bluuebunny/crossref_metadata_2025 huggingface dataset:
Private savings and transition
Authors: Schrooten Mechthild , Stephan Sabine
Published: April 2005

After the collapse in the early transition years, saving rates in Eastern European EU‐accession countries have recovered strongly. But is private saving in these countries now driven by the same forces as in the EU? A GMM estimator is applied to analyze the determinants of private saving in both country groups. The main results are: saving rates are rather persistent; income growth increases saving, whereas public saving crowds out private saving. There is evidence that in both country groups domestic saving and foreign capital operate at least partly as substitutes, which is an indicator for international financial integration. The long‐run effects of income growth and public saving are larger in the EU‐15 than in the EU‐accession countries.
Effects of bank insolvency on corporate incentives in transition economies
Authors: Hainz Christa
Published: April 2005

In transition countries, the real impact of banking crises has so far been rather moderate. We study the effect of bank insolvency on corporate incentives in a model where incumbent banks possess an informational advantage. We find that bank insolvency reduces the incentive to restructure for firms whose incumbent bank becomes insolvent. However, bank insolvency provides an additional incentive for firms that enter the credit market to develop new projects because it reduces asymmetric information between banks. Firms’ credit costs are thereby lowered. We also explain a path‐dependent development by demonstrating that the firms’ decision to develop new projects depends on the banks’ share of non‐performing loans.
Causes of privatization in China
Authors: Guo Kai , Yao Yang
Published: April 2005

We test five hypotheses regarding the causes of privatization in China by using firm‐level panel data collected in 11 cities in the period 1995–2001. We have found that privatization is positively linked with hardened firm budgets and the extent of market liberalization, but is constrained by excessive debts and worker redundancy. Firm efficiency and state‐owned enterprises’ financial liabilities imposed on local governments are not factors of influence. These findings match the broad flow of events in China and highlight the role of market building in bringing about efficient institutional changes.
Working memory impairment in a transgenic amyloid precursor protein TgCRND8 mouse model of Alzheimer's disease
Authors: Lovasic L. , Bauschke H. , Janus C.
Published: April 2005

The most profound deficits observed in Alzheimer's disease (AD) are in domains of episodic and working memory systems. Transgenic (Tg) mice expressing mutated human amyloid precursor protein (APP) genes offer a model to study the effect of AD pathology on cognition. We reported previously that APP TgCRND8 mice showed deficits in a reference and working memory evaluated in a Morris water‐maze test. In this study, we evaluated the working memory of TgCRND8 mice comparing two training paradigms in a six‐arm radial water maze. In the first paradigm, the exploration of the maze was constrained, forcing the mice to use a spatial mapping strategy. In the second paradigm, mice were unconstrained in their exploration of the maze. TgCRND8 mice proved to be significantly impaired in spatial working memory in both paradigms as compared with their non‐transgenic littermates. The analysis of data revealed that forcing mice to use a spatial strategy during training caused only a moderate improvement in the performance of all mice. However, unconstrained exploration of the maze not only resulted in a fast learning in control mice, but also facilitated the development of a chaining strategy in spatially impaired TgCRND8 mice. In conclusion, TgCRND8 mice showed impairment in spatial working memory but retained a plasticity to choose alternative search strategies.
A case for a non‐transgenic animal model of Alzheimer's disease
Authors: Stéphan A. , Phillips A. G.
Published: April 2005

Alzheimer's disease (AD) is associated with an early impairment in memory and is the major cause of dementia in the elderly. β‐Amyloid (Aβ) is believed to be a primary factor in the pathogenic pathway leading to dementia. Mounting evidence suggests that this syndrome begins with subtle alterations in synaptic efficacy prior to extensive neuronal degeneration and that the synaptic dysfunction could be caused by diffusible oligomeric assemblies of Aβ. This paper reviews the findings from behavioral analysis, electrophysiology, neuropathology and nootropic drug screening studies involving exogenous administration of Aβ in normal rodent brains. This non‐transgenic model of amyloid pathology in vivo is presented as a complementary alternative model to transgenic mice to study the cellular and molecular pathways induced by amyloid, which in turn may be a causal factor in the disruption of cognition. The data reviewed here confirm that the diffusible form of Aβ rapidly induces synaptic dysfunction and a secondary process involving cellular cascades induced by the fibrillar form of amyloid. The time–course of alteration in memory processes implicates at least two different mechanisms that may be targeted with selective therapies aimed at improving memory in some AD patients.
THE USE OF MICRO‐PERFORATED LIDDING FILM IN LOW‐OXYGEN STORAGE OF BEEF STEAKS
Authors: BEGGAN M. , ALLEN P. , BUTLER F.
Published: April 2005

M. longissimus thoracis et lumborum (LTL), M. semimembranosus (Sm) and M. psoas major (PM) steaks were MA packed under low oxygen conditions (mother packs and barrier trays) using micro‐perforated lidding film (with/without oxygen scavengers). After 18 days storage, steaks were aerobically displayed. Color measurements (over 96 h) were compared with steaks cut from vacuum stored primals and aerobically displayed (control). LTL steaks, with scavengers in trays, had a 96 h display life compared with 72–96 h for the control. LTL steaks without scavengers failed to bloom. Sm and PM steaks from mother packs failed to bloom. Metmyoglobin formation occurred on Sm steaks stored in barrier packs with scavengers, while PM steaks resisted oxidation. Oxygen levels introduced during mother packaging were high enough to result in metmyoglobin formation on Sm and PM. LTL steaks with scavengers can be stored in mother packs with micro‐perforated film using these scavengers. Pm and LTL were successfully stored in barrier treatments with scavengers.
THERMAL GELATION PROPERTIES OF MYOFIBRILLAR PROTEIN AND GELATIN COMBINATIONS
Authors: BREWER M.S. , PETERSON W.J. , CARR T.C. , MCCUSKER R. , NOVAKOFSKI J.
Published: April 2005

