bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase 1‐2 study of a farnesyltransferase inhibitor, tipifarnib, combined with idarubicin and cytarabine for patients with newly diagnosed acute myeloid leukemia and high‐risk myelodysplastic syndrome
Authors: Jabbour Elias , Kantarjian Hagop , Ravandi Farhad , Garcia‐Manero Guillermo , Estrov Zeev , Verstovsek Srdan , O'Brien Susan , Faderl Stefan , Thomas Deborah A. , Wright John J. , Cortes Jorge 
Published: October 2010

AbstractBACKGROUND:The authors conducted a phase 1/2 study of tipifarnib in combination with idarubicin and cytarabine (IA) in 95 patients with previously untreated acute myeloid leukemia (AML) or high‐risk myelodysplastic syndrome.METHODS:Induction consisted of idarubicin 12 mg/m2 a day on days 1‐3, cytarabine 1.5 g/m2 intravenously continuously daily on days 1‐4 (days 1‐3 if age ≥60 years), and tipifarnib, with the first cohort (n = 6) receiving 200 mg orally twice a day and all others receiving 300 mg twice a day for 21 days every 28 days. Consolidation consisted of 5 courses of idarubicin 8 mg/m2 a day on days 1‐2, cytarabine 0.75 g/m2 a day on days 1‐3, and tipifarnib 300 mg twice a day for 14 days every 4‐6 weeks. Maintenance with tipifarnib 300 mg twice a day for 21 days every 4‐6 weeks was continued for 6 months.RESULTS:With a median follow‐up of 33 months, 61 patients achieved complete remission (CR) (64%), and 9 achieved complete remission with incomplete platelet recovery (CRp) (9%). The median duration of CR was not reached. Median overall survival was 17 months. The most common grade 3 adverse events were gastrointestinal toxicities, liver dysfunction, and skin rash. Compared with historical IA, IA and tipifarnib showed a better CR duration (P = .04) and a trend toward a higher CR rate in patients with chromosome 5/7 abnormalities.CONCLUSIONS:The combination of IA and tipifarnib is safe and active. Further studies exploring different dosages and schedules are warranted, particularly in patients with poor‐risk AML. Cancer 2011. © 2010 American Cancer Society.
Prognostic factors for survival in melanoma patients with brain metastases
Authors: Davies Michael A. , Liu Ping , McIntyre Susan , Kim Kevin B. , Papadopoulos Nicholas , Hwu Wen‐Jen , Hwu Patrick , Bedikian Agop 
Published: October 2010

AbstractBACKGROUND:One of the most common and deadly complications of melanoma is brain metastases. The outcomes of advanced melanoma patients who developed brain metastases were reviewed to identify significant prognostic factors for overall survival (OS).METHODS:An institutional database of advanced melanoma patients enrolled on clinical trials in the Department of Melanoma Medical Oncology from 1986 to 2004 was reviewed and patients who developed brain metastases were identified. Date of diagnosis, patient age, pattern of brain involvement, timing relative to extracranial metastases, prior response to systemic therapy, and treatments given for brain metastases were assessed as potential prognostic factors for OS.RESULTS:Among 743 melanoma patients enrolled in clinical trials for regional or systemic metastatic disease, 330 (44%) patients developed brain metastases. The median OS after the diagnosis of brain metastases was 4.7 months. Diagnosis before 1996, increased number of parenchymal brain metastases, leptomeningeal involvement, and development of brain metastases after receiving systemic therapy for extracranial metastases were found to be significant prognostic factors for OS. Among patients who received systemic therapy as the initial treatment of brain metastases, patients who previously responded to systemic therapies had longer survival than patients who had not responded.CONCLUSIONS:The era, pattern, and timing of melanoma brain metastases were found to be strongly associated with survival. Previous responsiveness to systemic therapies did not predict better outcomes overall, but it did correlate with improved survival for patients with brain metastases who were treated with systemic therapies. These factors may be used in guiding patient management and for stratifying patients in clinical trials. Cancer 2011. © 2010 American Cancer Society.
Gemcitabine and radiotherapy plus cisplatin after transurethral resection as conservative treatment for infiltrating bladder cancer
Authors: Caffo Orazio , Fellin Gianni , Graffer Umberto , Mussari Salvatore , Tomio Luigi , Galligioni Enzo 
Published: October 2010

