bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune Reconstitution during Pneumocystis Lung Infection: Disruption of Surfactant Component Expression and Function by S-Nitrosylation
Authors: Atochina-Vasserman Elena N. , Gow Andrew J. , Abramova Helen , Guo Chang-Jiang , Tomer Yaniv , Preston Angela M. , Beck James M. , Beers Michael F.
Published: February 2009

Pneumocystis pneumonia (PCP), the most common opportunistic pulmonary infection associated with HIV infection, is marked by impaired gas exchange and significant hypoxemia. Immune reconstitution disease (IRD) represents a syndrome of paradoxical respiratory failure in patients with active or recently treated PCP subjected to immune reconstitution. To model IRD, C57BL/6 mice were selectively depleted of CD4+ T cells using mAb GK1.5. Following inoculation with Pneumocystis murina cysts, infection was allowed to progress for 2 wk, GK1.5 was withdrawn, and mice were followed for another 2 or 4 wk. Flow cytometry of spleen cells demonstrated recovery of CD4+ cells to >65% of nondepleted controls. Lung tissue and bronchoalveolar lavage fluid harvested from IRD mice were analyzed in tandem with samples from CD4-depleted mice that manifested progressive PCP for 6 wks. Despite significantly decreased pathogen burdens, IRD mice had persistent parenchymal lung inflammation, increased bronchoalveolar lavage fluid cellularity, markedly impaired surfactant biophysical function, and decreased amounts of surfactant phospholipid and surfactant protein (SP)-B. Paradoxically, IRD mice also had substantial increases in the lung collectin SP-D, including significant amounts of an S-nitrosylated form. By native PAGE, formation of S-nitrosylated SP-D in vivo resulted in disruption of SP-D multimers. Bronchoalveolar lavage fluid from IRD mice selectively enhanced macrophage chemotaxis in vitro, an effect that was blocked by ascorbate treatment. We conclude that while PCP impairs pulmonary function and produces abnormalities in surfactant components and biophysics, these responses are exacerbated by IRD. This worsening of pulmonary inflammation, in response to persistent Pneumocystis Ags, is mediated by recruitment of effector cells modulated by S-nitrosylated SP-D.
IFN-β Impairs Superoxide-Dependent Parasite Killing in Human Macrophages: Evidence for a Deleterious Role of SOD1 in Cutaneous Leishmaniasis
Authors: Khouri Ricardo , Bafica André , Silva Maria da Purificação Pereira , Noronha Almerio , Kolb Jean-Pierre , Wietzerbin Juana , Barral Aldina , Barral-Netto Manoel , Van Weyenbergh Johan
Published: February 2009

Type I IFNs (IFN-α/β) have only recently gained considerable attention as immunomodulators in nonviral infectious diseases. IFN-β has been shown to protect, in a NO-dependent manner, against murine Old World leishmaniasis caused by Leishmania major, but data in New World leishmaniasis are lacking. We found that IFN-β dose-dependently increases parasite burden in Leishmania amazonensis- as well as Leishmania braziliensis-infected human macrophages, independent of endogenous or exogenous NO. However, IFN-β significantly reduced superoxide release in Leishmania-infected as well as uninfected human macrophages. This decrease in superoxide production was paralleled by a significant IFN-β-mediated increase in superoxide dismutase 1 (SOD1) protein levels. Additionally, IFN-β inhibition of leishmanicidal activity was mimicked by SOD1 and antagonized by either pharmacological or small interfering RNA-mediated inhibition of SOD1. Finally, pronounced SOD1 expression in situ was demonstrated in biopsies from New World cutaneous leishmaniasis patients. These findings reveal a hitherto unknown IFN-β/SOD1 axis in Leishmania infection and suggest that inhibition of SOD-associated pathways could serve as strategy in the treatment of L. amazonensis as well as L. braziliensis infection, major human pathogens.
Accelerated Pathological and Clinical Nephritis in Systemic Lupus Erythematosus-Prone New Zealand Mixed 2328 Mice Doubly Deficient in TNF Receptor 1 and TNF Receptor 2 via a Th17-Associated Pathway
Authors: Jacob Noam , Yang Haitao , Pricop Luminita , Liu Yi , Gao Xiaoni , Zheng Song Guo , Wang Juhua , Gao Hua-Xin , Putterman Chaim , Koss Michael N. , Stohl William , Jacob Chaim O.
Published: February 2009

TNF-α has both proinflammatory and immunoregulatory functions. Whereas a protective role for TNF administration in systemic lupus erythematosus (SLE)-prone (New Zealand Black × New Zealand White)F1 mice has been established, it remains uncertain whether this effect segregates at the individual TNFR. We generated SLE-prone New Zealand Mixed 2328 mice genetically deficient in TNFR1, in TNFR2, or in both receptors. Doubly-deficient mice developed accelerated pathological and clinical nephritis with elevated levels of circulating IgG anti-dsDNA autoantibodies and increased numbers of CD4+ T lymphocytes, especially activated memory (CD44highCD62Llow) CD4+ T cells. We show that these cells expressed a Th17 gene profile, were positive for IL-17 intracellular staining by FACS, and produced exogenous IL-17 in culture. In contrast, immunological, pathological, and clinical profiles of mice deficient in either TNFR alone did not differ from those in each other or from those in wild-type controls. Thus, total ablation of TNF-α-mediated signaling was highly deleterious to the host in the New Zealand Mixed 2328 SLE model. These observations may have profound ramifications for the use of TNF and TNFR antagonists in human SLE and related autoimmune disorders, as well as demonstrate, for the first time, the association of the Th17 pathway with an animal model of SLE.
High-Affinity IgE Recognition of a Conformational Epitope of the Major Respiratory Allergen Phl p 2 As Revealed by X-Ray Crystallography
Authors: Padavattan Sivaraman , Flicker Sabine , Schirmer Tilman , Madritsch Christoph , Randow Stefanie , Reese Gerald , Vieths Stefan , Lupinek Christian , Ebner Christof , Valenta Rudolf , Markovic-Housley Zora
Published: February 2009

