Biomedical subjects

L Cremer

Publications and source records attributed to L Cremer.

8 recordsLinked to original sources

PubMed2006

Autism and environmental genomics.

Autism spectrum disorders (ASD) are defined by behavior and diagnosed by clinical history and observation but have no biomarkers and are presumably, etiologically and biologically heterogeneous. Given brain abnormalities and high monozygotic concordance, ASDs have been framed as neurobiologically based and highly genetic, which has shaped the research agenda and in particular criteria for choosing candidate ASD genes. Genetic studies to date have not uncovered genes of strong effect, but a move toward "genetic complexity" at the neurobiological level may not suffice, as evidence of systemic abnormalities (e.g. gastrointestinal and immune), increasing rates and less than 100% monozygotic concordance support a more inclusive reframing of autism as a multisystem disorder with genetic influence and environmental contributors. We review this evidence and also use a bioinformatic approach to explore the possibility that "environmentally responsive genes" not specifically associated with the nervous system, but potentially associated with systemic changes in autism, have not hitherto received sufficient attention in autism genetics investigations. We overlapped genes from NIEHS Environmental Genome Project, the Comparative Toxicogenomics Database, and the SeattleSNPs database of genes relevant to the human immune and inflammatory response with linkage regions identified in published autism genome scans. We identified 135 genes in overlap regions, of which 56 had never previously been studied in relation to autism and 47 had functional SNPs (in coding regions). Both our review and the bioinformatics exercise support the expansion of criteria for evaluating the relevance of genes to autism risk to include genes related to systemic impact and environmental responsiveness. This review also suggests the utility of environmental genomic resources in highlighting the potential relevance of particular genes within linkage regions. Environmental responsiveness and systems impacts consistent with system-wide findings in autism are thus supported as important considerations in identifying the numerous and complex modes of gene-environment interaction in autism.

Animals↗

PubMed1993

Identification of anti-idiotypic antibodies to anti-phosphotyrosine antibodies in human sera.

We have recently identified in SLE sera antibodies against phosphotyrosine. They were also detected in normal sera and gammaglobulin preparations, suggesting that they belong to natural autoantibodies. In this paper, the occurrence of anti-idiotypic antibodies against anti-phosphotyrosine antibodies, in the above mentioned samples, is investigated. In order to identify these anti-idiotypic antibodies ELISA, immunoprecipitation and immunoblotting are performed. Our data demonstrate the presence of anti-idiotypic antibodies specific to anti-phosphotyrosine antibodies in SLE sera as well as in normal sera, suggesting that these anti-idiotypic antibodies are also auto-anti-idiotypic antibodies. The densitometry of immunoblots reveals significantly higher levels of anti-idiotypic antibodies in SLE sera. Based on the competition inhibition studies we conclude that some of these anti-idiotypic antibodies belong to beta/gamma type.

Animals↗

PubMedDate not supplied

A purified green barley extract with modulatory properties upon TNF alpha and ROS released by human specialised cells isolated from RA patients.

Based on the finding that reactive oxygen species (ROS) play important roles in mediating proinflammatory cytokine production (e.g. TNF alpha) and that many plant extracts contain substances with antioxidant properties, we examined the antiinflammatory action of a green barley extract, commercially available as "Natural SOD". The results obtained in this study demonstrate that the antiinflammatory properties of "Natural SOD" due to its micromolecular substances, able to scavenge ROS and to down-regulate TNF alpha production, main inflammation mediators produced by specialised cells from peripheral blood (PB) and synovial fluid (SF) of patients with rheumatoid arthritis (RA). We prepared and tested a purified green barley extract (PE) containing micromolecular substances under 1 kDa, able to inhibit TNF alpha releasing--measured by an bioassay--from LPS stimulated human mononuclear cells (MNC) isolated both from PB and SF of RA patients. Luminol-dependent chemiluminescence has been used to measure the scavenging activity of PE on ROS releasing from activated neutrophils isolated from PB of RA patients. PE, containing high concentrations of substances with antioxidant and antiinflammatory properties, could be a more efficient natural drug for human use than "Natural SOD" in the treatment of RA patients.

Anti-Inflammatory Agents↗

PubMedDate not supplied

Anti-inflammatory non-steroidal drug able to modulate IL-10 in allergic asthma.

