bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone marrow versus thymic pathways of natural killer cell development
Authors: Di Santo James P. , Vosshenrich Christian A. J.
Published: November 2006

Summary:  Understanding natural killer (NK) cell developmental pathways is crucial for harnessing the potential therapeutic benefits of this specialized lymphocyte subset. The bone marrow (BM) plays a major role in NK cell development, providing the appropriate environmental cues for NK cell commitment and subsequent NK cell differentiation. Nevertheless, the molecular signals provided in this context remain enigmatic. It is widely assumed that BM seeds the periphery with NK cells. However, the precise origins of NK cells found in lymphoid organs and tissues are not defined. Recently, we found that thymic NK cells bear molecular markers and functional attributes that distinguish them from most peripheral NK cells. We find that NK cells are actively exported from the thymus to the periphery, suggesting that thymus‐derived NK cells may have unique roles both intrathymically and in secondary lymphoid organs. Here we compare the properties of thymic NK cells with properties of other NK cell subsets that have been identified in the mouse. We propose that heterogeneity in NK cell function can be achieved through distinct thymic and bone marrow pathways of NK cell development.
Dissecting natural killer cell activation pathways through analysis of genetic mutations in human and mouse
Authors: Tassi Ilaria , Klesney‐Tait Julia , Colonna Marco
Published: November 2006

Summary:  Natural killer (NK) cell cytotoxicity is mediated by multiple germ line‐encoded activating receptors that recognize specific ligands expressed by tumor cells and virally infected cells. These activating receptors are opposed by NK inhibitory receptors, which recognize major histocompatibility complex class I molecules on potential targets, raising the threshold for NK cell activation. Once an abnormal cell has been detected, NK cells are the sentinel source of cytolytic mediators, such as granzymes and perforins, as well as interferon‐γ, which can polarize the immune response to a T‐helper 1 cell type. Activation signals are transmitted by adhesion‐dependent pathways, immunoreceptor tyrosine‐based activation motif (ITAM)‐dependent pathways, DAP10 ITAM‐independent pathways, and by signaling through immunoreceptor tyrosine‐based switch motifs. These pathways activate downstream signaling partners to trigger NK cell cytotoxicity. Some of these downstream molecules are unique to the various pathways, and some of these molecules are shared. Because of the complexity of signals involved in NK cell–target cell interaction, the generation of mice with targeted mutations in signaling molecules involved in adhesion, activation, or inhibition is essential for a precise dissection of the mechanisms regulating NK cell effector functions. Here we review recent advances in the genetic analysis of the signaling pathways that mediate NK cell killing.
Cloning and identification of EDD gene from ultraviolet‐irradiated HaCaT cells
Authors: Gupta Nishma , Chakrobarty Amit , Raman Govindarajan , Banerjee Gautam
Published: November 2006

Ultraviolet (UV) radiation is one of the most important external stimuli that affects skin by inducing cancer, inflammation and cell death. To identify the regulation of genes regulated by UV during transformation, normal human keratinocyte cell line, HaCaT, was exposed to multiple doses of UVA+B (UVA – 150–200 mJ/cm2 and UVB – 15–20 mJ/cm2× 6). Malignant transformation was confirmed by formation of colonies on soft agar and DNA methylation assay. To identify the genes involved in this process, random amplification of polymorphic DNA using RNA from unexposed and multiple exposed cells was performed after each exposure. A few up‐regulated genes were identified, cloned and sequenced. One of the genes had homology to EDD (E3 identified by differential display) that was up‐regulated at second exposure but was down‐regulated in colony‐forming cells (cells that received six or more exposures) as determined by RT‐PCR. This is a progesterone‐induced gene and progesterone treatment reduced the extent of colony formation on soft agar plate. It is possible that hormone therapy may have some effects on skin cancer in vivo.
Who chooses anterior cruciate ligament reconstruction and why? A 2‐year prospective study
Authors: Swirtun L. R. , Eriksson K. , Renström P.
Published: November 2006

The purpose of this study was to investigate possible differences in age, gender, Tegner activity level prior to injury, knee joint laxity and the variables evaluated with knee osteoarthritis outcome score (KOOS) between patients who chose non‐operative treatment (NT), early reconstruction (ER) and late reconstruction (LR). A second aim was to study whether patients who choose ER choose surgical treatment for the same reasons as patients who choose LR. Seventy‐two patients with an acute (< 1 month) anterior cruciate ligament (ACL) tear, who had not yet decided to have surgery, were included in this study. They filled out the Tegner activity score, assessing preinjury activity level, KOOS and underwent KT–1000 arthrometer examination. The 36 subjects who later chose reconstruction were questioned about reasons for their decision. A high preinjury activity level was associated with the choice of ACL reconstruction, but the choice of treatment was not associated with age, gender or the outcome variables measured with KOOS or KT‐1000. Fifteen out of the 20 (75%) subjects who chose ER based their decision on assumptions of future problems and not on experience of knee function. Fourteen out of 16 (88%) subjects, who chose reconstructive surgery later, based their decision on experience of knee function.
Tendinopathy and Doppler activity: the vascular response of the achilles tendon to exercise
Authors: Boesen M. I. , Koenig M. J. , Torp‐Pedersen S. , Bliddal H. , Langberg H.
Published: November 2006

Background:Intratendinous Doppler activity has been interpreted as an equivalent of neovessels in the Achilles tendon and as a sign of tendinosis (AT).

