bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolism, nitrogen excretion, and heat shock proteins in the central mudminnow (Umbra limi), a facultative air-breathing fish living in a variable environment
Authors: Currie S. , Bagatto B. , DeMille M. , Learner A. , LeBlanc D. , Marks C. , Ong K. , Parker J. , Templeman N. , Tufts B. L. , Wright P. A.
Published: January 2010

The central mudminnow ( Umbra limi (Kirtland, 1841)) is a continuous, facultative air-breathing freshwater fish found in swamps of central Canada and northeastern USA. The first goal of this field and laboratory-based study was to characterize the physicochemical conditions of mudminnow habitat during the summer. Our second goal was to determine the metabolic, stress response, and nitrogen excretion strategies of this fish following variations in water temperature, dissolved oxygen, external ammonia, and short-term periods of air exposure. We report profound diurnal fluctuations in water temperature (13–31 °C), dissolved oxygen (2%–159% air saturation), and ammonia levels (10–240 μmol·L−1) in habitat of central mudminnow measured on three dates at six different sites over 24 h. The central mudminnow does not induce urea synthesis as a mechanism of ammonia detoxification, either in response to emersion (6 or 20 h) or elevated external ammonia (10 mmol·L–1). Acute exposure to high temperature (~31 °C), aquatic hypoxia, or air resulted in significant increases in blood glucose and liver heat shock protein (Hsp) 70 and hypoxia also caused an increased reliance on anaerobic metabolism. This is the first description of the heat shock response in a facultative air-breathing fish following either hypoxia or air exposure. These metabolic and molecular responses are part of a strategy that allows the mudminnow to thrive in extremely variable freshwater environments.
Risk perception of nesting Great Blue Herons: experimental evidence of habituation
Authors: Vennesland Ross G.
Published: January 2010

The nesting behaviour of the Great Blue Heron ( Ardea herodias L., 1758) was studied in western Canada in 1998 and 1999 to (i) investigate how individual parents assess risk when repeatedly exposed to a disturbance stimulus (an investigator) and (ii) experimentally test in the field whether any variation in their nest defense behaviour was due to experience with the disturbance stimuli or the stage of the nesting period. Heron response declined through the nesting period and the level of response varied among colonies, suggesting different perceptions of risk among groups of herons in the study. It was experimentally shown that variation in the response of herons through one nesting period was due to both behavioural habituation and the stage of the nesting period. Response was stronger in 1999 than in 1998, indicating that habituation did not hold between nesting periods. In general, habituation in herons may bode well for their potential to persist in areas with light human use. But irrespective of habituation, stimuli early in the nesting period and large or novel events may still cause herons to abandon their nests owing to the effects of the stage of the nesting period.
Honeydew and nectar sugars differentially affect flight performance in female black flies
Authors: Stanfield T. K. , Hunter F. F.
Published: January 2010

In the wild, black flies (Diptera: Simuliidae) feed on both floral nectar and homopteran honeydew. We tested the hypothesis that sugar meal composition affects flight performance using tethered black flies that had been flown to exhaustion. Individuals were then fed distilled water (dH2O), 10% (m/v) artificial nectar (AN), or 20% (m/v) artificial honeydew (AH) sugars, and the distance, speed, and duration of the resultant flights were recorded using a computerized flight mill. Following a dH2O meal, flies were unable to regain flight. There were three different artificial honeydew diets (AHlow, AHmed, AHhigh), each differing in the proportion and composition of simple sugars (glucose, fructose, sucrose) and complex sugars (melezitose, stachyose). Flies flew the farthest and longest on AH meals that contained higher levels of complex sugars (AHmed, AHhigh) compared with flies fed on AN (simple sugars only) or AHlow. On this flight mill, the mean flight speed was 10.6 ± 3.5 m/min and was not affected by the type of sugar meal ingested.
Chemosensory species recognition may reduce the frequency of hybridization between native and introduced lizards
Authors: Gabirot M. , Castilla A. M. , López P. , Martín J.
Published: January 2010

The introduction of alien species to islands by human activity can cause catastrophic consequences for small populations of island endemics. Hybridization between the endangered and endemic insular lizard Podarcis atrata (Boscá, 1916) from the Columbretes Islands (Mediterranean, Spain) and the common mainland lizard Podarcis hispanica (Steindachner, 1870) could potentially occur because mainland haplotypes have already been detected in the islands, the two species are closely genetically related, and the frequency of visitors to these islands is increasing. However, reproductive decisions of lizards are often mediated by species recognition mechanisms based on chemical cues. On the basis of this observation, even if some mainland P. hispanica lizards were introduced to the islands, interspecific recognition might make rare an eventual hybridization with the insular P. atrata. We examined interspecific chemical recognition between the insular P. atrata and the mainland P. hispanica. Our results showed that lizards of both sexes responded more strongly (i.e., directed a significantly higher number of tongue flicks) to scents of conspecific individuals than to scents of heterospecifics. Chemical recognition of conspecifics by endemic island P. atrata lizards may reduce the occurrence of hybridization with introduced mainland P. hispanica lizards and protect the insular gene pool.
A mechanism aiding simultaneously reciprocal mating in snails
Authors: Chase R. , Darbyson E. , Horn K. E. , Samarova E.
Published: January 2010

