bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of PI3K binding to activators by serine phosphorylation of PI3K regulatory subunit p85α Src homology-2 domains
Authors: Lee Jennifer Y. , Chiu Yu-Hsin , Asara John , Cantley Lewis C.
Published: August 2011

Class IA PI3Ks are activated by growth factor receptors and generate lipid second messengers that mediate downstream responses including cell growth, cell migration, and cell survival. The p85 regulatory subunit of PI3K contains Src homology-2 (SH2) domains that mediate binding to tyrosine-phosphorylated receptors or adaptor proteins to facilitate localization and activation of PI3K at the plasma membrane. We report here that persistent activation of PKC family members by phorbol ester stimulation in cells leads to phosphorylation of two serine residues at analogous sites on both SH2 domains of p85α (S361 and S652). The modified serine residues are located in the phospho-tyrosine binding pockets of the two SH2 domains, and in the crystal structures the phosphate moieties are predicted to occupy the same space as the phosphate moieties of bound phospho-tyrosine peptides. Consistent with this prediction, phosphorylation at these serine residues or mutation to aspartate inhibits binding of p85α to tyrosine-phosphorylated peptides. We provide evidence that protein kinase D, which is phosphorylated and activated by PKCs, mediates phosphorylation of S652 in the C-terminal SH2 domain. These results reveal cross talk between PKC signaling and PI3K signaling that impairs PI3K pathway activation under conditions of persistent PKC (and protein kinase D) activity.
Anterograde or retrograde transsynaptic labeling of CNS neurons with vesicular stomatitis virus vectors
Authors: Beier Kevin T. , Saunders Arpiar , Oldenburg Ian A. , Miyamichi Kazunari , Akhtar Nazia , Luo Liqun , Whelan Sean P. J. , Sabatini Bernardo , Cepko Constance L.
Published: August 2011

To understand how the nervous system processes information, a map of the connections among neurons would be of great benefit. Here we describe the use of vesicular stomatitis virus (VSV) for tracing neuronal connections in vivo. We made VSV vectors that used glycoprotein (G) genes from several other viruses. The G protein from lymphocytic choriomeningitis virus endowed VSV with the ability to spread transsynaptically, specifically in an anterograde direction, whereas the rabies virus glycoprotein gave a specifically retrograde transsynaptic pattern. The use of an avian G protein fusion allowed specific targeting of cells expressing an avian receptor, which allowed a demonstration of monosynaptic anterograde tracing from defined cells. Synaptic connectivity of pairs of virally labeled cells was demonstrated by using slice cultures and electrophysiology. In vivo infections of several areas in the mouse brain led to the predicted patterns of spread for anterograde or retrograde tracers.
Expansion of a unique CD57+NKG2Chinatural killer cell subset during acute human cytomegalovirus infection
Authors: Lopez-Vergès Sandra , Milush Jeffrey M. , Schwartz Brian S. , Pando Marcelo J. , Jarjoura Jessica , York Vanessa A. , Houchins Jeffrey P. , Miller Steve , Kang Sang-Mo , Norris Phillip J. , Nixon Douglas F. , Lanier Lewis L.
Published: August 2011

During human CMV infection, there is a preferential expansion of natural killer (NK) cells expressing the activating CD94–NKG2C receptor complex, implicating this receptor in the recognition of CMV-infected cells. We hypothesized that NK cells expanded in response to pathogens will be marked by expression of CD57, a carbohydrate antigen expressed on highly mature cells within the CD56dimCD16+NK cell compartment. Here we demonstrate the preferential expansion of a unique subset of NK cells coexpressing the activating CD94–NKG2C receptor and CD57 in CMV+donors. These CD57+NKG2ChiNK cells degranulated in response to stimulation through their NKG2C receptor. Furthermore, CD57+NKG2ChiNK cells preferentially lack expression of the inhibitory NKG2A receptor and the inhibitory KIR3DL1 receptor in individuals expressing its HLA-Bw4 ligand. Moreover, in solid-organ transplant recipients with active CMV infection, the percentage of CD57+NKG2ChiNK cells in the total NK cell population preferentially increased. During acute CMV infection, the NKG2C+NK cells proliferated, became NKG2Chi, and finally acquired CD57. Thus, we propose that CD57 might provide a marker of “memory” NK cells that have been expanded in response to infection.
Spontaneous prosocial choice by chimpanzees
Authors: Horner Victoria , Carter J. Devyn , Suchak Malini , de Waal Frans B. M.
Published: August 2011

The study of human and primate altruism faces an evolutionary anomaly: There is ample evidence for altruistic preferences in our own species and growing evidence in monkeys, but one of our closest relatives, the chimpanzee (
Pan troglodytes
), is viewed as a reluctant altruist, acting only in response to pressure and solicitation. Although chimpanzee prosocial behavior has been reported both in observational captive studies and in the wild, thus far Prosocial Choice Tests have failed to produce evidence. However, methodologies of previous Prosocial Choice Tests may have handicapped the apes unintentionally. Here we present findings of a paradigm in which chimpanzees chose between two differently colored tokens: one “selfish” token resulting in a reward for the actor only (1/0), and the other “prosocial” token rewarding both the actor and a partner (1/1). Seven female chimpanzees, each tested with three different partners, showed a significant bias for the prosocial option. Prosocial choices occurred both in response to solicitation by the partner and spontaneously without solicitation. However, directed requests and pressure by the partner reduced the actor's prosocial tendency. These results draw into question previous conclusions indicating that chimpanzees have a limited sensitivity to the needs of others and behave prosocially only in response to significant prompting.
Phenotype-information-phenotype cycle for deconvolution of combinatorial antibody libraries selected against complex systems
Authors: Zhang Hongkai , Torkamani Ali , Jones Teresa M. , Ruiz Diana I. , Pons Jaume , Lerner Richard A.
Published: August 2011

