bluuebunny/crossref_metadata_2025 huggingface dataset:
Paclitaxel Plus Ifosfamide Followed by High-Dose Carboplatin Plus Etoposide in Previously Treated Germ Cell Tumors
Authors: Kondagunta G. Varuni , Bacik Jennifer , Sheinfeld Joel , Bajorin Dean , Bains Manjit , Reich Lillian , Deluca John , Budnick Amy , Ishill Nicole , Mazumdar Madhu , Bosl George J. , Motzer Robert J.
Published: December 2006

Purpose

To evaluate the optimal dose of carboplatin as well as the efficacy and tolerability of sequential, dose-intense chemotherapy with paclitaxel and ifosfamide followed by carboplatin and etoposide (TICE) plus peripheral-blood stem-cell (PBSC) support in patients with germ cell tumors (GCT) who are likely to experience treatment failure with conventional-dose salvage treatment. This prospective trial followed a similarly designed report of TICE, which used a different means of carboplatin dosing.

Patients and Methods

The 48 patients entered onto this trial had progressive GCT and unfavorable prognostic features after chemotherapy. Two cycles of paclitaxel plus ifosfamide were administered with leukapheresis, followed by three cycles of carboplatin plus etoposide with reinfusion of PBSC.

Results

Twenty-three (49%) of 47 assessable patients achieved a complete response (CR) to chemotherapy. An additional three patients (6%) achieved a CR to chemotherapy and surgery. The CR rate was 55%. Six patients experienced relapse, but 24 patients (51%) are alive and free of disease at a median follow-up time of 40 months. Four patients who experienced relapse or achieved an incomplete response were rendered disease free by salvage surgical resection. When combined with results of the prior trial of similar design, TICE chemotherapy yielded an overall CR of 56% (n = 84), with 50% of patients alive with no evidence of disease.

Conclusion

TICE is an effective and tolerable dose-intense treatment for patients with previously treated metastatic GCT who have a poor predicted outcome to conventional-dose salvage chemotherapy.
Screening for Coronary Artery Disease After Mediastinal Irradiation for Hodgkin's Disease
Authors: Heidenreich Paul A. , Schnittger Ingela , Strauss H. William , Vagelos Randall H. , Lee Byron K. , Mariscal Carol S. , Tate David J. , Horning Sandra J. , Hoppe Richard T. , Hancock Steven L.
Published: December 2006

Purpose

Incidental cardiac irradiation during treatment of thoracic neoplasms has increased risks for subsequent acute myocardial infarction or sudden cardiac death. Identifying patients who have a high risk for a coronary event may decrease morbidity and mortality. The objective of this study was to evaluate whether stress imaging can identify severe, unsuspected coronary stenoses in patients who had prior mediastinal irradiation for Hodgkin's disease.

Patients and Methods

We enrolled 294 outpatients observed at a tertiary care cancer treatment center after mediastinal irradiation doses ≥ 35 Gy for Hodgkin's disease who had no known ischemic cardiac disease. Patients underwent stress echocardiography and radionuclide perfusion imaging at one stress session. Coronary angiography was performed at the discretion of the physician.

Results

Among the 294 participants, 63 (21.4%) had abnormal ventricular images at rest, suggesting prior myocardial injury. During stress testing, 42 patients (14%) developed perfusion defects (n = 26), impaired wall motion (n = 8), or both abnormalities (n = 8). Coronary angiography showed stenosis ≥ 50% in 22 patients (55%), less than 50% in nine patients (22.5%), and no stenosis in nine patients (22.5%). Screening led to bypass graft surgery in seven patients. Twenty-three patients developed coronary events during a median of 6.5 years of follow-up, with 10 acute myocardial infarctions (two fatal).

Conclusion

Stress-induced signs of ischemia and significant coronary artery disease are highly prevalent after mediastinal irradiation in young patients. Stress testing identifies asymptomatic individuals at high risk for acute myocardial infarction or sudden cardiac death.
Volume-Based Referral for Cancer Surgery: Informing the Debate
Authors: Hollenbeck Brent K. , Dunn Rodney L. , Miller David C. , Daignault Stephanie , Taub David A. , Wei John T.
Published: December 2006

Purpose

Mounting evidence suggests a relationship between hospital volume and outcomes after major cancer surgery; however, the absolute benefits of volume-based referral on a national basis are unclear.

Patients and Methods

Data from the Nationwide Inpatient Sample were used to measure the likelihood of operative mortality and a prolonged length of stay (LOS) after six cancer surgeries (prostatectomy, cystectomy, esophagectomy, pancreatectomy, pneumonectomy, and liver resection) between 1993 and 2003. Using sampling weights, the adjusted likelihood of the outcomes was used to calculate the number of lives saved (or prolonged LOS avoided) in the United States.

Results

The magnitude of the volume–operative mortality effect varied from an adjusted odds ratio (OR) of 1.3 (95% CI, 0.8 to 2.3) for cystectomy to 4.9 (95% CI, 2.4 to 10.1) for pancreatectomy. After accounting for varying rates of procedure utilization, the lives saved per 100 surgeries regionalized ranged from 0.2 (95% CI, 0.12 to 0.24 lives saved) for prostatectomy to 9.2 (95% CI, 6.7 to 10.4 lives saved) for pancreatectomy. The volume–prolonged LOS effect varied from an adjusted OR of 0.9 (95% CI, 0.5 to 1.6) for liver resection to 4.8 (95% CI, 3.5 to 6.7) for prostatectomy. After accounting for procedure use, the number of prolonged hospitalizations avoided ranged from −1.7 (95% CI, −11.3 to 3.6 hospitalizations) to 14.3 (95% CI, 12.9 to 15.4 hospitalizations) per 100 surgeries regionalized for liver resection and prostatectomy, respectively.

