bluuebunny/crossref_metadata_2025 huggingface dataset:
Additionality of public R&D grants in a transition economy
Authors: Czarnitzki Dirk , Licht Georg
Published: January 2006

This paper examines the input and output additionality of public R&D subsidies in Western and Eastern Germany. We estimate the impact of public R&D grants on firms’ R&D and innovation input. Based on the results of this first step we compare the impact of publicly funded private R&D on innovation output with the output effect of R&D funded out of firms’ own pockets. We employ microeconometric evaluation methods using firm‐level data derived from the Mannheim Innovation Panel. Our results point towards a large degree of additionality in public R&D grants with regard to innovation input measured as R&D expenditures and innovation expenditures, as well as with regard to innovation output measured by patent applications. Input additionality has been more pronounced in Eastern Germany during the transition period than in Western Germany. However, R&D productivity is still larger for the established Western German innovation system than for Eastern Germany. Hence, a regional redistribution of public R&D subsidies might improve the overall innovation output of the German economy.
Psoriasis confined strictly to vitiligo areas – a Koebner‐like phenomenon?
Authors: Berger TG , Kiesewetter F , Maczek C , Bauer N , Lueftl M , Schuler G , Simon M
Published: January 2006

Vitiligo and psoriasis are both common skin disorders. However, psoriasis strictly confined to pre‐existing vitiligo areas is rare and suggests a causal relationship. We report here on two patients with a strict anatomical colocalization of vitiligo and psoriasis. The histopathological examinations showed typical changes for both diseases together with a dense infiltrate of CD4+ and CD8+ T cells. By immunohistochemistry, intracytoplasmatic granzyme B and tumour necrosis factor alpha (TNF‐α) were detected within the T‐cell population, suggesting the functional activity of these cells and the creation of a local T helper 1 (Th1)‐cytokine milieu. Additionally, in one patient we could identify anti‐melanocytic T cells by tetramer staining and enzyme‐linked immunospot (ELISPOT) analysis. These skin‐infiltrating lymphocytes might trigger, by the local production of Th‐1 cytokines such as TNF‐α and interferon‐γ (IFN‐γ), the eruption of psoriatic plaques in patients with a genetic predisposition for psoriasis.
Febrile ulceronecrotic pityriasis lichenoides et varioliformis acuta with fatal outcome
Authors: Malnar T , Milavec‐Puretic V , Radoš J , Žarkovic K , Dobric I
Published: January 2006

Ulceronecrotic Mucha–Habermann disease is a severe, febrile form of pityriasis lichenoides et varioliformis acuta. The condition may sometimes have a fatal outcome, especially in elderly patients. In this paper, we are reporting on a 60‐year‐old male patient who suffered from the eruption of erythematous, haemorrhagic, ulceronecrotic papules accompanied by high temperature. Erosions and ulceronecrotic papules covered over 80% of his body. Three weeks after his admittance to our hospital, clinical signs resembling ileus together with the leucocytosis occurred. The patient was transferred to the department of internal medicine and later to the surgery department. The fulminant course of the disease could not be stopped, and the patient died of severe intestinal and colon gangrene caused by the massive thrombosis of superior mesenteric artery. Up to date, only 23 cases of this severe form of the disease have been reported, and even with the early recognition, fulminant course may lead to death.
Impaired Fasting Glucose Is Associated with Increased Arterial Stiffness in Elderly People without Diabetes Mellitus: The Rotterdam Study
Authors: Van Popele Nicole M. , Elizabeth Hak A. , Mattace‐Raso Francesco U. S. , Bots Michiel L. , Van Der Kuip Deirdre A.M. , Reneman Robert S. , Hoeks Arnold P. G. , Hofman Albert , Grobbee Diederick E. , Witteman Jacqueline C. M.
Published: January 2006

OBJECTIVES: To study the association between impaired fasting glucose (IFG) and arterial stiffness in older adults.

DESIGN: Cross‐sectional population‐based study.

SETTING: The Rotterdam Study, a Dutch population‐based cohort study.

PARTICIPANTS: Two thousand nine hundred eighty‐seven subjects aged 60 and older.

MEASUREMENTS: Arterial stiffness assessed by measuring common carotid arterial distensibility and glucose status classified into three categories: normal fasting glucose (NFG) (fasting glucose <6.1 mmol/L), IFG (fasting glucose 6.1–6.9 mmol/L), and diabetes mellitus (DM).

RESULTS: In the total cohort, common carotid distensibility decreased with increasing impairment of glucose metabolism. Subjects younger than 75 with IFG were comparable with subjects with NFG with respect to arterial stiffness. Subjects aged 75 and older with IFG had stiffer arteries than subjects with NFG, reaching the same arterial stiffness as subjects with DM. For subjects younger than 75, mean difference in distensibility coefficient between subjects with NFG and with IFG was 0.1 (95% confidence interval (CI)=−0.04–0.05, P=.88) and between subjects with NFG and with DM was 1.2 (95% CI=0.7–1.7, P<.001). For subjects aged 75 and older, the mean difference between these groups was 0.7 (95% CI=0.2–1.2, P=.007) and 0.8 (0.3–1.4; P=.002), respectively. In the total cohort, fasting glucose was strongly associated with carotid distensibility (β‐coefficient=−0.29, P<.001).

