bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression and secretion of human apolipoprotein A‐I in the heart
Authors: Baroukh Nadine , Lopez Camilo E , Saleh Maria-Carla , Recalde Delia , Vergnes Laurent , Ostos Maria A , Fiette Laurence , Fruchart Jean-Charles , Castro Graciela , Zakin Mario M , Ochoa Alberto
Published: December 2003

Various studies have correlated apolipoprotein (apo) A‐I, the major component high‐density lipoprotein, with protection against development of cardiovascular disease. Although apoA‐I expression has been previously detected in the liver and intestine, we have discovered that the human apoA‐I gene is also expressed in the heart. Using transgenic (Tg) mice generated with the human apoA‐I/C‐III/A‐IV gene cluster and Tg mice produced with just the 2.2 kb human apoA‐I gene, we have detected significant levels of apoA‐I expression in the heart. Furthermore, the detection of apoA‐I expression in the hearts of human apoA‐I Tg mice indicates that the minimal regulatory elements necessary for cardiac expression of the gene are located near its coding sequence. To determine if the apoA‐I gene is also expressed in the human heart, similar analyses were performed, where apoA‐I expression was found in both adult and fetal hearts. Furthermore in‐depth investigation of the various regions of human and Tg mouse hearts revealed that the apoA‐I mRNA was present in the ventricles and atria, but not in the aorta. In situ hybridization of Tg mouse hearts revealed that apoA‐I expression was restricted to the cardiac myocyte cells. Finally, heart explants and cardiac primary culture experiments with Tg mice showed secretion of particles containing the human apoA‐I protein, and metabolic labeling experiments have also detected a 28 kDa human apoA‐I protein secreted from the heart. From these novel findings, new insights into the role and function of apoA‐I can be extrapolated.
Blockade of v‐Src‐stimulated tumor formation by the Src homology 3 domain of Crk‐associated substrate (Cas)
Authors: Cheng Chi-Hung , Yu Kuo-Ching , Chen Hsin-Ling , Chen Shu-Yi , Huang Chi-Hui , Chan Po-Chao , Wung Chiung-Wha , Chen Hong-Chen
Published: December 2003

Crk‐associated substrate (Cas) is highly phosphorylated by v‐Src and plays a critical role in v‐Src‐induced cell transformation. In this study, we found that the Src homology (SH) 3 domain of Cas blocked v‐Src‐stimulated anchorage‐independent cell growth, Matrigel invasion, and tumor growth in nude mice. Biochemical analysis revealed that the Cas SH3 domain selectively inhibited v‐Src‐stimulated activations of AKT and JNK, but not ERK and STAT3. Attenuation of the AKT pathway by the Cas SH3 domain rendered v‐Src‐transformed cells susceptible to apoptosis. Inhibition of the JNK pathway by the Cas SH3 domain led to suppression of v‐Src‐stimulated invasion. Taken together, our results indicate that the Cas SH3 domain has an anti‐tumor function, which severely impairs the transforming potential of v‐Src.
The systemic inflammatory response syndrome in acute liver failure
Authors: Rolando Nancy , Wade Jim , Davalos Milagros , Wendon Julia , Philpott-Howard John , Williams Roger
Published: December 2003

The systemic inflammatory response syndrome (SIRS) in acute liver failure (ALF), in which infection is common, has not been studied. In this study, SIRS components were recorded on admission and during episodes of infection, in 887 ALF patients admitted to a single center during an 11-year period. Overall, 504 (56.8%) patients manifested a SIRS during their illness, with a maximum of 1, 2, and 3 concurrent SIRS components in 166, 238, and 100 patients, respectively. In 353 (39.8%) patients who did not become infected, a SIRS on admission was associated with a more critical illness, subsequent worsening of encephalopathy, and death. Infected patients more often developed a SIRS and one of greater magnitude. The magnitude of the SIRS in 273 patients with bacterial infection correlated with mortality, being 16.7%, 28.4%, 41.2%, and 64.7% in patients with 0, 1, 2, and 3 maximum concurrent SIRS components, respectively. Similar correlations with mortality were seen for SIRS associated with fungal infection, bacteremia, and bacterial chest infection. Fifty-nine percent of patients with severe sepsis died, as did 98% of those with septic shock. A significant association was found between progressive encephalopathy and infection. Infected patients with progressive encephalopathy manifested more SIRS components than other infected patients. For patients with a SIRS, the proportions of infected and noninfected patients manifesting worsening encephalopathy were similar. In ALF, the SIRS, whether or not precipitated by infection, appears to be implicated in the progression of encephalopathy, reducing the chances of transplantation and conferring a poorer prognosis.
Hepatocyte growth factor promotes cell survival from Fas-mediated cell death in hepatocellular carcinoma cells via Akt activation and Fas-death-inducing signaling complex suppression
Authors: Suzuki Atsushi , Hayashida Midori , Kawano Hirokazu , Sugimoto Kazushi , Nakano Takeshi , Shiraki Katsuya
Published: December 2003

