bluuebunny/crossref_metadata_2025 huggingface dataset:
Almost continuous solutions of geometric Hamilton–Jacobi equations
Authors: Siconolfi Antonio
Published: March 2003

We study the Hamilton–Jacobi equation

u_{t} + H\left(x,Du\right) = 0

in

R^{N} \times ] 0, + \infty[

, where

H

is a continuous positively homogeneous Hamiltonian with constant sign and verifying suitable assumptions but no convexity properties. We look for discontinuous (viscosity) solutions verifying certain initial conditions with discontinuous data. Our aim is to give representation formulae as well as uniqueness and stability results.

We find that the condition

\begin{matrix} \left(u^{\#}\right)_{\#} = u_{\#} & \text{and} & \left(u_{\#}\right)^{\#} = \\ \end{matrix}u^{\#}

where

u^\# (u_\#)

denotes the upper (lower) semicontinuous envelope of

u

, can be used as a uniqueness criterion and determines a class of solutions defined and continuous on certain dense subsets of

R^{N} \times ] 0, + \infty[

that we call almost continuous.

Such solutions can be represented by a formula which is a generalization of the Lax–Hopf one for the eikonal equation.

Nous étudions l’équation de Hamilton–Jacobi

u_{t} + H\left(x,Du\right) = 0

en

R^{N} \times ] 0, + \infty[

, où

H

est un Hamiltomien continu et positivement homogène qui ne change pas de signe et qui ne vérifie aucune hypothèse de convexité. On cherche des solutions de viscosité discontinues qui vérifient certaines conditions initiales avec des données discontinues. Le but est de donner des formules de représentation aussi bien que des résultats d’unicité et de stabilité.

Nous prouvons que la condition

\begin{matrix} \left(u^{\#}\right)_{\#} = u_{\#} & \text{et} & \left(u_{\#}\right)^{\#} = \\ \end{matrix}u^{\#}

oú

u^\# (u_\#)

est l’enveloppe s.c.s. (s.c.i.) de

u

, peut être utilisée comme un critère d’unicité et détermine une classe de solutions définies et continues sur des ensembles denses de

R^{N} \times ] 0, + \infty[

que nous appellons presque continues.

Nous représentons ces solutions à l’aide d’une formule qui généralise celle de Lax–Hopf pour l’équation eiconale.
Critical groups computations on a class of Sobolev Banach spaces via Morse index
Authors: Vannella Giuseppina , Cingolani Silvia
Published: March 2003

In this paper we deal with critical groups estimates for a functional

f:W_{0}^{1,p}\left(\Omega \right)\rightarrow \mathbb{R}\left(p > 2\right),\Omega

bounded domain of

\mathbb{R}^{N}

, defined by setting

f\left(u\right) = \frac{1}{p}\int \limits_{\Omega }\left|\nabla u\right|^{p}dx + \frac{1}{2}\int \limits_{\Omega }\left|\nabla u\right|^{2}dx\int \limits_{\Omega }G\left(u\right)dx

where

G\left(t\right) = \int _{0}^{t}g\left(s\right)ds

and

g

is a smooth real function on

ℝ

, growing subcritically. We remark that the second derivative of

f

in each critical point

u

is not a Fredholm operator from

W_{0}^{1,p}\left(\Omega \right)

to its dual space, so that the generalized Morse splitting lemma does not work. In spite of the lack of an Hilbert structure, we compute the critical groups of

f

in

u

via its Morse index.

Dans cet article, nous estimons les groupes critiques pour une fonctionnelle :

f:W_{0}^{1,p}\left(\Omega \right)\rightarrow \mathbb{R}\left(p > 2\right),\Omega

ensemble borné de

\mathbb{R}^{N}

, définie par

f\left(u\right) = \frac{1}{p}\int \limits_{\Omega }\left|\nabla u\right|^{p}dx + \frac{1}{2}\int \limits_{\Omega }\left|\nabla u\right|^{2}dx\int \limits_{\Omega }G\left(u\right)dx

où

G\left(t\right) = \int _{0}^{t}g\left(s\right)ds

et

g

est une fonction réelle et régulière sur

ℝ

, avec une croissance sous-critique. On observe que la dérive seconde de

f

en chaque point

u

n’est pas un opérateur de Fredholm entre

W_{0}^{1,p}\left(\Omega \right)

est son espace dual et la généralisation du Lemme de Morse ne peut être appliquée. Bien que la structure d’espace d’Hilbert n’existe pas, on est capable de calculer les groupes critiques de

f

en

u

grâce à l’index de Morse.
Multiplicity of solutions for quasilinear elliptic problems involving critical Sobolev exponents
Authors: Silva Elves A.B , Xavier Magda S
Published: March 2003

The main results of this paper establish, via the variational method, the multiplicity of solutions for quasilinear elliptic problems involving critical Sobolev exponents under the presence of symmetry. The concentration-compactness principle allows to prove that the Palais–Smale condition is satisfied below a certain level.

Les résultats principaux de cet article établissent, via la méthode variationnelle, la multiplicité de solutions pour des problèmes elliptiques quasi-linéaires qui font intervenir l’exposant limite de Sobolev en présence de symétrie. La méthode de concentration-compacité permet de montrer que la condition de Palais–Smale est satisfaite au-dessous d’un certain niveau.
Long time averaged reflection force and homogenization of oscillating Neumann boundary conditions
Authors: Arisawa Mariko
Published: March 2003

This paper concerns with two issues. The first issue is the existence and the uniqueness of the ergodic type number 

d

which appears in the oblique boundary condition. The second issue is the application of the number for the study of homogenizations of oscillating Neumann boundary conditions.

