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Biomedical subjects

A Germenis

Publications and source records attributed to A Germenis.

At least 19 recordsLinked to original sources

DHLAS: A web-based information system for statistical genetic analysis of HLA population data.

DHLAS (database HLA system) is a user-friendly, web-based information system for the analysis of human leukocyte antigens (HLA) data from population studies. DHLAS has been developed using JAVA and the R system, it runs on a Java Virtual Machine and its user-interface is web-based powered by the servlet engine TOMCAT. It utilizes STRUTS, a Model-View-Controller framework and uses several GNU packages to perform several of its tasks. The database engine it relies upon for fast access is MySQL, but others can be used a well. The system estimates metrics, performs statistical testing and produces graphs required for HLA population studies: (i) Hardy-Weinberg equilibrium (calculated using both asymptotic and exact tests), (ii) genetics distances (Euclidian or Nei), (iii) phylogenetic trees using the unweighted pair group method with averages and neigbor-joining method, (iv) linkage disequilibrium (pairwise and overall, including variance estimations), (v) haplotype frequencies (estimate using the expectation-maximization algorithm) and (vi) discriminant analysis. The main merit of DHLAS is the incorporation of a database, thus, the data can be stored and manipulated along with integrated genetic data analysis procedures. In addition, it has an open architecture allowing the inclusion of other functions and procedures.

Databases, Genetic↗

Soluble adhesion molecules are not involved in the development of retinopathy in type 2 diabetic patients.

Raised serum levels of adhesion molecules are believed to reflect endothelial activation and may contribute to the development of diabetic vascular complications. The aim of this study was to clarify the association between soluble adhesion molecules levels and retinopathy in type 2 diabetic patients. Levels of soluble E-selectin, ICAM-1 and VCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 47 type 2 diabetic patients classified in two subgroups according to the presence (n=34) or absence (n=13) of retinopathy as determined by fundus ophthalmoscopy; 22 control subjects were also studied. Soluble E-selectin levels were significantly elevated in both diabetic subgroups compared to control subjects (p<0.01), while no significant difference was found in sICAM-1 and sVCAM-1 levels. However, sE-selectin, sICAM-1 and sVCAM-1 levels were comparable in diabetic subgroups. The progression of retinopathy was not associated with an increase in soluble adhesion molecules levels. Stepwise multiple regression analysis revealed that only diabetes duration and microalbuminuria were independent determinants of retinopathy (p<0.01). Our results confirm the contribution of endothelial activation in the development of diabetic complications as indicated by increased levels of soluble adhesion molecules. However, a direct implication of adhesion molecules in the pathogenesis or progression of type 2 diabetic retinopathy cannot be supported.

Adult↗

Morning levels of fibrinogen in children with sleep-disordered breathing.

Elevated fibrinogen level is a predictor of cardiovascular disease in adults, and it is associated with sleep-disordered breathing. Levels of fibrinogen in adults are affected by other co-existing cardiovascular risk factors, which are not usually present in children. To investigate the association between fibrinogen and sleep-disordered breathing, a case-control study was carried out in children with and without habitual snoring. All snoring children underwent polysomnography. Morning fibrinogen values in 30 children with snoring and an apnoea-hypopnoea index (AHI) > or =5 episodes x h(-1) (median (interquartile range) 318 mg x dL(-1) (290-374)) were similar to values in 61 children with snoring and an AHI <5 episodes x h(-1) (307 (269-346)). Both groups had higher fibrinogen values than those in 23 controls without snoring (271 mg x dL(-1) (244-294)). There was no correlation between fibrinogen values and AHI, respiratory movement/arousal index or haemoglobin desaturation index. In conclusion, fibrinogen values are higher in children with snoring than in controls, but there is no association between these values and polysomnography indices.

Case-Control Studies↗

Nationwide collaborative study of HLA class II associations with distinct types of juvenile chronic arthritis (JCA) in Greece.

