bluuebunny/crossref_metadata_2025 huggingface dataset:
AIDS in Pregnancy, Part I: Epidemiology, Testing, Effect on Disease Progression, Opportunistic Infections, and Risk of Vertical Transmission
Authors: Rigopoulos Dimitris , Gregoriou Stamatis , Paparizos Vasilis , Katsambas Andreas
Published: February 2007

Contribution of acquired immunodeficiency syndrome/human immunodeficiency virus (HIV) infection to pregnancy mortality rates is difficult to estimate; however, it appears to be one of the leading causes of death, at least in developing countries. Prenatal HIV testing affords the best opportunity for the prevention of perinatal HIV transmission. Rapid HIV testing substantially increases the proportion of women who obtain HIV results compared with conventional enzyme‐linked immunosorbent assay testing, thus maximizing perinatal HIV interventions. Pregnancy appears to have no effect on the course of HIV disease. Infections due to a variety of pathogens influence the clinical course of the HIV infection and may complicate pregnancy and increase maternal mortality. The main risk factors for mother‐to‐child HIV transmission are high maternal viral load and CD4 cell count <700 cells/mm3. The main protective factor is antiretroviral therapy.
Identification and Functional Characterization of the Delta 6‐Fatty Acid Desaturase Gene from Thamnidium elegans
Authors: WANG DEPEI , LI MINGCHUN , WEI DONGSHENG , CAI YI , ZHANG YINGHUI , XING LAIJUN
Published: February 2007

ABSTRACT. A cDNA sequence was cloned from the filamentous fungus Thamnidium elegans As3.2806 using reverse transcription polymerase chain reaction (RT‐PCR) and rapid amplification of cDNA ends method (RACE). Sequence analysis indicated that this cDNA sequence has an open reading frame of 1,380 bp, which encodes a 52.4 kDa peptide of 459 amino acids. The designated amino acid sequence has high similarity with that found in fungal delta 6‐fatty acid desaturases: it shows three conserved histidine‐rich motifs and two hydrophobic domains. A cytochrome b5‐like domain was observed at the N‐terminus. To elucidate the function of this novel putative desaturase, the open reading frame was cloned into the intracellular expression vector pPIC3.5K and the gene was expressed heterologously in Pichia pastoris. Accumulation of γ‐linolenic acid to the level of 6.83% in total fatty acid demonstrated that the deduced amino acid sequence possesses of delta 6‐fatty acid desaturase activity.
A retrospective on the requirements for γδ T‐cell development
Authors: Hayes Sandra M. , Love Paul E.
Published: February 2007

Summary:  Since the discovery of γδ T cells two decades ago, considerable effort has been made to understand their developmental program, their antigen specificity, and their contribution to the immune response. In this review, we focus on what is known about γδ T‐cell development and on the advances that have been made in determining which genes are required. In addition, we compare the genetic requirements for αβ and γδ T‐cell development with the hope of gaining a better picture of the signaling pathways that govern the development of γδ lineage cells.
γδ T‐cell receptors: functional correlations
Authors: O’Brien Rebecca L. , Roark Christina L. , Jin Niyun , Kemal Aydintug M. , French Jena D. , Chain Jennifer L. , Wands J. M. , Johnston Molly , Born Willi K.
Published: February 2007

Summary:  The γδ T‐cell receptors (TCRs) are limited in their diversity, suggesting that their natural ligands may be few in number. Ligands for γδTCRs that have thus far been determined are predominantly of host rather than foreign origin. Correlations have been noted between the Vγ and/or Vδ genes a γδ T cell expresses and its functional role. The reason for these correlations is not yet known, but several different mechanisms are conceivable. One possibility is that interactions between particular TCR‐V domains and ligands determine function or functional development. However, a recent study showed that at least for one ligand, receptor specificity is determined by the complementarity‐determining region 3 (CDR3) component of the TCR‐δ chain, regardless of the Vγ and/or Vδ. To determine what is required in the TCR for other specificities and to test whether recognition of certain ligands is connected to cell function, more γδTCR ligands must be defined. The use of recombinant soluble versions of γδTCRs appears to be a promising approach to finding new ligands, and recent results using this method are reviewed.
Association of gene polymorphisms for plasminogen activators with alveolar bone loss
Authors: DeCarlo A. A. , Grenett H. , Park J. , Balton W. , Cohen J. , Hardigan P.
Published: February 2007

Background and Objective:  The plasminogen activating system is a protease/inhibitor system central to extracellular matrix remodeling with a suggested role in periodontal disease pathology. A few studies have reported polymorphisms in the genes of plasminogen activator inhibitors to be associated with periodontal disease severity. Two gene polymorphisms – a BamHI restriction fragment length polymorphism in the urokinase plasminogen activator gene (uPA) and a HindIII restriction fragment length polymorphism in the plasminogen activator inhibitor type 1 gene (PAI‐1) – have been associated with conditions having a vascular component, and our objective was to assess the association of these gene polymorphisms with alveolar bone loss in chronic periodontal disease of adults.

Material and Methods:  Genotype was determined by polymerase chain reaction amplification of whole blood, pertinent histories were obtained by interview, and alveolar bone loss was assessed from current radiographs.

