bluuebunny/crossref_metadata_2025 huggingface dataset:
Sensory Optimization of a Mayonnaise‐Type Spread Made with Rice Bran Oil and Soy Protein
Authors: Garcia Karen , Sriwattana Sujinda , No Hong Kyoon , Corredor Jose Andres Herrera , Prinyawiwatkul Witoon
Published: June 2009

ABSTRACT:  The optimum formulation for mayonnaise‐type spreads containing rice bran oil (RBO) and soy protein concentrate (SPC) was determined based on sensory acceptability. RBO and SPC were used due to their health benefit claims such as lowering risk of heart disease. The effects of the proportions of high‐impact ingredients (RBO, SPC, and water) on sensory acceptability of the spreads were determined. The 10 spread formulations, prepared following a 3‐component constrained simplex lattice mixture design, were subjected to a consumer acceptance test to identify sensory attributes driving consumer acceptance and purchase intent. Predictive regression models were used to plot mixture response surfaces of the critical sensory attributes (taste, mouthfeel, and overall liking) that influenced purchase intent. Areas within the contour plots of these critical sensory attributes, having acceptability scores ≥ 68 (“moderately like” on the 100‐mm bidirectional labeled affective magnitude scale) were chosen and superimposed to obtain a predicted optimum formulation range (37% to 43% RBO, 4% to 7% SPC, and 52% to 57% water). The formulation containing 37% RBO, 6% SPC, and 57% water, which was located within the optimum region, was selected as a base for further developing flavored (sour cream & onion, cheddar & sour cream, or Monterrey Jack dried cheese) products. All flavored spreads were significantly more acceptable than the plain formulation. Purchase intent of all flavored products also significantly increased once consumers had been given the information about potential health benefits associated with RBO and SPC in the spreads.
RIP3, an Energy Metabolism Regulator That Switches TNF-Induced Cell Death from Apoptosis to Necrosis
Authors: Zhang Duan-Wu , Shao Jing , Lin Juan , Zhang Na , Lu Bao-Ju , Lin Sheng-Cai , Dong Meng-Qiu , Han Jiahuai
Published: June 2009

The Grim RIPper

Cells can undergo regulated cell death through distinct processes known as apoptosis and necrosis. Regulation of apoptosis is better understood than that of necrosis. In a screen for gene products that participate in control of necrosis in cells treated with TNF (tumor necrosis factor),

D.-W. Zhang
et al.

(p.
332
; published online 4 June) identified a protein kinase, RIP3. In cells treated with TNF and a caspase inhibitor that inhibits apoptosis, seven metabolic enzymes interacted with RIP3, some of which are associated with mitochondria. Generation of reactive oxygen species was necessary for TNF-induced necrosis, and depletion of RIP3 reduced the generation of reactive oxygen species. Thus, RIP3 may participate in the mechanisms that link energy metabolism with mechanisms of cell death.
IRAP Identifies an Endosomal Compartment Required for MHC Class I Cross-Presentation
Authors: Saveanu Loredana , Carroll Oliver , Weimershaus Mirjana , Guermonprez Pierre , Firat Elke , Lindo Vivian , Greer Fiona , Davoust Jean , Kratzer Roland , Keller Susanna R. , Niedermann Gabriele , van Endert Peter
Published: June 2009

Let Me Present to You

The presentation of exogenous antigens by major histocompatibility (MHC) class I molecules is referred to as cross-presentation. Cross-presentation by dendritic cells plays a central role in the priming of cytolytic T lymphocyte responses to natural and vaccine antigens and also in the initiation of autoimmune diseases such as type 1 diabetes. A satisfactory cell biological model of cross-presentation is not available, which would be required to decipher the link, inherent in cross-presentation, between the secretory and the endocytic pathways.

Saveanu
et al.

(p.
213
, published online 4 June) identify an aminopeptidase, insulin-regulated aminopeptidase (IRAP), which interacts directly with MHC class I molecules. IRAP plays an exclusive and important role in MHC class I cross-presentation of receptor-targeted and phagocytosed antigens. In particular, a specific endosomal compartment, which carries IRAP as a unique marker, is implicated in cross-presentation of phagocytosed antigens.
Extending Universal Nodal Excitations Optimizes Superconductivity in Bi
2
Sr
2
CaCu
2
O
8+δ
Authors: Pushp Aakash , Parker Colin V. , Pasupathy Abhay N. , Gomes Kenjiro K. , Ono Shimpei , Wen Jinsheng , Xu Zhijun , Gu Genda , Yazdani Ali
Published: June 2009

Cuprate Analysis

Despite more than 20 years of intensive effort, the mechanism providing superconductivity in the cuprates remains elusive and contentious, partly because the cuprates are inhomogeneous. Scanning tunneling spectroscopy (STS) and high-resolution, angle-resolved photoemission spectroscopy provide energy and momentum information about the excitations in the high-temperature cuprate superconductors.

Pushp
et al.