Partially purified myofibrillar protein was prepared from post‐rigor beef muscle tissue. Gelation properties of myofibrillar protein (6–12%), commercial gelatin (1–12%) and combinations of gelatin and myofibrillar (8–12% protein) were compared. Gels were prepared by combining protein, buffer and 2% NaCl with appropriate volumes of water and heating to 70C at 1.4C/min. Samples were cooled to 4C and gel characteristics were evaluated using texture profile analyses. Gel strength increased as protein concentration increased in pure myofibrillar or pure gelatin gels. However, gelatin plus myofibrillar combinations were weaker than gels consisting of either protein alone at similar protein concentrations. The negative impact on gel strength of myofibrillar‐gelatin combinations suggests that the two proteins gel by different and apparently incompatible mechanisms producing an overall gel‐weakening effect. These results indicate that adding gelatin can be detrimental to gel characteristics of muscle food products.
An acute decrease in TCA cycle intermediates does not affect aerobic energy delivery in contracting rat skeletal muscle
Authors: Dawson Kristen D. , Baker David J. , Greenhaff Paul L. , Gibala Martin J.
Published: April 2005

We tested the hypothesis that an acute decrease in muscle TCA cycle intermediates during contraction would compromise aerobic energy delivery. Male Wistar rats were anaesthetized and the gastrocnemius–plantaris–soleus (GPS) muscle complex from one leg was isolated and perfused with a red cell medium containing either saline (Con) or cycloserine (Cyclo; 0.05 mg g−1), an inhibitor of alanine aminotransferase (AAT). After 1 h of perfusion, the GPS muscle was either snap frozen (Con‐Rest, n= 11; Cyclo‐Rest, n= 9) or stimulated to contract for 10 min (1 Hz, 0.3 ms, 2 V) with blood flow fixed at 30 ml min−1 (100 g)−1 and then snap frozen (Con‐Stim, n= 10; Cyclo‐Stim, n= 10). Maximal AAT activity was > 80% lower (P < 0.001) in both Cyclo‐treated groups (Rest: 0.61 ± 0.02; Stim: 0.63 ± 0.01 mmol (kg wet wt)−1 min−1; mean ±s.e.m.) compared to Con (Rest: 3.56 ± 0.16; Stim: 3.92 ± 0.29). The sum of five measured TCAI (ΣTCAI) was reduced by 23% in Cyclo‐Rest versus Con‐Rest but this was not different (P= 0.08). However, after 10 min of contraction, the ΣTCAI was 25% lower (P= 0.006) in Cyclo‐Stim compared to Con‐Stim (1.88 ± 0.15 versus 2.48 ± 0.11 mmol (kg dry wt)−1). Despite the acute decrease in TCAI after Cyclo treatment, the contraction‐induced changes in markers of non‐oxidative energy provision (phosphocreatine, ATP and lactate) and the decline in tension after 10 min of stimulation were similar compared to Con. These data do not support the hypothesis that the total muscle concentration of TCAI is causally linked to the rate of mitochondrial respiration during contraction.
Preserved contribution of nitric oxide to baseline vascular tone in deconditioned human skeletal muscle
Authors: Bleeker Michiel W. P. , Kooijman Miriam , Rongen Gerard A. , Hopman Maria T. E. , Smits Paul
Published: April 2005

Deconditioning is a risk factor for cardiovascular disease. Exercise reduces this risk, possibly by improving the vascular endothelial nitric oxide (NO) pathway. The effect of deconditioning on the NO pathway is largely unknown. This study was designed to assess baseline NO availability in the leg vascular bed after extreme, long‐term deconditioning (spinal cord‐injured individuals, SCI) as well as after moderate, short‐term deconditioning (4 weeks of unilateral lower limb suspension, ULLS). For this purpose, seven SCI were compared with seven matched controls. Additionally, seven healthy subjects were studied pre‐ and post‐ULLS. Leg blood flow was measured by venous occlusion plethysmography at baseline and during infusion of 5 incremental dosages of NG‐monomethyl‐l‐arginine (l‐NMMA) into the femoral artery. Sodium nitroprusside (SNP) was infused to test vascular responsiveness to NO. Baseline leg vascular resistance tended to be higher in SCI compared with controls (37 ± 4 versus 31 ± 2 arbitrary units (AU), P= 0.06). Deconditioning altered neither the vasoconstrictor response to l‐NMMA (increase in resistance in SCI versus controls: 102 ± 33%versus 69 ± 9%; pre‐ versus post‐ULLS: 95 ± 18%versus 119 ± 15%), nor the vascular responsiveness to NO. In conclusion, two human in vivo models of deconditioning show a preserved baseline NO availability in the leg skeletal muscle vascular bed.
Diversity of Genome Structure inSalmonella entericaSerovar Typhi Populations
Authors: Kothapalli Sushma , Nair Satheesh , Alokam Suneetha , Pang Tikki , Khakhria Rasik , Woodward David , Johnson Wendy , Stocker Bruce A. D. , Sanderson Kenneth E. , Liu Shu-Lin
Published: April 2005

