Association of HLA-DRB1 alleles with susceptibility to mixed connective tissue disease in Polish patients.

Mixed connective tissue disease (MCTD) is a systemic autoimmune disease, originally defined as a connective tissue inflammatory syndrome with overlapping features of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), polymyositis/dermatomyositis (PM/DM) and systemic sclerosis (SSc), characterized by the presence of antibodies against components of the U1 small nuclear ribonucleoprotein (U1snRNP). The aim of the study was to assess the frequency of (high-resolution-typed) DRB1 alleles in a cohort of Polish patients with MCTD (n = 103). Identification of the variants potentially associated with risk and protection was carried out by comparison with the DKMS Polish Bone Marrow Donor Registry (41306 alleles). DRB1*15:01 (odds ratio (OR): 6.06; 95% confidence interval (CI) 4.55-8.06), DRB1*04 (OR: 3.69; 95% CI 2.69-5.01) and *09:01 (OR: 8.12; 95% CI 2.15-21.75) were identified as risk alleles for MCTD, while HLA-DRB1*07:01 allele was found to be protective (OR: 0.50; 95% CI 0.28-0.83). The carrier frequency of the DRB1*01 was higher in MCTD patients compared with controls, although the differences were not statistically significant. Our results confirm the modulating influence of HLA-DRB1 genotypes on development of connective tissue diseases such as MCTD.

Association of single nucleotide polymorphisms in the IL27 gene with rheumatoid arthritis.

Rheumatoid arthritis (RA) is one of the autoimmune diseases, where different polymorphisms in cytokine genes play a pathogenic role. Interleukin 27 (IL-27) is a novel pro-/anti-inflammatory cytokine, an excellent candidate for chronic inflammatory disease studies. The aim of the study was to identify polymorphisms in the IL-27 gene and their possible association with susceptibility to and severity of RA. Two hundred and seventy-four patients with RA and of 295 healthy individuals were examined for -924A/G and 4730T/C IL27 gene polymorphisms using PCR-RFLP method and TaqMan SNP genotyping assay, respectively. Haplotype frequencies of IL-27 polymorphisms were estimated using SHEsis platform. Frequencies of the -924GG genotype and the -924G allele were statistically higher in RA patients comparing with the healthy control group (P = 0.008 and P = 0.004, respectively). Overall, strong LD was observed between the IL27 gene -924A/G and 4730 T/C polymorphisms (D' = 0.613, r2 = 0.199). From four possible haplotypes, frequencies of two (CA and CG) showed significant differences between both examined groups (respectively: P < 0.001 and P = 0.001062). The genotype-phenotype analysis showed significant association between the IL-27 4730 T/C polymorphism and HAQ score and means value of the ESR, additionally they revealed that individuals with the polymorphic allele -924G had more advanced disease than wild-type allele carriers. Present findings indicated that IL27 -924A/G polymorphism may be involved in susceptibility to RA in the Polish population.

Effect of sodium butyrate on the small intestine development in neonatal piglets fed [correction of feed] by artificial sow.

Feeding of neonates with artificial milk formulas delays the maturation of the gastrointestinal mucosa. Na-butyrate has a complex trophic effect on the gastrointestinal epithelium in adults. The present study aimed to determine the effect of milk formula supplementation with Na-butyrate on the gut mucosa in neonatal piglets. Sixteen 3 day old piglets were randomly divided into two groups: control (C, n = 8), and Na-butyrate (B, n = 8). Animals were feed for 7 days with artificial milk formula alone (C) or supplemented with Na-butyrate (B). At the 10(th) day of life the piglets were sacrificed and whole thickness samples of the upper gut were taken for analyses. Administration of Na-butyrate led to significant increase in daily body weight gain as compared to control. In the duodenum, the villi length and mucosa thickness were reduced, however, in the distal jejunum and ileum, the crypt depth, villi length and mucosa thickness were increased in Na-butyrate supplemented piglets as compared to control. Supplementation with Na-butyrate did not affect the intestinal brush border enzyme activities but increased plasma pancreatic polypeptide and cholecystokinin concentrations. These results suggest that supplementation with Na-butyrate may enhance the development of jejunal and ileal mucosa in formula-fed piglets.

[Molecular diagnosis of lymphomas and leukaemias]. / Diagnostyka molekularna chloniaków I bialaczek.

In the last years molecular diagnosis has become a routine method m the evaluation of haematological malignancies. Various techniques are used to assess B- and T-cell clonality, chromosomal rearrangements involving protooncogenes, monitoring of minimal residual disease as well as genome wide scanning methods such as comparative genomic hybridization or spectral karyotyping. The review explores some avenues in which molecular techniques can affect patient's retrospective and prospective diagnosis. The major advantages and disadvantages of some of these techniques are described and their place in the scheme of diagnosis and treatment is briefly summarised.

Association between minihaplotypes and mutations at the PAH locus in Polish hyperphenylalaninemic patients.

