bluuebunny/crossref_metadata_2025 huggingface dataset:
Photodynamic Effects of Novel XF Porphyrin Derivatives on Prokaryotic and Eukaryotic Cells
Authors: Maisch T. , Bosl C. , Szeimies R.-M. , Lehn N. , Abels C.
Published: March 2005

The worldwide rise in the rates of antibiotic resistance of bacteria underlines the need for alternative antibacterial agents. A promising approach to the killing of gram-positive antibiotic-resistant bacteria of the skin uses light in combination with a photosensitizer to induce a phototoxic reaction. Different concentrations (0 to 100 μM) of porphyrin-based photosensitizers (CTP1, XF70, and XF73) and different incubation times (5 min, 1 h, and 4 h) were used to determine phototoxicity against two methicillin-resistant
Staphylococcus aureus
strains, one methicillin-sensitive
S. aureus
strain, one methicillin-resistant
Staphylococcus epidermidis
strain, one
Escherichia coli
strain, and human keratinocytes and fibroblasts. Incubation with 0.005 μM XF70 or XF73, followed by illumination, yielded a 3-log
10
(≥99.9%) decrease in the viable cell numbers of all staphylococcal strains, indicating that the XF drugs have high degrees of potency against gram-positive bacteria and also that the activities of these novel drugs are independent of the antibiotic resistance pattern of the staphylococci examined. CTP1 was less potent against the staphylococci under the same conditions. At 0.005 μM, XF70 and XF73 demonstrated no toxicity toward fibroblasts or keratinocytes. No inactivation of
E. coli
was detected at this concentration. XF73 was confirmed to act via a reactive oxygen species from the results of studies with sodium azide (a quencher of singlet oxygen), which reduced the killing of both eukaryotic and prokaryotic cells. When a quencher of superoxide anion and the hydroxyl radical was used, cell killing was not inhibited. These results demonstrate that the porphyrin-based photosensitizers had concentration-dependent differences in their efficacies of killing of methicillin-resistant staphylococcal strains via reactive oxygen species without harming eukaryotic cells at the same concentrations.
Penicillin-Binding Proteins in the Pathogenic Intestinal Spirochete
Brachyspira pilosicoli
Authors: Dassanayake Rohana P. , Sarath Gautam , Duhamel Gerald E.
Published: March 2005

Penicillin-binding proteins (PBPs) of slightly different molecular masses (94, 62 or 68, 42 or 50, 25, and 22 kDa) were identified in one human and two porcine
Brachyspira pilosicoli
strains. Identification of PBPs of
B. pilosicoli
provides a basis for characterization of the genes encoding these proteins among pathogenic intestinal spirochetes of humans and animals.
Early Selection of a New UL97 Mutant with a Severe Defect of Ganciclovir Phosphorylation after Valaciclovir Prophylaxis and Short-Term Ganciclovir Therapy in a Renal Transplant Recipient
Authors: Hantz Sébastien , Michel Detlef , Fillet Anne-Marie , Guigonis Vincent , Champier Gaël , Mazeron Marie-Christine , Bensman Albert , Denis François , Mertens Thomas , Dehee Axelle , Alain Sophie
Published: March 2005

We describe the emergence of a new ganciclovir resistance mutation in the
UL97
gene of human cytomegalovirus, deletion of codon 601, after valaciclovir and short-term ganciclovir therapy following kidney transplantation. Its role in ganciclovir resistance was supported by decreased ganciclovir phosphorylation in a recombinant vaccinia virus system.
Different Rifampin Sensitivities of
Escherichia coli
and
Mycobacterium tuberculosis
RNA Polymerases Are Not Explained by the Difference in the β-Subunit Rifampin Regions I and II
Authors: Zenkin N. , Kulbachinskiy A. , Bass I. , Nikiforov V.
Published: March 2005

Mycobacterium tuberculosis
RNA polymerase is 1,000-fold more sensitive to rifampin than
Escherichia coli
RNA polymerase. Chimeric
E. coli
RNA polymerase in which the β-subunit segment encompassing rifampin regions I and II (amino acids [aa] 463 through 590) was replaced with the corresponding region from
M. tuberculosis
(aa 382 through 509) did not show an increased sensitivity to the antibiotic. Thus, the difference in amino acid sequence between the rifampin regions I and II of the two species does not account for the difference in rifampin sensitivity of the two polymerases.
Synergistic Activities of Fluconazole and Voriconazole with Terbinafine against Four
Candida
Species Determined by Checkerboard, Time-Kill, and Etest Methods
Authors: Cantón Emilia , Pemán Javier , Gobernado Miguel , Viudes Angel , Espinel-Ingroff Ana
Published: March 2005

The in vitro activities of fluconazole or voriconazole plus terbinafine were evaluated against 20
Candida
isolates by the checkerboard, time-kill, and Etest methods. Synergism (
C. albicans
,
C. glabrata
, and
C. tropicalis
) and indifference (
C. krusei
) were observed. Correlation among methods was good. The Etest is a suitable method to determine drug interactions.
Antifungal Activity of Flocculosin, a Novel Glycolipid Isolated from
Pseudozyma flocculosa
Authors: Mimee Benjamin , Labbé Caroline , Pelletier René , Bélanger Richard R.
Published: March 2005

Flocculosin, a glycolipid isolated from the yeast-like fungus
Pseudozyma flocculosa
, was investigated for in vitro antifungal activity. The compound displayed antifungal properties against several pathogenic yeasts. Synergistic activity was observed between flocculosin and amphotericin B, and no significant cytotoxicity was demonstrated when tested against human cell lines.
Impact of Clarithromycin Resistance on Eradication of
Helicobacter pylori
in Infected Adults
Authors: Lee Jong Hwa , Shin Ji-Hyun , Roe Im Hwan , Sohn Seung Ghyu , Lee Jung Hun , Kang Geun Ho , Lee Han-Ki , Jeong Byeong Chul , Lee Sang Hee
Published: March 2005