The genomes of most strains ofSalmonellaandEscherichia coliare highly conserved. In contrast, all 136 wild-type strains ofSalmonella entericaserovar Typhi analyzed by partial digestion with I-CeuI (an endonuclease which cuts within therrnoperons) and pulsed-field gel electrophoresis and by PCR have rearrangements due to homologous recombination between therrnoperons leading to inversions and translocations. Recombination betweenrrnoperons in culture is known to be equally frequent inS. entericaserovar Typhi andS. entericaserovar Typhimurium; thus, the recombinants inS. entericaserovar Typhi, but not those inS. entericaserovar Typhimurium, are able to survive in nature. However, even inS. entericaserovar Typhi the need for genome balance and the need for gene dosage impose limits on rearrangements. Of 100 strains of genome types 1 to 6, 72 were only 25.5 kb off genome balance (the relative lengths of the replichores during bidirectional replication fromoriCto the termination of replication [Ter]), while 28 strains were less balanced (41 kb off balance), indicating that the survival of the best-balanced strains was greater. In addition, the need for appropriate gene dosage apparently selected against rearrangements which moved genes from their accustomed distance fromoriC. Although rearrangements involving the sevenrrnoperons are very common inS. entericaserovar Typhi, other duplicated regions, such as the 25 IS200elements, are very rarely involved in rearrangements. Large deletions and insertions in the genome are uncommon, except for deletions ofSalmonellapathogenicity island 7 (usually 134 kb) from fragment I-CeuI-G and 40-kb insertions, possibly a prophage, in fragment I-CeuI-E. The phage types were determined, and the origins of the phage types appeared to be independent of the origins of the genome types.
Protein Diversity Confers Specificity in Plasmid Segregation
Authors: Fothergill Timothy J. G. , Barillà Daniela , Hayes Finbarr
Published: April 2005

The ParG segregation protein (8.6 kDa) of multidrug resistance plasmid TP228 is a homodimeric DNA-binding factor. The ParG dimer consists of intertwined C-terminal domains that adopt a ribbon-helix-helix architecture and a pair of flexible, unstructured N-terminal tails. A variety of plasmids possess partition loci with similar organizations to that of TP228, but instead of ParG homologs, these plasmids specify a diversity of unrelated, but similarly sized, partition proteins. These include the proteobacterial pTAR, pVT745, and pB171 plasmids. The ParG analogs of these plasmids were characterized in parallel with the ParG homolog encoded by the pseudomonal plasmid pVS1. Like ParG, the four proteins are dimeric. No heterodimerization was detectable in vivo among the proteins nor with the prototypical ParG protein, suggesting that monomer-monomer interactions are specific among the five proteins. Nevertheless, as with ParG, the ParG analogs all possess significant amounts of unordered amino acid residues, potentially highlighting a common structural link among the proteins. Furthermore, the ParG analogs bind specifically to the DNA regions located upstream of their homologousparF-like genes. These nucleoprotein interactions are largely restricted to cognate protein-DNA pairs. The results reveal that the partition complexes of these and related plasmids have recruited disparate DNA-binding factors that provide a layer of specificity to the macromolecular interactions that mediate plasmid segregation.
Comprehensive Characterization of the Contribution of Individual SigB-Dependent General Stress Genes to Stress Resistance ofBacillus subtilis
Authors: Höper Dirk , Völker Uwe , Hecker Michael
Published: April 2005

TheσB-dependent general stress regulon ofBacillus subtiliscomprises more than 150 members. Induction of this regulon by imposition of environmental or metabolic stress confers multiple, nonspecific, and preemptive stress resistance to nongrowing, nonsporulated cells ofB. subtilis. In this study we performed a regulon-wide phenotypic screening analysis to determine the stress sensitivity profiles of 94 mutants defective in candidate members of the general stress regulon that were previously identified in our transcriptional profiling study of the general stress response ofB. subtilis. The phenotypic screening analysis included analysis of adaptation to a growth-inhibiting concentration of ethanol (10%, vol/vol) or NaCl (10%, wt/vol), severe heat shock (54°C), and low temperature (survival at 4°C and growth at 12.5°C). Surprisingly, 85% of the mutants tested displayed increased sensitivity at an α confidence level of ≤0.01 to at least one of the four stresses tested, and 62% still exhibited increased sensitivity at anα of ≤0.001. In essence, we were able to assign 63 genes (28 genes with an α of ≤0.001) to survival after ethanol shock, 37 genes (28 genes with an α of ≤0.001) to protection from NaCl shock, 34 genes (24 genes with an α of≤ 0.001) to survival at 4°C, and 10 genes (3 genes with an α of ≤0.001) to management of severe heat shock. Interestingly, there was a substantial overlap between the genes necessary for survival during ethanol shock and the genes necessary for survival at 4°C, and there was also an overlap between genes required for survival during ethanol shock and genes required for survival during NaCl shock. Our data provide evidence for the importance of the σBregulon at low temperatures, not only for growth but also for survival. Moreover, the data imply that a secondary oxidative stress seems to be a common component of the severe stresses tested.
MinC Mutants Deficient in MinD- and DicB-Mediated Cell Division Inhibition Due to Loss of Interaction with MinD, DicB, or a Septal Component
Authors: Zhou Huaijin , Lutkenhaus Joe
Published: April 2005

