bluuebunny/crossref_metadata_2025 huggingface dataset:
In Defense of Incentive Compensation: Its Effect on Corporate Acquisition Policy
Authors: Datta Sudip , Iskandar‐Datta Mai , Raman Kartik
Published: February 2005

Financial economists have long recognized that compensation design, particularly the use of equity‐based compensation, can provide strong motivation for corporate managers to make value‐maximizing decisions. But the perception of excesses in equity‐based pay for U.S. executives has become pervasive and has led many to question its efficacy. The fundamental problem is one of measurement–while it is relatively easy to measure the cost of equity‐based compensation, it is difficult to determine the extent to which equitybased compensation actually causes managers to direct corporate resources into value‐maximizing ventures.

The authors of this article focus on corporate acquisition policy and argue that if equity‐based pay is an effective motivator, it should limit management's inclination to overpay for acquisitions and to make unwise acquisitions. In their study of 1,719 mergers and tender offers over the period 1993–1998, the authors found that bidding companies with higher proportions of equity‐based pay paid lower takeover premiums, acquired targets with stronger growth opportunities, and undertook acquisitions that were received more favorably by the market both upon announcement and over time.
Reappearing Dividends
Authors: Julio Brandon , Ikenberry David L.
Published: February 2005

During the last two decades of the 20th century, the propensity of U.S. companies to pay cash dividends declined significantly. The trend away from dividends accelerated during the late 1990s, leading some economists to conclude that dividend policy was shifting in a very fundamental way. But there was a sharp reversal in this trend starting in 2000.

This article investigates five possible explanations why dividends are reappearing. Given the explosion of new companies during the 1990s, the authors find that part of this rebound can be explained by the “maturity hypothesis”– by the need for such companies to pay out their excess “free cash fiow” to reassure investors that it will not be wasted on value‐destroying investments. The authors also report evidence that some companies have chosen to use dividends in part to restore investor confidence about the “quality” of corporate earnings in the wake of concerns over corporate governance. Third, the authors' findings suggest that U.S. companies have responded to the recent dividend tax cut, as one might expect, although the rebound in dividends started well before tax reform became a widely discussed possibility. Finally, the study finds little support for behavioralist explanations in which managers “cater” to irrational investor preferences for dividends. Although the authors hesitate to read too much into the recent rebound, their evidence is consistent with the idea that corporate payout policy has shifted back in favor of conventional cash dividends.
Control of Parathyroid Function in Patients with a Short History of Hemodialysis
Authors: Nishi Hiroshi , Sato Takashi , Kurihara Toru , Kurosawa Takeshi , Fukagawa Masafumi
Published: February 2005

Abstract:  Secondary hyperparathyroidism (SHPT) is one of the serious complications in patients with chronic kidney disease. Parathyroid glands secrete parathyroid hormone (PTH), stimulated partly by hyperphosphatemia and hypocalcemia complicating chronic kidney disease (CKD). Use of a calcium‐based phosphate binder might be sufficient to reduce serum PTH levels in mild SHPT, while the recent K/DOQI clinical guidelines recommended vitamin D therapy for dialysis patients with serum level of intact parathyroid hormone of 300 pg/mL or more. We conducted a 6‐month prospective controlled trial of 50 patients initiating hemodialysis therapy who were randomized to receive oral calcium carbonate alone or the drug plus oral vitamin D sterol, calcitriol or alfacalcidol. The primary end point was the proportion of randomized patients who had a mean PTH level of 300 pg/mL or less at the end of this study. The secondary end point included the percent change in the values for corrected calcium, phosphorus, the calcium–phosphorus product, and PTH. Eighty percent of patients receiving calcium carbonate without vitamin D sterols (20 of 25) reached the primary end point—a mean PTH level of 300 pg/mL or less after the period—as compared with 84% of those receiving calcium carbonate and vitamin D sterol (21 of 25) (Mantel‐Haenszel odds ratio 0.76, 95% confidence interval: 0.18–3.25, P = 0.71). The other effects of the two regimens on the secondary end points were not significantly different after 6 months. In SHPT of dialysis patients initiating hemodialysis, oral calcium carbonate use alone was not inferior to additional vitamin D sterol use with calcium carbonate in reducing serum PTH levels. Our result indicated that, if serum calcium and phosphorus levels are controlled primarily regardless of used agents, it will be followed by reduction of serum PTH level in these patients.
Functional and biochemical modifications in skeletal muscles from malarial mice
Authors: Brotto Marco A. P. , Marrelli Mauro T. , Brotto Leticia S. , Jacobs‐Lorena Marcelo , Nosek Thomas M.
Published: February 2005

Although it is well established that patients suffering from malaria experience skeletal muscle problems (contracture, aches, fatigue, weakness), detailed studies have not been performed to investigate changes in the contractile function and biochemical properties of intact and skinned skeletal muscles of mammals infected with malaria. To this end, we investigated such features in the extensor digitorium longus (EDL, fast‐twitch, glyocolytic) and in the soleus (SOL, slow‐twitch, oxidative) muscles from mice infected with Plasmodium berghei. We first studied maximal tetanic force (Tmax) produced by intact control and malaria‐infected muscles before, during and after fatigue. Triton‐skinned muscle fibres were isolated from these muscles and used to determine isometric contractile features as well as a basic biochemical profile as analysed by silver‐enhanced SDS‐PAGE. We found that the Tmax of intact muscles and the maximal Ca2+‐activated force (Fmax) of Triton‐skinned muscle fibres were reduced by ∼50% in malarial muscles. In addition, the contractile proteins of Triton‐skinned muscle fibres from malarial muscles were significantly less sensitive to Ca2+. Biochemical analysis revealed that there was a significant loss of essential contractile proteins (e.g. troponins and myosin) in Triton‐skinned muscle fibres from malarial muscles as compared to controls. The biochemical alterations (i.e., reduction of essential contractile proteins) seem to explain well the functional modifications resolved in both intact muscles and Triton‐skinned muscle fibres and may provide a suitable paradigm for the aetiology of muscle symptoms associated with malaria.
Chronic intermittent asphyxia increases platelet reactivity in rats
Authors: Dunleavy M. , Dooley M. , Cox D. , Bradford A.
Published: February 2005

