bluuebunny/crossref_metadata_2025_split huggingface dataset:
Double heterozygosity in the BRCA1 and BRCA2 genes in Italian family
Authors: Vietri Maria Teresa , Molinari Anna Maria , Caliendo Gemma , De Paola Maria Laura , Giovanna D’Elia , Gambardella Anna Laura , Petronella Pasquale , Cioffi Michele 
Published: August 2013

Abstract

Background: Double heterozygosity (DH) is an extremely rare event in which both BRCA1 and BRCA2 are mutated simultaneously in a family. To date, few cases of DH have been reported, especially in Ashkenazi populations. In Italy some cases of DH have been reported. In this study, we have described an Italian family with double heterozygosity in the BRCA genes.

Methods: The proband is a 43-year-old woman with bilateral breast cancer. She presented two pathogenic mutations in both BRCA genes, IVS8+2T>A (c.547+2T>A;p.Gln148Aspfsx51) in BRCA1, K944X (c.2830A>T;p.Lys944X) in BRCA2 and a novel variant IVS4–57A>G (c.426–57A>G) in BRCA2, not previously described. Both mutations were inherited from the paternal lineage in the proband’s family. We investigated all available members of this family and we identified other two family members with DH.

Results and conclusions: Our observations support the hypothesis of a non-specific severe phenotype in DH carriers in terms of age of disease onset, cumulative lifetime risk and multiple primary tumours. Furthermore, our findings confirm that in order to identify all cases of DH, it is important not to limit the identification of mutations in a single gene, but extend the analysis to BRCA1 and BRCA2 and other breast cancer susceptibility genes.
Measured temperature and moisture profiles during thermal modification of beech (Fagus sylvatica L.) and spruce (Picea abies L. Karst.) wood
Authors: Čermák Petr , Horáček Petr , Rademacher Peter 
Published: August 2013

Abstract
The temperature and moisture profiles during thermal modification of beech (Fagus sylvatica L.) and spruce (Picea abies L. Karst.) wood have been investigated. Specimens with dimensions of 80×80×200 mm3 were heat treated based on ThermoWood technology. Heat transfer was continuously measured by several thermocouples placed into various positions of the samples. In the course of the treatment, samples were removed from the chamber at different times, and their moisture content (MC) was measured by the so-called slicing technique. The complete data of heat and moisture movement during the heat treatment process are presented. Significant temperature gradients occur in the initial and modification stages of the process. In the latter, the chamber temperature was 200°C for 3 h, but exothermic reaction increased the sample temperatures to 240°C (beech) and 215°C (spruce). Thermodiffusion (Soret effect) at the beginning of the process was observed. Therefore, the MC under surfaces (in transverse and in longitudinal direction) was increasing ∼0.5%–3% for 5 h. The results provide a better insight into details of thermal modification of wood.
Pregnancy, obesity and insulin resistance: maternal overnutrition and the target windows of fetal development
Authors: Muhlhausler Beverly S. , Gugusheff Jessica R. , Ong Zhi Yi , Vithayathil Mini A. 
Published: August 2013

Abstract
A substantial body of literature has demonstrated that the nutritional environment an individual experiences before birth or in early infancy is a key determinant of their health outcomes across the life course. This concept, the developmental origins of health and disease (DOHaD) hypothesis, was initially focused on the adverse consequences of exposure to a suboptimal nutrient supply and provided evidence that maternal undernutrition, fetal growth restriction, and low birth weight were associated with heightened risk of central adiposity, insulin resistance, and cardiovascular disease. More recently, the epidemic rise in the incidence of maternal obesity has seen the attention of the DOHaD field turn toward identifying the impact on the offspring of exposure to an excess nutrient supply in early life. The association between maternal obesity and increased risk of obesity in the offspring has been documented in human populations worldwide, and animal models have provided critical insights into the biological mechanisms that drive this relationship. This review will discuss the important roles that programming of the adipocyte and programming of the central neural networks which control appetite and reward play in the early life programming of metabolic disease by maternal overnutrition. It will also highlight the important research gaps and challenges that remain to be addressed and provide a personal perspective on where the field should be heading in the coming 5–10 years.
Morphological study of PVDF/PMMA/TiO2 blend films prepared by melt casting process
Authors: Hosoda Tomonori , Yamada Toshiro 
Published: August 2013

