Michael Economou

Differential Effects of NOD2 Variants on Crohn's Disease Risk and Phenotype in Diverse Populations: A Metaanalysis

OBJECTIVES:Three variants of the CARD15/NOD2 gene (SNP8, SNP12, and SNP13) have been associated with Crohns disease (CD). We assessed the impact of NOD2 variants on the CD risk across diverse populations and examined possible associations with disease phenotype.METHODS:We performed a metaanalysis searching MEDLINE and EMBASE (last search 05/2004) and contacting field experts.RESULTS:Forty-two eligible studies contributed data on 206 comparisons. No variants were detected in Asians. In non-Jewish descent Caucasians carriage of SNP8, SNP12, or SNP13 had an odds ratio (OR) for CD of 2.20 (95% CI: 1.84–2.62), 2.99 (95% CI: 2.38–3.74), and 4.09 (95% CI: 3.23–5.18), respectively. For Jewish descent patients the corresponding ORs were 1.74, 1.93, and 2.45, respectively. The OR in carriers of at least two alleles was 17.1 (95% CI: 10.7–27.2). Large studies tended to yield more conservative estimates than smaller studies, so publication or other bias cannot be excluded. Among CD patients, carrying at least one high-risk variant increased slightly the risk for familial disease (OR = 1.49, (95% CI: 1.18–1.87)), modestly the risk of stenosing CD (OR = 1.94, (95% CI: 1.61–2.34)), and more prominently the risk of small bowel involvement (OR = 2.53, (95% CI: 2.01–3.16)).CONCLUSIONS:SNP8, SNP12, and SNP13 have differential effects on CD risk, with SNP13 having the strongest genetic effect. These NOD2 variants are also significant risk factors for CD phenotype, in particular ileal location.

Baseline cholesterol is associated with the response to antiviral therapy in chronic hepatitis C

Background:  Hepatitis C virus (HCV) partially interacts with low‐density lipoprotein (LDL) receptors, suggesting a role for lipids in regulating HCV clearance. Our aim was to study if baseline lipids can discriminate responders from non‐responders among patients with HCV infection.

Isolation and partial characterization of prothymosin α from porcine tissues

Prothymosin α, an immunoactive polypeptide of 12 kDa, has been isolated from porcine thymus, spleen, lung and kidney. It lacks aromatic and sulfur‐containing amino acids and has a high content of glutamic and aspartic acids. Tryptic digestion of porcine thymus prothymosin α yielded peptides which on separation, amino acid analysis and alignment with the known sequence of prothymosin α from rat and man showed that the amino terminal portion of the molecule is conserved and the few differences present are confined to the car☐y terminal.

Rectal Epstein-Barr virus-positive Hodgkin's lymphoma in a patient with Crohn's disease: case report and review of the literature.

We present the case of a 35-year-old man with Crohns disease diagnosed at the age of 27, several months after an operation for small-bowel adenocarcinoma. Seven years after the adenocarcinoma diagnosis, the patient presented with severe continuous anal pain and diarrhea. In parallel with antibiotic administration, the patient was given treatment with Infliximab, but without clinical symptom amelioration. Sigmoidoscopy and subsequent biopsies from an ulcerated rectal area supported the diagnosis of Epstein-Barr virus-positive (EBV(+)) primary Hodgkins lymphoma. Infliximab administration was immediately discontinued and the patient underwent oncological follow-up and began a course of chemotherapy. Only a few cases with primary gastrointestinal Hodgkins lymphoma in Crohns disease patients have so far been reported, including a variety of scenarios on the causal relationship including disease duration, presence of EBV, long-term immunosuppressive treatment and, recently, anti-TNFα administration.

Mechanism of Action of Prothynosin α in the Human Autologous Mixed Lymphocyte Response

AbstractProthymosin α(Prota), an immunologically active polypeptide derived initially from rat thymus, and now pig thymus, was tested for its effect on autoantigen-induced human T cell proliferation in vitro. Pig ProTa was found to enhance the autologous mixed lymphocyte response (auto-NLR). Optimum enhancement was achieved at doses which varied among different donors. Treatment of the stimulatory monocytes with ProTa resulted in considerably higher auto-MLR responses as compared to those with non treated monocytes. ProTa was without effect on T lymphocytes. In contrast, T lymphocytes exhibited enhanced proliferative activity when treated with ProTa in the environment of autologous monocytes. Horeover, supernatants from cultures of monocytes incubated with ProTa(ProTa-sup) were also shown to enhance the human auto-NLR either after addition in cultures or after preincubation with responder T lymphocytes. In addition, ProTa-sup did not demonstrate any detectable inter-leukin I (IL 1) or interleukin 2 (1L 2)...