Aim:To evaluate the vascular response as indicated by color Doppler activity after repeated loading of both symptomatic and non‐symptomatic Achilles tendons.

Material and methods:Ten non‐trained, healthy subjects ran 5 km. Ultrasound (US) Doppler activity was determined before and after the exercise. Eleven patients with chronic AT performed 3 × 15 heavy‐load eccentric exercise. The Achilles tendons were scanned before and immediately after the exercise.

Results:Non‐symptomatic: six Achilles tendons in five subjects had intratendinous Doppler activity before the exercise. All but two subjects (80%) had intratendinous Doppler activity after running. Symptomatic: all patients had Doppler activity in the tendons, with a median color fraction before eccentric exercise of 0.05 (range 0.01–0.33). The Doppler activity did not disappear after exercise. Tendons with a color fraction below the median at baseline increased significantly after the exercise (P=0.02).

Conclusion:The mere presence of Doppler in the Achilles tendon does notper seindicate disease. Eccentric exercise does not extinguish the flow during or after one training session in patients with chronic AT.
A capsular incision leads to a fast osteoarthritic response, but also elevated levels of activated osteogenic protein‐1 in rabbit knee joint cartilage
Authors: Fahlgren A. , Chubinskaya S. , Messner K. , Aspenberg P.
Published: November 2006

We studied whether a small capsular incision alone, or combined with meniscectomy could induce early osteoarthritic changes in the rabbit knee.

Thirty‐one rabbits were operated on with a capsular incision in the left knee and meniscectomy in the right knee. Another 12 rabbits were used as controls. The rabbits were killed 3, 6 and 12 weeks after surgery. Osteoarthritic changes in the articular cartilage were evaluated by the modified Mankin score. The subchondral bone was evaluated by scintimetry (99mTc‐HDP) and semiquantitative grading of histological changes. Osteogenic protein (OP‐1) in its mature and pro‐form was examined by immunohistochemistry.

Both a capsular incision and meniscectomy induced articular cartilage fibrillation and increased bone metabolic activity during the initial weeks after surgery. Capsular incision led to lesser changes than meniscectomy. Mature OP‐1 was elevated, and its pro‐form reduced, in meniscectomized knees. A similar pattern was observed in knees with capsular incision.

Already 3 weeks after surgery, the articular cartilage and subchondral bone showed typical signs of early osteoarthritis (OA), and a reparative response was suggested by increased intensity of OP‐1 staining. As these signs were also found in knees with capsular incision only, it appears that trauma‐related factors such as increased bleeding and inflammation are critical for the development of OA.
Motivation for physical activity of psychiatric patients when physical activity was offered as part of treatment
Authors: Sørensen M.
Published: November 2006

This study examined motivation variables, self‐determination and self‐schema, in relation to physical activity, among psychiatric patients with experience with physical activity as part of their treatment. Participants were patients (N=109) from 15 psychiatric hospitals or day‐care institutions. Data were collected by questionnaires. A positive relationship between physical activity level, positive experiences of the activity and higher degree of self‐determination and exercise self‐schema was expected. Intrinsically regulated motives (motivated by the experience of the activity in itself) were positively and significantly related to physical activity level and the experience of decrease in symptoms during physical activity, and extrinsically regulated motives were negatively correlated with physical activity level. Intrinsically regulated motives gave an odds ratio of 20.0 for being physically active rather than inactive. Holding an exercise self‐schema gave an odds ratio of 6.1 for being physically active. The majority of the patients (57.4%) reported that physical activity decreased their illness symptoms, but a few (11.9%) reported negative effects. The findings demonstrated that psychiatric patients do not differ from the normal population in relation to motivational mechanisms, even if they may experience more barriers to physical activities because of their illness. Therefore, in trying to motivate psychiatric patients, it is important to make physical activity as intrinsically motivating as possible by focusing on the positive experiences of the activity itself, as well as helping to develop an exercise self‐schema.
Sex‐specific characteristics of cardiac function, geometry, and mass in young adult elite athletes
Authors: Petersen S. E. , Hudsmith L. E. , Robson M. D. , Doll H. A. , Francis J. M. , Wiesmann F. , Jung B. A. , Hennig J. , Watkins H. , Neubauer S.
Published: November 2006

PURPOSE: To study young adult elite athletes with age‐ and sex‐matched sedentary controls to assess sex‐specific differences for left ventricular (LV) and right ventricular (RV) volumes and mass as well as for LV contraction and relaxation.

MATERIALS AND METHODS: A total of 23 male athletes (mean age 25±4 years, training 22±7 h/week in rowing, swimming, or triathlon) and 20 female athletes (mean age 24±4 years, training 19±5 h/week in rowing, swimming, or triathlon) and age‐ and sex‐matched sedentary controls (21 males/17 females) underwent cardiovascular magnetic resonance (CMR) imaging (1.5 T). Cardiac phase contrast imaging using a black‐blood k‐space segmented gradient echo sequence was used for analysis of cardiac contraction and relaxation and steady‐state free‐precession cine images were acquired for determination of cardiac volumes and mass.

