bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concurrent cyclophosphamide, methotrexate, and 5‐fluorouracil chemotherapy and radiotherapy for breast carcinoma
Authors: Isaac Neil , Panzarella Tony , Lau Anthea , Mayers Catherine , Kirkbride Peter , Tannock Ian F. , Vallis Katherine A. 
Published: October 2002

AbstractBACKGROUNDThe current study was conducted to assess the toxicity of concurrent adjuvant cyclophosphamide, methotrexate, and 5‐fluorouracil (CMF) chemotherapy and radiotherapy (RT) for early breast carcinoma.METHODSIn the current study, the authors reviewed the records of 680 consecutive breast carcinoma patients who received adjuvant CMF at the Princess Margaret Hospital between 1980–1990. Surgery was comprised of mastectomy in 64% of patients, breast conservation in 35% of patients, and was unknown in 1% of patients. Two hundred two patients received concurrent CMF/RT that was defined as an overlap in CMF and RT administration of at least 21 days. Forty‐seven patients received sequential CMF/RT (defined as no overlap or an overlap of < 7 days in CMF and RT administration). Other patients received CMF alone. Adverse effects of RT were graded retrospectively using the Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) system. Reasons for interruption or failure to complete RT were recorded. The magnitude of chemotherapy dose reductions and delays also were noted.RESULTSThe median age of the patients was 44 years (range, 26–68 years) and 88% of the patients had lymph node‐positive disease. RT was interrupted or discontinued due to side effects in 4% of patients (95% confidence interval [95% CI], 1.7–7.7%) and 0% (95% CI, 0–7.6%), respectively, of the concurrent and sequential groups (P = 0.36). The incidence of Grade 3 or Grade 4 RT toxicity was 1.5% (95% CI, 0.3–4.3%) and 2.1% (95% CI, 0.1–11.3%), respectively, for the concurrent and sequential groups (P = 0.57). The median relative dose intensity of chemotherapy for patients receiving concurrent CMF/RT, sequential CMF/RT, and CMF alone was 0.87, 0.84, and 0.85, respectively (P = 0.22).CONCLUSIONSThe results of the current study demonstrate that the concurrent administration of CMF and RT is associated with a low risk of serious toxicity and is an acceptable adjuvant regimen for patients with breast carcinoma. Cancer 2002;95:696–703. © 2002 American Cancer Society.DOI 10.1002/cncr.10744
Treatment of micropapillary serous ovarian carcinoma (the aggressive variant of serous borderline tumors)
Authors: Seidman Jeffrey D. , Kurman Robert J. 
Published: October 2002

Ovarian serous borderline tumors recently were categorized into benign and malignant types. A subset of these tumors, termed “micropapillary serous carcinoma (MPSC),” is reported to behave in a manner similar to low‐grade carcinoma. In this issue of Cancer, Bristow et al. report their experience with 26 patients with recurrent MPSC.See also pages 677–80 and pages 791–800.
Expression of the transcription factors GATA3 and Pax2 during development of the mammalian inner ear
Authors: Lawoko‐Kerali Grace , Rivolta Marcelo N. , Holley Matthew 
Published: October 2002

