bluuebunny/crossref_metadata_2025 huggingface dataset:
Lpa2 Is a Negative Regulator of Both Dendritic Cell Activation and Murine Models of Allergic Lung Inflammation
Authors: Emo Jason , Meednu Nida , Chapman Timothy J. , Rezaee Fariba , Balys Marlene , Randall Troy , Rangasamy Tirumalai , Georas Steve N.
Published: March 2012

Negative regulation of innate immune responses is essential to prevent excess inflammation and tissue injury and promote homeostasis. Lysophosphatidic acid (LPA) is a pleiotropic lipid that regulates cell growth, migration, and activation and is constitutively produced at low levels in tissues and in serum. Extracellular LPA binds to specific G protein-coupled receptors, whose function in regulating innate or adaptive immune responses remains poorly understood. Of the classical LPA receptors belonging to the Edg family, lpa2 (edg4) is expressed by dendritic cells (DC) and other innate immune cells. In this article, we show that DC from lpa2−/− mice are hyperactive compared with their wild-type counterparts and are less susceptible to inhibition by different LPA species. In transient-transfection assays, we found that lpa2 overexpression inhibits NF-κB–driven gene transcription. Using an adoptive-transfer approach, we found that allergen-pulsed lpa2−/− DC induced substantially more lung inflammation than did wild-type DC after inhaled allergen challenge. Finally, lpa2−/− mice develop greater allergen-driven lung inflammation than do their wild-type counterparts in models of allergic asthma involving both systemic and mucosal sensitization. Taken together, these findings identify LPA acting via lpa2 as a novel negative regulatory pathway that inhibits DC activation and allergic airway inflammation.
Bcl6 and Maf Cooperate To Instruct Human Follicular Helper CD4 T Cell Differentiation
Authors: Kroenke Mark A. , Eto Danelle , Locci Michela , Cho Michael , Davidson Terence , Haddad Elias K. , Crotty Shane
Published: March 2012

Follicular helper CD4 T (Tfh) cells provide B cells with signals that are important for the generation of high-affinity Abs and immunological memory and, therefore, are critical for the protective immunity elicited by most human vaccines. Transcriptional regulators of human Tfh cell differentiation are poorly understood. In this article, we demonstrate that Bcl6 controls specific gene modules for human Tfh cell differentiation. The introduction of Bcl6 expression in primary human CD4 T cells resulted in the regulation of a core set of migration genes that enable trafficking to germinal centers: CXCR4, CXCR5, CCR7, and EBI2. Bcl6 expression also induced a module of protein expression critical for T–B interactions, including SAP, CD40L, PD-1, ICOS, and CXCL13. This constitutes direct evidence for Bcl6 control of most of these functions and includes three genes known to be loci of severe human genetic immunodeficiencies (CD40L, SH2D1A, and ICOS). Introduction of Bcl6 did not alter the expression of IL-21 or IL-4, the primary cytokines of human Tfh cells. We show in this article that introduction of Maf (c-Maf) does induce the capacity to express IL-21. Surprisingly, Maf also induced CXCR5 expression. Coexpression of Bcl6 and Maf revealed that Bcl6 and Maf cooperate in the induction of CXCR4, PD-1, and ICOS. Altogether, these findings reveal that Bcl6 and Maf collaborate to orchestrate a suite of genes that define core characteristics of human Tfh cell biology.
Activated Mouse B Cells Lack Expression of Granzyme B
Authors: Hagn Magdalena , Belz Gabrielle T. , Kallies Axel , Sutton Vivien R. , Thia Kevin Y. , Tarlinton David M. , Hawkins Edwin D. , Trapani Joseph A.
Published: March 2012

Recently, it has been reported that human B cells express and secrete the cytotoxic protease granzyme B (GrB) after stimulation with IL-21 and BCR cross-linking. To date, there are few clues on the function of GrB in B cell biology. As experimental transgenic murine systems should provide insights into these issues, we assayed for GrB in C57BL/6 B cells using an extensive array of physiologically relevant stimuli but were unable to detect either GrB expression or its proteolytic activity, even when Ag-specific transgenic BCRs were engaged. Similar results were also obtained with B cells from DBA/2, CBA, or BALB/c mice. In vivo, infection with either influenza virus or murine γ-herpesvirus induced the expected expression of GrB in CTLs, but not in B cell populations. We also investigated a possible role of GrB on the humoral immune response to the model Ag 4-hydroxy-3-nitrophenylacetyl–keyhole limpet hemocyanin, but GrB-deficient mice produced normal amounts of Ab with typical affinity maturation and a heightened secondary response, demonstrating conclusively the redundancy of GrB for Ab responses. Our results highlight the complex evolutionary differences that have shaped the immune systems of mice and humans. The physiological consequences of GrB expression in human B cells remain unclear, and the current study suggests that experimental mouse models will not be helpful in addressing this issue.
The Drosophila Protein Mustard Tailors the Innate Immune Response Activated by the Immune Deficiency Pathway
Authors: Wang Zhipeng , Berkey Cristin D. , Watnick Paula I.
Published: March 2012

In this study, we describe a Drosophila melanogaster transposon insertion mutant with tolerance to Vibrio cholerae infection and markedly decreased transcription of diptericin as well as other genes regulated by the immune deficiency innate immunity signaling pathway. We present genetic evidence that this insertion affects a locus previously implicated in pupal eclosion. This genetic locus, which we have named mustard (mtd), contains a LysM domain, often involved in carbohydrate recognition, and a TLDc domain of unknown function. More than 20 Mtd isoforms containing one or both of these conserved domains are predicted. We establish that the mutant phenotype represents a gain of function and can be replicated by increased expression of a short, nuclearly localized Mtd isoform comprised almost entirely of the TLDc domain. We show that this Mtd isoform does not block Relish cleavage or translocation into the nucleus. Lastly, we present evidence suggesting that the eclosion defect previously attributed to the Mtd locus may be the result of the unopposed action of the NF-κB homolog, Relish. Mtd homologs have been implicated in resistance to oxidative stress. However, to our knowledge this is the first evidence that Mtd or its homologs alter the output of an innate immunity signaling cascade from within the nucleus.
Innate Immunity Mediates Follicular Transport of Particulate but Not Soluble Protein Antigen
Authors: Link Alexander , Zabel Franziska , Schnetzler Yvonne , Titz Alexander , Brombacher Frank , Bachmann Martin F.
Published: March 2012