The majority of hermaphroditic animals mate on a given occasion as either male or female, but terrestrial snails and slugs generally mate reciprocally with each partner participating in both sexual roles. This manner of mating requires that the genitalia be exactly opposed prior to copulation attempts, a task made difficult in snails and slugs by the absence of hearing and very limited vision. In the brown garden snail, Cornu aspersum (Müller, 1774), we found that a small protruding structure associated with the genital atrium plays an important role in positioning the snails prior to copulation. Lesions of the penial lobe reduced mating success rates, delayed mating, increased the number of attempted intromissions, and increased the number of unilateral intromissions. The sensory capacity of the penial lobe is demonstrated by histological and electrophysiological evidence, and behavioral data suggest that the lobe is also a stimulus for the partner snail. A literature review suggests that structures functionally equivalent to the penial lobe may be present in many gastropod molluscs that mate simultaneously and reciprocally, but in none that mate in other ways.
Neuronal signaling in schistosomes: current status and prospects for postgenomicsThe present review is one of a series of occasional review articles that have been invited by the Editors and will feature the broad range of disciplines and expertise represented in our Editorial Advisory Board.
Authors: Ribeiro Paula , Geary Timothy G.
Published: January 2010

Parasitic platyhelminths of the genus Schistosoma Weinland, 1858 (Trematoda, Digenea) are the etiological agents of human schistosomiasis, one of the most prevalent and debilitating parasitic diseases worldwide. Praziquantel is the only drug treatment available in most parts of the world and the effectiveness of the drug is threatened by the prospect of drug resistance. There is a pressing need to learn more about the basic biology of this organism and to identify molecular targets for new therapeutic drugs. The nervous system of schistosomes coordinates many activities that are essential for parasite survival, and as such is an attractive target for chemotherapeutic intervention. Until recently, very little was known about the molecular mechanisms of neuronal signaling in these organisms, but this is rapidly changing following the completion of the genome sequence and several recent developments in schistosome transgenesis and gene silencing. Here we review the current status of schistosome neurobiology and discuss prospects for future research as the field moves into a postgenomics era. One of the themes that will emerge from this discussion is that schistosomes have a rich diversity of neurotransmitters and receptors, indicating a more sophisticated system of neuronal communication than might be expected of a parasitic flatworm. Moreover, many of these transmitter receptors share little sequence homology with those of the human host, making them ideally suited for selective drug targeting. Strategies for characterization of these important parasite proteins will be discussed.
WEAK VECTOR AND SCALAR POTENTIALS: APPLICATIONS TO POINCARÉ'S THEOREM AND KORN'S INEQUALITY IN SOBOLEV SPACES WITH NEGATIVE EXPONENTS
Authors: AMROUCHE CHÉRIF , CIARLET PHILIPPE G. , CIARLET PATRICK
Published: January 2010

In this paper, we present several results concerning vector potentials and scalar potentials with data in Sobolev spaces with negative exponents, in a not necessarily simply-connected, three-dimensional domain. We then apply these results to Poincaré's theorem and to Korn's inequality.
VECTOR VALUED REPRODUCING KERNEL HILBERT SPACES AND UNIVERSALITY
Authors: CARMELI C. , DE VITO E. , TOIGO A. , UMANITÀ V.
Published: January 2010

This paper is devoted to the study of vector valued reproducing kernel Hilbert spaces. We focus on two aspects: vector valued feature maps and universal kernels. In particular, we characterize the structure of translation invariant kernels on abelian groups and we relate it to the universality problem.
QUASI-NONUNIQUENESS IN THE SCATTERED FIELD OF A DIELECTRIC CIRCULAR CYLINDER
Authors: DUNSTER T. M.
Published: January 2010

It is well known that the scattered field of a z polarized plane wave incident on a dielectric circular cylinder can be expanded as an infinite series involving Hankel functions. From numerical calculations of this expansion, Lam and Yedlin [5] observed that the mean square measure, over all space, of the difference of the scattered fields from two or more distinct values of the dielectric constant of the cylinder can take very small values, thereby almost contradicting the uniqueness property. We investigate this phenomenon rigorously using uniform asymptotic expansions of Bessel functions, and from our analysis we determine the spurious values of the dielectric constant which lead to this quasi-nonuniqueness.
OPTIMIZING THE RATE OF CONVERGENCE IN SOME NEW CLASSES OF SEQUENCES CONVERGENT TO EULER'S CONSTANT
Authors: MORTICI CRISTINEL
Published: January 2010

A new class of sequences convergent to Euler's constant is investigated. Special choices of parameters show that the class includes the original sequence defined by Euler, as well as more recently defined sequences due to DeTemple [1] and Vernescu [9]. It is shown how the rate of convergence of the sequences can be improved by computing optimal values of the parameters.
VOICED SPEECH ENHANCEMENT BASED ON ADAPTIVE FILTERING OF SELECTED INTRINSIC MODE FUNCTIONS
Authors: KHALDI KAIS , TURKI-HADJ ALOUANE MONIA , BOUDRAA ABDEL-OUAHAB
Published: January 2010

