bluuebunny/crossref_metadata_2025 huggingface dataset:
Seroprevalence of Human Toxocariasis in Denmark
Authors: Stensvold Christen R. , Skov Jakob , Møller Lone N. , Jensen Per M. , Kapel Christian M. O. , Petersen Eskild , Nielsen Henrik V.
Published: July 2009

The seroprevalence of
Toxocara
in the Danish population was assessed from 3,247 sera from individuals originally screened for toxoplasmosis. Of 87 enzyme-linked immunosorbent assay-positive sera, 79 were confirmed by Western blotting, yielding a crude seroprevalence of 2.4%. This indicates that the seroprevalence of toxocariasis in Denmark is low compared to those in other European countries.
Discarding the Initial Aliquot of Blood Does Not Reduce Contamination Rates in Intravenous-Catheter-Drawn Blood Cultures
Authors: Dwivedi Sukrut , Bhalla Rohit , Hoover Donald R. , Weinstein Melvin P.
Published: July 2009

Although venipuncture is the preferred method for obtaining blood cultures, specimens often are obtained from intravenous catheters (IVC). For IVC-drawn blood cultures, some authorities recommend discarding the initial 5 to 10 ml of blood to reduce contamination and remove potential inhibitory substances. To determine whether this practice reduced contamination rates (CR), we assessed the results of IVC-drawn blood cultures for adults. Thirty milliliters of blood was obtained aseptically. The first 10 ml, rather than being discarded, was inoculated into an aerobic culture vial. Using a second sterile syringe, 20 ml of blood was obtained and inoculated in 10-ml aliquots to aerobic and anaerobic culture vials. Positive cultures were evaluated to assess clinical significance (true versus contaminant). Out of 653 IVC-drawn blood culture pairs, both vials were contaminated in 38 pairs (5.8%); only the “discard” vial was contaminated in 33 (5.1%); and only the “standard” vial was contaminated in 31 (4.7%). Overall CR were 10.9% for the discard vial versus 10.5% for the standard vial (
P
= 0.90). We conclude that discarding an initial aliquot of blood when obtaining blood cultures from IVCs does not reduce CR.
Rapid Semiautomated Subtyping of Influenza Virus Species during the 2009 Swine Origin Influenza A H1N1 Virus Epidemic in Milwaukee, Wisconsin
Authors: Bose Michael E. , Beck Eric T. , Ledeboer Nate , Kehl Sue C. , Jurgens Lisa A. , Patitucci Teresa , Witt Lorraine , LaGue Elizabeth , Darga Patrick , He Jie , Fan Jiang , Kumar Swati , Henrickson Kelly J.
Published: July 2009

In the spring of 2009, a novel influenza A (H1N1) virus (swine origin influenza virus [S-OIV]) emerged and began causing a large outbreak of illness in Milwaukee, WI. Our group at the Midwest Respiratory Virus Program laboratory developed a semiautomated real-time multiplex reverse transcription-PCR assay (Seasonal), employing the NucliSENS easyMAG system (bioMérieux, Durham, NC) and a Raider thermocycler (HandyLab Inc., Ann Arbor, MI), that typed influenza A virus, influenza B virus, and respiratory syncytial virus (RSV) and subtyped influenza A virus into the currently circulating H1 and H3 subtypes, as well as a similar assay that identified H1 of S-OIV. The Seasonal and H1 S-OIV assays demonstrated analytical limits of detection of <50 50% tissue culture infective doses/ml and 3 to 30 input copies, respectively. Testing of the analytical specificities revealed no cross-reactivity with 41 and 26 different common organisms and demonstrated outstanding reproducibility of results. Clinical testing showed 95% sensitivity for influenza A virus and influenza B virus and 95 and 97% specificity compared to tissue culture. Comparisons of results from other molecular tests showed levels of positive agreement with the Seasonal and H1 S-OIV assay results of 99 and 100% and levels of negative agreement of 98 and 100%. This study has demonstrated the use of a semiautomated system for sensitive, specific, and rapid detection of influenza A virus, influenza B virus, and RSV and subtyping of influenza A virus into human H1 and H3 and S-OIV strains. This assay/system performed well in clinical testing of regular seasonal influenza virus subtypes and was outstanding during the 2009 Milwaukee S-OIV infection outbreak. This recent outbreak of infection with a novel influenza A (H1N1) virus also demonstrates the importance of quickly distributing information on new agents and of having rapid influenza virus subtyping assays widely available for clinical and public health decisions.
Mycoplasma hominis
-Associated Parapharyngeal Abscess following Acute Epstein-Barr Virus Infection in a Previously Immunocompetent Adult
Authors: Kennedy Karina J. , Prince Sam , Makeham Timothy
Published: July 2009

Mycoplasma hominis
most frequently causes diseases of the genitourinary tract. Extragenital infections are uncommon, with almost all occurring in immunosuppressed persons or those predisposed due to trauma or surgery. We present the case of a previously well man who developed an
M. hominis
-associated parapharyngeal abscess following acute Epstein-Barr virus infection.
Rapid, Point-of-Care Extraction of Human Immunodeficiency Virus Type 1 Proviral DNA from Whole Blood for Detection by Real-Time PCR
Authors: Jangam Sujit R. , Yamada Douglas H. , McFall Sally M. , Kelso David M.
Published: July 2009