RESULTS: Male and female athletes showed similar increases in LV and RV volume and mass indices when compared with controls (ranging between 15% and 42%). No sex‐specific differences in training effect on LV and RV volumes, mass indices, and ejection fractions, as well as LV to RV ratios of these volume and mass indices (parameters of balanced LV and RV dilatation and hypertrophy) were observed (all P for interaction >0.05). Similarly, no sex‐specific differences in training effect on cardiac contraction and relaxation were found (all P for interaction >0.05).

CONCLUSION: Young adult elite athletes do not show sex‐specific adaptive structural and functional changes to exercise training in accordance with the benign nature of the hypertrophy associated with athlete's heart.
Parents’ Perceptions of Curricular Issues Affecting Children’s Weight in Elementary Schools
Authors: Murnan Judy , Price James H. , Telljohann Susan K. , Dake Joseph A. , Boardley Debra
Published: November 2006

Abstract: The purpose of this study was to examine Ohio parents’ perceptions of the role of elementary schools in preventing childhood overweight. In the United States, overweight is the most widespread health threat facing children and adolescents. Schools may be a useful point of intervention in addressing the escalating prevalence of childhood overweight because children spend over half their day at school. A questionnaire was developed based primarily on the School Health Index, a tool developed by the Centers for Disease Control and Prevention to help schools assess and improve their physical activity, healthy eating, tobacco use prevention, and safety policies and programs. Seven hundred surveys were sent to a random sample of Ohio parents of elementary school‐aged children. This study (53% response rate) found that the majority (51‐73%) of parents identified 14 items as very important in preventing childhood overweight, which is indicative of their support for these curricular topics within the elementary school. All items from the physical education component had less than 50% of the parents identifying these items as very important. The item that was least supported (16%) by the parents was measuring a child’s body mass index. The majority (51%) of parents indicated their preference for elementary students’ access to vending machines only if they contained nutritious foods and beverages, while 42% of parents preferred that elementary students should not be allowed access to vending machines at all. The findings from this study suggest that Ohio parents would be supportive of school‐based interventions focusing on healthy eating, physical activity, and the school environment to help reduce the prevalence of overweight in elementary children. (J Sch Health. 2006;76(10):502‐511)
Different responses of plants and herbivore insects to a gradient of vegetation height: an indicator of the vertebrate grazing intensity and successional age
Authors: Pöyry Juha , Luoto Miska , Paukkunen Juho , Pykälä Juha , Raatikainen Katja , Kuussaari Mikko
Published: November 2006

Empirical studies have suggested that species richness of grassland insects usually decreases under grazing management. By contrast, grazing has been shown to increase the species density and richness of vascular plants, especially on productive soils. In order to test the suggested differences in response to management between plants and insects, we simultaneously studied species richness of vascular plants and their insect herbivores, butterflies and moths, in 68 semi‐natural grasslands with varying grazing intensity and frequency in SW Finland. Species richness of plants and insects was for the first time related to a quantitative measure of disturbance intensity and successional age, mean vegetation height, by using generalized additive models (GAM). The effects of soil nutrients on vegetation height were accounted for by using phosphorus concentration as a productivity surrogate.

The results showed that species richness of butterflies and moths peaked in taller vegetation compared with vascular plants, corresponding to a lower disturbance intensity and increasing time since abandonment. These patterns are discussed in the light of two hypotheses, the “structural diversity hypothesis” and “dynamic equilibrium model” of Huston, both suggesting a weaker disturbance tolerance of insects compared with plants. Butterflies and moths which are specialists in their larval host‐plant use (monophagous and oligophagous species) preferred lower vegetation (higher disturbances) compared with generalists (polyphagous species), as predicted by Huston's model. This difference indicates a stronger relationship with plant species richness for specialist than for generalist butterflies and moths. Our results support the application of regionally and temporally varying grazing intensities in grassland conservation management.
Effect of configuration-dependent intramolecular hydrodynamic interaction on elastocapillary thinning and breakup of filaments of dilute polymer solutions
Authors: Prabhakar R. , Prakash J. Ravi , Sridhar T.
Published: November 2006

We use a new constitutive model for the polymer stress in a dilute polymer solution to predict elastocapillary thinning and breakup of a thin filament of the solution. The constitutive model accounts for the effects of finite chain extensibility and configuration-dependent intramolecular hydrodynamic interaction, and is used in the simple stress balance equation proposed by Entov and Hinch [Entov, V. M., and E. J. Hinch, J. Non-Newtonian Fluid Mech. 72, 31–53 (1997)] for situations where inertial effects are negligible. In their seminal study, Entov and Hinch showed that during the period where the elastic polymer stresses are dominant, the filament radius decreases exponentially with time. We find that configuration-dependent hydrodynamic interactions cause the time constant in this exponential decay to depend on concentration, as observed in recent experiments. Moreover, the phenomenon of coil-stretch hysteresis permits a large polymer stress even though the transient Weissenberg number during elastocapillary thinning decreases below the critical value of 1∕2 for the coil-to-stretch transition of a dilute polymer solution in an extensional flow. As a consequence, the Weissenberg number does not have a lower bound of 2∕3 as predicted originally by Entov and Hinch using a simpler constitutive model that does not account for configuration-dependent hydrodynamic interactions.
Rheology of complex suspensions flocculated by associating polymers
Authors: Kamibayashi Masashi , Ogura Hironao , Otsubo Yasufumi
Published: November 2006