Results:  In 77 elderly patients with a normal distribution of alveolar bone loss, we demonstrated a significant association between levels of alveolar bone loss and these polymorphisms in the uPA and PAI‐1 genes. Controlling for the contributions of smoking or diabetes to periodontal bone loss, estimated odds ratios for predicting lower levels of alveolar bone loss, associated with a greater degree of periodontal health, were strongest when defined by the concurrent presence of a homozygous urokinase plasminogen activator genotype and the nuclease‐sensitive plasminogen activator inhibitor type 1 (HindIII) allele (odds ratio = 2.6; 95% confidence interval: 5.8–1.3).

Conclusion:  The urokinase plasminogen activator (BamHI) and plasminogen activator inhibitor type 1 (HindIII) genotypes may serve as useful markers for heritability of bone loss associated with periodontal disease.
Measurement of skin elasticity on the foot
Authors: Hashmi Farina , Malone‐Lee James
Published: February 2007

Background/purpose: The Cutometer® 580 MPA is a device that is designed to measure the viscoelastic properties of skin in response to the application of negative pressure. The aim of this study was to test the Cutometer® 580 MPA for the repeatable, quantitative measurement of the specific indices of elasticity of pedal skin. The device was used to measure and compare these indices at weight‐bearing and non‐weight‐bearing skin sites on the foot.

Methods: The relationship between the pressure application and skin displacement was determined. The inter‐ and intra‐tester repeatability was tested. These series of experiments were conducted on 20 individuals. Data were then collected from a group of 87 healthy people for the measurement of elasticity, viscoelasticity and plasticity on several sites on the foot. The possible influences of physiological variables such as age and sex on the indices of elasticity were analysed.

Results: The Hookian elastic behaviour of the skin was confirmed. The pressure application did not remain constant during the collection of displacement data, resulting in an error in these readings of between 1.71% and 3.73%. Intra‐tester and variability was minimal (CV<7%). The elasticity, viscoelasticity and plasticity indices were significantly greater (P<0.001) in dorsal skin compared with skin from medial longitudinal arch (MLA) and plantar aspect of the third metatarsophalangeal joint (PMA) sites. There was a negative correlation between age and elasticity on the dorsum and MLA skin sites (r=−0.216 and −0.261, respectively). Female skin exhibited greater plasticity than male skin on all three sites on the foot (P<0.05).

Conclusion: Under well‐controlled conditions, the Cutometer® 580 MPA has the ability to measure accurately the viscoelastic properties of pedal skin. Such non‐invasive measurements may be useful for the evaluation of changes in the skin in response to therapeutic interventions and for monitoring the progression of dermatological conditions associated with the foot.
Electrical impedance model for evaluation of skin irritation in rabbits and humans
Authors: Ferreira D. M. , Silva C. S. , Souza M. N.
Published: February 2007

Background/aim: The electrical impedance method has been used as a quantitative technique for evaluating changes in the skin during irritation within the invisible range. The purpose of this study was to apply an electrical model of skin to the interpretation of impedance data after the application of an irritant (SLS) in the skin of humans and rabbits.

Methods: Investigations were performed on 12 humans and 15 albino rabbits. Responses were evaluated by measuring electrical impedance before irritant exposure and 24 h after its removal and also by visual inspection. Using the raw impedance parameter, a novel index was developed and its value was correlated with visual scoring.

Results: The derived impedance index showed a significant correlation with visual scores and its value decreased (P<0.05) after irritant removal even without macroscopic signs of irritation.

Conclusion: The proposed electrical model of skin seems to be suitable for the detection and interpretation of changes in the impedance characteristics of skin induced by SLS in rabbits and humans.
Photodynamic treatment of cutaneous leishmaniasis
Authors: Sohl Sirius , Kauer Friederike , Paasch Uwe , Simon Jan C.
Published: February 2007

Leishmaniasis is a widespread arthropod‐borne protozoan zoonosis caused by more than 21 Leishmania species. Vectors are sandflies of different genera. The disease is classified into „Old World” versus „New World” leishmaniasis and further subclassified in cutaneous, mucocutaneous and visceral forms. Most therapeutic approaches are not evidence‐based. We report a patient with facial cuta‐neous Leishmania tropica infection which proved to be resistant to various therapeutic regimes. Excellent results were achieved with photody‐namic therapy.
One‐Stage Operative Procedure Using Two Different Implant Systems: A Prospective Study on Implant Overdentures in the Edentulous Mandible
Authors: Tawse‐Smith Andrew , Payne Alan G.T. , Kumara Rohana , Thomson W. Murray
Published: February 2007

Background: Evidence‐based reports are needed to support the application of a one‐stage surgical protocol for unsplinted implants supporting mandibular overdentures.

Purpose: To examine the feasibility and success of using two different dental implant systems (originally designed for two‐stage operative technique) using a one‐stage operative procedure in patients being rehabilitated with implant mandibular overdentures.

Materials and Methods: The study sample involved 24 edentulous subjects (aged 55–80 yr) randomly allocated to two different implant systems, one with a machined titanium implant surface (Steri‐Oss, Nobel Biocare, Göteborg, Sweden) and the other with a roughened titanium surface (Southern Implants, Ltd., Irene, South Africa). Two unsplinted implants to support implant overdentures were placed in the anterior mandible of all patients, using a standardized one‐stage surgical and prosthodontic procedure. Primary stability and bicortical anchorage of the implants was mandatory before healing abutments were connected at the time of implant placement. Implant overdentures and their respective matrices were inserted following a standard 12‐week healing period. Data relating to mobility tests, radiographs, and peri‐implant parameters were documented at 12, 16, and 52 weeks after surgery.