The Akt/PI-3 kinase pathway is a system essential for cell survival. In the current study, we showed that hepatocyte growth factor (HGF) activates the Akt/PI-3 kinase pathway to suppress Fas-mediated cell death in human hepatocellular carcinoma (HCC; 3 lines; SK-Hep1, HLE, and Chang Liver cell lines), hepatoblastoma (1 line; HepG2), and embryonic hepatocyte (1 line; WRL). Five tested cell lines showed the resistance to Fas-mediated cell death by the pretreatment of HGF. This HGF-induced cell survival was suppressed by wortmannin (Akt/PI-3 kinase pathway inhibitor), suggesting an involvement of Akt. When cells were pretreated with HGF, Fas-mediated cell death was suppressed, followed by Akt phosphorylation at Ser473. Fas-death-inducing signaling complex (DISC) formation, especially FADD and caspase 8 interaction, was suppressed by HGF and the suppression of the Akt/PI-3 kinase pathway by transient expression of PTEN, resulting in acquisition of Fas-DISC formation and Fas-mediated cell death in HGF-treated cells. We suggest that HGF promotes cell survival in hepatocyte-derived cell lines (HCC, hepatoblastoma, and embryonic hepatocyte) from Fas-mediated cell death via Fas-DISC suppression as a result of Akt activation.
Natural history of clinically compensated hepatitis C virus-related graft cirrhosis after liver transplantation
Authors: Berenguer Marina , Prieto Martín , Rayón José M. , Mora Julio , Pastor Miguel , Ortiz Vicente , Carrasco Domingo , Juan Fernando San , Burgueño Manuel-de-Juan , Mir José , Berenguer Joaquín
Published: December 2003

The natural history of clinically compensated hepatitis C virus (HCV) cirrhosis after liver transplantation is unknown. This information is relevant to transplant centers to improve the management of these patients and decide the optimal timing for retransplantation. The aims of the study were (1) to describe the natural history of patients with HCV-cirrhosis transplants in a center with annual liver biopsies, and (2) to determine predictors for clinical decompensation, retransplantation, and mortality rates. A total of 49 patients with HCV-graft cirrhosis, 39 clinically compensated at histologic diagnosis of cirrhosis (post-liver transplantation cirrhosis) were included and followed up for 1 year (15 days-3.5 years). All patients tested were infected with genotype 1b. Predictive variables included histologic activity index (HAI) at post-liver transplantation cirrhosis, liver function tests, age, sex, and maintenance immunosuppression. Eighteen of 39 patients developed at least 1 episode of decompensation after a median of 7.8 months (4 days-2.6 years; 93% ascites). The cumulative probability of decompensation was 8%, 17%, and 42% at 1, 6, and 12 months, respectively. Graft and patient survival rates were 100%, 85%, and 71% and 100%, 92%, and 74% at 1, 6, and 12 months, respectively. Patient survival rates dropped significantly once decompensation developed (93%, 61%, and 41% at 1, 6, and 12 months, respectively). Variables associated with decompensation, retransplantation, and mortality rate included a high Child-Pugh score (>A), low levels of albumin at post-liver transplantation cirrhosis, and a short interval between liver transplantation and post-liver transplantation cirrhosis. The natural history of clinically compensated HCV-graft cirrhosis is shortened when compared with immunocompetent patients. If retransplantation is considered, it should be performed promptly once decompensation develops.
Molecular diagnosis of a familial nonhemolytic hyperbilirubinemia (Gilbert’s syndrome) in healthy subjects
Authors: Borlak Jürgen , Thum Thomas , Landt Olfert , Erb Katharina , Hermann Robert
Published: December 2003

Recent research has shown that congenital nonhemolytic low grade hyperbilirubinemias in patients with Gilbert’s syndrome (GS) are linked to mutations in the TATA box upstream of the uridine 5′-diphosphoglucose glucuronosyltransferase (UGT1A1) gene leading to an impaired bilirubin glucuronidation. In routine clinical practice GS patients can, however, only be suspected by exclusion of other causes of hyperbilirubinemia or substantial liver diseases. We developed a new, sensitive, convenient, and economic polymerase chain reaction (PCR) method for the rapid and reliable identification of gene polymorphisms in the TATA box of the UGT1A1 gene using fluorescence resonance energy transfer (FRET). With this procedure the genotype frequency in a cohort of 266 unrelated individuals from Southern Germany was investigated and the allelic distribution for individual genotypes was 43:45:12 for the (TA)6TAA:(TA)6TAA/(TA)7TAA:(TA)7TAA alleles, respectively. The homozygous (TA)7TAA genotype was strongly associated with suspected Gilbert’s patients and its prevalence in our cohort of 266 Southern German individuals was 12.4%. In this cohort total mean serum bilirubin levels ranged from 5 μmol/L (wild-type 6/6 allele) to 57 μmol/L serum total bilirubin (mutant 7/7 homozygous allele). Median (interquartile range) serum total bilirubin levels were 12 (6) and 21 (13) for the homozygous wild-type and mutant allele, respectively. Our assay enables individual guidance for dose adjustment in suspected GS patients undergoing long-term drug therapies, especially if glucuronidation via UGT1A1 is a major metabolic pathway.
Flow over yawed circular cylinders: Wall pressure spectra and flow regimes
Authors: Snarski Stephen R.
Published: December 2003

