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Anastasios E Germenis

agermen@med.uth.gr

Journal articles

2008
 
DOI   
PMID 
Vaios Karanikas, Matthaios Speletas, Maria Zamanakou, Fani Kalala, Gedeon Loules, Theodora Kerenidi, Angeliki K Barda, Konstantinos I Gourgoulianis, Anastasios E Germenis (2008)  Foxp3 expression in human cancer cells.   J Transl Med 6: 04  
Abstract: OBJECTIVE: Transcription factor forkhead box protein 3 (Foxp3) specifically characterizes the thymically derived naturally occurring regulatory T cells (Tregs). Limited evidence indicates that it is also expressed, albeit to a lesser extent, in tissues other than thymus and spleen, while, very recently, it was shown that Foxp3 is expressed by pancreatic carcinoma. This study was scheduled to investigate whether expression of Foxp3 transcripts and mature protein occurs constitutively in various tumor types. MATERIALS AND METHODS: Twenty five tumor cell lines of different tissue origins (lung cancer, colon cancer, breast cancer, melanoma, erythroid leukemia, acute T-cell leukemia) were studied. Detection of Foxp3 mRNA was performed using both conventional RT-PCR and quantitative real-time PCR while protein expression was assessed by immunocytochemistry and flow cytometry, using different antibody clones. RESULTS: Foxp3 mRNA as well as Foxp3 protein was detected in all tumor cell lines, albeit in variable levels, not related to the tissue of origin. This expression correlated with the expression levels of IL-10 and TGFb1. CONCLUSION: We offer evidence that Foxp3 expression, characterizes tumor cells of various tissue origins. The biological significance of these findings warrants further investigation in the context of tumor immune escape, and especially under the light of current anti-cancer efforts interfering with Foxp3 expression.
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DOI   
PMID 
Matthaios Speletas, Anna Kioumi, Gedeon Loules, Prodromos Hytiroglou, John Tsitouridis, John Christakis, Anastasios E Germenis (2008)  Analysis of SLC40A1 gene at the mRNA level reveals rapidly the causative mutations in patients with hereditary hemochromatosis type IV.   Blood Cells Mol Dis 40: 3. 353-359 May/Jun  
Abstract: Mutations in the SLC40A1 gene result in a dominant genetic disorder [ferroportin disease; hereditary hemochromatosis type (HH) IV], characterized by iron overload with two different clinical manifestations, normal transferrin saturation with macrophage iron accumulation (the most prevalent type) or high transferrin saturation with hepatocyte iron accumulation (classical hemochromatosis phenotype). In previous studies, the mutational analysis of SLC40A1 gene has been performed at the genomic DNA level by PCR amplification and direct sequencing of all coding regions and flanking intron-exon boundaries (usually in 9 PCR reactions). In this study, we analyzed the SLC40A1 gene at the mRNA level, in two RT-PCR reactions, followed by direct sequencing and/or NIRCA (non-isotopic RNase cleavage assay). This protocol turned out to be rapid, sensitive and reliable, facilitating the detection of the SLC40A1 gene mutations in two patients with hyperferritinemia, normal transferrin saturation and iron accumulation predominantly in macrophages and Kupffer cells. The first one displayed the well-described alteration V162 Delta and the second a novel mutation (R178G) that was further detected in two relatives in a pedigree analysis. The proposed procedure would facilitate the wide-range molecular analysis of the SLC40A1 gene, contributing to better understanding the pathogenesis of the ferroportin disease.
