bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neck dissection in the combined‐modality therapy of patients with locoregionally advanced head and neck cancer
Authors: Argiris Athanassios , Stenson Kerstin M. , Brockstein Bruce E. , Mittal Bharat B. , Pelzer Harold , Kies Merrill S. , Jayaram Prathima , Portugal Louis , Wenig Barry L. , Rosen Fred R. , Haraf Daniel J. , Vokes Everett E. 
Published: April 2004

AbstractPurpose.The purpose of this study was to evaluate the role of neck lymph node (ND) in the combined dissection modality therapy for locoregionally advanced head and neck.Methods.We identified patients with N2–N3 head and neck cancers who were enrolled in three consecutive multicenter phase II studies of concurrent chemoradiotherapy utilizing 5‐fluorouracil and hydroxyurea on an alternate‐week schedule with radiotherapy twice daily plus either cisplatin (C‐FHX) or paclitaxel (T‐FHX). Patients with unknown primary tumors, nasopharyngeal or paranasal sinus primaries, nonsquamous histology, progression or death during therapy, or incomplete therapy were excluded.Results.A total of 131 patients were analyzed. Seventy‐nine percent had N2 stage. ND was performed in 92 patients (70%), either prior to enrollment (n = 31) or after chemoradiotherapy (n = 61). With a median follow‐up of 4.6 years, the 5‐year locoregional and neck progression‐free survival (PFS) rates were higher in patients with ND versus patients without ND: 88% versus 74% (p = .02) and 99% versus 82% (p = .0007). respectively; there was also a trend toward improved overall survival (OS) with ND, but PFS and distant PFS were comparable. In the subset of patients with N3 disease, ND was associated not only with better locoregional control but also with improved distant PFS. However, in patients with clinical complete response (n = 92), no significant differences in PFS (68% vs 75% at 5 years, p = .53) or any other survival parameters with or without ND were observed.Conclusions.ND improves neck control and is required for patients with clinically residual disease or N3 neck cancer but has no significant impact on the outcome of patients with N2 stage disease who are rendered clinically disease‐free with intensive concurrent chemoradiotherapy.© 2003 Wiley Periodicals, Inc. Head Neck 26: 447–455, 2004
Overexpression of p27BBP in head and neck carcinomas and their lymph node metastases
Authors: Rosso Paola , Cortesina Giorgio , Sanvito Francesca , Donadini Alessandra , Di Benedetto Barbara , Biffo Stefano , Marchisio Pier Carlo 
Published: April 2004

AbstractBackground.p27BBP is a regulator of ribosome assembly and an essential nuclear and cytoplasmic component of eukaryotes.Methods.We investigated the immunochemical distribution of p27BBP in head and neck carcinomas, in the associated normal mucosa, and in regional lymph nodes.Results.p27BBP is detectable in mucosal cells but is overexpressed in carcinomas, highly concentrated in large polymorphous nucleoli, and even larger and more evident in lymph node metastatic foci. Western blotting confirms increased p27BBP in carcinomas versus normal mucosa and also in metastatic versus normal lymph nodes. The overexpression of p27BBP corresponds to mRNA upregulation in carcinomas. Unexpectedly, a 52‐kDa band specifically reacting with antibodies to p27BBP was observed in several carcinomas.Conclusions.p27BBP alterations are common events in the transition to malignancy and are probably involved in squamous carcinoma progression. Immune reagents raised to p27BBP may provide additional diagnostic tools for surgical pathology of tumor boundaries and lymph nodes. The 52‐kDa band may represent an abnormal form of p27BBP expressed by transformed airway epithelia. © 2004 Wiley Periodicals, Inc. Head Neck 26: 408–417, 2004
Differential contributions of dorsal hippocampal subregions to memory acquisition and retrieval in contextual fear‐conditioning
Authors: Lee Inah , Kesner Raymond P. 
Published: April 2004

