bluuebunny/crossref_metadata_2025 huggingface dataset:
Performance of a component‐based allergen‐microarray in the diagnosis of cow's milk and hen's egg allergy
Authors: D'Urbano L. E. , Pellegrino K. , Artesani M. C. , Donnanno S. , Luciano R. , Riccardi C. , Tozzi A. E. , Ravà L. , De Benedetti F. , Cavagni G.
Published: July 2010

Background
The food challenge test (FCT) is the gold standard for the diagnosis of food allergy. This procedure is time consuming, costly and can induce potentially severe symptoms. An ideal in vitro test should allow to avoid the FCT.

Objective
To assess the clinical performance of microarray for specific IgE (sIgE) detection in children with challenge‐proven/excluded cow's milk (CM) or hen's egg (HE) allergy.

Methods
One‐hundred and four children with suspected IgE‐mediated hypersensitivity to CM or HE were studied. In all patients, skin prick test, ImmunoCAP, microarray and FCT were performed.

Results
The microarray components Bos d 8 for CM (27/58 patients) and Gal d 1 (20/46 patients) and Gal d 2 (24/46) for HE were the most frequently recognized allergens. Using the FCT results as the reference parameter, sIgE to Bos d 8 and Gal d 1 had the highest area under the curves. These were not significantly different from those obtained using the ImmunoCAP. Use of 95% clinical decision points (CDP) for sIgE to Bos d 8 and Gal d 1 resulted in higher negative predictive values (78% and 79%, respectively) than those obtained with the ImmunoCAP (57% and 59%).

Conclusions
Our results show that in children with suspected CM or HE allergy, the microarray has a good ability to predict the FCT results. In a clinical application perspective, the microarray could be used as a second‐level assay, if the ImmunoCAP sIgE is <95% CDP. This approach would lead to a decrease in the number of the FCT to be performed, as well as of positive FCTs with a subsequent decrease in severe reaction risk.

Cite this as: L. E. D'Urbano, K. Pellegrino, M. C. Artesani, S. Donnanno, R. Luciano, C. Riccardi, A. E. Tozzi, L. Ravà, F. De Benedetti and G. Cavagni, Clinical & Experimental Allergy, 2010 (40) 1561–1570.
Expression of CD203c and CD63 in human basophils: relationship to differential regulation of piecemeal and anaphylactic degranulation processes
Authors: MacGlashan D.
Published: July 2010

BackgroundActivation of human basophils results in the release of many different mediators and the expression of new cell surface proteins. The markers CD63 and CD203c have been used in recent years to assess basophil activation but there have been many studies that demonstrate that expression of these markers can be dissociated from histamine release.

ObjectiveTo determine the signal transduction requirements for CD203c and CD63 expression.

MethodsThe current study began by exploring the dependency of CD203c and CD63 expression on protein kinase C (PKC) using known selective inhibitors of PKC.

ResultsBetween 30 and 300 nm, Ro‐31‐8220 and bisindoylmaleimide II (Bis II) had no effect on formyl–met–leu–phe‐ or anti‐IgE‐induced CD63 or CD203c but enhanced IgE‐mediated expression of CD63 by an average of 15‐fold at concentrations >1 μm. These results led to the suggestion that these inhibitors altered the normal pathways of degranulation (by a non‐PKC dependent mechanism), shifting the normal presence of piecemeal degranulation to the process termed anaphylactic degranulation (AND). Morphological studies demonstrated that concentrations of Ro‐31‐8220 and Bis II>1 μmdramatically increased the presence of degranulation sacs, a morphological feature of AND.

ConclusionIt is proposed that CD63 expression results from only the AND form of histamine release.

Cite this as: D. MacGlashan Jr,Clinical & Experimental Allergy, 2010 (40) 1365–1377.
Anti-endothelial cell antibodies in rheumatic heart disease
Authors: Scalzi V , Hadi H Abu , Alessandri C , Croia C , Conti V , Agati L , Angelici A , Riccieri V , Meschini C , Al-Motarreb A , Al-Ansi A , Valesini G
Published: July 2010

To evaluate the anti-endothelial cell antibodies (AECA), anti-cardiolipin antibodies (aCL) and serum mannose-binding lectin (MBL) profiles of a large cohort of Yemeni patients with rheumatic heart disease (RHD) and to correlate these findings with clinical features of the disease. Patients (n = 140) were recruited from Al-Thawra Hospital in Sana'a, Yemen. All had RHD diagnosed according to modified Jones' criteria. We also studied 140 sex- and age-matched healthy blood donors from the same area. Echocardiography was performed according to the recommendations of the American Society of Echocardiography. Solid phase enzyme-linked immunosorbent assays (ELISAs) were used to measure AECA and aCL titres and serum MBL levels. Forty per cent of the patients were AECA-positive, but only 7·8% were positive for aCL antibodies. Serum MBL levels were significantly lower in the RHD group (median 4221 ng/ml versus 5166 ng/ml in healthy controls). AECA titres were correlated positively with patient age, duration of RHD and the severity of aortic stenosis, as determined by echocardiographic findings. In several autoimmune rheumatic diseases, such as systemic lupus erythematosus, vasculitis and scleroderma, AECA have been shown to play pathogenic roles by producing proinflammatory and procoagulant effects (increased expression of adhesion molecules and tissue factors, increased cytokine release) in endothelial cells. In RHD, these autoantibodies might represent a pathological link between activation of the valvular endothelium and valvular damage.
Immune receptor expressed on myeloid cells 1 (IREM-1) inhibits B cell activation factor (BAFF)-mediated inflammatory regulation of THP-1 cells through modulation of the activities of extracellular regulated kinase (ERK)
Authors: Lee S-M , Nam Y-P , Suk K , Lee W-H
Published: July 2010

