bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of endogenous retroviral reading frames in the human genome
Authors: Villesen Palle , Aagaard Lars , Wiuf Carsten , Pedersen Finn Skou 
Published: October 2004

Abstract
Background
Human endogenous retroviruses (HERVs) comprise a large class of repetitive retroelements. Most HERVs are ancient and invaded our genome at least 25 million years ago, except for the evolutionary young HERV-K group. The far majority of the encoded genes are degenerate due to mutational decay and only a few non-HERV-K loci are known to retain intact reading frames. Additional intact HERV genes may exist, since retroviral reading frames have not been systematically annotated on a genome-wide scale.

Results
By clustering of hits from multiple BLAST searches using known retroviral sequences we have mapped 1.1% of the human genome as retrovirus related. The coding potential of all identified HERV regions were analyzed by annotating viral open reading frames (vORFs) and we report 7836 loci as verified by protein homology criteria. Among 59 intact or almost-intact viral polyproteins scattered around the human genome we have found 29 envelope genes including two novel gammaretroviral types. One encodes a protein similar to a recently discovered zebrafish retrovirus (ZFERV) while another shows partial, C-terminal, homology to Syncytin (HERV-W/FRD).

Conclusions
This compilation of HERV sequences and their coding potential provide a useful tool for pursuing functional analysis such as RNA expression profiling and effects of viral proteins, which may, in turn, reveal a role for HERVs in human health and disease. All data are publicly available through a database at http://www.retrosearch.dk.
An international sepsis survey: a study of doctors' knowledge and perception about sepsis
Authors: Poeze Martijn , Ramsay Graham , Gerlach Herwig , Rubulotta Francesca , Levy Mitchel 
Published: October 2004

Abstract
Background
To be able to diagnose and treat sepsis better it is important not only to improve the knowledge about definitions and pathophysiology, but also to gain more insight into specialists' perception of, and attitude towards, the current diagnosis and treatment of sepsis.

Methods
The study was conducted as a prospective, international survey by structured telephone interview. The subjects were intensive care physicians and other specialist physicians caring for intensive care unit (ICU) patients.

Results
The 1058 physicians who were interviewed (including 529 intensivists) agreed that sepsis is a leading cause of death on the ICU and that the incidence of sepsis is increasing, but that the symptoms of sepsis can easily be misattributed to other conditions. Physicians were concerned that this could lead to under-reporting of sepsis. Two-thirds (67%) were concerned that a common definition is lacking and 83% said it is likely that sepsis is frequently missed. Not more than 17% agreed on any one definition.

Conclusion
There is a general awareness about the inadequacy of the current definitions of sepsis. Physicians caring for patients with sepsis recognise the difficulty of defining and diagnosing sepsis and are aware that they miss the diagnosis frequently.
Prospective evaluation of an internet-linked handheld computer critical care knowledge access system
Authors: Lapinsky Stephen E , Wax Randy , Showalter Randy , Martinez-Motta J Carlos , Hallett David , Mehta Sangeeta , Burry Lisa , Stewart Thomas E 
Published: October 2004

Abstract
Introduction
Critical care physicians may benefit from immediate access to medical reference material. We evaluated the feasibility and potential benefits of a handheld computer based knowledge access system linking a central academic intensive care unit (ICU) to multiple community-based ICUs.

Methods
Four community hospital ICUs with 17 physicians participated in this prospective interventional study. Following training in the use of an internet-linked, updateable handheld computer knowledge access system, the physicians used the handheld devices in their clinical environment for a 12-month intervention period. Feasibility of the system was evaluated by tracking use of the handheld computer and by conducting surveys and focus group discussions. Before and after the intervention period, participants underwent simulated patient care scenarios designed to evaluate the information sources they accessed, as well as the speed and quality of their decision making. Participants generated admission orders during each scenario, which were scored by blinded evaluators.

Results
Ten physicians (59%) used the system regularly, predominantly for nonmedical applications (median 32.8/month, interquartile range [IQR] 28.3–126.8), with medical software accessed less often (median 9/month, IQR 3.7–13.7). Eight out of 13 physicians (62%) who completed the final scenarios chose to use the handheld computer for information access. The median time to access information on the handheld handheld computer was 19 s (IQR 15–40 s). This group exhibited a significant improvement in admission order score as compared with those who used other resources (P = 0.018). Benefits and barriers to use of this technology were identified.