AbstractThe transcription factors GATA3 and Pax2 are expressed throughout development of the mouse inner ear. We have used antibodies to study their temporal and spatial expression patterns from embryonic days E8–E16.5. The two factors show reciprocal relationships in the regional patterning of the early otocyst and cellular patterning within the sensory epithelia. GATA3 is expressed in the whole otic placode at E8. In the otocyst at E9.5–10.5, the distribution is lateral and complementary to the medial expression pattern of Pax2. Only Pax2 is expressed in the endolymphatic duct, but both factors are expressed in the cochlea. At E11.5–13.5, GATA3 is expressed strongly in the cochlea, but in the dorsal, vestibular region it is downregulated. In all sensory epithelia, downregulation coincides with sensory innervation. Pax2 is expressed in all sensory and some nonsensory epithelia, but within sensory epithelia at E16.5 it is restricted to hair cells. GATA3 is expressed throughout key periods of cell proliferation, fate determination, and differentiation and is not specifically associated with any of these processes. Expression persists most strongly in the main components of the developing auditory system. These include the auditory sensory epithelium, the afferent and efferent nerves, and the mesenchymal and ectodermal cells in regions that form key parts of the middle and outer ear. GATA3 is thus expressed in functionally distinct groups of cells that integrate to form a complete sensory system. The results suggest that both factors may be involved in tissue compartmentalisation, morphogenesis, and cell signalling. J. Comp. Neurol. 442:378–391, 2002. © 2002 Wiley‐Liss, Inc.
Glutamate transporters alterations in the reorganizing dentate gyrus are associated with progressive seizure activity in chronic epileptic rats
Authors: Gorter Jan A. , Van Vliet Erwin A. , Proper Evelien A. , De Graan Pierre N.E. , Ghijsen Wim E.J.M. , Lopes Da Silva Fernando H. , Aronica Eleonora 
Published: October 2002

AbstractThe expression of glial and neuronal glutamate transporter proteins was investigated in the hippocampal region at different time points after electrically induced status epilepticus (SE) in the rat. This experimental rat model for mesial temporal lobe epilepsy is characterized by cell loss, gliosis, synaptic reorganization, and chronic seizures after a latent period. Despite extensive gliosis, immunocytochemistry revealed only an up‐regulation of both glial transporters localized at the outer aspect of the inner molecular layer (iml) in chronic epileptic rats. The neuronal EAAC1 transporter was increased in many somata of individual CA1‐3 neurons and granule cells that had survived after SE; this up‐regulation was still present in the chronic epileptic phase. In contrast, a permanent decrease of EAAC1 immunoreactivity was observed in the iml of the dentate gyrus. This permanent decrease in EAAC1 expression, which was only observed in rats that experienced progressive spontaneous seizure activity, could lead to abnormal glutamate levels in the iml once new abnormal glutamatergic synaptic contacts are formed by means of sprouted mossy fibers. Considering the steady growth of reorganizing mossy fibers in the iml, the absence of a glutamate reuptake mechanism in this region could contribute to progression of spontaneous seizure activity, which occurs with a similar time course. J. Comp. Neurol. 442:365–377, 2002. © 2002 Wiley‐Liss, Inc.
Connections between the central posterior/prepacemaker nucleus and hypothalamic areas in the weakly electric fish Apteronotus leptorhynchus: Evidence for an indirect, but not a direct, link
Authors: Corrêa Sônia A.L. , Zupanc Günther K.H. 
Published: October 2002

AbstractThe central posterior/prepacemaker nucleus (CP/PPn) of the weakly electric fish Apteronotus leptorhynchus consists of a few thousands of neurons in the dorsal thalamus. Subpopulations of this complex play a crucial role in neural control of transient modulations of the otherwise extremely constant electric organ discharges. Because both the propensity to execute these modulations and the type of modulations produced may vary enormously with the behavioral situation, it has been hypothesized that this behavioral plasticity is, partially, mediated by peptidergic neuromodulators originating from hypothalamic areas. To define the structural basis of this proposed modulatory input, we have in the present study examined the connections between the CP/PPn proper and hypothalamic areas by employing an in vitro tract‐tracing technique. Neither anterograde nor retrograde tracing experiments could provide evidence for the existence of a direct link between the CP/PPn proper and hypothalamic areas. However, the results of our investigation suggest an indirect connection between the CP/PPn proper and two hypothalamic regions, the hypothalamus ventralis and the hypothalamus lateralis, with the preglomerular nucleus serving as a relay station. J. Comp. Neurol. 442:348–364, 2002. © 2002 Wiley‐Liss, Inc.
Patterns of expression of calcium binding proteins and neuronal nitric oxide synthase in different populations of hippocampal GABAergic neurons in mice
Authors: Jinno Shozo , Kosaka Toshio 
Published: October 2002