We report the three-dimensional structure of the complex between the major respiratory grass pollen allergen Phl p 2 and its specific human IgE-derived Fab. The Phl p 2-specific human IgE Fab has been isolated from a combinatorial library constructed from lymphocytes of a pollen allergic patient. When the variable domains of the IgE Fab were grafted onto human IgG1, the resulting Ab (huMab2) inhibited strongly the binding of allergic patients’ IgE to Phl p 2 as well as allergen-induced basophil degranulation. Analysis of the binding of the allergen to the Ab by surface plasmon resonance yielded a very low dissociation constant (KD = 1.1 × 10−10 M), which is similar to that between IgE and Fcε;RI. The structure of the Phl p 2/IgE Fab complex was determined by x-ray crystallography to 1.9 Å resolution revealing a conformational epitope (876 Å2) comprised of the planar surface of the four-stranded anti-parallel β-sheet of Phl p 2. The IgE-defined dominant epitope is discontinuous and formed by 21 residues located mostly within the β strands. Of the 21 residues, 9 interact directly with 5 of the 6 CDRs (L1, L3, H1, H2, H3) of the IgE Fab predominantly by hydrogen bonding and van der Waals interactions. Our results indicate that IgE Abs recognize conformational epitopes with high affinity and provide a structural basis for the highly efficient effector cell activation by allergen/IgE immune complexes.
Plasma Osteopontin Modulates Chronic Restraint Stress-Induced Thymus Atrophy by Regulating Stress Hormones: Inhibition by an Anti-Osteopontin Monoclonal Antibody
Authors: Wang Kathryn X. , Shi Yufang F. , Ron Yacov , Kazanecki Christian C. , Denhardt David T.
Published: February 2009

Osteopontin (OPN) is a cytokine implicated in mediating responses to certain stressors, including mechanical, oxidative, and cellular stress. However, the involvement of OPN in responding to other physical and psychological stress is largely unexplored. Our previous research revealed that OPN is critical for hind limb-unloading induced lymphoid organ atrophy through modulation of corticosteroid production. In this study, we demonstrate that OPN−/− mice are resistant to chronic restraint stress (CRS)-induced lymphoid (largely thymus) organ atrophy; additionally, the stress-induced up-regulation of corticosterone production is significantly reduced in OPN−/− mice. Underlying this observation is the fact that normal adrenocorticotropic hormone levels are substantially reduced in the OPN−/− mice. Our data demonstrate both that injection of OPN into OPN-deficient mice enhances the CRS-induced lymphoid organ atrophy and that injection of a specific anti-OPN mAb (2C5) into wild-type mice ameliorates the CRS-induced organ atrophy; changes in corticosterone levels were also partially reversed. These studies reveal that circulating OPN plays a significant role in the regulation of the hypothalamus-pituitary-adrenal axis hormones and that it augments CRS-induced organ atrophy.
A Specific Epitope of Protein Inhibitor of Activated STAT3 Is Responsible for the Induction of Apoptosis in Rat Transformed Mast Cells
Authors: Yagil Zohar , Kay Gillian , Nechushtan Hovav , Razin Ehud
Published: February 2009

Protein inhibitor of activated STAT3 (PIAS3) functions in vivo as a key molecule in suppressing the transcriptional activity of both microphthalmia transcription factor (MITF) and STAT3, two transcription factors that play a major role in the development, phenotypic expression, and survival of mast cells and melanocytes. In the present study we have investigated the role played by PIAS3 in the regulation of cell cycle in mast cells and melanocytes. We have characterized the biological role of a 23-aa domain derived from PIAS3 that induces apoptosis in these cells by inhibiting the transcriptional activity of both MITF and STAT3. This PIAS3 inhibitor peptide could serve as the beginning of an in depth study for the development of peptide inhibitors for MITF and STAT3.
A Kinase-Dead Allele of Lyn Attenuates Autoimmune Disease Normally Associated with Lyn Deficiency
Authors: Verhagen Anne M. , Wallace Morgan E. , Goradia Ankita , Jones Sarah A. , Croom Hayley A. , Metcalf Donald , Collinge Janelle E. , Maxwell Mhairi J. , Hibbs Margaret L. , Alexander Warren S. , Hilton Douglas J. , Kile Benjamin T. , Starr Robyn
Published: February 2009

Lyn kinase, a member of the Src family of tyrosine kinases, functions as both a positive and negative regulator of B cell activation. In the absence of Lyn, BCR signaling is unregulated, leading to perturbed B cell development, hyperactive B cells, and lethal Ab-mediated autoimmune disease. We have generated a mutant mouse pedigree, termed Mld4, harboring a novel mutation in the gene encoding Lyn, which renders the protein devoid of kinase activity. Despite similarities between the phenotypes of LynMld4/Mld4 and Lyn−/− mice, the spectrum of defects in LynMld4/Mld4 mice is less severe. In particular, although defects in the B cell compartment are similar, splenomegaly, myeloid expansion, and autoantibody production, characteristic of Lyn−/− mice, are absent or mild in LynMld4/Mld4 mice. Critically, immune complex deposition and complement activation in LynMld4/Mld4 glomeruli do not result in fulminant glomerulonephritis. Our data suggest that BCR hypersensitivity is insufficient for the development of autoimmune disease in Lyn−/− mice and implicate other cell lineages, particularly proinflammatory cells, in autoimmune disease progression. Furthermore, our results provide evidence for an additional role for Lyn kinase, distinct from its catalytic activity, in regulating intracellular signaling pathways.
Resistin-Like Molecule α Decreases Glucose Tolerance during Intestinal Inflammation
Authors: Munitz Ariel , Seidu Luqman , Cole Eric T. , Ahrens Richard , Hogan Simon P. , Rothenberg Marc E.
Published: February 2009