(p.
1689
, published online 4 June) provide a STS study of the cuprate Bi
2
Sr
2
CaCu
2
O
8+δ
over a range of doping levels and temperatures. This methodology for analyzing the spectra takes into account the inhomogeneity and may provide insight into how a superconducting pairing mechanism evolves from the parent insulating state.
Isolation and Characterization of a Novel Lysine Racemase from a Soil Metagenomic Library
Authors: Chen I-Chien , Lin Wei-De , Hsu Shin-Kuang , Thiruvengadam Venkatesan , Hsu Wen-Hwei
Published: June 2009

A lysine racemase (
lyr
) gene was isolated from a soil metagenome by functional complementation for the first time by using
Escherichia coli
BCRC 51734 cells as the host and
d
-lysine as the selection agent. The
lyr
gene consisted of a 1,182-bp nucleotide sequence encoding a protein of 393 amino acids with a molecular mass of about 42.7 kDa. The enzyme exhibited higher specific activity toward lysine in the
l
-lysine-to-
d
-lysine direction than in the reverse reaction.
Polyarticular Septic Arthritis with Bilateral Psoas Abscesses following Acupuncture
Authors: Ogasawara Michihiro , Oda Keisuke , Yamaji Ken , Takasaki Yoshinari
Published: June 2009

We report a case of polyarticular septic arthritis with bilateral psoas abscesses. A 50-year-old woman was admitted with fever, multiple joint swelling and pain. She had a clinical history of acupuncture therapy for treatment of her chronic lower back pain two days before the appearance of her symptoms. Methicillin-sensitive Staphylococcus aureus was isolated from blood culture, knee joint fluids and psoas abscess. After a long course of antibiotics for 70 days together with drainage of the abscess, the condition completely resolved. The acupuncture is the probable cause of the infection, and this case report reveals the importance of asking about a clinical history of acupuncture treatment and of making repeated bacterial examinations in undiagnosed polyarthritis patients.
Postoperative Pain Management and Acupuncture: A Case Report of Meniscal Cyst Excision
Authors: Galanis Nikiforos , Stavraka Chara , Boutsiadou Triantafyllia , Kirkos John M , Kapetanos George
Published: June 2009

We report a case of pain management after a meniscal cyst excision, with the use of electroacupuncture (EA). There are a few reports which indicate that postoperative pain management is prerequisite for the patient's optimal recovery, but surveys in the UK and the USA have identified an unacceptable prevalence of poor pain control after surgery, which might increase the risk of a chronic pain state. The conventional treatment of postoperative pain includes systemic medications such as opioids, non-steroidal anti-inflammatory drugs and other non-opioid agents. In our case, the rehabilitation lasted for 6 months without significant benefit. After that period our patient was treated with EA. By the end of the first EA session the relief of pain was notable and after a course of 10 treatments the patient reported complete relief of the symptoms with no recurrence during a 2 year follow up period. In conclusion, this might indicate that EA could be useful for postoperative pain management.
Modulation of Involuntary Movements in Cerebral Palsy with Acupuncture
Authors: Watson Paul
Published: June 2009

This case describes the treatment of severe involuntary movements in a 10-year-old boy suffering from cerebral palsy.

Needling GB34 and ST36 bilaterally for 25 minutes resulted in immediate temporary cessation of involuntary extension contractions of the erector spinae muscles for the duration of the treatment, resulting in increased functionality in the patient. This response occurred regularly on repeated treatment, but was not maintained between treatments.

Involuntary movements are a major disabling feature of cerebral palsy, which impair quality of life and often prove difficult to treat successfully. This case is reported with the hope that this simple technique may provide relief for other patients suffering similar symptoms.
Nice Guideline on Osteoarthritis: Is it Fair to Acupuncture? Yes
Authors: Latimer Nicholas
Published: June 2009

The NICE Osteoarthritis Guideline Development Group (GDG) has been challenged for not using the available acupuncture evidence in the most appropriate manner in three crucial areas. This response explains the methods used by the GDG with particular reference to the economic analysis, and illustrates that the methods used were those most appropriate for developing a NICE clinical guideline. The cost-effectiveness conclusions made by the GDG are supported by the currently available evidence.
Nice Guideline on Osteoarthritis: Is it Fair to Acupuncture? No
Authors: White Adrian
Published: June 2009

A new guideline on the care and management of osteoarthritis has recently been published by the National Institute for Health and Clinical Excellence, and makes wide-ranging and authoritative recommendations. The guideline states that there is insufficient evidence to recommend acupuncture. There appears to be three areas where the guidelines may have not used the available evidence in the most appropriate manner. First, data on the long-term effectiveness of acupuncture may have been misinterpreted. Second, the specific rejection of electroacupuncture indicates a restricted understanding of acupuncture as a treatment, and is based on a cost-effectiveness analysis which may not be ideal. Third, the cost-effectiveness calculations used comparisons with sham acupuncture (“placebo”) when comparison with standard care would have been more appropriate. The guideline may therefore lead some patients with osteoarthritis to miss out on a treatment that may be effective for them.
AN APPROACH FOR MULTIPLE ATTRIBUTE GROUP DECISION MAKING BASED ON INTUITIONISTIC FUZZY INFORMATION
Authors: YUE ZHONGLIANG , JIA YUYING , YE GUODONG
Published: June 2009

Intuitionistic fuzzy set, was introduced by Atanassov, has been applied to many different fields, such as logic programming, pattern recognition, and decision making, etc. However, so far there has been few investigation on how to transform attribute tested values of alternative into a intuitionistic fuzzy number, and then complete decision making by intuitionistic fuzzy information. In this paper, the original attribute value (objective information) are characterized by crisp number which are given by decision maker. We define the concepts of supporting, opposing and neutral set of alternative respectively, develop an approach for transform attribute values into intuitionistic fuzzy number, and determine the order of alternatives based on the score and the degree of accuracy of the intuitionistic fuzzy number. Finally, a practical example is provided to illustrate the developed method.
SOME PROPERTIES OF CONTINUOUS UNCERTAIN MEASURE
Authors: GAO XIN
Published: June 2009

