bluuebunny/crossref_metadata_2025 huggingface dataset:
Fusion of the BCR and the fibroblast growth factor receptor‐1 (FGFR1) genes as a result of t(8;22)(p11;q11) in a myeloproliferative disorder: The first fusion gene involving BCR but not ABL
Authors: Fioretos Thoas , Panagopoulos Ioannis , Lassen Carin , Swedin Agneta , Billström Rolf , Isaksson Margareth , Strömbeck Bodil , Olofsson Tor , Mitelman Felix , Johansson Bertil
Published: August 2002

Constitutive activation of tyrosine kinases as a consequence of chromosomal translocations, forming fusion genes, plays an important role in the development of hematologic malignancies, in particular, myeloproliferative syndromes (MPSs). In this respect, the t(9;22)(q34;q11) that results in the BCR/ABL fusion gene in chronic myeloid leukemia is one of the best‐studied examples. The fibroblast growth factor receptor 1 (FGFR1) gene at 8p11 encodes a transmembrane receptor tyrosine kinase and is similarly activated by chromosomal translocations, in which three alternative genes—ZNF198 at 13q12, CEP110 at 9q34, and FOP at 6q27—become fused to the tyrosine kinase domain of FGFR1. These 8p11‐translocations are associated with characteristic morphologic and clinical features, referred to as “8p11 MPS.” In this study, we report the isolation and characterization of a novel fusion gene in a hematologic malignancy with a t(8;22)(p11;q11) and features suggestive of 8p11 MPS. We show that the breakpoints in the t(8;22) occur within introns 4 and 8 of the BCR and FGFR1 genes, respectively. On the mRNA level, the t(8;22) results in the fusion of BCR exons 1–4 in‐frame with the tyrosine kinase domain of FGFR1 as well as in the expression of a reciprocal FGFR1/BCR chimeric transcript. By analogy with data obtained from previously characterized fusion genes involving FGFR1 and BCR/ABL, it is likely that the oligomerization domain contributed by BCR is critical and that its dimerizing properties lead to aberrant FGFR1 signaling and neoplastic transformation. © 2001 Wiley‐Liss, Inc.
Sedimentological and stratigraphic observations in El Mirón, a late Quaternary cave site in the Cantabrian Cordillera, Northern Spain
Authors: Straus Lawrence G. , González Morales Manuel , Farrand William R. , Hubbard William J.
Published: August 2002

El Mirón cave on the northern edge of the Cantabrian Cordillera is one of the first montane sites in this area to be the object of modern interdisciplinary research. Five excavation seasons have revealed an archaeological sequence attributable to the Medieval, Bronze, Chalcolithic, Neolithic, Mesolithic, Azilian, Magdalenian, and Solutrean periods, and early Upper and Middle Paleolithic levels have just been reached. Forty‐four radiocarbon ages range from 900 to 41,000 14C yr B.P. Sediments in the vestibule include sediment redeposited from an ancient colluvial fill in the inner cave, limestone rock fragments, biogenic CaCO3 generated by cryptogamic and vegetation growth on the cave ceiling, eolian silts, bird droppings, and anthropogenic lithic and faunal remains. Sedimentological analyses of the cave fill reported here document the transition from a sandy silt facies with rounded cobbles in the inner vestibule to a carbonate‐rich silt facies with angular limestone clasts near the cave mouth. There is no clear regional paleoclimatic signal in the bulk sediment analyses because of the heavy influence of local input and human disturbance. Micromorphology by M.‐A. Courty (see Courty and Vallverdu [this issue]; and also Courty et al. [1989]) reveals subtle evidence for some short‐term variations that can be correlated with regional paleoclimates, such as the Younger Dryas event. © 2001 John Wiley & Sons, Inc.
Cell and tissue requirements for the gene eed during mouse gastrulation and organogenesis
Authors: Morin‐Kensicki Elizabeth M. , Faust Cynthia , LaMantia Christian , Magnuson Terry
Published: August 2002

