bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of negative dispersion by a nonlocal poroelastic theory
Authors: Chakraborty Abir
Published: January 2008

The objective of this work is to show that the negative dispersion of ultrasonic waves propagating in cancellous bone can be explained by a nonlocal version of Biot’s theory of poroelasticity. The nonlocal poroelastic formulation is presented in this work and the exact solutions for one- and two-dimensional systems are obtained by the method of Fourier transform. The nonlocal phase speeds for solid- and fluid-borne waves show the desired negative dispersion where the magnitude of dispersion is strongly dependent on the nonlocal parameters and porosity. Dependence of the phase speed and attenuation is studied for both porosity and frequency variation. It is shown that the nonlocal parameter can be easily estimated by comparing the theoretical dispersion rate with experimental observations. It is also shown that the modes of Lamb waves show similar negative dispersion when predicted by the nonlocal poroelastic theory.
Nonconscious control of fundamental voice frequency
Authors: Hafke Honorata Zofia
Published: January 2008

The aim of this paper is to answer the question whether “perception-action” dissociation, which is well documented in vision, may also be found in auditory information processing. Trained singers were asked to produce vowel sounds into a microphone. The sound that each singer produced was fed back to their ears via headphones. Two seconds after the sound production had begun, the auditory feedback was shifted in pitch by a certain degree (9, 19, 50, or 99 cents in either direction). In every set of sounds, instances without any pitch shifts also appeared. After each trial, participants reported whether they were aware of a pitch change or not. It was found that even though the participants were unaware of subtle pitch changes, the fundamental frequency of their vowel production was found to shift slightly in the opposite direction to the pitch shift. These results show that auditory information is processed by two separate systems: one for perception and one for action. They also show that the function of the auditory control system differs from the visual control system. The latter is used to control bodily movements while the function of the former is a nonconscious, instant control of vocalization.
Middle-ear circuit model parameters based on a population of human ears
Authors: O’Connor Kevin N. , Puria Sunil
Published: January 2008

Middle-ear circuit model parameters are selected to produce overall magnitude and phase agreement with pressure to stapes velocity transfer function measurements made on 16 human temporal bones, up to approximately 12kHz. The circuit model, which was previously used for the cat, represents the tympanic membrane (TM) as a distributed parameter acoustic transmission line, and ossicular chain and cochlea as a network of lumped circuit elements. For some ears the TM transmission line primarily affects the magnitude of the response, while for others it primarily affects the phase. Model responses also compare favorably with velocity ratio data between the umbo and stapes footplate as well as between the umbo and incus, and exhibit similar characteristics to three previous input impedance measurements, including two from living ears. Similarities are also shown between the model magnitude and adjusted pressure to stapes velocity measurements from living ears, suggesting that the model may suitably approximate the behavior of living ears. In addition to fitting individual measurements, a set of parameters is selected to produce agreement with the mean of the 16 measurements up to 10kHz, to allow the main features of the ensemble to be reproduced from a single parameter set.
Measurements and predictions of hooded crow (Corvus corone cornix) call propagation over open field habitats
Authors: Jensen Kenneth Kragh , Larsen Ole Næsbye , Attenborough Keith
Published: January 2008

In a study of hooded crow communication over open fields an excellent correspondence is found between the attenuation spectra predicted by a “turbulence-modified ground effect plus atmospheric absorption” model, and crow call attenuation data. Sound propagation predictions and background noise measurements are used to predict an optimal frequency range for communication (“sound communication window”) from an average of crow call spectra predicted for every possible combination of the sender/receiver separations 300, 600, 900, and 1200m and heights 3,6,9m thereby creating a matrix assumed relevant to crow interterritorial communication. These predictions indicate an optimal frequency range for sound communication between 500Hz and 2kHz. Since this corresponds to the frequency range in which crow calls have their main energy and crow hearing in noise is particularly sensitive, it suggests a specific adaptation to the ground effect. Sound propagation predictions, together with background noise measurements and hearing data, are used to estimate the radius of the hooded crow active space. This is found to be roughly 1km in moderately windy conditions. It is concluded that the propagation modeling of the sort introduced here could be used for assessing the impact of human noise on animal communication.
Spectral tilt change in stop consonant perception
Authors: Alexander Joshua M. , Kluender Keith R.
Published: January 2008

There exists no clear understanding of the importance of spectral tilt for perception of stop consonants. It is hypothesized that spectral tilt may be particularly salient when formant patterns are ambiguous or degraded. Here, it is demonstrated that relative change in spectral tilt over time, not absolute tilt, significantly influences perception of /b/ vs /d/. Experiments consisted of burstless synthesized stimuli that varied in spectral tilt and onset frequency of the second formant. In Experiment 1, tilt of the consonant at voice onset was varied. In Experiment 2, tilt of the vowel steady state was varied. Results of these experiments were complementary and revealed a significant contribution of relative spectral tilt change only when formant information was ambiguous. Experiments 3 and 4 replicated Experiments 1 and 2 in an /aba/-/ada/ context. The additional tilt contrast provided by the initial vowel modestly enhanced effects. In Experiment 5, there was no effect for absolute tilt when consonant and vowel tilts were identical. Consistent with earlier studies demonstrating contrast between successive local spectral features, perceptual effects of gross spectral characteristics are likewise relative. These findings have implications for perception in nonlaboratory environments and for listeners with hearing impairment.
Site-Specific Contributions of Glutamine-Dependent Regulator GlnR and GlnR-Regulated Genes to Virulence of
Streptococcus pneumoniae
Authors: Hendriksen Wouter T. , Kloosterman Tomas G. , Bootsma Hester J. , Estevão Silvia , de Groot Ronald , Kuipers Oscar P. , Hermans Peter W. M.
Published: January 2008