The outcome of
Helicobacter pylori
infection was analyzed in 114 dyspeptic patients treated with triple-drug therapy including clarithromycin. Clarithromycin resistance (in 20.2% of our isolates) was mainly caused by an A2142G mutation in the 23S rRNA gene of
H
.
pylori
.
H
.
pylori
eradication was obtained in all patients with clarithromycin-susceptible isolates but not in any patients with clarithromycin-resistant isolates (
P
= 0.0001). Therefore, it would be useful to conduct
H
.
pylori
antimicrobial susceptibility testing of the first gastric biopsy culture before choosing the first three drugs for therapy of infected patients.
Secretion of Proinflammatory Cytokines and Chemokines during Amphotericin B Exposure Is Mediated by Coactivation of Toll-Like Receptors 1 and 2
Authors: Razonable Raymund R. , Henault Martin , Lee Linda N. , Laethem Carmen , Johnston Paul A. , Watson Harold L. , Paya Carlos V.
Published: March 2005

Amphotericin B (AmB) is a ligand of toll-like receptor 2 (TLR2). Here, we demonstrate the participation of TLR1 in AmB-induced cell activation that led to the secretion of tumor necrosis factor alpha, interleukin 6 (IL-6), and IL-8. Hence, TLR2-TLR1 coactivation serves as the underlying mechanism for the proinflammatory toxicities associated with AmB.
Pharmacokinetics of Oral Doxycycline during Combination Treatment of Severe Falciparum Malaria
Authors: Newton Paul N. , Chaulet Jean-François , Brockman Alan , Chierakul Wirongrong , Dondorp Arjen , Ruangveerayuth Ronatrai , Looareesuwan Sornchai , Mounier Cyril , White Nicholas J.
Published: March 2005

The pharmacokinetics of oral doxycycline administered at 200 mg every 24 h were investigated in 17 patients recovering from severe
Plasmodium falciparum
malaria. The data suggest that the doses of doxycycline currently recommended (circa 3.5 mg/kg of body weight daily) may not be optimal.
Pharmacokinetic Profile of Tigecycline in Serum and Skin Blister Fluid of Healthy Subjects after Multiple Intravenous Administrations
Authors: Sun Heather K. , Ong Christine T. , Umer Ambreen , Harper Dawn , Troy Steven , Nightingale Charles H. , Nicolau David P.
Published: March 2005

The pharmacokinetics of tigecycline, when given as a 100-mg loading dose followed by 50 mg every 12 h, were determined in serum and blister fluid. The peak tigecycline concentration and half-life in serum were greater than those in blister fluid. Tigecycline penetrates into blister fluid well, with a mean penetration rate of 74%.
Mutant Prevention Concentrations of ABT-492, Levofloxacin, Moxifloxacin, and Gatifloxacin against Three Common Respiratory Pathogens
Authors: Hermsen Elizabeth D. , Hovde Laurie B. , Konstantinides George N. , Rotschafer John C.
Published: March 2005

The purpose of this study was to compare the mutant prevention concentration (MPC) of ABT-492 to those of levofloxacin, moxifloxacin, and gatifloxacin against
Streptococcus pneumoniae
,
Haemophilus influenzae
, and
Moraxella catarrhalis
. The fluoroquinolones had comparable mutation selection windows, which is the ratio of MPC/MIC, for all isolates.
Levofloxacin and Ciprofloxacin Decrease Procainamide andN-Acetylprocainamide Renal Clearances
Authors: Bauer Larry A. , Black Douglas J. , Lill Jennifer S. , Garrison Julie , Raisys Vidmantas A. , Hooton Thomas M.
Published: March 2005

Ten healthy adults participated in a randomized, crossover drug interaction study testing procainamide only, procainamide plus levofloxacin, and procainamide plus ciprofloxacin. During levofloxacin therapy, most procainamide andN-acetylprocainamide (NAPA) pharmacokinetic parameters, including decreased renal clearances and renal clearance/creatinine clearance ratios, changed (P< 0.05). During ciprofloxacin treatment, only procainamide and NAPA renal clearances decreased significantly.
In Vitro and In Vivo Cytotoxicities and Antileishmanial Activities of Thymol and Hemisynthetic Derivatives
Authors: Robledo Sara , Osorio Edison , Muñoz Diana , Jaramillo Luz Marina , Restrepo Adriana , Arango Gabriel , Vélez Iván
Published: March 2005

The in vitro and in vivo antileishmanial and cytotoxic activities of thymol and structural derivatives in comparison to those of Glucantime were studied. The results showed here suggest that thymol and hemisynthetic derivatives have promising antileishmanial potential and could be considered as new lead structures in the search for novel antileishmanial drugs.
Injuries in women’s professional soccer
Authors: Giza E , Mithöfer K , Farrell L , Zarins B , Gill T
Published: March 2005

Objective:The injury data from the first two seasons of the Women’s United Soccer Association (WUSA) were analysed to determine the injury incidence, anatomic location of injuries, and relation of player position.

Methods:Injury data on 202 players from eight teams during the first two seasons of the WUSA were prospectively collected and analysed.

Results:A total of 173 injuries occurred in 110 players with an overall injury incidence rate of 1.93 injuries per 1000 player hours. The incidence of injury during practice and games was 1.17 and 12.63 per 1000 player hours, respectively. Of the injuries 82% were acute and 16% were chronic. Most of the injuries (60%) were located in the lower extremities. Strains (30.7%), sprains (19.1%), contusions (16.2%), and fractures (11.6%) were the most common diagnoses and the knee (31.8%) and head (10.9%) were the most common sites of injury. Anterior cruciate ligament (ACL) injuries accounted for 4.6% of all injuries and the incidence of ACL tears was 0.09 per 1000 player hours (practice 0.04, game 0.90). Midfielders suffered the most injuries (p<0.007).