Resistin-like molecule α (Relm-α) is a secreted cysteine-rich protein belonging to a newly defined family of proteins, including resistin, Relm-β, and Relm-γ. Resistin was initially defined based on its insulin resistance activity, but the family members are highly up-regulated in various inflammatory states, especially those involving intestinal inflammation. In this study, we report the role of Relm-α at baseline and following an experimental model of colitis. Relm-α was readily detected in the serum at baseline (4–5 ng/ml), and its level was regulated by energy uptake. Retnla−/− mice had decreased baseline circulating leptin levels, but displayed normal glucose, glucose clearance, and insulin levels. Following exposure to the oral innate trigger dextran sodium sulfate (DSS), a nonredundant proinflammatory role for Relm-α was uncovered as Retnla−/− mice were markedly protected from DSS-induced disease activity and histopathological features. Relm-α regulated eosinophil-directed cytokines (e.g., IL-5, CCL11/eotaxin-1, and CCL5/RANTES) and IL-17 ex vivo. Consistently, DSS-treated Retnla−/− mice displayed substantially decreased eosinophil accumulation and decreased phosphorylation of NF-κB, ERK1/2, and p38 in macrophages and eosinophils. Following DSS exposure, serum level of Relm-α was up-regulated, and DSS-treated Retnla−/− mice were markedly protected from hyperglycemia induced by glucose injection independent of changes in insulin levels. Retnla−/− mice were protected from increases in gut hormone serum levels of gastric inhibitory polypeptide and peptide YY that were induced following DSS treatment. These findings demonstrate a central proinflammatory role for Relm-α in the regulation of colonic inflammation and a novel link between colonic injury, glucose tolerance, and energy intake.
A Synthetic Carbohydrate-Protein Conjugate Vaccine Candidate against Shigella flexneri 2a Infection
Authors: Phalipon Armelle , Tanguy Myriam , Grandjean Cyrille , Guerreiro Catherine , Bélot Frédéric , Cohen Dani , Sansonetti Philippe J. , Mulard Laurence A.
Published: February 2009

The protective Ag of Shigella, the Gram-negative enteroinvasive bacterium causing bacillary dysentery, or shigellosis, is its O-specific polysaccharide (O-SP) domain of the LPS, the major bacterial surface component. As an alternative to the development of detoxified LPS-based conjugate vaccines, recent effort was put into the investigation of neoglycoproteins encompassing synthetic oligosaccharides mimicking the protective Ags of the O-SP. We previously reported that when coupled to tetanus toxoid via single point attachment, a synthetic pentadecasaccharide representing three biological repeating units of the O-SP of Shigella flexneri 2a (SF2a), one of the most common Shigella serotypes, elicits a better serum anti-LPS 2a Ab response in mice than shorter synthetic O-SP sequences. In this study, we show that the pentadecasaccharide-induced anti-LPS 2a Abs protect passively administered naive mice from Shigella infection. Therefore, this three repeating units sequence, which is recognized by anti-SF2a sera from infected patients, acts as a functional mimic of the native polysaccharide Ag. Analyses of parameters influencing immunogenicity revealed that an investigational SF2a vaccine displaying a pentadecasaccharide:tetanus toxoid molar loading of 14:1 triggers a high and sustained anti-LPS Ab response, without inducing anti-linker Ab, when administered four times at a dose corresponding to 1 μg of carbohydrate. In addition, the profile of the anti-LPS Ab response, dominated by IgG1 production (Th2-type response), mimics that observed in human upon natural SF2a infection. This synthetic carbohydrate-based conjugate may be a candidate for a SF2a vaccine.
Allergic Airway Hyperresponsiveness-Enhancing γδ T Cells Develop in Normal Untreated Mice and Fail to Produce IL-4/13, Unlike Th2 and NKT Cells
Authors: Jin Niyun , Roark Christina L. , Miyahara Nobuaki , Taube Christian , Aydintug M. Kemal , Wands J. M. , Huang Yafei , Hahn Youn-Soo , Gelfand Erwin W. , O'Brien Rebecca L. , Born Willi K.
Published: February 2009

Allergic airway hyperresponsiveness (AHR) in OVA-sensitized and challenged mice, mediated by allergen-specific Th2 cells and Th2-like invariant NKT (iNKT) cells, develops under the influence of enhancing and inhibitory γδ T cells. The AHR-enhancing cells belong to the Vγ1+ γδ T cell subset, cells that are capable of increasing IL-5 and IL-13 levels in the airways in a manner like Th2 cells. They also synergize with iNKT cells in mediating AHR. However, unlike Th2 cells, the AHR enhancers arise in untreated mice, and we show here that they exhibit their functional bias already as thymocytes, at an HSAhigh maturational stage. In further contrast to Th2 cells and also unlike iNKT cells, they could not be stimulated to produce IL-4 and IL-13, consistent with their synergistic dependence on iNKT cells in mediating AHR. Mice deficient in IFN-γ, TNFRp75, or IL-4 did not produce these AHR-enhancing γδ T cells, but in the absence of IFN-γ, spontaneous development of these cells was restored by adoptive transfer of IFN-γ-competent dendritic cells from untreated donors. The i.p. injection of OVA/aluminum hydroxide restored development of the AHR enhancers in all of the mutant strains, indicating that the enhancers still can be induced when they fail to develop spontaneously, and that they themselves need not express TNFRp75, IFN-γ, or IL-4 to exert their function. We conclude that both the development and the cytokine potential of the AHR-enhancing γδ T cells differs critically from that of Th2 cells and NKT cells, despite similar influences of these cell populations on AHR.
Cytolysins Augment Superantigen Penetration of Stratified Mucosa
Authors: Brosnahan Amanda J. , Mantz Mary J. , Squier Christopher A. , Peterson Marnie L. , Schlievert Patrick M.
Published: February 2009

