bluuebunny/crossref_metadata_2025 huggingface dataset:
Probing the Effect of Binding Site and Metal Centre Variation in Pentadentate Oligopyridylimine‐Bearing Bimetallic (Fe2, Co2, Ni2) Ethylene Oligomerisation Catalysts
Authors: Armitage Andrew P. , Champouret Yohan D. M. , Grigoli Hubert , Pelletier Jérémie D. A. , Singh Kuldip , Solan Gregory A.
Published: September 2008

The symmetrical and unsymmetrical pentaaza 2,6‐oligopyridylimines, 6,6″‐[(2,6‐iPr2C6H3)N=CMe]2‐2,2′:6′,2″‐C15H9N3 (L1) and 6‐[(2,6‐iPr2C6H3)N=CMe]‐2,2′:6′,2″:6″,2″′‐C20H13N4 (L2), have been prepared in good yield using a combination of palladium(0)‐mediated cross‐coupling and condensation strategies. Treatment of L1 or L2 with two equivalents of MX2 in nBuOH at elevated temperatures affords the paramagnetic bimetallic complexes [(L1)M2X4] [M = Fe, X = Cl (1); M = Co, X = Cl (2a); M = Co, X = Br (2b); M = Ni, X = Br (3)] and [(L2)M2X4] [M = Fe, X = Cl (4); M = Co, X = Cl (5a); M = Co, X = Br (5b); M = Ni, X = Br (6)] in high yield, respectively. The molecular structures of 2a along with the acetonitrile adduct of 5b, [5b(NCMe)], have been determined and reveal that L1 and L2 compartmentalise the MX2 units into mixed pyridylimine/dipyridylimine (2a) and pyridylimine/terpyridine [5b(NCMe)] binding sites. Unexpectedly during crystallisation of 6 from acetonitrile, the salt [(L2)Ni2Br2(μ‐Br)(NCMe)2]2[NiBr4] (7) was obtained as the only crystalline product. On activation with MAO (methylaluminoxane), 4–6 show only low activities for ethylene oligomerisation (6/MAO > 5/MAO) or are inactive (4/MAO). On the other hand, 1–3 are considerably more active (3/MAO > 2/MAO > 1/MAO) with the most productive system, dinickel‐based 3/MAO (450 g mmol–1 h–1 bar–1), yielding methyl‐branched waxes composed of mostly internal unsaturation along with lower levels of α‐olefins; conversely the diiron (1/MAO) and dicobalt (2/MAO) systems give uniquely linear α‐olefins. For purposes of comparison the synthesis, structure and catalytic activity of mono‐nickel [(6‐{(2,6‐iPr2C6H3)N=CMe}‐2,2′‐C10H7N2)NiBr2] (8) are also reported. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
The Binary Ph2PCl/GaCl3 System: A Room‐Temperature Molten Medium for P–P Bond Formation
Authors: Weigand Jan J. , Burford Neil , Decken Andreas
Published: September 2008

An equimolar reaction mixture of Ph2PCl and GaCl3 at room temperature results in the formation of a melt M consisting of the donor–acceptor complex Ph2PCl→GaCl3 (1a), the chloro(diphenylphosphanyl)diphenylphosphonium cation (2a), and the counteranions [GanCl3n+1]– (n = 1, 2, 3). The melt has been characterized by Raman and NMR spectroscopy and is compared with the reaction mixture of Ph2PCl and GaCl3 observed in solution (CH2Cl2). The melt provides a facile and reactive source of the diphenylphosphenium cation, as demonstrated with use for P–P bond insertion into (PhP)5, to give the 2,3,4,5‐tetraphosphanyl‐1,4‐diphosphonium dication (3), and reductive coupling with gallium metal to give the diadduct Cl3GaPPh2PPh2GaCl3 (5).(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
N‐Heterocyclic Carbene‐Catalyzed Domino Reactions of Formylcyclopropane 1,1‐Diesters: A New Synthesis of Coumarins
Authors: Du Ding , Wang Zhongwen
Published: September 2008

N‐Heterocyclic carbenes (NHCs) catalyze the reaction of formylcyclopropane 1,1‐diesters with salicylaldehydes in a domino redox esterification/cyclization reaction to give coumarins in moderate to excellent yields. In addition, we also report the intramolecular conversion of compound 2f to dihydropyranone 4 catalyzed by NHC D. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Synthesis of the L‐Acid (C1–C18) Fragment of Pamamycin‐593 and De‐N‐methylpamamycin‐579
Authors: Miura Ayako , Takigawa Shin‐ya , Furuya Yukito , Yokoo Yusuke , Kuwahara Shigefumi , Kiyota Hiromasa
Published: September 2008

The L‐acid (C1–C18) fragment of pamamycin‐593 and de‐N‐methylpamamycin‐579, strong aerial mycelium‐inducers of Streptomyces alboniger, was synthesized using a cis‐selective iodoetherification and a nucleophilic addition of a cerium acetylide to an aldehyde as the key steps. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Diastereoselective Synthesis of Heteroaromatic Glycine Derivatives
Authors: Andreassen Trygve , Hansen Lars‐Kristian , Gautun Odd R.
Published: September 2008

A TMSOTf promoted addition of an N‐tert‐butanesulfinyl α‐imino ester to five‐membered aromatic heterocycles furnishes optically active heteroaromatic glycine derivatives with moderate‐to‐good yield in diastereomeric ratios up to 99 %. The absolute configuration of two of the addition products were solved by X‐ray analysis. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Gold Catalysis and Chiral Sulfoxides: Enantioselective Synthesis of Dihydroisoindol‐4‐ols
Authors: Hashmi A. Stephen K. , Schäfer Sascha , Bats Jan W. , Frey Wolfgang , Rominger Frank
Published: September 2008

