bluuebunny/crossref_metadata_2025 huggingface dataset:
Facile promoter deletion in Escherichia coli in response to leaky expression of very robust and benign proteins from common expression vectors
Authors: Kawe Martin , Horn Uwe , Plückthun Andreas
Published: January 2009

Background

Overexpression of proteins in Escherichia coli is considered routine today, at least when the protein is soluble and not otherwise toxic for the host. We report here that the massive overproduction of even such "benign" proteins can cause surprisingly efficient promoter deletions in the expression plasmid, leading to the growth of only non-producers, when expression is not well repressed in the newly transformed bacterial cell. Because deletion is so facile, it might impact on high-throughput protein production, e.g. for structural genomics, where not every expression parameter will be monitored.

Results

We studied the high-level expression of several robust non-toxic proteins using a T5 promoter under lac operator control. Full induction leads to no significant growth retardation. We compared expression from almost identical plasmids with or without the lacI gene together in strains expressing different levels of LacI. Any combination without net overexpression of LacI led to an efficient promoter deletion in the plasmid, although the number of growing colonies and even the plasmid size – all antibiotic-resistant non-producers – was almost normal, and thus the problem not immediately recognizable. However, by assuring sufficient repression during the initial establishment phase of the plasmid, deletion was completely prevented.

Conclusion

The deletions in the insufficiently repressed system are caused entirely by the burden of high-level translation. Since the E. coli Dps protein, known to protect DNA against stress in the stationary phase, is accumulated in the deletion mutants, the mutation may have taken place during a transient stationary phase. The cause of the deletion is thus distinct from the well known interference of high-level transcription with plasmid replication. The deletion can be entirely prevented by overexpressing LacI, a useful precaution even without any signs of stress caused by the protein.
Intraductal and invasive adenocarcinoma of duct of Luschka, mimicking chronic cholecystitis and cholelithiasis
Authors: Jahan Mumtaz , Xiao Philip , Go Alan , Cheema Muhammad , Hameed Arif
Published: January 2009

Background

Intraductal and invasive adenocarcinoma of duct of Luschka is rare. To the best of our knowledge, this is the second case report of intraductal and invasive carcinoma arising from ducts of Luschka.

Case presentation

Patient presented to hospital with signs and symptoms of chronic cholecystitis and cholelithiasis. Ultrasound examination revealed thickening of gallbladder wall with abnormal septation around liver bed. Patient underwent laparoscopic cholecystectomy and resection of the adjacent liver bed. Histologic examination confirmed an intraductal and invasive adenocarcinoma arising from Luschka ducts.

Conclusion

Adenocarcinoma of ducts of Luschka should be considered among differential diagnoses for the patients with typical clinical presentations of chronic cholecystitis and cholelithiasis.
Molecular Etiology of Hearing Impairment in Inner Mongolia: mutations in SLC26A4 gene and relevant phenotype analysis
Authors: Dai Pu , Yuan Yongyi , Huang Deliang , Zhu Xiuhui , Yu Fei , Kang Dongyang , Yuan Huijun , Wu Bailin , Han Dongyi , Wong Lee-Jun C
Published: January 2009

Background

The molecular etiology of hearing impairment in Chinese has not been thoroughly investigated. Study of GJB2 gene revealed that 30.4% of the patients with hearing loss in Inner Mongolia carried GJB2 mutations. The SLC26A4 gene mutations and relevant phenotype are analyzed in this study.

Methods

One hundred and thirty-five deaf patients were included. The coding exons of SLC26A4 gene were sequence analyzed in 111 patients, not including 22 patients carrying bi-allelic GJB2 mutations or one patient carrying a known GJB2 dominant mutation as well as one patient with mtDNA 1555A>G mutation. All patients with SLC26A4 mutations or variants were subjected to high resolution temporal bone CT scan and those with confirmed enlarged vestibular aqueduct and/or other inner ear malformation were then given further ultrasound scan of thyroid and thyroid hormone assays.

Results

Twenty-six patients (19.26%, 26/135) were found carrying SLC26A4 mutation. Among them, 17 patients with bi-allelic SLC26A4 mutations were all confirmed to have EVA or other inner ear malformation by CT scan. Nine patients were heterozygous for one SLC26A4 mutation, including 3 confirmed to be EVA or EVA and Mondini dysplasia by CT scan. The most common mutation, IVS7-2A>G, accounted for 58.14% (25/43) of all SLC26A4 mutant alleles. The shape and function of thyroid were confirmed to be normal by thyroid ultrasound scan and thyroid hormone assays in 19 of the 20 patients with EVA or other inner ear malformation except one who had cystoid change in the right side of thyroid. No Pendred syndrome was diagnosed.