Abstract
The influence of chill roll temperature and thermal annealing on the morphology and dynamic mechanical behavior of poly(vinylidene fluoride) (PVDF)/poly(methyl methacrylate) (PMMA)/titanium dioxide blend films prepared by a melt casting process was studied. The β phase of PVDF was formed at the chill roll temperature of 30°C. Furthermore, with the increase in this chill roll temperature, its structural conversion to the α phase was observed. No change in the crystal structure of either the β or α phase occurred on account of thermal annealing at 115°C for 24 h. The decrement in the storage modulus above the glass transition temperature ascribed to the mixed amorphous phase became smaller, as the chill roll temperature increased. Based on morphological observations, we deduced that the reason for this decrement is not that the film cast at 115°C was more crystalline than that cast at 30°C but that the actual weight fraction of PMMA in the mixed amorphous phase of the film cast at 115°C was lower than that of the one cast at 30°C.
Neopterin, soluble adhesion molecules and soluble cytokine receptors correlate with disease activity in rheumatoid arthritis
Authors: Nassonov El , Samsonov My , Tilz Gp , Chichasova Ny , Widner B , Demel U , Nikiphorova El , Fuchs D 
Published: August 2013

Abstract
Serum concentrations of soluble intercellular adhesion molecules, sICAM-I , sICAM-3 and sP-selectin, of serum soluble cytokine receptors, sIL-2R, and sTNF-R55 and of neopterin were measured by commercially available immunoassays in 35 patients with rheumatoid arthritis (RA). Serum sICAM-I, sICAM-3 and sPselectin were significantly elevated in patients with RA compared with healthy controls. Concentrations of sPselectin and sICAM-3 correlated with disease activity and severity indices. sICAM-3 levels significantly correlated with sTNF-R55 and neopterin. There were significant correlations between neopterin and sIL-2R and between sTNF-R55 and sIL-2R. The measurement of sP-selectin and sICAM-3 levels in patients with RA might become useful for monitoring disease activity.
Hydrogen Peroxide Stimulates the LPS-induced Tetrahydrobiopterin Synthesis in Mouse Brain Microvascular Endothelial Cells
Authors: Shiota Kazuhiro , Shimizu Shumchi , Ishii Masakazu , Yamamoto Shinichiro , Iwasaki Michiko , Yamamoto Toshinori , Kiuchi Yuji 
Published: August 2013

Abstract
Tetrahydrobiopterin (BH4) is one of the cofactors for nitric oxide synthase (NOS), and also has a protective effect against reactive oxygen species (ROS)- and/or nitric oxide (NO)-induced cytotoxicities. Lipopolysaccharide (LPS) induces NO production and BH4 synthesis, and also ROS release. This study examined whether hydrogen peroxide, one of the ROS, has a regulatory role in BH4 synthesis in vascular endothelial cells. Addition of LPS to the endothelial cells increased the BH4 content. Although the LPS-induced increase in BH4 content was not affected by the treatment with superoxide dismutase and catalase, co-treatment with hydrogen peroxide further stimulated the LPS-induced increase in BH4 content. Moreover, the hydrogen peroxide-induced increase in BH4 content in the presence of LPS was completely inhibited by the treatment with 2,4-diamino-6-hydroxypyrimidine, an inhibitor of GTP-cyclohydrolase I (GTPCH). These findings suggest that hydrogen peroxide may stimulate LPS-induced BH4 synthesis through the induction and/or activation of GTPCH. Under inflammation, hydrogen peroxide seems to stimulate BH4 synthesis.
3-Hydroxy-3-methylglutaryl-CoA Reductase Inhibitors Enhance Cytokine-mediated Induction of Nitric Oxide Synthesis in Vascular Smooth Muscle Cells
Authors: Hattori Yoshiyuki , Nakanishi Nobuo , Suzuki Manabu , Yoshida Mika , Kasai Kikuo 
Published: August 2013

