bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human epidermal growth factor receptor 2 (HER2) extracellular domain levels are associated with progression‐free survival in patients with HER2‐positive metastatic breast cancer receiving lapatinib monotherapy
Authors: Lipton Allan , Leitzel Kim , Ali Suhail M. , Carney Walter , Platek Greg , Steplewski Klaudia , Westlund Ron , Gagnon Robert , Martin Anne‐Marie , Maltzman Julie 
Published: March 2011

AbstractBACKGROUND:Changes in serum human epidermal growth factor receptor 2 (HER2) levels associated with clinical outcomes, including objective response rate, progression‐free survival (PFS), and overall survival have been reported in patients with metastatic breast cancer (MBC) receiving trastuzumab and chemotherapy. This study investigated whether baseline or changes in serum HER2 correlated with overall response rate (ORR) and/or PFS in patients with MBC receiving first‐line lapatinib monotherapy.METHODS:The EGF20009 study investigated lapatinib monotherapy in 138 HER2‐positive patients with MBC previously untreated for their metastatic disease. Serum was collected and assessed at baseline and every 4 weeks for 16 weeks after treatment initiation. Disease assessment was performed at weeks 8 and 12 and every 12 weeks thereafter. A ≥20% decrease or increase in serum HER2 was defined as a significant change.RESULTS:Seventy‐nine percent of patients had elevated baseline serum HER2. Baseline serum HER2 was associated with ORR (P = .043) but not PFS. Patients with a ≥20% decrease from baseline of serum HER2 at weeks 4, 8, 12, and 16 had a significantly increased ORR and prolonged PFS. Conversely, those with a ≥20% increase from baseline had a significantly lower ORR and shorter PFS.CONCLUSION:Significant decreases in serum HER2 levels during the first 16 weeks of lapatinib monotherapy were associated with better clinical outcome (longer PFS and increased ORR) in HER2‐positive MBC patients. Cancer 2011;. © 2011 American Cancer Society.
Racial/ethnic differences in receipt of pelvic lymph node dissection among men with localized/regional prostate cancer
Authors: Hayn Matthew H. , Orom Heather , Shavers Vickie L. , Sanda Martin G. , Glasgow Mark , Mohler James L. , Underwood Willie 
Published: March 2011

AbstractBACKGROUND:Black and Hispanic men have a lower prostate cancer (PCa) survival rate than white men. This racial/ethnic survival gap has been explained in part by differences in tumor characteristics, stage at diagnosis, and disparities in receipt of definitive treatment. Another potential contributing factor is racial/ethnic differences in the timely and accurate detection of lymph node metastases. The current study was conducted to examine the association between race/ethnicity and the receipt of pelvic lymph node dissection (PLND) among men with localized/regional PCa.METHODS:Logistic regression was used to estimate the adjusted odds of undergoing PLND among men who were diagnosed during 2000 to 2002 with PCa, who underwent radical prostatectomy or PLND without radical prostatectomy, and who were diagnosed in regions covered by the Surveillance, Epidemiology, and End Results database (n = 40,848).RESULTS:Black men were less likely to undergo PLND than white men (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.84‐0.98). When the analysis was stratified by PCa grade, black men with well differentiated PCa (OR, 0.48; 95% CI, 0.27‐0.84) and poorly differentiated PCa (OR, 0.73; 95% CI, 0.60‐0.89) were less likely to undergo PLND than their white counterparts, but racial differences were not observed among men with moderately differentiated PCa (OR, 0.96; 95% CI, 0.88‐1.05).CONCLUSIONS:Among men with poorly differentiated PCa, failure to undergo PLND was associated with worse survival. Racial disparities in the receipt of PLND, especially among men with poorly differentiated PCa, may contribute to racial differences in prostate cancer survival. Cancer 2011;. © 2011 American Cancer Society.
A phase 1/2 study of orally administered synthetic hypericin for treatment of recurrent malignant gliomas
Authors: Couldwell William T. , Surnock Amy A. , Tobia Alfonso J. , Cabana Bernard E. , Stillerman Charles B. , Forsyth Peter A. , Appley Alan J. , Spence Alexander M. , Hinton David R. , Chen Thomas C. 
Published: March 2011

