bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Myogenic Autoregulation in Cyclosporine Nephrotoxicity in the Rat
Authors: Kaskel Frederick J. , Deverajan Prasad , Birzgalis Aija , Moore Leon C.
Published: November 2008

The mechanisms responsible for the impairment of renal blood flow (RBF) autoregulation in cyclosporine nephrotoxicity were investigated with clearance and micropuncture studies in anesthetized rats. Early chronic cyclosporine nephrotoxicity (CCN) was induced in male rats by daily intramuscular injection of 10 mg/kg/day cyclosporine-A in olive oil for 7 days; control (CON) rats received vehicle injections. Glomerular filtration rate and RBF were both reduced by 33% in CCN when compared to CON rats. RBF autoregulation was also significantly impaired in CCN, with an autoregulation index (AI) of 0.53 ± 0.03 vs. 0.16 ± 0.01 in CON rats. Micropuncture studies showed that the tubuloglomerular feedback (TGF) system is not impaired in CCN. Rather, in CCN there was a slight resetting such that the maximun TGF response was greater and the onset occurred at lower rates of perfusion than in CON. In contrast, further micropuncture studies demonstrated that TGF-independent autoregulation of glomerular capillar pressure was significantly impaired in CCN, with an AI of 0.86 ± 0.09 vs. 0.57 ± 0.06 in CON. These results indicate that the loss of autoregulatory ability in rats with CCN results from substantial impairment of the myogenic autoregulatory mechanism that is an intrinsic property of the preglomerular vasculature of the kidney.
Role of Cathepsin B and L in Anti-Glomerular Basement Membrane Nephritis in Rats
Authors: Baricos William H. , Shah Sudhir V.
Published: November 2008

We have examined the potential role of the cysteine proteinases, cathepsin B and L, in renal tubular protein degradation and increased permeability of the glomerular basement membrane (GBM) which occurs in a neutrophil- and complement-independent model of anti-GBM antibody disease. The specific activity of cathepsin L, but not cathepsin B was significantly increased (157%, p > 0.01) in cortical homogenates (85-90% tubules) prepared from anti-GBM-treated rats compared to saline-treated controls. Using highly purified cathepsin B and L, we documented the ability of these proteinases to degrade albumin in vitro (Km 5.92 and 0.22 µM for B and L, respectively). In two separate studies, treatment of rats with trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane, (E-64), a specific and irreversible inhibitor of cysteine proteinases, significantly reduced proteinuria (-45 and -41%, p < 0.01) in the 24-hour period following injection of the anti-GBM IgG. Taken together, these data suggest an important role for cysteine proteinases in the increased tubular protein degradation which occurs in response to increased filtered protein loads and in the increased GBM permeability (proteinuria) characteristic of glomerular disease.
Ion Channels in Mammalian Proximal Renal Tubules
Authors: Gögelein Heinz
Published: November 2008

In the plasma membranes of mammalian proximal renal tubules single ion channels were investigated mainly in isolated tubules perfused on one side, in isolated nonperfused (collapsed) tubules and in primary cell cultures. With these techniques, the following results were obtained: in the luminal membrane of isolated one-sided perfused tubules of rabbit and mouse S3 segments, K+-selective channels with single-channel conductance (g) of 33 pS and 63 pS, respectively, were recorded. In primary cultures of rabbit SI segments, a small-conductance (42 pS) as well as a large-conductance (200 pS) K+ channel were observed. The latter was Ca2+- and voltage-sensitive. In cultured cells a Ca2+-activated, nonselective cation channel with g = 25 pS was also recorded. On the other hand, an amiloride-sensitive channel with g = 12 pS, which was highly selective for Na+ over K+, was observed in the isolated perfused S3 segment. In the basolateral membrane of isolated perfused S3 segments, two types of K+ channels with g = 46 pS and 36 pS, respectively, were observed. The latter channel was not dependent on cytosolic Ca2+ in cell-excised patches. A K+ channel with g = 54 pS was recorded in osolated nonperfused SI segments. This channel showed inward rectification and was more active at depolarizing potentials. In isolated perfused S3 segments, in addition to the K+ channels also a nonselective cation channel with g = 28 pS was observed. This channel was highly dependent on cytosolic Ca2+ in cell-free patches. It can be concluded that the K+ channels both in the luminal and contraluminal cell membrane are involved in the generation of the cell potential. Na+ channels in the luminal membrane may participate in Na+ reabsorption, whereas the function of a basolateral cation channel remains unclear. Recently, single anion-selective channels were recorded in membranes of endocytotic vesicles, isolated from rat proximal tubules. Vesicles were enlarged by the dehydration/rehydration method and investigated with the patch clamp technique. The Cl- channel had a conductance of 73 pS, the current-voltage curve was linear and the channel inactivated at high negative clamp potentials. It is suggested that this channel is responsible for charge neutrality during active H+ uptake into the endosomes.
Assessment of Heavy Metal Nephrotoxicity in vitro Using Isolated Rat Glomeruli and Proximal Tubular Fragments
Authors: Wilks Martin F. , Kwizera Enoch N. , Bach Peter H.
Published: November 2008

