Interaction between the amino and carbonyl groups in copoly(2-dimethylaminoethyl methacrylate/N-phenylmaleimide)

Interactions between the carbonyl and amino groups in copolymers of 2-dimethylaminoethyl methacrylate with N-phenylmaleimide are reported. The existence of interactions ensues from potentiometric measurements and UV-VIS spectra. Interactions in these copolymers result in the formation of energetically very advantageous chromophores, reflected in an intense red colour of the substances obtained.     

De novo mutations of GCK,HNF1A and HNF4A may be more frequent in MODY than previously assumed

Aims/hypothesis

MODY is mainly characterised by an early onset of diabetes and a positive family history of diabetes with an autosomal dominant mode of inheritance. However, de novo mutations have been reported anecdotally. The aim of this study was to systematically revisit a large collection of MODY patients to determine the minimum prevalence of de novo mutations in the most prevalent MODY genes (i.e. GCK, HNF1A, HNF4A).

Methods

Analysis of 922 patients from two national MODY centres (Slovakia and the Czech Republic) identified 150 probands (16%) who came from pedigrees that did not fulfil the criterion of two generations with diabetes but did fulfil the remaining criteria. The GCK, HNF1A and HNF4A genes were analysed by direct sequencing.

Results

Mutations in GCK, HNF1A or HNF4A genes were detected in 58 of 150 individuals. Parents of 28 probands were unavailable for further analysis, and in 19 probands the mutation was inherited from an asymptomatic parent. In 11 probands the mutations arose de novo.

Conclusions/interpretation

In our cohort of MODY patients from two national centres the de novo mutations in GCK, HNF1A and HNF4A were present in 7.3% of the 150 families without a history of diabetes and 1.2% of all of the referrals for MODY testing. This is the largest collection of de novo MODY mutations to date, and our findings indicate a much higher frequency of de novo mutations than previously assumed. Therefore, genetic testing of MODY could be considered for carefully selected individuals without a family history of diabetes.     

Second cancers in MPN: Survival analysis from an international study

One out of ten patients with Philadelphia-negative myeloproliferative neoplasms (MPN) develop a second cancer (SC): in such patients we aimed at assessing the survival impact of SC itself and of MPN-specific therapies. Data were therefore extracted from an international nested case-control study, recruiting 798 patients with SC diagnosed concurrently or after the MPN. Overall, 2995 person-years (PYs) were accumulated and mortality rate (MR) since SC diagnosis was 5.9 (5.1-6.9) deaths for every 100 PYs. A “poor prognosis” SC (stomach, esophagus, liver, pancreas, lung, ovary, head-and-neck or nervous system, osteosarcomas, multiple myeloma, aggressive lymphoma, acute leukemia) was reported in 26.3% of the patients and was the cause of death in 65% of them (MR 11.0/100 PYs). In contrast, patients with a “non-poor prognosis” SC (NPPSC) incurred a MR of 4.6/100 PYs: 31% of the deaths were attributed to SC and 15% to MPN evolution. At multivariable analysis, death after SC diagnosis was independently predicted (HR and 95% CI) by patient age greater than 70 years (2.68; 1.88-3.81), the SC prognostic group (2.57; 1.86-3.55), SC relapse (1.53; 10.6-2.21), MPN evolution (2.72; 1.84-4.02), anemia at SC diagnosis (2.32; 1.49-3.59), exposure to hydroxyurea (1.89; 1.26-2.85) and to ruxolitinib (3.63; 1.97-6.71). Aspirin was protective for patients with a NPPSC (0.60; 0.38-0.95). In conclusion, SC is a relevant cause of death competing with MPN evolution. Prospective data are awaited to confirm the role of cytoreductive and anti-platelet drugs in modulating patient survival after the occurrence of a SC.     

Reductive Modification of Carbon Nitride Structure by Metals—The Influence on Structure and Photocatalytic Hydrogen Evolution

Pt, Ru, and Ir were introduced onto the surface of graphitic carbon nitride (g-C₃N₄) using the wet impregnation method. A reduction of these photocatalysts with hydrogen causes several changes, such as a significant increase in the specific surface area, a C/N atomic ratio, a number of defects in the crystalline structure of g-C₃N₄, and the contribution of nitrogen bound to the amino and imino groups. According to the X-ray photoelectron spectroscopy results, a transition layer is formed at the g-C₃N₄/metal nanoparticle interphase, which contains metal at a positive degree of oxidation bonded to nitrogen. These structural changes significantly enhanced the photocatalytic activity in the production of hydrogen through the water-splitting reaction. The activity of the platinum photocatalyst was 24 times greater than that of pristine g-C₃N₄. Moreover, the enhanced activity was attributed to significantly better separation of photogenerated electron–hole pairs on metal nanoparticles and structural distortions of g-C₃N₄.     