PCR detection of human immunodeficiency virus type 1 (HIV-1) proviral DNA is the method recommended for use for the diagnosis of HIV-1 infection in infants in limited-resource settings. Currently, testing must be performed in central laboratories, which are usually located some distance from health care facilities. While the collection and transportation of samples, such as dried blood spots, has improved test accessibility, the results are often not returned for several weeks. To enable PCR to be performed at the point of care while the mothers wait, we have developed a vertical filtration method that uses a separation membrane and an absorbent pad to extract cellular DNA from whole blood in less than 2 min. Cells are trapped in the separation membrane as the specimen is collected, and then a lysis buffer is added. The membrane retains the DNA, while the buffer washes away PCR inhibitors, which get wicked into the absorbent blotter pad. The membrane containing the entrapped DNA is then added to the PCR mixture without further purification. The method demonstrates a high degree of reproducibility and analytical sensitivity and allows the quantification of as few as 20 copies of HIV-1 proviral DNA from 100 μl of blood. In a blinded study with 182 longitudinal samples from infants (ages, 0 to 72 weeks) obtained from the Women and Infants Transmission Study, our assay demonstrated a sensitivity of 99% and a specificity of 100%.
Latency-Associated Transcript (LAT) Exon 1 Controls Herpes Simplex Virus Species-Specific Phenotypes: Reactivation in the Guinea Pig Genital Model and Neuron Subtype-Specific Latent Expression of LAT
Authors: Bertke Andrea S. , Patel Amita , Imai Yumi , Apakupakul Kathleen , Margolis Todd P. , Krause Philip R.
Published: July 2009

Herpes simplex virus 1 (HSV-1) and HSV-2 cause similar acute infections but differ in their abilities to reactivate from trigeminal and lumbosacral dorsal root ganglia. During latency, HSV-1 and HSV-2 also preferentially express their latency-associated transcripts (LATs) in different sensory neuronal subtypes that are positive for A5 and KH10 markers, respectively. Chimeric virus studies showed that LAT region sequences influence both of these viral species-specific phenotypes. To further map the LAT region sequences responsible for these phenotypes, we constructed the chimeric virus HSV2-LAT-E1, in which exon 1 (from the LAT TATA to the intron splice site) was replaced by the corresponding sequence from HSV-1 LAT. In intravaginally infected guinea pigs, HSV2-LAT-E1 reactivated inefficiently relative to the efficiency of its rescuant and wild-type HSV-2, but it yielded similar levels of viral DNA, LAT, and ICP0 during acute and latent infection. HSV2-LAT-E1 preferentially expressed the LAT in A5+ neurons (as does HSV-1), while the chimeric viruses HSV2-LAT-P1 (LAT promoter swap) and HSV2-LAT-S1 (LAT sequence swap downstream of the promoter) exhibited neuron subtype-specific latent LAT expression phenotypes more similar to that of HSV-2 than that of HSV-1. Rescuant viruses displayed the wild-type HSV-2 phenotypes of efficient reactivation in the guinea pig genital model and a tendency to express LAT in KH10+ neurons. The region that is critical for HSV species-specific differences in latency and reactivation thus lies between the LAT TATA and the intron splice site, and minor differences in the 5′ ends of chimeric sequences in HSV2-LAT-E1 and HSV2-LAT-S1 point to sequences immediately downstream of the LAT TATA.
Stable Docking of Neutralizing Human Immunodeficiency Virus Type 1 gp41 Membrane-Proximal External Region Monoclonal Antibodies 2F5 and 4E10 Is Dependent on the Membrane Immersion Depth of Their Epitope Regions
Authors: Dennison S. Moses , Stewart Shelley M. , Stempel Kathryn C. , Liao Hua-Xin , Haynes Barton F. , Alam S. Munir
Published: July 2009

The binding of neutralizing antibodies 2F5 and 4E10 to human immunodeficiency virus type 1 (HIV-1) gp41 involves both the viral membrane and gp41 membrane proximal external region (MPER) epitopes. In this study, we have used several biophysical tools to examine the secondary structure, orientation, and depth of immersion of gp41 MPER peptides in liposomes and to determine how the orientation of the MPER with lipids affects the binding kinetics of monoclonal antibodies (MAbs) 2F5 and 4E10. The binding of 2F5 and 4E10 both to their respective nominal epitopes and to a biepitope (includes 2F5 and 4E10 epitopes) MPER peptide-liposome conjugate was best described by a two-step encounter-docking model. Analysis of the binding kinetics and the effect of temperature on the binding stability of 2F5 and 4E10 to MPER peptide-liposome conjugates revealed that the docking of 4E10 was relatively slower and thermodynamically less favorable. The results of fluorescence-quenching and fluorescence resonance energy transfer experiments showed that the 2F5 epitope was more solvent exposed, whereas the 4E10 epitope was immersed in the polar-apolar interfacial region of the lipid bilayer. A circular dichroism spectroscopic study demonstrated that the nominal epitope and biepitope MPER peptides adopted ordered structures with differing helical contents when anchored to liposomes. Furthermore, anchoring of MPER peptides to the membrane via a hydrophobic anchor sequence was required for efficient MAb docking. These results support the model that the ability of 2F5 and 4E10 to bind to membrane lipid is required for stable docking to membrane-embedded MPER residues. These data have important implications for the design and use of peptide-liposome conjugates as immunogens for the induction of MPER-neutralizing antibodies.
Overlapping Genes Produce Proteins with Unusual Sequence Properties and Offer Insight into De Novo Protein Creation
Authors: Rancurel Corinne , Khosravi Mahvash , Dunker A. Keith , Romero Pedro R. , Karlin David
Published: July 2009

