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Biomedical subjects

I Matei

Publications and source records attributed to I Matei.

At least 19 recordsLinked to original sources
PubMed2002

Cytokine patterns and pathogenicity in autoimmune diseases.

Cytokines are a large family of small proteins secreted by leukocytes and having an essential role in mediating the immune function. Many cytokines have multiple cellular sources and targets, as well as many natural inducers and inhibitors. These features and moreover the functional particularities of cytokines (autocrine and paracrine mode of action, overlapped activities, pleiotropic action, functioning as a complex regulatory network, and reciprocal down-regulation of the Th1 and Th2 cytokine groups) hampered the investigation of cytokines' role in autoimmune diseases (ADs). Despite this, the experimental and clinical studies have firmly documented the implication of cytokines in major pathophysiological and pathogenetic mechanisms associated with both the acute (onset and/or recurrence) and the chronic stages of ADs. The enhanced production of cytokines during the acute phase of systemic lupus erythematosus, rheumatoid arthritis and vasculitis has pathogenic effects such as appearance of anti-neutrophil cytoplasmic antibodies, initiation of vascular thrombosis and/or an increased production of autoantigens. The potent proinflammatory cytokines IL-1 and TNFalpha and also IL-8 and IFNalpha,gamma stimulate cells in different tissues to release harmful proteinases and reactive oxygen species, contributing to tissue damage. Some correlations have been found between serum cytokine levels and disease activity in certain systemic ADs. Studies investigating the cytokine pattern in ADs revealed the prevalence of the proinflammatory Th1-type cytokines in the target organ of patients with organ-specific ADs, such as multiple sclerosis and autoimmune thyroid disease, and heterogeneous cytokine profiles in patients with systemic ADs. A lot of factors, including the mechanism of tissue damage, the type of antigen-presenting cells and costimulatory molecules, and also the hormonal status, favor secretion of cytokines of Th1- or Th2-type in these patients. Beneficial effects have been obtained in patients with rheumatoid arthritis and Crohn disease by administering biotechnologically manufactured anti-TNFalpha antibodies or TNFalpha receptors. The risks of these cytokine-targeting therapeutical interventions are also discussed.

Arthritis, Rheumatoid↗
PubMed2001

Somatic frameshift mutations in the Bloom syndrome BLM gene are frequent in sporadic gastric carcinomas with microsatellite mutator phenotype.

BACKGROUND: Genomic instability has been reported at microsatellite tracts in few coding sequences. We have shown that the Bloom syndrome BLM gene may be a target of microsatelliteinstability (MSI) in a short poly-adenine repeat located in its coding region. To further characterize the involvement of BLM in tumorigenesis, we have investigated mutations in nine genes containing coding microsatellites in microsatellite mutator phenotype (MMP) positive and negative gastric carcinomas (GCs). METHODS: We analyzed 50 gastric carcinomas (GCs) for mutations in the BLM poly(A) tract aswell as in the coding microsatellites of the TGFbeta1-RII, IGFIIR, hMSH3, hMSH6, BAX, WRN, RECQL and CBL genes. RESULTS: BLM mutations were found in 27% of MMP+ GCs (4/15 cases) but not in any of the MMP negative GCs (0/35 cases). The frequency of mutations in the other eight coding regions microsatellite was the following: TGFbeta1-RII (60 %), BAX (27%), hMSH6 (20%),hMSH3 (13%), CBL (13%), IGFIIR (7%), RECQL (0%) and WRN (0%). Mutations in BLM appear to be more frequently associated with frameshifts in BAX and in hMSH6and/or hMSH3. Tumors with BLM alterations present a higher frequency of unstable mono- and trinucleotide repeats located in coding regions as compared with mutator phenotype tumors without BLM frameshifts. CONCLUSIONS: BLM frameshifts are frequent alterations in GCs specifically associated with MMP+tumors. We suggest that BLM loss of function by MSI may increase the genetic instability of a pre-existent unstable genotype in gastric tumors.

Adenosine Triphosphatases↗
PubMed1999

p56lck activity and expression in peripheral blood lymphocytes from patients with systemic lupus erythematosus.

In this study we analyzed the activity and the expression of p56lck protein tyrosine kinase in peripheral blood lymphocytes (PBLs) from systemic lupus erythematosus (SLE) patients and from healthy donors. The p56lck activity, determined by a non-radioactive Tyrosine Kinase Assay Kit, was significantly higher in active SLE PBLs and discriminated this group of patients from inactive SLE patients (p = 0.002) and healthy donors (p = 0.009). p56lck level decreased in SLE lymphocytes (especially for inactive SLE lymphocytes, p = 0.005) when compared to healthy donors. These differences were also reflected by the specific activity of p56lck that was clearly elevated in active SLE lymphocytes when compared to inactive SLE (p = 0.022) or healthy donors lymphocytes (p = 0.006). A positive correlation between the activity of p56lck and the tyrosine phosphorylation level in active SLE lymphocytes was found.