In this paper, we discuss some properties in uncertainty theory when uncertain measure is continuous. Firstly, the judgement conditions of continuous uncertain measure are proposed. Secondly, basic properties of uncertainty distribution and critical values of uncertain variable are proved. Finally, the convergence theorems for expected value are discussed.
ITERATIVE NON-SEQUENTIAL PROTEIN STRUCTURAL ALIGNMENT
Authors: SALEM SAEED , ZAKI MOHAMMED J. , BYSTROFF CHRISTOPHER
Published: June 2009

Structural similarity between proteins gives us insights into their evolutionary relationships when there is low sequence similarity. In this paper, we present a novel approach called SNAP for non-sequential pair-wise structural alignment. Starting from an initial alignment, our approach iterates over a two-step process consisting of a superposition step and an alignment step, until convergence. We propose a novel greedy algorithm to construct both sequential and non-sequential alignments. The quality of SNAP alignments were assessed by comparing against the manually curated reference alignments in the challenging SISY and RIPC datasets. Moreover, when applied to a dataset of 4410 protein pairs selected from the CATH database, SNAP produced longer alignments with lower rmsd than several state-of-the-art alignment methods. Classification of folds using SNAP alignments was both highly sensitive and highly selective. The SNAP software along with the datasets are available online at
Silencing the myotrophin gene by RNA interference leads to the regression of cardiac hypertrophy
Authors: Gupta Sudhiranjan , Maitra Ratan , Young Dave , Gupta Anasuya , Sen Subha
Published: June 2009

Myotrophin-induced activation of NF-κB has been shown to be associated with cardiac hypertrophy (CH) that progresses to heart failure (HF). In the present study, we examined the cause-and-effect relationship between myotrophin and NF-κB activation using small hairpin RNA (shRNA) against myotrophin both in vitro (using neonatal rat myocytes) and in vivo [using myotrophin transgenic (Myo-Tg) mice, which overexpress myotrophin in the heart, develop CH, and gradually progress to HF]. Among several lentiviral vectors expressing myotrophin shRNAs, L-sh-109 showed the best silencing effect at both the mRNA (155.3 ± 5.9 vs. 32.5 ± 5.5, P < 0.001) and protein levels associated with a significant reduction of atrial natriuretic factor (ANF) and NF-κB. In vivo, when L-sh-109 was delivered directly into the hearts of 10-wk-old Myo-Tg mice, we observed a significant regression of cardiac mass (8.0 vs. 5.7 mg/g, P < 0.001) and myotrophin gene expression (54.5% over untreated Myo-Tg mice, P < 0.001) associated with a reduction in ANF and NF-κB signaling components. Our data suggest that using RNA interference to silence the myotrophin gene prevents NF-κB activation, associated with an attenuation of CH. This strategy could be an excellent therapeutic means for the treatment of CH and HF.
Pulmonary Fluid Balance in the Human Newborn Infant
Authors: Helve Otto , Pitkänen Olli , Janér Cecilia , Andersson Sture
Published: June 2009

At birth, the infant’s lungs must be cleared of fetal lung fluid. This process is mediated through the activation of airway epithelial sodium channels (ENaC). In animals, ENaC is considered crucial for postnatal pulmonary adaptation. In humans, postnatal ENaC expression is gestational age dependent and its activity, measured as nasal potential difference, correlates with lung compliance. It is therefore likely that in the human newborn infant ENaC is also important for physiologic postnatal adaptation. Low pulmonary expression or activity of ENaC in the perinatal period may cause delayed clearance of lung fluid and thereby contribute to development of respiratory distress in both term and preterm infants.
Current Trials in the Treatment of Respiratory Failure in Preterm Infants
Authors: Soll Roger F.
Published: June 2009

The end of the 20th century brought significant improvements in the outcome of extremely low-birth-weight infants related to the increased use of antenatal corticosteroids and the introduction of postnatal surfactant to prevent or treat respiratory distress syndrome. As we complete the first decade of the 21st century, less progress in improving clinical outcome in this population has been accomplished. Newer modes of ventilation and the use of inhaled nitric oxide have made few demonstrable improvements in outcome. Surprisingly, the greatest hope for improvement may come from the refinement of currently available care including less invasive respiratory support and the combining of various known therapies (such as continuous positive airway pressure and surfactant).
C1584: Effect on von Willebrand Factor Proteolysis and von Willebrand Factor Antigen Levels
Authors: Davies James Anthony , Collins Peter William , Hathaway Lee Sarah , Bowen Derrick John
Published: June 2009

The present review provides a clearer picture of the effect of C1584 on the level and properties of von Willebrand factor (VWF). The C1584 variant is associated with decreased VWF levels (especially in combination with blood group O) and VWF function, and with slightly enhanced VWF proteolysis, and there is evidence to support its association with enhanced VWF clearance. These properties help explain the enrichment for C1584 in mild type 1 VWD and the observed marked association of the variant and blood group O in this mild bleeding disorder. It has been proposed that the mildly enhanced VWF proteolysis associated with C1584 (and also with blood group O) may compromise clot formation, offering a further rationale for the enrichment of the variant in type 1 VWD. C1584 shows variable penetrance and this is still not fully understood. It reflects the interaction of C1584 with other variables, one of which is clearly blood group O. Genome-wide association studies aimed at identifying loci involved in the control of the VWF level may provide further insights into C1584 penetrance and, more generally, into mechanisms underlying type 1 VWD and also cardiovascular disease.
Factor VIII-von Willebrand Factor Binding Defects in Autosomal Recessive von Willebrand Disease Type Normandy and in Mild Hemophilia A
Authors: Jacquemin Marc
Published: June 2009