CONCLUSION: IFG is related to arterial stiffness in elderly subjects. An advanced stage of arterial stiffness, comparable with that of subjects with DM, is only reached at the age of 75.
Involvement of estrogen receptor α, β and oxytocin in social discrimination: a detailed behavioral analysis with knockout female mice
Authors: Choleris E. , Ogawa S. , Kavaliers M. , Gustafsson J.‐Å. , Korach K. S. , Muglia L. J. , Pfaff D. W.
Published: January 2006

Social recognition, processing, and retaining information about conspecific individuals is crucial for the development of normal social relationships. The neuropeptide oxytocin (OT) is necessary for social recognition in male and female mice, with its effects being modulated by estrogens in females. In previous studies, mice whose genes for the estrogen receptor‐α (α‐ERKO) and estrogen receptor‐β (β‐ERKO) as well as OTKO were knocked out failed to habituate to a repeatedly presented conspecific and to dishabituate when the familiar mouse is replaced by a novel animal (Choleris et al. 2003, Proc Natl Acad Sci USA 100, 6192–6197). However, a binary social discrimination assay, where animals are given a simultaneous choice between a familiar and a previously unknown individual, offers a more direct test of social recognition. Here, we used α‐ERKO, β‐ERKO, and OTKO female mice in the binary social discrimination paradigm. Differently from their wild‐type controls, when given a choice, the KO mice showed either reduced (β‐ERKO) or completely impaired (OTKO and α‐ERKO) social discrimination. Detailed behavioral analyses indicate that all of the KO mice have reduced anxiety‐related stretched approaches to the social stimulus with no overall impairment in horizontal and vertical activity, non‐social investigation, and various other behaviors such as, self‐grooming, digging, and inactivity. Therefore, the OT, ER‐α, and ER‐β genes are necessary, to different degrees, for social discrimination and, thus, for the modulation of social behavior (e.g. aggression, affiliation).
RAPID HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC DETECTION OF FUROSINE (ε‐N‐2‐FUROYLMETHYL‐L‐LYSINE) IN YOGURT AND CHEESE MARKETED IN TURKEY*
Authors: TOKUŞOĞLU ÖZLEM , AKALIN A. SİBEL , UNAL KEMAL
Published: January 2006

Furosine (ε‐N‐2‐furoylmethyl‐L‐lysine) content determination in the yogurt and different cheese types (pickled white, kasar, processed, canned tulum, blue‐veined and mozzarella cheeses) marketed in Turkey was performed using ion‐pair reversed‐phase high performance liquid chromatography (RP‐HPLC). Calibration study (R2 = 0.9999), analytical method validation and recovery studies gave satisfactory results. The lowest furosine values were observed in pickled white cheeses (5.35 ± 0.01 to 7.28 ± 0.02 mg/100 g protein). All cheeses except pickled white showed furosine values between 182.16 ± 0.12 (canned tulum) and 261.32 ± 0.10 mg/100 g protein (ripened kasar). The highest content of furosine was observed in whole yogurt (316.47 ± 0.17 mg/100 g protein) which could be because of severe heat treatment and the addition of milk powder during the manufacturing process. The method provides a rapid, reproducible and accurate determination of this Amadori compound (ε‐deoxy‐fructosyl‐lysine) in yogurt and cheese samples.
PREVALENCE OF LISTERIA MONOCYTOGENES IN SOME TURKISH FOODSTUFFS
Authors: ÖKTEM AYSEL BAYHAN , BAYRAM GÖKTUĞ , CEYLAN AHMET ERIŞ , YENTÜR GÜLDEREN
Published: January 2006

In this study, the presence of Listeria monocytogenes was evaluated in basic groups of foods in Ankara, Turkey between 2001 and 2002. Eighty prepared ground meat, 100 white cheese and 100 parsley samples were obtained from different markets where they were offered for consumption. L. monocytogenes was detected according to the method of ISO Draft International Standard. Fraser Broth was used for enrichment process, and isolation of Listeria spp. was carried out by Oxford Agar. L. monocytogenes was then identified by biochemical and serological tests.

L. monocytogenes was isolated from 13.75, 4 and 2% of 80 prepared ground beef, 100 white cheese and 100 parsley samples, respectively. The results indicate that these foodstuffs have risk of L. monocytogenes. Contamination of L. monocytogenes was not detected in packaged ground beef and white cheese samples. High incidence rate of L. monocytogenes was noted for the samples from open and local market.
FATTY ACID COMPOSITION OF DIFFERENT MARGARINES AND BUTTERS FROM PAKISTAN WITH SPECIAL EMPHASIS ON TRANS UNSATURATED CONTENTS
Authors: ANWAR FAROOQ , BHANGER M.I. , IQBAL SHAHID , SULTANA BUSHRA
Published: January 2006

Fatty acid (FA) composition and isomeric trans unsaturated contents in selected brands of margarines and butter, which are more popular among general consumers of Pakistan, has been reported in this study. A sum of 10 butter and 10 margarine samples, collected from different bakers, confectioners and retail outlets, was analyzed. FA methyl esters were prepared, and quantitative measurements were made using a methyl lignoserate‐coated stationary phase, capillary column (SP‐2340, 60 m × 0.25 mm, 0.20 μm), with flame ionization detection. The contents of saturated FA, cis monounsaturated FA and cis polyunsaturated FA were in the following ranges: margarines 38.9–53.1, 21.9–35.8, 7.45–21.5% and butter 63.7–68.5, 23.0–27.0 and 1.20–2.94%, respectively. Results showed significantly higher amounts of trans FA (TFA) in margarines ranged from 2.45 to 21.1%, whereas butter samples contained less than 5.00% of TFA.
COMPARISON OF METHODS FOR ANALYZING REPLICATED PREFERENCE TESTS
Authors: CHANG COCHRANE CHUN‐YEN , DUBNICKA SUZANNE , LOUGHIN THOMAS
Published: January 2006