In this paper a new method for voiced speech enhancement combining the Empirical Mode Decomposition (EMD) and the Adaptive Center Weighted Average (ACWA) filter is introduced. Noisy signal is decomposed adaptively into intrinsic oscillatory components called Intrinsic Mode Functions (IMFs). Since voiced speech structure is mostly distributed on both medium and low frequencies, the shorter scale IMFs of the noisy signal are beneath noise, however the longer scale ones are less noisy. Therefore, the main idea of the proposed approach is to only filter the shorter scale IMFs, and to keep the longer scale ones unchanged. In fact, the filtering of longer scale IMFs will introduce distortion rather than reducing noise. The denoising method is applied to several voiced speech signals with different noise levels and the results are compared with wavelet approach, ACWA filter and EMD–ACWA (filtering of all IMFs using ACWA filter). Relying on exhaustive simulations, we show the efficiency of the proposed method for reducing noise and its superiority over other denoising methods, i.e. to improve Signal-to-Noise Ratio (SNR), and to offer better listening quality based on a Perceptual Evaluation of Speech Quality (PESQ). The present study is limited to signals corrupted by additive white Gaussian noise.
AE2 Cl−/HCO3−exchanger is required for normal cAMP-stimulated anion secretion in murine proximal colon
Authors: Gawenis Lara R. , Bradford Emily M. , Alper Seth L. , Prasad Vikram , Shull Gary E.
Published: January 2010

Anion secretion by colonic epithelium is dependent on apical CFTR-mediated anion conductance and basolateral ion transport. In many tissues, the NKCC1 Na+-K+-2Cl−cotransporter mediates basolateral Cl−uptake. However, additional evidence suggests that the AE2 Cl−/HCO3−exchanger, when coupled with the NHE1 Na+/H+exchanger or a Na+-HCO3−cotransporter (NBC), contributes to HCO3−and/or Cl−uptake. To analyze the secretory functions of AE2 in proximal colon, short-circuit current ( Isc) responses to cAMP and inhibitors of basolateral anion transporters were measured in muscle-stripped wild-type (WT) and AE2-null (AE2−/−) proximal colon. In physiological Ringer, the magnitude of cAMP-stimulated Iscwas the same in WT and AE2−/−colon. However, the Iscresponse in AE2−/−colon exhibited increased sensitivity to the NKCC1 inhibitor bumetanide and decreased sensitivity to the distilbene derivative SITS (which inhibits AE2 and some NBCs), indicating that loss of AE2 results in a switch to increased NKCC1-supported anion secretion. Removal of HCO3−resulted in robust cAMP-stimulated Iscin both AE2−/−and WT colon that was largely mediated by NKCC1, whereas removal of Cl−resulted in sharply decreased cAMP-stimulated Iscin AE2−/−colon relative to WT controls. Inhibition of NHE1 had no effect on cAMP-stimulated Iscin AE2−/−colon but caused a switch to NKCC1-supported secretion in WT colon. Thus, in AE2−/−colon, Cl−secretion supported by basolateral NKCC1 is enhanced, whereas HCO3−secretion is diminished. These results show that AE2 is a component of the basolateral ion transport mechanisms that support anion secretion in the proximal colon.
Transgenic expression of pancreatic secretory trypsin inhibitor-1 rescues SPINK3-deficient mice and restores a normal pancreatic phenotype
Authors: Romac Joelle M.-J. , Ohmuraya Masaki , Bittner Cathy , Majeed M. Faraz , Vigna Steven R. , Que Jianwen , Fee Brian E. , Wartmann Thomas , Yamamura Ken-ichi , Liddle Rodger A.
Published: January 2010

Endogenous trypsin inhibitors are synthesized, stored, and secreted by pancreatic acinar cells. It is believed that they play a protective role in the pancreas by inhibiting trypsin within the cell should trypsinogen become prematurely activated. Rodent trypsin inhibitors are highly homologous to human serine protease inhibitor Kazal-type 1 (SPINK1). The mouse has one pancreatic trypsin inhibitor known as SPINK3, and the rat has two trypsin inhibitors commonly known as pancreatic secretory trypsin inhibitors I and II (PSTI-I and -II). Rat PSTI-I is a 61-amino acid protein that shares 65% sequence identity with mouse SPINK3. It was recently demonstrated that mice with genetic deletion of the Spink3 gene ( Spink3−/−) do not survive beyond 15 days and lack normal pancreata because of pancreatic autophagy. We have shown that targeted transgenic expression of the rat Psti1 gene to acinar cells in mice [ TgN(Psti1)] protects mice against caerulein-induced pancreatitis. To determine whether the autophagic phenotype and lethality in Spink3−/−mice were due to lack of pancreatic trypsin inhibitor, we conducted breeding studies with Spink3+/−heterozygous mice and TgN(Psti1) mice. We observed that, whereas Spink3+/+, Spink3+/−, and Spink3−/−/TgN(Psti1) mice had similar survival rates, no Spink3−/−mice survived longer than 1 wk. The level of expression of SPINK3 protein in acini was reduced in heterozygote mice compared with wild-type mice. Furthermore, endogenous trypsin inhibitor capacity was reduced in the pancreas of heterozygote mice compared with wild-type or knockout mice rescued with the rat Psti1 gene. Surprisingly, the lesser amount of SPINK3 present in the pancreata of heterozygote mice did not predispose animals to increased susceptibility to caerulein-induced acute pancreatitis. We propose that a threshold level of expression is sufficient to protect against pancreatitis.
Role of the gap junction in ischemic preconditioning in the heart
Authors: Miura Tetsuji , Miki Takayuki , Yano Toshiyuki
Published: January 2010

