bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of an epitope derived from the cancer testis antigen HOM-TES-14/SCP1 and presented by dendritic cells to circulating CD4+ T cells
Authors: Neumann Frank , Wagner Claudia , Preuss Klaus-Dieter , Kubuschok Boris , Schormann Claudia , Stevanovic Stefan , Pfreundschuh Michael 
Published: July 2005

AbstractBecause of their frequent expression in a wide spectrum of malignant tumors but not in normal tissue except testis, cancer testis antigens are promising targets. However, except for HOM-TES-14/SCP1, their expression in malignant lymphomas is rare. SCP1 (synaptonemal complex protein 1) has been shown to elicit antibody responses in the autologous host, but no T-cell responses against HOM-TES-14/SCP1 have been reported. Using the SYFPEITHI algorithm, we selected peptides with a high binding affinity to major histocompatibility complex class 2 (MHC 2) molecules. The pentadecamer epitope p635-649 induced specific CD4+ T-cell responses that were shown to be restricted by HLA-DRB1*1401. The responses could be blocked by preincubation of T cells with anti-CD4 and antigen-presenting cells with anti–HLA-DR, respectively, proving the HLA-DR–restricted presentation of p635-649 and a CD4+ T-cell–mediated effector response. Responding CD4+ cells did not secrete interleukin-5 (IL-5), indicating that they belong to the TH1 subtype. The natural processing and presentation of p635-649 were demonstrated by pulsing autologous and allogeneic dendritic cells with a protein fragment covering p635-649. Thus, p635-649 is the first HOM-TES-14/SCP1–derived epitope to fulfill all prerequisites for use as a peptide vaccine in patients with HOM-TES-14/SCP1–expressing tumors, which is the case in two thirds of peripheral T-cell lymphomas.
Relationship of patient survival and chromosome anomalies detected in metaphase and/or interphase cells at diagnosis of myeloma
Authors: Dewald Gordon W. , Therneau Terry , Larson Dirk , Lee You Kyoung , Fink Stephanie , Smoley Stephanie , Paternoster Sarah , Adeyinka Adewale , Ketterling Rhett , Van Dyke Daniel L. , Fonseca Rafael , Kyle Robert 
Published: July 2005

AbstractThe clinical efficacy of evaluating genetic anomalies in metaphase cells versus interphase nuclei for multiple myeloma (MM) is poorly understood. Therefore, survival for 154 patients with newly diagnosed untreated MM was compared with results from analysis of metaphase and interphase cells. Metaphases were studied by conventional cytogenetics and fluorescent-labeled DNA probes (fluorescence in situ hybridization [FISH]), whereas inter-phase nuclei were evaluated only by FISH. All FISH studies were done using DNA probes to detect t(4;14)(p16;q32), t(11;14)(q13;q32), t(14;16)(q32;q23), del(17) (p13.1), and chromosome 13 anomalies. Metaphases were abnormal by cytogenetics and/or metaphase FISH in 61 (40%) patients. Abnormal interphase nuclei were observed in 133 (86%) patients, including each patient with abnormal metaphases. FISH was a necessary adjunct to cytogenetics to detect t(4;14) and t(14;16) in metaphase cells. Patient survival was especially poor for patients with greater than 50% abnormal interphase nuclei, although this result was more likely due to level of plasma cells than specific chromosome anomalies. For metaphase data, patients with t(4;14), t(14;16), del(17) (p13.1), and/or chromosome 13 anomalies (primarily monosomy 13) had poor survival. A different outcome was observed for interphase data as patients with t(4;14) or t(14;16) had poor survival, whereas patients with chromosome 13 anomalies had intermediate survival: interphase FISH did not substitute for metaphase analysis.
Long-Term Survival Results of a Randomized Trial Comparing Gemcitabine Plus Cisplatin, With Methotrexate, Vinblastine, Doxorubicin, Plus Cisplatin in Patients With Bladder Cancer
Authors: von der Maase Hans , Sengelov Lisa , Roberts James T. , Ricci Sergio , Dogliotti Luigi , Oliver T. , Moore Malcolm J. , Zimmermann Annamaria , Arning Michael 
Published: July 2005