Associating polymers are hydrophilic long-chain molecules containing a small amount of hydrophobic groups (hydrophobes), and behave as flocculants in aqueous suspensions. The effects of associating and nonassociating polymers with molecular weights of about 2.5×104 on the rheological behavior are studied for silica, latex, and mixed suspensions. Because the hydrophobes adsorb onto hydrophobic surfaces and water-soluble chains onto hydrophilic surfaces, two single suspensions are highly flocculated by a bridging mechanism. The complex suspensions which are prepared by mixing the silica and latex suspensions with the associating polymer at the same concentration show a drastic reduction in viscosity. Since the long chains of associating polymer attach to the surface at many points, the adsorption onto silica surfaces is dominant in the complex suspensions. The hydrophobes extending from the chains adsorbed onto silica particles can adsorb onto latex particles. The associating polymer acts as a binder and the hetero-flocculation between silica and latex is induced. The formation of composite particles in which the silica particles are covered with latex particles is primarily responsible for the drastic decrease in viscosity.
Immunostimulatory Effects of the Anionic Alkali Mineral Complex BARODON on Equine Lymphocytes
Authors: Koo HyeCheong , Ryu Seung-Ho , Ahn Hyung Jin , Jung Woo Kyung , Park Young Kyung , Kwon Nam Hoon , Kim So Hyun , Kim Jun Man , Yoo Byung Woo , Choi Soo Il , Davis William C. , Park Yong Ho
Published: November 2006

Previous studies have shown that the anionic alkali mineral complex BARODON has an immunoenhancing effect on pigs as an adjuvant and as a nonspecific immunostimulant. Likewise, the equine immune system has been defined with various monoclonal antibodies specific to equine leukocyte differentiation antigens to determine the possibility of enhancing equine resistance to respiratory diseases and promoting other immunostimulatory effects with the application of BARODON. Compared with the control group, after 3 weeks of treatment, BARODON-treated groups showed higher proportions of cells (P< 0.05) expressing major histocompatibility complex class II and CD2, CD4+, CD4+CD25+, CD8+, and CD8+CD25+T lymphocytes, dendritic cells, and surface immunoglobulin M+B lymphocytes in peripheral blood, as well as enhanced cell proliferative responses with phytohemagglutinin and increased phagocytic activity againstStreptococcus equiandStaphylococcus aureusstrains with high antibiotic resistance, the bacteria frequently identified as etiologic agents of equine respiratory diseases at the Seoul Race Park in Seoul, Korea. This study shows that BARODON may act as an immunostimulator and can be an effective alternative to antimicrobial feed additives for nonspecific improvements in equine immune responses, particularly against respiratory diseases.
Mycobacterium tuberculosis
Malate Synthase- and MPT51-Based Serodiagnostic Assay as an Adjunct to Rapid Identification of Pulmonary Tuberculosis
Authors: Achkar Jacqueline M. , Dong Yuxin , Holzman Robert S. , Belisle John , Kourbeti Irene S. , Sherpa Tsering , Condos Rany , Rom William N. , Laal Suman
Published: November 2006

The 81-kDa malate synthase (MS; Rv 1837c) and the 27-kDa MPT51 (Rv 3803c) of
Mycobacterium tuberculosis
are immunodominant antigens recognized by serum antibodies from ∼80% of human immunodeficiency virus-negative smear-positive tuberculosis patients from India. We now provide evidence that the use of the MS/MPT51-based serodiagnostic assay can serve as an adjunct to sputum microscopy in the rapid diagnosis of pulmonary tuberculosis.
Measurement of Plasma-Derived Substance P: Biological, Methodological, and Statistical Considerations
Authors: Campbell Donald E. , Raftery Nancy , Tustin Richard , Tustin Nancy B. , DeSilvio Michelle L. , Cnaan Avital , Aye Pyone Pyone , Lackner Andrew A. , Douglas Steven D.
Published: November 2006

The undecapeptide substance P (SP) is a member of the tachykinin family of neurotransmitters, which has a pivotal role in the regulation of inflammatory and immune responses. One of the major barriers to the study of the in vivo role of SP in a number of immune disorders is the accurate measurement of SP in fluids. This is reflected in the variability of reported SP levels in serum and plasma of humans in both healthy and diseased states. This study was initiated in order to identify sources of variability by the comparative evaluation of the influences of sample preparation and analytical detection methods on the measurement of SP in plasma. The results indicate that sample preparation (peptide extraction versus no extraction) and the choice of analytical method for SP quantitation may yield significantly different values and may contribute to the variability in SP values reported in the literature. These results further emphasize the need for careful consideration in the selection of methods for SP quantitation, as well as caution in the interpretation and comparison of data reported in the literature.
Validation of a Competitive Enzyme-Linked Immunosorbent Assay for Detection of Antibodies against
Babesia bovis
Authors: Goff Will L. , Molloy John B. , Johnson Wendell C. , Suarez Carlos E. , Pino Ignacio , Rhalem Abdelkebir , Sahibi Hamid , Ceci Luigi , Carelli Grazia , Adams D. Scott , McGuire Travis C. , Knowles Donald P. , McElwain Terry F.
Published: November 2006