This concise review is focused on genetic, molecular and clinical aspects of von Willebrand disease (VWD) type 2N and of mild hemophilia A due to mutations impairing FVIII-von Willebrand factor (VWF) interactions. Missense mutations in the VWF gene impairing the binding to FVIII do not impair the structure of VWF multimers nor the ability of VWF to aggregate platelets but causes an accelerated clearance of FVIII. Missense mutations in the FVIII gene impairing the binding to VWF are a common cause of mild/moderate hemophilia A. The implications of these observations for the treatment of patients with coagulation factor concentrates and desmopressin are discussed.
Managing Patients with von Willebrand Disease Type 1, 2 and 3 with Desmopressin and von Willebrand Factor-Factor VIII Concentrate in Surgical Settings
Authors: Michiels Jan Jacques , van Vliet Huub H.D.M. , Berneman Zwi , Schroyens Wilfried , Gadisseur Alain
Published: June 2009

Guidelines and recommendations for the acute and prophylactic treatment of bleeding in von Willebrand disease (VWD) patients with von Willebrand factor (VWF)/factor VIII (FVIII) concentrates should be based on the analysis of the content of VWF/FVIII concentrates and on pharmacokinetic studies in patients with different severity of VWD (type 1, type 2 or type 3). The VW/FVIII concentrates should be assessed using the parameters FVIII:coagulant activity (C), VWF:ristocetin cofactor activity (RCo), VWF:collagen binding and VWF multimeric patterns for the presence of large multimers to determine their predicted efficacy and safety in prospective management studies. As the bleeding tendency is moderate in VWD type 2 and severe in type 3 and because the FVIII:C levels are subnormal in type 2 but very low in type 3 VWD patients, new guidelines using VWF:RCo unit dosing for the acute and prophylactic treatment of bleeding episodes are proposed. Such guidelines should be stratified for the severity of bleeding, the type of surgery (minor or major) and also for the bleeding score in either VWD type 1, 2 or 3.
ADAMTS13 in Health and Disease
Authors: Feys Hendrik B. , Deckmyn Hans , Vanhoorelbeke Karen
Published: June 2009

We raised a set of monoclonal antibodies (mAb) against recombinant human ADAMTS13, constructed the first antigen test fully based on mAbs and compared ADAMTS13 antigen and enzymatic activity levels in a large set of plasma samples collected from different patients and healthy controls. Assessing both ADAMTS13 antigen and activity helps to understand whether or not the protease is fully active in pathological conditions, e.g. liver cirrhosis, inflammatory bowel disease, cardiac surgery, pregnancy and oral contraceptive intake, in the neonatal state and in normal individuals. Our ADAMTS13 antigen assay showed less variability than the collagen binding-based activity assay. Antigen values correlated well with activity in normal individuals, but differed to various degrees in neonates, pregnancies at later maternal age and cardiac surgery. No discrepancies were noted in liver cirrhosis and inflammatory bowel disease, which were both associated with low plasma levels of ADAMTS13. In conclusion, parallel measurement of ADAMTS13 activity and antigen provides a new tool for understanding the behavior of the VWF-cleaving protease in health and disease.
Advances in Radiotherapy in Operable Rectal Cancer
Authors: Suppiah Aravind , Hartley John E. , Monson John R.T.
Published: June 2009

Aims: Radiotherapy (RT) reduces local recurrence in rectal cancer but the optimal treatment schedule is unknown. Relevant questions in designing optimal therapy are set out. This review identifies evidence that influences current practice and shapes future trials in treatment of operable rectal cancer. Methods: PubMed and MEDLINE search. Results: RT reduces local recurrence and pre-operative treatment is superior to post-operative treatment. Longer interval to surgery and concurrent chemotherapy are associated with greater downstaging, although influence on sphincter preservation and survival is minimal. Short-course RT (SCRT) demonstrates lower recurrence, but with long-term dysfunction and minimal survival benefit. The role of SCRT should be re-evaluated to encompass new criteria/areas. Conclusion: SCRT should be used selectively rather than as a blanket treatment policy. SCRT compounds functional morbidity caused by mesorectal excision which may be excessive in some patient groups, especially early-stage rectal cancer or frail elderly patients. RT and local excision may be a feasible surgical alternative in these groups. Alternatively, SCRT and delayed surgery may be a future alternative to current long-course chemoradiotherapy. As survival is only marginally affected despite low local recurrence, future trials should aim to address metastatic disease. End points which incorporate function and quality of life must be used.
Correlates of Unsafe Equipment Sharing among Injecting Drug Users in St. Petersburg, Russia
Authors: Gyarmathy V. Anna , Li Nan , Tobin Karin E. , Hoffman Irving F. , Sokolov Nikolai , Levchenko Julia , Batluk Julia , Kozlov Andrei A. , Kozlov Andrei P. , Latkin Carl A.
Published: June 2009