Purpose To compare long-term survival in patients with locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium treated with gemcitabine/cisplatin (GC) or methotrexate/vinblastine/doxorubicin/cisplatin (MVAC). Patients and Methods Efficacy data from a large randomized phase III study of GC versus MVAC were updated. Time-to-event analyses were performed on the observed distributions of overall and progression-free survival. Results A total of 405 patients were randomly assigned: 203 to the GC arm and 202 to the MVAC arm. At the time of analysis, 347 patients had died (GC arm, 176 patients; MVAC arm, 171 patients). Overall survival was similar in both arms (hazard ratio [HR], 1.09; 95% CI, 0.88 to 1.34; P = .66) with a median survival of 14.0 months for GC and 15.2 months for MVAC. The 5-year overall survival rates were 13.0% and 15.3%, respectively (P = .53). The median progression-free survival was 7.7 months for GC and 8.3 months for MVAC, with an HR of 1.09. The 5-year progression-free survival rates were 9.8% and 11.3%, respectively (P = .63). Significant prognostic factors favoring overall survival included performance score (> 70), TNM staging (M0 v M1), low/normal alkaline phosphatase level, number of disease sites (≤ three), and the absence of visceral metastases. By adjusting for these prognostic factors, the HR was 0.99 for overall survival and 1.01 for progression-free survival. The 5-year overall survival rates for patients with and without visceral metastases were 6.8% and 20.9%, respectively. Conclusion Long-term overall and progression-free survival after treatment with GC or MVAC are similar. These results strengthen the role of GC as a standard of care in patients with locally advanced or metastatic TCC.
Tumor-Specific Expression of Vascular Endothelial Growth Factor Receptor 2 but Not Vascular Endothelial Growth Factor or Human Epidermal Growth Factor Receptor 2 Is Associated With Impaired Response to Adjuvant Tamoxifen in Premenopausal Breast Cancer
Authors: Rydén Lisa , Jirström Karin , Bendahl Pär-Ola , Fernö Mårten , Nordenskjöld Bo , Stål Olle , Thorstenson Sten , Jönsson Per-Ebbe , Landberg Göran 
Published: July 2005

Purpose Vascular endothelial growth factor A (VEGF-A) and vascular endothelial growth factor receptor 2 (VEGFR2) are often coexpressed in breast cancer, and potentially affect cellular pathways and key proteins such as the estrogen receptor (ER) targeted by endocrine treatment. We therefore explored the association between adjuvant tamoxifen treatment in breast cancer and expression of VEGF-A and VEGFR2, as well as human epidermal growth factor receptor 2 (HER2), which represents a candidate gene product involved in tamoxifen resistance. Patients and Methods Immunohistochemical expression of tumor-specific VEGF-A, VEGFR2, and HER2 was evaluated in tumor specimens from premenopausal breast cancer patients randomly assigned to 2 years of tamoxifen or no treatment (n = 564), with 14 years of follow-up. Hormone receptor status was determined in 96% of the tumors. Results VEGF-A, VEGFR2, and HER2 were assessable in 460, 472, and 428 of the tumors, respectively. In patients with ER–positive and VEGFR2-low tumors, adjuvant tamoxifen significantly increased recurrence-free survival (RFS; [HR] hazard ratio for RFS, 0.53; P = .001). In contrast, tamoxifen treatment had no effect in patients with VEGFR2-high tumors (HR for RFS, 2.44; P = .2). When multivariate interaction analyses were used, this difference in treatment efficacy relative to VEGFR2 expression status was statistically significant for both ER-positive (P = .04) plus ER-positive and progesterone receptor–positive tumors. We found no significant difference in tamoxifen treatment effects in relation to VEGF-A or HER2 status. Conclusion Tumor-specific expression of VEGFR2 was associated with an impaired tamoxifen effect in hormone receptor–positive premenopausal breast cancer. Tamoxifen in combination with VEGFR2 inhibitors might be a novel treatment approach for VEGFR2-expressing breast cancer, and such a treatment might restore the tamoxifen response.
Effects of Excess Weight on Cancer Incidences Depending on Cancer Sites and Histologic Findings Among Men: Korea National Health Insurance Corporation Study
Authors: Oh Sang Woo , Yoon Yeong Sook , Shin Soon-Ae 
Published: July 2005

