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Biomedical subjects

A Mackiewicz

Publications and source records attributed to A Mackiewicz.

At least 55 records · Page 3Linked to original sources
PubMed1996

[Evaluation of SCC antigen in patients with advanced cervix cancer treated with radiation].

The TA-4 antigen was isolated and described in 1977 by Kato and Torigoe. The antigen called SCC-squamous cell carcinoma is subfraction TA-4 isolated of liver metastases from cervix uteri. The cut-off limits for SCC-antigen is counted as 1.5-2.5 ng/ml. The level of SCC-antigen was determined in the serum of 41 women with advanced cervix uteri cancer-IIIB and IV FIGO stage. The value of SCC-antigen was evaluated twice: before and after the treatment. The increasing of SCC-level was observed in the serum of 80% women. The conclusion are: There was the lowering of SCC-antigen value in patients after the irradiation. In cases of patients who still had high SCC-antigen level after the treatment and it exceeded 8 ng/ml., progression of cancer also was found. The progression of cancer after the treatment was found in women with pretreatment level of SCC-antigen higher than 30 ng/ml.

Adult↗
PubMed1995

Interleukin-6-type cytokine-induced changes in acute phase protein glycosylation.

The plasma levels and the glycosylation of acute-phase proteins (APP) are subject to marked changes during acute and chronic inflammation. The pathophysiological variations in different glycoforms of APP in serum most likely result from changes in the glycosylation process during their biosynthesis in the parenchymal cells of the liver. This is suggested from in vitro studies with isolated hepatocytes and hepatoma cell lines. Inflammatory cytokines appear to regulate the changes in glycosylation independent from the rate of synthesis of the APP. In addition, other humoral factors like corticosteroids and growth factors are involved. The interplay of these factors is determined by the stage of the disease (as in rheumatoid arthritis) or the physiological situation (as in pregnancy). The changes in glycosylation of specific APP might affect the operation of the immune system.

Acute-Phase Proteins↗
PubMed1995

Interleukin-6-type cytokines and their receptors for gene therapy of melanoma.

B-78-H1 melanoma cells were stably transfected with cDNAs encoding human IL-6, human LIF, murine sIL-6R and murine sLIFR. The mock transfected and transfected cells demonstrated no detectable H-2Kb molecules. B-78 transfected cells were subcutaneously (s.c.) and intravenously (i.v.) injected to B57BL/6 x C3H mice. Control B-78 cells formed tumors and lung metastases in injected animals. Cells transfected with IL-6, LIF and sIL-6R showed greatly reduced tumor and metastases formation. Transfection of IL-6, sIL-6R or LIF had similar protective effects while the combination of IL-6 and sIL-6R was most effective. In contrast, cells transfected with sLIFR showed reduced metastasis formation but increased tumor growth compared to mock transfected cells. Kinetic analysis demonstrated a 3 weeks lag period between the formation of tumors by B-78 cells and the combination of B-78 cells transfected with IL-6 and sIL-6R. No such lag phase was seen when B-78-IL-6 or B-78-sIL-6R cells were injected alone. Mice primarily injected s.c. with a mixture of IL-6 and sIL-6R transfected cells and rechallenged after 2 weeks with parental B-78 cells demonstrated long-lasting antitumor immunity. IL-6 and sIL-6 transfected cells used alone for immunization had only limited effect. Injection of transfected cells into SCID mice which are characterized by greatly reduced number of T and B cells, showed a protective effect of sIL-6R on metastasis formation by B-78 cells. beta 2m knockout mice lacking CD8+ T cells, injected with B-78 cells developed tumors and died after 2 weeks. However, B-78 cells transfected with IL-6 developed tumors in only 50% of animals. Mice without tumors rechallenged with B-78 cells demonstrated required immunity against parental melanoma cells. The results obtained indicate that studied IL-6-type cytokines and their respective soluble receptors affect murine melanoma growth and metastasis formation. The major finding of these studies is that IL-6 complexed with sIL-6R demonstrated qualitatively different biological activity than IL-6 alone especially in stimulating long lasting anti-melanoma immunity. The proposed mechanism of action of such complexes beside activation of cytotoxic T lymphocytes is activation of NK cells.