Use of large combinatorial antibody libraries and next-generation sequencing of nucleic acids are two of the most powerful methods in modern molecular biology. The libraries are screened using the principles of evolutionary selection, albeit in real time, to enrich for members with a particular phenotype. This selective process necessarily results in the loss of information about less-fit molecules. On the other hand, sequencing of the library, by itself, gives information that is mostly unrelated to phenotype. If the two methods could be combined, the full potential of very large molecular libraries could be realized. Here we report the implementation of a phenotype-information-phenotype cycle that integrates information and gene recovery. After selection for phage-encoded antibodies that bind to targets expressed on the surface of
Escherichia coli
, the information content of the selected pool is obtained by pyrosequencing. Sequences that encode specific antibodies are identified by a bioinformatic analysis and recovered by a stringent affinity method that is uniquely suited for gene isolation from a highly degenerate collection of nucleic acids. This approach can be generalized for selection of antibodies against targets that are present as minor components of complex systems.
Broadly neutralizing human antibody that recognizes the receptor-binding pocket of influenza virus hemagglutinin
Authors: Whittle James R. R. , Zhang Ruijun , Khurana Surender , King Lisa R. , Manischewitz Jody , Golding Hana , Dormitzer Philip R. , Haynes Barton F. , Walter Emmanuel B. , Moody M. Anthony , Kepler Thomas B. , Liao Hua-Xin , Harrison Stephen C.
Published: August 2011

Seasonal antigenic drift of circulating influenza virus leads to a requirement for frequent changes in vaccine composition, because exposure or vaccination elicits human antibodies with limited cross-neutralization of drifted strains. We describe a human monoclonal antibody, CH65, obtained by isolating rearranged heavy- and light-chain genes from sorted single plasma cells, coming from a subject immunized with the 2007 trivalent influenza vaccine. The crystal structure of a complex of the hemagglutinin (HA) from H1N1 strain A/Solomon Islands/3/2006 with the Fab of CH65 shows that the tip of the CH65 heavy-chain complementarity determining region 3 (CDR3) inserts into the receptor binding pocket on HA1, mimicking in many respects the interaction of the physiological receptor, sialic acid. CH65 neutralizes infectivity of 30 out of 36 H1N1 strains tested. The resistant strains have a single-residue insertion near the rim of the sialic-acid pocket. We conclude that broad neutralization of influenza virus can be achieved by antibodies with contacts that mimic those of the receptor.
Preexisting helminth infection induces inhibition of innate pulmonary anti-tuberculosis defense by engaging the IL-4 receptor pathway
Authors: Potian Julius A. , Rafi Wasiulla , Bhatt Kamlesh , McBride Amanda , Gause William C. , Salgame Padmini
Published: August 2011

Tuberculosis and helminthic infections coexist in many parts of the world, yet the impact of helminth-elicited Th2 responses on the ability of the host to control Mycobacterium tuberculosis (Mtb) infection has not been fully explored. We show that mice infected with the intestinal helminth Nippostrongylus brasiliensis (Nb) exhibit a transitory impairment of resistance to airborne Mtb infection. Furthermore, a second dose of Nb infection substantially increases the bacterial burden in the lungs of co-infected mice. Interestingly, the Th2 response in the co-infected animals did not impair the onset and development of the protective Mtb-specific Th1 cellular immune responses. However, the helminth-induced Th2 environment resulted in the accumulation of alternatively activated macrophages (AAMs) in the lung. Co-infected mice lacking interleukin (IL) 4Rα exhibited improved ability to control Mtb infection, which was accompanied by significantly reduced accumulation of AAMs. Moreover, IL-4Rα−/− mice adoptively transferred with wild-type macrophages had a significantly higher Mtb load in their lungs compared with those that received IL-4Rα−/− macrophages, suggesting a direct contribution for the IL-4R pathway to the heightened susceptibility of co-infected animals. The Th2 response can thus enhance the intracellular persistence of Mtb, in part by mediating the alternative activation of macrophages via the IL-4Rα signaling pathway.
A Head-to-Head Comparison of Hydrogen Peroxide Vapor and Aerosol Room Decontamination Systems
Authors: Holmdahl T. , Lanbeck P. , Wullt M. , Walder M. H.
Published: August 2011

Objective.

New technologies have emerged in recent years for the disinfection of hospital rooms and equipment that may not be disinfected adequately using conventional methods. There are several hydrogen peroxide–based area decontamination technologies on the market, but no head-to-head studies have been performed.

Design.

We conducted a head-to-head in vitro comparison of a hydrogen peroxide vapor (HPV) system (Bioquell) and an aerosolized hydrogen peroxide (aHP) system (Sterinis).

Setting.

The tests were conducted in a purpose-built 136-m3 test room.

Methods.

One HPV generator and 2 aHP machines were used, following recommendations of the manufacturers. Three repeated tests were performed for each system. The microbiological efficacy of the 2 systems was tested using 6-log Tyvek-pouched Geobacillus stearo-thermophilus biological indicators (BIs). The indicators were placed at 20 locations in the first test and 14 locations in the subsequent 2 tests for each system.

