bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase I/II Study of Infusional Vinblastine with the P-Glycoprotein Antagonist Valspodar (PSC 833) in Renal Cell Carcinoma
Authors: Bates Susan E. , Bakke Susan , Kang Min , Robey Robert W. , Zhai Suoping , Thambi Paul , Chen Clara C. , Patil Sheela , Smith Tom , Steinberg Seth M. , Merino Maria , Goldspiel Barry , Meadows Beverly , Stein Wilfred D. , Choyke Peter , Balis Frank , Figg William D. , Fojo Tito 
Published: September 2005

Abstract
Purpose: P-glycoprotein (Pgp) inhibitors have been under clinical evaluation for drug resistance reversal for over a decade. Valspodar (PSC 833) inhibits Pgp-mediated efflux but delays drug clearance, requiring reduction of anticancer drug dosage. We designed an infusional schedule for valspodar and vinblastine to mimic infusional vinblastine alone. The study was designed to determine the maximally tolerated dose of vinblastine, while attempting to understand the pharmacokinetic interactions between vinblastine and valspodar and to determine the response rate in patients with metastatic renal cell cancer.
Patients and Methods: Thirty-nine patients received continuous infusion valspodar and vinblastine. Vinblastine was administered for 3 days to compensate for the expected delay in clearance and the required dose reduction. Valspodar was administered initially at a dose of 10 mg/kg/d; the dose of vinblastine varied.
Results: The maximum-tolerated dose of vinblastine was 1.3 mg/m2/d. As suggested previously, serum valspodar concentrations exceeded those needed for Pgp inhibition. Consequently, the dose of valspodar was reduced to 5 mg/kg, allowing a vinblastine dose of 2.1 mg/m2/d to be administered. Pharmacodynamic studies demonstrated continued inhibition of Pgp at lower valspodar doses by functional assay in Pgp-expressing CD56+ cells and by 99mTc-sestamibi imaging. A 15-fold range in cytochrome P450 activity was observed, as measured by midazolam clearance. No major responses were observed.
Conclusions: These results suggest that the pharmacokinetic impact of cytochrome P450 inhibition by valspodar can be reduced although not eliminated, while preserving Pgp inhibition, thus separating the pharmacokinetic and pharmacodynamic activities of valspodar.
Pretreatment with Dexamethasone Increases Antitumor Activity of Carboplatin and Gemcitabine in Mice Bearing Human Cancer Xenografts
Authors: Wang Hui , Li Mao , Rinehart John J. , Zhang Ruiwen 
Published: September 2005

AbstractPurpose: The present study was undertaken to determine the effects of dexamethasone (DEX) pretreatment on antitumor activity and pharmacokinetics of the cancer chemotherapeutic agents carboplatin and gemcitabine.Experimental Design: Antitumor activities of carboplatin and gemcitabine with or without DEX pretreatment were determined in six murine-human cancer xenograft models, including cancers of colon (LS174T), lung (A549 and H1299), and breast (MCF-7 and MDA-MB-468) and glioma (U87-MG). Effects of DEX on plasma and tissue pharmacokinetics of carboplatin and gemcitabine were also determined by using the LS174T, A549, and H1299 models.Results: Although DEX alone showed minimal antitumor activity, DEX pretreatment significantly increased the efficacy of carboplatin, gemcitabine, or a combination of both drugs by 2–4-fold in all xenograft models tested. Without DEX treatment, the tumor exposure to carboplatin, measured by the area under the curve, was markedly lower than normal tissues. However, DEX pretreatment significantly increased tumor carboplatin levels, including 200% increase in area under the curve, 100% increase in maximum concentration, and 160% decrease in clearance. DEX pretreatment similarly increased gemcitabine uptake in tumors.Conclusions: To our knowledge, this is the first report that DEX significantly enhances the antitumor activity of carboplatin and gemcitabine and increases their accumulation in tumors. These results provide a basis for further evaluation of DEX as a chemosensitizer in patients.
Frequency of Chromosomal Aberrations Involving
MALT1
in Mucosa-Associated Lymphoid Tissue Lymphoma in Patients with Sjögren’s Syndrome
Authors: Streubel Berthold , Huber Daniela , Wöhrer Stefan , Chott Andreas , Raderer Markus 
Published: September 2005