The gap junction plays roles not only in electrical coupling of cardiomyocytes but also in intercellular transport of biologically active substances. Furthermore, the gap junction participates in decision making on cell survival versus cell death in various types of cells, and a part of reperfusion injury in the heart has been indicated to be gap junction mediated. The contribution of gap junction communication (GJC) and/or mitochondrial “hemichannels” to protective signaling during the trigger phase of ischemic preconditioning (IPC) is suggested by observations that IPC failed to protect the heart when GJC was blocked during IPC. Although ischemia suppresses both electrical and chemical GJC, chemical GJC persists for a considerable time after electrical GJC is lost. IPC facilitates the ischemia-induced suppression of chemical GJC, whereas IPC delays the reduction of electrical GJC after ischemia. The inhibition of GJC during sustained ischemia and reperfusion by GJC blockers mimics the effect of IPC on myocardial necrosis. IPC induces distinct effects on the interaction of connexin-43 with protein kinases, and the phosphorylation of connexin-43 at Ser368 by PKCε is a primary mechanism of inhibition of chemical GJC by IPC. Several lines of evidence support the notion that the modulation of GJC is a part of the mechanism of IPC-induced protection against myocardial necrosis and arrhythmias, though what percentage of IPC protection is attributable to the inhibition of GJC during ischemia-reperfusion still remains unclear.
Maternal endotoxin exposure attenuates allergic airway disease in infant rats
Authors: Cao Lei , Wang Jinxia , Zhu Yingchun , Tseu Irene , Post Martin
Published: January 2010

Prenatal exposures to immunogenic stimuli, such as bacterial LPS, have shown to influence the neonatal immune system and lung function. However, no detailed analysis of the immunomodulatory effects of LPS on postnatal T helper cell differentiation has been performed. Using a rat model, we investigated the effect of prenatal LPS exposure on postnatal T cell differentiation and experimental allergic airway disease. Pregnant rats were injected with LPS on day 20 and 21 (term = 22 days). Some of the offspring were sensitized and challenged with ovalbumin. Positive control animals were placebo exposed to saline instead of LPS, whereas negative controls were sensitized with saline. Expression of T cell-related transcription factors and cytokines was quantified in the lung, and airway hyperresponsiveness was measured. Prenatal LPS exposure induced a T helper 1 (TH1) immune milieu in the offspring of rats [i.e., increased T-bet and TH1 cytokine expression while expression of TH2-associated transcription factors (GATA3 and STAT6) and cytokines was decreased]. Prenatal LPS exposure did not trigger TH17 cell differentiation in the offspring. Furthermore, prenatal LPS exposure reduced ovalbumin-induced (TH2-mediated) airway inflammation, eosinophilia, and airway responsiveness. Thus, in utero exposure to endotoxin promotes a TH1 immune environment, which suppresses the development of allergic airway disease later in life.
Carbon dioxide chemoreception and hypoventilation syndromes with autonomic dysregulation
Authors: Carroll Michael S. , Patwari Pallavi P. , Weese-Mayer Debra E.
Published: January 2010

Respiratory and autonomic disorders of infancy, childhood, and adulthood are a group of disorders that have varying presentation, combined with a range of severity of respiratory control and autonomic nervous system dysfunction. Within this group, congenital central hypoventilation syndrome and rapid onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation, exhibit the greatest respiratory control deficits, requiring supported ventilation as a mainstay of care. The discovery of the key role of the paired-like homeobox 2B gene in autonomic nervous system development, along with the identification of paired-like homeobox 2B gene mutations causing congenital central hypoventilation syndrome, has led to a fruitful dialog between basic scientists and physician-scientists, producing an explosion of knowledge regarding genotype-phenotype correlations in this disorder, as well as important animal models of chemosensory regulation deficit. Though the etiology of rapid onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation is still to be determined, recent studies have begun to carefully delineate the phenotype, suggesting that it too may provide fertile ground for research that both advances our knowledge and improves patient care.
Effect of 10 days of bedrest on metabolic and vascular insulin action: a study in individuals at risk for type 2 diabetes
Authors: Sonne Mette P. , Alibegovic Amra C. , Højbjerre Lise , Vaag Allan , Stallknecht Bente , Dela Flemming
Published: January 2010

Physical inactivity is a known risk factor for type 2 diabetes. We studied whole body and forearm insulin sensitivity in subjects at increased risk for type 2 diabetes [persons with low birth weight (LBW group; n = 20) and first-degree relatives to type 2 diabetic patients (FDR group; n = 13)] as well as a control (CON) group ( n = 20) matched for body mass index, age, and physical activity levels before and after 10 days of bedrest. Subjects were studied by hyperinsulinemic isoglycemic clamp combined with arterial and deep venous catheterization of the forearm. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. All groups responded with a decrease in whole body insulin sensitivity in response to bedrest [CON group: 6.8 ± 0.5 to 4.3 ± 0.3 mg·min−1·kg−1( P < 0.0001), LBW group: 6.2 ± 0.5 to 4.3 ± 0.3 mg·min−1·kg−1( P < 0.0001), and FDR group: 4.3 ± 0.7 to 3.1 ± 0.3 mg·min−1·kg−1( P = 0.068)]. The percent decrease was significantly greater in the CON group compared with the FDR group (CON group: 34 ± 4%, LBW group: 27 ± 4%, and FDR group: 10 ± 13%). Forearm insulin-stimulated glucose clearance decreased significantly in the CON and LBW groups in response to bedrest; in the FDR group, clearance was very low before bedrest and no change was observed. Before bedrest, the CON and LBW groups demonstrated a significant increase in FBF during hyperinsulinemia; after bedrest, an increase in FBF was observed only in the CON group. In conclusion, bedrest induced a pronounced reduction in whole body, skeletal muscle, and vascular insulin sensitivity in the CON and LBW groups. The changes were most pronounced in the CON group. In the FDR group, insulin resistance was already present before bedrest, but even this group displayed a high sensitivity to changes in daily physical activity.
Contribution of serial and parallel microperfusion to spatial variability in pulmonary inter- and intra-acinar blood flow
Authors: Clark A. R. , Burrowes K. S. , Tawhai M. H.
Published: January 2010