Results.

All BIs were inactivated for the 3 HPV tests, compared with only 10% in the first aHP test and 79% in the other 2 aHP tests. The peak hydrogen peroxide concentration was 338 ppm for HPV and 160 ppm for aHP. The total cycle time (including aeration) was 3 and 3.5 hours for the 3 HPV tests and the 3 aHP tests, respectively. Monitoring around the perimeter of the enclosure with a handheld sensor during tests of both systems did not identify leakage.

Conclusion.

One HPV generator was more effective than 2 aHP machines for the inactivation of G. stearothermophilus BIs, and cycle times were faster for the HPV system.
Clinical and Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus among Patients in an Ambulatory Hemodialysis Center
Authors: Patel Gopi , Jenkins Stephen G. , Mediavilla José R. , Kreiswirth Barry N. , Radbill Brian , Salgado Cassandra D. , Calfee David P.
Published: August 2011

Objective.

To describe the epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) carriage and transmission in an ambulatory hemodialysis population.

Design.

Prospective cohort study.

Setting.

Outpatient hemodialysis facility affiliated with a large academic medical center.

Participants.

Of the 170 facility patients, 103 (61%) participated in the study.

Methods.

Swab specimens of the nares, axillae, and vascular access site were collected from participants weekly for 3 weeks and then monthly for 5 months. Demographic and clinical data were collected monthly for 12 months. Molecular analysis of MRSA isolates was performed.

Results.

The baseline MRSA carriage prevalence was 12%. Factors associated with MRSA carriage included a history of MRSA; failed renal transplantation; hospital admission within 6 months; and receipt of a first-generation cephalosporin, cefepime, or vancomycin. Six subjects acquired MRSA after enrollment (incidence, 1.2 per 100 patient-months at-risk; overall prevalence, 18%). Molecular analysis suggested that transmission occurred within the facility. The incidence of MRSA infection among carriers was 1.76 per 100 patient-months. Community-associated strains (ie, USA300) were isolated from 28% of carriers and at least 25% of infections.

Conclusions.

The prevalence of MRSA carriage and the incidence of infection among carriers were high among ambulatory hemodialysis patients, and community-associated MRSA was responsible for a large portion of the MRSA burden. A relatively high rate of MRSA acquisition was observed, with indirect evidence of intrafacility transmission. Additional studies are needed to confirm these findings and to identify effective and feasible methods to prevent MRSA transmission and infection among hemodialysis patients.
Metannogen: annotation of biological reaction networks
Authors: Gille Christoph , Hübner Katrin , Hoppe Andreas , Holzhütter Hermann−Georg
Published: August 2011

Motivation: Semantic annotations of the biochemical entities constituting a biological reaction network are indispensable to create biologically meaningful networks. They further heighten efficient exchange, reuse and merging of existing models which concern present-day systems biology research more often. Two types of tools for the reconstruction of biological networks currently exist: (i) several sophisticated programs support graphical network editing and visualization. (ii) Data management systems permit reconstruction and curation of huge networks in a team of scientists including data integration, annotation and cross-referencing. We seeked ways to combine the advantages of both approaches.

Results: Metannogen, which was previously developed for network reconstruction, has been considerably improved. From now on, Metannogen provides sbml import and annotation of networks created elsewhere. This permits users of other network reconstruction platforms or modeling software to annotate their networks using Metannogen's advanced information management. We implemented word-autocompletion, multipattern highlighting, spell check, brace-expansion and publication management, and improved annotation, cross-referencing and team work requirements. Unspecific enzymes and transporters acting on a spectrum of different substrates are efficiently handled. The network can be exported in sbml format where the annotations are embedded in line with the miriam standard. For more comfort, Metannogen may be tightly coupled with the network editor such that Metannogen becomes an additional view for the focused reaction in the network editor. Finally, Metannogen provides local single user, shared password protected multiuser or public access to the annotation data.

Availability: Metannogen is available free of charge at: http://www.bioinformatics.org/strap/metannogen/ or http://3d-alignment.eu/metannogen/.

Contact:  christoph.gille@charite.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
A biclustering algorithm for extracting bit-patterns from binary datasets
Authors: Rodriguez-Baena Domingo S. , Perez-Pulido Antonio J. , Aguilar−Ruiz Jesus S.
Published: August 2011

Motivation: Binary datasets represent a compact and simple way to store data about the relationships between a group of objects and their possible properties. In the last few years, different biclustering algorithms have been specially developed to be applied to binary datasets. Several approaches based on matrix factorization, suffix trees or divide-and-conquer techniques have been proposed to extract useful biclusters from binary data, and these approaches provide information about the distribution of patterns and intrinsic correlations.

Results: A novel approach to extracting biclusters from binary datasets, BiBit, is introduced here. The results obtained from different experiments with synthetic data reveal the excellent performance and the robustness of BiBit to density and size of input data. Also, BiBit is applied to a central nervous system embryonic tumor gene expression dataset to test the quality of the results. A novel gene expression preprocessing methodology, based on expression level layers, and the selective search performed by BiBit, based on a very fast bit-pattern processing technique, provide very satisfactory results in quality and computational cost. The power of biclustering in finding genes involved simultaneously in different cancer processes is also shown. Finally, a comparison with Bimax, one of the most cited binary biclustering algorithms, shows that BiBit is faster while providing essentially the same results.

