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Biomedical subjects

A Falus

Publications and source records attributed to A Falus.

At least 19 recordsLinked to original sources
PubMed2006

A soluble factor(s) released by MRC-5 cells early and late after human cytomegalovirus infection induces maturation of monocyte-derived dendritic cells.

A human cytomegalovirus (HCMV) strain passaged 10 times on MRC-5 human fibroblast cells failed to express immediate early (IE) antigens in immature dendritic cells (iDCs) after infection. However, both the early and the late HCMV conditioning medium, harvested from MRC-5 cells at 24 h or 7-9 days after infection, respectively, induced a higher ratio of DCs expressing maturation markers (CD40, CD83, CD86 and HLA-DR) on the surface of the cells. HCMV conditioning medium, ultracentrifuged to remove virus particles, exhibited a similarly enhanced expression of DC maturation markers. DCs treated with HCMV conditioning medium harvested late after infection increased the percentages of autologous CD4+ and CD8+ cells of seropositive donors to produce IFN-gamma and stimulated HCMV-specific lymphoproliferative responses. The early HCMC conditioning medium was also able to induce the functional maturation of DCs, as demonstrated by supplementing this medium with a Chlamydia pneumoniae antigen.

B7-2 Antigen↗
PubMed2006

Histamine regulates placental cytokine expression--in vivo study on HDC knockout mice.

Successful pregnancy is closely related to polarization toward a Th2 type immune response. As histamine is known to initiate Th2 dominance during inflammatory processes we raised the question whether histamine has any effect on the actual tuning of proper cytokine balance for the proceeding of the gestation. Histamine has multiple functions in the process of pregnancy, different studies have shown the direct and/or indirect presence of histamine action in the placenta as well. As HDC is the unique histamine producing enzyme in eukaryotes, we used HDC (so endogenous histamine)-deficient knockout mice as reliable model for studying histamine-related processes in vivo. We examined the placental histamine content and the expression of histamine receptors and Th1/Th2/Th3 type cytokines in the placenta. We showed for the first time the influence of histamine on the orchestrated regulation of placental cytokine expression. In the absence of local histamine the cytokine balance is shifted toward Th1 types at the maternal-placental interface, threatening pregnancy. We also measured splenic lymphocyte subpopulation ratios in pregnant and non-pregnant mice and found that in pregnancy they are independent of the presence of histamine.

Animals↗
PubMed2006

The role of insertion allele of angiotensin converting enzyme gene in higher endurance efficiency and some aspects of pathophysiological and drug effects.

BACKGROUND: None of the genetic markers are selectively associated with elite athletes, but potential candidates are found in the renin-angiotensin system, which plays a key role in the regulation of cardiovascular physiology. The most extensively examined gene in connection with the hemodynamics category is the angiotensin converting enzyme (ACE). This review paper has focused on ACE I/D allele polymorphism regarding the evidence of the effects of physiological and pathophysiological drugs and has completed with an original work in the exercise physiology. METHODS: In this study we examined genetic polymorphisms of ACE in female (n=26) and male (n=24) athletes as well as in a well-trained control group (n=24). MVV(ex), VE and VO(2max) were determined at rest and during an exhaustive step test. RESULTS: The frequency of the ACE I allele was significantly higher (p<0.041) in the group showing a higher intensity of breathing metabolism. The ACE D allele frequency was significantly higher in the excellent endurance athletes group than in unsuccessful athletes (p<0.054). CONCLUSION: The ACE I allele is a genetic marker for higher endurance efficiency in acute physical activity and higher adaptation of the cardiovascular system. The measurement of acute physical status needs to be completed with examination of genotype, which is related to the athletic excellence also, because the D allele could be associated with good performance by endurance athletes in future world championships. Further studies are needed to assess the view that the ACE D allele has a significant role in athletic efficiency.

Adult↗
PubMed2005

Increased interferon-gamma- and interleukin-4-synthesizing subsets of circulating T lymphocytes in pregnant asthmatics.

BACKGROUND: Pregnancy frequently interferes with the course of bronchial asthma, and asthmatic pregnant women experience less successful pregnancies. T lymphocytes synthesizing IL-4 or IFN-gamma are important in allergic mechanisms of the airways as well as in materno-fetal immunity. OBJECTIVE: We hypothesized that pregnancy (a T helper-2 polarized state) of asthmatics will enhance the number of circulating T2 lymphocytes, but decrease the subset-producing IFN-gamma (T1 lymphocytes) and thereby cause a culminating T2 dominance with possible clinical consequences. METHODS: IL-4- or IFN-gamma-producing T lymphocytes were determined by flow cytometry in healthy (n=8) and asthmatic (n=13) non-pregnant women and healthy (n=18) and asthmatic (n=48) pregnant women of similar chronological and gestational (2nd-3rd trimester) age and asthma severity (Global Initiative for Asthma II-III). RESULTS: In the blood of non-pregnant women--healthy or asthmatic--the numbers of IL-4- and IFN-gamma+ T cells were very low (<10/microL blood). In contrast, in asthmatic pregnant women, the cell counts were 182+/-27 and 39+/-6 for IFN-gamma+ and IL-4+ T cells/microL blood, respectively (both P<0.05 vs. respective control values of non-pregnant asthmatics). Within the asthmatic pregnant group, significant negative correlations were revealed between the numbers of IFN-gamma+ or IL-4+ T cells and maternal peak expiratory flow as well as birth weight of newborns (both P<0.05). CONCLUSION: These data show a previously unknown immunological interference between asthma and pregnancy. The culminating proliferation of IFN-gamma+ and IL-4+ T lymphocytes may potentially impair maternal airway symptoms as well as fetal development.

