bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractPC12 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.
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

AbstractThere 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.
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

OBJECTIVESThe 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 SETTINGThis 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.RESULTSCompared 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.CONCLUSIONIn 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

OBJECTIVEEvidence 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 DESIGNWe 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.RESULTSThe 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.CONCLUSIONOur 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.SIGNIFICANCETo 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

OBJECTIVEAlthough 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 SETTINGA 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.RESULTSGroup 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 SIGNIFICANCEVR 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

OBJECTIVEThe 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 SETTINGEight 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.RESULTSEight 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.CONCLUSIONCombined 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

OBJECTIVEWe sought to define the incidence of neuroma formation after neck dissection in a large series of patients.METHODSOne 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.RESULTSOperative 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.CONCLUSIONNo 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

OBJECTIVESThe 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.SETTINGWe conducted an office‐based study.STUDY DESIGNIn 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.RESULTSThe 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.CONCLUSIONExaggerated 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.
Screening of Gene-Associated Polymorphisms by Use of In-Gel Competitive Reassociation and EST (cDNA) Array Hybridization
Authors: Gotoh Koshichi , Oishi Michio 
Published: March 2003

In-gel competitive reassociation (IGCR) is a method of differential subtraction to enrich polymorphic DNA restriction fragments between two DNA samples without probes or specific sequence information. Here, we show that by combining IGCR and expressed sequence tags (EST) array hybridization, polymorphic DNA fragments associated with genes in complex higher organisms (Arabidopsis thaliana) can be effectively screened, demonstrating that this procedure offers a simple and efficient way to obtain gene-associated polymorphic DNA markers.[The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: N. Sakurai, D. Shibata, and C. Kuwata.]
Segmental Duplications in Euchromatic Regions of Human Chromosome 5: A Source of Evolutionary Instability and Transcriptional Innovation
Authors: Courseaux Anouk , Richard Florence , Grosgeorge Josiane , Ortola Christine , Viale Agnes , Turc-Carel Claude , Dutrillaux Bernard , Gaudray Patrick , Nahon Jean-Louis 
Published: March 2003

Recent analyses of the structure of pericentromeric and subtelomeric regions have revealed that these particular regions of human chromosomes are often composed of blocks of duplicated genomic segments that have been associated with rapid evolutionary turnover among the genomes of closely related primates. In the present study, we show that euchromatic regions of human chromosome 5—5p14, 5p13, 5q13, 5q15–5q21—also display such an accumulation of segmental duplications. The structure, organization and evolution of those primate-specific sequences were studied in detail by combining in silico and comparative FISH analyses on human, chimpanzee, gorilla, orangutang, macaca, and capuchin chromosomes. Our results lend support to a two-step model of transposition duplication in the euchromatic regions, with a founder insertional event at the time of divergence betweenPlatyrrhiniandCatarrhini(25–35 million years ago) and an apparent burst of inter- and intrachromosomal duplications in theHominidaelineage. Furthermore, phylogenetic analysis suggests that the chronology and, likely, molecular mechanisms, differ regarding the region of primary insertion—euchromatic versus pericentromeric regions. Lastly, we show that as their counterparts located near the heterochromatic region, the euchromatic segmental duplications have consistently reshaped their region of insertion during primate evolution, creating putative mosaic genes, and they are obvious candidates for causing ectopic rearrangements that have contributed to evolutionary/genomic instability.[Supplemental material is available online atwww.genome.org. The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: D. Le Paslier, A. McKenzie, J. Melki, C. Sargent, J. Scharf and S. Selig.]
Large-Scale Identification of Single-Feature Polymorphisms in Complex Genomes
Authors: Borevitz Justin O. , Liang David , Plouffe David , Chang Hur-Song , Zhu Tong , Weigel Detlef , Berry Charles C. , Winzeler Elizabeth , Chory Joanne 
Published: March 2003