Availability: The source and binary codes, the datasets used in the experiments and the results can be found at: http://www.upo.es/eps/bigs/BiBit.html

Contact:  dsrodbae@upo.es

Supplementary information:  Supplementary data are available at Bioinformatics online.
Construction and first applications of a global cost of fishing database
Authors: Lam Vicky W. Y. , Sumaila Ussif Rashid , Dyck Andrew , Pauly Daniel , Watson Reg
Published: August 2011

Lam, V. W. Y., Sumaila, U. R., Dyck, A., Pauly, D., and Watson, R. 2011. Construction and first applications of a global cost of fishing database. – ICES Journal of Marine Science, 68: 1996–2004. The development of a new global database of fishing cost is described, and an overview of fishing cost patterns at national, regional, and global scales is provided. This fishing cost database provides economic information required for assessing the economics of fisheries at various scales. It covers variable and fixed costs of maritime countries, representing ∼98% of global landings in 2005. Linked to country and gear-type combinations, cost estimates can be mapped to a database of spatially allocated fisheries catches for future analysis in both spatial and temporal dimensions. The global average variable cost per tonne of catch in 2005 is estimated to range between US$639 and $1217, and the total cost per tonne from $763 to $1477, with mean values of $928 and $1120, respectively. The total global variable fishing cost is estimated to be in the range US$50–96 billion per year, with a mean of $73 billion per annum in 2005 dollar equivalents.
Tsc1 mutant neural stem/progenitor cells exhibit migration deficits and give rise to subependymal lesions in the lateral ventricle
Authors: Zhou Jing , Shrikhande Gayatri , Xu Jing , McKay Renée M. , Burns Dennis K. , Johnson Jane E. , Parada Luis F.
Published: August 2011

Subependymal nodules (SENs) and subependymal giant cell astrocytomas (SEGAs) are common brain lesions found in patients with tuberous sclerosis complex (TSC). These brain lesions present a mixed glioneuronal phenotype and have been hypothesized to originate from neural stem cells. However, this hypothesis has not been tested empirically. Here, we report that loss of Tsc1 in mouse subventricular zone (SVZ) neural stem/progenitor cells (NSPCs) results in formation of SEN- and SEGA-like structural abnormalities in the lateral ventricle, the consequence of abnormal migration of NSPCs following Tsc1 loss.
HEB and E2A function as SMAD/FOXH1 cofactors
Authors: Yoon Se-Jin , Wills Andrea E. , Chuong Edward , Gupta Rakhi , Baker Julie C.
Published: August 2011

Nodal signaling, mediated through SMAD transcription factors, is necessary for pluripotency maintenance and endoderm commitment. We identified a new motif, termed SMAD complex-associated (SCA), that is bound by SMAD2/3/4 and FOXH1 in human embryonic stem cells (hESCs) and derived endoderm. We demonstrate that two basic helix–loop–helix (bHLH) proteins—HEB and E2A—bind the SCA motif at regions overlapping SMAD2/3 and FOXH1. Furthermore, we show that HEB and E2A associate with SMAD2/3 and FOXH1, suggesting they form a complex at critical target regions. This association is biologically important, as E2A is critical for mesendoderm specification, gastrulation, and Nodal signal transduction inXenopus tropicalisembryos. Taken together, E proteins are novel Nodal signaling cofactors that associate with SMAD2/3 and FOXH1 and are necessary for mesendoderm differentiation.
Mechanism of CRL4Cdt2, a PCNA-dependent E3 ubiquitin ligase
Authors: Havens Courtney G. , Walter Johannes C.
Published: August 2011

Eukaryotic cell cycle transitions are driven by E3 ubiquitin ligases that catalyze the ubiquitylation and destruction of specific protein targets. For example, the anaphase-promoting complex/cyclosome (APC/C) promotes the exit from mitosis via destruction of securin and mitotic cyclins, whereas CRL1Skp2 allows entry into S phase by targeting the destruction of the cyclin-dependent kinase (CDK) inhibitor p27. Recently, an E3 ubiquitin ligase called CRL4Cdt2 has been characterized, which couples proteolysis to DNA synthesis via an unusual mechanism that involves display of substrate degrons on the DNA polymerase processivity factor PCNA. Through its destruction of Cdt1, p21, and Set8, CRL4Cdt2 has emerged as a master regulator that prevents rereplication in S phase. In addition, it also targets other factors such as E2F and DNA polymerase η. In this review, we discuss our current understanding of the molecular mechanism of substrate recognition by CRL4Cdt2 and how this E3 ligase helps to maintain genome integrity.
The Proteome Folding Project: Proteome-scale prediction of structure and function
Authors: Drew Kevin , Winters Patrick , Butterfoss Glenn L. , Berstis Viktors , Uplinger Keith , Armstrong Jonathan , Riffle Michael , Schweighofer Erik , Bovermann Bill , Goodlett David R. , Davis Trisha N. , Shasha Dennis , Malmström Lars , Bonneau Richard
Published: August 2011

The incompleteness of proteome structure and function annotation is a critical problem for biologists and, in particular, severely limits interpretation of high-throughput and next-generation experiments. We have developed a proteome annotation pipeline based on structure prediction, where function and structure annotations are generated using an integration of sequence comparison, fold recognition, and grid-computing-enabled de novo structure prediction. We predict protein domain boundaries and three-dimensional (3D) structures for protein domains from 94 genomes (including human,Arabidopsis, rice, mouse, fly, yeast,Escherichia coli, and worm). De novo structure predictions were distributed on a grid of more than 1.5 million CPUs worldwide (World Community Grid). We generated significant numbers of new confident fold annotations (9% of domains that are otherwise unannotated in these genomes). We demonstrate that predicted structures can be combined with annotations from the Gene Ontology database to predict new and more specific molecular functions.
Prevention of hematogenous metastasis by neutralizing mice and its chimeric anti‐Aggrus/podoplanin antibodies
Authors: Nakazawa Youya , Takagi Satoshi , Sato Shigeo , Oh‐hara Tomoko , Koike Sumie , Takami Miho , Arai Hiroyuki , Fujita Naoya
Published: August 2011