Abstract
Purpose: Mucosa-associated lymphoid tissue (MALT) lymphoma develops in the context of longstanding antigenic stimulation such as infection with Helicobacter pylori or autoimmune disease, including Sjögren’s syndrome (SS). Recently, two chromosomal aberrations involving the MALT1 gene, i.e., t(11;18)(q21;q21) and t(14;18)(q32;q21) have been reported as genetic events specific for MALT lymphoma. In view of the association between SS and the development of MALT lymphoma, we have analyzed the frequency of t(11;18)(q21;q21) and t(14;18)(q32;q21) in patients with MALT lymphomas arising in the background of SS.
Experimental Design: A retrospective analysis of patients diagnosed with MALT lymphoma and SS was performed. The t(11;18)(q21;q21) was analyzed using reverse transcriptase-PCR, whereas t(14;18)(q32;q21) was assessed by two-color interphase fluorescence in situ hybridization.
Results: Twenty-six patients (20 female and 6 male) with MALT lymphoma and SS could be identified. The lymphoma was located in the parotid (n = 14), orbit (n = 2), and submandibular gland (n = 1), whereas 9 patients had gastric MALT lymphoma. Seven of 26 patients (27%) harbored t(11;18)(q21;q21). Interestingly, only 1 of 17 patients (6%) with extragastrointestinal lymphoma was positive, as opposed to 6 of 9 patients (67%) with gastric MALT lymphoma. Four of 26 patients were positive for t(14;18)(q32;q21): 3 of 17 extragastrointestinal (18%) and 1 of 9 gastric lymphomas (11%).
Conclusions: The overall frequency of MALT1 rearrangement appears to be low in patients with extragastrointestinal MALT lymphoma associated with SS. By contrast, MALT1 rearrangement was demonstrated in 7 of 9 patients (78%) with gastric MALT lymphoma and SS. This finding may explain at least in part why gastric MALT lymphomas in patients with SS are refractory to H. pylori eradication therapy.
Therapeutic Synergy Between Irinotecan and 5-Fluorouracil against Human Tumor Xenografts
Authors: Azrak Rami G. , Cao Shousong , Slocum Harry K. , Tóth Károly , Durrani Farukh A. , Yin Ming-biao , Pendyala Lakshmi , Zhang Wanghai , McLeod Howard L. , Rustum Youcef M. 
Published: September 2005

Abstract
Purpose: Although the combination of irinotecan and 5-Fluorouracil is clinically active, it is associated with significant toxicity and resistance. Studies were carried out to define the optimal dosage, sequence, and timing for the combination in mice bearing xenografted human tumors.
Experimental Design: The maximum tolerated dose of irinotecan and 5-Fluorouracil in combination was determined in nude mice. Therapeutic efficacy against established human colon carcinoma xenografts, HCT-8 and HT-29, and human head and neck squamous cell carcinoma xenografts, FaDu and A253, was determined using the rugs individually, simultaneously, and in sequence with various intervals in between. Treatments were i.v. weekly × 4. Immunohistochemical and reverse transcription-PCR measurements of relevant drug-metabolizing enzymes, apoptosis-related proteins, cell cycle distribution, cyclin A, and S phase fraction expression were carried out and compared with the therapeutic outcome.
Results: The maximum tolerated dose of irinotecan resulted in cure rates of 30% or less in all xenografts. No cures were achieved with FUra alone. Concurrent administration of irinotecan and FUra, or of FUra 24 h before irinotecan, resulted in cure rates of &lt;20%, except for FaDu (60%). Administration of irinotecan 24 h before FUra resulted in the highest cure rates, 80% in HCT-8, 0% in HT-29, 100% in FaDu, and 10% in A253.
Conclusions: The optimal therapeutic synergy was achieved when irinotecan was administered 24 h before 5-Flurouracil. Sensitivity to this combination was associated with poor differentiation status, higher cyclin A index, recruitment of cells into S phase, and induction of Bax expression and apoptosis.
Altered Expression of FAS System Is Related to Adverse Clinical Outcome in Stage I-II Breast Cancer Patients Treated with Adjuvant Anthracycline-Based Chemotherapy
Authors: Botti Claudio , Buglioni Simonetta , Benevolo Maria , Giannarelli Diana , Papaldo Paola , Cognetti Francesco , Vici Patrizia , Di Filippo Franco , Del Nonno Franca , Venanzi Franco Maria , Natali Pier Giorgio , Mottolese Marcella 
Published: September 2005