Summary: Mouse embryos homozygous for the allele eedl7Rn5‐3354SB of the Polycomb Group gene embryonic ectoderm development (eed) display a gastrulation defect in which epiblast cells move through the streak and form extraembryonic mesoderm derivatives at the expense of development of the embryo proper. Here we demonstrate that homozygous mutant ES cells have the capacity to differentiate embryonic cell types both in vitro as embryoid bodies and in vivo as chimeric embryos. In chimeric embryos, eed mutant cells can respond to wild‐type signals and participate in normal gastrulation movements. These results indicate a non–cell‐autonomous function for eed. Evidence of mutant cell exclusion from the forebrain and segregation within somites, however, suggests that eed has cell‐autonomous roles in aspects of organogenesis. A requirement for eed in the epiblast during embryonic development is supported by the fact that high‐contribution chimeras could not be rescued by a wild‐type extraembryonic environment. genesis 31:142–146, 2001. © 2001 Wiley‐Liss, Inc.
Codon‐improved Cre recombinase (iCre) expression in the mouse
Authors: Shimshek D.R. , Kim J. , Hübner M.R. , Spergel D.J. , Buchholz F. , Casanova E. , Stewart A.F. , Seeburg P.H. , Sprengel R.
Published: August 2002

Summary: By applying the mammalian codon usage to Cre recombinase, we improved Cre expression, as determined by immunoblot and functional analysis, in three different mammalian cell lines. The improved Cre (iCre) gene was also designed to reduce the high CpG content of the prokaryotic coding sequence, thereby reducing the chances of epigenetic silencing in mammals. Transgenic iCre expressing mice were obtained with good frequency, and in these mice loxP‐mediated DNA recombination was observed in all cells expressing iCre. Moreover, iCre fused to two estrogen receptor hormone binding domains for temporal control of Cre activity could also be expressed in transgenic mice. However, Cre induction after administration of tamoxifen yielded only low Cre activity. Thus, whereas efficient activation of Cre fusion proteins in the brain needs further improvements, our studies indicate that iCre should facilitate genetic experiments in the mouse. genesis 32:19–26, 2002. © 2002 Wiley‐Liss, Inc.
Genetic manipulation of mouse embryonic stem cells by mutant λ integrase
Authors: Christ Nicole , Dröge Peter
Published: August 2002

Summary: Mutant λ integrases catalyze site‐specific recombination reactions inside mammalian cells. Here we demonstrate that the integrase system can be used to eliminate resistance marker genes from the genome of mouse embryonic stem cells. So‐called integrative and excisive recombination pathways led to the precise deletion of the neomycin gene, which was inserted together with a flanking pair of directly repeated recombination sites into the ROSA26 locus by standard targeting techniques. The excision of the resistance gene led to the expression of enhanced green fluorescence protein, which served as a means to sort out cells that had undergone site‐specific recombination. Southern analysis and DNA sequencing confirmed that strand exchange reactions had occurred in the genome as expected. Hence, the integrase system may be used in conjunction with other site‐specific recombinases as a tool in genome manipulation protocols. genesis 32:203–208, 2002. © 2002 Wiley‐Liss, Inc.
Cooperative E‐box regulation of human GLI1 by TWIST and USF
Authors: Villavicencio Elisabeth H. , Yoon Joon Won , Frank Daniel J. , Füchtbauer Ernst‐Martin , Walterhouse David O. , Iannaccone Philip M.
Published: August 2002

Summary: Sonic hedgehog signaling plays a critical role in vertebrate patterning, and signaling defects are associated with severe birth defects and cancer in man. GLI1 encodes a critical transcription activator in this pathway. GLI1 is expressed in human basal cell carcinomas and sarcomas. Despite the significance of the GLI1 gene in human disease, few immediate upstream regulators of GLI1 expression are known. We previously demonstrated that a 5′ region, including 5′ flanking sequence, an untranslated exon, and 425 bp of the first intron, regulates the human GLI1 gene. Here we show that inactivating mutations in E‐box, GC box, AP‐2, GATA, GSG, PuF, and Zeste sites identified three critical regulatory elements, including a GC box that binds Sp1 and two intronic E‐boxes that bind USF proteins or Twist. Expression of Twist but not a frame shift mutation of Twist activates the wild‐type human GLI1 regulatory sequences but not with inactivating mutations of the E‐boxes. Twist activates GLI1 reporter expression through E‐box +482 but requires binding of USF proteins to E‐box +157. Twist mutations cause human birth defects and Twist is overexpressed in many rhabdomyosarcomas, suggesting that one of Twist's primary roles is the regulation of GLI1. genesis 32:247–258, 2002. © 2002 Wiley‐Liss, Inc.
Achieving efficient delivery of morpholino oligos in cultured cells
Authors: Morcos Paul A.
Published: August 2002