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2007
 
PMID 
E T Petridou, C Chavelas, S K Dikalioti, N Dessypris, A Terzidis, D I Nikoulis, C Markopoulos, Y Papadiamantis, A E Germenis (2007)  Breast cancer risk in relation to most prevalent IgE specific antibodies: a case control study in Greece.   Anticancer Res 27: 3B. 1709-1713 May/Jun  
Abstract: BACKGROUND: This study aims to explore the debatable role of allergy in breast cancer (BC) by using country-specific biological markers, namely levels of the most prevalent allergen-specific immunoglobulin E in Greece. PATIENTS AND METHODS: Blood samples and clinical information were collected over a 30-month period from 103 women with histologically-confirmed BC and 103 controls from two university hospitals in Athens. Allergen-specific IgE, against the 12 prevailing allergens in Greece were determined; thereafter, a score comprising the sum of the individual values for this battery of serological IgE determinations was created. Bivariate and multiple logistic regression analyses were undertaken using case-control status as the outcome and IgE-scores as the predictor variable, controlling for socio-demographic, gynecological and lifestyle confounders. RESULTS: The serum IgE score seemed to be positively related to BC (OR: approximately 1.73; CI: 0.95-3.14; p-value: 0.07). A positive correlation between serological evidence and allergic history among controls was also found (p-value: 0.06). CONCLUSION: This investigation suggests an IgE-mediated allergic response among women with BC in comparison to their controls. The finding needs confirmation by immuno-epidemiological investigation to clarify the directionality of this association and whether laboratory-ascertained atopy can be considered as a risk-marker of susceptibility in the development of BC.
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A E Germenis, V Karanikas (2007)  Immunoepigenetics: the unseen side of cancer immunoediting.   Immunol Cell Biol 85: 1. 55-59 Jan  
Abstract: Cancer immunosurveillance representing, till recently, the explanatory framework relating cancer and the immune system, does not convincingly explain tumor escape. At the beginning of the decade, a new theory emerged, namely the immunoediting theory, and it comprehensively defines the role of the immune system in carcinogenesis. The core of this theory embraces the concept that the immune system on the one hand protects the body from cancer and on the other it shapes the immunogenicity of these cancers, thus presents a persuasive rationalization of the resistance of tumors against the immune response. With the immune system playing, in this context, such a pivotal role in shaping the tumor immune profile and in subsequent oncogenesis, it seems rather paradoxical to accept the immunocompetent host's immune system as a constant moiety. While DNA mutations of immune genes create a rather polymorphic condition, their frequency is much lower than that of other genetic events. Of these, epigenetic alterations give rise to new epialleles, which can reach up to 100% per locus. Bearing in mind that cancer is characterized by a tremendous amount of epigenetic aberrations, in both gene and global level, it is reasonable to postulate that, for the same unknown causes, analogous aberrations could affect the immune genes. Should this be the case, the relation between oncogenesis and the immune system appears much more dynamic and complex. Such an immunoepigenetic approach to carcinogenesis could improve our understanding of a series of common cancer-related aspects, such as environmental risk factors, effectiveness of demethylating agents, failure of current immunotherapies, etc. Moreover, this immunoepigenetic paradigm will take the current perception of the immune system and cancer interrelation further and beyond, constituting that the immunoresistant cancer cell phenotype is not shaped by the immune system acting as a steady and rigid evolutionary pressure, but rather as an extremely dynamic variable.
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Maria Zamanakou, Anastasios E Germenis, Vaios Karanikas (2007)  Tumor immune escape mediated by indoleamine 2,3-dioxygenase.   Immunol Lett 111: 2. 69-75 Aug  
Abstract: Amongst the numerous mediators contributing towards the escape of tumors from the host's immune response against them, the enzyme indoleamine 2,3-dioxygenase (IDO) has recently attracted special attention. By catabolizing tryptophan to N-formyl-kynurenine, IDO starves T cells from this important amino acid rendering them incapable of mounting appropriate immune responses. Originally, IDO has been associated to peripheral tolerance and maternal tolerance towards the fetus. The recent identification of IDO-expressing tumor cells has implicated this molecule as a key mediator of the tumor immune escape. Mounting evidence indicates that, within the tumor microenvironment, not only tumor cells but also other infiltrating cells such as dendritic cells, monocytes and others can be sources of IDO. IDO-induced tryptophan depletion from the tumor microenvironment could be the result of either elevated levels of the enzyme or augmented tryptophan consumption by both tumor cells and antigen presenting cells of the host. Beyond the tryptophan depletion, accumulation of its metabolites into the tumor environment seems to also propagate the suppression of anti-tumor immune responses. Finally, evidence emerges indicating that IDO possibly promotes tumor immune escape by inducing an immunoregulatory or an anergic T cell phenotype at a systemic level. In this context, anti-IDO therapeutic approaches are already under investigation, considering 1-methyl-tryptophan, its analogues as well as newly identified chemicals and natural extracts.