AbstractBACKGROUND:Cystectomy is the standard treatment for patients with infiltrating bladder cancer, but conservative treatment with cystoscopic resection followed by radiochemotherapy may be an alternative for highly selected patients. The addition of gemcitabine to cisplatin and radiotherapy may enhance disease control.METHODS:The long‐term clinical outcomes of 26 patients enrolled in a previously published dose‐finding study and a prematurely discontinued phase 2 trial were evaluated. All the patients underwent transurethral tumor resection followed by a radical dose of external radiotherapy administered at the same time as cisplatin and weekly gemcitabine therapy.RESULTS:After a median follow‐up of 74 months, the projected 5‐year clinical outcomes were a 70.1% overall survival rate, a 78.9% disease‐specific survival rate, and a 73.8% bladder‐intact survival rate.CONCLUSIONS:The long‐term follow‐up data from the current study confirmed that the addition of gemcitabine to radiotherapy and cisplatin is safe and leads to good local and distant disease control. The concomitant administration of cisplatin may explain the good long‐term organ preservation that was observed. Conducting confirmatory and comparative trials could satisfy an unmet need but requires the multidisciplinary cooperation of urologists in selecting the right patients for a bladder‐sparing strategy. Cancer 2011. © 2010 American Cancer Society.
The selective Trk inhibitor AZ623 inhibits brain‐derived neurotrophic factor–mediated neuroblastoma cell proliferation and signaling and is synergistic with topotecan
Authors: Zage Peter E. , Graham Timothy C. , Zeng Lizhi , Fang Wendy , Pien Christine , Thress Ken , Omer Charles , Brown Jeffrey L. , Zweidler ‐McKay Patrick A. 
Published: October 2010

AbstractBACKGROUND:TrkB expression is associated with poor prognosis for patients with neuroblastoma. AZ623 is a novel potent and selective inhibitor of the Trk family of tyrosine kinases. The authors hypothesized that AZ623 would inhibit TrkB‐mediated signaling in neuroblastoma tumor cells and would be synergistic when combined with chemotherapy.METHODS:Neuroblastoma cell lines were screened for TrkB receptor mRNA expression and for their proliferation rates in response to brain‐derived neurotrophic factor (BDNF). The effects of AZ623 on Trk receptor phosphorylation, signaling, and cell growth were evaluated in BDNF‐treated neuroblastoma cells. Mice with human neuroblastoma xenograft tumors were treated with AZ623 alone and in combination with topotecan, and tumor growth rates were determined during and after treatment.RESULTS:Neuroblastoma cell lines expressed various levels of the TrkB receptor and demonstrated increased proliferation in response to BDNF. BDNF treatment stimulated TrkB phosphorylation and downstream signaling that could be inhibited by AZ623. Neuroblastoma cells demonstrated in vitro sensitivity to AZ623, with concentration that inhibits 50% (IC50) values between 0.8 to 7 μM. AZ623 treatment was found to inhibit BDNF‐mediated neuroblastoma cell proliferation. Mice with human neuroblastoma xenograft tumors demonstrated tumor growth inhibition when treated with AZ623 and with AZ623 combined with topotecan. Limited tumor regrowth was noted in mice with tumors treated with AZ623 combined with topotecan after treatment discontinuation.CONCLUSIONS:AZ623 is a novel selective Trk inhibitor that inhibits BDNF‐mediated signaling and neuroblastoma cell proliferation. AZ623 treatment inhibits the growth of human neuroblastoma xenograft tumors, and treatment with AZ623 combined with topotecan results in the prolonged inhibition of tumor regrowth. On the basis of these results, further preclinical development is warranted. Cancer 2011. © 2010 American Cancer Society.
Innervation of the rat uterus at estrus: A study in full‐thickness, immunoperoxidase‐stained whole‐mount preparations
Authors: Gnanamanickam Greta J.E. , Llewellyn‐Smith Ida J. 
Published: October 2010