The platelet aggregation‐inducing factor, Aggrus (also known as podoplanin), is reported to contribute to cancer metastasis by mediating cancer cell–platelet interaction. Aggrus has been shown to be upregulated in many different types of cancers. Thus, not only the functional inhibition of Aggrus, but also its application as a cancer‐specific antigen has therapeutic potential. Among a series of anti‐Aggrus mAb established previously, no mouse anti‐human Aggrus mAb exists that possesses the ability to neutralize platelet aggregation. For precise preclinical examinations of mouse and monkey models, the establishment of Aggrus‐neutralizing mouse mAb and their chimeric Abs is needed. In this study, we established two mouse anti‐human Aggrus mAb, P2‐0 and HAG‐3. A precise analysis of their epitopes revealed that P2‐0 recognized the conformation near the bioactive O‐glycosylation site at the Thr52 residue. In contrast, HAG‐3 recognized the amino‐terminus side at a short distance from the conformation recognized by P2‐0. We observed that only P2‐0 attenuated Aggrus‐induced platelet aggregation and Aggrus binding to its platelet receptor, that is, the C‐type lectin‐like receptor‐2. Consistent with these data, only P2‐0 prevented the experimental metastasis of human Aggrus‐overexpressing CHO cells. Subsequently, we cloned the complementary determining region of P2‐0 and produced the murine/human chimeric P2‐0 antibody. This chimeric antibody maintained its inhibitory activity of Aggrus‐induced platelet aggregation and experimental metastasis. Thus, P2‐0 and its chimeric antibody are expected to aid the development of preclinical and clinical examinations of Aggrus‐targeted cancer therapy. (Cancer Sci 2011; 102: 2051–2057)
Acromegaly surgery in Manchester revisited – The impact of reducing surgeon numbers and the 2010 consensus guidelines for disease remission
Authors: Wang Yi Yuen , Higham Claire , Kearney Tara , Davis Julian R.E. , Trainer Peter , Gnanalingham Kanna K.
Published: August 2011

Introduction  Surgical remission rates for acromegaly vary and are dependent on the tumour morphology, biochemical definition of disease remission and surgical expertise. A previous report from the Manchester region in 1998 reported an overall surgical remission rate of 27% using accepted criteria for biochemical remission at the time. The establishment of the 2010 Consensus guidelines further tightens biochemical criteria for remission. This report aims to assess the impact of establishing a specialist pituitary surgery service in Manchester in 2005, with reduced surgeon numbers on the remission rates for acromegaly surgery.

Methods  Patients with acromegaly undergoing first time endoscopic transsphenoidal surgery between 2005 and 2010 were studied. Surgery was performed by a single surgeon. Review of a prospectively collected acromegaly surgery database was performed with documentation of pre‐ and postoperative biochemical tests [oral glucose tolerance test (oGTT) and IGF‐1], as well as clinical, pathological and radiological data. Definition of disease remission was according to the 2010 Consensus criteria (GH nadir <0·4 μg/l following an oGTT and normalized population matched IGF‐1).

Results  There were 43 consecutive patients with acromegaly, with 13 (30%) microadenomas and 12 (28%) invasive adenomas. Overall, surgical remission was achieved in 29 (67%) patients. The remission rates were similar between micro (77%), macro (63%) and giant (67%) adenomas. There were nonsignificant trends towards higher remission rates for noninvasive tumours compared with invasive tumours (74%vs 50%) and for patients with a preoperative GH nadir <10 μg/l (73%vs 54%) and IGF‐1 standard deviation score <15 (72%vs 54%).

Conclusions  Remission rates for acromegaly surgery have improved following establishment of a specialist surgical service, with a reduction in surgeon numbers. Endoscopic trans‐sphenoidal surgery remains an effective first‐line treatment for achieving biochemical remission in acromegaly, despite the introduction of the more stringent 2010 consensus guidelines.
Full‐length visfatin levels are associated with inflammation in women with polycystic ovary syndrome
Authors: Lajunen Taina K. , Purhonen Anna‐Kaisa , Haapea Marianne , Ruokonen Aimo , Puukka Katri , Hartikainen Anna‐Liisa , Savolainen Markku J. , Morin‐Papunen Laure , Tapanainen Juha S. , Franks Stephen , Järvelin Marjo‐Riitta , Herzig Karl‐Heinz
Published: August 2011

Eur J Clin Invest 2012; 42 (3): 321–328

Background  Polycystic ovary syndrome (PCOS) is the most common gynaecological endocrinopathy characterized by oligomenorrhea, amenorrhoea, clinical and/or biochemical hyperandrogenism and polycystic ovaries. Abdominal deposition of excess body fat and metabolic diseases like insulin resistance and compensatory hyperinsulinemia are commonly observed in PCOS subjects. It has been suggested that visfatin is an adipokine secreted from the abdominal fat influencing glucose metabolism and might therefore contribute to the metabolic disturbances in PCOS.