Summary: One of the many features that make morpholino oligos unique among the antisense structural types is an uncharged backbone. While this feature eliminates the nonspecific interactions of traditional S‐oligos, it also renders the morpholino undeliverable via the traditional lipid‐based delivery systems. This article describes a highly efficient method of delivering morpholino oligos into adherent and nonadherent cultured cells. In this system, a nonionic morpholino oligo is paired to a complementary DNA “carrier.” The DNA is then bound electrostatically to a partially ionized, weakly‐basic ethoxylated polyethylenimine (EPEI). This morpholino/DNA/EPEI complex is efficiently endocytosed, and when the pH drops within the endosome, the EPEI more fully ionizes, resulting in permeabilization of the endosomal membrane and release of the morpholino into the cytosol. This article describes optimization of delivery in HeLa cells and provides the basis for delivery in any cultured endocytic cell type. genesis 30:94–102, 2001. © 2001 Wiley‐Liss, Inc.
Action of morpholinos in Ciona embryos
Authors: Satou Yutaka , Imai Kaoru S. , Satoh Nori
Published: August 2002

Summary: First, using morpholino against lacZ, we demonstrate that the morpholino specifically suppresses the translation of the gene introduced exogenously into Ciona eggs. Second, using morpholino against an alkaline phosphatase gene, we show that the morpholino suppresses the translation of the endogenous gene as well. Third, using morpholino against β‐catenin gene, we confirm that the suppression by the morpholino can be rescued by injection of β‐catenin mRNA. All of these results indicate that morpholino act in Ciona embryos to specifically block the function of endogenous genes as well as exogenously introduced genes. genesis 30: 103–106, 2001. © 2001 Wiley‐Liss, Inc.
Bidirectional transcriptional activity of PGK‐neomycin and unexpected embryonic lethality in heterozygote chimeric knockout mice
Authors: Scacheri P.C. , Crabtree J.S. , Novotny E.A. , Garrett‐Beal L. , Chen A. , Edgemon K.A. , Marx S.J. , Spiegel A.M. , Chandrasekharappa S.C. , Collins F.S.
Published: August 2002

Summary: In an effort to create a conventional knockout mouse model for multiple endocrine neoplasia type 1 (MEN1), we targeted disruption of the mouse Men1 gene through homologous recombination in ES cells. Men1 exons 2–4 were replaced by a PGK‐neomycin cassette inserted in the opposite direction of Men1 transcription (Men1MSK/+). Unexpectedly, the Men1 conventional knockout was lethal in heterozygous, chimeric animals. Analysis of embryos revealed late gestational lethality with some embryos showing omphalocele. This was a very surprising phenotype, given that humans and mice that are heterozygotes for loss of function mutations in MEN1 are phenotypically normal except for a risk of endocrine tumors. Northern analysis of Men1MSK/+ embryonic stem cell RNA revealed the presence of an abundant, novel transcript of 2.1 kb, in addition to the expected wild‐type transcripts of 2.7 kb and 3.1 kb. RT‐PCR analysis identified this aberrant transcript as arising from the antisense strand of the PGK promoter. We hypothesize that this transcript is producing either a toxic effect at the RNA level, or a dominant negative effect through the production of an amino‐terminal truncated protein product. This example serves as a cautionary reminder that mouse knockouts using PGK‐neo may sometimes display phenotypes that reflect more than just the loss of function of the targeted gene. genesis 30:259–263, 2001. Published 2001 Wiley‐Liss, Inc.
Functional expression of Kir 6.1/SUR1‐KATP channels in frog retinal Müller glial cells
Authors: Skatchkov Serguei N. , Rojas Legier , Eaton Misty J. , Orkand Richard K. , Biedermann Bernd , Bringmann Andreas , Pannicke Thomas , Veh Rüdiger W. , Reichenbach Andreas
Published: August 2002