AbstractThe hippocampus is an essential neural structure in developing contextual memory in a situation in which rapid development of associative learning should occur. We tested a subregion‐specific contribution in the hippocampus to memory acquisition and retrieval, using the contextual fear‐conditioning paradigm. The current results suggest that all three subregions (i.e., CA3, CA1, and dentate gyrus) of the hippocampus contribute to rapid acquisition of contextual memory in the initial phase of acquisition. The involvement of CA3 seems to be important at the earliest stage of acquisition, presumably for developing instant representation of a context. The role of CA3, however, was minimal in retrieving contextual memory after a long time period (i.e., 24 h), whereas the other subregions (i.e., CA1 and dentate gyrus) were critically involved. The results indicate time‐dependent differential contributions of the hippocampal subregions to memory acquisition and retrieval in contextual fear‐conditioning. © 2004 Wiley‐Liss, Inc.
Amygdala‐kindling induces alterations in neuronal density and in density of degenerated fibers
Authors: von Bohlen und Halbach Oliver , Schulze Katrin , Albrecht Doris 
Published: April 2004

AbstractKindling is characterized by a progressive intensification of seizure activity culminating in generalized seizures following repeated administration of an initially subconvulsive electrical or chemical stimulus. Since it is known that epilepsy induces morphological alterations in the limbic system, we examined the neuropathological consequences of kindling with a sensitive silver‐staining method for the visualization of damaged neurons and Nissl staining for the estimation of the neuronal densities in different limbic areas. Wistar rats implanted with electrodes in the left basolateral nucleus were stimulated until 15 consecutive stage V seizures (scale of Racine). Amygdala‐kindled animals had reduced cell density in the amygdala and increased density of fragments of degenerated axons. Reduced neuronal density and the occurrence of degenerated axons in kindled animals were more prominent in the ipsilateral than in the contralateral hemisphere. In addition, more degenerated axons were found in cortical structures of kindled than sham‐operated animals. These results indicate that kindling induced morphological alterations that were not restricted to either the ipsilateral hemisphere or the stimulated region. These morphological changes might be responsible for the emotional and behavioral disturbances that can accompany epilepsy. © 2004 Wiley‐Liss, Inc.
Expression, interaction, and proteolysis of death‐associated protein kinase and p53 within vulnerable and resistant hippocampal subfields following seizures
Authors: Araki Tomohiro , Shinoda Sachiko , Schindler Clara K. , Quan‐Lan Jing , Meller Robert , Taki Waro , Simon Roger P. , Henshall David C. 
Published: April 2004

AbstractDeath‐associated protein (DAP) kinase is a novel regulator of cell death whose in vivo target(s) and role in neuronal cell death remain uncertain. Since DAP kinase has been implicated in p53‐mediated apoptosis, a pathway activated following epileptic brain injury, we examined the relationship between DAP kinase and p53 following seizures. Rats underwent brief (40‐min) seizures evoked by intraamygdala kainic acid, which caused the death of ipsilateral CA3 neurons while preserving the contralateral CA3 subfield. Seizures caused a small decline in levels of the ∼160‐kD DAP kinase within injured ipsilateral hippocampus, commensurate with the appearance of an ∼60‐kD fragment, and proteolysis of the p53 inhibitor, murine double minute gene 2 (MDM2). Expression of p53 increased within the ipsilateral hippocampus, and DAP kinase was detected within p53 immunoprecipitates. In contrast, DAP kinase and MDM2 were not proteolyzed within the seizure damage‐resistant contralateral hippocampus. Furthermore, DAP kinase and p53 did not interact within the contralateral hippocampus, and p53 cellular localization redistributed from the nucleus to cytoplasm commensurate with p53 proteolysis. These data suggest that DAP kinase may be involved in the p53 pathway during seizure‐induced neuronal death. © 2004 Wiley‐Liss, Inc.
Neuregulin1 downregulates postsynaptic GABAa receptors at the hippocampal inhibitory synapse
Authors: Okada Masayoshi , Corfas Gabriel 
Published: April 2004