Furfurals and enantomerically pure sulfinamides have been condensed to N‐sulfinylimines. Addition of organolithium or ‐magnesium compounds to these imines allowed a 1,2‐induction. After propargylation, the sulfinamides gave low conversion with gold catalysts. Oxidation to chiral sulfonamides, propargylation and gold‐catalysed cycloisomerization to the phenol delivered non‐racemic dihydroisoindol‐4‐ols in good yields. In situ NMR studies prove the intermediacy of the arene oxide even with the AuCl3 catalyst.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
An Improved Iron‐Catalyzed Epoxidation of Aromatic and Aliphatic Olefins with Hydrogen Peroxide as Oxidant
Authors: Bitterlich Bianca , Schröder Kristin , Tse Man Kin , Beller Matthias
Published: September 2008

A convenient and practical method for the iron‐catalyzed epoxidation of aromatic and aliphatic olefins is described. The iron catalyst system is generated in situ from iron trichloride hexahydrate, pyridine‐2,6‐dicarboxylic acid (H2pydic), and benzylamines. By variation of the benzylamine ligand, a variety of aliphatic and aromatic olefins were oxidized in high yield (up to 96 %) and good‐to‐excellent selectivity in the presence of hydrogen peroxide as the terminal oxidant. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Dendritic Silver/Silicon Dioxide Nanocomposite Modified Electrodes for Electrochemical Sensing of Hydrogen Peroxide
Authors: Yuan Peixi , Zhuo Ying , Chai Yaqin , Ju Huangxian
Published: September 2008

A novel biosensor for hydrogen peroxide was prepared by immobilizing horseradish peroxidase (HPR) on newly synthesized dendritic silver/silicon dioxide nanocomposites, which were coated on a glassy carbon electrode. The modified electrode was characterized with XPS, SEM, and electrochemical methods. This biosensor showed a very fast amperometric response to hydrogen peroxide with a linear range from 0.7 to 120 μM, a limit of detection of 0.05 μM and a sensitivity of 1.02 mA mM−1 cm−2. The Michaelis‐Menten constant of the immobilized HRP was estimated to be 0.21 mM, indicating a high affinity of the HRP to H2O2 without loss of enzymatic activity. The preparation of the proposed biosensor was convenient, and it showed high sensitivity and good stability.
Cryptic and partial deletions of PRDM16 and RUNX1 without t(1;21)(p36;q22) and/or RUNX1–PRDM16 fusion in a case of progressive chronic myeloid leukemia: A complex chromosomal rearrangement of underestimated frequency in disease progression?
Authors: Deluche Lauréline , Joha Sami , Corm Sélim , Daudignon Agnès , Geffroy Sandrine , Quief Sabine , Villenet Céline , Kerckaert Jean‐Pierre , Laï Jean‐Luc , Preudhomme Claude , Roche‐Lestienne Catherine
Published: September 2008

Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the presence in leukemic stem cells of the Philadelphia chromosome (Ph) and the formation of the BCR‐ABL1 fusion. Untreated, the disease progresses to accelerate phase and blast crisis in which hematopoietic differentiation has become arrested. CML progression is frequently associated with cytogenetic evidence of clonal evolution, defined as additional chromosomal aberrations. We here report a CML resistant to tyrosine kinase inhibitors that rapidly progressed to blastic phase. At this time, array CGH performed on CD34+ cells revealed cryptic partial deletions of both PRDM16 and RUNX1 and duplication of the der(21) chromosome. These genomic rearrangements were confirmed by FISH with probes targeting the deletion on chromosome 21 (24 kb), and with BAC probes flanking the deletion on 1p36 (220 kb). However, no cryptic t(1;21)(p36;q22) and/or RUNX1‐PRDM16 were detected, suggesting that these deletions are the residual hallmarks of a more complex mechanism of chromosomal rearrangement, as indicated by the additional inversion of the region bounded by 1p36.32 and 1p36.12 breaks. At the molecular level, these abnormalities lead to the overexpression of the PR‐domain negative oncogenic isoform of PRDM16, associated with two deleted copies within the runt domain of C‐teminal aberrant RUNX1. These events are not detectable by conventional cytogenetic and molecular strategies, and may be of underestimated frequency in disease progression. © 2008 Wiley‐Liss, Inc.
The complex genomic profile of ETV6‐RUNX1 positive acute lymphoblastic leukemia highlights a recurrent deletion of TBL1XR1
Authors: Parker Helen , An Qian , Barber Kerry , Case Marian , Davies Teresa , Konn Zoë , Stewart Adam , Wright Sarah , Griffiths Mike , Ross Fiona M. , Moorman Anthony V. , Hall Andy G. , Irving Julie A. , Harrison Christine J. , Strefford Jon C.
Published: September 2008

The ETV6‐RUNX1 fusion is the molecular consequence of the t(12;21)(p13;q22) seen in ∼25% of children with acute lymphoblastic leukemia (ALL). Studies have shown that the fusion alone is insufficient for the initiation of leukemia; additional genetic changes are required. Genomic profiling identified copy number alterations at high frequencies in these patients. Focal deletions of TBL1XR1 were observed in 15% of cases; 3 patients exhibited deletions distal to the gene. Fluorescence in situ hybridization confirmed these deletions and quantitative RT‐PCR showed that the TBL1XR1 gene was significantly under‐expressed. TBL1XR1 is a key component of the SMRT and N‐CoR compressor complexes, which control hormone–receptor mediated gene expression. Differential expression of the retinoic acid target genes, RARB, CRABP1, and CRABP2, indicated that deletion of TBL1XR1 compromised the function of SMRT/N‐CoR in the appropriate control of gene expression. This study identifies deletions of TBL1XR1 as a recurrent abnormality in ETV6‐RUNX1 positive ALL. We provide evidence that implicates this deletion in the inappropriate control of gene expression in these patients. The target of the interaction between TBL1XR1 and the signaling pathways described here may be exploited in cancer therapy. © 2008 Wiley‐Liss, Inc.
Oncogenetic tree model of somatic mutations and DNA methylation in colon tumors
Authors: Sweeney Carol , Boucher Kenneth M. , Samowitz Wade S. , Wolff Roger K. , Albertsen Hans , Curtin Karen , Caan Bette J. , Slattery Martha L.
Published: September 2008

