Impact of FDG PET/CT on detection of synchronous and metachronous malignancies and clinical management in patients with multiple primary cancers.

Multiple primary cancers are usually defined as primary malignant tumors of different histological origins in one person. Recently, there has been an increase in the number of patients diagnosed with multiple primary cancers. The study aims to evaluate the role of PET/CT in detecting second primary and subsequent tumors as well as to demonstrate the influence on the treatment management in patients with histologically proven synchronous or metachronous tumors.

Detection of Ureteral Stump Transitional Cell Carcinoma, Presenting as Bone Metastases from Unknown Primary by 18F-FDG PET/CT: A Case Report with Review of Literature.

A case of occult carcinoma of the ureteral stump is reported. A 67-year-old man presented with pain syndrome due to multiple bone metastases from unknown primary origin detected by previous imaging studies as magnetic resonance imaging, whole body contrast-enhanced computed tomography (CT), and technetium-99m methyldiphosphonate bone scan. He had undergone a right nephrectomy for a benign disease previously.

Changes in Root-Shoot Allometric Relations in Alpine Norway Spruce Trees After Strip Cutting.

Silvicultural interventions such as strip cuttings can change the resource availability of the edge trees. This may alter tree allometry, as light regime, water, and nutrient availability can change at the forest edge. Increased root growth may optimize resource uptake and/or enhance tree anchorage to withstand the altered wind regime.

Fine-Root Traits Reveal Contrasting Ecological Strategies in European Beech and Norway Spruce During Extreme Drought.

Trees adjust multiple structural and functional organ-specific characteristics, "traits", to cope with diverse soil conditions. Studies on traits are widely used to uncover ecological species adaptability to varying environments. However, fine-root traits are rarely studied for methodological reasons.

The impact of 18F-FDG PET/CT in the clinical management of patients with lymph node metastasis of unknown primary origin.

The aim of this study was to evaluate the diagnostic performance and the utility of F-18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) in the clinical management of patients presenting with lymph node metastasis of undefined primary origin (CUP). A total of 53 patients (34 males, 19 females) with a diagnosis of lymph node metastasis according to the histopathology and/or conventional imaging were enrolled in this retrospective study. Patients were divided into four groups according to the initial location of their metastasis - group 1, cervical lymph nodes (n=39), group 2, axillary lymph nodes (n=6), group 3, mediastinal lymph nodes (n=2) and group 4, abdominal and pelvic lymph nodes (n=6).

The clinical benefit of array-based comparative genomic hybridization for detection of copy number variants in Czech children with intellectual disability and developmental delay.

Background: Chromosomal microarray analysis has been shown to be a valuable and cost effective assay for elucidating copy number variants (CNVs) in children with intellectual disability and developmental delay (ID/DD).

Methods: In our study, we performed array-based comparative genomic hybridization (array-CGH) analysis using oligonucleotide-based platforms in 542 Czech patients with ID/DD, autism spectrum disorders and multiple congenital abnormalities. Prior to the array-CGH analysis, all the patients were first examined karyotypically using G-banding.

Novel de novo frameshift variant in the ASXL3 gene in a child with microcephaly and global developmental delay.

De novo sequence variants, including truncating and splicing variants, in the additional sex‑combs like 3 gene (ASXL3) have been described as the cause of Bainbridge‑Ropers syndrome (BRS). This pathology is characterized by delayed psychomotor development, severe intellectual disability, growth delay, hypotonia and facial dimorphism. The present study reports a case of a girl (born in 2013) with severe global developmental delay, central hypotonia, microcephaly and poor speech.

Impact of Air Pollution and Outdoor Temperature on the Rate of Chronic Obstructive Pulmonary Disease Exacerbations.

Background: Environmental pollution can be one of the main risk factors for acute exacerbations of chronic obstructive pulmonary disease (COPD).

Aim: To study the relationship between air pollution, outdoor temperature and exacerbations of COPD.

Materials And Methods: COPD patients (n=1432) were followed up for one year.

Consequences of point mutations in melanoma-associated antigen 4 (MAGE-A4) protein: Insights from structural and biophysical studies.

The Melanoma-Associated Antigen A4 (MAGE-A4) protein is a target for cancer therapy. The function of this protein is not well understood. We report the first comprehensive study on key cancer-associated MAGE-A4 mutations and provide analysis on the consequences of these mutations on the structure, folding and stability of the protein.

Comparison of δ(18)O and δ(13)C values between tree-ring whole wood and cellulose in five species growing under two different site conditions.

Rationale: We investigated the applicability of tree-ring whole-wood material for δ(18)O and δ(13)C analysis in comparison with the more time- and resource-intensive use of cellulose, by considering possible variability between (i) five different tree species (Fagus sylvatica, Quercus robur, Picea abies, Abies alba, Pseudotsuga menziesii), (ii) two sites that differ in soil moisture, and (iii) climate conditions within a 10-year period.