AbstractThe innervation of the nonpregnant rat uterus has been studied in histological sections, which contain only small samples of nerves and are unlikely to afford a complete picture of uterine innervation. Here we used whole‐mount preparations of entire full‐thickness uterine horns from nonpregnant rats in estrus to visualize autonomic or sensory nerves with peroxidase immunohistochemistry. Immunoreactivity was studied for tyrosine hydroxylase (TH)‐labeled sympathetic nerves; vesicular acetylcholine transporter (VAChT), parasympathetic nerves; and substance P (SP) and calcitonin gene‐related peptide (CGRP), sensory nerves. Neuropeptide Y (NPY) and nitric oxide synthase (NOS) identified more than one of these functionally distinct nerve types. Axons of all neurochemical classes entered the uterus at the mesometrium and innervated the uterine smooth muscle. The linea uteri, a dense band of longitudinal muscle opposite the mesometrium, contained more TH‐, NPY‐, CGRP‐, and VAChT‐immunoreactive axons than the remaining smooth muscle. Axons immunoreactive for NPY, SP, NOS, and VAChT formed a plexus near the circular muscle‐endometrium interface. Rare TH‐ and NPY‐immunoreactive axons and occasional CGRP‐immunoreactive axons occurred close to uterine glands. Blood vessels had dense perivascular plexuses of TH‐ and NPY‐containing axons and less dense NOS‐, SP‐, CGRP‐, and VAChT‐positive plexuses. The circular muscle plexus and glands were absent opposite the mesometrium. Uterine arterioles formed an interconnected network throughout the uterus. This article provides the first comprehensive description of the autonomic and sensory innervation of the nonpregnant rat uterus and will be a foundation for future studies on changes in uterine innervation caused by normal physiological or pathophysiological challenges J. Comp. Neurol. 519:621–643, 2011. © 2010 Wiley‐Liss, Inc.
Bombyx orcokinins are brain‐gut peptides involved in the neuronal regulation of ecdysteroidogenesis
Authors: Yamanaka Naoki , Roller Ladislav , Žitňan Dušan , Satake Honoo , Mizoguchi Akira , Kataoka Hiroshi , Tanaka Yoshiaki 
Published: October 2010

AbstractBiosynthesis of ecdysteroids, the insect steroid hormones controlling gene expression during molting and metamorphosis, takes place primarily in the prothoracic gland (PG). The activity of the PG is regulated by various neuropeptides. In the silkworm Bombyx mori, these neuropeptides utilize both hormonal and neuronal pathways to regulate the activity of the PG, making the insect an excellent model system to investigate the complex signaling network controlling ecdysteroid biosynthesis. Here we report another group of neuropeptides, orcokinins, as neuronal prothoracicotropic factors. Using direct mass spectrometric profiling of the axons associated with the PG, we detected several peptide peaks which correspond to orcokinin gene products in addition to the previously described Bommo‐FMRFamides (BRFas). In situ hybridization and immunohistochemistry revealed that orcokinins are produced in the prominent neurosecretory cells in the ventral ganglia, as well as in numerous small neurons throughout the central nervous system and in midgut endocrine cells. One of the two pairs of BRFa‐expressing neurosecretory cells in the prothoracic ganglion coexpresses orcokinin, and these neurons project axons through the transverse nerve and terminate on the surface of the PG. Using an in vitro PG bioassay, we show that orcokinins have a clear prothoracicotropic activity and are able to cancel the static effect of BRFas on ecdysteroid biosynthesis, whereas the suppressive effect of BRFas on cAMP production remained unchanged in the presence of orcokinins. The discovery of a second regulator of PG activity in these neurons further illustrates the potential importance of the PG innervation in the regulation of insect development. J. Comp. Neurol. 519:238‐246, 2011. © 2010 Wiley‐Liss, Inc.
Spatial distribution of neural activity in the anterior olfactory nucleus evoked by odor and electrical stimulation
Authors: Kay Rachel B. , Meyer Elizabeth Amory , Illig Kurt R. , Brunjes Peter C. 
Published: October 2010

AbstractSeveral lines of evidence indicate that complex odorant stimuli are parsed into separate data streams in the glomeruli of the olfactory bulb, yielding a combinatorial “odotopic map.” However, this pattern does not appear to be maintained in the piriform cortex, where stimuli appear to be coded in a distributed fashion. The anterior olfactory nucleus (AON) is intermediate and reciprocally interconnected between these two structures, and also provides a route for the interhemispheric transfer of olfactory information. The present study examined potential coding strategies used by the AON. Rats were exposed to either caproic acid, butyric acid, limonene, or purified air and the spatial distribution of Fos‐immunolabeled cells was quantified. The two major subregions of the AON exhibited different results. Distinct odor‐specific spatial patterns of activity were observed in pars externa, suggesting that it employs a topographic strategy for odor representation similar to the olfactory bulb. A spatially distributed pattern that did not appear to depend on odor identity was observed in pars principalis, suggesting that it employs a distributed representation of odors more similar to that seen in the piriform cortex. J. Comp. Neurol. 519:277‐289, 2011. © 2010 Wiley‐Liss, Inc.
Regular mosaic of synaptic contacts among three retinal neurons
Authors: Koizumi Amane , Jakobs Tatjana C. , Masland Richard H. 
Published: October 2010