Dans cette article, nous traitons deux problèmes. Le premier est l’existence et l’unicité d’un nombre du type ergodique

d

qui apparaît dans la condition oblique sur le bord. Le second est l’application de ce nombre pour la recherche des homogénéizationses conditions Neumann sur des bords oscillants.
The initial phase of fracture healing is specifically sensitive to mechanical conditions
Authors: Klein Petra , Schell Hanna , Streitparth Florian , Heller Markus , Kassi Jean‐Pierre , Kandziora Frank , Bragulla Hermann , Haas Norbert P. , Duda Georg N.
Published: March 2003

Interfragmentary movements affect the quality and quantity of callus formation. The mounting plane of monolateral external fixators may give direction to those movements. Therefore, the aim of this study was to determine the influence of the fixator mounting plane on the process of fracture healing.

Identically configured fixators were mounted either medially or anteromedially on the tibiae of sheep. Interfragmentary movements and ground reaction forces were evaluated in vivo during a nine week period. Histomorphological and biomechanical parameters described the bone healing processes.

Changing only the mounting plane led to a modification of interfragmentary movements in the initial healing phase. The difference in interfragmentary movements between the groups was only significant during the first post‐operative period. However, these initial differences in mechanical conditions influenced callus tissue formation significantly. The group with the anteromedially mounted fixator, initially showing significantly more interfragmentary movements, ended up with a significantly smaller callus diameter and a significantly higher callus stiffness as a result of advanced fracture healing. This demonstrates that the initial phase of healing is sensitive to mechanical conditions and influences the course of healing. Therefore, initial mechanical stability of an osteosynthesis should be considered an important factor in clinical fracture treatment. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Proline induces oxidative stress in cerebral cortex of rats
Authors: Delwing Daniela , Bavaresco Caren S. , Wannmacher Clóvis M.D. , Wajner Moacir , Dutra‐Filho Carlos S. , Wyse Angela T.S.
Published: March 2003

In the present study we investigated the in vivo and in vitro effects of proline on some parameters of oxidative stress, such as chemiluminescence, total radical‐trapping antioxidant potential (TRAP) and the activity of the antioxidant enzymes catalase, glutathione peroxidase and superoxide dismutase in rat cerebral cortex. Ten‐day‐old rats received one subcutaneous injection of proline (12.8 μmol/g body weight), while control rats received saline in the same volumes. The animals were killed 1 h after injection, the cerebral cortex was isolated and the assays immediately carried out. For the in vitro studies, homogenates from cerebral cortex of 10‐day‐old untreated rats were incubated for 1 h at 37 °C with various concentrations of proline (3.0 μM–1.0 mM). Results showed that proline‐treated rats presented a decrease of TRAP (30%) and an increase of chemiluminescence (78%). In contrast, the activities of catalase, glutathione peroxidase and superoxide dismutase were not modified by proline acute treatment. Furthermore, the presence of proline in the medium increased chemiluminescence, decreased TRAP and the activity of superoxide dismutase at proline concentrations similar to those observed in tissues of hyperprolinemic patients (0.5–1.0 mM). However, catalase and glutathione peroxidase activities were not affected by the presence of proline in the medium. The results indicate that proline induces oxidative stress in the brain, which may be related, at least in part, to the neurological dysfunction observed in hyperprolinemia.
Localization of focal adhesion kinase isoforms in cells of the central nervous system
Authors: Contestabile Andrea , Bonanomi Dario , Burgaya Ferran , Girault Jean‐Antoine , Valtorta Flavia
Published: March 2003

Focal adhesion kinase (FAK) is a non‐receptor tyrosine kinase which in non‐neuronal cells is localized to focal adhesions, where it participates to adhesion‐dependent intracellular signalling. FAK is highly expressed in the central nervous system both during development and in the adult. FAK+, a splice isoform of FAK selectively enriched in neurons, contains a three‐amino acid insertion in the carboxy‐terminal sequence responsible for the localization of FAK to focal adhesions. Enhanced green fluorescent protein‐tagged constructs were used to study the targeting of FAK and FAK+ in neuronal and non‐neuronal cells of the central nervous system. In transfected non‐neuronal cells, both fusion proteins colocalized with vinculin in focal contacts. When expressed in hippocampal neurons in culture, both chimeras were locally concentrated in the growth cone, where they overlapped with F‐actin enrichments but not with vinculin. In the growth cone of living neurons, the FAK+ chimera showed a dynamic relocalization to membrane ruffles and to the tips of the membrane protrusions induced by cytochalasin D treatment, indicating a dependence of FAK distribution on F‐actin organization. Since virtually identical patterns of distribution were found for FAK and FAK+ chimeras, it follows that the additional insertion in FAK+ is not responsible for the localization of the kinase. Finally, we showed that the carboxy‐terminal domain of both FAK and FAK+ is sufficient to mediate the localization of the proteins to focal adhesions in non‐neuronal cells and to maintain their correct intracellular targeting in neurons.
PC12 cell activation by epidermal growth factor receptor: role of autophosphorylation sites
Authors: Tyson Darren R. , Larkin Selena , Hamai Yousuke , Bradshaw Ralph A.
Published: March 2003