Conclusion

For patients undergoing major cancer surgery, the benefits of volume-based referral depend on the interplay between procedure utilization, the magnitude of effect, and the outcome chosen.
Incidence of Venous Thromboembolism and the Impact on Survival in Breast Cancer Patients
Authors: Chew Helen K. , Wun Theodore , Harvey Danielle J. , Zhou Hong , White Richard H.
Published: December 2006

Purpose

The incidence of venous thromboembolism (VTE) and the risk factors associated with development of VTE have not been reported in a large population-based study of breast cancer patients.

Patients and Methods

The California Cancer Registry was merged with the Patient Discharge Data Set, and the number of VTE events determined among patients diagnosed between 1993 and 1999.

Results

Among 108,255 patients with breast cancer, the 2-year cumulative VTE incidence was 1.2%, with a rate of 1.2 and 0.6 events/100 patient-years during the first and second half-year, respectively. The 1-year incidence of VTE was significantly increased compared with the general population (standardized incidence ratio of VTE, 4.2; 95% CI, 3.9 to 4.4). In a multivariate model, significant predictors of developing VTE within 2 years were: age (hazard ratio [HR], 2.0 if > 75 years v < 45; 95% CI, 1.6 to 2.6), the number of chronic medical comorbidities (HR, 2.9 if 3 v 0; 95% CI, 2.4 to 3.5), and advancing cancer stage (HR, 6.3; 95% CI, 5.3 to 7.5 for metastatic v local disease). In multivariate models, VTE was a significant predictor of decreased 2-year survival (HR, 2.3; 95% CI, 2.1 to 2.6) and when stratified by initial cancer stage, the effect was highest in patients with localized (HR, 5.1; 95% CI, 3.6 to 7.1) or regional stage (HR, 3.5; 95% CI, 2.5 to 4.8) cancer compared with patients with metastatic disease (HR, 1.9; 95% CI, 1.5 to 2.4).

Conclusion

Approximately 1% of breast cancer patients developed VTE within 2 years, with the highest incidence in the first 6 months after diagnosis. Metastatic disease and comorbidities were the strongest predictors. The diagnosis of VTE was associated with a higher risk of death within 2 years.
Phase III Trial of Capecitabine Plus Oxaliplatin As Adjuvant Therapy for Stage III Colon Cancer: A Planned Safety Analysis in 1,864 Patients
Authors: Schmoll Hans-Joachim , Cartwright Thomas , Tabernero Josep , Nowacki Marek P. , Figer Arie , Maroun Jean , Price Timothy , Lim Robert , Van Cutsem Eric , Park Young-Suk , McKendrick Joseph , Topham Claire , Soler-Gonzalez Gemma , de Braud Filipo , Hill Mark , Sirzén Florin , Haller Daniel G.
Published: December 2006

Purpose

To report the results of a planned safety analysis from a phase III trial comparing capecitabine plus oxaliplatin (XELOX) with bolus fluorouracil/leucovorin (FU/LV) as adjuvant therapy for stage III colon cancer.

Patients and Methods

Patients with stage III colon carcinoma were randomly assigned to receive either XELOX (intravenous oxaliplatin plus oral capecitabine; 3-week cycle for eight cycles) or standard intravenous bolus FU/LV administered as the Mayo Clinic (Mayo; Rochester, MN) or Roswell Park (RP; Buffalo, NY) regimen for a similar length of time. A total of 1,886 patients were randomly assigned.

Results

The safety population comprised 1,864 patients, of whom 938 received XELOX and 926 received FU/LV. Most treatment-related adverse events (AEs) occurred at similar rates in both treatment arms. However, patients receiving XELOX experienced less all-grade diarrhea, alopecia, and more neurosensory toxicity, vomiting, and hand-foot syndrome than those patients receiving FU/LV. Compared with Mayo, XELOX showed fewer grade 3/4 hematologic AE and more grade 3/4 gastrointestinal AE. Compared with RP, XELOX showed less grade 3/4 gastrointestinal AE and more grade 3/4 hematologic AE. As expected grade 3/4 neurosensory toxicity and grade 3 hand-foot syndrome were higher with XELOX. Treatment-related mortality within 28 days from the last study dose was 0.6% in the XELOX group and 0.6% in the FU/LV group.

Conclusion

XELOX has a manageable tolerability profile in the adjuvant setting. Efficacy data will be available within the next 24 months.
Antithyroid Drugs Inhibit Thyroid Hormone Receptor-Mediated Transcription
Authors: Moriyama Kenji , Tagami Tetsuya , Usui Takeshi , Naruse Mitsuhide , Nambu Takuo , Hataya Yuji , Kanamoto Naotetsu , Li Yu-shu , Yasoda Akihiro , Arai Hiroshi , Nakao Kazuwa
Published: December 2006

Context: Methimazole (MMI) and propylthiouracil (PTU) are widely used as antithyroid drugs (ATDs) for the treatment of Graves’ disease. Both MMI and PTU reduce thyroid hormone levels by several mechanisms, including inhibition of thyroid hormone synthesis and secretion. In addition, PTU decreases 5′-deiodination of T4 in peripheral tissues. ATDs may also interfere with T3 binding to nuclear thyroid hormone receptors (TRs). However, the effect of ATDs on the transcriptional activities of T3 mediated by TRs has not been studied.