AbstractWe examined the expression of calcium binding proteins parvalbumin (PV), calretinin (CR), and calbindin D28K (CB), and neuronal nitric oxide synthase (nNOS) in γ‐aminobutyric acid (GABA)ergic neurons of the mouse hippocampus, with particular reference to areal and dorsoventral differences. First, we estimated the colocalization of the calcium binding proteins and nNOS. GABAergic neurons containing both PV and nNOS, i.e., PV‐immunoreactive (‐IR)/nNOS‐IR neurons, were rare in Ammon's horn but frequent in the dentate gyrus (DG). CR‐IR/nNOS‐IR neurons and CB‐IR/nNOS‐IR neurons were frequent in Ammon's horn but rare in the DG. In the entire hippocampus, the percentage of CR‐IR neurons containing nNOS was significantly higher at the ventral level (44.3%) than at the dorsal level (17.0%). The percentage of CB‐IR neurons containing nNOS was also significantly higher at the ventral level (42.3%) than at the dorsal level (29.3%). Next, we estimated the numerical densities (NDs) of calcium binding protein‐containing GABAergic neurons. The ND of PV‐IR neurons was comparable at the dorsal (1.16 × 103/mm3) and ventral levels (1.23 × 103/mm3), respectively. The ND of CR‐IR neurons was less at the dorsal level (0.52 × 103/mm3) than at the ventral level (0.64 × 103/mm3). The ND of CB‐IR neurons was also less at the dorsal level (0.91 × 103/mm3) than at the ventral level (1.57 × 103/mm3). Overall, approximately half of the GABAergic neurons contained one of the three calcium binding proteins (45% at the dorsal level and 47% at the ventral level). These data establish a baseline for examining potential roles of GABAergic neurons in hippocampal network activity in mice. J. Comp. Neurol. 449:1–25, 2002. © 2002 Wiley‐Liss, Inc.
Reduced postischemic apoptosis in the hippocampus of mice deficient in interleukin‐1
Authors: Mizushima Hidekatsu , Zhou Cheng J.i. , Dohi Kenji , Horai Reiko , Asano Masahide , Iwakura Yoichiro , Hirabayashi Takahiro , Arata Satoru , Nakajo Shigeo , Takaki Atsushi , Ohtaki Hirokazu , Shioda Seiji 
Published: October 2002

AbstractThe cytokine interleukin‐1 (IL‐1) has been implicated in ischemic brain damage, because the IL‐1 receptor antagonist markedly inhibits experimentally induced neuronal loss. However, to date, no studies have demonstrated the involvement of endogenous IL‐1α and IL‐ 1β in neurodegeneration. We report here, for the first time, that mice lacking IL‐1α/β (double knockout) exhibit markedly reduced neuronal loss and apoptotic cell death when exposed to transient cardiac arrest. Furthermore, we show that, despite the reduced neuronal loss, phosphorylation of JNK/SAPK (c‐Jun NH2‐ terminal protein kinase/stress activated protein kinase) and p38 enzymes remain elevated in IL‐1 knockout mice. In contrast, the inducible nitric oxide (iNOS) immunoreactivity after global ischemia was reduced in IL‐1 knockout mice as compared with wild‐type mice. The levels of nitrite (NO2−) and nitrate (NO3−) in the hippocampus of wild‐type mice were increased with time after ischemia‐reperfusion, whereas the increase was significantly inhibited in IL‐1 knockout mice. These observations strongly suggest that endogenous IL‐1 contributes to ischemic brain damage, and this influence may act through the release of nitric oxide by iNOS. J. Comp. Neurol. 448:203–216, 2002. © 2002 Wiley‐Liss, Inc.
WDR1 colocalizes with ADF and actin in the normal and noise‐damaged chick cochlea
Authors: Oh Seung‐Ha , Adler Henry J. , Raphael Yehoash , Lomax Margaret I. 
Published: October 2002