Materials and methods  We measured circulating full‐length visfatin levels with a specific enzyme immunoassay (AdipoGen Inc, Incheon, South‐Korea) in 57 women with self‐reported symptoms of PCOS (hirsutism and/or oligomenorrhea) and ultrasound confirmed polycystic ovaries, and in 57 controls from the Northern Finland 1966 Birth Cohort and explored its association with metabolic and inflammatory parameters.

Results  Polycystic ovary syndrome cases had higher body mass index (BMI) (25·7 vs. 24·1 kg/m2) and waist circumference (83·2 vs. 78·8 cm) compared to controls, yet there was no difference in plasma visfatin levels between them. In contrast, visfatin significantly correlated with C‐reactive protein (CRP) in the control group and with white blood cell count (WBC) in both groups. In linear regression analysis, adjusted for PCOS, smoking, socioeconomic status, BMI or waist circumference, serum lipids and markers of glucose metabolism and hormone status, only WBC remained significantly associated with plasma visfatin levels.

Conclusion  Our results suggest that circulating visfatin levels correlate with WBC and CRP but are not associated with PCOS, obesity or metabolic markers, suggesting that visfatin may act as a proinflammatory cytokine.
Mother–Young Relationships in Sheep: A Model for a Multidisciplinary Approach of the Study of Attachment in Mammals
Authors: Nowak R. , Keller M. , Lévy F.
Published: August 2011

The onset of maternal responsiveness and the development of mother–young attachment in sheep are under the combined influence of hormonal and sensory stimulations. In the mother, the prepartum rise in oestrogen and vaginocervical stimulation caused by expulsion of the foetus act on the main olfactory system and on hypothalamic regions. This induces maternal care through the central release of oxytocin, modulated by opiates and corticotrophin‐releasing hormone. In parallel, activation of the main olfactory network enables the learning of individual lamb odour and maternal attachment. In the neonate, the first suckling episodes and the concomitant activation of the cholecystokinin, opioids and oxytocin systems facilitate the development of a preference for the mother. Gastrointestinal signals activate the brain stem, the hypothalamus and the amygdala. Within 72 h of parturition, the mother–young attachment shifts from proximal to distal recognition based on visual and auditory cues after which vocal cues become more salient. Although olfaction remains a key element in the display of selective maternal nursing, maternal attachment relies on a multisensory mental image of the lamb. These findings support the view that sheep are amongst the most appropriate animal models for the study of maternal and filial attachment in mammals.
Composite vertical bite reconstructions in eroded dentitions after 5·5 years: a case series
Authors: ATTIN T. , FILLI T. , IMFELD C. , SCHMIDLIN P. R.
Published: August 2011

Summary  In the following case series, we report on six cases of erosive worn dentitions (75 posterior teeth), which have been reconstructed using a template‐based technique with direct composite resin restorations and already examined after 3 years in service. In all patients either one or both tooth arches were completely restored using direct resin composite restorations. A wax‐up‐based template was used to avoid freehand build‐up techniques and to ensure optimal anatomy and function. All patients were re‐assessed after a mean service time of 5·5 years (mean 67 ± 4 months) using United States Public Health Service criteria. The overall quality of the restorations was good with predominantly ‘alpha’ and ‘bravo’ scores, respectively. However, the restorations showed some deterioration with respect to marginal quality, marginal discoloration, surface texture and anatomy as compared to the 3‐year investigation. The marginal impairments could be resolved by polishing. It is concluded that this non‐invasive technique provides a possible treatment option at least for the displayed observation period of 5·5 years.
Response shift in oral health‐related quality of life measurement in patients with partial edentulism
Authors: KIMURA A. , ARAKAWA H. , NODA K. , YAMAZAKI S. , HARA E. S. , MINO T. , MATSUKA Y. , MULLIGAN R. , KUBOKI T.
Published: August 2011

Summary  The purposes of this study were to determine whether a response shift was observable after partial denture treatment and to identify the predictors that influenced the response shift magnitude and direction. A total of 173 consecutive patients with no more than eight missing teeth who received implant‐supported, fixed or removable partial dentures at Okayama University Dental Hospital were asked to complete a full‐version Oral Health‐Related Quality of Life (OHRQoL) questionnaire before (pre‐test) and after treatment (post‐test). Additionally, a short form (then‐test) consisting of seven questions selected from the full version had its reliability verified and was utilised to retrospectively assess the pre‐treatment OHRQoL status. The difference between the summary scores of the then‐test and the pre‐test determined the response shift magnitude and direction. The then‐test mean score (22·9 ± 6·6) was significantly lower (worse OHRQoL) than that of the pre‐test (26·4 ± 5·2). The response shift effect size was of moderate magnitude and negative direction (d = −0·78). A multiple regression analysis showed that age (younger patients) (P < 0·01), number of replaced teeth (fewer) (P < 0·01) and pre‐test scores (lower) (P < 0·01) were the significant predictors for response shift. In conclusion, a response shift phenomenon with negative and moderate effect size was observed after partial denture treatment. The significant predictor variables were young age, fewer numbers of replaced teeth and lower pre‐test scores
Developing abbreviated OHIP versions for use with TMD patients
Authors: Van Der MEULEN M. J. , JOHN M. T. , NAEIJE M. , LOBBEZOO F.
Published: August 2011