The
min
locus encodes a negative regulatory system that limits formation of the cytokinetic Z ring to midcell by preventing its formation near the poles. Of the three Min proteins, MinC is the inhibitor and prevents Z-ring formation by interacting directly with FtsZ. MinD activates MinC by recruiting it to the membrane and conferring a higher affinity on the MinCD complex for a septal component. MinE regulates the cellular location of MinCD by inducing MinD, and thereby MinC, to oscillate between the poles of the cell, resulting in a time-averaged concentration of MinCD on the membrane that is lowest at midcell. MinC can also be activated by the prophage-encoded protein DicB, which targets MinC to the septum without recruiting it first to the membrane. Previous studies have shown that the C-terminal domain of MinC is responsible for the interaction with MinD, DicB, and the septal component. In the present study, we isolated mutations in the C-terminal domain of MinC that affected its interaction with MinD, DicB, and the septal component. Among the mutations isolated, R133A and S134A are specifically deficient in the interaction with MinD, E156A is primarily affected in the interaction with DicB, and R172A is primarily deficient in the interaction with the septum. These mutations differentiate the interactions of MinC with its partners and further support the model of MinCD- and MinC-DicB-mediated cell division inhibition.
Genetic and Structural Analysis of the
Bacteroides
Conjugative Transposon CTn341
Authors: Bacic M. , Parker A. C. , Stagg J. , Whitley H. P. , Wells W. G. , Jacob L. A. , Smith C. J.
Published: April 2005

The genetic structure and functional organization of a
Bacteroides
conjugative transposon (CTn), CTn341, were determined. CTn341 was originally isolated from a tetracycline-resistant clinical isolate of
Bacteroides vulgatus
. The element was 51,993 bp long, which included a 5-bp coupling sequence that linked the transposon ends in the circular form. There were 46 genes, and the corresponding gene products fell into three major functional groups: DNA metabolism, regulation and antibiotic resistance, and conjugation. The G+C content and codon usage observed in the functional groups suggested that the groups belong to different genetic lineages, indicating that CTn341 is a composite, modular element. Mutational analysis of genes representing the different functional groups provided evidence for the gene assignments and showed that the basic conjugation and excision genes are conserved among
Bacteroides
spp. A group IIA1 intron, designated B.f.I1, was found to be inserted into the
bmhA
methylase gene. Reverse transcriptase PCR analysis of CTn341 RNA showed that B.fr.I1 was functional and was spliced out of the
bmhA
gene. Six related CTn-like elements were found in the genome sequences of
Bacteroides fragilis
NCTC9343 and
Bacteroides thetaiotaomicron
VPI5482. The putative elements were similar to CTn341 primarily in the
tra
and
mob
regions and in the
exc
gene, and several appeared to contain intron elements. Our data provide the first reported sequence for a complete
Bacteroides
CTn, and they should be of considerable benefit to further functional and genetic analyses of antibiotic resistance elements and genome evolution in
Bacteroides
.
Role of the Rep Helicase Gene in Homologous Recombination in
Neisseria gonorrhoeae
Authors: Kline Kimberly A. , Seifert H. Steven
Published: April 2005

In
Escherichia coli
, the Rep helicase has been implicated in replication fork progression, replication restart, homologous recombination, and DNA repair. We show that a
Neisseria gonorrhoeae rep
mutant is deficient in the homologous-recombination-mediated processes of DNA transformation and pilus-based colony variation but not in DNA repair.
A cost benefit analysis of an enhanced seat belt enforcement program in South Africa
Authors: Harris G T , Olukoga I A
Published: April 2005

Objective:To examine whether a program to increase the wearing of seat belts in a South African urban area would be worthwhile in societal terms.

Design:A cost benefit analysis of a one year enhanced seat belt enforcement program in eThekwini (Durban) Municipality.

Methods:Data were drawn from two main sources—a 1998 study of the cost of road crashes in South Africa and, given the absence of other data, a meta-analysis of the effectiveness of various types of interventions to reduce road crash casualties in the United States—and were analyzed using cost benefit analysis.

Results:A program designed to enforce greater wearing of seat belts, estimated to cost 2 million rand in one year, could be reasonably expected to increase seat belt usage rates by 16 percentage points and reduce fatalities and injuries by 9.5%. This would result in saved social costs of 13.6 million rand in the following year or a net present value of 11.6 million rand. There would also be favorable consequences for municipal finances.

Conclusions:Investment in a program to increase seat belt wearing rates is highly profitable in societal terms.
Working conditions and fatigue in professional truck drivers at Israeli ports
Authors: Sabbagh-Ehrlich S , Friedman L , Richter E D
Published: April 2005

Background:Trucks represent 6% of all vehicles, but truck crashes account for 20% of road deaths in Israel, even though travel distances are usually short (<200 km) and overnight travel is uncommon.

Objective:To determine occupational and individual predictors of fatigue, falling asleep at the wheel, and involvement in crashes with injuries and deaths in truck drivers.

Setting and methods:We carried out field interviews of 160 port truck drivers regarding driver characteristics, workplace and driving conditions, employer-employee relations, medical conditions, sleep quality and fatigue, falling asleep at the wheel, and involvement in road crashes.

Results:One day before interview, 38.1% of the drivers had worked more than the 12 hour legal limit. More than 30% reported falling asleep at the wheel recently, and 13% had prior involvement in a sleep related crash. Sixty seven (41.9%) drivers said that their employer forced them to work beyond the legal 12 hour daily limit. Involvement in a crash with casualties was associated with poor sleep quality (adjusted OR = 2.9; p = 0.042) and frequent difficulty finding parking when tired (OR = 3.7; p = 0.049). Self assessment of fatigue underestimated fatigue from the Pittsburgh Sleep Quality Questionnaire. However fatigue occurred in many drivers without sleep problems and many crashes occurred without fatigue.