The aim of this study was to investigate the association of different groups and subgroups of juvenile chronic arthritis (JCA) with HLA class II (DR, DP, DQ) alleles and/or haplotypes. Groups and subgroups were mainly distinguished on the basis of the type of onset, the course and complications of the disease, and some predefined disease markers according to the criteria proposed by the ILAR Standing Committee (Chile, 1994). On the basis of these criteria the following five JCA groups and their subgroups were included in the study: (1) define systemic onset (n = 25) and systemic progressing to persistent arthritis (n = 14); (2) JCA of oligoarthritis onset (O-JCA, n = 124) and of oligoarthritis onset and course (n = 98), O-JCA of early (< 6 years) or late (> 6 years) onset (EOO-JCA n = 71 and LOO-JCA n = 44), O-JCA with ANA positive (n = 69) or negative (n = 55) and O-JCA progressing to extended arthritis (n = 22); (3) JCA of polyarthritis onset (P-JCA) with rheumatic factor (RF) negative (n = 29), and P-JCA RF negative with antinuclear antibodies (ANA) positive (n = 13) or negative (n = 16); (4) JCA complicated with chronic anterior uveitis (CAU, n = 32); (5) juvenile psoriatic arthritis (n = 20). To assess the HLA allele frequencies in the above 223 Greek children with JCA, these frequencies were compared to those of 98 age-matched and 250 adult controls. The main findings were the following. A common HLA-DRB1* allele was not involved in the JCA groups and subgroups studied; on the other hand, the DQA1*0501 allele was found to be associated with different JCA groups/subgroups (O-JCA, P-JCA RF-negative ANA-positive, JCA with CAU), probably suggesting a closer relationship of this locus with the immunogenetic background of JCA. The DPB1*0201 allele was associated with the development of either EOO-JCA or CAU. Susceptibility to CAU was stronger when the DPB1*0201 was combined with the presence of DRB1*13. Another allele, DQB1*0301, was also associated with O-JCA and CAU. Finally, no specific HLA class II allele was found to be related to the presence of ANA or psoriatic lesions or to the severity of the arthritis. Our findings suggest that the wide clinical and laboratory spectrum of JCA is associated with an immunogenetic background that is linked with HLA alleles of more than one locus. Some of them, such as the DPB1*0201 allele, confer susceptibility to certain clinical onsets and courses or complications of the disease. The rapidly advancing techniques of typing of DNA profiles may lead to more definite conclusions.

Adolescent↗

The immunomodulatory effect of leflunomide in rat cardiac allotransplantation.

Leflunomide, a novel immunosuppressant, has been the subject of recent preclinical studies using solid organ allo- and xenotransplantation models. The objectives of this study were to evaluate the efficacy and toxicity of leflunomide using a rat cardiac allotransplant model in two different strain combinations (DA x PVG and DA x Lew). Leflunomide, at doses ranging between 5 and 30 mg/kg, prolonged graft survival in both strain combinations as effectively as CsA and FK506 1 mg/kg (P < 0.05). A dose-dependent effect was seen only after a longer treatment course. When ongoing rejection was intercepted early (postoperative day 2), 5 mg/kg was as effective as 1 mg/kg FK506 (P > 0.05) but was inferior to CsA in the DA x PVG combination (P < 0.05). However, in the DA x Lew combination, leflunomide was equally as efficacious as 15 mg/kg CsA and 1 mg/kg FK506 (P > 0.05). If ongoing rejection was treated at postoperative day 4, 10 mg/kg leflunomide was not only as effective as 15 mg/kg CsA and 1 mg/kg FK506, but demonstrated a dose-dependent increase in graft survival in both strain combinations. The toxicity of leflunomide at doses of especially 5-20 mg/kg was minimal in comparison to therapeutic doses of CsA and FK506 using body weight and biochemical parameters of renal and liver function. These in vivo observations convincingly show leflunomide to be equally as potent an immunosuppressant as CsA and FK506 in transplant rejection. It is also well tolerated on long-term administration and, by virtue of this fact, is a potentially suitable candidate for clinical transplantation.

Animals↗

Concentrations of main serum opsonins in early infancy.

The evolution of the main serum opsonins in neonates and infants of varying gestational age was investigated to provide reference values for these opsonins in early infancy. Serum concentrations of immunoglobulins, IgG subclasses, C3, C4 and fibronectin were serially measured from birth until the age of 6 months in term and preterm infants. Measurements were performed by rate nephelometry. Five hundred and sixty six neonates (gestational age 26-41 weeks) were examined at birth, 233 at 1 month, 218 at 3 months, and 147 at 6 months, respectively. The same measurements were performed in 54 pairs of neonatal/maternal samples and in 230 apparently healthy adults. Gestational age had a significant impact on serum IgG, IgG subclasses, C3 and C4 up till the third month, and on fibronectin until the first month. No such impact was observed for IgA and IgM. Sixteen per cent of the neonates had IgM concentrations higher than 0.2 g/l at birth, suggesting that the critical concentration of serum IgM at birth for suspected intrauterine infection should be reconsidered. Concentrations of all opsonins at birth were significantly lower than adult reference values. They only approached or even reached adult values by the third or the sixth month. Data from analysis of the neonatal and the corresponding maternal sera indicate that there is a preferential active transplacental transport of IgG subclasses in the order of IgG1, IgG3, IgG2 and IgG4. These results show that concentrations of immunoglobulins, C3, C4 and fibronectin undergo changes during the first months of life, depending not only on the infants' postnatal age but also on gestational age.

