bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colon cancer patient information seeking and the adoption of targeted therapy for on‐label and off‐label indications
Authors: Gray Stacy W. , Armstrong Katrina , DeMichele Angela , Schwartz J. Sanford , Hornik Robert C. 
Published: February 2009

AbstractBACKGROUND:Despite the rise in publicly available cancer information, little is known about the association between patient information seeking and the adoption of cancer technologies. The authors of this report investigated the relation between patient information seeking and awareness about and receipt of novel targeted therapy (TT) for colon cancer among patients for whom therapy is approved by the US Food and Drug Administration (FDA) and among patients for whom therapy is not FDA approved.METHODS:A retrospective, population‐based survey of 633 colon cancer patients were identified through the Pennsylvania Cancer Registry. Outcome measures were self‐reported awareness about and receipt of TT (bevacizumab and cetuximab).RESULTS:After adjusting for sociodemographic characteristics, high levels of treatment information seeking were associated strongly with hearing about TT (odds ratio [OR], 2.83; 95% confidence interval [CI], 1.49‐5.38) and receiving TT (OR, 3.22; 95% CI, 1.36‐7.62). These associations were present for patients with metastatic disease, for whom the use of TT is FDA approved, and for patients with localized disease, for whom the use of TT is not FDA approved (P for interactions = .29). Internet use (OR, 2.88; 95% CI, 1.40‐5.94) and newspaper/magazine use (OR, 3.44; 95% CI, 1.34‐8.84) were associated with hearing about TT. Seeking information from nontreating physicians was associated with hearing about TT (OR, 1.95; 95% CI, 1.03‐3.68) and receiving TT (OR, 2.64; 95% CI, 1.16‐5.97).CONCLUSIONS:Patient information seeking was related to the adoption of TT for colon cancer in both appropriate and inappropriate clinical settings. These findings emphasize the importance of exploring patient influence on physician prescribing patterns and understanding the impact of information seeking on cancer outcomes. Cancer 2009. © 2009 American Cancer Society.
Neoplastic meningitis
Authors: Chamberlain Marc C. , Johnston Sandra K. 
Published: February 2009

AbstractBACKGROUND:This retrospective comparison evaluated survival in 2 well‐matched cohorts of patients with neoplastic meningitis (NM) presenting with or without positive cerebrospinal fluid (CSF) cytology.METHODS:Two patient cohorts were studied: 42 individuals with (Group A) and 42 without (Group B) positive CSF cytology. Groups were matched with respect to age; primary tumor; Karnofsky performance status; site of NM disease (cranial nerves or spinal cord); treatment (radiotherapy and chemotherapy; systemic and intraventricular); and absence of CSF compartmentalization, NM‐related encephalopathy, and neuroradiographic bulky central nervous system disease. Primary tumor histology included breast (28 patients), non‐Hodgkin lymphoma (14 patients), nonsmall cell lung cancer (14 patients), melanoma (12 patients), and others (16 patients). NM at presentation revealed cranial neuropathy (40 patients) or spinal cord dysfunction (58 patients). Radiotherapy was administered to 69 patients (whole brain only in 14 patients [7 each in Groups A and B], restricted spine only in 51 patients [25 in Group A and 26 in Group B], and both whole brain and restricted spine in 4 patients [2 each in Groups A and B]). All patients received intraventricular chemotherapy and 60 (30 each in Groups A and B) received concurrent tumor‐specific systemic chemotherapy.RESULTS:The median, 3‐month, 6‐month, and 12‐month survival rates for patients with NM were not significantly different between those patients with positive CSF cytology (18 weeks, 83%, 33%, and 9.5%, respectively) and those without positive CSF cytology (20 weeks, 90.5%, 40.5%, and 9.5%, respectively). All patients demonstrated progressive disease and died of either NM or systemic cancer.CONCLUSIONS:In patients with NM who were matched for known prognostic variables, the presence or absence of CSF cytology did not appear to influence survival. Cancer 2009. © 2009 American Cancer Society.
Spinal cord compression injury in adult rats initiates changes in dorsal horn remodeling that may correlate with development of neuropathic pain
Authors: Kalous Adrianna , Osborne Peregrine B. , Keast Janet R. 
Published: February 2009

