bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular cloning, tissue expression, and partial characterization of the major fish CNS myelin protein 36k
Authors: Moll Wolfgang , Lanwert Carsten , Jeserich Gunnar 
Published: September 2003

AbstractA full‐length cDNA clone encoding the major structural protein of trout CNS myelin 36K was isolated and sequenced. The deduced amino acid sequence did not reveal a putative transmembrane domain and exhibited no structural homology with any of the known myelin proteins. 36K instead shared characteristic structural elements with enzymes of the short‐chain dehydrogenase family. The highest similarity in the database (60%), however, was obtained with a human protein of unknown function. By Northern blotting, a single mRNA species of about 2 kb was identified, which was expressed in brain tissue but not in liver. By in situ hybridization, a selective labeling of myelinating glial cells in the trout CNS but not in the PNS was revealed. The developmental appearance of the 36K transcript closely coincided with a period of active myelin deposition in most regions of the trout brain. As a first step in elucidating the structural and biochemical role of 36K for myelin formation and maintenance, we have overexpressed it in Escherichia coli as a soluble His‐tag fusion protein and purified it in high yield by Ni+‐chelated affinity chromatography. By SDS‐PAGE, a single band of the expected molecular size was revealed, which heavily cross‐reacted with polyclonal antibodies generated against the native protein. The results of circular dichroism spectroscopy are compatible with a βαβ‐barrel structure (Rossman fold), confirming the results of computer‐assisted secondary structure predictions. © 2003 Wiley‐Liss, Inc.
Endothelin‐1 increases 2‐arachidonoyl glycerol (2‐AG) production in astrocytes
Authors: Walter Lisa , Stella Nephi 
Published: September 2003

AbstractAstrocytes play an important role in neuroprotective responses. Recent studies indicate that endothelin‐1, a neuropeptide upregulated during brain injury, increases levels of the endocannabinoid anandamide, a lipid with neuroprotective properties, in astrocytes in primary cultures. However, whether this neuropeptide also alters levels of 2‐arachidonoyl glycerol (2‐AG), the most abundant endocannabinoid in the CNS, in astrocytes remains unknown. In addition, 2‐AG levels in astrocytes have never been measured. In this report we use chemical ionization gas chromatography/mass spectrometry to quantify picomole amounts of 2‐AG in primary cultures of mouse astrocytes. We also demonstrate that endothelin‐1 increases 2‐AG production by 5‐fold in these cells, a response that requires extracellular calcium and endothelin‐1(A) receptor engagement. Immunocytochemistry showed that although cultured mouse neurons and microglia express cannabinoid receptors, cultured astrocytes do not. The data suggest that endothelin‐1 modulates 2‐AG production in astrocytes and that this endocannabinoid may participate in paracrine signaling toward neurons and microglia. © 2003 Wiley‐Liss, Inc.
Astrocytic ceruloplasmin expression, which is induced by IL‐1β and by traumatic brain injury, increases in the absence of the IL‐1 type 1 receptor
Authors: Kuhlow Christopher J. , Krady J. Kyle , Basu Anirban , Levison Steven W. 
Published: September 2003

AbstractIL‐1α and IL‐1β are induced immediately after insults to the brain, and signaling through the type 1 IL‐1 receptor is essential for a normal microglial and astroglial response to injury. To better understand which genes are induced in astrocytes by IL‐1β, we used the unbiased technique of differential display to analyze mouse astroglial gene expression after IL‐1β treatment. Two novel genes were induced, as well as the gene for ceruloplasmin, a ferroxidase with antioxidant properties. Ceruloplasmin was analyzed further by Northern and Western blot. RNA and protein levels of ceruloplasmin were increased when astrocytes were treated with IL‐1β. To determine whether the IL‐1 type 1 receptor (IL‐1R1) is essential for the injury‐induced expression of ceruloplasmin, a Western blot analysis was performed after a traumatic brain injury on mice that were IL‐1R1‐deficient. Ceruloplasmin increased significantly above controls after injury; however, injury‐induced levels of ceruloplasmin were lower in IL‐1R1‐deficient (2.7‐fold increase) than in the wild‐type animals (3.5‐fold increase). These data indicate that while IL‐1R1 deletion has a slight effect on ceruloplasmin expression, it is not essential for either the basal or the induced expression of ceruloplasmin in vivo. Since ceruloplasmin buffers free copper, oxidizes ferrous iron, and catalyzes the dismutation of free radicals, increased levels of ceruloplasmin likely protect neurons and glia from sustaining damage after injury. Furthermore, as the IL‐1R1 has been proposed to be a target for achieving neuroprotection after injury, these data suggest that the protection afforded by ceruloplasmin will be retained even when the IL‐1R1 is antagonized. © 2003 Wiley‐Liss, Inc.
erbB3 is dispensable for oligodendrocyte development in vitro and in vivo
Authors: Schmucker Johannes , Ader Marius , Brockschnieder Damian , Brodarac Andreja , Bartsch Udo , Riethmacher Dieter 
Published: September 2003