Sleep‐disordered breathing is associated with chronic intermittent asphyxia and with a variety of cardiovascular abnormalities. Cardiovascular morbidity and mortality are linked to altered platelet function, and platelet function is affected in sleep‐disordered breathing. As there is evidence that chronic continuous hypoxia may alter platelet number and function, the aim of the present study was to test the hypothesis that chronic intermittent asphyxia affects platelet count, activation and aggregation. Rats were treated with a hypercapnic hypoxic gas mixture (minimum of 6–8% O2, maximum of 10–14% CO2) for 15 s, twice per minute for 8 h per day for 3 weeks. Blood was analysed for platelet count, platelet activation (CD62p expression using flow cytometry), response to low dose ADP, haematocrit, red cell count and haemoglobin concentration. A platelet function analyser measured the closure time of an aperture, dependent on platelet aggregation. Compared to controls (n= 16), chronic intermittent asphyxia (n= 13) reduced body weight and increased right ventricular weight but had no significant effect on platelet count (control, 880.4 ± 20.1; treated: 914.1 ± 35.2 × 103μl−1; mean ±s.e.m.), on the reduction in platelet count in response to ADP (control, reduced to 206.7 ± 49.0; treated, reduced to 193.8 ± 35.9 × 103μl−1), or on the percentage of platelets positive for CD62p (control, 5.2 ± 0.7; treated, 6.0 ± 0.8%). Chronic intermittent asphyxia significantly (P= 0.037) reduced the closure time (control, 90.9 ± 7.7; treated, 77.7 ± 3.8 s), indicating greater adhesion and aggregation. There was no significant difference in haematocrit, red cell count and haemoglobin concentration. In conclusion, chronic intermittent asphyxia has no effect on platelet count but does increase platelet aggegation in rats. These data support the idea that chronic intermittent asphyxia alters platelet function in sleep‐disordered breathing.
Antiadenovirus Activities of Several Classes of Nucleoside and Nucleotide Analogues
Authors: Naesens L. , Lenaerts L. , Andrei G. , Snoeck R. , Van Beers D. , Holý Antonin , Balzarini Jan , De Clercq Erik
Published: February 2005

The absence of any formally licensed antiadenovirus drugs and the increasing incidence of life-threatening adenovirus infections in immunosuppressed patients warrant the development of effective antiadenovirus compounds. A detailed study was performed on the antiadenovirus activities of several classes of nucleoside and nucleotide analogues in human embryonic lung fibroblast cells. The antiadenovirus activities were evaluated by three methods, viz., evaluating the adenoviral cytopathic effect, monitoring cell viability by a colorimetric assay, and real-time PCR quantitation of viral DNA as a direct parameter for virus replication. The most active and selective compounds were the acyclic nucleoside phosphonate analogues cidofovir, its adenine analogue (
S
)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [(
S
)-HPMPA], and the new derivative (
S
)-2,4-diamino-6-[3-hydroxy-2-(phosphonomethoxy)propoxy]pyrimidine [(
S
)-HPMPO-DAPy]; the N7-substituted acyclic derivative 2-amino-7-(1,3-dihydroxy-2-propoxymethyl)purine (S-2242); and the 2′,3′-dideoxynucleoside analogues zalcitabine and alovudine. No antiadenovirus activity was observed for the antiviral drugs ribavirin, foscarnet, acyclovir, penciclovir, and brivudin, while ganciclovir displayed modest activity. However, in human osteosarcoma cells transfected with herpes simplex virus thymidine kinase, ganciclovir demonstrated highly potent antiadenovirus activity, suggesting that the efficacy of ganciclovir against adenovirus is limited by inefficient phosphorylation in adenovirus-infected cells, rather than by insufficient inhibition at the viral DNA polymerase level. Collectively, our antiviral data show that the adenovirus DNA polymerase exhibits sensitivity to a relatively broad spectrum of inhibitors and should be studied further as an antiviral target in antiadenovirus drug development programs.
c-di-GMP (3′-5′-Cyclic Diguanylic Acid) Inhibits
Staphylococcus aureus
Cell-Cell Interactions and Biofilm Formation
Authors: Karaolis David K. R. , Rashid Mohammed H. , Chythanya Rajanna , Luo Wensheng , Hyodo Mamoru , Hayakawa Yoshihiro
Published: February 2005

Staphylococcus aureus
is an important pathogen of humans and animals, and antibiotic resistance is a public health concern. Biofilm formation is essential in virulence and pathogenesis, and the ability to resist antibiotic treatment results in difficult-to-treat and persistent infections. As such, novel antimicrobial approaches are of great interest to the scientific, medical, and agriculture communities. We recently proposed that modulating levels of the cyclic dinucleotide signaling molecule, c-di-GMP (cyclic diguanylate [3′,5′-cyclic diguanylic acid], cGpGp), has utility in regulating phenotypes of prokaryotes. We report that extracellular c-di-GMP shows activity against human clinical and bovine intramammary mastitis isolates of
S. aureus
, including methicillin-resistant
S. aureus
(MRSA) isolates. We show that chemically synthesized c-di-GMP is soluble and stable in water and physiological saline and stable following boiling and exposure to acid and alkali. Treatment of
S. aureus
with extracellular c-di-GMP inhibited cell-to-cell (intercellular) adhesive interactions in liquid medium and reduced (>50%) biofilm formation in human and bovine isolates compared to untreated controls. c-di-GMP inhibited the adherence of
S. aureus
to human epithelial HeLa cells. The cyclic nucleotide analogs cyclic GMP and cyclic AMP had a lesser inhibitory effect on biofilms, while 5′-GMP had no major effect. We propose that cyclic dinucleotides such as c-di-GMP, used either alone or in combination with other antimicrobial agents, represent a novel and attractive approach in the development of intervention strategies for the prevention of biofilms and the control and treatment of infection.
Activity of Gemifloxacin against Quinolone-Resistant
Streptococcus pneumoniae
Strains In Vitro and in a Mouse Pneumonia Model
Authors: Azoulay-Dupuis E. , Bédos J. P. , Mohler J. , Moine P. , Cherbuliez C. , Peytavin G. , Fantin B. , Köhler T.
Published: February 2005

