bluuebunny/crossref_metadata_2025 huggingface dataset:
Sonographic findings in intussusception caused by a lipoma in the muscular layer of the colon
Authors: Alkim Canan , Şaşmaz Nurgül , Alkim Hüseyin , Çağlikülekçi Mehmet , Turhan Nesrin
Published: October 2004

Lipomas of the gastrointestinal tract are uncommon tumors. Almost all gastrointestinal lipomas are submucosal or subserosal, and most are asymptomatic, although they may cause abdominal pain, bowel obstruction, and gastrointestinal bleeding. The diagnosis of gastrointestinal lipoma is usually not made before surgery. We present a case of colonic intussusception caused by a lipoma that was located in the muscular layer of the colon and was diagnosed preoperatively by sonography. The descending colon appeared edematous and thick. There was layering within the lumen of the descending colon, mimicking the target sign. At the distal end of the intussusception, there was a 4.7‐cm, hyperechoic, rounded lesion with a smooth margin. Surgery revealed a polypoid mass originating from the splenic flexure and causing intussusception of the colon, and pathologic analysis confirmed the diagnosis of lipoma of the muscular layer of the colon. © 2001 John Wiley & Sons, Inc. J Clin Ultrasound 29:298–301, 2001.
Power Doppler sonography of the kidney: Effect of Valsalva's maneuver
Authors: Takano Ryuichi , Ando Yasuhiro , Taniguchi Nobuyuki , Itoh Kouichi , Asano Yasushi
Published: October 2004

Purpose

It has been reported that an intra‐abdominal pressure (IAP) above 15 mm Hg may cause oliguria and that an IAP above 25 mm Hg may cause anuria. Because Valsalva's maneuver yields an IAP exceeding 180 mm Hg, it is presumed to affect renal perfusion. We evaluated the ability of power Doppler sonography to depict the changes in renal blood flow during Valsalva's maneuver.

Methods

Seven healthy men aged 21–24 years and 1 50‐year‐old man with massive ascites participated in the study. With each healthy subject lying in a supine position, longitudinal power Doppler sonograms of the kidney were obtained and analyzed semiquantitatively during Valsalva's maneuver. Also, in the patient with massive ascites, power Doppler sonography was performed before and after paracentesis.

Results

Along with an increase in IAP, monitored as expiratory pressure during Valsalva's maneuver, power Doppler signals decreased as indicated by both visual impression and computer scores. In the patient with massive ascites, signal intensity increased after paracentesis.

Conclusions

Our results demonstrated that an increase in IAP within the physiologic range affects renal perfusion and that power Doppler sonography depicts semiquantitatively the change in renal blood flow. © 2001 John Wiley & Sons, Inc. J Clin Ultra‐ 29:384–388, 2001.
Ultrasound‐guided piezoelectric extracorporeal shock wave lithotripsy of parotid gland calculi
Authors: Külkens Christoph , Quetz Joachim U. , Lippert Burkard M. , Folz Benedikt J. , Werner Jochen A.
Published: October 2004

Purpose

The introduction of piezoelectric extracorporeal shock wave lithotripsy (ESWL) has changed therapy for salivary calculi. This method seems especially suitable for treating calculi in the parotid gland. The purpose of this study was to evaluate ESWL in patients with such calculi.

Methods

From November 1990 to November 1999, all patients with sialolithiasis of the parotid gland were treated with piezoelectric ESWL. Three different lithotriptors were used over the 9‐year study period. Results were analyzed according to both the patients' clinical status and follow‐up sonograms.

Results

In total, 42 patients (21 women, 21 men; mean age, 59 years) were treated with ESWL. The mean follow‐up period for all patients was 63 months (range, 7–96 months). After ESWL had been performed, 71% of the patients were completely free of symptoms, and 21% had marked improvement of their symptoms. Sixty‐seven percent were completely free of calculi, and 27% had a marked reduction in the size of their calculi. Adverse effects of ESWL included temporary glandular swelling (4 patients), blood‐tinged salivary secretions (9 patients), petechiae on the skin surface (3 patients), and parotid abscess (1 patient).

Conclusions

ESWL is an outpatient procedure that can be performed without anesthesia and with scarcely any discomfort for patients. Conventional surgical procedures such as subtotal parotidectomy may be almost entirely replaced by ESWL because of the excellent treatment results and a very low rate of complications associated with ESWL. ESWL should be considered the treatment of choice for parotid calculi. © 2001 John Wiley & Sons, Inc. J Clin Ultrasound 29:389–394, 2001.
On disjoint configurations in infinite graphs
Authors: Andreae Thomas
Published: October 2004

For a graph A and a positive integer n, let nA denote the union of n disjoint copies of A; similarly, the union of ℵ0 disjoint copies of A is referred to as ℵ0A. It is shown that there exist (connected) graphs A and G such that nA is a minor of G for all nϵℕ, but ℵ0A is not a minor of G. This supplements previous examples showing that analogous statements are true if, instead of minors, isomorphic embeddings or topological minors are considered. The construction of A and G is based on the fact that there exist (infinite) graphs G1, G2,… such that Gi is not a minor of Gj for all i ≠ j. In contrast to previous examples concerning isomorphic embeddings and topological minors, the graphs A and G presented here are not locally finite. The following conjecture is suggested: for each locally finite connected graph A and each graph G, if nA is a minor of G for all n ϵ ℕ, then ℵ0A is a minor of G, too. If true, this would be a far‐reaching generalization of a classical result of R. Halin on families of disjoint one‐way infinite paths in graphs. © 2002 Wiley Periodicals, Inc. J Graph Theory 39: 222–229, 2002; DOI 10.1002/jgt.10016
Minimizer graphs for a class of extremal problems
Authors: Ismailescu Dan , Stefanica Dan
Published: October 2004