Conclusion:We conclude that the injury incidence in the WUSA is lower than the 6.2 injuries per 1000 player hours found in the corresponding male professional league (Major League Soccer); however, knee injuries predominate even in these elite female athletes.
Modafinil in sports: ethical considerations
Authors: Kaufman K R
Published: March 2005

Performance enhancing agents are prohibited in athletic competition so that only athletic skills can determine outcomes. Modafinil is a novel non-addicting psychostimulant approved for treatment of narcolepsy. Does its use, especially for medical indications, violate the Olympic Movement Anti-Doping Code? This is discussed with reference to a current high profile case.
Summary and agreement statement of the 2nd International Conference on Concussion in Sport, Prague 2004
Authors: McCrory P , Johnston K , Meeuwisse W , Aubry M , Cantu R , Dvorak J , Graf-Baumann T , Kelly J , Lovell M , Schamasch P
Published: March 2005

In November 2001, the 1st International Symposium on Concussion in Sport was held in Vienna, Austria to provide recommendations for the improvement of safety and health of athletes who suffer concussive injuries in ice hockey, football (soccer), and other sports. The 2nd International Symposium on Concussion in Sport was organised by the same group and held in Prague, Czech Republic in November 2004. It resulted in a revision and update of the Vienna consensus recommendations, which are presented here.
Educational inequalities in smoking among men and women aged 16 years and older in 11 European countries
Authors: Huisman M , Kunst A E , Mackenbach J P
Published: March 2005

Objective:To determine those groups who are at increased risk of smoking related diseases, we assessed in which male and female generations smoking was more prevalent among lower educated groups than among the higher educated, in 11 European countries.

Design:Cross sectional analysis of data on smoking, covering the year 1998, from a social survey designed for all member states of the European Union.

Subjects:Higher and lower educated men and women aged 16 years and older from 11 member states of the European Union.

Outcome measures:Age standardised prevalence rates by education and prevalence odds ratios of current and ever daily smoking comparing lower educated groups with higher educated groups.

Results:A north–south gradient in educational inequalities in current and ever daily smoking was observed for women older than 24 years, showing larger inequalities in the northern countries. Such a gradient was not observed for men. A disadvantage for the lower educated in terms of smoking generally occurred later among women than among men. Indications of inequalities in smoking in the age group 16–24 years were observed for all countries, with the exception of women from Greece and Portugal.

Conclusions:Preventing and reducing smoking among lower educated subgroups should be a priority of policies aiming to reduce inequalities in health in Europe. If steps are not taken to control tobacco use among the lower educated groups specifically, inequalities in lung cancer and other smoking related diseases should be anticipated in all populations of the European Union, and both sexes.
Higher cigarette prices influence cigarette purchase patterns
Authors: Hyland A , Bauer J E , Li Q , Abrams S M , Higbee C , Peppone L , Cummings K M
Published: March 2005

Objective:To examine cigarette purchasing patterns of current smokers and to determine the effects of cigarette price on use of cheaper sources, discount/generic cigarettes, and coupons.

Background:Higher cigarette prices result in decreased cigarette consumption, but price sensitive smokers may seek lower priced or tax-free cigarette sources, especially if they are readily available. This price avoidance behaviour costs states excise tax money and dampens the health impact of higher cigarette prices.

Methods:Telephone survey data from 3602 US smokers who were originally in the COMMIT (community intervention trial for smoking cessation) study were analysed to assess cigarette purchase patterns, use of discount/generic cigarettes, and use of coupons.

Results:59% reported engaging in a high price avoidance strategy, including 34% who regularly purchase from a low or untaxed venue, 28% who smoke a discount/generic cigarette brand, and 18% who report using cigarette coupons more frequently that they did five years ago. The report of engaging in a price avoidance strategy was associated with living within 40 miles of a state or Indian reservation with lower cigarette excise taxes, higher average cigarette consumption, white, non-Hispanic race/ethnicity, and female sex.

Conclusion:Data from this study indicate that most smokers are price sensitive and seek out measures to purchase less expensive cigarettes, which may decrease future cessation efforts.
Emotions for sale: cigarette advertising and women’s psychosocial needs
Authors: Anderson S J , Glantz S A , Ling P M
Published: March 2005

Objective:To explore messages of psychosocial needs satisfaction in cigarette advertising targeting women and implications for tobacco control policy.

Methods:Analysis of internal tobacco industry documents and public advertising collections.

Results:Tobacco industry market research attempted to identify the psychosocial needs of different groups of women, and cigarette advertising campaigns for brands that women smoke explicitly aimed to position cigarettes as capable of satisfying these needs. Such positioning can be accomplished with advertising that downplays or excludes smoking imagery. As women’s needs change with age and over time, advertisements were developed to reflect the needs encountered at different stages in women’s lives. Cigarette brands for younger women stressed female camaraderie, self confidence, freedom, and independence; cigarette brands for older women addressed needs for pleasure, relaxation, social acceptability, and escape from daily stresses.