It is widely assumed that new proteins are created by duplication, fusion, or fission of existing coding sequences. Another mechanism of protein birth is provided by overlapping genes. They are created de novo by mutations within a coding sequence that lead to the expression of a novel protein in another reading frame, a process called “overprinting.” To investigate this mechanism, we have analyzed the sequences of the protein products of manually curated overlapping genes from 43 genera of unspliced RNA viruses infecting eukaryotes. Overlapping proteins have a sequence composition globally biased toward disorder-promoting amino acids and are predicted to contain significantly more structural disorder than nonoverlapping proteins. By analyzing the phylogenetic distribution of overlapping proteins, we were able to confirm that 17 of these had been created de novo and to study them individually. Most proteins created de novo are orphans (i.e., restricted to one species or genus). Almost all are accessory proteins that play a role in viral pathogenicity or spread, rather than proteins central to viral replication or structure. Most proteins created de novo are predicted to be fully disordered and have a highly unusual sequence composition. This suggests that some viral overlapping reading frames encoding hypothetical proteins with highly biased composition, often discarded as noncoding, might in fact encode proteins. Some proteins created de novo are predicted to be ordered, however, and whenever a three-dimensional structure of such a protein has been solved, it corresponds to a fold previously unobserved, suggesting that the study of these proteins could enhance our knowledge of protein space.
Impact of Rac1 and Cdc42 Signaling during Early Herpes Simplex Virus Type 1 Infection of Keratinocytes
Authors: Petermann Philipp , Haase Ingo , Knebel-Mörsdorf Dagmar
Published: July 2009

Keratinocytes of the skin or mucosa are the primary entry portals for herpes simplex virus type 1 (HSV-1) in vivo. We hypothesized that dynamics of cell motility and adhesion contribute to the initial steps of HSV-1 infection of epithelial cells, and thus, we investigated the impact of Rac1 and Cdc42, which serve as key regulators of actin dynamics. Measurement of endogenous Rac1 and Cdc42 in the human keratinocyte cell line HaCaT indicated temporary changes in activity levels of Rac1/Cdc42 upon HSV-1 infection. Overexpression of Rac1/Cdc42 mutants in HaCaT cells demonstrated a decrease of infection efficiency with constitutively active Rac1 or Cdc42, while dominant-negative Rac1 had no effect. Accordingly, we addressed whether the absence of Rac1 and/or Cdc42 influenced infection, and we performed RNA interference studies. Both in HaCaT cells and in primary human keratinocytes, reduction of Rac1 and/or Cdc42 did not suppress infection. When mouse epidermis was infected ex vivo, we observed early HSV-1 infection in basal keratinocytes. Similar results were obtained upon infection of mouse epidermis with a keratinocyte-restricted deletion of the rac1 gene, indicating no inhibitory effect on HSV-1 infection in the absence of Rac1. Our results suggest that HSV-1 infection of keratinocytes does not depend on pathways involving Rac1 and Cdc42 and that constitutively active Rac1 and Cdc42 have the potential to interfere with HSV-1 infectivity.
Association of
Rice Gall Dwarf Virus
with Microtubules Is Necessary for Viral Release from Cultured Insect Vector Cells
Authors: Wei Taiyun , Uehara-Ichiki Tamaki , Miyazaki Naoyuki , Hibino Hiroyuki , Iwasaki Kenji , Omura Toshihiro
Published: July 2009

Vector insect cells infected with
Rice gall dwarf virus
, a member of the family
Reoviridae
, contained the virus-associated microtubules adjacent to the viroplasms, as revealed by transmission electron, electron tomographic, and confocal microscopy. The viroplasms, putative sites of viral replication, contained the nonstructural viral proteins Pns7 and Pns12, as well as core protein P5, of the virus. Microtubule-depolymerizing drugs suppressed the association of viral particles with microtubules and prevented the release of viruses from cells without significantly affecting viral multiplication. Thus, microtubules appear to mediate viral transport within and release of viruses from infected vector cells.
Human Cytomegalovirus Exploits ESCRT Machinery in the Process of Virion Maturation
Authors: Tandon Ritesh , AuCoin David P. , Mocarski Edward S.
Published: July 2009

The endosomal sorting complex required for transport (ESCRT) machinery controls the incorporation of cargo into intraluminal vesicles of multivesicular bodies. This machinery is used during envelopment of many RNA viruses and some DNA viruses, including herpes simplex virus type 1. Other viruses mature independent of ESCRT components, instead relying on the intrinsic behavior of viral matrix and envelope proteins to drive envelopment. Human cytomegalovirus (HCMV) maturation has been reported to proceed independent of ESCRT components (A. Fraile-Ramos et al. Cell. Microbiol. 9:2955-2967, 2007). A virus complementation assay was used to evaluate the role of dominant-negative (DN) form of a key ESCRT ATPase, vacuolar protein sorting-4 (Vps4
DN
) in HCMV replication. Vps4
DN
specifically inhibited viral replication, whereas wild-type-Vps4 had no effect. In addition, a DN form of charged multivesicular body protein 1 (CHMP1
DN
) was found to inhibit HCMV. In contrast, DN tumor susceptibility gene-101 (Tsg101
DN
) did not impact viral replication despite the presence of a PTAP motif within pp150/ppUL32, an essential tegument protein involved in the last steps of viral maturation and release. Either Vps4
DN
or CHMP1
DN
blocked viral replication at a step after the accumulation of late viral proteins, suggesting that both are involved in maturation. Both Vps4A and CHMP1A localized in the vicinity of viral cytoplasmic assembly compartments, sites of viral maturation that develop in CMV-infected cells. Thus, ESCRT machinery is involved in the final steps of HCMV replication.
T-Cell Vaccination Reduces Simian Immunodeficiency Virus Levels in Semen
Authors: Whitney James B. , Luedemann Corinne , Hraber Peter , Rao Srinivas S. , Mascola John R. , Nabel Gary J. , Letvin Norman L.
Published: July 2009

Recent findings suggest that most sexual transmission of human immunodeficiency virus type 1 (HIV-1) occurs during the acute phase of infection when viral replication is most intense. Here, we show that vaccine-elicited cellular immune responses can significantly reduce simian immunodeficiency virus levels in the semen during the period of primary infection in monkeys. A vaccine that decreases the quantity of HIV-1 in the semen of males during primary infection might decrease HIV-1 transmission in human populations and therefore affect the spread of AIDS.
Low concentrations of vancomycin stimulate biofilm formation in some clinical isolates ofStaphylococcus epidermidis
Authors: Cargill J S , Upton M
Published: July 2009

Aims:

To examine the response ofStaphylococcus epidermidisisolates from prosthetic orthopaedic infections to vancomycin concentrations below the minimum inhibitory concentration.

