bluuebunny/crossref_metadata_2025_split huggingface dataset:
RB1 gene mutation up-date, a meta-analysis based on 932 reported mutations available in a searchable database
Authors: Valverde José R , Alonso Javier , Palacios Itziar , Pestaña Ángel 
Published: November 2005

Abstract

Background
Retinoblastoma, a prototype of hereditary cancer, is the most common intraocular tumour in children and potential cause of blindness from therapeutic eye ablation, second tumours in germ line carrier's survivors, and even death when left untreated. The molecular scanning of RB1 in search of germ line mutations lead to the publication of more than 900 mutations whose knowledge is important for genetic counselling and the characterization of phenotypic-genotypic relationships.

Results
A searchable database (RBGMdb) has been constructed with 932 published RB1 mutations. The spectrum of these mutations has been analyzed with the following results: 1) the retinoblastoma protein is frequently inactivated by deletions and nonsense mutations while missense mutations are the main inactivating event in most genetic diseases. 2) Near 40% of RB1 gene mutations are recurrent and gather in sixteen hot points, including twelve nonsense, two missense and three splicing mutations. The remainder mutations are scattered along RB1, being most frequent in exons 9, 10, 14, 17, 18, 20, and 23. 3) The analysis of RB1 mutations by country of origin of the patients identifies two groups in which the incidence of nonsense and splicing mutations show differences extremely significant, and suggest the involvement of predisposing ethnic backgrounds. 4) A significant association between late age at diagnosis and splicing mutations in bilateral retinoblastoma patients suggests the occurrence of a delayed-onset genotype. 5) Most of the reported mutations in low-penetrance families fall in three groups: a) Mutations in regulatory sequences at the promoter resulting in low expression of a normal Rb; b) Missense and in-frame deletions affecting non-essential sequence motifs which result in a partial inactivation of Rb functions; c) Splicing mutations leading to the reduction of normal mRNA splicing or to alternative splicing involving either true oncogenic or defective (weak) alleles.

Conclusion
The analysis of RB1 gene mutations logged in the RBGMdb has shown relevant phenotype-genotype relationships and provided working hypothesis to ascertain mechanisms linking certain mutations to ethnicity, delayed onset of the disease and low-penetrance. Gene profiling of tumors will help to clarify the genetic background linked to ethnicity and variable expressivity or delayed onset phenotypes.
Fluid-structure interaction in abdominal aortic aneurysms: effects of asymmetry and wall thickness
Authors: Scotti Christine M , Shkolnik Alexander D , Muluk Satish C , Finol Ender A 
Published: November 2005

Abstract

Background
Abdominal aortic aneurysm (AAA) is a prevalent disease which is of significant concern because of the morbidity associated with the continuing expansion of the abdominal aorta and its ultimate rupture. The transient interaction between blood flow and the wall contributes to wall stress which, if it exceeds the failure strength of the dilated arterial wall, will lead to aneurysm rupture. Utilizing a computational approach, the biomechanical environment of virtual AAAs can be evaluated to study the affects of asymmetry and wall thickness on this stress, two parameters that contribute to increased risk of aneurysm rupture.

Methods
Ten virtual aneurysm models were created with five different asymmetry parameters ranging from β = 0.2 to 1.0 and either a uniform or variable wall thickness to study the flow and wall dynamics by means of fully coupled fluid-structure interaction (FSI) analyses. The AAA wall was designed to have a (i) uniform 1.5 mm thickness or (ii) variable thickness ranging from 0.5 – 1.5 mm extruded normally from the boundary surface of the lumen. These models were meshed with linear hexahedral elements, imported into a commercial finite element code and analyzed under transient flow conditions. The method proposed was then compared with traditional computational solid stress techniques on the basis of peak wall stress predictions and cost of computational effort.

Results
The results provide quantitative predictions of flow patterns and wall mechanics as well as the effects of aneurysm asymmetry and wall thickness heterogeneity on the estimation of peak wall stress. These parameters affect the magnitude and distribution of Von Mises stresses; varying wall thickness increases the maximum Von Mises stress by 4 times its uniform thickness counterpart. A pre-peak systole retrograde flow was observed in the AAA sac for all models, which is due to the elastic energy stored in the compliant arterial wall and the expansion force of the artery during systole.