Our studies target alternative/adjuvant therapies in allergic diseases, able to qualitatively/quantitatively modify cytokine profiles produced by both CD4+ T-cell subsets (mainly Th1 and Th2) and B-cells, macrophages, etc. Current investigations aim to identify compounds capable to down-regulate IL-10 as an exponent of Th2 cell function and, consequently, to up-regulate Th1 cytokine levels. Experiments on ten allergic asthmatic patients and ten healthy subjects as control were performed. Cytokine production, triggered in PBMCs culture systems by PHA, was modulated with Indomethacin, a non-steroidal anti-inflammatory drug and IL-10 was measured in 24 hours culture supernatants. According to our experimental data, IL-10 level of asthmatic patients' PBMCs in the resting state is not significantly different from control. PHA-activated PBMCs from asthmatic patients do not display significantly higher IL-10 levels than the normal subjects. The results obtained up-to-date reveal the fact that Indomethacin strongly down-regulates IL-10 levels in PBMCs cultures, in both asthmatic allergic patients and healthy subjects. It is obvious that the inhibitory effect of Indomethacin on IL-10 released by PBMCs is higher in the case of allergic asthmatic patients. The results obtained in this study demonstrate that Indomethacin is a possible therapeutic candidate in allergic asthma.

Adolescent↗

PubMedDate not supplied

Anti-phosphotyrosine antibodies--obtaining and purification.

Anti-phosphotyrosine antibodies were obtained by rabbits immunization using bovine serum albumin-phosphotyrosine complex. Hyperimmune rabbit serum was purified on affinity chromatography column obtained by phosphotyramine binding on Sepharose 4 B, CNBr-activated. The antibodies obtained after purification were tested by ELISA and immunoblotting.

Animals↗

PubMedDate not supplied

Anti-phosphotyrosine and anti-phosphoserine antibodies in SLE sera.

By using an ELISA method, we identified antiPTyr and antiPSer antibodies in the sera of some SLE patients. Afterwards, antiPTyr and antiPSer antibodies were purified by affinity chromatography on phosphotyramine-CNBr-Sepharose column and on phosphoethanolamine-CNBr-Sepharose, respectively, and the specificity of the purified antibodies was demonstrated by inhibition assays. The study pointed out a higher incidence of antiPTyr than anti PSer antibodies in the sera of these patients, which suggests that some "autoantigens" from membrane might be involved.

Antibodies↗

PubMedDate not supplied

The presence and significance of some anti-enzyme antibodies (anti-plasminogen, anti-trypsin, anti-phospholipase C) in rheumatoid arthritis (RA) and reactive arthritis (rA).

It is a well known fact that during the course of RA and rA, due to some cellular and molecular mechanisms, a number of proteolytic enzymes and membranal phospholipases are either activated or their concentration rises significantly. With this aim in view in the present work we have aimed to investigate if, in an inflammatory process associated to RA and rA, the human organism produces or not anti-enzyme antibodies. Using an enzyme-linked immunosorbent assay (ELISA), in the sera of 19 patients of RA and 19 of rA, the presence of the following antibodies has been ascertained: antiplasminogen (antiPAb), antitrypsin (antiTAb) and antiphospholipase C (antiPLCAb). Out of RA cases, 47.3% presented antiPAb, 36.8% antiTAb and 26.3% antiPLCAb. As it was expected, in the rA cases, these antibodies were found in a higher proportion of cases, i.e.: 85.7%, 71.4% and 57.1% respectively. When following the same cases before and during or after the treatment with nonsteroidal antiinflammatory agents (NSAIAs), the antibodies levels were significantly decreased especially in the RA cases. The results obtained indicated a significant rise of seric concentration of antiPAb, antiTAb and antiPLCAb, as well in RA as in rA. While the rise of antiPLCAb in RA and especially in rA could be explained due to microbial infections, the rise of the antiproteolytic enzymes antibody levels as well as the decrease of the antibody titres during or after NSAIAs treatment could be explained, in our opinion, on the basis of some autoimmune processes.

Antibody Specificity↗

PubMedDate not supplied

Inhibitory capacity of some fractions isolated from a green barley extract upon TNF alpha production by the cells of the THP-1 human monocytes line.

A green barley extract commercialized as an antiinflammatory product under the name of "Natural SOD" was fractionated based on the molecular weights principle. Knowing that the TNF alpha cytokine plays an important role in inducing inflammatory phenomena, by the use of two determination methods (ELISA and cytotoxicity), the fractions obtained were analysed for their capacity to modulate TNF alpha production/release by an LPS-activated human monocytes line (THP-1). The results pointed to the existence of 3 groups of substances (fractions 3, 4 and 9) apt to modulate TNF alpha production, fraction 4 being the most active. Of the TNF alpha determination methods, ELISA proved to be more sensitive as it detected not only free TNF alpha identified also by the cytotoxicity test, but also TNF alpha complexed with its soluble receptors. The presence of these substances in Natural SOD, fractions with modulatory action upon TNF alpha production, might partly account for the clinical efficiency of this product in the treatment of inflammatory affections reported in humans.

Anti-Inflammatory Agents, Non-Steroidal↗