Ag retention on follicular dendritic cells (FDCs) is essential for B cell activation and clonal selection within germinal centers. Protein Ag is deposited on FDCs after formation of immune complexes with specific Abs. In this study, by comparing the same antigenic determinant either as soluble protein or virus-like particle (VLP), we demonstrate that VLPs are transported efficiently to murine splenic FDCs in vivo in the absence of prior immunity. Natural IgM Abs and complement were required and sufficient to mediate capture and transport of VLPs by noncognate B cells. In contrast, soluble protein was only deposited on FDCs in the presence of specifically induced IgM or IgG Abs. Unexpectedly, IgG Abs had the opposite effect on viral particles and inhibited FDC deposition. These findings identify size and repetitive structure as critical factors for efficient Ag presentation to B cells and highlight important differences between soluble proteins and viral particles.
Mapping of Clinical and Expression Quantitative Trait Loci in a Sex-Dependent Effect of Host Susceptibility to Mouse-Adapted Influenza H3N2/HK/1/68
Authors: Boivin Gregory A. , Pothlichet Julien , Skamene Emil , Brown Earl G. , Loredo-Osti J. Concepción , Sladek Robert , Vidal Silvia M.
Published: March 2012

Seasonal influenza outbreaks and recurrent influenza pandemics present major challenges to public health. By studying immunological responses to influenza in different host species, it may be possible to discover common mechanisms of susceptibility in response to various influenza strains. This could lead to novel therapeutic targets with wide clinical application. Using a mouse-adapted strain of influenza (A/HK/1/68-MA20 [H3N2]), we produced a mouse model of severe influenza that reproduces the hallmark high viral load and overexpression of cytokines associated with susceptibility to severe influenza in humans. We mapped genetic determinants of the host response using a panel of 29 closely related mouse strains (AcB/BcA panel of recombinant congenic strains) created from influenza-susceptible A/J and influenza-resistant C57BL/6J (B6) mice. Combined clinical quantitative trait loci (QTL) and lung expression QTL mapping identified candidate genes for two sex-specific QTL on chromosomes 2 and 17. The former includes the previously described Hc gene, a deficit of which is associated with the susceptibility phenotype in females. The latter includes the phospholipase gene Pla2g7 and Tnfrsf21, a member of the TNFR superfamily. Confirmation of the gene underlying the chromosome 17 QTL may reveal new strategies for influenza treatment.
The SWI/SNF-like BAF Complex Is Essential for Early B Cell Development
Authors: Choi Jinwook , Ko Myunggon , Jeon Shin , Jeon Yoon , Park Kyungsoo , Lee Changjin , Lee Ho , Seong Rho H.
Published: March 2012

During the process of B cell development, transcription factors, such as E2A and Ebf1, have been known to play key roles. Although transcription factors and chromatin regulators work in concert to direct the expression of B lineage-specific genes, little is known about the involvement of regulators for chromatin structure during B lymphopoiesis. In this article, we show that deletion of Srg3/mBaf155, a scaffold subunit of the SWI/SNF-like BAF complex, in the hematopoietic lineage caused defects at both the common lymphoid progenitor stage and the transition from pre–pro-B to early pro-B cells due to failures in the expression of B lineage-specific genes, such as Ebf1 and Il7ra, and their downstream target genes. Moreover, mice that were deficient in the expression of Brg1, a subunit of the complex with ATPase activity, also showed defects in early B cell development. We also found that the expression of Ebf1 and Il7ra is directly regulated by the SWI/SNF-like BAF complex. Thus, our results suggest that the SWI/SNF-like BAF complex facilitates early B cell development by regulating the expression of B lineage-specific genes.
The TIGIT/CD226 Axis Regulates Human T Cell Function
Authors: Lozano Ester , Dominguez-Villar Margarita , Kuchroo Vijay , Hafler David A.
Published: March 2012

T cell Ig and ITIM domain (TIGIT) is a newly identified receptor expressed on T cells that binds to CD155 on the dendritic cell surface, driving them to a more tolerogenic phenotype. Given that TIGIT contains an ITIM motif in its intracellular domain and considering the potential importance of the TIGIT/CD226 pathway in human autoimmune disease, we investigated the specific role of TIGIT in human CD4+ T cells. Using an agonistic anti-TIGIT mAb, we demonstrate a direct inhibitory effect on T cell proliferation with a decrease in expression of T-bet, GATA3, IFN regulatory factor 4, and retinoic acid-related orphan receptor c with inhibition of cytokine production, predominantly IFN-γ. Knockdown of TIGIT expression by short hairpin RNA resulted in an increase of both T-bet and IFN-γ mRNA and protein expression with concomitant decrease in IL-10 expression. Increases in IFN-γ with TIGIT knockdown could be overcome by blocking CD226 signaling, indicating that TIGIT exerts immunosuppressive effects by competing with CD226 for the same CD155 ligand. These data demonstrate that TIGIT can inhibit T cell functions by competing with CD226 and can also directly inhibit T cells in a T cell-intrinsic manner. Our results provide evidence for a novel role of this alternative costimulatory pathway in regulating human T cell responses associated with autoimmune disease.
Self-inflicted transparietal intraventricular nail: case report and surgical technique
Authors: Udoh DO , Okundia P , Airiohuodion E
Published: March 2012