The immune receptor expressed on myeloid cells 1 (IREM-1) has been known to regulate the activities of myeloid cells through its immunoreceptor tyrosine-based inhibition motifs (ITIMs) in its intracellular region. In order to investigate its effect on macrophage activation, a human macrophage cell line (THP-1) was tested after stimulation of its membrane-bound form of B cell activation factor (BAFF), which has been shown to modulate inflammatory activities through induction of proinflammatory mediator expression and suppression of phagocytosis. IREM-1-specific monoclonal antibodies detected the expression of high levels of IREM-1 in THP-1 cells. Cross-linking of IREM-1 with these antibodies resulted in the blockage of the BAFF-mediated expression of interleukin (IL)-8 and matrix metalloproteinase (MMP)-9 through inhibition of the activation of extracellular regulated kinase (ERK) and phosphorylation/degradation of IκB. Furthermore, cross-linking of IREM-1 also reversed the BAFF-mediated inhibition of phagocytosis. In order to demonstrate the role of ITIM in the IREM-1-mediated suppression of BAFF signalling, a decapeptide containing YADL (an ITIM in IREM-1) was fused with HIV–TAT48–57 which was required for the internalization of the synthetic polypeptide (TAT–YADL). TAT–YADL, but not control peptides, recapitulated the effect of the anti-IREM-1 monoclonal antibody. These observations indicate that IREM-1 exerted its inhibitory effect on BAFF-medicated signalling through ITIM-mediated regulation of ERK activities in THP-1 cells.
The effect of ageing on macrophage Toll-like receptor-mediated responses in the fight against pathogens
Authors: Dunston C R , Griffiths H R
Published: July 2010

The cellular changes during ageing are incompletely understood yet immune system dysfunction is implicated in the age-related decline in health. The acquired immune system shows a functional decline in ability to respond to new pathogens whereas serum levels of cytokines are elevated with age. Despite these age-associated increases in circulating cytokines, the function of aged macrophages is decreased. Pathogen-associated molecular pattern receptors such as Toll-like receptors (TLRs) are vital in the response of macrophages to pathological stimuli. Here we review the evidence for defective TLR signalling in normal ageing. Gene transcription, protein expression and cell surface expression of members of the TLR family of receptors and co-effector molecules do not show a consistent age-dependent change across model systems. However, there is evidence for impaired downstream signalling events, including inhibition of positive and activation of negative modulators of TLR induced signalling events. In this paper we hypothesize that despite a poor inflammatory response via TLR activation, the ineffective clearance of pathogens by macrophages increases the duration of their activation and contributes to perpetuation of inflammatory responses and ageing.
Specific antibodies to soluble alpha-synuclein conformations in intravenous immunoglobulin preparations
Authors: Patrias L M , Klaver A C , Coffey M P , Loeffler D A
Published: July 2010

Alpha-synuclein is the major protein in Lewy bodies, the hallmark pathological finding in Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Although normally intracellular, it also can be secreted, so extracellular alpha-synuclein may contribute to neuronal injury. Serum antibodies to alpha-synuclein could exert protective effects by increasing alpha-synuclein's movement out of the brain and, if they cross the blood–brain barrier, by inhibiting its neurotoxic effects. The objective of this study was to measure antibody concentrations to alpha-synuclein monomer and soluble oligomers in three intravenous immunoglobulin (IVIG) preparations, Gamunex (Talecris Biotherapeutics), Gammagard (Baxter Healthcare) and Flebogamma (Grifols Biologicals). Antibodies were measured in native IVIG preparations and after antibody–antigen complex dissociation. IVIG's non-specific binding was subtracted from its total binding to alpha-synuclein to calculate specific anti-alpha-synuclein antibody concentrations. Specific antibodies to alpha-synuclein monomer and/or soluble oligomers were detected in all IVIG products. In native IVIG preparations, the highest anti-monomer concentrations were in Gammagard and the highest anti-oligomer concentrations were in Gamunex; the extent to which lot-to-lot variation may have contributed to these differences was not determined. Antibody–antigen complex dissociation had variable effects on these antibody levels. The IVIG preparations did not inhibit alpha-synuclein oligomer formation, although they changed the distribution and intensity of some oligomer bands on Western blots. The presence of antibodies to soluble alpha-synuclein conformations in IVIG preparations suggests that their effects should be studied in animal models of synucleinopathies, as a first step to determine their feasibility as a possible treatment for PD and other synucleinopathies.
Peroxiredoxin 2 is a novel autoantigen for anti-endothelial cell antibodies in systemic vasculitis
Authors: Karasawa R , Kurokawa M S , Yudoh K , Masuko K , Ozaki S , Kato T
Published: July 2010