AbstractBACKGROUND:Hypericin is a potent inhibitor of glioma growth in vitro. To examine whether synthetic oral hypericin can be tolerated by patients with recurrent malignant gliomas (anaplastic astrocytoma and glioblastoma) and to investigate its efficacy against these tumors, the authors undertook an open‐label, sequential dose escalation/de‐escalation tolerance study.METHODS:Patients with documented recurrent or progressive malignant gliomas who had received standard radiation therapy with or without chemotherapy were included. Patients were excluded for previous treatment with agents known to contain hypericin or treatment within 30 days with medications known to cause photosensitivity. Enrolled patients were given gradually increasing dosages of oral synthetic hypericin (0.05‐0.50 mg/kg) for up to 3 months if no toxicity was observed, and patient response to treatment was noted. The patients were examined each month and underwent magnetic resonance imaging to evaluate tumor status at 3 months.RESULTS:Synthetic hypericin administered orally appeared to provide stabilization or a slight (<50%) decrease in tumor volume (coded as stable disease) at 3 months for 7 of 42 patients (17%) and produced a tumor reduction >50% (partial response) in 2 patients (5%). Seventeen patients (40%) survived for 3 months on daily synthetic hypericin at dose levels of 0.33 ± 0.070 mg/kg daily. The mean maximum tolerated dose was 0.40 ± 0.098 mg/kg daily. Twelve patients continued on hypericin therapy beyond 3 months. The median survival was 26 weeks (Kaplan‐Meier method).CONCLUSIONS:The results of this study indicated that synthetic, oral hypericin is well tolerated in this patient group. The response results were comparable to those reported from other studies of salvage therapies for recurrent malignant brain tumors. Cancer 2011;. © 2011 American Cancer Society.
Morphologic integration of hilar ectopic granule cells into dentate gyrus circuitry in the pilocarpine model of temporal lobe epilepsy
Authors: Cameron Michael C. , Zhan Ren‐Zhi , Nadler J. Victor 
Published: March 2011

AbstractAfter pilocarpine‐induced status epilepticus, many granule cells born into the postseizure environment migrate aberrantly into the dentate hilus. Hilar ectopic granule cells (HEGCs) are hyperexcitable and may therefore increase circuit excitability. This study determined the distribution of their axons and dendrites. HEGCs and normotopic granule cells were filled with biocytin during whole‐cell patch clamp recording in hippocampal slices from pilocarpine‐treated rats. The apical dendrite of 86% of the biocytin‐labeled HEGCs extended to the outer edge of the dentate molecular layer. The total length and branching of HEGC apical dendrites that penetrated the molecular layer were significantly reduced compared with apical dendrites of normotopic granule cells. HEGCs were much more likely to have a hilar basal dendrite than normotopic granule cells. They were about as likely as normotopic granule cells to project to CA3 pyramidal cells within the slice, but were much more likely to send at least one recurrent mossy fiber into the molecular layer. HEGCs with burst capability had less well‐branched apical dendrites than nonbursting HEGCs, their dendrites were more likely to be confined to the hilus, and some exhibited dendritic features similar to those of immature granule cells. HEGCs thus have many paths along which to receive synchronized activity from normotopic granule cells and to transmit their own hyperactivity to both normotopic granule cells and CA3 pyramidal cells. They may therefore contribute to the highly interconnected granule cell hubs that have been proposed as crucial to development of a hyperexcitable, potentially seizure‐prone circuit. J. Comp. Neurol. 519:2175–2192, 2011. © 2011 Wiley‐Liss, Inc.
Axonal projections of medullary swallowing neurons in guinea pigs
Authors: Sugiyama Yoichiro , Shiba Keisuke , Nakazawa Ken , Suzuki Takeshi , Umezaki Toshiro , Ezure Kazuhisa , Abo Naoko , Yoshihara Toshio , Hisa Yasuo 
Published: March 2011

AbstractA central pattern generator (CPG) for swallowing in the medulla oblongata generates spatially and temporally coordinated movements of the upper airway and alimentary tract. To reveal the medullary neuronal network of the swallowing CPG, we examined the cytoarchitecture of the swallowing CPG and axonal projections of its individual neurons by extracellular recording and juxtacellular labeling of swallowing‐related neurons (SRNs) in the medulla in urethane‐anesthetized and paralyzed guinea pigs. Three major types of neuronal discharge patterns were identified during fictive swallowing induced by stimulation of the superior laryngeal nerve: early (burst‐like activation during the pharyngeal stage), late (activation after the pharyngeal stage), and inhibited (inhibition during the pharyngeal stage) types. Sixteen neurons were successfully labeled in the nucleus tractus solitarii (NTS) and in the medullary reticular formation (RF). No motoneuron was labeled. The SRNs in the NTS had axons projecting to the NTS, RF, nucleus ambiguus, nucleus hypoglossus, and dorsal motor nucleus of the vagus on the ipsilateral side. Some NTS SRNs projected only within the NTS. The axons of SRNs in the RF projected also to the NTS, RF, motor nuclei on the ipsilateral side, and to the other side RF. These findings show anatomic substrates for the neuronal network of the CPG for swallowing, which consists of complex neuronal connections among SRNs in the NTS, RF, and motor nuclei. J. Comp. Neurol. 519:2193–2211, 2011. © 2011 Wiley‐Liss, Inc.
Long‐term changes in the morphology and synaptic distributions of adult‐born neurons
Authors: Livneh Yoav , Mizrahi Adi 
Published: March 2011