Conclusion
An updateable handheld computer system is feasible as a means of point-of-care access to medical reference material and may improve clinical decision making. However, during the study, acceptance of the system was variable. Improved training and new technology may overcome some of the barriers we identified.
Akt Phosphorylation Is Not Sufficient for Insulin-Like Growth Factor-Stimulated Myogenin Expression but Must Be Accompanied by Down-Regulation of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Phosphorylation
Authors: Tiffin Nicki , Adi Saleh , Stokoe David , Wu Nan-Yan , Rosenthal Stephen M. 
Published: October 2004

AbstractIGF-I has a unique biphasic effect on skeletal muscle differentiation. Initially, IGF-I inhibits expression of myogenin, a skeletal muscle-specific regulatory factor essential for myogenesis. Subsequently, IGF-I switches to stimulating expression of myogenin. The mechanisms that mediate this switch in IGF action are incompletely understood. Several laboratories have demonstrated that the phosphatidylinositol-3-kinase/Akt signaling pathway is essential for myogenic differentiation and have suggested that this pathway mediates IGF-I stimulation of myogenin mRNA expression, an early critical step in the differentiation process. These studies, however, did not address concurrent Akt and MAPK/ERK1/2 phosphorylation, the latter of which is also known to regulate myogenic differentiation. In the present study in rat L6E9 muscle cells, we have manipulated ERK1/2 phosphorylation with either an upstream inhibitor or activator and examined concurrent levels of Akt and ERK1/2 phosphorylation and of myogenin mRNA expression in response to treatment with IGF-I. We find that even in the presence of phosphorylated Akt, it is only when ERK1/2 phosphorylation is inhibited that IGF-I can stimulate myogenin mRNA expression. Thus, although Akt phosphorylation may be necessary, it is not sufficient for induction of myogenic differentiation by IGF-I and must be accompanied by a decrease in ERK1/2 phosphorylation.
Adjunctive Granulocyte Colony-Stimulating Factor Therapy for Diabetic Foot Infections
Authors: Reed Kelly S , Pai Manjunath P 
Published: October 2004

OBJECTIVE To evaluate the role of granulocyte colony-stimulating factor (G-CSF) as adjunctive therapy for the treatment of diabetic foot infections in non-neutropenic patients. DATA SOURCES Clinical literature was accessed through MEDLINE (1965–April 2004). Key search terms included G-CSF, infection, and diabetes. In addition, relevant references from primary and secondary article bibliographies were extracted. DATA SYNTHESIS Three clinical trials evaluating G-CSF for diabetic foot infections were identified. These data demonstrated positive effects of G-CSF on improvement of foot infections and risk of amputations. CONCLUSIONS Controlled trials are necessary to validate the role of adjunctive G-CSF at reducing amputations in patients with diabetic foot infections.
Trivalent Intranasal Influenza Vaccine, Live
Authors: McCarthy Michelle W , Kockler Denise R 
Published: October 2004

OBJECTIVE To review human data on the efficacy, safety, and clinical use of trivalent intranasal influenza vaccine, live (TIIVL). DATA SOURCES A MEDLINE search (1966–3rd week of January 2004) using the terms influenza vaccine, intranasal administration, and FluMist was conducted. References from pertinent articles were also reviewed. STUDY SELECTION AND DATA EXTRACTION Studies conducted in humans and published in English were selected. Double-blind, controlled trials evaluating the efficacy and safety of TIIVL were evaluated. DATA SYNTHESIS Administration of TIIVL results in mucosal and humoral immunity to influenza. Results of clinical trials in children and adults have demonstrated that TIIVL reduces the incidence of influenza. In children, TIIVL was also associated with a decrease in febrile illness and febrile otitis media. In adults, reductions in workday absences and medical visits due to febrile upper respiratory tract illness were also documented. TIIVL is well tolerated, with rhinorrhea or nasal congestion and sore throat occurring more frequently than with placebo. CONCLUSIONS TIIVL is an alternative to intramuscular inactivated influenza vaccine in healthy individuals between 5 and 49 years of age. However, the vaccine is contraindicated in the majority of patient populations for whom annual influenza vaccination is recommended. THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT ACPE UNIVERSAL PROGRAM NUMBER: 407-000-04-037-H01
Exocyclic DNA Adducts as Oxidative Stress Markers in Colon Carcinogenesis: Potential Role of Lipid Peroxidation, Dietary Fat and Antioxidants
Authors: Bartsch Helmut , Nair Jagadeesan , Owen Robert W. 
Published: October 2004