AbstractRetinal bipolar, amacrine, and ganglion cells contact each other within precisely defined synaptic laminae, but the spatial distribution of contacts between the cells is generally treated as random. Here we show that not to be the case. Excitatory inputs to inner retinal neurons were visualized by introduction of a plasmid coding for the postsynaptic protein PSD95‐GFP. Our initial finding was that synapses on the dendrites of retinal ganglion cells are regularly spaced, at 2–3‐μm intervals, along the dendrites. Thus, the presence of a PSD95 punctum creates a nearby zone from which other inputs appear to be excluded. Despite their great variation in size and different morphologies, the spacing is similar for the arbors of different retinal ganglion cell types. Regular spacing was also observed for the starburst amacrine cells. This regularity is mirrored in the spacing of axonal varicosities of the stratified bipolar cells, which have a regular, nonrandom interval consistent with that of the PSD95 puncta on ganglion cells. Thus, for each level of the inner plexiform layer all three cell types participate in a single 2D mosaic of synaptic contacts. These findings raise a new set of questions: How does the self‐avoidance of synaptic sites along an individual dendrite arise and how is it physically maintained? Why is a regular spacing of inputs important for the computational function of the cells? Finally, which of the three players, if any, is developmentally responsible for the initial establishment of the pattern? J. Comp. Neurol. 519:341‐357, 2011. © 2010 Wiley‐Liss, Inc.
Decline in adult neurogenesis during aging follows a topographic pattern in the mouse hippocampus
Authors: Jinno Shozo 
Published: October 2010

AbstractIn the rodent brain, diverse functions are topographically distributed within the hippocampus. For instance, the dorsal (septal) hippocampus is involved in spatial memory, whereas the ventral (temporal) hippocampus is related to emotion and anxiety. Accumulating evidence shows that age‐dependent decline in hippocampal neurogenesis is associated with impairments of these functions. However, little is known about whether the decline in dentate granule cell production during aging follows a topographic pattern. Here we quantitatively estimated specific populations of adult‐born cells in young adult and middle‐aged mice by using endogenous markers and determined whether age‐dependent reductions in adult neurogenesis exhibited topographic differences. The numerical densities (NDs) of putative primary progenitors, intermediate neuronal progenitors, and neuronal lineages were higher in the dorsal dentate gyrus (DG) than in the ventral DG both in young adult and in middle‐aged mice, but the ratios of the NDs in the dorsal DG to the NDs in the ventral DG noticeably increased with age. The age‐related reductions in the numbers of these populations were larger in the ventral DG than in the dorsal DG. By contrast, the NDs of glial lineages were higher in the ventral DG than in the dorsal DG during life, and the numbers of glial lineages showed no significant age‐related changes. Our findings suggest that neurogenesis, but not gliogenesis, wanes faster in the ventral hippocampus than in the dorsal hippocampus during aging. Such age‐related topographic changes in hippocampal neurogenesis might be implicated in memory and affective impairments in older people. J. Comp. Neurol. 519:451–466, 2011. © 2010 Wiley‐Liss, Inc.
Spin‐Labeled Heparins as Polarizing Agents for Dynamic Nuclear Polarization
Authors: Dollmann Björn C. , Kleschyov Andrei L. , Sen Vasily , Golubev Valery , Schreiber Laura M. , Spiess Hans W. , Münnemann Kerstin , Hinderberger Dariush 
Published: October 2010

AbstractA potentially biocompatible class of spin‐labeled macromolecules, spin‐labeled (SL) heparins, and their use as nuclear magnetic resonance (NMR) signal enhancers are introduced. The signal enhancement is achieved through Overhauser‐type dynamic nuclear polarization (DNP). All presented SL‐heparins show high 1H DNP enhancement factors up to E=−110, which validates that effectively more than one hyperfine line can be saturated even for spin‐labeled polarizing agents. The parameters for the Overhauser‐type DNP are determined and discussed. A striking result is that for spin‐labeled heparins, the off‐resonant electron paramagnetic resonance (EPR) hyperfine lines contribute a non‐negligible part to the total saturation, even in the absence of Heisenberg spin exchange (HSE) and electron spin‐nuclear spin relaxation (T1ne). As a result, we conclude that one can optimize the use of, for example, biomacromolecules for DNP, for which only small sample amounts are available, by using heterogeneously distributed radicals attached to the molecule.
Canonical Wnt/β‐catenin signaling is required for maintenance but not activation of Pitx2 expression in neural crest during eye development
Authors: Zacharias Amanda L. , Gage Philip J. 
Published: October 2010