This study presents a theoretical model of combined series and parallel perfusion in the human pulmonary acinus that maintains computational simplicity while capturing some important features of acinar structure. The model provides a transition between existing models of perfusion in the large pulmonary blood vessels and the pulmonary microcirculation. Arterioles and venules are represented as distinct elastic vessels that follow the branching structure of the acinar airways. These vessels are assumed to be joined at each generation by capillary sheets that cover the alveoli present at that generation, forming a “ladderlike” structure. Compared with a model structure in which capillary beds connect only the most distal blood vessels in the acinus, the model with combined serial and parallel perfusion provides greater capacity for increased blood flow in the lung via capillary recruitment when the blood pressure is elevated. Stratification of acinar perfusion emerges in the model, with red blood cell transit time significantly larger in the distal portion of the acinus compared with the proximal portion. This proximal-to-distal pattern of perfusion may act in concert with diffusional screening to optimize the potential for gas exchange.
Evidence for microRNA involvement in exercise-associated neutrophil gene expression changes
Authors: Radom-Aizik Shlomit , Zaldivar Frank , Oliver Stacy , Galassetti Pietro , Cooper Dan M.
Published: January 2010

Exercise leads to a rapid change in the profile of gene expression in circulating neutrophils. MicroRNAs (miRNAs) have been discovered to play important roles in immune function and often act to attenuate or silence gene translation. We hypothesized that miRNA expression in circulating neutrophils would be affected by brief exercise. Eleven healthy men (19–30 yr old) performed 10, 2-min bouts of cycle ergometer exercise interspersed with 1-min rest at a constant work equivalent to ∼76% of maximal oxygen uptake (V̇o2max). We used the Agilent Human miRNA V2 Microarray. A conservative statistical approach was used to determine that exercise significantly altered 38 miRNAs (20 had lower expression). Using RT-PCR, we verified the expression level changes from before to after exercise of seven miRNAs. In silico analysis showed that collectively 36 miRNAs potentially targeted 4,724 genes (2 of the miRNAs had no apparent gene targets). Moreover, when we compared the gene expression changes ( n = 458) in neutrophils that have been altered by exercise, as previously reported, with the miRNAs altered by exercise, we identified three pathways, Ubiquitin-mediated proteolysis, Jak-STAT signaling pathway, and Hedgehog signaling pathway, in which an interaction of miRNA and gene expression was plausible. Each of these pathways is known to play a role in key mechanisms of inflammation. Brief exercise alters miRNA profile in circulating neutrophils in humans. These data support the hypothesis that exercise-associated changes in neutrophil miRNA expression play a role in neutrophil gene expression in response to physical activity.
Genotypic Interaction and Gender Specificity of Common Genetic Variants in the p53/mdm2 Network in Crohn’s Disease
Authors: Zimmer V. , Widmann T. , Müller M. , Ong M.F. , Stein J.M. , Pfreundschuh M. , Lammert F. , Roemer K. , Assmann G.
Published: January 2010

Background/Aims: Defective p53-mediated apoptosis and cell cycle control have been implicated in the immunopathogenesis of Crohn’s disease (CD). Since common functional variants of p53 (SNP72 G/C) and its key negative regulator mdm2 (SNP309 T/G) have been reported to affect cellular apoptotic and cell cycle arrest capacities, we assessed the effects of these variants on CD susceptibility and their relationship to NOD2/CARD15 as a well-established genetic CD risk factor. Methods: The variants SNP72 G/C and SNP309 T/G were genotyped in 149 European CD patients and 478 healthy controls. Subgroup analysis was performed in relation to NOD2/CARD15 status and to demographic/clinical characteristics. Results: The p53 SNP72 CC genotype tended to be less frequent in CD. This reached statistical significance only in the male cohort (0 vs. 7.3%; p = 0.037). Genotype and allele frequencies of both single-nucleotide polymorphisms (SNPs) were otherwise not significantly different. In the combined genotypic analysis, the genotype p53 SNP72 CC was significantly underrepresented in mdm2 SNP309 TT homozygotes (0 vs. 9.7%; p = 0.034). No association was observed between NOD2/CARD15 and the respective SNPs. Conclusion: We report on a gender-specific protective effect of the low-apoptotic SNP72 CC genotype, and a gender-unrestricted genotypic interaction between SNP309 TT and SNP72 CC, which, for the first time, links sequence variation of the p53/mdm2 network to CD, independent of NOD2/CARD15.
Do Patients with Ulcerative Colitis Diagnosed at a Young Age Have More Severe Disease Activity than Patients Diagnosed when Older?
Authors: Lee Jin Ha , Cheon Jae Hee , Moon Chang Mo , Park Jae Jun , Hong Sung Pil , Kim Tae Il , Kim Won Ho
Published: January 2010