Preference testing is commonly used in consumer sensory evaluation. Traditionally, it is done without replication, effectively leading to a single 0/1 (binary) measurement on each panelist. However, to understand the nature of the preference, replicated preference tests are a better approach, resulting in binomial counts of preferences on each panelist. Variability among panelists then leads to overdispersion of the counts when the binomial model is used and to an inflated Type I error rate for statistical tests of preference. Overdispersion can be adjusted by Pearson correction or by other models such as correlated binomial or beta‐binomial. Several methods are suggested or reviewed in this study for analyzing replicated preference tests and their Type I error rates and power are compared. Simulation studies show that all methods have reasonable Type I error rates and similar power. Among them, the binomial model with Pearson adjustment is probably the safest way to analyze replicated preference tests, while a normal model in which the binomial distribution is not assumed is the easiest.
Role of the Nuclei in Eyeblink Conditioning
Authors: LAVOND DAVID G.
Published: January 2006

Abstract: Evidence to date supports the strong conclusion that the cerebellum learns. Classical conditioning of the eyeblink response is critically dependent upon the cerebellum. The issue addressed here is whether cerebellar cortex or deep nuclei form the basic association. Learning occurs with large cerebellar cortical aspirations in rabbits and with a Purkinje‐cell‐deficient mutation in mice. The learned response is poorly timed, small in amplitude, and inconsistent in its occurrence. Learning nevertheless occurs. Lesions of the interpositus, on the other hand, prevent new learning and abolish previously learned conditioned responses. Small electrolytic lesions, kainic acid lesions, and temporary inactivation (cooling, muscimol, anisomycin) localize learning to the dorsolateral anterior interpositus nucleus. Learning‐related unit activity—the signature of the engram—recorded throughout the brain depends on the interpositus. Electrical stimulation of interpositus afferents are needed for conditioning, and the conditioned interpositus has a lowered threshold. Finally, a recent anatomical study with electron microscopy shows synaptic changes in the excitatory inputs to the interpositus with conditioning. The interpositus is responsible for making the basic association between conditioned and unconditioned stimuli, which in turn allows ancillary learning to occur in cerebellar cortex, and possibly brainstem and forebrain.
Vestibularly Evoked Climbing‐Fiber Responses Modulate Simple Spikes in Rabbit Cerebellar Purkinje Neurons
Authors: BARMACK NEAL H. , YAKHNITSA VADIM
Published: January 2006

Abstract: The nodulus receives a primary vestibular afferent input from the ipsilateral labyrinth and a vestibularly related climbing‐fiber input originating from the contralateral labyrinth. Previously we demonstrated that increased discharge of vestibularly evoked climbing‐fiber responses (CFRs) in nodular Purkinje cells was correlated with decreased discharge of simple spikes (SSs). This left unresolved the question of whether vestibularly evoked antiphasic behavior of CFRs and SSs reflects a common neural mechanism or the activation of two separate parallel pathways. We answered this question using natural vestibular stimulation to modulate the discharge of uvula‐nodular Purkinje cells recorded extracellularly in unilaterally labyrinthectomized, chloralose urethane‐anesthetized rabbits. In such animals, vestibular primary afferents projecting to the uvula‐nodulus as mossy fibers remained intact on the side contralateral to the unilateral labyrinthectomy. The discharge of CFRs recorded in ipsilateral nodular Purkinje cells was increased by ipsilateral roll‐tilt while the discharge of SSs was increased by contralateral roll‐tilt. These polarities were reversed for Purkinje cells recorded in the contralateral uvula‐nodulus. The polarity of SS discharge recorded from Purkinje cells on both sides of the nodulus was opposite to that of the vestibular primary mossy‐fiber afferents. SSs continued to respond to contralateral roll‐tilt even when the primary vestibular afferent mossy‐fiber pathway was destroyed by the unilateral labyrinthectomy. Although the discharge of SSs recorded in the contralateral uvula‐nodulus was increased by contralateral roll‐tilt, this modulation was reduced relative to that observed in Purkinje cells recorded in the ipsilateral uvula‐nodulus. We conclude that vestibularly evoked CFRs caused the modulation of SS discharge.
The Cerebellum and Event Timing
Authors: IVRY RICHARD B. , SPENCER REBECCA M. , ZELAZNIK HOWARD N. , DIEDRICHSEN JÖRN
Published: January 2006

Abstract: Damage to the cerebellum disrupts performance on a range of tasks that require precise timing including the production of skilled movements, eyeblink conditioning, and perceptual tasks such as duration discrimination. We hypothesize that such tasks involve event timing, a form of representation in which the temporal goals are explicitly represented. For example, during finger tapping, the goal to produce evenly paced intervals invokes an explicit temporal representation of the time between successive contact points with the tapping surface. In contrast, timing can be an emergent property in other actions, reflecting temporal consistencies that arise through the control of other movement parameters. One example is continuous circle drawing, a task in which temporal consistency can be achieved by maintaining a constant angular velocity or minimizing higher‐order derivatives (e.g., jerk). Temporal consistency on event and emergent timing tasks is not correlated and patients with cerebellar damage show no increase in temporal variability during continuous circle drawing. While the cerebellum likely contributes to performance of a wide range of skilled behaviors, it appears to be especially important when the tasks entail event timing.
Analysis of Cx36 Knockout Does Not Support Tenet That Olivary Gap Junctions Are Required for Complex Spike Synchronization and Normal Motor Performance
Authors: KISTLER W. M. , de JEU M. T. G. , ELGERSMA Y. , VAN DER GIESSEN R. S. , HENSBROEK R. , LUO C. , KOEKKOEK S. K. E. , HOOGENRAAD C. C. , HAMERS F. P. T. , GUELDENAGEL M. , SOHL G. , WILLECKE K. , de ZEEUW C. I.
Published: January 2006