AbstractSpinal cord injury commonly causes chronic, neuropathic pain. The mechanisms are poorly understood but may include structural plasticity within spinal and supraspinal circuits. Our aim was to determine whether structural remodeling within the dorsal horn rostral to an incomplete injury differs from a complete spinal cord transection. Four immunohistochemical populations of primary afferent C‐fibers, and descending catecholamine and serotonergic projections, were examined in segments T9–T12 at 2 and 12 weeks after a T13 clip‐compression injury in adult male rats. Dorsal root ganglia were also examined. Two weeks after injury, fibers immunoreactive for calcitonin gene‐related peptide (CGRP) or GDNF‐family receptors (GFRα1, GFRα2, GFRα3) showed distinct injury responses within the superficial dorsal horn. CGRP fibers decreased, but GFRα1, GFRα2 and GFRα3 fibers did not change. In contrast, all groups were decreased by 12 weeks after injury. Catecholamine fibers showed a decrease at 2 weeks followed by an increase in density at 12 weeks, whereas serotonergic fibers showed a decrease (restricted to deep dorsal horn) at 12 weeks. These results show that the dorsal horn of the spinal cord undergoes substantial structural plasticity rostral to a compression injury, with the most profound effect being a prolonged and possibly permanent loss of primary afferent fibers. This loss was more extensive and more prolonged than the loss that follows spinal cord transection. Our results provide further evidence that anatomical reorganization of sensory and nociceptive dorsal horn circuits rostral to an injury could factor in the development or maintenance of spinal cord injury pain. J. Comp. Neurol. 513:668–684, 2009. © 2009 Wiley‐Liss, Inc.
Systemic hypothermia improves histological and functional outcome after cervical spinal cord contusion in rats
Authors: Lo Thomas Pang , Cho Kyoung‐Suok , Garg Maneesh Sen , Lynch Michael Patrick , Marcillo Alexander Eduardo , Koivisto Denise Leigh , Stagg Monica , Abril Rosa Marie , Patel Samik , Dietrich W. Dalton , Pearse Damien Daniel 
Published: February 2009

AbstractHypothermia has been employed during the past 30 years as a therapeutic modality for spinal cord injury (SCI) in animal models and in humans. With our newly developed rat cervical model of contusive SCI, we investigated the therapeutic efficacy of transient systemic hypothermia (beginning 5 minutes post‐injury for 4 hours, 33°C) with gradual rewarming (1°C per hour) for the preservation of tissue and the prevention of injury‐induced functional loss. A moderate cervical displacement SCI was performed in female Fischer rats, and behavior was assessed for 8 weeks. Histologically, the application of hypothermia after SCI resulted in significant increases in normal‐appearing white matter (31% increase) and gray matter (38% increase) volumes, greater preservation (four‐fold) of neurons immediately rostral and caudal to the injury epicenter, and enhanced sparing of axonal connections from retrogradely traced reticulospinal neurons (127% increase) compared with normothermic controls. Functionally, a faster rate of recovery in open field locomotor ability (BBB score, weeks 1–3) and improved forelimb strength, as measured by both weight‐supported hanging (43% increase) and grip strength (25% increase), were obtained after hypothermia. The current study demonstrates that mild systemic hypothermia is effective for retarding tissue damage and reducing neurological deficits following a clinically relevant contusive cervical SCI. J. Comp. Neurol. 514:433–448, 2009. © 2009 Wiley‐Liss, Inc.
Variability in the occurrence of nitric oxide synthase immunoreactivity in different populations of rat sympathetic preganglionic neurons
Authors: Hinrichs Julia M. , Llewellyn‐Smith Ida J. 
Published: February 2009

AbstractThe proportion of sympathetic preganglionic neurons (SPN) showing nitric oxide synthase (NOS) immunoreactivity appears to vary with innervation target and blood pressure level. For normotensive Sprague‐Dawley rats (SD), we evaluated peroxidase immunolabelling for choline acetyltransferase (ChAT) plus NOS in spinal cord segments T1–L2 and assessed NOS immunofluorescence in SPN retrogradely labelled with cholera toxin B subunit from the adrenal medulla (AM) or superior cervical (SCG), coeliac (CG), or major pelvic (MPG) ganglia. We also compared the distributions and numbers of NOS‐positive and NOS‐negative/ChAT‐positive lateral horn neurons in SD with those in normotensive Wistar‐Kyoto (WKY) and spontaneously hypertensive rats (SHR). In SD, WKY, and SHR, rostrocaudal, dorsoventral, and mediolateral differences occurred in the distributions of NOS‐positive and NOS‐negative/ChAT‐positive neurons in the intermediolateral cell column (IML), whereas the two groups were similarly distributed throughout the central autonomic area (CAA). Among the four retrogradely labelled populations of SPN, the percentages showing NOS immunoreactivity differed (CG‐projecting, 54.8% ± 0.7%; SCG‐projecting, 75.3% ± 1.2%; MPG‐projecting, 89% ± 1.1% and AM‐projecting, 98.6% ± 0.2%). Within each retrogradely labelled group of SPN, the NOS‐positive proportion also varied with subnuclear location (e.g., 25.5% ± 4.0% of CG‐projecting SPN in the CAA vs. 82.7% ± 7.6% of CG‐projecting SPN in the dorsolateral funiculus). The numbers of NOS‐positive and NOS‐negative/ChAT‐positive neurons in T9–T11 were the same in SD and SHR but differed in WKY. Our results show that the expression of NOS within SPN varies depending on the target that they innervate and also on their subnuclear location. Our data indicate that there are no anatomical differences between nitric oxide‐synthesizing SPN in normotensive SD and hypertensive SHR. J. Comp. Neurol. 514:492–506, 2009. © 2009 Wiley‐Liss, Inc.
Regulation of neonatal development of retinal ganglion cell dendrites by neurotrophin‐3 overexpression
Authors: Liu Xiaorong , Robinson Michael L. , Schreiber Ann Marie , Wu Vincent , Lavail Matthew M. , Cang Jianhua , Copenhagen David R. 
Published: February 2009