PC12 cells have been used as a model system for neuronal differentiation due to their ability to alter their phenotype to a sympathetic neuron‐like cell in response to nerve growth factor or fibroblast growth factor. Under some conditions, epidermal growth factor (EGF) can also induce PC12 cells to differentiate. To study signaling from the EGF receptor without the confounding effects of endogenous EGF receptors we generated a chimeric receptor comprised of the ectodomain of platelet‐derived growth factor (PDGF) receptor in‐frame with the transmembrane and cytoplasmic domains of EGF receptor, termed PER. Expression of PER in PC12 cells confers the ability of PDGF to induce differentiation whereas PDGF has no effect on untransfected PC12 cells. This response is kinase activity‐dependent since a kinase‐deficient mutant (K721M) fails to induce differentiation in response to PDGF. Mutation of five tyrosine residues that are autophosphorylated in response to EGF either individually or in combination had minimal effects on the ability of these receptors to induce morphological PC12 cell differentiation. The PER mutant with all five autophosphorylation sites mutated to phenylalanine (5YF) was equivalently capable of interacting with several important signaling molecules, including Shc, Grb2, Gab1, phospholipase Cγ, and Cbl. Furthermore, both the phosphatidylinositol 3‐kinase (PI3K)/Akt and Ras/Erk pathways were activated in a sustained manner when PER or 5YF‐expressing cells were stimulated with PDGF. Our results show that the five autophosphorylation sites in the extra‐kinase C‐terminal domain of EGFR are not required for the ability of EGFR to induce morphological differentiation of PC12 cells.
Mastering space in Eurasia: Russia’s geopolitical thinking after the Soviet break-up
Authors: Tsygankov A.P.
Published: March 2003

This essay assumes the significance of spatial imagination in shaping the political and cultural boundaries of the post-Soviet Eurasia and reviews the newly emerged geopolitical arguments in Russia. Rather than perceiving Eurasianist views in Russia as relatively homogeneous, I argue that such thinking is highly diverse and varies from West-friendly versions to those that are openly isolationist and expansionist. To support my argument, I select six recently published Russian volumes and group them into five distinct schools of Russia’s geopolitical thinking, each with their own intellectual assumptions, worldviews, and bases of support in the society. While writing on the same subject of the Eurasian geopolitics, each author proposes principally different solutions to the problems that emerged over the 10 years of Russia’s post-communist experience. The argument invites us to rethink the nature of Russia’s spatial thinking and activities in Eurasia and to seriously consider engaging Russia as an equal participant in a larger collective security-based arrangement in the region.
The rise, fall, and transformation of the rural social contract in Russia
Authors: Wegren S.K.
Published: March 2003

The Russian countryside was among the biggest losers during market reforms in the 1990s. The combination of an emasculated state, vocal rural leadership which opposed reform, and rural conservatism would seem to portend rural instability. Yet, mass protests did not occur, and in general the countryside was quiet. Why?

This article analyzes sources of rural stability in Russia through the prism of the social contract. Rural quiescence occurred because of a transformation in the rural social contract. As market reforms unfolded, the Soviet era rural social contract ended, or at the very least was rendered untenable, and a new relationship between state and the countryside emerged. This transformation of the rural social contract was characterized by movement from statedependence to relative household independence. The nature of the rural social contract changed in three important ways: (1) the ‘contract’ was changed from below, not above; (2) rural households became less dependent upon the state for their income and welfare; and (3) the content of the ‘contract’ changed from the Soviet era exchange of increasing standards of living for quiescence/compliance to increased economic freedom for political quiescence/compliance.
Management of chronic heart failure due to systolic left ventricular dysfunction by cardiologist and non‐cardiologist physicians
Authors: McKee Sinéad P. , Leslie Stephen J. , LeMaitre John P. , Webb David J. , Denvir Martin A.
Published: March 2003

There are now a number of guidelines outlining the diagnosis and management of patients with chronic heart failure (CHF). The extent to which these guidelines are used and the effects on patient outcomes are not well known. The aim of this study was to examine the implementation of a heart failure guideline among cardiologist and non‐cardiologist physicians in a university hospital setting. Case record data were examined from 400 patients with a primary diagnosis of CHF. Management of these patients was assessed using a systolic heart failure guideline (Scottish Intercollegiate Guideline Network, number 35) as a benchmark. Hospital admission data were examined contemporaneously over a 17‐month period to assess associations between adherence to drug therapies and number of admissions. Overall, there was poor adherence to the guideline, with relatively high use of angiotensin‐converting enzyme (ACE) inhibitors/angiotensin II receptor blockers (ARBs) (80%), low use of beta‐blockers (32%) and digoxin (36%), and very low use of spironolactone (13%). Cardiologists used more beta‐blockers (37 vs. 21%, P=0.003) and digoxin in sinus rhythm (18 vs. 5%, P<0.001) than non‐cardiologists. Hospital admission rate was individually associated with increasing age, NYHA status, beta‐blocker, diuretic and spironolactone prescription (all P<0.001). At multivariable analysis, only age, NYHA status and increased diuretic prescription were associated with more frequent admission (P<0.001, R2=0.15). Despite carefully designed guidelines, the implementation of evidence‐based therapies for CHF remains inadequate, even in a university hospital environment. This may reflect a lack of organisational developments to facilitate the increasingly complex management of patients with CHF.
Lead Poisoning in Pregnancy: A Case Study with Implications for Midwives
Authors: Hackley Barbara , Katz‐Jacobson Anne
Published: March 2003

Lead poisoning remains a significant problem in the United States affecting the health of women and children. Although the damage is greatest at higher levels of accumulation, no level of lead has been found to be safe. Over the last 25 years, the blood level of lead thought to be associated with toxicity has dropped dramatically, from to 60 mcg/dL in 1960 to 10 mcg/dL today. Studies confirm that exposure to lead causes kidney damage, encephalopathy, and impaired cognitive function in children and in adults. Recent evidence indicates children with levels less than 10 mcg/dL may suffer from compromised development and intellectual performance later in life. This article discusses the case of a woman found to have lead poisoning during pregnancy. Environmental sources of lead, implications for the immediate and future health of the fetus and mother, and techniques clinicians can use in their practice to minimize the adverse effect of lead on their clients are reviewed.
Length of Normal Labor in Women of Hispanic Origin
Authors: Jones Marcia , Larson Elaine
Published: March 2003