Abstract: Electrotonic coupling by gap junctions between neurons in the inferior olive has been claimed to underly complex spike (CS) synchrony of Purkinje cells in the cerebellar cortex and thereby to play a role in the coordination of movements. Here, we investigated the motor performance of mice that lack connexin36 (Cx36), which appears necessary for functional olivary gap junctions. Cx36 null‐mutants are not ataxic, they show a normal performance on the accelerating rotorod, and they have a regular walking pattern. In addition, they show normal compensatory eye movements during sinusoidal visual and/or vestibular stimulation. To find out whether the normal motor performance in mutants reflects normal CS activity or some compensatory mechanism downstream of the cerebellar cortex, we determined the CS firing rate, climbing‐fiber pause, and degree of CS synchrony. None of these parameters in the mutants differed from those in wildtype littermates. Finally, we investigated whether the role of coupling becomes apparent under challenging conditions, such as during application of the tremorgenic drug harmaline, which specifically turns olivary neurons into an oscillatory state at a high frequency. In both the mutants and wildtypes this application induced tremors of a similar duration with similar peak frequencies and amplitudes. Thus surprisingly, the present data does not support the notion that electrotonic coupling by gap junctions underlies synchronization of olivary spike activity and that these gap junctions are essential for normal motor performance.
Effects of exercise‐induced arterial hypoxaemia and work rate on diaphragmatic fatigue in highly trained endurance athletes
Authors: Vogiatzis Ioannis , Georgiadou Olga , Giannopoulou Ifigenia , Koskolou Maria , Zakynthinos Spyros , Kostikas Konstantinos , Kosmas Epaminondas , Wagner Harrieth , Peraki Eleni , Koutsoukou Antonia , Koulouris Nickolaos , Wagner Peter D. , Roussos Charis
Published: January 2006

Diaphragmatic fatigue occurs in highly trained athletes during exhaustive exercise. Since approximately half of them also exhibit exercise‐induced arterial hypoxaemia (EIAH) during high‐intensity exercise, the present study sought to test the hypothesis that arterial hypoxaemia contributes to exercise‐induced diaphragmatic fatigue in this population. Ten cyclists (: 70.0 ± 1.6 ml kg−1 min−1; mean ±s.e.m.) completed, in a balanced ordering sequence, one normoxic (end‐exercise arterial O2 saturation (S): 92 ± 1%) and one hyperoxic (F: 0.5% O2; S : 97 ± 1%) 5 min exercise test at intensities equal to 80 ± 3 and 90 ± 3% of maximal work rate (WRmax), respectively, producing the same tidal volume (VT) and breathing frequency (f) throughout exercise. Cervical magnetic stimulation was used to determine reduction in twitch transdiaphragmatic pressure (Pdi,tw) during recovery. Hyperoxic exercise at 90% WRmax induced significantly (P= 0.022) greater post‐exercise reduction in Pdi,tw (15 ± 2%) than did normoxic exercise at 80% WRmax (9 ± 2%), despite the similar mean ventilation (123 ± 8 and 119 ± 8 l min−1, respectively), breathing pattern (VT: 2.53 ± 0.05 and 2.61 ± 0.05 l, f: 49 ± 2 and 46 ± 2 breaths min−1, respectively), mean changes in Pdi during exercise (37.1 ± 2.4 and 38.2 ± 2.8 cmH2O, respectively) and end‐exercise arterial lactate (12.1 ± 1.4 and 10.8 ± 1.1 mmol l−1, respectively). The difference found in diaphragmatic fatigue between the hyperoxic (at higher leg work rate) and the normoxic (at lower leg work rate) tests suggests that neither EIAH nor lactic acidosis per se are likely predominant causative factors in diaphragmatic fatigue in this population, at least at the level of S tested. Rather, this result leads us to hypothesize that blood flow competition with the legs is an important contributor to diaphragmatic fatigue in heavy exercise, assuming that higher leg work required greater leg blood flow.
Concanavalin‐A reports agonist‐induced conformational changes in the intact GluR6 kainate receptor
Authors: Fay Anne‐Marie L. , Bowie Derek
Published: January 2006

The agonist‐binding domain of ionotropic glutamate receptors (iGluRs) has recently been crystallized as two polypeptide chains with a linker region. Although work on the structure of this isolated ligand‐binding core has been invaluable, there is debate over how it relates to conformations adopted by intact receptors. iGluR crystals are proposed to represent the activated state as their degree of domain closure correlates well with agonist efficacy. However, iGluR crystals exhibit high agonist affinity that more closely matches that of desensitized receptors. Consequently, conformations adopted by iGluR crystals may represent this state. To test this, we have employed the plant lectin, concanavalin‐A (Con‐A) to report conformational changes elicited by kainate (KA) iGluR agonists during desensitization. When GluR6 KA receptors (KARs) were pre‐incubated with Con‐A, equilibrium responses evoked by the full agonist,l‐glutamate (l‐Glu), increased almost 30‐fold. However, in the continued presence ofl‐Glu, Con‐A exerted no effect suggesting that it has restricted access to its binding sites when the agonist is bound. However, Con‐A does not discriminate well between agonist‐bound or ‐unbound states with the weak partial agonist, domoate. Accessibility experiments with KA were intermediate in nature consistent with its equilibrium efficacy at GluR6 KARs. Our results suggest that full and partial agonists elicit distinct conformational changes in KARs during desensitization. This finding can be reconciled with crystallographic data if the agonist‐binding domain adopts the same conformation in the activated and desensitized states. However, other interpretations are possible suggesting future work is required if this issue is to be resolved.
Multiwavelength Spectrophotometric Determination of Acidity Constants of Morin in Methanol-Water Mixtures
Authors: Niazi Ali , Yazdanipour Ateesa , Ghasemi Jahanbakhsh , Kubista Mikael
Published: January 2006