Background Deliberate self-harm with stone- or hammer-driven nail through the cranium is unusual. The need is stressed for comprehensive radiological evaluation with computed tomography (CT) scan, with or without angiography, and removal through an open cranial procedure under general anaesthesia, rather than extraction through a burrhole under local anesthetic infiltration. Methods We present here a 27-year old male who presented at our Teaching Hospital setting with a self-inflicted hand-driven intracranial nail to the left parietal region. He had a detailed neurological examination, was evaluated pre-operatively with computerised tomography of the brain and underwent an open cranial procedure under general anaesthesia for nail retrieval. Psychiatric unit evaluated and managed him for chronic depression. Results The transparietal, intraventricular 10cm long nail was retrieved and associated abscess evacuated by an open cranial procedure. Pre-operative neurological impairments regressed and his mood stabilized with anti-depressants. He was discharged without further deficits and has remained well for over four years Conclusion Self-inflicted hand-driven intracranial nail is a very rare form of penetrating cranio-cerebral trauma. Preoperative computerised tomography scan of the brain, meticulous open cranial removal under general anaesthesia and psychiatric management enable discharge without further injury or deficits. On the other hand, removal through a burrhole or just pulling out the nail would not allow intraoperative visualisation of associated lesions; the latter also predispose to further vascular and parenchymal brain injuries, worsening neurolological impairments.Key words: Intracranial Nail; Open Cranial Procedure; Psychiatric Evaluation.
Effects of Nifedipine on Cation Transport and Na - K-ATPase Activity in Erythrocytes and Electrolyte Homeostasis in Rats
Authors: Shaheen Najma , Mahboob Tabassum
Published: March 2012

Calcium channel antagonists have been reported to reduce blood pressure in those individuals at risk of cardiac and cerebrovascular events. There is no specific study available regarding the role of electrolyte alterations in blood pressure lowering effects of nifedipine. The present study was designed to investigate the role of electrolyte homeostasis, changes in ouabain-sensitive Na+ K+ adenosine triphosphatase (ATPase) activity, and net sodium efflux and potassium influx across blood cell membranes. Rats were divided into two experimental groups . Nifedipine (20mg/ kg body weight ) was administered by gastric tube to the test group . Control group received same volume of deionize water .The intra-erythrocyte sodium, serum sodium, potassium, calcium and sodium, calcium content of heart and kidney tissues were decreased significantly. Whereas, intra-erythrocyte potassium was slightly decreased or remained normal in nifedipine treated rats as compared to normal healthy rats. The Na - K - ATPase activity, serum magnesium, potassium and magnesium content in heart and kidney tissues were increased significantly. Results confirmed that nifedipine represses ion channels, transporters and calcium-binding proteins in tissues. Erythrocyte studies indicate that nifedipine blocks the entrance of calcium into the cells but also stimulate Na - K - ATPase activity, resulting in reduction of intracellular sodium concentration, thus suggesting direct nifedipine-induced blood pressure reduction.
Microfaunal Assemblage of the Sui Main Limestone from Sui Gas Field, Pakistan
Authors: Rafi Salma , Khursheed S.H. , Mohsin Syed Iqbal
Published: March 2012

Sui Main Limestone (SML) is the best reservoir in the Middle Indus Basin of Pakistan. It is an important reservoir that has produced gas for the last fifty (50) years and continues to produce 600 MMCF per day. The characteristic microfossil assemblages within the SML have been studied from fifty two thin sections of the reservoir rock from four Sui wells for understanding the reservoir architecture and quality. There are two distinctive fossil assemblages within SML Formation. The major lower part (>300m) is a carbonate facies of massive fossiliferous limestone dominated by Nummulites along with Alveolina, Discocyclina and Miliolids. The upper part (20m) consists of argillaceous fossiliferous limestone interbedded with calcareous shale layers, making a transition to the overlying Ghazij shales. Assilina is the characteristic fossil with its associated assemblage
Efficacy of Different Organophosphate Pesticides against Jassid Feeding on Okra (Abelmoschus esculentus)
Authors: Eijaz Saleem , Khan M. Farhanullah , Mahmood Khalid , Shaukat Sohail , Siddiqui Afaq Ahmed
Published: March 2012

Field studies were conducted for the determination of efficacy of different organophosphate pesticides viz Profenofos, Dimethoate , Acephate and Malathion against jassid (Amrasca devastans) feeding on okra crop. Seeds of okra crop were planted in randomized block design with 3 replicates. The pretreatment observations were recorded at 24 hour before spray, while, the post-treatment observations were taken after 1, 2, 3,4,5,6 and 7 days of treatment. The crop was sprayed four times repeatedly with 7 day interval during the experimental period. The results revealed that all of the tested pesticides reduced the population of Amrasca devastans except Profenofos. Though the Profenofos was unable to reduce the pest population but it was able to somewhat control the further proliferation of pest. In contrary Dimethoate was found as the most effective against the jassid with significant reduction in pest population against the control and other treatments.The results obtained from the research concluded that the organophosphate pesticides including Dimethoate, Acephate, and Malathion were found effective for controlling the jassid population feeding on okra but the low dose of pesticides including Profenfos were found ineffective.
Survey and Trend of Some Zoometric Parameters Correlated to the Growth of Male Subjects of Mediterranean Italian Buffalo for Meat Production
Authors: Coletta A. , Di Rubbo M. , Caso C. , Fez C. , Rossi N. , Vittoria R.
Published: March 2012