Abstract
Purpose: To determine the prognostic value of Fas receptor and Fas ligand (FasL) as apoptosis-related biomarkers in the context of chemoresponsiveness in breast cancer (BC) patients submitted to anthracycline-based adjuvant therapy.
Experimental Design: Fas and FasL were investigated by immunohistochemistry in surgical samples collected from 167 stage I-IIa-b BC patients enrolled in a prospective clinical trial using epirubicin plus cyclophosphamide in the adjuvant setting.
Results: Fas and FasL were significantly associated with tumor stage (P &lt; 0.0001). Multivariate analysis indicated that stage, loss of Fas (relative risk, 8.5 and 9.12; P &lt; 0.0001) and FasL up-regulation (relative risk, 2.38 and 2.88; P = 0.01) were independent prognostic variables influencing both disease-free survival (DFS) and overall survival (OS). A Cox analysis using a four-category Fas/FasL phenotype (+/−, +/+, −/+, −/−) as a stratification factor evidenced a highly positive association between Fas/FasL phenotype and the cumulative hazard of relapse and death in the entire series of patients. We also estimated the DFS and OS for different combinations of the pathological-tumor-node-metastasis (TNM) stage and Fas/FasL by using the K sample log-rank exact test demonstrating that significantly shorter DFS and OS were observed in Fas-negative and FasL-positive patients in both stage I-IIa and IIb.
Conclusions: Data presented herein demonstrated that, according to a number of in vitro studies, the prognosis for BC patients receiving adjuvant anthracycline-based chemotherapy strongly depends on the Fas/FasL status. Therefore, a concomitant altered pattern of Fas/FasL expression seems to configure an aggressive tumor phenotype linked to disease progression.
Pretreatment with Rituximab Does Not Inhibit the Human Immune Response against the Immunogenic Protein LMB-1
Authors: Hassan Raffit , Williams-Gould Juanita , Watson Thelma , Pai-Scherf Lee , Pastan Ira 
Published: September 2005

Abstract
Purpose: Rituximab, a humanized monoclonal antibody directed to the CD20 antigen present on B lymphocytes, could potentially abrogate the humoral immune response to murine monoclonal antibodies or immunotoxins by depleting antibody-producing B cells.
Experimental Design: A Phase II study of LMB-1, an immunotoxin targeting the Lewis Y tumor antigen, in combination with rituximab was conducted to test the hypothesis that rituximab could abolish or diminish the development of human antibodies to LMB-1. Five patients were treated in this study and received 375 mg/m2 rituximab on days 1 and 7 followed by 45 μg/kg/day LMB-1 on days 10, 12, and 14. The development of human antibodies against LMB-1 was detected using a serum neutralization and ELISA.
Results: All five of the patients had a total suppression of circulating CD20/CD19 B-cell population before the administration of the first dose of the immunotoxin. Before rituximab treatment, the mean percentage of CD20/CD19-positive B cells in the five treated patients was 19.8% (range, 4.5–29.8%) of the total peripheral lymphocytes. After two doses of rituximab, CD20/CD19-positive B lymphocytes constituted ≤0.1% of the total peripheral lymphocytes. Despite absent circulating antibody-producing B cells, before and during LMB-1 treatment, all of the patients developed neutralizing antibodies to the immunotoxin by day 21 of drug administration, which prevented retreatment.
Conclusions: Even though rituximab caused complete depletion of circulating CD20/CD19-positive B cells, it had no effect in suppressing the human antibody response to LMB-1 and may be of limited utility in suppressing human antibody responses to other immunogenic proteins.
Native and Nonnative Speakers' Processing of a Miniature Version of Japanese as Revealed by ERPs
Authors: Mueller Jutta L. , Hahne Anja , Fujii Yugo , Friederici Angela D. 
Published: September 2005

Abstract
Several event-related potential (ERP) studies in second language (L2) processing have revealed a differential vulnerability of syntax-related ERP effects in contrast to purely semantic ERP effects. However, it is still debated to what extent a potential critical period for L2 acquisition, as opposed to the attained proficiency level in the L2, contributes to the pattern of results reported in previous ERP studies. We studied L2 processing within the model of a miniature version of a natural language, namely Japanese, specifically constructed to assure high proficiency of the learners. In an auditory ERP experiment, we investigated sentence processing of the “Mini-Japanese” in Japanese native speakers and German volunteers before and after training. By making use of three different types of violation, namely, word category, case, and classifier violations, native and nonnative ERP patterns were compared. The three types of violation elicited three characteristic ERP patterns in Japanese native speakers. The word category violation elicited an anteriorly focused, broadly distributed early negativity followed by a P600, whereas the case violation evoked a P600 which was preceded by an N400. The classifier violation led solely to a late left distributed negativity with an anterior focus. Although the P600 was similar for Japanese natives and learners, the N400 and the anterior negativities were not present in the learner group. The differences across groups suggest deviant neural processes in on-line syntactic and thematic processing in the L2 learners despite high behavioral skills.
Investigating the Neural Basis of the Auditory Continuity Illusion
Authors: Husain Fatima T. , Lozito Thomas P. , Ulloa Antonio , Horwitz Barry 
Published: September 2005