Serum Antibodies Positivity to 12 Helicobacter pylori Virulence Antigens in Patients with Benign or Malignant Gastroduodenal Diseases – Cross-sectional Study

Aim

To investigate the association of gastric histological and endoscopic findings in patients with Helicobacter pylori (H. pylori), according to presence of seropositivity to 12 bacterial virulence antigens.

Methods

This is a cross-sectional single-center study of 360 consecutive outpatients referred in the period of one year to upper gastrointestinal endoscopy because of dyspeptic complaints. Patients sera were tested by Western blot method to determine the presence of serum antibodies to bacterial virulence antigens – p120 (CagA – cytotoxin-associated antigen), p95 (VacA – vacuolating cytotoxin), p67 (FSH – flagellar sheath protein), p66 (UreB – urease enzyme heavy subunit), p57 (HSP homologue – heath shock protein homologue), p54 (flagellin), p33, p30 (OMP – outer membrane protein), p29 (UreA – urease enzyme light subunit), p26, p19, and p17. Upper gastrointestinal endoscopy was performed, endoscopic diagnosis recorded, and 4 mucosal biopsy samples were obtained and assessed according to Updated Sydney protocol.

Results

The sera of 207 patients were analyzed. Thirty patients had gastric adenocarcinoma, 126 peptic ulcers, and 51 normal finding. p120 (CagA) seropositivity was significantly more often present in patients with higher activity grade in the antrum (P = 0.025), p30 in patients with greater inflammation in the antrum (P = 0.025) and the corpus (P = 0.010), p33 in patients with greater inflammation in the corpus (P = 0.050), and p19 (OMP) in patients with lower intestinal metaplasia grades in the corpus (P = 0.025). Seroreactivity to all other bacterial proteins showed no association with the histological status of the stomach mucosa. Except for the seropositivity to protein p95 (VacA), which was more often present in patients with duodenal ulcer (P = 0.006), there was no difference in seroreactivity to other bacterial proteins and upper gastrointestinal endoscopic findings.

Conclusions

p120 (CagA), p33, p 30 (OMP), and p19 (OMP) seropositivity was more often present in patients with higher grades of the histological parameters of gastritis and seropositivity to protein p95 (VacA) with endoscopic presence of duodenal ulcer. Histological parameters of gastritis are more associated with bacterial virulence than endoscopic findings.Helicobacter pylori (H. pylori) is recognized as a major gastric pathogen with worldwide distribution (1). Estimated prevalence of H. pylori infection in Croatia is 60.4% (2). The persistent colonization induces gastritis and in some patients peptic ulcer disease, atrophic gastritis, or gastric carcinoma (3). However, most of patients infected with H. pylori never develop cancer or ulcer disease and there is a need to identify additional factors that may influence the risk for development of such diseases. The outcome of H. pylori infection is associated with specific (virulence associated) bacterial genotypes, environmental factors, and host’s immune status (4). A number of putative virulence factors for H. pylori infection have been identified, including CagA (cytotoxin-associated antigen), VacA (vacuolating cytotoxin), IceA (induced by epithelium antigen), BabA (blood-group antigen-binding adhesin), etc. It is likely that every other factor that results in increased inflammation will also consequently increase the risk of a disease occurrence.Presently, the only reliable way to identify the disease associated with H. pylori infection remains endoscopic examination combined with histological assessment of the gastric mucosa (5). The bacterial virulence antigens elicit specific antibodies during infection. However, the value of these antibodies as predictive factors for the severity of the disease remains controversial (6-15). So far, several investigations on the subject have been done, such as detecting the level, specificity, or presence of isotypes of serum H. pylori antibodies (16-22). Because disease outcome depends on both the strain characteristics and the host’s response, the serum antibody response to virulence antigens could provide clues in predicting the presence and severity of associated diseases (23,24). On the other hand, since subjects without manifest disease also have strains bearing this or other virulence antigens, it seems that the disease could not be attributed to one virulence antigen alone. Thus, other virulence antigens may also be important. The exact role of other bacterial virulence antigens – p67 (FSH – flagellar sheath protein), p66 (UreB – urease enzyme heavy subunit), p57 (HSP homologue – heath shock protein homologue), p54 (flagellin), p33, p30 (OMP – outer membrane protein), p29 (UreA – urease enzyme light subunit), p26, p19 (OMP), and p17 in the pathogenesis of gastrointestinal diseases is still unclear.In this study, we aimed to investigate the association of gastric histological and endoscopic findings in H. pylori-positive patients according to presence of seropositivity to 12 bacterial virulence antigens. Since both bacterial virulence antigens and pattern of H. pylori gastritis may contribute to development of clinically relevant gastroduodenal disease, we wanted to determine the antibodies which are most associated with higher grades of histology findings of gastritis, atrophy, or intestinal metaplasia and different clinical diseases (peptic ulcer, gastric cancer, and non-ulcer dyspepsia).     