Hereditary hyperphenylalaninemia (HPA) is a disorder of amino acid metabolism and results from an insufficiency of hepatic phenylalanine hydroxylase (PAH). HPA phenotypes form a spectrum ranging from classical phenylketonuria (PKU) to mild hyperphenylalaninemia (MHP). The phenotypic diversity reflects heterogeneity at the molecular level, and more than 320 different mutations in the PAH gene are known to date. The association of 3 mutations (R408W, IVS10 and A403V) common in different European populations with a variable number tandem repeat (VNTR) and short tandem repeat sites (minihaplotype) in the PAH gene was examined in a group of Polish PKU and MHP patients. Additionally, minihaplotypes were established for another 16 mutations. The presented data support the hypothesis that the R408W/VNTR3/STR238 allele originated among pre-Indo-Europeans on the territory in present-day Lithuania and Belarus. Mutation IVS10nt-11g-->a (IVS10) is strongly associated with VNTR7/STR250 minihaplotype and is possibly of Mediterranean origin.

[Biomedical science in the era of complete sequence of human genome]. / Nauki biomedyczne w dobie poznania genomu jadrowego czlowieka.

Human Genome Project has already produced a draft sequence of the human genome. The article discusses scientific and some social aspects of the Human Genome Project, especially its influence on practice and the future of molecular medicine.

[Tissue plasminogen activator and inhibitor and the severity and extensiveness of vascular lesions in peripheral atherosclerosis of the legs]. / Tkankowy aktywator plazminogenu i inhibitor aktywatora plazminogenu a stopien zaawansowania i rozleglosc zmian naczyniowych w miazdzycy tetnic konczyn dolnych.

The aim of work was to study whether activity and antigen level of tissue plasminogen activator (t-PA) and activity of plasminogen activator inhibitor (PAI-1) were related to severity and extensiveness of vascular lesions in peripheral obliterative atherosclerotic disease (POAD). The study group consisted of 25 patients in II (13), III (10) and IV (2) degrees of disease acc. to Fontaine'a. In the blood t-PA activity and antigen and activity of PAI-1 were determined. In the patients with more severe POAD higher t-PA antigen and increased t-PA complexed with PAI-1 were observed. In patients with unisegmental POAD twice t-PA activity than in patients with polysegmental atherosclerotic lesions was detected.

[Effect of vascular surgery on values of thrombin-antithrombin III complexes in patients with atherosclerosis of lower limb arteries]. / Wplyw zabiegu naczyniowego na wartosci kompleksów trombina-antytrombina III u chorych na miazdzyce tetnic konczyn dolnych.

In 25 patients with atherosclerosis of lower limb arteries (ALLA) in whom vascular operation was performed, the level of thrombin-antithrombin III (TAT) complexes and antithrombin III (AT III) activity were determined in comprehensive studies of the blood clotting system. The comparative group for the assessment of operation effect on primarily not disturbed haemostasis in humans included 10 men operated on for inguinal hernia, while the control group consisted of 54 healthy people. Blood for the determinations was taken before the operation, on the day of the operation (0-30 minutes after the operation), on the first day after it, and also on the third day in patients with hernia, and on the 7th day in patients with ALLA. In the patients with ALLA, blood hypercoagulation features were found, expressed as increased level of TAT complexes in spite of lack of abnormalities in comprehensive coagulation studies, while in the patients with hernia only increased AT III activity was found. The surgical operation caused in the patients with ALLA enhancing of hypercoagulation which was evidenced by over threefold increase of TAT complexes on the day of the operation.

[Effect of vinylsorb SS on the morphology and coagulability of blood during perfusion in vitro]. / Wplyw vinylsorbu SS na morfologie i krzepliwosc krwi podczas perfuzji in vitro.

In the paper the changes appearing in in vitro during perfusion of citrated blood through a column filled with Vinylsorb SS in temperature of 22 and 37 degrees C were evaluated. In both temperatures there was a slight decrease of the number of leucocytes and thrombocytes, both in the examined and the control system. The remaining number of thrombocytes ensured hemostasia. The authors think that the main factor causing decrease of the number of morphotic elements of blood as well as activating slightly coagulation system was the effect of drains, a peristaltic pump, blood container and perfusion column and not the sorbent. Vinylsorb turned out to be a good and safe sorbent which should be applied in the process of hemoperfusion in people.

[Tissue plasminogen activator, its inhibitor and other parameters of fibrinolysis in blood of patients operated for mild hypertrophy of the prostate]. / Tkankowy aktywator plazminogenu i jego inhibitor oraz inne parametry ukladu fibrynolizy we krwi chorych operowanych z powodu lagodnego przerostu gruczolu krokowego.

An increased blood fibrinolytic activity manifested by increased tissue plasminogen activator (t-PA) and decreased tissue plasminogen activator inhibitor (PAI-1) and increased FDP levels are seen in 40 patients with mild hypertrophy of prostate. Surgical treatment increased blood fibrinolytic activity manifested in the increase in t-PA, decrease in PAI-1, shortening of ELT, increase in FDP, and decrease in plasminogen and 2-AP activities. Blood fibrinolytic activity was the highest immediately after surgery with tendency to the gradual normalization. Positive ethanol test and decrease in thrombocyte count indicate and activation of blood clotting system induced by the tissue thrombo-elastins released during surgery. Subclinical DCI with the secondary increased fibrinolysis activation is present in patients with mild hypertrophy of the prostate both prior to and after surgery.