AbstractPitx2 is a paired‐like homeodomain gene that acts as a key regulator of eye development. Despite its significance, upstream regulation of Pitx2 expression during eye development remains incompletely understood. We use neural crest‐specific ablation of Ctnnb1 to demonstrate that canonical Wnt signaling is not required for initial activation of Pitx2 in neural crest. However, canonical Wnt signaling is subsequently required to maintain Pitx2 expression in the neural crest. Eye development in Ctnnb1‐null mice appears grossly normal early but significant phenotypes emerge following loss of Pitx2 expression. LEF‐1 and β‐catenin bind Pitx2 promoter sequences in ocular neural crest, indicating a likely direct effect of canonical Wnt signaling on Pitx2 expression. Combining our data with previous reports, we propose a model wherein a sequential code of retinoic acid followed by canonical Wnt signaling are required for activation and maintenance of Pitx2 expression, respectively. Other key transcription factors in the neural crest, including Foxc1, do not require intact canonical Wnt signaling. Developmental Dynamics 239:3215–3225, 2010. © 2010 Wiley‐Liss, Inc.
cineSubstitution and the Cu Effect in Stille Cross‐Coupling Reactions: Mechanistic Perspectives and Synthetic Utility
Authors: Peng Yu , Li Wei‐Dong Z. 
Published: October 2010

AbstractcineSubstitution arising from slow transmetallation occasionally occurs in classic Pd‐catalyzed Stille cross‐coupling reactions with sterically hindered vinyltin components. Mechanistic explanations of this “abnormal” cross‐coupling mode and the intriguing co‐catalytic effects of metallic Cu species in restoring theipsoselectivity are summarized. Typical synthetic applications of this unique Cu effect and the advent of Cu‐catalyzed Stille‐type cross‐coupling are also demonstrated.
Application of Fenton process for decolorization of reactive black 5 from synthetic wastewater: Kinetics and thermodynamics
Authors: Argun Mehmet Emin , Karatas Mustafa 
Published: October 2010

AbstractThe decolorization and degradation efficiency of the azo dye Reactive Black 5 (RB5) by Fenton system were investigated in this study. The operation parameters such as Fe2+:H2O2 ratio, pH value, initial concentration of RB5, reaction time, and temperature were examined. Maximum decolorization (99%) and degradation (88% COD removal) efficiencies were achieved at the Fe2+:H2O2 ratio of 0.05 and pH 3 for 15‐min reaction time. The decolorization kinetic of RB5 followed pseudo‐second‐order reaction kinetic. The increase of temperature caused decreasing of obtained rate constants and increasing of corresponding half‐lives. The article also discussed thermodynamic parameters including changes in Gibbs free energy, enthalpy, and entropy for the decolorization of RB5 by Fenton and exposed that the oxidation process was spontaneous and exothermic under natural conditions. © 2010 American Institute of Chemical Engineers Environ Prog, 2010
Effectiveness for Interpersonal Problem‐Solving is Reduced in Women with Binge Eating Disorder
Authors: Svaldi Jennifer , Dorn Christina , Trentowska Monika 
Published: October 2010

AbstractObjectiveTherapeutic programs for binge eating disorder (BED) often include the mediation of problem‐solving skills to deal with the desire to binge. In women with BED, problem‐solving abilities have not been studied yet. Knowing that reasons for binge episodes are often linked to interpersonal topics, we expected women with BED to have poorer problem‐solving abilities than healthy controls (HC).MethodsTwenty‐five women with BED and 30 overweight HC were given a shortened version of the Means‐Ends Problem‐Solving Procedure (MEPS). Dependent variables were the number of relevant means, the effectiveness and the specificity of the generated solution.ResultsGenerated solutions in the group of women with BED were significantly less effective and less specific compared to HC. Moreover, reduced effectiveness of interpersonal problem‐solving was related to increased binge frequency.ConclusionsThe results support the importance of teaching problem‐solving ability in individuals with BED to promote behaviour change. Copyright © 2010 John Wiley & Sons, Ltd and Eating Disorders Association.
Invalidating Childhood Environments and Core Beliefs in Women with Eating Disorders
Authors: Ford Gillian , Waller Glenn , Mountford Victoria 
Published: October 2010

AbstractIt can be hypothesised that invalidating environments in childhood influence the negative core beliefs that are found in the eating disorders. This study of eating‐disordered women aimed to test the relationships between perceived childhood invalidating environments and negative core beliefs. Forty‐one eating‐disordered females completed the measures of childhood invalidating experiences and core beliefs. Such core beliefs were most closely related to the individuals' perceptions of having grown up in a ‘chaotic’ family environment. Future clinical practice should continue to target core beliefs in formulating cases of eating disorders. Explaining those core beliefs may depend on understanding the individual's experiences of invalidation in early years. Copyright © 2010 John Wiley & Sons, Ltd and Eating Disorders Association.