We consider the family of graphs with a fixed number of vertices and edges. Among all these graphs, we are looking for those minimizing the sum of the square roots of the vertex degrees. We prove that there is a unique such graph, which consists of the largest possible complete subgraph plus only one other non‐isolated vertex. The same result is proven for any power of the vertex‐degrees less than one half. © 2002 Wiley Periodicals, Inc. J Graph Theory 39: 230–240, 2002; DOI 10.1002/jgt.10025
Forcing a Kr minor by high external connectivity
Authors: Kühn Daniela
Published: October 2004

We investigate the minimal structure a graph H is required to have if H is to force a large complete minor in any graph in which it has high external connectivity. We observe that such graphs H must contain a large binary tree with some small additions, and prove that some canonical instances of this structure are also sufficient to force a large complete minor. © 2002 Wiley Periodicals, Inc. J Graph Theory 39: 241–264, 2002; DOI 10.1002/jgt.10026
Features of mono‐ and multinucleated bone resorbing cells of the zebrafish Danio rerio and their contribution to skeletal development, remodeling, and growth
Authors: Witten P. Eckhard , Hansen Anne , Hall Brian K.
Published: October 2004

To provide basic data about bone resorbing cells in the skeleton during the life cycle of Danio rerio, larvae, juveniles, and adults (divided into six age groups) were studied by histological procedures and by demonstration of the osteoclast marker enzyme tartrate‐resistant acid phosphatase (TRAP). Special attention was paid to the lower jaw, which is a standard element for fish bone studies. The presence of osteoclasts at endosteal surfaces of growing bones of all animals older than 20 days reveals that resorption is an important part of zebrafish skeletal development. The first bone‐resorbing cells to form are mononucleated. They appear in 20‐day‐old animals concurrently in the craniofacial skeleton and vertebral column. Mononucleated osteoclasts are predominant in juveniles. Regional differences characterize the appearance of osteoclasts; at thin skeletal elements (neural arches, nasal) mononucleated osteoclasts are predominant even in adults. Multinucleated bone‐resorbing cells were first observed in 40‐day‐old animals and are the predominant osteoclast type of adults. Both mono‐ and multinucleated osteoclasts contribute to allometric bone growth but multinucleated osteoclasts are also involved in lacunar bone resorption and repeated bone remodeling. Resorption of the dentary follows the pattern described above (mononucleated osteoclasts precede multinucleated cells) and includes the partial removal of Meckel's cartilage. Bone marrow spaces created by resorption are usually filled with adipose tissue. In conclusion, bone resorption is primarily subjected to the demands of growth, the appearance of mono‐ and multinucleated osteoclasts is site‐ and age‐related, and bone remodeling occurs. The results are discussed in relation to findings in other teleosts and in mammals. J. Morphol. 250:197–207, 2001. © 2001 Wiley‐Liss, Inc.
In vivo cellular uptake of glutamate is impaired in the rat hippocampus during and after transient cerebral ischemia: A microdialysis extraction study
Authors: Bruhn Torben , Christensen Thomas , Diemer Nils Henrik
Published: October 2004

Using microdialysis in CA1 of the rat hippocampus, we studied the effect of transient cerebral ischemia on in vivo uptake and on extracellular levels of glutamate during, and at different time points after ischemia. 3H‐D‐aspartate (test substance), and 14C‐mannitol (reference substance), were added to the dialysis perfusate, and the cellular extraction of 3H‐D‐aspartate was calculated from scintillation analysis of fractionated dialysate samples. The extraction of 3H‐D‐aspartate was studied both in a tracer like condition with a perfusate concentration of 0.2 μM, and in a condition of high saturation level, with 1.0 mM D‐aspartate added to the perfusate. In between radioisotope perfusions, dialysate was sampled for analysis of amino acid content by HPLC. During ischemia, extraction of 3H‐D‐aspartate (0.2 μM) declined to a maximum reduction of 68%. In the hours after ischemia, extraction of 3H‐D‐aspartate (0.2 μM) was decreased by 32%. In the days after ischemia, there was a progressive decline in extraction of 3H‐D‐aspartate (1.0 mM), reaching a reduction of 89% on Day 4 after ischemia. Extracellular glutamate remained at control levels at all time points after ischemia. The present study is the first to investigate uptake of glutamate in the intact rat brain in relation to cerebral ischemia. Evidence is provided that uptake of Glu is restrained during ischemia, and that in the hours after ischemia, the extracellular turnover of glutamate is decreased. In the course of the days after ischemia, degeneration of CA1 pyramidal cells occurs concomitantly with a progressive decline in glutamate transport ability, possibly of pathogenetic importance to CA1 pyramidal cell loss. J Neurosci. Res. 66:1118–1126, 2001. © 2001 Wiley‐Liss, Inc.
Polyamine metabolism and glutamate receptor agonists‐mediated excitotoxicity in the rat brain
Authors: Camón L. , de Vera N. , Martínez E.
Published: October 2004