Adult↗
PubMed2004

Different patterns of the L-histidine decarboxylase (HDC) gene expression in mice resistant and susceptible to experimental cutaneous leishmaniasis.

OBJECTIVE AND DESIGN: In the present study the experimental murine Leishmania major ( L. major) infection model was used to investigate the role of histamine biosynthesis in cutaneous leishmaniasis. SUBJECTS, TREATMENT AND METHODS: A novel RNase Protection Assay (RPA) was developed and applied for the assessment of L-histidine decarboxylase (HDC) gene expression in organs of resistant C57BL/6 and susceptible BALB/c mice after infection with L. major. RESULTS: In the acute phase of infection a rapid but transient induction of HDC expression was observed in the infected lymph nodes of both strains correlating both temporally and spatially with parasite spread. The signal was present in the draining popliteal lymph nodes of both hosts, however, only susceptible mice known to be unable to control parasite dissemination showed induction of HDC in their distant periaortic lymph nodes as well. During the chronic phase of infection only the heavily parasitized organs of BALB/c mice showed high HDC gene expression. CONCLUSIONS: These data suggest that expression of the histamine-producing enzyme HDC in the decisive acute phase of leishmaniasis is not coupled with development of either appropriate Th1 or inadequate Th2 responses to L. major. We hypothesize, however, that during the chronic phase of infection elevated HDC levels, possibly of mast cell origin, are associated with Th2-dominated responses and serious disease development.

Acute Disease↗
PubMed2004

Possibilities and results in the wide-scale genomic analysis of inflammation. Looking for the child among many midwives.

Only recently, available microarray methods have been extended to the investigation of such complex pathophysiological conditions as inflammatory disease. Genome analysis gives the possibility of looking for susceptibility gene loci and their allelic combinations. By the analysis of mRNAs (transcriptome), novel players, functional groups of participants and regulatory pathways involved in the inflammation can be revealed. The possibility of comparing several samples is ideal to increase our knowledge about the kinetics of inflammation. The effects and post-receptor signalling events of individual pro- or anti-inflammatory mediators can also be tested. The use of human post mortem samples could yield otherwise inaccessible information on molecular mechanisms of chronic inflammatory diseases. However, the analysis and interpretation of a huge amount of data, the selection of appropriate experimental systems and time points may hide some pitfalls, which emphasize the need to confirm results with independent methods such as e.g. semi-quantitative Northern, real time PCR, RNA-ase protection assay as well as functional studies.

Acute-Phase Reaction↗
PubMed2004

Hepatic acute-phase reaction in histamine-deficient gene targeted mice.

Histamine is a versatile mediator that, according to in vitro studies, affects the synthesis of inflammatory cytokines and acute-phase proteins. The histidine-decarboxylase knockout (HDC-/-) mouse is a model of in vivo investigation of the physiologic and metabolic integration of the acutephase response. These mice do not synthesise histamine and feeding them with histamine-poor diet they are almost completely histamine-deficient. We compared the serum concentrations of representatives of acute-phase plasma proteins, as well as the levels IL-6 and IL-1alpha in wild type and HDC-/- mice during local (turpentine-induced) or systemic (LPS-induced) inflammation. The level of some acute-phase proteins significantly differed in wild-type and HDC-/- mice while others remained unaffected. The IL-6 levels are also differ in the wild-type and histamine-deficient animals, suggesting that the effect of histamine is attained through IL-6, although direct effect is not disclosed yet.

Acute-Phase Proteins↗
PubMed2003

Targeted deletion of histidine decarboxylase gene in mice increases bone formation and protects against ovariectomy-induced bone loss.

