Search

Objectives: Cancer progression is influenced by tumor microenvironment and communication of stromal cells and tumor cells. Interactions may enhance epithelial-mesenchymal transition (EMT) of tumor cells through signaling proteins such as Wnt/beta-catenin and matrix metalloproteinases (MMP), as well as loss of cellular integrity, which affects invasion, progression, and metastasis of head and neck squamous cell carcinoma (HNSCC). In this study, we are testing the hypothesis that interactions of human mesenchymal stromal cells (MSCs) with HNSCC might influence the expression of markers of EMT and tumor progression by co-culturing human MSC with the PCI-13 HNSCC line. Materials and methods: Pooled MSCs were derived from the iliac bone marrow of seven patients and co-cultured in transwell permeable membrane wells with tumor cells of the established HNSCC cell line PCI-13 (UICC: T3, N1, M0). MSCs were characterized through fluorescence-activated cell sorting (FACS) analysis. Expression of Wnt3, E-cadherin, beta-catenin, MMP14, cathepsin b, and ETS1 was assessed by quantitative RT-PCR. Results: We were able to show that co-culture of MSCs and PCI-13 leads to a significantly reduced expression of Wnt3, MMP14, and beta-catenin compared to controls, whereas the expression of cathepsin b and ETS1 was not significantly different between co-cultures and controls. Conclusion: Our results suggest that the interaction between MSCs and PCI-13 may suppress EMT in cancer cells. Clinical relevance: The influence of MSCs can suppress the onset of EMT in HNSCC, affecting tumor progression and therapy. [ABSTRACT FROM AUTHOR]

The prevalence and clinical and laboratory associations of IgM, IgG and IgA rheumatoid factors (RF) were determined in 352 patients with systemic lupus erythematosus (SLE). IgM, IgG, and IgA class RF were detected in 17.9%, 20.5%, and 20.5% of the sera, respectively. RF were associated with sicca syndrome, hypergammaglobulinemia, high titer of antinuclear antibodies, anemia, SSA- and SSB-antibodies, and with the presence of HLA-DR3. RF correlated negatively with nephritis and livedo racemosa. Moreover, we observed an association of RF and parameters of inflammatory activity such as elevated erythrocyte sedimentation rate (ESR) and leukopenia. Analysis of immunoglobulin classes revealed that laboratory parameters of inflammatory activity, SSA- and SSB-antibodies and HLA-DR3 correlated with IgA RF only. IgA RF define a subgroup of SLE patients characterized by distinct autoimmune phenomena and high disease activity in the absence of nephritis. [ABSTRACT FROM AUTHOR]

Thrombomodulin is an endothelial cell membrane glycoprotein and is detected in plasma and serum after endothelial injury. In our study comprising 311 patients with systemic lupus erythematosus (SLE) clinical and laboratory associations of elevated thrombomodulin serum concentrations were examined. Elevated thrombomodulin concentrations were detected in 7.1% of the SLE patients and were associated with nephritis including the laboratory parameters proteinuria and erythrocyte casts, vasculitis and neurological involvement of the central nervous system. These correlations remained significant after consideration of the influence of renal function. In SLE, the serum thrombomodulin concentration may become a marker to monitor damage of endothelial cells and involvement of the central nervous system. [ABSTRACT FROM AUTHOR]

Antibodies against dsDNA of the IgM class were measured in sera of 352 patients with systemic lupus erythematosus, 81 blood donors and 189 patients with rheumatoid arthritis using a new ELISA based on human recombinant dsDNA as antigen. IgM anti-dsDNA antibodies were found in 52.3% of the sera from patients with systemic lupus erythematosus, but in none of the sera from 81 normal controls and 189 patients with rheumatoid arthritis. The association of these autoantibodies with 31 clinical and 37 laboratory parameters was calculated. There was a highly significant negative correlation between IgM anti-dsDNA antibodies and nephritis as well as all the laboratory parameters indicating renal disease (elevated serum creatinine concentration, proteinuria, erythrocyte casts in the urine). IgM anti-dsDNA antibodies indicate protection of lupus patients against the development of lupus nephritis. Further experiments will show whether application of IgM anti-dsDNA antibodies is effective in treating lupus nephritis. [ABSTRACT FROM AUTHOR]

By using three different assay methods, circulating immune complexes have been detected in 85% of sera from patients with malignant melanoma, and in 77% of sera from patients with breast cancer. These methods were a C1q-binding assay, a double-antibody conglutinin-binding ELISA, and a polyethylene glycol 6000 precipitation technique followed by quantitative determination of immunoglobulins in the redissolved precipitate. Detection rates of circulating immune complexes using any one of these methods separately ranged from 33% to 56%, indicating the presence of different types of circulating immune complexes in cancer patients' sera. The combined use of the three methods mentioned resulted in an increased diagnostic sensitivity and a doubling of the predictive value. However, tests for circulating immune complexes cannot be considered as useful parameters for early diagnosis of cancer, since the comparatively low incidence of malignancies in the population at large, together with the presence of circulating immune complexes in other, nonmalignant, diseases of considerable prevalence, appears to preclude effective application of any nonspecific method for early diagnosis of cancer in general. [ABSTRACT FROM AUTHOR]