A previously developed competitive enzyme-linked immunosorbent assay (cELISA) based on a species-specific, broadly conserved, and tandemly repeated B-cell epitope within the C terminus of rhoptry-associated protein 1 of
Babesia bovis
was refined and validated for use internationally. Receiver operating characteristic analysis revealed an assay with a specificity and positive predictive value of 100% and a sensitivity of 91.1%, with various negative predictive values depending on the level of disease prevalence. The cELISA was distributed to four different laboratories, along with a reference set of 100 defined bovine sera, including known-positive, known-negative, and field samples. Pairwise concordances among the four laboratories ranged from 94% to 88%. Analysis of variance of the resulting optical densities and a test of homogeneity indicated no significant difference among the laboratories. Overall, the cELISA appears to have the attributes necessary for international application.
Recombinant Bovine Herpesvirus 4 (BoHV-4) Expressing Glycoprotein D of BoHV-1 Is Immunogenic and Elicits Serum-Neutralizing Antibodies against BoHV-1 in a Rabbit Model
Authors: Donofrio Gaetano , Cavirani Sandro , Vanderplasschen Alain , Gillet Laurent , Flammini Cesidio Filippo
Published: November 2006

Several biological characteristics of bovine herpesvirus 4 (BoHV-4) make it a good candidate as a gene delivery vector for vaccination purposes. These characteristics include little or no pathogenicity, unlikely oncogenicity, the capability to accommodate large amounts of foreign genetic material, the ability to infect several cell types coming from different animal species, and the ability to maintain transgene expression in both undifferentiated and differentiated cells. Starting from BoHV-4 cloned as a bacterial artificial chromosome (BAC), we used MuA transposase-mediated in vitro transposition to generate recombinant BoHV-4 expressing the immunodominant glycoprotein D (gD) of BoHV-1, one of the most important pathogens of cattle. Although a
cis
-acting element from woodchuck hepatitis virus (the woodchuck hepatitis virus posttranscriptional regulatory element [WPRE]) in the 3′ end of the gD expression cassette was required for maximal gD expression from plasmids in transient transfection assays, this element was not necessary for efficient expression of gD from recombinant BoHV-4 genomes. BoHV-4 recombinants containing gD expression cassettes with or without the WPRE expressed gD at similarly high levels. Several cell lines originating from different animal species expressed gD when infected with BoHV-4 recombinants. When rabbits were immunized with one of the recombinants, high levels of serum neutralizing antibodies against BoHV-1 were generated. This work is one of the first demonstrations of the use BoHV-4 as a vector for vaccine purposes and may provide the basis for BoHV-1 vaccination of cattle with recombinant BoHV-4.
Confirmation of Tick Bite by Detection of Antibody toIxodesCalreticulin Salivary Protein
Authors: Alarcon-Chaidez Francisco , Ryan Raymond , Wikel Stephen , Dardick Kenneth , Lawler Caroline , Foppa Ivo M. , Tomas Patricio , Cushman Alexis , Hsieh Ann , Spielman Andrew , Bouchard Keith R. , Dias Filiciano , Aslanzadeh Jaber , Krause Peter J.
Published: November 2006

Ticks introduce a variety of pharmacologically active molecules into their host during attachment and feeding in order to obtain a blood meal. People who are repeatedly exposed to ticks may develop an immune response to tick salivary proteins. Despite this response, people usually are unaware of having been bitten, especially if they are not repeatedly exposed to ticks. In order to develop a laboratory marker of tick exposure that would be useful in understanding the epidemiology of tick-borne infection and the immune response to tick bite, we developed an enzyme-linked immunosorbent assay (ELISA) to detect antibody to a recombinant form of calreticulin protein found in the salivary glands ofIxodes scapularis, a member of a complex ofIxodesticks that serve as the vectors for Lyme disease, human babesiosis, and human granulocytic anaplasmosis. Using this assay, we tested sera obtained from C3H/HeN and BALB/c mice before and after experimental deer tick infestation. These mice developed antibody toIxodescalreticulin antigen after infestation. We then used the same assay to test sera obtained from people before and after they experienced deer tick bite(s). People experiencing deer tick bite(s) developedIxodescalreticulin-specific antibody responses that persisted for up to 17 months. ThisIxodesrecombinant calreticulin ELISA provides objective evidence of deer tick exposure in people.
Compartmentalization of Interleukin-6 Response in a Patient with Septic Meningococcal Peritonitis
Authors: de Souza Alexandre Leite , Sztajnbok Jaques , Marques Salgado Maristela , Romano Carla C. , das Graças Adelino Alkmin Maria , Duarte Alberto J. S. , Seguro Antonio Carlos
Published: November 2006

We report the first case of
Neisseria meningitidis
-induced septic peritonitis diagnosed by PCR assay of peritoneal fluid. Concentrations of interleukin-6 were notably higher in the peritoneal fluid than in the blood. PCR diagnosis of septic meningococcal peritonitis and the pathogenesis of the disease are discussed.
The Evolution of Genetic Architecture
Authors: Hansen Thomas F.
Published: November 2006

Genetic architecture, the structure of the mapping from genotype to phenotype, determines the variational properties of the phenotype and is instrumental in understanding its evolutionary potential. Throughout most of the history of evolutionary biology, genetic architecture has been treated as a given set of parameters and not as a set of dynamic variables. The past decade has seen renewed interest in incorporating the genotype-phenotype map as a dynamical part of population genetics. This has been aided by several conceptual advances. I review these developments with emphasis on recent theoretical work on the evolution of genetic architecture and evolvability.
Resolution Phase of Inflammation: Novel Endogenous Anti-Inflammatory and Proresolving Lipid Mediators and Pathways
Authors: Serhan Charles N.
Published: November 2006