Gemifloxacin is a novel fluoronaphthyridone quinolone with enhanced in vitro activity against
Streptococcus pneumoniae
. We investigated the activities of gemifloxacin and trovafloxacin, their abilities to select for resistance in vitro and in vivo, and their efficacies in a mouse model of acute pneumonia. Immunocompetent Swiss mice were infected with 10
5
CFU of a virulent, encapsulated
S. pneumoniae
strain, P-4241, or its isogenic
parC
,
gyrA
,
parC gyrA
, and efflux mutant derivatives (serotype 3); and leukopenic mice were infected with 10
7
CFU of two poorly virulent clinical strains (serotype 11A) carrying either a
parE
mutation or a
parC
,
gyrA
, and
parE
triple mutation. The drugs were administered six times every 12 h, starting at either 3 or 18 h postinfection. In vitro, gemifloxacin was the most potent agent against strains with and without acquired resistance to fluoroquinolones. While control mice died within 6 days, gemifloxacin at doses of 25 and 50 mg/kg of body weight was highly effective (survival rates, 90 to 100%) against the wild-type strain and against mutants harboring a single mutation, corresponding to area under the time-versus-serum concentration curve at 24 h (AUC
24
)/MIC ratios of 56.5 to 113, and provided a 40% survival rate against a mutant with a double mutation (
parC
and
gyrA
). A total AUC
24
/MIC ratio of 28.5 was associated with poor efficacy and the emergence of resistant mutants. Trovafloxacin was as effective as gemifloxacin against mutants with single mutations but did not provide any protection against the mutant with double mutations, despite treatment with a high dose of 200 mg/kg. Gemifloxacin preferentially selected for
parC
mutants both in vitro and in vivo.
Transcriptional Analysis of the
vanC
Cluster from
Enterococcus gallinarum
Strains with Constitutive and Inducible Vancomycin Resistance
Authors: Panesso Diana , Abadía-Patiño Lorena , Vanegas Natasha , Reynolds Peter E. , Courvalin Patrice , Arias Cesar A.
Published: February 2005

The
vanC
glycopeptide resistance gene cluster encodes enzymes required for synthesis of peptidoglycan precursors ending in
d
-Ala-
d
-Ser.
Enterococcus gallinarum
BM4174 and SC1 are constitutively and inducibly resistant to vancomycin, respectively. Analysis of peptidoglycan precursors in both strains indicated that UDP-MurNAc-tetrapeptide and UDP-MurNAc-pentapeptide[
d
-Ser] were synthesized in
E. gallinarum
SC1 only in the presence of vancomycin (4 μg/ml), whereas the “resistance” precursors accumulated in the cytoplasm of BM4174 cells under both inducing and noninducing conditions. Northern hybridization and reverse transcription-PCR experiments revealed that all the genes from the cluster,
vanC-1
,
vanXY
C
,
vanT
,
vanR
C
, and
vanS
C
, were transcribed from a single promoter. In the inducible SC1 isolate, transcriptional regulation appeared to be responsible for inducible expression of resistance. Promoter mapping in
E. gallinarum
BM4174 revealed that the transcriptional start site was located 30 nucleotides upstream from
vanC-1
and that the −10 promoter consensus sequence had high identity with that of the
vanA
cluster. Comparison of the deduced sequence of the
vanS
C
genes from isolates with constitutive and inducible resistance revealed several amino acid substitutions located in the X box (R200L) and in the region between the F and G2 boxes (D312N, D312A, and G320S) of the putative sensor kinase proteins from isolates with constitutive resistance.
CmeR Functions as a Transcriptional Repressor for the Multidrug Efflux Pump CmeABC in
Campylobacter jejuni
Authors: Lin Jun , Akiba Masato , Sahin Orhan , Zhang Qijing
Published: February 2005

CmeABC, a resistance-nodulation-division (RND) type of efflux pump, contributes to
Campylobacter
resistance to a broad spectrum of antimicrobial agents and is also essential for
Campylobacter
colonization of the animal intestinal tract by mediation of bile resistance. As one of the main systems for
Campylobacter
adaptation to different environments, CmeABC is likely subject to control by regulatory elements. We describe the identification of a transcriptional repressor for CmeABC. Insertional mutagenesis of
cmeR
, an open reading frame immediately upstream of the
cmeABC
operon, resulted in overexpression of
cmeABC
, as determined by transcriptional fusion (P

cmeABC-lacZ

) and immunoblotting with CmeABC-specific antibodies. Overexpression of the efflux pump was correlated with a moderate increase in the level of resistance of the
cmeR
mutant to several antimicrobials. In vitro, recombinant CmeR bound specifically to the promoter region of
cmeABC
, precisely, to the inverted repeat sequences in the
cmeABC
promoter. A single nucleotide deletion between the two half sites of the inverted repeat reduced the level of CmeR binding to the promoter sequence and resulted in overexpression of
cmeABC
. Together, these findings indicate that
cmeR
encodes a transcriptional repressor that directly interacts with the
cmeABC
promoter and modulates the expression of
cmeABC
. Mutation either in CmeR or in the inverted repeat impedes the repression and leads to enhanced production of the MDR efflux pump.
Simocyclinone D8, an Inhibitor of DNA Gyrase with a Novel Mode of Action
Authors: Flatman Ruth H. , Howells Alison J. , Heide Lutz , Fiedler Hans-Peter , Maxwell Anthony
Published: February 2005