Purpose The effects of excess weight on the development of cancers are controversial, and little is known for populations outside the United States and Europe. We conducted this study to assess the effects of excess weight with a large cohort of Koreans. Methods We assessed the relationship between body mass index (BMI) and various cancers in a 10-year follow-up cohort of 781,283 Korean men who were free of prior cancer at baseline. Weight and height were measured, and questionnaires related to health behaviors and medical history were completed. Data on newly developed cancers were obtained from two organizations in Korea. A proportional hazards model was used to examine the relationship between BMI and cancer. Results Adenocarcinoma in the colon and rectosigmoid, hepatocellular carcinoma, cholangiocarcinoma, adenocarcinoma in the prostate, renal cell carcinoma, papillary carcinoma in the thyroid, small-cell carcinoma in the lung, non-Hodgkin's lymphoma, and melanoma had positive dose-dependent relationships with BMI (all P < .05). Although no linear trend was found (P = .267), obese men who never smoked with a BMI of ≥ 30 kg/m2 had an increased risk of developing gastric adenocarcinoma (relative risk = 1.73). Other cancers, such as leukemia, multiple myeloma, and gallbladder and pancreatic cancer, did not show significant associations. Conclusion These findings show that, even in Koreans, obesity clearly increases the risk of many types of cancers and the strength of the associations varies with the organ and histologic type. Because these obesity-related cancers are reported to be rapidly increasing in Korea and many other Asian countries, controlling obesity epidemics could be an effective tool for preventing these cancers in these areas.
Enrolling Older Persons in Cancer Trials: The Effect of Sociodemographic, Protocol, and Recruitment Center Characteristics
Authors: Gross Cary P. , Herrin Jeph , Wong Natalie , Krumholz Harlan M. 
Published: July 2005

Purpose To determine the effect of patient, protocol, geographic, and institutional factors on enrollment of older persons onto cancer trials. Methods We conducted a cross-sectional analysis of patients enrolled onto National Cancer Institute–sponsored lung, breast, colorectal, and prostate cancer trials during 1996 to 2002. We used a cross-classified logistic multilevel model to examine the associations between patient, hospital, county, and protocol characteristics, and the likelihood of participants being elderly (≥ 65 years old). Results The final study sample consisted of 36,167 patients enrolled onto 33 trials. After accounting for cancer type, only 6% of the variation in elderly enrollment onto cancer trials was at the protocol level. In contrast, more than 55% of the variation in elderly enrollment was attributable to patient level variation. In multivariate analysis, nonwhite patients were significantly less likely to be elderly than whites (odds ratio [OR] for blacks, 0.51; 95% CI, 0.44 to 0.58; and OR for Hispanics, 0.49; 95% CI, 0.40 to 0.59 v whites). Participants living less than 7 miles from their recruitment center were significantly more likely to be elderly (OR, 1.31; 95% CI, 1.24 to 1.38). Among the 910 recruitment centers, the median adjusted proportion of patients who were elderly was 24.9% (interquartile range, 24.0% to 26.9%). There were a significantly higher number of outlier centers (≤ 20.8% or ≥ 29.3% elderly) than would be expected by a normal distribution (68 observed v six expected; P < .0001). Conclusion Race and proximity to trial enrollment centers were significantly related to age of trial participants after adjusting for protocol factors. Additional work should explore why some recruitment centers were outliers regarding enrollment of older persons.
Tiotropium: A Bronchodilator for Chronic Obstructive Pulmonary Disease
Authors: Somand Heather , Remington Tami L 
Published: July 2005

OBJECTIVE: To review the scientific literature evaluating the efficacy and tolerability of tiotropium bromide, a new bronchodilator indicated for treatment of chronic obstructive pulmonary disease (COPD). DATA SOURCES: Articles were identified through searches of MEDLINE (1966–January 2005) using the key words tiotropium, BA 679 BR, chronic obstructive pulmonary disease, and anticholinergic agents. Additional citations were identified from bibliographies of publications cited. STUDY SELECTION AND DATA EXTRACTION: Experimental and observational studies of tiotropium bromide were selected. Trials of the efficacy of the drug in humans were the focus of the review. DATA SYNTHESIS: Tiotropium bromide is an effective bronchodilator for patients with COPD. It produces clinically important improvements in lung function, symptoms of dyspnea, quality of life, and exacerbation rates compared with placebo. In comparative studies, tiotropium does not appear to be more efficacious than salmeterol or ipratropium. CONCLUSIONS: Tiotropium is an effective inhaled anticholinergic agent that is recommended among preferred long-acting bronchodilators for the chronic management of moderate to very severe COPD. Although similar to ipratropium in efficacy and tolerability, it has the advantage of once-daily dosing.
Supratherapeutic Response to Ezetimibe Administered with Cyclosporine
Authors: Koshman Sheri L , Lalonde Lucille D , Burton Ilene , Tymchak Wayne J , Pearson Glen J 
Published: July 2005

