bluuebunny/crossref_metadata_2025 huggingface dataset:
Signalling activity of beta-catenin targeted to different subcellular compartments
Authors: HAGEN Thilo , SETHI Jaswinder K. , FOXWELL Neale , VIDAL-PUIG Antonio
Published: April 2004

β-Catenin plays a dual role as an adhesion molecule in adherens junctions at the plasma membrane and as a key intermediate in the canonical Wnt signalling pathway. The cytosolic soluble pool of β-catenin, involved in the transmission of the Wnt signal, is normally subjected to rapid protein degradation. On activation of the Wnt cascade, β-catenin becomes stabilized and then translocates into the nucleus where it co-activates transcription factors of the TCF (T-cell factor)/LEF (lymphoid enhancer factor) family. The expression of plasma membrane-targeted forms of β-catenin has been shown to also activate TCF/LEF-dependent transcription and different mechanisms have been put forward. In the present study, we have undertaken a systematic analysis of the signalling capability of non-degradable forms of β-catenin targeted to different cellular compartments. β-Catenin targeted to the plasma membrane activated transcription to a greater extent compared with non-targeted β-catenin, and led to a marked stabilization of cytosolic soluble β-catenin. These effects were independent of the competition with endogenous β-catenin for binding to E-cadherin at the plasma membrane, since targeting non-degradable β-catenin to other cellular compartments, i.e. the outer mitochondrial membrane and the endoplasmic reticulum membrane, also resulted in the accumulation of cytosolic wild-type β-catenin and activation of β-catenin-dependent signalling. In contrast, nuclear-targeted β-catenin was without significant effect on cytosolic wild-type β-catenin and did not activate transcription. Our results suggest that cytosolic accumulation of β-catenin is a prerequisite for the activation of TCF/LEF-dependent transcription in the nucleus.
Mechanisms of the interaction of nitroxyl with mitochondria
Authors: SHIVA Sruti , CRAWFORD Jack H. , RAMACHANDRAN Anup , CEASER Erin K. , HILLSON Tess , BROOKES Paul S. , PATEL Rakesh P. , DARLEY-USMAR Victor M.
Published: April 2004

It is now thought that NO• (nitric oxide) and its redox congeners may play a role in the physiological regulation of mitochondrial function. The inhibition of cytochrome c oxidase by NO• is characterized as being reversible and oxygen dependent. In contrast, peroxynitrite, the product of the reaction of NO• with superoxide, irreversibly inhibits several of the respiratory complexes. However, little is known about the effects of HNO (nitroxyl) on mitochondrial function. This is especially important, since HNO has been shown to be more cytotoxic than NO•, may potentially be generated in vivo, and elicits biological responses with some of the characteristics of NO and peroxynitrite. In the present study, we present evidence that isolated mitochondria, in the absence or presence of substrate, convert HNO into NO• by a process that is dependent on mitochondrial concentration as well as the concentration of the HNO donor Angeli's salt. In addition, HNO is able to inhibit mitochondrial respiration through the inhibition of complexes I and II, most probably via modification of specific cysteine residues in the proteins. Using a proteomics approach, extensive modification of mitochondrial protein thiols was demonstrated. From these data it is evident that HNO interacts with mitochondria through mechanisms distinct from those of either NO• or peroxynitrite, including the generation of NO•, the modification of thiols and the inhibition of complexes I and II.
Cardiac output by Portapres®
Authors: PITT Marjorie S. , MARSHALL Paul , DIESCH Jonathan P. , HAINSWORTH Roger
Published: April 2004

Portapres® derives continuous estimates of cardiac output from the peripheral pulse and has the potential to be an extremely valuable physiological and clinical tool. We assessed Portapres® estimates of cardiac output in healthy subjects at rest, during maximal treadmill exercise (n=8) and during decreases caused by orthostatic stress (n=8). Comparison with a rebreathing method indicated that Portapres® tended to overestimate cardiac output. The random errors of the estimates (precision), expressed as ±2 S.D. of the differences between paired estimates during steady states, ranged between 1.2 and 2.6 litres/min. We conclude that these errors indicate that the method is probably only useful for assessing changes in individual subjects where large changes are anticipated, as during exercise. When smaller changes occur, as during orthostasis, the errors preclude the use of individual subject data and only permit group average data to be examined.
Cardiac output by Modelflow® method from intra-arterial and fingertip pulse pressure profiles
Authors: KENFACK Marcel AZABJI , LADOR Federic , LICKER Marc , MOIA Christian , TAM Enrico , CAPELLI Carlo , MOREL Denis , FERRETTI Guido
Published: April 2004