The transcriptional regulator GlnR of
Streptococcus pneumoniae
is involved in the regulation of glutamine and glutamate metabolism, controlling the expression of the
glnRA
and
glnPQ
-
zwf
operons, as well as the
gdhA
gene. To assess the contribution of the GlnR regulon to virulence, D39 wild-type and mutant strains lacking genes of this regulon were tested in an in vitro adherence assay and murine infection models. All of the mutants, except the Δ
glnR
mutant, were attenuated in adherence to human pharyngeal epithelial Detroit 562 cells, suggesting a contribution of these genes to adherence during the colonization of humans. During murine colonization, only the Δ
glnA
mutant and the
glnP
-
glnA
double mutant (Δ
glnAP
) were attenuated, in contrast to Δ
glnP
, indicating that the effect is caused by the lack of GlnA expression. In our pneumonia model, only Δ
glnP
and Δ
glnAP
showed a significantly reduced number of bacteria in the lungs and blood, indicating that GlnP is required for survival in the lungs and possibly for dissemination to the blood. In intravenously infected mice,
glnP
and
glnA
were individually dispensable for survival in the blood whereas the Δ
glnAP
mutant was avirulent. Finally, transcriptome analysis of the Δ
glnAP
mutant showed that many genes involved in amino acid metabolism were upregulated. This signifies the importance of glutamine/glutamate uptake and synthesis for full bacterial fitness and virulence. In conclusion, several genes of the GlnR regulon are required at different sites during pathogenesis, with
glnA
contributing to colonization and survival in the blood and
glnP
important for survival in the lungs and, possibly, efficient transition from the lungs to the blood.
Repression ofhlabyrotIs Dependent onsaeinStaphylococcus aureus
Authors: Li Dongmei , Cheung Ambrose
Published: January 2008

The regulatory locussaeis a two-component system inStaphylococcus aureusthat regulates many important virulence factors, including alpha-toxin (encoded byhla) at the transcriptional level. The SarA homologs Rot and SarT were previously shown to be repressors ofhlain selectedS. aureusbackgrounds. To delineate the interaction ofrotandsaeand the contribution ofsarTtohlaexpression, an assortment ofrotandsaeisogenic single mutants, arot saedouble mutant, and arot sae sarTmarkerless triple mutant were constructed from wild-type strain COL. Using Northern blot analysis and transcriptional reporter gene green fluorescent protein, fusion, and phenotypic assays, we found that the repression ofhlabyrotis dependent onsae. Arot sae sarTtriple mutant was not able to rescue thehladefect of therot saedouble mutant. Among the threesaepromoters, the distalsaeP3 promoter is the strongest in vitro. Interestingly, thesaeP3 promoter activities correlate withhlaexpression inrot,rot sae, androt sae sarTmutants of COL. Transcriptional study has also shown thatrotrepressedsae, especially at thesaeP3 promoter. Collectively, our data implicated the importance ofsaein therot-mediated repression ofhlainS. aureus.
Clinical and Microbiological Aspects of Linezolid Resistance Mediated by the
cfr
Gene Encoding a 23S rRNA Methyltransferase
Authors: Arias Cesar A. , Vallejo Martha , Reyes Jinnethe , Panesso Diana , Moreno Jaime , Castañeda Elizabeth , Villegas Maria V. , Murray Barbara E. , Quinn John P.
Published: January 2008

The
cfr
(chloramphenicol-florfenicol resistance) gene encodes a 23S rRNA methyltransferase that confers resistance to linezolid. Detection of linezolid resistance was evaluated in the first
cfr
-carrying human hospital isolate of linezolid and methicillin-resistant
Staphylococcus aureus
(designated MRSA CM-05) by dilution and diffusion methods (including Etest). The presence of
cfr
was investigated in isolates of staphylococci colonizing the patient's household contacts and clinical isolates recovered from patients in the same unit where MRSA CM-05 was isolated. Additionally, 68 chloramphenicol-resistant Colombian MRSA isolates recovered from hospitals between 2001 and 2004 were screened for the presence of the
cfr
gene. In addition to
erm
(B), the
erm
(A) gene was also detected in CM-05. The isolate belonged to sequence type 5 and carried staphylococcal chromosomal cassette
mec
type I. We were unable to detect the
cfr
gene in any of the human staphylococci screened (either clinical or colonizing isolates). Agar and broth dilution methods detected linezolid resistance in CM-05. However, the Etest and disk diffusion methods failed to detect resistance after 24 h of incubation. Oxazolidinone resistance mediated by the
cfr
gene is rare, and acquisition by a human isolate appears to be a recent event in Colombia. The detection of
cfr
-mediated linezolid resistance might be compromised by the use of the disk diffusion or Etest method.
Molecular Characterization of
Mycobacterium massiliense
and
Mycobacterium bolletii
in Isolates Collected from Outbreaks of Infections after Laparoscopic Surgeries and Cosmetic Procedures
Authors: Viana-Niero Cristina , Lima Karla Valéria Batista , Lopes Maria Luiza , da Silva Rabello Michelle Christiane , Marsola Lourival Rodrigues , Brilhante Vânia Cristina Ribeiro , Durham Alan Mitchel , Leão Sylvia Cardoso
Published: January 2008