The fluctuating wall pressure on a circular cylinder in cross flow has been investigated experimentally in a water tunnel to examine the effect of yaw angle on the spectral characteristics of the wall pressure field and to provide insight into the periodic and turbulent structures of the flow. Wall pressure was measured at five azimuthal positions around the periphery of the cylinder for seven yaw angles from α=90° (normal flow) to α=0° (axial flow) at three subcritical Reynolds numbers (ReD=7200, 13 500, 27 600). As the yaw angle is varied from α=90° to 0°, large systematic and nonmonotonic variations in both the narrowband (periodic vortex shedding) and broadband (turbulent) spectral levels occur. The results provide additional insight into the structural characteristics of the yawed cylinder flow regimes over that which has been identified previously through measurements of mean wall forces and flow field characteristics. Significant Reynolds number effects were also observed over the range of the measurements, particularly at small yaw angles, that may indicate fundamental shifts in the structure of the wake or underlying regime transition mechanisms. Possible effects due to vortex-induced cylinder vibrations are not entirely clear but predominantly confined to the larger yaw angles. Simultaneous wall pressure, cylinder vibration, radiated acoustic pressure, and wake velocity measurements are required to appropriately isolate the various potential contributions to the wall pressure field and thus provide a clearer understanding of the underlying boundary layer separation, transitional wake, and fluid-structural coupling mechanisms.
Spray characterization during vibration-induced drop atomization
Authors: Vukasinovic Bojan , Smith Marc K. , Glezer Ari
Published: December 2003

Vibration-induced drop atomization is a process of rapid droplet ejection from a larger liquid drop. This occurs when a liquid drop resting on a thin diaphragm is vibrated under the appropriate forcing conditions using an attached piezoelectric actuator. The resulting spray of small droplets is characterized in this work using high-speed imaging and particle-tracking techniques. The results show that the average spatial and velocity distributions of the spray droplets are fairly axisymmetric during all stages of the atomization. The mean diameter of the droplets depends on the forcing frequency to the −2/3 power. The ejection velocity of the spray droplets depends on both the magnitude and the rate of change of the forcing amplitude. Thus, controlling the characteristics of the forcing signal may lead to strategies for controlling the spray process in specific applications.
On self-similarity of detonation diffraction
Authors: Wescott B. L. , Stewart D. Scott , Bdzil J. B.
Published: December 2003

We consider diffraction of a detonation into an unconfined region of explosive. One might expect detonation flow to be self-similar, as in inert shock diffraction, when the reaction zone length is short compared to a geometric flow scale. One might expect that at very early time after the detonation has turned the corner, the region of explosive along the wall behaves according to the self-similar expansion for an inert flow, or as a self-similar Taylor blast wave of fixed strength. We use direct numerical simulations and study dynamic transients in self-similar coordinates to explore these hypotheses. We consider state-insensitive and state-sensitive reaction rate laws that mimic condensed explosives. We find through an analysis of shock arrival times, that the cylindrical detonation is useful in describing the dynamics of the expansion region in a two-dimensional detonation diffraction event. Therefore, we believe that detailed study of cylindrical (or spherical) detonations can be used to develop simplified or analytic models of detonation diffraction.
Chemical pattern formation driven by a neutralization reaction. I. Mechanism and basic features
Authors: Eckert Kerstin , Acker Margret , Shi Ying
Published: December 2003

We study the chemohydrodynamic pattern formation during interfacial mass transfer accompanied by a neutralization reaction. The system, which is placed in a Hele-Shaw cell, is a configuration of two immiscible liquid phases in contact along a plane interface. In the upper, organic layer a carboxylic acid is dissolved, the concentration of which is far beyond the equilibrium partition ratio. Interfacial acid transfer initiates the neutralization with an organic base dissolved in the lower, aqueous layer. Focus is on the exploration of a novel instability consisting of a regular cellular structure penetrating into the aqueous bulk solution. By several complementary experimental methods, including shadowgraph visualization with different magnifications, particle image velocimetry, differential interferometry, and detailed measurements of relevant material properties, the driving mechanism of the instability is identified. Synthesis of the experimental results suggests that lateral differences in buoyancy are responsible for the convection.
Effect of different vitrification protocols for human ovarian tissue on reactive oxygen species and apoptosis
Authors: Rahimi Gohar , Isachenko Eugenia , Sauer Heinrich , Isachenko Vladimir , Wartenberg Maria , Hescheler Jürgen , Mallmann Peter , Nawroth Frank
Published: December 2003

The aim of the present study was to evaluate the effect of different vitrification protocols on reactive oxygen species (ROS) and apoptosis in human ovarian tissue. Human ovarian tissue pieces were exposed to different vitrification solutions. The intracellular redox state level was measured using the fluorescent dye dichlorodihydrofluorescein diacetate. Imaging of apoptotic cells was monitored by anti-caspase-3 immunolabelling after vitrification and warming. Following equilibration in either 40% ethylene glycol (EG) (v/v), 0.35 M sucrose + 10% egg yolk extract (v/v) or 40% EG (v/v), 18% Ficoll-70 (w/v) + 0.35 M sucrose for 6 min, ovarian pieces were cooled to −196°C using four different protocols. Tissue that was cooled very rapidly (plunged directly into liquid nitrogen in straws or on grids or plunged directly into metal filings precooled to −196°C) showed no statistically significant increase in either tissue ROS levels or the number of apoptotic cells after warming. In contrast, cooling using a less rapid method (nitrogen vapour at −120°C) resulted in significantly elevated ROS levels and apoptosis after warming. There were no significant differences between the two vitrification solutions. This indicates that human ovarian tissue pieces should be vitrified using very rapid cooling rates.
Use of a new drug delivery formulation of the gonadotrophin-releasing hormone analogue Deslorelin for reversible long-term contraception in male dogs
Authors: Junaidi A. , Williamson P. E. , Cummins J. M. , Martin G. B. , Blackberry M. A. , Trigg T. E.
Published: December 2003