Aims: To assess among injecting drug users (IDUs) in St. Petersburg, Russia, the urban environment, social norms and individual correlates of unsafe injecting. Methods: Between December 2004 and January 2007, 446 IDUs were interviewed in St. Petersburg, Russia. Results: Prevalence of HCV was 96% and HIV 44%. 17% reported receptive syringe sharing after an HIV-infected IDU, 49% distributive syringe sharing, 76% sharing cookers, 73% sharing filters and 71% syringe-mediated drug sharing when not all syringes were new. Urban environmental characteristics correlated with sharing cookers and syringe-mediated sharing, and social norms correlated with receptive and distributive syringe sharing and sharing cookers. Individual correlates included cleaning used syringes (all 5 dependent variables) and self-report of HIV infection (receptive and distributive syringe sharing). Conclusion: HIV status disclosure is an unreliable but frequently used HIV prevention method among IDUs in St. Petersburg, who reported alarmingly high levels of injecting equipment sharing. Voluntary counseling and testing should be widely available for this population. Ethnography is needed to assess the effectiveness of the syringe cleaning process. Prevention interventions need to be ongoing among IDUs in St. Petersburg, and should incorporate urban environmental factors and social norms, which may involve peer education and social network interventions.
Outcomes and Management Strategies after Nondiagnostic Stereotactic Biopsies of Brain Lesions
Authors: Zoeller Garrett K. , Benveniste Ronald J. , Landy Howard , Morcos Jacques J. , Jagid Jonathan
Published: June 2009

Background/Aims: A significant minority of stereotactic biopsies (SBs) of brain lesions is nondiagnostic, yet there are no optimal strategies for preventing nondiagnostic SB (NDSB) and for managing patients after NDSB. We performed this study in order to identify risk factors for NDSB, to determine how diagnoses are eventually reached in these patients, and to ascertain whether NDSB affects clinical outcomes. Methods: Retrospective chart review of patients at our institution who underwent SB of brain lesions. Results: Twenty-four out of 100 SBs were nondiagnostic. NDSB was less likely in contrast-enhancing brain lesions in immunocompetent patients, with larger lesions and in the setting of diagnostic findings on intraoperative frozen section analysis. Of 16 patients with adequate postoperative follow-up, a diagnosis was eventually reached in 11, via further review of the pathology, retrieval of additional tissue specimens or additional noninvasive testing. Survival times for patients with NDSB and eventual tumor diagnoses were within expected ranges for patients with similar tumors. Three of the 5 patients who never received a final diagnosis enjoyed prolonged survival without progressive symptoms. Conclusions: Surgeons should consider taking additional specimens in the case of nondiagnostic intraoperative frozen section during SB. If a tumor is suspected and final pathology is nondiagnostic, outside review of the slides may be helpful, and sampling further tissue should be considered. For diseases other than tumors, the diagnosis will generally be made without a repeat biopsy. The delays in diagnosis resulting from NDSB do not appear to affect survival, at least in patients eventually found to have brain tumors.
Efficiency and Dose Planning Comparisons between the Perfexion and 4C Leksell Gamma Knife Units
Authors: Niranjan Ajay , Novotny Jr. Josef , Bhatnagar Jagdish , Flickinger John C. , Kondziolka Douglas , Lunsford L.Dade
Published: June 2009

Aims: We analyzed the efficiency of the Leksell Gamma Knife Perfexion (LGK PFX) in the treatment of multiple metastases and benign tumors. We also compared treatment planning conformity between LGK PFX and LGK 4C for benign tumors. Method: Over a 6-week interval, 37 patients (21 with multiple brain metastases and 16 with benign tumors) underwent radiosurgery using LGK PFX at the University of Pittsburgh. We created dose plans for all patients using Leksell Gamma Plan for LGK PFX and LGK 4C. The same doses were prescribed for both LGK PFX and LGK 4C. Results: No significant difference was observed between LGK 4C and LGK PFX for total beam-on time. The median reduction in setup time on the LGK PFX was 53 min per patient (range 19–125 min) for multiple metastases. The median reduction in setup time on the LGK PFX for benign tumors was 16 min per patient (range 5–53 min). There was no significant difference in the dose conformality between LGK 4C and LGK PFX. Conclusions: This study demonstrated that in addition to its enhanced cranial reach, LGK PFX provided a significant improvement in efficiency for patients with multiple brain metastases. For benign tumor radiosurgery LGK PFX provided improvement in efficiency without a significant difference in conformality.
BCG Priming of Dendritic Cells Enhances T Regulatory and Th1 Function and Suppresses Allergen-Induced Th2 Function in vitro and in vivo
Authors: Ahrens B. , Grüber C. , Rha R.-D. , Freund T. , Quarcoo D. , Awagyan A. , Hutloff A. , Dittrich A.M. , Wahn U. , Hamelmann E.
Published: June 2009