AbstractThe morphology of dendrites constrains and reflects the nature of synaptic inputs to neurons. The visual system has served as a useful model to show how visual function is determined by the arborization patterns of neuronal processes. In retina, light ON and light OFF responding ganglion cells selectively elaborate their dendritic arbors in distinct sublamina, where they receive, respectively, inputs from ON and OFF bipolar cells. During neonatal maturation, the bilaminarly distributed dendritic arbors of ON‐OFF retinal ganglion cells (RGCs) are refined to more narrowly localized monolaminar structures characteristic of ON or OFF RGCs. Recently, brain‐derived neurotrophic factor (BDNF) has been shown to regulate this laminar refinement, and to enhance the development of dendritic branches selectively of ON RGCs. Although other related neurotrophins are known to regulate neuronal process formation in the central nervous system, little is known about their action in maturing retina. Here, we report that overexpression of neurotrophin‐3 (NT‐3) in the eye accelerates RGC laminar refinement before eye opening. Furthermore, NT‐3 overexpression increases dendritic branch number but reduces dendritic elongation preferentially in ON‐OFF RGCs, a process that also occurs before eye opening. NT‐3 overexpression does affect dendritic maturation in ON RGCs, but to a much less degree. Taken together, our results suggest that NT‐3 and BDNF exhibit overlapping effects in laminar refinement but distinct RGC‐cell‐type specific effects in shaping dendritic arborization during postnatal development. J. Comp. Neurol. 514:449–458, 2009. © 2009 Wiley‐Liss, Inc.
Efferent projections of thyrotropin‐releasing hormone‐synthesizing neurons residing in the anterior parvocellular subdivision of the hypothalamic paraventricular nucleus
Authors: Wittmann Gábor , Füzesi Tamás , Singru Praful S. , Liposits Zsolt , Lechan Ronald M. , Fekete Csaba 
Published: February 2009

AbstractThe anterior parvocellular subdivision of the PVN (aPVN) contains nonhypophysiotropic thyrotropin‐releasing hormone (TRH) neurons that are densely innervated by feeding‐related neuronal groups of the hypothalamic arcuate nucleus. To determine how these TRH neurons are integrated within the brain, the major projection fields of this cell group were studied by anterograde and retrograde tract‐tracing methods. Projection sites were identified by injection of the anterograde tracerPhaseolus vulgarisleucoagglutinin (PHAL) into the aPVN, and subsequent double immunofluorescent staining was used to visualize axons containing both PHAL and pro‐TRH. To distinguish between the projection sites of TRH neurons residing in the aPVN and the closely situated perifornical area, the retrograde tracer cholera toxin B subunit (CTB) was injected into regions where PHAL/pro‐TRH‐containing axons were densely accumulated. TRH neurons in the aPVN were found to project to the hypothalamic arcuate, dorsomedial and ventral premammillary nuclei, medial preoptic region, tuber cinereum area, paraventricular thalamic nucleus, bed nucleus of the stria terminalis, lateral septal nucleus, and central amygdaloid nucleus. Projection fields of perifornical TRH neurons were in partial overlap with those of the aPVN TRH cells. In addition, these neurons also innervated the hypothalamic ventromedial nucleus, the medial amygdaloid nucleus, and the amygdalohippocampal area. The data suggest that, through its efferent connections, aPVN TRH neurons may be involved in the regulation of energy homeostasis coordinately with effects on behavior, locomotor activity, and thermogenesis. In addition, the major differences in the projection fields of aPVN and perifornical TRH neurons suggest that these two TRH‐synthesizing neuronal groups are functionally different. J. Comp. Neurol. 515:313–330, 2009. © 2009 Wiley‐Liss, Inc.
Altered cutaneous nerve regeneration in a simian immunodeficiency virus / macaque intracutaneous axotomy model
Authors: Ebenezer Gigi J. , Laast Victoria A. , Dearman Brandon , Hauer Peter , Tarwater Patrick M. , Adams Robert J. , Zink M. Christine , McArthur Justin C. , Mankowski Joseph L. 
Published: February 2009

