bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Click Approach to Structurally Diverse Conjugates Containing a Central Di‐1,2,3‐triazole Metal Chelate
Authors: Mindt Thomas L. , Schweinsberg Christian , Brans Luc , Hagenbach Adelheid , Abram Ulrich , Tourwé Dirk , Garcia‐Garayoa Elisa , Schibli Roger 
Published: February 2009

AbstractAssemble & chelate: Click chemistry enables the efficient and selective synthesis of structurally diverse conjugates containing a central di‐1,2,3‐triazole chelator for complexation with [99mTc(CO)3]+. Use of appropriate building blocks allows the modulation of pharmacological relevant characteristics of the conjugate, or the introduction of secondary probes suitable for imaging modalities other than single photon emission computed tomography (SPECT).magnified imageThe selective and efficient synthesis of novel tridentate metal chelating systems containing two 1,4‐disubstituted 1,2,3‐triazole heterocycles obtained via the copper(I)‐catalyzed cycloaddition of alkynes and azides (click reaction) is described. The constructs are shown to be efficient ligand systems for the chelation of fac‐[M(CO)3(H2O)3]+ (M=99mTc, Re) yielding well‐ defined and stable complexes. The organometallic 99mTc conjugates are suitable for application as diagnostic radiotracers for single photon emission computed tomography (SPECT) as demonstrated in vivo with a fragment of the tumor‐targeting bombesin peptide functionalized with a di‐1,2,3‐triazole chelator and radiolabeled with [99mTc(CO)3]+. Starting from readily available dialkyne precursors, the central chelating systems are formed as the conjugates are assembled by click reaction with azide‐functionalized entities. Depending on the nature of the azide substrates employed (e.g. lipophilic or hydrophilic residues) pharmacologically relevant characteristics of the final metal conjugate such as hydrophilicity or overall charge can be readily modulated. The procedures described also enable the facile introduction of other probes into the metal conjugate, providing access to potential multimodal imaging agents.
Adjuvant chemotherapy for the “oldest old” ovarian cancer patients
Authors: Moore Kathleen N. , Frank Summer G. , Alward Erin K. , Landrum Lisa M. , Myers Tashanna K. , Walker Joan L. , Gold Michael A. , McMeekin D. Scott , Vesely Sara K. , Mannel Robert S. 
Published: February 2009

AbstractBACKGROUND:Patients aged ≥80 years who are diagnosed with advanced ovarian cancer (OC) have been reported to have a poor prognosis. In the current study, chemotherapy‒related toxicity data were evaluated between patients aged ≥80 years and those aged <80 years.METHODS:Patients with OC who underwent cytoreductive surgery with chemotherapy were included. Self‐reported toxicity data were obtained from National Cancer Institute Common Toxicity Criteria (CTC) forms. Objective indicators of status including albumin level, weight, and creatinine clearance were abstracted both before and after therapy. Data were compared between patients by decade of age.RESULTS:A total of 246 patients were included. A presenting Karnofsky performance status >2 was recorded in 17% of patients aged ≥80 years versus 0% to 4% of patients aged <80 years (P = .002). Platinum‐based chemotherapy was used in all patients. For patients aged <80 years, combination chemotherapy was used in >90% versus 69% in those aged ≥80 years (P < .0001). Standard‒dose combination therapy was used in 72% to 86% of patients aged <80 years versus 28% of patients aged ≥80 years (P < .0001). Patients aged ≥80 years completed ≥6 cycles of therapy approximately 57% of the time versus 84% to 97% of the time for those aged <80 years (P = .0001). CTC forms identified no self‐reported toxicities to be more common among patients aged ≥80 years. Multivariate logistic regression identified creatinine clearance <65 mL/minute (odds ratio [OR] of 4.6), 5% weight loss (OR of 2.5), prechemotherapy albumin level of <2 g/dL (OR of 3.65), and initiation of therapy with a single agent (OR of 3.9) as independent predictors of failure to complete chemotherapy.CONCLUSIONS:Despite initial treatment modifications as well as toxicity assessment, only 57% of patients aged ≥80 years completed planned chemotherapy. It was confirmed that further studies into the pharmacokinetics of chemotherapy in the elderly and more sensitive assessment of therapy‒related toxicity are required. Cancer 2009. © 2009 American Cancer Society.
Mandatory second opinion in cytopathology
Authors: Lueck Nathan , Jensen Chris , Cohen Michael B. , Weydert Jamie A. 
Published: February 2009