Putrescine (PUT) increases have been seen in a range of models of neuropathological disturbances. The present study was designed to compare the ability of various types of glutamate receptor agonist to promote excitotoxic brain damage and to examine whether a PUT increase is a general marker of excitotoxic brain damage. To that end, we evaluated features of brain damage associated with the excitotoxicity induced by both ionotropic glutamate receptor (iGluR) and metabotropic glutamate receptor (mGluR) agonists in the conscious rat and the changes produced in the regulation of polyamine metabolism. Intracerebroventricular infusion of N‐methyl‐D‐aspartate (NMDA; 80 nmol), α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid (AMPA; 15 nmol), kainic acid (KA; 2.3 nmol), (R,S)‐3,5‐dihydroxyphenylglycine (3,5‐DHPG; 1.5 μmol), and (1S,3R)‐1‐aminocyclopentane‐1,3‐dicarboxylic acid (1S,3R‐ACPD; 2 μmol) produced similar seizure incidences (76–84%) in the rat. The convulsant episodes appeared sooner after iGluR (13–22 min) than after mGluR agonists (50–179 min). Histological analysis of the hippocampus 24 hr after seizures indicated several degrees of excitotoxic injury after equiconvulsive doses of the iGluR and mGluR agonists assayed. The agonists can be placed in the following order, according to the degree of damage they produce: AMPA > 3,5‐DHPG ≃ KA > NMDA > 1S,3R‐ACPD. In the frontal cortex, moderate to low levels of damage were observed after all GluR agonists. Both iGluR‐ and mGluR‐induced seizures produced an overshoot in the hippocampal and cortical PUT concentration, whereas spermidine and spermine levels were similar to control. Moreover, a concurrence of increased PUT levels and brain damage was observed, indicating that PUT is a general marker of excitotoxic brain damage. J Neurosci. Res. 66:1101–1111, 2001. © 2001 Wiley‐Liss, Inc.
Temporospatial sequence of cellular events associated with etoposide‐induced neuronal cell death: Role of antiapoptotic protein Bcl‐XL
Authors: Kim Ji‐Eun , Han Baek S. , Choi Won‐Seok , Eom Dae‐Seok , Lee Eun‐Hee , Oh Tae H. , Markelonis George J. , Saido Takaomi C. , Lee Gun‐Eui , Chung In‐Kwon , Oh Young J.
Published: October 2004

Etoposide‐induced death comprises such nuclear events as the formation of topoisomerase II‐DNA cleavable complex and cytosolic events including caspase activation. By first establishing the temporospatial death sequence triggered by etoposide in a neuronal cell line, MN9D overexpressing Bcl‐XL (MN9D/Bcl‐XL) or control vector (MN9D/Neo), we examined whether formation of this complex is primarily responsible for cell death and at which strategic points and how Bcl‐XL blocks etoposide‐induced neuronal death. Etoposide induced death that was dependent on caspase, cycloheximide, and calpain in MN9D/Neo cells. Etoposide also induced death in enucleated MN9D/Neo cells, although this was less severe. The level of topoisomerase II‐DNA cleavable complex reached at a maximum of 2 hr after etoposide treatment was identical in MN9D/Neo and MN9D/Bcl‐XL cells. In MN9D/Neo cells, cytochrome c release into the cytosol and caspase activation occurred as early as 2 hr and 3–6 hr after etoposide treatment, respectively. Etoposide‐induced DNA laddering potentially via caspase appeared as early as 12 hr after drug treatment, followed by nuclear swelling in MN9D/Neo cells (>18–20 hr). Subsequently, nuclear condensation started by 24–28 hr and became apparent thereafter. All of these events except for nuclear swelling were substantially blocked in MN9D/Bcl‐XL. At the later stage of cell death (<32–36 hr), a specific cleavage of Bax and fodrin appeared that was completely blocked by calpain inhibitor or by Bcl‐XL. Taken together, our data suggest that Bcl‐XL prevents etoposide‐induced neuronal death by exerting its anticaspase and anticalpain effect on cellular events after the formation of topoisomerase II‐DNA cleavable complex that may not be a major contributor to cell death. J Neurosci. Res. 66:1074–1082, 2001. © 2001 Wiley‐Liss, Inc.
Structure–function correlation in transient amacrine cells of goldfish retina: Basic and multifractal analyses of dendritic trees in distinct synaptic layers
Authors: Djamgoz M.B.A. , Krasowska M. , Martinoli O. , Sericano M. , Vallerga S. , Grzywna Z.J.
Published: October 2004

Amacrine cells generating light‐evoked transient ON–OFF responses were stained by intracellular injection of horseradish peroxidase after determining their input–output (voltage response vs. light intensity) profiles. Ten cells specifically having bistratified dendritic trees were analyzed. The cross‐sectional area of the dendrites in each sublamina (a and b) of the inner plexiform layer was initially measured. Although some variability was observed, there was no statistically significant overall difference in the cross‐sectional areas of the dendritic trees in sublaminae a and b. Also, the amplitudes of the ON and OFF responses, generated by a midrange criterion stimulus, could not be correlated with the cross‐sectional areas or the number of branches of the dendrites in sublaminae b and a, respectively. On the other hand, determination of the generalized fractal spectra revealed that the negative (up to –3) and zero‐order fractal dimensions of the dendritic trees in sublamina a were consistently higher than those for sublamina b. Furthermore, there was a positive correlation between response amplitude and some part of the generalized fractal dimension in the respective parts of the dendritic trees. It is concluded that dendritic tree characteristics differ in the two halves of the inner plexiform layer and that these can be related to the cells' light‐evoked response amplitudes. Furthermore, generalized fractal analysis appears to be a useful method for correlating structure and function in retinal amacrine cells with complex dendritic trees. J Neurosci. Res. 66:1208–1216, 2001. © 2001 Wiley‐Liss, Inc.
Distribution of high‐voltage‐activated calcium channels in cultured γ‐aminobutyric acidergic neurons from mouse cerebral cortex
Authors: Timmermann Daniel B. , Westenbroek Ruth E. , Schousboe Arne , Catterall William A.
Published: October 2004