We have characterized the interaction of a new class of antibiotics, simocyclinones, with bacterial DNA gyrase. Even though their structures include an aminocoumarin moiety, a key feature of novobiocin, coumermycin A
1
, and clorobiocin, which also target gyrase, simocyclinones behave strikingly differently from these compounds. Simocyclinone D8 is a potent inhibitor of gyrase supercoiling, with a 50% inhibitory concentration lower than that of novobiocin. However, it does not competitively inhibit the DNA-independent ATPase reaction of GyrB, which is characteristic of other aminocoumarins. Simocyclinone D8 also inhibits DNA relaxation by gyrase but does not stimulate cleavage complex formation, unlike quinolones, the other major class of gyrase inhibitors; instead, it abrogates both Ca
2+
- and quinolone-induced cleavage complex formation. Binding studies suggest that simocyclinone D8 interacts with the N-terminal domain of GyrA. Taken together, our results demonstrate that simocyclinones inhibit an early step of the gyrase catalytic cycle by preventing binding of the enzyme to DNA. This is a novel mechanism for a gyrase inhibitor and presents new possibilities for antibacterial drug development.
Telavancin, a Multifunctional Lipoglycopeptide, Disrupts both Cell Wall Synthesis and Cell Membrane Integrity in Methicillin-Resistant
Staphylococcus aureus
Authors: Higgins Deborah L. , Chang Ray , Debabov Dmitri V. , Leung Joey , Wu Terry , Krause Kevin M. , Sandvik Erik , Hubbard Jeffrey M. , Kaniga Koné , Schmidt Donald E. , Gao Qiufeng , Cass Robert T. , Karr Dane E. , Benton Bret M. , Humphrey Patrick P.
Published: February 2005

The emergence and spread of multidrug-resistant gram-positive bacteria represent a serious clinical problem. Telavancin is a novel lipoglycopeptide antibiotic that possesses rapid in vitro bactericidal activity against a broad spectrum of clinically relevant gram-positive pathogens. Here we demonstrate that telavancin's antibacterial activity derives from at least two mechanisms. As observed with vancomycin, telavancin inhibited late-stage peptidoglycan biosynthesis in a substrate-dependent fashion and bound the cell wall, as it did the lipid II surrogate tripeptide
N
,
N
′-diacetyl-
l
-lysinyl-
d
-alanyl-
d
-alanine, with high affinity. Telavancin also perturbed bacterial cell membrane potential and permeability. In methicillin-resistant
Staphylococcus aureus
, telavancin caused rapid, concentration-dependent depolarization of the plasma membrane, increases in permeability, and leakage of cellular ATP and K
+
. The timing of these changes correlated with rapid , concentration-dependent loss of bacterial viability, suggesting that the early bactericidal activity of telavancin results from dissipation of cell membrane potential and an increase in membrane permeability. Binding and cell fractionation studies provided direct evidence for an interaction of telavancin with the bacterial cell membrane; stronger binding interactions were observed with the bacterial cell wall and cell membrane relative to vancomycin. We suggest that this multifunctional mechanism of action confers advantageous antibacterial properties.
Membrane Topology of the
Escherichia coli
AmpG Permease Required for Recycling of Cell Wall Anhydromuropeptides and AmpC β-Lactamase Induction
Authors: Chahboune Aicha , Decaffmeyer Marc , Brasseur Robert , Joris Bernard
Published: February 2005

Escherichia coli
, and presumably most other gram-negative bacteria, possesses an efficient protein machinery for recycling its peptidoglycan during cell growth. The major recycled peptidoglycan product is
N
-acetylglucosamine-1,6-anhydro-
N
-acetylmuramic acid-tetrapeptide. Its uptake from the periplasm into the cytoplasm is carried out via the AmpG protein, an intrinsic membrane protein. In gram-negative bacteria carrying an
ampC
β-lactamase-inducible gene on their chromosomes, the induction mechanism is directly linked to peptidoglycan recycling. After identification of the different putative hydrophobic segments by computing, the AmpG topology was experimentally determined by using β-lactamase fusion. In the proposed model, AmpG contains 10 transmembrane segments and two large cytoplasmic loops.
Extended-Spectrum Beta-Lactamases among
Enterobacter
Isolates Obtained in Tel Aviv, Israel
Authors: Schlesinger Jacob , Navon-Venezia Shiri , Chmelnitsky Inna , Hammer-Münz Orly , Leavitt Azita , Gold Howard S. , Schwaber Mitchell J. , Carmeli Yehuda
Published: February 2005

The extended-spectrum beta-lactamase (ESBL)-producing phenotype is frequent among
Enterobacter
isolates at the Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. We examined the clonal relatedness and characterized the ESBLs of a collection of these strains. Clonal relatedness was determined by pulsed-field gel electrophoresis. Isoelectric focusing (IEF) and transconjugation experiments were performed. ESBL gene families were screened by colony hybridization and PCR for
bla
TEM
,
bla
SHV
,
bla
CTX-M
,
bla
IBC
,
bla
PER
,
bla
OXA
,
bla
VEB
, and
bla
SFO
; and the PCR products were sequenced. The 17
Enterobacter
isolates studied comprised 15 distinct genotypes. All isolates showed at least one IEF band (range, one to five bands) whose appearance was suppressed by addition of clavulanate; pIs ranged from 5.4 to ≥8.2. Colony hybridization identified at least one family of beta-lactamase genes in 11 isolates: 10 harbored
bla
TEM
and 9 harbored
bla
SHV
. PCR screening and sequence analysis of the PCR products for
bla
TEM
,
bla
SHV
, and
bla
CTX-M
identified TEM-1 in 11 isolates, SHV-12 in 7 isolates, SHV-1 in 1 isolate, a CTX-M-2-like gene in 2 isolates, and CTX-M-26 in 1 isolate. In transconjugation experiments with four isolates harboring
bla
TEM-1
and
bla
SHV-12
, both genes were simultaneously transferred to the recipient strain
Escherichia coli
HB101. Plasmid mapping, PCR, and Southern analysis with TEM- and SHV-specific probes demonstrated that a single transferred plasmid carried both the TEM-1 and the SHV-12 genes. The widespread presence of ESBLs among
Enterobacter
isolates in Tel Aviv is likely due not to clonal spread but, rather, to plasmid-mediated transfer, at times simultaneously, of genes encoding several types of enzymes. The dominant ESBL identified was SHV-12.
Antiamoebic and Toxicity Studies of a Carbamic Acid Derivative and Its Therapeutic Effect in a Hamster Model of Hepatic Amoebiasis
Authors: Ordaz-Pichardo Cynthia , Shibayama Mineko , Villa-Treviño Saúl , Arriaga-Alba Myriam , Angeles Enrique , de la Garza Mireya
Published: February 2005