Objective: The present study was undertaken to determine whether ATDs have an effect on the gene transcription regulated by T3 and TRs in vitro.

Methods: Transient gene expression experiments and GH secretion assays were performed. To elucidate possible mechanisms of the antagonistic action of ATDs, the interaction between TR and nuclear cofactors was examined.

Results: In the transient gene expression experiments, both MMI and PTU significantly suppressed transcriptional activities mediated by the TR and T3 in a dose-dependent manner. In mammalian two-hybrid assays, both drugs recruited one of the nuclear corepressors, nuclear receptor corepressor, to the TR in the absence of T3. In addition, PTU dissociated nuclear coactivators, such as steroid receptor coactivator-1 and glucocorticoid receptor interacting protein-1, from the TR in the presence of T3. Finally, MMI decreased the GH release that was stimulated by T3.

Conclusions: ATDs inhibit T3 action by recruitment of transcriptional corepressors and/or dissociation of coactivators. This is the first report to show that ATDs can modulate T3 action at the transcriptional level.
Follicular Phase Dynamics with Combined Aromatase Inhibitor and Follicle Stimulating Hormone Treatment
Authors: Bedaiwy Mohamed A. , Mousa Noha A. , Esfandiari Navid , Forman Rachel , Casper Robert F.
Published: December 2006

Objective: The objective of this study was to evaluate follicular phase parameters during ovarian stimulation with FSH alone or with the aromatase inhibitor letrozole.

Methods: Two groups of women undergoing intrauterine insemination (IUI): group I (389 patients; mean age 35 ± 4.3 yr) underwent 630 IUI cycles stimulated with letrozole and FSH; and group II (134 patients; mean age 36.0 ± 4.6 yr) underwent 166 IUI cycles stimulated with FSH only. Each group was stratified into ovulatory and anovulatory cycles. Patients were monitored by ultrasound for folliculometry and blood sampling for hormonal assay on d 3, 7, 9, or 10 of the cycle, and on the day of human chorionic gonadotropin administration.

Results: Group I had a significantly lower follicular count greater than 10 mm on d 7, greater than 12 mm on d 9 or 10, and greater than 15 mm on the day of human chorionic gonadotropin administration compared to group II (P = 0.006, <0.001, and <0.001, respectively). After stratifying patients by diagnosis, this relationship was maintained only for patients with ovulatory infertility (P = 0.003, <0.001, and <0.001, respectively). Serum estradiol (E2) was significantly lower in the group I ovulatory and anovulatory at the last three monitoring visits (P < 0.001). However, the difference in E2 levels decreased in the preovulatory period with similar E2 levels per mature follicle. No premature preovulatory progesterone rise was observed in either group. However, significantly lower progesterone levels were observed in the second half of the follicular phase in group I (P = 0.02 and <0.001). Endometrial thickness was significantly lower in group I at the second and third visits (P < 0.001, 0.01) but was comparable to group II at the last monitoring visit. Although, the pregnancy rates were similar between the two groups, the multiple pregnancy rate was significantly higher in the FSH-only group (P = 0.039).

Conclusion: The addition of letrozole modifies the follicular, hormonal, and endometrial dynamics of FSH-stimulated cycles with possible positive effects on the overall cycle outcome.
Foxl2 Up-Regulates Aromatase Gene Transcription in a Female-Specific Manner by Binding to the Promoter as Well as Interacting with Ad4 Binding Protein/Steroidogenic Factor 1
Authors: Wang De-Shou , Kobayashi Tohru , Zhou Lin-Yan , Paul-Prasanth Bindhu , Ijiri Shigeho , Sakai Fumie , Okubo Kataaki , Morohashi Ken-ichirou , Nagahama Yoshitaka
Published: December 2006

Increasing evidence suggests the crucial role of estrogen in ovarian differentiation of nonmammalian vertebrates including fish. The present study has investigated the plausible role of Foxl2 in ovarian differentiation through transcriptional regulation of aromatase gene, using monosex fry of tilapia. Foxl2 expression is sexually dimorphic, like Cyp19a1, colocalizing with Cyp19a1 and Ad4BP/SF-1 in the stromal cells and interstitial cells in gonads of normal XX and sex-reversed XY fish, before the occurrence of morphological sex differentiation. Under in vitro conditions, Foxl2 binds to the sequence ACAAATA in the promoter region of the Cyp19a1 gene directly through its forkhead domain and activates the transcription of Cyp19a1 with its C terminus. Foxl2 can also interact through the forkhead domain with the ligand-binding domain of Ad4BP/SF-1 to form a heterodimer and enhance the Ad4BP/SF-1 mediated Cyp19a1 transcription. Disruption of endogenous Foxl2 in XX tilapia by overexpression of its dominant negative mutant (M3) induces varying degrees of testicular development with occasional sex reversal from ovary to testis. Such fish display reduced expression of Cyp19a1 as well as a drop in the serum levels of 17β-estradiol and 11-ketotestosterone. Although the XY fish with wild-type tilapia Foxl2 (tFoxl2) overexpression never exhibited a complete sex reversal, there were significant structural changes, such as tissue degeneration, somatic cell proliferation, and induction of aromatase, with increased serum levels of 17β-estradiol and 11-ketotestosterone. Altogether, these results suggest that Foxl2 plays a decisive role in the ovarian differentiation of the Nile tilapia by regulating aromatase expression and possibly the entire steroidogenic pathway.
Electrical Conductance Measurement of Oligothiophene Molecular Wires Using Nanogap Electrodes Prepared by Electrochemical Plating
Authors: Hatanaka Natsumu , Endo Masaru , Okumura Shigeki , Ie Yutaka , Yamada Ryo , Aso Yoshio , Tanaka Kazuyoshi , Tada Hirokazu
Published: December 2006