Methods: Stem cores of 30 individual trees (n = 3 trees per each species and site) were sampled from two sites in south Germany (Bavaria), and tree rings within sapwood of the years 2001-2010 were separated. The δ(18)O and δ(13)C values from homogenized tree-ring whole wood and from extracted cellulose were measured by mass spectrometry.

Insights into the conformations of three structurally diverse proteins: cytochrome c, p53, and MDM2, provided by variable-temperature ion mobility mass spectrometry.

Thermally induced conformational transitions of three proteins of increasing intrinsic disorder-cytochrome c, the tumor suppressor protein p53 DNA binding domain (p53 DBD), and the N-terminus of the oncoprotein murine double minute 2 (NT-MDM2)-have been studied by native mass spectrometry and variable-temperature drift time ion mobility mass spectrometry (VT-DT-IM-MS). Ion mobility measurements were carried out at temperatures ranging from 200 to 571 K. Multiple conformations are observable over several charge states for all three monomeric proteins, and for cytochrome c, dimers of significant intensity are also observed.

Structure and stability insights into tumour suppressor p53 evolutionary related proteins.

The p53 family of genes and their protein products, namely, p53, p63 and p73, have over one billion years of evolutionary history. Advances in computational biology and genomics are enabling studies of the complexities of the molecular evolution of p53 protein family to decipher the underpinnings of key biological conditions spanning from cancer through to various metabolic and developmental disorders and facilitate the design of personalised medicines. However, a complete understanding of the inherent nature of the thermodynamic and structural stability of the p53 protein family is still lacking.

Intrinsic disorder in proteins: a challenge for (un)structural biology met by ion mobility-mass spectrometry.

The link between structure and function of a given protein is a principal tenet of biology. The established approach to understand the function of a protein is to 'solve' its structure and subsequently investigate interactions between the protein and its binding partners. However, structure determination via crystallography or NMR is challenging for proteins where localized regions or even their entire structure fail to fold into a three-dimensional form.

[Psychophysiological reactivity and personality traits of left- and right-handers during mental stress].

The aim of the present study was to establish whether there is dependence of vascular reactivity to mental stress on the levels of neuroticism and anxiety in left- and right-handers. Thirty-two left-handed and 32 righthanded volunteers (16 males and 16 females in each group) between 18 and 30 years of age were studied. During mental stress both groups demonstrated a "standard" type of response, indicating an increase of the sympathetic-adrenal activity.

Optimized assay and storage conditions for enzyme activity profiling of ectomycorrhizae.

The aim of a joint effort by different research teams was to provide an improved procedure for enzyme activity profiling of field-sampled ectomycorrhizae, including recommendations on the best conditions and maximum duration for storage of ectomycorrhizal samples. A more simplified and efficient protocol compared to formerly published procedures was achieved by using manufactured 96-filter plates in combination with a vacuum manifold and by optimizing incubation times. Major improvements were achieved by performing the series of eight enzyme assays with a single series of root samples instead of two series, reducing the time needed for sample preparation, minimizing error-prone steps such as pipetting and morphotyping, and facilitating subsequent DNA analyses due to the reduced sequencing effort.

Season of birth, Geschwind and Galaburda hypothesis, and handedness.

Geschwind and Galaburda (1985a, 1985b) suggested that the season of conception is a non-genetic random variable that may affect laterality and handedness, probably due to seasonal variations in the hormonal influences on the foetal brain. According to this suggestion it is logical to expect seasonal anisotropy in the incidence of birth of right- and non-right-handers. The present study analysed data obtained from a sample of 3182 young Bulgarians: 2825 right-handers and 357 non-right-handers.

Enhanced ozone strongly reduces carbon sink strength of adult beech (Fagus sylvatica)--resume from the free-air fumigation study at Kranzberg Forest.

Ground-level ozone (O(3)) has gained awareness as an agent of climate change. In this respect, key results are comprehended from a unique 8-year free-air O(3)-fumigation experiment, conducted on adult beech (Fagus sylvatica) at Kranzberg Forest (Germany). A novel canopy O(3) exposure methodology was employed that allowed whole-tree assessment in situ under twice-ambient O(3) levels.

Mutants of the tumour suppressor p53 L1 loop as second-site suppressors for restoring DNA binding to oncogenic p53 mutations: structural and biochemical insights.