Staphylococcus aureus and Streptococcus pyogenes colonize mucosal surfaces of the human body to cause disease. A group of virulence factors known as superantigens are produced by both of these organisms that allows them to cause serious diseases from the vaginal (staphylococci) or oral mucosa (streptococci) of the body. Superantigens interact with T cells and APCs to cause massive cytokine release to mediate the symptoms collectively known as toxic shock syndrome. In this study we demonstrate that another group of virulence factors, cytolysins, aid in the penetration of superantigens across vaginal mucosa as a representative nonkeratinized stratified squamous epithelial surface. The staphylococcal cytolysin α-toxin and the streptococcal cytolysin streptolysin O enhanced penetration of toxic shock syndrome toxin-1 and streptococcal pyrogenic exotoxin A, respectively, across porcine vaginal mucosa in an ex vivo model of superantigen penetration. Upon histological examination, both cytolysins caused damage to the uppermost layers of the vaginal tissue. In vitro evidence using immortalized human vaginal epithelial cells demonstrated that although both superantigens were proinflammatory, only the staphylococcal cytolysin α-toxin induced a strong immune response from the cells. Streptolysin O damaged and killed the cells quickly, allowing only a small release of IL-1β. Two separate models of superantigen penetration are proposed: staphylococcal α-toxin induces a strong proinflammatory response from epithelial cells to disrupt the mucosa enough to allow for enhanced penetration of toxic shock syndrome toxin-1, whereas streptolysin O directly damages the mucosa to allow for penetration of streptococcal pyrogenic exotoxin A and possibly viable streptococci.
1,25-Dihydroxyvitamin D3 Is an Autonomous Regulator of the Transcriptional Changes Leading to a Tolerogenic Dendritic Cell Phenotype
Authors: Széles Lajos , Keresztes Gábor , Töröcsik Dániel , Balajthy Zoltán , Krenács László , Póliska Szilárd , Steinmeyer Andreas , Zuegel Ulrich , Pruenster Monika , Rot Antal , Nagy László
Published: February 2009

Activation of vitamin D receptor (VDR) by 1,25-dihydroxyvitamin D3 (1,25-vitD) reprograms dendritic cells (DC) to become tolerogenic. Previous studies suggested that 1,25-vitD could inhibit the changes brought about by differentiation and maturation of DCs. Underpinning the described phenotypic and functional alterations, there must be 1,25-vitD-coordinated transcriptional events. However, this transcriptional program has not been systematically investigated, particularly not in a developmental context. Hence, it has not been explored how 1,25-vitD-regulated genes, particularly the ones bringing about the tolerogenic phenotype, are connected to differentiation. We conducted global gene expression analysis followed by comprehensive quantitative PCR validation to clarify the interrelationship between 1,25-vitD and differentiation-driven gene expression patterns in developing human monocyte-derived and blood myeloid DCs. In this study we show that 1,25-vitD regulates a large set of genes that are not affected by differentiation. Interestingly, several genes, impacted both by the ligand and by differentiation, appear to be regulated by 1,25-vitD independently of the developmental context. We have also characterized the kinetics of generation of 1,25-vitD by using three early and robustly regulated genes, the chemokine CCL22, the inhibitory receptors CD300LF and CYP24A1. We found that monocyte-derived DCs are able to turn on 1,25-vitD sensitive genes in early phases of differentiation if the precursor is present. Our data collectively suggest that exogenous or endogenously generated 1,25-vitD regulates a large set of its targets autonomously and not via inhibition of differentiation and maturation, leading to the previously characterized tolerogenic state.
TNF-Like Weak Inducer of Apoptosis (TWEAK) Activates Proinflammatory Signaling Pathways and Gene Expression through the Activation of TGF-β-Activated Kinase 1
Authors: Kumar Mukesh , Makonchuk Denys Y. , Li Hong , Mittal Ashwani , Kumar Ashok
Published: February 2009

TWEAK, TNF-like weak inducer of apoptosis, is a relatively recently identified proinflammatory cytokine that functions through binding to Fn14 receptor in target cells. Although TWEAK has been shown to modulate several biological responses, the TWEAK-induced signaling pathways remain poorly understood. In this study, we tested the hypothesis that TAK1 (TGF-β-activated kinase 1) is involved in TWEAK-induced activation of NF-κB and MAPK and expression of proinflammatory protein. TWEAK increased the phosphorylation and kinase activity of TAK1 in cultured myoblast and fibroblast cells. The activation of NF-κB was significantly inhibited in TAK1-deficient (TAK1−/−) mouse embryonic fibroblasts (MEF) compared with wild-type MEF. Deficiency of TAK1 also inhibited the TWEAK-induced activation of IκB kinase and the phosphorylation and degradation of IκBα protein. However, there was no difference in the levels of p100 protein in TWEAK-treated wild-type and TAK1−/− MEF. Furthermore, TWEAK-induced transcriptional activation of NF-κB was significantly reduced in TAK1−/− MEF and in C2C12 myoblasts transfected with a dominant-negative TAK1 or TAK1 short interfering RNA. TAK1 was also required for the activation of AP-1 in response to TWEAK. Activation of JNK1 and p38 MAPK, but not ERK1/2 or Akt kinase, was significantly inhibited in TAK1−/− MEF compared with wild-type MEF upon treatment with TWEAK. TWEAK-induced expression of proinflammatory genes such as MMP-9, CCL-2, and VCAM-1 was also reduced in TAK1−/− MEF compared with wild-type MEF. Furthermore, the activation of NF-κB and the expression of MMP-9 in response to TWEAK involved the upstream activation of Akt kinase. Collectively, our study demonstrates that TAK1 and Akt are the important components of TWEAK-induced proinflammatory signaling and gene expression.
Macrophage NADPH Oxidase Flavocytochrome b Localizes to the Plasma Membrane and Rab11-Positive Recycling Endosomes
Authors: Casbon Amy-Jo , Allen Lee-Ann H. , Dunn Kenneth W. , Dinauer Mary C.
Published: February 2009