AbstractDuring development and in the adult, erbB2, erbB3, and erbB4 are expressed in many tissues and as heterodimers (B2/B3, B2/B4) serve as receptors for neuregulins. The general importance of neuregulin receptors for development is underlined by the observed embryonic (erbB2, erbB4) or perinatal (erbB3) lethality in mouse mutants. These mutants further revealed the fundamental role of the erbB2/erbB3 heterodimer for proper Schwann cell development, the ensheathing glia of the peripheral nervous system. However, only little is known about the functions of neuregulins and their receptors during postnatal development and in the adult. erbB2 and erbB3 during late embryogenesis and postnatally are expressed in different areas and cell types of the central nervous system, including oligodendrocytes, the ensheathing glia of the central nervous system. As terminal differentiation of oligodendrocytes peaks during postnatal development, it is not possible to use the neuregulin receptor mouse mutants to study terminal differentiation of oligodendrocytes in their absence in vivo. In order to investigate possible functions of the erbB3 gene in oligodendrocytes, we employed two different techniques. First, we directed the differentiation of erbB3‐deficient embryonic stem cells into neural cell types to analyze the development of oligodendrocytes in the absence of erbB3 in vitro. Second, we grafted neural stem cells from spinal cords of erbB3 mutants into the retina of young mice to monitor oligodendrocyte differentiation and myelination in vivo. Results of both experimental approaches clearly show that erbB3 is not required for normal oligodendrocyte development and myelination. © 2003 Wiley‐Liss, Inc.
Chronic glial activation, neurodegeneration, and APP immunoreactive deposits following acute administration of double‐stranded RNA
Authors: Melton Lisa M. , Keith Alexander B. , Davis Sue , Oakley Arthur E. , Edwardson James A. , Morris Christopher M. 
Published: September 2003

AbstractSeveral neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, are associated with immunocompetent microglia, leading to the suggestion that chronic glial‐mediated inflammation contributes to the neurodegeneration seen in these diseases. Little direct evidence supports this hypothesis, and no suitable rodent models exist that do not involve the use of blunt trauma or ischaemia, events that are infrequently encountered in the human disease state. In the present study, we report that administration of double‐stranded RNA, a classical inducer of interferon‐γ (IFN‐γ), causes rapid and persistent activation of microglia and astrocytes, as well as induction of interleukin‐1β (IL‐β) and nitric oxide synthase. In close temporal succession to glial activation, there is neurodegeneration, with neuron loss involving apoptosis in selected brain regions including the septal nucleus, hippocampus, cortex and thalamus, along with hippocampal atrophy. This neuronal loss is accompanied by punctate deposits of material that are immunoreactive for amyloid precursor protein, β‐amyloid peptide (Aβ), and apolipoprotein E. The findings may have clinical relevance, since the administration of the nonsteroidal antiinflammatory agent (NSAID) ibuprofen markedly reduces the neurodegeneration observed in the absence of significant glial inhibition. These findings may be relevant to the pathogenesis of Alzheimer's disease in particular, and to other neurodegenerative diseases involving inflammation. © 2003 Wiley‐Liss, Inc.
Dissociation of human and computer voices in the brain: Evidence for a preattentive gestalt‐like perception
Authors: Lattner Sonja , Maess Burkhard , Wang Yunhua , Schauer Michael , Alter Kai , Friederici Angela D. 
Published: September 2003