Conclusion

In Inner Mongolia, China, mutations in SLC26A4 gene account for about 12.6% (17/135) of the patients with hearing loss. Together with GJB2 (23/135), SLC26A4 are the two most commonly mutated genes causing deafness in this region. Pendred syndrome is not detected in this deaf population. We established a new strategy that detects SLC26A4 mutations prior to the temporal bone CT scan to find EVA and inner ear malformation patients. This model has a unique advantage in epidemiologic study of large deaf population.
Characterization of culture-positive adenovirus serotypes from respiratory specimens in Toronto, Ontario, Canada: September 2007–June 2008
Authors: Yeung Rani , Eshaghi AliReza , Lombos Ernesto , Blair Joanne , Mazzulli Tony , Burton Laura , Drews Steven J
Published: January 2009

This study describes the prevalence of culture-positive adenovirus serotypes in culture-positive respiratory specimens sent to the Central Public Health Laboratory, Toronto, Ontario, Canada for the period September 2007–June 2008. Total nucleic acid was extracted from virus cultures using an automated extraction method followed by polymerase chain reaction and Sanger sequencing of the adenovirus hexon gene hypervariable region 7. 73% of specimens (n = 70) were from patients ≤ 4 years of age. Of the 96 adenovirus isolates, the most common identified serotypes were serotype 3 (n = 44, 46%), serotype 2 (n = 25, 26%), serotype 1 (n = 17, 18%), and serotype 21 (n = 5, 5%). Adenovirus serotype 14 was not found in this study group. The leading serotype, Ad3, was identified throughout the duration of the study period. Molecular methods allow for the determination of circulating adenovirus serotypes and be used to document the spread of highly virulent adenoviral serotypes into a region.
Gene expression profile analysis of human hepatocellular carcinoma using SAGE and LongSAGE
Authors: Dong Hui , Ge Xijin , Shen Yan , Chen Linlei , Kong Yalin , Zhang Hongyi , Man Xiaobo , Tang Liang , Yuan Hong , Wang Hongyang , Zhao Guoping , Jin Weirong
Published: January 2009

Background

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and the second cancer killer in China. The initiation and malignant transformation of cancer result from accumulation of genetic changes in the sequences or expression level of cancer-related genes. It is of particular importance to determine gene expression profiles of cancers on a global scale. SAGE and LongSAGE have been developed for this purpose.

Methods

We performed SAGE in normal liver and HCC samples as well as the liver cancer cell line HepG2. Meanwhile, the same HCC sample was simultaneously analyzed using LongSAGE. Computational analysis was carried out to identify differentially expressed genes between normal liver and HCC which were further validated by real-time quantitative RT-PCR.

Results

Approximately 50,000 tags were sequenced for each of the four libraries. Analysis of the technical replicates of HCC indicated that excluding the low abundance tags, the reproducibility of SAGE data is high (R = 0.97). Compared with the gene expression profile of normal liver, 224 genes related to biosynthesis, cell proliferation, signal transduction, cellular metabolism and transport were identified to be differentially expressed in HCC. Overexpression of some transcripts selected from SAGE data was validated by real-time quantitative RT-PCR. Interestingly, sarcoglycan-ε (SGCE) and paternally expressed gene (PEG10) which is a pair of close neighboring genes on chromosome 7q21, showed similar enhanced expression patterns in HCC, implicating that a common mechanism of deregulation may be shared by these two genes.

Conclusion

Our study depicted the expression profile of HCC on a genome-wide scale without the restriction of annotation databases, and provided novel candidate genes that might be related to HCC.
Epicuticular lipids induce aggregation in Chagas disease vectors
Authors: Figueiras Alicia N Lorenzo , Girotti Juan R , Mijailovsky Sergio J , Juárez M Patricia
Published: January 2009

Background

The triatomine bugs are vectors of the protozoan parasite Trypanosoma cruzi, the causative agent of Chagas disease. Aggregation behavior plays an important role in their survival by facilitating the location of refuges and cohesion of aggregates, helping to keep them safely assembled into shelters during daylight time, when they are vulnerable to predators. There are evidences that aggregation is mediated by thigmotaxis, by volatile cues from their faeces, and by hexane-extractable contact chemoreceptive signals from their cuticle surface. The epicuticular lipids of Triatoma infestans include a complex mixture of hydrocarbons, free and esterified fatty acids, alcohols, and sterols.

Results

We analyzed the response of T. infestans fifth instar nymphs after exposure to different amounts either of total epicuticular lipid extracts or individual lipid fractions. Assays were performed in a circular arena, employing a binary choice test with filter papers acting as aggregation attractive sites; papers were either impregnated with a hexane-extract of the total lipids, or lipid fraction; or with the solvent. Insects were significantly aggregated around papers impregnated with the epicuticular lipid extracts. Among the lipid fractions separately tested, only the free fatty acid fraction promoted significant bug aggregation. We also investigated the response to different amounts of selected fatty acid components of this fraction; receptiveness varied with the fatty acid chain length. No response was elicited by hexadecanoic acid (C16:0), the major fatty acid component. Octadecanoic acid (C18:0) showed a significant assembling effect in the concentration range tested (0.1 to 2 insect equivalents). The very long chain hexacosanoic acid (C26:0) was significantly attractant at low doses (≤ 1 equivalent), although a repellent effect was observed at higher doses.