Nanogap electrodes were prepared by electroplating. The starting electrodes of gold were patterned by conventional photolithography and lift-off techniques, and the gap separation was reduced by depositing gold in electroplating solution. Careful control of deposition conditions by monitoring the current through the electrodes enabled us to obtain the electrodes with the separation of less than 10 nm. Electrical conductunce of newly designed oligothiophene wires was measuerd with the nanogap electrodes prepared.
Polycyclic Aromatic Compounds-mediated Electrochemical Reduction of Alkyl Mesylates
Authors: Senboku Hisanori , Takahashi Megumi , Fukuhara Tsuyoshi , Hara Shoji
Published: December 2006

Electrochemical reduction of alkyl mesylates was successfully carried out by using an undivided cell equipped with a Pt cathode and an Mg anode in the presence of biphenyl and t-BuOH. The reaction could proceed efficiently under mild conditions to give the corresponding alkanes in moderate to good yields. This procedure could also be applicable to chemoselective reduction of mesylates having functional groups such as epoxide, olefin, acetal, hydroxy, or cyano groups.
Promotion of Laccase Activities of Escherichia coli Cuprous Oxidase, CueO by Deleting the Segment Covering the Substrate Binding Site
Authors: Kurose Shinji , Kataoka Kunishige , Otsuka Kaori , Tsujino Yoshio , Sakurai Takeshi
Published: December 2006

Total and partial deletions of the region covering the substrate-binding site of the Escherichia coli cuprous oxidase, CueO evidenced that the unique specificity for cuprous ion originates in the steric hindrance to interfere the access of laccase substrates towards the type I Cu site.
An Investigation of Wind-Shear Models and Experimental Data Trends for Different Terrains
Authors: Elkinton M. R. , Rogers A. L. , McGowan J. G.
Published: December 2006

The importance of characterizing the wind-shear at a given site for a utility-scale wind turbine cannot be overemphasized. Such characterization is needed for an accurate prediction of its power output. Thus, the objective of this work based on the use of several US tall tower wind data sets was to determine the accuracies of different wind-shear enumeration methods, especially when used at sites having hills and/or forests. In addition, average wind-shear variations with respect seasonal and annual effects and data length are presented for various long data sets, recorded to between 1995 and 2005. Wind direction and atmospheric stability were not a factor in the analysis. At some of the sites the greatest average wind-shear was found during the summer. For the site with the most complex terrain, the average annual all-direction wind-shear varied by up to 7% between different years; this was partly due to year-to-year variations of the direction distribution. There was found to be no significant difference between the performance of the log and power laws; using either may give inaccurate predictions of hub-height mean wind speeds.
Analysis of the Impact of Interconnecting Wind Turbine Generators to the Utility Grid
Authors: Jayashri R. , Devi R. P. Kumudini
Published: December 2006

A preliminary analysis on the impact of wind power penetration into the grid is presented. This develops consistent simulation tools to analyze the steady-state impact of the interconnection of wind turbine generators to the utility grid for (i) power flow analysis, and (ii) reactive power compensation. Simulation results show that parallel compensation improves the effective power-factor of the wind farm, whereas series compensation improves the power developed by the induction machines. The advantages of both series and parallel compensation with AC capacitors are utilized by ‘series-parallel’ compensation. Simulation studies done on a 9-bus radial system, using the C++ programming language, show that this combination produces a very satisfactory voltage profile at the point of common coupling.
Calculation of Wind Speed Variation with Height over the Sea
Authors: Högström Ulf , Smedman Ann-Sofi , Bergström Hans
Published: December 2006

Two one-dimensional wind models have been tested for their ability to describe the wind profile at sea up to a height of 125 m. The first model is based on Monin-Obukhov similarity theory with due consideration of effects of surface waves. The second model is a combination of Monin-Obukhov similarity for a surface layer and an Ekman layer above, with requirements for continuity of the wind components and their vertical derivatives at the top of the surface layer. Model predictions are compared with data from an instrumented tower up to 29 m and from a limited set of pilot balloon data up to greater heights. The first of these two models gives good predictions of the wind up to 29 m but not acceptable results for 75 m and 125 m. The second model gives quite good results for 29 m, 75 m and 125 m. Required input data for this latter model are measured wind at one height (typically 10 m) and measured temperature difference between two levels (e.g. 2 and 10 m). The test has been restricted to cases with long (>150 km) undisturbed over-water fetch. For wind energy assessment at other sites, the combined MO and Ekman layer model is recommended for sectors with such characteristics, but dedicated models must be used to deal with limited-fetch effects for other sectors.
Mass spectrometry-based detection of transfer RNAs by their signature endonuclease digestion products
Authors: Hossain Mahmud , Limbach Patrick A.
Published: December 2006