Anti-endothelial cell antibodies (AECA) have been frequently detected in systemic vasculitis, which affects blood vessels of various sizes. To understand the pathogenic roles of AECA in systemic vasculitis, we attempted to identify target antigens for AECA comprehensively by a proteomic approach. Proteins extracted from human umbilical vein endothelial cells (HUVEC) were separated by two-dimensional electrophoresis, and Western blotting was subsequently conducted using sera from patients with systemic vasculitis. As a result, 53 autoantigenic protein spots for AECA were detected, nine of which were identified by mass spectrometry. One of the identified proteins was peroxiredoxin 2 (Prx2), an anti-oxidant enzyme. Frequency of anti-Prx2 autoantibodies, measured by enzyme-linked immunosorbent assay (ELISA), was significantly higher in systemic vasculitis (60%) compared to those in collagen diseases without clinical vasculitis (7%, P < 0·01) and healthy individuals (0%, P < 0·01). Further, the titres changed in parallel with the disease activity during time–courses. The presence of anti-Prx2 autoantibodies correlated significantly with elevation of serum d-dimers and thrombin–antithrombin complex (P < 0·05). Immunocytochemical analysis revealed that live endothelial cells expressed Prx2 on their surface. Interestingly, stimulation of HUVEC with rabbit anti-Prx2 antibodies increased secretion of interleukin (IL)-6, IL-1β, IL-1ra, growth regulated oncogene (GRO)-α, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM–CSF), IL-8 and monocyte chemoattractant protein (MCP)-1 more than twofold compared to that of with rabbit immunoglobulin (Ig)G. Taken together, our data suggest that anti-Prx2 autoantibodies would be a useful marker for systemic vasculitis and would be involved in the inflammatory processes of systemic vasculitis.
Enrichment of short interspersed transposable elements to embryonic stem cell‐specific hypomethylated gene regions
Authors: Muramoto Hiroki , Yagi Shintaro , Hirabayashi Keiji , Sato Shinya , Ohgane Jun , Tanaka Satoshi , Shiota Kunio
Published: July 2010

Embryonic stem cells (ESCs) have a distinctive epigenome, which includes their genome‐wide DNA methylation modification status, as represented by the ESC‐specific hypomethylation of tissue‐dependent and differentially methylated regions (T‐DMRs) of Pou5f1 and Nanog. Here, we conducted a genome‐wide investigation of sequence characteristics associated with T‐DMRs that were differentially methylated between ESCs and somatic cells, by focusing on transposable elements including short interspersed elements (SINEs), long interspersed elements (LINEs) and long terminal repeats (LTRs). We found that hypomethylated T‐DMRs were predominantly present in SINE‐rich/LINE‐poor genomic loci. The enrichment for SINEs spread over 300 kb in cis and there existed SINE‐rich genomic domains spreading continuously over 1 Mb, which contained multiple hypomethylated T‐DMRs. The characterization of sequence information showed that the enriched SINEs were relatively CpG rich and belonged to specific subfamilies. A subset of the enriched SINEs were hypomethylated T‐DMRs in ESCs at Dppa3 gene locus, although SINEs are overall methylated in both ESCs and the liver. In conclusion, we propose that SINE enrichment is the genomic property of regions harboring hypomethylated T‐DMRs in ESCs, which is a novel aspect of the ESC‐specific epigenomic information.
Critical thinking skills in nursing students: comparison of simulation‐based performance with metrics
Authors: Fero Laura J. , O’Donnell John M. , Zullo Thomas G. , Dabbs Annette DeVito , Kitutu Julius , Samosky Joseph T. , Hoffman Leslie A.
Published: July 2010

fero l.j., o’donnell j.m., zullo t.g., dabbs a.d., kitutu j., samosky j.t. & hoffman l.a. (2010) Critical thinking skills in nursing students: comparison of simulation‐based performance with metrics. Journal of Advanced Nursing 66(10), 2182–2193.

Aim  This paper is a report of an examination of the relationship between metrics of critical thinking skills and performance in simulated clinical scenarios.

Background  Paper and pencil assessments are commonly used to assess critical thinking but may not reflect simulated performance.

Methods  In 2007, a convenience sample of 36 nursing students participated in measurement of critical thinking skills and simulation‐based performance using videotaped vignettes, high‐fidelity human simulation, the California Critical Thinking Disposition Inventory and California Critical Thinking Skills Test. Simulation‐based performance was rated as ‘meeting’ or ‘not meeting’ overall expectations. Test scores were categorized as strong, average, or weak.

Results  Most (75·0%) students did not meet overall performance expectations using videotaped vignettes or high‐fidelity human simulation; most difficulty related to problem recognition and reporting findings to the physician. There was no difference between overall performance based on method of assessment (P = 0·277). More students met subcategory expectations for initiating nursing interventions (P ≤ 0·001) using high‐fidelity human simulation. The relationship between videotaped vignette performance and critical thinking disposition or skills scores was not statistically significant, except for problem recognition and overall critical thinking skills scores (Cramer’s V = 0·444, P = 0·029). There was a statistically significant relationship between overall high‐fidelity human simulation performance and overall critical thinking disposition scores (Cramer’s V = 0·413, P = 0·047).

Conclusion  Students’ performance reflected difficulty meeting expectations in simulated clinical scenarios. High‐fidelity human simulation performance appeared to approximate scores on metrics of critical thinking best. Further research is needed to determine if simulation‐based performance correlates with critical thinking skills in the clinical setting.
Individual variation in rates of senescence: natal origin effects and disposable soma in a wild bird population
Authors: Bouwhuis Sandra , Charmantier Anne , Verhulst Simon , Sheldon Ben C.
Published: July 2010

1. Longitudinal studies of various vertebrate populations have recently demonstrated senescent declines in reproductive performance and/or survival probability with age to be almost ubiquitous in nature. Little is known, however, about the extent to which rates of senescence vary between individuals, and about causes or consequences of such variation. Quantifying these links in natural populations is important for understanding the constraints and adaptive processes underlying the evolution of senescence.