Conclusion
Both wall thickness and geometry asymmetry affect the stress exhibited by a virtual AAA. Our results suggest that an asymmetric AAA with regional variations in wall thickness would be exposed to higher mechanical stresses and an increased risk of rupture than a more fusiform AAA with uniform wall thickness. Therefore, it is important to accurately reproduce vessel geometry and wall thickness in computational predictions of AAA biomechanics.
Osteoporosis, inflammation and ageing
Authors: Ginaldi Lia , Di Benedetto Maria Cristina , De Martinis Massimo 
Published: November 2005

Abstract
Osteoporosis is a condition characterized by low bone mass and increased bone fragility, putting patients at risk of fractures, which are major causes of morbidity substantially in older people. Osteoporosis is currently attributed to various endocrine, metabolic and mechanical factors. However, emerging clinical and molecular evidence suggests that inflammation also exerts significant influence on bone turnover, inducing osteoporosis. Numerous proinflammatory cytokines have been implicated in the regulation of osteoblasts and osteoclasts, and a shift towards an activated immune profile has been hypothesized as important risk factor. Chronic inflammation and the immune system remodelling characteristic of ageing, as well as of other pathological conditions commonly associated with osteoporosis, may be determinant pathogenetic factors. The present article will review the current perspectives on the interaction between bone and immune system in the elderly, providing an interpretation of osteoporosis in the light of inflamm-ageing.
Mobile phone-induced myocardial oxidative stress: protection by a novel antioxidant agent caffeic acid phenethyl ester
Authors: Ozguner Fehmi , Altinbas Ahmet , Ozaydin Mehmet , Dogan Abdullah , Vural Huseyin , Kisioglu A Nesimi , Cesur Gokhan , Yildirim Nurhan Gumral 
Published: November 2005

Electromagnetic radiation (EMR) or radiofrequency fields of cellular mobile phones may affect biological systems by increasing free radicals, which appear mainly to enhance lipid peroxidation, and by changing the antioxidant defense systems of human tissues, thus leading to oxidative stress. Mobile phones are used in close proximity to the heart, therefore 900 MHz EMR emitting mobile phones may be absorbed by the heart. Caffeic acid phenethyl ester (CAPE), one of the major components of honeybee propolis, was recently found to be a potent free radical scavenger and antioxidant, and is used in folk medicine. The aim of this study was to examine 900 MHz mobile phone-induced oxidative stress that promotes production of reactive oxygen species (ROS) and the role of CAPE on myocardial tissue against possible oxidative damage in rats. Thirty rats were used in the study. Animals were randomly grouped as follows: sham-operated control group (N: 10) and experimental groups: (a) group II: 900 MHz EMR exposed group (N: 10); and (b) group III: 900 MHz EMR exposed+CAPE-treated group (N: 10). A 900 MHz EMR radiation was applied to groups II and III 30 min/day, for 10 days using an experimental exposure device. Malondialdehyde (MDA, an index of lipid peroxidation), and nitric oxide (NO, a marker of oxidative stress) were used as markers of oxidative stress-induced heart impairment. Superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status. In the EMR exposed group, while tissue MDA and NO levels increased, SOD, CAT and GSH-Px activities were reduced. CAPE treatment in group III reversed these effects. In this study, the increased levels of MDA and NO and the decreased levels of myocardial SOD, CAT and GSH-Px activities demonstrate the role of oxidative mechanisms in 900 MHz mobile phone-induced heart tissue damage, and CAPE, via its free radical scavenging and antioxidant properties, ameliorates oxidative heart injury. These results show that CAPE exhibits a protective effect on mobile phone-induced and free radical mediated oxidative heart impairment in rats.
Muscle biochemistry and the ontogeny of flight capacity during behavioral development in the honey bee,Apis mellifera
Authors: Roberts Stephen P. , Elekonich Michelle M. 
Published: November 2005

