bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gemcitabine and carboplatin in advanced transitional cell carcinoma of the urinary tract
Authors: Nogué‐Aliguer Miquel , Carles Joan , Arrivi Antonio , Juan Oscar , Alonso Lorenzo , Font Albert , Mellado Begoña , Garrido Pilar , Sáenz Alberto 
Published: April 2003

AbstractBACKGROUNDCisplatin‐based combinations are considered to be the standard treatment for advanced transitional cell carcinoma (TCC) of the urothelium. Many of the patients are elderly with concomitant diseases or impaired renal function. We studied the tolerance and activity of the gemcitabine/carboplatin combination as a therapeutic alternative.METHODSPatients with locally advanced or metastatic TCC of the urothelium were treated with gemcitabine 1000 mg/m2 on Days 1 and 8 and carboplatin area under the concentration‐time curve 5 on Day 1 every 21 days. Patients with creatinine clearance of 30 mL/min or above and Karnofsky performance status (KPS) scores 60 or above were enrolled.RESULTSA total of 227 cycles were administered to 41 patients, with an average of 5.5 cycles per patient (range, 1–8 cycles). Creatinine clearance was below 60 mL/min in 54% of patients, KPS was 70 or below in 37% of patients, and 37% of patients were 70 years old or older. Hematologic toxicity was mainly Grade 3/4 neutropenia in 63%, Grade 3/4 thrombocytopenia in 32%, and Grade 3/4 anemia in 54% of patients. There were only three episodes of febrile neutropenia and one death from neutropenic sepsis. Nonhematologic toxicity was mild, with asthenia as the most frequently reported event. We obtained 6 complete and 17 partial responses, for an overall response rate of 56.1% (95% confidence interval [CI], 40.6–71.6%). Progression‐free survival was 7.2 months (95% CI, 5.7–8.5) and median survival was 10.1 months (95% CI, 8.8–12.2).CONCLUSIONSThe combination of gemcitabine plus carboplatin achieves a similar result to doublets using cisplatin. It has an acceptable toxicity profile and enables patients with impaired renal function and/or poor performance status and elderly patients to be treated. Cancer 2003;97:2180–6. © 2003 American Cancer Society.DOI 10.1002/cncr.10990
A multigene test for the risk of sporadic breast carcinoma
Authors: Comings David E. , Gade‐Andavolu Radhika , Cone Lawrence A. , Muhleman Donn , MacMurray James P. 
Published: April 2003

AbstractBACKGROUNDAlthough the identification of the BRCA1 and BRCA2 genes have been of great interest, these genes account for less than 5% of all breast carcinoma cases. The remaining cases are sporadic. Reanalysis of a large twin study suggested that genetic factors may play a significant role in sporadic breast and other carcinomas. Sporadic breast carcinoma is polygenically inherited. Multiple genes are likely to have an additive effect, each gene accounting for a fraction of the variance. One factor that may have an impact on the development of hormonally responsive breast tumors is the duration of exposure of the breast to estrogen. Therefore, one of the demographic risk factors for breast carcinoma is an early age of onset of menarche. The current study was based on the hypothesis that genes that play a role in demographic risk factors may be breast carcinoma risk genes in their own right. The authors hypothesized that six genes relevant to the timing of the onset of menarche and related risk factors might be candidate genes for breast carcinoma. These were the leptin gene (LEP), the leptin receptor gene (LEPR), the catechol‐0‐methyltransferase gene (COMT), the dopamine D2 receptor gene (DRD2), the estrogen 1 receptor gene (ESR1), and the androgen receptor gene (AR).METHODSThe authors examined 67 women with postmenopausal sporadic breast carcinoma and 145 gender and race‐matched controls.RESULTSFive of these genes accounted for a significant percent of the variance (r2) of breast carcinoma. The following r2 and P values were calculated: LEP: 0.073, P ≤ 0.0001; LEPR: 0.064, P ≤ 0.0002; COMT: 0.073, P ≤ 0.0001; AR: 0.040, P ≤ 0.0035; and DRD2: 0.018, P ≤ 0.05. When evaluated in a multivariate regression analysis, they accounted collectively for 24% of the variance of breast carcinoma (P ≤ 0.0001). These genes accounted for 40% of the variance (P ≤ 0.00001) in a subset of age‐matched cases. Individual gene scores were added to form a breast carcinoma risk score (BCRS) that ranged from 0 to 17. When the BCRS was evaluated in a receiver operator characteristic plot, the area under the curve was 0.80 for the full set and 0.869 for the age‐matched set. The relative breast carcinoma risk for the different BCRS scores ranged from 0.10 to 11.9.CONCLUSIONSThese results demonstrate a potentially powerful method of evaluating the additive effect of multiple breast carcinoma risk genes to form a potentially clinically useful assessment of women's risk for sporadic breast carcinoma. Cancer 2003;97:2160–70. © 2003 American Cancer Society.DOI 10.1002/cncr.11340
Large cholinergic nerve terminals on subsets of motoneurons and their relation to muscarinic receptor type 2
Authors: Hellström Johan , Oliveira Alexandre L.R. , Meister Björn , Cullheim Staffan 
Published: April 2003