Conclusions:Psychosocial needs satisfaction can be communicated without reference to cigarettes or smoking. This may explain why partial advertising bans are ineffective and comprehensive bans on all forms of tobacco marketing are effective. Counter-advertising should attempt to expose and undermine the needs satisfaction messages of cigarette advertising campaigns directed at women.
Drebrin E2 is differentially expressed and phosphorylated in parietal cells in the gastric mucosa
Authors: Chew Catherine S. , Okamoto Curtis T. , Chen Xunsheng , Thomas Ruby
Published: March 2005

Developmentally regulated brain proteins (drebrins) are highly expressed in brain where they may regulate actin filament formation in dendritic spines. Recently, the drebrin E2 isoform was detected in certain epithelial cell types including the gastric parietal cell. In gastric parietal cells, activation of HCl secretion is correlated with actin filament formation and elongation within intracellular canaliculi, which are the sites of acid secretion. The aim of this study was to define the pattern of drebrin expression in gland units in the intact rabbit oxyntic gastric mucosa and to initiate approaches to define the functions of this protein in parietal cells. Drebrin E2 expression was limited entirely or almost entirely to parietal cells and depended upon the localization of parietal cells along the gland axis. Rabbit drebrin E2 was cloned and found to share 86% identity with human drebrin 1a and to possess a number of cross-species conserved protein-protein interaction and phosphorylation consensus sites. Two-dimensional Western blot and phosphoaffinity column analyses confirmed that drebrin is phosphorylated in parietal cells, and several candidate phosphorylation sites were identified by mass spectrometry. Overexpression of epitope-tagged drebrin E2 led to the formation of microspikes and F-actin-rich ring-like structures in cultured parietal cells and suppressed cAMP-dependent acid secretory responses. In Madin-Darby canine kidney cells, coexpression of epitope-tagged drebrin and the Rho family GTPase Cdc42, which induces filopodial extension, produced an additive increase in the length of microspike projections. Coexpression of dominant negative Cdc42 with drebrin E2 did not prevent drebrin-induced microspike formation. These findings suggest that 1) drebrin can induce the formation of F-actin-rich membrane projections by Cdc42-dependent and -independent mechanisms; and that 2) drebrin plays an active role in directing the secretagogue-dependent formation of F-actin-rich filaments on the parietal cell canalicular membrane. Finally, the differential distribution of drebrin in parietal cells along the gland axis suggests that drebrin E2 may be an important marker of parietal cell differentiation and functionality.
Liver disease with altered bile acid transport in Niemann-Pick C mice on a high-fat, 1% cholesterol diet
Authors: Erickson Robert P. , Bhattacharyya Achyut , Hunter Robert J. , Heidenreich Randall A. , Cherrington Nathan J.
Published: March 2005

Cholestatic hepatitis is frequently found in Niemann-Pick C (NPC) disease. We studied the influence of diet and the low density lipoprotein receptor (LDLR, Ldlr in mice, known to be the source of most of the stored cholesterol) on liver disease in the mouse model of NPC. Npc1−/−mice of both sexes, with or without the Ldlr knockout, were fed a 18% fat, 1% cholesterol (“high-fat”) diet and were evaluated by chemical and histological methods. Bile acid transporters [multidrug resistance protein (Mrps) 1–5; Ntcp, Bsep, and OatP1, 2, and 4] were quantitated by real-time RT-PCR. Many mice died prematurely (within 6 wk) with hepatomegaly. Histopathology showed an increase in macrophage and hepatocyte lipids independent of Ldlr genotype. Non-zone-dependent diffuse fibrosis was found in the surviving mice. Serum alanine aminotransferase was elevated in Npc1−/−mice on the regular diet and frequently became markedly elevated with the high-fat diet. Serum cholesterol was increased in the controls but not the Npc1−/−mice on the high-fat diet; it was massively increased in the Ldlr−/−mice. Esterified cholesterol was greatly increased by the high-fat diet, independent of Ldlr genotype. γ-Glutamyltransferase was also elevated in Npc1−/−mice, more so on the high-fat diet. Mrps 1–5 were elevated in Npc1−/−liver and became more elevated with the high-fat diet; Ntcp, Bsep, and OatP2 were elevated in Npc1−/−liver and were suppressed by the high-fat diet. In conclusion, Npc1−/−mice on a high-fat diet provide an animal model of NPC cholestatic hepatitis and indicate a role for altered bile acid transport in its pathogenesis.
Cyclic GMP-specific phosphodiesterase 5 regulates growth and apoptosis in pulmonary endothelial cells
Authors: Zhu Bing , Strada Samuel , Stevens Troy
Published: March 2005

Sustained increases in intracellular cGMP concentrations ([cGMP]i) inhibit cell growth and induce apoptosis. We now report that a cGMP-specific phosphodiesterase, PDE5, plays a dominant role in regulating [cGMP]i transitions that inhibit cell growth and control susceptibility to apoptosis in pulmonary endothelium. Atrial natriuretic peptide (ANP) activates guanylyl cyclase A/B and induces a rapid [cGMP]i rise 2–5 min after its application, in both pulmonary arterial endothelial cells (PAECs) and pulmonary microvascular endothelial cells (PMVECs). However, increased [cGMP]i in PAECs is transient and decays within 10 min due to cytosolic PDE5 hydrolytic activity. Increased [cGMP]i in PMVECs is sustained for >3 h due to the absence of PDE5. Indeed, at any ANP concentration, the sustained (30 min) [cGMP]i rise is greater in PMVECs than in PAECs, unless PAECs are also treated with the PDE5 inhibitor zaprinast. Using RT-PCR, Western blot analysis, immunoprecipitation, and DEAE chromatography, we resolved the expression and activity of PDE 5A1/A2 only in PAECs. Similarly, PDE5 expression was restricted to extra-alveolar endothelium in vivo. ANP induced growth inhibition and apoptosis in PMVECs, but similar effects were not seen in PAECs unless ANP treatment was combined with zaprinast. ANP blocked the VEGF-induced proliferation and migration in PMVECs. Collectively, these data suggest that PDE5-regulated [cGMP]i controls endothelial cell growth and apoptosis, representing a mechanism of heterogeneity between two endothelial phenotypes.
Baroreflex regulation of renal sympathetic nerve activity and heart rate in renal wrap hypertensive rats
Authors: Vitela M. , Herrera-Rosales M. , Haywood J. R. , Mifflin S. W.
Published: March 2005