Methods:

Staphylococcal biofilms were grown in 96-well flat-bottomed cell culture plates under a variety of culture conditions and stained using an ammonium crystal violet solution. Optical density (450 nm wavelength) was recorded to estimate the biofilm density for each strain. Population analysis and time-kill studies were also performed on selected isolates.

Results:

A range of responses were observed, including increased biofilm density at drug concentrations approaching the minimum inhibitory concentration. This increased density was associated with the presence of a more resistant population identified on population analysis but without an apparent effect on the time-kill curves.

Conclusions:

The ability of some strains to show increased biofilm density could be a factor in the failure of vancomycin therapy reported in some cases. The demonstration that low concentrations of vancomycin may increase the density of newly formingS epidermidisbiofilms may indicate an area of potential concern in the use of vancomycin in orthopaedic implants and intravascular catheter locks, and may partially account for some cases of treatment failure.
ON THE COMPLEXITY OF MAPPING LINEAR CHAIN APPLICATIONS ONTO HETEROGENEOUS PLATFORMS
Authors: BENOIT ANNE , ROBERT YVES , THIERRY ERIC
Published: July 2009

In this paper, we explore the problem of mapping linear chain applications onto large-scale heterogeneous platforms. A series of data sets enter the input stage and progress from stage to stage until the final result is computed. An important optimization criterion that should be considered in such a framework is the latency, or makespan, which measures the response time of the system in order to process one single data set entirely. For such applications, which are representative of a broad class of real-life applications, we can consider one-to-one mappings, in which each stage is mapped onto a single processor. However, in order to reduce the communication cost, it seems natural to group stages into intervals. The interval mapping problem can be solved in a straightforward way if the platform has homogeneous communications: the whole chain is grouped into a single interval, which in turn is mapped onto the fastest processor. But the problem becomes harder when considering a fully heterogeneous platform. Indeed, we prove the NP-completeness of this problem. Furthermore, we prove that neither the interval mapping problem nor the similar one-to-one mapping problem can be approximated in polynomial time by any constant factor (unless P=NP).
TOWARDS ENERGY AWARE RESERVATION INFRASTRUCTURE FOR LARGE-SCALE EXPERIMENTAL DISTRIBUTED SYSTEMS
Authors: LEFÈVRE LAURENT , ORGERIE ANNE-CECILE
Published: July 2009

While an extensive set of research projects deal with the issue of power-saving for battery-based electronic devices, few have an interest in permanently-plugged Large-Scale Experimental Distributed Systems (LSEDS). However, a rapid study shows that each computer, member of a distributed system platform, consumes a substantial quantity of power, especially when those resources are idle. Today, given the number of processing resources involved in large-scale computing infrastructures, we are convinced that we can save a lot of electric power by proposing and applying "green policies". Introduced in this article, those policies propose to alternatively switch computer nodes On and Off in a clever way. Based on the analysis of some experimental large-scale system's usage, we propose a resource-reservation infrastructure which takes the energy issue into account. We validate our infrastructure on the large-scale experimental Grid'5000a platform and present the energy gains obtained.
THEORETICAL STUDY OF NEUTRAL AND IONIC SinO(n = 1-13) CLUSTERS
Authors: ZHU YU-HONG , LI BAO-XING , LIANG FANG-SHU , XU JIE
Published: July 2009

A systematic theoretical study of the structural properties and stabilities for neutral Si n O (n = 1-13) clusters and their ions has been carried out using the full-potential linear-muffin-tin-orbital molecular-dynamics (FP-LMTO-MD) method and the Amsterdam Density Functional (ADF) program with TZ2P basis set in conjunction with self-consistent field (SCF). Their ionization potentials (IPs), electron affinities (EAs), dipole moments μ, constant volume heat capacity Cv are computed. Based on the Mulliken population analyses, it is found that part of electronic charge is transferred from the Si atoms into the oxygen atom. Compared with other structures, the adsorption structures with an edge or a surface O atom are more stable. Calculations also show that the Si n O clusters with larger HOMO–LUMO gap exhibit high stability.
TWO ONE-DIMENSIONAL INTERACTING PARTICLES IN A HARMONIC TRAP
Authors: WEI BO-BO
Published: July 2009

In this brief report, two one-dimensional interacting particles interacting with a delta interaction in a harmonic trap is discussed. For strong interactions, we derive the asymptotic expressions for all the energy levels. In addition, the variational method is used to obtain asymptotic ground state energy and wave function. The variational results are compared with the exact solution and they turn out to agree very well.
DOMAIN WALL RENORMALIZATION GROUP ANALYSIS OF TWO-DIMENSIONAL ISING MODEL
Authors: AOKI KEN-ICHI , KOBAYASHI TAMAO , TOMITA HIROSHI
Published: July 2009

Using a recently proposed new renormalization group method (tensor renormalization group), we analyze the Ising model on the two-dimensional square lattice. For the lowest-order approximation with two-domain wall states, it realizes the idea of coarse graining of domain walls. We write down explicit analytic renormalization transformation and prove that the picture of the coarse graining of the physical domain walls does hold for all physical renormalization group flows. We solve it to get the fixed point structure and obtain the critical exponents and the critical temperature. These results are very near to the exact values. We also briefly report the improvement using four-domain wall states.
SUGENO INTEGRAL AND THE COMONOTONE COMMUTING PROPERTY
Authors: OUYANG YAO , MESIAR RADKO
Published: July 2009