The retinae and brains of larval and adult amphibians survive long‐lasting anoxia; this finding suggests the presence of functional KATP channels. We have previously shown with immunocytochemistry studies that retinal glial (Müller) cells in adult frogs express the KATP channel and receptor proteins, Kir6.1 and SUR1, while retinal neurons display Kir6.2 and SUR2A/B (Skatchkov et al., 2001a: NeuroReport 12:1437–1441; Eaton et al., in press: NeuroReport). Using both immunocytochemistry and electrophysiology, we demonstrate the expression of Kir6.1/SUR1 (KATP) channels in adult frog and tadpole Müller cells. Using conditions favoring the activation of KATP channels (i.e., ATP‐ and spermine‐free cytoplasm‐dialyzing solution containing gluconate) in Müller cells isolated from both adult frogs and tadpoles, we demonstrate the following. First, using the patch‐clamp technique in whole‐cell recordings, tolbutamide, a blocker of KATP channels, blocks nearly 100% of the transient and about 30% of the steady‐state inward currents and depolarizes the cell membrane by 5–12 mV. Second, inside‐out membrane patches display a single‐channel inward current induced by gluconate (40 mM) and blocked by ATP (200 μM) at the cytoplasmic side. The channels apparently show two sublevels (each of ∼27–32 pS) with a total of 85‐pS maximal conductance at −80 mV; the open probability follows a two‐exponential mechanism. Thus, functional KATP channels, composed of Kir6.1/SUR1, are present in frog Müller cells and contribute a significant part to the whole‐cell K+ inward currents in the absence of ATP. Other inwardly rectifying channels, such as Kir4.1 or Kir2.1, may mediate the remaining currents. KATP channels may help maintain glial cell functions during ATP deficiency. GLIA 38:256–267, 2002. © 2002 Wiley‐Liss, Inc.
Proteasome dynamics during cell cycle in rat Schwann cells
Authors: Lafarga Miguel , Fernández Rosario , Mayo Isabel , Berciano María T. , Castaño José G.
Published: August 2002

The proteasome is responsible for most of the protein degradation that takes place in the cytoplasm and nucleus. Immunofluorescence and electron microscopy are used to study proteasome dynamics during the cell cycle in rat Schwann cells. During interphase, the proteasome is present in the nucleus and cytoplasm and shows no colocalization with cytoskeletal components. Some cytoplasmic proteasomes always localize in the centrosome both in interphase and in mitotic cells and only associate with microtubules during mitosis. The proteasome exits the nucleus during prophase. In anaphase, the proteasome becomes prominent in the region between the two sets of migrating chromosomes and in association with interzonal microtubules and stem bodies. In telophase, the proteasome begins to reenter the nucleus and is prominent in the midbody region until the end of cytokinesis. The proteasome does not colocalize with actin or vimentin during mitosis, except for colocalization with actin in the sheet‐like lamellipodia, which serve as substrate attachments for the cell during mitosis. During S phase, nuclear proteasomes colocalize with foci of BrdU incorporation, but this association changes with time: maximal at early S phase and declining as S phase progresses to the end. These results are discussed in relation to the biochemical pathways involved in cell cycle progression. GLIA 38:313–328, 2002. © 2002 Wiley‐Liss, Inc.
New method of purification for establishing primary cultures of ensheathing cells from the adult olfactory bulb
Authors: Nash Holly H. , Borke Rosemary C. , Anders Juanita J.
Published: August 2002