AbstractThe adult mammalian olfactory bulb (OB) is continuously supplied with adult‐born neurons. While some new neurons die shortly after arrival into the OB, others persist throughout the life of the animal. Here we followed the long‐term morphological changes in adult‐born periglomerular neurons and granule cells from the mouse OB well after they mature. We present a dataset of dendritic morphology and synaptic distributions from >100 adult‐born neurons as imaged in vivo and reconstructed in 3D. The dataset currently includes a substantial range of neuronal ages (0.5–11 months old). Using this dataset, we show that the morphological steady‐state which adult‐born periglomerular neurons reach soon after maturation is not maintained in older neurons. Rather, total dendritic length decreases after 6 months of age. We find that this morphological decrease in “old” periglomerular neurons is regulated by the age of the animal, and is independent of neuronal age. This suggests that morphological development of adult‐born neurons is regulated extrinsically. Our dendritic morphology dataset of 3D reconstructions is made available to the scientific community so it may serve as a useful resource for comparative morphological studies of the OB, and in particular of adult neurogenesis. J. Comp. Neurol. 519:2212–2224, 2011. © 2011 Wiley‐Liss, Inc.
Localization of cerebellin‐2 in late embryonic chicken brain: Implications for a role in synapse formation and for brain evolution
Authors: Reiner Anton , Yang Mao , Cagle Michael C. , Honig Marcia G. 
Published: March 2011

AbstractCerebellin‐1 (Cbln1), the most studied member of the cerebellin family of secreted proteins, is necessary for the formation and maintenance of parallel fiber–Purkinje cell synapses. However, the roles of the other Cblns have received little attention. We previously identified the chicken homolog of Cbln2 and examined its expression in dorsal root ganglia and spinal cord (Yang et al. [2010] J Comp Neurol 518:2818–2840). Interestingly, Cbln2 is expressed by mechanoreceptive and proprioceptive neurons and in regions of the spinal cord where those afferents terminate, as well as by preganglionic sympathetic neurons and their sympathetic ganglia targets. These findings suggest that Cbln2 may demonstrate a tendency to be expressed by synaptically connected neuronal populations. To further assess this possibility, we examined Cbln2 expression in chick brain. We indeed found that Cbln2 is frequently expressed by synaptically connected neurons, although there are exceptions, and we discuss the implications of these findings for Cbln2 function. Cbln2 expression tends to be more common in primary sensory neurons and in second‐order sensory regions than it is in motor areas of the brain. Moreover, we found that the level of Cbln2 expression for many regions of the chicken brain is very similar to that of the mammalian homologs, consistent with the view that the expression patterns of molecules playing fundamental roles in processes such as neuronal communication are evolutionarily conserved. There are, however, large differences in the pattern of Cbln2 expression in avian as compared to mammalian telencephalon and in other regions that show the most divergence between the two lineages. J. Comp. Neurol. 519:2225–2251, 2011. © 2011 Wiley‐Liss, Inc.
Nerve growth factor promoter activity revealed in mice expressing enhanced green fluorescent protein
Authors: Kawaja Michael D. , Smithson Laura J. , Elliott Janet , Trinh Gina , Crotty Anne‐Marie , Michalski Bernadeta , Fahnestock Margaret 
Published: March 2011

AbstractNerve growth factor (NGF) and its precursor proNGF are perhaps the best described growth factors of the mammalian nervous system. There remains, however, a paucity of information regarding the precise cellular sites of proNGF/NGF synthesis. Here we report the generation of transgenic mice in which the NGF promoter controls the ectopic synthesis of enhanced green fluorescent protein (EGFP). These transgenic mice provide an unprecedented resolution of both neural cells (e.g., neocortical and hippocampal neurons) and non‐neural cells (e.g., renal interstitial cells and thymic reticular cells) that display NGF promoter activity from postnatal development to adulthood. Moreover, the transgene is inducible by injury. At 2 days after sciatic nerve ligation, a robust population of EGFP‐positive cells is seen in the proximal nerve stump. These transgenic mice offer novel insights into the cellular sites of NGF promoter activity and can be used as models for investigating the regulation of proNGF/NGF expression after injury. J. Comp. Neurol. 519:2522–2545, 2011. © 2011 Wiley‐Liss, Inc.
Synaptotagmins I and II in the developing rat auditory brainstem: Synaptotagmin I is transiently expressed in glutamate‐releasing immature inhibitory terminals
Authors: Cooper Alan P. , Gillespie Deda C. 
Published: March 2011