2. Here, we analyse breeding data from 1029 female great tits Parus major to quantify the effect of natal conditions and early life reproduction on rates of reproductive senescence, reproductive life span and lifetime reproductive success.

3. Although for locally born females we find no evidence that natal conditions influence rates of reproductive senescence, we show that immigrant females suffer from faster rates of senescence than locally born females, and that this difference contributes to immigrants having a lower lifetime reproductive success.

4. Additionally, and independently, we find rates of reproductive senescence to increase with rates of early life reproduction, as predicted by the disposable soma hypothesis. Despite accelerated senescence late in life, high early life reproduction is, however, positively associated with lifetime reproductive success across individuals.

5. Female immigrant status and early life reproduction do not relate to reproductive life span.

6. We thus show that both immigration into our population, and high levels of early life reproduction, are associated with reduced late life reproductive performance in female great tits, but that fitness can be increased by high levels of early life reproduction at the expense of accelerated reproductive senescence. These results suggest disposable soma to be a likely mechanism underlying senescence in these birds, and encourage further study of the genetic basis (i.e. antagonistic pleiotropy) of such an early vs. late life trade‐off.
Pharmacovigilance in veterinary medicine in Chile: a pilot study
Authors: IRAGÜEN D. , URCELAY S. , SAN MARTÍN B.
Published: July 2010

Iragüen, D., Urcelay, S., San Martín, B. Pharmacovigilance in veterinary medicine in Chile: a pilot study.J. vet. Pharmacol. Therap.34, 108–115.

In Chile, there is no present government policy to survey and analyse adverse drug reactions (ADRs) in the field of veterinary medicine. The intent of this study is to assess, for the first time, ADR frequency in treated animals. To this purpose, a 6‐month period pilot study based on WHO recommendations was conducted to monitor ADRs in cats and dogs for frequently used drugs and common labelled signs. Of a total of 149 detected ADRs, 29 (6 in cats and 23 in dogs) were notified by means of ADR report forms, while the rest was identified after reviewing patient clinical records, thus evidencing strong under‐reporting problems. More than 70% of ADRs were related to antimicrobials, vaccines and tranquilizers. In dogs, there was a significant effect on ADRs’ presentation when acepromazine, amoxicillin, carprofen, ivermectin, sextuple vaccine (polyvalent vaccine that confers immunity against canine distemper virus, canine parvovirus,Leptospira canicola, L. icterohemmoragiae, canine adenovirus type 2 and canine parainfluenza virus) and phytomenadione (subcutaneous injection) were administered. In the case of cats, a significant influence on ADRs was detected when acepromazine, amoxicillin or vitamin K was administered. Present results suggest the need for a pharmacovigilance programme in veterinary medicine for timely ADR‐presenting drug detection and drug safety improvement.
Depletion study of three formulations of flumequine in edible tissues and drug transfer into chicken feathers
Authors: CORNEJO J. , LAPIERRE L. , IRAGÜEN D. , PIZARRO N. , HIDALGO H. , MARTÍN B. SAN
Published: July 2010

Cornejo, J., Lapierre, L., Iragüen, D., Pizarro, N., Hidalgo, H., San Martín, B. Depletion study of three formulations of flumequine in edible tissues and drug transfer into chicken feathers.J. vet. Pharmacol. Therap.34, 168–175.

To ensure the delivery of safe animal products to consumers, withdrawal times (WDT) of drugs must be respected. Drugs administered in therapies can also reach nonedible tissues (for humans) such as feathers; this transfer is of concern as feather meal is used in diets of food producing animals, being this a possible source of residue contamination of final products for human consumption. WDTs of three flumequine formulations (10%, 80% premix powder and 20% solution) as well as the transfer of this drug into feathers were determined. One hundred and twenty broiler chickens were allocated into four experimental groups (36 birds each). Three of them were treated with 24 mg/kg bw orally for five consecutive days of each flumequine formulation, whereas one group remained untreated (12 birds as control group). After the treatment ended, six chickens of each experimental group and two controls were slaughtered daily for 6 days. Samples of muscle, liver and feathers were collected and analyzed by liquid chromatography tandem mass spectrometry (LC MS/MS). The WDTs showed differences between formulations. Flumequine concentrations found in feathers remained high during WDT and after this period, thus suggesting that the WDTs estimated for the pharmaceutical formulation of flumequine do not guarantee the absence of this drug in chicken nonedible tissues such as feathers.
Ultrasound‐guided peripheral nerve blocks: What are the benefits?
Authors: KOSCIELNIAK‐NIELSEN Z. J.
Published: July 2010

Background: Use of ultrasound by anaesthesiologists performing regional blocks is rapidly gaining popularity. The aims of this review were to summarize and update accumulating evidence on ultrasound‐guided nerve blocks, with an emphasis on the clinical relevance of the results and to critically appraise changing standards in regional anaesthesia.

Methods: A search of MEDLINE and EMBASE (1966 to 31 December 2007) was conducted using the following free terms: ‘ultrasound and regional anesthesia’, ‘ultrasound and peripheral block’ and ‘ultrasound and nerve and block’. These were combined with the MESH terms ‘nerve block’ and ‘ultrasonography’. The following limits were applied: studies with abstracts, only in humans, published in core clinical journals. Trial type: meta‐analysis, randomized‐controlled trial and clinical trial.

