean percentage of CD3/CD4++ T cell subset in patients (14 +/- 12%) proved to be significantly decreased in comparison with the normal control value (34 +/- 16%) presumably due to secondary immunodeficiency. The workshop antibodies proved to be reactive with three T cell subsets expressing the examined antigens. Based on the results of the adhesion molecule workshop new CD categories have been introduced: CD156b as a transmembrane protein, CD167a as an epithelial tyrosin kinase receptor, CD168 as a receptor for hyaluronan mediated motility (RHAMM) and CD171 as a co-stimulatory adhesion molecule. There were significant differences in the expression of the CD167a and CD156b antigens on the CD3/CD4++ subset between the samples of patients compared with the controls characterizing the CD4+ T lymphocyte subpopulation in chronic graft versus host disease.


Subject(s)
Antigens, CD/metabolism , Graft vs Host Disease/immunology , Membrane Proteins , Receptors, Antigen, T-Cell, gamma-delta/metabolism , T-Lymphocyte Subsets/immunology , ADAM Proteins , Adult , CD3 Complex/metabolism , CD4 Antigens/metabolism , CD8 Antigens/metabolism , Chronic Disease , Extracellular Matrix Proteins/metabolism , Female , Hematopoietic Stem Cell Transplantation , Humans , Hyaluronan Receptors/metabolism , Immunophenotyping , Male , Metalloendopeptidases/metabolism , Middle Aged , T-Lymphocyte Subsets/metabolism , Transplantation, Homologous
14.
Acta Haematol ; 109(3): 124-8, 2003.
Article in English | MEDLINE | ID: mdl-12714821

ABSTRACT

Homogeneous immunoglobulins are frequently detected in the serum of patients undergoing allogeneic bone marrow transplantation (BMT). The aim of the present study was to further characterize the incidence of this phenomenon and its correlations with laboratory and clinical data. Serum samples were gathered from 29 patients undergoing allogeneic or syngeneic BMT for chronic myeloid leukemia (CML), and serial protein (IgG, IgA and IgM) quantification, electrophoresis and immunofixation were performed. Transient mono- or oligoclonal gammopathies were observed in 23 out of 29 patients between days 20 and 1,750 following transplantation. The presence of homogeneous immunoglobulins was not correlated with the following clinical parameters: graft-versus-host disease, bacterial sepsis, Epstein-Barr virus or cytomegalovirus infection or invasive fungal infection. Therefore, the development of mono- or oligoclonal immunoglobulins may represent a complex disorder of B cell regeneration which may be caused by an intrinsic B cell defect, or a failure in the regenerating T cell system, or both, manifesting itself in a restricted antibody diversity after allogeneic BMT.


Subject(s)
Bone Marrow Transplantation/immunology , Immunoglobulins/blood , Adolescent , Adult , Antibodies, Monoclonal/blood , Antibody Diversity , B-Lymphocytes/immunology , Female , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/immunology , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/therapy , Male , Middle Aged , Models, Immunological , Transplantation, Homologous , Transplantation, Isogeneic
15.
Cytokine ; 18(6): 340-3, 2002 Jun 21.
Article in English | MEDLINE | ID: mdl-12160523

ABSTRACT

We have investigated the influence of apo(a) genetics on the relationship between interleukin (IL)-6, and lipoprotein (a) [Lp(a)] levels in 154 patients with monoclonal gammopathy and 189 healthy subjects. No significant differences in Lp(a) levels and distribution of subjects with different sizes of apo(a) isoforms were found between patients and healthy controls. Relationship between IL-6 and Lp(a) levels was strongly dependent on the size of apo(a) isoforms. In patients with high-size apo(a) isoforms Lp(a) levels positively correlated (r=0.475, P=0.0007) to IL-6 concentrations, whereas no correlation was found in patients with low apo(a) isoforms. Our present finding may provide a plausible explanation for the contradictory findings about the acute phase protein nature of Lp(a).