We have developed a high-throughput genotyping platform by hybridizing genomic DNA from Arabidopsis thaliana accessions to an RNA expression GeneChip (AtGenome1). Using newly developed analytical tools, a large number of single-feature polymorphisms (SFPs) were identified. A comparison of two accessions, the reference strain Columbia (Col) and the strain Landsberg erecta (Ler), identified nearly 4000 SFPs, which could be reliably scored at a 5% error rate. Ler sequence was used to confirm 117 of 121 SFPs and to determine the sensitivity of array hybridization. Features containing sequence repeats, as well as those from high copy genes, showed greater polymorphism rates. A linear clustering algorithm was developed to identify clusters of SFPs representing potential deletions in 111 genes at a 5% false discovery rate (FDR). Among the potential deletions were transposons, disease resistance genes, and genes involved in secondary metabolism. The applicability of this technique was demonstrated by genotyping a recombinant inbred line. Recombination break points could be clearly defined, and in one case delimited to an interval of 29 kb. We further demonstrate that array hybridization can be combined with bulk segregant analysis to quickly map mutations. The extension of these tools to organisms with complex genomes, such as Arabidopsis, will greatly increase our ability to map and clone quantitative trait loci (QTL).[Supplemental material is available online atwww.genome.org.]
Large-Scale Analysis of the Meningococcus Genome by Gene Disruption: Resistance to Complement-Mediated Lysis
Authors: Geoffroy Marie-Claude , Floquet Stéphanie , Métais Arnaud , Nassif Xavier , Pelicic Vladimir 
Published: March 2003

The biologic role of a majority of the Neisseria meningitidis 2100 predicted coding regions is still to be assigned or experimentally confirmed. Determining the phenotypic effect of gene disruption being a fundamental approach to understanding gene function, we used high-density signature-tagged transposon mutagenesis, followed by a large-scale sequencing of the transposon insertion sites, to construct a genome-wide collection of mutants. The sequencing results for the first half of the 4548 mutants composing the library suggested that we have mutations in 80%–90% of N. meningitidisnonessential genes. This was confirmed by a whole-genome identification of the genes required for resistance to complement-mediated lysis, a key to meningococcal virulence. We show that all the genes we identified, including four previously uncharacterized, were important for the synthesis of the polysialic acid capsule or the lipooligosaccharide (LOS), suggesting that these are likely to be the only meningococcal attributes necessary for serum resistance. Our work provides a valuable and lasting resource that may lead to a global map of gene function in N. meningitidis.[Supplemental material is available online at www.genome.org. The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: E. Carbonnelle, M. Joussemet, D. Caugant, M.-J. Quentin-Millet.]
The Development of a Highly Informative Mouse Simple Sequence Length Polymorphism (SSLP) Marker Set and Construction of a Mouse Family Tree Using Parsimony Analysis
Authors: Witmer Philip D. , Doheny Kimberly F. , Adams Marcia K. , Boehm Corinne D. , Dizon Jane S. , Goldstein Janet L. , Templeton Tira M. , Wheaton Ariana M. , Dong Penny N. , Pugh Elizabeth W. , Nussbaum Robert L. , Hunter Kent , Kelmenson Jennifer A. , Rowe Lucy B. , Brownstein Michael J. 
Published: March 2003

To identify highly informative markers for a large number of commonly employed murine crosses, we selected a subset of the extant mouse simple sequence length polymorphism (SSLP) marker set for further development. Primer pairs for 314 SSLP markers were designed and typed against 54 inbred mouse strains. We designed new PCR primer sequences for the markers selected for multiplexing using the fluorescent dyes FAM, VIC, NED, and ROX. The number of informative markers for C57BL/6J × DBA/2J is 217, with an average spacing of 6.8 centiMorgans (cM). For all other pairs of strains, the mean number of informative markers per cross is 197.0 (SD 37.8) with a mean distance between markers of 6.8 cM (SD 1.1). To confirm map positions of the 224 markers in our set that are polymorphic betweenMus musculusandMus spretus, we used The Jackson Laboratory (TJL) interspecific backcross mapping panel (TJL BSS); 168 (75%) of these markers had not been previously mapped in this cross by other investigators, adding new information to this community map resource. With this large data set, we sought to reconstruct a phylogenetic history of the laboratory mouse using Wagner parsimony analysis. Our results are largely congruent with the known history of inbred mouse strains.[The following individuals kindly provided reagents, samples, or unpublished information as indicated in the paper: E. Eicher, T. Golovkina, J. Cheverud, S. Cropp, P. Denny, and A. Southwell.]