The separation of biologically active, pure, and specific tRNAs is difficult due to the overall similarity in secondary and tertiary structures of different tRNAs. Because prior methods do not facilitate high-resolution separations of the extremely complex mixture represented by a cellular tRNA population, global studies of tRNA identity and/or abundance are difficult. We have discovered that the enzymatic digestion of an individual tRNA by a ribonuclease (e.g., RNase T1) will generate digestion products unique to that particular tRNA, and we show that a comparison of an organism's complete complement of tRNA RNase digestion products yields a set of unique or “signature” digestion product(s) that ultimately enable the detection of individual tRNAs from a total tRNA pool. Detection is facilitated by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and proof-of-principle is demonstrated on the whole tRNA pool from Escherichia coli. This method will enable the individual identification of tRNA isoacceptors without requiring specific affinity purification or extensive chromatographic and/or electrophoretic purification. Further, experimental identifications of tRNAs or other RNAs will now be possible using this signature digestion product approach in a manner similar to peptide mass fingerprinting used in proteomics, allowing RNomic studies of RNA at the post-transcriptional level.
Are ethnic minority adolescents at risk for problem behaviour? Acculturation and intergenerational acculturation discrepancies in early adolescence
Authors: Atzaba‐Poria Naama , Pike Alison
Published: December 2006

The present study investigated the adjustment of Indian adolescents living in Britain as well as the links between parents' and adolescents' acculturation styles and the adolescents' problem behaviours. The sample consisted of 68 young adolescents (31 Indian and 37 English) between the ages of 10 and 13, and their mothers and fathers. Mothers, fathers and adolescents reported about their own acculturation style, and parents also reported on their adolescents' problem behaviour. Overall Indian adolescents exhibited more internalizing problems than did their English peers. Furthermore, within the Indian group, the more Westernized mothers were in their acculturation style, the higher the level of externalizing problem behaviour their adolescents exhibited. In addition, the more traditional adolescents were the more internalizing problems they displayed. Finally, Indian adolescents experienced more internalizing problems when their parents were more Western or less traditional than the adolescents themselves. These findings highlight the importance of examining not only parental acculturation style, but also the parent–child acculturation discrepancy as a risk factor for problem behaviour.
Sexual fantasy in paedophile offenders: Can any model explain satisfactorily new findings from a study of Internet and contact sexual offenders?
Authors: Sheldon Kerry , Howitt Dennis
Published: December 2006

Purpose.There is widespread acceptance that sexual fantasy plays a role in sexual offences but little clarity as the nature of this relationship. This paper seeks to understand better the role of fantasy in offending behaviour through the study of sexual fantasy in Internet child pornography offenders when compared with contact offenders. Differences in the patterns of sexual fantasy associated with the different offender types are explored in order to understand how fantasy content is associated with contact offences with children and desisting from such direct acting out.

Methods.Participants were all convicted of child sexual offences and recruited with the help of the probation and prison services. Out of these, 16 were Internet‐only offenders, 25 were contact offenders with no history of Internet offending and 10 were offenders with a mixed contact and Internet offending history. A variety of self‐completion questionnaires including fantasy were completed on an individual basis together with a detailed interview.

Results.The most common sexual fantasies were typical adult‐male heterosexual fantasies though a variety of child‐oriented and other fantasies were also common. Contact offenders reported fewer girl‐oriented sexual fantasies although the groups did not differ in terms of terms of boy‐oriented fantasies. There was evidence that confrontational fantasies were commoner among contact offenders than Internet offenders. There are relationships between early sexual experiences and fantasy but peer sexual contacts seemed to be important rather than sexual abuse.

Conclusion.Generally, the contact offenders seem to have less sexual fantasy pertinent to their offending than did Internet offenders. Fantasy deficit may be involved in contact offending against children.
Genetic Alterations in Thyroid Cancer: The Role of Mouse Models
Authors: Knostman K. A. B. , Jhiang S. M. , Capen C. C.
Published: December 2006

Thyroid carcinomas are the most common endocrine neoplasms in humans, with a globally increasing incidence. Thyroid follicular cells and neuroendocrine (parafollicular) C cells are each susceptible to neoplastic transformation, resulting in thyroid cancers of differing phenotypes with unique associated genetic mutations and clinical outcomes. Over the past 15 years, several sophisticated genetically engineered mouse models of thyroid cancer have been created to further our understanding of the genetic events leading to thyroid carcinogenesis in vivo. The most significant mouse models of papillary, follicular, anaplastic, and medullary thyroid carcinoma are highlighted, with particular emphasis on the relationship between the relevant oncogenes in these models and genetic events in the naturally occurring human disease. Limitations of each model are presented, and the need for additional models to better recapitulate certain aspects of the human disease is discussed.
Fibrosing Gastrointestinal Leiomyositis as a Cause of Chronic Intestinal Pseudo-Obstruction in an 8-Month-Old Dog
Authors: Johnson C. S. , Fales-Williams A. J. , Reimer S. B. , Lotsikas P. J. , Haynes J. S.
Published: December 2006

An 8-month-old, female, mixed-breed dog presented to the Iowa State University Veterinary Teaching Hospital with a 1-month history of vomiting and diarrhea. An exploratory laparotomy was performed revealing markedly distended and fluid-filled small and large intestines that were not obstructed. The clinical condition of the dog did not improve subsequent to exploratory surgery, and it was euthanized. At necropsy, both the small and large intestines were distended (approximately 4 cm in diameter) and fluid-filled, and the wall was thin. The abdominal cavity contained approximately 500 ml of a brownish clear fluid. Microscopic lesions of the intestines were confined to the intestinal tunica muscularis and muscularis mucosae and consisted of locally extensive-to-diffuse replacement of the smooth muscle by fibrous tissue and multifocal infiltration by a moderately dense mononuclear inflammatory infiltrate. A unique finding was the presence of similar microscopic lesions in the tunica muscularis of the urinary bladder and stomach.
Verminous Encephalitis in a Horse Produced by Nematodes in the Family Protostrongylidae
Authors: Tanabe M. , Kelly R. , de Lahunta A. , Duffy M. S. , Wade S. E. , Divers T. J.
Published: December 2006