An outbreak of infections affecting 311 patients who had undergone different invasive procedures occurred in 2004 and 2005 in the city of Belém, in the northern region of Brazil. Sixty-seven isolates were studied; 58 were from patients who had undergone laparoscopic surgeries, 1 was from a patient with a postinjection abscess, and 8 were from patients who had undergone mesotherapy. All isolates were rapidly growing nonpigmented mycobacteria and presented a pattern by PCR-restriction enzyme analysis of the
hsp65
gene with BstEII of bands of 235 and 210 bp and with HaeIII of bands of 200, 70, 60, and 50 bp, which is common to
Mycobacterium abscessus
type 2,
Mycobacterium bolletii
, and
Mycobacterium massiliense
.
hsp65
and
rpoB
gene sequencing of a subset of 20 isolates was used to discriminate between these three species.
hsp65
and
rpoB
sequences chosen at random from 11 of the 58 isolates from surgical patients and the postinjection abscess isolate presented the highest degrees of similarity with the corresponding sequences of
M. massiliense.
In the same way, the eight mesotherapy isolates were identified as
M. bolletii
. Molecular typing by pulsed-field gel electrophoresis (PFGE) grouped all 58 surgical isolates, while the mesotherapy isolates presented three different PFGE patterns and the postinjection abscess isolate showed a unique PFGE pattern. In conclusion, molecular techniques for identification and typing were essential for the discrimination of two concomitant outbreaks and one case, the postinjection abscess, not related to either outbreak, all of which were originally attributed to a single strain of
M. abscessus
.
Genetic Classification and Distinguishing of
Staphylococcus
Species Based on Different Partial
gap
, 16S rRNA,
hsp60
,
rpoB
,
sodA
, and
tuf
Gene Sequences
Authors: Ghebremedhin B. , Layer F. , König W. , König B.
Published: January 2008

The analysis of 16S rRNA gene sequences has been the technique generally used to study the evolution and taxonomy of staphylococci. However, the results of this method do not correspond to the results of polyphasic taxonomy, and the related species cannot always be distinguished from each other. Thus, new phylogenetic markers for
Staphylococcus
spp. are needed. We partially sequenced the
gap
gene (∼931 bp), which encodes the glyceraldehyde-3-phosphate dehydrogenase, for 27
Staphylococcus
species. The partial sequences had 24.3 to 96% interspecies homology and were useful in the identification of staphylococcal species (F. Layer, B. Ghebremedhin, W. König, and B. König, J. Microbiol. Methods 70:542-549, 2007). The DNA sequence similarities of the partial staphylococcal
gap
sequences were found to be lower than those of 16S rRNA (∼97%),
rpoB
(∼86%),
hsp60
(∼82%), and
sodA
(∼78%). Phylogenetically derived trees revealed four statistically supported groups:
S. hyicus
/
S. intermedius
,
S. sciuri
,
S. haemolyticus
/
S. simulans
, and
S. aureus
/
epidermidis
. The branching of
S. auricularis
,
S. cohnii
subsp.
cohnii
, and the heterogeneous
S. saprophyticus
group, comprising
S. saprophyticus
subsp.
saprophyticus
and
S. equorum
subsp.
equorum
, was not reliable. Thus, the phylogenetic analysis based on the
gap
gene sequences revealed similarities between the dendrograms based on other gene sequences (e.g., the
S. hyicus
/
S. intermedius
and
S. sciuri
groups) as well as differences, e.g., the grouping of
S. arlettae
and
S. kloosii
in the
gap
-based tree. From our results, we propose the partial sequencing of the
gap
gene as an alternative molecular tool for the taxonomical analysis of
Staphylococcus
species and for decreasing the possibility of misidentification.
Reactivity: an issue for short-term pedometer studies?: Figure 1
Authors: Clemes S A , Matchett N , Wane S L
Published: January 2008

Objectives:

To investigate the influence of wearing a pedometer and recording daily step counts on ambulatory activity.

Methods:

During the first visit to the laboratory, 50 healthy volunteers, blinded to the study aim, were provided with a sealed pedometer (New-Lifestyles NL-2000) and informed that it was a “body posture monitor” (sealed condition). Participants wore the pedometer throughout waking hours for one week. Upon returning to the laboratory step counts were downloaded and participants were informed that the device was actually a pedometer. They were requested to wear it unsealed for a second one-week period, and to record their step counts in an activity log (unsealed condition).

Results:

Mean (SD) daily step counts reported in the sealed condition (9541 (3186) steps/day) were significantly lower than step counts reported in the unsealed condition (11385 (3763) steps/day) (p<0.001).

Conclusions:

Step counts increased significantly in the unsealed condition. Possible mechanisms for this include the knowledge of wearing a pedometer, the visible step count display and the completion of the activity log. This has validity implications for short-term studies (duration ⩽1 week) investigating habitual pedometer-determined activity levels.
GENERATING QUANTUM ENTANGLEMENT IN SCALABLE SUPERCONDUCTING CHARGE QUBITS
Authors: HUO WEN YI , LONG GUI LU
Published: January 2008

We propose an efficient scheme to generate quantum entanglement in scalable superconducting charge qubits with a one-dimensional superconducting transmission line resonator (STLR) as data bus. The coupling between qubit and data bus may be turned on and off by controlling the DC gate voltage and externally applied flux of the superconducting charge qubit. In our proposal, the entanglement between two arbitrary qubits and W states of three qubits can be generated quickly and easily.
CHOP deficiency attenuates cholestasis-induced liver fibrosis by reduction of hepatocyte injury
Authors: Tamaki Nobuyuki , Hatano Etsuro , Taura Kojiro , Tada Masaharu , Kodama Yuzo , Nitta Takashi , Iwaisako Keiko , Seo Satoru , Nakajima Akio , Ikai Iwao , Uemoto Shinji
Published: January 2008

CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) is a key component in endoplasmic reticulum (ER) stress-mediated apoptosis. The goal of the study was to investigate the role of CHOP in cholestatic liver injury. Acute liver injury and liver fibrosis were assessed in wild-type (WT) and CHOP-deficient mice following bile duct ligation (BDL). In WT livers, BDL induced overexpression of CHOP and Bax, a downstream target in the CHOP-mediated ER stress pathway. Liver fibrosis was attenuated in CHOP-knockout mice. Expression levels of α-smooth muscle actin and transforming growth factor-β1 were reduced, and apoptotic and necrotic hepatocyte death were both attenuated in CHOP-deficient mice. Hepatocytes were isolated from WT and CHOP-deficient mice and treated with 400 μM glycochenodeoxycholic acid (GCDCA) for 8 h to examine bile acid-induced apoptosis and necrosis. GCDCA induced overexpression of CHOP and Bax in isolated WT hepatocytes, whereas CHOP-deficient hepatocytes had reduced cleaved caspase-3 expression and a lower propidium iodide index after GCDCA treatment. In conclusion, cholestasis induces CHOP-mediated ER stress and triggers hepatocyte cell death, and CHOP deficiency attenuates this cell death and subsequent liver fibrosis. The results demonstrate an essential role of CHOP in development of liver fibrosis due to cholestatic liver damage.
Fixed feeding potentiates interdigestive gastric motor activity in rats: importance of eating habits for maintaining interdigestive MMC
Authors: Ariga Hajime , Imai Kenji , Chen Cindy , Mantyh Christopher , Pappas Theodore N. , Takahashi Toku
Published: January 2008

Endogenous ghrelin regulates the occurrence of interdigestive gastric phase III-like contractions in rats. However, the fasted motor pattern is not as regular and potent in humans and dogs. We hypothesize that eating habits play an important role in maintaining a regular interdigestive gastric contractions. We studied the effect of fixed-feeding regimen on interdigestive gastric contractions and plasma acyl ghrelin levels. The fixed-fed rats were trained to the assigned meal feeding regimen, once daily at 12:00 PM to 4:00 PM for 14 days. Free-fed rats were maintained with free access to food. As ghrelin regulates gastric emptying as well, solid gastric emptying was also studied in fixed-fed rats and free-fed rats. In free-fed rats, two of six rats did not show interdigestive gastric phase III-like contractions. In contrast, phase III-like contractions were observed in all rats 14 days after starting the fixed-feeding regimen. The maximal amplitude of phase III-like contractions significantly increased from 8.4 ± 0.6 to 16.3 ± 1.8 g ( n = 6, P < 0.05) 14 days after the start of the fixed feeding. Fasted and postprandial plasma ghrelin levels were significantly increased after 14 days of fixed feeding. Solid gastric emptying was significantly accelerated in fixed-fed rats (72.1 ± 4.2%) compared with that of free-fed rats (58.7 ± 2.7%, n = 6, P < 0.05). Our present findings suggest that fixed feeding increases plasma ghrelin levels, potent interdigestive contractions, and acceleration of gastric emptying.
Age-related decline in rate of torque development is accompanied by lower maximal motor unit discharge frequency during fast contractions
Authors: Klass Malgorzata , Baudry Stéphane , Duchateau Jacques
Published: January 2008

The aim of this study was to investigate the association between the rate of torque development and maximal motor unit discharge frequency in young and elderly adults as they performed rapid submaximal contractions with the ankle dorsiflexors. Recordings were obtained of the torque exerted by the dorsiflexors during the isometric contractions and the surface and intramuscular electromyograms (EMGs) from the tibialis anterior. The maximal rate of torque development and integrated EMG (percentage of total EMG burst) at peak rate of torque development during fast contractions were lower in elderly than young adults by 48% ( P < 0.05) and 16.5% ( P < 0.05), respectively. The young adults, but not the elderly adults, exhibited a positive association ( r2 = 0.33; P < 0.01) between the integrated EMG computed up to the peak rate of torque development and the maximal rate of torque development achieved during the fast contractions. These age-related changes during fast voluntary contractions were accompanied by a decline ( P < 0.001) in motor unit discharge frequency (19, 28, and 34% for first 3 interspike intervals, respectively) and in the percentage of units (45%; P < 0.05) that exhibited double discharges (doublets) at brief intervals (<5 ms). Because aging decreased the maximal rate of torque development of fast voluntary contractions to a greater extent (∼10%) than that of an electrically evoked twitch, collectively the results indicate that the age-related decline in maximal motor unit discharge frequency likely limit, in addition to the slowing of muscle contractile properties, the performance of fast voluntary contractions.
Development of a low-dose anti-resorptive drug regimen reveals synergistic suppression of bone formation when coupled with disuse
Authors: Lloyd Shane A.J. , Travis Neil D. , Lu Teng , Bateman Ted A.
Published: January 2008