Complement C3↗

Serum concentrations of 10 acute-phase proteins in healthy term and preterm infants from birth to age 6 months.

Aiming to define the evolution pattern of 10 acute-phase proteins in early infancy, we measured nephelometrically the serum concentrations of albumin, prealbumin, retinol-binding protein, transferrin, ceruloplasmin, hemopexin, haptoglobin, alpha 1-acid glycoprotein, alpha 2-macroglobulin, and alpha 1-antitrypsin in 395 term and preterm infants (gestational ages 26-41 weeks). Measurements were performed within 24 h after birth and then at the end of 1 (n = 171), 3 (n = 155), and 6 (n = 90) months afterwards. Data obtained from 250 healthy adults were used as adult reference values. All proteins increased progressively with postnatal age, except for alpha 1-antitrypsin, which remained stable from birth to the 6th month. Concentrations of almost all measured proteins were significantly lower in preterm than in term infants in the first 3 months. Compared with adult values, alpha 2-macroglobulin and alpha 1-antitrypsin were higher in infants throughout the 6 months. The other proteins were significantly lower at birth than adult values but after 6 months, only albumin, prealbumin, retinol-binding protein, and alpha 1-acid glycoprotein still remained lower in infants. Thus both gestational and postnatal age should be considered when interpreting concentrations of these proteins in early infancy.

Acute-Phase Proteins↗

Serum protein groups (Hp, GC, C3) in patients with gastric carcinoma.

The phenotypes and gene frequencies of 3 serum protein systems (Hp, GC and C3) were studied in 114 consecutive patients from all over Greece with gastric carcinoma. Healthy Greeks studied previously in our Department served as controls. No significant differences were found between patients and controls concerning Hp. Significant differences were found in the GC and C3 systems; GC 2-1 and C3F phenotype as well as C3*F gene frequencies were significantly higher in patients than in controls.

Adult↗

Thalassemic patients are at high risk for transfusion-transmitted cytomegalovirus infections.

The prevalence of total as well as IgM antibodies against cytomegalovirus (CMV) was determined by enzyme immunoassay in a group of 287 multitransfused thalassemia major patients aged 5-39 years and in another group of 1,220 healthy controls. A significantly higher prevalence of CMV antibodies was observed in thalassemic patients of all age-groups compared with controls. The prevalence among splenectomized thalassemia patients was higher than among nonsplenectomized thalassemics. It is concluded concluded that patients with thalassemia, especially if splenectomized, are at high risk for transfusion-transmitted CMV infections. The high prevalence of CMV infections might be responsible, at least in part, for the immunological disturbances and the susceptibility to other infections observed in thalassemic patients. On the basis of these results, it is suggested that safe blood should be provided for anti-CMV-negative thalassemics, with priority to anti-HIV-positives and those who are to receive bone marrow transplantation.

Adolescent↗

Function of reticuloendothelial system in splenectomised thalassemics.

The activity of reticuloendothelial system (RES) was estimated in 19 patients with beta-thalassemia major, 20 +/- 4 years old, who had undergone successful splenectomy 6 +/- 5 years previously. The kinetics of 125I denatured human serum albumin in low and large doses was applied for this purpose and the parameters derived (effective RES blood flow-ERBF- and maximum phagocytic capacity-PCmax) were compared to those of nonsplenectomized thalassemics, detected in previous works, as well as to those of 13 healthy controls. In splenectomised thalassemics both parameters of RES activity were found significantly lower than those of nonsplenectomized patients (p less than 0.001). Compared to those of healthy controls, PCmax of splenectomised thalassemics was found not to be significantly different, while ERBF was significantly lower (p less than 0.001). No correlation was noted between the above parameters of RES function and the age of the patients, the age at which splenectomy was performed, the time lapsed since the operation, the amount of blood transfused to the patients after splenectomy or their serum ferritin levels. A pilot study performed in 6 out of the 19 splenectomised patients did not reveal any effect of blood transfusion on RES function parameters, by contrast to observations in nonsplenectomized thalassemics. The results of this study suggest that in splenectomised thalassemics the remaining RES reacts to the continuing hemolytic stimulus in a manner different than that of splenic RES of nonsplenectomized patients and account for, at least in part, the predisposition of the former group to infections.