In this study was evaluated the presence of hereditary disposition to meat production in Mediterranean Italian buffaloes through the analysis of variation of certain important parameters related to the production of meat, in 40 young subjects having the same age. The parameters studied were: live weight, daily weight gain (DWG), withers height, thoracic circumference and trunk length. These values were investigated by controls every 21 days during the period of major growth of the animals, that is from the 240th day of life up to the attainment of slaughter weight. This work has pointed out that there are significant differences in growth between animals of the same age. The data suggested that hasn’t yet been made any selection about the presence of hereditary disposition to meat production in Mediterranean Italian Buffalo.
Anthelmintic Activity of Hygrophila difformis Blume
Authors: Samanta Krishanu , Hossain Emdad , Pal Dilip Kumar
Published: March 2012

This study evaluated the anthelmintic activity of the petroleum ether, benzene, chloroform, ethanol extracts of aerial parts of Hygrophila difformis (Family: Acanthaceae). The Pheretima posthuma were used for all the experimental protocol due to their anatomical and physiological resemblance with the intestinal roundworms of ruminants and human beings. The worms were treated with the extract solutions containing three different concentrations (10, 25 and 30 mg/ml), for each extracts supplemented with 1% gum acacia in normal saline at 37 ± 1°C. Albendazole at a dose of 10 mg/ml was used as reference. The effectiveness of the extracts was judged on the basis of the loss of spontaneous movement and/or death of the worms. Qualitative phytochemical analysis of different extracts of the plant was carried out following the standard procedure. All extracts at different dose levels effectively paralyzed and killed the worm in dose-dependent fashion (p < 0.001). Maximum anthelmintic activity was found with benzene extract. Cardiac glycosides, tannins, steroids, flavonoids and saponins were found positive in phytochemical analysis. The present study established the anthelmintic activity of H. difformis and can be utilized for the ruminants.
Serum Profile of Thyroid Hormones from Birth to Puberty in Buffalo Calves and Heifers
Authors: Ingole Shailesh Dayaram , Deshmukh B.T. , Nagvekar A.S. , Bharucha S.V.
Published: March 2012

Growth is outcome of interactions among several factors, where thyroid hormones play a key role in coordination of these factors and the information of thyroid hormones in relation to growth in buffalo calves and heifers is not adequate. Thus the study was conducted on Murrah female buffalo calves and heifers, varying in age from newborn to 30 months. The study investigated the serum thyroid patterns in female Murrah buffalo calves and heifers from birth to puberty. The thyroid stimulating hormone concentration did not differ and remained almost the same from birth to 4 – 6 months. The thyroid stimulating hormone then gradually increased and reached a highest value at 24 – 30 months. The concentration recorded at 21 – 24 months and 24 – 30 month i.e. at the age of attaining the puberty, was about 3 – 4 times higher than recorded at birth. The T3 concentration recorded at 0 – 7 days of age was significantly higher than recorded for other age groups, except at 18 – 21 months, 21 – 24 months and 24 – 30 months. The T3 concentration did not exhibit specific trend during the ages 16 days – 1 month to 15 – 18 months. The highest T4 concentration was recorded in 0 – 7 days old buffalo calves. The concentration decreased to lower value at 1 - 2 months. The T4 concentration from 2 – 4 months of age increased significantly and the values remained almost similar with minor fluctuations upto 24 – 30 months. The T4: T3 ratio recorded at different ages did not exhibit specific trend
Prevalence and Antibacterial Susceptibility in Mastitis in Buffalo and Cattle in District Lahore-Pakistan
Authors: Mustafa Y.S. , Awan F.N. , Zaman T. , Chaudhry S.R. , Zoyfro V.
Published: March 2012

A total of 450 milk samples including both 272 buffalo and 178 cattle were randomly collected in and around District Lahore to study the incidence of mastitis and antibiotic sensitivity by performing Culture and Sensitivity test. The prevalence of mastitis in buffalo was found 20.98% while in cattle 24.71%. The prevalence of both Clinical and subclincal mastitis in buffalo were 40.35%, 59.64% and in cattle 61.26%, 30.63% respectively. The milk samples mixed with both mucus and blood in buffalo and cattle were 5.51% and 4.49% respectively. Quarters wise prevalence was 47.72%, 11.36%, 36.36% and 4.54% in the left fore, left hind, right fore and right hind quarters in cattle while In buffaloes, the prevalence was 0%, 68.96%, 11.49% and 19.54% in the left fore, left hind, right fore and right hind quarters respectively. The Ciprofloxacin antibiotic was found highly Sensitive in buffalo while Gentamicin in cattle.
The Roles of the Ge‐Te Core Network and the Sb‐Te Pseudo Network During Rapid Nucleation‐Dominated Crystallization of Amorphous Ge2Sb2Te5
Authors: Ohara Koji , Temleitner László , Sugimoto Kunihisa , Kohara Shinji , Matsunaga Toshiyuki , Pusztai László , Itou Masayoshi , Ohsumi Hiroyuki , Kojima Rie , Yamada Noboru , Usuki Takeshi , Fujiwara Akihiko , Takata Masaki
Published: March 2012

Ge2Sb2Te5 (GST) has demonstrated its outstanding importance among rapid phase‐change (PC) materials, being applied for optical and electrical data storage for over three decades. The mechanism of nanosecond phase change in GST, which is vital for its application, has long been disputed: various, quite diverse scenarios have been proposed on the basis of various experimental and theoretical approaches. Nevertheless, one central question still remains unanswered: why is amorphous GST stable at room temperature for long time while it can rapidly transform to the crystalline phase at high temperature? Here it is revealed for the first time, by modelling the amorphous structure based on synchrotron radiation anomalous X‐ray scattering data, that germanium and tellurium atoms form a “core” Ge‐Te network with ring formation. It is also suggested that the Ge‐Te network can stabilize the amorphous phase at room temperature and can persist in the crystalline phase. On the other hand, antimony does not contribute to ring formation but constitutes a “pseudo” network with tellurium, in which the characteristic Sb–Te distance is somewhat longer than the covalent Sb–Te bond distance. This suggests that the Sb‐Te pseudo network may act as a precursor to forming critical nuclei during the crystallization process. The findings conclude that the Ge‐Te core network is responsible for the outstanding stability and rapid phase change of the amorphous phase while the Sb‐Te pseudo network is responsible for triggering critical nucleation.
Occupational rhinitis and asthma due to EDTA‐containing detergents or disinfectants
Authors: Laborde‐Castérot Hervé , Villa Antoine F. , Rosenberg Nicole , Dupont Patricia , Lee Hwee Min , Garnier Robert
Published: March 2012

Background

Detergents and disinfectants are an emerging cause of work‐related rhinitis and asthma. These products may contain ethylenediamine tetraacetic acid (EDTA). The authors report 10 cases of EDTA‐related asthma and/or rhinitis.