Results: When peripheral nerves are adequately imaged by ultrasound, the concomitant use of nerve stimulation offers no further advantage. However, several studies reported problems with obtaining satisfactory images in some patients. Ultrasound guidance significantly shortened the block performance time and/or reduced the number of needle passes to reach the target in all comparative studies. The occurrence of paraesthesia during block performance was also reduced, but not the incidence of short‐lasting post‐operative neuropraxia. The frequency of accidental vascular punctures may be lower, but the data are contradictory. Block onset time was significantly shortened. Block duration was longer in children, but not in adults. Ultrasound also allowed dose reduction of the local anaesthetic (LA).

Conclusions: Ultrasound guidance shortens the block performance time, reduces the number of needle passes and shortens the block onset time. Blocks may be performed using lower LA doses.
Characterisation of seeds of a C4 phosphoenolpyruvate carboxylase‐deficient mutant of Amaranthus edulis
Authors: Álvarez R. , Gandullo J. , Feria A. B. , Dever L. V. , Vidal J. , Echevarría C.
Published: July 2010

Seeds from the C4 plant Amaranthus edulis were studied as part of the characterisation of a mutant (designated LaC4 2.16), which contains reduced amounts (5% of wild type) of the photosynthetic leaf form of phosphoenolpyruvate carboxylase (PEPC). On a per seed basis, the amount of PEPC activity was not significantly altered, while the weight and protein content of the mutant seeds were 34% lower than that of the wild type. Western gel blot analysis detected two PEPC polypeptides with molecular masses of 105 kDa (minor) and 100 kDa (major). The determination of in vitro phosphorylation in reconstituted assays revealed the presence of both calcium‐dependent and calcium‐independent PEPC‐kinase activities in protein extracts of wild‐type and mutant seeds. However, PEPC proteins were phosphorylated in dry seeds, and PEPC phosphorylation did not occur in vivo during seed imbibition in the presence of 32P‐phosphate. In contrast, 32P‐phosphate was incorporated into a range of proteins in wild‐type seeds, but not in mutant seeds. In addition, ATP content was much reduced in germinating mutant seeds and this did not increase following the supply of phosphate. Collectively, these data suggest that the deficiency in C4 PEPC in mutant A. edulis leaves has no effect on C3‐type PEPC content and phosphorylation state in seeds, but causes impairment of energy production, thereby accounting for the reduced germination of the mutant.
Identification and characterisation of human pathogenic filamentous fungi and susceptibility to Thymus schimperi essential oil
Authors: Pagiotti Rita , Angelini Paola , Rubini Andrea , Tirillini Bruno , Granetti Bruno , Venanzoni Roberto
Published: July 2010

Twenty‐eight clinical fungal isolates were characterised by morphological (macro‐ and micro‐features and growth response at 25, 30 and 37 °C) and molecular (nuclear rDNA‐internal transcriber spacer, calmodulin, cytochrome c oxidase 1 and the largest subunit of RNA polymerase II) analyses. The clinical fungal isolates were ascribed to the following taxa: Penicillium chrysogenum, Verticillium sp., Aspergillus tubingensis, Aspergillus minutus, Beauveria bassiana and Microsporum gypseum. In addition, in vitro susceptibility testing of the isolates to conventional antifungal agents and to two chemically well‐defined chemotypes of Thymus schimperi essential oil was performed. Most of the isolates were resistant to amphotericin B (except A. minutus), and itraconazole, while terbinafine was quite active on these fungi. T. schimperi essential oil showed antifungal activity against all of the tested fungal isolates with minimal inhibitory concentration values similar or lower than those of terbinafine. Transmission electron microscopy analyses revealed that fungal growth inhibition by essential oil was accompanied by marked morphological and cytological changes.
Risk factors in a cohort of patients with multiple primary melanoma
Authors: McMeniman Erin , De'Ambrosis Kathryn , De'Ambrosis Brian
Published: July 2010

Background: There are various known familial and environmental risk factors that influence the risk for melanoma. This study sought to define the risk factors for multiple primary melanoma.

Methods: A telephone survey of patients with multiple primary melanomas was conducted from a private practice in south‐east Queensland, in order to examine various risk factors in this cohort.

Results: Our findings of high rates of family history of melanoma (37%), and of dysplastic naevi (42%) support the influence of genotype in this high‐risk group. A family history of multiple primary melanomas, seen in 17% of our patients, is a risk factor not previously reported in similar cohort studies. Sixty‐eight per cent of patients had an equal or lesser degree of invasive malignancy in subsequent melanomas. Most multiple primary melanoma patients in this group (86.6%) were conducting self skin examination at least once per month. With regards to sun‐protective behaviour, 85% reported regular sunscreen use and 92% reported regular use of sun‐protective clothing; however, fewer had done this in childhood.

Conclusions: Enhanced knowledge of the genetic and environmental risk factors for multiple primary melanomas can assist clinicians in assessing risk and planning surveillance of patients.
Expression of cardiac myosin light chain 2 during embryonic heart development in medaka fish, Oryzias latipes, and phylogenetic relationship with other myosin light chains
Authors: Shimada Eriko , Kinoshita Masato , Murata Kenji
Published: July 2010