summary  The aim of this study was to evaluate the psychometric characteristics of three versions of the Dutch Oral Health Impact Profile (OHIP‐NL), for clinical use with temporomandibular disorder (TMD) patients. To that end, two abbreviated OHIP versions (OHIP‐NL14 and OHIP‐NL5) were developed by respectively selecting 14 and five items from the officially translated and culturally adapted original 49‐item OHIP‐NL questionnaire. A total of 245 consecutive patients, referred by their dentist to the TMD clinic of the Academic Centre for Dentistry Amsterdam (77% women; mean age ± s.d. = 41·0 ± 14·9 years), completed the Research Diagnostic Criteria for TMD (RDC/TMD) axis II questionnaire and the OHIP‐NL. Reliability and validity of all three OHIP versions were compared, and their associations with four psychological axis II variables, indicating the level of impairment of patients with TMD, were examined. According to guidelines for clinical application, internal consistency scores were sufficient for OHIP‐NL and OHIP‐NL14, but insufficient for OHIP‐NL5. Test–retest reliability (n = 64) was excellent for OHIP‐NL and OHIP‐NL14 and fair to good for OHIP‐NL5. For all three versions, there was evidence for score validity: associations between OHIP summary scores on the one hand and validation variables and other RDC/TMD axis II variables on the other hand met the expectations and were statistically significant (P < 0·001). In conclusion, the OHIP‐NL and OHIP‐NL14 both performed comparatively well and better than the OHIP‐NL5. When the length of the questionnaire (i.e. the time needed for its completion) is an issue, the OHIP‐14 would therefore be the preferred version.
The clinical presentation and surgical treatment of verrucous dermatitis lesions in a draught horse
Authors: Poore Luke A. B. , Else Rod W. , Licka Theresia L.
Published: August 2011

Verrucous pastern dermatitis is a progressive inflammatory skin disease commonly involving the palmar or plantar aspects of the pasterns of horses. There are no reports of successful surgical treatment for multifocal circumscribed verrucous masses in the chronic stages of verrucous pastern dermatitis. A combination of sharp dissection and electrocautery was used to resect numerous multifocal circumscribed verrucous masses from the distal hindlimb of an 11‐year‐old gelding draught horse. There was no evidence of significant regrowth or complications at a 24 month postoperative examination.
Alternatives to Human Blood and Blood Resources
Authors: Prowse C.V.
Published: August 2011

Biotechnology is increasingly providing alternatives to established transfusion products, with the promise of freedom from infectivity and unlimited supply. Such products must demonstrate a safety and efficacy at least as great as current products, and thereafter an improved cost‐benefit ratio. Alternatives to established products may be categorised as:

Alternatives made from blood donations.

Substitutes (acting by distinct mechanisms).

Recombinant analogs.

Cellular therapies (including gene therapy).

This overview covers the current status in each of these categories, and likely trends in the near future. Recombinant therapeutic proteins are already established in certain indications, and are likely to be extended to a wider range of applications as the methods for bulk production are improved. Alternative products from donated blood should find niche indications, especially for acute therapy, but cellular therapy is unlikely to be widely implemented on this timescale, except as an adjunct in life‐threatening indications. Substitutes are perhaps the most interesting category and are expected to have a major impact, particularly through the use of “poietins” to stimulate endogenous production of circulating cell populations.
Circulatory Effects of Whole Blood, Packed Red Cells, Albumin, Starch, and Crystalloids in Resuscitation of Shock and Acute Critical Illness
Authors: Shoemaker W.C. , Wo C.C.J.
Published: August 2011

Circulatory deficiencies and the effectiveness of transfusion and fluid therapy may be evaluated by invasive and noninvasive monitoring after high risk surgery, hemorrhage, trauma, and sepsis in the ED, OR, and ICU. Earlier recognition and therapy of circulatory problems in emergency and critically ill patients to achieve optimal goals empirically defined by the survivors' patterns is recommended to improve outcome. WB, Prbc, and colloids markedly and statistically significantly improved pressure, flow, and tissue perfusion and best achieved these goals. Noninvasive monitoring may be used in the ED and OR shortly after admission to identify circulatory deficiencies and to titrate therapy, or they may be used initially as the front‐end of subsequent invasive monitoring.
Gene and Cell Transfer for Specific Immunotherapy
Authors: Brenner M.K. , Heslop H.E. , Rooney C.M.
Published: August 2011

The realisation that human tumor cells may express and process tumor specific and tumor associated antigens has increased interest in immunotherapeutic approaches to cancer treatment. This interest has been coupled with a burgeoning ability to genetically modify tumor cells and components of the immune system, in an effort to maximize the anti‐neoplastic response. In a number of settings, gene modified tumor vaccines, cytotoxic T cells and dendritic cells are producing both immunomodulation and clinically evident benefits. Continued exploration of this approach seems well justified.
Cord Blood Banking and Transplant in Europe
Authors: Gluckman E. , Rocha V. , Chastang C. ,   Eurocord
Published: August 2011