Conclusion

The detection of contact aggregation pheromones has practical application in Chagas disease vector control. These data may be used to help design new tools against triatomine bugs.
Posterior lung herniation after a coughing spell: a case report
Authors: Jastrow Kenneth M , Chu Danny , Jaroszewski Dawn , Huh Joseph , Bakaeen Faisal
Published: January 2009

Lung hernias are rare, occurring most commonly after trauma or surgery. Spontaneous lung hernias are even rarer and have only been reported as occurring anteriorly. We present a 72-year-old male who developed a spontaneous posterior lung hernia after a severe coughing episode. We describe the evaluation and surgical management of this unusual condition and provide a brief review of the literature.
Bone marrow lesions from osteoarthritis knees are characterized by sclerotic bone that is less well mineralized
Authors: Hunter David J , Gerstenfeld Lou , Bishop Gavin , Davis A David , Mason Zach D , Einhorn Tom A , Maciewicz Rose A , Newham Pete , Foster Martyn , Jackson Sonya , Morgan Elise F
Published: January 2009

Introduction

Although the presence of bone marrow lesions (BMLs) on magnetic resonance images is strongly associated with osteoarthritis progression and pain, the underlying pathology is not well established. The aim of the present study was to evaluate the architecture of subchondral bone in regions with and without BMLs from the same individual using bone histomorphometry.

Methods

Postmenopausal female subjects (n = 6, age 48 to 90 years) with predominantly medial compartment osteoarthritis and on a waiting list for total knee replacement were recruited. To identify the location of the BMLs, subjects had a magnetic resonance imaging scan performed on their study knee prior to total knee replacement using a GE 1.5 T scanner with a dedicated extremity coil. An axial map of the tibial plateau was made, delineating the precise location of the BML. After surgical removal of the tibial plateau, the BML was localized using the axial map from the magnetic resonance image and the lesion excised along with a comparably sized bone specimen adjacent to the BML and from the contralateral compartment without a BML. Cores were imaged via microcomputed tomography, and the bone volume fraction and tissue mineral density were calculated for each core. In addition, the thickness of the subchondral plate was measured, and the following quantitative metrics of trabecular structure were calculated for the subchondral trabecular bone in each core: trabecular number, thickness, and spacing, structure model index, connectivity density, and degree of anisotropy. We computed the mean and standard deviation for each parameter, and the unaffected bone from the medial tibial plateau and the bone from the lateral tibial plateau were compared with the affected BML region in the medial tibial plateau.

Results

Cores from the lesion area displayed increased bone volume fraction but reduced tissue mineral density. The samples from the subchondral trabecular lesion area exhibited increased trabecular thickness and were also markedly more plate-like than the bone in the other three locations, as evidenced by the lower value of the structural model index. Other differences in structure that were noted were increased trabecular spacing and a trend towards decreased trabecular number in the cores from the medial location as compared with the contralateral location.

Conclusions

Our preliminary data localize specific changes in bone mineralization, remodeling and defects within BMLs features that are adjacent to the subchondral plate. These BMLs appear to be sclerotic compared with unaffected regions from the same individual based on the increased bone volume fraction and increased trabecular thickness. The mineral density in these lesions, however, is reduced and may render this area to be mechanically compromised, and thus susceptible to attrition.
Profiling RE1/REST-mediated histone modifications in the human genome
Authors: Zheng Deyou , Zhao Keji , Mehler Mark F
Published: January 2009

Background

The transcriptional repressor REST (RE1 silencing transcription factor, also called NRSF for neuron-restrictive silencing factor) binds to a conserved RE1 motif and represses many neuronal genes in non-neuronal cells. This transcriptional regulation is transacted by several nucleosome-modifying enzymes recruited by REST to RE1 sites, including histone deacetylases (for example, HDAC1/2), demethylases (for example, LSD1), and methyltransferases (for example, G9a).

Results

We have investigated a panel of 38 histone modifications by ChIP-Seq analysis for REST-mediated changes. Our study reveals a systematic decline of histone acetylations modulated by the association of RE1 with REST (RE1/REST). By contrast, alteration of histone methylations is more heterogeneous, with some methylations increased (for example, H3K27me3, and H3K9me2/3) and others decreased (for example, H3K4me, and H3K9me1). Furthermore, the observation of such trends of histone modifications in upregulated genes demonstrates convincingly that these changes are not determined by gene expression but are RE1/REST dependent. The outcomes of REST binding to canonical and non-canonical RE1 sites were nearly identical. Our analyses have also provided the first direct evidence that REST induces context-specific nucleosome repositioning, and furthermore demonstrate that REST-mediated histone modifications correlate with the affinity of RE1 motifs and the abundance of RE1-bound REST molecules.

Conclusions

Our findings indicate that the landscape of REST-mediated chromatin remodeling is dynamic and complex, with novel histone modifying enzymes and mechanisms yet to be elucidated. Our results should provide valuable insights for selecting the most informative histone marks for investigating the mechanisms and the consequences of REST modulated nucleosome remodeling in both neural and non-neural systems.
Association of headache with childhood adversity and mental disorder: cross-national study
Authors: Lee Sing , Tsang Adley , Von Korff Michael , de Graaf Ron , Benjet Corina , Haro Josep Maria , Angermeyer Matthias , Demyttenaere Koen , de Girolamo Giovanni , Gasquet Isabelle , Merikangas Kathleen , Posada-Villa José , Takeshima Tadashi , Kessler Ronald C.
Published: January 2009

Background

Community studies about the association of headache with both childhood family adversities and depression/anxiety disorders are limited.

Aims

To assess the independent and joint associations of childhood family adversities and early-onset depression and anxiety disorders with risks of adult-onset headache.

Method

Data were pooled from cross-sectional community surveys conducted in ten Latin and North American, European and Asian countries (n=18 303) by using standardised instruments. Headache and a range of childhood family adversities were assessed by self-report.