AbstractThe growth factor neuregulin 1 (NRG1) has been proposed to contribute to the formation and maturation of neuromuscular and interneuronal synapses by upregulating the expression of specific neurotransmitter receptor subunits. In the present report, we show that, in the hippocampus, NRG1 is expressed in a pattern suggesting that it regulates synapse development in the CA1 region. However, in contrast to what has been shown in other synapses, NRG1 reduces the expression of γ‐aminobutyric acid (GABA)A receptors α subunits in hippocampal slices, and the mean amplitude of GABAergic miniature inhibitory postsynaptic currents (IPSCs) in hippocampal CA1 pyramidal neurons, without affecting IPSC kinetics or frequency. These effects of NRG1 occur without concomitant changes in glutamate receptors and other synaptic proteins. We propose that the role of NRG1 in the formation and maturation in the hippocampal inhibitory synapse is downregulation, rather than upregulation, of receptor subunit expression. These results suggest that NRG1 may contribute to the reduction in GABAergic synaptic activity in hippocampal CA1 pyramidal neurons that normally occurs during early postnatal development, and that alterations in NRG1 signaling in the hippocampus may contribute to schizophrenia and epilepsy. © 2004 Wiley‐Liss, Inc.
Stress generates emotional memories and retrograde amnesia by inducing an endogenous form of hippocampal LTP
Authors: Diamond David M. , Park Collin R. , Woodson James C. 
Published: April 2004

AbstractModels of the neurobiology of memory have been based on the idea that information is stored as distributed patterns of altered synaptic weights in neuronal networks. Accordingly, studies have shown that post‐training treatments that alter synaptic weights, such as the induction of long‐term potentiation (LTP), can interfere with retrieval. In these studies, LTP induction has been relegated to the status of a methodological procedure that serves the sole purpose of disturbing synaptic activity in order to impair memory. This perspective has been expressed, for example, by Martin and Morris (2002: Hippocampus 12:609–636), who noted that post‐training LTP impairs memory by adding “behaviorally meaningless” noise to hippocampal neural networks. However, if LTP truly is a memory storage mechanism, its induction should represent more than just a means with which to disrupt memory. Since LTP induction produces retrograde amnesia, the formation of a new memory should also produce retrograde amnesia. In the present report, we suggest that one type of learning experience, the storage of fear‐related (i.e., stressful) memories, is consistent with this prediction. Studies have shown that stress produces potent effects on hippocampal physiology, generates long‐lasting memories, and induces retrograde amnesia, all through mechanisms in common with LTP. Based on these findings, we have developed the hypothesis that a stressful experience generates an endogenous form of hippocampal LTP that substitutes a new memory representation for preexisting representations. In summary, our hypothesis implicates the induction of endogenous synaptic plasticity by stress in the formation of emotional memories and in retrograde amnesia. © 2004 Wiley‐Liss, Inc.
Ontogeny of seizure‐induced increases in BDNF immunoreactivity and TrkB receptor activation in rat hippocampus
Authors: Danzer Steve C. , He Xiaoping , McNamara James O. 
Published: April 2004

AbstractThe present work tested the hypothesis that the anatomic and developmental patterns of status epilepticus‐induced increases of brain‐derived neurotrophic factor (BDNF) protein coincided with status epilepticus‐induced increases of phospho‐Trk immunoreactivity, a measure of TrkB receptor activation, in rat hippocampus. In P22 rats, robust increases of phospho‐Trk immunoreactivity were detected in the mossy fiber pathway of the hippocampus one day following kainate‐induced status epilepticus. Conversely, no change in phospho‐Trk immunoreactivity was detected in P8 or P14 rats. In P17 rats, intermediate levels of increased phospho‐Trk immunoreactivity were detected, again in the mossy fiber pathway. Like phospho‐Trk immunoreactivity, marked increases of BDNF immunoreactivity were detected in the mossy fiber pathway of P22 but not P14 rats. Dissociations were found in P17 rats following status epilepticus in that striking increases of BDNF, but not phospho‐Trk immunoreactivity were detected. Immunoprecipitation and Western blot analyses of hippocampal extracts after status epilepticus showed increased phospho‐TrkB, but not TrkB immunoreactivity in P22 rats, thereby confirming and extending the immunohistochemical findings. While most of the findings support the hypothesis, important dissociations among individual animals at P17 were identified. Together the findings are consistent with the proposal that status epilepticus‐induced increase of BDNF content in the mossy fibers is necessary, but not sufficient, to effect activation of TrkB, as revealed by phospho‐Trk immunoreactivity. Furthermore, these results provide the first characterization of seizure‐induced increases in BDNF protein and TrkB receptor activation in developing animals. © 2004 Wiley‐Liss, Inc.
Intraseptal infusion of the cholinergic agonist carbachol impairs delayed‐non‐match‐to‐sample radial arm maze performance in the rat
Authors: Bunce Jamie G. , Sabolek Helen R. , Chrobak James J. 
Published: April 2004