Despite its usefulness as a nongenetic model of hypertension, little information is available regarding baroreflex function in the Grollman, renal wrap model of hypertension in the rat. Baroreflex regulation of renal sympathetic nerve activity (RSNA) and heart rate (HR) were studied in male, Sprague-Dawley rats hypertensive (HT) for 1 or 4–6 wk after unilateral nephrectomy and figure-8 ligature around the remaining kidney or normotensive (NT) after sham surgery. Rats were anesthetized with Inactin and RSNA, and HR was recorded during intravenous infusions of sodium nitroprusside or phenylephrine to lower or raise mean arterial pressure (MAP). Response curves were analyzed using a logistic sigmoid function. In 1- and 4-wk HT rats the midpoints of RSNA and HR reflex curves were shifted to the right ( P < 0.05). Comparing NT to 1- or 4-wk HT rats, the gain of RSNA-MAP curves was no different; however, gain was reduced in the HR-MAP curves at both 1 and 4 wk in HT rats ( P < 0.05). In anesthetized rats the HR range was small; therefore, MAP and HR were measured in conscious rats during intravenous injections of three doses of phenylephrine and three doses of sodium nitroprusside. Linear regressions revealed a reduced slope in both 1- and 4-wk HT rats compared with NT rats ( P < 0.05). The results indicate that baroreflex curves are shifted to the right, to higher pressures, in hypertension. After 1–4 wk of hypertension the gain of baroreflex regulation of RSNA is not altered; however, the gain of HR regulation is reduced.
Effects of tidal volume and respiratory frequency on lung lymph flow
Authors: Pearse David B. , Searcy Robert M. , Mitzner Wayne , Permutt Solbert , Sylvester J. T.
Published: March 2005

Ventilation (V̇) increases lung lymph flow (Q̇l), but the separate effects of tidal volume (Vt) and frequency (f) and the role of V̇-induced changes in edema formation are poorly understood. An isolated, in situ sheep lung preparation was used to examine these effects. In eight sheep with f = 10 min−1, results obtained during 30-min periods with Vt = 5 or 20 ml/kg were compared with values obtained during bracketed 30-min control periods (Vt = 12.5 ml/kg). Eight other sheep with constant Vt (12.5 ml/kg) were studied at f = 5 or 20 min−1 and compared with f = 10 min−1. Three additional groups of six sheep were perfused for 100 min with control V̇ (10 ml/kg, 10 min−1). Vt was then kept constant or changed to 20 or 3 ml/kg during a second 100-min period. Increases in Vt or f increased Q̇l and vice versa, without corresponding effects on the rate of edema formation. For the same change in V̇, changing Vt had a greater effect on Q̇l than changing f. The change in Q̇l caused by an increase in Vt was significantly greater after the accumulation of interstitial edema. The change in Q̇l caused by a sustained increase in Vt was transient and did not correlate with the rate of edema formation, suggesting that V̇ altered Q̇l through direct mechanical effects on edema-filled compartments and lymphatic vessels rather than through V̇-induced changes in fluid filtration.
In vivo insulin signaling through PI3-kinase is impaired in skeletal muscle of adult rat offspring exposed to ethanol in utero
Authors: Chen Li , Yao Xing-Hai , Nyomba B. L. G.
Published: March 2005

It is now known that prenatal ethanol (EtOH) exposure is associated with impaired glucose tolerance and insulin resistance in rat offspring, but the underlying mechanism(s) is not known. To test the hypothesis that in vivo insulin signaling through phosphatidylinositol 3 (PI3)-kinase is reduced in skeletal muscle of adult rat offspring exposed to EtOH in utero, we gave insulin intravenously to these rats and probed steps in the PI3-kinase insulin signaling pathway. After insulin treatment, EtOH-exposed rats had decreased tyrosine phosphorylation of the insulin receptor β-subunit and of insulin receptor substrate-1 (IRS-1), as well as reduced IRS-1-associated PI3-kinase in the gastrocnemius muscle compared with control rats. There was no significant difference in basal or insulin-stimulated Akt activity between EtOH-exposed rats and controls. Insulin-stimulated PKC isoform ζ phosphorylation and membrane association were reduced in EtOH-exposed rats compared with controls. Muscle insulin binding and peptide contents of insulin receptor, IRS-1, p85 subunit of PI3-kinase, Akt/PKB, and atypical PKC isoform ζ were not different between EtOH-exposed rats and controls. Thus insulin resistance in rat offspring exposed to EtOH in utero may be explained, at least in part, by impaired insulin signaling through the PI3-kinase pathway in skeletal muscle.
Quantification of muscle fiber strain during in vivo repetitive stretch-shortening cycles
Authors: Butterfield Timothy A. , Herzog Walter
Published: March 2005

Muscles subjected to lengthening contractions exhibit evidence of subcellular disruption, arguably a result of fiber strain magnitude. Due to the difficulty associated with measuring fiber strains during lengthening contractions, fiber length estimates have been used to formulate relationships between the magnitude of injury and mechanical measures such as fiber strain. In such protocols, the series compliance is typically minimized by removing the distal tendon and/or preactivating the muscle. These in vitro and in situ experiments do not represent physiological contractions well where fiber strain and muscle strain may be disassociated; thus the mechanisms of in vivo muscle injury remain elusive. The purpose of this paper was to quantify fiber strains during lengthening contractions in vivo and assess the potential role of fiber strain in muscle injury following repetitive stretch-shortening cycles. Using intact New Zealand White rabbit dorsiflexors, fiber strain and joint torque were measured during 50 stretch-shortening cycles. We were able to show that fiber length changes are disassociated from muscle tendon unit length changes and that complex fiber dynamics during these cycles prevent easy estimates of fiber strains. In addition, fiber strains vary, depending on how they are defined, and vary from repetition to repetition, thereby further complicating the potential relationship between muscle injury and fiber strain. We conclude from this study that, during in vivo stretch-shortening cycles, the relationship between fiber strain and muscle injury is complex. This is due, in part, to temporal effects of repeated loading on fiber strain magnitude that may be explained by an increasing compliance of the contractile element as exercise progresses.
Analysis of Gas6 in Human Platelets and Plasma
Authors: Balogh Istvan , Hafizi Sassan , Stenhoff Jonas , Hansson Karin , Dahlbäck Björn
Published: March 2005

Objective—

Gas6 is a member of the vitamin K-dependent protein family. Gas6-deficient mice were found to be resistant to thrombosis because of defective platelet function. Mouse Gas6 was demonstrated to be present in platelets and found to be involved in platelet aggregation. The aim of this study was to investigate the presence of Gas6 in human platelets and plasma and determine its role in platelet function.