Background: The inverse correlation of mycobacterial infection with asthma prevalence and the inhibitory effects of vaccination with Bacille Calmette-Guérin (BCG) on airway hyperreactivity in asthma models suggest modulation of dendritic cell (DC) and T cell functions by mycobacterial compounds. Methods: To delineate these immunological effects, the immunogenicity of BCG Copenhagen, BCG Chicago and BCG Pasteur was compared in a mouse model. Bone marrow-derived dendritic cells (BMDCs) from BALB/c mice were stimulated with ovalbumin (OVA) with or without BCG. BMDCs were phenotypically characterized by flow cytometry, and we used ELISA to measure the cytokine production of BMDCs as well as of co-cultivated allergen-specific T cells in response to OVA-pulsed. Immunomodulatory effects of BCG were studied in a model of allergic airway inflammation by adoptive transfer of allergen-pulsed BMDCs. Results: Immunomodulation with BCG induced production of IL-10 and IL-12 by BMDCs. Co-cultured allergen-specific T cells produced less IL-5, IL-13 and IFN-γ but more IL-10. Also the number of FoxP3+ regulatory T cells was enhanced. Strongest effects were seen with BCG Chicago and BCG Pasteur. In vivo, administration of BCG modulated OVA-pulsed BMDCs then reduced eosinophilic airway inflammation but enhanced infiltration with granulocytes. Airway hyperreactivity and mucus production were reduced and more FoxP3+ T cells were observed. Conclusion: BCG-induced suppression of Th2-type allergic airway inflammation was associated with enhancement of regulatory T cell function but also of Th1-associated neutrophilic airway inflammation. These findings raise concerns regarding the safety profile of BCG as a potential tool for prevention and therapy of allergic airway disease.
Differential Protein Expression by Dendritic Cells from Atopic and Non-Atopic Individuals after Stimulation by the Major House Dust Mite Allergen Der p 1
Authors: Horlock C. , Shakib F. , Jones N.S. , Sewell H.F. , Ghaemmaghami A.M.
Published: June 2009

Background: Dendritic cells (DCs) are sentinels of the immune system and are known to play a key role in allergic responses. However, it is not clear how DCs that have been exposed to an allergen support Th2 type immune responses. It is possible that DCs from atopic individuals are inherently programmed to support allergic disease, or it is the exposure of dendritic cells to allergens that is key to the development of allergic sensitisation. Methods: We used 2D gel electrophoresis and MALDI mass spectrometry to compare the proteome of DCs from atopic and non-atopic individuals in both the resting state and after stimulation with the major house dust mite allergen Der p 1. Results: Our data show that unstimulated DCs from atopic and non-atopic individuals are very similar at the whole cell proteome level, showing few differentially expressed proteins. However, upon stimulation with Der p 1, a number of additional proteins are differentially expressed, and of these several were of potential relevance to Th2 cell differentiation and the allergic response, including GTP-binding regulatory protein Gi alpha-2, frabin and cathepsin D. Conclusion: Whilst there are inherent differences between DCs from atopic and non-atopic individuals, it seems that exposure to allergen plays a key role in differential expression of proteins by these key immune cells. Further studies should now focus on establishing the biological relevance of these proteins as biomarkers in house dust mite allergy and their role in allergen induced Th2 cell differentiation.
Longitudinal Evaluation of Patients with a Homozygous R450H Mutation of the TSH Receptor Gene
Authors: Mizuno Haruo , Kanda Keisuke , Sugiyama Yukari , Imamine Hiroki , Ito Tetsuya , Kato Ineko , Togari Hajime , Kamoda Tomohiro , Onigata Kazumichi
Published: June 2009

Background/Aim: The R450H mutation of the TSH receptor (TSHR) gene has been frequently observed in Japanese patients with resistance to TSH. The purpose of this study was to clarify the phenotype of patients with a homozygous R450H mutation of the TSHR gene; the mutant receptor has previously demonstrated moderately impaired function in vitro. Methods: We performed a clinical investigation of 5 Japanese patients who had hyperthyrotropinemia as neonates, in whom a homozygous R450H mutation of the TSHR gene had been demonstrated by genetic sequencing analysis. Results: The thyroid hormone levels of the patients were normal in early infancy, although their serum levels of TSH were mildly elevated. After supplemental treatment with levothyroxine sodium (L-T4) was started, we had to increase the dose to maintain the level of TSH within the normal range in all patients. Thyroid dysfunction became obvious in one patient at reexamination during adolescence when L-T4 treatment was stopped for 1 month. Four patients were examined for intelligence quotient and their scores were normal. Conclusions: Thyroid hormone replacement therapy should be considered based on biological data in patients with hyperthyrotropinemia who have a homozygous R450H mutation of the TSHR gene even if they do not exhibit obvious hypothyroidism in infancy.
Long-Term Follow-Up of GH-Treated Girls with Turner Syndrome: BMI, Blood Pressure, Body Proportions
Authors: Bannink Ellen M.N. , van der Palen Roel L.F. , Mulder Paul G.H. , de Muinck Keizer-Schrama Sabine M.P.F.
Published: June 2009

Aims: To investigate whether long-term growth hormone (GH) treatment influenced blood pressure (BP), body proportions and BMI in young Turner syndrome (TS) women several years after GH discontinuation. Methods: A follow-up study of a randomized GH dose-response trial with 3 GH dosages (1.3, 2.0, and 2.7 mg/m2/day). 39 TS patients (20.0 ± 2.1 years) participated 4.8 (1.9) years after GH discontinuation. Mean GH duration was 8.7 (2.0) years. Measurements: BP, BMI and body proportions. Results: During GH treatment, DBP had decreased. At the long-term follow-up study, DBP had increased and was similar to pretreatment levels. DBP was negatively influenced by GH dose. SBP was not influenced by GH dose or duration. The BMI increased gradually during and after GH therapy. During GH therapy, shape values of sitting height had decreased to normal values, of foot had increased, and both remained constant after GH discontinuation. Conclusions: GH therapy in girls with TS has, besides height, additional beneficial effects on BP and body proportions, except foot length. Nearly 5 years after ending GH, the favorable effect of GH on BP was still noticeable. The BMI increased gradually over the years, not influenced by GH.
Antihypertensive Treatment after Stroke and All-Cause Mortality – An Analysis of the General Practitioner Research Database (GPRD)
Authors: Toschke André Michael , Wolfe Charles D.A. , Heuschmann Peter Ulrich , Rudd Anthony G. , Gulliford Martin
Published: June 2009