Nephrotoxic metals are thought to affect mainly the proximal tubule, but the pathophysiology of acute renal failure (ARF) caused by some of these compounds cannot be explained by damage to this part of the nephron alone. To compare toxic effects on different parts of the nephron, metabolic studies (de novo protein synthesis as assessed by amino acid incorporation and fatty acid oxidation) were performed in freshly isolated rat glomeruli and proximal tubular fragments (PTF) in the presence of increasing concentrations of mercury (Hg), chromium (Cr), and cadmium (Cd) salts. Glomerular protein synthesis was very sensitive to Hg (concentration to reduce protein synthesis by 50%: 3.4 µM) and Cr (15 µM), while in PTF amino acid incorporation was similarly affected by Cd and Hg (32 and 34 µM). Glomerular fatty acid synthesis was also more sensitive to Hg than that in PTF (3.2 vs 55 µM, p < 0.005). In experiments to study the effects of reduced glutathione (0.5 and 1 mM) on the metal toxicity, preincubation of the fragments with reduced glutatione failed to protect glomeruli against subsequent exposure to the metals, but partially protected PTF ( > 100 µM for Hg and Cd). These data show that isolated glomeruli are more susceptible to those metals with the potential to cause ARF in vivo, with Hg being the most potent toxin. The results suggest that the glomerular sensitivity to Hg may indicate an important target region of the nephron in the development of ARF which has previously not been recognized.
Intracellular Chloride Activity in Cultured Mesangial Cells
Authors: Mallis Laurie , Guber Helena , Adler Sharon G. , Palant Carlos E.
Published: November 2008

Glomerular mesangial cells require Cl ions for the development of a variety of metabolic and functional properties. In the present study the electrochemical distribution for Cl- was examined in cultured rat mesangial cells with Cl--sensitive intracellular microelectrodes. It was determined that the intracellular Cl activity exceeded the levels predicted for a passively distributed ion. This was further substantiated by exposing mesangial cells to 10-5M bumetanide which drove intracellular Cl to a value close to electrochemical equilibrium. We conclude that Cl accumulates in mesangial cells, against its electrochemical gradient, through a transport pathway that is highly sensitive to bumetanide.
Effect of Hippurate on Glucose Utilization in Rat Kidney Cortex Slices
Authors: Spustová Viera , Dzúrik Rastislav
Published: November 2008

Hippurate action on glucose utilization was evaluated in rat kidney cortex slices. Studies have shown the following. (1) Hippurate inhibits markedly basal as well as insulin-stimulated glucose utilization and basal gluconeogenesis. (2) Ca deficiency and specific Ca channel blockers diltiazem and isradipine abolish the hippurate inhibition of glucose utilization. (3) K+ channel blockers, i.e. the increased K+ concentration in incubation medium, procaine and sulfonylurea drugs also abolish the hippurate inhibition of glucose utilization. It is concluded that hippurate and benzoate operate through the ATP-dependent K+ channel.
Tubular Function by Lithium Clearance, Plasma Amino Acids and Hormones following a Meat Meal in Childhood
Authors: De Santo Natale Gaspare , Coppola Salvatore , Coscarella Giulia , Anastasio Pietro , Capasso Giovambattista , Bellini Luigi , Spagnuolo Giuliano , Strazzullo Pasquale , Lombardi Attilio , De Mercato Renato , Alfieri Raffaele , Barba Gianvincenzo , Massimo Liliana
Published: November 2008

Tubular function was measured by lithium clearance (CLi) and by its derived formulae before and after the transient increase (lasting 90min) in glomerular filtration rate (GFR) following a meat meal (2g protein/kg body weight) in 12 normal children. Three baseline and 4 clearances after the meal were obtained, each lasting 30min. The mean baseline CLi was 23.1 ± 1.64ml/min/1.73m2. At peak GFR response (60min from starting the meal), CLi averaged 27.6 ± 2.4ml/min/1.73m2 (p < 0.025vs. baseline) and it was further increased (32.2 ± 5.04ml/ min/1.73m2, p < 0.01 vs. baseline) 120min after starting the meal, while GFR returned to baseline values. Fractional lithium excretion averaged 0.23 ± 0.04 at baseline and increased continuously after the meat meal and, at completion of the study, it averaged 0.38 ± 0.07 (p < 0.025vs. baseline). The distal absolute and fractional sodium reabsorption increased throughout the studies following the meal and peaked at 120 min. The functional changes were associated with a statistically significant increase in the plasma concentration of insulin, glucagon, and total amino acids after the meal. The latter at the end of the study was almost doubled (5,600 ± 780 versus 3,200 µM at baseline, p < 0.01). The data indicate that the tubulo glomerular feedback mechanism operates normally after a meat meal. The finding on increased distal sodium reabsorption might point to the existence of an insulin-dependent mechanism.
Effects of Endothelin on the Renal Microcirculation of the Split Hydronephrotic Rat Kidney
Authors: Fretschner M. , Endlich K. , Gulbins E. , Lang R.E. , Schlottmann K.S. , Steinhausen M.
Published: November 2008