Animals↗
PubMed1995

Soluble interleukin 6 receptor is biologically active in vivo.

A cancer cell transfection model was used to evaluate biological activity of soluble IL-6 receptor (sIL-6R) in vivo. B-78 melanoma cells were stably transfected with cDNAs encoding human IL-6, murine sIL-6R and human leukaemia inhibitory factor (LIF). Control and transfected cells were intravenously (i.v.) and/or subcutaneously (s.c.) injected into B57BL/6 x C3H or SCID mice. Whereas B-78 cells formed tumours and lung metastasis in injected animals, transfected animals, transfected cells showed greatly reduced tumour and metastasis formation. Transfection of IL-6, sIL-6R or LIF had similar protective effects. The combination of IL-6 and sIL-6R was most effective. Kinetic analysis demonstrated a 3 week lag period between formation of tumours by B-78 cells and the combination of B-78 cells transfected with IL-6 and sIL-6R. No such lag phase was seen when B-78-IL-6 or B-78-IL-6 or B-78-sIL-6R were injected alone. These results indicate that IL-6 alone exhibits a different quality of activity when compared to the IL-6-soluble receptor complex. Our results demonstrate for the first time that sIL-6R is a biologically active molecule in vivo.

Animals↗
PubMed1995

Glycoforms of serum alpha 1-acid glycoprotein as markers of inflammation and cancer.

alpha 1-acid glycoprotein (AGP) is a serum acute phase glycoprotein which possesses five N-linked complex type heteroglycan side chains which may be present as bi-, tri- and tetraantennary structures. Depending upon the content of biantennary structure on AGP, up to four glycoforms of AGP are present in serum. These glycoforms can be easily estimated in body fluids by means of crossed affinity-immunoelectrophoresis (CAIE) with the lectin, Concanavalin A (Con A). Con A selectively binds biantennary structures; the more biantennary structures on AGP, the stronger the binding. In acute inflammation, a relative increase of AGP glycoforms with biantennary units is observed-a type I glycosylation change. In some chronic inflammatory states there is an relative decrease of AGP glycoforms with biantennary heteroglycans-a type II glycosylation change. Moreover, in certain other states such as pregnancy, estrogen administration or liver damage, type II glycosylation changes are also seen. A detailed analysis of the clinical applications of the assessment of AGP glycoforms in sera of patients with rheumatic diseases, AIDS and various types of cancers is presented. Accumulated data shows that AGP glycoforms may be very useful in the detection of intercurrent infections in the course of rheumatoid arthritis, systemic lupus erythematosus, or myeloblastic leukaemia, and in the detection of secondary infections in human immunodeficiency virus infected individuals. AGP glycoforms are also very useful in differentiation between various forms of trophoblastic disease and are helpful in monitoring the treatment of these patients. Finally, AGP glycoforms provide valuable information for differentiation between primary and secondary liver cancer.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Sustained high levels of circulating chaperoned interleukin-6 after active specific cancer immunotherapy.