Our understanding of somatic alterations in colon cancer has evolved from a concept of a series of events taking place in a single sequence to a recognition of multiple pathways. An oncogenetic tree is a model intended to describe the pathways and sequence of somatic alterations in carcinogenesis without assuming that tumors will fall in mutually exclusive categories. We applied this model to data on colon tumor somatic alterations. An oncogenetic tree model was built using data on mutations of TP53, KRAS2, APC, and BRAF genes, methylation at CpG sites of MLH1 and TP16 genes, methylation in tumor (MINT) markers, and microsatellite instability (MSI) for 971 colon tumors from a population‐based series. Oncogenetic tree analysis resulted in a reproducible tree with three branches. The model represents methylation of MINT markers as initiating a branch and predisposing to MSI, methylation of MHL1 and TP16, and BRAF mutation. APC mutation is the first alteration in an independent branch and is followed by TP53 mutation. KRAS2 mutation was placed a third independent branch, implying that it neither depends on, nor predisposes to, the other alterations. Individual tumors were observed to have alteration patterns representing every combination of one, two, or all three branches. The oncogenetic tree model assumptions are appropriate for the observed heterogeneity of colon tumors, and the model produces a useful visual schematic of the sequence of events in pathways of colon carcinogenesis. © 2008 Wiley‐Liss, Inc.
Minimally invasive video‐assisted thyroidectomy: Expanded indications and oncologic completeness
Authors: Lai Stephen Y. , Walvekar Rohan R. , Ferris Robert L.
Published: September 2008

Background

Minimally invasive video‐assisted thyroidectomy (MIVAT) has received increasing attention as a technique applicable for a subset of thyroid nodules.

Methods

We prospectively assessed 51 MIVAT procedures in 40 patients. Demographic and clinical data were collected, relating to indications, outcome, and oncologic completeness.

Results

Twenty‐nine (29) benign and 22 malignant lesions up to 5.9 cm were removed (median, 1.7 cm). All surgical margins of resection were negative. Residual thyroid tissue in the operative bed was assessed by radioiodine uptake in 16 patients (median, 1.76%). Eighty percent (41/51) of procedures were performed on an outpatient basis, and 94% (48/51) did not require a suction drain. No bleeding events or permanent injuries to the recurrent laryngeal nerve occurred.

Conclusions

MIVAT is a safe, thorough, and adaptable procedure. An expanded set of indications makes this procedure available to a broader population of patients. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Increased plate and osteosynthesis related complications associated with postoperative concurrent chemoradiotherapy in oral cancer
Authors: Sharan Rajeev , Iyer Subramania , Chatni Shilpa S. , Samuel Jacob , Sundaram Karimassery R. , Cohen Richard F. , Pavithran Keechilat , Kuriakose Moni Abraham
Published: September 2008

Background.

Plate osteosynthesis is a widely used technique in head and neck reconstructive surgery. The objective of this study was to determine whether postoperative chemoradiotherapy, which was recently introduced for high‐risk head and neck cancer, affects plate and osteosynthesis related complications.

Methods.

Fifty‐two consecutive patients, who had undergone plate osteosynthesis for mandibular reconstruction between October 2003 and September 2006, were included in the study. The patients were divided into 3 groups: (1) surgery alone (n = 19), (2) surgery with postoperative radiotherapy (n = 14), and (3) surgery with concurrent chemoradiotherapy (n = 19). Outcome measures included any bone or plate related complications.

Results.

The plate and osteosynthesis related complications occurred in 10.5% of patients in surgery‐alone group, 28.6% in surgery with postoperative radiation group, and 63.2% in surgery with postoperative concurrent chemoradiotherapy group. The differences in the complication rates among these 3 groups were statistically significant (p = .003). In univariate analysis, postoperative radiation (p = .007) and concurrent chemotherapy (p = .003) were found to be significantly associated with complications. In multivariate analysis, only concurrent chemotherapy was found to be statistically significant (p = .002) with odds ratio of 7.72.

Conclusion.

Postoperative concurrent chemoradiotherapy significantly increases plate and osteosynthesis related complications in oral cancer. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Planned fractionated boron neutron capture therapy using epithermal neutrons for a patient with recurrent squamous cell carcinoma in the temporal bone: A case report
Authors: Haginomori Shin‐Ichi , Miyatake Shin‐Ichi , Inui Takaki , Araki Michitoshi , Kawabata Shinji , Takamaki Atsuko , Lee Koutetsu , Takenaka Hiroshi , Kuroiwa Toshihiko , Uesugi Yasuo , Kumada Hiroaki , Ono Koji
Published: September 2008

Background.

We describe the first case of extensive squamous cell carcinoma in the temporal bone recurring after surgery, conventional radiotherapy, and chemotherapy, which was treated using planned fractionated boron neutron capture therapy (BNCT).

Methods.

A 42‐year‐old patient received BNCT twice with a 1‐month interval to ensure neutron capture in the deep lesion. We used an epithermal neutron beam as the neutron source and boronophenylalanine as the boron compound. The total radiation doses in the tumor beneath the skin, at the deepest point of the tumor, and in the skin around the right auricle were estimated as 41.8, 36.9, and 15.8 Gy‐Eq, respectively.