AbstractThe cholinergic C‐bouton is a large nerve terminal found exclusively apposing motoneuron cell somata and proximal dendrites. The origin and function of the C‐bouton is not known. An antiserum against the vesicular acetylcholine transporter was used to identify large cholinergic nerve terminals putatively of the C‐type in close apposition to motoneuron cell somata. This type of nerve terminal was present in the rat spinal cord ventral horn, but only in some cranial motor nuclei. Fluoro‐Gold tracing showed that subsets of spinal motoneuron cell somata were contacted by different numbers of putative C‐boutons. Thus, motoneurons innervating an intrinsic foot muscle were contacted by about half the number of cholinergic terminals found on motoneurons of the predominantly fast‐twitch gastrocnemius muscle. Slow‐twitch soleus motoneurons showed an intermediate innervation. There was a strong correlation between the presence of putative C‐boutons and muscarinic receptor 2 (m2)‐like immunoreactivity (‐LI) within a motor nucleus. By using confocal laser microscopy, the m2‐LI appeared to be confined to the motoneuron cell membrane and strongly enriched beneath the C‐type nerve terminal. Thus, our results suggested a differential distribution of large cholinergic C‐boutons, depending on motoneuron type, and that the presence of this nerve terminal type is associated with m2‐LI in the postsynaptic membrane. J. Comp. Neurol. 460:476–486, 2003. © 2003 Wiley‐Liss, Inc.
Spatiotemporal distribution of neuronal calcium sensor‐1 in the developing rat spinal cord
Authors: Kawasaki Takayuki , Nishio Takeshi , Kurosawa Hisashi , Roder John , Jeromin Andreas 
Published: April 2003

AbstractThe present study revealed the localization of neuronal calcium sensor (NCS)‐1 immunoreactivity (IR) in the developing rat spinal cord. The NCS‐1 IR first appeared at embryonic day 12 in the peripheral nerves and their somata. Intense NCS‐1 IR was expressed in ascending and descending tracts in the white matter during the late prenatal period, which gradually decreased to the faint level during postnatal development. Intense NCS‐1 IR was colocalized with growth associated protein (GAP)‐43 IR in the marginal zone and with the glutamate‐aspartate transporter (GLAST) IR in the radial processes traversing the marginal zone. In the adult rat white matter, radially oriented astrocytes and astrocytes in the glia limitans were double‐labeled for NCS‐1 and glial fibrillary acidic protein (GFAP), whereas small dots on finger‐like dendritic projections were double‐labeled for NCS‐1 and synaptophysin. In the developing gray matter, the NCS‐1 IR appeared at embryonic day 12 and gradually increased in the neuronal somata and neuropil, reaching a plateau after the end of the 4th postnatal week. The small dots in neuropil were colabeled for NCS‐1 and GFAP or NCS‐1 and synaptophysin in the adult rat gray matter. These results strongly suggest that NCS‐1 is involved in axogenesis and synaptogenesis in the developing rat spinal cord. NCS‐1 can serve as a Ca2+‐sensor not only in neurons but also in radial glial cells or even in radially oriented astrocytes in the adult rat spinal cord. J. Comp. Neurol. 460:465–475, 2003. © 2003 Wiley‐Liss, Inc.
Nectin‐dependent localization of ZO‐1 at puncta adhaerentia junctions between the mossy fiber terminals and the dendrites of the pyramidal cells in the CA3 area of adult mouse hippocampus
Authors: Inagaki Maiko , Irie Kenji , Deguchi‐Tawarada Maki , Ikeda Wataru , Ohtsuka Toshihisa , Takeuchi Masakazu , Takai Yoshimi 
Published: April 2003