Ensheathing cells exclusively enfold olfactory axons. The ability of olfactory axons to reinnervate the adult mammalian olfactory bulb throughout the lifetime of an organism is believed to result from the presence of this unique glial cell in the olfactory system. This theory has been substantiated by research demonstrating the ability of transplanted ensheathing cells to promote axonal regrowth in areas of the central nervous system that are normally nonpermissive. A simple method for purifying ensheathing cells resulting in a large yield of cells is therefore invaluable for transplantation studies. We have developed such a method based on the differing rates of attachment of the various harvested cell types. The greatest percentage of cells (70.4%) that attached during the first step of the separation was determined to be fibroblasts. The remainder of the cells were classified as astrocytes (20.8%) and ensheathing cells (6.8%). The percentage of attached astrocytes (67.6%) was greatly increased during the second purification step while the percentage of fibroblasts decreased greatly (27.9%) and the percentage of ensheathing cells (5.3%) slightly decreased. In the final cultures, 93.2 % of the attached cells were ensheathing cells, while astrocytes (5.9%) and fibroblasts (1.4%) were only minor components. This simple, inexpensive method of purifying ensheathing cells will facilitate their use in central nervous system regeneration research. GLIA 34:81–87, 2001. © 2001 Wiley‐Liss, Inc.
Glyt‐1 expression in cultured human Müller cells and intact retinae
Authors: Reye Peter , Penfold Philip , Pow David V.
Published: August 2002

In this study, we demonstrate that Müller cells cultured from human retinas are capable of strongly expressing the glycine transporter Glyt‐1 as assessed by immunocytochemistry. By contrast, intact normal and pathological human retinas exhibit Glyt‐1 immunoreactivity only in neurons. These data suggest that Glyt‐1 expression in cultured Müller cells is an epiphenomenon associated with culturing in vitro, rather than a normal physiological or even pathophysiological phenomenon in vivo. GLIA 34:311–315, 2001. © 2001 Wiley‐Liss, Inc.
Rumpshaker‐like proteolipid protein (PLP) ratio in a mouse model with unperturbed structural and functional integrity of the myelin sheath and axons in the central nervous system
Authors: Uschkureit Thomas , Spörkel Olaf , Büssow Heinrich , Stoffel Wilhelm
Published: August 2002

The gene plp on the X chromosome encodes the isoforms proteolipid protein (PLP) and DM20, two dominant integral membrane proteins of central nervous system (CNS) myelin. DM20 results from the activation of the cryptic splice site in exon III of the PLP gene. We inserted a sense‐orientated loxP flanked neomycin‐gene into intron III of the plp sequence, using homologous recombination in embryonic stem cells and generated the homozygous neoS mouse line. Unlike the previously described complete PLP/DM20 ablation (plp−/−), which has been obtained by introducing a neo‐gene in antisense‐orientation in the same position of intron III, the plp expression surprisingly revealed reduced mRNA levels. The PLP isoform was reduced to 50%, but DM20 expression was unaffected. This protein pattern resembles the expression profile of the PLP isoforms in the natural occurring rumpshaker mutant. Electron microscopic examination revealed a normal compaction of CNS‐myelin and maintenance of axon integrity. PLP expression levels of the wt control were recovered by Cre excision of the neo‐selection gene after intercrossing neoS mice and oligodendrocyte‐specific Cre‐mice. These data strongly hint at different functions of intron III in PLP/DM20‐specific splicing and mRNA stability. Furthermore evidence is provided for functionally affected translation products of the PLP gene in the rumpshaker mutant, whereas no PLP‐isoform occur in plp−/− mice generated by introducing a selectable marker into intron III in antisense orientation. GLIA 35:63–71, 2001. © 2001 Wiley‐Liss, Inc.
T‐ and B‐cell responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis and multiple sclerosis
Authors: Iglesias Antonio , Bauer Jan , Litzenburger Tobias , Schubart Anna , Linington Christopher
Published: August 2002

The identification of myelin oligodendrocyte glycoprotein (MOG) as a target for autoantibody‐mediated demyelination in experimental autoimmune encephalomyelitis (EAE) resulted in the re‐evaluation of the role of B cell responses to myelin autoantigens in the immunopathogenesis of multiple sclerosis. MOG is a central nervous system specific myelin glycoprotein that is expressed preferentially on the outermost surface of the myelin sheath. Although MOG is only a minor component of CNS myelin it is highly immunogenic, inducing severe EAE in both rodents and primates. In rat and marmoset models of MOG‐induced EAE demyelination is antibody‐dependent and reproduces the immunopathology seen in many cases of MS. In contrast, in mice inflammation in the CNS can result in demyelination in the absence of a MOG‐specific B cell response, although if present this will enhance disease severity and demyelination. Clinical studies indicate that autoimmune responses to MOG are enhanced in many CNS diseases and implicate MOG‐specific B cell responses in the immunopathogenesis of multiple sclerosis. This review provides a summary of our current understanding of MOG as a target autoantigen in EAE and MS, and addresses the crucial question as to how immune tolerance to MOG may be maintained in the healthy individual. GLIA 36:220–234, 2001. © 2001 Wiley‐Liss, Inc.
Müller cells in long‐term full‐thickness retinal transplants
Authors: Ghosh Fredrik
Published: August 2002