AbstractBACKGROUND:Mandatory review of outside pathologic material is intended to detect interpretive errors that may have a clinically significant impact on patient care. Prior to definitive treatment of referred patients, the University of Iowa Carver College of Medicine requires a review of pertinent pathologic material previously obtained at outside institutions. The aims of this study were to determine if this local standard of practice has a measurable impact on patient care.METHODS:The pathologic diagnoses of 499 second opinion cytology cases seen at the University of Iowa Carver College of Medicine were studied. Each second opinion was classified as “no diagnostic disagreement”, “minor disagreement”, or “major disagreement” with respect to the originating institution's interpretation. The clinical impact of major disagreement cases was determined by pathologic and clinical follow‐up via chart review.RESULTS:Second opinion cytology resulted in 37 cases (7.4% of total cases) with major diagnostic disagreements. Clinical and pathologic follow‐up was available in 30 of the major disagreement cases; second opinion diagnosis was better supported in 22 of these cases compared to the outside diagnosis. The second opinion in 6 major disagreement cases prompted changes in clinical management.CONCLUSIONS:Major disagreements in second opinion cytology are common, likely reflective of the challenges inherent in the interpretation of cytologic specimens. Although mandatory second opinion of outside cytologic material prompted changes in clinical management in only a small fraction of cases (1.2%), this rate was similar to those previously published for surgical pathology second opinion. These findings support the notion that mandatory second opinion policy as an important part of patient care. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.
Distribution of growth hormone‐releasing hormone‐like peptide: Immunoreactivity in the central nervous system of the adult zebrafish (Danio rerio)
Authors: Castro Antonio , Becerra Manuela , Manso María Jesús , Tello Javier , Sherwood Nancy M. , Anadón Ramón 
Published: February 2009

AbstractThe distribution of growth hormone‐releasing hormone‐like peptides (GHRH‐LP) in the central nervous system of the zebrafish was investigated by using immunohistochemical techniques with polyclonal antibodies. ELISAs showed that the antiserum raised against salmon (s)GHRH‐LP recognized both zebrafish GHRH‐LP1 and ‐2, whereas the antiserum raised against carp (c)GHRH‐LP was more sensitive but detected only zebrafish GHRH‐LP1. Neither antiserum detected the true GHRH. Large cells in the nucleus lateralis tuberis were immunoreactive with both antisera, which suggests that they contained zebrafish GHRH‐LP1, but not excluding GHRH‐LP2. Also, immunoreactive fibers, which putatively originated from these hypothalamic neurons, were present in the hypophysis; both antisera detected fibers, although only sGHRH‐LP antiserum stained fibers in the neurointermediate lobe. These fibers may have a neuroendocrine role. Candidates for a role in feeding include several areas in which both antisera labeled cells and fibers, implying a strong reaction for GHRH‐LP1 and possibly GHRH‐LP2. These areas include the isthmus with cells in the secondary gustatory/visceral nucleus, which were also calretinin immunoreactive. Numerous GHRH‐LP‐immunoreactive fibers (also labeled by both antisera) probably originate from the gustatory/visceral nucleus to innervate the ventral area of the telencephalon, preglomerular nuclei, torus lateralis and hypothalamic diffuse nucleus, habenula, torus semicircularis, and dorsolateral funiculus of the spinal cord. Present results in the zebrafish brain suggest involvement of GHRH‐LP in both neuroendocrine and feeding‐associated nervous circuits. The present data on the location of the two GHRH‐LPs are the first clue to the possible functions of these two hormones. J. Comp. Neurol. 513:685–701, 2009. © 2009 Wiley‐Liss, Inc.
Widespread changes in dendritic and axonal morphology in Mecp2‐mutant mouse models of rett syndrome: Evidence for disruption of neuronal networks
Authors: Belichenko Pavel V. , Wright Elena E. , Belichenko Nadia P. , Masliah Eliezer , Li Hong Hua , Mobley William C. , Francke Uta 
Published: February 2009