AbstractThe medial septal nucleus regulates the physiology and emergent functions (e.g., memory formation) of the hippocampal formation. This nucleus is particularly rich in cholinergic receptors and is a putative target for the development of cholinomimetic cognitive enhancing drugs. A large number of studies have demonstrated that direct intraseptal drug infusions can produce amnestic or promnestic effects. While a few studies have examined the effects of direct intraseptal infusion of cholinomimetics on spatial memory performance (with drug “on‐board” at the time of testing), the effects of post‐acquisition infusions have not been assessed. We hypothesized that post‐acquisition intraseptal infusion of cholinomimetics, by promoting hippocampal theta and suppressing the occurrence of hippocampal sharp waves, may disrupt the long‐term retention and consolidation of memory. The present study examined the effects of intraseptal infusion of the cholinergic agonist carbachol in a delayed‐non‐match‐to‐sample radial maze task. Treatments were administered immediately following (within 1 min) the sample session with a retention session 2 h later. Carbachol infusions (12.5–125 ng in 0.5 μl) produced a linear dose‐dependent decrease in correct entries and increase in retroactive errors, without any change in proactive errors or latency‐per‐choice. These findings suggest that post‐acquisition intraseptal cholinergic treatments can produce amnesia. These findings are discussed with regard to multi‐stage models of hippocampal‐dependent memory formation and the further development of therapeutic strategies in the treatment of mild cognitive impairment as well as age‐related cognitive decline and Alzheimer's dementia. © 2004 Wiley‐Liss, Inc.
Effect of early isolation on the synaptic function in the dentate gyrus and field CA1 of the guinea pig
Authors: Bartesaghi Renata 
Published: April 2004

AbstractWe previously reported that neonatal isolation shapes neuron morphology remarkably in the dentate gyrus and hippocampus of the guinea pig, a precocial rodent whose brain is at an advanced stage of maturation at birth. The aim of the present work was to investigate the effects of early isolation on the physiology of the hippocampal trisynaptic circuit. Male and female guinea pigs were assigned at 6–7 days of age to either a social or an isolated environment. After 90–100 days, the animals were anesthetized and electrophysiological experiments were carried out. The monosynaptic response evoked by medial perforant path stimulation in the dentate gyrus (DG) and the following response trisynaptically evoked in field CA1 by the DG‐CA3 system were evaluated with several stimulus protocols: (1) current source‐density (CSD) analysis; (2) input/output function; (3) paired‐pulse potentiation (PPP); and (4) long‐term potentiation (LTP). Isolated animals exhibited a reduction in the magnitude of the current sinks in the middle molecular layer and granule cell layer of the DG and in the input/output function of the granule cell population excitatory postsynaptic potential (EPSP) and population spike (PS) over a wide range of stimuli. The latter effect was larger in males. The ratio between the PS and EPSP of the granule cells was reduced in isolated compared to control males, but the opposite occurred in females. Isolation affected PPP of the granule cell response in males only, causing a larger facilitation of the PS. No isolation‐related effects were found in the magnitude of the LTP of the DG response in either sex. Isolated animals exhibited a reduction in the current sinks in stratum radiatum and stratum pyramidale of field CA1 and in the input/output function of the EPSP and PS of field CA1. These effects were larger in males. The results show that early isolation causes a reduction in the synaptic function of the DG‐CA3‐CA1 system, driven by perforant path volleys. The isolation‐induced impairment in signal processing along the hippocampal network suggests that the outcome of early isolation may be an impairment in the memory functions in which the entorhinal‐hippocampal system plays a key role. © 2004 Wiley‐Liss, Inc.
Pharmacological dissection of calcium channel subtype‐related components of strontium inflow in large mossy fiber boutons of mouse hippocampus
Authors: Tokunaga Takashi , Miyazaki Kenichi , Koseki Makoto , Mobarakeh Jalal Izadi , Ishizuka Toru , Yawo Hiromu 
Published: April 2004