Results: A success rate of 95.8% for the Steri‐Oss and 100% for the Southern Implants was found, without any statistically significant differences in the marginal bone loss. Significant changes in Periotest values were observed for both types between 12 and 52 weeks (p <.001). Minor changes were observed in the peri‐implant parameters evaluated.

Conclusions: These preliminary findings show a successful application of this one‐stage approach for unsplinted implants supporting mandibular overdentures with Steri‐Oss and Southern Implant Systems.
APPLICATION of LASER DOPPLER ANEMOMETRY to MEASURE VELOCITY DISTRIBUTION INSIDE the SCREW CHANNEL of A TWIN‐SCREW EXTRUDER
Authors: KARWE MUKUND V. , SERNAS VALENTINAS
Published: February 2007

Velocity measurements inside the screw channels of a co‐rotating, self‐wiping twin‐screw extruder (ZSK‐30) have been carried out using the noninvasive technique of Laser Doppler Anemometry. A two‐dimensional Argon‐ion laser Doppler system was used to measure tangential and axial velocity components in one of the screws, away from the intermeshing zone. Heavy corn syrup with naturally occurring particles was used in the extrusion experiments. the measured tangential velocity distribution agreed with the expected distribution for a Newtonian fluid. Measurements also indicated that near the screw root and away from the flights, shear rates were substantially lower as compared to the shear rates near the barrel. the results indicated that this technique is suitable for making velocity measurements in a twin‐screw extruder using model fluids.
New Developments in the Meaning of Life
Authors: Metz Thaddeus
Published: February 2007

In this article I survey philosophical literature on the topic of what, if anything, makes a person's life meaningful, focusing on systematic texts that are written in English and that have appeared in the last five years. My aims are to present overviews of the most important, fresh, Anglo‐American positions on meaning in life and to raise critical questions about them worth answering in future work.
Reliability of Sampling Inspection Schemes Applied to Replacement Steam Generators
Authors: Roussel Guy , Cizelj Leon
Published: February 2007

The basis for determining the size of the random sample of tubes to be inspected in replacement steam generators is revisited in this paper. A procedure to estimate the maximum number of defective tubes left in the steam generator after no defective tubes have been detected in the randomly selected inspection sample is proposed. A Bayesian estimation is used to obtain closed-form solutions for uniform, triangular, and binomial prior densities describing the number of failed tubes in steam generators. It is shown that the particular way of selecting the random inspection sample (e.g., one sample from both SG, one sample from each SG, etc.) does not affect the results of the inspection and also the information obtained about the state of the uninspected tubing, as long as the inspected steam generators belong to the same population. Numerical examples further demonstrate two possible states of the knowledge existing before the inspection of the tubing. First, virtually no knowledge about the state of the steam generator tubing before the inspection is modeled using uniform and triangular prior densities. It is shown that the knowledge about the uninspected part of the tubing strongly depends on the size of the sample inspected. Further, even small inspection samples may significantly improve our knowledge about the uninspected part. On the other hand, rather strong belief on the state of the tubing prior to the inspection is modeled using binomial prior density. In this case, the knowledge about the uninspected part of the tubing is virtually independent on the size of the sample. Furthermore, it is shown qualitatively and quantitatively that such inspection brings no additional knowledge on the uninspected part of the tubing.
Localized Structures in Vertically Vibrated Granular Materials
Authors: Zamankhan Piroz , Huang Jun
Published: February 2007

Granular materials exhibit unusual kinds of behavior, including pattern formations during the shaking of the granular materials; the characteristics of these various patterns are not well understood. Vertically shaken granular materials undergo a transition to convective motion that can result in the formation of bubbles. A detailed overview is presented of collective processes in gas-particle flows that are useful for developing a simplified model for molecular dynamic type simulations of dense gas-particle flows. The governing equations of the gas phase are solved using large eddy simulation technique. The particle motion is predicted by a Lagrangian method. Particles are assumed to behave as viscoelastic solids during interactions with their neighboring particles. Interparticle normal and tangential contact forces are calculated using a generalized Hertzian model. The other forces that are taken into account are gravitational and drag force resulting from velocity difference with the surrounding gas. A simulation of gas-particle flow is performed for predicting the flow dynamics of dense mixtures of gas and particles in a vertical, pentagonal, prism shaped, cylindrical container. The base wall of the container is subjected to sinusoidal oscillation in the vertical direction that spans to the bottom of the container. The model predicts the formation of oscillon type structures on the free surface. In addition, the incomplete structures are observed. Interpretations are proposed for the formation of the structures, which highlights the role played by the surrounding gas in dynamics of the shaken particles.
Use of an Inhibition Enzyme-Linked Immunosorbent Assay for Quantification of Capsular Polysaccharide or Proteins in Vaccines
Authors: Inzana Thomas J. , Champion Anna
Published: February 2007