AbstractTo characterize the regenerative pattern of cutaneous nerves in simian immunodeficiency virus (SIV)‐infected and uninfected macaques, excisional axotomies were performed in nonglabrous skin at 14‐day intervals. Samples were examined after immunostaining for the pan‐axonal marker PGP 9.5 and the Schwann cell marker p75 nerve growth factor receptor. Collateral sprouting of axons from adjacent uninjured superficial dermal nerve bundles was the initial response to axotomy. Both horizontal collateral sprouts and dense vertical regeneration of axons from the deeper dermis led to complete, rapid reinnervation of the epidermis at the axotomy site. In contrast to the slower, incomplete reinnervation previously noted in humans after this technique, in both SIV‐infected and uninfected macaques epidermal reinnervation was rapid and completed by 56 days postaxotomy. p75 was densely expressed on the Schwann cells of uninjured nerve bundles along the excision line and on epidermal Schwann cell processes. In both SIV‐infected and uninfected macaques, Schwann cell process density was highest at the earliest timepoints postaxotomy and then declined at a similar rate. However, SIV‐infection delayed epidermal nerve fiber regeneration and remodeling of new sprouts at every timepoint postaxotomy, and SIV‐infected animals consistently had lower mean epidermal Schwann cell densities, suggesting that Schwann cell guidance and support of epidermal nerve fiber regeneration may account for altered nerve regeneration. The relatively rapid regeneration time and the completeness of epidermal reinnervation in this macaque model provides a useful platform for assessing the efficacy of neurotrophic or regenerative drugs for sensory neuropathies including those caused by HIV, diabetes mellitus, medications, and toxins. J. Comp. Neurol. 514:272–283, 2009. © 2009 Wiley‐Liss, Inc.
Erythropoietin receptor expression is concordant with erythropoietin but not with common β chain expression in the rat brain throughout the life span
Authors: Sanchez Pascal E. , Navarro Fabrice P. , Fares Raafat P. , Nadam Jérémie , Georges Béatrice , Moulin Colette , Le Cavorsin Marion , Bonnet Chantal , Ryvlin Philippe , Belmeguenai Amor , Bodennec Jacques , Morales Anne , Bezin Laurent 
Published: February 2009

AbstractBrain effects of erythropoietin (Epo) are proposed to involve a heteromeric receptor comprising the classical Epo receptor (Epo‐R) and the common β chain (βc). However, data documenting the pattern of βc gene expression in the healthy brain, in comparison with that of the Epo‐R gene, are still lacking. The present study is the first to investigate at the same time βc, Epo‐R, and Epo gene expression within different rat brain areas throughout the life span, from neonatal to elderly stages, using quantitative RT‐PCR for transcripts. Corresponding proteins were localized by using immunohistochemistry. We demonstrate that the βc transcript level does not correlate with that of Epo‐R or Epo, whereas the Epo‐R transcript level strongly correlates with that of Epo throughout the life span in all brain structures analyzed. Both Epo and Epo‐R were detected primarily in neurons. In the hippocampus, the greatest Epo‐R mRNA levels were measured during the early postnatal period and in middle‐aged rats, associated with an intense neuronal immunolabeling. Conversely, βc protein was barely detectable in the brain at all ages, even in neurons expressing high levels of Epo‐R. Finally, βc transcript could not be detected in PC12 cells, even after nerve growth factor‐induced neuritogenesis, which is a condition that dramatically enhances Epo‐R transcript level. Altogether, our data suggest that most neurons are likely to express high levels of Epo‐R but low, if not null, levels of βc. Given that Epo protects extended populations of neurons after injury, a yet‐to‐be‐identified receptor heterocomplex including Epo‐R may exist in the large population of brain neurons that does not express βc. J. Comp. Neurol. 514:403–414, 2009. © 2009 Wiley‐Liss, Inc.
De novo expression of the neurokinin 1 receptor in spinal lamina I pyramidal neurons in polyarthritis
Authors: Almarestani L. , Waters S.M. , Krause J.E. , Bennett G.J. , Ribeiro‐Da‐Silva A. 
Published: February 2009