AbstractNectin and afadin constitute a novel intercellular adhesion system that organizes adherens junctions in cooperation with the cadherin‐catenin system in epithelial cells. Nectin is a Ca2+‐independent immunoglobulin‐like adhesion molecule and afadin is an actin filament (F‐actin)‐binding protein that connects nectin to the actin cytoskeleton. At the puncta adhaerentia junctions (PAs) between the mossy fiber terminals and the dendrites of the pyramidal cells in the CA3 area of the adult mouse hippocampus, the nectin‐afadin system also colocalizes with the cadherin‐catenin system and has a role in the formation of synapses. ZO‐1 is another F‐actin‐binding protein that localizes at tight junctions (TJs) and connects claudin to the actin cytoskeleton in epithelial cells. The nectin‐afadin system is able to recruit ZO‐1 to the nectin‐based cell–cell adhesion sites in nonepithelial cells that have no TJs. In the present study, we investigated the localization of ZO‐1 in the mouse hippocampus. Immunofluorescence and immunoelectron microscopy revealed that ZO‐1 also localized at the PAs between the mossy fiber terminals and the dendrites of the pyramidal cells in the CA3 area of the adult mouse hippocampus, as described for afadin. ZO‐1 colocalized with afadin during the development of synaptic junctions and PAs. Microbeads coated with the extracellular fragment of nectin, which interacts with cellular nectin, recruited both afadin and ZO‐1 to the bead–cell contact sites in cultured rat hippocampal neurons. These results indicate that ZO‐1 colocalizes with nectin and afadin at the PAs and that the nectin‐afadin system is involved in the localization of ZO‐1. J. Comp. Neurol. 460:514–524, 2003. © 2003 Wiley‐Liss, Inc.
Structural characteristics and barrier properties of the choroid plexuses in developing brain of the opossum (Monodelphis Domestica)
Authors: Ek Carl Joakim , Habgood Mark David , Dziegielewska Katarzyna Magdalena , Saunders Norman Ruthven 
Published: April 2003

AbstractThe structural and functional development of the choroid plexuses, the site of the blood‐cerebrospinal fluid (CSF) barrier, in an opossum (Monodelphis domestica) was studied. Marsupial species are extremely immature at birth compared with more conventional eutherian species. Choroid plexus tissue of each brain ventricle, from early stages of development, was collected for light and electron microscopy. During development, the choroidal epithelium changes from a pseudostratified to a cuboidal layer. Individual epithelial cells appear to go through a similar maturation process even though the timing is different between and within each plexus. The ultrastructural changes during development in the choroidal epithelial cells consist of an increase in the number of mitochondria and microvilli, and changes in structure of endoplasmic reticulum. There are also changes in the core of plexuses with age. In contrast, the structure of the tight junctions between epithelial cells does not appear to change with maturation. In addition, the route of penetration for lipid insoluble molecules from blood to CSF across the choroid plexuses was examined using a small biotin‐dextran. This showed that the tight junctions already form a functional barrier in early development by preventing the paracellular movement of the tracer. Intracellular staining shows that there may be a transcellular route for these molecules through the epithelial cells from blood to CSF. Apart from lacking a glycogen‐rich stage, cellular changes in the developing opossum plexus seem to be similar to those in other species, demonstrating that this is a good model for studies of mammalian choroid plexus development. J. Comp. Neurol. 460:451–464, 2003. © 2003 Wiley‐Liss, Inc.
Expression of Prox1 defines regions of the avian otocyst that give rise to sensory or neural cells
Authors: Stone Jennifer S. , Shang Jia‐Lin , Tomarev Stanislav 
Published: April 2003