Comonotone maxitivity and minitivity of Sugeno integral can be seen as commuting of the Sugeno integral and max, resp. min operator for comonotone functions. In the paper, we look for the other operators commuting with the Sugeno integral when comonotone functions are considered. We give full description of all such commuting operators, which can be classified into 18 classes.
FUZZY LINGUISTIC MODELING OF EASE OF DOING BUSINESS INDICATORS
Authors: ROHAM MEHRDAD , GABRIELYAN ANAIT R. , ARCHER NORMAN P.
Published: July 2009

Ease of Doing Business (EDB) indicators are essential to overall understanding and evaluation of national business environment, and strategy formulation for business policy and regulations. The World Bank does an annual study of these indicators for over 170 nations, but there are many complications and uncertainties involved in the work. This paper proposes a new systematic approach that employs fuzzy set theory to generate composite EDB indicators for ranking and classification problems. We implemented this approach and illustrate its steps and procedures. A case study example for Canada is also presented in which EDB indicators are evaluated, linguistically identified, and ranked. This approach demonstrates the ease of using this fuzzy application, and its potential benefits for future research. We also compare ranking results, obtained from our proposed approach, with the World Bank's results.
SPATIAL OLIGOPOLIES WITH COOPERATIVE DISTRIBUTION
Authors: SANDSMARK MARIA
Published: July 2009

The main objects here are Nash equilibria in spatial Cournot oligopolies when profits depend on coordinated distribution. Production is non-cooperative, but the subsequent transportation must be performed jointly to minimize costs. Cournot-Nash equilibria for this two-stage game with partial coalitional strategies are determined by means of a mathematical-based algorithm. A numerical illustration is presented.
Spontaneous calcium release in tissue from the failing canine heart
Authors: Hoeker Gregory S. , Katra Rodolphe P. , Wilson Lance D. , Plummer Bradley N. , Laurita Kenneth R.
Published: July 2009

Abnormalities in calcium handling have been implicated as a significant source of electrical instability in heart failure (HF). While these abnormalities have been investigated extensively in isolated myocytes, how they manifest at the tissue level and trigger arrhythmias is not clear. We hypothesize that in HF, triggered activity (TA) is due to spontaneous calcium release from the sarcoplasmic reticulum that occurs in an aggregate of myocardial cells (an SRC) and that peak SCR amplitude is what determines whether TA will occur. Calcium and voltage optical mapping was performed in ventricular wedge preparations from canines with and without tachycardia-induced HF. In HF, steady-state calcium transients have reduced amplitude [135 vs. 170 ratiometric units (RU), P < 0.05] and increased duration (252 vs. 229 s, P < 0.05) compared with those of normal. Under control conditions and during β-adrenergic stimulation, TA was more frequent in HF (53% and 93%, respectively) compared with normal (0% and 55%, respectively, P < 0.025). The mechanism of arrhythmias was SCRs, leading to delayed afterdepolarization-mediated triggered beats. Interestingly, the rate of SCR rise was greater for events that triggered a beat (0.41 RU/ms) compared with those that did not (0.18 RU/ms, P < 0.001). In contrast, there was no difference in SCR amplitude between the two groups. In conclusion, TA in HF tissue is associated with abnormal calcium regulation and mediated by the spontaneous release of calcium from the sarcoplasmic reticulum in aggregates of myocardial cells (i.e., an SCR), but importantly, it is the rate of SCR rise rather than amplitude that was associated with TA.
Isometric contractions reduce plantar flexor moment, Achilles tendon stiffness, and neuromuscular activity but remove the subsequent effects of stretch
Authors: Kay Anthony D. , Blazevich Anthony J.
Published: July 2009

The effects of isometric contractions and passive stretching on muscle-tendon mechanics and muscle activity were studied in 16 healthy human volunteers. First, peak concentric and passive ankle joint moment data were recorded on an isokinetic dynamometer with electromyographic monitoring of the triceps surae; real-time motion analysis of the lower leg and ultrasound imaging of the Achilles-medial gastrocnemius muscle-tendon junction were simultaneously conducted. Second, the subjects performed six 8-s maximal voluntary isometric contractions (MVICs) before repeating the passive and active trials. Although there was no decrease in isometric joint moment after MVICs, peak concentric moment was significantly reduced (11.5%, P < 0.01). This was accompanied by, and correlated with ( r = 0.90, P < 0.01), significant reductions in peak triceps surae electromyographic amplitude (21.0%, P < 0.01). Achilles tendon stiffness (10.9%, P < 0.01) and passive joint moment (4.9%, P < 0.01) were also significantly reduced. Third, the subjects performed three 60-s static plantar flexor stretches before being retested 2 and 30 min after stretch. The stretch protocol caused no significant change in any measure. At 30 min after stretching, significant recovery in concentric moment and muscle activity was detected at dorsiflexed joint angles, while Achilles tendon stiffness and passive joint moment remained significantly reduced. These data show that the performance of MVICs interrupts the normal stretch-induced losses in active and passive plantar flexor joint moment and neuromuscular activity, largely because concentric strength and tendon properties were already affected. Importantly, the decrease in Achilles tendon stiffness remained 30 min later, which may be an important etiological factor for muscle-tendon strain injury risk.
Genetic Polymorphisms in Cytotoxic T-Lymphocyte Antigen 4 and Cancer: The Dialectical Nature of Subtle Human Immune Dysregulation
Authors: Sun Tong , Hu Zhibin , Shen Hongbing , Lin Dongxin
Published: July 2009