AbstractSpinal lamina I (LI) neurons play a major role in the transmission and integration of pain‐related information that is relayed to higher centers. Alterations in the excitability of these neurons influence chronic pain development, and expression of the neurokinin 1 receptor (NK‐1r) is thought to play a major role in such changes. Novel expression of NK‐1r may underlie hyperexcitability in new populations of LI neurons. LI projection neurons can be classified morphologically into fusiform, pyramidal, and multipolar cells, differing in their functional properties, with the pyramidal type being nonnociceptive. In agreement with this, we have shown that spinoparabrachial pyramidal neurons seldom express NK‐1r, in contrast with the other two cell types. In this study we investigated in the rat the long‐term changes in NK‐1r expression by spinoparabrachial LI neurons following the unilateral injection in the hindpaw plantar surface of complete Freund's adjuvant (CFA). Cholera toxin subunit B (CTb) was injected unilaterally into the parabrachial nucleus. Our results revealed that, ipsilaterally, pyramidal neurons were seldom immunoreactive for NK‐1r both in saline‐injected and in CFA‐injected rats, up to 10 days post‐CFA. However, a considerable number of pyramidal cells were immunoreactive for NK‐1r at 15, 21, and 30 days post‐CFA. Our data raise the possibility—which needs to be confirmed by electrophysiology—that most LI projection neurons of the pyramidal type are likely nonnociceptive in naive animals but might become nociceptive following the development of arthritis. J. Comp. Neurol. 514:284–295, 2009. © 2009 Wiley‐Liss, Inc.
Functional remodeling of glutamate receptors by inner retinal neurons occurs from an early stage of retinal degeneration
Authors: Chua Jacqueline , Fletcher Erica L. , Kalloniatis Michael 
Published: February 2009

AbstractRetinitis pigmentosa reflects a family of diseases that result in retinal photoreceptor death and functional blindness. The natural course of retinal changes secondary to photoreceptor degeneration involves anatomical remodeling (cell process alterations and soma displacement) and neurochemical remodeling. Anatomical remodeling predominantly occurs late in the disease process and cannot explain the significant visual deficits that occur very early in the disease process. Neurochemical remodeling includes modified glutamate receptor disposition and altered responses secondary to functional activation of glutamate receptors. We investigated the neurochemical remodeling of retinal neurons in the rd/rd (rd1) mouse retina by tracking the functional activation of glutamate receptors with a cation probe, agmatine. We provide evidence that bipolar cells and amacrine cells undergo selective remodeling of glutamate receptors during the early phases of retinal degeneration. These early neurochemical changes in the rd/rd mouse retina include the expression of aberrant functional ionotropic glutamate receptors on the cone ON bipolar cells from postnatal day 15 (P15), poor functional activation of metabotropic glutamate receptors on both rod and cone ON bipolar cells throughout development/degeneration, and poor functional activation of N‐methyl‐D‐aspartate receptors on amacrine cells from P15. Our results suggest that major neurochemical remodeling occurs prior to anatomical remodeling, and likely accounts for the early visual deficits in the rd/rd mouse retina. J. Comp. Neurol. 514:473–491, 2009. © 2009 Wiley‐Liss, Inc.
Distribution of EphA5 receptor protein in the developing and adult mouse nervous system
Authors: Cooper Margaret A. , Crockett David P. , Nowakowski Richard S. , Gale Nicholas W. , Zhou Renping 
Published: February 2009

AbstractThe EphA5 receptor tyrosine kinase plays key roles in axon guidance during development. However, the presence of EphA5 protein in the nervous system has not been fully characterized. To examine EphA5 localization better, mutant mice, in which the EphA5 cytoplasmic domain was replaced with β‐galactosidase, were analyzed for both temporal and regional changes in the distribution of EphA5 protein in the developing and adult nervous system. During embryonic development, high levels of EphA5 protein were found in the retina, olfactory bulb, cerebral neocortex, hippocampus, pretectum, tectum, cranial nerve nuclei, and spinal cord. Variations in intensity were observed as development proceeded. Staining of pretectal nuclei, tectal nuclei, and other areas of the mesencephalon became more diffuse after maturity, whereas the cerebral neocortex gained more robust intensity. In the adult, receptor protein continued to be detected in many areas including the olfactory nuclei, neocortex, piriform cortex, induseum griseum, hippocampus, thalamus, amygdala, hypothalamus, and septum. In addition, EphA5 protein was found in the claustrum, stria terminalis, barrel cortex, and striatal patches, and along discrete axon tracts within the corpus callosum of the adult. We conclude that EphA5 function is not limited to the developing mouse brain and may play a role in synaptic plasticity in the adult. J. Comp. Neurol. 514:310–328, 2009. © 2009 Wiley‐Liss, Inc.