Emanuel Friedman in the 1950s established means and statistical guidelines for normal lengths of labor. The childbearing population in the United States has changed considerably since Friedman's research was conducted. This study documented the duration of labor in a cohort of 240 Hispanic women who had normal vaginal births of singleton term infants from January 1995 through December 1998 and compared these results with the mean duration of the first and second stages of labor as established by Friedman. The mean duration of the active phase first stage labor duration for nulliparous Hispanic women was 6.2 hours, and for multiparous Hispanic women was 4.4 hours, both significantly longer than Friedman's group (P < .01). The mean duration of the second stage of labor in nulliparous Hispanic women was 54.2 minutes and for multiparous Hispanic women was 22.2 minutes, not significantly different from Friedman's group (P = .5 and P = .09, respectively).
Changes in Postpartum Perineal Muscle Function in Women With and Without Episiotomies
Authors: Fleming Nancy , Newton Edward R. , Roberts Joyce
Published: March 2003

This report presents results of a comparison perineal muscle function between antepartum and postpartum measurements in a cohort of women with different perineal conditions after childbirth. Data were obtained by using prospective electromyographic perineometry measurements to objectively determine perineal muscle function before and after delivery in 102 women. In addition, 24 nulliparous, non‐pregnant women were studied to determine the effect of pregnancy on perineal muscle function. Pregnancy is associated with a decrease in perineal muscle strength and endurance compared with the postpartum state. The degree to which women improved or did not improve perineal muscle function after birth was related to perineal trauma at delivery. After controlling for parity, maternal age, birthweight, smoking status, and antepartum scores, the order of best to worst performance was cesarean birth, intact perineum, first‐degree perineal injury, second‐ or third‐degree perineal injury, and episiotomy. Pre‐ and postdelivery scores were compared for each woman and analyzed according to perineal outcome. Although all other perineal outcome groups increased muscle function by 6 months postpartum, women with an episiotomy had a mean net loss of perineal muscle performance after birth. These observations do not support the use of episiotomy for the purpose of preserving perineal muscle function.
Nodal Yield in Neck Dissection and the Likelihood of Metastases
Authors: Agrama Mark T. , Reiter David , Cunnane Mary F. , Topham Allan , Keane William M.
Published: March 2003

OBJECTIVES

The purpose of this study was to begin investigating the relationship between nodal yield in neck dissection and the likelihood of finding cervical metastases in T1 and T2 head and neck squamous cell carcinoma (HNSCC). No clinical implications are drawn from this preliminary work.

STUDY DESIGN AND SETTING

This study was a retrospective analysis of 564 patients with T1 and T2 HNSCC of the oral cavity, oropharynx, or hypopharynx from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) Program registry. A multivariate analysis was performed to evaluate the relationship between nodal yield in neck dissection and the discovery of cervical metastases. Other independent factors included in the analysis were gender, age, race, and primary site of tumor.

RESULTS

Compared with nodal yield < 13, cervical metastases were more likely to be found for nodal yield 21–28 (P < 0.001, odds ratio (OR) = 3.68), 29–40 (P = 0.021, OR = 1.98), and >40 (P < 0.001, OR = 3.52). Increased age, male sex, and oropharynx and hypopharynx primaries were also associated with a significantly increased likelihood of finding cervical metastases.

CONCLUSION

In T1 and T2 cases of HNSCC, nodal yield >20, increased age, male sex, and primary site correspond with an increased likelihood of finding cervical metastases.
A Comparison of Nasal Clearance after Treatment of Perennial Allergic Rhinitis with Budesonide and Mometasone
Authors: Naclerio Robert M. , Baroody Fuad M. , Bidani Nalini , Marcy De Tineo , Penney Bill C.
Published: March 2003

OBJECTIVE

Evidence in vitro suggests that benzalkonium chloride, a preservative in many intranasal preparations, interferes with ciliary function and thus could potentially interfere with mucociliary transport, the mechanism for clearing secretions from the nasal cavity.

STUDY DESIGN

We performed a parallel randomized study with 10 subjects in each arm comparing Rhinocort AQUA (an intranasal steroid (budesonide) spray without benzalkonium chloride) and Nasonex (an intranasal steroid (mometasone furoate) spray with benzalkonium chloride). Before and after 2 weeks of treatment, subjects completed a Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) and underwent a measurement of nasal clearance of a radioactive colloidal spray into the nose.

RESULTS

The groups were matched at entry for nasal clearance, even though there was variability among subjects. The amount of change after 2 weeks of treatment (Δ before versus after treatment) showed a significant difference in nasal clearance favoring budesonide. After 2 weeks of treatment, both budesonide and mometasone demonstrated overall improvement in quality of life as assessed by the RQLQ. Both treatments were well tolerated.

CONCLUSION

Our study extends the observation in vitro that demonstrates the adverse effect of benzalkonium chloride on cilia to a measurement in vivo of clearance. The effects after 2 weeks might not reflect changes after longer periods of treatment.

SIGNIFICANCE

To determine the clinical significance of the small improvement in mucociliary transport will require large clinical trials.
Vestibular Rehabilitation: Useful but not Universally so
Authors: David E. Krebs , Kathleen M. Gill‐Body , Stephen W. Parker , Jose V. Ramirez , Mara Wernick‐Robinson
Published: March 2003

OBJECTIVE

Although vestibular rehabilitation (VR) is gaining popularity, few data support its utility in improving locomotor stability, and no good predictors exist of whom will benefit most.