We have examined the effects of endothelin (ET) on the renal microcirculation by in vivo microscopy using the model of the split hydronephrotic rat kidney. ET, a potent vasoconstrictor peptide synthesized by vascular endothehal cells, showed marked and long-lasting effects on glomerular blood flow and vessel diameters in various segments of the renal vascular bed. Intravenously applied ET (100 ng/min/kg) increased systemic blood pressure from 123 ± 7 to 156 ± 4 mm Hg, decreased glomerular blood flow by 70%, and preferentially constricted larger preglomerular vessels, e.g. the arcuate artery. The competitive leukotriene antagonist FPL55712 significantly attenuated the vascoconstrictor response of the larger vessels. Local ET adminstration decreased glomerular blood flow in a dose-dependent manner (50% reduction at a concentration of 2.6 ± 0.7 · 10-9M) and constricted smaller vessel segments, e.g. the afferent and efferent arterioles near the glomerulus. The constriction induced by ET was not significantly affected by the Ca2+ channel blocker nitrendipine (2.8 · 10-6 to 1.1 · 10-5M). We conclude that intravenous ET effects are probably mediated by leukotrienes, inducing constriction of larger renal vessels. Locally administered ET acts directly on the renal vasculature, especially on smaller vessels.
Brain-Gut Peptides and the Renal Hemodynamic Response to an Oral Protein Load: A Study of Gastrin, Bombesin, and Glucagon in Man
Authors: De Santo Natale G. , Capasso Giovambattista , Anastasio Pietro , Coppola Salvatore , Bellini Luigi , Lombardi Attilio
Published: November 2008

With the aim of disclosing a possibility for gastrin and bombesin to participate in the postprandial regulation of the renal hemodynamic response, 10 healthy males were studied before and after a meat meal (2 g/kg BW of proteins as cooked red meat). We evaluated the time course changes of glomerular filtration rate (GFR) renal plasma flow (RPF) and the plasma concentrations of gastrin, bombesin, glucagon, and total amino acids. After the meat meal a significant increase in GFR and RPF was seen, within 30min, along with an increase in plasma gastrin and glucagon. Bombesin and amino acid concentrations increased at a later time. The data suggest but cannot demonstrate a causal role for gastrin and glucagon in the genesis of the hyperfiltration response to acute protein administration.
Measurement of Human Active Renin Heterogeneity
Authors: Katz Stephen A. , Abraham Paul A. , Opsahl John A.
Published: November 2008

A method for the separation and quantitation of multiple forms of active renin in human plasma is described. Shallow gradient isoelectric focusing of plasma resolved active renin into seven distinct components in each of 10 healthy normal individuals. Plasma renin activity focused at isoelectric points of 5.71,5.57,5.47,5.22,5.08,4.93, and 4.82 with corresponding proportions of 16.3, 15.4, 21.1, 20.3, 14.0, 10.0, and 2.5%. Silicon dioxide treatment of plasma significantly increased the yield of renin in the focusing gels. Although each individual plasma sample contained the same seven renin forms, there was variability in the relative proportions of the multiple renin forms between individuals. This variance was significantly greater than the variance introduced by the determination itself. The same seven active renin forms were also present in human renal cortical tissue. In conclusion, a method for the determination of multiple renin forms in plasma and renal cortical tissue is presented. At least seven active multiple renin forms were resolved in human plasma and renal cortex.
Acute Lowering of Plasma Oncotic Pressure Increases Filtration Fraction and Sodium Excretion in Conscious Sheep
Authors: Fleming S.J. , Dallemagne C.R. , Endre Z.H. , Yesberg N.E. , Cross R.B.
Published: November 2008

We examined the effect of acutely lowering the colloid osmotic pressure by removing plasma (36.2 ± 3.1 ml/kg) and replacing it with Hartmann’s solution (93.0 ± 8.2 ml/kg) in 6 conscious merino sheep. The colloid osmotic pressure was reduced significantly (p < 0.05) from 20.3 ± 0.9 to 8.5 ± 2.5 mm Hg 0 h after plasmapheresis and to 15.2 ± 0.8 mm Hg 20 h after treatment. The filtration fraction increased from 0.16 ± 0.02 to 0.27 ± 0.02 at 0 h (p < 0.05 vs. control) and to 0.20 ± 0.02 at 20 h after treatment (p < 0.05 vs. control). At 0 h after plasmapheresis there was an increase in both sodium excretion from 187 ± 69 to 459 ± 82 µmol · min-1(p < 0.05) and in fractional sodium excretion from 1.6 ± 0.4 to 4.4 ± 1.0% (p < 0.05). The results are consistent with the hypothesis that acute alteration of Starling forces produce clinically significant effects on both glomerular filtration and tubular reabsorption.
C-Reactive Protein and Parental History Improve Global Cardiovascular Risk Prediction
Authors: Ridker Paul M , Paynter Nina P. , Rifai Nader , Gaziano J. Michael , Cook Nancy R.
Published: November 2008

Background—

High-sensitivity C-reactive protein and family history are independently associated with future cardiovascular events and have been incorporated into risk prediction models for women (the Reynolds Risk Score for women); however, no cardiovascular risk prediction algorithm incorporating these variables currently exists for men.

Methods and Results—

Among 10 724 initially healthy American nondiabetic men who were followed up prospectively over a median period of 10.8 years, we compared the test characteristics of global model fit, discrimination, calibration, and reclassification in 2 prediction models for incident cardiovascular events, one based on age, blood pressure, smoking status, total cholesterol, and high-density lipoprotein cholesterol (traditional model) and the other based on these risk factors plus high-sensitivity C-reactive protein and parental history of myocardial infarction before age 60 years (Reynolds Risk Score for men). A total of 1294 cardiovascular events accrued during study follow-up. Compared with the traditional model, the Reynolds Risk Score had better global fit (likelihood ratio test
P
<0.001), a superior (lower) Bayes information criterion, and a larger C-index (
P
<0.001). For the end point of all cardiovascular events, the Reynolds Risk Score for men reclassified 17.8% (1904/10 724) of the study population (and 20.2% [1392/6884] of those at 5% to 20% 10-year risk) into higher- or lower-risk categories, with markedly improved accuracy among those reclassified. For this model comparison, the net reclassification index was 5.3%, and the clinical net reclassification index was 14.2% (both
P
<0.001). In models based on the Adult Treatment Panel III preferred end point of coronary heart disease and limited to men not taking lipid-lowering therapy, 16.7% of the study population (and 20.1% of those at 5% to 20% 10-year risk) were reclassified to higher- or lower-risk groups, again with significantly improved global fit, larger C-index (
P
<0.001), and markedly improved accuracy among those reclassified. For this model, the net reclassification index was 8.4% and the clinical net reclassification index was 15.8% (both
P
<0.001).