Methods and Results—

The presence of Gas6 in human platelets and plasma was analyzed using sensitive immunologic methods. Mass spectrometry and ELISA were used to identify and quantify Gas6 in plasma. Gas6 was demonstrated to be present in human plasma, at a concentration determined to be 13 to 23 ng/mL (0.16 to 0.28 nM). Furthermore, plasma Gas6 levels were found to be lower in patients administered with warfarin. However, Gas6 was undetectable in human platelets.

Conclusions—

This is the first report to identify and quantify Gas6 in human plasma. However, Gas6 protein was not detected in human platelets, suggesting that any potential platelet-specific function could be because of Gas6 from the circulation. These findings open up new directions regarding the role of Gas6 in normal and pathophysiological situations such as inflammation, autoimmune disease, thrombosis and arteriosclerosis.
Oxidative Enzymopathies and Vascular Disease
Authors: Leopold Jane A. , Loscalzo Joseph
Published: March 2005

In the vasculature, reactive oxygen species (ROS) generated by both mitochondrial respiration and enzymatic sources serve as integral components of cellular signaling and homeostatic mechanisms. Because ROS are highly reactive biomolecules, the cellular redox milieu is carefully maintained by small-molecule antioxidants and antioxidant enzymes to prevent the deleterious consequences of ROS excess. When this redox balance is perturbed, because of either increased ROS production or decreased antioxidant capacity, oxidant stress is increased in the vessel wall and, if not offset, vascular dysfunction ensues. A number of heritable polymorphisms of pro-oxidant enzymes, including 5-lipoxygenase, cyclooxygenase-2, nitric oxide synthase-3, and NAD(P)H oxidase, have been identified and found to modulate ROS production and, thereby, the risk of atherothrombotic cardiovascular disease in individuals with these genetic polymorphisms. Similarly, heritable deficiency of the antioxidant enzymes catalase, glutathione peroxidases, glutathione-
S
-transferases, heme oxygenase, and glucose-6-phosphate dehydrogenase favors ROS accumulation, and has been associated with an increased risk of vascular disease. Individually, each of these polymorphisms imposes a state of uncompensated oxidant stress on the vasculature and collectively comprise the oxidative enzymopathies.
Characterization of a Novel PKA Phosphorylation Site, Serine-2030, Reveals No PKA Hyperphosphorylation of the Cardiac Ryanodine Receptor in Canine Heart Failure
Authors: Xiao Bailong , Jiang Ming Tao , Zhao Mingcai , Yang Dongmei , Sutherland Cindy , Lai F. Anthony , Walsh Michael P. , Warltier David C. , Cheng Heping , Chen S. R. Wayne
Published: March 2005

Hyperphosphorylation of the cardiac Ca
2+
release channel (ryanodine receptor, RyR2) by protein kinase A (PKA) at serine-2808 has been proposed to be a key mechanism responsible for cardiac dysfunction in heart failure (HF). However, the sites of PKA phosphorylation in RyR2 and their phosphorylation status in HF are not well defined. Here we used various approaches to investigate the phosphorylation of RyR2 by PKA. Mutating serine-2808, which was thought to be the only PKA phosphorylation site in RyR2, did not abolish the phosphorylation of RyR2 by PKA. Two-dimensional phosphopeptide mapping revealed two major PKA phosphopeptides, one of which corresponded to the known serine-2808 site. Another, novel, PKA phosphorylation site, serine 2030, was identified by Edman sequencing. Using phospho-specific antibodies, we showed that the novel serine-2030 site was phosphorylated in rat cardiac myocytes stimulated with isoproterenol, but not in unstimulated cells, whereas serine-2808 was considerably phosphorylated before and after isoproterenol treatment. We further showed that serine-2030 was stoichiometrically phosphorylated by PKA, but not by CaMKII, and that mutations of serine-2030 altered neither the FKBP12.6-RyR2 interaction nor the Ca
2+
dependence of [
3
H]ryanodine binding. Moreover, the levels of phosphorylation of RyR2 at serine-2030 and serine-2808 in both failing and non-failing canine hearts were similar. Together, our data indicate that serine-2030 is a major PKA phosphorylation site in RyR2 responding to acute β-adrenergic stimulation, and that RyR2 is not hyperphosphorylated by PKA in canine HF.
[Ca
2+
]
i
Reduction Increases Cellular Proliferation and Apoptosis in Vascular Smooth Muscle Cells
Authors: Kip Sertac N. , Hunter Larry W. , Ren Qun , Harris Peter C. , Somlo Stefan , Torres Vicente E. , Sieck Gary C. , Qian Qi
Published: March 2005

Cardiovascular complications are the leading cause of morbidity and mortality in autosomal dominant polycystic kidney disease.
Pkd2

+

/−
vascular smooth muscle cells (VSMCs) have an abnormal phenotype and defective intracellular Ca
2+
([Ca
2+
]
i
) regulation. We examined cAMP content in vascular smooth muscles from
Pkd2

+

/−
mice because cAMP is elevated in cystic renal epithelial cells. We found cAMP concentration was significantly increased in
Pkd2