The localization of voltage‐gated calcium channel (VGCC) α1 subunits in cultured GABAergic mouse cortical neurons was examined by immunocytochemical methods. Cav1.2 and Cav1.3 subunits of L‐type VGCCs were found in cell bodies and dendrites of GABA‐immunopositive neurons. Likewise, the Cav2.3 subunit of R‐type VGCCs was expressed in a somatodendritic pattern. Cav2.2 subunits of N‐type channels were found exclusively in small varicosities that were identified as presynaptic nerve terminals based on their expression of synaptic marker proteins. Two splice variants of the Cav2.1 subunit of P/Q‐type VGCCs showed widely differing expression patterns. The rbA isoform displayed a purely somatodendritic staining pattern, whereas the BI isoform was confined to axon‐like fibers and nerve terminals. The nerve terminals of these cultured GABAergic neurons express Cav2.2 either alone or in combination with Cav2.1 (BI isoform) but never express Cav2.1 alone. The functional association between VGCCs and the neurotransmitter release machinery was probed using the FM1‐43 dye‐labeling technique. N‐type VGCCs were found to be tightly coupled to exocytosis in these cultured cortical neurons, and P‐type VGCCs were also important in a fraction of the cells. The predominant role of N‐type VGCCs in neurotransmitter release and the specific localization of the BI isoform of Cav2.1 in the nerve terminals of these neurons distinguish them from previously studied central neurons. The complementary localization patterns observed for two different isoforms of the Cav2.1 subunits provide direct evidence for alternative splicing as a means of generating functional diversity among neuronal calcium channels. © 2002 Wiley‐Liss, Inc.
Vestibular compensation after ganglionectomy: Ultrastructural study of the tangential vestibular nucleus and behavioral study of the hatchling chick
Authors: Aldrich Eric M. , Peusner Kenna D.
Published: October 2004

The tangential nucleus is a major part of the avian vestibular nuclear complex, and its principal cells are structurally distinctive neurons participating in the vestibuloocular and vestibulocollic reflexes. After unilateral peripheral vestibular lesion, a behavioral recovery of function defined as vestibular compensation is observed. Because sprouting and hypertrophy of synapses have been reported in other regions of immature animals after central nervous system injury, we investigated whether this also occurs in the vestibular nuclei during compensation. To test this hypothesis, unilateral vestibular ganglionectomy was performed on 4–6‐day‐old hatchlings and vestibular function was tested during the next 2 months. Degeneration and evidence for regeneration of synapses were studied in the tangential nucleus at 1, 3, 7, and 56 days after surgery. Spoon endings, large vestibular terminals on the principal somata, degenerated 1–3 days after surgery. However, the small synaptic terminals showed no significant change in the percentage or number covering the soma or in mean terminal lengths in the deafferented or contralateral tangential nucleus. Furthermore, there was no evidence of neuron death in the tangential nucleus. Vestibular compensation occurred in three stages: 0–3 days, when vestibular synapses degenerated and severe behavioral deficits were seen; 4–9 days, when primary vestibular fibers degenerated centrally and marked improvement in both the static and the dynamic symptoms were observed; and 10–56 days, when changes in neuronal morphology were not detected but the dynamic symptoms gradually improved. Accordingly, after unilateral vestibular ganglionectomy, vestibular compensation proceeded without ultrastructural evidence of sprouting or hypertrophy of axosomatic synapses in the hatchling tangential nucleus. This rapid behavioral recovery of function distinguishes the vestibular system from other sensory systems, which, in general, exhibit much less robust recovery after injury to their peripheral receptors. © 2002 Wiley‐Liss, Inc.
p27Kip1 Enhances myelin basic protein gene promoter activity
Authors: Miskimins Robin , Srinivasan Rekha , Marin‐Husstege Mireya , Miskimins W. Keith , Casaccia‐Bonnefil Patrizia
Published: October 2004

The process of oligodendrocyte differentiation is a complex event that requires cell cycle withdrawal, followed by the activation of a specific transcriptional program responsible for the synthesis of myelin genes. Because growth arrest precedes differentiation, we sought to investigate the role of cell cycle molecules in the activation of myelin gene promoters. We hypothesized that the cell cycle inhibitor p27Kip1, which is primarily responsible for arresting proliferating oligodendrocyte progenitors, may be involved in the transcriptional regulation of myelin genes. In agreement with this hypothesis, overexpression of p27Kip1 in the CG4 cell line, but not in 3T3 fibroblasts, enhances the expression of luciferase driven by the myelin basic protein (MBP) promoter. Interestingly, this effect is specific for p27Kip1; overexpression of other cell cycle inhibitors had no effect. Additionally, this effect is independent of halting the cell cycle; treatment with the cell cycle blocker roscovitine did not affect MBP promoter usage. We conclude that p27Kip1 contributes to oligodendrocyte differentiation by regulating transcription of the MBP gene. © 2002 Wiley‐Liss, Inc.
Upregulation of the HLH Id gene family in neural progenitors and glial cells of the rat spinal cord following contusion injury
Authors: Tzeng Shun‐Fen , Bresnahan Jacqueline C. , Beattie Michael S. , de Vellis Jean
Published: October 2004