Conclusions—

As previously shown in women, a prediction model in men that incorporates high-sensitivity C-reactive protein and parental history significantly improves global cardiovascular risk prediction.
Georges Rouault and the Rhetoric of Expressionism
Authors: Cernuschi Claude
Published: November 2008

Endorsing the artist's statements, Georges Rouault's admirers have repeated and helped sustain the myth of the painter as an isolated, solitary genius. Although there are many points of intersection between Rouault's work and German Expressionism (an emphasis on process and visual distortion, thematic affinities such as religious imagery, a fascination with self-portraiture, as well as with clowns and prostitutes), any potential connection with this movement has either been ignored or cursorily mentioned in the literature. This essay will explore the extent and depth of this relationship, as well as provide a critical assessment of the strikingly similar rhetorical strategies Rouault and the Expressionists employed to valorize their work.
Divided We Fall: Subtitles, Sound, and the Postwar Reconstruction of Language
Authors: Neufeld James
Published: November 2008

This essay considers the ethical significance of language in a Czech film (Divided We Fall, 2000) about the Nazi occupation of Czechoslovakia during the Second World War. It argues that linguistic shifts from Czech to German, to French, and to Yiddish, in both the dialogue and the lyrics to background music, expose the politically and ethically contested terrain of the film. Bilingual Czech nationals make subtle language choices depending on their circumstances, and those language choices gradually assume ethical significance as they highlight both the characters' prejudices and their small acts of heroism. Language itself thus becomes a guidepost to the film's examination of the ethically complicated choices which Nazi authority imposed on ordinary citizens. By paying close attention to language, one can see even the reviled Nazi collaborator in the film as attempting to assert some small measure of the human charity which his status as a collaborator contradicts. The paper concludes with a suggestion that the linguistic choices of the film contribute to a larger project of reclaiming the German language itself from the corruption it suffered because of its wartime use as the language of Nazi ideology and propaganda.
Work Stress and Coping amongst Lawyers in Singapore
Authors: Geok-choo Lim , Yiu-chung Ko , Kwok-bun Chan
Published: November 2008

This paper studied the work stressors and coping strategies of lawyers in Singapore. Data collection involved the use of both quantitative and qualitative research methods — a survey of 450 lawyers and in-depth interviews with 27 lawyers. This study found that while time pressure and work overload were the most stressful aspects of lawyering work, social interactions and interpersonal relationships at work proved to be a salient work stressor, when lawyers were dealing with clients, fellow lawyers and judges — that is, interpersonal stress. This study explains how lawyers constantly monitor and adjust their actions to negotiate for control or 'power' over others in their attempts to cope with work stress. In examining the correlation between lawyers' perceptions of work stress and their coping behaviours, this paper reveals that while lawyers tended to report more problem-focused than emotion-focused coping ways, the correlation analysis informed that emotion-focused and help-seeking coping ways were significantly correlated with interpersonal stress, such as in dealing with clients and colleagues. This study further shows that lawyers invoke social and psychological coping resources to position themselves strategically within prevailing power relations to cope with their interpersonal stress at work.
Conceptualising the Network Society in Malaysia
Authors: Ibrahim Mohamad Zaki , Chan Geraldine
Published: November 2008

Various studies have confirmed the existence of a network society in Malaysia. They generally identify its presence through aggregated individual level attributes, such as possession and usage of computer and the Internet, access to computer and the Internet, and benefits received by the network societal members. This society is widely said to be the outcome of the Malaysian government's efforts to counter increasing challenges and impacts of globalisation and ICT waves since the 1990s; in particular, the digital divide within the society. However, a review of the studies has led the authors of this article to highlight some limitations in the conceptualisation of the notions 'network society' and 'network'. Thus, the nature of the network society has not been well-understood. In this article, the authors draw upon some illuminating characteristics that have been provided by the studies to produce a conceptual framework that will serve as a useful analytical tool for a broader alternative and sociological understanding of the character of the network society and digital divide issues in Malaysia.
Global Market Integration and China's Rubber Industry: Challenges and the Way Forward
Authors:   Viswanathan
Published: November 2008