An inhibition enzyme-linked immunosorbent assay (ELISA) is described for quantification of capsular polysaccharide or proteins in vaccines and other samples containing whole cells or extracts ofActinobacillus pleuropneumoniae. The assay can be used to quantify any antigen that can be purified and for which highly specific antibodies are not available. The assay can be carried out by any laboratory capable of performing an ELISA.
Human Models of Low-Grade Inflammation: Bolus versus Continuous Infusion of Endotoxin
Authors: Taudorf S. , Krabbe K. S. , Berg R. M. G. , Pedersen B. K. , Møller K.
Published: February 2007

Systemic low-grade inflammation is recognized in an increasing number of chronic diseases. With the aim of establishing an experimental human in vivo model of systemic low-grade inflammation, we measured circulating inflammatory mediators after intravenous administration of
Escherichia coli
endotoxin (0.3 ng/kg of body weight) either as a bolus injection or as a 4-h continuous intravenous infusion, as well as after saline administration, in 10 healthy male subjects on three separate study days. Only bolus endotoxin caused an increase in heart rate, whereas a slight increase in rectal temperature was observed in both endotoxin groups. Tumor necrosis factor alpha (TNF-α), interleukin-6, and neutrophil responses were earlier and more pronounced in the bolus trial compared with the infusion trial results, whereas lymphocytes increased after endotoxin bolus injection as well as infusion without any difference between groups. Finally, endotoxin activated the hypothalamo-pituitary-adrenal axis slightly earlier in the bolus compared to the infusion trial. The continuous endotoxin infusion model may be more representative of human low-grade inflammation than the bolus injection model due to a less dynamic and more sustained increase in circulating levels of inflammatory mediators over time. In conclusion, low-dose endotoxin infusion elicits an inflammatory response, as assessed by a rise in TNF-α, and the responses are significantly different according to whether low-dose endotoxin is applied as a bolus injection or as a continuous infusion.
Reduction of Worm Fecundity and Canine Host Blood Loss Mediates Protection against Hookworm Infection Elicited by Vaccination with Recombinant
Ac-
16
Authors: Fujiwara Ricardo T. , Zhan Bin , Mendez Susana , Loukas Alex , Bueno Lilian L. , Wang Yan , Plieskatt Jordan , Oksov Yelena , Lustigman Sara , Bottazzi Maria Elena , Hotez Peter , Bethony Jeffrey M.
Published: February 2007

Hookworm infection is one of most important parasitic infection of humans, occurring in 740 million people. Here we report the protective vaccination of dogs with
Ac
-16, an immunodominant surface antigen from the hookworm
Ancylostoma caninum
. We show that immunization with
Ac
-16 formulated with AS03 elicited specific humoral and cellular immune responses and provided partial protection against hookworm infection and morbidity as evidenced by a significant reduction of hookworm egg counts (64% reduction;
P
= 0.0078) and worm-induced blood loss (
P
< 0.05). Moreover, specific anti-
Ac
-16 antibodies recognized the native protein on the surface of third-stage larvae and blocked their migration through tissue in vitro. Our data support the use of
Ac
-16 as a potential candidate for vaccination against hookworm infection.
Serological Assays for Identification of Human Gastric Colonization by
Helicobacter pylori
Strains Expressing VacA m1 or m2
Authors: Ghose Chandrabali , Perez-Perez Guillermo I. , Torres Victor J. , Crosatti Marialuisa , Nomura Abraham , Peek Richard M. , Cover Timothy L. , Francois Fritz , Blaser Martin J.
Published: February 2007

The
Helicobacter pylori vacA
gene encodes a secreted protein (VacA) that alters the function of gastric epithelial cells and T lymphocytes.
H. pylori
strains containing particular
vacA
alleles are associated with differential risk of disease. Because the VacA midregion may exist as one of two major types, m1 or m2, serologic responses may potentially be used to differentiate between patients colonized with
vacA m1
- or
vacA m2
-positive
H. pylori
strains. In this study, we examined the utility of specific antigens from the m regions of VacA as allele-specific diagnostic antigens. We report that serological responses to P44M1, an
H. pylori
m1-specific antigen, are observed predominantly in patients colonized with
m1
-positive strains, whereas responses to VacA m2 antigens, P48M2 and P55M2, are observed in patients colonized with either
m1
- or
m2
-positive strains. In an Asian-American population, serologic responses to VacA m region-specific antigens were not able to predict the risk of development of gastric cancer.
Two Gene Determinants Are Differentially Involved in the Biogenesis of Fap1 Precursors inStreptococcus parasanguis
Authors: Wu Hui , Bu Su , Newell Peter , Chen Qiang , Fives-Taylor Paula
Published: February 2007