Modelflow®, when applied to non-invasive fingertip pulse pressure recordings, is a poor predictor of cardiac output (Q, litre·min-1). The use of constants established from the aortic elastic characteristics, which differ from those of finger arteries, may introduce signal distortions, leading to errors in computing Q. We therefore hypothesized that peripheral recording of pulse pressure profiles undermines the measurement of Q with Modelflow®, so we compared Modelflow® beat-by-beat Q values obtained simultaneously non-invasively from the finger and invasively from the radial artery at rest and during exercise. Seven subjects (age, 24.0±2.9 years; weight, 81.2±12.6 kg) rested, then exercised at 50 and 100 W, carrying a catheter with a pressure head in the left radial artery and the photoplethysmographic cuff of a finger pressure device on the third and fourth fingers of the contralateral hand. Pulse pressure from both devices was recorded simultaneously and stored on a PC for subsequent Q computation. The mean values of systolic, diastolic and mean arterial pressure at rest and exercise steady state were significantly (P<0.05) lower from the finger than the intra-arterial catheter. The corresponding mean steady-state Q obtained from the finger (Qporta) was significantly (P<0.05) higher than that computed from the intra-arterial recordings (Qpia). The line relating beat-by-beat Qporta and Qpia was y=1.55x-3.02 (r2=0.640). The bias was 1.44 litre·min-1 and the precision was 2.84 litre·min-1. The slope of this line was significantly higher than 1, implying a systematic overestimate of Q by Qporta with respect to Qpia. Consistent with the tested hypothesis, these results demonstrate that pulse pressure profiles from the finger provide inaccurate absolute Q values with respect to the radial artery, and therefore cannot be used without correction with a calibration factor calculated previously by measuring Q with an independent method.
Analysis of the Defibrillation Efficacy for 5‐ms Waveforms
Authors: GUAN DONGXU , MALKIN ROBERT
Published: April 2004

Introduction: Empirical studies have shown that biphasic defibrillation waveforms are more efficacious than monophasic waveforms. However, a more systematic approach to waveform development might be more productive. This study tested 147 multiphasic waveforms uniformly sampled from all possible 5‐ms waveforms.

Methods and Results: One hundred ninety‐eight guinea pigs (850–1,050 g) received 30 episodes of ventricular fibrillation followed by transthoracic defibrillation. The first 10 shocks were used to determine the ED50 for a biphasic control. Then, 20 waveforms including 2 controls were tested once at the ED50. Of the 147 waveforms tested here, 21 waveforms showed equivalent or greater efficacies than the biphasic control, with one being statistically more efficacious (P < 0.05). Two fundamental assumptions were addressed: (1) similarly efficacious waveforms are analytically similar, and (2) a single optimal waveform can be described. The mean percentage of similarly efficacious waveforms with similar shapes was greater than zero in the most efficacious 21 waveforms (P = 0.023), but less efficacious waveforms showed randomly distributed shapes. Cluster analysis revealed that the best waveforms share a major phase containing most of the defibrillation energy. The optimal waveform shape extrapolated from the sample waveforms was a 2.5/1‐ms biphasic‐type waveform (highest correlation r = 0.701, P < 0.001).

Conclusion: This work supports the assumption that efficacious waveforms are similarly shaped and the notion that one single optimum exists. (J Cardiovasc Electrophysiol, Vol. 15, pp. 447‐454, April 2004)
Use of Double‐Potential Barrier to Identify Functional Isthmus at the Cavotricuspid Isthmus for Facilitating Catheter Ablation of Isthmus‐Dependent Atrial Flutter
Authors: LAI LING‐PING , LIN JIUNN‐LEE , LIN JIH‐MIN , DU CHAO‐CHENG , TSENG YUNG‐ZU , HUANG SHOEI K. STEPHEN
Published: April 2004

Introduction: The aim of the study was to identify an alternative target for more effective radiofrequency catheter ablation (RFCA) of isthmus‐dependent atrial flutter (AFL).

Methods and Results: We hypothesized that a functional isthmus formed by preexisting double potential barrier at the cavotricuspid isthmus (CTI) could serve as a new target site for facilitating RFCA of AFL. Forty‐three consecutive patients with recurrent isthmus‐dependent AFL were studied using three‐dimensional navigated magnetic mapping and ablation technique. Twenty patients (47%, group A) were shown to have a narrower functional channel at the CTI (functional isthmus). The remaining 23 patients did not have this feature (53%, group B). In group A, double potentials were clustered near the border of the inferior vena cava (IVC) of the CTI and served as a functional channel along the tricuspid annulus (TA). The interspike interval of double potentials was 87 ± 26 ms near the IVC border and 45 ± 17 ms (P < 0.0001) near the TA border of CTI. RFCA targeting at the functional isthmus in group A resulted in interruption of bidirectional transisthmus conduction with fewer radiofrequency pulses (6.7 ± 4.7 in group A vs 21.1 ± 17.1 pulses in group B, P < 0.001), shorter ablation line (11.6 ± 4.0 mm vs 37.8 ± 7.2 mm, P < 0.0001) with no arrhythmia recurrence. These functional isthmuses were found to be located at the lateral third of CTI in 12 patients, middle third in 7, and medial third in 1. This finding is different from that obtained by the conventional method in group B (lateral in 5, middle in 16, medial in 2, P < 0.038).

Conclusion: In our study, a functional, rather than anatomic, isthmus formed by preexisting double‐potential barrier at the CTI was identified in 47% of patients with isthmus‐dependent AFL. It is a useful guide to facilitate RFCA of isthmus‐dependent AFL. (J Cardiovasc Electrophysiol, Vol. 15, pp. 396‐401, April 2004)
Assessment of Pulmonary Vein Anatomic Variability by Magnetic Resonance Imaging:
Authors: MANSOUR MOUSSA , HOLMVANG GODTFRED , SOSNOVIK DAVID , MIGRINO RAYMOND , ABBARA SUHNY , RUSKIN JEREMY , KEANE DAVID
Published: April 2004

Introduction: Pulmonary vein (PV) isolation for atrial fibrillation (AF) currently is performed using either an ostial or an extra‐ostial approach. The objective of this study was to analyze by three‐dimensional (3D) magnetic resonance angiography (MRA) the anatomy of the PVs in order to detect structural variability that would impact the choice of ablation approach.