Resolution of inflammation and the return of tissues to homeostasis are essential. Efforts to identify molecular events governing termination of self-limited inflammation uncovered pathways in resolving exudates that actively generate, from essential omega fatty acids, new families of local-acting mediators. These chemical mediator families, termed resolvins and protectins, are potent stereoselective agonists that control the duration and magnitude of inflammation, joining the lipoxins as signals in resolution. This review examines the mapping of these circuits and recent advances in our understanding of the biosynthesis and actions of these novel proresolving lipid mediators. Aspirin jump-starts resolution by triggering biosynthesis of specific epimers of these mediators. In addition to their origins in inflammation resolution, these compounds also display potent protective roles in neural systems, liver, lung, and eye. Given the potent actions of lipoxins, resolvins, and protectins in models of human disease, deficiencies in resolution pathways may contribute to many diseases and offer exciting new potential for therapeutic control via resolution.
Comparison of endothelial function, O2−· and H2O2 production, and vascular oxidative stress resistance between the longest-living rodent, the naked mole rat, and mice
Authors: Labinskyy Nazar , Csiszar Anna , Orosz Zsuzsanna , Smith Kira , Rivera Aracelie , Buffenstein Rochelle , Ungvari Zoltan
Published: November 2006

Vascular aging is characterized by decreased nitric oxide (NO) bioavailability, oxidative stress, and enhanced apoptotic cell death. We hypothesized that interspecies comparative assesment of vascular function among rodents with disparate longevity may offer insight into the mechanisms determining successful vascular aging. We focused on four rodents that show approximately an order of magnitude range in maximum longevity (ML). The naked mole rat (NMR; Heterocephalus glaber) is the longest-living rodent known (ML > 28 yr), Damara mole rats (DMRs, Cryptomys damarensis; ML ∼ 16 yr) and guinea pigs (GPs, Cavia porcellus; ML ∼ 6 yr) have intermediate longevity, whereas laboratory mice are short living (ML ∼ 3.5 yr). We compared interspecies differences in endothelial function, O2−· and H2O2 production, and resistance to apoptotic stimuli in blood vessels. Sensitivity to acetylcholine-induced, NO-mediated relaxation was smaller in carotid arteries from NMRs, GPs, and DMRs than in mouse vessels. Measurements of production of O2−· (lucigenin chemiluminescence and ethidium bromide fluorescence) and H2O2 (dichlorofluorescein fluorescence) showed that free radical production in vascular endothelial and smooth muscle cells is comparable in vessels of the three longer-living species and in arteries of shorter-living mice. In mouse arteries, H2O2 (from 10−6 to 10−3 mol/l) and heat exposure (42°C for 15–45 min) enhanced apoptotic cell death, as indicated by an increased DNA fragmentation rate and increased caspase 3/7 activity. In NMR vessels, only the highest doses of H2O2 enhanced apoptotic cell death, whereas heat exposure did not increase DNA fragmentation rate. Interspecies comparison showed there is a negative correlation between H2O2-induced apoptotic cell death and ML. Thus endothelial vasodilator function and vascular production of reactive oxygen species do not correlate with maximal lifespan, whereas increased lifespan potential is associated with an increased vascular resistance to proapoptotic stimuli.
Expressional and Epigenetic Alterations of Placental Serine Protease Inhibitors
Authors: Chelbi Sonia T. , Mondon Françoise , Jammes Hélène , Buffat Christophe , Mignot Thérèse-Marie , Tost Jorg , Busato Florence , Gut Ivo , Rebourcet Régis , Laissue Paul , Tsatsaris Vassili , Goffinet François , Rigourd Virginie , Carbonne Bruno , Ferré Françoise , Vaiman Daniel
Published: November 2006

Preeclampsia is the major pregnancy-induced hypertensive disorder. It modifies the expression profile of placental genes, including several serine protease inhibitors (
SERPINs
). The objective of this study was to perform a systematic expression analysis of these genes in normal and pathological placentas and to pinpoint epigenetic alterations inside their promoter regions. Expression of 18 placental
SERPINs
was analyzed by quantitative RT-PCR on placentas from pregnancies complicated by preeclampsia, intrauterine growth restriction, or both and was compared with normal controls.
SERPINA3, A5, A8, B2, B5
, and
B7
presented significant differences in expression in ≥1 pathological situation. In parallel, the methylation status of the CpG islands located in their promoter regions was studied on a sample of control and preeclamptic placentas. Ten
SERPIN
promoters were either totally methylated or totally unmethylated, whereas
SERPINA3, A5
, and
A8
presented complex methylation profiles. For
SERPINA3
, the analysis was extended to 81 samples and performed by pyrosequencing. For the
SERPINA3
CpG island, the average methylation level was significantly diminished in preeclampsia and growth restriction. The hypomethylated CpGs were situated at putative binding sites for developmental and stress response (hypoxia and inflammation) factors. Our results provide one of the first observations of a specific epigenetic alteration in human placental diseases and provide new potential markers for an early diagnosis.
Estimation of 10-Year Risk of Fatal and Nonfatal Ischemic Cardiovascular Diseases in Chinese Adults
Authors: Wu Yangfeng , Liu Xiaoqing , Li Xian , Li Ying , Zhao Liancheng , Chen Zuo , Li Yihe , Rao Xuxu , Zhou Beifan , Detrano Robert , Liu Kiang
Published: November 2006

Background—

Stroke is much more prevalent than coronary heart disease in China; thus, any risk prediction model only for coronary heart disease may not be appropriate in application. Our objective is to develop a cardiovascular risk prediction model appropriate for the Chinese population.