Results.

Radiological studies performed 6 months after the first BNCT showed obvious tumor shrinkage and no evidence of residual tumor.

Conclusion.

We believe that planned fractionated BNCT is an effective treatment option for patients with inoperative extended carcinomas in the temporal bone. © 2008 Wiley Periodicals, Inc. Head Neck, 2009
CYP1A1 polymorphisms and the risk of upper aerodigestive tract cancers in an Indian population
Authors: Sam Soya Sisy , Thomas Vinod , Reddy Sathyanarayana Kanipakapatanam , Surianarayanan Gopalakrishnan , Chandrasekaran Adithan
Published: September 2008

Background.

The inter‐individual differences in upper aerodigestive tract (UADT) cancer risk may be partly attributed to the polymorphic variability in the CYP1A1 gene that is involved in the metabolic activation of xenobiotics to carcinogenic reactive metabolites.

Methods.

The hospital‐based case‐control study evaluated CYP1A1*2A and CYP1A1*2C polymorphisms in 408 histopathologically confirmed cases and 220 controls using polymerasechain reaction‐restriction fragment length polymorphism methods.

Results.

The multivariate logistic regression analyses demonstrated that CYP1A1 *1A/*2A (odds ratio [OR] 1.76; 95% Confidence interval [CI] 1.19–2.60) and *2A/*2A (OR 2.83; 95% CI 1.43–5.61) genotypes were significantly associated with increased risk for UADT cancers. The gene–environment interaction analyses revealed a significant interaction among tobacco smokers and chewers carrying CYP1A1*2A mutant genotypes on the multiplicative scale.

Conclusion.

CYP1A1*2A polymorphic genotypes are associated with an enhanced risk to UADT cancers, in particular, among the habitual tobacco smokers and chewers carrying mutant genotypes in the Tamilians of the Indian population. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Management of the neck in Merkel cell carcinoma of the head and neck: University of Miami experience
Authors: Shnayder Yelizaveta , Weed Donald T. , Arnold David J. , Gomez‐Fernandez Carmen , Bared Anthony , Goodwin W. Jarrard , Civantos Francisco J.
Published: September 2008

Background.

We reviewed management of the cervical lymph nodes in patients with Merkel cell carcinoma (MCC) of the head and neck.

Methods.

Records of 15 patients with MCC of the head and neck area were evaluated for the type of surgical treatment, including wide local excision, sentinel lymph node (SLN) biopsy, neck dissection, postoperative radiation therapy, and clinical outcomes.

Results.

Median follow‐up was 24 months (range, 5–84 months). Ten patients were treated with wide local excision plus SLN, with or without neck dissection. Five patients were treated with wide local excision only or wide local excision plus neck dissection. One patient died of distant metastases (7%), and 14 patients remain alive (93%), over a mean follow‐up of 24 months.

Conclusion.

Wide excision and SLN biopsy for primary MCC with N0 neck is feasible for early‐stage, previously untreated lesions. SLN biopsy was helpful in determining the nodal levels to be dissected or irradiated. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Accuracy of 18F‐FDG‐PET/CT for staging of oral squamous cell carcinoma
Authors: Pentenero Monica , Cistaro Angela , Brusa Mario , Ferraris Maria Maddalena , Pezzuto Carla , Carnino Riccardo , Colombini Edro , Valentini Maria Consuelo , Giovanella Luca , Spriano Giuseppe , Gandolfo Sergio
Published: September 2008

Background.

This study prospectively assessed 2‐[F18]‐fluoro‐2‐deoxy‐D‐glucose–positron emission tomography (18F‐FDG‐PET)/CT (PET/CT) in oral squamous cell carcinoma.

Methods.

Twenty‐three patients completed preoperative TNM staging (CT, MR, whole‐body fusion imaging PET/CT). In patients who underwent surgical therapy (19 of 23), TNM staging based on PET/CT scan was compared with pTNM.

Results.

PET/CT correctly staged 16 of 19 primary tumors (accuracy 84.2%, sensitivity 84.2%, positive predictive value 100%) and correctly ruled out bone invasion in 3 patients with false‐positive results according to CT and/or MR. PET/CT incorrectly identified neck involvement in 5 of 15 patients (3 false positives, 2 false negatives) who underwent neck dissection (accuracy 66.7%, specificity 76.9%, negative predictive value 83.3%). False‐negative cases showed a nodal size not exceeding 10 mm. One patient with a bronchial synchronous primary tumor was identified.

Conclusion.

PET/CT scan showed good accuracy in determining the extension and/or depth of invasion of the primary tumor. Nevertheless, PET/CT was not accurate to rule out nodal metastases. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Outcomes following parotidectomy for metastatic squamous cell carcinoma with microscopic residual disease: Implications for facial nerve preservation
Authors: Iyer N. Gopalakrishna , Clark Jonathan R. , Murali Rajmohan , Gao Kan , O'Brien Christopher J.
Published: September 2008

Background.

Metastatic cutaneous squamous cell carcinoma (SCC) of the parotid is an aggressive disease, requiring combined modality treatment of surgery and adjuvant radiotherapy to achieve cure. This study aims to determine whether facial nerve preservation followed by radiotherapy is a reasonable option in patients with microscopic residual disease involving the facial nerve.

Methods.

One hundred seventy‐six patients with metastatic cutaneous SCC involving the parotid were analyzed.

Results.

In this cohort, 15 patients who underwent nerve‐sparing surgery and adjuvant radiotherapy were found to have involved margins adjacent to the facial nerve. Comparing this group to patients with clear margins showed no difference in local recurrence or survival. Only 3 patients in this group developed local recurrence, and all successfully salvaged by further surgery.