Methods and Results: Three‐dimensional MRA was performed in 105 patients undergoing PV isolation. The ostial diameter, branching pattern, and PV angulation were analyzed. Fifty‐nine (56%) patients had the typical pattern of 4 PVs with 4 separate ostia, 30 (29%) patients had an additional PV, and 18 (17%) patients had a left common PV trunk. In two patients, there were three right‐sided veins and a common left‐sided trunk, giving rise to four ostia: three on the right and one on the left. Two different populations of right middle PVs were noted: one where the additional vein projected anteriorly to drain the right middle lobe and one posterior to drain the superior portion of the right lower lobe. The average intrapatient variability in PV diameter was 7.9 ± 4.2 mm. The PV ostium was <10 mm in 26 (25%) patients and >25 mm in 15 (14%) patients. The first branch originated 6.7 ± 2.3 mm from the ostium. The left superior, right superior, right inferior, and left inferior PVs were found to enter the left atrium at the following angles: 32 ± 13°, 131 ± 11°, 206 ± 16°, and 329 ± 14°, respectively. Forty‐nine patients (47%) had at least one funnel shaped PV.

Conclusion: This largest PV imaging study to date demonstrates that MRA is a valuable tool that allows detection of marked intrapatient and interpatient anatomic variability of the PVs. These findings suggest that, at least in some patients, circumferential extra‐ostial left atrial encirclement of the PVs may be preferable to ostial PV isolation. These findings also may have significant implications on the future development of coil‐ and balloon‐based catheter ablation designs for AF ablation. (J Cardiovasc Electrophysiol, Vol. 15, pp. 387‐393, April 2004)
Effects of Systemic Steroid Treatment in Chronic Polypoid Rhinosinusitis Evaluated with Magnetic Resonance Imaging
Authors: Damm Michael , Jungehülsing Markus , Eckel Hans E. , Schmidt Matthias , Theissen Peter
Published: April 2004

BACKGROUND

The aim of this prospective study was to evaluate the efficacy of a combined (local and systemic) steroid therapy on the extent of chronic polypoid rhinosinusitis and patient symptoms.

METHODS AND PATIENTS

Subjects of this study were 20 patients with severe chronic polypoid rhinosinusitis with total or subtotal narrowing of the all sinuses. A nasal budesonide spray (2 × 0.1 mg/day) and an oral fluocortolone medication with a daily reduction during a 12‐day period (total dose: 560 mg = group 1) and a 20‐day period (total dose: 715 mg = group 2), respectively, were administered. Before and after the steroid treatment we evaluated the extent of the sinusitis with MRI and patient symptoms with symptom‐related questionnaires.

RESULTS

A significant reduction (>30%) of the chronic polypoid rhinosinusitis was observed in 50% of MRI findings. The steroid effect on polypoid masses was heterogeneous in different anatomic areas (maxillary sinus 40%, anterior ethmoid 19%, posterior ethmoid 33%, sphenoidal sinus 61%, frontal sinus 46%). Most sinusitis‐related symptoms were distinctly diminished in most patients (80%). No major side effects were observed.

CONCLUSIONS

A combined short‐term steroid therapy is highly effective in chronic polypoid rhinosinusitis, reducing the mucosal inflammation mainly in the large sinuses and reducing the incidence of symptoms significantly. However, this therapy was insufficient in the anterior ethmoid and cannot replace the current surgical treatment concept of the osteomeatal complex in CPR. The indication for such a short‐term steroid therapy is the preoperative treatment. It facilitates functional endoscopic sinus surgery by reducing the extent of surgical procedures, the time, and thereby the risks of sinus surgery. (Otolaryngol Head Neck Surg 1999;120:517‐23.)
Relationship of the Posterior Cricoarytenoid Muscle to the Posterior Cricoid Lamina
Authors: Goding George S. , Bierbaum Ralph W.
Published: April 2004

OBJECTIVE

Early experiments in functional electrical stimulation of the posterior cricoarytenoid muscle (PCA) in human beings have involved placement of the electrode along the undersurface of the PCA. The anatomy of the posterior cricoid lamina (PCL) was examined to obtain a quantitative understanding of this region.

METHODS

Thirty fresh‐frozen cadaver larynges were dissected. Measurements of the cricoid cartilage and PCA were obtained with a caliper or calibrated probe.

RESULTS

Twenty male and 10 female adult larynges were examined. Sex differences were found for the height of the PCL. All larynges had approximately 4 mm of exposed cartilage along the inferior surface of the PCL. The origin of the PCA on the PCL was thinner in the medial‐vertical attachment than in the inferior‐horizontal. The average inferolateral to superomedial diagonal width of the PCA was 4 mm greater in the male than in the female larynges. Asymmetry between the left and right sides was seen.