Background: Randomised controlled trials have shown a beneficial effect of antihypertensive treatment on stroke recurrence. The effect of antihypertensive treatment on survival and recurrence in an unselected sample of the general population, using the General Practice Research Database, was analysed. Methods: Cox regression estimating the effect of antihypertensive treatment on survival and stroke recurrence >1 year among 44,244 first-ever strokes in the UK from 1997 to 2006 was adjusted by propensity score analysis considering gender, age, general practice, stroke year, drug prescriptions and diagnostic codes from other diseases. Results: The EU standardised stroke incidence was 118 per 100,000 (95% CI = 117–120). The 90-day case fatality was 19%. By 90 days after stroke 20,147 (58%) were diagnosed as having hypertension, of whom 75% had received antihypertensive treatment after stroke. After 5 years 68% of the hypertensive stroke patients receiving antihypertensive treatment were alive, while this proportion for patients not prescribed antihypertensive treatment was 59%. This could not be explained by potential confounders with an adjusted relative risk of 0.62 (95% CI = 0.58–0.66; p < 0.001) for antihypertensive treatment and premature death. The adjusted relative risk of antihypertensive treatment on stroke recurrence after 1 year, which was observed in 35% until 5 years after stroke, was 0.92 (95% CI = 0.84–1.01; p = 0.092). Conclusions: A high proportion of hypertensive stroke patients did not receive antihypertensive treatment. The protective effect of antihypertensive treatment on survival was higher in this general population than reported in randomised controlled trials, while an effect of antihypertensive treatment on late stroke recurrence was borderline, but not significant.
Selective Use of Recombinant Human Erythropoietin in Pregnant Patients with Severe Anemia or Nonresponsive to Iron Sucrose Alone
Authors: Krafft Alexander , Bencaiova Gabriela , Breymann Christian
Published: June 2009

Objective: To evaluate the effectiveness of a stepwise use of recombinant human erythropoietin (rhEPO) in pregnant patients with severe anemia or nonresponsive to intravenously administered iron only. Methods: All subjects had iron deficiency anemia, i.e., a hemoglobin (Hb) level <10.0 g/dl and ferritin ≤15 μg/l. Patients with an Hb level ≥9.0 g/dl and <10.0 g/dl received 200 mg iron sucrose intravenously twice weekly. If response to therapy was poor, patients additionally received 10,000 U rhEPO twice weekly. Patients with an Hb level <9.0 g/dl primarily received iron sucrose and rhEPO likewise. Results: Of the 84 patients, 59 had a baseline Hb level between 9.0 and 9.9 g/dl, of whom 32 responded poorly, thus receiving additional rhEPO. Twenty-five patients had a baseline Hb level <9.0 g/dl. The overall Hb level after therapy was 11.0 g/dl (±0.5, range 10.0–12.6 g/dl). Mean duration of therapy was 3.5 weeks (7 infusions). Conclusion: This study shows an effective treatment regimen for patients with various degrees of anemia in pregnancy. Iron sucrose is a safe and effective treatment option. In cases of severe iron deficiency anemia or poor response to parenteral iron therapy additional administration of rhEPO might be considered. However, the mechanism for not responding to intravenous iron therapy despite iron deficiency anemia still remains unclear to a large extent.
Monocytes and Neutrophils Exhibit Both Distinct and Common Mechanisms in Penetrating the Vascular Basement Membrane In Vivo
Authors: Voisin Mathieu-Benoît , Woodfin Abigail , Nourshargh Sussan
Published: June 2009

Objectives—

Leukocyte migration through venular walls is a fundamental event during inflammation, but many aspects of this response, including the mechanisms associated with leukocyte migration through the vascular basement membrane (BM) in vivo, are poorly understood. Here we investigated and compared the means by which neutrophils and monocytes migrate through the venular BM. Specifically, as we have previously reported on the existence of neutrophil permissive sites (termed matrix protein low expression regions; LERs) within the venular BM, we have now investigated the role of these sites in monocyte transmigration in vivo.

Methods and Results—

Analysis of CCL2-stimulated mouse cremaster muscles by immunofluorescent staining and confocal microscopy demonstrated that both neutrophils and monocytes use LERs for penetrating venular walls, but independent and distinct mechanisms are used by the 2 cell types. Collectively, (1) neutrophil but not monocyte transmigration led to enlargement of LERs, (2) monocytes showed a greater extent of deformability in migrating through the venular BM, and (3) only extravasated neutrophils were associated with the carriage of laminin fragments.

Conclusions—

The findings provide novel insights into mechanisms of leukocyte transmigration by presenting the first in vivo evidence for distinct modes used by neutrophils and monocytes in penetrating the vascular BM.
Simultaneous Occurrence and Interaction of Hypoperfusion and Embolism in a Patient With Severe Middle Cerebral Artery Stenosis
Authors: Schreiber Stefanie , Serdaroglu Mine , Schreiber Frank , Skalej Martin , Heinze Hans-Jochen , Goertler Michael
Published: June 2009

Background and Purpose—

The coincidence of hemodynamic and embolic findings in patients with stroke from large artery stenosis has suggested an interaction of both pathologies. This has emerged into the hypothesis of an impaired washout of emboli in the presence of hypoperfusion. We propose an additional link between both pathologies.