Results

The number of childhood family adversities was associated with adult-onset headache after adjusting for gender, age, country and early-onset depression/anxiety disorder status (for one adversity, hazard ratio (HR)=1.22–1.6; for two adversities, HR=1.19–1.67; for three or more adversities, HR=1.37–1.95). Early and current onset of depression/anxiety disorders were independently associated (HR=1.42–1.89) with adult-onset headache after controlling for number of childhood family adversities.

Conclusions

The findings call for a broad developmental perspective concerning risk factors for development of headache.
Trends in the administration of electroconvulsive therapy in England
Authors: Bickerton David , Worrall Adrian , Chaplin Robert
Published: January 2009

Aims and Method

We measured the use of electroconvulsive therapy (ECT) over 3 months in England in 2006 and compared that with studies from 1999 and 2002. Questionnaires were completed by hospital ECT staff and returned by post with data collected prospectively on ECT use from National Health Service organisations.

Results

Two-thirds (56 of 76) of the trusts providing ECT at 109 clinics responded. the number of clinics providing ECT and the number of patients receiving ECT has declined. There has been an increase in the proportion of people receiving ECT when detained under the Mental Health Act 1983.

Clinical Implications

The number of ECT clinics is likely to continue to decrease and psychiatrists may have decreasing experience of treating patients with ECT.
Poor Survival for Infants WithMYCN-Amplified Metastatic Neuroblastoma Despite Intensified Treatment: The International Society of Paediatric Oncology European Neuroblastoma Experience
Authors: Canete Adela , Gerrard Mary , Rubie Hervé , Castel Victoria , Di Cataldo Andrea , Munzer Caroline , Ladenstein Ruth , Brichard Bénédicte , Bermúdez José D. , Couturier Jerôme , de Bernardi Bruno , Pearson Andrew J. , Michon Jean
Published: January 2009

Purpose

To report the results of a prospective, nonrandomized European study on infants with neuroblastoma and MYCN gene amplification.

Patients and Methods

Infants with neuroblastoma (stage 2, 3, 4, and 4s) and MYCN gene amplification who were diagnosed between 1999 and 2004 were eligible for enrollment onto the study. After diagnosis, staging, and mandatory biologic studies, induction chemotherapy (IC) with conventional drugs was administered, followed by delayed surgery, megatherapy (busulfan-melphalan as a conditioning regimen), and local radiotherapy.

Results

Of the 46 infants enrolled onto the study, 35 infants were eligible; of these 35 infants, 97% had metastatic spread (24 infants had stage 4, and 10 infants had stage 4s). Two-year overall survival (OS) was 30% (SE, 0.08), with median survival time of 12 months, and 23 deaths due to disease. Two-year, event-free survival (EFS) was 29% (SE, 0.07). The treatment was well tolerated with no deaths as a result of toxicity or severe toxicity. Despite protocol adherence, 30% of the patients who were assessable for response to IC experienced disease progression or did not respond. Stage and high lactate dehydrogenase reached significance in the univariate analysis (P = .028 and .039, respectively for OS; and P = .05 and .031 respectively, for EFS). Ten of 16 patients who received megatherapy are still alive.

Conclusion

Although treatment was well tolerated, survival was poor and our IC failed to achieve a satisfactory response in 30% of our patients. New therapeutic approaches and more intense world-wide collaboration are needed to achieve a cure in this population.
Iodine-131—Metaiodobenzylguanidine Double Infusion With Autologous Stem-Cell Rescue for Neuroblastoma: A New Approaches to Neuroblastoma Therapy Phase I Study
Authors: Matthay Katherine K. , Quach Alekist , Huberty John , Franc Benjamin L. , Hawkins Randall A. , Jackson Hollie , Groshen Susan , Shusterman Suzanne , Yanik Gregory , Veatch Janet , Brophy Patricia , Villablanca Judith G. , Maris John M.
Published: January 2009

Purpose

Iodine-131—metaiodobenzylguanidine (131I-MIBG) provides targeted radiotherapy with more than 30% response rate in refractory neuroblastoma, but activity infused is limited by radiation safety and hematologic toxicity. The goal was to determine the maximum-tolerated dose of 131I-MIBG in two consecutive infusions at a 2-week interval, supported by autologous stem-cell rescue (ASCR) 2 weeks after the second dose.

Patients and Methods

The 131I-MIBG dose was escalated using a 3 + 3 phase I trial design, with levels calculated by cumulative red marrow radiation index (RMI) from both infusions. Using dosimetry, the second infusion was adjusted to achieve the target RMI, except at level 4, where the second infusion was capped at 21 mCi/kg.

Results

Twenty-one patients were enrolled onto the study at levels 1 to 4, with 18 patients assessable for toxicity and 20 patients assessable for response. Cumulative 131I-MIBG given to achieve the target RMI ranged from 22 to 50 mCi/kg, with cumulative RMI of 3.2 to 8.92 Gy. No patient had a dose-limiting toxicity. Reversible grade 3 nonhematologic toxicity occurred in six patients at level 4, establishing the recommended cumulative dose as 36 mCi/kg. The median time to absolute neutrophil count more than 500/μL after ASCR was 13 days (4 to 27 days) and to platelet independence was 17 days (6 to 47 days). Responses included two partial responses, eight mixed responses, three stable disease, and seven progressive disease. Responses by semiquantitative MIBG score occurred in eight patients, soft tissue responses occurred in five of 11 patients, but bone marrow responses occurred in only two of 13 patients.