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DOI   
PMID 
Giorgos S Metsios, Andreas D Flouris, Athanasios Z Jamurtas, Andres E Carrillo, Demetrios Kouretas, Anastasios E Germenis, Konstantinos Gourgoulianis, Theodoros Kiropoulos, Manolis N Tzatzarakis, Aristeidis M Tsatsakis, Yiannis Koutedakis (2007)  A brief exposure to moderate passive smoke increases metabolism and thyroid hormone secretion.   J Clin Endocrinol Metab 92: 1. 208-211 Jan  
Abstract: CONTEXT: Active smoking influences normal metabolic status and thyroid function. OBJECTIVE: The objective was to assess experimentally the effects of 1 h of moderate passive smoking in a controlled simulated bar/restaurant environment on the metabolism and thyroid hormone levels in healthy nonsmokers. PARTICIPANTS: Eighteen (nine females, nine males) healthy individuals (mean +/- sd: age, 25.3 +/- 3.1 yr; height, 174.0 +/- 10.1 cm; weight, 65.2 +/- 13.7 kg) participated in the study. DESIGN: In repeated-measures randomized blocks, participants visited the laboratory on 2 consecutive days. In the experimental condition, they were exposed to 1 h of moderate passive smoking at a carbon monoxide concentration of 23 +/- 1 ppm in an environmental chamber, whereas in the control condition participants remained in the same chamber for 1 h breathing normal atmospheric air. MAIN OUTCOME MEASURES: In both conditions, cotinine serum and urine levels, resting energy expenditure (REE), as well as concentration of T3, free T4, and TSH were assessed before participants entered the chamber and immediately after their exit. Heart rate and blood pressure were tested in 10-min intervals during all REE assessments. RESULTS: The mean +/- sd difference of serum and urine cotinine levels (-0.27 +/- 3.94 vs. 14.01 +/- 6.54 and 0.05 +/- 2.07 vs. 7.23 +/- 3.75, respectively), REE (6.73 +/- 98.06 vs. 80.58 +/- 120.91) as well as T3 and free T4 (0.05 +/- 0.11 vs. 0.13 +/- 0.12 and 0.02 +/- 0.15 vs. 0.22 +/- 0.20) were increased in the experimental compared with the control condition at baseline and follow-up (P < 0.05). No statistically significant variation was observed in the mean difference of the remaining parameters (P > 0.05). Serum and urine cotinine values were linearly associated with REE (P < 0.05). CONCLUSION: One hour of passive smoking at bar/restaurant levels is accompanied by significant increases in metabolism and thyroid hormone levels.
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PMID 
Vaios Karanikas, Maria Zamanakou, Theodora Kerenidi, Jubrail Dahabreh, Athanasios Hevas, Marianna Nakou, Konstantinos I Gourgoulianis, Anastasios E Germenis (2007)  Indoleamine 2,3-dioxygenase (IDO) expression in lung cancer.   Cancer Biol Ther 6: 8. 1258-1262 Aug  
Abstract: BACKGROUND: The expression of indoleamine 2,3-dioxygenase (IDO) by tumor cells has been considered as a major tumor immune escape mechanism. The aim of this study was to investigate the expression of IDO in lung cancer cell lines as well as in surgically resected lung cancer specimens comparing the latter, to the expression in autologous samples from the corresponding non malignant lung tissue. Correlations of IDO expression with clinicopathological parameters of the disease were performed. METHODS: Nine human lung cancer cell lines and 28 patients with various types of primary lung cancer were enrolled in the study. IDO expression was determined by quantitative real-time PCR using a sample of lung hamartoma as reference. RESULTS: IDO expression was detected in all but three patients' tumor samples, in all but four autologous non malignant lung tissues and in three out of the nine cell lines that were examined. The relative expression of IDO in lung cancer cell lines (4.7 +/- 11.1) was significantly lower than that of all patients' tumor samples (p = 0.006) as well as than that of the autologous non affected lung tissues (p = 0.027). No statistically significant differences were noted between ADC and SCC regarding either the tumor samples or the autologous non affected samples. No significant correlations between IDO expression and clinicopathological parameters were found. CONCLUSION: Direct evidence is provided demonstrating that IDO mRNA can be constitutively expressed by lung cancer cells. The higher IDO expression observed in patients' samples can be attributed to the production of the enzyme by other cells recruited in the tumor microenvironment and the peri-tumoral lung area and/or to its induction by soluble factors of tumor origin.