Spinal cord injury (SCI) leads to a complex sequence of cellular responses, including astrocyte activation, oligodendrocyte death, and ependymal cell proliferation. Inhibitors of DNA binding (Id1, Id2, Id3) belong to a helix‐loop‐helix (HLH) gene family. Id genes have been implicated in playing a vital role in the proliferation of many cell types, including astrocytes and myoblasts. In the present study, the expression of Id family members in spinal cord after contusion injury was investigated by in situ hybridization. Id1, Id2, and Id3 mRNA expression was upregulated 5 mm rostral and caudal to the lesion center, and reached maximal levels 3 days after SCI. In addition, cell populations expressing Id1, Id2, and Id3 mRNA were maximally increased 3 days after SCI. The increase in Id2 and Id3 mRNA expression and Id2 and Id3 mRNA+ cells was still observed at 8 days. The Id mRNA expressing cells were phenotyped by combining immunostaining of cell‐specific markers with in situ hybridization. Glial fibrillary acidic protein (GFAP)+ astrocytes were found to express all three Id mRNA, whereas S‐100α+ astrocytes only expressed high levels of Id2 and Id3 mRNA. Cells having a neural progenitor morphology and the marker nestin appeared after SCI and they expressed Id1, Id2, and Id3 mRNA. Interestingly, some Rip+ oligodendrocytes located in the areas close to the central canal expressed Id3 mRNA after injury. In conclusion, Id genes are upregulated in a time‐dependent manner in astrocytes, oligodendrocytes, and neural progenitor subpopulations after SCI, suggesting that they play major roles in cellular responses following SCI. J Neurosci. Res. 66:1161–1172, 2001. © 2001 Wiley‐Liss, Inc.
Auditory processing of interaural timing information: New insights
Authors: Bernstein Leslie R.
Published: October 2004

Differences in the time‐of‐arrival of sounds at the two ears, or interaural temporal disparities (ITDs), constitute one of the major binaural cues that underlie our ability to localize sounds in space. In addition, ITDs contribute to our ability to detect and to discriminate sounds, such as speech, in noisy environments. For low‐frequency signals, ITDs are conveyed primarily by “cycle‐by‐cycle” disparities present in the fine‐structure of the waveform. For high‐frequency signals, ITDs are conveyed by disparities within the time‐varying amplitude, or envelope, of the waveform. The results of laboratory studies conducted over the past few decades indicate that ITDs within the envelopes of high‐frequency are less potent than those within the fine‐structure of low‐frequency stimuli. This is true for both measures of sensitivity to changes in ITD and for measures of the extent of the perceived lateral displacement of sounds containing ITDs. Colburn and Esquissaud (1976) hypothesized that it is differences in the specific aspects of the waveform that are coded neurally within each monaural (single ear) channel that account for the greater potency of ITDs at low frequencies rather than any differences in the more central binaural mechanisms that serve these different frequency regions. In this review, the results of new studies are reported that employed special high‐frequency “transposed” stimuli that were designed to provide the high‐frequency channels of the binaural processor with envelope‐based information that mimics waveform‐based information normally available only in low‐frequency channels. The results demonstrate that these high‐frequency transposed stimuli (1) yield sensitivity to ITDs that approaches, or is equivalent to, that obtained with “conventional” low‐frequency stimuli and (2) yield large extents of laterality that are similar to those measured with conventional low‐frequency stimuli. These findings suggest that by providing the high‐frequency channels of the binaural processor with information that mimics that normally available only at low frequencies, the potency of ITDs in the two frequency regions can be made to be similar, if not identical. These outcomes provide strong support for Colburn and Esquissaud's (1976) hypothesis. The use of high‐frequency transposed stimuli, in both behavioral and physiological investigations offers the promise of new and important insights into the nature of binaural processing. J Neurosci. Res. 66:1035–1046, 2001. © 2001 Wiley‐Liss, Inc.
Calcium/calmodulin‐dependent protein kinase IIβ isoform is expressed in motor neurons during axon outgrowth and is part of slow axonal transport
Authors: Lund Linda M. , McQuarrie Irvine G.
Published: October 2004

Previously, we identified calcium/calmodulin‐dependent protein kinase IIβ (CaMKIIβ) mRNA in spinal motor neurons with 372 bp inserted in what corresponds to the “association” domain of the protein. This was interesting because known additions and deletions to CaMKIIβ mRNA are usually less than 100 bp in size and found in the “variable” region. Changes in the association domain of CaMKIIβ could influence substrate specificity, activity or intracellular targeting. We show that three variations of this insert are found in CNS neurons or sciatic motor neurons of Sprague–Dawley rats. We used PCR and nucleic acid sequencing to identify inserts of 114, 243, or 372 bases. We also show that addition of the 372 bases is associated with outgrowth of the axon (the standard CaMKIIβ downregulates when axon outgrowth occurs). Radiolabeling, immunoblots, and 2D PAGE identified this larger CaMKIIβ as part of the group of soluble proteins moving at the slowest rate of axonal transport (SCa) in sciatic motor neurons (∼1 mm/day). This group is composed mainly of structural proteins (e.g., tubulin) used to assemble the cytoskeleton of regrowing axons. Published 2002 Wiley‐Liss, Inc.
Glial transporters for glutamate, glycine, and GABA III. Glycine transporters
Authors: Gadea Ana , María López‐Colomé Ana
Published: October 2004

Glial cells possess transport systems for the three major amino acid neurotransmitters glutamate, γ‐aminobutyric acid (GABA) and glycine, involved in the arrest of neurotransmission mediated by these compounds. Two glycine transporters have been cloned: GLYT1, mainly expressed by glial cells and shown to colocalize with NMDA receptors, and GLYT2, exclusively expressed by neurons and colocalized with the inhibitory glycine receptors. The way in which the regulation of extracellular glycine concentration by glial glycine transporters affects physiological and pathological conditions is discussed. The presence, differential pharmacology and specific regulation of glycine transporters in glial cells strongly support an important role for glia in the modulation of both, excitatory and inhibitory neurotransmission. J. Neurosci. Res. 64:218–222, 2001. © 2001 Wiley‐Liss, Inc.
Absence of hippocampal mossy fiber sprouting in transgenic mice overexpressing brain‐derived neurotrophic factor
Authors: Qiao Xiaoxi , Suri Chitra , Knusel Beat , Noebels Jeffrey L.
Published: October 2004