Conclusion

The lack of toxicity with this approach allowed dramatic dose intensification of 131I-MIBG, with minimal toxicity and promising activity.
Phase I Study of Lapatinib in Combination With Chemoradiation in Patients With Locally Advanced Squamous Cell Carcinoma of the Head and Neck
Authors: Harrington Kevin J. , El-Hariry Iman A. , Holford Clare S. , Lusinchi Antoine , Nutting Christopher M. , Rosine Dominique , Tanay Mary , Deutsch Eric , Matthews Jennifer , D'Ambrosio Consuelo , Turner Simon J. , Pandeshwara Jagannatha S. , Bourhis Jean
Published: January 2009

Purpose

This study (EGF100262) sought to establish the recommended phase II dose of lapatinib with chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN).

Patients and Methods

Patients were enrolled onto cohorts of escalating lapatinib dose (500, 1,000, and 1,500 mg/d). Patients received 1 week of lapatinib alone followed by 6.5 to 7 weeks of the same dose of lapatinib plus radiotherapy 66 to 70 Gy and cisplatin 100 mg/m2 on days 1, 22, and 43 of radiotherapy. End points included safety/tolerability and clinical activity.

Results

Thirty-one patients were enrolled (seven patients in each of the 500- and 1,000-mg cohorts and three in the 1,500-mg cohort; an additional 14 patients were enrolled at 1,500 mg in a safety cohort). Dose-limiting toxicities (DLTs) included perforated ulcer in one patient in the 500-mg cohort and transient elevation of liver enzymes in one patient in the 1,000-mg cohort. No DLTs were observed in the 1,500-mg cohort. Therefore, the recommended phase II dose was defined as lapatinib 1,500 mg/d with chemoradiotherapy. The most common grade 3 to 4 adverse events were radiation mucositis, radiation dermatitis, lymphopenia, and neutropenia. No patients experienced drug-related symptomatic cardiotoxicity, and no interstitial pneumonitis was reported. The overall response rate was 81% (65% at the recommended phase II dose).

Conclusion

The recommended phase II dose is lapatinib 1,500 mg/d with chemoradiotherapy in patients with LA SCCHN; this regimen is associated with an acceptable tolerability profile. Given these findings, randomized phase II and III studies of lapatinib plus chemoradiotherapy have been initiated.
Phase I Trial of Oral Irinotecan and Temozolomide for Children With Relapsed High-Risk Neuroblastoma: A New Approach to Neuroblastoma Therapy Consortium Study
Authors: Wagner Lars M. , Villablanca Judith G. , Stewart Clinton F. , Crews Kristine R. , Groshen Susan , Reynolds C. Patrick , Park Julie R. , Maris John M. , Hawkins Randall A. , Daldrup-Link Heike E. , Jackson Hollie A. , Matthay Katherine K.
Published: January 2009

Purpose

Irinotecan and temozolomide have single-agent activity and schedule-dependent synergy against neuroblastoma. Because protracted administration of intravenous irinotecan is costly and inconvenient, we sought to determine the maximum-tolerated dose (MTD) of oral irinotecan combined with temozolomide in children with recurrent/resistant high-risk neuroblastoma.

Patients and Methods

Patients received oral temozolomide on days 1 through 5 combined with oral irinotecan on days 1 through 5 and 8 through 12 in 3-week courses. Daily oral cefixime was used to reduce irinotecan-associated diarrhea.

Results

Fourteen assessable patients received 75 courses. Because neutropenia and thrombocytopenia were initially dose-limiting, temozolomide was reduced from 100 to 75 mg/m2/d for subsequent patients. Irinotecan was then escalated from 30 to 60 mg/m2/d. First-course grade 3 diarrhea was dose-limiting in one of six patients treated at the irinotecan MTD of 60 mg/m2/d. Other toxicities were mild and reversible. The median SN-38 lactone area under the plasma concentration versus time curve at this dose was 72 ng · hr/mL. One patient with bulky soft tissue disease had a complete response through six courses. Six additional patients received a median of seven courses (range, three to 22 courses) before progression.

Conclusion

This all-oral regimen was feasible and well tolerated in heavily pretreated children with resistant neuroblastoma, and seven (50%) of 14 assessable patients had response or disease stabilization for three or more courses in this phase I trial. SN-38 lactone exposures were similar to those reported with protracted intravenous irinotecan. The dosages recommended for further study in this patient population are temozolomide 75 mg/m2/d plus irinotecan 60 mg/m2/d when given with cefixime.
Safety of Ovarian Preservation in Premenopausal Women With Endometrial Cancer
Authors: Wright Jason D. , Buck Adam M. , Shah Monjri , Burke William M. , Schiff Peter B. , Herzog Thomas J.
Published: January 2009

Purpose

Oophorectomy is commonly performed in premenopausal women with endometrial cancer who undergo hysterectomy. The benefits of oophorectomy in this setting are unknown, and the procedure subjects women to the long-term sequelae of estrogen deprivation. We examined the safety of ovarian preservation in young women with endometrial cancer who underwent hysterectomy.