This paper, while reviewing the development and growth of the rubber production sector in China from a historical perspective, discusses the major challenges confronting the sustainable growth of rubber-based industries in the era of global market integration. The challenges arise from the growing shortage of resources (both natural and synthetic rubber) against the fast-growing automobile and tyre manufacturing industries. While the dynamic growth of the rubber industry in the pre-reforms era was achieved under a heavy import-oriented trade policy regime, the sustaining of the same is fraught with serious challenges in the context of market integration. Following a comprehensive analysis of the development of the rubber industry in retrospect, this paper suggests some important policy options for carrying forward and, thereby, sustaining the growth dynamism of the industry in the country in the emerging scenario. It emerges from the study that the sustainable growth of the rubber-based industry in China calls for a thorough revamping of state policies and devising new institutional development strategies covering a broad spectrum of activities, including: (a) demand and supply management; (b) redefining the status of natural rubber as a strategic commodity and industrial raw material; (c) restructuring the production sector favouring smallholder producers; and (d) R&D investments facilitating rubber expansion to agro-ecologically suitable areas. Given that global market integration would continue to stimulate the growth of the domestic rubber industry, this paper highlights that issues at the production sector are to be tackled on a priority basis. However, this would need China to make a rational choice between one or a combination of alternatives, including: (a) strengthening the existing domestic natural rubber production sector; (b) continue with the prevailing natural and synthetic rubber import policies; (c) increased substitution between natural and synthetic rubber; and (d) strengthening rubber investment programmes (including domestic and foreign direct investment) in neighbouring countries, namely, Laos, Vietnam, Cambodia, Myanmar and the Philippines.
“A certain degree of unclarity” Observations on The Local and the Universal Dimensions of the Church from a Roman Catholic Perspective
Authors: De Mey Peter
Published: November 2008

In this assessment of The Local and the Universal Dimensions of the Church ecclesiological issues such as the relation between Church and Trinity, the sacramentality and the catholicity of the Church, the threefold ministry and the appeal to divine right are treated. The plea for an adequate parallelism in Church structures is investigated in dialogue with The Church as Konionia of Salvation (2005). The decision of this document to opt for the term 'intermediate level' because of its unclarity is positively welcomed.
Moving beyond Christendom and Missiondom to World Church: Some Perspectives from Global South, Asia on Church Local and Universal
Authors: Wilson
Published: November 2008

With the end of the western colonial rule, and the vitality of the ministerial and mission outreach of Christian communities in the non-western world, Christian communities world over have come to a new situation of being a world church. No region of the world has any more a monopoly on Christianity. The world church reality calls for appropriate recasting of traditional ecclesiologies and critically engaging with the emerging ecclesiologies to facilitate healthy communion among churches around the globe. To achieve this, western European Christianity has to move beyond Christendom and Asian Christianity beyond the mentality of missiondom. Failing to move in that direction will only contribute to further instability among historic western churches and rigidity in their parochial understanding of the nature of the church.
Sacrament of the Kingdom of God
Authors: van Eijk Ton
Published: November 2008

This third text issuing from the Catholic/Reformed dialogue reverts to the first, The Presence of Christ in Church and World (1977). But the focus has undoubtedly changed from Christ to the Kingdom. The present text also sheds light on the Church as the pivotal theme of the second result of this dialogue, Towards a Common Understanding of the Church (1990). By viewing the Church in the wider perspective of the Kingdom the authors of the text declare themselves able to confirm their assessment in the second text that 'sacrament of grace' and 'creation of the Word' are complementary qualifications of the church. However, the question that seems not satisfactorily answered yet is, whether and in what sense all ecclesial activities can be called sacramental.
Chinese Astronomy for the Early Modern European Reader
Authors: Hsia Florence
Published: November 2008

Around 1716, the French astronomer and academician Joseph-Nicolas Delisle (1688-1768) took up a new project: the twinned topics of Chinese chronology and astronomy. Unable to access Chinese sources and not knowing any fellow savants who shared this particular interest, Delisle methodically made extracts and compiled data from the existing European literature. Among Delisle's papers at the Observatoire de Paris still exist the results of this research, including a list of the books he found relevant. This paper develops a close reading of Delisle's notes from this period to stage his journey into a recondite arena of technical and textual analysis, and to examine the scholarly practices and generic conventions through which early modern European savants confronted the Chinese astronomical tradition.
A Small Member State and European Foreign Policy: Shaping or Taking? The Case of Belgium and the African Great Lakes
Authors: Nasra Skander
Published: November 2008

The European integration process has altered the conditions under which national foreign policies in Europe are made. Departing from this assumption, this article explores whether and under what conditions a small EU member state can influence European foreign policy. To this end, the role that Belgium has played in the construction of European foreign policy towards the African Great Lakes is examined. This article argues that a small EU member state can significantly influence European foreign policy, resulting in reinforcement of its national foreign policy. Yet this influence is conditioned by two intertwined factors: the nature of EU involvement; and the characteristics of the Union's foreign policy system. Depending on these elements, a small member state can supersede the quantifiable notion of 'smallness' and actively shape the construction of European foreign policy.
Genetic Factors in Athetoid Cerebral Palsy
Authors: Amor David J. , Craig Jan E. , Delatycki Martin B. , Reddihough Dinah
Published: November 2008