The acid-base properties of morin (2',3,4',5,7-pentahydroxyflavone) in mixtures of methanol- water at 25 °C and an ionic strength of 0.1 M are studied by a multiwavelength spectrophotometric method. To evaluate the pH-absorbance data, a resolution method based on the combination of soft- and hard-modeling is applied. The acidity constants of all related equilibria are estimated using the whole spectral fitting of the collected data to an established factor analysis model. DATAN program was used for determination of acidity constants. The corresponding pKa values in methanol-water mixtures were determined. There is a linear relationship between acidity constants and the mole fraction of methanol in the solvent mixtures. The effect of solvent properties on acid-base behavior is discussed.
Analysis of G(-174)C IL-6 polymorphism and plasma concentrations of inflammatory markers in patients with type 2 diabetes and peripheral arterial disease
Authors: Libra M , Signorelli S S , Bevelacqua Y , Navolanic P M , Bevelacqua V , Polesel J , Talamini R , Stivala F , Mazzarino M C , Malaponte G
Published: January 2006

Aims:To determine whether the G(−174)C interleukin 6 (IL-6) polymorphism influences the development of peripheral arterial disease (PAD) in individuals with type 2 diabetes. This was investigated by comparing the distribution of G(−174)C genotypes between patients with type 2 diabetes and PAD (PAD+) and those with type 2 diabetes but without PAD (PAD−). Plasma concentrations of IL-6, fibrinogen, C reactive protein (CRP), and vascular endothelial growth factor (VEGF) were also compared in PAD+and PAD−patients.

Methods:Blood samples were collected from 146 PAD+and 144 PAD−patients.SfaNI was used to determine the G(−174)C genotype. Plasma concentrations of IL-6, fibrinogen, CRP, and VEGF were measured by an enzyme linked immunosorbent assay.

Results:The GG genotype was more common in PAD+patients than in PAD−patients. PAD+patients also had increased mean plasma concentrations of IL-6, fibrinogen, CRP, and VEGF compared with PAD−patients. Mean plasma concentrations of IL-6, fibrinogen, and CRP in both PAD+and PAD−patients were higher in those with the GG genotype than in those with the GC or CC genotypes. In contrast, mean plasma concentrations of VEGF in PAD+and PAD−patients were not significantly different between those with different G(−174)C genotypes.

Conclusions:These results support a model in which the GG genotype promotes PAD development among individuals with type 2 diabetes by inducing increased release of IL-6. Higher concentrations of IL-6 among those with the GG genotype is associated with increased plasma concentrations of fibrinogen and CRP.
The NHS breast screening programme (pathology) EQA: experience in recent years relating to issues involved in individual performance appraisal
Authors: Parham D M , Coleman D , Kodikara S , Moss S , Ellis I O , Al-sam S , Anderson N , Bobrow L , Buley I , Connolly C E , Dallimore N S , Hales S , Hanby A , Humphreys S , Knox F , Lowe J , Macartney J , Nash R , Patnick J , Pinder S E , Quinn C M , Robertson A J , Shrimankar J , Walker R A , Wells C , Winder R , Patel N
Published: January 2006

Background:The original role of the National Health Service breast screening programme (pathology) external quality assessment (EQA) scheme was educational; it aimed to raise standards, reinforce use of common terminology, and assess the consistency of pathology reporting of breast disease in the UK.

Aims/Methods:To examine the performance (scores) of pathologists participating in the scheme in recent years. The scheme has evolved to help identify poor performers, reliant upon setting an acceptable cutpoint. Therefore, the effects of different cutpoint strategies were evaluated and implications discussed.

Results/Conclusions:Pathologists who joined the scheme improved over time, particularly those who did less well initially. There was no obvious association between performance and the number of breast cancer cases reported each year. This is not unexpected because the EQA does not measure expertise, but was established to demonstrate a common level of performance (conformity to consensus) for routine cases, rather than the ability to diagnose unusual/difficult cases. A new method of establishing cutpoints using interquartile ranges is proposed. The findings also suggest that EQA can alter a pathologist’s practice: those who leave the scheme (for whatever reason) have, on average, marginally lower scores. Consequently, with the cutpoint methodology currently used (which is common to several EQA schemes) there is the potential for the cutpoint to drift upwards. In future, individuals previously deemed competent could subsequently be erroneously labelled as poor performers. Due consideration should be given to this issue with future development of schemes.
Colocalisation of intraplaque C reactive protein, complement, oxidised low density lipoprotein, and macrophages in stable and unstable angina and acute myocardial infarction
Authors: Meuwissen M , van der Wal A C , Niessen H W M , Koch K T , de Winter R J , van der Loos C M , Rittersma S Z H , Chamuleau S A J , Tijssen J G P , Becker A E , Piek J J
Published: January 2006

Background:C reactive protein (CRP), an important serum marker of atherosclerotic vascular disease, has recently been reported to be active inside human atherosclerotic plaques.

Aims:To investigate the simultaneous presence of macrophages, CRP, membrane attack complex C5b–9 (MAC), and oxidised low density lipoprotein (oxLDL) in atherectomy specimens from patients with different coronary syndromes.

Methods:In total, 54 patients with stable angina (SA; n = 21), unstable angina (UA; n = 15), and myocardial infarction (MI; n = 18) underwent directional coronary atherectomy for coronary lesions. Cryostat sections of atherosclerotic plaques were immunohistochemically stained with monoclonal antibodies: anti-CD68 (macrophages), anti-5G4 (CRP), aE11 (MAC), and 12E7 (oxLDL). Immunopositive areas were evaluated in relation to fibrous and neointima tissues, atheroma, and media. Quantitative analysis was performed using image cytometry with systematic random sampling (percentage immunopositive/total tissue area).