Flavocytochrome b558, the catalytic core of the phagocytic NADPH oxidase, mediates the transfer of electrons from NADPH to molecular oxygen to generate superoxide for host defense. Flavocytochrome b is a membrane heterodimer consisting of a large subunit gp91phox (NOX2) and a smaller subunit, p22phox. Although in neutrophils flavocytochrome b has been shown to localize to the plasma membrane and specific granules, little is known about its distribution in macrophages. Using immunofluorescent staining and live cell imaging of fluorescently tagged gp91phox and p22phox, we demonstrate in a Chinese hamster ovary cell model system and in RAW 264.7 and primary murine bone marrow-derived macrophages that flavocytochrome b is found in the Rab11-positive recycling endocytic compartment, as well as in Rab5-positive early endosomes and plasma membrane. Additionally, we show that unassembled p22phox and gp91phox subunits localize to the endoplasmic reticulum, which redistribute to the cell surface and endosomal compartments following heterodimer formation. These studies show for the first time that flavocytochrome b localizes to intracellular compartments in macrophages that recycle to the plasma membrane, which may act as a reservoir to deliver flavocytochrome b to the cell surface and phagosome membranes.
Relationship between N-terminal pro-B type natriuretic peptide and extensive echocardiographic parameters in mild to moderate aortic stenosis
Authors: Cemri M , Arslan U , Kocaman SA , Cengel A
Published: February 2009

Context:

The N-terminal pro-B type natriuretic peptide levels (NT pro-BNP) are increased in cases of volume or pressure overload.

Aims:

To examine NT pro-BNP levels and enclose whether any relationship is present between the levels of NT pro-BNP and extensive echocardiographic parameters in asymptomatic patients with mild to moderate aortic stenosis (AS).

Settings and Design:

A cross-sectional study about the NT pro-BNP levels was conducted in 37 asymptomatic AS patients and compared with 40 controls.

Methods:

Patients <70 years old with mild to moderate AS with a peak transaortic gradient <20 mm Hg in transthoracic echocardiogram were included in our study. Extensive echocardiographic parameters and NT pro-BNP levels were obtained from these patients and these indices were compared with the control population selected from the patients who had similar clinical characteristics with the AS patients.

Statistical Analysis:

NT-proBNP values were found to be distribution free. Spearman correlation coefficient was used for correlation analysis. Mean values were compared by the Kruskal-Wallis test.

Results:

The NT pro-BNP levels were increased in patients with AS (median; interquartiles range: 686 [449-855] pg/mL vs. 140 [116-150] pg/mL, P < 0.001). Among patients with AS, when correlation analysis was performed mean transaortic gradient, aortic valve area index, myocardial performance index, Em /Am ratio, left-ventricular mass index (LVMI) and E/Em ratio had correlations (r=0.38, P = 0.026; r=-0.46, P =0.008; r=0.19, P =0,049; r=-0.22, P =0.04, r=0.49, P =0.003 and r=0.53, P <0.001 respectively) with plasma NT pro-BNP levels. The LVMI (r = 0.49, P = 0.003) and E/Em ratio (r = 0.53 P < 0.001) have the strongest correlations when compared to other parameters.

Conclusion:

Plasma NT pro-BNP levels are increased in even asymptomatic patients with AS and correlated with several echocardiographic parameters related to severity of AS and degree of diastolic dysfunction. As a result, NT pro-BNP levels may be used in the follow-up of asymptomatic patients having mild to moderate AS.
Repeated fracture of pacemaker leads with migration into the pulmonary circulation and temporary pacemaker wire insertion via the azygous vein
Authors: Udyavar AR , Pandurangi UM , Latchumanadhas K , Mullasari A S
Published: February 2009

Repeated implantation of pacemaker in the same patient is a common occurrence because of the increased longevity of patients. However, repeated lead fracture in the same patient and migration of the pacemaker lead into the pulmonary circulation is rare. We describe a 56-year- old gentleman who had undergone pacemaker implantations thrice due to repeated lead fractures (thrice) and also had migration of the pacemaker lead into the pulmonary circulation. He also had an azygous vein which was noticed while placing the temporary pacemaker wire.
Citrobacter freundii infection in glutaric aciduria type 1
Authors: Mukhopadhyay C , Dey A , Bairy I
Published: February 2009

Glutaric aciduria type 1 (GA1) is an inborn error of organic acid metabolism, where the brain is the principal organ affected with exposure to toxic metabolic product, 3-hydroxyglutaric acid (3-OHGA). A 2-year-old boy with GA1 and delayed developmental milestones had an acute neurological crisis leading to massive brain abscess with Citrobacter freundi infection, a rare cause of neonatal meningitis and often associated with brain abscess. Both 3-OHGA and C. freundii can damage the blood-brain barrier and can cause significant trauma which demands immediate and appropriate management. Encephalopathic manifestations of GA1 may consequently increase the risk of meningeal infection and it has not been previously documented.
Implications of HLA sequence-based typing in transplantation
Authors: Shankarkumar U , Pawar A , Ghosh K
Published: February 2009

Serology-based conventional microlymphocytotoxicity HLA typing method, which has been regarded as the gold standard in organ and hematopoietic stem cell transplantation, has been replaced now by DNA-based typing. Many laboratories all over the world have already switched over to molecular methods. Microlymphocytotoxicity-based tissue typing was done using commercial sera, while the molecular typing by genomic DNA based. DNA quality and its quantity obtained using various DNA extraction protocols was found to be an important factor in the molecular method of tissue typing in transplant outcome. Many polymerase chain reaction-based molecular techniques have been adopted with far reaching clinical outcome. The sequence-based typing (SBT) has been the ultimate technique, which has been of the highest reliability in defining the HLA alleles. The nonavailability of specific HLA antisera from native populations, large number of blank alleles yet to be defined and comparable low resolution of HLA alleles in SSP or SSOP technique, suggests that highly refined DNA-based methods like SBT should be used as an adjunct to HLA serology and/or low/intermediate/high resolution HLA typing in order to achieve a better transplant outcome.
Chilaiditi′s sign possibly associated with malposition of chest tube placement
Authors: Gulati MS , Wafula J , Aggarwal S
Published: February 2009