AbstractThe lateral superior olive (LSO), a nucleus in the auditory brainstem, computes interaural intensity differences for sound localization by comparing converging excitatory and inhibitory inputs that carry tonotopically matched information from the two ears. Tonotopic refinement in the inhibitory projection pathway from the medial nucleus of the trapezoid body (MNTB) is known to be established during the first postnatal week in rats. During this period, immature MNTB terminals in the LSO contain vesicular transporters for both inhibitory and excitatory amino acids and release glutamate. The primary Ca2+ sensors for vesicular release in the CNS are understood to be synaptotagmins, and in adult auditory brainstem synaptotagmin 2 is the predominant synaptotagmin. We asked here whether a different Ca2+ sensor might be expressed in the immature auditory brainstem. We have found that synaptotagmin 1 is indeed expressed transiently in the immature auditory brainstem, most highly in those areas that receive glutamate‐releasing immature inhibitory inputs from the MNTB, and that during the first postnatal week synaptotagmin 1 co‐localizes with the vesicular glutamate transporter VGLUT3, a marker of glutamate‐releasing immature inhibitory terminals from the MNTB. We suggest that immature MNTB terminals may contain two populations of synaptic vesicles, one expressing the vesicular inhibitory amino acid transporter together with synaptotagmin 2 and another expressing VGLUT3 together with synaptotagmin 1. Because Ca2+ sensing is an important determinant of release properties for the presynaptic terminal, differential expression of the synaptotagmins might allow the differential release of excitatory and inhibitory neurotransmitters in response to differing patterns of neural activity. J. Comp. Neurol. 519:2417–2433, 2011. © 2011 Wiley‐Liss, Inc.
Vasopressin innervation of the mouse (Mus musculus) brain and spinal cord
Authors: Rood Benjamin D. , De Vries Geert J. 
Published: March 2011

AbstractThe neuropeptide vasopressin (AVP) has been implicated in the regulation of numerous physiological and behavioral processes. Although mice have become an important model for studying this regulation, there is no comprehensive description of AVP distribution in the mouse brain and spinal cord. With C57BL/6 mice, we used immunohistochemistry to corroborate the location of AVP‐containing cells and to define the location of AVP‐containing fibers throughout the mouse central nervous system. We describe AVP‐immunoreactive (‐ir) fibers in midbrain, hindbrain, and spinal cord areas, which have not previously been reported in mice, including innervation of the ventral tegmental area, dorsal and median raphe, lateral and medial parabrachial, solitary, ventrolateral periaqueductal gray, and interfascicular nuclei. We also provide a detailed description of AVP‐ir innervation in heterogenous regions such as the amygdala, bed nucleus of the stria terminalis, and ventral forebrain. In general, our results suggest that, compared with other species, the mouse has a particularly robust and widespread distribution of AVP‐ir fibers, which, as in other species, originates from a number of different cell groups in the telencephalon and diencephalon. Our data also highlight the robust nature of AVP innervation in specific regulatory nuclei, such as the ventral tegmental area and dorsal raphe nucleus among others, that are implicated in the regulation of many behaviors. J. Comp. Neurol. 519:2434–2474, 2011. © 2011 Wiley‐Liss, Inc.
Colocalization of hyperpolarization‐activated, cyclic nucleotide‐gated channel subunits in rat retinal ganglion cells
Authors: Stradleigh Tyler W. , Ogata Genki , Partida Gloria J. , Oi Hanako , Greenberg Kenneth P. , Krempely Kalen S. , Ishida Andrew T. 
Published: March 2011