AbstractRett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the X‐linked gene MECP2. Girls with RTT show dramatic changes in brain function, but relatively few studies have explored the structure of neural circuits. Examining two mouse models of RTT (Mecp2B and Mecp2J), we previously documented changes in brain anatomy. Herein, we use confocal microscopy to study the effects of MeCP2 deficiency on the morphology of dendrites and axons in the fascia dentata (FD), CA1 area of hippocampus, and motor cortex following Lucifer yellow microinjection or carbocyanine dye tracing. At 3 weeks of age, most (33 of 41) morphological parameters were significantly altered in Mecp2B mice; fewer (23 of 39) were abnormal in Mecp2J mice. There were striking changes in the density and size of the dendritic spines and density and orientation of axons. In Mecp2B mice, dendritic spine density was decreased in the FD (∼11%), CA1 (14–22%), and motor cortex (∼16%). A decreased spine head size (∼9%) and an increased spine neck length (∼12%) were found in Mecp2B FD. In addition, axons in the motor cortex were disorganized. In Mecp2J mice, spine density was significantly decreased in CA1 (14–26%). In both models, dendritic swelling and elongated spine necks were seen in all areas studied. Marked variation in the type and extent of changes was noted in dendrites of adjacent neurons. Electron microscopy confirmed abnormalities in dendrites and axons and showed abnormal mitochondria. Our findings document widespread abnormalities of dendrites and axons that recapitulate those seen in RTT. J. Comp. Neurol. 514:240–258, 2009. © 2009 Wiley‐Liss, Inc.
Collateral projection from the locus coeruleus to whisker‐related sensory and motor brain regions of the rat
Authors: Lee Sat‐Byol , Beak Suk K. , Park Seung H. , Waterhouse Barry D. , Lee Hyun S. 
Published: February 2009

AbstractThe primary goal of this study was to examine whether the locus coeruleus (LC) provides collateral projections to whisker‐related, sensorimotor brain regions. After injections of retrograde tracers into the primary sensory (S1) barrel field/primary whisker motor (M1) cortices, ventroposteromedial (VPM)/ventrolateral (VL) thalamic nuclei, or principal sensory trigeminal (Pr5)/facial motor (Mo7) nuclei, the distribution of double‐labeled neurons within the LC was examined. Our observations indicated that a large number of individual LC cells provided axon collaterals to S1‐M1 or VPM‐VL regions, whereas only a few projected to Pr5‐Mo7 nuclei. The laterality and the distribution of dual‐projecting LC neurons were as follows. 1) The neurons projecting to the S1‐M1 cortices were predominantly ipsilateral (96% ± 0.7%). Labeled neurons were located ventrally at the rostral pole but were evenly distributed along the dorsoventral aspect of the principal LC. 2) The cells projecting to the VPM‐VL nuclei were bilateral, with ipsilateral (68% ± 2.3%) dominance. Neurons were observed at the rostrocaudal extent of the LC, where the labeling was most pronounced at the ventral, principal LC. 3) The neurons projecting to the Pr5‐Mo7 regions exhibited slightly contralateral (56% ± 2.9%) dominance, where labeled cells were confined within the ventral margin of the principal subdivision. Taken together, the present observations demonstrate that each subdivision of the LC possesses a differential functional organization with respect to its collateral projection to whisker‐related sensorimotor targets, suggesting that the nucleus might play a modulatory role in vibrissal sensorimotor integration that allows the guidance of behavioral action essential for the survival of the animal. J. Comp. Neurol. 514:387–402, 2009. © 2009 Wiley‐Liss, Inc.
Corticofugal projections to trigeminal motoneurons innervating antagonistic jaw muscles in rats as demonstrated by anterograde and retrograde tract tracing
Authors: Yoshida Atsushi , Taki Ikuro , Chang Zheng , Iida Chie , Haque Tahsinul , Tomita Akiko , Seki Shinichiro , Yamamoto Shinya , Masuda Yuji , Moritani Masayuki , Shigenaga Yoshio 
Published: February 2009