In a phase 1 study of recombinant interleukin-6 (rIL-6) in patients with advanced solid tumors (n = 15), we discovered that the endogenous IL-6 levels, in pretreatment plasma or serum samples, were distributed into two groups. One set of patients (designated "type 1"; n = 9) was characterized by low plasma IL-6 levels (48 to 1,700 pg/mL) as measured using enzyme-linked immunosorbent assays (ELISA) for IL-6. In the second set of patients (designated "type 2"; n = 6), IL-6 ELISAs showed high levels of plasma IL-6 (50 to 600 ng/mL). Neither group had detectable B9 hybridoma cell growth factor activity associated with the IL-6 in their pretreatment plasma or serum. Plasma C-reactive protein (CRP) levels were markedly elevated in type II patients suggesting that the circulating IL-6 was biologically active in vivo. In both groups of patients there was a small but significant increase in B9 activity in the plasma within three hours after rIL-6 administration (n = 5). Gel filtration profiles showed that circulating IL-6 in type 1 patients, 15 to 120 minutes after rIL-6 administration was of approximate mass 20 to 40 kD, whereas in type 2 patients, the IL-6 before and after exogenous rIL-6 administration was indistinguishable and was of an approximate mass of 200 kD. IL-6 immunoaffinity purification of the 200 kD complexes showed these to contain multiple isoforms of IL-6 (14 to 31 kD) and the soluble IL-6 receptor (sIL-6R; 50 to 55 kD). A distinguishing clinical history was that all of the type 2 patients had been actively immunized with an anti-idiotypic monoclonal antibody (MoAb) (MK2-23) 3 to 12 months before initiation of this study for advanced melanoma. An analysis of the plasma IL-6 content in other melanoma patients (n = 16) during antiidiotypic MoAb immunization indicated that marked (up to 600 ng/mL) and sustained (several months) elevations of circulating "chaperoned" IL-6 were induced by active immunization regimens.

Antibodies, Monoclonal↗
PubMed1994

Glycoforms of alpha 1-acid glycoprotein in sera of human immunodeficiency virus-infected persons.

In acute infections thus far studied, there is a relative increase in plasma protein glycoforms rich in biantennary complex type N-glycans (type I), while in some diseases with chronic inflammatory changes, there is increase in glycoforms with more branched N-glycans (type II). In sera of 109 human immunodeficiency virus (HIV)-infected persons, 38 rheumatoid arthritis patients, and 44 healthy subjects, the composition of alpha 1-acid glycoprotein (AGP) glycoforms was studied using crossed immunoaffinity electrophoresis with concanavalin A as a ligand. In patients in CDC classifications I, II, and III, distribution of AGP glycoforms was analogous to that in normal subjects. Type I alterations were observed in patients in group IV who had no signs of arthritis. Type II changes, analogous to those found in rheumatoid arthritis, were seen in group IV patients who developed arthritis. Most significant type I changes were associated with Pneumocystis carinii pneumonia (specificity, 100%; sensitivity, 96%).

Arthritis↗
PubMed1993

The soluble interleukin-6 receptor is generated by shedding.

The ligand-binding subunit (gp80) of the human interleukin-6 receptor (IL-6R) was transiently expressed in COS-7 cells. The metabolically labeled protein was shown to be quantitatively released from the membrane within 20 h. We identified the protein released from the transfected COS-7 cells after purification to homogeneity and N-terminal sequencing as a soluble form of the gp80/IL-6R. Shedding of the gp80 protein was strongly induced by 4 beta-phorbol-12-myristate-13-acetate, indicating that the process was regulated by protein kinase C (PKC). This was further corroborated by the finding that co-transfection of a PKC expression plasmid led to enhanced shedding of the gp80 protein. Since shedding of gp80 could not be prevented by treatment of the cells with inhibitors of all known classes of proteases, a novel protease seems to be involved. As a control, an unrelated membrane protein (vesicular stomatitis virus glycoprotein) was transfected into COS-7 cells and analyzed for shedding. Since the turnover of this protein was not mediated by shedding, we conclude that the release of gp80 from COS-7 cells is a specific process. The shed gp80 protein specifically binds IL-6, and this complex shows biological activity on human hepatoma cells. Human peripheral blood monocytes released a soluble form of the gp80 protein into the culture medium upon PMA treatment indicating that PKC-regulated shedding is the physiological mechanism of generation of the soluble IL-6R.

Cell Line↗
PubMed1993

C-reactive protein and alpha-1-acid glycoprotein in monitoring of patients with chronic arterial occlusion of the lower limbs.