In the present study, we tested the effect of treatment with a slow-release implant containing the gonadotrophin-releasing hormone agonist DeslorelinTM (Peptech Animal Health Australia, North Ryde, NSW, Australia) on pituitary and testicular function in mature male dogs. Four dogs were treated with Deslorelin (6-mg implant) and four were used as controls (blank implant). In control dogs, there were no significant changes over the 12 months of the study in plasma concentrations of luteinising hormone (LH) or testosterone, or in testicular volume, semen output or semen quality. In Deslorelin-treated dogs, plasma concentrations of LH and testosterone were undetectable after 21 and 27 days, testicular volume fell to 35% of pretreatment values after 14 weeks and no ejaculates could be obtained after 6 weeks. Concentrations returned to the detectable range for testosterone after 44 weeks and for LH after 51 weeks and both were within the normal range after 52 weeks. Semen characteristics had recovered completely by 60 weeks after implantation. At this time, the testes and prostate glands were similar histologically to those of control dogs. We conclude that a single slow-release implant containing 6 mg Deslorelin has potential as a long-term, reversible antifertility agent for male dogs.
A Material Theory of Induction
Authors: Norton John D.
Published: December 2003

Contrary to formal theories of induction, I argue that there are no universal inductive inference schemas. The inductive inferences of science are grounded in matters of fact that hold only in particular domains, so thatall inductive inference is local.Some are so localized as to defy familiar characterization. Since inductive inference schemas are underwritten by facts, we can assess and control the inductive risk taken in an induction by investigating the warrant for its underwriting facts. In learning more facts, we extend our inductive reach by supplying more localized inductive inference schemes. Since a material theory no longer separates the factual and schematic parts of an induction, it proves not to be vulnerable to Hume's problem of the justification of induction.
Causal Explanations of Behavior
Authors: Salmon Merrilee H.
Published: December 2003

Most discussions of causal explanations of behavior focus on the problem of whether it makes sense to regard reasons as causes of human behavior, whether there can be laws connecting reasons with behavior, and the like. This essay discusses explanations of human behavior that do not appeal to reasons. Such explanations can be found in several areas of the social sciences. Moreover, these explanations are both causal and non-reductionist. Historical linguists, for example, offer causal explanations of changes in how words are pronounced—and linguistic change in general—without appealing to human intentions. I use examples from linguistics, anthropology, and evolutionary psychology to discuss the importance of this sort of explanation and to examine its compatibility with recent philosophical accounts of causation.
Does the Concept of “Clade Selection” Make Sense?
Authors: Okasha Samir
Published: December 2003

The idea that clades might be units of selection, defended by a number of biologists and philosophers of biology, is critically examined. I argue that only entities which reproduce, i.e. leave offspring, can be units of selection, and that a necessary condition of reproduction is that the offspring entity be able, in principle, to outlive its parental entity. Given that clades are monophlyetic by definition, it follows that clades do not reproduce, so it makes no sense to talk about a clade's fitness, so clade selection is impossible. Three possible responses to this argument are examined and found wanting.
A Philosopher Looks at Quantum Information Theory
Authors: Hagar Amit
Published: December 2003

Recent suggestions to supply quantum mechanics (QM) with realistic foundations by reformulating it in light of quantum information theory (QIT) are examined and are found wanting by pointing to a basic conceptual problem that QIT itself ignores, namely, the measurement problem. Since one cannot ignore the measurement problem and at the same time pretend to be a realist, as they stand, the suggestions to reformulate QM in light of QIT are nothing but instrumentalism in disguise.
Non-seperability, Non-supervenience, and Quantum Ontology
Authors: Belousek Darrin W.
Published: December 2003

An argument to the effect that quantum mechanics commits us to the existence of non-supervenient relations, and therefore that we should admit such relations into our quantum ontology as fundamental entities, has been given by Teller and reformulated by French. This paper aims, first, to explicate and evaluate that argument; second, to extend its premises in order to assess its relevance for other interpretations of quantum mechanics; and, third, to clarify its implications for holism and individuation in quantum ontology.
Peddling Science: An Essay Review of Science Bought and Sold: Essays in the Economics of Science
Authors: Zamora Bonilla Jesús P.
Published: December 2003

Science Bought and Sold collects a large portion of the most relevant works on the ‘economics of scientific knowledge production,’ as well as other more recent and unpublished papers on the topic, and the long introductory essay by the editors is an illuminating guide to the field. In this critical notice, I argue that economic theorising about scientific research is providing a peaceful meeting point for many of the combatants in the ‘science wars,’ one from which both epistemic and political questions about science can be more rationally set forth.
Hydroxyapatite Cement in Temporal Bone Surgery: A 10 Year Experience
Authors: Kveton John F. , Coelho Daniel H.
Published: December 2003

Objectives To describe the indications for successful use of hydroxyapatite cement (HAC) in temporal bone surgery.

Study Design Retrospective case review.

Methods One hundred nine temporal bone defects related to surgical approaches to the skull base, infection, neoplasms, or congenital defect in 102 adults and children were corrected using HAC over a 10‐year period. The results and complications were obtained through retrospective chart review.

Results Ninety‐seven percent of temporal bone defects were successfully repaired using HAC, and the reconstruction remained stable over the course of this study. There was one case of postoperative cerebrospinal fluid leak. Wound infection occurred in three patients, which required reoperation and removal of the biomaterial.