Genetic polymorphisms in the human genome are an important component of genotypic variability including one's immune status. Single nucleotide polymorphisms (SNPs) in the cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene have been linked to susceptibility to autoimmune disease. Interestingly, we have recently shown that an SNP in the CTLA-4 coding region (49A > G) is also associated with susceptibility to human cancer, but the risk allele for susceptibility to cancer (allele A) is the opposite of that found for susceptibility to autoimmune disease (allele G), which has been confirmed by a meta-analysis of reported studies. These findings indicate an important role of the dialectical nature of T-cell immune dysregulation in human disorders, such as autoimmune disease and cancer. The requisites of CTLA-4 polymorphisms for susceptibility to cancer and response to targeted therapy are discussed in this review. [Cancer Res 2009;69(15):6011–4]
HIPK2 Regulation by MDM2 Determines Tumor Cell Response to the p53-Reactivating Drugs Nutlin-3 and RITA
Authors: Rinaldo Cinzia , Prodosmo Andrea , Siepi Francesca , Moncada Alice , Sacchi Ada , Selivanova Galina , Soddu Silvia
Published: July 2009

In the past few years, much effort has been devoted to show the single-target specificity of nongenotoxic, p53 reactivating compounds. However, the divergent biological responses induced by the different compounds, even in the same tumor cells, demand additional mechanistic insights, whose knowledge may lead to improved drug design or selection of the most potent drug combinations. To address the molecular mechanism underlying induction of mitotic arrest versus clinically more desirable apoptosis, we took advantage of two MDM2 antagonists, Nutlin-3 and RITA, which respectively produce these two outcomes. We show that, along with p53 reactivation, the proapoptotic p53-activator HIPK2 is degraded by MDM2 in Nutlin-3–treated cells, but activated by transiently reduced MDM2 levels in RITA-treated ones. Gain- and loss-of-function experiments revealed the functional significance of MDM2-mediated HIPK2 regulation in cell decision between mitotic arrest and apoptosis in both types of p53 reactivation. These data indicate that strategies of p53 reactivation by MDM2 inhibition should also take into consideration MDM2 targets other than p53, such as the apoptosis activator HIPK2. [Cancer Res 2009;69(15):6241–8]
Racial Survival Disparity in Head and Neck Cancer Results from Low Prevalence of Human Papillomavirus Infection in Black Oropharyngeal Cancer Patients
Authors: Settle Kathleen , Posner Marshall R. , Schumaker Lisa M. , Tan Ming , Suntharalingam Mohan , Goloubeva Olga , Strome Scott E. , Haddad Robert I. , Patel Shital S. , Cambell Earl V. , Sarlis Nicholas , Lorch Jochen , Cullen Kevin J.
Published: July 2009

The burden of squamous cell carcinoma of the head and neck (SCCHN) is greater for blacks than for whites, especially in oropharyngeal cases. We previously showed retrospectively that disease-free survival was significantly greater in white than in black SCCHN patients treated with chemoradiation, the greatest difference occurring in the oropharyngeal subgroup. Oropharyngeal cancer is increasing in incidence and in its association with human papillomavirus (HPV) infection; HPV-positive oropharyngeal cancer patients have significantly better outcomes (versus HPV-negative). These collective data led to the present analyses of overall survival (OS) in our retrospective cohort and of OS and HPV status (tested prospectively in pretreatment biopsy specimens) in the phase 3, multicenter TAX 324 trial of induction chemotherapy followed by concurrent chemoradiation in SCCHN patients. Median OS in the retrospective cohort of 106 white and 95 black SCCHN patients was 52.1 months (white) versus only 23.7 months (black; P = 0.009), due entirely to OS in the subgroup of patients with oropharyngeal cancer—69.4 months (whites) versus 25.2 months (blacks; P = 0.0006); no significant difference by race occurred in survival of non-oropharyngeal SCCHN (P = 0.58). In TAX 324, 196 white patients and 28 black patients could be assessed for HPV status. Median OS was significantly worse for black patients (20.9 months) than for white patients (70.6 months; P = 0.03) and dramatically improved in HPV-positive (not reached) versus HPV-negative (26.6 months, 5.1 hazard ratio) oropharyngeal patients (P < 0.0001), 49% of whom were HPV-16 positive. Overall, HPV positivity was 34% in white versus 4% in black patients (P = 0.0004). Survival was similar for black and white HPV-negative patients (P = 0.56). This is the first prospective assessment of confirmed HPV status in black versus white SCCHN patients. Worse OS for black SCCHN patients was driven by oropharyngeal cancer outcomes, and that for black oropharyngeal cancer patients by a lower prevalence of HPV infection. These findings have important implications for the etiology, prevention, prognosis, and treatment of SCCHN.
Oropharyngeal Cancer, Race, and the Human Papillomavirus
Authors: Brawley Otis W.
Published: July 2009

This perspective on Settle et al. (beginning on p. 776 in this issue of the journal) discusses the racial disparity in oropharyngeal cancer survival in relation to the biological factor human papillomavirus and its association with sexual behavior. This discussion is expanded to a more general consideration of biological and nonbiological (e.g., socioeconomic and cultural) factors affecting racial disparities in disease.
Reference Values of Static Back Extensor Muscle Endurance in Healthy Nigerian Adults
Authors: Mbada Chidozie Emmanuel , Ayanniyi Olusola , Adedoyin Rufus A.
Published: July 2009