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PMID 
Karanikas, Tsochas, Boukas, Kerenidi, Nakou, Dahabreh, Poularakis, Gourgoulianis, Germenis (2007)  Co-expression patterns of tumor-associated antigen genes by non-small cell lung carcinomas: Implications for immunotherapy.   Cancer Biol Ther 7: 3. Dec  
Abstract: Background: Polyvalent vaccination represents a recent attempt to improve the effectiveness of lung cancer immunotherapy. This study aimed to investigate whether a gene expression pattern of tumor-associated antigens (TAA) would exist indicating that their use will be most appropriate for the polyvalent vaccination of Caucasian non-small cell lung carcinoma (NSCLC) patients. We examined the concomitant expression of genes belonging to different TAA families for which expression frequencies either have never been detected in NSCLC or vary widely in the literature. Methods: Tumor material from 23 patients with NSCLC (12 adenocarcinomas, 8 squamous cell carcinomas, 3 bronchiolo - carcinomas) was examined. mRNA transcripts were detected for 5 genes of the survivin family, 5 MAGE-A genes as well as the genes of human telomerase reverse transcriptase (hTERT) and p53, by the use of quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) or semi-quantitative RT-PCR. Results: 15/23 (65%) and 8/23 (35%) tumor samples were found expressing 6-11 and 2-5 out of the 12 examined TAAs, respectively, at levels >1% of the testis reference sample. The most prevalent TAA patterns observed were those of survivin standard (survivin-std)/survivin-2B expressed by 22/23 (95.5%) tumor samples and of survivinstd/ survivin-2B/hTERT expressed by 19/23 (82.5%) tumor samples. The expression levels of the survivin-std gene strongly positively correlated to those of the survivin-2B (p=0.001) and the hTERT genes (p=0.031). The number of concomitantly expressed genes was found to be positively correlated to the age of the patients (p=0.001) and the tumor size (p=0.048). Conclusion: This study provides evidence that, in Caucasian patients with NSCLC, highly prevalent expression patterns of TAA genes, predominantly of overexpressed TAAs, do exist. This result implies that the combined use of these TAA could help in designing more effective NSCLC immunotherapeutic protocols.
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DOI   
PMID 
Violeta Roka, Spyros P Potamianos, Andreas N Kapsoritakis, Efthalia E Yiannaki, George N Koukoulis, Ioannis Stefanidis, George K Koukoulis, Anastasios E Germenis (2007)  Prevalence of coeliac disease in the adult population of central Greece.   Eur J Gastroenterol Hepatol 19: 11. 982-987 Nov  
Abstract: OBJECTIVES: Recent studies from several countries have shown that coeliac disease (CD) is increasingly being diagnosed in adults, as the availability of new, accurate serologic tests has made screening in the general population possible. No data exist regarding the prevalence of CD in Greece. The aim of this study was the implementation of a serologic screening procedure for CD in the adult general population of Thessaly, an area of central Greece, using a novel diagnostic algorithm. METHODS: The study included 2230 participants (1226 women, 1004 men, median age 46 years, range 18-80 years), selected by systematic random sampling, from the adult general population of Thessaly. All the serum samples were tested for total immunoglobulin A (IgA)-serum levels, to exclude IgA deficiency. Samples with total IgA within the normal range were tested for IgA antibodies against native human-tissue transglutaminase (anti-tTG); samples that were anti-tTG positive were tested for IgA antiendomysial antibodies (EmA). Samples from participants with selective IgA deficiency were examined for IgG antigliadin antibodies. Participants who were EmA-positive or antigliadin antibody-positive were referred for intestinal biopsy and human leucocyte antigen (HLA) typing. RESULTS: No participant with selective IgA deficiency was detected. Four individuals tested positive for EmA, all of whom were biopsy-proven coeliacs. Therefore, the CD prevalence in this general population sample is 1 : 558 or 1.8 per 1000 (SE 0.13). The four new patients with abnormal histology (two men, two women) were aged between 18 and 35 years. Two of them were considered to be asymptomatic and two presented with a subclinical course. All four had the heterodimer HLA-DQ2. CONCLUSIONS: This first serological screening study for CD in Greece has demonstrated that CD prevalence in Thessaly is among the lowest reported in Europe.