To assess the potential of mutations from the L1 loop of the tumour suppressor p53 as second-site suppressors, the effect of H115N and S116M on the p53 'hot spot' mutations has been investigated using the double-mutant approach. The effects of these two mutants on the p53 hot spots in terms of thermal stability and DNA binding were evaluated. The results show that: (i) the p53 mutants H115N and S116M are thermally more stable than wild-type p53; (ii) H115N but not S116M is capable of rescuing the DNA binding of one of the most frequent p53 mutants in cancer, R248Q, as shown by binding of R248Q/H115N to gadd45 (the promoter of a gene involved in cell-cycle arrest); (iii) the double mutant R248Q/H115N is more stable than wild-type p53; (iv) the effect of H115N as a second-site suppressor to restore DNA-binding activity is specific to R248Q, but not to R248W; (v) molecular-dynamics simulations indicate that R248Q/H115N has a conformation similar to wild-type p53, which is distinct from that of R248Q.

Belowground effects of enhanced tropospheric ozone and drought in a beech/spruce forest (Fagus sylvatica L./Picea abies [L.] Karst).

The effects of experimentally elevated O(3) on soil respiration rates, standing fine-root biomass, fine-root production and delta(13)C signature of newly produced fine roots were investigated in an adult European beech/Norway spruce forest in Germany during two subsequent years with contrasting rainfall patterns. During humid 2002, soil respiration rate was enhanced under elevated O(3) under beech and spruce, and was related to O(3)-stimulated fine-root production only in beech. During dry 2003, the stimulating effect of O(3) on soil respiration rate vanished under spruce, which was correlated with decreased fine-root production in spruce under drought, irrespective of the O(3) regime.

Fine root dynamics of mature European beech (Fagus sylvatica L.) as influenced by elevated ozone concentrations.

Fine root dynamics (diameter < 1 mm) in mature Fagus sylvatica, with the canopies exposed to ambient or twice-ambient ozone concentrations, were investigated throughout 2004. The focus was on the seasonal timing and extent of fine root dynamics (growth, mortality) in relation to the soil environment (water content, temperature). Under ambient ozone concentrations, a significant relationship was found between fine root turnover and soil environmental changes indicating accelerated fine root turnover under favourable soil conditions.

Molecular interactions of ASPP1 and ASPP2 with the p53 protein family and the apoptotic promoters PUMA and Bax.

The apoptosis stimulating p53 proteins, ASPP1 and ASPP2, are the first two common activators of the p53 protein family that selectively enable the latter to regulate specific apoptotic target genes, which facilitates yes yet unknown mechanisms for discrimination between cell cycle arrest and apoptosis. To better understand the interplay between ASPP- and p53-family of proteins we investigated the molecular interactions between them using biochemical methods and structure-based homology modelling. The data demonstrate that: (i) the binding of ASPP1 and ASPP2 to p53, p63 and p73 is direct; (ii) the C-termini of ASPP1 and ASPP2 interact with the DNA-binding domains of p53 protein family with dissociation constants, K(d), in the lower micro-molar range; (iii) the stoichiometry of binding is 1:1; (iv) the DNA-binding domains of p53 family members are sufficient for these protein-protein interactions; (v) EMSA titrations revealed that while tri-complex formation between ASPPs, p53 family of proteins and PUMA/Bax is mutually exclusive, ASPP2 (but not ASPP1) formed a complex with PUMA (but not Bax) and displaced p53 and p73.

The p73 DNA binding domain displays enhanced stability relative to its homologue, the tumor suppressor p53, and exhibits cooperative DNA binding.

The p53 protein family is involved in the control of an intricate network of genes implicated in cell cycle, through to germ line integrity and development. Although the role of p53 is well-established, the intrinsic nature of its homologue p73 has yet to be fully elucidated. Here, the biochemical characterization and homology-based modeling of the p73 protein is presented and the implications for its function(s) examined.

Cytokine gene polymorphism in kidney transplantation--impact of TGF-beta 1, TNF-alpha and IL-6 on graft outcome.

Chronic allograft nephropathy (CAN) is one of the main causes of graft loss in renal transplantation. Polymorphisms with functional significance in the promoter and coding regions of cytokine genes have been suggested as a possible factor for graft rejection. The aim of this study was to investigate the impact of cytokine gene polymorphism of pro and anti-inflammatory cytokines on development of CAN in a group of renal transplant patients and donors.

Association of cytokine gene polymorphisms with malignant melanoma in Caucasian population.

It has been hypothesized that polymorphisms expected to result in functional changes in cytokine genes may influence susceptibility to cancer, including malignant melanoma (MM). Here, we have screened 24 potentially functional polymorphisms in five cytokine genes by PCR-SBT and PCR-SSP methods in 122 MM cell lines derived from Caucasian patients. The polymorphic positions studied were: TNFA -1031, -863, -857, -851, -574, -376, -308, -238, +488; TGFB1 -988, -800, -509, +869, +915, +652, +673, +713, +788; IL10 -1082, -819, -592; IL6 -174; IFNG -333, +874.