Excess neuronal activity upregulates the expression of two neurotrophins, nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF) in adult hippocampus. Nerve growth factor has been shown to contribute the induction of aberrant hippocampal mossy fiber sprouting in the inner molecular layer of the dentate gyrus, however the role of prolonged brain‐derived neurotrophic factor exposure is uncertain. We examined the distribution and plasticity of mossy fibers in transgenic mice with developmental overexpression of brain‐derived neurotrophic factor. Despite 2–3‐fold elevated BDNF levels in the hippocampus sufficient to increase the intensity of neuropeptide Y immunoreactivity in interneurons, no visible changes in mossy fiber Timm staining patterns were observed in the inner molecular layer of adult mutant hippocampus compared to wild‐type mice. In addition, no changes of the mRNA expression of two growth‐associated proteins, GAP‐43 and SCG‐10 were found. These data suggest that early and persistent elevations of brain‐derived neurotrophic factor in granule cells are not sufficient to elicit this pattern of axonal plasticity in the hippocampus. J. Neurosci. Res. 64:268–276, 2001. © 2001 Wiley‐Liss, Inc.
Adrenocorticosteroid receptor blockade and excitotoxic challenge regulate adrenocorticosteroid receptor mRNA levels in hippocampus
Authors: McCullers Deanna L. , Herman James P.
Published: October 2004

The mineralocorticoid receptor (MR) and glucocorticoid receptor (GR) are glucocorticoid‐activated transcription factors essential for maintenance of cellular homeostasis. Differential activation of these adrenocorticosteroid receptors (ACR) is thought to influence neuronal viability, particularly under challenging cellular conditions. The present study is designed to determine the effects of receptor blockade and excitotoxic insult on MR and GR mRNA expression and neuronal viability in hippocampus. Male Sprague–Dawley rats were pretreated for 48 hr with vehicle, MR antagonist spironolactone (SPIRO) (50 mg/kg, twice daily, s.c.), or GR antagonist RU486 (25 mg/kg, twice daily, s.c.) and subsequently injected with saline or the glutamate analog kainic acid (KA) (12 mg/kg i.p.). Twenty‐four hr post‐insult, MR and GR mRNA levels were assessed by in situ hybridization analysis, and hippocampal neurons were counted to assess KA‐induced cell loss. MR blockade with SPIRO increased basal MR mRNA levels in hippocampal subregions CA1, CA3, and dentate gyrus (DG) and increased basal GR mRNA levels in CA3. GR blockade with RU486 increased basal GR mRNA levels in CA3. The excitotoxin KA decreased MR mRNA levels in CA1 and CA3, decreased GR mRNA levels in DG, and negated all antagonist‐induced increases of ACR mRNAs. Cell counts quantifying KA damage indicated increased CA3 vulnerability to KA insult after treatment with MR antagonist spironolactone but demonstrated no significant cell loss in any other group or region. These results demonstrate dynamic regulation of hippocampal MR and GR mRNAs after ACR antagonist treatment and kainate toxicity, underscoring the potential importance of MR and GR availability to neuronal viability after insult. J. Neurosci. Res. 64:277–283, 2001. © 2001 Wiley‐Liss, Inc.
Role of oxidative stress in the apoptotic cell death of cultured cerebellar granule neurons
Authors: Valencia Antonio , Morán Julio
Published: October 2004

When cultured cerebellar granule neurons (CGN) are transferred from 25 mM KCl (K25) to 5 mM KCl (K5) caspase‐3 and caspase‐8, but not caspase‐1 or caspase‐9,activities are induced and cells die apoptotically. CGN death was triggered by a [Ca2+]imodification when [Ca2+]iwas reduced from 300 nM to 50 nM in a K5 medium. The [Ca2+]ichanges were followed by an increase in ROS levels. The generation of both cytosolic and mitochondrial reactive oxygen species (ROS) occurred at three different times, 10 min, 30 min and 3–4 hr but only those ROS produced after 3–4 hr are involved in the process of cell death. When CGN cultured in a K5 medium are treated with different antioxidants like scavengers of ROS (mannitol, DMSO) or antioxidant enzymes (superoxide dismutase and catalase) phosphatidylserine translocation, caspase activity, chromatin condensation and cell death is markedly diminished. The protective effect of antioxidants is not mediated through a modification in [Ca2+]i. Caspase activation, PS translocation and chromatin condensation were downstream of ROS production. In contrast to H2O2, ROS produced by a xanthine/xanthine oxidase system in CGN cultured in K25 were able to directly induce caspase‐3 activation and death that resulted sensitive to z‐VAD, a caspase inhibitor. These findings indicate that a reduction in [Ca2+]itriggers CGN death by inducing a generation of ROS after 3–4 hr, which could play a critical role in the initial phases of the apoptotic process including PS translocation, chromatin condensation and the activation of initiator and executor caspases. J. Neurosci. Res. 64:284–297, 2001. © 2001 Wiley‐Liss, Inc.
Identifying genes involved in regulating differentiation of neuroblastoma cells
Authors: Hovland Alicia Rudie , Nahreini Piruz , Andreatta Cynthia P. , Edwards‐Prasad Judith , Prasad Kedar N.
Published: October 2004