CONCLUSIONS

The PCA can be divided into 2 muscle groups based on its origin on the PCL as well as its insertion into the muscular process of the arytenoid. The quantitative information obtained has implications for electrode design and placement for laryngeal stimulation. (Otolaryngol Head Neck Surg 1999;120:493‐8.)
Use of a Revascularized, Tubed Costal Myoperiosteal Graft for Repair of Circumferential, Segmental Tracheal Defects
Authors: Hoff Paul T. , Esclamado Ramon M.
Published: April 2004

Reconstruction of extensive laryngotracheal stenosis continues to pose a significant surgical challenge. Previous work in our laboratory has demonstrated the utility of vascularized perichondrium for reconstruction of cervical tracheal defects in a rabbit model. Because most potential vascularized donor sites in human beings are periosteal, it was important to demonstrate that vascularized periosteum was also useful for laryngotracheal reconstruction in a larger animal model. We therefore performed a 2‐stage reconstruction of a circumferential, segmental cervical tracheal defect using a revascularized, tubed myoperiosteal graft in a canine model (n = 8). A rigid, patent tube was produced in 6 animals (75%) after completion of the first stage (7 to 10 weeks). After transfer of the vascularized free graft to the tracheal defect, 5 of 6 animals survived from 4 to 18 weeks. Severe stenosis (<90%) was present in 2 animals, and moderate stenosis (40% to 60%) was present in the remaining 3 animals. One animal was observed for 18 weeks and was found to have a 40% circumferential stenosis at autopsy. Light microscopy revealed exuberant bone proliferation in all specimens. Unrestrained osteogenesis may limit the utility of vascularized periosteum in reconstruction of extensive tracheal defects.
Role of Screening Chest Computed Tomography in Patients with Advanced Head and Neck Cancer
Authors: Tan Luke K. S. , Greener Christopher C. , Seikaly Hadi , Rassekh Christopher H. , Calhoun Karen H.
Published: April 2004

OBJECTIVE

The presence of pulmonary metastases significantly alters the treatment of patients with head and neck cancers. Currently, a chest radiograph (CXR) is used as a screening examination, although a chest CT (CCT) can detect smaller lesions. The aim of this study was to evaluate the benefit of CCT as a screening tool in patients with newly diagnosed advanced head and neck cancers.

METHOD

New patients with stage III and IV head and neck squamous cell carcinomas were enrolled in this prospective study from August 1994 to December 1995. Twenty‐five patients underwent CXR ($71) and CCT ($597) within 2 weeks of diagnosis of the index cancer.

RESULTS

In 20 patients neither the CXR nor the CCT showed any evidence of pulmonary malignancy. Two patients had normal CXRs but possible metastases on CCT. Both the pulmonary lesions resolved on follow‐up evaluation. Two patients had suspicious lesions on CXR, 1 of whom had a normal CCT. The second patient underwent CT‐guided biopsy which was negative for malignancy. Both the CXR and CCT of the final patient, who had a bronchogenic carcinoma, were suspicious.

CONCLUSION

In 2 patients CCT detected suspicious lesions missed on CXR, although neither revealed malignancy. Three patients with suspicious CXRs would have had CCTs anyway. Thus 22 of 25 CCTs done at the additional cost of $13,314 did not add to the sensitivity of the screening for pulmonary metastasis or second lung primary.
Laser Surgery for Allergic Rhinitis: The Effect on Seromucinous Glands
Authors: Elwany Samy , Salaam Sedik Abel
Published: April 2004

Ten patients with perennial allergic rhinitis were subjected to CO2 laser turbinectomy. Tiny (1 mm3) biopsy specimens were taken at the time of surgery and 1 month thereafter. The biopsy specimens were processed for transmission electron microscopy. Also, the activity of succinic dehydrogenase and cholinesterase enzymes was measured. The study showed that laser turbinectomy was followed by reduction in the number and activity of the glandular acini in the laser‐treated areas. This reduction is ascribed to the local destructive effect of laser energy on the glandular acini and on the surrounding cholinergic nerve fibers. The enzymatic activity of the cholinergic nerve fibers themselves, however, did not diminish, indicating that laser surgery has no inhibitory effect on the local allergic reaction.
Exophytic and Papillary Squamous Cell Carcinomas of the Larynx: A Clinicopathologic Series of 104 Cases
Authors: Thompson Lester D. R. , Wenig Bruce M. , Heffner Dennis K. , Gnepp Douglas R.
Published: April 2004

Exophytic and papillary squamous cell carcinomas (SCCs) are uncommon variants of SCC of the upper aerodigestive tract mucosa. The histomorphologic distinction between these variants has not been previously attempted or correlated with prognostic outcome. One hundred four cases of exophytic and papillary SCCs of the larynx were identified in the files of the Armed Forces Institute of Pathology from 1971 to 1991. The patients included 25 women and 79 men, aged 27 to 89 years (average 60.7 years). Patients had hoarseness at presentation, and many patients were using tobacco (n = 87) and/or alcohol (n = 49). Tumors measured up to 6 cm in greatest dimension. The larger tumors were associated with vocal cord impairment (n = 39). Histologically, the SCCs were divided into 2 growth patterns: papillary‐frond (n = 12) or broad‐based, exophytic (n = 92). Patients were treated with excisional biopsy, vocal cord stripping, and/or laryngectomy, in conjunction with radiation therapy (n = 70). Eighty‐seven patients had no evidence of disease at last follow‐up (average follow‐up 8.6 years). Seventeen patients with an exophytic pattern died with disease (10 disseminated disease; 7 local disease). No patients with papillary patterns died of disease, although there had been 4 recurrences. In conclusion, patients with papillary and exophytic SCCs have a better prognosis than those with conventional SCCs, and the prognosis for those with papillary SCCs is even better.
Endoscopic Septoplasty: Indications, Technique, and Results
Authors: Hwang Peter H. , Mclaughlin Robert B. , Lanza Donald C. , Kennedy David W.
Published: April 2004