AbstractLittle is known about the organization of corticofugal projections controlling antagonistic jaw muscles. To address this issue, we employed retrograde (Fluorogold; FG) and anterograde (biotinylated dextran amine; BDA) tracing techniques in rats. Three groups of premotoneurons were identified by injecting FG into the jaw‐closing (JC) and ‐opening (JO) subdivisions of the trigeminal motor nucleus (Vmo). These were 1) the intertrigeminal region (Vint) and principal trigeminal sensory nucleus for JC nucleus; 2) the reticular region medial to JO nucleus (RmJO) for JO nucleus; and 3) the parabrachial (Pb) and supratrigeminal (Vsup) nuclei, reticular regions medial and ventral to JC nucleus, rostrodorsomedial oralis (Vor), and juxtatrigeminal region (Vjuxt) containing a mixture of premotoneurons to both the nuclei. Subsequently, FG was injected into the representative premotoneuron structures. The JC and JO premotoneurons received main afferents from the lateral and medial agranular fields of motor cortex (Agl and Agm), respectively, whereas afferents to the nuclei with both JC and JO premotoneurons arose from Agl also and from primary somatosensory cortex (S1). Finally, BDA was injected into each of the three cortical areas representing the premotoneuron structures to complement the FG data. The Agl and Agm projected to reticular regions around the Vmo, whereas the Pb, Vsup, Vor, and Vjuxt received input from Agl. The S1 projected to the trigeminal sensory nuclei as well as to the Pb, Vsup, and Vjuxt. These results suggest that corticofugal projections to Vmo via premotoneuron structures consist of multiple pathways, which influence distinct patterns of jaw movements. J. Comp. Neurol. 514:368–386, 2009. © 2009 Wiley‐Liss, Inc.
Binge‐like postnatal alcohol exposure triggers cortical gliogenesis in adolescent rats
Authors: Helfer Jennifer L. , Calizo Lyngine H. , Dong Willie K. , Goodlett Charles R. , Greenough William T. , Klintsova Anna Y. 
Published: February 2009

AbstractThe long‐term effects of binge‐like postnatal alcohol exposure on cell proliferation and differentiation in the adolescent rat neocortex were examined. Unlike the hippocampal dentate gyrus, where proliferation of progenitors results primarily in addition of granule cells in adulthood, the vast majority of newly generated cells in the intact mature rodent neocortex appear to be glial cells. The current study examined cytogenesis in the motor cortex of adolescent and adult rats that were exposed to 5.25 g/kg/day of alcohol on postnatal days (PD) 4–9 in a binge manner. Cytogenesis was examined at PD50 (through bromodeoxyuridine [BrdU] labeling) and survival of these newly generated cells was evaluated at PD80. At PD50, significantly more BrdU‐positive cells were present in the motor cortex of alcohol‐exposed rats than controls. Confocal analysis revealed that the majority (>60%) of these labeled cells also expressed NG2 chondroitin sulfate proteoglycan (NG2 glia). Additionally, survival of these newly generated cortical cells was affected by neonatal alcohol exposure, based on the greater reduction in the number of BrdU‐labeled cells from PD50 to PD80 in the alcohol‐exposed animals compared to controls. These findings demonstrate that neonatal alcohol exposure triggers an increase in gliogenesis in the adult motor cortex. J. Comp. Neurol. 514:259–271, 2009. © 2009 Wiley‐Liss, Inc.
Distinct roles of neuropilin 1 signaling for radial and tangential extension of callosal axons
Authors: Hatanaka Yumiko , Matsumoto Tomoko , Yanagawa Yuchio , Fujisawa Hajime , Murakami Fujio , Masu Masayuki 
Published: February 2009

