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Biomedical subjects

A Pituch-Noworolska

Publications and source records attributed to A Pituch-Noworolska.

At least 19 recordsLinked to original sources

Vancomycin down-regulates lipopolysaccharide-induced tumour necrosis factor alpha (TNF alpha) production and TNF alpha-mRNA accumulation in human blood monocytes.

The cytokines play an important role in the cascade of the pathological events leading to septic shock. The TNF alpha produced by monocytes/macrophages upon stimulation with bacterial fragments may contribute to induction of this cytokine cascade. Moreover, the antibiotics used for antimicrobial therapy may cause the increase of TNF alpha production due to massive bacterial killing and exposure of monocytes/macrophages to bacterial cell constituents. To investigate the effect of Vancomycin on TNF alpha production, an in vitro model of LPS-stimulated monocytes was used. The level of TNF alpha protein or TNF biological activity were tested in the culture supernatants of monocytes with LPS. Vancomycin down-regulated, in dose-dependent manner, the TNF alpha production. Vancomycin also inhibited TNF alpha-mRNA accumulation in LPS-stimulated monocytes, as assessed by fluorescence in situ hybridization (FISH) in cell suspension. The down-regulation of TNF alpha production in LPS-stimulated monocytes may indicate that inhibition of this cytokine release is one of the important therapeutic effects of Vancomycin in sepsis.

Animals

The photodynamic effect of Victoria blue BO on peripheral blood mononuclear and leukemic cells.

The photodynamic effect of Victoria blue BO (VB-BO) and photoirradiation on peripheral blood mononuclear cells was studied. The cells were preincubated with VB-BO followed by photoirradiation and overnight culture. The highest percentage of dead cells (propidium iodide assay in flow cytometry) was seen in the monocyte population. The lymphocytes showed a lower sensitivity to VB-BO photodynamic action than the monocytes (12% vs 80% of PI-positive cells). The effect of VB-BO and phototreatment on lymphocyte function was studied using a mitogen-induced proliferation assay. A decrease of mitogen response was observed. The VB-BO and photoirradiation were also used on leukemic cells. The leukemic cells from acute myeloid leukemia and B precursors leukemia were sensitive to VB-BO photodynamic action. The high VB-BO sensitivity of monocytes and leukemic cells (myeloid and lymphoid B derived) suggests possible application of VB-BO for selective depletion of monocytes or sensitive leukemic cells.

Antineoplastic Agents

[The diagnostic significance of blast immunophenotype assay in patients with acute leukemia].

A detailed analysis of immunophenotypes of 120 adult newly diagnosed patients with acute leukaemias was performed. Using the immunopheno-typing, it was possible to defined 96,7% of leukemia cases. The proportion of leukemia subtypes was: AML in 62,5%, ALL in 32,5%, acute biphenotypic leukaemia 1,7% and acute undifferentiated leukaemia (AUL) in 3,3%. The diagnosis initially made according FAB criterias in 12,5% cases after the immunophenotyping was verified. Above analyses showed the existence of the atypical blasts phenotypes in 31%: co-expression of CD 19, CD2 and CD7 markers in AML, co-expression of CD 33 marker in ALL, co-expression of CD 19 marker in T cell ALL and biphenotypic (mixed-lineage) leukaemia.

Adolescent

Isotype-specific regulation of MHC class II gene expression in human monocytes by exogenous and endogenous tumor necrosis factor.

The control of expression of MHC class II molecules on antigen-presenting cells is important for the induction of immunity, while aberrant expression of these molecules plays a role in the immunopathology of autoimmune diseases. This study explored the role of tumor necrosis factor alpha (TNF) in controlling the level of HLA class II mRNA in human monocytes. Exposure of monocytes to exogenous recombinant TNF (rTNF) selectively up-regulated DR alpha-mRNA but not DP or DQ alpha-mRNA. Inhibitors of TNF synthesis, pentoxifylline (PTX) and thalidomide, inhibited TNF mRNA accumulation in LPS-activated monocytes and down-regulated DR mRNA but not DP or DQ mRNA. The inhibitory effect of anti-TNF monoclonal antibody (MAb) indicated that endogenously generated TNF acted extracellularly. Anti-p75 TNF-R2 receptor and to a lesser extent anti-p55 TNF-R1 MAbs inhibited TNF-mediated up-regulation of DR mRNA and TNF mRNA. Taken together, this implies that endogenously generated TNF plays a role in controlling isotype-specific MHC class II gene expression in human monocytes/macrophages. These results may have some implications for anti-tumor response and autoimmunity.

Antibodies, Monoclonal

Prevalence of autoantibodies in the very elderly: association with symptoms of ischemic heart disease.

The mechanisms leading to the increased expression of autoantibodies in the elderly are poorly understood. The aim of this study was to investigate whether the presence of ischemic heart disease (IHD) is associated with the prevalence of autoantibodies in the elderly over 85 years of age. Anti-nuclear (ANA), anti-smooth muscle (SMA), anti-mitochondrial (AMA), thyroid anti-microsomal autoantibodies (anti-Tg) and antibodies to gastric parietal cells (PCA) were determined in selected groups of healthy subjects and patients with IHD. In IHD patients, the following autoantibodies were detected: ANA in 42.1% of subjects, SMA in 10.5%, AMA in 5.3%, anti-Tg in 5.3%, and PCA in 5.3%. In control healthy subjects, ANA were detected in 10%, AMA in 5%, and PCA in 15%. In conclusion, autoantibodies were more common in patients with IHD than in control healthy subjects, but no significant differences were found.