Results:Macrophages, CRP, MAC, and oxLDL were simultaneously present in a higher proportion of fibrous tissue and atheroma of atherectomy specimens from patients with UA and MI compared with SA (p<0.05). Quantitative analysis showed significantly higher mean percentages of macrophages in plaques from patients with MI (44%) than UA (30%; p<0.01) and SA (20%; p<0.001). Significantly higher mean percentages of CRP were also seen in MI (25%) and UA (25%) compared with SA (12%; p<0.05).

Conclusions:The presence of CRP, complement, and oxLDL in a high proportion of plaque tissue from patients with unstable coronary artery disease implies that these surrogate markers have important proinflammatory effects inside atherosclerotic plaques. This may increase vulnerability to plaque rupture and thrombosis, with subsequent clinical sequelae.
Effects of high-sucrose feeding on insulin resistance and hemodynamic responses to insulin in spontaneously hypertensive rats
Authors: Mélançon Sébastien , Bachelard Hélène , Badeau Mylène , Bourgoin Frédéric , Pitre Maryse , Larivière Richard , Nadeau André
Published: January 2006

This study was designed to investigate the effects of a sucrose diet on vascular and metabolic actions of insulin in spontaneously hypertensive rats (SHR). Male SHR were randomized to receive a sucrose or regular chow diet for 4 wk. Age-matched, chow-fed Wistar-Kyoto (WKY) rats were used as normotensive control. In a first series of experiments, the three groups of rats had pulsed Doppler flow probes and intravascular catheters implanted to determine blood pressure, heart rate, and blood flows. Insulin sensitivity was assessed during a euglycemic hyperinsulinemic clamp performed in conscious rats. In a second series of experiments, new groups of rats were used to examine glucose transport activity in isolated muscles and to determine endothelial nitric oxide synthase (eNOS) protein expression in muscles and endothelin content in vascular tissues. Sucrose feeding was shown to markedly enhance the pressor response to insulin and its hindquarter vasoconstrictor effect when compared with chow-fed SHR. A reduction in eNOS protein content in muscle, but no change in vascular endothelin-1 protein, was noted in sucrose-fed SHR when compared with WKY rats, but these changes were not different from those noted in chow-fed SHR. Similar reductions in insulin-stimulated glucose transport were observed in soleus muscles from both groups of SHR when compared with WKY rats. In extensor digitorum longus muscles, a significant reduction in insulin-stimulated glucose transport was only seen in sucrose-fed rats when compared with the other two groups. Environmental factors, that is, high intake of simple sugars, could possibly potentiate the genetic predisposition in SHR to endothelial dysfunction and insulin resistance.
Strain-specific differences in sensitivity to ischemia-reperfusion lung injury in mice
Authors: Dodd-o Jeffrey M. , Hristopoulos Maria L. , Welsh-Servinsky Laura E. , Tankersley Clarke G. , Pearse David B.
Published: January 2006

Ischemia-reperfusion (I/R) lung injury is characterized by increased pulmonary endothelial permeability and edema, but the genetic basis for this injury is unknown. We utilized an in vivo mouse preparation of unilateral lung I/R to evaluate the genetic determinants of I/R lung injury. An index of pulmonary vascular protein permeability was measured by the ratio of left-to-right lung Evans blue dye of eight inbred mouse strains after 30 min of left lung ischemia and 150 min of reperfusion. The order of strain-specific sensitivity to I/R lung injury was BALB/c < SJL/J < CBA/J < C57BL/6J < 129/J < A/J < C3H/H3J < SWR/J. The reciprocal F1 offspring of the BALB/c and SWR/J progenitor strains had intermediate phenotypes but a differing variance. A similar pattern of right lung Evans blue dye content suggested the presence of contralateral injury because baseline vascular permeability was not different. Lung I/R injury was attenuated by NADPH oxidase inhibition, indicating a role for NADPH oxidase-derived reactive oxygen species (ROS). There was no strain-dependent difference in lung NADPH oxidase expression. Strain-related differences in zymosan-stimulated neutrophil ROS production did not correlate with I/R lung injury in that neutrophil ROS production in SWR/J mice was greater than C57BL/6J but not different from BALB/c mice. These data indicate the presence of a genetic sensitivity to lung I/R injury that involves multiple genes including a maternal-related factor. Although neutrophil-derived ROS production is also modulated by genetic factors, the pattern did not explain the genetic sensitivity to lung I/R injury.
Temporal response of desmin and dystrophin proteins to progressive resistance exercise in human skeletal muscle
Authors: Woolstenhulme Mandy T. , Conlee Robert K. , Drummond Micah J. , Stites Aaron W. , Parcell Allen C.
Published: January 2006