Although diaphragmatic paralysis is a rare recognized complication of chest tube malposition, Chilaiditi's sign occurring as a result of this complication has never been reported in literature to the best of our knowledge. We describe one such case, which had an interesting clinical sequence of events and radiographic findings and suggest that the medial end of the chest tube should be positioned at least 2 cm from the mediastinum on the frontal chest radiograph to avoid these complications.
A comparative study of the skeletal morphology of the temporo-mandibular joint of children and adults
Authors: Meng F , Liu Y , Hu K , Zhao Y , Kong L , Zhou S
Published: February 2009

Background:

The skeletal morphology of the temporo-mandibular joint (TMJ) is constantly remodeled.

Aims and Objectives:

A comparative study was undertaken to determine and characterize the differences in the skeletal morphology of TMJ of children and adults.

Materials and Methods:

The study was conducted on 30 children cadavers and 30 adult volunteers. Parameters that could reflect TMJ skeletal morphology were measured with a new technology combining helical computed tomography (CT) scan with multi-planar reformation (MPR) imaging.

Results:

Significant differences between children cadavers and adults were found in the following parameters (P< 0.05): Condylar axis inclination, smallest area of condylar neck/largest area of condylar process, inclination of anterior slope in inner, middle, and outer one-third of condyle, anteroposterior/mediolateral dimension of condyle, length of anterior slope/posterior slope in inner and middle one-third of condyle, anteroposterior dimension of condyle/glenoid fossa, mediolateral dimension of condyle/glenoid fossa, inclination of anterior slope of glenoid fossa, depth of glenoid fossa, and anteroposterior/mediolateral dimension of glenoid fossa.

Conclusion:

There are significant differences of TMJ skeletal morphology between children and adults.
Recurrence of primary hyperoxaluria
Authors: Madiwale C , Murlidharan P , Hase NK
Published: February 2009

Primary hyperoxaluria is a rare autosomal recessive disease due to deficiency of an oxalate-metabolizing liver enzyme, which results in nephrolithiasis and renal failure. Concomitant liver and kidney transplant is recommended as isolated kidney transplant is inevitably complicated by recurrence of the disease. We present a 25-year-old man with end-stage nephrolithiatic renal disease who underwent bilateral nephrectomy, followed by kidney transplantation. There was progressive worsening of kidney function two weeks post transplant. Review of nephrectomy and transplant kidney biopsy showed abundant calcium oxalate crystals and further workup revealed hyperoxaluria, which was previously unsuspected. Later he developed fever, breathlessness, hemiparesis and died 10 weeks after transplant. Autopsy revealed multi-organ deposits of oxalate crystals as well as widespread zygomycosis. This case emphasizes the need for careful pre-transplant evaluation of patients with renal calculus disease in order to exclude primary hyperoxaluria.
Development and Application of a New General Method for the Asymmetric Synthesis of (E)‐(2‐En‐3‐ynyl)‐amines
Authors: Yin Chao , Hui Xin‐Ping , Xu Peng‐Fei , Niu Liang‐Feng , Chen Yong‐Fei , Wang Binghe
Published: February 2009

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The first direct approach for the asymmetric synthesis of (E)‐2‐arylidene‐1,4‐diphenylbut‐3‐yn‐1‐amines by addition of alkynylzinc to chiral N‐tert‐butylsulfinylimines is reported with excellent diastereoselectivity and good yield. This asymmetric addition reaction provides a practical, economical and concise synthesis of multifunctional molecules with the 1,3‐enyne side chain and an amino group. In addition, this methodology can be applied to the synthesis of substituted vinyl iodide compounds, and substituted chiral dihydropyrroles.
Regionally reduced brain volume, altered serotonin neurochemistry, and abnormal behavior in mice null for the circadian rhythm output gene Magel2
Authors: Mercer Rebecca E. , Kwolek Erin M. , Bischof Jocelyn M. , van Eede Matthijs , Henkelman R. Mark , Wevrick Rachel
Published: February 2009

Magel2 belongs to the MAGE/necdin family of proteins, which have roles in cell cycle, differentiation, and apoptosis. The Magel2 gene is expressed in various brain regions, most notably the hypothalamus. Mice with a targeted deletion of Magel2 display hypoactivity, blunted circadian rhythm, decreased fertility, and increased adiposity. The human ortholog, MAGEL2, is one of a set of paternally expressed, imprinted genes inactivated in most cases of Prader–Willi syndrome, a complex neurodevelopmental disorder. To explore the role of Magel2, brain morphology, brain neurochemistry, and behavior were measured in Magel2‐null mice. Brain volume was reduced in specific regions, particularly in the parieto‐temporal lobe of the cerebral cortex, the amygdala, the hippocampus, and the nucleus accumbens, as measured by quantitative magnetic resonance imaging. Abnormal neurochemistry was detected in brain samples from adult mice, consisting of decreased serotonin and 5‐hydroxyindoleacetic acid in the cortex and the hypothalamus, and decreased dopamine in the hypothalamus. Magel2‐null mice displayed relatively normal motor and learning abilities, but exhibited abnormal behavior in novel environments. This study lends support to the important role of the circadian rhythm output gene Magel2 in brain structure and behavior. © 2009 Wiley‐Liss, Inc.
Food choices and habitat use by the Tana River yellow baboons (Papio cynocephalus): a preliminary report on five years of data
Authors: Bentley‐Condit Vicki K.
Published: February 2009