Expression and potential role of fibroblast growth factor 2 and its receptors in human embryonic stem cells

Although the detection of several components of the fibroblast growth factor (FGF) signaling pathway in human embryonic stem cells (hESCs) has been reported, the functionality of that pathway and effects on cell fate decisions are yet to be established. In this study we characterized expression of FGF-2, the prototypic member of the FGF family, and its receptors (FGFRs) in undifferentiated and differentiating hESCs; subsequently, we analyzed the effects of FGF-2 on hESCs, acting as both exogenous and endogenous factors. We have determined that undifferentiated hESCs are abundant in several molecular-mass isoforms of FGF-2 and that expression pattern of these isoforms remains unchanged under conditions that induce hESC differentiation. Significantly, FGF-2 is released by hESCs into the medium, suggesting an autocrine activity. Expression of FGFRs in undifferentiated hESCs follows a specific pattern, with FGFR1 being the most abundant species and other receptors showing lower expression in the following order: FGFR1 --> FGFR3 --> FGFR4 --> FGFR2. Initiation of differentiation is accompanied by profound changes in FGFR expression, particularly the upregulation of FGFR1. When hESCs are exposed to exogenous FGF-2, extracellular signal-regulated kinases are phosphorylated and thereby activated. However, the presence or absence of exogenous FGF-2 does not significantly affect the proliferation of hESCs. Instead, increased concentration of exogenous FGF-2 leads to reduced outgrowth of hESC colonies with time in culture. Finally, the inhibitor of FGFRs, SU5402, was used to ascertain whether FGF-2 that is released by hESCs exerts its activities via autocrine pathways. Strikingly, the resultant inhibition of FGFR suppresses activation of downstream protein kinases and causes rapid cell differentiation, suggesting an involvement of autocrine FGF signals in the maintenance of proliferating hESCs in the undifferentiated state. In conclusion from our data, we propose that this endogenous FGF signaling pathway can be implicated in self-renewal or differentiation of hESCs.     

Human papillomavirus infection and P53 codon 72 genotypes in a Hispanic population at high-risk for cervical cancer

Cervical cancer mortality is high in Texas, especially among Hispanic women living in south Texas and adjacent Mexico. Though human papillomavirus (HPV) infection has a causal role in the development of cervical cancer, there are no published data on the prevalence of HPV genotypes in this underscreened region. We studied 398 Hispanic women on both sides of the border along the lower Rio Grande River to determine the prevalence of HPV genotypes and risk factors for cervical cancer. Using a nested PCR system HPV was detected in 62% of cervical specimens, including all the known high-risk HPV genotypes, with HPV16 and HPV18 the most frequent (30.6% and 23.0%, respectively). Multiple infections were common (29.4% of the infected specimens), and where this occurred we were more likely to find high-risk HPV genotypes. We examined host p53 codon 72 genotype frequencies and found that patients with cervical abnormalities and women with HPV16 and HPV18 infections had a lower genotype frequency of the homozygous (AA) previously reported to be associated with cervical cancer, than uninfected women with no abnormalities. In this US/Mexico border population high rates of potentially oncogenic HPV viruses and multiple infections are consistent with observed elevated cervical cancer rates. These data are further evidence that in this underserved population HPV infections are associated with high rates of malignancy, but that host p53 genotypic variations are unlikely to be primary factors in oncogenesis.