Patients and Methods

Women ≤ 45 years of age with stage I endometrial cancer recorded from 1988 to 2004 in the Surveillance, Epidemiology, and End Results Database were examined. We developed Cox proportional hazards models and Kaplan-Meier curves to compare women who underwent oophorectomy with those who had ovarian preservation.

Results

A total of 3,269 women, including 402 patients (12%) who had ovarian preservation, were identified. Younger age (P < .0001), later year of diagnosis (P = .04), residence in the eastern United States (P = .02), and low tumor grade (P < .0001) were associated with ovarian preservation. In a multivariate Cox model, ovarian preservation had no effect on either cancer-specific (hazard ratio [HR] = 0.58; 95% CI, 0.14 to 2.44) or overall (HR = 0.68; 95% CI, 0.34 to 1.35) survival. The findings were unchanged when women who received pelvic radiotherapy were excluded.

Conclusion

Ovarian preservation in premenopausal women with early-stage endometrial cancer may be safe and not associated with an increase in cancer-related mortality.
Androgen-Induced Progression of Arterial Calcification in Apolipoprotein E-Null Mice Is Uncoupled from Plaque Growth and Lipid Levels
Authors: McRobb L. , Handelsman D. J. , Heather A. K.
Published: January 2009

Arterial calcification has prognostic significance for cardiovascular outcomes, but its pathogenesis remains unclear. Calcification increases with age, but its prevalence in men suggests hormonal influence. In this study we analyzed the effect of exogenous androgens on calcification of advanced atherosclerotic lesions in the arterial tree of gonadally intact 34-wk-old male and female apolipoprotein E-null mice. Testosterone (T) increased calcification 3- to 4-fold (P < 0.05) in lesions of the innominate artery and aortic sinus. A nonaromatizable androgen, dihydrotestosterone, also increased lesion calcification in the innominate artery (2.4-fold, P < 0.05) but not the aortic sinus. The androgen-induced effects were independent of sex and occurred despite corresponding reductions in plaque area, the latter correlating inversely with increased serum high-density lipoprotein cholesterol levels. Androgen-induced calcification in the innominate artery was observed with up-regulation of local androgen receptor (AR) expression in response to T and dihydrotestosterone for both males and females but neither androgen influenced innominate artery estrogen receptor (ER)-α or -β expression in either sex. Conversely, T-induced calcification in the aortic sinus was associated with down-regulation of ERα but not ERβ expression in both sexes, whereas androgen-induced AR expression was increased in female but decreased in male mice. This study demonstrates for the first time that calcification of advanced atherosclerotic lesions is an androgen-sensitive process and postulates potential roles for both AR- and ER-mediated pathways in androgen-induced vascular calcification. We demonstrate a novel direct link between vascular calcification and the major male hormone, T, uncoupled from conventional relationships with plaque growth and lipid levels.

Calcification of advanced atherosclerotic lesions is an androgen-sensitive process whereby testosterone uncouples conventional relationships between plaque growth and lipid levels.
Mechanisms of Resistance to Structurally Diverse Antiestrogens Differ under Premenopausal and Postmenopausal Conditions: Evidence from in Vitro Breast Cancer Cell Models
Authors: Fan Ping , Yue Wei , Wang Ji-Ping , Aiyar Sarah , Li Yan , Kim Tae-Hyun , Santen Richard J.
Published: January 2009

This study questioned whether the mechanisms of resistance to antiestrogens differ when acquired under premenopausal (Pre-M) vs. postmenopausal (PM) conditions and whether structurally diverse antiestrogens induce adaptation of differing signaling pathways. To address this issue, we conducted systematic studies under Pre-M vs. PM culture conditions with long-term exposure to different antiestrogens and examined the resultant “specific biologic signatures” of the various resistant cells. Estradiol stimulated growth and inhibited apoptosis of “pre-menopausal” antiestrogen-resistant cells but exerted opposite effects on their “post-menopausal” counterparts. Under Pre-M conditions, tamoxifen (TAM)-resistant cells exhibited a marked translocation of estrogen receptor α from the nucleus into the cytoplasm, whereas this occurred to a lesser extent under PM conditions. MCF-7 cells exposed to PM but not Pre-M conditions exhibited up-regulation of basal epidermal growth factor (EGF) receptor (EGFR) levels, an effect exaggerated in cells exposed to 4-hydroxytamoxifen. Differing effects occurred in response to structurally divergent antiestrogens. Long-term treatment with both 4-hydroxytamoxifen and ICI182,780 increased EGFR levels, but this was not seen in response to TAM. Surprisingly, EGF administration slightly increased cell number in TAM-resistant cells, whereas only increasing cell weight and decreasing cell number in EGFR overexpressing-resistant cells. To assess potential differences among various parental cell lines, we induced resistance in cell lines obtained from other laboratories and confirmed the results from our own parental cells with minor differences. Together, these data demonstrate that culture of breast cancer cells under Pre-M and PM conditions and structurally diverse antiestrogens results in adaptive responses with differing biological signatures.
Interaction of visual and odour cues in the mushroom body of the hawkmothManduca sexta
Authors: Balkenius Anna , Bisch-Knaden Sonja , Hansson Bill
Published: January 2009