AbstractAuditory hair cells of birds, unlike hair cells in the mammalian organ of Corti, can regenerate following sound‐induced loss. We have identified several genes that are upregulated following such an insult. One gene, WDR1, encodes the vertebrate homologue of actin‐interacting protein 1, which interacts with actin depolymerization factor (ADF) to enhance the rate of actin filament cleavage. We examined WDR1 expression in the developing, mature, and noise‐damaged chick cochlea by in situ hybridization and immunocytochemistry. In the mature cochlea, WDR1 mRNA was detected in hair cells, homogene cells, and cuboidal cells, all of which contain high levels of F‐actin. In the developing inner ear, WDR1 mRNA was detected in homogene cells and cuboidal cells by embryonic day 7, in the undifferentiated sensory epithelium by day 9, and in hair cells at embryonic day 16. We also demonstrated colocalization of WDR1, ADF, and F‐actin in all three cell types in the normal and noise‐damaged cochlea. Immediately after acoustic overstimulation, WDR1 mRNA was seen in supporting cells. These cells contribute to the structural integrity of the basilar papilla, the maintenance of the ionic barrier at the reticular lamina, and the generation of new hair cells. These results indicate that one of the immediate responses of the supporting cell after noise exposure is to induce WDR1 gene expression and thus to increase the rate of actin filament turnover. These results suggest that WDR1 may play a role either in restoring cytoskeletal integrity in supporting cells or in a cell signaling pathway required for regeneration. J. Comp. Neurol. 448:399–409, 2002. © 2002 Wiley‐Liss, Inc.
Up‐regulation of tyrosine kinase (Trka, Trkb) receptor expression and phosphorylation in lumbosacral dorsal root ganglia after chronic spinal cord (T8–T10) injury
Authors: Qiao Liya , Vizzard Margaret A. 
Published: October 2002

AbstractPrevious studies have demonstrated changes in urinary bladder neurotrophic factors after bladder dysfunction. We have hypothesized that retrograde transport of neurotrophin(s) from the bladder to lumbosacral dorsal root ganglia (DRG) may play a role in bladder reflex reorganization after spinal cord injury (SCI). In this study, we determined whether the expression of tyrosine kinase receptors (TrkA, TrkB) is altered in lumbosacral DRG after SCI through immunofluorescence techniques. Complete transection of the spinal cord (T8–T10) was performed in female Wistar rats (120–150 g), and animals were studied 5–6 weeks after SCI. One week before killing, Fast Blue (FB) was injected into the bladder to label bladder afferent cells in the L1, L2, L6, and S1 DRG. After SCI, a significant increase in the number of TrkA‐immunoreactive (IR) positive cells was detected in the L6‐S1 DRG (L6: 1.9‐fold, P ≤ 0.01; S1: 1.7‐fold, P ≤ 0.05) and in the L1 DRG (3.0‐fold; P ≤ 0.01) but not in the L4‐L5 DRG compared with spinal‐intact (control) rats. After SCI, a significant increase in the number of TrkB‐IR cells was also detected in the L6‐S1 DRG (L6: 2.2‐fold, P ≤ 0.01; S1: 1.5‐fold, P ≤ 0.05) and in the L1‐L2 DRG (L1: 1.5‐fold, P ≤ 0.01; L2: 1.3‐fold, P ≤ 0.05) but not in the L4‐L5 DRG compared with control rats. After SCI, the percentage of FB‐labeled cells expressing TrkA immunoreactivity (∼68%) or TrkB immunoreactivity (∼65%) in L1 and L6 DRG significantly (P ≤ 0.01) increased compared with control (20–30%) DRG. After SCI, the percentage of TrkA‐IR cells expressing phosphorylated (p)‐Trk immunoreactivity significantly increased (1.5‐ to 2.3‐fold increase) in the L1, L6, and S1 DRG. The percentage of TrkB‐IR cells expressing p‐Trk immunoreactivity after SCI also increased (1.3‐fold increase) in the L1 and L6 DRG. These results demonstrate that (1) TrkA and TrkB immunoreactivity is increased in bladder afferent cells after SCI and (2) TrkA and TrkB receptors are phosphorylated in DRG after SCI. Neuroplasticity of lower urinary tract reflexes after SCI may be mediated by both nerve growth factor and brain‐derived neurotrophic factor. J. Comp. Neurol. 449:217–230, 2002. © 2002 Wiley‐Liss, Inc.
Cellular localization and development of neuronal intranuclear inclusions in striatal and cortical neurons in R6/2 transgenic mice
Authors: Meade Christopher A. , Deng Yun‐Ping , Fusco Francesca R. , Del Mar Nobel , Hersch Steven , Goldowitz Dan , Reiner Anton 
Published: October 2002