+

/−
vessels compared with wild-type vessels. Furthermore, reducing the wild-type VSMC [Ca
2+
]
i
by Verapamil or BAPTA-AM significantly increased cellular cAMP concentration (mainly by phosphodiesterase [PDE] inhibition), the rate of VSMC proliferation (determined by direct cell counting,
3
H-incorporation, FACS analysis of cells entering S phase, and quantitative Western PCNA and ERK1/2 analyses), and the rate of apoptosis (by Hoechst staining, FACS analysis of the Annexin-V positive cells, and quantitative Western Bax, cytochrome
c
, and activated caspase 9 and 3 analyses). The low [Ca
2+
]
i
induced VSMC proliferation was independent of cAMP/B-Raf signaling, while that of apoptosis was promoted by cAMP. In summary,
Pkd2

+

/−
VSMCs have elevated cAMP levels. This elevation can also be induced by reducing [Ca
2+
]
i
in wild-type VSMCs. The [Ca
2+
]
i
reduction and cAMP accumulation can cause an increase in both cellular proliferation and apoptosis, resembling
Pkd
mutant phenotype.
Liver X Receptor Agonists Inhibit Cytokine-Induced Osteopontin Expression in Macrophages Through Interference With Activator Protein-1 Signaling Pathways
Authors: Ogawa Daisuke , Stone Jeffrey F. , Takata Yasunori , Blaschke Florian , Chu Van H. , Towler Dwight A. , Law Ronald E. , Hsueh Willa A. , Bruemmer Dennis
Published: March 2005

Osteopontin (OPN) is a proinflammatory cytokine and adhesion molecule implicated in the chemoattraction of monocytes and in cell-mediated immunity. We have recently reported that genetic OPN-deficiency attenuates the development of atherosclerosis in apoE
−/−
mice identifying OPN as potential target for pharmacological intervention in atherosclerosis. Synthetic agonists for the Liver X Receptor (LXR), members of the nuclear hormone receptor superfamily, prevent the development of atherosclerosis by regulating cholesterol homeostasis and suppressing inflammatory gene expression in macrophages. We demonstrate here that LXR ligands inhibit cytokine-induced OPN expression in macrophages. Two synthetic LXR ligands, T0901317 and GW3965, inhibited TNF-α, IL-1β, INF-γ and lipopolysaccharide induced OPN mRNA and protein expression in RAW 264.7 macrophages. Transient transfection experiments revealed that LXR ligands suppress cytokine-induced OPN promoter activity. Deletion analysis, heterologous promoter assays, and site-directed mutagenesis identified an activator protein-1 (AP-1) consensus site at -76 relative to the initiation site that supports OPN transcription in macrophages and mediates the effects of LXR ligands to inhibit OPN transcription. Electrophoretic mobility shift and chromatin immunoprecipitation assays indicated that LXR agonists inhibit cytokine-induced c-Fos and phospho-c-Jun binding to this AP-1 site. Cytokine-induced c-Fos and phospho-c-Jun protein expression was inhibited by LXR ligands and overexpression of c-Fos and c-Jun reversed the inhibitory effect of LXR ligands on OPN promoter activity in transactivation assays. Finally, treatment of C57BL/6J mice with LXR ligands inhibited OPN expression in peritoneal macrophages indicating that the observed effects of LXR ligands to inhibit OPN expression are applicable in vivo. These observations identify the regulation of macrophage OPN expression as a mechanism whereby LXR ligands may impact macrophage inflammatory responses and atherosclerosis. The full text of this article is available online at http://circres.ahajournals.org.
AMP-Activated Protein Kinase Signaling Stimulates VEGF Expression and Angiogenesis in Skeletal Muscle
Authors: Ouchi Noriyuki , Shibata Rei , Walsh Kenneth
Published: March 2005

AMP-activated protein kinase (AMPK) is regulated by various cellular stresses. Vascular endothelial growth factor (VEGF), a key regulator of angiogenesis, is also upregulated by several stress-inducible factors such as hypoxia and stimulation by cytokines and growth factors. Here, we investigated whether AMPK signaling in muscle has a role in regulating VEGF-mediated angiogenic processes. AICAR stimulated VEGF mRNA and protein levels in C2C12 myotube cultures. Transduction with dominant-negative AMPK abolished AICAR-induced VEGF expression at both steady state mRNA and protein levels. AICAR increased VEGF mRNA stability without affecting VEGF promoter activity. AICAR also stimulated p38 mitogen-activated protein kinase (p38 MAPK) phosphorylation. Activation of p38 MAPK was suppressed by transduction with dominant-negative AMPK, suggesting that AMPK is upstream of p38 MAPK. The p38 MAPK inhibitor SB203580 blocked AICAR-induced increase in VEGF mRNA and protein levels, indicating that AICAR-mediated VEGF induction is dependent on p38 MAPK signaling. AICAR treatment increased VEGF expression and accelerated angiogenic repair of ischemic hindlimbs in mice in an AMPK-dependent manner. These data indicate that AMPK-p38 MAPK signaling cascade can increase VEGF production in muscle and promote angiogenesis in response to ischemic injury.
Adenoviral Gene Transfer of Mutant Phospholamban Rescues Contractile Dysfunction in Failing Rabbit Myocytes With Relatively Preserved SERCA Function
Authors: Ziolo Mark T. , Martin Jody L. , Bossuyt Julie , Bers Donald M. , Pogwizd Steven M.
Published: March 2005