AbstractWe investigated the early (“preattentive”) cortical processing of voice information, using the so‐called “mismatch response.” This brain potential allows inferences to be made about the sensory short‐term store. Most importantly, the mismatch potential also provides information about the organization of long‐term memory traces in the auditory system. Such traces have reliably been reported for phonemes. However, it is unclear whether they also exist for human voice information. To explore this issue, 10 healthy subjects were presented with a single word stimulus uttered by voices of different prototypicality (natural, manipulated, synthetic) in a mismatch experiment (stimulus duration 380 msec, onset‐to‐onset interval 900 msec). The event‐related magnetic fields were recorded by a 148‐channel whole‐head magnetometer and a source current density modeling of the magnetic field data was performed using a minimum‐norm estimate. Each deviating voice signal in a series of standard‐voice stimuli evoked a mismatch response that was localized in temporal brain regions bilaterally. Increased mismatch related magnetic flux was observed in response to decreased prototypicality of a presented voice signal, but did not correspond to the acoustic similarity of standard voice and deviant voices. We, therefore, conclude that the mismatch activation predominantly reflects the ecological validity of the voice signals. We further demonstrate that the findings cannot be explained by mere acoustic feature processing, but rather point towards a holistic mapping of the incoming voice signal onto long‐term representations in the auditory memory. Hum. Brain Mapping 20:13–21, 2003. © 2003 Wiley‐Liss, Inc.
Brain activations during conscious self‐monitoring of speech production with delayed auditory feedback: An fMRI study
Authors: Hashimoto Yasuki , Sakai Kuniyoshi L. 
Published: September 2003

AbstractWhen a speaker's voice returns to one's own ears with a 200‐ms delay, the delay causes the speaker to speak less fluently. This phenomenon is called a delayed auditory feedback (DAF) effect. To investigate neural mechanisms of speech processing through the DAF effect, we conducted a functional magnetic resonance imaging (fMRI) experiment, in which we designed a paradigm to explore the conscious overt‐speech processing and the automatic overt‐speech processing separately, while reducing articulatory motion artifacts. The subjects were instructed to (1) read aloud visually presented sentences under real‐time auditory feedback (NORMAL), (2) read aloud rapidly under real‐time auditory feedback (FAST), (3) read aloud slowly under real‐time auditory feedback (SLOW), and (4) read aloud under DAF (DELAY). In the contrasts of DELAY‐NORMAL, DELAY‐FAST, and DELAY‐SLOW, the bilateral superior temporal gyrus (STG), the supramarginal gyrus (SMG), and the middle temporal gyrus (MTG) showed significant activation. Moreover, we found that the STG activation was correlated with the degree of DAF effect for all subjects. Because the temporo‐parietal regions did not show significant activation in the comparisons among NORMAL, FAST, and SLOW conditions, we can exclude the possibility that its activation is due to speech rates or enhanced attention to altered speech sounds. These results suggest that the temporo‐parietal regions function as a conscious self‐monitoring system to support an automatic speech production system. Hum. Brain Mapping 20:22–28, 2003. © 2003 Wiley‐Liss, Inc.
Stimulus repetition and hemodynamic response refractoriness in event‐related fMRI
Authors: Soon Chun‐Siong , Venkatraman Vinod , Chee Michael W.L. 
Published: September 2003

AbstractWe investigated the extent of hemodynamic recovery following the paired presentation of either identical or different faces at two different inter‐stimulus intervals (ISI). Signal recovery was consistently better at an ISI of 6 sec compared to 3 sec. Significantly less signal recovery was associated with identical faces compared to different faces in bilateral mid‐fusiform and right prefrontal regions but not in the calcarine and posterior fusiform regions. Repetition suppression effects contributed significantly to incomplete signal recovery in a region‐specific manner. Simulations using empirically derived data suggest that experiments with shorter ISI (average 4.5–6.0 sec) are as sensitive as experiments with intermediate ISI (average 9 sec) in detecting response differences if experimental duration is equivalent. However, designs using intermediate ISI may be more appropriate if the expected difference in responses is small and if the number of suitable stimuli is limited. Hum. Brain Mapping 20:1–12, 2003. © 2003 Wiley‐Liss, Inc.
Directly mapping magnetic field effects of neuronal activity by magnetic resonance imaging
Authors: Xiong Jinhu , Fox Peter T. , Gao Jia‐Hong 
Published: September 2003

AbstractMagnetic resonance imaging (MRI) of brain functional activity relies principally on changes in cerebral hemodynamics, which are more spatially and temporally distributed than the underlying neuronal activity changes. We present a novel MRI technique for mapping brain functional activity by directly detecting magnetic fields induced by neuronal firing. Using a well‐established visuomotor paradigm, the locations and latencies of activations in visual, motor, and premotor cortices were imaged at a temporal resolution of 100 msec and a spatial resolution of 3 mm, and were found to be in consistent with the electrophysiological and functional MRI (fMRI) literature. Signal strength was comparable to traditional event‐related fMRI methods: about 1% of the baseline signal. The magnetic‐source MRI technique greatly increases the temporal accuracy in detecting neuronal activity, providing a powerful new tool for mapping brain functional organization in human and animals. Hum. Brain Mapping 20:41–49, 2003. © 2003 Wiley‐Liss, Inc.
Functional magnetic resonance imaging of verbal fluency and confrontation naming using compressed image acquisition to permit overt responses
Authors: Abrahams Sharon , Goldstein Laura H. , Simmons Andy , Brammer Michael J. , Williams Steve C.R. , Giampietro Vincent P. , Andrew Chris M. , Leigh P. Nigel 
Published: September 2003