Abstract
We investigated the effects of by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, cerivastatin and fluvastatin, on the induction of nitric oxide (NO) production in vascular smooth muscle cells ( VSMC) stimulated by interleukin-1β (1L-1) or in combination with interferon-γ (IFN). IL-1 activated VSMC to synthesize and release NO, which was significantly potentiated by IFN. NO production induced by IL-1 or IL-1/lFN was dosedependently enhanced by both HMG-CoA reductase inhibitors. Incubating VSMC with IL-1/IFN stimulated inducible NO synthase (iNOS) mRNA expression. Both HMG-CoA reductase inhibitors significantly upreguiated IL/IFN-stimulated iNOS mRNA expression, and enhanced iNOS gene transcription as shown by nuclear run-on assays. Both IIMG-CoA reductase inhibitors slightly modulated IL-1/IFN-induced NF-kB activation, which was not associated with their effect on NO production. Cytokines induce the de novo synthesis of tetrahydrobiopterin (BH4) in VSMC. This event is essential for the induction of NO synthesis, which requires transcriptional induction of the genes that encode not only iNOS but also guanosine triphosphate cyclohydrolase I (GTPCH), the first and rate-limiting enzyme in de novo BH4 synthesis. The synthesis of BH4 and GFPCH mRNA induced by IL-1/IFΝ were enhanced by both HMG-CoA reductase inhibitors. Exogenous mevalonate significantly prevented and geranylgeranylpyrophosphate reversed the stimulatory effect of HMG-CoA reductase inhibitors. Thus, the effect of HMG-CoA reductase inhibitors on NO production is due at least partly through blocking the biosynthesis of mevalonate, which prevents isoprenoid biosynthesis. Our data demonstrated that HMG-CoA reductase inhibitors enhance immunostimulants-induced NO production by increasing iNOS gene expression at the transcriptional level via an NF-kB-independent pathway. In addition to augmenting iNOS expression, HMG-CoA reductase inhibitors potentiate GTPCH gene expression and BH4 synthesis, thereby prevents a relative shortage of BH4 which may shift in the balance between NOS-catalyzed generation of protective NO and deletorious reactive oxygen species.
Association Between Neopterin Production and other Parameters in a Population of Blood Donors
Authors: Schennach Harald , Murr Christian , Gächter Elmar , Mayersbach Peter , Schönitzer Diether , Fuchs Dietmar 
Published: August 2013

Abstract
Neopterin is released from human monocyte-derived macrophages preferentially upon stimulation with the Thlcell cytokine interferon-γ. In humans, increased concentrations of neopterin in serum and urine have been found in viral infections including human immunodeficiency virus type 1, various malignant disorders, autoimmune diseases and during allograft rejection episodes. In order to find additional parameters which might influence neopterin production, serum neopterin concentrations of 1156 blood donors were compared with other parameters routinely determined in blood transfusion. There existed correlations between serum neopterin concentration and blood donors' age (Spearman's rank correlation: rs = 0.259, ρ <0.0001), arterial diastolic blood pressure (rs 0.132, ρ <0.0001) and body mass index (rs = 0.084, ρ <0.01). Serum neopterin concentrations were lower in smokers compared to nonsmokers (Mann-Whitney test, ρ <0.0001). The data demonstrate that higher neopterin concentrations are associated with older age, higher diastolic blood pressure and higher body mass index, whereas lower neopterin concentrations are found in smokers compared to nonsmokers. It is assumed that immunopathogenetic pathways underlie these relationships, but the exact background of these associations still needs to be resolved.
Stimulation of Tetrahydrobiopterin Synthesis by Basic Fibroblast Growth Factor in Vascular Endothelial Cells
Authors: Shimizu Shunichi , Miyasaka Yoshiyuki , Yamamoto Shinichiro , Ishii Masakazu , Kiuchi Yuji 
Published: August 2013

Abstract
The purpose of this study was to examine whether basic fibroblast growth factor (bFGF) stimulates tetrahydrobiopterin (BH4) synthesis in mouse brain microvascular endothelial cells. BH4 content was determined by oxidation under acidic conditions as biopterin and analysed with reversed-phase high Performance liquid chromatography. Measurement of the mRNA level of QTP-cyclohydrolase I (GTPCH), which is the rate-limiting enzyme of the de novo pathway of BH4 synthesis. The addition of bFGF to endothelial cells increased the BH4 content and GTPCH mRNA levels in an incubation period- and a concentration-dependent manner. 2,4-Diamino-6- hydroxypyrimidine, an inhibitor of GTPCH, strongly reduced the bFGF-induced increase in BH4 content. These findings suggest that bFGF stimulates BH4 synthesis via a de novo pathway with the induction of GTPCH.
Homocysteine, Β Vitamins and Immune Activation in Coronary Heart Disease
Authors: Frick Barbara , Rudzite Vera , Schröcksnadel Katharina , Kalnins Uldis , Erglis Andrejs , Trusinskis Karlis , Fuchs Dietmar 
Published: August 2013