In 23 patients 18 to 73 years old transcutaneous $${\text{P}}_{{\text{O}}_{\text{2}} } $$ , relative local perfusion and cardiorespirogram during induction and end stage of anaesthesia were monitored. This method allows continuous sufficiently exact estimation of $${\text{Pa}}_{{\text{O}}_{\text{2}} } $$ . The comparison between $${\text{tcP}}_{{\text{O}}_{\text{2}} } $$ and corresponding blood gas analysis from arterial samples showed a good correlation of r = 0.94. Thus continuous $${\text{tcP}}_{{\text{O}}_{\text{2}} } $$ registration enables quick diagnosis of hypoxia and its therapy. [ABSTRACT FROM AUTHOR]

The spin dynamics in the reentrant spin glass ( Fe0.65 Ni0.35)1-x Mn_x has been studied by zero, longitudinal and transverse field μSR. In the ferromagnetic reentrant and pure spin glass regimes (x\leqslant 0.175), zero field experiments reveal a stretched exponential muon relaxation with a universal behaviour of the dynamic exponent \beta above the spin glass transition. There are no qualitative differences between the ferromagnetic and paramagnetic phases. In transversal field μSR experiments the divergence of the relaxation rate close to the spin glass transition is suppressed for manganese doping up to x=0.113 but enhanced for slightly higher doping (x\geqslant 0.12). We understand this behaviour as a crossover from an itinerant to a more localized state of the 3d electron system. This is also supported by the fact that in the highly doped regime with dominant antiferromagnetic interactions the muon relaxation rate diverges above the antiferromagnetic transition temperature. [ABSTRACT FROM AUTHOR]

Previously it has been suggested that the presence of antibodies against dsDNA of the IgA class may define a subset of systemic lupus erythematosus (SLE) patients suffering from nephritis and arthritis. Therefore, these autoantibodies were measured in sera of 352 patients with SLE, 81 blood donors, and 189 patients with rheumatoid arthritis using a new ELISA based on human recombinant dsDNA as antigen. IgA anti-dsDNA antibodies were found in 19.9% of the sera from patients with SLE, but in none of the sera from 81 normal controls and 189 patients with rheumatoid arthritis. The association of these autoantibodies with 31 clinical and 36 laboratory parameters was calculated. IgA anti-dsDNA antibodies were found to be associated with parameters of disease activity such as elevated erythrocyte sedimentation rate and consumption of complement component C3, and the clinical parameters vasculitis, acral necrosis and erythema, but not with nephritis and arthritis. Therefore, IgA anti-dsDNA antibodies define a subset of SLE patients, and monitoring of IgA anti-dsDNA antibodies may be helpful as a prognostic parameter in patients with SLE. [ABSTRACT FROM AUTHOR]

In a multicentre study anticardiolipin antibodies of the IgG and IgM isotypes were measured by a solid phase enzyme immunoassay in 368 patients with systemic lupus erythematosus (SLE) who were not selected on the basis of features of antiphospholipid syndrome. Clinical and laboratory associations of increased levels of anticardiolipin antibodies were evaluated. IgG and IgM antibodies to cardiolipin were documented in 224 (60.9%) and 128 (34.8%) patients, respectively. Regarding the symptoms of antiphospholipid syndrome, elevated amounts of anticardiolipin IgG were significantly associated with spontaneous abortion ( P<0.001), thrombocytopenia ( P<0.01), livedo reticularis ( P<0.01) and a positive direct Coombs test ( P<0.05), but not with thrombosis or central nervous system diseases such as epilepsy and psychosis. IgM antibodies to cardiolipin were associated with a positive direct Coombs test ( P<0.01), but with no other symptom of antiphospholipid syndrome. The predictive values of anticardiolipin antibody determinations in unselected SLE patients were poor for all features of antiphospholipid syndrome because of high proportions of false-positive and false-negative results. As for other manifestations of SLE, positive correlations between raised antibodies to double-stranded DNA and the occurrence of anticardiolipin antibodies of the IgG isotype were observed, and anticardiolipin IgM was negatively associated with nephritis. [ABSTRACT FROM AUTHOR]

Antibodies against recombinant 52 kD-Ro, recombinant 60 kD-Ro and recombinant La protein were determined by ELISA in over 300 central European patients with systemic lupus erythematosus (SLE). A strong association with HLA-DR3 was found for antibodies against 52 kD-Ro and La, but not for recombinant 60 kD-Ro antibodies in the absence of antibodies against 52 kD-Ro or La. Ro/La negative SLE patients still showed an increased frequency of HLA-DR3 as compared to healthy controls. These results indicated that the preferential formation of Ro and La antibodies was not due to an unspecific stimulatory effect of HLA-DR3 but that the antibody response to certain defined proteins (52 kD-Ro and La) was influenced by MHC genes in SLE. Furthermore, the association of SLE with HLA-DR3 was independent of the effects of DR3 on the formation of 52 kD-Ro and La antibodies. [ABSTRACT FROM AUTHOR]