Endoscopic septoplasty is an attractive alternative to traditional “headlight” approaches to septoplasty. The primary advantage of the technique is the ability to reduce morbidity and postoperative swelling in isolated septal deviations by limiting the dissection to the area of the deviation. This ability to markedly reduce the extent of subperichondrial dissection is particularly valuable in patients who have undergone prior septal cartilage resection. Other advantages include improved visualization, particularly in posterior septal deformities; improved surgical transition between septoplasty and sinus surgery; and its use as an effective teaching tool. We present our experience with endoscopic septoplasty in a series of 111 patients. Surgical indications, technique, and complications are discussed.
Current Evaluation and Treatment of Patients with Swallowing Disorders
Authors: Broniatowski Michael , Sonies Barbara C. , Rubin John S. , Bradshaw Charles R. , Spiegel Joseph R. , Bastian Robert W. , Kelly James H.
Published: April 2004

To determine the varied causes of oropharyngeal dysphagia and their respective pathophysiology, a working understanding of the normal anatomy and function of the highly integrated mechanism of swallowing is outlined. This information is presented as the basis for a reasoned and detailed approach to the history, physical examination, and endoscopic evaluation of normal and altered oropharyngeal swallowing. The management of swallowing disorders depends on the nature and magnitude of the responsible clinical condition. Conservative and surgical approaches are discussed. These modalities and their indications are described in detail. (Otolaryngol Head Neck Surg 1999;120:464‐73.)
In Vivo Resistance to Bacterial Biofilm Formation on Tympanostomy Tubes as a Function of Tube Material
Authors: Saidi Iyad S. , Biedlingmaier John F. , Whelan Philip
Published: April 2004

Adherent bacterial biofilms have been implicated in the irreversible contamination of implanted medical devices. We evaluated the resistance of various tympanostomy (pressure equalization [PE]) tube materials to biofilm formation using an in vivo model. PE tubes of silicone, silver oxide‐impregnated silicone, fluoroplastic, silver oxide‐impregnated fluoroplastic, and ion‐bombarded silicone were inserted into the tympanic membranes of 18 Hartley guinea pigs. Staphylococcus aureus was then inoculated into the middle ears. An additional 8 guinea pigs were used as controls; the PE tubes were inserted without middle ear inoculation. All PE tubes were removed on day 10 and analyzed for bacterial contamination using culture, immunofluorescence, and scanning electron microscopy (SEM). All infected ears developed otitis media with otorrhea, but none of the animal control ears drained. Fluorescence imaging of the animal control tubes showed large cellular components consistent with inflammation. The infected tubes showed heavy DNA fluorescence consistent with bacteria and inflammatory cells. All animal control tubes except the ion‐bombarded silicone tubes showed adherent inflammatory film on SEM. Also, all tubes placed in infected ears except the ion‐bombarded silicone tubes showed adherent bacterial and inflammatory films on SEM. Nonadherent surface properties such as the ion‐bombarded silicone may be helpful in preventing chronic PE tube contamination.
Radiofrequency Tongue Base Reduction in Sleep‐Disordered Breathing: A Pilot Study
Authors: Powell Nelson B. , Riley Robert W. , Guilleminault Christian
Published: April 2004

OBJECTIVE

This pilot study investigates the new technology of radiofrequency energy (RFe), as applied to the tongue base, for the purpose of assessing feasibility, safety, and possible efficacy in the treatment of sleep‐disordered breathing (SDB).

METHODS

Eighteen patients with SDB, in whom at least palatopharyngoplasty had failed, were entered in this study. The mean respiratory disturbance index was 39.6, with a mean nadir oxygen (SaO2) of 81.9%. A radiofrequency electrode delivered energy to the subsurface tongue base with local anesthetic. Polysomnography, quantitative speech and swallowing studies, questionnaires, and visual analog scales were used to assess outcomes. MRI assessed changes in tongue volume.

RESULTS

Separate RFe treatments (mean 5.5) at 4‐week intervals were given (mean 1543 J for 9 minutes at 80°C), for a mean energy total of 8490 J per patient. The posttreatment mean respiratory disturbance index was 17.8, and the SaO2 nadir was 88.3%. Weight increased slightly; speech and swallowing did not change. Questionnaires and visual analog scale scores showed improvement in study variables. Tongue volume was reduced by a mean of 17%. Pain was controlled by hydrocodone for 3 to 4 days. One infection was seen and resolved with incision and drainage.

CONCLUSION

This pilot study demonstrates feasibility, safety, and efficacy in reducing tongue volume using RFe. Additional cumulative energy may improve the cure rate for SDB.

The application of radiofrequency energy (RFe) for medical and surgical purposes has been extensively researched in the past.1–4 We have recently applied these basic RFe principles to 3 consecutive investigations, which included 1 animal tongue model5 and 2 human airway models (palate and turbinates).6,7 These studies were done to specifically evaluate the biophysics and safety of RFe and to establish a scientific basis for the application of RFe to the human tongue in sleep‐disordered breathing (SDB). The primary goal of this pilot investigation was to evaluate whether RFe could, in those with SDB and hypopharyngeal obstruction, reduce tongue volume and possibly improve SDB.
What Explains the Uneven Take-Up of ISO 14001 at the Global Level? A Panel-Data Analysis
Authors: Neumayer Eric , Perkins Richard
Published: April 2004