Amoebiasis is an important public health problem in developing countries.
Entamoeba histolytica
, the causative agent of amoebiasis, may develop resistance to nitroimidazoles, a group of drugs considered to be the most effective against this parasitic disease. Therefore, research on new drugs for the treatment of this common infection still constitutes an important therapeutic demand. In the present study we determined the effects of a carbamate derivative, ethyl 4-chlorophenylcarbamate (C4), on trophozoites of
E. histolytica
strain HM-1:IMSS. C4 was subject to various toxicity tests, including the determination of mutagenicity for bacterial DNA and changes in the enzymatic activities of eukaryotic cells. Genotoxicity studies were performed by the mutagenicity Ames test (plate incorporation and preincubation methods) with
Salmonella enterica
serovar Typhimurium, with or without metabolic activation produced by the S9 fraction of rat liver. C4 toxicity studies were performed by measuring enzymatic activity in eukaryotic cells by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-formazan test with Fischer 344 rat hepatocytes. C4 did not induce either frame-shift mutations in
S. enterica
serovar Typhimurium TA97 or TA98 or base pair substitutions in strains TA100 and TA102. The compound was not toxic for cultured rat hepatic cells. Trophozoites treated with 100 μg of C4 per ml were inhibited 97.88% at 48 h of culture; moreover, damage to the amoebae was also confirmed by electron microscopy. The antiamoebic activity of C4 was evaluated by using an in vivo model of amoebic liver abscess in hamsters. Doses of 75 and 100 mg/100 g of body weight reduced the extent of the amoebic liver abscess by 84 and 94%, respectively. These results justify further studies to clearly validate whether C4 is a new suitable antiamoebic drug.
A Novel Engineered Peptide, a Narrow-Spectrum Antibiotic, is Effective against Vancomycin-Resistant
Enterococcus faecalis
Authors: Qiu Xiao-Qing , Zhang Jie , Wang He , Wu George Y.
Published: February 2005

A novel antienterococcal peptide was prepared by fusing the enterococcal cCF10 pheromone to the channel-forming domain of colicin Ia, forming
Enterococcus faecalis
pheromonicin (PMC-EF). This peptide was bactericidal against vancomycin-resistant
Enterococcus faecalis
(VRE) organisms. Electron microscopy and vital dyes confirmed increased membrane permeability. All mice made bacteremic with VRE strains survived when they were treated with PMC-EF, while all controls died.
Deletion of the Multiple-Drug Efflux Pump AcrAB in
Escherichia
coli
Prolongs the Postantibiotic Effect
Authors: Stubbings William , Bostock Julieanne , Ingham Eileen , Chopra Ian
Published: February 2005

The mechanism of the postantibiotic effect (PAE) was examined in
Escherichia
coli
. Drugs exhibited longer-lasting PAEs in an
acrAB
mutant, suggesting that intracellular drug concentrations influence the duration of the PAE. With specific assays for tetracycline and erythromycin, a direct link between intracellular persistence of antibiotics and maintenance of the PAE was established.
Inhaled Nitric Oxide Treatment of Patients with Pulmonary Tuberculosis Evidenced by Positive Sputum Smears
Authors: Long Richard , Jones Richard , Talbot James , Mayers Irvin , Barrie James , Hoskinson Michael , Light Bruce
Published: February 2005

Endogenous nitric oxide (NO) has antimycobacterial properties. We tested the hypothesis that exogenous (inhaled) NO can be safely delivered and can accelerate airway disinfection for pulmonary tuberculosis patients treated with standard therapy. Exogenous NO administered at 80 ppm for 72 h can be safely delivered but does not accelerate airway disinfection.
mecA
Is Not Involved in the σ
B
-Dependent Switch of the Expression Phenotype of Methicillin Resistance in
Staphylococcus epidermidis
Authors: Knobloch Johannes K.-M. , Jäger Sebastian , Huck Jörn , Horstkotte Matthias A. , Mack Dietrich
Published: February 2005

A lack of σ
B
activity reduces methicillin resistance in heterogeneous
Staphylococcus epidermidis
1057, whereas inactivation of the anti-sigma factor RsbW switched the phenotype to homogeneous expression of resistance. Oxacillin induction of
mecA
transcription is reduced in a σ
B
-negative strain. However,
mecA
is not involved in the switch of expression phenotype.
Synergistic Killing of
Streptococcus pneumoniae
with the Bacteriophage Lytic Enzyme Cpl-1 and Penicillin or Gentamicin Depends on the Level of Penicillin Resistance
Authors: Djurkovic Svetolik , Loeffler Jutta M. , Fischetti Vincent A.
Published: February 2005

A combination of Cpl-1, a bacteriophage lytic enzyme, and penicillin, gentamicin, levofloxacin, or azithromycin was tested against
Streptococcus pneumoniae
strains with various susceptibilities to penicillin. Activities of Cpl-1 and gentamicin were increasingly synergistic with a decreasing penicillin MIC, while Cpl-1 and penicillin showed synergy against an extremely penicillin-resistant strain.
Molecular Epidemiology and Prevalence of Macrolide Efflux Genes
mef
(A) and
mef
(E) in
Streptococcus pneumoniae
Obtained in Canada from 1997 to 2002
Authors: Wierzbowski Aleksandra K. , Swedlo Dean , Boyd Dave , Mulvey Michael , Nichol Kim A. , Hoban Daryl J. , Zhanel George G.
Published: February 2005