Parasitic granulomatous eosinophilic inflammation was observed in the central nervous system (CNS) of a 6-month-old Arabian colt from New York state. Inflammation was associated with eggs, larvae, and adult nematodes in the cerebellum. Nematodes had histological characteristics of the superfamily Metastrongyloidea. The presence of dorsal-spined larvae in the CNS was further indicative of infection with a nematode in the family Protostrongylidae. Infections were most compatible with Parelaphostrongylus tenuis but specific diagnosis was not possible. This is the first definitive report of a protostrongylid nematode infection in a horse.
Prevalence and Histopathologic Characteristics of Pancreatitis in Cats
Authors: De Cock H. E. V. , Forman M. A. , Farver T. B. , Marks S. L.
Published: December 2006

Despite the high prevalence of feline pancreatic disease, no detailed description on the histopathologic nature of this disease is currently available in the literature. In this study we characterize the distribution and histopathologic changes commonly found in feline pancreases, correlate the lesions with age and gastrointestinal GI and extra-gastrointestinal disease, and compare the pancreatic lesions in cats with those in humans. The entire pancreas was removed and examined from 115 cats presented for necropsy irrespective of the cause of death. Histologic sections from left limb, right limb, and body were scored for lesions of acute (AP) and chronic pancreatitis (CP) with a scoring system based on similar systems used in human and veterinary literature. The lesions of CP in cats resemble CP in humans, with fibrosis being more prominent than inflammatory changes. Cystic degeneration gradually increased as other lesions of CP were more prominent. A distinct nodular change of zymogen depletion and acinar cell dysplasia not associated with pancreatitis was prominent in 15.6% of the pancreases. Histologically, AP consisted of neutrophilic inflammation associated with interstitial edema and necrosis of mesenteric fat.

An overall prevalence of 67%, and 45% in clinically normal animals, was identified. CP was found in 69 (60.0%) pancreases, and 58 (50.4%) had CP only, with a significant correlation between age and occurrence of CP. There was a statistically significant higher prevalence of CP in the left limb in animals with gastrointestinal disease. AP was present in 18 animals (15.7%) of which 7 animals had AP only (6.1%).
Translation Initiation inSaccharomyces cerevisiaeMitochondria: Functional Interactions Among Mitochondrial Ribosomal Protein Rsm28p, Initiation Factor 2, Methionyl-tRNA-Formyltransferase and Novel Protein Rmd9p
Authors: Williams Elizabeth H , Butler Christine A , Bonnefoy Nathalie , Fox Thomas D
Published: December 2006

Rsm28p is a dispensable component of the mitochondrial ribosomal small subunit in Saccharomyces cerevisiae that is not related to known proteins found in bacteria. It was identified as a dominant suppressor of certain mitochondrial mutations that reduced translation of the COX2 mRNA. To explore further the function of Rsm28p, we isolated mutations in other genes that caused a synthetic respiratory defective phenotype together with rsm28Δ. These mutations identified three nuclear genes: IFM1, which encodes the mitochondrial translation initiation factor 2 (IF2); FMT1, which encodes the methionyl-tRNA-formyltransferase; and RMD9, a gene of unknown function. The observed genetic interactions strongly suggest that the ribosomal protein Rsm28p and Ifm1p (IF2) have similar and partially overlapping functions in yeast mitochondrial translation initiation. Rmd9p, bearing a TAP-tag, was localized to mitochondria and exhibited roughly equal distribution in soluble and membrane-bound fractions. A small fraction of the Rmd9-TAP sedimented together with presumed monosomes, but not with either individual ribosomal subunit. Thus, Rmd9 is not a ribosomal protein, but may be a novel factor associated with initiating monosomes. The poorly respiring rsm28Δ, rmd9-V363I double mutant did not have a strong translation-defective phenotype, suggesting that Rmd9p may function upstream of translation initiation, perhaps at the level of localization of mitochondrially coded mRNAs.
The Carnegie Protein Trap Library: A Versatile Tool for Drosophila Developmental Studies
Authors: Buszczak Michael , Paterno Shelley , Lighthouse Daniel , Bachman Julia , Planck Jamie , Owen Stephenie , Skora Andrew D , Nystul Todd G , Ohlstein Benjamin , Allen Anna , Wilhelm James E , Murphy Terence D , Levis Robert W , Matunis Erika , Srivali Nahathai , Hoskins Roger A , Spradling Allan C
Published: December 2006

Metazoan physiology depends on intricate patterns of gene expression that remain poorly known. Using transposon mutagenesis in Drosophila, we constructed a library of 7404 protein trap and enhancer trap lines, the Carnegie collection, to facilitate gene expression mapping at single-cell resolution. By sequencing the genomic insertion sites, determining splicing patterns downstream of the enhanced green fluorescent protein (EGFP) exon, and analyzing expression patterns in the ovary and salivary gland, we found that 600–900 different genes are trapped in our collection. A core set of 244 lines trapped different identifiable protein isoforms, while insertions likely to act as GFP-enhancer traps were found in 256 additional genes. At least 8 novel genes were also identified. Our results demonstrate that the Carnegie collection will be useful as a discovery tool in diverse areas of cell and developmental biology and suggest new strategies for greatly increasing the coverage of the Drosophila proteome with protein trap insertions.
Ammonia, pH, and Plankton in Sunshine Bass Nursery Ponds: The Effect of Inorganic Fertilizer or Sodium Bicarbonate
Authors: Ludwig Gerald M , Hobbs Melissa , Perschbacher Peter
Published: December 2006