STUDY DESIGN AND SETTING

A double‐blind, placebo‐controlled randomized trial of vestibular rehabilitation was conducted at a large tertiary care hospital on 124 patients (59 ± 18 years old) with unilateral (n = 51) or bilateral (n = 73) vestibular hypofunction, of whom 86 completed a 12‐week intervention. Of these 86, 27 returned for long‐term (1‐year) follow‐up testing. The primary outcome measure was locomotor stability.

RESULTS

Group A (6 weeks of VR) significantly (P < 0.01) increased their gait velocity and stability compared with group B (6 weeks of strengthening exercise), but there was a smaller difference (P = 0.05) between groups at 12 weeks, when both had had VR; there were no group differences at 1 year. Of the 86 who completed the intervention, 52 (61%) had clear locomotor gains.

CONCLUSION AND SIGNIFICANCE

VR is helpful for most patients in providing locomotor stability, but further work is needed to determine the factors that prevent VR from being effective for all patients with vestibulopathy.
Combined Positron Emission Tomography/Computed Tomography Imaging of Recurrent Thyroid Cancer
Authors: Zimmer Lee A. , McCook Barry , Meltzer Carolyn , Fukui Melanie , Bascom Daphne , Snyderman Carl , Townsend David W. , Johnson Jonas T.
Published: March 2003

OBJECTIVE

The study goal was to evaluate the use of combined positron emission tomography/computed tomography (PET/CT) imaging for localization of recurrent disease in thyroid cancer patients.

STUDY DESIGN AND SETTING

Eight patients with suspected recurrence of thyroid cancer on the basis of elevated serum thyroglobulin or calcitonin levels underwent combined PET/CT imaging on a prototype device. All 8 patients had previously undergone total thyroidectomy and 131I ablation for thyroid carcinoma. Patients with papillary carcinoma had negative 131I scans.

RESULTS

Eight patients underwent combined PET/CT scanning. Four (50%) of 8 patients underwent PET/CT indicating recurrence in the head and neck. A total of 11 lesions in these 4 patients were suspicious for recurrence on combined PET/CT imaging. Three patients with 8 lesions suspicious for recurrence on PET/CT underwent surgical removal of disease. All 3 patients had pathologic confirmation of recurrence, with 6 (75.0%) of 8 lesions being positive.

CONCLUSION

Combined PET/CT imaging is a valuable tool for the diagnosis and anatomic localization of recurrent thyroid cancer.
Amputation Neuromas after Neck Dissection
Authors: Talmi Yoav P. , Bedrin Lev , Dori Shay , Horowitz Zeev , Wolf Michael , Yahalom Ran , Peleg Michael , Teicher Shlomo , Kronenberg Jona
Published: March 2003

OBJECTIVE

We sought to define the incidence of neuroma formation after neck dissection in a large series of patients.

METHODS

One hundred fifty‐three patients who were seen during a 2‐year period (followed for 3 months to 10 years; mean, 52 months) were evaluated for neuroma formation after neck dissection (185 procedures). Cut nerve edges were not routinely ligated or cauterized.

RESULTS

Operative records indicated that except for 4 cases, the stumps of the great auricular nerve and cervical branches were left intact after resection. No cases of palpable neuromas were found. In one case of a revised neck, a small macroscopically indiscernible nodule was histologically defined as neuroma.

CONCLUSION

No neuromas were discovered in our series of neck dissection cases. If found, it is imperative these lesions be differentiated from recurrent cancer. Our results do not support any interference with cut nerve edges.
The Use of Cortical Evoked Response Audiometry in the Assessment of Noise‐Induced Hearing Loss
Authors: Stephen W. Hone , Garry Norman , Ivan Keogh , Vivian Kelly
Published: March 2003

OBJECTIVES

The study aims were to determine the incidence of exaggerated hearing thresholds in individuals complaining of noise‐induced hearing loss (NIHL) as a result of impulse noise using cortical evoked response audiometry (CERA) and to identify any associated audiometric features.

SETTING

We conducted an office‐based study.

STUDY DESIGN

In this prospective case series, 1154 males complaining of NIHL were assessed with pure tone audiometry; 673 had CERA. Pure tone averages (PTA) and hearing disability were calculated using the Irish and American Medical Association systems. A PTA of >10 dB worse than the CERA average was considered evidence of exaggerated thresholds.

RESULTS

The mean PTA was 33 dB. Seventy‐two percent had a hearing disability of an average of 26% when assessed by the Irish system. Fifty‐four percent had a hearing disability of an average of 30% when assessed by the American Medical Association system. Twenty‐six percent of subjects had exaggerated thresholds based on CERA. A binaural hearing threshold of >25 dB at 500 Hz had a sensitivity of 94% and a specificity of 59% for the detection of exaggerated thresholds.