Safe and effective countermeasures to spaceflight-induced osteoporosis are required to mitigate the potential for mission-critical fractures and ensure long-term bone health in astronauts. Two anti-resorptive drugs, the bisphosphonate zoledronic acid (ZOL) and the anti-receptor activator of NF-κB ligand protein osteoprotegerin (OPG), were investigated to find the minimum, comparable doses that yield a maximal increase in bone quality, while minimizing deleterious effects on turnover and mineralization. Through a series of five trials in normally loaded female mice ( n = 56/trial), analysis of trabecular volume fraction and connectivity using microcomputed tomography, along with biomechanical testing, quantitative histomorphometry, and compositional analysis, was used to select 45 μg/kg ZOL and 500 μg/kg OPG as doses that satisfy these criteria. These doses were then examined for their ability to mitigate bone loss following short-term unloading through hindlimb suspension (HLS). Seventy-two mice were prophylactically administered ZOL, OPG, or PBS and assigned to loaded control or 2-wk HLS groups ( n = 12 for each of 6 groups). Both anti-resorptives were able to preserve trabecular microarchitecture and femoral elastic and maximum force in HLS mice (+30–40% ZOL/OPG vs. PBS). In HLS mice, anti-resorptive dosing reduced resorption perimeter at the femoral endocortical surface by 30% vs. PBS. In loaded control mice, anti-resorptives produced no change in bone formation rate; however, reductions in bone formation rate brought about by HLS were exacerbated by anti-resorptive treatment, suggesting synergistic inhibition of osteoblasts during disuse. Refined anti-resorptive dosing will tend to target countermeasures to the period of disuse, resulting in faster recovery and less adverse effects for astronauts.
Axillary and Rectal Temperature Measurements Poorly Agree in Newborn Infants
Authors: Hissink Muller P.C.E. , van Berkel L.H. , de Beaufort A.J.
Published: January 2008

Aim: Evaluation of the agreement between axillary temperature measurements and rectal temperature measurements in neonates. Methods: Rectal and axillary body temperatures were simultaneously measured for 3 min in 33 neonates (gestational age 25–42 weeks, weight 840–4,005 g). Two investigators performed paired measurements, one in each neonate. A single type of thermometer was used in this study: one thermometer for each rectal and another thermometer for each axillary measurement. The Bland-Altman method was used (95% ‘limits of agreement’: mean ± 2 SD) to determine the level of agreement between axillary and rectal measurements. Results: The axillary temperature was significantly lower than the rectal temperature (mean ± SD 0.27 ± 0.20°C, p < 0.05). The ‘95% limits of agreement’ ranged from –0.13 to +0.67°C. Increasing postnatal age (days) showed a significant increase in temperature difference (rectal minus axillary; r = 0.54; p < 0.05). Conclusions: The mean difference between axillary and rectal temperature shows a wide variation. Axillary temperature measurements cannot be used interchangeably with rectal measurements in neonates.
Norcantharidin Ameliorates Proteinuria, Associated Tubulointerstitial Inflammation and Fibrosis in Protein Overload Nephropathy
Authors: Liu Fu You , Li Ying , Peng You Ming , Ye Kun , Li Jun , Liu Ying-Hong , Duan Shao-Bin , Ling Guang-Hui , Xu Xiang-Qing , Zhou Le-Tian
Published: January 2008

Norcantharidin (NCTD), the demethylated analog of cantharidin isolated from Mylabris, is an anticancer drug routinely used against various human cancers in China. The aims of this study are to learn if NCTD has a protective action against severe proteinuria and consequent interstitial inflammation and fibrosis, and if the inhibition of nuclear factor-ĸB (NF-ĸB) and connective tissue growth factor (CTGF) by NCTD might be involved. Male Sprague-Dawley rats with protein overload nephropathy induced by intraperitoneally injected bovine serum albumin were used as a model. The histopathological examination of kidney tissue in the 9th week by light microscopy and scanning electron microscopy revealed that inflammatory cells had extensively infiltrated into the tubulointerstitial areas with interstitial fibrosis. The administration of NCTD at 0.1 mg/kg/day to the bovine-serum-albumin-injected animal models effectively reduced the proteinuria, and prevented the proteinuria-induced interstitial inflammation and fibrosis. Expressions of the NF-ĸB p65 subunit and CTGF, detected by immunohistochemistry, Western blotting and reverse-transcription polymerase chain reaction, were upregulated in protein overload nephropathy and were attenuated by NCTD. Inhibition of the expressions of the NF-ĸB p65 subunit and CTGF was one beneficial effect of NCTD. These results suggest that in addition to the antiproteinuric action of NCTD, due to its anti-inflammatory and antifibrotic effects as shown in the present study, it may become a therapeutic agent for proteinuria and its associated chronic inflammatory and fibrotic nephropathy.
Diagnostic Accuracy of Consensus Diagnostic Criteria for Frontotemporal Dementia in a Memory Clinic Population
Authors: Pijnenburg Yolande A.L. , Mulder Jacqueline L. , van Swieten John C. , Uitdehaag Bernard M.J. , Stevens Martijn , Scheltens Philip , Jonker Cees
Published: January 2008

Background/Aims: The goal of the present study was to evaluate the diagnostic accuracy of the core diagnostic criteria for frontotemporal dementia (FTD) [Neary D, et al: Neurology 1998;51:1546–1554] within a memory clinic population. Methods: The 5 core diagnostic criteria for FTD were operationalised in an informant-based written questionnaire. For a diagnosis of FTD the total clinical picture was weighted with findings on additional investigations and possible exclusion criteria, with follow-up of at least 1 year. Results: The operationalised core criteria for FTD had a sensitivity of 79% (95% CI = 57–92) and a specificity of 90% (95% CI = 85–94). Conclusion: The core diagnostic criteria for FTD applied in a caregiver questionnaire have good diagnostic accuracy among subjects without advanced dementia attending a memory clinic. This stresses the importance of the informant-based history in the differential diagnosis of dementia.
Resistance in Malignant Tumors: Can Resistance Assays Optimize Cytostatic Chemotherapy?
Authors: Lippert Theodor Hermann , Ruoff Hans-Jörg , Volm Manfred
Published: January 2008