When sunshine bass (female white bass Morone chrysops × male striped bass M. saxatilis) fingerling production ponds are filled and fertilized according to recommended practices, high pH and high un-ionized ammonia levels often develop at the time recommended for stocking of 5-d-old fry. These levels often exceed those found to be lethal to sunshine bass. We compared the effects of organic fertilizer only, both organic and inorganic fertilizer, and both organic and inorganic fertilizers with sodium bicarbonate on 0.04-ha culture ponds. Rice bran, the organic fertilizer, was applied at 278 kg/ha during the first week and 55.6 kg/ha during the second week. Liquid 9-27-0 NPK (urea and mono-ammonium phosphate), the inorganic fertilizer, was applied at 48 kg/ha during both weeks. Sodium bicarbonate was applied at 56, 112, or 224 kg/ha. Primary productivity, pH, and the concentrations of ammonia, chlorophyll a, phytoplankton, and zooplankton were compared among treatments. We include results from the 12-14 d after ponds were filled and fertilized, the period when fry are usually stocked. Sodium bicarbonate application did not reduce (P > 0.05) pH in culture ponds. However, ponds that only received organic fertilizer had pH values that were significantly lower than those of the other treatments on 75% of the experiment days. Chlorophyll-a, total ammonia nitrogen, and un-ionized ammonia nitrogen concentrations were also significantly lower in organic-only fertilized ponds than in the other two treatments on most days and were well below sunshine bass fry tolerance limits. For most water chemistry variables tested, use of sodium bicarbonate did not improve water quality. Although total nutrient input was lowest in the organic-only fertilized ponds, the densities of phytoplankton, rotifers, copepod nauplii, copepod adults, and cladocerans were not significantly different from those of other treatments. These results indicate that sodium bicarbonate does not ameliorate high pH; however, use of only organic fertilizer does reduce pH without reducing zooplankton standing crops.
Validation of a Fecal Collection Method for Determination of Apparent Digestibility Coefficients of Diets in Gulf of Mexico Sturgeon
Authors: Venero Jesus A , Miles Richard D , Chapman Frank A
Published: December 2006

Apparent digestibility coefficients (ADCs) of dry matter, energy, and crude protein in the diet of Gulf of Mexico sturgeon Acipenser oxyrinchus desotoi were determined by two methods, dissection and hand stripping of feces from the lower spiral valve-rectal area of the digestive tract. Hand stripping resulted in ADC values of 58, 69, and 85% and the dissection method resulted in values of 54, 64, and 78% for dietary dry matter, energy, and crude protein, respectively. No significant differences in the ADC values obtained between the two methods were observed. Gulf of Mexico sturgeon are protected in the Gulf Coast region of the United States and listed as a threatened species under the U.S. Endangered Species Act. The hand stripping method is recommended over dissection for Gulf of Mexico sturgeon since it is an accurate and reliable procedure that does not require killing the fish.
Disease Susceptibility of Hatchery Snake River Spring–Summer Chinook Salmon with Different Juvenile Migration Histories in the Columbia River
Authors: Arkoosh Mary R. , Kagley Anna N. , Anulacion Bernadita F. , Boylen Deborah A. , Sandford Benjamin P. , Loge Frank J. , Johnson Lyndal L. , Collier Tracy K.
Published: December 2006

Various methods have been developed to mitigate the effects of dams on juvenile Pacific salmon Oncorhynchus spp. migrating to the Pacific Ocean through the Columbia River basin. In this study, we examined the health of hatchery Snake River spring and summer Chinook salmon relative to two mitigating strategies: dam bypass and transportation (e.g., barging). The health of out-migrants was assessed in terms of the difference in the incidence of mortality among fish, categorically grouped into no-bypass, bypass, and transportation life histories, in response to challenge with the marine pathogen Listonella anguillarum during seawater holding. These three life histories were defined as follows: (1) fish that were not detected at any of the juvenile bypass systems above Bonneville Dam were classified as having a no-bypass life history; (2) fish that were detected at one or more juvenile bypass systems above Bonneville Dam were classified as having a bypass life history; and (3) fish that were barged were classified as having the transportation life history. Barged fish were found to be less susceptible to L. anguillarum than in-river fish—whether bypassed or not—which suggests that transportation may help mitigate the adverse health effects of the hydropower system of the Columbia River basin on Snake River spring–summer Chinook salmon. The findings of this study are not necessarily transferable to other out-migrant stocks in the Columbia River basin, given that only one evolutionarily significant unit, that is, Snake River spring–summer Chinook salmon, was used in this study.
Tumor Prevalence in Mummichogs from the Delaware Estuary Watershed
Authors: Pinkney Alfred E. , Harshbarger John C.
Published: December 2006