Objective: This study aimed to establish gender and age reference values of static back extensor muscle endurance in healthy Nigerian adults. Subjects and Methods: This study involved 373 consecutive participants aged between 21 and 60 years who were grouped into four age strata. A modification of the Sørensen test of Static Muscular Endurance (BSME) was used to quantify static endurance. The mean, standard deviation, range and 25th, 50th, and 75th percentile scores were determined for four gender/age categories. Results: Endurance time differed significantly across the age groups (F = 47.286; p = 0.000). Males exhibited higher mean endurance than females (t = 2.583; p = 0.010). Using percentiles, 25th (poor endurance), 25th–75th (medium endurance) and >75th (good endurance) percentile were 72, 72–161, and >161–240 s, respectively, for males; and 64, 64–142, and >142–236 s, respectively, for females. There was an age and gender variation in the median values. The results suggest that the significant age and anthropometric differences between the categories of participants could contribute to endurance differences. Conclusion: This study established a set of reference values for static back endurance in healthy Nigerians. These values can be used to compare a patient’s score at intake or as an outcome measure in clinical practice.
Primary Myelodysplastic Syndrome in Jordan: A Single-Centre Experience
Authors: Awidi Abdalla , Magableh Ahmad , Taimeh Ziad , Ayyad Hashim , Bsoul Nazzal , Tarawneh Musleh
Published: July 2009

Objective: Study of the disease patterns and clinical evaluation of myelodysplastic syndrome (MDS). Subjects and Methods: A retrospective analysis was carried out on 85 patients, with MDS who were followed up over a period of 23 years at Jordan University Hospital, Amman, Jordan. Cases were analyzed according to the French, American and British Classification. Results: Of the 85 patients, 42 (49.4%) were females and 43 (50%) males; mean age was 59 ± 19 years (range 18–88). Most subtypes found in patients were refractory anemia (RA) in 27 (31.8%) and RA with excess blasts (RAEB) in 28 (32.9%). Adverse prognostic indicators were RAEB subtype and requirement for blood transfusion. Conclusion: Our findings showed that MDSs appeared at a younger age and tended to be of the aggressive subtype. Chronic myelomonocytic leukemia subtype seemed to appear dominantly in men.
Does Imatinib Mesylate Therapy Cause Growth Hormone Deficiency?
Authors: Kebapcilar L. , Bilgir O. , Alacacioglu I. , Payzin B. , Bilgir F. , Oner P. , Sari I. , Calan M. , Binicier O.
Published: July 2009

Objective: The purpose of this study was to determinewhether or not imatinib mesylate therapy induces growth hormone deficiency (GHD). Subjects and Methods: Seventeen patients with chronic myloid leukemia (CML) were enrolled in the study. The glucagon stimulation test (GST), and standard deviation scores (SDSs) of insulin-like growth fac- tor 1 (IGF-I) and insulin-like growth factor binding protein (IGFBP-3) were used to determine GHD. The L-dopa test was performed on those with IGF-I SDSs above the –1.8 cut-off level. Results: Of the 17 patients in the study, 12 (70%) had severe GHD (serum GH level <3 μg/l after GST). IGF-I SDSs and IGFBP-3 SDSs were below –1.8 in 12 patients (70%) and below –0.9 in 10 subjects (58%). Four of the 5 remaining subjects with IGF-I SDS >–1.8 showed insufficient GH response to L-dopa stimulation. Nine subjects (52%) had both severe GHD based on GST response and IGF-I SDS below –1.8. If an IGF-I SDS cut-off value l<–3 were used,5 out of 17 subjects (30%) would be classified as GH deficient. These same patients also showed severe GHD based on GST response. Conclusions: The data showed that a large number of patients on imatinib mesylate therapy had GH deficiency. A study involving a larger number of patients with a matched control group is needed to confirm the present observations.
Anemia Prevalence among Pregnant Women and Birth Weight in Five Areas in China
Authors: Ma A.G. , Schouten E. , Wang Y. , Xu R.X. , Zheng M.C. , Li Y. , Sun Y.Y. , Wang Q.Z.
Published: July 2009

Objectives: To investigate the current prevalence of anemia among pregnant women in different areas of China and the association with birth weight and educational level. Methods: A total of 6,413 women aged 24–37 in the third trimester of pregnancy from five areas were randomly selected from all gravidas who gave birth in the hospitals from 1999 to 2003. Blood hemoglobin concentration (Hb) was measured by the cyanomethemoglobin method; Hb <110 g/l was considered as anemia. Results: The overall prevalence of anemia was 58.6%, ranging from 48.1 to 70.5% in the five areas. There was a significant difference in the prevalence of anemia between women who have mental jobs and those who have physical jobs (52.3 vs. 61.1%, p < 0.01). The prevalence of anemia depended on the level of education: with 52.9, 62.4 and 66.5%, for college, secondary school and primary education, respectively, and the difference was statistically significant (p = 0.005). Results showed that higher birth weight was associated with Hb concentrations ranging from 90 to 140 g/l, whereas lower birth weight occurred below 80 g/l and above 140 g/l Hb. Conclusions: The prevalence of anemia in Chinese pregnant women was high both in rural areas and towns. Area of residence, education level and type of job influenced the prevalence of anemia. Low maternal Hb concentrations influenced birth weight.
Cementless Bilateral Total Hip Arthroplasty in a Patient with a History of Pelvic Irradiation for Sarcoma Botryoides
Authors: Demircay Emre , Unay Koray , Sener Nadir
Published: July 2009

Objective: To report a case of bilateral secondary coxarthrosis in a patient with a history of pelvic irradiation for sarcoma botryoides. Clinical Presentation and Intervention: The patient had surgery and radiation therapy for sarcoma botryoides when she was 18 months old. Left and right cementless total hip arthroplasties were performed at the age of 36 and 40 years, respectively. Harris hip scores improved from 28.4 to 93 on the left hip after 84 months of follow-up and from 29.5 to 91.3 on the right hip after 38 months of follow-up. Conclusion: Cementless total hip arthroplasty may be considered for irradiated hips, if radiation damage in bone has been stable for a long period of time.
Fatal Strongyloidiasis in Three Kidney Recipients in Kuwait
Authors: Mokaddas Eiman M. , Shati Shama , Abdulla Aneesa , Nampoori Narayanan R. , Iqbal Jamshaid , Nair Prasad M. , Said Tareq , Abdulhalim Medhat , Hira Parsotam R.
Published: July 2009