Aged

The expression of multidrug resistance (MDR) molecule in acute leukemia and lymphoma.

Multidrug resistance (MDR) is associated with expression of P-glycoprotein in the malignant cells as the one of known mechanisms for this phenomenon. The isolated blast cells of 60 patients with acute leukemia and non-Hodgkin's lymphoma (NHL) were assayed for the expression of P-glycoprotein (P-170) with MRK16 antibody. The frequency of P-170 expression was studied in the different subtypes of leukemia and NHL based on blasts phenotype. In acute leukemia and lymphoma with B cell lineage of blast cells the percentage of P-170 positive samples was 41.3%, in the non-lymphoblastic leukemia--35.3% and the T cell lineage--75% of P-170 positive samples. The expression of P-170 molecule was associated with: 1. T cell origin of blasts, 2. lymphoma form of proliferation. The P-170 assay selects the group of patients with higher risk of drug resistance for modified therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem

[Bone marrow stem cells].

The paper summarizes the up-to-date knowledge about the stem cells of human bone marrow. The role of bone marrow stromal cells, their products in the regulation of hematopoiesis and the role of growth factors and cytokines are discussed.

Cytokines

Clinical manifestation of IgA deficiency.

Thirty patients, 2-12 years of age, with selective IgA deficiency or low level of IgA were investigated. Among them we found 5 children with coeliac disease, 15 with milk protein intolerance. Recurrent respiratory tract infections, otitis, septicemia and urinary tract infections were also frequently noted.

Celiac Disease

[Prevalence of autoantibodies in serum of healthy persons over 85 years of age].

Aging is believed to be associated with the increase in the frequency of autoantibodies. However, as the recent studies suggest the immunological defects are not the consequence of the aging process but they could be a result of underlying diseases. We investigated the prevalence of the anti-nuclear (ANA), anti-mitochondrial (AMA), anti-smooth muscle (SMA), antibodies to gastric parietal cells (PCA) and thyroid anti-microsomal autoantibodies (anti-Tg) in the sera of the selected healthy elderly over 85 years of age. We discovered ANA in 10% of subjects, AMA-5% and PCA in 15% in the group that we examined. Anti-smooth muscle and thyroid anti-microsomal antibodies have not been observed. Autoantibodies were less frequent than in other studies, but our results have shown slight increase of some autoantibodies in the healthy elderly.

Aged

[Incidence of humoral immunodeficiency in children with recurrent infections].

The screening of humoral immunity was performed in 6280 children with recurrent infections. The low level of immunoglobulins was detected in 287 children. The most frequently were: the decreased level of IgA (142 children), and selective IgA deficiency (78 children). The decreased level of all classes of immunoglobulins was rare. Within this group of children severe immunodeficiency diseases (Omenn syndrome, Seemanov syndrome, SCID with NK predominance or MHC class II deficiency) were diagnosed.

Antibody Formation

Immunological classification of high grade non-Hodgkin's lymphomas (NHL) in children.

The immunological classification of 28 high grade non-Hodgkin's lymphomas (NHL) in children was shown. The morphological classification was based on Working Formulation, the immunological classification--on acute lymphoblastic leukemia subtypes. The phenotypes were assayed cytofluorometrically with monoclonal antibodies and compared to ontogenic stages in B and T cell development. Small non-cleaved cell lymphoma (Burkitt's type) was seen in 13 patients, lymphoblastic lymphoma in 12 patients, low differentiated in 3 patients. Immunological classification showed B-lymphocyte origin of blast cells in 15 patients including 11 small non-cleaved Burkitt's lymphoma (mature B and cALL phenotype), 3 undifferentiated cases (pro-B and mature B cell) and 1 case of lymphoblastic lymphoma (cALL type). T-cell origin of blast cells was demonstrated in 13 patients. The immunological classification used routinely was helpful in selection of patients with unfavourable prognosis. The more precise description of blast cells was valuable for better adjustment of therapy and better prognosis.

Adolescent

[Evaluation of cell cycle in acute leukemias and non-Hodgkin's lymphomas in children].

The DNA profile of blast cells was assayed in 61 children with acute leukemias (51 patients) and non-Hodgkins lymphomas (NHL--10 patients). The value of S phase (synthesis of DNA) and G2M phase (mitotic stage) was compared between the subtypes of acute leukemia and lymphoma based on blast cell phenotype. In acute lymphoblastic leukemia (ALL) the lowest S phase of blast cells was seen in null-ALL subtype, the highest in T-ALL. In non-lymphoblastic leukemia (ANLL) the value of S phase was below S phase observed in ALL. B cell NHL showed higher S phase as compared to T-lymphocyte derived NHL cells. Aneuploidy was noted as hyperdiploidy (8 cases), hypodiploidy (4 cases) and two leukemia cell lines (3 ALL patients). The DNA profile as marker of proliferative activity of blastic cells provides an important information associated with the prognosis of patient.