CONCLUSION

Exaggerated hearing thresholds are common. A hearing threshold of >25dB at 500 Hz should be considered an indication for CERA testing.
Efficacy of Surgical Treatment of Chronic Otitis Media
Authors: Laércio M. Cruz Oswaldo , Kasse Cristiane A. , Leonhart Fernando D.
Published: March 2003

This article presents our results of surgical treatment of chronic otitis media (COM) and discusses its efficacy regarding the control of disease and hearing results. A retrospective chart review of 84 ears was performed. Forty‐one ears with noncholesteatomatous COM underwent tympanomastoidectomy, 43 ears with cholesteatoma were managed according to the extension of the disease, closed mastoidectomy was indicated in 19 cases, and open mastoidectomy was performed in 24 ears. In the group without cholesteatoma, a stable ear with closed tympanic membrane was obtained in 85% of cases after the first procedure. The speech response threshold before and after surgery was 38 and 26 dB. In patients with cholesteatoma, a dry ear was achieved in 79% of cases on both techniques after the first intervention. The recurrence rate of cholesteatoma was 10% for the closed technique and 4% for the open technique. The mean preoperative and postoperative SRTs for the closed technique were 30 and 29 dB and for the open technique were 50 and 54 dB. The surgical treatment for COM can be a rewarding procedure if a correct technique is indicated. The surgery should be tailored regarding the clinical stage and intraoperative findings in each case.
Origin and evolution of circadian clock genes in prokaryotes
Authors: Dvornyk Volodymyr , Vinogradova Oxana , Nevo Eviatar
Published: March 2003

Regulation of physiological functions with approximate daily periodicity, or circadian rhythms, is a characteristic feature of eukaryotes. Until recently, cyanobacteria were the only prokaryotes reported to possess circadian rhythmicity. It is controlled by a cluster of three genes:
kaiA
,
kaiB
, and
kaiC
. Using sequence data of ≈70 complete prokaryotic genomes from the various public depositories, we show here that the
kai
genes and their homologs have quite a different evolutionary history and occur in Archaea and Proteobacteria as well. Among the three genes,
kaiC
is evolutionarily the oldest, and
kaiA
is the youngest and likely evolved only in cyanobacteria. Our data suggest that the prokaryotic circadian pacemakers have evolved in parallel with the geological history of the earth, and that natural selection, multiple lateral transfers, and gene duplications and losses have been the major factors shaping their evolution.
Progesterone receptors mediate male aggression toward infants
Authors: Schneider Johanna S. , Stone Marielle K. , Wynne-Edwards Katherine E. , Horton Teresa H. , Lydon John , O'Malley Bert , Levine Jon E.
Published: March 2003

Neuroendocrine mechanisms that mediate male aggression toward infants are poorly understood. Although testosterone is known to enhance aggression in other social contexts, evidence that it modulates aggression toward infants is equivocal. We have found that male progesterone receptor knockout (PRKO) mice exhibit no infanticidal behavior and little aggression toward young. Male PRKO mice also display significantly enhanced parental behaviors. In wild-type mice, blockade of PR induces a behavioral phenotype similar to that of the PRKO males, whereas progesterone exacerbates aggressive tendencies toward infants. Aggressive behaviors directed toward adult males, by contrast, are unaffected by progesterone, PR antagonism, or PR gene deletion. Previously thought to be of diminished importance in male animals, PRs play a critical and specific role in modulating infant-directed behaviors in male mice.
The role of E2F4 in adipogenesis is independent of its cell cycle regulatory activity
Authors: Landsberg Rebecca L. , Sero Julia E. , Danielian Paul S. , Yuan Tina L. , Lee Eunice Y. , Lees Jacqueline A.
Published: March 2003

The E2F and pocket protein families are known to play an important role in the regulation of both cellular proliferation and terminal differentiation. In this study, we have used compound E2F and pocket protein mutant mouse embryonic fibroblasts to dissect the role of these proteins in adipogenesis. This analysis shows that loss of E2F4 allows cells to undergo spontaneous differentiation. The ability of E2F4 to prevent adipogenesis seems to be quite distinct from the known properties of E2F. First, it can be separated from any change in either E2F-responsive gene expression or cell cycle regulation. Second, it is a specific property of E2F4, and not other E2Fs, and it occurs independently of E2F4's ability to interact with pocket proteins. In addition, E2F4 loss does not override the differentiation defect resulting from pRB loss even though it completely suppresses the proliferation defect of
Rb
−/−
mouse embryonic fibroblasts. This finding definitively separates the known, positive role of pRB in adipogenesis from its cell cycle function and shows that this pocket protein is required to act downstream of E2F4 in the differentiation process.
The Cdc23 (Mcm10) protein is required for the phosphorylation of minichromosome maintenance complex by the Dfp1-Hsk1 kinase
Authors: Lee Joon-Kyu , Seo Yeon-Soo , Hurwitz Jerard
Published: March 2003

Previous studies in
Saccharomyces cerevisiae
have defined an essential role for the Dbf4-Cdc7 kinase complex in the initiation of DNA replication presumably by phosphorylation of target proteins, such as the minichromosome maintenance (Mcm) complex. We have examined the phosphorylation of the Mcm complex by the Dfp1-Hsk1 kinase, the
Schizosaccharomyces pombe
homologue of Dbf4-Cdc7.
In vitro
, the purified Dfp1-Hsk1 kinase efficiently phosphorylated Mcm2p. In contrast, Mcm2p, present in the six-subunit Mcm complex, was a poor substrate of this kinase and required Cdc23p (homologue of Mcm10p) for efficient phosphorylation. In the presence of Cdc23p, Dfp1-Hsk1 phosphorylated the Mcm2p and Mcm4p subunits of the Mcm complex. Cdc23p interacted with both the Mcm complex and Dfp1-Hsk1 by selectively binding to the Mcm4/6/7 subunits and Dfp1p, respectively. The N terminus of Cdc23p was found to interact directly with Dfp1-Hsk1 and was essential for phosphorylation of the Mcm complex. Truncated derivatives of Cdc23p that complemented the temperature-sensitive phenotype of
cdc23
mutant cells also stimulated the phosphorylation of Mcm complex, implying that this activity might be a critical role of Cdc23p
in vivo
. These results suggest that Cdc23p participates in the activation of prereplicative complex by recruiting the Dfp1-Hsk1 kinase and stimulating the phosphorylation of the Mcm complex.
Cloning, expression, and characterization of a membrane progestin receptor and evidence it is an intermediary in meiotic maturation of fish oocytes
Authors: Zhu Yong , Rice Charles D. , Pang Yefei , Pace Margaret , Thomas Peter
Published: March 2003