Conclusions:Prevention requires measures to reduce work stresses, screening drivers, speed control, and modal shifts. The work risks and adverse outcomes of truck drivers in large countries with long overnight journeys occur in a small country with small distances, relatively short work journeys, and little overnight travel.
CORE CONCEPTS FOR DYNAMIC TU GAMES
Authors: KRANICH LAURENCE , PEREA ANDRÉS , PETERS HANS
Published: April 2005

This paper is concerned with the question of how to define the core when cooperation takes place in a dynamic setting. The focus is on dynamic cooperative games in which the players face a finite sequence of exogenously specified TU-games. Three different core concepts are presented: the classical core, the strong sequential core and the weak sequential core. The differences between the concepts arise from different interpretations of profitable deviations by coalitions. Sufficient conditions are given for nonemptiness of the classical core in general and of the weak sequential core for the case of two players. Simplifying characterizations of the weak and strong sequential core are provided. Examples highlight the essential difference between these core concepts.
EFFICIENT UNSUPERVISED MINING FROM NOISY CO-OCCURRENCE DATA
Authors: MAMITSUKA HIROSHI
Published: April 2005

We consider the problem of mining from noisy unsupervised data sets. The data point we call noise is an outlier in the current context of data mining, and it has been generally defined as the one locates in low probability regions of an input space. The purpose of the approach for this problem is to detect outliers and to perform efficient mining from noisy unsupervised data. We propose a new iterative sampling approach for this problem, using both model-based clustering and the likelihood given to each example by a trained probabilistic model for finding data points of such low probability regions in an input space. Our method uses an arbitrary probabilistic model as a component model and repeats two steps of sampling non-outliers with high likelihoods (computed by previously obtained models) and training the model with the selected examples alternately. In our experiments, we focused on two-mode and co-occurrence data and empirically evaluated the effectiveness of our proposed method, comparing with two other methods, by using both synthetic and real data sets. From the experiments using the synthetic data sets, we found that the significance level of the performance advantage of our method over the two other methods had more pronounced for higher noise ratios, for both medium- and large-sized data sets. From the experiments using a real noisy data set of protein–protein interactions, a typical co-occurrence data set, we further confirmed the performance of our method for detecting outliers from a given data set. Extended abstracts of parts of the work presented in this paper have appeared in Refs. 1 and 2.
Immunolocalization and expression of kinin B1R and B2R receptors in human inflammatory bowel disease
Authors: Stadnicki Antoni , Pastucha Ezbieta , Nowaczyk Grazyna , Mazurek Urszula , Plewka Danuta , Machnik Grzegorz , Wilczok Tadeusz , Colman Robert W.
Published: April 2005

Bradykinin is a mediator of inflammation, responsible for pain, vasodilation, and capillary permeability. Bradykinin receptor 1 (B1R) and bradykinin receptor 2 (B2R) are G protein-coupled receptors that mediate kinin effects. The latter is constitutive and rapidly desensitized; the former is induced by inflammatory cytokines and resistant to densensitization. The distribution of bradykinin receptors in human intestinal tissue was studied in patients with inflammatory bowel disease (IBD), namely ulcerative colitis (UC) and Crohn's disease (CD). Both B2R and B1R proteins are expressed in the epithelial cells of normal and IBD intestines. B1R protein is visualized in macrophages at the center of granulomas in CD. B2R protein is normally present in the apexes of enterocytes in the basal area and intracellularly in inflammatory tissue. In contrast, B1R protein is found in the basal area of enterocytes in normal intestine but in the apical portion of enterocytes in inflamed tissue. B1R protein is significantly increased in both active UC and CD intestines compared with controls. In patients with active UC, B1R mRNA is significantly higher than B2R mRNA. However, in inactive UC patients, the B1R and B2R mRNA did not differ significantly. Thus bradykinin receptors in IBD may reflect intestinal inflammation. Increased B1R gene and protein expression in active IBD provides a structural basis of the important role of bradykinin in chronic inflammation.
Hypothalamic-pituitary disconnection in fetal sheep blocks the peripartum increases in adrenal responsiveness and adrenal ACTH receptor expression
Authors: Valego Nancy K. , Su Yixin , Carey Luke C. , Young Sharla F. , Tatter Stephen B. , Wang Jinjuan , Rose James C.
Published: April 2005

Although it has been recognized for over a decade that hypothalamic-pituitary disconnection (HPD) in fetal sheep prevents the late gestation rise in plasma cortisol concentrations, the underlying mechanisms remain unclear. We hypothesized that reductions in adrenal responsiveness and ACTH receptor (ACTH-R) expression may be mediating factors. HPD or sham surgery was performed at 120 days of gestation, and catheters were placed for blood sampling. At ∼138 days of gestation, fetuses were killed, and adrenals were removed for cell culture and analyses of ACTH-R mRNA and protein. After 48 h, adrenocortical cells were stimulated with ACTH for 2 h, and the medium was collected for cortisol measurement. The same cells were incubated overnight with medium or medium containing ACTH or forskolin (FSK), followed by ACTH stimulation (as above) and cortisol and cellular ACTH-R mRNA analyses. HPD prevented the late gestation increase in plasma cortisol and bioactive ACTH and reduced adrenal ACTH-R mRNA and protein levels by over 35%. HPD cells secreted significantly less cortisol than sham cells (3.2 ± 1.2 vs. 47.3 ± 11.1 ng·ml−1·2 h−1) after the initial ACTH stimulation. Overnight incubation of HPD cells with ACTH or FSK restored cortisol responses to acute stimulation to levels seen in sham cells initially. ACTH-R mRNA levels in cells isolated from HPD fetuses were decreased by over 60%, whereas overnight incubation with ACTH or FSK increased levels by approximately twofold. Our findings indicate that the absence of the cortisol surge in HPD fetuses is a consequence, at least in part, of decreased ACTH-R expression and adrenal responsiveness.
Reduced nitric oxide bioavailability contributes to skeletal muscle microvessel rarefaction in the metabolic syndrome
Authors: Frisbee Jefferson C.
Published: April 2005