Conclusions HAC is a biomaterial that should be used as the primary method to reconstruct temporal bone defects. Proper use of this biomaterial results in restoration of the integrity of the temporal bone and elimination of cerebrospinal fluid leak as a postoperative complication.
Ossicular Reconstruction with Titanium Prosthesis
Authors: Martin Angela D. , Harner Stephen G.
Published: December 2003

Objectives To evaluate the results when using titanium total ossicular replacement prosthesis (TORP) or partial ossicular replacement prosthesis (PORP) in chronic ear disease.

Study Design Retrospective chart review was performed.

Methods Sixty‐eight ossicular procedures using a titanium TORP (n = 30) or PORP (n = 38) were performed at a tertiary referral center between December 1999 and June 2002. The ossiculoplasty was performed either alone or in combination with other chronic ear surgery. Cartilage grafts were used universally. Nineteen percent were primary operations, and 6% were planned second stages. The majority were revision procedures. Follow‐up ranged from 3 months to 2.5 years.

Results The prosthesis is easy to insert, well tolerated, and has a low extrusion rate. Average air‐bone gap (ABG) improvement was 13 dB with closure of the ABG to within 20 dB in 57% of cases. Hearing results were better for primary versus revision cases for PORPs versus TORPs and for intact canal wall (ICW) procedures versus canal wall‐down (CWD) procedures.

Conclusion Titanium is a satisfactory material for use in ossicular reconstruction because of its ease of insertion, tissue tolerance, and low rate of extrusion. Caution is advised when selecting candidates for this procedure during revision surgery, especially if the canal wall and stapes superstructure are absent.
Bilateral Bone‐Anchored Hearing Aids (BAHAs): An Audiometric Evaluation
Authors: Priwin Claudia , Stenfelt Stefan , Granström Gösta , Tjellström Anders , Håkansson Bo
Published: December 2003

Objectives Since the technique to implant bone‐anchored hearing aids (BAHAs) with the use of osseointegrated implants was developed in 1977, more than 15,000 patients have been fitted with BAHAs worldwide. Although the majority have bilateral hearing loss, they are primarily fitted unilaterally. The main objective of this study was to reveal benefits and drawbacks of bilateral fitting of BAHAs in patients with symmetric or slight asymmetric bone‐conduction thresholds. The possible effects were divided into three categories: hearing thresholds, directional hearing, and binaural hearing.

Study Design Prospective study of 12 patients with bilateral BAHAs.

Methods Baseline audiometry, directional hearing, speech reception thresholds in quiet and in noise, and binaural masking level difference were tested when BAHAs were fitted unilaterally and bilaterally.

Results Eleven of the 12 patients used bilateral BAHAs on a daily basis. Tests performed in the study show a significant improvement in sound localization with bilateral BAHAs; the results with unilateral fitting were close to the chance level. Furthermore, with bilateral application, the improvement of the speech reception threshold in quiet was 5.4 dB. An improvement with bilateral fitting was also found for speech reception in noise.

Conclusions Overall, the results with bilateral fitted BAHAs were better than with unilaterally fitted BAHA; the benefit is not only caused simply by bilateral stimulation but also, to some extent, by binaural hearing. Bilateral BAHAs should be considered for patients with bilateral hearing loss otherwise suitable for BAHAs.
Long‐Term Results after Interval Therapy with Intratympanic Gentamicin for Menière's Disease
Authors: Lange Gert , Maurer Jan , Mann Wolf
Published: December 2003

Objectives The new single‐shot and interval treatment for Menière's disease with gentamicin was designed to avoid cochlear damage during treatment with gentamicin.

Methods To date, 90 patients were treated with the single‐shot or interval gentamicin therapy. Fifty‐seven cases of Menière's disease were followed up prospectively between 2 and 4 years. During one treatment series, a maximum of three intratympanic gentamicin injections within 15 days were applied, each consisting of 0.3 mL (12 mg) of gentamicin (days 1, 8, and 15). Thirty of these 57 patients (53%) needed only one injection to be controlled (single‐shot treatment).

Results Vertigo attacks were completely controlled in 95% and partially controlled in 5%, whereas hearing remained unchanged or even improved. Tinnitus as well as aural fullness were controlled in approximately 50% of the cases.

Conclusion Our results with this group of patients after interval‐treatment or single‐shot application of intratympanic gentamicin demonstrate the effectiveness of this treatment modality with very low side effects, and, although our experience is still limited, it allows for expanding the indication on early cases of Menière's disease before permanent hearing loss occurs. Even cases of bilateral Menière's disease can be treated successfully using this method. Cochleotoxic side effects can be prevented by treatment intervals of 7 days.
Endoscopic Surgery for Recurrent Inverted Papilloma
Authors: Lee Ta‐Jen , Huang Shiang‐Fu , Lee Li‐Ang , Huang Chi‐Che
Published: December 2003

Objectives/Hypothesis Inverted papilloma of the nose and paranasal sinuses is noted for its high rate of recurrence. The feasibility of endoscopic treatment for inverted papilloma has been shown in the literature; however, reports discussing the efficacy of endoscopic surgery for recurrent diseases are rare. The study determined the effectiveness of endoscopic surgery for recurrent inverted papilloma and described when endoscopic medial maxillectomy was indicated.

Study Design Retrospective.