AbstractSeveral subtypes of voltage‐dependent calcium channels (VDCCs) are present in the presynaptic terminals. In the mammalian hippocampus, P/Q‐, N‐, and R‐ but not L‐type VDCCs are involved in the fast transmitter release from large mossy fiber (MF) boutons, which are associated with CA3 pyramidal cell dendrites. We investigated whether L‐type VDCCs are indeed absent in these large MF boutons. With the use of Sr2+ as the Ca2+ substitute, the stimulus‐evoked Sr2+ increment (Δ[Sr2+]pre) was evaluated fluorometrically. Δ[Sr2+]pre appeared to be proportional to Sr2+ inflow through VDCCs and was specifically attenuated by conventional VDCC subtype‐selective antagonists. The P/Q‐type selective ω‐agatoxin IVA (AgTxIVA) blocked Δ[Sr2+]pre with an IC50 of 28 nM and by 30–35% at its maximum effective concentration of 0.5 μM. The N‐type selective ω‐conotoxin GVIA (CgTxGVIA) blocked Δ[Sr2+]pre with an IC50 of 15 nM and by 20–25% at its maximum effective concentration of 1 μM. The R‐type selective SNX‐482 blocked Δ[Sr2+]pre with an IC50 of 79 nM and by 20–25% at its maximum effective concentration of 1 μM. The effects of these toxins did not overlap at their maximum effective concentrations and about 70–80% of Δ[Sr2+]pre was blocked by the simultaneous exposure to these toxins. Δ[Sr2+]pre component that is resistant to AgTxIVA, CgTxGVIA, and SNX‐482 was significantly potentiated by an L‐type agonist, (S)‐(−)‐Bay K8644, and attenuated by an L‐type antagonist, nimodipine, suggesting that L‐type VDCCs are present in large MF terminals. The L‐type agonist, (±)‐Bay K8644, also potentiated Sr2+ inflow into individual boutons identified as large MF boutons under confocal microscopy. Almost similar results were observed for Ca2+ inflow‐dependent fluorescence increments. L‐type VDCCs appear to be present in large MF boutons and mediate a substantial Ca2+ inflow into presynaptic terminals during action potentials. © 2004 Wiley‐Liss, Inc.
Co‐expression of calretinin and γ‐aminobutyric acid in neurons of the entorhinal cortex of the common marmoset monkey
Authors: Pothuizen Helen H.J. , Feldon Joram , Jongen‐Rêlo Ana L. 
Published: April 2004

AbstractThe γ‐aminobutyric acid (GABA)‐containing interneuron population in the entorhinal cortex has been shown to consist of several subpopulations. In addition to GABA, these neurons contain another neurochemical substance, such as a neuropeptide or a calcium binding protein. In the present study, we examined the co‐localization of calretinin and GABA in the entorhinal cortex of the common marmoset Callithrix jacchus, a New World monkey. Although the function of calretinin remains unclear, there are indications that it might have a protective role against cell death in a number of neuropathological diseases. Furthermore, it might have a regulatory role in the neurotransmission of GABAergic neurons. In contrast to the rat brain, sparse data exist regarding the degree of co‐expression of these two markers in the monkey brain. Using immunofluorescence and confocal laser scanning microscopy, we found that an average of 56% of the calretinin‐positive neurons in the monkey entorhinal cortex contained GABA, whereas about 27% of the GABA‐positive neurons co‐expressed calretinin. Interestingly, these numbers were higher in the superficial layers of the entorhinal cortex in comparison with the deep layers. However, no differences were found in co‐localization percentages between the different entorhinal subfields. In general, the degree of co‐localization was higher in comparison to findings in the rat entorhinal cortex. The higher amount of co‐localization observed in the present study might reflect species differences between the primate and the non‐primate brain. © 2004 Wiley‐Liss, Inc.