The Tana River Primate National Reserve, Kenya (TRPNR) yellow baboons' (Papio cynocephalus) long‐term habitat usage and food preferences are relatively under‐reported. The author presents a preliminary food catalog and analyses of 5 years of data (January 88–October 92; n=55 mo; 875 observation days; 4,893 hourly scans) for the Mchelelo troop (x̄=75 individuals). The author predicted that the TRPNR baboons would spend more time on the much larger savanna, show a seasonal preference for fruits/seeds, and show rainfall‐influenced food preferences. Although more time was spent on the proportionately larger savanna than in the forests, more than 42% of the observations occurred in forests that accounted for only 8.7% of the area regularly used by the baboons. Fruits/seeds consumption was high throughout the period and a significantly higher proportion of each month's observations reflected fruits/seeds rather than grasses/herbs/corms consumption. Two forest species' (Phoenix reclinata and Hyphaene compressa) were particularly important. Regression analysis showed fruits/seeds consumption predicted most of the grasses/herbs/corms consumption variance. There was no statistical difference in rainy vs. non‐rainy season fruits/seeds or grasses/herbs/corms consumption. One implication of these data is the baboons' potential impact on the critically endangered Tana River mangabeys (Cercocebus galeritus), which also rely heavily on P. reclinata and H. compressa. Another is what the “savanna” designation may or may not tell us about baboons. Am. J. Primatol. 71:432–436, 2009. © 2009 Wiley‐Liss, Inc.
Assembly of Nanocrystal Arrays by Block‐Copolymer‐Directed Nucleation
Authors: Morin Stephen A. , La Young‐Hye , Liu Chi‐Chun , Streifer Jeremy A. , Hamers Robert J. , Nealey Paul F. , Jin Song
Published: February 2009

In Reih' und Glied: Mithilfe der oberflächenchemischen Eigenschaften von selbstorganisierenden nanostrukturierten Blockcopolymeren lässt sich steuern, an welchen Stellen auf einer Oberfläche Nanokristalle von Metallsulfid‐Halbleitern direkt aus einer wässrigen Lösung nukleieren und wachsen. Dieser Prozess bietet sich als neue und allgemeine Strategie für den „Bottom‐up“‐Aufbau funktioneller nanokristalliner Materialien an.

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Asymmetrische intramolekulare Carbocyanierung von Alkenen durch C‐C‐Aktivierung
Authors: Nájera Carmen , Sansano José M.
Published: February 2009

Vielseitig: Bei der intramolekularen Aryl‐ und Acylcyanierung von Alkenen werden Ni0‐ und Pd0‐Komplexe als Katalysatoren eingesetzt (siehe Schema). Die Reaktionen ergeben nicht nur hohe Ausbeuten und Selektivitäten, sie gelingen auch in Gegenwart zahlreicher funktioneller Gruppen. Als Produkte entstehen Heterocyclen wie Oxindole.

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Stereoselektive Synthese enantiomerenreiner Nupharamin‐Alkaloide aus dem Castoreum (Bibergeil)
Authors: Stoye Alexander , Quandt Gabriele , Brunnhöfer Björn , Kapatsina Elissavet , Baron Julia , Fischer André , Weymann Markus , Kunz Horst
Published: February 2009

Tierische Parfümalkaloide: Eine stereoselektive Mannich‐Michael‐Reaktion an N‐Galactosylfurylaldimin zu 1 (Piv = Pivaloyl), anschließende konjugierte Cuprataddition und stereoselektive Protonierung des gebildeten Enolats, alle kontrolliert vom Kohlenhydrat, ermöglichen erstmals die Totalsynthese des all‐cis‐Nupharamins 2 aus dem Castoreum. Enolatprotonierung nach Abspaltung des Kohlenhydrats führt alternativ zum Epimer 3.

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Assembly of an R3N52− Chain by Cycloaddition of a Hydrazinediide and an Azide at Zirconium and its Thermal Fragmentation
Authors: Gehrmann Thorsten , Lloret Fillol Julio , Wadepohl Hubert , Gade Lutz H.
Published: February 2009

Gesprengte Kette: Formale [2+3]‐Cycloadditionen eines Zirconiumhydrazindiids mit organischen Aziden führen zu 2‐Pentazen‐1,4‐diyl‐Komplexen wie dem abgebildeten [Zr(N2TBSNpy){N(Ad)N3NPh2}] (C grau, N blau, Si grün, Zr türkis). Die Bindungsverhältnisse in der N5‐Kette wurden mithilfe von Dichtefunktionalrechnungen untersucht. Beim Erhitzen spalten die Komplexe N2 ab, und es resultieren side‐on‐gebundene Diazenide.

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Rhodium(I)‐Catalyzed Intramolecular Carbonylative [2+2+1] Cycloaddition of Bis(allene)s: Bicyclo[6.3.0]undecadienones and Bicyclo[5.3.0]decadienones
Authors: Inagaki Fuyuhiko , Narita Syu , Hasegawa Takuma , Kitagaki Shinji , Mukai Chisato
Published: February 2009

Ohne Templat: Die Titelreaktion führt leicht und in hohen Ausbeuten zu Bicyclo[6.3.0]undecadienonen (siehe Schema), wobei der Ringschluss auch ohne Templateffekt effizient abläuft. Die vorgestellte Methode kann zum Aufbau von Bicyclo[5.3.0]‐ und Bicyclo[4.3.0]‐Ringsystemen verwendet werden. Ts=p‐Toluolsulfonyl.

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A Thermally and Hydrolytically Stable Microporous Framework Exhibiting Single‐Chain Magnetism: Structure and Properties of [Co2(H0.67bdt)3]⋅20 H2O
Authors: Ouellette Wayne , Prosvirin Andrey V. , Whitenack Kelly , Dunbar Kim R. , Zubieta Jon
Published: February 2009

Fixing a hole: Hydrothermal chemistry has been exploited in the preparation of a 3D framework material exhibiting 48 % accessible void volume and 1.5 % hydrogen uptake by weight at 120 kPa (see picture). The title compound also exhibits single‐chain magnetic behavior and reversible changes in magnetic properties upon solvation and desolvation.