Animals↗
PubMed1996

Tyrosine phosphorylation in peripheral lymphocytes from patients with systemic lupus erythematosus.

A comparative study of tyrosine phosphorylation was performed on peripheral blood lymphocytes from systemic lupus erythematosus (SLE) patients and from healthy donors. Freshly isolated SLE lymphocytes presented an elevated tyrosine phosphorylation level when compared to healthy donors lymphocytes (p = 0.005). Among all phosphorylated proteins, those called p120, p110, p80 and p55-p60 were more phosphorylated. The level of tyrosine phosphorylation of p120 and p110 proteins discriminated significantly (p = 0.0048, respectively, p = 0.02) between SLE patients and healthy donors. Lymphocytes form SLE patients and healthy donors were then stimulated by cross-linking T cell antigens (CD3, CD4, CD8) to further distinguish the signal transduction between normal and pathologic lymphocytes. No statistical differences in the tyrosine phosphorylation pattern, following CD4 or CD8 cross-linking, were observed between SLE patients and healthy donors lymphocytes. CD3 cross-linking induced an effect on tyrosine phosphorylation different in SLE patients versus healthy donors lymphocytes. Thus, the lymphocytes of SLE patients were refractile in anti-CD3 stimulation in comparison with the healthy donors lymphocytes. Chi-square analysis demonstrated that a significantly larger number of healthy donors responded to anti-CD3 stimulation compared to SLE patients (p = 0.03). The high frequency of tyrosine phosphorylation of p110 and p80 proteins, following CD3 stimulation, in normal versus SLE lymphocytes, suggested that these proteins could be involved in abnormal signal transduction in SLE cells.

CD3 Complex↗
PubMedDate not supplied

Treatment with alpha-interferon in chronic hepatitis.

The treatment of chronic viral hepatitis with Interferon has been introduced in clinical practice over the past decade an represents an important step in the management of those diseases. The data existing in literature are conflicting about the dose and period of treatment with Interferon, many treatment schedules being proposed. There are also a lot of markers used or proposed to be used to determine the response to treatment, their predicting efficacy being largely studied. The response to alpha-Interferon in a standard 6 month regimen in chronic hepatitis B, chronic hepatitis C and chronic hepatitis B and C is studied; alanine-aminotransferase (ALAT) and aspartate-aminotransferase (ASAT) are the markers used to determine the response to treatment.

Adolescent↗
PubMedDate not supplied

Study of chemotactic activity developed by neutrophils from rheumatoid arthritis patients.

Neutrophils are the predominant cells accumulated in the synovial fluid (SF) of rheumatoid arthritis (RA) patients. Accumulation of neutrophils may be regarded as a possible way by which neutrophils exert cytotoxic functions. The aim of the present study was to analyze the chemotactic response of neutrophils (PMNs) isolated from the peripheral blood or SF of patients with RA by performing the chemotaxis assay, in which N-formyl-methionyl-leucyl-phenylalanine (FMLP) was used as chemotactic agent. Our results showed that FMLP induced response of peripheral blood neutrophils from 12 patients with RA was similar with the response of 15 healthy controls. A decreased chemotactic response to FMLP was, however, observed in PMNs isolated from the SF of RA patients as comlipared with peripheral blood cells. Therefore, this defective chemotactic ability of neutrophil, was inversely correlated with the number of infiltrating cells in SF. These results indicate that chemotactic ability of neutrophils may be reduced after migration to the SF. Because PMNs chemotaxis in vivo has likely occurred in the presence of serum or SF, we tried to simulate the same conditions in vitro. Therefore, we analyzed the effect of serum or SF on the RA-PMNs chemotaxis. Heat-inactivated serum produced a marked reduction of chemotactic activity developed by PMNs isolated from patients with RA. Notably, a significant increase of chemotactic activity was observed when FMLP and serum stimuli were used together, as compared with the same stimuli used alone. The results suggested that complement activation might interfere with neutrophils chemotaxis. SF amplifies the chemotactic activity of PMNs isolated from peripheral blood of RA patients, but does not affect the chemotaxis developed by PMNs isolated from SF. The data might suggest that several components of SF (IL-8, leukotrien B4, thrombin, platelet-activating factor, etc.) could serve as a potent stimulus for recruitment of neutrophils from periphery into the RA joint. In conclusion, serum or SF components seem to contribute to chemotaxis of neutrophils and play a role in differential killing of PMNs and incidence of infection.

Arthritis, Rheumatoid↗