Background/Aims: To compare the clinical features and disease behavior of ulcerative colitis (UC) according to the age at onset. Methods: This retrospective study included 455 patients with UC who were diagnosed and treated between 1990 and 2008 at a single tertiary institution in Korea. The patients were divided into 2 groups according to their age at diagnosis of UC: an elderly group (≧40 years) and a young group (<40 years). Clinical findings at diagnosis, extent of disease, treatment modalities used, cumulative admission rates, cumulative relapse rates, and surgery rates were analyzed according to these age groups. Results: Two hundred and forty-two patients with UC (53.2%) were diagnosed before the age of 40 years. Disease severity at initial presentation as assessed by diarrhea frequency, the presence of pancolitis, and the use of steroids were higher in the young group; however, clinical disease course including cumulative admission rates, cumulative relapse rates, and surgery rates were not significantly different between the 2 groups. Conclusions: Certain clinical features and the extent of disease in UC patients appear to be more severe when the disease is diagnosed at younger age; however, their disease course and prognosis might not be different from those of their older counterparts.
Patterns of Loss of Basic Activities of Daily Living in Alzheimer Patients: A Cross-Sectional Study of the French REAL Cohort
Authors: Lechowski Laurent , Van Pradelles Sophie , Le Crane Marine , d’Arailh Lydie , Tortrat Danièle , Teillet Laurent , Vellas Bruno
Published: January 2010

Background/Aims: To characterize loss of basic activities of daily living (BADL) in 687 Alzheimer’s disease (AD) community-dwelling patients included in the French REAL cohort. Methods: Patients had mild to moderately severe AD, and the mean age was 77.8 years. Patterns of loss of the 6 BADL were described at inclusion using the Lawton scale. Results: With 6 binary BADL scores, each patient presented at inclusion a set of losses. For 53% of women, the sets of losses were included within each other or were identical, adding losses in physical ambulation, grooming, bathing, dressing, toilet and feeding, respectively. For 47% of men, a similar sequence was identified, with loss of dressing occurring secondly. A global cohesion of sets of losses was found for 87% of women and 86% of men. The Lawton scale is very useful for the assessment of AD patients.
Very Mild to Severe Dementia and Mortality: A 14-Year Follow-Up – The Odense Study
Authors: Andersen Kjeld , Lolk Annette , Martinussen Torben , Kragh-Sørensen Per
Published: January 2010

Background/Aims: To examine the mortality of very mildly to severely demented persons compared to nondemented persons. Methods: Participants in a randomly drawn population-based cohort study on dementia were followed for 14 years from 1992 to 2006. Participants were examined at baseline (3,065 nondemented and 234 prevalent demented), after 2 years (2,286 nondemented and 145 incident demented) and again after 5 years (1,669 nondemented and 124 new cases of dementia). Causes of death were ascertained in 884 nondemented and 286 demented participants. Survival for demented compared to nondemented persons was analyzed with the Cox proportional hazards model with time-dependent covariates adjusted for gender and age. Results: The hazard ratio of death (95% confidence interval) increased from 1.82 (1.55–2.14) for the very mildly demented to 9.52 (6.60–13.74) for the severely demented subjects. The demented participants died significantly more often of neurological causes other than dementia and of pneumonia than the nondemented participants. No other significant differences in causes of death were found. Conclusion: Dementia increased the risk of death. Even in the very early stages of dementia the risk of death was increased.
Immune Modulation by Non-Hodgkin Lymphoma in a Patient with Two Primary Intestinal T-Cell Lymphomas and Long-Standing Celiac Disease
Authors: Mühr-Wilkenshoff F. , Friedrich M. , Foss H.-D. , Hummel M. , Zeitz M. , Daum S.
Published: January 2010

Tumors may influence immunologic reactions. Here, we report on a 72-year-old patient who suffered from celiac disease (CD) that had been diagnosed 20 years before. Under a normal diet but without any evidence of enteropathy or CD-associated antibodies, the patient developed a jejunal T-cell lymphoma. It was resected due to perforation and four courses of IMVP-16 were added. The patient started and kept a strict gluten-free diet (GFD). Two years later, he presented with weight loss and a clonally divergent refractory sprue type II with loss of antigen (CD8; T-cell receptor-β) expression in intraepithelial lymphocytes. At this time point, he showed high titers of CD-associated antibodies, although he was on a strict GFD. This case report highlights several questions: the missing enteropathy under a gluten-containing diet supports the notion of immune suppression in malignant diseases, especially non-Hodgkin lymphoma. Secondly, the patient developed an early form of a second independent T-cell lymphoma (refractory sprue type II) under a strict GFD, then with CD-associated antibodies, which raises the question whether the clonal intraepithelial lymphocytes were stimulating antibody production. Thus, the single detection of CD-associated antibodies in patients with CD is not itself proof of noncompliance with GFD.
Kaposi’s Sarcoma after Long-Acting Steroids: Time until Remission and Drug Washout
Authors: Nassar D. , Schartz N.E.C. , Bouché C. , Lévy A. , Kerob D. , Agbalika F. , Lafaurie M. , Lebbé C.
Published: January 2010

Long-acting steroids (LAS) are widely used to treat various inflammatory diseases and allergies. They have many adverse effects including the inhibition of the hypothalamopituitary axis that can last several months. LAS are also strong immunosuppressors and can result in severe opportunistic infections and immunodeficiency-related malignancies. However, the time needed for immune recovery after withdrawal of LAS is unknown. Here we report a case of Kaposi’s sarcoma (KS) and severe immunosuppression after a chronic triamcinolone acetonide (TA) treatment. Six months after withdrawal, traces of TA were still detected in the serum by HPLC mass spectrometry. At 8 months, the drug became undetectable, and clinical and biological signs of immune recovery – beginning of KS regression, normalization of IgG levels and CD4 T lymphocyte counts – became noticeable. We then provide a review of the literature on the time until remission of KS after immunosuppression reduction. We also reviewed the cases of KS induced by TA, and the metabolic side effects of TA when compared to standard glucocorticoids.
Control of Widespread Hypertrophic Lupus Erythematosus with T-Cell-Directed Biologic Efalizumab
Authors: Navarini Alexander A. , Kerl Katrin , French Lars E. , Trüeb Ralph M.
Published: January 2010