AbstractVerbal fluency and confrontation naming, two tests of word retrieval, are of great utility in the field of cognitive neuroscience. However, in the context of functional magnetic resonance imaging (fMRI), movement artefact has necessitated the use of covert paradigms, which has limited clinical application. We developed two overt fMRI paradigms that allowed for performance measurement and hence were appropriate for use with patient groups. The paradigms incorporated a blocked‐design and compressed‐acquisition methodology where cues were presented and responses made in a “silent” period allowing for performance measurement. The slow response pace was specifically designed for older and potentially cognitively impaired participants. Verbal fluency was associated with activation in the middle frontal gyrus (Brodmann areas 46 and 9), anterior cingulate gyrus and inferior frontal gyrus (area 44 and 45). Confrontation naming activated areas of the temporo‐occipital cortices (areas 18, 19, and 37) and the inferior frontal gyrus. The two paradigms successfully activated regions involved in executive and word retrieval processes and overcame the potential artefacts resulting from overt speech during image acquisition, providing useful neuropsychological tools to investigate cognitive deficits in clinical populations. Hum. Brain Mapping 20:29–40, 2003. © 2003 Wiley‐Liss, Inc.
Betulinic acid: A new cytotoxic compound against malignant head and neck cancer cells
Authors: Thurnher Dietmar , Turhani Dritan , Pelzmann Martina , Wannemacher Bettina , Knerer Birgit , Formanek Michael , Wacheck Volker , Selzer Edgar 
Published: September 2003

AbstractBackground.A new compound, betulinic acid, has been found to be cytotoxic against a variety of tumor cells originating from the neural crest. Its efficacy against head and neck squamous cellular carcinoma cell lines has so far not been tested.Methods.Cell numbers were assayed by automated counting; caspase activation and programmed cell death were determined using an antibody specific for an apoptosis‐associated epitope in epithelial cells. The expression pattern of Bcl‐2 family members was assessed by Western blotting.Results.In two HNSCC cell lines betulinic acid induced apoptosis, which was characterized by a dose‐dependent reduction in cell numbers, emergence of apoptotic cells, and an increase in caspase activity. Western blot analysis of the expression of various Bcl‐2 family members in betulinic acid–treated cells showed, surprisingly, a suppression of the expression of the proapoptotic protein Bax but no changes in Mcl‐1 or Bcl‐2 expression.Conclusion.These data clearly demonstrate for the first time that betulinic acid has apoptotic activity against HNSCC cells. © 2003 Wiley Periodicals, Inc. Head Neck 25: 732–740, 2003
Salvage laryngectomy and pharyngocutaneous fistulae after primary radiotherapy for head and neck cancer: A national survey from DAHANCA
Authors: Grau Cai , Johansen Lars Vendelbo , Hansen Hanne Sand , Andersen Elo , Godballe Christian , Andersen Lisbeth Juhler , Hald Jesper , Møller Henrik , Overgaard Marie , Bastholt Lars , Greisen Ole , Harbo Grethe , Hansen Olfred , Overgaard Jens 
Published: September 2003