Mature Fap1, a 200-kDa fimbria-associated adhesin, is required for fimbrial biogenesis and biofilm formation inStreptococcus parasanguis. Fap1-like proteins are found in the genomes of many streptococcal and staphylococcal species. Fap1 is a serine-rich glycoprotein modified by O-linked glycan moieties. In this study, we identified a seven-gene cluster includingsecY2,orf1,orf2,orf3,secA2,gtf1, andgtf2that is localized immediately downstream offap1. The lower G+C contents and the presence of a putative transposase element suggest that this gene cluster was horizontally transferred from other bacteria and represents a genomic island. At least two genes in this island mediated Fap1 biogenesis. Mutation of a glucosyltransferase (Gtf1) gene led to accumulation of a Fap1 precursor, which had no detectable glycan moieties. Inactivation of a gene coding for an accessory Sec protein (SecY2) resulted in expression of a distinct Fap1 precursor, which reacted with one glycan-specific Fap1 antibody but not with another glycan-specific antibody. Furthermore, partially glycosylated Fap1 was detected on the cell surface and in the culture supernatant. These data suggest that SecY2 has a role in complete glycosylation of Fap1 and imply that SecY2 is not the only translocation channel for the Fap1 precursor and that alternative secretion machinery exists. Together, Gtf1 and SecY2 are involved in biogenesis of two distinct Fap1 precursors inS. parasanguis. Discovery of the effect of an accessory Sec protein on Fap1 glycosylation suggests that Fap1 secretion and glycosylation are coupled during Fap1 biogenesis.
Role of Streptococcal T Antigens in Superficial Skin Infection
Authors: Lizano Sergio , Luo Feng , Bessen Debra E.
Published: February 2007

FCT region genes ofStreptococcus pyogenesencode surface proteins that includefibronectin- andcollagen-binding proteins and the serological markers known asTantigens, some of which give rise to pilus-like appendages. It remains to be established whether FCT region surface proteins contribute to virulence by in vivo models of infection. In this study, a highly sensitive and ecologically relevant humanized mouse model was used to measure superficial skin infection. Three genes encoding FCT region surface proteins essential for T-serotype specificity were inactivated. Both the Δcpaand ΔprtF2mutants were highly attenuated for virulence when topically applied to the skin following exponential growth but were fully virulent when delivered in stationary phase. In contrast, the ΔfctAmutant was virulent at the skin, regardless of its initial growth state. Immunoblots of cell extracts revealed anti-FctA-reactive, ladder-like polymers characteristic of streptococcal pili. In addition, FctA formed a heteropolymer with the putative collagen-binding protein Cpa. The ΔfctAmutant showed a loss in anti-Cpa-reactive polymers, whereas anti-FctA-reactive polymers were reduced in the Δcpamutant. The findings suggest that both FctA and Cpa are required for pilus formation, but importantly, an intact pilus is not essential for Cpa-mediated virulence. Although it is an integral part of the T-antigen complex, the fibronectin-binding protein PrtF2 is not covalently linked to the FctA- and Cpa-containing heteropolymer derived from cell extracts. The data provide direct evidence that streptococcal T antigens function as virulence factors in vivo, but they also reveal that a pilus-like structure is not essential for the most common form of streptococcal skin disease.
Significant Genetic and Antigenic Variability within the
env
Gene of Systemic Human Immunodeficiency Virus Type 1 Group O Populations during the Natural Course of a Heterosexual Infection: a Pilot Study
Authors: Andréoletti Laurent , Réveil Brigitte , Moret Hélène , Brodard Véronique , Philbert Frédérique , Tabary Thierry , Cohen Jacques Henri Max
Published: February 2007

We assessed the genetic and the antigenic variability within the
env
gene of peripheral blood human immunodeficiency virus (HIV) type 1 (HIV-1) group O populations during the natural course of a female heterosexual infection. Our data revealed the existence of a significant increase in amino acid sequence variability within the C2-V3 and gp41 regions (
P
= 0.023 and
P
< 0.001, respectively) in association with substitutions within neutralizing epitope sequences usually selected for HIV serological assays. These antigenic variations might significantly decrease the sensitivity of classical HIV enzyme-linked immunosorbent assays with blood samples of subjects heterosexually infected by HIV-1 group O strains. These findings may be of significant use both to devise diagnostic tools and to pursue suitable therapeutic modalities in cases of heterosexual infection by outlier HIV-1 strains.
Outbreak of Gastroenteritis Due to Sapovirus
Authors: Hansman Grant S. , Saito Hiroyuki , Shibata Chihiro , Ishizuka Shizuko , Oseto Mitsuaki , Oka Tomoichiro , Takeda Naokazu
Published: February 2007

An outbreak of gastroenteritis occurred at a kindergarten in Yokote City, Japan, between February 2006 and March 2006. Sapovirus was identified in 19 of 26 stool specimens by reverse transcription-PCR. A high viral shedding pattern was found for this strain, which was shown to be antigenically distinct from other genogroups.
Report of the First Human Case of
Caulobacter
sp. Infection
Authors: Justesen Ulrik S. , Holt Hanne M. , Thiesson Helle C. , Blom Jens , Nielsen Xiaohui C. , Dargis Rimtas , Kemp Michael , Christensen Jens J.
Published: February 2007

A
Caulobacter
sp. isolate was recovered from the dialysis fluid of a patient undergoing peritoneal dialysis. Bacterial identification included electron microscopy and 16S rDNA sequencing. To our knowledge, this is the first report of human
Caulobacter
infection. Special growth requirements suggest that
Caulobacter
spp. may be overlooked in the clinical microbiology laboratory.
Arginine Methylation of the Human Immunodeficiency Virus Type 1 Tat Protein by PRMT6 Negatively Affects Tat Interactions with both Cyclin T1 and the Tat Transactivation Region
Authors: Xie Baode , Invernizzi Cédric F. , Richard Stéphane , Wainberg Mark A.
Published: February 2007