Methods

Review of the medical charts of patients who presented with work‐related rhinitis (alone or with asthma), with a history of exposure to aerosols of EDTA‐containing products and who underwent a nasal provocation test (NPT) with tetrasodium EDTA (1–4%) in our occupational health unit.

Results

Twenty‐eight patients underwent a NPT with EDTA, which was positive in 10 cases. These patients, mostly cleaners or healthcare workers, used spray formulations of cleaning products.

Conclusions

This case series is the first report of EDTA‐related respiratory disease, documented by a specific test. An irritant mechanism is unlikely. Further studies are required to distinguish between an immunoallergic response and a pharmacological mechanism possibly resulting from calcium chelation, as suggested by animal experiments. A ban of spray preparations would be sufficient to prevent respiratory disease induced by EDTA inhalation, regardless of its mechanism. Am. J. Ind. Med. 55:677–682, 2012. © 2012 Wiley Periodicals, Inc.
Thermal Hydrogen‐Atom Transfer from Methane: The Role of Radicals and Spin States in Oxo‐Cluster Chemistry
Authors: Dietl Nicolas , Schlangen Maria , Schwarz Helmut
Published: March 2012

Hydrogen‐atom transfer (HAT), as one of the fundamental reactions in chemistry, is investigated with state‐of‐the‐art gas‐phase experiments in conjunction with computational studies. The focus of this Minireview concerns the role that the intrinsic properties of gaseous oxo‐clusters play to permit HAT reactivity from saturated hydrocarbons at ambient conditions. In addition, mechanistic implications are discussed which pertain to heterogeneous catalysis. From these combined experimental/computational studies, the crucial role of unpaired spin density at the abstracting atom becomes clear, in distinct contrast to recent conclusions derived from solution‐phase experiments.
A new “tool” for transcatheter atrial defect closure: The St. Jude SL2™ sheath
Authors: Lee Simon , Sutton Nicole , Lopez Leo , Farooqi Kanwal , Mahgerefteh Joseph , Blancas Imelissa , Pass Robert H.
Published: March 2012

Background

Orienting the left atrial disc of an atrial septal defect (ASD) closure device parallel to the septum is important, particularly in cases of ASD with deficient retroaortic rim. Standard vascular sheaths can make this challenging. We report the use of an electrophysiologic sheath, the SL2™ St. Jude Vascular sheath (St. Jude Medical, St. Paul, MN) for closure of ASD.

Methods

All patients undergoing ASD closure between July 2010 and February 2011 at The Children's Hospital at Montefiore in which the SL2 sheath was used were reviewed.

Results

Nine patients underwent transcatheter ASD or PFO (1/9) closure with the SL2 sheath. Mean age was 22.7 years (range, 3–58); weight was 46.5 kg (range, 14.7–78.6). The Amplatzer ASD Occluder (AGA Medical Corp., Plymouth, MN) was used in all cases. The mean measurement of the ASDs via “stop‐flow” technique was 13.3 mm (range, 4–19). The mean device size was 13.9 mm (range, 5–20) or 105% the size of the defect. The retroaortic rim was deficient (<2 mm) in 3 of 9. ASD closure was achieved in 9 of 9. In all, the left atrial disk was brought toward the atrial septum parallel to the atrial septum, and repositioning or recapturing of the device was unnecessary in any case. Mean fluoroscopy time was 9.3 min (range, 2.2–18). No significant complications.

Conclusions

The SL2 sheath was useful to position the ASD device parallel to the atrial septum, eliminating the need for redeployment during the procedure. This sheath was useful in those cases of deficient retroaortic rim in this study. © 2012 Wiley Periodicals, Inc.
Impact of radial‐to‐aorta vascular anatomical variants on risk of failure in trans‐radial coronary procedures
Authors: Burzotta Francesco , Brancati Marta Francesca , Trani Carlo , Tommasino Antonella , Porto Italo , Niccoli Giampaolo , Leone Antonio Maria , Coluccia Valentina , Di Noi Paola , Crea Filippo
Published: March 2012

Objectives

To assess the impact of an “operative” classification of vascular anatomic variants on the feasibility of trans‐radial approach.

Background

Vascular anatomic variants located from the wrist to the aorta may influence the feasibility of trans‐radial procedures. Recently, a new “operative” classification of these variants was proposed.

Methods

Consecutive trans‐radial diagnostic or interventional catheterizations were considered. Vascular anatomic variants were classified according to 10 categories and sub‐grouped according to the ABC classification (A: radial‐brachial arterial axis; B: axillary‐subclavian‐anonymous axis; C: aortic arch). Primary study end‐point was failure of trans‐radial approach (necessity to cross‐over to another approach to complete the procedure).

Results

Three thousand four hundred seventy‐seven consecutive radial procedures were considered. Anatomic variants were diagnosed in 308 procedures (8.8%): A variants: 7.2%, B variants: 1.9%; C variants: 0.3%. Failure occurred in 2.0% of procedures. Failure rate was 0.7% in the absence of variants vs.15.2% in the presence of any variant (P < 0.0001, OR 27.7, 95%CI 16.3–46.9). Each of the 10 variants was significantly associated with increased failure rate. Each of the three level‐subgroups of variants was significantly associated to the risk of failure (failure 14.7% in A level, 13.9% in B level, 33.3% in C level; P < 0.0001 vs. absence of variants).