One hundred forty M phenotype
Streptococcus pneumoniae
isolates were evaluated by PCR-restriction fragment length polymorphism, serotyping, and pulsed-field gel electrophoresis. Molecular genotyping revealed that the predominant macrolide resistance mechanism in
S. pneumoniae
in Canada is
mef
(E) and resistance dissemination is due to both spread of the genetic element MEGA as well as clonal dissemination of penicillin- and/or macrolide-resistant strains.
Bactericidal Effects of Toluidine Blue-Mediated Photodynamic Action on
Vibrio vulnificus
Authors: Wong Tak-Wah , Wang Yin-Yi , Sheu Hamm-Ming , Chuang Yin-Ching
Published: February 2005

Vibrio vulnificus
is a gram-negative, highly invasive bacterium responsible for human opportunistic infections. We studied the antibacterial effects of toluidine blue O (TBO)-mediated photodynamic therapy (PDT) for
V. vulnificus
wound infections in mice. Fifty-three percent (10 of 19) of mice treated with 100 μg of TBO per ml and exposed to broad-spectrum red light (150 J/cm
2
at 80 mW/cm
2
) survived, even though systemic septicemia had been established with a bacterial inoculum 100 times the 50% lethal dose. In vitro, the bacteria were killed after exposure to a lower light dose (100 J/cm
2
at 80 mW/cm
2
) in the presence of low-dose TBO (0.1 μg/ml). PDT severely damaged the cell wall and reduced cell motility and virulence. Cell-killing effects were dependent on the TBO concentration and light doses and were mediated partly through the reactive oxygen species generated during the photodynamic reaction. Our study has demonstrated that PDT can cure mice with otherwise fatal
V. vulnificus
wound infections. These promising results suggest the potential of this regimen as a possible alternative to antibiotics in future clinical applications.
Global Expression of Prophage Genes in
Escherichia coli
O157:H7 Strain EDL933 in Response to Norfloxacin
Authors: Herold Sylvia , Siebert Jutta , Huber Andrea , Schmidt Herbert
Published: February 2005

We investigated the influence of a low concentration of the gyrase inhibitor norfloxacin on the transcriptome of enterohemorrhagic
Escherichia coli
O157:H7 strain EDL933. For this purpose, we used a commercial DNA microarray containing oligonucleotides specific for
E. coli
O157:H7 strains EDL933 and RIMD0509952 and
E. coli
K-12 strain MG1655. Under the conditions applied, 5,963 spots (94% of all spots) could be analyzed. Among these, 118 spots (
P
< 0.05) indicated transcriptional upregulation and 122 spots (
P
< 0.05) indicated transcriptional downregulation of the
E. coli
genes present on the array. Eighty-five upregulated EDL933 genes were phage borne. Fifty-two of them could be ascribed to the Shiga toxin-encoding phages (Stx phages) BP-933W and CP-933V; the other 33 genes belonged to non-Stx prophage elements in the EDL933 genome. Genes present in the BP-933W prophage genome were induced most strongly up to 158-fold in the case of

stxA
2

upon induction with norfloxacin. Twenty-two additional upregulated genes appeared to be
E. coli
O157:H7 strain RIMD0509952-specific phage elements, and the remaining 11 genes were related mainly to recombination and stress functions. Downregulation was indicated predominantly for genes responsible for bacterial primary metabolism, such as energy production, cell division, and amino acid biosynthesis. Interestingly, some genes present in the locus of enterocyte effacement appeared to be downregulated. The results of the study have shown that a low concentration of norfloxacin has profound effects on the transcriptome of
E. coli
O157:H7.
Open-Label, Dose Escalation Study of the Safety and Pharmacokinetic Profile of Tefibazumab in Healthy Volunteers
Authors: Reilley Sandra , Wenzel Eric , Reynolds Laurie , Bennett Beth , Patti Joseph M. , Hetherington Seth
Published: February 2005

Tefibazumab (Aurexis) is a humanized monoclonal antibody being evaluated as adjunctive therapy for the treatment of
Staphylococcus aureus
infections. This open-label, dose escalation study evaluated the safety and pharmacokinetics of tefibazumab in 19 healthy volunteers aged 18 to 69 years. Each subject received a single administration of tefibazumab at a dose of 2, 5, 10, or 20 mg/kg of body weight infused over 15 min. Plasma samples for pharmacokinetic assessments were obtained before infusion as well as 1, 6, 12, and 24 h and 3, 4, 7, 21, 28, 42, and 56 days after dosing. Plasma concentrations of tefibazumab were detected 1 h after the end of the infusion, with a mean maximum concentration of drug in serum (
C
max
) of 59, 127, 252, and 492 μg/ml following doses of 2, 5, 10, and 20 mg/kg, respectively. The median time to maximum concentration of drug in serum (
T
max
) was 1.0 h for each dose. The mean elimination half-life (
t
1/2
) was approximately 22 days. The volume of distribution (
V
) was 4.7, 6.7, 7.2, and 7.2 liters after doses of 2, 5, 10, and 20 mg/kg, respectively. Clearance (CL) was 6.0, 9.2, 10.2, and 9.9 ml/hr, respectively. At the highest dose, plasma levels of tefibazumab were >100 μg/ml for 21 days. On day 56, the mean plasma concentrations were 6.3, 10.0, 16.4, and 30.5 μg/ml for the 2, 5, 10, and 20 mg/kg doses, respectively. Tefibazumab exhibited linear kinetics across doses of 5, 10, and 20 mg/kg. No anti-tefibazumab antibodies were detected after dosing in any subject. There were no serious adverse events, and tefibazumab was well tolerated over the entire dose range.
Pulmonary Damage and Bacterial Load in Assessment of the Efficacy of Simulated Human Treatment-Like Amoxicillin (2,000 Milligrams) Therapy of Experimental Pneumococcal Pneumonia Caused by Strains for Which Amoxicillin MICs Differ
Authors: Gracia Matilde , Martínez-Marín Carmina , Huelves Lorena , Giménez Maria J. , Aguilar Lorenzo , Carcas Antonio , Ponte Carmen , Soriano Francisco
Published: February 2005