AbstractThe cellular localization and development of neuronal intranuclear inclusions (NIIs) in cortex and striatum of R6/2 HD transgenic mice were studied to ascertain the relationship of NIIs to symptom formation in these mice and gain clues regarding the possible relationship of NII formation to neuropathology in Huntington's disease (HD). All NIIs observed in R6/2 mice were ubiquitinated, and no evidence was observed for a contribution to them from wild‐type huntingtin; they were first observed in cortex and striatum at 3.5 weeks of age. In cortex, NIIs increased rapidly in size and prevalence after their appearance. Generally, cortical projection neurons developed NIIs more rapidly than cortical interneurons containing calbindin or parvalbumin. Few cortical somatostatinergic interneurons, however, formed NIIs. In striatum, calbindinergic projection neurons and parvalbuminergic interneurons rapidly formed NIIs, but they formed more gradually in cholinergic interneurons, and few somatostatinergic interneurons developed NIIs. Striatal NIIs tended to be smaller than those in cortex. The early accumulation of NIIs in cortex and striatum in R6/2 mice is consistent with the early appearance of motor and learning abnormalities in these mice, and the eventual pervasiveness of NIIs at ages at which severe abnormalities are evident is consistent with their contribution to a neuronal dysfunction underlying the abnormalities. That cortex develops larger NIIs than striatum, however, is inconsistent with the preferential loss of striatal neurons in HD but is consistent with recent evidence of early morphological abnormalities in cortical neurons in HD. That calbindinergic and parvalbuminergic striatal neurons develop large NIIs is consistent with a contribution of nuclear aggregate formation to their high degree of vulnerability in HD. J. Comp. Neurol. 449:241–269, 2002. © 2002 Wiley‐Liss, Inc.
TRPC6 immunoreactivity is colocalized with neuronal nitric oxide synthase in extrinsic fibers innervating guinea pig intrinsic cardiac ganglia
Authors: Calupca Michelle A. , Locknar Sarah A. , Parsons Rodney L. 
Published: October 2002