Abstract
Moderate hyperhomocysteinemia is associated with an increased risk of coronary heart disease (CHD). An inverse relationship usually exists between homocysteine and folate concentrations, and folate supplementation is often able to lower homocysteine concentrations. Thus, insufficient dietary intake of folate and/or vitamin B12 is considered to be responsible for the development of hyperhomocysteinemia. Inflammation and immune activation appear also to be important in the pathogenesis of CHD and may influence availability of folate. Blood concentrations of homocysteine, Β vitamins and neopterin were examined in 35 patients with CHD verified by coronary angiography, (2 1 patients with one-artery disease, 9 with two- or three-artery disease, 5 with restenosis). Compared to 30 healthy controls, a significant proportion of patients presented with increased homocysteine concentrations. Hyperhomocysteinemia coincided with lower folate and also with higher neopterin concentrations indicating immune system activation. In addition, correlations existed between neopterin and homocysteine (r = 0.472, ρ < 0.01) and folate (r = -0.370, ρ = 0.01). We conclude that higher homocysteine is not only associated with lower circulating folate but also with higher neopterin. Immune activation could be involved to cause an increased demand for folate resulting in hyperhomocysteinemia even when dietary folate intake is within the recommended range.
Concentrations of Neopterin and Interleukin-10 in Peritoneal Fluid and in Serum of Women with Endometriosis
Authors: Kondera-Anasz Zdzislawa , Sikora Justyna , Mertas Anna , Miciñski Piotr , Bednarz Bartlomiej 
Published: August 2013

Abstract
Endometriosis is a gynaecological disorder characterized by increased number and activation of peritoneal macrophages and release of macrophage-derived cytokines and growth factors. The aim of our work was t(5 study the level of neopterin and interleukin (TL)-10 in peritoneal fluid and serum of women with endometriosis in relation to stage of disease. Concentrations of neopterin and IL-10 were measured by enzyme linked immunosorbent assay in PF and serum of 58 women; 43 with endometriosis and 15 without endometriosis. In our study present of neopterin in PF of women with endometriosis whereas neopterin could not be detected in the control group. Neopterin serum concentrations were significantly higher in affected women compared with control. Significantly increased neopterin concentrations were observed in peritoneal fluid and serum of women with advanced endometriosis. The mean peritoneal fluid and serum IL-10 concentrations were significantly higher ainong studied women than control. In women with early endometriosis, significantly increased concentration of IL-10 in peritoneal fluid and serum was observed. In conclusions, both increased concentrations of neopterin and IL-10 in the peritoneal fluid and serum suggest an important role of these Compounds in pathogenesis of endometriosis and indicate an enhanced macrophage activity in this disease.
Elevated Post-transplant Levels of Neopterin are Associated with Poorer long-term Graft Outcome
Authors: Grebe S. O. , Kuhlmann U. , Müller T. F. 
Published: August 2013