This study tested the hypothesis that chronically elevated oxidant stress contributes to impaired active hyperemia in skeletal muscle of obese Zucker rats (OZR) vs. lean Zucker rats (LZR) through progressive deteriorations in microvascular structure. Twelve-week-old LZR and OZR were given 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (tempol) in the drinking water for ∼4 wk. Subsequently, perfusion of in situ gastrocnemius muscle was determined during incremental elevations in metabolic demand, while a contralateral skeletal muscle arteriole and the gastrocnemius muscle was removed to determine dilator reactivity, vessel wall mechanics, and microvessel density. Under control conditions, active hyperemia was impaired at all levels of metabolic demand in OZR, and this was correlated with a reduced microvessel density, increased arteriolar stiffness, and impaired dilator reactivity. Chronic tempol ingestion improved perfusion during moderate to high metabolic demand only and was associated with improved arteriolar reactivity and microvessel density; passive vessel mechanics were unaltered. Combined antioxidant therapy and nitric oxide synthase inhibition in OZR prevented much of the restored perfusion and microvessel density. In LZR, treatment with Nω-nitro-l-arginine methyl ester (l-NAME) hydrochloride and hydralazine (to prevent hypertension) impaired active hyperemia, dilator reactivity, and microvessel density, although arteriolar distensibility was not altered. These results suggest that with the development of the metabolic syndrome, chronic reductions in nitric oxide bioavailability, in part via the scavenging actions of oxidative free radicals, contribute to a loss of skeletal muscle microvessels, leading to impaired muscle perfusion with elevated metabolic demand.
Quantitative analysis of voltage-gated potassium currents from primary equine (Equus caballus) and elephant (Loxodonta africana) articular chondrocytes
Authors: Mobasheri A. , Gent T. C. , Womack M. D. , Carter S. D. , Clegg P. D. , Barrett-Jolley R.
Published: April 2005

In this comparative study, we have established in vitro models of equine and elephant articular chondrocytes, examined their basic morphology, and characterized the biophysical properties of their primary voltage-gated potassium channel (Kv) currents. Using whole cell patch-clamp electrophysiological recording from first-expansion and first-passage cells, we measured a maximum Kv conductance of 0.15 ± 0.04 pS/pF ( n = 10) in equine chondrocytes, whereas that in elephant chondrocytes was significantly larger (0.8 ± 0.4 pS/pF, n = 4, P ≤ 0.05). Steady-state activation parameters of elephant chondrocytes ( V = −22 ± 6 mV, k = 11.8 ± 3 mV, n = 4) were not significantly different from those of horse chondrocytes ( V = −12.5 ± 4.3 mV, k = 12 ± 2, n = 10). This suggests that there would be slightly more resting Kv activation in elephant chondrocytes than in their equine counterparts. Kinetic analysis revealed that both horse and elephant chondrocyte Kv currents had similar activation and inactivation parameters. Pharmacological investigation of equine chondrocyte Kv currents showed them to be powerfully inhibited by the potassium channel blockers tetraethylammonium and 4-aminopyridine but not by dendrotoxin-I. Immunohistochemical studies using polyclonal antibodies to Kv1.1–Kv1.5 provided evidence for expression of Kv1.4 in equine chondrocytes. This is the first electrophysiological study of equine or elephant chondrocytes. The data support the notion that voltage-gated potassium channels play an important role in regulating the membrane potential of articular chondrocytes and will prove useful in future modeling of electromechanotransduction of fully differentiated articular chondrocytes in these and other species.
Roles of Slc13a1 and Slc26a1 sulfate transporters of eel kidney in sulfate homeostasis and osmoregulation in freshwater
Authors: Nakada Tsutomu , Zandi-Nejad Kambiz , Kurita Yukihiro , Kudo Hisayuki , Broumand Vadjista , Kwon Charles Y. , Mercado Adriana , Mount David B. , Hirose Shigehisa
Published: April 2005

Sulfate is required for proper cell growth and development of all organisms. We have shown that the renal sulfate transport system has dual roles in euryhaline eel, namely, maintenance of sulfate homeostasis and osmoregulation of body fluids. To clarify the physiological roles of sulfate transporters in teleost fish, we cloned orthologs of the mammalian renal sulfate transporters Slc13a1 (NaSi-1) and Slc26a1 (Sat-1) from eel ( Anguilla japonica) and assessed their functional characteristics, tissue localization, and regulated expression. Full-length cDNAs coding for ajSlc13a1 and ajSlc26a1 were isolated from a freshwater eel kidney cDNA library. Functional expression in Xenopus oocytes revealed the expected sulfate transport characteristics; furthermore, both transporters were inhibited by mercuric chloride. Northern blot analysis, in situ hybridization, and immunohistochemistry demonstrated robust apical and basolateral expression of ajSlc13a1 and ajSlc26a1, respectively, within the proximal tubule of freshwater eel kidney. Expression was dramatically reduced after the transfer of eels from freshwater to seawater; the circulating sulfate concentration in eels was in turn markedly elevated in freshwater compared with seawater conditions (19 mM vs. 1 mM). The reabsorption of sulfate via the apical ajSlc13a1 and basolateral ajSlc26a1 transporters may thus contribute to freshwater osmoregulation in euryhaline eels, via the regulation of circulating sulfate concentration.
SARS-CoV Infection Was from at Least Two Origins in the Taiwan Area
Authors: Shih Mu-Chin , Peck Konan , Chan Wen-Ling , Chu Yen-Ping , Chen Jui-Chang , Tsai Chang-Hai , Chang Jan-Gowth
Published: April 2005