AbstractMolecular pathways to colorectal cancer involve multiple genetic changes, whereby extensive oxyradical damage causes mutations in cancerrelated genes and leads to a cycle of cell death and regeneration. Besides direct oxidative DNAdamage, reactive oxygen and nitrogen species can induce etheno ()DNA adducts mainly via trans-4-hydroxy-2-nonenal, generated as the major aldehyde by lipid peroxidation (LPO) of ω-6 PUFAs. Patients with familial adenomatous polyposis (FAP) develop multiple colorectal adenomas. In affected tissues increased LPO could be triggered due to increased arachidonic acid metabolism as a result of elevated cyclooxygenases. Our studies demonstrated an increased DNA adduct level in affected colon epithelia of FAP patients. DNA adducts are promutagenic and can cause genomic instability that drives colorectal adenoma to malignancy. We have further investigated the potential chemopreventive properties of olive oil and its polyphenolic components. Mediterranean diet, of which olive oil is a major fatty acid source, has protective effects against human breast and colorectal cancers. Olive oil extracts and the newly identified lignan fractions showed high antioxidant capacity in vitro. As DNA adducts are biomarkers for oxidative stress and LPO induced DNA damage, they can verify the efficacy of newly identified antioxidants, e.g. from olive oil, as chemopreventive agents against colon carcinogenesis.
Functional Genomics of C190T Single Nucleotide Polymorphism in Human N-Acetyltransferase 2
Authors: Zhu Yuanqi , Doll Mark A. , Hein David W. 
Published: October 2004

AbstractNacetyltransferase 2 (NAT2) catalyzes Nacetylation and Oacetylation of many drugs and environmental carcinogens. Genetic polymorphisms in the NAT2 gene have been associated with differential susceptibility to cancers and drug toxicity from these compounds. Single nucleotide polymorphisms (SNPs) have been identified in the human NAT2 coding region. A new allele, NAT2*19, possessing the C190T (R64W) exchange, was recently identified. In order to understand the effect of this new SNP, recombinant NAT2*4 (reference) and NAT2*19 were expressed in yeast (Schizosaccharomyces pombe). The C190T (R64W) SNP in NAT2*19 caused substantial reduction in the NAT2 protein level and stability, but did not cause significant reduction in transformation efficiency or mRNA level. The enzymatic activities for Nacetylation of two arylamine carcinogens (2-aminofluorene, 4-aminobiphenyl), and a sulfonamide drug (sulfamethazine) were over 100-fold lower for NAT2 19 compared to reference NAT2 4. Kinetic studies showed a reduction in Vmax but no significant change in substrate Km. In addition, the SNP caused significant reduction in the Oacetylation of the Nhydroxy 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine. These results show that NAT2*19 possessing the C190T (R64W) SNP encodes a slow acetylator phenotype for both N and Oacetylation, due to a reduction in the amount and stability of the NAT2 19 allozyme.
Specificity Determinants in the Interaction of Apolipoprotein(a) Kringles with Tetranectin and LDL
Authors: Caterer N. R. , Graversen J. H. , Jacobsen C. , Moestrup S. K. , Sigurskjold B. W. , Etzerodt M. , Thøgersen H.C. 
Published: October 2004

AbstractLipoprotein(a) is composed of low density lipoprotein and apolipoprotein(a). Apolipoprotein(a) has evolved from plasminogen and contains 10 different plasminogen kringle 4 homologous domains [KIV(1 110)]. Previous studies indicated that lipoprotein(a) noncovalently binds the Nterminal region of lipoprotein B100 and the plasminogen kringle 4 binding plasma protein tetranectin. In this study recombinant KIV(2), KIV(7) and KIV(10) derived from apolipoprotein(a) were produced in E. coli and the binding to tetranectin and low density lipoprotein was examined. Only KIV(10) bound to tetranectin and binding was similar to that of plasminogen kringle 4 to tetranectin. Only KIV(7) bound to LDL. In order to identify the residues responsible for the difference in specificity between KIV(7) and KIV(10), a number of surfaceexposed residues located around the lysine binding clefts were exchanged. Ligand binding analysis of these derivatives showed that Y62, and to a minor extent W32 and E56, of KIV(7) are important for LDL binding to KIV(7), whereas R32 and D56 of KIV(10) are required for tetranectin binding of KIV(10).
The Primary Structure of Three Hemoglobin Chains from the Indigo Snake (Drymarchon corais erebennus, Serpentes): First Evidence for αD Chains and Two β Chain Types in Snakes
Authors: Stoeckelhuber M. , Gorr T. , Kleinschmidt T. 
Published: October 2004