Appearance of thymosin α1 in supernatants of monocytes incubated with prothymosin α

Abstract Prothymosin α, a polypeptide of 109 to 111 amino acid residues, contains the entire thymosin α 1 sequence (residues 1–28) at its amino terminal. Human peripheral blood monocytes incubated with prothymosin α release thymosin α 1 in the culture supernatants. In addition total RNA is found to increase. The production of thymosin α 1 involves de novo protein synthesis as shown by the kinetics of this release and its inhibition by actinomycin D and cycloheximide. Thymosin α 1 release, possibly in association with HLA-DR, stimulates the proliferation of the T Cell population.

Characteristics of ascitic fluid in cardiac ascites.

Objective. Cardiac ascites remains a rare entity with unique clinical and pathogenetic features that are not adequately recognized by clinicians. The purpose of this study was to contribute towards elucidating the nature of cardiac ascites. Material and methods. We describe a series of 26 ascitic fluid samples from eight patients with cardiac ascites that were referred and further evaluated for the etiology and nature of their ascites. Results. In all samples ascitic fluid was an exudate with an increased serum-ascitic fluid albumin gradient, a pattern unique in ascites. Other causes of ascites were excluded, often through a protracted differential diagnostic procedure. Conclusions. The unique pattern of cardiac ascites should allow for rapid diagnosis and characterization: The clinical implications of furosemide use in its response and biochemical properties warrant further description.

Octreotide in the treatment of refractory ascites of cirrhosis

Dietary sodium restriction and diuretic treatment have been shown to be effective in the treatment of ascites in the majority of cirrhotic patients. However, approximately 5 to 10% of patients develop refractory ascites, which is defined as ascites that does not respond to intensive diuretic therapy (diuretic-resistant) or ascites that cannot be controlled because the patient develops diuretic-induced complications that prevent the use of an effective diuretic dose (diuretic-intractable). Current therapeutic approaches for refractory ascites include repeated large-volume paracentesis and transjugular intrahepatic portosystemic shunting. In the present report, subcutaneous octreotide treatment improved renal function and hemodynamics and diuretic response in two patients with refractory ascites in line with a marked decrease in renin and aldosterone secretion. We consider that octreotide could be of value in the management of refractory ascites in cirrhotic patients.

Immunohistochemical expression of FHIT gene product in inflammatory bowel disease

Objective To investigate the expression of Fhit protein in 53 patients with ulcerative colitis and Crohns disease, as well as in 13 ulcerative-colitis-associated adenocarcinomas, and its eventual relationship with clinicopathological data and response to therapy. Materials and methods We performed immunohistochemistry in archival material of formalin-fixed, paraffin-embedded tissues using the anti-Fhit antibody and the streptavidin-biotin peroxidase method. Results In 35/38 cases of ulcerative colitis, Fhit protein (pFhit) was absent or reduced. In the remaining three cases, it was expressed normally. In 12/15 cases of Crohns disease, pFhit was absent or reduced, as it was in 4/13 cases of ulcerative-colitis-associated adenocarcinoma. Statistically significant differences of pFhit expression were observed between the active phase and the chronic healed phase of ulcerative colitis, and between the active phase and the normal colon mucosa. Also, statistically significant differences of pFhit expression were observed between (1) the resolving phase of ulcerative colitis and normal colon mucosa, (2) the chronic healed phase and normal colon mucosa, and (3) Crohns disease and normal colon mucosa. Interestingly, a statistically very significant difference in pFhit expression was noticed between ulcerative colitis and ulcerative-colitis-associated adenocarcinoma. Conclusions Our results show that immunohistochemical expression of pFhit is completely absent or very reduced in idiopathic bowel disease (IBD) as well as in several ulcerative-colitis-associated adenocarcinomas in north-western Greece. These findings suggest that the FHIT gene might be involved in IBD and in a subgroup of ulcerative-colitis-associated carcinogenesis, although larger series should be tested.

A sensitive and specific competition microELISA for the immunoactive polypeptide parathymosin and detection of this peptide in porcine tissues

A sensitive and specific microELISA assay is described for the immunoactive polypeptide parathymosin. Antibodies against a synthetic peptide corresponding to the rat parathymosin sequence 5-30 were raised in rabbits immunised with this peptide conjugated to keyhole limpet hemocyanin (KLH). The useful range of the assay was 0.25-30 pmol (3-330 ng) of parathymosin and the assay was specific. The related immunoactive polypeptides prothymosin alpha or thymosin alpha 1 showed no cross-reactivity. In spiking experiments the recovery of the assay was found to be greater than 92% at all concentrations tested. The intra-assay variation was 17%, whereas the inter-assay variation was 26%. Using this assay the highest concentration of parathymosin was found in porcine liver, followed by kidney, lung, thymus and spleen. This assay compares favorably with one microELISA and two RIA methods already published, in that it is more sensitive by at least an order of magnitude, and it is simpler and quicker.