Abstract
Chronic allograft nephropathy (CAN) and death with functioning graft due to cardiovascular disease (CVD) are the key determinants for long-term renal allograft survival. Chronic allograft nephropathy and cardiovascular disease are seen as manifestations of a single disease entity with a common pathogenesis including inflammation and accelerated atherogenesis. Therefore we investigated the relation between early post-transplant inflammatory burden and long-term graft survival.
In 64 consecutive renal transplant patients the acute phase reactants serum amyloid A (SAA) and serum C-reactive protein (S-CRP) as well as the macrophage product neopterin in urine (U-NEOP) and serum (S-NEOP) were determined daily during the immediate postoperative period (mean p.o.obs. χ = 29.2 ± 8.7 days, total of Σ = 1869 days). SAA and CRP were measured with high-sensitive assays (in mg/1; immune nephelometry, Dade Behring Co., Marburg, Germany), NEOP was measured with ELISA-technique (Brahms, Berlin, Germany) and related to serum and urine creatinine levels, resp. (in μπιοΐ/mol creatinine). The association between the mean values of these parameters and the survival distribution function of the 64 patients was tested using the log rank test and the Wilcoxon-test. In this analysis graft loss was defined as either resumption of dialysis treatment or patient death with functioning graft.
The 1- and 5- year graft survival rates in our patients were 93% and 76%, resp. The markers showed the following mean post-transplant levels: S-CRP χ = 21.3 ± 16.1 mg/1, SAA χ = 10.1 ± 6.5 mg/1, U-NEOP χ = 602 ± 427 mmol/mol creatinine and S-NEOP χ = 81 ± 60 μπιοΐ/mol creatinine. Both log rank test and Wilcoxon-test provided evidence that the graft survival is negatively related to the post-transplant levels of U-NEOP (p = 0.009 and ρ = 0.027, resp.). The markers S-NEOP (p = 0.074 and ρ = 0.116, resp.), SAA (p = 0.599 and ρ = 0.294, resp.), and S-CRP (p = 0.059 and ρ = 0.358, resp.) did not reach statistical significance. These findings support the impact of the inflammatory burden on graft survival. In particular, elevated post-transplant neopterin values, reflecting activated innate and adaptive responses, are predictive for long-term graft outcome.
Neopterin to Monitor Clinical Pathologies Involving Interferon-γ Production
Authors: Schroecksnadel Katharina , Murr Christian , Winkler Christiana , Wirleitner Barbara , Fuith Lothar C. , Fuchs Dietmar 
Published: August 2013

Abstract
Upon stimulation with the cytokine interferon-γ human monocytes/macrophages produce neopterin. Accordingly, measurement of neopterin concentrations in body fluids like blood, urine or cerebrospinal fluid provides information about activation of immune response involving type 1 Τ helper cells. Increased neopterin production is found in infections by viruses including human immunodeficiency virus (HIV), infections by intracellular living bacteria and parasites, autoimmune diseases, malignant tumor diseases and in allograft rejection episodes, but also in some neurodegenerative and in cardiovascular diseases. Major diagnostic applications of neopterin measurements are monitoring of the immune status of allograft recipients, detection of infectious diseases in blood donations and monitoring of therapy in HIV-infected individuals. Neopterin concentrations also provide prognostic information in HIV-infected individuals and in several malignant tumor diseases, high neopterin production at the moment of diagnosis is associated with poorer survival expectations. As high neopterin production is associated with increased production of reactive oxygen species and with low serum concentrations of antioxidants like α-tocopherol, neopterin can be regarded as a marker of oxidative stress caused by an activated immune system. Therefore, by neopterin measurements not only the extent of cellular immune activation, but also the extent of tissue damage caused by reactive oxygen specics may be estimated.
Serum Neopterin as a Marker for Screening of Hepatocellular Carcinoma
Authors: Tsuda Yasuhiro , Fukuda Akira , Kobayashi Hiroyuki , Itou Dai , Yoshimoto Satomine , Iwata Kazunari , Hanafusa Toshiaki 
Published: August 2013

Abstract
As Screening markers for hepatocellular Carcinoma (HCC), alpha-fetoprotein (AFP) and protein induced by an absence of vitamin K or antagonist-II (PIVKA-II) are widely used, but the sensitivity and specificity are not satisfactory enough. Neopterin is a biological marker for increased cell-mediated immunity, but has not been fully studied on HCC. To assess the clinical significance of serum neopterin as a screening marker for HCC, fifty-six HCC patients with liver cirrhosis (LC) and thirty-two LC patients without HCC as controls were studied. Serum neopterin level (n mol/L) was determined by immunoenzymatic assay. The sensitivity and specificity were analyzed by using ROC analysis. The mean level oi neopterin in HCC was significantly higher than that in LC (20.4 YS. 7.7 nmol/L, P<0.001). There was no significant relationship among serum AFP, PIVKA-II, and neopterin in HCC patients. When the cut-off value was set at 12 n mol/L, the sensitivity and specificity of neopterin was 88% and 73%, respectively. In patients with early HCC (<3cm), the detection rate of AFP, PIVKA-II, and neopterin was 35%, 35%, and 70 %, respectively. When all three markers were used, 95% of all HCC patients and 90% of early HCC patients could be detected. The detection rate of neopterin was not affected by ALT level, PLT count, liver function, angiographic pattern, histology, TNM stage, and type of tumor. These findings suggests that serum neopterin can be useful as a Screening marker for HCC and makes it possible to detect HCC at its earlier stage when used in combination with AFP or PIVKA-II.