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2006
 
DOI   
PMID 
Elias Zintzaras, Anastasios E Germenis (2006)  Performance of antibodies against tissue transglutaminase for the diagnosis of celiac disease: meta-analysis.   Clin Vaccine Immunol 13: 2. 187-192 Feb  
Abstract: A meta-analysis of studies investigating the diagnostic accuracy of enzyme-linked immunosorbent assays (ELISA) for antibodies against tissue transglutaminases (tTG) of various origins in celiac disease (CD) diagnosis was carried out. Twenty-one studies, with untreated CD patients and healthy/CD-free controls, were included in the meta-analysis. The diagnostic accuracy was estimated using a summary receiver operating characteristic (SROC) curve and pooled sensitivity (Se) and specificity (Sp). Multiple assays within a study were treated by considering all the assays within a study and by analyzing the most popular assay (i.e., the commercial anti-tTTG ELISA most frequently utilized in the papers in which multiple assays were included). The SROC curve indicated the absence of heterogeneity, and the superiority of recombinant human tTG (rh-tTG) and purified human tTG (ph-tTG) compared to guinea pig-tTG (gp-tTG). The sensitivities (most popular assay) for rh-tTG, ph-tTG, and gp-tTG were 94%, 90%, and 92%, respectively, and the specificities were 97%, 92%, and 96%, respectively. A sensitivity analysis (exclusion of studies with bias) altered the results of ph-tTG: Se, 95%; Sp, 98%. The sensitivities (all individual assays) for rh-tTG, ph-tTG, and gp-tTG were 94%, 94%, and 91%, respectively, and the specificities were 95%, 94%, and 89%, respectively. Human tTG ELISA is sensitive and specific, and it can be used for mass screening. Sensitivity analysis showed that ph-tTG might perform better.
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2005
 
DOI   
PMID 
Mary S Boulbou, George N Koukoulis, Erini D Makri, Efthymia A Petinaki, Konstantinos I Gourgoulianis, Anastasios E Germenis (2005)  Circulating adhesion molecules levels in type 2 diabetes mellitus and hypertension.   Int J Cardiol 98: 1. 39-44 Jan  
Abstract: BACKGROUND: Risk factors for atherosclerosis such as hypertension, type 2 diabetes, obesity and dyslipidemia affect endothelial function and stimulate adhesion molecules expression. The aim of the study was to examine endothelial activation in type 2 diabetes and hypertension as indicated by adhesion molecule levels and further to investigate whether the coexistence of the above conditions has a different effect. METHODS: Serum levels of soluble E-selectin, ICAM-1 and VCAM-1 were measured in 17 hypertensive type 2 diabetic patients (DM-HY), 32 normotensive type 2 diabetic patients (DM), 11 hypertensive nondiabetic patients (HY) and 15 healthy subjects. RESULTS: In diabetic patients (either DM-HY or DM), soluble E-selectin levels were significantly increased compared to healthy subjects (p<0.001). In HY patients, both sE-selectin (66.44+/-71.59 vs. 29.42+/-15.56 ng/ml, p=0.033) and sVCAM-1 (1529+/-433.33 vs. 1027+/-243.56 ng/ml, p=0.03) levels were found significantly higher compared to healthy subjects (p<0.05). The coexistence of diabetes and hypertension (DM-HY) did not have an additive effect on circulating adhesion molecules levels compared with the levels observed in either diabetes or hypertension. Systolic and diastolic blood pressure (BP) were independent factors correlated respectively with sE-selectin and sVCAM-1 levels (R=0.454, p=0.034 and R=0.578, p=0.005) in nondiabetic subjects (hypertensive and normotensive). CONCLUSIONS: Type 2 diabetes mellitus and hypertension induce endothelial activation as indicated by elevated levels of soluble adhesion molecules. This effect is not different when comorbidity is present.