SUMMARYA fundamental issue in physiology and behavior is understanding the functional and genetic mechanisms that underlie major behavioral shifts in organisms as they adopt new environments or life history tactics. Such transitions are common in nature and include the age-related switch from nest/hive work to foraging in social insects such as honey bees (Apis mellifera). Because of their experimental tractability, recently sequenced genome and well understood biology, honey bees are an ideal model system for integrating molecular, genetic, physiological and sociobiological perspectives to advance understanding of behavioral and life history transitions. When honey bees (Apis mellifera) transition from hive work to foraging, their flight muscles undergo changes that allow these insects to attain the highest rates of flight muscle metabolism and power output ever recorded in the animal kingdom. Here, we review research to date showing that honey bee flight muscles undergo significant changes in biochemistry and gene expression and that these changes accompany a significant increase in the capacity to generate metabolic and aerodynamic power during flight. It is likely that changes in muscle gene expression, biochemistry, metabolism and functional capacity may be driven primarily by behavior as opposed to age, as is the case for changes in honey bee brains.
Expression and functional analysis of mussel taurine transporter, as a key molecule in cellular osmoconforming
Authors: Hosoi Masatomi , Takeuchi Kazuharu , Sawada Hideki , Toyohara Haruhiko 
Published: November 2005

SUMMARYMost aquatic invertebrates adapt to environmental osmotic changes primarily by the cellular osmoconforming process, in which osmolytes accumulated in their cells play an essential role. Taurine is one of the most widely utilized osmolytes and the most abundant in many molluscs. Here, we report the structure, function and expression of the taurine transporter in the Mediterranean blue mussel (muTAUT), as a key molecule in the cellular osmoconforming process. Deduced amino acid sequence identity among muTAUT and vertebrate taurine transporters is lower (47-51%) than that among vertebrate taurine transporters (&gt;78%). muTAUT has a lower affinity and specificity for taurine and a requirement for higher NaCl concentration than vertebrate taurine transporters. This seems to reflect the internal environment of the mussel; higher NaCl and taurine concentrations. In addition to the hyperosmotic induction that has been reported for cloned taurine transporters,the increase in muTAUT mRNA was unexpectedly observed under hypoosmolality,which was depressed by the addition of taurine to ambient seawater. In view of the decrease in taurine content in mussel tissue under conditions of hypoosmolality reported previously, our results lead to the conclusion that muTAUT does not respond directly to hypoosmolality, but to the consequent decrease in taurine content. By immunohistochemistry, intensive expression of muTAUT was observed in the gill and epithelium of the mantle, which were directly exposed to intensive osmotic changes of ambient seawater.
Actin cytoskeleton of rabbit intestinal cells is a target for potent marine phycotoxins
Authors: Ares I. R. , Louzao M. C. , Vieytes M. R. , Yasumoto T. , Botana L. M. 
Published: November 2005

SUMMARYBiotoxins produced by harmful marine microalgae (phycotoxins) can be accumulated into seafood, representing a great risk for public health. Some of these phycotoxins are responsible for a variety of gastrointestinal disturbances; however, the relationship between their mechanism of action and toxicity in intestinal cells is still unknown. The actin cytoskeleton is an important and highly complicated structure in intestinal cells, and on that basis our aim has been to investigate the effect of representative phycotoxins on the enterocyte cytoskeleton. We have quantified for the first time the loss of enterocyte microfilament network induced by each toxin and recorded fluorescence images using a laser-scanning cytometer and confocal microscopy. Our data show that pectenotoxin-6, maitotoxin, palytoxin and ostreocin-D cause a significant reduction in the actin cytoskeleton. In addition, we found that the potency of maitotoxin, palytoxin and ostreocin-D to damage filamentous actin is related to Ca2+ influx in enterocytes. Those results identify the cytoskeleton as an early target for the toxic effect of those toxins.
Unbound Free Fatty Acids and Heart-Type Fatty Acid–Binding Protein: Diagnostic Assays and Clinical Applications
Authors: Azzazy Hassan ME , Pelsers Maurice MAL , Christenson Robert H 
Published: November 2005