AbstractCortical excitatory neurons migrate from their origin in the ventricular zone (VZ) toward the pial surface. During migration, these neurons exhibit a stellate shape in the intermediate zone (IZ), transform into bipolar cells, and then initiate radial migration, extending a trailing process, which may lead to an axon. Here we examined the role of neuropilin 1 (NRP1) in these developmental events. Both NRP1 mRNA and protein were highly expressed in the IZ, where stellate‐shaped cells were located. DiI labeling experiments showed that neuronal migration occurred normally in Nrp1 mutant mice up to embryonic day (E) 14.5, the latest day to which the mutant survives, with only subtle axonal defasciculation. However, interference with Nrp1 signaling at a later stage caused pathfinding errors: when a dominant negative form of Nrp1 was electroporated into the cortical VZ cells at E12.5 or E15.5 and examined perinatally, guidance errors were found in tangential axonal extension toward the midline. In contrast, no significant effect was noted on the migration of cortical excitatory neurons. These findings indicate that NRP1 plays an important role in the guidance of callosal axons originating from cortical excitatory neurons but does not support a role in their migration. Moreover, insofar as radial axonal extension within the cortical plate was unaffected, the present findings imply that molecular mechanisms for the axonal extension of excitatory neurons within the cortical plate are distinct from those in the white matter. J. Comp. Neurol. 514:215–225, 2009. © 2009 Wiley‐Liss, Inc.
Human neural stem cell grafts in the spinal cord of SOD1 transgenic rats: Differentiation and structural integration into the segmental motor circuitry
Authors: Xu Leyan , Ryugo David K. , Pongstaporn Tan , Johe Karl , Koliatsos Vassilis E. 
Published: February 2009

AbstractCell replacement strategies for degenerative and traumatic diseases of the nervous system depend on the functional integration of grafted cells into host neural circuitry, a condition necessary for the propagation of physiological signals and, perhaps, targeting of trophic support to injured neurons. We have recently shown that human neural stem cell (NSC) grafts ameliorate motor neuron disease in SOD1 transgenic rodents. Here we study structural aspects of integration of neuronally differentiated human NSCs in the motor circuitry of SOD1 G93A rats. Human NSCs were grafted into the lumbar protuberance of 8‐week‐old SOD1 G93A rats; the results were compared to those on control Sprague‐Dawley rats. Using pre‐embedding immuno‐electron microscopy, we found human synaptophysin (+) terminals contacting the perikarya and proximal dendrites of host α motor neurons. Synaptophysin (+) terminals had well‐formed synaptic vesicles and were associated with membrane specializations primarily in the form of symmetrical synapses. To analyze the anatomy of motor circuits engaging differentiated NSCs, we injected the retrograde transneuronal tracer Bartha‐pseudorabies virus (PRV) or the retrograde marker cholera toxin B (CTB) into the gastrocnemius muscle/sciatic nerve of SOD1 rats before disease onset and also into control rats. With this tracing, NSC‐derived neurons were labeled with PRV but not CTB, a pattern suggesting that PRV entered NSC‐derived neurons via transneuronal transfer from host motor neurons but not via direct transport from the host musculature. Our results indicate an advanced degree of structural integration, via functional synapses, of differentiated human NSCs into the segmental motor circuitry of SOD1‐G93A rats. J. Comp. Neurol. 514:297–309, 2009. © 2009 Wiley‐Liss, Inc.
The GABAergic system in the retina of neonate and adultOctodon degus, studied by immunohistochemistry and electroretinography
Authors: Delgado Luz M. , Vielma Alex H. , Kähne Thilo , Palacios Adrián G. , Schmachtenberg Oliver 
Published: February 2009