Methods Seventeen patients with recurrent inverted papilloma were treated over a 10‐year period. Krouse's staging system was used for tumor grading. Because of the extent of the tumor in the majority (70.6%) of the patients, en bloc resection could not be regularly achieved; therefore, sequential segmental endoscopic surgery was the chosen treatment. Some diseases that extensively involved the maxillary sinus were treated by the combination of endoscopic medial maxillectomy (EMM) and sequential segmental surgery (SSES) to extirpate the whole disease.

Results Efficacy was evaluated strictly by radiographic study. Successful treatment was accomplished in 14 (82.4%) patients. Three (17.6%) patients had residual disease; each required one revision surgery. None of the patients had recurrence at the time of writing. There were no major complications or associated malignancies encountered in the patients.

Conclusion Endoscopic surgery is an effective treatment for recurrent inverted papilloma. Precise determination of the sites of tumor origin and attachment during the operation is the key to the successful treatment. Recurrent inverted papilloma tends to behave more aggressively and has a higher postoperative recurrence rate than the primary lesion. Stage III disease had a higher recurrence rate (27.3%) than that of other stages (0%).
Sleep Disordered Breathing: Surgical Outcomes in Prepubertal Children
Authors: Guilleminault Christian , Li Kasey K. , Khramtsov Andrei , Pelayo Rafael , Martinez Sandra
Published: December 2003

Objective To evaluate the treatment outcomes of sleep disordered breathing (SDB) in prepubertal children 3 months following surgical intervention.

Study Design Retrospective investigation of 400 consecutively seen children with SDB who were referred to otolaryngologists for treatment.

Method After masking the identities and conditions of the children, the following were tabulated: clinical symptoms, results of clinical evaluation and polysomnography at entry, the treatment chosen by the otolaryngologists, and clinical and polysomnographic results 3 months after surgery.

Results Treatment ranged from nasal steroids to various surgical procedures. Adenotonsillectomy was performed in only 251 of 400 cases (68%). Four cases included adenotonsillectomy in conjunction with pharyngoplasty (closure of the tonsillar wound by suturing the anterior and posterior pillar to tighten the airway). Persistent SDB was seen in 58 of 400 children (14.5%), and an additional 8 had persistent snoring. Best results were with adenotonsillectomy.

Conclusion SDB involves obstruction of the upper airway, which may be partially due to craniofacial structure involvement. The goal of surgical treatment should be aimed at enlarging the airway, and not be solely focused on treating inflammation or infection of the lymphoid tissues. This goal may not be met in some patients, thus potentially contributing to residual problems seen after surgery. The possibility of further treatment, including collaboration with orthodontists to improve the craniofacial risk factors, should be considered in children with residual problems.
Viscoelasticity of Rabbit Vocal Folds After Injection Augmentation
Authors: Dahlqvist Åke , Gärskog Ola , Laurent Claude , Hertegård Stellan , Ambrosio Luigi , Borzacchiello Assunta
Published: December 2003

Objectives/Hypothesis Vocal fold function is related to the viscoelasticity of the vocal fold tissue. Augmentation substances used for injection treatment of voice insufficiency may alter the viscoelastic properties of vocal folds and their vibratory capacity. The objective was to compare the mechanical properties (viscoelasticity) of various injectable substances and the viscoelasticity of rabbit vocal folds, 6 months after injection with one of these substances.

Study Design Animal model.

Methods Cross‐linked collagen (Zyplast), double cross‐linked hyaluronan (hylan B gel), dextranomers in hyaluronan (DHIA), and polytetrafluoroethylene (Teflon) were injected into rabbit vocal folds. Six months after the injection, the animals were killed and the right‐ and left‐side vocal folds were removed. Dynamic viscosity of the injected substances and the vocal folds was measured with a Bohlin parallel‐plate rheometer during small‐amplitude oscillation.

Results All injected vocal folds showed a decreasing dynamic viscosity with increasing frequency. Hylan B gel and DiHA showed the lowest dynamic viscosity values, and vocal folds injected with these substances also showed the lowest dynamic viscosity (similar to noninjected control samples). Teflon (and vocal folds injected with Teflon) showed the highest dynamic viscosity values, followed by the collagen samples.

Conclusion Substances with low viscoelasticity alter the mechanical properties of the vocal fold to a lesser degree than substances with a high viscoelasticity. The data indicated that hylan B gel and DiHA render the most natural viscoelastic properties to the vocal folds. These substances seem to be appropriate for preserving or restoring the vibratory capacity of the vocal folds when glottal insufficiency is treated with augmentative injections.
Clinical and Histological Healing of Surgical Wounds Treated With Mitomycin C
Authors: Ribeiro Fernando de Andrade Quintanilha , Guaraldo Lusiele , Borges Janaina de Pádua , Zacchi Flávia Fernanades Silva , Eckley Claudia A.
Published: December 2003

Objectives/Hypothesis The proven ability of mitomycin C to inhibit fibroblasts in vitro has stimulated its use in research animals and in humans to control healing. The objective of the study was to follow the healing process of surgical wounds in the dorsum of rats treated topically with mitomycin C.

Study Design Prospective experimental study.

Methods Two distinct surgical wounds were made to the dorsum of 10 adult rats. One of the wounds received topical mitomycin C diluted at 0.5 mg/mL during a 5‐minute period, and the other wound was used as a control. The healing process was followed clinically and histologically after the rats were killed at different post‐treatment periods. The degree of fibrosis was evaluated histologically by two different pathologists.

