The concentrations of soluble HLA-G protein are elevated during mid-gestation and decreased in pre-eclampsia

The aim of our study was to investigate the dynamics of the alterations of soluble human leukocyte antigen-G (sHLA-G) concentrations in sera of healthy non-pregnant women, as well as healthy pregnant women and patients with pre-eclampsia. Thirty five patients with pre-eclampsia, 52 healthy pregnant women, and 24 healthy non-pregnant women were included in the study. Sera concentrations of sHLA-G protein were determined using the immunoenzymatic ELISA method. Statistical analysis was performed using ANOVA and Mann-Whitney U tests. The concentrations of sHLA-G protein in sera of pregnant women in the first, as well as the second and third, trimesters of normal pregnancy were significantly higher in comparison with healthy nonpregnant women. The sera concentrations of sHLA-G in pregnant women in the second trimester of pregnancy were significantly higher compared to the first and third trimesters. The concentrations of sHLA-G in sera of patients with pre-eclampsia were significantly lower than in pregnant women in the third trimester of physiological pregnancy. The results of our study suggest that normal physiological pregnancy is associated with elevated sera concentrations of sHLA-G molecule. The increased concentrations of sHLA-G molecule in mid-gestation could suggest a role for the protein in the second phase of a physiological invasion of extravillous cytotrophoblast to spiral arteries. Furthermore, the results could suggest a role for the decreased sera concentrations of sHLA-G in the pathogenesis of pre-eclampsia.     

Classification and stability of global inhomogeneous solutions of a macroscopic model of cell motion

Many micro-organisms use chemotaxis for aggregation, resulting in stable patterns. In this paper, the amoeba Dictyostelium discoideum serves as a model organism for understanding the conditions for aggregation and classification of resulting patterns. To accomplish this, a 1D nonlinear diffusion equation with chemotaxis that models amoeba behavior is analyzed. A classification of the steady state solutions is presented, and a Lyapunov functional is used to determine conditions for stability of inhomogenous solutions. Changing the chemical sensitivity, production rate of the chemical attractant, or domain length can cause the system to transition from having an asymptotic steady state, to having asymptotically stable single-step solution and multi-stepped stable plateau solutions.     

Long-term follow-up in adult patients with low-grade glioma (WHO II) postoperatively irradiated. Analysis of prognostic factors

AimTo report the long-term follow-up of a cohort of adult patients with LGG post-operatively irradiated in one institution, and to identify prognostic factors for progression free survival.BackgroundThere is little consensus about the optimal treatment for low-grade glioma (LGG), and the clinical management of LGG is one of the most controversial areas in neurooncology. Radiation therapy is one option for treatment of patients with LGG, whereas other options include postoperative observation.Materials and methodsBetween 1975 and 2005, 180 patients with LGG (WHO II) received postoperative irradiation after non radical (subtotal or partial) excision. Patients had to be 18 years of age or older, and have histologic proof of supratentorial fibrillary (FA), protoplasmic (PA) or gemistocytic astrocytoma (GA). Radiotherapy was given within 3–10 weeks after surgery. Treatment fields were localized and included the preoperative tumor volume, with a 1–2 cm margin, treated to a total dose of 50–60 Gy in 25–30 fractions over 5–6 weeks.ResultsActuarial ten-year progression free survival (APFS) in the whole group was 19%. The worse prognosis was observed in patients with GA. Ten-year APFS rates for GA, PA and FA were 10%, 18% and 22%, respectively.ConclusionThe findings from our long-term cohort of 180 patients with LGG confirmed by uni- and multivariate analysis demonstrated that only astrocytoma histology significantly determined the prognosis. The best survival was observed in patients with the fibrillary variant, and the worst for the gemistocytic one.     

Identification of four Treponema species in subgingival samples by nested-PCR and their correlation with clinical diagnosis

The relationship between different species of oral Treponemas and inflammation in periodontal disease progression is complex. The purpose of this study was to analyze and compare the subgingival plaque samples collected from periodontally healthy subjects and from chronic gingivitis and periodontitis patients in order to detect the presence of T. denticola, T. pectinovorum, T. socranskii and T. vincentii using nested-PCR technology. After DNA extraction from the samples using QIAmp DNA Mini Kit (QIAGEN, the four Treponema species were determined with nested-polymerase chain reaction which requires two sets of primers to amplify a specific DNA fragment in two separate runs of PCR. Pearson chi-square was implemented to compare the three groups as to the presence of four Treponema species. Results of this investigation showed significant differences between groups regarding subject proportion of T. denticola, T. socranskii, T. pectinovorum, T. vincentii, with a higher percentage of patients from associated-disease groups of patients harboring these four species than healthy subjects. These differences were more pronounced in presence of Treponema denticola and Treponema socranskii. Our findings suggest that Treponema denticola and Treponema socranskii concurrent presence indicate more accurately the association with chronic gingivitis and periodontitis.     