Within the cerebral palsy syndromes, athetosis is most commonly causally associated with serious perinatal complications. Genetic factors are thought to play a lesser role, although the risk of recurrence in siblings has been suggested to be as high as 10%. We have conducted a clinical study of 22 subjects with a diagnosis of athetoid cerebral palsy and a review of the literature aiming to identify instances of familial recurrence of athetoid cerebral palsy. The birth history, family history, and previous investigations of subjects with athetoid cerebral palsy were studied and subjects were clinically examined for evidence of an underlying genetic etiology. Factors suggesting a genetic cause were specifically sought, such as advanced paternal age, progression of symptoms, and associated congenital abnormalities. No subjects in the study group had similarly affected relatives, and additional features suggesting a genetic cause were not observed. A literature search identified 16 instances of familial recurrence of athetoid cerebral palsy. Familial cases were typically associated with significant spasticity, microcephaly, intellectual disability, seizures, and a lack of history of birth asphyxia, and most could be explained by either autosomal-recessive or X-linked-recessive inheritance. The genetic contribution to athetoid cerebral palsy is small, with an overall risk of recurrence in siblings of about 1%. This risk is lower than previously suggested in the literature. ( J Child Neurol 2001;16:793—797).
Patterns of Cerebral Glucose Metabolism in Early and Late Stages of Rasmussen's Syndrome
Authors: Lee Joon Soo , Juhasz Csaba , Kaddurah Ahmad K. , Chugani Harry T.
Published: November 2008

Rasmussen's syndrome is a chronic encephalitis characterized by intractable focal epilepsy and progressive neurologic deterioration with lateralized brain destruction. In the early stages of the disease, the diagnosis can be difficult to make, and brain biopsy is often performed. We evaluated the patterns of cerebral glucose metabolism using 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography (PET) in 15 children (age range 2.9—15.4 years, mean age 8.7 ± 4.3 years) with Rasmussen's syndrome. In 6 patients evaluated early (≤ 1 year of onset of seizures), the PET scan showed areas of abnormal metabolism restricted mostly to the frontal and temporal regions, whereas the posterior cortex was preserved. Pathologic changes seen in the resected cortex were more pronounced in cortical areas of abnormal metabolism than in regions showing normal metabolism. In 9 patients evaluated later (>1 year after onset of seizures), the PET scan showed more diffuse hemispheric metabolic abnormalities including the occipital cortex, but the abnormalities remained highly lateralized. These patterns of glucose metabolic abnormalities in the early and late stages of the disease may facilitate the diagnosis of Rasmussen's syndrome and assist guidance of biopsy in early cases, when structural neuroimaging is still normal. ( J Child Neurol 2001;16:798—805).
Clinical Experience With Topiramate Dosing and Serum Levels in Children 12 Years or Under With Epilepsy
Authors: Schwabe Michael J. , Wheless James W.
Published: November 2008

Only a limited topiramate dosing range (5—9 mg/kg/day) is approved by the U.S. Food and Drug Administration (FDA). We reviewed our topiramate dosing (mg/kg/d) and corresponding serum levels (μg/mL) ( n = 77) in 41 children who were treated to clinical response or tolerability. The patients were divided into older (6—12 years [ n = 21]) and younger (≤5 years [ n = 20]) groups. Topiramate was given as monotherapy ( n = 9), with an enzyme-inducing antiepileptic drug ( n = 16) (phenobarbital, phenytoin, or carbamazepine), or as polytherapy ( n =17) (another antiepileptic drug). In the older children, there was a good dosage to serum level correspondence. However, younger children on topiramate monotherapy or co-therapy with an enzyme-inducing antiepileptic drug had relatively lower serum levels, but the serum level was increased if they were on polytherapy without an enzyme-inducing drug. This study supports a wider dosing range (7—22 mg/kg/day) of topiramate and dosage escalation beyond the approved range. Serum levels are useful in guiding topiramate dosing, especially in young children. ( J Child Neurol 2001;16:806—808).
Etiology and Pathophysiology of Autistic Behavior: Clues From Two Cases With an Unusual Variant of Neuroaxonal Dystrophy
Authors: Weidenheim Karen M. , Goodman Linda , Dickson Dennis W. , Gillberg Christopher , Rästam Maria , Rapin Isabelle
Published: November 2008

Two unrelated individuals with autistic behavior had numerous swollen axon terminals (spheroids) located in specific brain regions relevant to their behavioral symptoms. Spheroids are characteristic of neuroaxonal dystrophy, but the clinical profile and anatomic distribution of the lesions in these two patients differed from those of previously described patients with neuroaxonal dystrophy. Spheroids were numerous in the sensory nuclei of the spinal cord and medulla, specific nuclei and the reticular formation of the brainstem tegmentum, hypothalamus, anterior and dorsomedial thalamus, hippocampus, and cingulate and orbitofrontal cortices. Spheroids were sparse in the primary and association cortices and basal ganglia and absent in the hemispheric white matter. Cerebellar atrophy was present in both cases but associated with spheroids in only one case. These cases represent a new variant of neuroaxonal dystrophy in which behavioral symptoms characteristic of autism dominated the clinical picture. Neuroaxonal dystrophy should be included in the list of diseases that may be found in persons with autism. ( J Child Neurol 2001;16:809—819).
Prednisone Therapy in Becker's Muscular Dystrophy
Authors: Johnsen Stanley D. , Clinic Blue Bird
Published: November 2008

Two boys with Becker's muscular dystrophy had a dramatic and sustained improvement in strength with therapeutic use of prednisone. Both had documented Xp-21 defects on DNA testing. Concurrently with improvement, there was a decrease in their serum creatine kinase levels. One patient had two muscle biopsies, the first before prednisone treatment and the second during treatment. Both biopsies demonstrated an immunoblot decrease in the quantity of muscle dystrophin. Routine histology on the first biopsy was consistent with muscle dystrophy, and the second biopsy was normal. These two patients suggest that a small percentage of patients with Becker's muscular dystrophy have a dramatic and sustained improvement in strength with the use of therapeutic corticosteroids. All patients with Becker's muscular dystrophy should be given a careful trial of prednisone to define those who benefit. ( J Child Neurol 2001;16:870—871).
Proinflammatory tachykinins that signal through the neurokinin 1 receptor promote survival of dendritic cells and potent cellular immunity
Authors: Janelsins Brian M. , Mathers Alicia R. , Tkacheva Olga A. , Erdos Geza , Shufesky William J. , Morelli Adrian E. , Larregina Adriana T.
Published: November 2008