Adolescent

Reactivity of bronchoalveolar space cells in lung asbestosis.

Preliminary studies to evaluate lymphocyte subsets bronchoalveolar lavage (BAL) and blood were carried out in a group of patients with lung asbestosis. The assessments were made by an indirect immunofluorescent method using monoclonal antibodies as a marker. The results were recorded on a flow cytofluorometer FASC-can. As compared with a control group, the patients with lung asbestosis showed a slight decrease in the total level of T lymphocytes (CD3) in BAL, however with a clearly disturbed proportion between T-helper (CD4) and T-suppressor (CD8) lymphocytes, which led to a decreased CD4/CD8 ratio. The blood level of T lymphocytes and their subsets in these patients approximated that in the controls. Heavy smoking was also found to enhance disorders in their number and proportion. The assessment of B lymphocytes (by using polyclonal antihuman immunoglobulins (sIg/FITC) showed a significantly high level of these lymphocytes in BAL with simultaneously low levels in blood in the same patients with lung asbestosis. We did not find a clear synergic effect of cigarette smoking on the levels of B lymphocytes in the studied group.

Adult

MHC class II determinants on peripheral blood monocytes from newly diagnosed IDDM patients.

The expression of MHC class II determinants (HLA-DR, HLA-DP and Ia7) on peripheral blood monocytes (OKM1+ cells) was studied in 20 children with newly diagnosed IDDM. Monocytes of 10 children with IDDM and familial predisposition showed a statistically significant increase of HLA-DR expression when compared to control group (10 healthy children). There were no significant differences concerning Ia7 expression. HLA-DP expression was similar in all studied groups.

Adolescent

Monocyte-T-cell interactions in pokeweed mitogen-activated cultures.

Monocyte-T-cell interactions were studied in pokeweed mitogen (PWM)-activated cell cultures. We addressed the question of monocyte changes in PWM-stimulated cultures of T cells and monocytes and found, by flow cytometric analysis, that PWM activation led to a loss of cells with monocyte or macrophage phenotype (CD14, HLA-DR, HLA-DQ) within 48 hr of culture in the presence of T cells (CD4+ T cells), but not in cultures of pure monocytes. Chemiluminescence measurements revealed that phagocytic stimulation of monocytic superoxide release was impaired in PWM-stimulated cultures of monocytes plus T cells, but not in PWM-stimulated cultures of pure monocytes. Furthermore, PWM induced the secretion of interferon-gamma (IFN-gamma) in primary cultures of T cells supplemented with 20% of monocytes, whereas in subsequent secondary cultures of these cells PWM induced IFN-gamma only when monocytes were added. We conclude from these flow cytometric and functional analyses that monocytes are efficiently eliminated from PWM-activated T-cell/monocyte cultures by CD4+ T lymphocytes.

Antigens, Differentiation, Myelomonocytic

The altered expression of MHC-class II determinants on monocytes of cancer patients.

The expression of MHC class II determinants Ia.7 (detected by cross reactive mouse anti-Iak antibody) and HLA-DR on monocytes (MO) of gastric and colorectal cancer patients was examined. An increased proportion of MO bearing the Ia.7 determinant was found, while the number of MO expressing DR was not elevated. In gastric cancer patients the increased expression of the Ia.7 determinant was most pronounced in advanced cancer (stage IVA and IVB). The increased expression of this determinant was related to the presence of the tumour as the number of MO expressing Ia.7 decreased 6 months following surgical resection of the tumour. Further, the increased expression of Ia.7 on MO correlated with the tumour infiltration of the serosa. The Ia.7 determinants were mainly expressed on MO which also expressed the receptor for the Fc part of immunoglobulin. Immunostaining in cellular infiltrates surrounding the tumour revealed that Ia.7+ macrophages (MO) were more numerous than in normal gastric mucosa and severe chronic gastritis and were mostly present in close proximity to tumour cells, while DR+MO were mainly localized within the stromal tissue of the tumour and their number was not increased in cancer infiltrates. These observations indicate that the Ia.7+ subpopulation of MO may be involved in the anti-tumour response of the host.

Epitopes

Human recombinant interferon-alpha-2 in the treatment of patients with hairy cell leukemia.

During the last 2 years, we have treated 14 hairy cell leukemia (HCL) patients with human recombinant interferon-2 alpha (Boehringer Ingelheim). The above group consisted of eight nonsplenectomized and six previously splenectomized progressive HCL patients. The patients received daily doses of 5 x 10(6) units of IFN for 3 months and two doses per week for the next 3 months thereafter by i.m. route. The therapy resulted in the complete (nine cases, = 64.3%) or partial (two cases = 14.3%) clinical and hematological remission (response rate 78.6%), with either disappearance or marked reduction in circulating and bone marrow hairy cells, decreased spleen size, and recovery of normal hemopoiesis. Apart from a transient flulike syndrome during the first 2 weeks of therapy, no other side effects were observed.

Adult