Background/Aims: Hypertrophic lupus erythematosus (HLE) produces not only disfiguring and long-lasting skin changes, but also proves to be particularly resistant to therapy. In a patient with a disease refractory to conventional therapy, we observed a predominantly CD4+ T cell infiltrate that we sought to target therapeutically. Methods: The patient was treated with the CD11a-directed monoclonal antibody efalizumab together with 10 mg isotretinoin and 5 mg prednisone. Results: Within 6 months, the inflammatory hyperkeratotic plaques were almost completely healed, with minimal residual erythema and scarring. The cutaneous lupus activity and severity index score decreased from 8 to 4 of a total of 14 points, and pseudoepitheliomatous hyperplasia and CD4 T cell infiltrates within the lesions were reduced. Conclusion: HLE features interface dermatitis and epidermal hyperplasia, which are both explainable by T-cell-mediated immunologic effects. Correspondingly, our case responded well to the treatment with efalizumab. While the withdrawal of efalizumab from the market leaves patients with psoriasis many other options for effective therapy, it disproportionately affects patients with T-cell-mediated orphan diseases like refractory HLE.
Tumescent Liposuction: Efficacy of a Lower Lidocaine Dose (400 mg/l)
Authors: Böni Roland
Published: January 2010

Background: Local anesthesia has been widely accepted as the standard of care in liposuction. Anesthesia is achieved with a standard tumescent solution, and lidocaine is most often used at a concentration of 500 mg/l. Objective: To evaluate the efficacy of a 400 mg/l lidocaine concentration in tumescent liposuction. Methods: We performed a randomized clinical trial on 200 consecutive patients undergoing lipoaspiration. Patients were divided into two groups: group A (n = 100) received tumescent solution with a lidocaine concentration of 500 mg/l, in group B (n = 100) lidocaine levels were reduced to 400 mg/l. Pain was assessed twice during the procedure, at infiltration and while liposuction was performed. Patients rated their pain level on a numeric rating scale from 0 to 10, with 10 being the worst possible pain. Results: Tumescent solution containing a lidocaine concentration of 400 mg/l provided effective local anesthesia during lipoaspiration. There was no statistically significant difference in the pain level between the two groups. Conclusion: We propose the use of a lower lidocaine concentration of 400 mg/l in the tumescent solution compared to the originally described solution containing 500 mg/l. This is of particular interest when multiple body parts or larger areas are to be treated to avoid lidocaine toxicity.
Vascular Cell-Like Potential of Undifferentiated Ligament Fibroblasts to Construct Vascular Cell-Specific Marker-Positive Blood Vessel Structures in a PI3K Activation-Dependent Manner
Authors: Okubo Naoto , Ishisaki Akira , Iizuka Tadashi , Tamura Masato , Kitagawa Yoshimasa
Published: January 2010

Objective: To evaluate whether fibroblasts derived from periodontal ligament retain the ability to differentiate into putative vascular cells and construct vascular cell-specific marker-positive blood vessel structures. We also evaluated the morphological features of the structure and investigated the intracellular molecular mechanism underlying the angiogenic activity of these cells. Methods: Single cell-derived cultures (SCDCs) were established from primary rat ligament fibroblast cultures, and their expression of ligament cell-, mesenchymal stem cell- and vascular cell-specific markers was evaluated by RT-PCR and immunocytochemistry. The ability of the cells to construct a blood vessel structure was evaluated in a three-dimensional type I collagen scaffold. The morphological and immunohistological characteristics of the structure were then evaluated. Results: Each SCDC expressed endothelial cell (EC)-specific and smooth muscle cell-specific markers, in addition to mesenchymal stem cell- and ligament cell-specific markers. SCDC2 cells, which abundantly expressed the EC markers Flk-1 and Tie-2, vigorously constructed a blood vessel structure in a phosphoinositide 3-kinase activation-dependent manner. Conclusion: Periodontal ligament fibroblasts have the potential to construct an EC marker-positive blood vessel-like structure. Consequently, the fibroblastic lineage in ligament tissue could be a candidate precursor for construction of a vascular system around damaged ligament tissue to facilitate its regeneration.
Onychomycosis Insensitive to Systemic Terbinafine and Azole Treatments Reveals Non-Dermatophyte Moulds as Infectious Agents
Authors: Baudraz-Rosselet Florence , Ruffieux Catherine , Lurati Massimo , Bontems Olympia , Monod Michel
Published: January 2010

Background: Dermatophytes are the main cause of onychomycoses, but various non-dermatophyte filamentous fungi are often isolated from abnormal nails. Objective: Our aim was the in situ identification of the fungal infectious agent in 8 cases of onychomycoses which could not be cured after systemic terbinafine and itraconazole treat- ment. Methods: Fungal DNA was extracted from nail samples, and infectious fungi were identified by restriction fragment length polymorphism (RFLP) of amplified fungal ribosomal DNA using a previously described PCR/RFLP assay. Results: PCR/RFLP identification of fungi in nails allows the identification of the infectious agent: Fusarium sp., Acremonium sp. and Aspergillus sp. were found as a sole infectious agent in 5, 2 and 1 cases, respectively. Conclusions:Fusarium spp. and other non-dermatophyte filamentous fungi are especially difficult to cure in onychomycoses utilising standard treatment with terbinafine and itraconazole. PCR fungal identification helps demonstrate the presence of moulds in order to prescribe alternative antifungal treatments.
Contrasting Effects of Steroids and Mizoribine on Macrophage Activation and Glomerular Lesions in Rat Thy-1 Mesangial Proliferative Glomerulonephritis
Authors: Ikezumi Yohei , Suzuki Toshiaki , Karasawa Tamaki , Hasegawa Hiroya , Kawachi Hiroshi , Nikolic-Paterson David J. , Uchiyama Makoto
Published: January 2010