AbstractBackground: A biomarker that reliably detects myocardial ischemia in the absence of necrosis would be useful for initial identification of unstable angina patients and for differentiating patients with chest pain of an etiology other than coronary ischemia, and could provide clinical utility complementary to that of cardiac troponins, the established markers of necrosis. Unbound free fatty acids (FFAu) and their intracellular binding protein, heart-type fatty acid–binding protein (H-FABP), have been suggested to have clinical utility as indicators of cardiac ischemia and necrosis, respectively.Methods: We examined results of clinical assessments of FFAu and H-FABP as biomarkers of cardiac ischemia and necrosis. Data published on FFAu and H-FABP over the past 30 years were used as the basis for this review.Results: Although little clinical work has been done on FFAu since the initial reports, recent studies documented an association between increased serum FFAs and ventricular dysrhythmias and death in patients with acute myocardial infarction (AMI). Recent data suggest that serum FFAu concentrations increase well before markers of cardiac necrosis and are sensitive indicators of ischemia in AMI. H-FABP is abundant in cardiac muscle and is presumed to be involved in myocardial lipid homeostasis. Similar to myoglobin, plasma H-FABP increases within 3 h after AMI and returns to reference values within 12–24 h.Conclusions: FFAu may have a potential role in identifying patients with cardiac ischemia. H-FABP is useful for detecting cardiac injury in acute coronary syndromes and predicting recurrent cardiac events in acute coronary syndromes and in congestive heart failure patients. Assays are available for both markers that could facilitate further clinical investigations to assess their possible roles as markers of cardiac ischemia and/or necrosis.
Assay for the Measurement of Copeptin, a Stable Peptide Derived from the Precursor of Vasopressin
Authors: Morgenthaler Nils G , Struck Joachim , Alonso Christine , Bergmann Andreas 
Published: November 2005

AbstractBackground: Arginine vasopressin (AVP) is a key regulator of water balance, but its instability makes reliable measurement difficult and precludes routine use. We present a method for quantifying AVP release by use of copeptin, a glycopeptide comprising the C-terminal part of the AVP prohormone.Methods: We measured copeptin in 50-μL serum and plasma samples from healthy individuals and from critically ill patients with sepsis. Our sandwich immunoluminometric assay used 2 polyclonal antibodies to amino acids 132–164 of pre-provasopressin.Results: The assay yielded results within 3 h. The analytical detection limit was 1.7 pmol/L, and the interlaboratory CV was &lt;20% for values &gt;2.25 pmol/L. The assay was linear on dilution of the analyte. Ex vivo copeptin stability (&lt;20% loss of analyte) for at least 7 days at room temperature and 14 days at 4 °C was shown for serum and EDTA-, heparin-, and citrate plasma. Copeptin (median, 4.2 pmol/L; range, 1–13.8 pmol/L) was detectable in 97.5% of 359 healthy individuals and was not associated with age. Median concentrations were considerably higher in men than women, increased significantly after exercise, and were influenced by fasting and water load. Copeptin was significantly (P &lt;0.001) increased in 60 critically ill patients with sepsis (median, 79.5 pmol/L; range, 10.6–228.0 pmol/L). The correlation between copeptin and AVP for 110 samples was r = 0.78 (P &lt;0.0001).Conclusions: Copeptin is stable for days after blood withdrawal and can be quickly and easily measured. The copeptin assay may be a useful alternative to direct measurement of AVP concentration.
Kinetics of the oxidation of Pu(IV) by manganese dioxide
Authors: Morgenstern A. , Choppin Gregory R. 
Published: November 2005

SummaryThe kinetics of the oxidation of plutonium(IV) by manganese dioxide were studied in 1.0 M NaCl over the pH range from 2.5 to 8.2 with variable concentrations of manganese dioxide from 0.01 m2/L to 4.97 m2/L at a constant temperature of 19 ± 2 °C. The concentration of plutonium in solution was 6.0(± 1.0) × 10−10M. Fractions of Pu(IV), (V) and (VI) as a function of time were determined by removal of plutonium from the solid phase followed by an ultrafiltration/solvent extraction procedure using TTA and HDEHP as extractants. Appropriate removal conditions were established for Pu(IV), Pu(V) and Pu(VI) using Th(IV), Np(V) and U(VI) as oxidation state analogs.In the pH range from 2.0 to 3.5, the oxidation of Pu(IV) by manganese dioxide was first order with respect to the concentration of manganese dioxide and −0.21 with respect to the hydrogen ion concentration. Consequently, assuming a first order dependence with respect to the concentration of Pu(IV), the oxidation reaction can be described by the following rate equation:withk= 3.72(± 0.13) × 10−3(m−2L)(mol−1L)−0.21(min)−1. Using the kinetic data determined in this study, the influence of manganese dioxide on the oxidation state distribution of plutonium under various environmental conditions as well as in waste solutions can be estimated.
Single-column extraction chromatographic separation of U, Pu, Np and Am
Authors: Morgenstern A. , Apostolidis C. , Carlos-Marquez R. , Mayer K. , Molinet R. 
Published: November 2005