We have investigated the adaptations of the cytoskeletal proteins desmin and dystrophin in relationship to known muscular adaptations of resistance exercise. We measured desmin, dystrophin, and actin protein contents, myosin heavy chain (MHC) isoform distribution, muscle strength, and muscle cross-sectional area (CSA) during 8 wk of progressive resistance training or after a single bout of unaccustomed resistance exercise. Muscle biopsies were taken from the vastus lateralis of 12 untrained men. For the single-bout group ( n = 6) biopsies were taken 1 wk before the single bout of exercise ( week 0) and 1, 2, 4, and 8 wk after this single bout of exercise. For the training group ( n = 6), biopsies were taken 1 wk before the beginning of the program ( week 0) and at weeks 1, 2, 4, and 8 of the progressive resistance training program. Desmin, dystrophin, and actin protein levels were determined with immunoblotting, and MHC isoform distribution was determined using SDS-PAGE at each time point for each group. In the training group, desmin was significantly increased compared with week 0 beginning at week 4 (182% of week 0; P < 0.0001) and remained elevated through week 8 (172% of week 0; P < 0.0001). Desmin did not change at any time point for the single-bout group. Actin and dystrophin protein contents were not changed in either group at any time point. The percentage of MHC type IIa increased and MHC type IIx decreased at week 8 in the training group with no changes occurring in the single-bout group. Strength was significantly increased by week 2 (knee extension) and week 4 (leg press), and it further increased at week 8 for both these exercises in the training group only. Muscle CSA was significantly increased at week 4 for type II fibers in the training group only (5,719 ± 382 and 6,582 ± 640 μm2, weeks 0 and 4, respectively; P < 0.05). Finally, a significant negative correlation was observed between the desmin-to-actin ratio and the percentage of MHC IIx ( R = −0.31; P < 0.05, all time points from both groups). These data demonstrate a time course for muscular adaptation to resistance training in which desmin increases shortly after strength gains and in conjunction with hypertrophy, but before changes in MHC isoforms, whereas dystrophin remains unchanged.
Subclinical Carotid Atherosclerosis in HIV-Infected Patients
Authors: Jericó Carlos , Knobel Hernando , Calvo Nahum , Sorli María L. , Guelar Ana , Gimeno-Bayón Juan L. , Saballs Pere , López-Colomés José L. , Pedro-Botet Juan
Published: January 2006

Background and Purpose—

Whether or not combination antiretroviral therapy (CART) alone directly contributes to accelerating atherosclerosis in HIV-infected patients has not been studied in depth. This study aimed to ascertain the relationship between this therapy and subclinical carotid atherosclerosis according to cardiovascular risk.

Methods—

Sixty-eight HIV-infected patients with ≤1 cardiovascular risk factors and 64 with ≥2 risk factors completed the study protocol consisting of clinical, laboratory, and vascular evaluation by carotid high-resolution B-mode ultrasonography. Univariate and multivariate logistic regression analyses were performed with the presence of subclinical carotid atherosclerosis, defined by carotid intima-media thickness >0.8 mm or the presence of plaque being the dependent variable.

Results—

Among the 132 enrolled patients, 93 (70.5%) were on CART and 39 (29.5%) had never been on antiretroviral therapy. In accordance with cardiovascular risk stratification, subclinical carotid atherosclerosis was found in 26.6% (17 of 64 patients) of the very low–risk group (10-year coronary risk <5%), 35.3% (12 of 34 patients) of the low-risk group (10-year coronary risk between 5% and 9%) and 76.5% (26 of 34 patients) of the moderate/high-risk group (10-year coronary risk ≥10%). Thus, 55 (41.7%) of the 132 HIV-infected patients had subclinical carotid atherosclerosis, and independent variables associated with carotid atherosclerosis (odds ratio; 95% CI) were: CART exposure (10.5; 2.8 to 39) and 10-year coronary risk ≥10% (4.2; 1.5 to 12). In very low coronary risk patients (<5%), age (per 10-year increment: 4.01; 1.12 to 14.38), systolic blood pressure (per unit mm Hg 1.07; 1.01 to 1.14), and CART exposure (8.65; 1.54 to 48.54) were independently associated with subclinical carotid atherosclerosis.

Conclusions—

CART should be considered a strong, independent predictor for the development of subclinical atherosclerosis in HIV-infected patients, regardless of known major cardiovascular risk factors and atherogenic metabolic abnormalities induced by this therapy.
Interactions Among High School Cross‐Country Runners and Coaches: Creating a Cultural Context for Athletes' Embodied Experiences
Authors: Smith Pamela M. , Ogle Jennifer Paff
Published: January 2006

This study explored the culture of a high school girls' cross‐country team. Of interest was whether and how interactions with coaches and athletes contributed to athletes'body‐related attitudes and behaviors. Data were collected via participant observation and in‐depth interviews. Constant comparison processes were used to analyze the data. Findings revealed a team culture emphasizing values of unity/harmony and healthfulness. In turn, these values framed individual experiences of the body and team interactions. All athletes expressed relatively positive feelings about the body, and none of the athletes reported regularly dieting. Two patterns of body‐related athlete‐athlete interactions emerged: fat talk and deferential avoidance. Three patterns of body‐related coach‐athlete interactions were identified: verbal interventions for regulation of athlete attitudes and behaviors, deferential avoidance, and condemnations and censures. Analyses suggested that in a variety of ways, these interaction patterns set a context for the athletes' body‐related attitudes and behaviors.
Mobilization as a preparative regimen for hematopoietic stem cell transplantation
Authors: Chen Jing , Larochelle André , Fricker Simon , Bridger Gary , Dunbar Cynthia E. , Abkowitz Janis L.
Published: January 2006

Current myeloablative conditioning regimens for hematopoietic stem cell (HSC) transplantation are associated with significant morbidity and mortality. Thus, alternative strategies to promote engraftment of infused HSCs with increased safety warrant investigation. Using parabiotic mice, we determined that, after mobilization with AMD3100 (a CXCR4 antagonist), HSCs exited from marrow, transited blood, and engrafted in open niches in partner marrow. We then hypothesized that mobilization before transplantation might vacate niches and improve HSC engraftment. When PeP3b mice were treated with AMD3100 at 2 hours before the transplantation of 4 × 107 marrow cells, donor cell engraftment was higher (4.6% ± 1.1%) than in control animals (no AMD3100; 1.0% ± 0.24%, P < .001). When mice received weekly injections of AMD3100 on 3 consecutive weeks and marrow cells were transplanted 2 hours after each mobilization, donor cell engraftment further increased (9.1% ± 1.7%, P = .001). In contrast, in similar experiments with Balb/cByJ mice that mobilize poorly, there was no difference between the donor cell engraftment of AMD3100-treated and control recipients. These results indicate that the number of available niches regulates the number of HSCs. In addition, mobilization with AMD3100 may provide a safer preparative approach for HSC transplantation in genetic and other nonmalignant disorders.
Epstein-Barr virus nuclear antigen 2 induces FcRH5 expression through CBF1
Authors: Mohan Joanne , Dement-Brown Jessica , Maier Sabine , Ise Tomoko , Kempkes Bettina , Tolnay Mate
Published: January 2006