Conclusion.

This study suggests that patients with metastatic cutaneous SCC to the parotid with microscopic residual disease involving the facial nerve and normal function can be successfully treated with a facial nerve–sparing approach and timely postoperative radiotherapy. © 2008 Wiley Periodicals, Inc. Head Neck, 2009
Clinical value of optical coherence tomography in laryngology
Authors: Kraft Marcel , Glanz Hiltrud , von Gerlach Susanne , Wisweh Henning , Lubatschowski Holger , Arens Christoph
Published: September 2008

Background.

Optical coherence tomography (OCT) is a new, noninvasive imaging technology for the evaluation of superficial lesions. The objective of this study is to evaluate microlaryngoscopy in combination with OCT compared with microlaryngoscopy alone (ie, without OCT) in supplying a specific diagnosis, predicting invasive tumor growth and epithelial dysplasia in the larynx.

Methods.

This was a prospective study including 217 laryngeal lesions in a total of 193 patients undergoing surgery. Intraoperative suspicion diagnosis gained by microlaryngoscopy with and without OCT was compared with conventional histopathology after excisional biopsy.

Results.

Microlaryngoscopy with OCT supplied a specific diagnosis in 89% of cases, but in only 80% of cases with microlaryngoscopy alone. In particular, our results in malignant and benign pathologies were correct in 93% each, and the exact grade of dysplasia could be predicted in 71% of precancerous lesions. Microlaryngoscopy with OCT presented a higher sensitivity than microlaryngoscopy alone in predicting invasive tumor growth (93% vs 87%) and epithelial dysplasia (78% vs 66%), but the specificity and accuracy were comparable in both methods.

Conclusions.

OCT is a simple, rapid, and reliable aid in the diagnostic investigation and intraoperative monitoring of laryngeal disease. © 2008 Wiley Periodicals, Inc. Head Neck, 2008
Liposarcoma of the head and neck: The University of Texas M. D. Anderson Cancer Center experience
Authors: Davis Erica C. , Ballo Matthew T. , Luna Mario A. , Patel Shreyakumar R. , Roberts Dianna B. , Nong Xiaolin , Sturgis Erich M.
Published: September 2008

Background.

Our aim was to review our experience with liposarcoma of the head and neck region.

Methods.

This is a retrospective case series at a comprehensive cancer center (1945–2005).

Results.

Of 30 patients, 10 (33%) were initially misdiagnosed. Local recurrences were common (overall rate = 53%), and 4 patients (13%) developed distant metastases. Decreased crude disease‐specific survival rates were significantly associated with recurrence (especially distant recurrence [0%]), age less than 38 years (40%), and pleomorphic subtype (45%); however, in Kaplan‐Meier analyses, only larger tumor size, negative margins, round cell subtype, and pleomorphic subtype were associated with significantly decreased disease‐specific survival (log‐rank test p = .048, .041, .021, and .012, respectively).

Conclusions.

Based on this limited experience and existing literature, we continue to recommend surgery with negative margins as the treatment of choice and that adjuvant therapies should be considered in patients with high‐grade histology, large tumors, positive margins, or certain subsites. © 2008 Wiley Periodicals, Inc. Head Neck, 2009
Wound‐healing modulation in upper airway stenosis—Myths and facts
Authors: Hirshoren Nir , Eliashar Ron
Published: September 2008

Wound healing plays a major role in the development of acquired subglottic stenosis. Pharmacologic treatment of subglottic stenosis must address both physiologic and pathologic healing processes. The relevant Pubmed and Ovid databases from 1960 to 2007 were systematically searched. Several modulating agents have been tested. Most of them were poorly investigated. Three modalities were thoroughly studied—steroids and antibiotics, mitomycin, and antireflux medications. However, there are conflicting data regarding their role in preventing and treating subglottic stenosis. Current data support to some extent the textbook suggestions of antibiotics, steroids, and antireflux treatment. As no other treatment options exist, we recommend using these modalities for pharmacologic modulation of subglottic stenosis. Mitomycin should still be considered as an unproven treatment; its use may be considered as an adjunct. © 2008 Wiley Periodicals, Inc. Head Neck, 2009
Impairment of in vivo theta‐burst long‐term potentiation and network excitability in the dentate gyrus of synaptopodin‐deficient mice lacking the spine apparatus and the cisternal organelle
Authors: Jedlicka Peter , Schwarzacher Stephan W. , Winkels Raphael , Kienzler Friederike , Frotscher Michael , Bramham Clive R. , Schultz Christian , Bas Orth Carlos , Deller Thomas
Published: September 2008

The function of the spine apparatus in dendritic spines and the cisternal organelles in axon initial segments is little understood. The actin‐associated protein, synaptopodin, is essential for the formation of these organelles which are absent in synaptopodin −/− mice. Here, we used synaptopodin −/− mice to explore the role of the spine apparatus and the cisternal organelle in synaptic plasticity and local circuit excitability in response to activation of the perforant path input to the dentate gyrus in vivo. We found impaired long‐term potentiation following theta‐burst stimulation, whereas tetanus‐evoked LTP was unaffected. Furthermore, paired‐pulse inhibition of the population spike was reduced and granule cell excitability was enhanced in mutants, hence revealing an impairment of local network inhibition. In summary, our data represent the first electrophysiological evidence that the lack of the spine apparatus and the cisternal organelle leads to a defect in long‐term synaptic plasticity and alterations in local circuit control of granule cell excitability under adult in vivo conditions. © 2008 Wiley‐Liss, Inc.
MR‐determined hippocampal asymmetry in full‐term and preterm neonates
Authors: Thompson Deanne K. , Wood Stephen J. , Doyle Lex W. , Warfield Simon K. , Egan Gary F. , Inder Terrie E.
Published: September 2008