The structures of membrane receptors mediating rapid, nongenomic actions of steroids have not been identified. We describe the cloning of a cDNA from spotted seatrout ovaries encoding a protein that satisfies the following seven criteria for its designation as a steroid membrane receptor: plausible structure, tissue specificity, cellular distribution, steroid binding, signal transduction, hormonal regulation, and biological relevance. For plausible structure, computer modeling predicts that the protein has seven transmembrane domains, typical of G protein-coupled receptors. The mRNA (4.0 kb) is only detected in the brain and reproductive tissues on Northern blots. Antisera only detect the protein (40 kDa) in plasma membranes of reproductive tissues. The recombinant protein produced in an
Escherichia coli
expression system has a high affinity (
K
d
= 30 nM), saturable, displaceable, single binding site specific for progestins. Progestins alter signal transduction pathways, activating mitogen-activated protein kinase and inhibiting adenylyl cyclase, in a transfected mammalian cell line. Inhibition of adenylyl cyclase is pertussis toxin sensitive, suggesting the receptor may be coupled to an inhibitory G protein. Progestins and gonadotropin up-regulate both mRNA and protein levels in seatrout ovaries. Changes in receptor abundance in response to hormones and at various stages of oocyte development, its probable coupling to an inhibitory G protein and inhibition of progestin induction of oocyte maturation upon microinjection of antisense oligonucleotides are consistent with the identity of the receptor as an intermediary in oocyte maturation. These characteristics suggest the fish protein is a membrane progestin receptor mediating a “nonclassical” action of progestins to induce oocyte maturation in fish.
The purine salvage enzyme hypoxanthine guanine xanthine phosphoribosyl transferase is a major target antigen for cell-mediated immunity to malaria
Authors: Makobongo Morris O. , Riding George , Xu Huji , Hirunpetcharat Chakrit , Keough Dianne , de Jersey John , Willadsen Peter , Good Michael F.
Published: March 2003

Although there is good evidence that immunity to the blood stages of malaria parasites can be mediated by different effector components of the adaptive immune system, target antigens for a principal component, effector CD4+T cells, have never been defined. We generated CD4+T cell lines to fractions of native antigens from the blood stages of the rodent parasite,Plasmodium yoelii, and identified fraction-specific T cells that had a Th1 phenotype (producing IL-2, IFN-γ, and tumor necrosis factor-α, but not IL-4, after antigenic stimulation). These T cells could inhibit parasite growth in recipient severe combined immunodeficient mice. N-terminal sequencing of the fraction showed identity with hypoxanthine guanine xanthine phosphoribosyl transferase (HGXPRT). Recombinant HGXPRT from the human malaria parasite,Plasmodium falciparum, activated the T cellsin vitro, and immunization of normal mice with recombinant HGXPRT reduced parasite growth rates in all mice after challenge.
The endocrine-gland-derived VEGF homologue Bv8 promotes angiogenesis in the testis: Localization of Bv8 receptors to endothelial cells
Authors: LeCouter Jennifer , Lin Rui , Tejada Max , Frantz Gretchen , Peale Franklin , Hillan Kenneth J. , Ferrara Napoleone
Published: March 2003

We recently identified an angiogenic mitogen, endocrine-gland-derived vascular endothelial growth factor (EG-VEGF), with selective activity for endothelial cells of endocrine tissues. Here we describe the characterization of a highly related molecule, Bv8, also known as prokineticin-2. Human Bv8 shares 60% identity and 75% similarity with EG-VEGF. The human and mouse Bv8 genes share a common structure. Like EG-VEGF, Bv8 is able to induce proliferation, survival and migration of adrenal cortical capillary endothelial cells. Bv8 gene expression is induced by hypoxic stress. Bv8 expression occurs predominantly in the testis and is largely restricted to primary spermatocytes. Adenoviral delivery of Bv8 or EG-VEGF to the mouse testis resulted in a potent angiogenic response. We have localized the expression of the Bv8/EG-VEGF receptors within the testis to vascular endothelial cells. The testis exhibits relatively high turnover of endothelial cells. Therefore, Bv8 and EG-VEGF, along with other factors such as VEGF-A, may maintain the integrity and also regulate proliferation of the blood vessels in the testis.
Rnf2
(
Ring1b
) deficiency causes gastrulation arrest and cell cycle inhibition
Authors: Voncken Jan Willem , Roelen Bernard A. J. , Roefs Mieke , de Vries Stijn , Verhoeven Els , Marino Silvia , Deschamps Jacqueline , van Lohuizen Maarten
Published: March 2003