AbstractThe current‐passing pore of mammalian hyperpolarization‐activated, cyclic nucleotide‐gated (HCN) channels is formed by subunit isoforms denoted HCN1–4. In various brain areas, antibodies directed against multiple isoforms bind to single neurons, and the current (Ih) passed during hyperpolarizations differs from that of heterologously expressed homomeric channels. By contrast, retinal rod, cone, and bipolar cells appear to use homomeric HCN channels. Here, we assess the generality of this pattern by examining HCN1 and HCN4 immunoreactivity in rat retinal ganglion cells, measuring Ih in dissociated cells, and testing whether HCN1 and HCN4 proteins coimmunoprecipitate. Nearly half of the ganglion cells in whole‐mounted retinae bound antibodies against both isoforms. Consistent with colocalization and physical association, 8‐bromo‐cAMP shifted the voltage sensitivity of Ih less than that of HCN4 channels and more than that of HCN1 channels, and HCN1 coimmunoprecipitated with HCN4 from membrane fraction proteins. Finally, the immunopositive somata ranged in diameter from the smallest to the largest in rat retina, the dendrites of immunopositive cells arborized at various levels of the inner plexiform layer and over fields of different diameters, and Ih activated with similar kinetics and proportions of fast and slow components in small, medium, and large somata. These results show that different HCN subunits colocalize in single retinal ganglion cells, identify a subunit that can reconcile native Ih properties with the previously reported presence of HCN4 in these cells, and indicate that Ih is biophysically similar in morphologically diverse retinal ganglion cells and differs from Ih in rods, cones, and bipolar cells. J. Comp. Neurol. 519:2546–2573, 2011. © 2011 Wiley‐Liss, Inc.
Molecular and neuroanatomical characterization of single neurons in the mouse medullary gigantocellular reticular nucleus
Authors: Martin E.M. , Devidze N. , Shelley D.N. , Westberg L. , Fontaine C. , PFAFF D.W. 
Published: March 2011

AbstractMedullary gigantocellular reticular nucleus (mGi) neurons have been ascribed a variety of behaviors, many of which may fall under the concepts of either arousal or motivation. Despite this, many details of the connectivity of mGi neurons, particularly in reference to those neurons with ascending axons, remain unknown. To provide a neuroanatomical and molecular characterization of these cells, with reference to arousal and level‐setting systems, large medullary reticular neurons were characterized with retrograde dye techniques and with real‐time reverse transcriptase PCR (RT‐PCR) analyses of single‐neuron mRNA expression in the mouse. We have shown that receptors consistent with participation in generalized arousal are expressed by single mGi neurons and that receptors from different families of arousal‐related neurotransmitters are rarely coexpressed. Through retrograde labeling, we have shown that neurons with ascending axons and neurons with descending axons tend to form like‐with‐like clusters, a finding that is consistent across age and gender. In comparing the two groups of retrogradely labeled neurons in neonatal animals, those neurons with axons that ascend to the midbrain show markers for GABAergic or coincident GABAergic and glutamatergic function; in contrast, approximately 60% of the neurons with axons that descend to the spinal cord are glutamatergic. We discuss the mGi's relationship to the voluntary and emotional motor systems and speculate that neurons in the mGi may represent a mammalian analogue to Mauthner cells, with a separation of function for neurons with ascending and descending axons. J. Comp. Neurol. 519:2574–2593, 2011. © 2011 Wiley‐Liss, Inc.
CD117+CD3−CD56−OX40Lhigh cells express IL‐22 and display an LTi phenotype in human secondary lymphoid tissues
Authors: Kim Soochan , Han Sinsuk , Withers David R. , Gaspal Fabrina , Bae Jingyu , Baik Song , Shin Hyun‐Chool , Kim Kyung‐Su , Bekiaris Vasileios , Anderson Graham , Lane Peter , Kim Mi‐Yeon 
Published: March 2011

AbstractHere, we identify cells within human adult secondary lymphoid tissues that are comparable in phenotype and location to the lymphoid tissue inducer (LTi) cells that persist in the adult mouse. Identified as CD117+CD3−CD56− cells, like murine LTi cells, they lack expression of many common lineage markers and express CD127, OX40L and TRANCE. These cells were detected at the interface between the B‐ and T‐ zones, as well as at the subcapsular sinus in LNs, the location where LTi cells reside in murine spleen and LNs. Furthermore, like murine LTi cells, these cells expressed high levels of IL‐22 and upregulated IL‐22 expression upon IL‐23 stimulation. Importantly, these cells were not an NK cell subset since they showed no expression of IFN‐γ and perforin. Interestingly, a subset of the CD117+CD3−CD56−OX40L+ population expressed NKp46, again similar to recent findings in mice. Finally, these cells supported memory CD4+ T‐cell survival in an OX40L‐dependent manner. Combined, these data indicate that the CD117+CD3−CD56−OX40L+ cells in human secondary lymphoid tissues are comparable in phenotype, location and function to the LTi cells that persist within adult murine secondary lymphoid tissues.