The responses to bimodal stimuli consisting of odour and colour were recorded using calcium-sensitive optical imaging in the mushroom bodies of the hawkmoth Manduca sexta. The results show that the activity in the mushroom bodies is influenced by both olfaction and vision. The interaction between the two modalities depends on the odour and the colour of the visual stimulus. A blue stimulus suppressed the response to a general flower scent(phenylacetaldehyde). By contrast, the response to a green leaf scent(1-octanol) was enhanced by the presence of the blue stimulus. A green colour had no influence on these odours but caused a marked increase in the response to an odour component (benzaldehyde) of the hawkmoth-pollinated Petunia axillaris.
Prediction of structure-borne noise caused by the powertrain on the basis of the hybrid transfer path
Authors: Kim S J , Lee S-K
Published: January 2009

In the early development stage, the prediction of interior noise due to powertrain vibration is important for enhancement of the noise vibration harshness (NVH) performance. Traditional transfer path analysis (TPA) technology has been used to estimate interior noise on the basis of experiment by using real parts of the powertrain. When a structural modification of the powertrain is necessary to reduce interior noise, it is efficient to use a finite element (FE) model of the powertrain components to identify the effect of that modification. In this paper, hybrid TPA is employed. Until now, no paper has been presented on predicting the interior noise caused by a powertrain on the basis of hybrid TPA with a real vehicle. The hybrid TPA uses a simulated excitation force as the input force, which excites the flexible body of a car at the mount point, whereas the traditional TPA uses the measured force. This simulated force is obtained by numerical analysis for the FE model of a powertrain. The interior noise is predicted by multiplying the simulated force by the vibroacoustic transfer function (VATF) of the vehicle. The trend of the predicted interior noise based on the hybrid TPA corresponds very well to the measured interior noise.
Studies of trims, stability, controllability, and some flying qualities of a tandem rotor helicopter
Authors: Cao Yihua , Li Guozhi , Yang Qian
Published: January 2009

Two mathematical models for determining the trims of a tandem rotor helicopter were constructed separately using two technologies (momentum theory and vortex theory). A computational method for the stability and control derivatives was proposed based on the linear perturbation theory and the five-point central difference algorithm. The stability roots of a CH-47B tandem rotor helicopter in the uncoupled mode were calculated. As a verification, the calculated, referenced, and test data of comparable trims and stability roots were shown to have acceptable agreement. Analysis presented included stability and controllability features of the tandem rotor helicopter, based on the momentum theory model. According to ADS-33E-PRF, the flying qualities of the tandem rotor helicopter in hovering were studied mainly with respect to four aspects: bandwidth, attitude quickness, interaxis coupling, and disturbance of the lateral gust. Indications of all the work are summarized at the end of this article.
Inconsistencies in children's recall of witnessed events: The role of age, question format and perceived reason for question repetition
Authors: Howie Pauline , Kurukulasuriya Nadezhda , Nash Laura , Marsh Annabel
Published: January 2009

Purpose. Children's inconsistencies when answering repeated questions about past events are a source of concern in forensic, educational, and other contexts. Theoretical accounts of these inconsistencies have predominantly assumed that children shift because they infer adult dissatisfaction with their initial answer. This study aimed to test this account via examination of the effects of question format on shifting, as well as via direct questioning of children.

Method. Four‐, five‐, and seven‐year‐olds (N = 226) were asked 17 recall questions about a recent classroom activity, with eight target questions repeated in one of four formats: no‐correct (mildly misleading questions to which the correct answer was ‘no’), yes‐correct (mildly misleading questions to which the correct answer was ‘yes’), specific open wh‐ questions, and forced‐choice questions. They were then asked about the adult's reasons for repetition. Accuracy, shifting, and interpretations of question repetition were examined.

Results. Shifting from accuracy decreased with age, and was affected by question format in 4‐year‐olds only, who shifted more to no‐correct than to forced‐choice questions. Shifting towards accuracy was more common in forced‐choice questions than either no‐correct or open questions, but there were no significant age differences. First‐answer‐unsatisfactory interpretations of question repetition were rare, especially in the two younger groups. The oldest group offered a wider range of interpretations and also showed some evidence of an association between first‐answer‐unsatisfactory interpretations and shifting.

Conclusions. Overall, our findings present a challenge to first‐answer‐unsatisfactory explanations of young children's shifting in recall settings, at least where overt pressure to shift is low. Forensic implications are considered.
Psychological processing of transplantation in lung recipients: A quantitative study of organ integration and the relationship to the donor
Authors: Goetzmann Lutz , Irani Sarosh , Moser Karin S. , Schwegler Kyrill , Stamm Martina , Spindler Anja , Buddeberg Claus , Schmid Christoph , Boehler Annette , Klaghofer Richard
Published: January 2009

Objectives Lung recipients undergo a complex psychological process, including organ integration and processing of attitudes towards the organ donor.

Design Seventy‐six lung recipients were asked to participate in a cross‐sectional questionnaire study on the psychological processing of lung transplants.

Methods The questionnaire consisted of statements describing aspects of organ integration and the patient's relationship with the donor. Furthermore, chronic stress/psychological distress (Screening Scale of the Trier Inventory; Symptom Checklist SCL‐K‐9) and the emotional effects of transplantation/immunosuppression (Transplant Effects Questionnaire; Medication Experience Scale for Immunosuppressants) were assessed.