AbstractThe simple primordium of the inner ear (otocyst) differentiates into many cell types, including sensory neurons and hair cells. We examined expression of the divergent homeobox transcription factor, cProx1, during otocyst development in chickens. Nuclear cProx1 protein is not evident in the otic placode but emerges in the otic cup by stage 12. At stage 16, cProx1‐positive nuclei are scattered continuously throughout the neuroepithelium, from anteroventral to posteromedial. These labeled cells are neural precursors; they express βIII‐tubulin and migrate to the cochleovestibular ganglion between stages 13 and 21. By stage 18, two areas develop a dense pattern of cProx1 expression in which every nucleus is labeled. These areas emerge at the anterior and posterior extremes of the band of scattered cProx1 expression and express the sensory markers cSerrate1 and Cath1 by stage 23. Four discrete patches of dense cProx1 expression appear by stage 23 that correspond to the future superior crista, lateral crista, saccular macula, and posterior crista, as confirmed by immunolabeling for hair cell antigen (HCA) by stage 29. The remaining sensory epithelia display a dense pattern of cProx1 expression and label for HCA by stage 29. In the basilar papilla, nuclear cProx1 expression is down‐regulated in most hair cells by stage 37 and in many supporting cells by stage 40. Our findings show that regions of the otocyst that give rise to neurons or hair cells are distinguished by their relative density of cProx1‐positive nuclei, and suggest a role for cProx1 in the genesis of these cell types. J. Comp. Neurol. 460:487–502, 2003. Published 2003 Wiley‐Liss, Inc.
Fos expression by glutamatergic neurons of the solitary tract nucleus after phenylephrine‐induced hypertension in rats
Authors: Weston Matthew , Wang Hong , Stornetta Ruth L. , Sevigny Charles P. , Guyenet Patrice G. 
Published: April 2003

AbstractThe baroreflex pathway might include a glutamatergic connection between the nucleus of the solitary tract (NTS) and a segment of the ventrolateral medulla (VLM) called the caudal ventrolateral medulla. The main goal of this study was to seek direct evidence for such a connection. Awake rats were subjected to phenylephrine‐ (PE‐) induced hypertension (N=5) or received saline (N=5). Neuronal activation was gauged by the presence of Fos‐immunoreactive (Fos‐ir) nuclei. Fos‐ir neurons that contained vesicular glutamate transporter 2 mRNA (glutamatergic neurons) or glutamic acid decarboxylase mRNA (GABAergic neurons) were mapped throughout the medulla oblongata. Saline‐treated rats had very few Fos‐ir neurons. In PE‐treated rats, Fos‐ir neurons were detected in both NTS and VLM. In NTS, 72% of Fos‐ir neurons were glutamatergic and 26% were GABAergic. In the VLM, 41% of Fos‐ir neurons were glutamatergic and 56% were GABAergic. In VLM, Fos‐ir glutamatergic neurons were evenly distributed and were often catecholaminergic, whereas Fos‐ir GABAergic cells were clustered around Bregma −13.0 mm. This region of the VLM was injected with Fluoro‐Gold (FG) in eight rats, four of which received PE and the rest saline. Fos‐ir NTS neurons retrogradely labeled with FG were detected only in PE‐treated rats. These cells were exclusively glutamatergic and were concentrated within the NTS subnuclei that receive the densest inputs from arterial baroreceptors. In conclusion, PE, presumably via baroreceptor stimulation, induces Fos in glutamatergic and GABAergic neurons in both NTS and VLM. At least 29% of the Fos‐ir glutamatergic neurons of NTS project to the vicinity of the VLM GABAergic interneurons that are presumed to mediate the sympathetic baroreflex. J. Comp. Neurol. 460:525–541, 2003. © 2003 Wiley‐Liss, Inc.
Aging alters dendritic morphology, input resistance, and inhibitory signaling in dentate granule cells of the rhesus monkey
Authors: Luebke Jennifer I. , Rosene Douglas L. 
Published: April 2003

AbstractThe neural substrates of age‐related hippocampal dysfunction in primates are poorly understood. This issue was addressed with combined intracellular biocytin filling and whole‐cell patch clamp recordings of intrinsic membrane properties and inhibitory postsynaptic currents (IPSCs) in dentate granule cells in in vitro slices prepared from behaviorally characterized young (<11 years old) and aged (>24 years old) rhesus monkeys. Six of nine aged monkeys were significantly impaired in performance on the hippocampally mediated delayed nonmatch to sample (DNMS) task at a 2‐minute delay. Morphometric analyses showed that cells from aged monkeys had significantly reduced vertical dendritic extents and distal dendritic branching but increased proximal dendritic branching. Intrinsic membrane and action potential properties did not differ between cells from young and aged monkeys with the exception of a small but significant increase in input resistance with age. The frequency, amplitude, and rise time of γ‐aminobutyric acid (GABA)A receptor‐mediated miniature IPSCs were not significantly different in cells from young vs. aged monkeys. However, the miniature IPSC decay time constant and the benzodiazepine potentiation of this decay time constant were both significantly increased in cells from aged monkeys. These differences in the properties of dentate granule cells correlated positively with age but not specifically with impairment on the DNMS 2‐minute delay task. Nevertheless, these changes in dendritic morphology, input resistance, and inhibitory signaling properties may be part of a constellation of subtle functional changes contributing to age‐associated cognitive impairment. J. Comp. Neurol. 460:573–584, 2003. © 2003 Wiley‐Liss, Inc.
Rabbit forebrain cholinergic system: Morphological characterization of nuclei and distribution of cholinergic terminals in the cerebral cortex and hippocampus
Authors: Varga Csaba , Härtig Wolfgang , Grosche Jens , Keijser Jan , Luiten Paul G.M. , Seeger Johannes , Brauer Kurt , Harkany Tibor 
Published: April 2003