The genes regulating the induction of differentiation in neurons are not definitively known. Some neuronal tumors retain the ability to differentiate into mature, functional neurons in response to pharmacological agents, despite the presence of genetic anomalies. We hypothesized that some of the genes whose expression is altered between undifferentiated and differentiated states may be those responsible for inducing differentiation. To investigate this, we used a mouse neuroblastoma (NB) cell line, NBP2, in which ≥90% of the cells in the culture terminally differentiate upon elevation of intracellular adenosine 3′,5′‐cyclic monophosphate (cAMP) levels. Gene expression was analyzed using cDNA array blots containing 588 known genes. mRNA from cultures of undifferentiated and differentiated NB cells was used to make cDNA probes for blot hybridization. We identified several genes that are predominantly expressed in either undifferentiated or differentiated NB cells. In addition, numerous genes are moderately up‐ or down‐regulated during differentiation of NB cells. We identified the N‐myc protooncogene, cyclin B1, and protease nexin 1 as genes that are expressed in undifferentiated NB cells and whose levels are significantly down‐regulated upon differentiation. In contrast, the c‐fes and c‐fos protooncogenes and the RAG‐1 gene activator are genes whose expression is significantly up‐regulated during differentiation of NB cells. These findings were confirmed by RT‐PCR analysis. The transcript size and expression level of N‐myc, cyclin B1, protease nexin 1, c‐fes, and c‐fos were verified by Northern blotting. These genes may represent key mediators involved in the regulation of NB cell differentiation. J. Neurosci. Res. 64:302–310, 2001. © 2001 Wiley‐Liss, Inc.
Molecular organization of the nodal region is not altered in spontaneously diabetic BB‐Wistar rats
Authors: Brown Alexander A. , Xu Theodore , Arroyo Edgardo J. , Levinson S. Rock , Brophy Peter J. , Peles Elior , Scherer Steven S.
Published: October 2004

We examined the organization of the molecular components of the nodal region in spontaneously diabetic BB‐Wistar rats. Frozen sections and teased fibers from the sciatic nerves were immunostained for nodal (voltage‐gated Na+ channels, ankyrinG, and ezrin), paranodal (contactin, Caspr, and neurofascin 155 kDa), and juxtaparanodal (Caspr2, the Shaker‐type K+ channels Kv1.1 and Kv1.2, and their associated subunit Kvβ2) proteins. All of these proteins were properly localized in myelinated fibers from rats that had been diabetic for 15–44 days, compared to age‐matched, nondiabetic animals. These results demonstrate that the axonal membrane is not reorganized, so nodal reorganization is not likely to be the cause of nerve conduction slowing in this animal model of acute diabetes. J. Neurosci. Res. 65:139–149, 2001. © 2001 Wiley‐Liss, Inc.
Ezrin, radixin, and moesin are components of Schwann cell microvilli
Authors: Scherer Steven S. , Xu Theodore , Crino Peter , Arroyo Edgardo J. , Gutmann David H.
Published: October 2004

Ezrin, radixin, and moesin (ERM proteins), as well as the neurofibromatosis 2 (NF2) tumor suppressor merlin/schwannomin, all belong to the protein 4.1 family, yet only merlin is a tumor suppressor in Schwann cells. To gain insight into the possible functions of ERM proteins in Schwann cells, we examined their localization in peripheral nerve, because we have previously shown that merlin is found in paranodes and in Schmidt‐Lanterman incisures. All three ERM proteins were highly expressed in the microvilli of myelinating Schwann cells that surround the nodal axolemma as well as in incisures and cytoplasmic puncta in the vicinity of the node. In all of these locations, ERM proteins were colocalized with actin filaments. In contrast, ERM proteins did not surround nodes in the CNS. The colocalization of ERM proteins with actin indicates that they have functions different from those of merlin in myelinating Schwann cells. J. Neurosci. Res. 65:150–164, 2001. © 2001 Wiley‐Liss, Inc.
Improvement of macromolecular clearance via lymph flow in hamster gingiva by low‐power carbon dioxide laser‐irradiation
Authors: Shimotoyodome Akira , Okajima Miyuki , Kobayashi Hisataka , Tokimitsu Ichiro , Fujimura Akira
Published: October 2004

Background and Objective

Although therapeutic effects of low‐power laser‐irradiation on periodontal disease have been reported, little is known about the biological effects of laser‐irradiation in the gingiva. Recently we reported that topical warming stimulated macromolecular clearance via lymph flow in hamster gingiva. This study was conducted to investigate whether low‐power laser‐irradiation affects macromolecular clearance via the lymph flow in the gingiva.

Study Design/Materials and Methods

We injected 14C‐methylated albumin into the mandibular gingiva of anesthetized hamsters followed by topical carbon dioxide (CO2) laser‐irradiation (30 seconds, 0.5–1.5 W). We measured the clearance of radiolabeled albumin from the gingiva and its drainage into submandibular lymph nodes during 10 minutes.

Results

The clearance of the radiolabeled albumin from the gingiva and the influx into the submandibular lymph nodes were increased by CO2 laser‐irradiation.

Conclusion

Low‐power CO2 laser‐irradiation improves macromolecular clearance via the lymph flow in hamster gingiva. Lasers Surg. Med. 29:442–447, 2001. © 2001 Wiley‐Liss, Inc.
Photothermal properties of shape memory polymer micro‐actuators for treating stroke*
Authors: Maitland Duncan J. , Metzger Melodie F. , Schumann Daniel , Lee Abraham , Wilson Thomas S.
Published: October 2004

Background and Objectives

In this paper the photothermal engineering issues of novel shape memory polymer (SMP) microactuators for treating stroke are presented. The engineering issues for using lasers to heat and subsequently actuate these SMP devices are presented in order to provide design criteria and guidelines for intravascular, laser activated SMP devices.