Since its release in the mid-1990s, close to 37 000 facilities have been certified to ISO 14001, the international voluntary standard for environmental management systems. Yet, despite claims that the standard can be readily adapted to very different corporate and geographic settings, its take-up has been highly geographically variable. This paper contributes to a growing body of work concerned with explaining the uneven diffusion of ISO 14001 at the global level. Drawing from the existing theoretical and empirical literature we develop a series of hypotheses about how various economic, market, and regulatory factors influence the national count of ISO 14001 certifications. These hypotheses are then tested using econometric estimation techniques with data for a panel of 142 developed and developing countries. We find that per capita ISO 14001 counts are positively correlated with income per capita, stock of foreign direct investment, exports of goods and services to Europe and Japan, and pressure from civil society. Conversely, productivity and levels of state intervention are negatively correlated. The paper finishes by offering a number of recommendations to policymakers concerned with accelerating the diffusion of voluntary environmental standards.
The Use of Modal Accessibility Gap as an Indicator for Sustainable Transport Development
Authors: Kwok Rebecca C W , Yeh Anthony G O
Published: April 2004

Transport plays an important role in sustainable development because it uses a lot of energy. In order to plan for sustainable transport development, there is a need to develop indicators for assessing and monitoring transport development. In this paper we develop a sustainable transport development indicator by making use of the concepts of accessibility and geographical information systems. A modal accessibility gap index is proposed, which is calculated by finding the difference between the accessibility indices of public and private transport, which are in turn determined by accessibilities to opportunities such as the number of population, jobs, shops, and schools by public and private transport. Considering energy-efficiency, public transport will achieve sustainable transport more than private transport. A higher accessibility gap may mean more sustainable development. In the present study, the accessibility gap of Hong Kong in 1991 is compared with that in 1996 to examine whether transport development has been more sustainable. We also discuss how to use the accessibility gap indicator to test land-use and transport-development policies and scenarios to determine the more sustainable ones.
Health-Related Environmental Indices and Environmental Equity in England and Wales
Authors: Wheeler Benedict W
Published: April 2004

This study developed small-area health-related environmental indices for England and Wales in the context of an investigation into socioeconomic inequity in the distribution of environmental risk. Selection of environmental hazards, relevant datasets, and their attribution to standard small-area geography using a geographic information system are described. Four indices for 1991 Census wards are proposed, relating to ambient air quality, atmospheric chemical releases from large-scale industrial processes, landfills, and sites registered under Control of Major Accident Hazard regulations. Ecological measures of association between these indices and the Carstairs material deprivation index and its components are presented in the context of variations by urban–rural status. Based on these analyses, the study generally supports previous findings of environmental inequity in England and Wales, but highlights that associations are dependent on the environmental and deprivation measures under consideration, and urban–rural context. It is proposed that environmental indices such as those described here should be included in considerations of area deprivation, could assist with equitable environmental decisionmaking and planning, and that measures of environmental inequity could be considered as indicators of progress towards sustainable development.
Estimation of Lifted Weight and Produced Effort through Perception of Point-Light Display
Authors: Shim Jaeho , Carlton Les G , Kim Jitae
Published: April 2004

It has been shown that human observers can estimate the weight of a box from the observation of a point-light display of a lifting motion. We asked observers to report the weight of the box and the effort produced by five lifters ranging in size and strength to determine if observers can perceive lifter size. In experiment 1, five or six weights from each of five lifters were shown to fourteen observers in a random order. Observers showed less error in estimating the amount of effort each lifter produced than in estimating the actual weight of the box. In experiment 2, the lifters were presented individually to forty observers to remove any effect observing a previous lift might have had on estimating the subsequent lift by a different lifter. The results showed an improvement in estimated weight but not in estimated effort. In experiment 3, the actual size of the lifters was given to thirty-four observers, and the estimations of both weight and effort improved. In experiment 4, observers did not improve when observing practice trials and estimating either only weight or only effort. The results from the four experiments suggest that observers are more sensitive to lifter's effort than to the weight lifted, and that observers tend to use changes in the velocity profile of the lift when making their estimates.
Visual and Haptic Discrimination of Symmetry in Unfamiliar Displays Extended in the z-Axis
Authors: Ballesteros Soledad , Reales José M
Published: April 2004

We investigated, in two experiments, the discrimination of bilateral symmetry in vision and touch using four sets of unfamiliar displays. They varied in complexity from 3 to 30 turns. Two sets were 2-D flat forms (raised-line shapes and raised surfaces) while the other two were 3-D objects constructed by extending the 2-D shapes in height (short and tall objects). Experiment 1 showed that visual accuracy was excellent but latencies increased for raised-line shapes compared with 3-D objects. Experiment 2 showed that unimanual exploration was more accurate for asymmetric than for symmetric judgments, but only for 2-D shapes and short objects. Bimanual exploration at the body midline facilitated the discrimination of symmetric shapes without changing performance with asymmetric ones. Accuracy for haptically explored symmetric stimuli improved as the stimuli were extended in the third dimension, while no such a trend appeared for asymmetric stimuli. Unlike vision, haptic response latency decreased for 2-D shapes compared with 3-D objects. The present results are relevant to the understanding of symmetry discrimination in vision and touch.
Confusion of Space and Time in the Flash-Lag Effect
Authors: Kreegipuu Kairi , Allik Jüri
Published: April 2004