Results Surgical wounds treated with mitomycin C presented delayed healing when compared with the untreated wounds, with remission of scabs 7 days after the control wounds. Histological analysis at 1 month after treatment revealed a significant reduction in fibrosis of the wounds treated with mitomycin C when compared with the untreated wounds. After the third month the degree of fibrosis was comparable in both wounds.

Conclusion Topical mitomycin C delays the healing of surgical wounds in rats up to the fourth week following treatment, but the degree of fibrosis is comparable in both treated and untreated wounds after 12 weeks. In otolaryngology this characteristic of the drug may be useful in the treatment of external ear canal stenosis, choanal atresias, nasal cicatricial stenosis, laryngeal stenosis, and keloids.
Technique of En Block Laser Endoscopic Frontolateral Laryngectomy for Glottic Cancer
Authors: Zeitels Steven M. , Dailey Seth H. , Burns James A.
Published: December 2003

During the last 30 years, there has been expansion of the role of endoscopic partial laryngectomy procedures since Jako, Strong, and Vaughan explored the possibilities of CO2 laser microlaryngeal procedures. Despite the fact that a number of investigators have verified the validity of endolaryngeal laser resection of mid‐sized glottic cancer, there are many who are unfamiliar with the technique and others who are uncomfortable with sectioning the tumor to facilitate its resection. In the past 3 years, 15 patients underwent successful en block resection of mid‐sized glottic cancer (T1b 2, T2b 11, T3 2). Because en block resection is more consistent with open oncologic approaches, this method should widen the acceptance of this approach in selected lesions. The nuances of en block endoscopic frontolateral laryngectomy are presented with the hope that more surgeons will adopt this philosophy as an aspect of their armamentarium.
Translational Coupling to an Upstream Gene Promotes Folding of the Mycobacterial Plasmid pAL5000 Replication Protein RepB and Thereby Its Origin Binding Activity
Authors: Basu Abhijit , Chatterjee Sujoy , Das Gupta Sujoy K.
Published: December 2003

In the mycobacterial plasmid pAL5000 replication region, the replication genes
repA
and
repB
are organized in an operon. Earlier, a RepB-dependent origin binding activity was detected in
Escherichia coli
cells expressing the
repA
-
repB
operon. This activity was maximal when expression of the two genes was coupled (A. Basu, M. Chawla-Sarkar, S. Chakrabarti, and S. K. Das Gupta, J. Bacteriol. 184:2204-2214, 2002). In this study we have shown that translational coupling makes a significant difference in the structure and function of RepB. When
repB
expression was coupled to
repA
, the polypeptide folded into an active structure (referred to as RepB*), which possessed higher helical content than RepB expressed independently. RepB* could also be distinguished from the less active RepB on the basis of sensitivity to OmpT, an outer membrane protease of
E. coli
: RepB* was sensitive to the protease, whereas RepB was resistant. Similar conformational differences between RepB* and RepB could be observed when
repA
was replaced with an unrelated gene,
malE
(encoding maltose binding protein). These results show that translational coupling of
repB
to an upstream gene is necessary for better folding and origin binding activity. It is speculated that in coupled systems where translation machinery is passed on from the upstream to the downstream open reading frame, cotranslational folding of the polypeptide expressed from the downstream open reading frame is enhanced due to increased folding competence of translationally primed ribosomes.
A Multicomponent System Is Required for Tetracycline-Induced Excision of Tn
4555
Authors: Parker Anita C. , Smith C. Jeffrey
Published: December 2003

Bacteroides
spp. are the predominant organisms in the intestinal tract, and they also are important opportunistic pathogens. Antibiotic therapy of
Bacteroides
infections often is complicated by the prevalence of drug-resistant organisms which acquire resistance genes from a variety of mobile genetic elements including conjugative transposons (CTns) and mobilizable transposons (MTns). Tn
4555
is an MTn that encodes β-lactam resistance, and it is efficiently mobilized by the
Bacteroides
CTns via a tetracycline (TET)-inducible mechanism. In this study a model system with CTn341 and a Tn
4555
minielement was used to examine Tn
4555
excision from the chromosome. Using PCR and mobilization assays it was established that excision was stimulated by TET in the presence of CTn341. In order to determine which Tn
4555
genes were required for excision,
int
,
tnpA
,
tnpC
,
xis
, and
mobA
mutants were examined. The results indicated that
int
plus two additional genes,
tnpC
and
xis
, were required for optimal excision. In addition, there was no requirement for the
mobA
gene, as had been shown for another MTn, NBU1. The Xis protein sequence is related to a family of plasmid excisionases, but the TnpC gene product did not match anything in the sequence databases. Evidence also was obtained that suggested that Xis is involved in the control of TET-induced excision and in control of mobilization by CTn341. Overall, these results indicate that excision of MTns is a complex process that requires multiple gene products.
A Phosphoprotein from the Archaeon
Sulfolobus solfataricus
with Protein-Serine/Threonine Kinase Activity
Authors: Lower Brian H. , Potters M. Ben , Kennelly Peter J.
Published: December 2003