Arginine methylation has been shown to regulate signal transduction, protein subcellular localization, gene transcription, and protein-protein interactions that ultimately alter gene expression. Although the role of cellular protein arginine methyltransferases (PRMT) in viral gene expression is largely unknown, we recently showed that the Tat protein of human immunodeficiency virus type 1 (HIV-1) is a substrate for one such enzyme, termed PRMT6. However, the mechanism by which arginine methylation impairs the transactivation potential of Tat and the sites of arginine methylation within Tat remain obscure. We now show that Tat is a specific in vitro and in vivo substrate of PRMT6 which targets the Tat R52 and R53 residues for arginine methylation. Such Tat methylation led to decreased interaction with the Tat transactivation region (TAR) of viral RNA. Furthermore, arginine methylation of Tat negatively affected Tat-TAR-cyclin T1 ternary complex formation and diminished cyclin T1-dependent Tat transcriptional activation. Overexpression of wild-type PRMT6, but not a methylase-inactive PRMT6 mutant, reduced levels of Tat transactivation of HIV-1 long terminal repeat chloramphenicol acetyltransferase and luciferase reporter plasmids in a dose-dependent manner. In cell-based assays, knockdown of PRMT6 resulted in increased HIV-1 production and faster viral replication. Thus, PRMT6 can compromise Tat transcriptional activation and may represent a form of innate cellular immunity in regard to HIV-1 replication. Finding a way of inhibiting or stimulating PRMT6 activity might help to drive quiescently infected cells out of latency or combat HIV-1 replication, respectively.
Herpesvirus Saimiri Episomal Persistence Is Maintained via Interaction between Open Reading Frame 73 and the Cellular Chromosome-Associated Protein MeCP2
Authors: Griffiths Rhoswyn , Whitehouse Adrian
Published: February 2007

Herpesvirus saimiri (HVS) is the prototype gamma-2 herpesvirus, which naturally infects the squirrel monkey
Saimiri sciureus
, causing an asymptomatic but persistent infection. The latent phase of gamma-2 herpesviruses is characterized by their ability to persist in a dividing cell population while expressing a limited subset of latency-associated genes. In HVS only three genes, open reading frame 71 (ORF71), ORF72, and ORF73, are expressed from a polycistronic mRNA. ORF73 has been shown to be the only gene essential for HVS episomal maintenance and can therefore be functionally compared to the human gammaherpesvirus latency-associated proteins, EBNA-1 and Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA). HVS ORF73 is the positional homologue of KSHV LANA and, although it shares limited sequence homology, has significant structural and functional similarities. Investigation of KSHV LANA has demonstrated that it is able to mediate KSHV episomal persistence by tethering the KSHV episome to host mitotic chromosomes via interactions with cellular chromosome-associated proteins. These include associations with core and linker histones, several bromodomain proteins, and the chromosome-associated proteins methyl CpG binding protein 2 (MeCP2) and DEK. Here we show that HVS ORF73 associates with MeCP2 via a 72-amino-acid domain within the ORF73 C terminus. Furthermore, we have assessed the functional significance of this interaction, using a variety of techniques including small hairpin RNA knockdown, and show that association between ORF73 and MeCP2 is essential for HVS chromosomal attachment and episomal persistence.
Bluetongue Virus Entry into Cells
Authors: Forzan Mario , Marsh Mark , Roy Polly
Published: February 2007

Bluetongue virus
(BTV) is a member of the
Orbivirus
genus within the
Reoviridae
family. Like those of other members of the family, BTV particles are nonenveloped and contain two distinct capsids, namely, an outer capsid and an inner capsid or core. The two outer capsid proteins, VP2 and VP5, are involved in BTV entry into cells and in the delivery of the transcriptionally active core to the target cell cytoplasm. However, very little is known about the precise mechanism of BTV entry. In this report, using RNA interference, we demonstrate that inhibition of the clathrin-dependent endocytic pathway correlates with reduced BTV internalization and subsequent replication. Furthermore, by using the ATPase inhibitor bafilomycin A1, we show that exposure of the virus to acidic pH is required for productive infection. Moreover, microscopic analysis of cells incubated with BTV indicated that the virus is internalized into early endosomes, where separation of the outer capsid and inner core occurs. Together, our data indicate that BTV undergoes low-pH-induced penetration in early endosomes following clathrin-mediated endocytosis from the plasma membrane, supporting a stepwise model for BTV entry and penetration.
Efficiency of Human Immunodeficiency Virus Type 1 Postentry Infection Processes: Evidence against Disproportionate Numbers of Defective Virions
Authors: Thomas James A. , Ott David E. , Gorelick Robert J.
Published: February 2007

The vast majority of human immunodeficiency virus type 1 particles are claimed to be noninfectious, but there is disagreement as to whether they are defective or simply lack the opportunity to initiate an infection. We have examined the efficiencies of reverse transcription and integration and find that approximately 1 of every 8 virions that initiate reverse transcription form proviruses, a quantity significantly different from the commonly reported ratio of 1 in 1,000. In addition, results from two different infectivity assays demonstrate that the titers are not equivalent to the number of infectious particles. The apparent predominance of noninfectious particles is due to infrequent occurrences of successful virus-cell interactions.
Ageing and the gut
Authors: D'Souza A L
Published: February 2007