AbstractThe hemoglobin of the indigo snake (Drymarchon corais erebennus, Colubrinae) consists of two components, HbA and HbD, in the ratio of 1:1. They differ in both their α and β chains. The amino acid sequences of both α chains (αA and αD) and one β chain (βI) were determined. The presence of an αDchain in a snake hemoglobin is described for the first time. A comparison of all snake β chain sequences revealed the existence of two paralogous β chain types in snakes as well, which are designated as βI and βII type. For the discussion of the physiological properties of Drymarchon hemoglobin, the sequences were compared with those of the human α and β chains and those of the closely related water snake Liophis miliaris where functional data are available. Among the heme contacts, the substitution αD58(E7)His->Gln is unusual but most likely without any effect. The residues responsible for the main part of the Bohr effect are the same as in mammalian hemoglobins. In each of the three globin chains only two residues at positions involved in the α1/_2 interface contacts, most important for the stability and the properties of the hemoglobin molecule, are substituted with regard to human hemoglobin. On the contrary, nine, eleven, and six α1/β1 contact residues are replaced in the αA, αD, βI chains, respectively.
Identification and Characterization of an IgG Binding Protein in the Secretion of the Rat Coagulating Gland
Authors: Wilhelm B. , Keppler C. , Henkeler A. , Schilli-Westermann M. , Linder D. , Aumüller G. , Seitz J. 
Published: October 2004

AbstractA merocrine released protein (named 115k protein) was highly enriched from the secretion of the rat coagulating gland. The protein has a molecular mass of 115 kDa as calculated by SDSPAGE under reducing conditions. Furthermore, the 115 kDa protein is glycosylated, and carries Man, GlcNAc, Gal, Fuc and sialic acid residues. For identification, Nterminal amino acid and nucleotide sequence analyses were performed. The sequences obtained showed 86 to 100% identity with human and mouse IgGFc binding proteins. The functional capacity of IgG binding of the 115 kDa protein was shown by overlay experiments, indicating its membership in the IgG binding protein family.
X-ray structure of fumarylacetoacetate hydrolase family member Homo sapiens FLJ36880
Authors: Manjasetty Babu A. , Niesen Frank H. , Delbrück Heinrich , Götz Frank , Sievert Volker , Büssow Konrad , Behlke Joachim , Heinemann Udo 
Published: October 2004

Abstract
The human protein FLJ36880 belongs to the fumarylacetoacetate hydrolase family. The X-ray structure of FLJ36880 has been determined to 2.2 Å resolution employing the semi-automated high-throughput structural genomics approach of the Protein Structure Factory. FLJ36880 adopts a mixed β-sandwich roll fold and forms homodimers in crystals as well as in solution. One Mg2+ ion is bound to each subunit of the dimeric protein by coordination to three carboxylate oxygens and three water molecules. These metal binding sites are accessible from the same surface of the dimer, partly due to the disorder of the undecapeptide stretch D29 to L39. The overall structure and metal binding site of FLJ36880 bear clear similarities to the C-terminal domain of the bifunctional enzyme HpcE from Escherichia coli C, fumarylacetoacetate hydrolase from Mus musculus and to YcgM (Apc5008) from E. coli 1262. These similarities provide a framework for suggesting biochemical functions and evolutionary relationships of FLJ36880. It appears highly probable that the metal binding sites are involved in an enzymatic activity related to the catabolism of aromatic amino acids. Two point mutations in the active-site of FAH, responsible for the metabolic disease hereditary tyrosinemia type I (HTI) in humans, affect residues that are structurally conserved in FLJ36880 and located in the putative catalytic site.
Segregation of partly melted molecules: isolation of CpG islands by polyacrylamide gel electrophoresis
Authors: Shiraishi Masahiko , Oates Adam J. , Li Xu , Chuu Ying H. , Sekiya Takao 
Published: October 2004