CYP17 and CYP19 genetic variants are not associated with age at natural menopause in Polish women

The aim of the study was to investigate associations between two common polymorphisms of CYP17 and CYP19, encoding key enzymes of estrogen biosynthesis, and age at menopause in Polish women. One hundred fifty women after menopause (49.5 ± 3.8 years), with no previous history of hormone replacement therapy took part in the study. The genetic control group consisted of 150 newborns from the same population. We investigated an association between the age at menopause and the single nucleotide polymorphism T → C in the 5′ untranslated region (promoter) of the CYP17 gene (c.-34T>C; rs743572 – MspA1) or the number of tetranucleotide repeats [TTTA]_n (rs60271534) including deletion/insertion (D/I) of a 3 bp sequence in intron 4 of the CYP19 gene. CYP17 polymorphism was analyzed by PCR-RFLP and CYP19 by PCR and capillary electrophoresis. In the case of CYP17 polymorphism, 28.7% and 36.7% wild homozygous (TT), 50.7% and 46.0% heterozygous (TC), as well as 20.6% and 17.3% mutated homozygous (CC) types were identified in the subjects and controls, respectively. The frequency of mutated alleles (C) was 46.0% vs. 40.3% (p = 0.19). In the case of CYP19 polymorphism, 34.0% and 32.0% of homozygotes (1_1), 50.7% and 51.3% of heterozygotes (1_2), 15.3% and 16.7% of homozygotes (2_2) were identified in the subjects and controls, respectively. No association between the studied CYP17 or CYP19 polymorphisms and age at menopause was found in Polish women.     

Low molecular weight cyclin E is associated with p27-resistant,high-grade,high-stage and invasive bladder cancer

Expression of low molecular weight (LMW) isoforms of cyclin E is a strong predictor of poor outcome in patients with breast cancer. The purpose of this study was to examine the expression of full-length and LMW cyclin E in bladder cancer cell lines and patient tumors. We used western blotting, immunoprecipitation and kinase assays to examine the expression and activity of key cell cycle-regulatory proteins in various human bladder cell lines, both tumorigenic and non-tumorigenic. We also analyzed cyclin E expression, kinase activity and immune complex binding partners in 43 tissue samples from grade 2 and 3 transitional cell carcinomas. Cyclin E was overexpressed and LMW isoforms were present only in bladder cancer cells. Overexpression of LMW isoforms of cyclin E and increased cyclin E kinase activity were both significantly associated with tumorigenicity of the bladder cell lines (p = 0.005 and 0.022, respectively). Binding of the cyclin-dependent kinase inhibitors p21 and p27 to LMW cyclin E did not inhibit the kinase activity of cyclin E and cyclin-dependent kinase 2 in primary tumor samples overexpressing LMW cyclin E. Full-length and LMW cyclin E were significantly overexpressed in grade 3 tumors compared with grade 2 tumors (p = 0.004). Finally, LMW cyclin E levels were significantly associated with a non-papillary growth pattern (p = 0.031) and invasiveness (p = 0.021) of the bladder tumors and poor overall survival (p = 0.06). These results suggest that LMW cyclin E can be used as a new prognostic marker for bladder cancer.Key words: cyclin E, p27, Cdk2 kinase, bladder cancer, cell cycle     

Cannabinoid Receptor 1 Signaling in Embryo Neurodevelopment

In utero exposure to tetrahydrocannabinol, the psychoactive component of marijuana, is associated with an increased risk for neurodevelopmental defects in the offspring by interfering with the functioning of the endocannabinoid (eCB) system. At the present time, it is not clearly known whether the eCB system is present before neurogenesis. Using an array of biochemical techniques, we analyzed the levels of CB1 receptors, eCBs (AEA and 2‐AG), and the enzymes (NAPE‐PLD, DAGLα, DAGLβ, MAGL, and FAAH) involved in the metabolism of the eCBs in chick and mouse models during development. The findings demonstrate the presence of eCB system in early embryo before neurogenesis. The eCB system might play a critical role in early embryogenesis and there might be adverse developmental consequences of in utero exposure to marijuana and other drugs of abuse during this period.     

Resilience of the iron environment in heme proteins

Conformational flexibility is essential to the functional behavior of proteins. We use an effective force constant introduced by Zaccai, the resilience, to quantify this flexibility. Site-selective experimental and computational methods allow us to determine the resilience of heme protein active sites. The vibrational density of states of the heme Fe determined using nuclear resonance vibrational spectroscopy provides a direct experimental measure of the resilience of the Fe environment, which we compare quantitatively with values derived from the temperature dependence of atomic mean-squared displacements in molecular dynamics simulations. Vibrational normal modes in the THz frequency range dominate the resilience. Both experimental and computational methods find a higher resilience for cytochrome c than for myoglobin, which we attribute to the increased number of covalent links to the peptide in the former protein. For myoglobin, the resilience of the iron environment is larger than the average resilience previously determined for hydrogen sites using neutron scattering. Experimental results suggest a slightly reduced resilience for cytochrome c upon oxidation, although the change is smaller than reported in previous Mössbauer investigations on a bacterial cytochrome c, and is not reproduced by the simulations. Oxidation state also has no significant influence on the compressibility calculated for cyt c, although a slightly larger compressibility is predicted for myoglobin.