Summary of Case—

A 48-year-old woman presented with a recurrent symptomatic severe left middle cerebral artery stenosis. MRI depicted left hemispheric ischemic infarcts in the deep and subcortical white matter and in the cortical border zone. One-hour transcranial Doppler monitoring detected 64 microembolic signals distal to the arterial stenosis. Monitoring also revealed recurrent thrombus formation at the stenotic plaque with decline of poststenotic flow velocity followed by embolism with abrupt excessive flow velocity increase and subsequent normalization at the initial baseline level. Cerebrovascular reserve in the distribution territory of the stenosed artery as assessed by transcranial Doppler after carbon dioxide stimulation revealed a normal reserve capacity in periods with baseline poststenotic flow velocity and an exhausted reserve capacity when flow velocity was decreased due to stenotic thrombus formation.

Conclusion—

In our patient, adherent thrombus formation resulted in an increasing severity of the stenosis with subsequent vasodilatation and diminution of flow resistance in the depending vascular distribution territory. MRI suggested that adherent thrombi were predominantly washed into terminal supply and border zone brain regions, ie, into regions with supposed maximum vasodilatation and least flow resistance immediately before thrombus avulsion. Preferred wash-in of emboli into regions with low blood flow resistance might be an additional mechanism besides impaired washout in patients with severe large artery disease.
Stroke Incidence and Mortality Rates 1987 to 2006 Related to Secular Trends of Cardiovascular Risk Factors in Gothenburg, Sweden
Authors: Harmsen Per , Wilhelmsen Lars , Jacobsson Anders
Published: June 2009

Background and Purpose—

Stroke incidence rates were unchanged whereas fatality rates declined during the period 1971 to 1987 in Gothenburg (Göteborg), Sweden. For the period 1987 to 2006, we now report on trends in stroke incidence and mortality with concurrent risk factor trends in the same population. Since 1976 the incidence of myocardial infarction decreased by 50%.

Methods—

Through the National Hospital Discharge Register linked with the Cause of Death Register, 12 904 males and 15 250 females with first strokes were detected for the period 1987 to 2006. Cardiovascular risk factor data were available for random population samples of men and women aged 50 years from 1963 to 2003.

Results—

Incidence and mortality rates for all-stroke were unchanged. Rates for subarachnoid hemorrhage declined for the age group 45 to 54 in men, but not significantly in any other age group of men or women. Mortality rates of intracerebral hemorrhage declined for women aged 65 to 74, with no significant changes in any other age group. Ischemic stroke incidence did not change, but mortality increased for men and women aged 75 and older, whereas mortality declined for the age group 20 to 44 for men. In the general population there were significant reductions in smoking, total cholesterol, and blood pressure levels in both men and women, whereas diabetes prevalence, body weight, and BMI increased among both sexes, and triglycerides increased in men.

Conclusion—

Contrary to myocardial infarction, stroke incidence and mortality did not change. Monitoring of cardiovascular risk factors in the community is important.
Recurrent Cellulitis in a Case of Aagenaes Syndrome
Authors: Dang Sumit , Sigal Yakov , Davies Dele
Published: June 2009

Aagenaes syndrome, also called Lymphedema Cholestasis Syndrome (LSC 1), is a form of idiopathic familial intrahepatic cholestasis associated with lymphedema of the lower extremities. It is named after the Norwegian pediatrician Oyestein Aagenaes, who described the syndrome in 1968. The presence of lymphedema is likely the predisposing factor for development of recurrent infections in such patients.1 Recurrent cellulitis as such has never been described in the literature with Aagenaes syndrome. This case highlights recurrent cellulitis as one of the potential complications of Aagenaes syndrome.
The Role of Empathic Accuracy in Adolescents' Peer Relations and Adjustment
Authors: Gleason Katie A. , Jensen-Campbell Lauri A. , Ickes William
Published: June 2009

This study investigated whether children's empathic accuracy is associated with their peer relationships and adjustment. It also examined whether, and how, empathic accuracy moderated the known influence of peer relations on adjustment. Participants were 116 (58 boys) fifth-through eighth-graders. At school, child participants completed measures assessing their peer relationships. In the lab, child participants completed a performance-based measure of empathic accuracy and measures of adjustment. Teachers and parents also provided assessments. Results revealed that children who were less adept at inferring other people's thoughts and feelings were more likely to experience adjustment problems. Empathic accuracy acted as a buffer against adjustment problems when peer relationships were poor: Previously found links between poor peer relationships and poor adjustment were found for adolescents with low empathic accuracy but not for those with high empathic accuracy.
Biogeography and landscape ecology: the way forward — gradients and graph theory
Authors: Kent Martin
Published: June 2009

Following the previous report on this subject, published in 2007, there has been a very substantial increase in publications relevant to landscape ecology and this is illustrated by the growth in citations for articles in the core journal Landscape Ecology over the period 2000—2007. The continuing ‘identity crisis’ of landscape ecology is described and recent literature in the field is then summarized under the following headings: ‘Landscape ecology and climate change research’; ‘Alternatives to fragmentation and the patch-based model — the links between pattern and process’; ‘Fragmentation research’; ‘Methodology and techniques in landscape ecology’; and ‘Connectivity and graph theoretical approaches’. The review concludes that landscape ecology now represents one important focus within biogeography, linked to ecological biogeography, and takes its place alongside other key foci, including macroecology, palaeoecology and soil science/pedology. Nevertheless, both physical and human geographers still need to embrace landscape ecology even more enthusiastically than they have up until now.