Objective: It was the aim of this study to report 3 rare fatal cases of strongyloidiasis in Kuwaiti renal transplant patients. Clinical Presentation and Intervention: All 3 cases received allografts from cadaveric donors of Asian origin, the first 2 from an Indian (transplanted on the same day) and the third from a Bangladeshi. In all 3 cases, Strongyloides stercoralis larvae were first isolated from bronchoalveolar lavage. All 3 patients were on immunosuppressive therapy which included prednisolone, thereby leading to the hyperinfection syndrome. All patients presented with gastrointestinal symptoms (abdominal pain, vomiting, diarrhea, constipation and paralytic ileus), as well as pulmonary symptoms (cough, dyspnea and blood-stained sputum). Albendazole 800 mg twice daily orally was started. Cyclosporine A was started after discontinuing prograf. The patients continued to deteriorate with a fall in blood pressure and platelets. All 3 patients died from adult respiratory distress syndrome following hyperinfection with S. stercoralis.Conclusion: Hyperinfection with S. stercoralis is a rare but preventable complication of immunosuppressive therapy. A high index of suspicion is required for the diagnosis of this infection. Persistent examination of sputum, bronchial washings and upper intestinal aspirates should be done as part of surveillance following cadaveric renal transplantation. Adult respiratory distress syndrome is indeed a red flag in patients who are on steroids, not on cyclosporine and receiving a kidney from donors in endemic countries of S. stercoralis.
An Unusual Case of Extensive Xanthogranulomatous Orchitis in a Diabetic Patient
Authors: Rifat Mannan Abul Ala Syed , Kahvic Mirza , Abu Sara Yahya , Bharati Chandramouli
Published: July 2009

Objective: We report an unusual case of extensive xanthogranulomatous orchitis (XGO) in association with poorly controlled diabetes mellitus. Clinical Presentation and Intervention: A 65-year-old Kuwaiti man with poorly controlled diabetes mellitus presented with a painful left testicular swelling of 1 year duration. Testicular tumor markers were normal. Scrotal ultrasonography showed a mass lesion of mixed echotexture, which almost replaced the testicular parenchyma. Left-sided orchiectomy was performed with the clinical diagnosis of testicular neoplasia. Subsequent examination revealed the diagnosis of XGO, and the patient is well 2 years after the operation. Conclusion: Extensive tumorous XGO associated with diabetes mellitus has not been previously reported. We offer this case to highlight the implied role of poorly controlled diabetes mellitus in the pathogenesis of XGO.
Zebrafish as a Genetic Model in Biological and Behavioral Gerontology: Where Development Meets Aging in Vertebrates – A Mini-Review
Authors: Kishi Shuji , Slack Barbara E. , Uchiyama Junzo , Zhdanova Irina V.
Published: July 2009

Understanding the molecular mechanisms of aging in vertebrates is a major challenge of modern biology and biomedical science. This is due, in part, to the complexity of the aging process and its multifactorial nature, the paucity of animal models that lend themselves to unbiased high-throughput screening for aging phenotypes, and the difficulty of predicting such phenotypes at an early age. We suggest that the zebrafish genetic model offers a unique opportunity to fill in this gap and contributes to advances in biological and behavioral gerontology. Our recent studies demonstrated that this diurnal vertebrate with gradual senescence is an excellent model in which to study age-dependent changes in musculoskeletal and eye morphology, endocrine factors, gene expression, circadian clock, sleep and cognitive functions. Importantly, we have also found that the presence of a senescence-associated biomarker (‘senescence-associated β-galactosidase’) can be documented during early zebrafish development and is predictive of premature aging phenotypes later in adult life. The availability of mutant ‘genotypes’ with identified aging ‘phenotypes’ in zebrafish, in combination with a wealth of information about zebrafish development and genetics, and the existence of multiple mutant and transgenic lines, should significantly facilitate the use of this outstanding vertebrate model in deciphering the mechanisms of aging, and in developing preventive and therapeutic strategies to prolong the productive life span (‘health span’) in humans.
Association between Insulin Resistance and Carotid Arterial Stiffness in Nondiabetic Hemodialysis Patients
Authors: Zhou YiLun , Yu ZeXing , Jia HuiMin , Sun Fang , Ma LiJie , Guo RuiJun , Peng LiRen , Cui TaiGen
Published: July 2009

Background: Patients with end-stage renal disease are known to have insulin resistance and advanced arterial stiffness. The present study was undertaken to investigate whether insulin resistance was correlated with carotid arterial stiffness in hemodialysis patients. Methods: Eighty nondiabetic hemodialysis patients were recruited. Stiffness index β of the common carotid artery was assessed by ultrasound using echo-tracking system. Insulin resistance was evaluated by the homeostasis model assessment method (HOMA-IR). Serum albumin, lipid profile, calcium, phosphorus, intact parathyroid hormone, high-sensitivity C-reactive protein and oxidized low-density lipoprotein (ox-LDL) were also measured. Results: Patients with higher HOMA-IR levels had higher BMI, ox-LDL, and stiffness index β than patients with lower HOMA-IR levels. HOMA-IR was independently correlated with stiffness index β (β = 0.260, p = 0.016). BMI and ox-LDL were independent contributors to HOMA-IR. Conclusion: Insulin resistance assessed by HOMA-IR is closely associated with carotid arterial stiffness in nondiabetic hemodialysis patients.