Cardiac myosin light chain 2 (MLC‐2) plays a key role in heart development, contraction, and embryo and adult heart maintenance. In some animals, defects in the function of cardiac MLC‐2 cause hypertrophic cardiomyopathy. To illuminate the functions of cardiac MLC‐2 in embryonic heart formation and contraction, and into the evolution of MLC‐2, we characterized the expression and requirement for medaka cardiac MLC‐2 gene in the developing heart. Medaka cardiac MLC‐2 cDNA (mcmlc2) was isolated and its gene expression pattern was determined. The mcmlc2 was found to be expressed in the bilateral cardiac mesoderm, the formed heart tube, and in both the differentiated ventricle and atrium. Knockdown of mcmlc2 function caused severe cardiac disorders, including edema in the atrium and sinus venosus. Using phylogenetic analysis, we found that physiological variations in the MLC‐2 molecules evolved due to amino acid changes in the Ca2+ binding domain during molecular evolution. Our findings concerning the function and expression of mcmlc2 are nearly identical with those of other MLC‐2 genes, and our phylogenetic analysis suggests that during evolution, the variations in physiological function within the MLC‐2 gene family have arisen from a change in the amino acids in the Ca2+ binding domain in the MLC‐2 molecule.
Continuous neurogenesis in the adult brain
Authors: Imayoshi Itaru , Sakamoto Masayuki , Ohtsuka Toshiyuki , Kageyama Ryoichiro
Published: July 2010

Neurogenesis occurs throughout adulthood in the mammalian brain by coordinated proliferation and differentiation of adult neural stem cells. Newborn neurons are incorporated into the functional networks of both the olfactory bulb and the hippocampal dentate gyrus, suggesting significant roles of adult neurogenesis in brain functions. In this review, we discuss the recent findings about the integration mode of new neurons into the existing neural circuits. We further address the potential significance of adult neurogenesis in higher brain functions such as olfactory and spatial memory.
Role of echocardiographic left ventricular mass and carotid intima‐media thickness in the cardiovascular risk assessment of asymptomatic patients with type 2 diabetes mellitus
Authors: Poppe K. K. , Whalley G. A. , Somaratne J. B. , Keelan S. , Bagg W. , Triggs C. M. , Doughty R. N.
Published: July 2010

Background: Standard cardiovascular (CV) risk assessment may underestimate risk in people with type 2 diabetes mellitus (T2DM). Cardiac and vascular imaging to detect subclinical disease may augment risk prediction. This study investigated the association between CV risk, left ventricular hypertrophy (LVH) and carotid intima‐media thickness (CIMT) in patients with T2DM free of CV symptoms.

Methods: People with T2DM without known CV disease were recruited from general practice. The 5‐year risk of CV events was calculated using an adjusted Framingham equation and the prevalence of LVH and abnormal CIMT across bands of CV risk assessed. In those at intermediate risk, the number needed to scan (NNS) to reclassify one person to high risk was calculated across the group and compared in those above and below 55 years. The association between LV mass and CIMT was also assessed.

Results: Mean age 57 years (SD11), 51% female. Median 5‐year CV risk 14.3% (interquartile range 10.3, 19.5), 51% had LVH (American Society of Echocardiography criteria) and 31% an abnormal CIMT (age and sex criteria). In the 52% at intermediate risk, 37% had LVH and 36% an abnormal CIMT. The NNS was 1.7 using both imaging techniques, 2.7 using cardiac imaging alone or 2.8 using vascular imaging alone. Almost twice as many people >55 years had an abnormal CIMT than those <55 years.

Conclusions: Cardiac and vascular imaging to detect subclinical disease can be used to augment prediction of CV risk in people with T2DM at intermediate risk. The value of reclassifying risk is as yet unproven and requires outcome data from intervention studies.
Current discharge management of acute coronary syndromes: baseline results from a national quality improvement initiative
Authors: Wai A. , Pulver L. K. , Oliver K. , Thompson A.
Published: July 2010

Background: Evidence–practice gaps exist in the continuum of care for patients with acute coronary syndromes (ACS), particularly at hospital discharge.

Aim: We aimed to describe the methodology and baseline results of the Discharge Management of Acute Coronary Syndromes (DMACS) project, focusing on the prescription of guideline‐recommended medications, referral to cardiac rehabilitation and communication between the hospital, patient and their primary healthcare professionals.

Methods: DMACS employed Drug Use Evaluation methodology involving data collection, evaluation and feedback, and targeted educational interventions. Adult patients with ACS discharged during a 4‐month period were eligible to participate. Data were collected (maximum 50 patients) at each site through an inpatient medical record review, a general practitioner (GP) postal/fax survey conducted 14 days post discharge and a patient telephone survey 3 months post discharge.

Results: Forty‐nine hospitals participated in the audit recruiting 1545 patients. At discharge, 57% of patients were prescribed a combination of antiplatelet agent(s), beta‐blocker, statin and angiotensin‐converting enzyme inhibitor and/or angiotensin II‐antagonist. At 3 months post discharge, 48% of patients reported using the same combination. Some 67% of patients recalled being referred to cardiac rehabilitation; of these, 33% had completed the programme. In total, 83% of patients had a documented ACS management plan at discharge. Of these, 90% included a medication list, 56% a chest pain action plan and 54% risk factor modification advice. Overall, 65% of GPs rated the quality of information received in the discharge summary as ‘very good’ to ‘excellent’.

Conclusions: The findings of our baseline audit showed that despite the robust evidence base and availability of national guidelines, the management of patients with ACS can be improved. These findings will inform a multifaceted intervention strategy to improve adherence to guidelines for the discharge management of patients with ACS.
Estrogen + progestin therapy and cognition: A randomized placebo‐controlled double‐blind study
Authors: Alhola Paula , Tuomisto Hanna , Saarinen Reetta , Portin Raija , Kalleinen Nea , Polo‐Kantola Päivi
Published: July 2010

Aims:  The use of hormone therapy (HT) is a relevant and topical issue in the treatment of menopausal symptoms in women. Information regarding the effects of combination treatment with estrogen and progesterone as well as treatment timing on cognitive function is lacking and was evaluated in healthy pre‐ and postmenopausal women.