OBJECTIVE: To report the case of a patient who underwent orthotopic heart transplant (OHT) and demonstrated a supratherapeutic response to ezetimibe when administered with cyclosporine. CASE SUMMARY: Ezetimibe 10 mg/day was added to the lipid-lowering regimen (atorvastatin 40 mg/day) of a 64-year-old male patient after OHT to achieve a target low-density lipoprotein cholesterol (LDL-C) level ≤97 mg/dL, as recommended by national guidelines. After 2 months of ezetimibe, the patient's LDL-C level had decreased by 60% to 51 mg/dL. Subsequently, the dose of ezetimibe was reduced to 5 mg/day and, after another 2 months, a repeat lipid panel revealed LDL-C 57 mg/dL. DISCUSSION: Hyperlipidemia is a common problem among heart transplant recipients. Combination therapy using a statin plus ezetimibe appears to be an attractive option to achieve target lipid levels in this population. However, the manufacturer warns that ezetimibe should be administered cautiously in patients concomitantly receiving cyclosporine. Unpublished data suggest a pharmacokinetic interaction between ezetimibe and cyclosporine that results in a significant 2.3- to 12-fold increase in exposure to total ezetimibe. An objective causality assessment in this case revealed that this supratherapeutic LDL-C reduction was probably related to coadministration of ezetimibe and cyclosporine. A potential mechanism to explain this interaction might be an alteration in glucuronidation induced by cyclosporine. CONCLUSIONS: When ezetimibe is prescribed for patients concomitantly receiving cyclosporine, it should be initiated at a lower than recommended dose (≤5 mg/day) and titrated upward. Careful and consistent monitoring of patients on this combination is also advised.
Endocannabinoid Signaling in Rat Somatosensory Cortex: Laminar Differences and Involvement of Specific Interneuron Types
Authors: Bodor Ágnes L. , Katona István , Nyíri Gábor , Mackie Ken , Ledent Catherine , Hájos Norbert , Freund Tamás F. 
Published: July 2005

Endocannabinoid-mediated retrograde signaling exerts powerful control over synaptic transmission in many brain areas. However, in the neocortex, the precise laminar, cellular, and subcellular localization of the type 1 cannabinoid receptor (CB1) as well as its function has been elusive. Here we combined multiple immunolabeling with whole-cell recordings to investigate the morpho-functional characteristics of cannabinoid signaling in rat somatosensory cortex.Immunostaining for CB1revealed axonal and somatic labeling with striking layer specificity: a high density of CB1-positive fibers was seen in layers II-III, in layer VI, and in upper layer V, whereas other layers had sparse (layer IV) or hardly any (layer I) staining. Membrane staining for CB1was only found in axon terminals, all of which contained GABA and formed symmetric synapses. Double immunostaining also revealed that CB1-positive cells formed two neurochemically distinct subpopulations: two-thirds were cholecystokinin positive and one-third expressed calbindin, each subserving specific inhibitory functions in cortical networks.In addition, cannabinoid sensitivity of GABAergic input showed striking layer specificity, as revealed by both electrophysiological and anatomical experiments. We found a unique population of large pyramidal neurons in layer VB that received much less perisomatic innervation from CB1-expressing GABAergic axon terminals and, accordingly, showed no depolarization-induced suppression of inhibition, unlike pyramidal cells in layer II, and a population of small pyramidal cells in layer V. This suggests that inhibitory control of pyramidal cells involved in intracortical or corticostriatal processing is fine-tuned by activity-dependent endocannabinoid signaling, whereas inhibition of pyramidal cells relaying cortical information to lower subcortical effector centers often lacks this plasticity.
Effects of Multiple Low-Head Dams on Fish, Macroinvertebrates, Habitat, and Water Quality in the Fox River, Illinois
Authors: Santucci Victor J. , Gephard Stephen R. , Pescitelli Stephen M. 
Published: July 2005