Conclusions

Failure of trans‐radial procedures is associated to anatomic variants located from the wrist to the aorta. The “operative” ABC classification of anatomic variants is useful not only to categorize these anatomic variants, but also to predict the risk of failure of trans‐radial approach. © 2012 Wiley Periodicals, Inc.
Treatment of an iatrogenic femoral artery pseudoaneurysm with concomitant arteriovenous fistula with percutaneous implantation of an amplatzer vascular plug
Authors: Shetty Ranjith , Lotun Kapildeo
Published: March 2012

Iatrogenic pseudoaneurysms can occur following percutaneous cardiac and peripheral procedures. There are multiple modalities available for the treatment of pseudoaneurysms including ultrasound guided compression repair, ultrasound guided thrombin injection, or endovascular repair with covered stent placement. If these methods are not indicated or unsuccessful, patients typically require open surgical repair. We report a case of a woman with a post‐procedural pseudoaneurysm with concomitant arteriovenous fistula who was treated percutaneously with the implantation of an Amplatzer vascular plug. This novel technique was safe and effective and allowed our patient to avoid the morbidity and mortality associated with surgical repair. © 2012 Wiley Periodicals, Inc.
Difficulties with horizontal aortic root in transcatheter aortic valve implantation
Authors: Chan Pak Hei , Alegria‐Barrero Eduardo , Mario Carlo Di
Published: March 2012

Transcatheter aortic valve implantation (TAVI) emerged to be a viable treatment option for failing bioprosthesis in the aortic position. Transfemoral approach is the most common access route for TAVI and associated with most favorable clinical outcome. However, in the presence of unfavorable aortic root anatomy, TAVI via transfemoral approach provides inadequate support for device manipulation during valve positioning, particularly performed for the indication of severe aortic regurgitation. We report our experience on TAVI utilizing CoreValve for a patient with regurgitant failing bioprosthesis with horizontal aortic root where we encountered difficulties during implantation and retrieval of valve delivery system. © 2012 Wiley Periodicals, Inc.
Heme Oxygenase Inhibition by α‐(1H‐Imidazol‐1‐yl)‐ω‐phenylalkanes: Effect of Introduction of Heteroatoms in the Alkyl Linker
Authors: Vlahakis Jason Z. , Lazar Carmen , Roman Gheorghe , Vukomanovic Dragic , Nakatsu Kanji , Szarek Walter A.
Published: March 2012

Several α‐(1H‐imidazol‐1‐yl)‐ω‐phenylalkanes were synthesized and evaluated as novel inhibitors of heme oxygenase (HO). These compounds were found to be potent and selective for the stress‐induced isozyme HO‐1, showing mostly weak activity toward the constitutive isozyme HO‐2. The introduction of an oxygen atom in the alkyl linker produced analogues with decreased potency toward HO‐1, whereas the presence of a sulfur atom in the linker gave rise to analogues with greater potency toward HO‐1 than the carbon‐containing analogues. The most potent compounds studied contained a five‐atom linker between the imidazolyl and phenyl moieties, whereas the most HO‐1‐selective compounds contained a four‐atom linker between these groups. The compounds with a five‐atom linker containing a heteroatom (O or S) were found to be the most potent inhibitors of HO‐2; 1‐(N‐benzylamino)‐3‐(1H‐imidazol‐1‐yl)propane dihydrochloride, with a nitrogen atom in the linker, was found to be inactive.
Comparative Binding Energy (COMBINE) Analysis Supports a Proposal for the Binding Mode of Epothilones to β‐Tubulin
Authors: Coderch Claire , Klett Javier , Morreale Antonio , Díaz J. Fernando , Gago Federico
Published: March 2012

The conformational preferences of epothilone A (EPA) and a 12,13‐cyclopropyl C12‐epimerized analogue were explored in aqueous solution using molecular dynamics simulations. The simulated conformers that provided an optimal fit in the paclitaxel binding site of mammalian β‐tubulin were then selected. The resulting modeled complexes were simulated before and after refinement of the M‐loop to improve the fitting and assess ligand stability within the binding pocket. The tubulin‐bound conformation of EPA was found to be unlike a previously reported solution obtained through mixed crystallographic/NMR/modeling studies. However, our conformation was in agreement with an NMR‐based proposal although the exact binding pose within the site was different. Molecular models were built for the complexes of 14 epothilone derivatives with β‐tubulin. A projection to latent structures regression method succeeded in providing a good prediction of the experimentally measured binding enthalpies for the whole set of ligands by assigning weights to a selection of interaction energy terms. These receptor‐based, quantitative structure–activity relationships support the proposed binding mode, help confirm and interpret previously acquired experimental data, shed additional light on the effect of several β‐tubulin mutations on ligand binding, and can potentially direct further experimental studies.
Nonspecific predictors of weight gain in the early stages of outpatient cognitive behavioral therapy for adults with anorexia nervosa: Replication and extension
Authors: Marcoulides Olivia Kyriacou , Waller Glenn
Published: March 2012

Objective:

This study extends previous work, examining psychological factors that influence the level of weight gain across the first 20 sessions of cognitive behavioral therapy (CBT) for anorexia nervosa.

Method:

Thirty‐two patients with anorexia nervosa (mean body mass index (BMI) = 16.0; SD = 1.11) completed measures of eating attitudes and comorbid axis 1 pathology at the outset of CBT, and their weight gain was measured at the 6th and 20th sessions of the therapy.