Abstract
In this study, we investigated one type of auditory perceptual grouping phenomena—the auditory continuity illusion (also called temporal induction). We employed a previously developed, neurobiologically realistic, large-scale neural network model of the auditory processing pathway in the cortex, ranging from the primary auditory cortex to the prefrontal cortex, and simulated temporal induction without changing any model parameters. The model processes tonal contour stimuli, composed of combinations of upward and downward FM sweeps and tones, in a delayed match-to-sample task. The local electrical activities of the neuronal units of the model simulated accurately the experimentally observed electrophysiological data, where available, and the model's simulated BOLD-fMRI data were quantitatively matched with experimental fMRI data. In the present simulations, intact stimuli were matched with fragmented versions (i.e., with inserted silent gaps). The ability of the model to match fragmented stimuli declined as the duration of the gaps increased. However, when simulated broadband noise was inserted into these gaps, the matching response was restored, indicating that a continuous stimulus was perceived. The electrical activities of the neuronal units of the model agreed with electrophysiological data, and the behavioral activity of the model matched human behavioral data. In the model, the predominant mechanism implementing temporal induction is the divergence of the feedforward connections along the auditory processing pathway in the temporal cortex. These simulation results not only attest to the robustness of the model, but further predict the primary role of the anatomical connectivity of the auditory processing areas in mediating the continuity illusion.
Holistic Processing of Faces: Learning Effects with Mooney Faces
Authors: Latinus Marianne , Taylor Margot J. 
Published: September 2005

Abstract
The specialness of faces is seen in the face inversion effect, which disrupts the configural, but not the analytic, processing of faces. Mooney faces, which are processed holistically, allowed us to determine the contribution of holistic processing to the face inversion effect. As inverted Mooney faces are difficult to recognize as faces, we also included an intermediary training period for Mooney face recognition for half of the subjects. Early face-sensitive ERPs (N170 and P1) and P2 were measured.
Behavioral data showed an increase in correct responses to inverted and upright Mooney faces after the learning phase for the experimental group. No effects were seen on P1. N170 latency did not vary with stimulus type before the intermediary phase, however, N170 amplitude was consistently larger for upright than inverted Mooney faces. After the intermediary exercise, N170 was delayed for inverted compared to upright Mooney faces. In contrast, for both groups of subjects P2 amplitude was larger for nonface stimuli, and P2 amplitude decreased after the intermediate task only for the subjects trained to recognize Mooney faces.
As the usual inversion effect seen with photographic faces (delayed and larger N170) was not seen with Mooney faces, these data suggest that this effect on N170 is due to the recruitment of analytic processing. P2 reflected learning and a deeper processing of the stimuli that were not identifiable as faces.
Female dispersal, inbreeding avoidance and mate choice in Thomas langurs (Presbytis thomasi)
Authors: van Hooff Jan A.R.A.M , Willems Erik P. , Wich Serge A. , Sterck Elizabeth H.M. 
Published: September 2005

AbstractFemale social dispersal in primates differs from the general mammalian pattern of locational dispersal. Both nulliparous and parous females may disperse to another group. Several hypotheses can explain female social dispersal: reduction of predation risk, inbreeding avoidance, and offspring protection through mate choice. We tested these hypotheses with an extended data set of Thomas langurs (Presbytis thomasi) and investigated parameters of male behaviour that females may use in their dispersal decisions. Data were collected over a 12.5-year period from a wild population in Sumatra, Indonesia, allowing for some critical tests of the hypotheses. Females dispersed to a group smaller than their original one, thereby refuting the predation risk hypothesis. Maturing nulliparous females only dispersed when their father was resident. Therefore, dispersal by nulliparous females was best explained through inbreeding avoidance. Parous females transferred to young, adult males. These males provided better protection to offspring against predation and infanticide than the old, late tenure males. Therefore, females transfer to better protector males. The male behavioural cues that females use to assess male quality were unclear. Females, however, may use proxies of male age, such as group composition and acoustical characteristics of loud calls, as indicators of male quality. The results suggest that female mate choice is an important function of social dispersal by parous females. Its importance in locational dispersal remains to be investigated.
Federico García Lorca and Salāh 'Abd al-Sabūr as Composers of Modern Ballads: A Comparative Study
Authors: Azouqa Aida 
Published: September 2005