Adolescent↗

Assessment of splenic and RES function of patients with thalassemia major long after partial splenic embolization: in vivo clearance study.

The activity of the remaining reticuloendothelial system (RES) and the function of the splenic remnants was estimated in 5 thalassemic patients who had undergone successful partial splenic embolization (PSE) 6 yr previously. The kinetics of 125I-heat-denatured human albumin as well as that of 51Cr-heat-damaged homologous red blood cells were applied for this purpose and the parameters derived were compared to those of nonsplenectomized as well as splenectomized thalassemics with the following results: (a) The parameters of splenic function in embolized thalassemics were found to be within the limits observed in nonsplenectomized patients. (b) Their maximum phagocytic capacity was significantly lower, not only than that found in nonsplenectomized, but also than in thalassemic patients splenectomized at about the same time. It is concluded that, 6 yr after PSE has been performed, a reorientation of the altered circulatory dynamics has taken place in the splenic remnants allowing previously blockaded areas to gain normal function. It therefore seems that, despite the continuing hemolytic stimulus, RES hyperplasia is prevented, resulting in the stable, low-level transfusion requirements that have been observed in embolized thalassemics.

Adolescent↗

Kinetics of heat-damaged homologous red blood cells in patients with homozygous beta-thalassemia in relation to blood transfusion.

The kinetics of heat-damaged homologous red blood cells (HDE) was studied prior to and 7-10 d following blood transfusion in 14 patients with homozygous beta-thalassemia. On the basis of our results, beta-thalassemic patients were classified into two distinct groups. In the first group the pretransfusion HDE extraction efficiency of the spleen was significantly lower than that of the second group and it increased dramatically following blood transfusion. On the contrary, the relatively higher pretransfusion HDE extraction efficiency of the patients of the second group showed a significant decrease after blood transfusion. These differences between the two groups of beta-thalassemics might be attributed to the different qualitative as well as quantitative alterations of the splenic vascular bed occurring in these patients during the course of their disease. Furthermore, there was convincing evidence that part of the HDE mixture was extracted by RES sites outside the spleen, a function which is also affected by blood transfusion.

Adolescent↗

C3 polymorphism in Greece.

The polymorphism of the third component of the human complement (C3) was investigated in a sample of 1,055 unrelated healthy individuals from nine different areas of Greece. The estimated gene frequencies were: C3S = 0.786 and C3F = 0.211. Three individuals were found to have rare variant C3 types. The allele frequencies resemble those reported for other Caucasian populations.

Alleles↗

Plasma fibronectin (Fn) study in homozygous beta-thalassemia: relation to splenectomy and transfusion.

The concentration of plasma Fn was determined in non-splenectomized and splenectomized patients with homozygous beta-thalassemia, before and 7-10 days after blood transfusion. The mean Fn concentration of non-splenectomized patients before transfusion did not differ from that of matched normal controls but appeared significantly decreased following blood transfusion. On the other hand, in splenectomized thalassemics, Fn levels were increased but were unrelated to transfusion. It is concluded that Fn plays some homeostatic function when RES activity of thalassemic patients is altered either as a result of splenectomy or blood transfusion.

Adolescent↗

Genetic markers in renal adenocarcinoma.

The distribution of phenotypes and gene frequencies of the 3rd component of complement (C3), group-specific component (Gc), haptoglobin (Hp) and transferrin (Tf) were studied in 50 patients with renal adenocarcinoma. The statistical analysis of our findings in comparison to the frequency of these genes in the general population does not reveal any correlation between the distribution of the Hp and Tf phenotypes and the disease. On the contrary, a statistically significant association was found between renal adenocarcinoma and C3F and Gc2 genes. The relative risk incidence of this malignancy is 2.07 and 1.94 respectively for the carriers of these genes. These data indicate that genetic factors, possibly related to the immune mechanisms and calcium metabolism, play a role in the pathogenesis of renal adenocarcinoma.

Adenocarcinoma↗

C3 polymorphism in beta-thalassemia.

The distribution of phenotypes and gene frequencies of the third component of complement (C3) were studied in 106 beta-thalassemic patients and in 112 carriers of the beta-thalassemia trait. A statistically significant association was found between the C3F gene and homozygous beta-thalassemia. It can be suggested that this association may be related with the high incidence of infections encountered in these patients.

Adolescent↗