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PMID 
D Mastellos, A E Germenis, J D Lambris (2005)  Complement: an inflammatory pathway fulfilling multiple roles at the interface of innate immunity and development.   Curr Drug Targets Inflamm Allergy 4: 1. 125-127 Feb  
Abstract: Complement has been long perceived as an innate immune system that plays a pivotal role in the maintenance of host defense against infectious agents and the propagation of pro-inflammatory responses in the context of human disease. Complement activation has been associated with the onset of acute inflammatory reactions leading to complications such as acute graft rejection, local tissue injury and multi-organ failure. However, recent studies have indicated that various complement activation products may exert a beneficial effect by contributing to critical developmental and regenerative processes. Appreciating this extraordinary 'versatility' of complement proteins provides a framework for revisiting the design of effective complement therapeutics. A balanced strategy will have to consider limiting the detrimental proinflammatory effects of complement while preserving those activities that promote tissue repair and regeneration, cell survival and early development.
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Anastasios E Germenis, Efthalia E Yiannaki, Kalliopi Zachou, Violeta Roka, Sotirios Barbanis, Christos Liaskos, Kalliopi Adam, Andreas N Kapsoritakis, Spyros Potamianos, Georgios N Dalekos (2005)  Prevalence and clinical significance of immunoglobulin A antibodies against tissue transglutaminase in patients with diverse chronic liver diseases.   Clin Diagn Lab Immunol 12: 8. 941-948 Aug  
Abstract: The prevalence of celiac disease (CD) and the prevalence and clinical significance of anti-tissue transglutaminase (tTG) antibodies (tTGAbs) in a large series of patients with chronic liver diseases were assessed. We studied 738 patients (462 with chronic viral hepatitis, 117 with autoimmune liver diseases, 113 with alcoholic or nonalcoholic fatty liver disease, and 46 with other liver disorders) and 1,350 healthy controls (HC). Immunoglobulin A (IgA) tTGAbs were measured by enzyme-linked immunosorbent assay and a microsphere-based flow cytometric assay. Positive sera were investigated for IgA antiendomysial antibodies (EmA). IgA tTGAb-positive subjects were invited to undergo a small-intestinal biopsy and HLA-DQ allele typing. Four of 1,350 HC (0.3%) tested tTGAb(+) EmA(+) and underwent a biopsy (CD confirmation in all). Four of 738 liver disease patients tested tTGAbs(+) EmA(+) (0.54%; not statistically significant). Two were HCV infected (1.24%; not statistically significant), and two had transaminasemia of unknown origin. Forty-three patients tested tTGAbs(+) EmA(-) (5.8%; P<0.001 compared to HC). Inhibition experiments verified the existence of specific IgA anti-tTG reactivity. Twenty-six of 43 patients underwent a biopsy (all negative for CD). Binary logistic regression analysis revealed age (P=0.008), cirrhosis (P=0.004), alkaline phosphatase (P=0.026), and antinuclear antibodies (P=0.012) as independent risk factors for tTGAb reactivity among the patients. It was concluded that CD prevalence is the same in HC and patients with chronic liver diseases. The prevalence of tTGAbs is higher in hepatic patients compared to HC, but their specificity for CD diagnosis in this group of patients is low. tTGAbs in patients appear to be associated with the presence of autoimmunity, cirrhosis, and cholestasis, irrespective of the origin of the liver disease.
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2004
 
PMID 
Efthalia E Yiannaki, Elias Zintzaras, Apostolos Analatos, Catherine Theodoridou, Georgios N Dalekos, Anastasios E Germenis (2004)  Evaluation of a microsphere-based flow cytometric assay for diagnosis of celiac disease.   J Immunoassay Immunochem 25: 4. 345-357  
Abstract: The multiplexed particle-based flow cytometric technology proposes a new approach for the diagnosis of autoimmune diseases combining the advantages of conventional methods with the ability to quantitatively determine multiple autoantibodies in the same sample, simultaneously and rapidly. Recently, a commercial kit (FIDIS Celiac, Biomedical Diagnostics, Mane la Vallé, France) was introduced for the simultaneous detection of IgA anti-tissue transglutaminase (anti-tTG), IgG, and IgA anti-gliadin antibodies (AGA). This study was undertaken to evaluate and compare the FIDIS Celiac kit with standardized commercial ELISAs (QUANTA Lite, INOVA Diagnostics Inc., San Diego, CA). A disease group consisted of 21 samples from untreated patients with biopsy confirmed celiac disease (CD), and two control groups of historical sera (207 from regular blood donors and 181 from chronically infected hepatitis patients) were studied. All control sera were negative for IgA anti-endomysial antibodies (EmA) and had an IgA concentration above the lower normal limit. Concerning the reproducibility, intra- and inter-assay coefficients of variation (CVs) ranging between 2% and 12%, and between 3% and 21%, respectively, were observed. Regarding the diagnostic quality, each assay was compared to the disease diagnosis using the McNemar test and the kappa (K) parameter, while ROC analysis was applied. Generally, the performance of FIDIS assay was proved almost equally adequate to that of ELISA in the detection of IgA anti-tTG antibodies, IgA and IgG AGA. However, the performance of FIDIS assay was found surmounting that of ELISA among hepatitis patients, possibly due to the avoidance of debris and unbound cross contaminants and, hence, the "noise" of such materials in samples under analysis. Taking our results together with the simplicity and the high throughput of FIDIS assay, its overall performance in the diagnosis of CD seems better than that of ELISA.