Methods:  Sixteen premenopausal (45–51 years) and 16 postmenopausal (58–70 years) women were randomly assigned to receive either estrogen + progestin therapy (HT) or placebo (PL) for six months. The study was double‐blind. Cognitive performance was measured at baseline and follow up with tests of verbal and visuomotor functions, verbal and visual memory, and attention.

Results:  In premenopausal women, cognitive attention, when compared to baseline, improved with HT but declined slightly with PL in the two‐choice reaction time task (P = 0.049), while PL was associated with better performance in tests of shared attention (P = 0.024) and auditory attention (P < 0.05). In postmenopausal women, HT was associated with improved performance in verbal episodic memory (P = 0.024) and a minor decline in auditory attention (P = 0.025).

Conclusions:  HT, with estradiol valerate and norethisterone, in healthy women showed only minor effects on attention around the menopausal transition and on memory in postmenopause.
Long‐lasting modulation of synaptic plasticity in rat hippocampus after early‐life complex febrile seizures
Authors: Notenboom Robbert G. E. , Ramakers Geert M. J. , Kamal Amer , Spruijt Berry M. , De Graan Pierre N. E.
Published: July 2010

A small fraction of children with febrile seizures appears to develop cognitive impairments. Recent studies in a rat model of hyperthermia‐induced febrile seizures indicate that prolonged febrile seizures early in life have long‐lasting effects on the hippocampus and induce cognitive deficits. However, data on network plasticity and the nature of cognitive deficits are conflicting. We examined three specific measures of hippocampal plasticity in adult rats with a prior history of experimental febrile seizures: (i) activity‐dependent synaptic plasticity (long‐term potentiation and depression) by electrophysiological recordings of Schaffer collateral/commissural‐evoked field excitatory synaptic potentials in CA1 of acute hippocampal slices; (ii) Morris water maze spatial learning and memory; and (iii) hippocampal mossy fiber plasticity by Timm histochemistry and quantification of terminal sprouting in CA3 and the dentate gyrus. We found enhanced hippocampal CA1 long‐term potentiation and reduced long‐term depression but normal spatial learning and memory in adult rats that were subjected to experimental febrile seizures on postnatal day 10. Furthermore, rats with experimental febrile seizures showed modest but significant sprouting of mossy fiber collaterals into the inner molecular layer of the dentate gyrus in adulthood. We conclude that enhanced CA1 long‐term potentiation and mild mossy fiber sprouting occur after experimental febrile seizures, without affecting spatial learning and memory in the Morris water maze. These long‐term functional and structural alterations in hippocampal plasticity are likely to play a role in the enhanced seizure susceptibility in this model of prolonged human febrile seizures but do not correlate with overt cognitive deficits.
Organization of central synapses by adhesion molecules
Authors: Tallafuss Alexandra , Constable John R. L. , Washbourne Philip
Published: July 2010

Synapses are the primary means for transmitting information from one neuron to the next. They are formed during the development of the nervous system, and the formation of appropriate synapses is crucial for the establishment of neuronal circuits that underlie behavior and cognition. Understanding how synapses form and are maintained will allow us to address developmental disorders such as autism, mental retardation and possibly also psychological disorders. A number of biochemical and proteomic studies have revealed a diverse and vast assortment of molecules that are present at the synapse. It is now important to untangle this large array of proteins and determine how it assembles into a functioning unit. Here we focus on recent reports describing how synaptic cell adhesion molecules interact with and organize the presynaptic and postsynaptic specializations of both excitatory and inhibitory central synapses.
AMPA‐receptor trafficking and injury‐induced cell death
Authors: Beattie Michael S. , Ferguson Adam R. , Bresnahan Jacqueline C.
Published: July 2010

AMPA receptors (AMPARs) are critical for synaptic plasticity, and are subject to alterations based on subunit composition and receptor trafficking to and from the plasma membrane. One of the most potent regulators of AMPAR trafficking is the pro‐inflammatory cytokine tumor necrosis factor (TNF)α, which is involved in physiological regulation of synaptic strength (Beattie et al., (2002) Science, 295, 2282–2285; Stellwagen and Malenka, (2006) Nature, 440, 1054–1059) and is also present at high concentrations after CNS injury. Here, we review evidence that TNF can rapidly alter the surface expression of AMPARs so that the proportion of Ca++‐permeable receptors is increased and that this increase, in combination with increased levels of extracellular glutamate after injury, plays an important role in enhancing excitotoxic cell death after CNS injury. Thus, the pathophysiological hijacking of a critical regulator of synaptic plasticity and homeostasis by the secondary injury cascade may represent a new therapeutic target for neuroprotection.
Synapse formation and maintenance by C1q family proteins: a new class of secreted synapse organizers
Authors: Yuzaki Michisuke
Published: July 2010