Dendritic cells (DCs) are the preferred targets for immunotherapy protocols focused on stimulation of cellular immune responses. However, regardless of initial promising results, ex vivo generated DCs do not always promote immune-stimulatory responses. The outcome of DC-dependent immunity is regulated by proinflammatory cytokines and neuropeptides. Proinflammatory neuropeptides of the tachykinin family, including substance P (SP) and hemokinin-1 (HK-1), bind the neurokinin 1 receptor (NK1R) and promote stimulatory immune responses. Nevertheless, the ability of pro-inflammatory tachykinins to affect the immune functions of DCs remains elusive. In the present work, we demonstrate that mouse bone marrow–derived DCs (BMDCs) generated in the presence of granulocyte macrophage–colony stimulating factor (GM-CSF) and interleukin-4 (IL-4), express functional NK1R. Signaling via NK1R with SP, HK-1, or the synthetic agonist [Sar9Met(O2)11]-SP rescues DCs from apoptosis induced by deprivation of GM-CSF and IL-4. Mechanistic analysis demonstrates that NK1R agonistic binding promotes DC survival via PI3K-Akt signaling cascade. In adoptive transfer experiments, NK1R-signaled BMDCs loaded with Ag exhibit increased longevity in draining lymph nodes, resulting in enhanced and prolonged effector cellular immunity. Our results contribute to the understanding of the interactions between the immune and nervous systems that control DC function and present a novel approach for ex vivo–generation of potent immune-stimulatory DCs.
Gene expression profiling in chicken heterophils with Salmonella enteritidis stimulation using a chicken 44 K Agilent microarray
Authors: Chiang Hsin-I , Swaggerty Christina L , Kogut Michael H , Dowd Scot E , Li Xianyao , Pevzner Igal Y , Zhou Huaijun
Published: November 2008

Background

Salmonella enterica serovar Enteritidis (SE) is one of the most common food-borne pathogens that cause human salmonellosis and usually results from the consumption of contaminated poultry products. The mechanism of SE resistance in chickens remains largely unknown. Previously, heterophils isolated from broilers with different genetic backgrounds (SE-resistant [line A] and -susceptible [line B]) have been shown to be important in defending against SE infections. To dissect the interplay between heterophils and SE infection, we utilized large-scale gene expression profiling.

Results

The results showed more differentially expressed genes were found between different lines than between infection (SE-treated) and non-infection (control) samples within line. However, the numbers of expressed immune-related genes between these two comparisons were dramatically different. More genes related to immune function were down-regulated in line B than line A. The analysis of the immune-related genes indicated that SE infection induced a stronger, up-regulated gene expression of line heterophils A than line B, and these genes include several components in the Toll-like receptor (TLR) signaling pathway, and genes involved in T-helper cell activation.

Conclusion

We found: (1) A divergent expression pattern of immune-related genes between lines of different genetic backgrounds. The higher expression of immune-related genes might be more beneficial to enhance host immunity in the resistant line; (2) a similar TLR regulatory network might exist in both lines, where a possible MyD88-independent pathway may participate in the regulation of host innate immunity; (3) the genes exclusively differentially expressed in line A or line B with SE infection provided strong candidates for further investigating SE resistance and susceptibility. These findings have laid the foundation for future studies of TLR pathway regulation and cellular modulation of SE infection in chickens.
Skin-impedance in Fabry Disease: A prospective, controlled, non-randomized clinical study
Authors: Gupta Surya N , Ries Markus , Murray Gary J , Quirk Jane M , Brady Roscoe O , Lidicker Jeffrey R , Schiffmann Raphael , Moore David F
Published: November 2008

Background

We previously demonstrated improved sweating after enzyme replacement therapy (ERT) in Fabry disease using the thermo-regularity sweat and quantitative sudomotor axon reflex tests. Skin-impedance, a measure skin-moisture (sweating), has been used in the clinical evaluation of burns and pressure ulcers using the portable dynamic dermal impedance monitor (DDIM) system.

Methods

We compared skin impedance measurements in hemizygous patients with Fabry disease (22 post 3-years of bi-weekly ERT and 5 ERT naive) and 22 healthy controls. Force compensated skin-moisture values were used for statistical analysis. Outcome measures included 1) moisture reading of the 100threpetitive reading, 2) rate of change, 3) average of 60–110threading and 4) overall average of all readings.

Results

All outcome measures showed a significant difference in skin-moisture between Fabry patients and control subjects (p < 0.0001). There was no difference between Fabry patients on ERT and patients naïve to ERT. Increased skin-impedance values for the four skin-impedance outcome measures were found in a small number of dermatome test-sites two days post-enzyme infusions.