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1999
 
PMID 
A E Germenis (1999)  Beyond the Ingelfinger Rule: the intellectual property ethics after the end of biomedical journals' monopoly.   Med Inform Internet Med 24: 3. 165-170 Jul/Sep  
Abstract: According to the so-called Ingelfinger Rule (IR), biomedical journals do not accept for publication papers which have already been publicized elsewhere. This rule was subjected to fierce criticism which was mainly based on the fact that authors transfer the intellectual rights of their work to the journals. With the emergence of the Internet, the scientific community has a golden opportunity to re-evaluate the IR concept. Scientists no longer have to depend on the debatable benefits (i.e. publicity and review) stemming from journal publications; rather they can be free to explore novel communication opportunities and, subsequently, to tackle the emerging intellectual property issues. This approach should take into account the tight bond between applied research and the world economy, the need for teamwork instead of individual effort for effective scientific research, and the added value of journal publications. Based on such an analysis, it would appear that the inherent characteristics of the Internet promote a re-assessment of the intellectual property theory on three levels: the cognitive (the way in which knowledge is made up from its building blocks), the morphological (the use of hypertext) and finally the sociological (the formation of virtual scientific communities). It is concluded that publishing on the Internet necessitates a different approach to the question of intellectual property based on the primal values of science. This can be achieved only if the scientific community embraces and nourishes the academic nature of the Internet as well as laying down the rules to control the dissemination of ideas without the intervention of non-scientific third parties.
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1997
 
PMID 
A E Germenis, P A Kokkinides, C Stavropoulos-Giokas (1997)  Non-indexed medical journals in the Web: new perspectives in the medical literature.   Int J Med Inform 47: 1-2. 65-68 Nov  
Abstract: Many medical journals, publishing in national languages, meet serious financial problems and difficulties when they attempt to become indexed in the international indices. Obviously, this not only affects the scientific quality of non-indexed medical journals (NIMJs) but also affects the awareness of the scientific community of topics with apparently local but potentially broader scientific significance. This is a reality for over 100 Greek medical journals, none of which has a life longer than 30 years or more than 2000 subscribers. Among them, the 'Archives of Hellenic Medicine' (AHM) is published and sponsored by the Athens Medical Society (the oldest medical society in Greece founded in 1835). This peer-reviewed Journal is being published for 13 years, bimonthly, in Greek. Attempting to overcome the above mentioned problems and to be involved in the process of discovering the most effective way of scientific 'skywriting', 2 years ago, the AHM entered full-text in the Web and it was decided that up to 500% of its volume should be covered by English-language papers. As a result, the AHM are now included in the main Web lists of medical journals and their home page is linked in many academic pages having approximately 500 hits/month. Furthermore, 45 retrievals of AHM's English-language papers or English abstracts of Greek-language articles were reported by e-mail response from abroad. Considered apart from the paper-publishing, the expenses of the digital publishing of the AHM are about half of those of paper-publishing, as they were before the appearance of the Journal in the Web. Up to now, about 40% of the Journal's digital publishing cost is covered by advertisements included in its pages and by a modification of its paper-publishing policy. It is concluded that the international scientific community is not indifferent for information published in NIMJs. Medical national minorities working abroad express special interest for this type of information. The Web makes the NIMJs accessible to these potential readers, who would never have the chance to acquire them in their printed form.