AbstractTachykinins depolarize guinea pig intracardiac neurons by activating nonselective cationic channels. Recently, members of the transient receptor potential family of membrane channels (TRPC) have been implicated in the generation of G protein‐coupled receptor‐activated nonselective cationic currents. We have investigated whether guinea pig cardiac neurons exhibit immunoreactivity to TRPC. Our results showed that nerve fibers within guinea pig intrinsic cardiac ganglia exhibited immunoreactivity to TRPC6. After culture of cardiac ganglia whole‐mount explants for 72 hours, the TRPC6‐IR fiber networks were absent. Therefore, the TRPC6‐IR fibers were derived from sources extrinsic to the heart. A small percentage (∼3%) of intracardiac neurons also exhibited TRPC6 immunoreactivity in control preparations, and the percentage of cells exhibiting TRPC6 immunoreactivity was not changed following explant culture for 72 hours. The few intrinsic TRPC6‐IR neurons also exhibited nitric oxide synthase (NOS) immunoreactivity, indicating that they were nitrergic as well. We compared the immunohistochemical staining patterns of TRPC6‐IR fibers with the staining patterns of a number of other neurotransmitters or neurotransmitter synthetic enzymes that mark specific extrinsic inputs to the intrinsic cardiac ganglia. The TRPC6‐IR fibers were not immunoreactive for choline acetyltransferase, tyrosine hydroxylase, or substance P. However, the TRPC6‐IR fibers exhibited immunoreactivity to neuronal NOS. Therefore, we propose that the TRPC6‐IR fibers within the guinea pig intrinsic cardiac ganglia are vagal sensory fibers that also contain NOS. We found, in support of this conclusion, that TRPC6‐IR cells were also present in sections of nodose ganglia. J. Comp. Neurol. 450:283–291, 2002. © 2002 Wiley‐Liss, Inc.
Immunolocalization of PICK1 in the ascending auditory pathways of the adult rat
Authors: McInvale Andrew C. , Staudinger Jeff , Harlan Richard E. , Garcia Meredith M. 
Published: October 2002

AbstractProtein that interacts with C‐kinase α (PICK1) is a PDZ domain protein that interacts with many binding partners in the central nervous system (CNS), including activated protein kinase Cα and subunits of the AMPA subtype of glutamate receptor. Almost nothing is known about the anatomic distribution of PICK1 in the intact adult CNS. By using PICK1 antisera and peroxidase immunocytochemistry, we report on the distribution of PICK1 in the ascending pathways of the central auditory system of the adult rat. PICK1‐immunoreactivity (ir) was observed in many component nuclei of the central auditory system, including the dorsal cochlear nucleus, anteroventral cochlear nucleus, posteroventral cochlear nucleus, some divisions of the superior olivary complex, inferior colliculus, medial geniculate body, and primary auditory cortex. The general staining pattern for PICK1‐immunoreactivity was somatodendritic with scattered puncta in neuropil and somatodendritic regions. The distribution of PICK1 partially overlaps with PKCα and glutamate receptor subunits such as GluR2. These data suggest that PICK1 may function in the regulation of PKCα and GluR2 localization in components of the rat auditory system, which may be a fundamental mechanism of synaptic transmission and/or plasticity. J. Comp. Neurol. 450:382–394, 2002. © 2002 Wiley‐Liss, Inc.
Groundwater parameter estimation via the unsteady adjoint variable formulation of discrete sensitivity analysis
Authors: Burg C. O. E. 
Published: October 2002

AbstractDiscrete sensitivity analysis (DSA) is a method that efficiently estimates the derivatives of a numerically approximated objective function with respect to a set of parameters at a fraction of the cost of using finite differences. Coupled with an optimization algorithm, this method can be used to locate the optimal set of parameters for the objective function. The time dependent adjoint variable formulation of discrete sensitivity analysis is derived and applied to a time‐dependent, two‐dimensional groundwater code. The derivatives agreed with finite difference derivatives to between 6 and 8 significant digits, at approximately ⅛ the computational cost. Using the BFGS optimization algorithm to update the parameters, the parameter estimation technique successfully identified the target values, for problems with small number of parameters. Copyright © 2002 John Wiley & Sons, Ltd.
A beam finite element for through‐cracked tubular node behaviour modelling
Authors: Rouhan A. , Wielgosz C. 
Published: October 2002

AbstractThis paper deals with the problem of a through‐cracked tubular joint behaviour modelling. A new beam finite element has been created, in order to take into account the loss of stiffness of the joint due to through‐thickness crack presence, and the coupling between axial force and bending momentum. This allows to study at a low computing time large damaged offshore structures, using beam elements. The mechanical model used to build the finite element is first described. An analytical identification of its internal parameters (eccentricity and stiffness) is then performed. Finally, some results are presented. Copyright © 2002 John Wiley & Sons, Ltd.