Subject(s)
Apolipoproteins A/biosynthesis , Apolipoproteins A/chemistry , Interleukin-6/biosynthesis , Lipoprotein(a)/biosynthesis , Paraproteinemias/metabolism , Adult , Aged , Case-Control Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Interleukin-6/blood , Male , Middle Aged , Multiple Myeloma/metabolism , Polymorphism, Genetic , Protein Isoforms , Waldenstrom Macroglobulinemia/metabolism
16.
Haematologia (Budap) ; 32(3): 175-90, 2002.
Article in English | MEDLINE | ID: mdl-12611479

ABSTRACT

Stem cells have traditionally been characterized as either embryonic (pluripotent) or tissue-specific (multipotent). Thus, tissue-specific stem cells generate the cell types comprising a particular tissue in embryos and, in some cases, adults. A recent series of studies, however, has challenged the notion of lineage restriction in multipotent stem cells. These experiments have been interpreted as evidence that stem cells from one tissue can be induced to differentiate into cells of other organs, either in vitro or after transplantation in vivo. This paper reviews the current evidence for stem cell plasticity. Some of the potential caveats to the current work are also discussed and, finally, the potential underlying mechanisms of stem cell plasticity are examined.


Subject(s)
Stem Cells/cytology , Animals , Cell Differentiation , Cell Lineage , Humans , Multipotent Stem Cells/cytology , Pluripotent Stem Cells/cytology , Signal Transduction , Transcription Factors/physiology
17.
Haematologia (Budap) ; 32(3): 265-9, 2002.
Article in English | MEDLINE | ID: mdl-12611486

ABSTRACT

Telomerase is the enzyme responsible for synthesizing telomeric repeats at the ends of chromosomes to maintain telomere length. Recent studies have suggested that telomere shortening may serve as a surrogate marker of the progression of malignant disorders and seems to be accelerated in allogeneic bone marrow transplant recipients. In this study, the results of the telomere length of nine cord blood mononuclear cell samples are presented. Telomere length was measured by the flow-FISH method, using a peptide nucleic acid probe. The proportion of cord blood cell subsets (CD19/CD34/CD3) was also evaluated. The telomere length of the internal control 1301 cell line was estimated to be 100%. The mean telomere length of cord blood cells was 18.5 +/- 3.9%, compared with the internal control. The progenitor CD34+ cells were detected as 2.6 +/- 0.7% in the lymphoid gate measured. Linear correlation analysis did not find any connection between the cell subsets (CD3+, CD34+, CD19+) and the telomere length. The findings confirm that the telomere flow-FISH method is sufficient for estimation of the telomere length. Assessment of the current procedures of collection, manipulation, and ex vivo expansion of cord blood cells in terms of their effect on telomere shortening might be important.


Subject(s)
Fetal Blood/cytology , In Situ Hybridization, Fluorescence , Telomere/ultrastructure , Blood Specimen Collection , Cell Culture Techniques , Humans , Methods
18.
Haematologia (Budap) ; 32(4): 519-27, 2002.
Article in English | MEDLINE | ID: mdl-12803128

ABSTRACT

An unusual case of hepatosplenic gamma delta T-cell lymphoma with leukemic phase in a 39-year-old woman is reported. At the first presentation she had splenomegaly and pancytopenia diagnosed as hypersplenia treated by splenectomy. Subsequently, she developed hepatomegaly and progressive neoplastic lymphocytosis. The bone marrow showed a sinusoidal infiltrate of medium-sized cells. Flowcytometric analysis of peripheral blood mononuclear cells demonstrated expression of CD3, CD7, CD16, CD56 antigens and T-cell receptor gamma delta. A monoclonal TCR gamma- and beta-chain gene rearrangement were detected by polymerase chain reaction. The patient was treated by traditional chemotherapy and alpha-interferon, unsuccessfully. Therefore, 2-chlorodeoxyadenosine was introduced resulting in a complete remission for 6 months. The reported case demonstrates the usefulness of 2-chlorodeoxyadenosine in treatment of hepatosplenic gamma delta T-cell lymphoma.


Subject(s)
Antineoplastic Agents/therapeutic use , Cladribine/therapeutic use , Lymphoma, T-Cell/drug therapy , Lymphoma, T-Cell/immunology , Receptors, Antigen, T-Cell, gamma-delta/metabolism , Adult , Female , Hepatomegaly/drug therapy , Humans , Lymphoma, T-Cell/pathology , Recurrence , Remission Induction , Splenomegaly/drug therapy
19.
Pathol Oncol Res ; 3(1): 44-46, 1997.
Article in English | MEDLINE | ID: mdl-11173624

ABSTRACT

10 consecutive patients with HSV-associated chronic oral lesions were treated with Egiferon for ten days. There were a statistically significant increase in the Large Granule Lymphocyte (LGL) counts and the number of spontaneous E rosette forming cells by the end of the treatment period. Interferon alpha brought about a preferential expression of CD8, CD11b, CD14, CD25 and CD45RO cell surface molecules without any effect on the expression of CD2, CD3, CD4, CD20 and HLA-DR.

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