Methods and Results—

Cox proportional hazards regression was used to develop sex-specific optimal 10-year risk prediction models for ischemic cardiovascular disease (ICVD; including ischemic stroke and coronary events) from 17 years of follow-up data from the USA-PRC Collaborative Study of Cardiovascular Epidemiology cohort, in which 9903 participants were followed up every 2 years until 2000, and 371 ICVD events (266 strokes and 105 coronary heart disease events) occurred. The models showed ICVD was positively related to age, systolic blood pressure, serum total cholesterol, body mass index, current smoking status, and diabetes mellitus in both men and women. When the models were applied to the 17 329 participants in the China Multicenter Collaborative Study of Cardiovascular Epidemiology cohort, the areas under the receiver operating characteristic curve were 0.796±0.036 for men and 0.791±0.036 for women. The simplified point score model resulted in similar c statistics. Comparison of the observed with the estimated incidence of ICVD at different risk levels showed satisfactory precision. Meanwhile, application of recalibrated Framingham models significantly overestimated the coronary heart disease risk in both men (by ≈97%) and women (by ≈228%).

Conclusions—

The Cox regression prediction models and simplified point score model have satisfying predictive capability for estimating the 10-year integrated cardiovascular risk in Chinese, in whom stroke is the predominant cardiovascular disease.
Regulated Overexpression of the A
1
-Adenosine Receptor in Mice Results in Adverse but Reversible Changes in Cardiac Morphology and Function
Authors: Funakoshi Hajime , Chan Tung O. , Good Julie C. , Libonati Joseph R. , Piuhola Jarkko , Chen Xiongwen , MacDonnell Scott M. , Lee Ling L. , Herrmann David E. , Zhang Jin , Martini Jeffrey , Palmer Timothy M. , Sanbe Atsushi , Robbins Jeffrey , Houser Steven R. , Koch Walter J. , Feldman Arthur M.
Published: November 2006

Background—

Both the A
1
- and A
3
-adenosine receptors (ARs) have been implicated in mediating the cardioprotective effects of adenosine. Paradoxically, overexpression of both A
1
-AR and A
3
-AR is associated with changes in the cardiac phenotype. To evaluate the temporal relationship between AR signaling and cardiac remodeling, we studied the effects of controlled overexpression of the A
1
-AR using a cardiac-specific and tetracycline-transactivating factor–regulated promoter.

Methods and Results—

Constitutive A
1
-AR overexpression caused the development of cardiac dilatation and death within 6 to 12 weeks. These mice developed diminished ventricular function and decreased heart rate. In contrast, when A
1
-AR expression was delayed until 3 weeks of age, mice remained phenotypically normal at 6 weeks, and >90% of the mice survived at 30 weeks. However, late induction of A
1
-AR still caused mild cardiomyopathy at older ages (20 weeks) and accelerated cardiac hypertrophy and the development of dilatation after pressure overload. These changes were accompanied by gene expression changes associated with cardiomyopathy and fibrosis and by decreased Akt phosphorylation. Discontinuation of A
1
-AR induction mitigated cardiac dysfunction and significantly improved survival rate.

Conclusions—

These data suggest that robust constitutive myocardial A
1
-AR overexpression induces a dilated cardiomyopathy, whereas delaying A
1
-AR expression until adulthood ameliorated but did not eliminate the development of cardiac pathology. Thus, the inducible A
1
-AR transgenic mouse model provides novel insights into the role of adenosine signaling in heart failure and illustrates the potentially deleterious consequences of selective versus nonselective activation of adenosine-signaling pathways in the heart.
Diagnostic Accuracy of Noninvasive Coronary Angiography in Patients After Bypass Surgery Using 64-Slice Spiral Computed Tomography With 330-ms Gantry Rotation
Authors: Ropers Dieter , Pohle Falk-Karsten , Kuettner Axel , Pflederer Tobias , Anders Katharina , Daniel Werner G. , Bautz Werner , Baum Ulrich , Achenbach Stephan
Published: November 2006

Background—

Multidetector computed tomographic angiography (MDCT) has been shown to allow detection of coronary artery bypass graft (CABG) occlusions and stenoses. However, the assessment of native coronary arteries in addition to CABG has thus far not been sufficiently validated.

Methods and Results—

Fifty patients with a total of 138 CABG (34 mammary grafts, 3 radial grafts, 101 venous grafts) were investigated by MDCT (0.6-mm collimation, 32 detector rows, 2 focal points, 330-ms rotation) 9 to 252 months (mean, 106 months) after surgery. CABG and all native coronary arteries with a diameter of >1.5 mm were evaluated for the presence of significant stenoses (≥50% diameter reduction). Results were compared with quantitative coronary angiography. By MDCT, all CABG were evaluable and were correctly classified as occluded (n=38) or patent (n=100). Sensitivity for stenosis detection in patent grafts was 100% (16/16) with a specificity of 94% (79/84). For the per-segment evaluation of native coronary arteries and distal runoff vessels, sensitivity in evaluable segments (91%) was 86% (87/101) with a specificity of 76% (354/465). If evaluation was restricted to nongrafted arteries and distal runoff vessels, sensitivity was 86% (38/44) with a specificity of 90% (302/334). On a per-patient basis, classifying patients with at least 1 detected stenosis in a CABG, a distal runoff vessel, or a nongrafted artery or with at least 1 unevaluable segment as “positive,” MDCT yielded a sensitivity of 97% (35/36) and specificity of 86% (12/14).