The apparent lagging of a short flash in the relation to a moving object, the flash-lag effect (FLE), has so far been measured mainly in terms of illusory spatial offset. We propose a method of measuring the perceived temporal asynchrony of the FLE separately from its perceived spatial offset. We presented a moving stimulus that changed its colour at a certain moment. The observer indicated, in two different tasks, where and when the colour change occurred in relation to a stationary reference flash. Results show that the perceived time of the colour change was not congruent with the perceived location of the colour change: the colour change is perceived simultaneously with the flash, but is shifted in position. The presentation of the reference in the form of a flash is not critical for the occurrence of the FLE, because the same effect was obtained with a constantly visible reference signal, the position of which or time when it changed its colour were varied. The observer was not able to ignore the irrelevant dimension of the reference signal: the apparent time of the colour change was influenced by the position of the reference signal, and the apparent location of the colour change was influenced by the presentation time of the reference signal. The observer's inability to separate the spatial and temporal aspects of the moving stimulus clearly imposes certain limits on theories that are attempting to explain the FLE exclusively in terms of the perceived space and time.
Gender Differences in Perception of Self-Orientation: Software or Hardware?
Authors: Tremblay Luc , Elliott Digby , Starkes Janet L
Published: April 2004

We evaluated the contribution of attentional strategy to the perception of self-orientation with and without a body tilt in the median plane. Reinking et al (1974 Journal of Personality and Social Psychology30 807–811) found that the frame dependence of females on the rod-and-frame test could be mediated by instructions prompting them to focus on internal cues (ie arising from inside of the body). Here, we measured the influence of attentional instructions on the perception of the morphological horizon. Eleven females and thirteen males estimated their morphological horizon in an upright and a 45° body tilt in the median plane under three instruction conditions. All participants first performed without attentional instructions. Then, participants performed under both internal and external attentional instructions. For females, but not for males, perception of morphological horizon was more footward in the supine than in the upright orientation. Although instructions did not eliminate gender differences, internal instructions allowed females to reduce their perceptual bias in the supine orientation.
Oscillation of functions with a spectral gap
Authors: Eremenko A. , Novikov D.
Published: April 2004

We prove an old conjecture on oscillation of functions that have a spectral gap at the origin. Suppose that the Fourier transform of a real measure
f
on the real line satisfies
f̂(x)
=
0
for
x
∈ (–
a, a
). Then, when
r
→ ∞, the asymptotic lower density of the sequence of sign changes of
f
on the intervals [0,
r
) is at least
a
/π. This still holds for some wider classes of measures characterized by their rate of growth at infinity, but if the growth is faster than a certain threshold, the above statement is no longer true.
Catalytic asymmetric synthesis of all-carbon quaternary stereocenters
Authors: Douglas Christopher J. , Overman Larry E.
Published: April 2004

Only a few catalytic asymmetric C—C bond-forming reactions have been shown to be useful for constructing all-carbon quaternary stereocenters. This Perspective examines the current state of such methods.
Desymmetrization of enone-diones via rhodium-catalyzed diastereo- and enantioselective tandem conjugate addition-aldol cyclization
Authors: Bocknack Brian M. , Wang Long-Cheng , Krische Michael J.
Published: April 2004

Catalytic tandem conjugate addition-enolate trapping represents an effective strategy for the design of catalytic transformations that enable formation of multiple C—C bonds. Recently, using enantioselective rhodium-catalyzed conjugate addition methodology, we developed a catalytic tandem conjugate addition-aldol cyclization of keto-enones. Here, we report related desymmetrizations and parallel kinetic resolutions involving the use of diones as terminal electrophiles. The Rh-enolate generated on enone carbometallation effectively discriminates among four diastereotopic π-faces of the appendant dione, ultimately providing products that embody four contiguous stereocenters, including two adjacent quaternary centers, with quantitative diastereoselection and high levels of enantiomeric excess. This methodology allows concise entry to optically enrichedseco-B ring steroids possessing a 14-hydroxy cis-fused C-D ring junction, as found in naturally occurring cardiotonic steroids derived from digitalis.
Catalytic asymmetric reactions for organic synthesis: The combined C—H activation/Cope rearrangement
Authors: Davies Huw M. L. , Jin Qihui
Published: April 2004

The development of new catalytic asymmetric reactions can lead to exciting new strategies for organic synthesis. This article describes the synthetic utility of the combined C—H activation/Cope rearrangement, achieved by dirhodium tetraprolinate-catalyzed reaction of vinyldiazoacetates with compounds containing allylic C—H bonds. The transformation is highly diastereoselective and enantioselective. The product distribution, however, is highly substrate dependent, the major side products being either direct C—H activation or cyclopropanation.
Forces generated during actin-based propulsion: A direct measurement by micromanipulation
Authors: Marcy Yann , Prost Jacques , Carlier Marie-France , Sykes Cécile
Published: April 2004

Dynamic actin networks generate forces for numerous types of movements such as lamellipodia protrusion or the motion of endocytic vesicles. The actin-based propulsive movement of
Listeria monocytogenes
or of functionalized microspheres have been extensively used as model systems to identify the biochemical components that are necessary for actin-based motility. However, quantitative force measurements are required to elucidate the mechanism of force generation, which is still under debate. To directly probe the forces generated in the process of actin-based propulsion, we developed a micromanipulation experiment. A comet growing from a coated polystyrene bead is held by a micropipette while the bead is attached to a force probe, by using a specially designed “flexible handle.” This system allows us to apply both pulling and pushing external forces up to a few nanonewtons. By pulling the actin tail away from the bead at high speed, we estimate the elastic modulus of the gel and measure the force necessary to detach the tail from the bead. By applying a constant force in the range of –1.7 to 4.3 nN, the force–velocity relation is established. We find that the relation is linear for pulling forces and decays more weakly for pushing forces. This behavior is explained by using a dimensional elastic analysis.
Stereoselective terminal functionalization of small peptides for catalytic asymmetric synthesis of unnatural peptides
Authors: Maruoka Keiji , Tayama Eiji , Ooi Takashi
Published: April 2004