AbstractAlthough the rabbit brain, in particular the basal forebrain cholinergic system, has become a common model for neuropathological changes associated with Alzheimer's disease, detailed neuroanatomical studies on the morphological organization of basal forebrain cholinergic nuclei and on their output pathways are still awaited. Therefore, we performed quantitative choline acetyltransferase (ChAT) immunocytochemistry to localize major cholinergic nuclei and to determine the number of respective cholinergic neurons in the rabbit forebrain. The density of ChAT‐immunoreactive terminals in layer V of distinct neocortical territories and in hippocampal subfields was also measured. Another cholinergic marker, the low‐affinity neurotrophin receptor (p75NTR), was also employed to identify subsets of cholinergic neurons. Double‐immunofluorescence labeling of ChAT and p75NTR, calbindin D‐28k (CB), parvalbumin, calretinin, neuronal nitric oxide synthase (nNOS), tyrosine hydroxylase, or substance P was used to elucidate the neuroanatomical borders of cholinergic nuclei and to analyze the neurochemical complexity of cholinergic cell populations. Cholinergic projection neurons with heterogeneous densities were found in the medial septum, vertical and horizontal diagonal bands of Broca, ventral pallidum, and magnocellular nucleus basalis (MBN)/substantia innominata (SI) complex; cholinergic interneurons were observed in the caudate nucleus, putamen, accumbens nucleus, and olfactory tubercule, whereas the globus pallidus was devoid of cholinergic nerve cells. Cholinergic interneurons were frequently present in the hippocampus and to a lesser extent in cerebral cortex. Cholinergic projection neurons, except those localized in SI, abundantly expressed p75NTR, and a subset of cholinergic neurons in posterior MBN was immunoreactive for CB and nNOS. A strict laminar distribution pattern of cholinergic terminals was recorded both in the cerebral cortex and in CA1–CA3 and dentate gyrus of the hippocampus. In summary, the structural organization and chemoarchitecture of rabbit basal forebrain may be considered as a transition between that of rodents and that of primates. J. Comp. Neurol. 460:597–611, 2003. © 2003 Wiley‐Liss, Inc.
Short‐term and long‐term survival of new neurons in the rat dentate gyrus
Authors: Dayer Alexandre G. , Ford Abigail A. , Cleaver Kathryn M. , Yassaee Mina , Cameron Heather A. 
Published: April 2003

AbstractNew neurons continue to be generated in the dentate gyrus throughout adulthood. Previous studies have shown that a significant proportion of new granule cells labeled with the thymidine analogue bromodeoxyuridine (BrdU) are lost from the adult dentate gyrus within 2 weeks. How long this loss continues and the extent to which it represents cell death, as opposed to dilution of label, is unclear. To address these questions, adult rats were injected with BrdU, and BrdU labeling in the dentate gyrus was compared at several survival time points. Double labeling with BrdU and the cell cycle marker Ki‐67 showed that BrdU is detectable for up to 4 days in some cells that continue to divide, indicating that any decrease in the number of BrdU‐labeled cells after 4 days is likely to reflect cell death rather than BrdU dilution. Death of new cells in the granule cell layer occurred at a steady rate between 6 and 28 days after labeling, resulting in loss of 50% of BrdU‐labeled cells over this 22‐day period. New granule cells that survived this first month lived for at least 5 additional months. In contrast, 26% of the granule cells labeled with BrdU at the peak of dentate gyrus development on postnatal day (P) 6 died between 1 and 6 months after labeling. These findings suggest that granule cells born during adulthood that become integrated into circuits and survive to maturity are very stable and may permanently replace granule cells born during development. J. Comp. Neurol. 460:563–572, 2003. Published 2003 Wiley‐Liss, Inc.