The frequent resistance of malignant tumors to chemotherapy documents the fact that numerous patients are uselessly traumatized by highly toxic drugs. Investigations into this resistance have shown that many different mechanisms exist which can abolish the antitumor action of chemotherapeutics. So far, no safe method has been found to counteract this resistance. To date, the only way to avoid harm by an ineffective chemotherapeutic is to refrain from its use when resistance to it is detected. The present survey reports on the available assays that diagnose resistance reliably; sensitivity tests are excluded as being unreliable. Resistance assays are still not fully recognized in hospitals, despite the fact that they are able to optimize chemotherapy by eliminating treatment that is ineffective and merely harmful. Since the number of chemotherapeutics will increase enormously in the future, pharmacological cancer treatment cannot dispense with resistance assays.
Leukotriene D4 Upregulates MUC2 Gene Transcription in Human Epithelial Cells
Authors: Suzuki Shinya , Takeuchi Kazuhiko , Ishinaga Hajime , Basbaum Carol , Majima Yuichi
Published: January 2008

Background/Aims: Leukotriene (LT) D4 has been shown to induce mucus secretion in the airways. Excessive mucus secretion characterizes airway inflammatory disease such as asthma, allergic rhinitis. However, little is known about the effect of LTD4 on mucin gene expression. The aim of this study was to investigate the effect of LTD4 on MUC2 gene expression in cultured epithelial cells (HM3-MUC2 cells). Methods: HM3-MUC2 cells were treated with LTD4 for 2 or 6 h. Reporter gene assay was mainly used for analysis.MUC2 protein levels were measured using an enzyme-linked immunosorbent assay. Results: LTD4 significantly increased MUC2 gene transcriptional activity in a dose-dependent manner. Pranlukast, which is a selective antagonist of CysLT1 receptor, inhibited LTD4-induced MUC2 gene transcriptional activity in a dose-dependent manner. LTD4-induced MUC2 gene transcriptional activity was also suppressed by a G-protein inhibitor (pertussis toxin),a protein kinase C (PKC) inhibitor (bisindolylmaleimide), a mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor (PD98059), an extracellular signal regulated kinase-2 (ERK-2) inhibitor (AG126) and a nuclear factor ĸB (NF-ĸB) inhibitor. In addition, pranlukast inhibited LTD4-induced NF-ĸB activity. Conclusion: These results suggest that LTD4 upregulates MUC2 gene transcription via a signaling pathway involving CysLT1 receptor, G-protein, PKC, MEK, ERK and NF-ĸB.
Antidepressant-Like Effects of the Novel Kappa Opioid Antagonist MCL-144B in the Forced-Swim Test
Authors: Reindl J.D. , Rowan K. , Carey A.N. , Peng X. , Neumeyer J.L. , McLaughlin J.P.
Published: January 2008

Previous studies have demonstrated that kappa opioid receptor (KOR) antagonists reduce stress- and depression-like behaviors. We hypothesized that administration of a novel opioid mixed agonist/antagonist capable of antagonist activity at the KOR would attenuate forced-swim stress (FSS)-induced immobility, an animal model of depression-like behavior. C57Bl/6J mice were exposed to antinociceptive and repeated FSS testing after pretreatment with a graded dose of a novel bivalent morphinan compound, bis(N-cyclobutylmethylmorphinan-3-yl) sebacoylate dihydrochloride (MCL-144B). MCL-144B demonstrated dose- and time-dependent antinociception and KOR-mediated antagonism. In support of the hypothesis, pretreatment with MCL-144B dose-dependently attenuated stress-induced antinociception and immobility in the forced-swim test.
The Roles of PET and PET/CT in the Diagnosis and Management of Prostate Cancer
Authors: Takahashi Nobukazu , Inoue Tomio , Lee Jin , Yamaguchi Takako , Shizukuishi Kazuya
Published: January 2008

2-18F-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) imaging in prostate cancer is challenging because glucose utilization in well-differentiated prostate cancer is often lower than in other tumor types. Nonetheless, FDG-PET has a high positive predictive value for untreated metastases in viscera, but not lymph nodes. A positive FDG-PET can provide useful information to aid the clinician’s decision on future management in selected patients who have low prostate-specific antigen levels and visceral changes as a result of metastases. On the other hand, FDG-PET is limited in the identification of prostate tumors, as normal urinary excretion of radioisotope can mask pathological uptake. Moreover, there is an overlap in the degree of uptake between prostate cancer, benign prostatic hyperplasia and inflammation. The tracer choice is also important. 11C-choline has the advantage of reduced urinary excretion, and thus 11C-choline PET may provide more accurate information on the localization of main primary prostate cancer lesions than MRI or MR spectroscopy. 11C-choline PET is sensitive and accurate in the preoperative staging of pelvic lymph nodes in prostate cancer. A few studies are available but there were no PET or PET/CT studies with a large number of patients for tissue confirmation of prostate cancer; further investigations are required.
Metabolic Syndrome Pandemic
Authors: Grundy Scott M.
Published: January 2008

The metabolic syndrome is a multiplex risk factor that consists of several risk correlates of metabolic origin. In addition, to dyslipidemia, hypertension, and hyperglycermia, the syndrome carries a prothrombotic state and a proinflammatory state. Persons with the metabolic syndrome are at essentially twice the risk for cardiovascular disease compared with those without the syndrome. It further raises the risk for type 2 diabetes by about 5-fold. Although some investigators favor keeping risk factors separate for purposes of clinical management, others believe that identifying individuals with an aggregation of risk factors provides additional useful information to guide clinical management. In particular it focuses attention on obesity and sedentary life habits that are the root of the syndrome. This review addresses the prevalence of this clustering phenomenon throughout the world. Such seems appropriate because of the increasing prevalence of obesity in almost all countries. The available evidence indicates that in most countries between 20% and 30% of the adult population can be characterized as having the metabolic syndrome. In some populations or segments of the population, the prevalence is even higher. On the other hand, in parts of developing world in which young adults predominate, the prevalence is lower; but with increasing affluence and aging of the population, the prevalence undoubtedly with rise.
Association Between Cardiovascular Risk Profiles and the Presence and Extent of Different Types of Coronary Atherosclerotic Plaque as Detected by Multidetector Computed Tomography
Authors: Bamberg Fabian , Dannemann Nina , Shapiro Michael D. , Seneviratne Sujith K. , Ferencik Maros , Butler Javed , Koenig Wolfgang , Nasir Khurram , Cury Ricardo C. , Tawakol Ahmed , Achenbach Stephan , Brady Thomas J. , Hoffmann Udo
Published: January 2008

Objective—

To assess the association between cardiovascular risk factors and extent of noncalcified- (NCAP), mixed- (MCAP), and calcified coronary atherosclerotic plaque (CAP).