Hippocampi are asymmetrical in children and adults, where the right hippocampus is larger. To date, no literature has confirmed that hippocampal asymmetry is evident at birth. Furthermore, gender differences have been observed in normal hippocampal asymmetry, but this has not been examined in neonates. Stress, injury, and lower IQ have been associated with alterations to hippocampal asymmetry. These same factors often accompany preterm birth. Therefore, prematurity is possibly associated with altered hippocampal asymmetry. There were three aims of this study: First, we assessed whether hippocampi were asymmetrical at birth, second whether there was a gender effect on hippocampal asymmetry, and third whether the stress of preterm birth altered hippocampal asymmetry. This study utilized volumetric magnetic resonance imaging to compare left and right hippocampal volumes in 32 full‐term and 184 preterm infants at term. Full‐term infants demonstrated rightward hippocampal asymmetry, as did preterm infants. In the case of preterm infants, hippocampal asymmetry was proportional to total hemispheric asymmetry. This study is the first to demonstrate that the normal pattern of hippocampal asymmetry is present this early in development. We did not find gender differences in hippocampal asymmetry at term. Preterm infants tended to have less asymmetrical hippocampi than full‐term infants, a difference which became significant after correcting for hemispheric brain tissue volumes. This study may suggest that hippocampal asymmetry develops in utero and is maintained into adulthood in infants with a normal neurological course. © 2008 Wiley‐Liss, Inc.
Technology‐related research in HRD publications: An analysis of content and metaperspectives from 2000 to 2006
Authors: Githens Rod P. , Dirani Khalil , Gitonga Jacqueline , Teng Ya‐Ting
Published: September 2008

This study explores the presence of technology‐related research in HRD, identifies what the research addressed, and analyzes how the research was addressed. We reviewed 1,675 papers in five publications. During the seven‐year period examined, 169 articles were technology‐related. Through a content analysis, we identified the topics of those articles, methodological approaches, organizational settings represented in the research, the fields of the researchers, and the papers' orientation toward research and practice. In comparison to the total articles in each publication, the highest percentage of technology research was published in conference proceedings.
The power of work experiences: Characteristics critical to developing expertise in strategic thinking
Authors: Goldman Ellen F.
Published: September 2008

The ability to think strategically is an increasingly important requirement for managers at all organizational levels. HRD professionals have attempted to help develop this ability through work experiences. However, research identifying which work experiences are most beneficial is limited. As a result, HRD efforts may be weakened. This paper presents findings indicating the importance of nine categories of work experiences to developing the ability to think strategically, and specifies their required characteristics. The characteristics vary with the experience but do follow some general themes.
Military leader development and autonomous learning: Responding to the growing complexity of warfare
Authors: Mensch Kirk G. , Rahschulte Tim
Published: September 2008

The complexity in today's operational military environment and the responsibility of leadership in this environment has exponentially increased over the past century. This trend will continue as global economies, political structures, and technologies continue to evolve. Learner autonomy is recognized as a paramount concern in leadership programs, including military programs. The purpose of this article is to increase awareness of the need for learner autonomy among military leaders; however, the implications may be generalizable to any organization responsible for developing leaders who operate in ambiguous and complex environments.
Effects of prolonged‐release melatonin, zolpidem, and their combination on psychomotor functions, memory recall, and driving skills in healthy middle aged and elderly volunteers
Authors: Otmani S. , Demazières A. , Staner C. , Jacob N. , Nir T. , Zisapel N. , Staner L.
Published: September 2008

Background

Melatonin is an important regulator of the sleep–wake cycle. A prolonged‐release formulation of melatonin (PR‐M) that essentially mimics the profile of the endogenous production of the hormone is effective in the treatment of insomnia in patients aged 55 years and older. Because hypnotics result in impairments of various cognitive skills, it is important to examine the cognitive effects associated with the use of PR‐M.

Objectives and methods

The effects of therapeutic oral doses of PR‐M (2 mg), zolpidem (10 mg) and their combination administered at bedtime on cognitive functions in healthy subjects aged 55 years and older (12 males + 4 females, age 59.4 ± 3.2 years) were assessed in a randomized, double‐blind, placebo‐controlled, and four‐way crossover study. Psychomotor functions, memory recall, and driving skills were assessed at 1 and 4 h following administration and the next morning.

Results

Compared to placebo, PR‐M alone did not impaired performances on any cognitive tasks. Zolpidem significantly impaired psychomotor and driving performance 1 h and 4 h post‐dosing, and early memory recall; these impairment were exacerbated with PR‐M co‐administration. No effects on next morning psychomotor or driving performance were observed except that the decline in memory recall after zolpidem was more pronounced in the next day. No pharmacokinetic interactions were found.

Conclusions

This study extends previous researches showing impairment of cognitive functions by zolpidem within 5 h post‐administration. Further, PR‐M use was not found associated with impairment of psychomotor functions, memory recall, and driving skills, and point to a pharmacodynamic interaction between melatonin and GABA‐A modulators. Copyright © 2008 John Wiley & Sons, Ltd.
Nucleotide excision repair polymorphisms may modify ionizing radiation‐related breast cancer risk in US radiologic technologists
Authors: Rajaraman Preetha , Bhatti Parveen , Doody Michele Morin , Simon Steven L. , Weinstock Robert M. , Linet Martha S. , Rosenstein Marvin , Stovall Marilyn , Alexander Bruce H. , Preston Dale L. , Sigurdson Alice J.
Published: September 2008