An experimental rat pneumonia model using two amoxicillin-susceptible (MICs, ≤0.015 and 2 μg/ml) and two non-amoxicillin-susceptible (MIC, 4 μg/ml)
Streptococcus pneumoniae
strains was developed for testing the efficacy of amoxicillin administered to simulate human serum kinetics after treatment with amoxicillin-clavulanate (2,000 and 125 mg, respectively, twice a day, for 2.5 days). The end points for efficacy were reductions in bacterial loads in the lungs and reductions in levels of pulmonary damage. For the amoxicillin-susceptible strains (serotypes 23F and 14), a decrease greater than 4.5 log
10
CFU/pair of lungs was obtained, and the time for which the serum antibiotic concentration (SAC) was higher than the MIC (
T
S
A
C
>
MIC
) was greater than 60% of the dosing interval. For non-amoxicillin-susceptible strains, the decrease in bacterial load was 1.34 to 1.75 log
10
CFU/pair of lungs, with a
T
S
A
C
>
MIC
of 46.7% of the dosing interval. An in vitro study showed that serotype 9V non-amoxicillin-susceptible strains behaved as tolerant-like to concentrations similar to those in the in vivo model. The high and maintained SACs (
T
S
A
C
>
MIC
, >46% for all strains) significantly diminished lung injury (affected area of the lung and lung weight), compared to that in controls, by all strains, regardless of the MIC, bactericidal behavior in in vitro killing curves, or the serotype of the infecting strain. These results show the importance of host therapeutic end points in the evaluation of antibiotic efficacy. The antibiotic was more efficacious, for one nonsusceptible strain tested, when the treatment was started early (1 h postinoculation [p.i.]) than when treatment was delayed (24 h p.i.).
Biological risk indicators for recurrent non-specific low back pain in adolescents
Authors: Jones M A , Stratton G , Reilly T , Unnithan V B
Published: February 2005

Objectives:A matched case-control study was carried out to evaluate biological risk indicators for recurrent non-specific low back pain in adolescents.

Methods:Adolescents with recurrent non-specific low back pain (symptomatic; n  =  28; mean (SD) age 14.9 (0.7) years) and matched controls (asymptomatic; n  =  28; age 14.9 (0.7) years) with no history of non-specific low back pain participated. Measures of stature, mass, sitting height, sexual maturity (Tanner self assessment), lateral flexion of the spine, lumbar sagittal plane mobility (modified Schöber), hip range of motion (Leighton flexometer), back and hamstring flexibility (sit and reach), and trunk muscle endurance (number of sit ups) were performed using standardised procedures with established reliability. Backward stepwise logistic regression analysis was performed, with the presence/absence of recurrent low back pain as the dependent variable and the biological measures as the independent variables.

Results:Hip range of motion, trunk muscle endurance, lumbar sagittal plane mobility, and lateral flexion of the spine were identified as significant risk indicators of recurrent low back pain (p<0.05). Follow up analysis indicated that symptomatic subjects had significantly reduced lateral flexion of the spine, lumbar sagittal plane mobility, and trunk muscle endurance (p<0.05).

Conclusions:Hip range of motion, abdominal muscle endurance, lumbar flexibility, and lateral flexion of the spine were risk indicators for recurrent non-specific low back pain in a group of adolescents. These risk indicators identify the potential for exercise as a primary or secondary prevention method.
Participation in leanness sports but not training volume is associated with menstrual dysfunction: a national survey of 1276 elite athletes and controls
Authors: Torstveit M K , Sundgot-Borgen J
Published: February 2005

Objective:To examine the prevalence of menstrual dysfunction in the total population of Norwegian elite female athletes and national representative controls in the same age group.

Methods:A detailed questionnaire that included questions on training and/or physical activity patterns, menstrual, dietary, and weight history, oral contraceptive use, and eating disorder inventory subtests was administered to all elite female athletes representing the country at the junior or senior level (aged 13–39 years, n  =  938) and national representative controls in the same age group (n  =  900). After exclusion, a total of 669 athletes (88.3%) and 607 controls (70.2%) completed the questionnaire satisfactorily.

Results:Age at menarche was significantly (p<0.001) later in athletes (13.4 (1.4) years) than in controls (13.0 (1.3) years), and differed among sport groups. A higher percentage of athletes (7.3%) than controls (2.0%) reported a history of primary amenorrhoea (p<0.001). A similar percentage of athletes (16.5%) and controls (15.2%) reported present menstrual dysfunction, but a higher percentage of athletes competing in leanness sports reported present menstrual dysfunction (24.8%) than athletes competing in non-leanness sports (13.1%) (p<0.01) and controls (p<0.05).

Conclusions:These novel data include virtually all eligible elite athletes, and thus substantially extend previous studies. Age at menarche occurred later and the prevalence of primary amenorrhoea was higher in elite athletes than in controls. A higher percentage of athletes competing in sports that emphasise thinness and/or a specific weight reported present menstrual dysfunction than athletes competing in sports focusing less on such factors and controls. On the basis of a comparison with a previous study, the prevalence of menstrual dysfunction was lower in 2003 than in 1993.
Enhancing the efficacy of the 20 m multistage shuttle run test
Authors: Flouris A D , Metsios G S , Koutedakis Y
Published: February 2005

Objective:Maximal oxygen uptake (Vo2max) of 44 ml kg−1min−1is an accepted criterion (Vo2CR) below which health and fitness for young male adults may be compromised. New algorithms validated for Vo2CRscreening using the 20 m multistage shuttle run test (20mMST) were developed.