Methods and Results—

In this cross-sectional study, we included consecutive subjects who presented with chest pain but had no history of coronary artery disease (CAD) and did not develop acute coronary syndrome. Contrast-enhanced 64-slice coronary MDCT was performed to determine the presence of NCAP, MCAP, and CAP for each coronary segment. Among 195 patients (91 women, mean age: 54.6±12.0) exclusively NCAP was detected in 11 patients (5.6%). The extent of NCAP decreased and the extent of MCAP and CAP increased with age (
P
=0.06,
P
=0.02, and
P
=0.13, respectively). Hyperlipidemia and family history of CAD were associated with the extent of NCAP after adjusting for other risk factors (
P
=0.02 and
P
=0.04, respectively) or for the extent of MCAP and CAP (
P
=0.02 and
P
=0.05, respectively).

Conclusions—

Our data suggest that only a small proportion of individuals have exclusively NCAP and indicate that the relation of NCAP and CAP changes with age. Among individual risk factors, hyperlipidemia and family history of CAD may be associated with the extent of NCAP. Larger observational trials are necessary to confirm our findings.
Translational Therapeutics of Dipyridamole
Authors: Kim Hyung-Hwan , Liao James K.
Published: January 2008

Dipyridamole (DP) is a phosphodiesterase inhibitor that increases the intracellular levels of cyclic adenosine monophosphate (cAMP) and cyclic guanine monophosphate (cGMP) by preventing their conversion to AMP and GMP, respectively. By increasing cAMP and cGMP levels in platelets, DP reversibly inhibits platelet aggregation and platelet-mediated thrombotic disease. In addition, DP may potentiate some of the vascular protective effects of endothelium-derived nitric oxide (NO), which increases cGMP by stimulating soluble guanylyl cyclase. Endothelium-derived NO is an important regulator of vascular tone, blood flow, and tissue perfusion. Indeed, endothelial NO synthase-deficient (eNOS
−/−
) mice exhibit elevated systemic blood pressure and have larger myocardial and cerebral infarct size after ischemic injury. Other NO/cGMP-dependent effects that may be potentiated by DP include inhibition of vascular smooth muscle proliferation and prevention of endothelial-leukocyte interaction. In addition, DP increases local concentrations of adenosine and prostacyclin, which could affect vascular tone and inflammation. Finally, DP has antioxidant properties, which could stabilize platelet and vascular membranes as well as prevent the oxidation of low-density lipoprotein. These platelet and nonplatelet actions of DP may contribute to some of its therapeutic benefits in vascular disease.
Aspirin: Promise and Resistance in the New Millennium
Authors: Patrono Carlo , Rocca Bianca
Published: January 2008

Although conceived at the end of the 19th century, aspirin remains the gold standard of antiplatelet therapy. Approximately 100 randomized clinical trials have established its efficacy and safety in the prevention of myocardial infarction, ischemic stroke, and vascular death among high-risk patients treated for a few weeks, at one end of the spectrum, and in low-risk subjects treated up to 10 years at the other. Despite this wealth of data, several issues continue to be debated concerning the use of aspirin as an antiplatelet agent, and novel opportunities appear on the horizon for this 110-year-old drug. These issues include: (1) the optimal dose for cardiovascular prophylaxis; (2) the uncertain threshold of cardiovascular risk for its use in primary prevention; (3) the apparent gender-related difference in its cardioprotective effects; (4) the increasingly popular theme of aspirin “resistance”; (5) the opportunities of chemoprevention in colorectal cancer; and (6) the renewed interest in aspirin as an analgesic agent in osteoarthritic patients at high cardiovascular risk. The aim of this review is to address these issues by integrating our current understanding of the molecular mechanism of action of the drug with the results of clinical trials and epidemiological studies of aspirin as an antiplatelet drug.
Kindlin-2 Is an Essential Component of Intercalated Discs and Is Required for Vertebrate Cardiac Structure and Function
Authors: Dowling James J. , Gibbs Elizabeth , Russell Mark , Goldman Daniel , Minarcik Jeremy , Golden Jeffrey A. , Feldman Eva L.
Published: January 2008