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1991
 
PMID 
P A Dimitriou, A E Germenis, A G Kasfiki, A K Depasquale, T E Karpathios, S E Antipas (1991)  The effect of blood transfusion on 51Cr-red blood cells surface-counting data in homozygous beta-thalassaemia.   Clin Lab Haematol 13: 4. 363-370  
Abstract: The effect of blood transfusion on 51Cr-red blood cells surface-counting patterns was studied in 22 patients with homozygous beta-thalassaemia being transfused during erythrocyte survival study. Surface-counting patterns of 15 thalassaemics who had not been submitted to blood transfusion during the erythrocyte survival study were served as controls. In 17 of the transfused patients (group A), spleen excess counts (SEC) appeared decreasing after blood transfusion, reaching a minimum (about 50% of the initial value) 3-4 days later, and increasing thereafter to reach again their initial value on 8th to 10th posttransfusion day. The SEC pattern of the remaining 5 transfused patients (group B) presented a continuously ascending curve. Corresponding changes were observed in excess liver counts and heart counts patterns. As a result of these changes spleen/liver ratio (S/L) was found significantly affected by blood transfusion in the majority of thalassaemic patients which were transfused during the erythrocyte survival study. Furthermore, the mean age of group A patients (12.1 +/- 5.5 years) has been found to be significantly lower than that of group B (21.8 +/- 3.3 years). On the contrary, in the control group the SEC pattern appeared permanently increasing and the S/L was found unaltered during the whole duration of the erythrocyte survival study. In conclusion, as far as the surface-counting data represent indexes for splenectomy in thalassaemic patients, the results of this study signify that the influence of blood transfusion on these has to be taken into account.
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1990
 
PMID 
P A Dimitriou, A K Depascouale, A E Germenis, S E Antipas (1990)  Kinetics of heat-damaged homologous erythrocytes. A five-compartmental analysis.   Eur J Nucl Med 17: 1-2. 49-54  
Abstract: A new theoretical five-compartmental model (5CM) was developed for analysis of the clearance of heat-damaged erythroctes (HDE) labelled with chromium 51. Besides the HDE-spleen interaction, this new model also takes into account the interaction between extrasplenic reticuloendothelial (RES) sites and HDE, i.e. the hepatic clearance of fragmented erythrocytes (FE). Accordingly, HDE clearance curves are analysed into three exponential components, the fastest of which describes the RES-FE interaction, whereas the others describe the splenic clearance of spherocytes. Therefore, an estimation of the effective liver blood flow for HDE (ELBF) was achieved, along with a series of parameters describing splenic function. The 5CM proved to be more efficient than a previously proposed three-compartmental model (3CM) in the mathematical description of HDE clearance. Comparison was made by applying both models to 37 experimental curves obtained from 20 patients with congenital hemolytic anemias. The values for the splenic function parameters calculated by 5CM analysis and the strong correlations observed among them offer evidence that this model provides an adequate approximation to the real conditions under which HDE clearance takes place. Furthermore, a detailed quantitative analysis of the pooling of spherocytes within the spleen was attempted in this work, and this phenomenon was found to compete with splenic irreversible spherocyte trapping. The ELBF proved to be closely correlated with the hemodynamic splenic parameters, following first-order kinetics, as do low-dose colloids.
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1987
 
PMID 
C Politis, D G Spigos, P Georgiopoulou, H Vrettou, I Economidou, A E Germenis, C Richardson, G Papaevangelou (1987)  Partial splenic embolisation for hypersplenism of thalassaemia major: five year follow up.   Br Med J (Clin Res Ed) 294: 6573. 665-667 Mar  
Abstract: Six patients with thalassaemia major were treated by partial splenic embolisation as an alternative to splenectomy and followed up for five years. Results were compared with those in a matched control group of seven patients treated by splenectomy. All patients treated by partial splenic embolisation showed a reduction in blood transfusion requirements comparable with those in the controls and which remained unchanged over the five years. Serious infections that commonly occur in patients splenectomised for thalassaemia did not occur after embolisation, presumably owing to preservation of some immune function by the splenic remnant. By contrast with the change in platelet counts seen after splenectomy, platelet counts remained normal after partial splenic embolisation, so reducing the risk of thromboses. On the other hand, pre-existing leucopenia and thrombocytopenia were corrected after embolisation. It is concluded that partial splenic embolisation provides an alternative to splenectomy for thalassaemia major and is equally effective and much safer.
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