Results:

Unhealthy eating attitudes at the start of therapy were associated with slower weight gain across the first 20 sessions of CBT. In contrast, higher levels of pretreatment axis 1 pathology were associated with slower weight gain only after the 6th session. The axis 1 features that moderated weight gain over 20 sessions of CBT were broader than those that had previously been shown to predict weight gain over the first 10 CBT sessions.

Discussion:

During CBT for anorexia nervosa, weight gain might be enhanced by addressing a range of aspects of axis 1 pathology (e.g., depression, hostility, and features of anxiety). However, the approach is likely to be less important at first than directly addressing eating pathology and overvalued ideas about eating, shape, and weight. © 2012 by Wiley Periodicals, Inc. (Int J Eat Disord 2012; 45:746–750)
DFT Studies on the Mechanism of Alcohol Oxidation Catalyzed by the NiIII/bipy Complex
Authors: Cheng Lin , Li Jie , Li Jianing , Zheng Hongna , Wu Zhijian
Published: March 2012

On the basis of our previous DFT calculations on the catalytic reaction cycle catalyzed by CuII/bipy (2,2′‐bipyridine), a new NiIII/bipy catalyst has been designed. By examining the mechanism of alcohol oxidation catalyzed by the NiIII/bipy catalyst, it was found that the barrier calculated for the rate‐determining step (16.3 kcal/mol) is 12.2 kcal/mol lower than that for the corresponding CuII/bipy catalyst. This indicates that the NiIII/bipy catalyst might be a potential catalyst for green alcohol oxidation. In addition, the reasons for the higher activity of the NiIII/bipy catalyst relative to the CuII/bipy catalyst are discussed. It was found that the unoccupied NiIII (d7) d orbital might be the reason for the higher activity of the NiIII/bipy catalyst. The singly occupied NiIII (d7) d orbital plays a very important role in producing the final product (CH3CHO) in the absence of an oxidation auxilliary.
Diversified Aminohydantoins from Ureas and Thioureas Tethered to Amides
Authors: Bepary Sukumar , Youn In Kwon , Lim Hee‐Jong , Lee Ge Hyeong
Published: March 2012

Intramolecular cyclization of thioureas or ureas tethered to amides afforded 2‐iminohydantoins and 2‐amino‐1H‐imidazol‐4(5H)‐ones in very high yields (87–100 %) regardless of the substituent (alkyls or aryls). This reaction proceeds through carbodiimides and iminium ions as intermediates. Among the reagents used to generate the carbodiimides, CBr4/Ph3P, CCl4/Ph3P, O,O′‐bis(2′‐pyridyl)thiocarbonate, and HgO were investigated.
Initial experience using a bipolar radiofrequency ablation device for hemostasis during thyroidectomy
Authors: Baldwin Keith , Haniff Michelle , Somasundar Ponnandai
Published: March 2012

Background

The purpose of this study was to evaluate a novel bipolar radiofrequency ablation (BRFA) device using nanotechnology for division of all named vessels during thyroidectomy.

Methods

All thyroidectomies from January 2008 to July 2010 at a single institution used the BRFA device (EnSeal, Ethicon Endo‐Surgery, Cincinnati, OH) for hemostasis. Clinicopathologic data and complications were recorded and compared with existing literature using other energy devices.

Results

Fifty‐eight thyroidectomies were performed. Mean age was 54.7 years, and mean operating room time was 81 minutes. The average estimated blood loss was 46 mL. Ninety percent of patients were discharged in <23 hours. There were no hemorrhages. There was 1 recurrent laryngeal nerve (RLN) injury, and 1 case of transient hypocalcemia.

Conclusion

This first small series using the BRFA device reveals initial safety and effectiveness for thyroid hemostasis, and warrants further study. The minimal thermal spread inherent in this device may make it an attractive option when structures such as the RLN may be near the zone of hemostasis. © 2012 Wiley Periodicals, Inc. Head Neck, 2013
Overexpression of the nuclear factor‐kappa B (p65) in association with local failure in patients with head and neck carcinoma undergong radiotherapy or chemoradiotherapy
Authors: Quintana Ana , Avilés Francesc X , Terra Ximena , Alcolea Sonia , Camacho Mercedes , Quer Miquel , Vila Luis , León Xavier
Published: March 2012

Background

The aim of this study was to evaluate nuclear factor‐kappa B (NF‐κB) expression as a biologic marker to predict local control in patients with head and neck squamous cell carcinoma (HNSCC) treated with radiotherapy or chemoradiotherapy.

Methods

The mRNA expression levels of the NF‐κB family genes were determined with real‐time–polymerase chain reaction in 77 patients with HNSCC treated with radiotherapy or chemoradiotherapy.

Results

The mRNA NF‐κB (p65) expression in pretreatment tumors was significantly related to local control (p = .03). The 5‐year local recurrence‐free survival rate in patients with low‐level NF‐κB (p65) expression (n = 42) was 79.9%, and in patients with a high level of expression it was 42.1% (p = .001). In a multivariate analysis, the mRNA NF‐κB (p65) expression level was the only variable related to local control of the tumor.