Background: Macrophages with a pro-inflammatory (M1) phenotype mediate renal injury in proliferative forms of glomerulonephritis, while alternatively activated (M2) macrophages are thought to be anti-inflammatory and promote repair. Glucocorticoids, the mainstay therapy for proliferative glomerulonephritis, can induce alternative macrophage activation in vitro, but it is unknown whether this occurs in vivo and if this is required for glucocorticoid responsiveness. In addition, clinical studies have suggested that the ability of mizoribine (MZR) to suppress steroid-resistant proliferative glomerulonephritis may operate via inhibiting pro-inflammatory macrophage activation. Methods: This study examined prednisolone (PSL) and/or MZR treatment of rat Thy-1 disease – a model in which macrophages promote mesangial proliferative glomerulonephritis. Results: PSL treatment of Thy-1 nephritis induced an M2-like macrophage phenotype, but failed to modify mesangial hypercellularity and actually exacerbated global glomerulosclerosis. In contrast, MZR treatment reduced hypercellularity and glomerulosclerosis and suppressing both M1 and M2 markers of macrophage activation, with a selective reduction in CD169+ macrophages. Combined PSL/MZR treatment suppressed glomerular lesions and prevented steroid induction of an M2-like macrophage phenotype. In vitro, MZR prevented steroid induction of an M2 macrophage phenotype. Conclusions: Glucocorticoid induced alternative macrophage activation failed to ameliorate rat mesangial proliferative glomerulonephritis, whereas MZR suppression of this disease model was attributed, in part, to inhibition of M1-like pro-inflammatory macrophage activation.
Sleep and Active Renin Levels – Interaction with Age, Gender, Growth Hormone and Cortisol
Authors: Schüssler Petra , Yassouridis Alexander , Uhr Manfred , Kluge Michael , Bleninger Philipp , Holsboer Florian , Steiger Axel
Published: January 2010

Aims: In young normal male subjects, plasma renin activity (PRA) shows large oscillations with a distinct association to the cyclic occurrence of rapid eye movement (REM) and non-REM (NREM) periods. Until now the sleep-related course of active renin levels is unknown. Furthermore, there are no data on the effects of age and gender on nocturnal renin and the interaction between these variables, sleep, growth hormone (GH) and cortisol. Methods: We investigated simultaneously sleep EEG (23:00–07:00 h) and the plasma concentrations (23:00–07:00 h) of active renin (in 10-min intervals) and of GH and cortisol (in 20-min intervals) in 47 healthy volunteers (24 women and 23 men) aged 19–69 years. Results: In the total sample, significant positive correlations were found between renin concentrations and NREM sleep and the sleep efficiency index, whereas a significant negative correlation exists to wakefulness. Renin shows also a positive correlation to GH levels which is restricted to the younger subjects (<40 years) during NREM sleep. No association exists between renin and cortisol. The averaged nocturnal mean renin levels were significantly lower in female than in male subjects, and in subjects older than 40 years than in younger subjects. Oscillations of active renin levels were found with increases during NREM periods and decreases during REM periods. Conclusions: In all, nocturnal averaged renin levels are lower in women than in men, decrease during ageing and correlate positively with GH, whereas the interaction between renin and sleep is independent from age and gender.
Chronic Sildenafil Treatment Corrects Endothelial Dysfunction and Improves Hypertension
Authors: Yaguas Keila , Bautista Rocio , Quiroz Yasmir , Ferrebuz Atilio , Pons Héctor , Franco Martha , Vaziri Nosratola D. , Rodriguez-Iturbe Bernardo
Published: January 2010

Background: Nitric oxide (NO) availability plays a critical role in the regulation of blood pressure, endothelial function and arterial structure. Many of the biological actions of NO are mediated by 3′5′-guanosine monophosphate (cGMP), which is rapidly degraded by cGMP phosphodiesterase (PDE). Short-term cardiovascular effects of PDE inhibitors have been studied but the changes resulting from their chronic administration in hypertension have not been evaluated. We investigated if retarding the degradation of cGMP by long-term inhibition of PDE-5 would have beneficial consequences in spontaneously hypertensive rats (SHR), a commonly used experimental model of human essential hypertension. Methods: Subgroups of hypertensive 13-week-old male SHR and normotensive Wistar-Kyoto rats were treated with sildenafil, 2.5 mg/kg/day, or vehicle, by gastric gavage for 6 months. Results: As expected, the untreated SHR had endothelial dysfunction and a steady increment of the blood pressure. In contrast, chronic sildenafil administration reversed endothelial dysfunction, reduced renal oxidative stress and renal macrophage accumulation, and ameliorated the severity of hypertension in SHR. Conclusions: These results demonstrate beneficial effects of long-term PDE-5 inhibition in SHR and suggest that its use as an adjunct therapy in essential hypertension should be investigated.