Exposure to ionizing radiation has been consistently associated with increased risk of female breast cancer. Although the majority of DNA damage caused by ionizing radiation is corrected by the base‐excision repair pathway, certain types of multiple‐base damage can only be repaired through the nucleotide excision repair pathway. In a nested case–control study of breast cancer in US radiologic technologists exposed to low levels of ionizing radiation (858 cases, 1,083 controls), we examined whether risk of breast cancer conferred by radiation was modified by nucleotide excision gene polymorphisms ERCC2 (XPD) rs13181, ERCC4 (XPF) rs1800067 and rs1800124, ERCC5 (XPG) rs1047769 and rs17655; and ERCC6 rs2228526. Of the 6 ERCC variants examined, only ERCC5 rs17655 showed a borderline main effect association with breast cancer risk (ORGC = 1.1, ORCC = 1.3; p‐trend = 0.08), with some indication that individuals carrying the C allele variant were more susceptible to the effects of occupational radiation (EOR/GyGG = 1.0, 95% CI = <0, 6.0; EOR/GyGC/CC = 5.9, 95% CI = 0.9, 14.4; phet = 0.10). ERCC2 rs13181, although not associated with breast cancer risk overall, statistically significantly modified the effect of occupational radiation dose on risk of breast cancer (EOR/GyAA = 9.1, 95% CI = 2.1−21.3; EOR/GyAC/CC = 0.6, 95% CI = <0, 4.6; phet = 0.01). These results suggest that common variants in nucleotide excision repair genes may modify the association between occupational radiation exposure and breast cancer risk. © 2008 Wiley‐Liss, Inc.
No increased risk for cervical cancer after a broader definition of a negative Pap smear
Authors: Rebolj Matejka , van Ballegooijen Marjolein , van Kemenade Folkert , Looman Caspar , Boer Rob , Habbema J. Dik F.
Published: September 2008

The definition of minimal relevant Pap smear abnormality is crucial for balancing the beneficial effects of screening (prevented mortality) with negative side‐effects (the high positivity rate). After inflammation ceased to be defined as a borderline abnormal smear outcome in The Netherlands in 1996, the proportion of these smears dropped from 10% to less than 2%. Because this may have caused a loss in smear sensitivity, we analysed the changes in the incidence of cervical cancer after a negative Pap smear. All negative smears made at ages 30–64 in 1990–1995 (n = 1,546,252) and 1998–2006 (n = 3,552,716), registered in the national registry of histo‐ and cytopathology (PALGA), were followed for up to 9 years. During follow‐up of the 1990–1995 smears, 377 women developed cervical cancer within 5,232,959 woman‐years at risk, while during the follow‐up of the 1998–2006 smears, 619 women developed cervical cancer within 11,210,675 woman‐years at risk. The cumulative incidence after the definition change was not significantly higher than before: e.g. at 6 years, the cumulative incidence for smears made in 1990–1995 was 46 per 100,000 (95% CI: 41–52), and for smears in 1998–2006 was 48 per 100,000 (95% CI: 43–54), p = 0.59. The hazard ratio for 1998–2006 compared to 1990–1995 adjusted for age, number of previous negative smears and history of abnormalities was 0.90 (95% CI: 0.78–1.03). In The Netherlands, a setting with high‐quality cytological screening, treating smears with only signs of inflammation as negative leads to a considerably lower positivity rate without increasing the risk for cervical cancer after a negative smear. © 2008 Wiley‐Liss, Inc.
Prospective evaluation of trans‐fatty acid intake and colorectal cancer risk in the Iowa Women's Health Study
Authors: Limburg Paul J. , Liu‐Mares Wen , Vierkant Robert A. , Wang Alice H. , Harnack Lisa , Flood Andrew P. , Sellers Thomas A. , Cerhan James R.
Published: September 2008

Concerns regarding the safety of dietary trans‐fatty acids (tFAs) have generated recent public interest, scientific discussion and legislative action. Although most widely recognized as a risk factor for cardiovascular disease, associations between tFA intake and incident cancer have also been proposed. With respect to colorectal cancer (CRC), existing observational data remain limited and inconclusive. Therefore, we conducted a prospective evaluation of tFA intake and CRC risk, overall and by anatomic subsite, among participants in the Iowa Women's Health Study (IWHS), a population‐based cohort of older women (ages 55–69 years at enrollment). Exposure data were collected at baseline using a semiquantitative food‐frequency questionnaire. Incident CRC cases were identified through annual linkage to the Iowa Cancer Registry. CRC risks were estimated using Cox proportional hazards regression models. In total, 35,216 women met our inclusion criteria and 1,229 CRC cases (631 proximal, 571 distal, 27 site not specified) were observed through 18 years of follow‐up. Adjusting for age and total energy consumption, tFA intake in the 4th versus 1st quartile was not significantly associated with overall CRC risk [relative risk (RR) = 1.12; 95% confidence interval (CI) = 0.96–1.32]. Similarly, risk estimates based on proximal (RR = 1.09; 95% CI = 0.87–1.37) and distal (RR = 1.18; 95% CI = 0.93–1.49) CRC subsites did not differ from unity. Multivariable adjustment yielded slightly attenuated risk estimates, but the observed associations were not meaningfully altered. Given these findings, tFA intake does not appear to be a major CRC risk factor, at least among older women. © 2008 Wiley‐Liss, Inc.
Leptin promotes motility and invasiveness in human colon cancer cells by activating multiple signal‐transduction pathways
Authors: Jaffe Tamara , Schwartz Betty
Published: September 2008