Materials and Methods

A total of three devices will be presented: two interventional ischemic stroke devices (coil and umbrella) and one device for releasing embolic coils (microgripper). The optical properties of SMP, methods for coupling laser light into SMP, heating distributions in the SMP devices, and the impact of operating the thermally activated material in a blood vessel are presented.

Results

Actuating the devices requires device temperatures in the range of 65–85°C. Attaining these temperatures under flow conditions requires critical engineering of the SMP optical properties, optical coupling into the SMP, and device geometries.

Conclusion

Laser‐activated SMP devices are a unique combination of laser‐tissue and biomaterial technologies. Successful deployment of the microactuator requires well‐engineered coupling of the light from the diffusing fiber through the blood into the SMP. Lasers Surg. Med. 30:1–11, 2002. © 2002 Wiley‐Liss, Inc.
Vascular response to laser photothermolysis as a function of pulse duration, vessel type, and diameter: Implications for port wine stain laser therapy
Authors: Kimel Sol , Svaasand Lars O. , Cao Danielle , Hammer‐Wilson Marie J. , Nelson J. Stuart
Published: October 2004

Background and Objective

Treatment of port wine stains (PWS) by photothermolysis can be improved by optimizing laser parameters on an individual patient basis. We have studied the critical role of pulse duration (tp) on the treatment efficacy.

Study Design/Materials and Methods

The V‐beam laser (Candela) allowed changing tp over user‐specified discrete values between 1.5 and 40 milliseconds by delivering a series of 100 microsecond spikes. For the 1.5 and 3 millisecond pulses, three spikes were observed at intervals tp/2 and for tp ≥ 6 milliseconds, four spikes separated by tp/3. The ScleroPlus laser (Candela) has a smooth output over its fixed 1.5 milliseconds duration. Blood vessels in the chick chorioallantoic membrane (CAM) were irradiated at fixed wavelength (595 nm), spot size (7 mm), radiant exposure (15 Jcm−2), and at variable tp. The CAM contains an extensive microvascular network ranging from capillaries with diameter D < 30 μm to blood vessels of D ≈ 120 μm. The CAM assay allows real‐time video documentation, and observation of blood flow in pre‐capillary arterioles (A) and post‐capillary venules (V). Vessel injury was graded from recorded videotapes. Mathematical modeling was developed to interpret results of vessel injury when varying tp and D. A modified thermal relaxation time was introduced to calculate vessel wall temperature following laser exposure.

Results

Arterioles. For increasing tp, overall damage was found to decrease. For fixed tp, damage decreased with vessel size. Venules. For all D, damage was smaller than for corresponding arterioles. There was no dependence of damage on tp. For given tp, no variation of damage with D was observed. Photothermolysis due to spiked (V‐beam) vs. smooth (Scleroplus) delivery of laser energy at fixed tp (1.5 milliseconds), showed similar vessel injuries for al values of D (P>0.05).

Conclusions

The difference between initial arteriole and venule damage could be explained by the threefold higher absorption coefficient at 595 nm in (oxygen‐poor!) arterioles. In human patients, PWS consist of ectatic venules (characterized by higher absorption), so that these considerations favor the use of 595‐nm irradiation for laser photothermolysis. For optimal treatment of PWS it is proposed that tp be between 0.1 and 1.5 milliseconds. This is based on a modified relaxation time τd′, defined as the time required for heat conduction into the full thickness of the vessel wall, which is assumed to have a thickness ΔD ≈ 0.1D. The corresponding τd′ will be a factor of about six smaller than given in the literature. For vessels with D between 30 and 300 μm, τd′ ranges from 0.1 to 1.5 milliseconds. Lasers Surg. Med. 30:160–169, 2002. © 2002 Wiley‐Liss, Inc.
Comparison of the in vivo efficiency of photofrin II‐, mTHPC‐, mTHPC‐PEG‐ and mTHPCnPEG‐mediated PDT in a human xenografted head and neck carcinoma
Authors: Reuther Tobias , Kübler Alexander C. , Zillmann Uwe , Flechtenmacher Christa , Sinn Hannsjörg
Published: October 2004

Background and Objective

One of the approaches to enhance the selectivity and efficiency of photodynamic therapy (PDT) was the conjugation of the photosensitizer meta‐tetrahydroxyphenylchlorin (mTHPC) to the water‐soluble polymer polyethylene glycol (PEG). Several studies have demonstrated that mTHPC‐PEG has a higher selectivity and a longer circulating half‐life than free mTHPC, whereas no in vivo effect of this benefit could be seen.

Study Design/Materials and Methods

In a model of RAG‐2‐mice bearing a human oral squamous cell carcinoma xenograft (XF 354), the in vivo efficiency assessed as growth retardation or remission caused by Photofrin II and free mTHPC was compared with mTHPC coupled in two different ways to polyethylene glycol (PEG). One hundred and fourty‐nine female RAG‐2‐mice were randomised into one control group and 13 therapy groups. Treatment parameters were adapted from those routinely applied in animal studies.

Results

Photofrin II‐mediated PDT and mTHPC‐mediated PDT were both in vivo highly effective, whereas mTHPC induced less scars. The in vivo results after mTHPC‐PEG‐mediated PDT were disappointing, whereas the effectiveness of mTHPCnPEG‐mediated PDT, a newly coupled macromolecular photosensitizer, were promising.

Conclusions

These results demonstrated the impact of the method of linkage between the photoactive agent mTHPC and polyethylene glycol (PEG) upon the in vivo effectiveness. mTHPC and mTHPCnPEG are promising photosensitizers for the future, especially for the cosmetic treatment needs of head and neck surgery. Lasers Surg. Med. 29:314–322, 2001. © 2001 Wiley‐Liss, Inc.