AbstractIn the vertebrate retina, gamma‐aminobutyric acid (GABA) mediates inhibitory processes that shape the visual response and is also thought to have neurotrophic functions during retinal development. To investigate the role of GABAergic signaling at the beginning of visual experience, we used immunohistochemistry to compare the distribution of GABA, the two isoforms of glutamic acid decarboxylase GAD65/67, and the GABA receptor types A, B, and C, in neonate versus adultOctodon degus, a native South American rodent with diurnal‐crepuscular activity and a high cone‐to‐rod ratio. In parallel, we used electroretinography to evaluate retinal functionality and to test the contribution of fast GABAergic transmission to light responses at both developmental stages. NeonateO. degusopened their eyes on postnatal day (P)0 and displayed an adult‐like retinal morphology at this time. GABA, its biosynthetic sources, and receptors had a similar cellular distribution in neonates and adults, but labeling of the outer plexiform layer and of certain amacrine and ganglion cells was more conspicuous at P0. In neonates, retinal sensitivity was 10 times lower than in adults, responses to ultraviolet light could not be detected, and oscillatory potentials were reduced or absent. Blockade of GABAA/Creceptors by bicuculline and TPMPA had no noticeable effect in neonates, while it significantly altered the electroretinogram response in adults. Conclusion: In spite of modest differences regarding retinal morphology and GABAergic expression, overall light response properties and GABAergic signaling are undeveloped in neonateO. deguscompared to adults, suggesting that full retinal functionality requires a period of neural refinement under visual experience. J. Comp. Neurol. 514:459–472, 2009. © 2009 Wiley‐Liss, Inc.
Leptin targets in the mouse brain
Authors: Scott Michael M. , Lachey Jennifer L. , Sternson Scott M. , Lee Charlotte E. , Elias Carol F. , Friedman Jeffrey M. , Elmquist Joel K. 
Published: February 2009

AbstractThe central actions of leptin are essential for homeostatic control of adipose tissue mass, glucose metabolism, and many autonomic and neuroendocrine systems. In the brain, leptin acts on numerous different cell types via the long‐form leptin receptor (LepRb) to elicit its effects. The precise identification of leptin's cellular targets is fundamental to understanding the mechanism of its pleiotropic central actions. We have systematically characterized LepRb distribution in the mouse brain using in situ hybridization in wildtype mice as well as by EYFP immunoreactivity in a novel LepRb‐IRES‐Cre EYFP reporter mouse line showing high levels of LepRb mRNA/EYFP coexpression. We found substantial LepRb mRNA and EYFP expression in hypothalamic and extrahypothalamic sites described before, including the dorsomedial nucleus of the hypothalamus, ventral premammillary nucleus, ventral tegmental area, parabrachial nucleus, and the dorsal vagal complex. Expression in insular cortex, lateral septal nucleus, medial preoptic area, rostral linear nucleus, and in the Edinger‐Westphal nucleus was also observed and had been previously unreported. The LepRb‐IRES‐Cre reporter line was used to chemically characterize a population of leptin receptor‐expressing neurons in the midbrain. Tyrosine hydroxylase and Cre reporter were found to be coexpressed in the ventral tegmental area and in other midbrain dopaminergic neurons. Lastly, the LepRb‐IRES‐Cre reporter line was used to map the extent of peripheral leptin sensing by central nervous system (CNS) LepRb neurons. Thus, we provide data supporting the use of the LepRb‐IRES‐Cre line for the assessment of the anatomic and functional characteristics of neurons expressing leptin receptor. J. Comp. Neurol. 514:518–532, 2009. © 2009 Wiley‐Liss, Inc.