The current concepts on diagnosis, clinical features, and management of common gastrointestinal conditions in the elderly population, taking into account physiological aspects of ageing, are evaluated. Gastrointestinal (GI) disorders are discussed with an emphasis on oesophageal problems, Helicobacter pylori infection, malabsorption, diverticular disease, and cancer. GI problems are acquiring greater importance in hospitals and in the community and their incidence is increasing. Newer treatments have less impact on patients' wellbeing and meticulously planned investigation and treatment is needed. Careful selection of patients and application of modern techniques has improved survival and outcomes, with comparable results to those in younger age groups.
Inappropriate prescribing of proton pump inhibitors in primary care
Authors: Batuwitage Bisanth Thushila , Kingham Jeremy G C , Morgan Nia Emma , Bartlett Ruth Louise
Published: February 2007

Objectives

To determine if an educational intervention initiated in secondary care can influence prescribing of proton pump inhibitors (PPIs) in the community.

Methods

A prospective study of PPI use in patients admitted to medical wards in a university hospital. A simple educational intervention was employed to reduce inappropriate prescribing of PPIs in the community.

Results

In the pre-intervention analysis 66/271 (24%) patients were receiving treatment with a PPI prescribed in the community. In 36/66 (54%) patients the PPI had been prescribed inappropriately. Six months after the intervention 91/344 (26%) patients were prescribed a PPI in the community. In only 45 of these 91 (49%) patients was there a recommended indication.

Conclusion

The intervention used in this study had no effect on the proportion of patients taking a PPI at the time of hospital admission or on the appropriateness of prescribing in the community.
Calcium/calmodulin-dependent protein kinase II-δ isoform regulation of vascular smooth muscle cell proliferation
Authors: House Suzanne J. , Ginnan Roman G. , Armstrong Shayn E. , Singer Harold A.
Published: February 2007

There is accumulating evidence that Ca2+-dependent signaling pathways regulate proliferation and migration of vascular smooth muscle (VSM) cells, contributing to the intimal accumulation of VSM that is a hallmark of many vascular diseases. In this study we investigated the role of the multifunctional serine/threonine kinase, calmodulin (CaM)-dependent protein kinase II (CaMKII), as a mediator of Ca2+ signals regulating VSM cell proliferation. Differentiated VSM cells acutely isolated from rat aortic media express primarily CaMKIIγ gene products, whereas passaged primary cultures of de-differentiated VSM cells express primarily CaMKIIδ2, a splice variant of the δ gene. Experiments examining the time course of CaMKII isoform modulation revealed the process was rapid in onset following initial dispersion and primary culture of aortic VSM with a significant increase in CaMKIIδ2 protein and a significant decrease in CaMKIIγ protein within 30 h, coinciding with the onset of DNA synthesis and cell proliferation. Attenuating the initial upregulation of CaMKIIδ2 in primary cultured cells using small-interfering RNA (siRNA) resulted in decreased serum-stimulated DNA synthesis and cell proliferation in primary culture. In passaged VSM cells, suppression of CaMKIIδ2 activity by overexpression of a kinase-negative mutant, or suppression of endogenous CaMKII content using multiple siRNAs, significantly attenuated serum-stimulated DNA synthesis and cell proliferation. Cell cycle analysis following either inhibitory approach indicated decreased proportion of cells in G1, an increase in proportion of cells in G2/M, and an increase in polyploidy, corresponding with accumulation of multinucleated cells. These results indicate that CaMKIIδ2 is specifically induced during modulation of VSM cells to the synthetic phenotypic and is a positive regulator of serum-stimulated proliferation.
Angiogenic Role of LYVE-1–Positive Macrophages in Adipose Tissue
Authors: Cho Chung-Hyun , Jun Koh Young , Han Jinah , Sung Hoon-Ki , Jong Lee Hyuek , Morisada Tohru , Schwendener Reto A. , Brekken Rolf A. , Kang Guson , Oike Yuichi , Choi Tae-Saeng , Suda Toshio , Yoo Ook-Joon , Koh Gou Young
Published: February 2007

Here we report the discovery of a characteristic dense vascular network (DVN) in the tip portion of epididymal adipose tissue in adult mice. The DVN is formed by angiogenesis rather than by vasculogenesis, and has functional blood circulation. This DVN and its subsequent branching may provide a new functional route for adipogenesis. The recruitment, infiltration, and accumulation of bone marrow-derived LYVE-1
+
macrophages in the tip region are crucial for the formation of the DVN. Matrix metalloproteinases (MMPs) and the VEGF-VEGFR2 system are responsible not only for the formation of the DVN, but also for the recruitment and infiltration of LYVE-1
+
macrophages into the epididymal adipose tissue tip region. SDF-1, but not the MCP-1-CCR2 system, is a critical factor in recruitment and ongoing retention of macrophages in this area. We also demonstrate that the tip region of epididymal adipose tissue is highly hypoxic, and thus provides a microenvironment conducive to the high expression and enhanced activities of VEGF, VEGFR2, MMPs, and SDF-1 in autocrine and paracrine manners, to create an ideal niche for the recruitment, retention, and angiogenic action of macrophages. These findings shed light on the complex interplay between macrophage infiltration, angiogenesis, and adipogenesis in the tip region of adult epididymal adipose tissue, and provide novel insight into the regulation of alternative outgrowth of adipose tissue.
Aging-Associated Vascular Phenotype in Mutant Mice With Low Levels of BubR1
Authors: Matsumoto Takuya , Baker Darren J. , d’Uscio Livius V. , Mozammel Gazi , Katusic Zvonimir S. , van Deursen Jan M.
Published: February 2007