The asymmetric phase-transfer catalytic alkylation of peptides has been achieved by the use of designed
C
2
-symmetric chiral quaternary ammonium bromide 1 as catalyst. Excellent stereoselectivities were uniformly observed in the alkylation with a variety of alkyl halides and the efficiency of the transmission of stereochemical information was not affected by the side-chain structure of the preexisting amino acid residues. This method also enables an asymmetric construction of noncoded α,α-dialkyl-α-amino acid residues at the peptide terminal. Since this chirality can be efficiently transferred to the adjacent amino acid moiety, our approach provides a general procedure not only for the highly stereoselective terminal functionalization of peptides but also for the sequential asymmetric construction of unnatural oligopeptides, which should play a vital role in the peptide-based drug discovery process.
Small potassium ion channel proteins encoded by chlorella viruses
Authors: Kang Ming , Moroni Anna , Gazzarrini Sabrina , DiFrancesco Dario , Thiel Gerhard , Severino Maria , Van Etten James L.
Published: April 2004

Kcv, a 94-aa protein encoded by
Paramecium bursaria
chlorella virus 1, is the smallest known protein to form a functional potassium ion channel and basically corresponds to the “pore module” of potassium channels. Both viral replication and channel activity are inhibited by the ion channel blockers barium and amantadine but not by cesium. Genes encoding Kcv-like proteins were isolated from 40 additional chlorella viruses. Differences in 16 of the 94 amino acids were detected, producing six Kcv-like proteins with amino acid substitutions occurring in most of the functional domains of the protein (N terminus, transmembrane 1, pore helix, selectivity filter, and transmembrane 2). The six proteins form functional potassium selective channels in
Xenopus
oocytes with different properties including altered current kinetics and inhibition by cesium. The amino acid changes together with the different properties observed in the six Kcv-like channels will be used to guide site-directed mutations, either singularly or in combination, to identify key amino acids that confer specific properties to Kcv.
RETRACTED: Mutations in the G-quadruplex silencer element and their relationship to c-MYC overexpression, NM23 repression, and therapeutic rescue
Authors: Grand Cory L. , Powell Tiffanie J. , Nagle Raymond B. , Bearss David J. , Tye Denise , Gleason-Guzman Mary , Hurley Laurence H.
Published: April 2004

We have demonstrated that a parallel G-quadruplex structure in the c-
MYC
promoter functions as a transcriptional repressor element. Furthermore, a specific G-to-A mutation in this element results in destabilization of the G-quadruplex repressor element and an increase in basal transcriptional activity. To validate this model in an
in vivo
context, we have examined the sequence of this region in human colorectal tumors and the surrounding normal tissue. We have found that ≈30% of tumors contain one of two specific G-to-A mutations, not present in the surrounding normal tissue, that destabilize the parallel G-quadruplex, which would be expected to give rise to abnormally high expression of c-
MYC
in these cells. In contrast, G-quadruplex-disruptive mutations were absent in 20 colon adenomas, suggesting that these mutations occur late in tumorigenesis. We have also demonstrated that these same mutations are found in established colorectal cell lines. NM23-H2 levels are lower in cancer tissues and cell lines that harbor these mutations. In cells with repressed levels of NM23-H2, the mutated and destabilized G-quadruplex silencer element can be reinstated by the addition of G-quadruplex-stabilizing compounds, providing an opportunity for therapeutic intervention for patients carrying these mutations.
Masking of CD22 by cis ligands does not prevent redistribution of CD22 to sites of cell contact
Authors: Collins Brian E. , Blixt Ola , DeSieno Alexis R. , Bovin Nicolai , Marth Jamey D. , Paulson James C.
Published: April 2004

CD22, a negative regulator of B cell signaling, is a member of the siglec family that binds to α2-6-linked sialic acids on glycoproteins. Previous reports demonstrated that binding of multivalent sialoside probes to CD22 is blocked, or “masked,” by endogenous (cis) ligands, unless they are first destroyed by sialidase treatment. These results suggest that cis ligands on B cells make CD22 functionally unavailable for binding to ligands in trans. Through immunofluorescence microscopy, however, we observed that CD22 on resting B cells redistributes to the site of contact with other B or T lymphocytes. Redistribution is mediated by interaction with trans ligands on the opposing cell because it does not occur with ligand-deficient lymphocytes from ST6GalI-null mice. Surprisingly, CD45, proposed as both a cis and trans ligand of CD22, was not required for redistribution to sites of cell contact, given that redistribution of CD22 was independent of CD45 and was observed with lymphocytes from CD45-deficient mice. Furthermore, CD45 is not required for CD22 masking as similar levels of masking were observed in the WT and null mice. Comparison of the widely used sialoside–polyacrylamide probe with a sialoside–streptavidin probe revealed that the latter bound a subset of B cells without sialidase treatment, suggesting that cis ligands differentially impacted the binding of these two probes in trans. The combined results suggest that equilibrium binding to cis ligands does not preclude binding of CD22 to ligands in trans, and allows for its redistribution to sites of contact between lymphocytes.