Results In general, lung recipients perceive the transplant as part of themselves (97.4%) and not as a foreign object (90%). One‐third of patients still have frequent thoughts about the donor, whilst the majority (80.3%) do not believe that they have adopted the donor's characteristic traits. Factor analysis reveals the two‐dimensional structure of the questionnaire items ‘organ integration’ (factor 1) and ‘relationship to the donor’ (factor 2). Poor organ integration predicts low adherence, low disclosure and high feelings of guilt, whilst a close donor relationship predicts chronic stress and psychological distress.

Conclusions Poor organ integration and a close relationship to the donor should be borne in mind in psychosocial treatment regarding the patient's adherence behaviour and psychological distress.
Pedometer-Measured Physical Activity of Adults With Intellectual Disability: Predicting Weekly Step Counts
Authors: Temple Viviene A. , Stanish Heidi I.
Published: January 2009

Pedometers are objective, inexpensive, valid, and reliable measures of physical activity. The minimum number of days of pedometer monitoring needed to estimate average weekly step counts was investigated. Seven days of pedometer data were collected from 154 ambulatory men and women (ns = 88 and 66, respectively) with intellectual disability. Correlations between average weekly steps and 3-day combinations ranged from .80 to .94, and adjusted R2 for 3 days of monitoring was .886. Results suggest that 3 days of pedometer wear is sufficient to predict average weekly steps among ambulatory adults with intellectual disability. This finding will allow researchers to reduce participant burden and study costs, may guide measurement procedures, and inform missing data protocols.
Efficacy of the Supports Intensity Scale (SIS) to Predict Extraordinary Support Needs
Authors: Wehmeyer Michael , Chapman Theodore E. , Little Todd D. , Thompson James R. , Schalock Robert , Tassé Marc J.
Published: January 2009

Data were collected on 274 adults to investigate the efficacy of the Supports Intensity Scale (SIS) as a tool to measure the support needs of individuals with intellectual and related developmental disabilities. Findings showed that SIS scores contributed significantly to a model that predicted greater levels of support need. Moreover, scores from different sections of the SIS made unique contributions to explaining variance associated with a variety of support need proxies. Finally, data suggest that the SIS measures a different construct than that measured by traditional assessments of personal competence. The implications of these findings for decision-making, including decisions affecting the disbursement of state developmental disability funding, are discussed.
Social Problem-Solving and Mild Intellectual Disabilities: Relations With Externalizing Behavior and Therapeutic Context
Authors: van Nieuwenhuijzen Maroesjka , de Castro Bram Orobio , Wijnroks Lex , Vermeer Adri , Matthys Walter
Published: January 2009

Relations among externalizing behavior, therapeutic context (community care vs. residential care), and social problem-solving by children with mild intellectual disabilities or borderline intelligence were examined. Participants were 186 children (12 to 14 years of age) who responded to a video-based social problem-solving task. Of these, 130 received residential care and the majority suffered from severe externalizing behavior problems. The results indicated that externalizing behavior was related to encoding, generation of aggressive responses, and negative evaluation of assertive responses. Therapeutic context was related to encoding, positive evaluation of assertive responses, and negative evaluation of aggressive responses. Results indicate a discrepancy between appropriate problem-solving skills and behavior in daily life. Implications for interventions are discussed.
Translation and Cultural Adaptation of the Supports Intensity Scale in French
Authors: Lamoureux-Hébert Mélanie , Morin Diane
Published: January 2009

The Supports Intensity Scale (SIS) was translated into French. The French version was then validated using a sample of 245 persons with intellectual disabilities between the ages of 16 and 75 years. The internal consistency was excellent (.98). Correlations with age and levels of intellectual disabilities were evidence of good construct validity. These psychometric results replicate the psychometric characteristics reported on the original SIS version. Our findings show that the SIS-F is a good measure of intensity of support needs of individuals with developmental disabilities.
Psychological Growth Among Siblings of Children With and Without Intellectual Disabilities
Authors: Findler Liora , Vardi Aya
Published: January 2009

The presence of a child with an intellectual disability is often perceived as a cloud hanging over the heads of their siblings, placing them at risk of developing a variety of problems. Only recently have siblings been examined for the positive aspects of this life situation, such as the potential to experience psychological growth. Adopting J. A. Schaffer and G. H. Moos' (1992) theoretical framework, this study investigated the contribution of perceived stress, self-differentiation, and parental preference to the personal, social, and spiritual growth of siblings. Participants comprised 101 siblings of children with intellectual disabilities and 89 siblings of children with typical development (age range = 13–19 years). Results indicated that siblings of children with intellectual disabilities evidence higher levels of growth, with self-differentiation and perceived maternal preference acting as the main contributors to this growth.
Reliability of the Supports Intensity Scale (French Version)
Authors: Morin Diane , Cobigo Virginie
Published: January 2009

The definition of intellectual disability, according to the American Association on Intellectual and Developmental Disabilities, includes the assumption that adequate supports should improve a person's functioning. Consequently, support needs have to be assessed to plan services for persons with intellectual disability. The Supports Intensity Scale (SIS; J. R. Thompson et al., 2004) is a standardized instrument for assessing support needs and their intensity. This study was designed to estimate the interrespondent, interinterviewer coefficients of the French version of the SIS. Approximately 40 persons with intellectual disabilities from Quebec, a Canadian province, participated in this study. For each participant, 2 respondents and 2 interviewers were identified and 3 French SIS questionnaires were filled out. Results are presented and discussed compared with those obtained with the original, English-based SIS.