Conclusion

Expression of the NF‐κB (p65) gene may be a radiosensitivity marker for patients with a HNSCC. © 2012 Wiley Periodicals, Inc. Head Neck, 2013
Efficient Synthesis of Novel Coumarin‐3‐carboxamides (=2‐Oxo‐2H‐1‐benzopyran‐3‐carboxamides) Containing Lipophilic Spacers
Authors: Balalaie Saeed , Bigdeli Mohammad Ali , Sheikhhosseini Enayatollah , Habibi Azizollah , Moghadam Hamed Piri , Naderi Mehrnoush
Published: March 2012

The novel coumarin‐3‐carboxamides (=2‐oxo‐2H‐1‐benzopyran‐3‐carboxamides) 5a–5g containing lipophilic spacers were synthesized through the Ugi‐four‐component reaction (Scheme 1). The reactions of aromatic aldehydes 1, 4,4′‐oxybis[benzenamine] or 4,4′‐methylenebis[benzenamine] as diamine 2, coumarin‐3‐carboxylic acid (=2‐oxo‐2H‐benzopyran‐3‐carboxylic acid; 3), and alkyl isocyanides 4 lead to the desired substituted coumarin‐3‐carboxamides 5a–5g at room temperature with high bond‐forming efficiency. These novel coumarin derivatives exhibit brilliant fluorescence at 544 nm in CHCl3.
‘Click Synthesis’ of Some Novel O‐Substituted Oximes Containing 1,2,3‐Triazole‐1,4‐diyl Residues as New Analogs of β‐Adrenoceptor Antagonists
Authors: Rad Mohammad Navid Soltani , Behrouz Somayeh , Karimitabar Fatemeh , Khalafi‐Nezhad Ali
Published: March 2012

The ‘click synthesis’ of some novel O‐substituted oximes, 7a–7t, which contain 1,2,3‐triazolediyl residues, as new analogs of β‐adrenoceptor antagonists is described (Schemes 1–4). The synthesis of these compounds was achieved in four to five steps. The formation of oximes of 9H‐fluoren‐9‐one and benzophenone, i.e., 9a and 9b, respectively, followed by their reaction with propargyl bromide, afforded O‐propargyl oximes 10a and 10b, respectively, which by a subsequent CuI‐catalyzed Huisgen cycloaddition with prepared β‐azido alcohols 11a–11j (Schemes 2 and 3), led to the target compounds 7a–7t in good yields.
Preparation of Pseudo‐Peptide Building Blocks with retro‐Thioamide Bond Mediated via Thiocarbamoyl Meldrum's Acid
Authors: Janikowska Karolina , Makowiec Sławomir , Rachoń Janusz
Published: March 2012

An easy and efficient synthesis of pseudo‐tripeptide containing a thiomalonamide moiety was developed. Isothiocyanate derivatives of amino acids react smoothly with 2,2‐dimethyl‐1,3‐dioxane‐4,6‐dione (Meldrum's acid) to yield new thiocarbamoyl derivatives of Meldrum's acids. Thermal decomposition of these new derivatives leads to thiocarbamoyl ketenes, which acylate amino acid esters to give pseudo‐tripeptides.
Exaltone® (=Cyclopentadecanone) from Isomuscone® (=Cyclohexadecanone), a One‐C‐Atom Ring‐Contraction Methodology via a Stereospecific Favorskii Rearrangement: Regioselective Application to (−)‐(R)‐Muscone
Authors: Chapuis Christian , Robvieux Fabrice , Cantatore Carole , Saint‐Léger Christine , Maggi Laurent
Published: March 2012

Treatment of cyclohexadecanone (1g; with I2 (2.2 mol‐euqiv.) and KOH in MeOH) furnished the unsaturated (Z)‐ester 2g in 83% yield, via a stereospecific Favorskii rearrangement (Scheme 1). Further treatment with 3‐chloroperbenzoic acid (m‐CPBA) afforded the unreported epoxy ester 3g (88% yield), which was cleaved in 33% yield to Exaltone® (=cyclopentadecanone; 1f) with NaOH in MeOH/H2O and then HCl at 65°. This methodology was similarly extended to higher (C17) and lower (C15 to C11) cyclic ketone analogues, as well as regioselectively to (−)‐(R)‐muscone (5c) and homomuscone (5f) (Scheme 2). Olfactive properties of the corresponding macrocyclic 1‐oxaspiro[2,n]alkanes and ‐alkenes 4 and 8, resulting from a CoreyChaykovsky oxiranylation, are also presented.
Characterization of drug resistance mutations in naïve and ART‐treated patients infected with HIV‐1 in Yaounde, Cameroon
Authors: Ceccarelli Laura , Salpini Romina , Moudourou Sylvie , Cento Valeria , Santoro Maria M. , Fokam Joseph , Takou Desire , Nanfack Aubin , Dori Luca , Torimiro Judith , Sarmati Loredana , Andreoni Massimo , Perno Carlo F. , Colizzi Vittorio , Cappelli Giulia
Published: March 2012

Currently the prevalence of HIV‐1 infection in Cameroon is 5.1%, CRF02_AG subtype is responsible for about 50% of infections. Since an HIV‐1 drug resistance test is not yet available widely, accurate data on the prevalence of resistant viral strains are missing. The objective of this study was to determine HIV‐1 genetic diversity and to characterize HIV‐1 mutations conferring drug resistance among antiretroviral therapy (ART)‐naïve and ART‐treated patients. A cohort of 239 patients infected with HIV were followed‐up between January 2007 and July 2010 in Cameroon. Two hundred and sixteen plasma samples were sequenced for phylogenetic analysis and identification of drug resistance mutations in the HIV‐1 pol region. A significant genetic diversity was found: Seven pure subtypes (A1, A3, D, F1, F2, G, H), nine circulating recombinant forms (CRFs: 01_AE, 02_AG, 06cpx, 09cpx, 11cpx, 13cpx, 16cpx, 18cpx, 37cpx) and one new unique recombinant form (URF) (G/F2). The rate of transmitted drug resistance (TDR) in naïve patients was 8.2% (4/49). Around 80% of patients failing a first‐line ART harbored a virus with at least one resistance mutation to two antiretroviral (ARV) classes, and 36% of those failing a second‐line regimen carried a virus with at least one resistant mutation to three ARV classes. The high level of drug resistance observed in the cohort is alarming because this occurred as a result of only few years of treatment. Adherence to therapy, adequate education of physicians, and the appropriate use of genotypic resistance assay are critical points of intervention for the improvement of patient care. J. Med. Virol. 84:721–727, 2012. © 2012 Wiley Periodicals, Inc.