Conclusions—

We found that 64-slice MDCT permits the evaluation of bypass grafts and the assessment of the native coronary arteries for the presence of stenosis.
Estrogen Receptors α and β Mediate Contribution of Bone Marrow–Derived Endothelial Progenitor Cells to Functional Recovery After Myocardial Infarction
Authors: Hamada Hiromichi , Kim Myeong Kon , Iwakura Atsushi , Ii Masaaki , Thorne Tina , Qin Gangjian , Asai Jun , Tsutsumi Yoshiaki , Sekiguchi Haruki , Silver Marcy , Wecker Andrea , Bord Evelyn , Zhu Yan , Kishore Raj , Losordo Douglas W.
Published: November 2006

Background—

Estradiol (E
2
) modulates the kinetics of circulating endothelial progenitor cells (EPCs) and favorably affects neovascularization after ischemic injury. However, the roles of estrogen receptors α (ERα) and β (ERβ) in EPC biology are largely unknown.

Methods and Results—

In response to E
2
, migration, tube formation, adhesion, and estrogen-responsive element–dependent gene transcription activities were severely impaired in EPCs obtained from ERα-knockout mice (ERαKO) and moderately impaired in ERβKO EPCs. The number of ERαΚΟ EPCs (42.4±1.5;
P
<0.001) and ERβKO EPCs (55.4±1.8;
P
=0.03) incorporated into the ischemic border zone was reduced as compared with wild-type (WT) EPCs (72.5±1.3). In bone marrow transplantation (BMT) models, the number of mobilized endogenous EPCs in E
2
-treated mice was significantly reduced in ERαKO BMT (WT mice transplanted with ERαKO bone marrow) (2.03±0.18%;
P
=0.004 versus WT BMT) and ERβKO BMT (2.62±0.07%;
P
=0.02 versus WT) compared with WT BMT (2.87±0.13%) (WT to WT BMT as control) mice. Capillary density at the border zone of ischemic myocardium also was significantly reduced in ERαKO BMT and ERβKO BMT compared with WT mice (WT BMT, 1718±75/mm
2
; ERαKO BMT, 1107±48/mm
2
; ERβKO BMT, 1567±50/mm
2
). ERα mRNA was expressed more abundantly on EPCs compared with ERβ. Moreover, vascular endothelial growth factor was significantly downregulated on ERαKO EPCs compared with WT EPCs both in vitro and in vivo.

Conclusions—

Both ERα and ERβ contribute to E
2
-mediated EPC activation and tissue incorporation and to preservation of cardiac function after myocardial infarction. ERα plays a more prominent role in this process. Moreover, ERα contributes to upregulation of vascular endothelial growth factor, revealing possible mechanisms of an effect of E
2
on EPC biology. Finally, these data provide additional evidence of the importance of bone marrow–derived EPC phenotype in ischemic tissue repair.
Impaired Chronotropic and Vasodilator Reserves Limit Exercise Capacity in Patients With Heart Failure and a Preserved Ejection Fraction
Authors: Borlaug Barry A. , Melenovsky Vojtech , Russell Stuart D. , Kessler Kristy , Pacak Karel , Becker Lewis C. , Kass David A.
Published: November 2006

Background—

Nearly half of patients with heart failure have a preserved ejection fraction (HFpEF). Symptoms of exercise intolerance and dyspnea are most often attributed to diastolic dysfunction; however, impaired systolic and/or arterial vasodilator reserve under stress could also play an important role.

Methods and Results—

Patients with HFpEF (n=17) and control subjects without heart failure (n=19) generally matched for age, gender, hypertension, diabetes mellitus, obesity, and the presence of left ventricular hypertrophy underwent maximal-effort upright cycle ergometry with radionuclide ventriculography to determine rest and exercise cardiovascular function. Resting cardiovascular function was similar between the 2 groups. Both had limited exercise capacity, but this was more profoundly reduced in HFpEF patients (exercise duration 180±71 versus 455±184 seconds; peak oxygen consumption 9.0±3.4 versus 14.4±3.4 mL · kg
−1
· min
−1
; both
P
<0.001). At matched low-level workload, HFpEF subjects displayed ≈40% less of an increase in heart rate and cardiac output and less systemic vasodilation (all
P
<0.05) despite a similar rise in end-diastolic volume, stroke volume, and contractility. Heart rate recovery after exercise was also significantly delayed in HFpEF patients. Exercise capacity correlated with the change in cardiac output, heart rate, and vascular resistance but not end-diastolic volume or stroke volume. Lung blood volume and plasma norepinephrine levels rose similarly with exercise in both groups.

Conclusions—

HFpEF patients have reduced chronotropic, vasodilator, and cardiac output reserve during exercise compared with matched subjects with hypertensive cardiac hypertrophy. These limitations cannot be ascribed to diastolic abnormalities per se and may provide novel therapeutic targets for interventions to improve exercise capacity in this disorder.