Background and Purpose—

Aging is a major risk for stroke and a highly complex biological process believed to involve multiple mechanisms. Mutant mice that express low levels of the spindle assembly checkpoint protein BubR1 are known to develop several aging-associated phenotypes at a very young age, including cataracts, lordokyphosis, loss of subcutaneous fat, and impaired wound healing. However, whether BubR1 acts to prevent vascular aging has not yet been established. The present study was designed to investigate the vascular phenotype of mutant mice with low levels of BubR1.

Methods—

Morphological, functional, and biochemical analyses were performed on aortas and carotid arteries of 3- to 5-month-old BubR1 mutant mice and wild-type littermates.

Results—

Arterial wall thickness and inner diameter were significantly reduced in BubR1 mutant mice. Arterial walls of BubR1 mutant mice had low numbers of medial smooth muscle cells. Masson trichrome staining showed profound fibrosis in arterial walls of BubR1 mutant. In agreement with these morphological changes, functional analysis of pressurized isolated carotid arteries of BubR1 mutant mice demonstrated reduced elastic properties. Endothelium-dependent relaxations to acetylcholine and endothelium-independent relaxations to the nitric oxide donor DEA-NONOate were significantly reduced in carotid arteries of BubR1 mutant mice. Furthermore, enzymatic activity of nitric oxide synthase and levels of cyclic GMP were significantly reduced in aortas of mutant mice, but production of superoxide anions was significantly increased.

Conclusions—

These findings demonstrate that BubR1 insufficiency in mice results in phenotypic changes reminiscent of vascular aging in humans and suggest a role for BubR1 in suppressing the vascular aging process.
Lecithinized Superoxide Dismutase Improves Outcomes and Attenuates Focal Cerebral Ischemic Injury via Antiapoptotic Mechanisms in Rats
Authors: Tsubokawa Tamiji , Jadhav Vikram , Solaroglu Ihsan , Shiokawa Yoshiaki , Konishi Yoshifumi , Zhang John H.
Published: February 2007

Background and Purpose—

Recent studies have shown the antiapoptotic neuroprotective effects of lecithinized superoxide dismutase (PC-SOD) in different forms of brain injury. We tested the effects of PC-SOD in focal cerebral ischemia in the rat middle cerebral artery occlusion model (MCAO).

Methods—

Adult male Sprague-Dawley rats were treated with PC-SOD (0.3, 1.0, and 3.0 mg/kg) administered intravenously after 90 minutes of occlusion (beginning of reperfusion). Physiological parameters, neurological score, and infarct volume were assessed at 24 and 72 hours in 3 groups of animals: sham-operated (n=18), MCAO treated with vehicle (n=26), and MCAO treated with PC-SOD (n=37). Oxidative stress was evaluated by malondialdehyde assay, and the apoptotic mechanisms were studied by Western blotting.

Results—

PC-SOD treatment significantly reduced infarct volume and improved neurological scores at different time points compared with the vehicle-treated group. PC-SOD treatment decreased malondialdehyde levels, cytochrome
c
, and cleaved caspase 3 expression and increased mitochondrial Bcl-2 expression.

Conclusions—

Inhibition of oxidative stress with PC-SOD treatment improves outcomes after focal cerebral ischemia. This neuroprotective effect is likely exerted by antiapoptotic mechanisms.
Arterial Stiffness, Cognitive Decline, and Risk of Dementia
Authors: Poels Mariëlle M.F. , van Oijen Marieke , Mattace-Raso Francesco U.S. , Hofman Albert , Koudstaal Peter J. , Witteman Jacqueline C.M. , Breteler Monique M.B.
Published: February 2007

Background and Purpose—

Arterial stiffness is associated with an increased risk of myocardial infarction and stroke, independent of classical vascular risk factors. Vascular factors and stroke are associated with cognitive function and dementia. We examined whether arterial stiffness was independently associated with cognitive function and dementia.

Methods—

The present study was based on the Rotterdam Study, a prospective population-based cohort study ongoing since 1990. During the third examination (1997–1999) arterial stiffness was measured by assessment of pulse wave velocity and carotid distensibility. Cognitive function was assessed during the third and fourth examination (2002–2004) with a neuropsychological test battery. We used linear and logistic regression to estimate the association of arterial stiffness with cognitive function and cognitive decline. From the third examination until January 1, 2005, we identified 156 incident dementia cases. Cox proportional hazard models were used to estimate the association between arterial stiffness and the risk of dementia.

Results—

After adjustment for cardiovascular risk factors we found an association of increased pulse wave velocity with poorer performance on the Stroop test (adjusted β-coefficient [95% confidence interval] 1.13 [0.26 to 1.99] per standard deviation increase in pulse wave velocity) but not with performance on other cognitive tests. No associations were found between measures of arterial stiffness and cognitive decline or risk of dementia after adjustment for cardiovascular factors.

Conclusions—

We did not identify arterial stiffness as an independent risk factor of cognitive decline or risk of dementia.