Objective: Severe acute respiratory syndrome (SARS) is caused by a new coronavirus. Genomic sequence analysis will provide the molecular epidemiology and help to develop vaccines. Methods: We developed a rapid method to amplify and sequence the whole SARS-CoV genome from clinical specimens. The technique employed one-step multiplex RT-PCR to amplify the whole SARS-CoV genome, and then nested PCR was performed to amplify a 2-kb region separately. The PCR products were sequenced. Results: We sequenced the genomes of SARS-CoV from 3 clinical specimens obtained in Taiwan. The sequences were similar to those reported by other groups, except that 17 single nucleotide variations and two 2-nucleotide deletions, and a 1-nucleotide deletion were found. All the variations in the clinical specimens did not alter the amino acid sequence. Of these 17 sequenced variants, two loci (positions 26203 and 27812) were segregated together as a specific genotype – T:T or C:C. Phylogenetic analysis showed two major clusters of SARS patients in Taiwan. Conclusion: We developed a very economical and rapid method to sequence the whole genome of SARS-CoV, which can avoid cultural influence. From our results, SARS patients in Taiwan may be infected from two different origins.
Significance of Serum Ribavirin Concentration in Combination Therapy of Interferon and Ribavirin for Chronic Hepatitis C
Authors: Arase Yasuji , Ikeda Kenji , Tsubota Akihito , Suzuki Fumitaka , Suzuki Yoshiyuki , Saitoh Satoshi , Kobayashi Masahiro , Akuta Norio , Someya Takashi , Hosaka Tetsuya , Sezaki Hitomi , Kobayashi Mariko , Kumada Hiromitsu
Published: April 2005

Objective: The purpose of this clinical retrospective cohort study was to determine the most suitable ribavirin concentration on combination therapy of interferon (IFN)-ribavirin. Methods: Entry criteria were serum HCV-RNA level ≧100 KIU/ml, HCV-genotype 1b, chronic hepatitis, and initial combination treatment of IFN-α-2b (6 million units daily for 2 weeks and then 3 times weekly for 6 weeks) and ribavirin (600–800 mg/day) for 8 weeks without stopping or decreasing the dosage of IFN and/or ribavirin. Sixty-eight consecutive patients who satisfied the above criteria were given maintenance therapy for another 16 weeks. Results: A sustained virological response (SVR) rate of 25.0% (17/68) was seen in all subjects. The SVR rate was 44.0% (11/25) in the high ribavirin group with a serum ribavirin concentration of ≧3,000 ng/ml at 8 weeks after initiation of combination therapy. SVR was significantly dependent at a serum ribavirin level of ≧3,000 ng/ml (p = 0.005). The incidence of discontinuations and dose modifications for combination therapy in patients having a serum ribavirin concentration of ≧3,500 ng/ml 8 weeks after initiation of therapy was 57.1% (4/7). This value was statistically higher than that in patents with <3,500 ng/ml (p = 0.033). Conclusion: Our results showed that the most suitable serum ribavirin concentrations are from 3,000 to 3,500 ng/ml 8 weeks after initiation of combination therapy.
Porcine Endogenous Retroviruses PERV-A and PERV-B Infect neither Mouse Cells in vitro nor SCID Mice in vivo
Authors: Irgang Markus , Karlas Alexander , Laue Christine , Specke Volker , Tacke Stefan J. , Kurth Reinhard , Schrezenmeir Jürgen , Denner Joachim
Published: April 2005

Objective: Porcine endogenous retroviruses (PERVs) pose a risk for xenotransplantations using pig materials as they are present in the genome of all pigs and are able to infect human cells in vitro. Until recently, transmission of PERVs in vivo was only described in severe combined immunodeficient (SCID) and nude mice inoculated with PERV-producing cells. However, in this series of experiments microchimerism could not be excluded. To overcome this problem, the risk of PERV infection was addressed in a similar way but using cell-free inoculation of mouse cells in vitro and SCID mice in vivo. Methods: Mouse cell lines and primary cells were incubated in vitro with PERV-A, with a recombinant PERV-A/C and with PERV-B. Provirus integration was assessed by PCR. Reverse transcriptase activity was measured in the cell supernatants. SCID mice were inoculated in vivo with cell-free virus at high titers. Results: None of the mouse cell lines and primary cells could be infected by PERV and no provirus integration was observed in different organs of the inoculated SCID mice. Conclusion: The data indicate that PERV-A, PERV-A/C and PERV-B could not infect different mouse cells. These data correlate with the recent finding that mouse cells lack a functional receptor for PERV-A. Although the receptor for PERV-B is still unknown, these data suggest that previously reported PERV transmissions to SCID and nude mice in vivo might be due to microchimerism or pseudotyping with murine viruses and indicate that normal mice are an inappropriate model for the study of PERV infection and pathogenesis.
Distribution of Viral RNA in Mouse Tissues during Acute Phase of Coxsackievirus B5 Infection
Authors: Moon Mi Sun , Joo Chul Hyun , Hwang In Seok , Ye Jeong Sook , Jun Eun Jung , Lee Hui Sun , Kim Donghou , Lee Min-Jae , Lee Heuiran , Kim Yoo Kyum
Published: April 2005