Summary
A rapid, single-column extraction chromatographic method using commercially available UTEVA resin has been developed for the separation of uranium, plutonium, neptunium and americium. The method yields recoveries superior to 90% and allows direct loading of separated fractions on filaments for subsequent analysis by thermal ionization mass spectrometry. The use of reagents compatible with robotized equipment allows automation of the separation process for routine analysis of nuclear materials. The redox reactions between plutonium, neptunium and hydrogen peroxide involved in the separation process were studied by UV/Vis/NIR absorption spectroscopy.
Aberrant Genomic Imprinting in Rhesus Monkey Embryonic Stem Cells
Authors: Fujimoto Akihisa , Mitalipov Shoukhrat M. , Kuo Hung-Chih , Wolf Don P. 
Published: November 2005

Abstract
Genomic imprinting involves modification of a gene or a chromosomal region that results in the differential expression of parental alleles. Disruption or inappropriate expression of imprinted genes is associated with several clinically significant syndromes and tumorigenesis in humans. Additionally, abnormal imprinting occurs in mouse embryonic stem cells (ESCs) and in clonally derived animals. Imprinted gene expression patterns in primate ESCs are largely unknown, despite the clinical potential of the latter in the cell-based treatment of human disease. Because of the possible implications of abnormal gene expression to cell or tissue replacement therapies involving ESCs, we examined allele specific expression of four imprinted genes in the rhesus macaque. Genomic and complementary DNA from embryos and ESC lines containing useful single nucleotide polymorphisms were subjected to polymerase chain reaction–based amplification and sequence analysis. In blastocysts, NDN expression was variable indicating abnormal or incomplete imprinting whereas IGF2 and SNRPN were expressed exclusively from the paternal allele and H19 from the maternal allele as expected. In ESCs, both NDN and SNRPN were expressed from the paternal allele while IGF2 and H19 showed loss of imprinting and biallelic expression. In differentiated ESC progeny, these expression patterns were maintained. The implications of aberrant imprinted gene expression to ESC differentiation in vitro and on ESC-derived cell function in vivo after transplantation are unknown.
High-Risk Localized Prostate Cancer: Integrating Chemotherapy
Authors: Oh William K. 
Published: November 2005

Abstract

Learning Objectives
After completing this course, the reader will be able to:Discuss the importance of prostate cancer to public health.Describe the evolving role of systemic treatment in managing high-risk and metastatic disease and discuss the factors that predict for high-risk local disease.Explain the importance of multimodality input in managing high-risk prostate cancer.
Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com
Docetaxel (Taxotere®; Aventis Pharmaceuticals Inc., Bridgewater, NJ, http://www.aventispharma-us.com) is the first agent to significantly extend survival in hormone-refractory prostate cancer. Because agents active in advanced cancers tend to be beneficial in earlier stage disease, docetaxel is now to be assessed, along with hormonal therapy, in the adjuvant setting among patients whose localized prostate cancer has features that put them at particular risk for recurrence and cancer-specific mortality. Data from a pilot study suggest that neo-adjuvant treatment with docetaxel may be appropriate for selected high-risk patients and that such treatment can be undertaken without increasing surgical morbidity. Gene-expression profiling of tissue before and after docetaxel treatment is providing further insight into its effects. A randomized trial, conducted by the Cancer and Leukemia Group B, will evaluate neoadjuvant docetaxel in high-risk patients, whereby patients will be randomized to either immediate radical prostatectomy or surgery preceded by hormonal therapy plus docetaxel. Another large randomized trial will be evaluating the effect of adjuvant hormonal therapy with or without docetaxel in high-risk men after radical prostatectomy.