C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP) levels were studied in the sera of 107 patients with chronic arterial ischaemia of the lower limbs. Depending on the degree of ischaemia, patients were divided into four groups: (i) intermittent claudication--20 patients; (ii) rest pain and ankle pressure above 50 mmHg--12 patients; (iii) rest pain and ankle pressure below 50 mmHg--25 patients; (iv) peripheral necrosis--50 patients. Reconstructive surgery was performed in 84 patients and primary major amputation in 23 cases. Levels of CRP and AGP increased with the severity of ischaemia. In uncomplicated cases, CRP and AGP concentrations decreased to normal values 7-10 days after surgery. In a group of 23 patients with postoperative necrotic complications, significant increases in CRP and AGP levels were found 7-10 days after surgery. These proteins, especially CRP, may be clinically useful in monitoring patients during the postoperative period with a CRP level greater than 50 mg/l predictive of complications with a sensitivity of 83% and a specificity of 94%.

Adult↗
PubMed1993

Leukemia inhibitory factor, interferon gamma and dexamethasone regulate N-glycosylation of alpha 1-protease inhibitor in human hepatoma cells.

Hepatocytes respond to inflammatory stimuli by changing the synthesis and N-glycosylation of acute phase plasma proteins (APP). So far, interleukin (IL) 6, transforming growth factor beta (TGF beta), tumor necrosis factor alpha (TNF) and IL-1 have been found to control N-glycosylation patterns of APP. Cytokines either increased (type I) or decreased (type II) the ratio of bi-relative to more branched N-glycans on APP. In this study, we describe the effect of leukemia inhibitory factor (LIF), interferon gamma (INF gamma) and dexamethasone (dex) on production of alpha 1-protease inhibitor (PI) and alpha 1-antichymotrypsin (ACT) and on glycosylation of PI in the human hepatoma cell line HepG2. Cytokines and dex were used separately and in various combinations including also IL-6 and TGF beta. Production of the antiproteases was quantitated by immunoelectrophoresis of the proteins accumulated in the culture medium. Glycosylation pattern of PI was assessed by crossed immunoaffinity electrophoresis (CIAE) with Concanavalin A (Con A) as a ligand. The production of ACT and PI was increased by LIF, decreased by INF gamma and unaffected by dex. LIF and INF gamma each like IL-6, decreased PI-Con A reactivity while dex like TGF beta enhanced PI-Con A reactivity. Combination of dex with LIF yielded additive effects while combination of dex with either INF gamma, L-6 or TGF beta acted synergistically on PI-Con A reactivity. Combinations of multiple cytokines and dex produced additive, inhibitory or synergistic effects. The type of glycosylation profile of PI secreted by HepG2 cells depended on the composition and amounts of interacting cytokines and dex.

Carcinoma, Hepatocellular↗
PubMed1992

Complex of soluble human IL-6-receptor/IL-6 up-regulates expression of acute-phase proteins.

IL-6 is a major regulator of acute phase protein synthesis in the liver. It exerts its action via a plasma membrane receptor consisting of two subunits, a ligand binding 80-kDa glycoprotein and a 130-kDa glycoprotein involved in signal transduction. We genetically generated a soluble form of the 80-kDa subunit of the human IL-6R (shIL-6R) in mouse fibroblasts (NIH/3T3 cells). The shIL-6R added to human hepatoma cells (HepG2) amplified the induction of alpha 1-antichymotrypsin and haptoglobin by IL-6 at the mRNA and protein level. Moreover, a model for a liver permanently exposed to high IL-6 concentrations has been developed; HepG2 cells were stably transfected with human IL-6-cDNA; 10(6) of the transfected cells (HepG2-IL-6) synthesized and secreted 2 micrograms of IL-6 within 24 h. Incubation of these cells with endogenous or exogenous IL-6 did not result in acute-phase protein induction. However, these IL-6-desensitized cells responded to other cytokines such as leukemia inhibitory factor, transforming growth factor beta 1, and IFN-gamma, known to modulate acute phase protein synthesis in the liver. Incubation of HepG2-IL-6 cells with shIL-6R reconstituted their responsiveness to IL-6 in a dose- and time-dependent manner. The possible biologic role that might be played by the shIL-6R in disease is discussed.

Acute-Phase Proteins↗