The highly homologous Rnf2 (Ring1b) and Ring1 (Ring1a) proteins were identified as
in vivo
interactors of the Polycomb Group (PcG) protein Bmi1. Functional ablation of
Rnf2
results in gastrulation arrest, in contrast to relatively mild phenotypes in most other PcG gene null mutants belonging to the same functional group, among which is
Ring1
. Developmental defects occur in both embryonic and extraembryonic tissues during gastrulation. The early lethal phenotype is reminiscent of that of the PcG-gene knockouts
Eed
and
Ezh2
, which belong to a separate functional PcG group and PcG protein complex. This finding indicates that these biochemically distinct PcG complexes are both required during early mouse development. In contrast to the strong skeletal transformation in
Ring1
hemizygous mice, hemizygocity for
Rnf2
does not affect vertebral identity. However, it does aggravate the cerebellar phenotype in a
Bmi1
null-mutant background. Together, these results suggest that Rnf2 or Ring1-containing PcG complexes have minimal functional redundancy in specific tissues, despite overlap in expression patterns. We show that the early developmental arrest in
Rnf2
-null embryos is partially bypassed by genetic inactivation of the
Cdkn2a
(
Ink4a/ARF
) locus. Importantly, this finding implicates Polycomb-mediated repression of the
Cdkn2a
locus in early murine development.
Quantitative proteomic analysis indicates increased synthesis of a quinolone by
Pseudomonas aeruginosa
isolates from cystic fibrosis airways
Authors: Guina Tina , Purvine Samuel O. , Yi Eugene C. , Eng Jimmy , Goodlett David R. , Aebersold Ruedi , Miller Samuel I.
Published: March 2003

The opportunistic bacterial pathogen
Pseudomonas aeruginosa
colonizes airways of individuals with cystic fibrosis (CF) with resultant chronic destructive lung disease.
P. aeruginosa
adaptation to the CF airway includes biofilm formation and antibiotic resistance. Isolates from asymptomatic individuals in the first 3 years of life have unique characteristics, suggesting that adaptation occurs before clinical symptoms. One defined early adaptation is expression of a specific proinflammatory lipopolysaccharide (LPS) that is associated with antimicrobial peptide resistance. This CF-specific LPS is induced when
P. aeruginosa
is grown in medium that is limited for magnesium. Therefore, qualitative and quantitative proteomic approaches were used to define 1,331
P. aeruginosa
proteins, of which 145 were differentially expressed on limitation of magnesium. Among proteins induced by low magnesium were enzymes essential for production of 2-heptyl 3-hydroxy 4-quinolone, the
Pseudomonas
quinolone signal (PQS), which interacts with the homoserine lactone signaling pathway. Measurement of PQS in
P. aeruginosa
isolates from asymptomatic children with CF indicated that strains with increased synthesis of PQS are present during early colonization of CF patient airways.
Identification, classification, and partial characterization of genes in humans and other vertebrates homologous to a fish membrane progestin receptor
Authors: Zhu Yong , Bond Jason , Thomas Peter
Published: March 2003

Recently we discovered a previously uncharacterized gene with the characteristics of a membrane progestin receptor (mPR) in a fish model, spotted seatrout. Here, we report the identification, cloning, and characteristics of other members of this hitherto unknown family of putative mPRs from several vertebrate species, including human, mouse, pig,Xenopus, zebrafish, andFugu, with highly conserved nucleotide and deduced amino acid sequences and similar structures to the spotted seatrout mPR. The 13 vertebrate genes identified seem to belong to an unknown gene family. Phylogenetic analysis indicates these cDNAs comprise three distinct groups (named α, β, and γ) within this gene family. Structural analyses of the translated cDNAs suggest they encode membrane proteins with seven transmembrane domains. The transcript sizes of the human α, β, and γ putative mPR mRNAs varied from 2.8 to 5.8 kb and showed distinct distributions in reproductive, neural, kidney and intestinal tissues, respectively. Recombinant human α, γ, and mouse β proteins produced in anEscherichia coliexpression system demonstrated high affinity (Kd= 20–30 nM) saturable binding for progesterone. Further analysis of binding to the γ-subtype revealed binding was specific for progestins and was displaceable, with rapid rates of association and dissociation (t1/2= 2–8 min). These results suggest this is a new family of steroid receptors unrelated to nuclear steroid receptors, but instead having characteristics of G protein-coupled receptors.
Gonadotrophin-releasing hormone drives melatonin receptor down-regulation in the developing pituitary gland
Authors: Johnston Jonathan D. , Messager Sophie , Ebling Francis J. P. , Williams Lynda M. , Barrett Perry , Hazlerigg David G.
Published: March 2003

Melatonin is produced nocturnally by the pineal gland and is a neurochemical representation of time. It regulates neuroendocrine target tissues through G-protein-coupled receptors, of which MT
1
is the predominant subtype. These receptors are transiently expressed in several fetal and neonatal tissues, suggesting distinct roles for melatonin in development and that specific developmental cues define time windows for melatonin sensitivity. We have investigated MT
1
gene expression in the rat pituitary gland. MT
1
mRNA is confined to the pars tuberalis region of the adult pituitary, but in neonates extends into the ventral pars distalis and colocalizes with luteinizing hormone β-subunit (LHβ) expression. This accounts for the well documented transient sensitivity of rat gonadotrophs to melatonin in the neonatal period. Analysis of an upstream fragment of the rat MT
1
gene revealed multiple putative response elements for the transcription factor pituitary homeobox-1 (Pitx-1), which is expressed in the anterior pituitary from Rathke's pouch formation. A Pitx-1 expression vector potently stimulated expression of both MT
1
-luciferase and LHβ-luciferase reporter constructs in COS-7 cells. Interestingly, transcription factors that synergize with Pitx-1 to
trans
-activate gonadotroph-associated genes did not potentiate Pitx-1-induced MT
1
-luciferase activity. Moreover, the transcription factor, early growth response factor-1, which is induced by gonadotrophin-releasing hormone (GnRH) and
trans
-activates LHβ expression, attenuated Pitx-1-induced MT
1
-luciferase activity. Finally, pituitary MT
1
gene expression was 4-fold higher in
hypogonadal
(
hpg
) mice, which do not synthesize GnRH, than in their wild-type littermates. These data suggest that establishment of a mature hypothalamic GnRH input drives the postnatal decline in pituitary MT
1
gene expression.