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Ionothermal Synthesis of Zirconium Phosphates and Their Catalytic Behavior in the Selective Oxidation of Cyclohexane
Authors: Liu Lei , Li Yang , Wei Haibo , Dong Mei , Wang Jianguo , Slawin Alexandra M. Z. , Li Jinping , Dong Jinxiang , Morris Russell E.
Published: February 2009

On their best behavior: Three zirconium compounds with one‐, two‐, and three‐dimensional structures have been successfully synthesized by the ionothermal approach. The 3D zirconium phosphate (see picture; F green, H white, O red, P pink, Zr yellow) exhibits high catalytic performance, with a cyclohexane conversion ratio of 32 % and cyclohexanone selectivity of up to 83 %.

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Rhodium(I)‐Catalyzed Enantioselective CC Bond Activation
Authors: Winter Christian , Krause Norbert
Published: February 2009

Relieving the strain: The rhodium(I)‐catalyzed activation of CC bonds in functionalized cyclobutanes opens a novel route to highly substituted carbo‐ and heterocycles. Particularly intriguing is the differentiation of enantiotopic CC bonds, which leads to the formation of highly enantiomerically enriched lactones, cyclopentanones, and cyclohexenones (see scheme).

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Asymmetric Intramolecular Carbocyanation of Alkenes by CC Bond Activation
Authors: Nájera Carmen , Sansano José M.
Published: February 2009

Versatility: Ni0 and Pd0 complexes act as catalysts in the intramolecular aryl‐ and acylcyanation reactions, respectively, of alkenes (see scheme). These reactions not only proceed with high yield and selectivity, they also tolerate a wide range of functional groups and can furnish valuable heterocycles such as oxindoles, which are precursors for a myriad of natural and/or biologically active products.

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Isolating and Probing the Hot Spot Formed between Two Silver Nanocubes
Authors: Camargo Pedro H. C. , Rycenga Matthew , Au Leslie , Xia Younan
Published: February 2009

Out of the frying pan: Hot spots can greatly increase the sensitivity of surface‐enhanced Raman scattering, but they remain poorly understood. A new strategy based on plasma etching (see picture) can be used to isolate and exclusively probe the SERS‐active molecules adsorbed in the hot‐spot region between two silver nanocubes.

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Preparation of cationic pigment dispersions by surface grafting of polystyrene‐maleic anhydride with glycidyltriethylammonium chloride
Authors: Fang Kuanjun , Zhou Jiada , Kai Weihua , Fu Shaohai , Zhang Xia
Published: February 2009

Novel cationic pigment dispersions, which have potential uses in inkjet inks and coloration of textile and paper, were prepared by grafting quarternary ammonium groups onto the surface of polystyrene‐maleic anhydride encapsulated C. I. pigment yellow 14 (PY 14) powder. It is shown that the Zeta potentials greatly rely on the reaction time and temperature. And also, when the weight ratio of glycidyltriethylammonium chloride (GTA) to encapsulated PY 14 powder was 3 : 1, the Zeta potential of modified pigment dispersion reached to + 35.05 mV. Just due to the high Zeta potential of the prepared cationic pigment dispersions, the prepared cationic pigment dispersion shows good dispersion stability and a narrow size distribution with the average particle size of 202.9 nm. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Synthesis of biodegradable amphiphilic thermo‐responsive multiblock polycarbonate and its self‐aggregation behavior in aqueous solution
Authors: Wang Yuexia , Tan Yebang , Huang Xiaoling , Che Yuju , Du Xu
Published: February 2009

Amphiphilic thermo‐responsive multiblock polycarbonates consisting of poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) were facilely synthesized using triphosgene as coupling agent. The structures and molecular characteristics of the polycarbonates were confirmed by 1H‐NMR, FT‐IR and Gel permeation chromatography (GPC). The crystallization behavior and thermal properties of the polycarbonates were studied using X‐ray diffraction (XRD), Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Surface tension measurements confirmed that the critical micelles concentration of polymeric micelles were concentration ranges, which varied from about 2–70 mg/L to 5–40 mg/L with increasing PEO/PPO composition ratio from 0.8 to 1. Dynamic light scattering (DLS) experiments showed bimodal size distributions, the aggregates size increased with increasing the concentration of the polycarbonates aqueous solutions. The size of the aggregates acquired from TEM was smaller than that from DLS owing to the fact that TEM gave size of the aggregates in dry state rather than the hydrodynamic diameter. The degradation process revealed that the degradation rate of the aggregates could be accelerated with an increase in temperature. Moreover, the more the polycarbonate was hydrophilic, the faster was its degradation. Rheological measurements suggested that these multiblock polycarbonates were thermo‐responsive and by regulating the PEO/PPO composition ratio they could form a gel at 37°C. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Reactive extrusion of poly(L‐lactic acid) with glycidol
Authors: Deenadayalan E. , Lele A. K. , Balasubramanian M.
Published: February 2009

Glycidol modified polylactic acid (PLLA) polymers have been prepared by reactive extrusion. Influences of residence time and the concentration of glycidol on the extent of reaction with different weight average molecular weight (45,000, 65,000, and 100,000) PLLA's were studied. Structure–property relationship has been established by measuring molecular, mesoscopic, and macroscopic properties. Under reactive extrusion conditions glycidol reacted with the end groups of PLLA to initiate chain extension. Low‐molecular weight PLLA reacted with glycidol faster than the medium molecular weight PLLA, whereas high‐molecular weight PLLA did not show significant reactions. The glass transition temperature, melting temperature, crystallization temperature, and heat of fusion were measured for unmodified and modified PLLA's. Chain extended PLLA had higher Tg and Tm than the unmodified samples. Time sweep rheological experiments were performed to test the melt stability of PLLA. Chain extended PLLA's were found to retain viscoelastic properties for much longer time than the unreacted samples. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009