Integrins and proteins that associate with integrins are implicated in normal cardiac muscle function and development. Unc-112 is a cytoplasmic adaptor protein required for the proper establishment of integrin junctions in
Caenorhabditis elegans
muscle. A vertebrate homolog of unc-112, kindlin-2, is an integrin-binding protein that is expressed in cardiac muscle, but its function is unknown. We sought to understand the role of kindlin-2 in the development and function of the mouse and zebrafish heart. In the mouse, we found that kindlin-2 is highly expressed in the heart and is enriched at intercalated discs and costameres. Targeted disruption of the murine kindlin-2 gene resulted in embryonic lethality before cardiogenesis. To better assess the role of kindlin-2 in cardiac muscle development, we used morpholinos to knockdown the kindlin-2 homolog in zebrafish (z-kindlin-2), which resulted in severe abnormalities of heart development. Morphant hearts were hypoplastic and dysmorphic and exhibited significantly reduced ventricular contractility. Ultrastructural analysis of these hearts revealed disrupted intercalated disc formation and a failure in the attachment of myofibrils to membrane complexes. We conclude that kindlin-2 is an essential component of the intercalated disc, is necessary for cytoskeletal organization at sites of membrane attachment, and is required for vertebrate myocardial formation and function. These findings provide the first characterization of the in vivo functions of this novel and critical regulator of cardiogenesis.
ADP Stimulates Human Endothelial Cell Migration via P2Y
1
Nucleotide Receptor–Mediated Mitogen-Activated Protein Kinase Pathways
Authors: Shen Jianzhong , DiCorleto Paul E.
Published: January 2008

Extensive research on the role of ADP in platelet activation led to the design of new anti-thrombotic drugs, such as clopidogrel (Plavix; sanofi-aventis); however, very little is known about the ADP-preferring nucleotide receptors (P2Y
1
, P2Y
12
, and P2Y
13
) in endothelium. Here, we show that ADP stimulates migration of cultured human umbilical vein endothelial cells (HUVECs) in both Boyden chamber and in vitro wound repair assays. This promigratory effect was mimicked by 2-MeSADP, but not by AMP, and was inhibited by MRS2179 (P2Y
1
receptor antagonist) but not by AR-C69931MX (P2Y
12/13
receptor antagonist). RT-PCR revealed abundant P2Y
1
, barely detectable P2Y
12
, and absent P2Y
13
receptor message in these cells. In addition, both ADP and 2-MeSADP, but not AMP, activated the mitogen-activated protein kinase pathways as evidenced by increased phosphorylation of extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK), and p38 kinase. ADP also stimulated phosphorylation of p90RSK, a downstream substrate of phosphorylated ERK1/2, and induced phosphorylation of such transcription factors downstream of the JNK and p38 pathways as c-Jun and activating transcription factor-2. These signaling events were inhibited by MRS2179 but not by AR-C69931MX. Furthermore, blockade of the ERK or JNK pathways by U0126 and SP600125, respectively, abolished ADP- and 2-MeSADP–stimulated HUVEC migration. However, inhibition of the p38 pathway by SB203580 partially suppressed ADP- and 2-MeSADP–induced HUVEC migration. We conclude that ADP promotes human endothelial cell migration by activating P2Y
1
receptor–mediated MAPK pathways, possibly contributing to reendothelialization and angiogenesis after vascular injury.
Occurrence and Clinical Impact of Microembolic Signals During or After Cardiosurgical Procedures
Authors: Dittrich Ralf , Ringelstein E. Bernd
Published: January 2008

Background and Purpose—

Microembolic signals (MESs) are detectable within the transcranial Doppler frequency spectrum downstream from vascular atherothrombotic or cardiothrombotic lesions. A frequent occurrence of MESs has also been shown during bypass surgery or after mechanical valve implantation. We sought to compile the knowledge on MES prevalence, the clinical impact of these cardiogenic MESs, and microemboli composition.

Summary of Review—

We performed a systematic MEDLINE search and summarized the currently available literature about MESs during or after cardiosurgical procedures for this state-of-the-art report.

Conclusions—

The nature of cardiogenic MESs is heterogeneous, and their prevalence is highly variable, reflecting their different origin from a broad spectrum of cardiosurgical conditions. The occurrence and number of MESs during cardiac catheterization and percutaneous coronary angioplasty seem to have a clinical impact but need to be explored further. In patients with prosthetic heart valves, in those with left ventricular assist devices, and during cardiac surgery, the occurrence of MESs has an important clinical impact, and MES monitoring has proven its reliability. Although the data encourage intensifying MES detection in cardiac disorders, their heterogeneous nature does not yet allow the use of MESs as a general surrogate parameter for neuronal damage or cardial thromboembolic risk.
A Systematic Review of Outcomes in Patients With Staged Carotid Artery Stenting and Coronary Artery Bypass Graft Surgery
Authors: Guzman Luis A. , Costa Marco A. , Angiolillo Dominick J. , Zenni Martin , Wludyka Peter , Silliman Scott , Bass Theodore A.
Published: January 2008

Background and Purpose—

Although current guidelines state that carotid endarterectomy is probably recommended before or concomitant to coronary artery bypass grafting (CABG) in patients with carotid stenosis,
s
ignificant controversies to this recommendation still persist. Carotid artery stenting has been recently introduced as an alternative revascularization modality in high-risk patients. The aim of this study was to define, based on the published information, if carotid artery stenting is beneficial in this setting.

Methods—

A search of MEDLINE and a manual search of the literature from selected articles were performed. A total of 6 studies with 277 patients reporting carotid stenting followed by staged CABG were available for this clinical outcome analysis. All were retrospective and single-center studies.

Results—

The mean age was 69 years; 78% were males. Asymptomatic carotid stenosis was present in 76% of patients. The mean time to CABG was 32 days. The incidence of stroke and death associated with the stent procedure was 4.7%. Only 6 patients (2.2%) developed stroke associated with CABG. The overall combined 30-day event rate after CABG, including all events during carotid artery stenting, were as follows: minor stroke, 2.9%; major stroke, 3.2%; mortality, 7.6%; and combined death and any stroke, 12.3%.

Conclusions—

In this pooled analysis, the combined incidence of death and stroke in patients undergoing carotid artery stenting and staged CABG remains elevated. These results confirm that the presence of carotid stenosis is per se a marker of risk that might persists independent of its treatment. A systematic or randomized evaluation appears warranted.