Abstract
We examined the effects of low-head dams on aquatic biota, habitat, and water quality in a 171-km reach of a midwestern warmwater river that was fragmented by 15 dams into a series of free-flowing and impounded habitats. Dams impounded 55% of the river's surface area within the study reach and influenced distributions of 30 species of fish by restricting upstream movements. Values for the Illinois index of biotic integrity (IBI) were higher in free-flowing areas (mean IBI = 46 out of a possible 60 at below-dam and midsegment free-flowing locations) than impounded areas (mean IBI &lt; 31 for above-dam and midsegment impounded locations). Likewise, scores from a macroinvertebrate condition index (MCI) were higher at stations in free-flowing reaches (mean MCI &gt; 415 out of a possible 700) than in nearshore areas of impounded reaches (mean MCI &lt; 210). Ponar dredge samples taken only from open-water impounded areas showed an offshore invertebrate community that consisted almost entirely of tolerant oligochaetes and chironomid larvae. Qualitative habitat evaluation index (QHEI) scores indicated good-quality habitat in free-flowing areas (mean QHEI &gt; 70 out of a possible 100) and severely degraded habitat at impounded sites (mean QHEI &lt; 45). In impounded reaches, dissolved oxygen and pH showed wide daily fluctuations (2.5–18.0 mg/L and 7.0–9.4 units) and often failed to meet Illinois water quality standards. In free-flowing portions of river, fluctuations in these parameters were less extreme and water quality standards typically were met. We found little evidence of cumulative effects of dams; however, our data suggest that low-head dams adversely affect warmwater stream fish and macroinvertebrate communities by degrading habitat and water quality and fragmenting the river landscape. These results should aid river managers and stakeholders in determining appropriate restoration practices (i.e., dam removal versus fish passage structures) for warmwater rivers and streams that contain low-head dams.
Effects of Waterbody Type and Management Actions on Bluegill Growth Rates
Authors: Porath Mark T. , Hurley Keith L. 
Published: July 2005

Abstract
Managers have conducted a number of activities to improve the growth rates of bluegill Lepomis macrochirus. However, attempts to compare the effectiveness of management actions often ignore basic differences in growth related to the type of water body in which populations reside. Bluegill age and growth data were collected from four different water body types in Nebraska between 1994 and 2001. Model analysis detected significant differences in the previous year's growth increments by water body type. When compared with other water body types, growth increments were greater in Sandhill lakes for age-2 and age-3 bluegills and mean length at capture was greater for age −6 and −7 bluegills. Several significant age × management activity interactions were detected within water body types. The application of supplemental feed and the absence of gizzard shad Dorosoma cepedianum increased bluegill growth increments in borrow and sand– gravel mining pits, while in flood control reservoirs, the presence of gizzard shad negatively impacted bluegill growth increments. Harvest regulation impacts were mixed in both of these water body types. Managers should recognize basic differences in growth patterns between water body types when determining which management actions should be implemented or when evaluating their success.
Spatial Habitat Dynamics Affecting Bluegill Abundance in Minnesota Bass–Panfish Lakes
Authors: Cross Timothy K. , McInerny Michael C. 
Published: July 2005

Abstract
A holistic approach to fisheries management requires an understanding of factors related to fish abundance over several spatial scales. We used geographic information systems to extract data describing habitat influences across three different spatial scales for a selected ecological class of Minnesota bass–panfish lakes (n = 113). These data were then analyzed by regression tree analysis to describe relationships between habitat and trap-net catch per effort (CPE) of bluegills Lepomis macrochirus. At the landscape scale of analysis, bluegill CPE increased among lakes with decreases in hydrologic connectivity (landscape position) and increases in geographic northing and easting gradients that corresponded to regional differences in geomorphology and edaphic characteristics. At the watershed–lake scale of analysis, a regression tree model with variables describing watershed area, cultivated land cover, forested land cover, and lake area explained 55% of the variation in bluegill CPE among lakes. At the site scale, a regression tree model with variables describing submerged plant cover and detritus substrates explained 57% of the variation in bluegill CPE among 72 sites spread among six lakes. However, much of the site-scale habitat influences on bluegill abundance was explained by broader landscape- and watershed-scale factors that influence the plant and bottom substrates in lakes. This study reinforces the importance of identifying habitat limitations and the influences of human activities at the landscape and watershed scales in addition to more commonly addressed site-scale habitat deficiencies.