Targeted disruption of the histidine decarboxylase gene (HDC(-/-)), the only histamine-synthesizing enzyme, led to a histamine-deficient mice characterized by undetectable tissue histamine levels, impaired gastric acid secretion, impaired passive cutaneous anaphylaxis, and decreased mast cell degranulation. We used this model to study the role of histamine in bone physiology. Compared with WT mice, HDC(-/-) mice receiving a histamine-free diet had increased bone mineral density, increased cortical bone thickness, higher rate of bone formation, and a marked decrease in osteoclasts. After ovariectomy, cortical and trabecular bone loss was reduced by 50% in HDC(-/-) mice compared with WT. Histamine deficiency protected the skeleton from osteoporosis directly, by inhibiting osteoclastogenesis, and indirectly, by increasing calcitriol synthesis. Quantitative RT-PCR showed elevated 25-hydroxyvitamin D-1alpha-hydroxylase and markedly decreased 25-hydroxyvitamin D-24-hydroxylase mRNA levels. Serum parameters confirming this indirect effect included elevated calcitriol, phosphorus, alkaline phosphatase, and receptor activator of NF-kappaB ligand concentrations, and suppressed parathyroid hormone concentrations in HDC(-/-) mice compared with WT mice. After ovariectomy, histamine-deficient mice were protected from bone loss by the combination of increased bone formation and reduced bone resorption.

Animals↗
PubMed2003

Some aspects of interindividual variations in the metabolism of xenobiotics.

Differences in drug metabolism among individuals are caused by numerous factors: differences in production and stability of mRNA of xenobiotic metabolizing enzymes, differences in the rate of enzyme synthesis and degradation, or enzyme inhibition. One of the most important reasons is genetic polymorphism of cytochrome P450 genes or cytochrome P450 regulatory factors. Nuclear receptors play great role in the regulation of these genes. The presence of the ligand induces the nuclear receptor to bind to the dimerisation partner and as a hetero/homodimer it can activate the DNA responsive element. In addition, several co-activators, co-repressors and other factors can modulate the effect of nuclear receptors. Hepatic levels of cytochrome P450 enzymes are reduced in multiple models of inflammation or infection. Cytochrome P450 enzymes of four families (CYP1-CYP4) are known to be involved in xenobiotic metabolism. Their genetic polymorphism and regulation are discussed in this review.

Cytochrome P-450 Enzyme System↗
PubMed2003

Expanded parietal cell pool in transgenic mice unable to synthesize histamine.

BACKGROUND: The histidine decarboxylase enzyme (HDC) is responsible for the synthesis of histamine in mammals. Histidine decarboxylase-deficient (HDC-/-) mice have recently been developed by targeted mutation of the HDC gene. METHODS: The impact of prolonged histamine deficiency was studied on gastric morphology (by immunohistochemistry and morphometry), gastric acid secretion (by a wash-through method for basal gastric acid secretion and by pylorus ligation for stimulated gastric acid secretion) and gastrin levels (by radioimmunoassay) in homozygous HDC-/- mice kept on a low-histamine diet. RESULTS: A double maximal gastric acid secretory response was found in knockouts after exogenous histamine administration. In contrast, the gastric acid secretion was significantly reduced after gastrinergic and cholinergic stimulation in the absence of histamine. The oxynthic gland area of HDC-/- mice was thickened with an increased parietal cell count compared to wild types. Substantially elevated serum and antral tissue gastrin levels of HDC-/- mice could be possible indications of both an expanded parietal cell mass and/or an increased histamine-induced maximal gastric acid secretory capacity of this genotype. CONCLUSIONS: These data suggest that not enough compensatory mechanisms develop in HDC-/- mice during a prolonged low-histamine diet to maintain/restore normal gastric acid secretion. An expanded parietal cell pool was also demonstrated in HDC-/- mice kept on a low-histamine diet, probably caused by a trophic effect of sustained hypergastrinaemia. The HDC-/- strain is a suitable model for studying the effects of achlorhydria and consequent hypergastrinaemia as an approach to human conditions such as atrophic gastritis or long-term antisecretory therapies.

Achlorhydria↗
PubMed2003

Elevated levels of synovial fluid antibodies reactive with the small proteoglycans biglycan and decorin in patients with rheumatoid arthritis or other joint diseases.

OBJECTIVES: To determine whether patients with rheumatoid arthritis (RA) express humoral immunity to the small proteoglycans biglycan and decorin and to compare the response to that of patients suffering from other joint diseases. METHODS: Serum and synovial fluid IgG and IgM antibody levels were determined by enzyme-linked immunosorbent assay. Antibodies to biglycan and decorin as well as to other known and extensively investigated cartilage matrix components such as type II collagen, aggrecan and fibronectin were investigated. Patients suffering from RA, osteoarthritis (OA), psoriatic arthritis and other seronegative spondylarthropathies were included in the study. Correlation between antibody levels and clinical/laboratory parameters was determined. RESULTS: Patients with RA expressed an increased humoral immunity to biglycan, while patients with seronegative spondylarthropathies displayed elevated decorin-specific synovial antibody levels compared with OA patients. CONCLUSION: These results indicate a significantly higher immunity to small proteoglycans in RA and seronegative spondylarthropathies than in OA suggesting a possible involvement in the pathogenesis of inflammatory rheumatic diseases.

Adult↗