Sulfolobus solfataricus
contains a membrane-associated protein kinase activity that displays a strong preference for threonine as the phospho-acceptor amino acid residue. When a partially purified detergent extract of the membrane fraction from the archaeon
S. solfataricus
that had been enriched for this activity was incubated with [γ-
32
P]ATP, radiolabeled phosphate was incorporated into roughly a dozen polypeptides, several of which contained phosphothreonine. One of the phosphothreonine-containing proteins was identified by mass peptide profiling as the product of open reading frame [ORF]
sso0469.
Inspection of the DNA-derived amino acid sequence of the predicted protein product of ORF
sso0469
revealed the presence of sequence characteristics faintly reminiscent of the “eukaryotic” protein kinase superfamily. ORF
sso0469
therefore was cloned, and its polypeptide product was expressed in
Escherichia coli
. The recombinant protein formed insoluble aggregates that could be dispersed using urea or detergents. The solubilized polypeptide phosphorylated several exogenous proteins in vitro, including casein, myelin basic protein, and bovine serum albumin. Mutagenic alteration of amino acids predicted to be essential for catalytic activity abolished or severely reduced catalytic activity. Phosphorylation of exogenous substrates took place on serine and, occasionally, threonine. This new archaeal protein kinase displayed no catalytic activity when GTP was substituted for ATP as the phospho-donor substrate, while Mn
2+
was the preferred cofactor.
The
Caulobacter crescentus
CgtA
C
Protein Cosediments with the Free 50S Ribosomal Subunit
Authors: Lin Bin , Thayer Desiree A. , Maddock Janine R.
Published: December 2003

The Obg family of GTPases is widely conserved and predicted to play an as-yet-unknown role in translation. Recent reports provide circumstantial evidence that both eukaryotic and prokaryotic Obg proteins are associated with the large ribosomal subunit. Here we provide direct evidence that the
Caulobacter crescentus
CgtA
C
protein is associated with the free large (50S) ribosomal subunit but not with 70S monosomes or with translating ribosomes. In contrast to the
Bacillus subtilis
and
Escherichia coli
proteins, CgtA
C
does not fractionate in a large complex by gel filtration, indicating a moderately weak association with the 50S subunit. Moreover, binding of CgtA
C
to the 50S particle is sensitive to salt concentration and buffer composition but not guanine nucleotide occupancy of CgtA
C
. Assays of epitope-tagged wild-type and mutant variants of CgtA
C
indicate that the C terminus of CgtA
C
is critical for 50S association. Interestingly, the addition of a C-terminal epitope tag also affected the ability of various

cgtA
C

alleles to function in vivo. Depletion of CgtA
C
led to perturbations in the polysome profile, raising the possibility that CgtA
C
is involved in ribosome assembly or stability.
A CURRENT REVIEW ON THE BIOLOGY AND TREATMENT OF ARTICULAR CARTILAGE DEFECTS (PART I & PART II)
Authors: Willers Craig , Wood David J. , Zheng Ming H.
Published: December 2003

Osteochondral injury occurs predominantly in physically active young adult males. Injury to the articular cartilage and/or subchondral bone may not only cause acute joint disease resulting in osseous intracapsular (synovitis) or extracapsular pain, but may also act to spawn arthritic conditions in later life. Since the 18th century, such injury has proven difficult to treat clinically, and much therapy has been essentially palliative. Past treatments such as abrasion arthroplasty, drilling, microfracture and arthroscopic lavage have been useful in removing articular debris and promoting the formation of the fibrin clot used in most native repair mechanisms. However, the limitation of these techniques is their inability to restore the damaged cartilage and subchondral bone to their normal tissue architecture. Recent developments in tissue engineering have concentrated on the utilization of autologous chondrocyte implantation, biomaterials and growth factors to promote the regeneration of biomechanically superior hyaline articular cartilage. This paper reviews the etiology, repair biology and therapeutic techniques of cartilage and/or osteochondral injury over the previous decades, and attempts to provide insight into interesting new research directions which offer much potential for improved treatment of these troublesome lesions.
A NEW SPINAL INSTRUMENTATION WITHOUT FUSION FOR THE TREATMENT OF PROGRESSIVE IDIOPATHIC SCOLIOSIS IN GROWING CHILDREN
Authors: Ye Q. B. , Wang Y. P. , Zhang J. , Wu Z. H. , Weng X. S.
Published: December 2003

Objective: To study on the therapeutic mechanism of an innovated instrumentation — Plate-Rod System for scoliosis (PRSS) and its effectiveness for the surgical management of idiopathic scoliosis in growing children.

Method: To avoid the necessity of repeated operative instrument lengthening, a new device — Plate-rod Spinal System (PRSS) was developed in our department. It can provide and maintain desirable correction of scoliosis in growing children in an one-stage operation. The instrumentation will extend itself to keep up with the growth of the spinal column, which is helpful in preventing truncal shortening and "crankshaft phenomenon". From October 1998 to March 2001, thirty-four young children with progressive idiopathic scoliosis of average 62.8° were treated using PRSS without fusion.

Results: The mean percentage of correction was 62.78%, the best being 87.2%. The average loss of correction of 8° was found in 15 cases at the time of average 28 months follow-up. The remaining cases have no loss of correction. An average of 13.5 mm spinal lengthening of the instrumental segments was achieved. When PRSS is in place, compressive stress found to exert on the convex side, while tensile stress on the concave side of the curvature, and more type X collagen mRNA to be expressed on convex side than concave side; this suggests that compressive stress leads to increase earlier cartilage degeneration of the end plate on convex side, so as to retard the growth of the end plate of this side, resulting in maximum spinal realignment. No severe complication was found in our series.

Conclusion: The PRSS, which dispenses with spinal fusion and allows extension along with the children's growth, is a new effective instrumentation for correcting scoliosis, especially in case of growing children.