In heart failure (HF) a main factor in reduced contractility is reduced SR Ca
2+
content and reversed force-frequency response (FFR), ie, from positive to negative. Our arrhythmogenic rabbit HF model exhibits decreased contractility mainly due to an increase in Na/Ca exchange (NCX) activity (with only modest decrease in SR Ca
2+
-ATPase (SERCA) function), similar to many end-stage HF patients. Here we test whether phospholamban (PLB) inhibition using a dominant-negative mutant PLB adenovirus (K3E/R14E, AdPLB-dn, with β-galactosidase adenovirus as control) could enhance SERCA function and restore Ca
2+
transients and positive FFR in ventricular myocytes from these HF rabbits. HF myocytes infected with AdPLB-dn (versus control) had enhanced Ca
2+
transient amplitude (2.0±0.1 versus 1.6±0.05 F/F
o
at 0.5 Hz,
P
<0.05) and had a positive FFR, whereas acutely isolated HF myocytes or those infected with Adβgal had negative FFR. Ca
2+
transients declined faster in AdPLB-dn versus Adβgal myocytes (RT
50%
: 317±29 versus 551±90 ms at 0.5 Hz,
P
<0.05) and had an increased SR Ca
2+
load (3.5±0.3 versus 2.6±0.2 F/F
o
at 0.5 Hz,
P
<0.05), indicative of increased SERCA function. Furthermore, this restoration of function was not due to changes in NCX or SERCA expression. Thus, increasing SERCA activity in failing myocytes by AdPLB-dn gene transfer reversed the contractile dysfunction (and restored positive FFR) by increasing SR Ca
2+
load. This approach could enhance contractile function in failing hearts of various etiologies, even here where reduced SERCA activity is not the main dysfunction.
Gain Control by Concerted Changes in IA and I H Conductances
Authors: Burdakov Denis
Published: March 2005

Stability of intrinsic electrical activity and modulation of input-output gain are both important for neuronal information processing. It is there-fore of interest to define biologically plausible parameters that allow these two features to coexist. Recent experiments indicate that in some biological neurons, the stability of spontaneous firing can arise from coregulated expression of the electrophysiologically opposing IA and IH currents. Here, I show that such balanced changes in IA and IH dramatically alter the slope of the relationship between the firing rate and driving current in a Hodgkin-Huxley-type model neuron. Concerted changes in IA and IH can thus control neuronal gain while preserving intrinsic activity.
Neural Modeling of an Internal Clock
Authors: Yamazaki Tadashi , Tanaka Shigeru
Published: March 2005

We studied a simple random recurrent inhibitory network. Despite its simplicity, the dynamics was so rich that activity patterns of neurons evolved with time without recurrence due to random recurrent connections among neurons. The sequence of activity patterns was generated by the trigger of an external signal, and the generation was stable against noise. Moreover, the same sequence was reproducible using a strong transient signal, that is, the sequence generation could be reset. Therefore, a time passage from the trigger of an external signal could be represented by the sequence of activity patterns, suggesting that this model could work as an internal clock. The model could generate different sequences of activity patterns by providing different external signals; thus, spatiotemporal information could be represented by this model. Moreover, it was possible to speed up and slow down the sequence generation.
Leave-One-Out Bounds for Support Vector Regression Model Selection
Authors: Chang Ming-Wei , Lin Chih-Jen
Published: March 2005

Minimizing bounds of leave-one-out errors is an important and efficient approach for support vector machine (SVM) model selection. Past research focuses on their use for classification but not regression. In this letter, we derive various leave-one-out bounds for support vector regression (SVR) and discuss the difference from those for classification. Experiments demonstrate that the proposed bounds are competitive with Bayesian SVR for parameter selection. We also discuss the differentiability of leave-one-out bounds.
Stochastic Optimal Control and Estimation Methods Adapted to the Noise Characteristics of the Sensorimotor System
Authors: Todorov Emanuel
Published: March 2005

Optimality principles of biological movement are conceptually appealing and straightforward to formulate. Testing them empirically, however, requires the solution to stochastic optimal control and estimation problems for reasonably realistic models of the motor task and the sensorimotor periphery. Recent studies have highlighted the importance of incorporating biologically plausible noise into such models. Here we extend the linear-quadratic-gaussian framework—currently the only framework where such problems can be solved efficiently—to include control-dependent, state-dependent, and internal noise. Under this extended noise model, we derive a coordinate-descent algorithm guaranteed to converge to a feedback control law and a nonadaptive linear estimator optimal with respect to each other. Numerical simulations indicate that convergence is exponential, local minima do not exist, and the restriction to nonadaptive linear estimators has negligible effects in the control problems of interest. The application of the algorithm is illustrated in the context of reaching movements. A Matlab implementation is available at www.cogsci.ucsd.edu/∼todorov .
Preaching, a Ponytail, and an Enthusiast: Rethinking the Public Sphere's Subversiveness in Eighteenth-century Prussia
Authors: Sauter Michael J.
Published: March 2005

Recent work on the eighteenth-century public sphere has recast the debate about the Enlightenment's responsibility for the French Revolution. Historians have argued that the print public sphere and its concomitant forms of sociability, such as salons, reading clubs, and coffee houses created social spaces from which criticism of the state emerged. This elite criticism corroded the Old Regime's foundations and the revolutionary crash of 1789, if it was not directly the intellectuals' fault, was sufficiently related to their mental labors to show that enlightened publicness had consequences.
The Reform of Labor Relations in the Russian Federation: Problems and Prospects
Authors:   Kudiukin,   Zenkin
Published: March 2005

No Abstract
Constitutional Order in Russia: A New Territory for Constitutionalism?
Authors:   Fogelklou
Published: March 2005

No Abstract
A Measure of Change: Legal Reform in the CIS
Authors:   Simons
Published: March 2005

No Abstract
A Note on Developments in Uzbek Securities Law: The Concept of Nominal Holder - Securities Trust Manager
Authors:   Nazarov
Published: March 2005

No Abstract
Starting from Scratch: The Legal and Institutional Steps to Viable Securities Markets in Transition Economies
Authors:   Coffee
Published: March 2005

No Abstract
Corporate Governance Revisited: Can the Stakeholder Paradigm Provide a Way Out of "Vulture" Capitalism in Eastern Europe?
Authors:   Simons,   Dragneva
Published: March 2005

No Abstract
Effects of Russian Tax Treaties and the EC Parent-Subsidiary Directive on the Tax Planning Strategies of European Multinational Groups Investing in Russia
Authors: Almakaeva
Published: March 2005

No Abstract