Methods:Vo2maxwas assessed in 110 males using a stationary gas analyser in a treadmill test (TT) and in 40 of these subjects using a portable gas analyser in the 20mMST. Vo2maxpredicted from the 20mMST in 70 subjects was used for cross validation. Two equations predicting Vo2maxduring 20mMST (EQMST) and TT (EQTT) were developed.

Results:Significant energy cost variance (ECV) was detected between TT and 20mMST (p<0.001), correlated significantly with subject height, and was a significant predictor of Vo2maxdifferences between TT and 20mMST. Ther2of EQMSTwas 0.92 (p<0.001). Predicted Vo2maxvalues from EQMSTcorrelated with directly measured 20mMST Vo2maxatr = 0.96 (p<0.001). ANOVA detected no mean difference (p>0.05) between predicted and measured values. Prevalence of low fitness based on Vo2CRwas 0.37. McNemar χ2indicated significant differences in sensitivity (p<0.001) and specificity (p<0.05) between the original 20mMST equation (EQLÉG) and EQTT, regarding Vo2CRscreening. Cohen’s κ demonstrated higher agreement with TT Vo2maxfor EQTT(p<0.001) than EQLÉG(p<0.05). TT Vo2maxcorrelated with the end result of both EQLÉGand EQTTatr = 0.75 (p<0.001). Unlike EQTT(p>0.05), mean predicted Vo2maxfrom EQLÉGwas significantly higher compared to TT Vo2max(p<0.001).

Conclusion:These algorithms increase the efficacy of 20mMST to accurately evaluate aspects of health and fitness.
Multiple osteochondroses and avulsion fracture of anterior superior iliac spine in a soccer player
Authors: Doral M N , Aydog S T , Tetik O , Atay O A , Turhan E , Demirel H A
Published: February 2005

Apophysitis describes a chronic traction injury at the insertion site of a tendon. There is a gradual onset of pain with no clear history of injury. Without adequate preventive methods, an avulsion fracture may result. The case is here reported of an apophyseal avulsion fracture of the anterior superior iliac spine in an adolescent caused by playing football before the end of treatment for apophysitis. An open reduction and internal fixation was performed followed by a rehabilitation programme. No complications occurred, and the patient had returned to his previous level of sporting activity after six weeks.
Effectiveness of extracorporeal shock wave therapy for tennis elbow (lateral epicondylitis)
Authors: Stasinopoulos D , Johnson M I
Published: February 2005

Randomised controlled trials were reviewed to evaluate the evidence of the effectiveness of extracorporeal shock wave therapy in the management of tennis elbow. Seven relevant trials were found, which had satisfactory methodology but conflicting results. Further research with well designed randomised control trials is needed to establish the absolute and relative effectiveness of this intervention for tennis elbow.
Genetic diversity of the Andean tetraploid cultivated potato (Solanum tuberosumL. subsp.andigenaHawkes) evaluated by chloroplast and nuclear DNA markers
Authors: Sukhotu Thitaporn , Kamijima Osamu , Hosaka Kazuyoshi
Published: February 2005

Andigena potatoes (Solanum tuberosum L. subsp. andigena Hawkes) (2n = 4x = 48) are native farmer-selected important cultivars that form a primary gene pool of the common potato (Solanum tuberosum L. subsp. tuberosum). The genetic diversity of 185 Andigena accessions and 6 Chilean native potatoes (S. tuberosum subsp. tuberosum) was studied using chloroplast DNA (ctDNA) microsatellites and nuclear DNA (nDNA) restriction fragment length polymorphism (RFLP) markers. Andigena potatoes had 14 ctDNA haplotypes and showed higher variability in the central Andes, particularly in Bolivia, whereas those in the northern regions of the distribution area were remarkably uniform with A1 ctDNA and Chilean subsp. tuberosum with T ctDNA. Most of 123 clearly scored RFLP bands using 30 single-copy probes were randomly distributed throughout the distribution area and proved the same gene pool shared among these widely collected accessions. Nevertheless, the geographic trend of the nDNA differentiation from north to south along the Andes and the correlated differentiation between nDNA and ctDNA (r = 0.120) could also be revealed by canonical variates analysis. These results suggest that the genetic diversity in Andigena was brought about primarily from cultivated diploid species but considerably modified through sexual polyploidization and intervarietal and (or) introgressive hybridization and long-distance dispersal of seed tubers by humans.Key words: Andigena, chloroplast DNA, nuclear DNA, RFLP, geographic trend, diversity.
Endonuclease banding reveals that atrazine-induced aneuploidy resembles spontaneous chromosome loss in Crassostrea gigas
Authors: Bouilly Karine , Leitão Alexandra , Chaves Raquel , Guedes-Pinto Henrique , Boudry Pierre , Lapègue Sylvie
Published: February 2005

Aneuploidy has previously been observed in the Pacific oyster, Crassostrea gigas, and shown to be negatively correlated with growth. Moreover, a significant impact of atrazine exposure has been described in C. gigas, and persistence of that effect has been observed between generations. Evidence of differential chromosome loss has been demonstrated in aneuploid karyotypes of C. gigas using the G-banding technique. Pairs 1, 5, 9, and 10 are characterized by the loss of 1 chromosome. As restriction enzyme (RE) digestion chromosome banding allows a better identification of chromosome pairs, we used this technique to identify which chromosomes are affected when aneuploidy is increased by exposure to atrazine. The progeny of oysters contaminated by atrazine were analysed using the restriction enzyme HaeIII. The study of 26 RE-banded aneuploid karyotypes showed that the same chromosome pairs (1, 5, 9, and 10) were affected by the loss of 1 chromosome (61%, 15%, 42%, and 42%, respectively). Further investigation is required to enable a better understanding of aneuploidy in oysters, especially with respect to why some chromosomes are more easily lost than others, and why cells tolerate the loss of these chromosomes.Key words: aneuploidy, atrazine, restriction enzyme digestion chromosome banding, Pacific oyster, Crassostrea gigas.