The number of cord blood transplants has been increasing very quickly with more than 250 cases reported to Eurocord Registry and more than 500 patients transplanted via the New York Cord Blood Bank. Cord blood transplants have been performed either with related or unrelated cord blood. Several cord blood banks established a group called Netcord whose goal is the standardization of the procedures, the organization of internal audits for accreditation and qualification, and the communication and exchange by internet of donor search on an international basis. More than 15000 units of frozen cord blood are currently available and this number is increasing rapidly worldwide. Analysis of the clinical results has shown that related cord blood transplants give better results than unrelated cord blood transplants. Factors associated with better survival in related and unrelated cord blood transplants were lower age, diagnosis, with better results in inborn errors and in good risk children with acute leukemia. A larger number of nucleated cells in the transplant and the recipient being negative for CMV serology were also favourable risk factors for survival. Engraftment was improved with higher numbers of cells and HLA identity. Graft versus Host disease was reduced when compared to transplants of adult allogeneic bone marrow or peripheral blood progenitor cells. HLA disparities did not influence GVH; the only factor associated with increased GVH was positive CMV serology in the recipient. This study shows that cord blood is an alternative source of hematopoietic stem cells for allogeneic transplantation in children and in some adults. HLA disparity is not a limiting factor but the number of cells infused is important; currently the use of a number of nucleated cells inferior to lx107/kg is not recommended. Several questions remain including the criteria of choice of the donor, the indications in children and in adults, the comparison of cord blood transplants to other sources of hematopoietic stem cells and the role of growth factors and expansion for improving the speed of engraftment.
Post‐Transfusion Hepatitis: Current Risks and Causes
Authors: Holland P.V.
Published: August 2011

Viral hepatitis which follows transfusions (post‐transfusion hepatitis) may be due to those transfusions, i.e., transfusion‐transmitted hepatitis (TTH), or may be incident to the reason for the transfusion and, thus, may be transfusion‐associated, but not transfusion‐transmitted. The current risks of TTH, today, are extremely small, but are still due, primarily, to the hepatitis B virus (HBV) and the hepatitis C virus (HCV), the latter, formerly being known as “non‐A, non‐B hepatitis.” The residual, now, of TTH which is non‐A, non‐B, and non‐C is extremely small and may be due to a variety of agents. Using volunteer (unpaid), repeat, blood donors, who are carefully screened for hepatitis risk factors and then tested for evidence of HBV infection, the risk of HBV being transmitted by a transfusion today is in the order of 1 per 63,000 units of blood. For transfusion‐transmitted HCV, with the same repeat, volunteer (unpaid) donors, careful screening and a sensitive assay for anti‐HCV, the risk is in the order of 1 in 125,000 units. These risks of HBV and HCV due to transfusions are so small that other means of acquiring these viruses should be sought when patients develop hepatitis following blood transfusions. However, efforts to further reduce the current risks of HBV and HCV transmission by transfusions should continue; these include restricting transfusions to those which are necessary or appropriate, utilizing alternatives to transfusion, employing novel assays to detect viral nucleic acids, and, finally, implementing various microbial inactivation techniques on blood, blood components and plasma derivatives.
HTLV Testing in Blood Transfusion
Authors: Couroucé A‐M. , Pillonel J. , Lemaire J‐M. , Saura C.
Published: August 2011

To improve the safety of the blood supply, HTLV screening of blood donations became mandatory in different countries.

In Japan and in Europe, the majority of HTLV‐infected donors are HTLV‐I whereas in the USA more than half of them are HTLV‐II‐positive.

The prevalence of HTLV‐infected donors is low in European Countries as is the rate of seroconversion. Consequently, to test donors only once would have a high efficiency. This procedure is already in use in certain countries.

Furthermore, if the use of leucodepleted cell concentrates is generalized, the policies for HTLV screening will still be further modified.
Inactivation of Viruses, Bacteria, Protozoa, and Leukocytes in Platelet Concentrates
Authors: Corash L.
Published: August 2011

Despite the increased safety of blood achieved through continued improvements in donor testing, concern remains about the safety of blood components. Transfusion of cellular components has been implicated in transmission of viral, bacterial, and protozoan diseases[l]. While it is commonly recognized that hepatitis B virus (HBV), hepatitis C virus (HCV), cytomegalovirus (CMV), and the retroviruses, such as human immunodeficiency virus (HIV) and the human lymphotrophic viruses (HTLV) can be transmitted through cellular components, other pathogens are emerging as potentially significant transfusion‐associated infectious agents. For example, transmission of protozoan infections due to trypanosomes[2–4] and babesia have been reported[5]. In addition to viral and protozoal infectious agents, bacterial contamination of platelet concentrates continues to be reported[6, 7]; and may be an under reported transfusion complication[8]. More importantly, new infectious agents may periodically enter the donor population before they can be definitively identified and tested for to maintain consistent safety of the blood supply. The paradigm for this possibility is the HIV pandemic which erupted in 1979. During the past decade a number of methods to inactivate infectious pathogens in blood components, including platelets, have been developed. This technology is now entering the clinical trial phase.
Immunomodulatory Effects of Allogeneic Blood Transfusions: Clinical Manifestations and Mechanisms
Authors: Blajchman M.A.
Published: August 2011

Recognition that allogeneic transfusion associated immunomodulation can increase morbidity in allogeneically transfused individuals has become a major concern for those involved in transfusion medicine. However, whether allogeneic blood transfusions predispose recipients to increased risk for cancer recurrence or to bacterial infections is still unproven. In contrast, data from studies in experimental animal models suggest that allogeneic blood transfusion associated immunomodulation is an immunologically mediated biological effect which is associated primarily with the infusion of allogeneic leukocytes. Moreover, the available experimental animal data suggest that pre‐storage leukoreduction, as opposed to post‐storage leukodepletion, is effective in ameliorating this tumor growth‐enhancing effect of allogeneic blood. While considerable data have accumulated in an attempt to unravel the mechanism of the immunomodulatory effect of allogeneic blood transfusions, the precise mechanism of this effect has not yet been elucidated.