Objective: To investigate histopathological changes and distribution of coxsackievirus B5 (CVB5) RNA in mouse heart, liver, and pancreas during the acute phase of infection. Methods: C3H/HeJ male mice, aged 3–4 weeks, were inoculated intraperitoneally with 5 × 105 plaque-forming units of CVB5 and sacrificed at 1, 2, 3, 4, 7 and 10 days postinfection (p.i.). Inflammation of the heart, liver, and pancreatic tissue sections was evaluated by hematoxylin and eosin staining, and virus was detected using antibody to viral coat protein VP1. A quantitative real-time RT-PCR method, using primers and probe targeted to the highly conserved sequences in the 5’-untranslated region of the virus, was used to evaluate the kinetics of CVB5 RNA during the development of myocarditis or pancreatitis. Results: Marginal inflammatory changes were observed in the heart tissues although viral RNA was constantly present between 1 and 10 days p.i., peaking at 4 days p.i. The pancreatic tissues displayed massive lymphocyte infiltration and loss of acinar cells at day 4 p.i. and viral RNA was detected between 1 and 10 days p.i., peaking at 2–3 days p.i. In the liver, viral RNA was detected between 1 and 7 days. No mortality was observed. Conclusions: CVB5 induced acute pancreatitis without subsequent development of myocarditis. Clearance of CVB5 RNA from the pancreas and heart was slower than clearance from the liver. Our real-time RT-PCR method, which is more sensitive than conventional plaque assay, may provide valuable insight into viral RNA kinetics during CVB5 infection.
Basal Cell Carcinomas of the Eyelids
Authors: Allali J. , D’Hermies F. , Renard G.
Published: April 2005

Basal cell carcinomas (BCC) are the more frequent malignant tumors seen in France as in other western countries. They represent 20% of eyelid tumors and 90% of eyelid malignancies. Due to their local growth, problems may arise when treating BCC, and curative exeresis must be the preferred choice each time it is possible. BCC of the eyelids have a high risk of recurrence. Recurrences are more aggressive, infiltrative and destructive and have a considerably poorer rate of cure than primary tumors. Eyelid reconstructions can entail use of complex methods which should only be carried out by a trained ophthalmologist who is also able to treat any associated age-related ocular pathologies. BCC is the most common cause leading to eyelid reconstructive surgery; a surgery which has a triple objective: tumor removal, functionality and an esthetic outcome.
Optical Coherence Tomographic Assessment of Diabetic Macular Edema: Comparison with Fluorescein Angiographic and Clinical Findings
Authors: Özdek Şengül C. , Erdinç M. Alper , Gürelik Gökhan , Aydın Bahri , Bahçeci Umut , Hasanreisoğlu Berati
Published: April 2005

Purpose: To compare the optical coherence tomographic (OCT) features with clinical and fluorescein angiographic (FA) findings in patients with diabetic retinopathy. Methods: In a retrospective study ophthalmologic examination together with FA and OCT images were obtained from 195 eyes of 110 patients with different stages of diabetic retinopathy and OCT images were obtained from 40 eyes of 20 control subjects. Fluorescein leakage characteristics were organized into five groups: no leakage (1), focal (2), diffuse (3), combined focal + diffuse leakage (4) and cystoid (5). The Pearson correlation test was used to test the correlation between visual acuity and central foveal thickness and ANOVA was used for the statistical comparison between the groups. Results: The OCT images demonstrated retinal swelling in 66.1% of eyes, cystoid macular edema (CME) in 11.8% of eyes, serous foveal detachment + swelling in 6.2% of eyes, serous foveal detachment + swelling + CME in 3.6% of eyes and normal foveal structure in 12.3% of eyes. The best-corrected visual acuity was significantly correlated with central foveal thickness (r: –0.528, p < 0.01). There was 77% agreement between clinical examination and OCT results. CME was detected with OCT in 15.4% of eyes in our study, 40% of which was not detected with slit-lamp biomicroscopy and 63.3% of which was not evident in FA. None of the serous foveal detachments could be detected during slit-lamp biomicroscopy or FA. Conclusions: OCT-3 provided objective documentation of foveal structural changes in eyes with diabetic retinopathy. Best-corrected visual acuity provided a significant correlation with the retinal thickness at the central fovea. These results indicate that OCT can facilitate deciding on the treatment protocol (surgical or medical) and follow-up of diabetic patients, which is especially important in the early stages of diabetic maculopathy when the structural changes are not yet evident with slit-lamp biomicroscopy or angiographically.
Long-Term Patient Satisfaction of External Dacryocystorhinostomy
Authors: Mansour K. , Sere M. , Oey A.G. , Bruin K.J. , Blanksma L.J.
Published: April 2005

Purpose: To evaluate patient’s opinion on the long-term success of external dacryocystorhinostomy using the same quantitative parameter pre- and postoperatively. Methods: A postal questionnaire was sent to 139 patients who had undergone external dacryocystorhinostomy. The only parameter for success of the treatment was the improvement of patient’s subjective pre- and postoperative symptoms score. The duration of this follow-up ranged from 1 year up to 5 years postoperatively. Statistical analyses were performed using the Wilcoxon Signed-Ranks test and the χ2 test. Results: According to the patient’s own evaluation, external dacryocystorhinostomy is a successful operation. After 1 year the success percentage was 89%, after 2–3 years it was 79% and after 4–5 years it was 71%. Conclusion: External dacryocystorhinostomy is appreciated by the patients and considered a successful operation. The subjective evaluation of this operation should yield more creditability than objective methods.