AbstractObjective.In 1998, the Danish Society for Head and Neck Oncology decided to conduct a nationwide survey at the five head and neck oncology centers with the aim of evaluating the surgical outcome of salvage laryngectomy after radiotherapy with special emphasis on identifying factors that could contribute to the development of pharyngocutaneous fistulae.Patients.A total of 472 consecutive patients undergoing postirradiation salvage laryngectomy in the period July 1, 1987–June 30, 1997 were recorded at the five head and neck oncology centers in Denmark. Age ranged from 36 to 84 years, median 63 years, 405 men and 67 women. Primary tumor site was glottic larynx (n = 242), supraglottic larynx (n = 149), other larynx (n = 45), pharynx (n = 27), and other (n = 9). All patients had received prior radiotherapy.Results.Median time between radiotherapy and laryngectomy was 10 months (range, 1–348 months). A total of 89 fistulae lasting at least 2 weeks were observed, corresponding to an overall average fistulae risk of 19%. The number of performed laryngectomies per year decreased linearly (from 58 to 37), whereas the annual number of fistulae increased slightly (from 7 to 11), which meant that the corresponding estimated fistulae risk increased significantly from 12% in 1987 to 30% in 1997. Other significant risk factors for fistulae in univariate analysis included younger patient age, primary advanced T and N stage, nonglottic primary site, resection of hyoid bone, high total radiation dose, and large radiation fields. Multiple logistic regression analysis of these parameters suggested that nonglottic tumor site, late laryngectomy period (1987–1992 vs 1993–1997), and advanced initial T stage were independent prognostic factors for fistulae risk. Surgical parameters like resection of thyroid/tongue base/trachea or radiotherapy parameters like overall treatment time or fractions per week did not influence fistulae risk.Conclusions.The risk of fistulae is especially high in patients initially treated with radiotherapy for nonglottic advanced stage tumors. A significant decrease in the number of performed salvage laryngectomies over the 10 years was seen. Over the same time period, the annual number of fistulae remained almost constant. The resulting more than doubling of fistulae rate could thus in part be explained by less surgical routine. © 2003 Wiley Periodicals, Inc. Head Neck 25: 711–716, 2003
Intratumoral cisplatin/epinephrine gel in advanced head and neck cancer: A multicenter, randomized, double‐blind, phase III study in North America
Authors: Castro Dan J. , Sridhar Kasi S. , Garewal Harinder S. , Mills Glenn M. , Wenig Barry L , Dunphy Frank R. , Costantino Peter D. , Leavitt Richard D. , Stewart Morgan E. , Orenberg Elaine K. 
Published: September 2003

AbstractBackground.The objective was to evaluate the efficacy and safety of a novel intratumoral cisplatin/epinephrine injectable gel (CDDP/epi gel) for local control and palliation of tumor‐related symptoms in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).Patients and Methods.Eighty‐seven patients were randomly assigned to either CDDP/epi or placebo gel in this phase III, double‐blind study. Tumors were ≤20 cm3; most recurrences (88%) were in a previously irradiated field. The most symptomatic or threatening tumor was designated as the target tumor. Dose: 0.25 mL CDDP/epi gel/cm3 tumor volume. Treatments: ≤6 weekly intratumoral injections in an 8‐week period. Primary outcomes: target tumor response and symptom relief.Results.During the blinded phase, 34% (21 of 62) of patients achieved an objective response (CR or PR) in the target tumor treated with CDDP/epi gel vs 0% (0 of 24) treated with placebo gel (p < .001). Responses occurred within a median of four treatments (range, 2–6) and were durable (median, 95 days; range, 34–168+ days). More patients treated with CDDP/epi gel achieved palliative benefit than did those treated with placebo gel (37% vs 12%, p = .036). Most frequent side effects were local pain and local cutaneous reactions, which resolved over 3–12 weeks. Renal and hematologic toxicities were rare.Conclusions.This phase III trial showed that CDDP/epi gel significantly reduces tumor burden, palliates tumor‐related symptoms, and is an effective local treatment for recurrent tumors. © 2003 Wiley Periodicals, Inc. Head Neck 25: 717–731, 2003
Does feeding tube placement predict for long‐term swallowing disability after radiotherapy for head and neck cancer?
Authors: Al‐Othman Majid O. F. , Amdur Robert J. , Morris Christopher G. , Hinerman Russell W. , Mendenhall William M. 
Published: September 2003

AbstractPurpose.To evaluate feeding tube use.Materials and Methods.Nine hundred thirty‐four patients were treated with radiotherapy (RT).Results.Feeding tubes were placed in 235 patients (25%): 212 patients (22.5%) for acute toxicity, 18 patients (2%) for late effects, and 5 patients (0.5%) for both. Median duration of tube dependence for acute toxicity was 3.8 months. Multivariate analysis revealed that feeding tube placement for acute toxicity was increased with higher RT dose (p < .0001), adjuvant chemotherapy (p = .0002), advanced age (p = .0002), and the presence of neck disease (p = .0045). The risk of a feeding tube for late effects was 2% at 5 years. The likelihood of feeding tube placement for late effects was greater for women (p = .0293), higher RT dose (p = .0345), and primary sites, including the hypopharynx and multiple synchronous primary tumors (p = .0360). Feeding tube placement for late effects was unrelated to tube placement for acute toxicity.Conclusion.Likelihood of long‐term feeding tube dependence was low and unrelated to placement for acute effects. © 2003 Wiley Periodicals, Inc. Head Neck 25: 741–747, 2003