AbstractAs a comparative study, this paper aims at revealing the impact of Federico García Lorca's (1898-1936) collection of poems in his Gypsy Ballads (1928) on the poetry of Salāh 'Abd al-Sabūr (1931-1981), particularly on his poems in the collection of al-Nās fī Bilādī [People in My Country, 1957]. The study shows that Lorca's in fluence was both generic and stylistic, and that these elements enabled 'Abd al-Sabūr to discard his initial Romantic subjectivism, engage his poetry in the pressing issues of his age, and modernize his poetry through using appropriate modes of expression that enabled him to speak the language of his times. Through reading Lorca's work, 'Abd al-Sabūr introduced the European popular ballad into Arabic poetry (and combined it with elements from the Egyptian popular narratives); he fused the ballad with poetic devices that Lorca had applied to the ballad, so as to modernize the genre, and use it as a means for expressing his poetical concerns. To achieve its purposes, the study compares three of 'Abd al-Sabūr's poems, namely "Hajāma al-Tatār" [The Tartars Attacked], "Shanq Zahrān," [The Execution of Zahrān], and al-Nās fī Bilādī [People in My Country] with Lorca's "Ballad of the Civil Guard."
Gibran's Unpublished Letters to Archbishop Antonious Bashīr
Authors: El-Hage George 
Published: September 2005

AbstractThese are some of Gibran's unpublished letters to Archbishop Antonious Bashīr. They were unknown and unpublished until November 11, 2004, when they appeared in the original Arabic in the Lebanese daily newspaper, Al-Nahār (Almulhaq). According to Al-Nahār, these letters remained hidden among the archives of the Greek Orthodox Diocese in North America. It appears that Archbishop Philip Salība one day was searching in the old files of his predecessor, Antonious Bashīr, when he accidentally found these letters. Apparently, Gibran had written them to his friend, Antonious Bash¬r, who was also the translator of the Prophet into Arabic. The Lebanese newspaper adds that these letters acquire great importance as they constitute, on the one hand, a dialogue between the author and his translator, and on the other, they form part of Gibran's great literary heritage of which many hidden treasures have not yet been discovered.
Population-based laboratory surveillance for Giardia sp. and Cryptosporidium sp. infections in a large Canadian health region
Authors: Laupland Kevin B , Church Deirdre L 
Published: September 2005

Abstract
Background
Giardia lamblia (intestinalis) and Cryptosporidium parvum are the two most important intestinal parasites infecting North Americans but there is a paucity of active population-based surveillance data from Canada. This study determined the incidence of and demographic risk factors for developing Giardia sp. and Cryptosporidium sp. infections in a general Canadian population.

Methods
Population-based laboratory surveillance was conducted among all residents of the Calgary Health Region (CHR; population ≅ 1 million) during May 1, 1999 and April 30, 2002.

Results
Giardia sp. infection occurred at a rate of 19.6 per 100,000 populations per year. Although the yearly incidence was stable, a significant seasonal variation was observed with a peak in late summer to early fall. Males were at higher risk for development of this infection as compared to females (21.2 vs. 17.9 per 100,000/yr; relative risk (RR) 1.19; 95% confidence interval (CI), 1.00–1.40, p = 0.047), and there was a significant decrease in risk associated with an increasing age. Cryptosporidium sp. infection occurred at an overall rate of 6.0 per 100,000 populations per year although a large outbreak of Cryptosporidium sp. infections occurred in the second half of the summer of 2001. During August and September of 2001, the incidence of cryptosporidiosis was 55.1 per 100,000 per year as compared to 3.1 per 100,000 per year for the remainder of the surveillance period (p < 0.0001). Cryptosporidiosis was largely a disease of children with an incidence of 17.8 per 100,000 per year occurring among those aged < 20 years of age compared to 1.25 per 100,000 per year for adults ≥ 20 years of age (RR 14.19; 95% CI, 9.77–21.11; p < 0.0001).

Conclusion
This study provides important information on the occurrence and demographic risk groups for acquisition of giardiasis and cryptosporidiosis in a non-selected Canadian population.