Conclusion

The instrument portability, ease of its use, a relatively short time required for the assessment, and the fact that DDIM system was able to detect the difference in skin-moisture renders the instrument a useful clinical tool.
Promoter hypermethylation of the SFRP2 gene is a high-frequent alteration and tumor-specific epigenetic marker in human breast cancer
Authors: Veeck Jürgen , Noetzel Erik , Bektas Nuran , Jost Edgar , Hartmann Arndt , Knüchel Ruth , Dahl Edgar
Published: November 2008

Background

We have previously reported that expression of the Wnt antagonist genesSFRP1andSFRP5is frequently silenced by promoter hypermethylation in breast cancer. SFRP2 is a further Wnt inhibitor whose expression was recently found being downregulated in various malignancies. Here we investigated whether SFRP2 is also implicated in human breast cancer, and if so whetherSFRP2promoter methylation might serve as a potential tumor biomarker.

Methods

We analyzedSFRP2mRNA expression andSFRP2promoter methylation in 10 breast cell lines, 199 primary breast carcinomas, 20 matched normal breast tissues and 17 cancer-unrelated normal breast tissues using RT-PCR, realtime PCR, methylation-specific PCR and Pyrosequencing, respectively. SFRP2 protein expression was assessed by immunohistochemistry on a tissue microarray. Proliferation assays after transfection with anSFRP2expression vector were performed with mammary MCF10A cells. Statistical evaluations were accomplished with SPSS 14.0 software.

Results

Of the cancerous breast cell lines, 7/8 (88%) lackedSFRP2mRNA expression due toSFRP2promoter methylation (P< 0.001).SFRP2expression was substantially restored in most breast cell lines after treatment with 5-aza-2'-deoxycytidine and trichostatin A. In primary breast carcinomas SFRP2 protein expression was strongly reduced in 93 of 125 specimens (74%).SFRP2promoter methylation was detected in 165/199 primary carcinomas (83%) whereas all cancer-related and unrelated normal breast tissues were not affected bySFRP2methylation.SFRP2methylation was not associated with clinicopathological factors or clinical patient outcome. However, loss of SFRP2 protein expression showed a weak association with unfavorable patient overall survival (P= 0.071). Forced expression ofSFRP2in mammary MCF10A cells substantially inhibited proliferation rates (P= 0.045).

Conclusion

TheSFRP2gene is a high-frequent target of epigenetic inactivation in human breast cancer. Its methylation leads to abrogation ofSFRP2expression, conferring a growth advantage to epithelial mammary cells. This altogether supports a tumor suppressive function ofSFRP2. Although clinical patient outcome was not associated withSFRP2methylation, the high frequency of this epimutation and its putative specificity to neoplastic cells may qualifySFRP2promoter methylation as a potential candidate screening marker helping to improve early breast cancer detection.
Prolonged Gabapentin Analgesia in an Experimental Mouse Model of Fibromyalgia
Authors: Nishiyori Michiko , Ueda Hiroshi
Published: November 2008

In a new mouse model for generalized pain syndrome, including fibromyalgia, which used intermittent cold stress (ICS), bilateral allodynia in the hindpaw was observed that lasted more than 12 days; thermal hyperalgesia lasted 15 days. During constant cold stress (CCS), mice showed only a transient allodynia. A female prevalence in ICS-induced allodynia was observed in gonadectomized but not in gonad intact mice. Systemic gabapentin showed complete anti-allodynic effects in the ICS model at the one-tenth dose for injury-induced neuropathic pain model, and central gabapentin showed long-lasting analgesia for 4 days in ICS, but not the injury model. These results suggest that the ICS model is useful for the study of generalized pain syndrome.
Performance of N-terminal-pro-B-type natriuretic peptide in critically ill patients: a prospective observational cohort study
Authors: Coquet Isaline , Darmon Michael , Doise Jean-Marc , Degrès Michel , Blettery Bernard , Schlemmer Benoît , Gambert Philippe , Quenot Jean-Pierre
Published: November 2008

Introduction

The purpose of this study was to assess the accuracy of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) as a diagnostic tool to recognize acute respiratory failure of cardiac origin in an unselected cohort of critically ill patients.

Methods

We conducted a prospective observational study of medical ICU patients. NT-proBNP was measured at ICU admission, and diagnosis of cardiac dysfunction relied on the patient's clinical presentation and echocardiography.

Results

Of the 198 patients included in this study, 102 (51.5%) had evidence of cardiac dysfunction. Median NT-proBNP concentrations were 5,720 ng/L (1,430 to 15,698) and 854 ng/L (190 to 3,560) in patients with and without cardiac dysfunction, respectively (P < 0.0001). In addition, NT-proBNP concentrations were correlated with age (ρ = 0.43, P < 0.0001) and inversely correlated with creatinine clearance (ρ = -0.58, P < 0.0001). When evaluating the performance of NT-proBNP concentrations to detect cardiac dysfunction, the area under the receiver operating characteristic (ROC) curve was 0.76 (95% confidence interval (CI) 0.69 to 0.83). In addition, a stepwise logistic regression model revealed that NT-proBNP (odds ratio (OR) = 1.01 per 100 ng/L, 95% CI 1.002 to 1.02), electrocardiogram modifications (OR = 11.03, 95% CI 5.19 to 23.41), and severity assessed by organ system failure score (OR = 1.63 per point, 95% CI 1.17 to 2.41) adequately predicted cardiac dysfunction. The area under the ROC curve of this model was 0.83 (95% CI 0.77 to 0.90).

Conclusions

NT-proBNP measured at ICU admission might represent a useful marker to exclude cardiac dysfunction in critically ill patients.