Abstract
The technique of segregation of partly melted molecules (SPM) is a convenient and efficient method to isolate DNA fragments associated with CpG islands. The approach is conceptually simple and uses denaturant gradient gel electrophoresis to separate DNA molecules digested with restriction endonucleases. The SPM methodology has successfully been applied to the identification of genes from anonymous, unsequenced DNA fragments and CpG islands methylated in human cancer. In this article the theoretical background and practical application of the SPM method is reviewed.
Measurement of Water Turnover Using Deuterium Dilution: Impact of Periodically Varying Turnover Rates on Precision and Accuracy
Authors: Fusch Christoph 
Published: October 2004

Abstract
Water metabolism may be non-invasively investigated
using deuterium elimination from the body. Evaluation
of elimination constants (kD) and pool sizes (N) becomes
complicated when turnover rates vary periodically - a realistic scenario in free-living subjects.
Unfortunately, phase and frequency of periodic variations
are not a priori known and can therefore not be
used for a sampling protocol. This study investigates
the impact of periodical flux variations on the measurement
of water turnover. For two models of periodic
variation with identical apparent kD, data sets of
tracer concentrations in body water were generated
for two-hour intervals using a monoexponential decay
equation. Data were analyzed using the two- and the
multi-point method increasing observation periods
stepwise. Apparent values for kD, N and water turnover
(RH₂O) were compared with values originally used
in the model. Periodically varying turnover rates introduce
considerable errors for kD and RH₂O when the two-point
method is used. The multi-point method gives a
more robust estimate of RH₂O already after short observation
periods, however, due to slope-intercept
correlations, still tends to overestimate RH₂O. Errors
are more pronounced the more uneven flux rates are
distributed. Stepwise analysis of tracer enrichments
using the multi-point approach identifies periodical
variation of flux rates.
Evaluating Agreement between Two Analytical Methods in Clinical Chemistry
Authors: Magari Robert T. 
Published: October 2004

Abstract
A test and a reference analytical method are usually
compared for agreement based on paired data obtained
from several independent subjects. Bias between
two methods can be classified as constant and
proportional. Bias is modeled as an average bias between
two methods (constant bias) and proportional
bias related to individual measurements. A weighted
least square approach is followed for estimating the
parameters. Estimates of constant and proportional
biases are tested individually and their significance
can be used to explain the sources of disagreement between
two methods and help deciding a remedial
strategy. The proposed model can also be used to determine
an optimum combination of subjects and runs
per subject and facilitate the allocation of the resources.
Evaluation of Two Automated Enzyme Immunoassays for Detection of Antinuclear Antibodies
Authors: Bossuyt Xavier 
Published: October 2004

Abstract
We evaluated two enzyme immunoassays (EIA) for detection
of antinuclear antibodies (ANA) which became
recently available and which were designed for application
on a fully automated system; (i) the EIA-ANA
screen kit from Sigma Diagnostics (St. Louis, MO, USA)
applied on APTUS™, an automated EIA analyser from
Sigma Diagnostics and (ii) the Cobas® Core Hep-2 EIA-ANA
assay applied on the fully automated Cobas Core
immunochemistry analyzer from Roche Diagnostics
(Basel, Switzerland). The evaluation was done by an
analytic comparison of the automated systems to an
established indirect immunofluorescence (IF) method
performed on SSA transfected human epitheloid cell
substrate slides. Three hundred and thirty six samples
were tested with the Sigma EIA-ANA assay and 603
samples with the Cobas® Core Hep-2 EIA-ANA assay.
For both EIA systems, there was a trend of generally
increasing signal from the assay system with increasing
IF-ANA titers. With an IF-ANA reference range of
< 1:160, concordance between Sigma® EIA-ANA and IFANA
was 86% and concordance between Roche® EIA-ANA and IF-ANA was 85%. When compared to IF-ANA
with a reference range of < 1:160, sensitivity and specificity
of the EIA-ANA screen was 0.65 and 0.92, respectively,
for Sigma® EIA-ANA and 0.61 and 0.91, respectively,
for the Cobas® Core assay. The low sensitivity
observed with both methods is a major concern. Sigma
EIA-ANA screen revealed the presence of autoantibodies
in 23 of the 29 samples containing antibodies to extractable
nuclear antigens (ENA) and/or double
stranded DNA and the Cobas® Core Hep-2 EIA-ANA assay
revealed the presence of autoantibodies in 40 of the
43 samples containing antibodies to ENA and/or double
stranded DNA.