Leptin serum levels are about 5 times higher in obese people than in normal individuals. We aimed at investigating the signaling pathways induced by leptin in the human colonic cell lines LS174T and HM7. Both cells expressed the leptin transmembrane Ob‐receptor. Leptin activated the mitogen‐activated protein kinase pathway, induced invasion of colonic cells and concomitantly increased the formation of lamellipodial structures. A direct and novel dose‐ and time‐dependent activation of RhoA, Cdc42 and Rac1 by leptin is demonstrated in these aggressive colon cancer cells. The activation of the Rho family of GTPases was amenable to specific inhibition: Wortmannin inhibited leptin‐induced Rac1 and Cdc42 activation but did not affect RhoA activation, and inhibited the formation of leptin‐induced lamellipodia and cell invasion. The Rac1 inhibitor NSC23766 inhibited only leptin‐induced Rac1 activation and concomitantly, lamellipodium formation and cell invasion. The Src kinase inhibitor II (SrcKI‐II) exerted a positive effect on RhoA activation, inhibited tyrosine phosphorylation of p190RhoGAP and inhibited leptin‐induced Cdc42 activation and leptin‐induced lamellopodium formation and cell invasion. The specific JAK2 inhibitor AG490 exerted a positive effect on Rac1 and Cdc42 activation by leptin and concomitantly inhibited RhoA activation. AG490 did not inhibit leptin‐induced lamellopodium formation or cell invasion. Our findings clearly indicate that leptin activates PI3K and Src kinase pathways in the metastatic colon cancer cells LS174T and HM7. These signaling pathways induce the activation of Rac1 and Cdc42, lamellopodium formation and concomitantly enhanced cell invasion, but leptin activation of RhoA is not associated with enhanced cell locomotion and invasion. Understanding in‐depth the pathways involved in leptin‐associated enhanced cell locomotion and invasion may contribute with the design of novel therapeutics to treat obesity‐associated advanced colorectal cancer. © 2008 Wiley‐Liss, Inc.
The resveratrol analogue 3,5,3′,4′,5′‐pentahydroxy‐trans‐stilbene inhibits cell transformation via MEK
Authors: Lee Ki Won , Kang Nam Joo , Rogozin Evgeny A. , Oh Sang‐Muk , Heo Yong Seok , Pugliese Angelo , Bode Ann M. , Lee Hyong Joo , Dong Zigang
Published: September 2008

Resveratrol, present in grapes and red wine, is reported to be a natural chemopreventive agent against cancer. However, the concentrations required to exert these effects may be difficult to achieve by drinking only 1 or 2 glasses of red wine a day. Therefore, developing more potent, nontoxic analogues of resveratrol may provide a feasible means of achieving an effective physiologic concentration. Here we report that the resveratrol analogue, 3,5,3′,4′,5′‐pentahydroxy‐trans‐stilbene (RSVL2), inhibits 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced neoplastic transformation in JB6 P+ mouse epidermal cells. Further, we identified MEK/ERK signaling as the direct molecular target for the anticancer effects of RSVL2 and demonstrated that RSVL2 inhibited MEK1, but not Raf1 or ERK2 kinase activity. RSVL2 also dose‐dependently suppressed MEK1 kinase activity induced by TPA and the inhibition of H‐Ras‐induced cell transformation was much stronger for RSVL2 than for PD098059 or resveratrol. Both in vitro and ex vivo pull‐down assays indicated that RSVL2, but not resveratrol, directly bound with GST‐MEK1, but did not compete with ATP for binding. Docking data indicated that the low inhibitory activity of resveratrol might be due to the lack of the hydroxyl group at the meta position of the B ring, thereby preventing resveratrol from forming a hydrogen bond with the backbone amide group of Ser212, which is the key interaction for stabilizing the inactive conformation of the activation loop. © 2008 Wiley‐Liss, Inc.
Prognostic value of Her‐2/neu and DNA index for progression, metastasis and prostate cancer‐specific death in men with long‐term follow‐up after radical prostatectomy
Authors: Isharwal Sumit , Miller Michael Craig , Epstein Jonathan I. , Mangold Leslie A. , Humphreys Elizabeth , Partin Alan W. , Veltri Robert W.
Published: September 2008

Abnormal DNA content in tumor cells represents large scale chromosomal alterations and reflects later changes of genetic instability. Her‐2/neu oncogene is amplified in 20–30% of breast and ovarian cancer patients and is associated with poor prognosis. Therefore, we evaluated prognostic value of Her‐2/neu expression and DNA content measurements in 252 clinically localized PCa patients with long‐term follow‐up after radical prostatectomy for progression, metastasis and PCa‐specific death. Her‐2/neu expression was determined by immunohistochemistry and DNA content measurements employed Feulgen‐stained cancer nuclei captured using static image cytometry system. Cox proportional hazard regression and Kaplan‐Meir plots were used to identify significant prognostic factors for progression, metastasis and PCa‐specific death. The proportions of Her‐2/neu positive and high %DNA index tumors significantly increased from nonprogressor to progressors without metastasis to progressors with metastasis (p < 0.0001; <0.0001). Further, the proportions of Her‐2/neu positive and high %DNA index tumors significantly increased from patients who died from another cause without progression to those who died from another cause with progression to those died with PCa‐specific death (p = 0.027; <0.0001). Her‐2/neu expression and %DNA index were significant prognosticators for progression (p ≤ 0.001), metastasis (p ≤ 0.01) PCa‐specific death (p ≤ 0.04) in univariate analyses. Multivariately, Her‐2/neu expression and %DNA index were also significant for progression (p = 0.001), metastasis (p = 0.001) and PCa‐specific death (p = 0.02). When all other clinicopathologic information is available, the increment in concordance index by addition of either Her‐2/neu or DNA index was ∼2% and of both biomarkers was ∼3% for progression, metastasis and PCa‐specific death free survival models. Therefore, patients with Her‐2/neu positive and high %DNA index are at a higher risk for disease progression, metastasis and PCa‐specific death. Further, Her‐2/neu expression and %DNA index may be used with clinicopathologic parameters for prediction of long‐term prognosis in PCa. © 2008 Wiley‐Liss, Inc.