Several C1q family members, especially the Cbln and C1q‐like subfamilies, are highly and predominantly expressed in the central nervous system. Cbln1, a member of the Cbln subfamily, plays two unique roles at parallel fiber (PF)–Purkinje cell synapses in the cerebellum: the formation and stabilization of synaptic contact, and the control of functional synaptic plasticity by regulating the postsynaptic endocytotic pathway. The delta2 glutamate receptor (GluD2), which is predominantly expressed in Purkinje cells, plays similar critical roles in the cerebellum. In addition, viral expression of GluD2 or the application of recombinant Cbln1 induces PF–Purkinje cell synaptogenesis in vitro and in vivo. Antigen‐unmasking methods were necessary to reveal the immunoreactivities for endogenous Cbln1 and GluD2 at the synaptic junction of PF synapses. We propose that Cbln1 and GluD2 are located at the synaptic cleft, where various proteins undergo intricate molecular interactions with each other, and serve as a bidirectional synaptic organizer.
Mechanisms underlying autoimmune synaptic encephalitis leading to disorders of memory, behavior and cognition: insights from molecular, cellular and synaptic studies
Authors: Moscato Emilia H. , Jain Ankit , Peng Xiaoyu , Hughes Ethan G. , Dalmau Josep , Balice‐Gordon Rita J.
Published: July 2010

Recently, several novel, potentially lethal and treatment‐responsive syndromes that affect hippocampal and cortical function have been shown to be associated with auto‐antibodies against synaptic antigens, notably glutamate or GABA‐B receptors. Patients with these auto‐antibodies, sometimes associated with teratomas and other neoplasms, present with psychiatric symptoms, seizures, memory deficits and decreased levels of consciousness. These symptoms often improve dramatically after immunotherapy or tumor resection. Here we review studies of the cellular and synaptic effects of these antibodies in hippocampal neurons in vitro and preliminary work in rodent models. Our work suggests that patient antibodies lead to rapid and reversible removal of neurotransmitter receptors from synaptic sites, leading to changes in synaptic and circuit function that in turn are likely to lead to behavioral deficits. We also discuss several of the many questions raised by these and related disorders. Determining the mechanisms underlying these novel anti‐neurotransmitter receptor encephalopathies will provide insights into the cellular and synaptic bases of the memory and cognitive deficits that are hallmarks of these disorders, and potentially suggest avenues for therapeutic intervention.
Hypoglycaemia increases aldosterone in a dose‐dependent fashion
Authors: Adler G. K. , Bonyhay I. , Curren V. , Waring E. , Freeman R.
Published: July 2010

Diabet. Med. 27, 1250–1255 (2010)

Aims  Intensive glycaemic control increases the incidence of hypoglycaemia. We sought to define the effects of hypoglycaemia on aldosterone, a hormone involved in cardiovascular injury and baroreflex impairment.

Methods  To contrast the effects of hypoglycaemia and euglycaemia on aldosterone and plasma renin activity, in Study 1, we assessed hormone levels in 13 subjects who participated in euglycaemic (5.0 mmol/l) and hypoglycaemic (2.8 mmol/l) hyperinsulinaemic clamp protocols in random order. To determine the relationship between aldosterone and the depth of hypoglycaemia, in Study 2, we assessed hormone levels in an additional 13 subjects who participated in a 3‐h stepped hypoglycaemic hyperinsulinaemic clamp protocol; blood glucose was reduced in 0.55 mmol/l steps from 5.0 to 2.2 mmol/l. Subjects were healthy and consumed controlled sodium diets.

Results  In Study 1, aldosterone increased approximately 2.5‐fold during hypoglycaemic hyperinsulinaemia, P < 0.001, but did not rise with euglycaemic hyperinsulinaemia. Plasma renin activity increased during both hyperinsulinaemic clamps; however, the increase was greater during hypoglycaemia (Δ = 1.5 ± 0.2 ng ml−1 h−1) vs. euglycaemia (Δ = 0.5 ± 0.1 ng ml−1 h−1), P < 0.005. In Study 2, aldosterone increased significantly at glucose levels of 2.8 mmol/l; this increase was amplified with glucose of 2.2 mmol/l. Aldosterone increases paralleled those of ACTH.

Conclusions  Hypoglycaemia increases aldosterone in a dose‐dependent fashion. This increase is likely attributable to activation of the renin‐angiotensin‐aldosterone system and increases in ACTH. Because aldosterone activation of the mineralocorticoid receptor is implicated in the pathophysiology of cardiovascular injury, including vascular dysfunction, inflammation, baroreflex impairment and cardiac arrhythmias, these findings may be of relevance in individuals who experience hypoglycaemia.
Exports, Domestic Demand, and Economic Growth in China: Granger Causality Analysis
Authors: Tsen Wong Hock
Published: July 2010

This study examines Granger causality among exports, domestic demand, and economic growth in China using time‐series data over the period from 1978 to 2002. This study uses three measures for domestic demand, namely household consumption, government consumption, and investment. The results show bidirectional Granger causality among these variables, namely exports, domestic demand, and economic growth. Thus, there is a dynamic relationship among exports, domestic demand, and economic growth. Exports and domestic demand are both important for economic growth in China. Moreover, economic growth in China has an impact on its exports and domestic demand. A successful and sustained economic growth requires growth in both exports and domestic demand.
Productivity Spillovers from Foreign Direct Investment in Developing Countries: A Meta‐Regression Analysis
Authors: Wooster Rossitza B. , Diebel David S.
Published: July 2010

This paper reviews the empirical literature on technology spillovers from foreign direct investment (FDI) in developing countries. Our meta‐analysis uses a sample of 32 studies to determine what aspects of study design and data characteristics explain the magnitude, significance, and direction of spillovers from FDI. Results suggest that spillover effects are more pronounced when studies measure the effect of FDI spillovers on output, and are more likely to be significant and positive for Asian countries. Results also highlight the possibility that the documented spillover effects from FDI in developing countries may be partly a product of model misspecification.