Mummichogs Fundulus heteroclitus were collected in 2002–2004 from six locations within the Delaware Estuary watershed and examined histopathologically. The objective was to compare the prevalence of skin and liver tumors in fish from locations with a range of sediment polynuclear aromatic hydrocarbons (PAHs) based on available data. Fish were collected from (1) three locations within the industrialized Christina River subwatershed (Hershey Run, Newport Marsh (upriver and downriver)); (2) one location in the Motiva Enterprises refinery discharge canal to the Delaware River; (3) one location in the St. Jones River; and (4) one location in Blackbird Creek. Adult mummichogs (≥70 mm; n = 21–30 fish per location) were seined and held for necropsy. No neoplastic skin lesions were diagnosed in any fish. No liver tumors were diagnosed in the St. Jones, Motiva, Newport Marsh upriver, or Newport Marsh downriver collections. One of 30 Blackbird Creek mummichogs had foci of hepatocellular alteration (a putative preneoplastic lesion) and one had hepatocellular carcinoma. There was a significant difference in hepatocellular carcinoma prevalence in Hershey Run mummichogs in 2002 (9 of 21 fish, or 43%) and in 2003 (3 of 29 fish, or 10%) compared with all other locations pooled (1 of 145 fish, or 0.7%). Hershey Run is contaminated with creosote from an adjacent Superfund site, where sediments were frequently reported to have total PAH concentrations greater than 100 mg of total PAH/kg and a maximum of 13,300 mg/kg. No other locations had reports of total PAHs higher than 11 mg/kg. In conclusion, liver neoplasia was associated with exposure to sediment containing high concentrations of PAHs derived from creosote. Studies that include tumor prevalence, biomarkers (e.g., DNA adducts and PAH metabolites in bile), and sediment and/or tissue chemistry are recommended to develop a weight of evidence for specific chemical classes.
Laboratory and Hatchery-Scale Evaluation of Sand Filters and Their Efficacy at Controlling Whirling Disease Infection
Authors: Arndt Ronney E. , Wagner Eric J. , Bobo Charles , John Thomas St
Published: December 2006

In two separate tests rapid sand filtration was evaluated as a means of removing the waterborne triactinomyxon actinospores (TAMs) of Myxobolus cerebralis, the causative agent of salmonid whirling disease, from contaminated water. In the first test we independently evaluated two sizes of sandblast sands: #4010 (effective size, (ES) = 250 μm) and #4060 (ES = 300 μm). The product number relates to the sand's size composition, and each had a different effective size. Effective size is defined by that size fraction at which only 10% of smaller particles remain. Rainbow trout Oncorhynchus mykiss were stocked into two separate systems with filters containing either one or the other size of sand, and TAMs were added to each system three times per week for all but the final 2 weeks of the 16-week test. A positive control (in which fish were exposed to the same number of TAMs without filtration) and a negative control (in which fish were not exposed to TAMs) were also included. Infection quantified by the pepsin−trypsin digest method showed no infection in fish from the two filter treatments. The average myxospore load among the positive controls was over 90,000 spores per fish head. In a final test, a nonreplicated comparison of filtration systems was conducted. The three systems used were as follows: (1) a drum filter in line with a UV filter, (2) a media filter followed by an ultraviolet (UV) unit, and (3) a sand filter containing three layers of sand. Water contaminated with TAMS was run through each filtration system, as well as through a positive control system, to raceways containing rainbow trout. Both of the dual-component commercial systems were 100% effective at preventing infection; the sand filter was 92% effective.
An Isolate of Piscirickettsia salmonis from White Seabass is Fully Virulent for Coho Salmon
Authors: House M. L. , Hedrick R. P. , Winton J. R. , Fryer J. L.
Published: December 2006

The virulence of the WSB-98 isolate of Piscirickettsia salmonis from white seabass Atractoscion nobilis was compared with that of the American Type Culture Collection type strain LF-89, which was originally isolated from coho salmon Oncorhynchus kisutch in Chile. In controlled laboratory challenges of juvenile coho salmon, the isolate from white seabass exhibited virulence that was equal to or greater than that of LF-89. The cumulative percent mortality (CPM) was similar between groups of coho salmon receiving an intraperitoneal injection of WSB-98 at 104.5 tissue culture infectious dose with 50% endpoint (TCID50)/fish (CPM = 98%) or an injection of LF-89 at 104.8 TCID50/fish (CPM = 95%). The mean day to death of 9.3 d for WSB-98 and 18.6 d for LF-89, however, differed significantly (P < 0.0001) between the two isolates. The virulence of an isolate of P. salmonis from white seabass for a salmonid species is consistent with the hypothesis that nonsalmonids can serve as natural marine hosts for the bacterium and potential sources for infection of salmonids.
Histopathological Examination of Wild American Eels Infected with Anguillicola crassus
Authors: Sokolowski Mark S. , Dove Alistair D. M.
Published: December 2006

We describe for the first time the histopathology caused in wild American eels Anguilla rostrata by the introduced nematode Anguillicola crassus. All of the American eels examined showed signs of previous or ongoing infections with A. crassus. Gross observations included opacity of the normally translucent swim bladder and dilation of blood vessels. The swim bladders of infected American eels showed focal, multifocal, and diffuse histological changes. Consistently observed pathologies included abnormal papillose appearance of the mucosa; hyperplasia of the lamina propria, muscularis mucosa, and submucosa; edema of the mucosa and muscularis mucosa; dilation of the blood vessels; and damage in the submucosa caused by migrating A. crassus L3 and L4 larvae. Less-common pathologies included fibrosis and lymphocytic aggregates around L3 and L4 larvae in the submucosa; destruction of the mucosa, which in some cases completely exposed the mucosal blood vessels; L2 larval penetration of the tissues of the swim bladder; bacterial infections in the submucosa and muscularis mucosa; and migration of an L4 larva through the rete mirabile.