Fc-receptor homolog 5 (FcRH5) is a recently identified B-cell membrane protein of unknown function. In Burkitt lymphoma cell lines with chromosome 1q21 abnormalities, FcRH5 expression is deregulated, implicating FcRH5 in lymphomagenesis. Epstein-Barr virus infects and immortalizes B cells, and is implicated in the etiology of several tumors of B-cell origin. Overexpression of genes located on 1q21-25 has been proposed as a surrogate for Epstein-Barr virus in Burkitt lymphoma. We now report that Epstein-Barr virus nuclear antigen 2 (EBNA2) markedly induces the expression of the FcRH5 gene, encoded on chromosome 1q21. Induction occurred in the absence of other viral proteins and did not require de novo protein synthesis. EBNA2 lacks a DNA-binding domain and can target responsive genes through the host DNA binding protein CBF1. We show that induction of FcRH5 by EBNA2 is strictly CBF1 dependent, as it was abolished in CBF1-deficient cells. Accordingly, EBNA2 targeted CBF1 binding sites present in the FcRH5 promoter in vivo, as detected by chromatin immunoprecipitation. These results identify FcRH5 as a novel, direct target of EBNA2 that may contribute to the development of Epstein-Barr virus–associated tumors.
Selective regulation of MAP kinases and Chemokine expression after ligation of ICAM-1 on human airway epithelial cells
Authors: Krunkosky Thomas M , Jarrett Carla L
Published: January 2006

Background

Intercellular adhesion molecule 1 (ICAM-1) is an immunoglobulin-like cell adhesion molecule expressed on the surface of multiple cell types, including airway epithelial cells. It has been documented that cross-linking ICAM-1 on the surface of leukocytes results in changes in cellular function through outside-inside signaling; however, the effect of cross-linking ICAM-1 on the surface of airway epithelial cells is currently unknown. The objective of this study was to investigate whether or not cross-linking ICAM-1 on the surface of airway epithelial cells phosphorylated MAP kinases or stimulated chemokine expression and secretion.

Methods

The human lung adenocarcinoma (A549) cells and primary cultures of normal human bronchial epithelial (NHBE) cells were used in these studies. To increase ICAM-1 surface expression, cultures were stimulated with TNFα to enhance ICAM-1 surface expression. Following ICAM-1 upregulation, ICAM-1 was ligated with a murine anti-human ICAM-1 antibody and subsequently cross-linked with a secondary antibody (anti-mouse IgG(ab')2) in the presence or absence of the MAP kinase inhibitors. Following treatments, cultures were assessed for MAPK activation and chemokine gene expression and secretion. Control cultures were treated with murine IgG1 antibody or murine IgG1 antibody and anti-mouse IgG(ab')2to illustrate specificity. Data were analyzed for significance using a one-way analysis of variance (ANOVA) with Bonferroni post-test correction for multiple comparisons, and relative gene expression was analyzed using the 2-ΔΔCT method.

Results

ICAM-1 cross-linking selectively phosphorylated both ERK and JNK MAP kinases as detected by western blot analysis. In addition, cross-linking resulted in differential regulation of chemokine expression. Specifically, IL-8 mRNA and protein secretion was not altered by ICAM-1 cross-linking, in contrast, RANTES mRNA and protein secretion was induced in both epithelial cultures. These events were specifically inhibited by the ERK inhibitor PD98059. Data indicates that ICAM-1 cross-linking stimulates a synergistic increase in TNFα-mediated RANTES production involving activation of ERK in airway epithelial cells.

Conclusion

Results demonstrate that cytokine induced ICAM-1 on the surface of airway epithelial cells induce outside-inside signaling through cross-linking ICAM-1, selectively altering intracellular pathways and cytokine production. These results suggest that ICAM-1 cross-linking can contribute to inflammation in the lung via production of the chemokine RANTES.
On the effects of cycloheximide on cell motility and polarisation in Dictyostelium discoideum
Authors: Clotworthy Margaret , Traynor David
Published: January 2006

Background

Cycloheximide is a protein synthesis inhibitor that acts specifically on the 60S subunit of eukaryotic ribosomes. It has previously been shown that a short incubation ofDictyostelium discoideumamoebae in cycloheximide eliminates fluid phase endocytosis.

Results

We found that treatment with cycloheximide also causes the amoebae to retract their pseudopodia, round up and cease movement. Furthermore, fluid phase endocytosis, phagocytosis and capping cease in the presence of 2 mM cycloheximide, although membrane uptake, as measured using FM1-43, is unaffected. In the presence of cycloheximide, aggregation-competent amoebae sensitive to cAMP, although round, can still localise CRAC, ABP120, PI3K and actin polymerisation in response to a micropipette filled with cAMP. The behaviour of wild-type amoebae in the presence of cycloheximide is surprisingly similar to that of amoebae having a temperature-sensitive version of NSF at the restrictive temperature.

Conclusion

Our results may suggest that, upon cycloheximide treatment, either a labile protein required for polarised membrane recycling is lost, or a control mechanism linking protein synthesis to membrane recycling is activated.