Müller cells are essential in creating and maintaining intricate neuroretinal architecture. The functions of this important glial cell are not limited to mere support of the retinal neurons, but also include interaction in synaptic transmission and activation in response to retinal insult. In this study, we have examined Müller cell morphology and degree of activation in embryonic full‐thickness rabbit neuroretinal grafts, which were positioned under the host retina using vitrectomy technique. After surviving 3–10 months, retinal specimens were examined with hematoxylin and eosin staining and immunohistochemical analysis of vimentin and glial fibrillary acidic protein (GFAP) expression. In the host retina covering the graft, outer layers were degenerated, and vimentin‐labeled Müller cells in this area appeared short, disorganized, and displayed strong GFAP labeling. In the graft, vimentin‐labeled Müller cells spanning the retinal layers in the normal manner were found. Müller cells in 3‐month grafts were well labeled by GFAP, whereas in older grafts, GFAP labeling was very weak or absent. Our results suggest that Müller cells in well‐laminated full‐thickness retinal grafts display many of the normal morphological features and retain a normal organization even after prolonged survival times. The loss of the initial degree of Müller cell activation indicates a long‐term stability of the graft. The degeneration and gliosis of the host retina covering the graft is best explained by the merangiotic nature of the rabbit retina and may limit the usefulness of the rabbit in retinal transplantation experiments. GLIA 37:76–82, 2002. © 2002 Wiley‐Liss, Inc.
Disability and mild cognitive impairment: a longitudinal population‐based study
Authors: Artero Sylvaine , Touchon Jacques , Ritchie Karen
Published: August 2002

Objective

To determine whether mild cognitive deficit is associated with parallel changes in ability to perform activities of daily living.

Background

While considerable research has been conducted on the effect of senile dementia and other neurodegenerative disorders on ability to perform everyday activities, little is known about the much larger group of elderly persons suffering from mild cognitive deficits.

Methods

Disability prevalence was estimated in 368 persons over the age of 65 years recruited from the general population via a general practitioner network. Subjects were followed over a 3‐year period using computerized cognitive assessment and observations of everyday functioning. Standardized neurological assessment in the third year permitted the identification of subjects who have evolved towards dementia.

Results

An overall disability prevalence was found in the general population of 26.3%, with 30.8% in subjects with sub‐clinical cognitive impairment. Longitudinal follow‐up showed cognitive decline over time without dementia to be paralleled by changes in activity performance, with visuospatial deficits having the most marked effect on overall functioning. High intelligence quotient (IQ) and education are seen to reduce the degree of activity loss, but only when senile dementia is not present.

Conclusions

Difficulties in the performance of everyday activities were found more frequently in non‐demented subjects with mild cognitive deficits than in the general population. High pre‐morbid levels of ability are seen to have a protective effect. A diagnosis of dementia should not therefore be required by persons with cognitive impairment applying for home help. Copyright © 2001 John Wiley & Sons, Ltd.
Application of an MEG eigenspace beamformer to reconstructing spatio‐temporal activities of neural sources
Authors: Sekihara Kensuke , Nagarajan Srikantan S. , Poeppel David , Marantz Alec , Miyashita Yasushi
Published: August 2002

We have applied the eigenspace‐based beamformer to reconstruct spatio‐temporal activities of neural sources from MEG data. The weight vector of the eigenspace‐based beamformer is obtained by projecting the weight vector of the minimum‐variance beamformer onto the signal subspace of a measurement covariance matrix. This projection removes the residual noise‐subspace component that considerably degrades the signal‐to‐noise ratio (SNR) of the beamformer output when errors in estimating the sensor lead field exist. Therefore, the eigenspace‐based beamformer produces a SNR considerably higher than that of the minimum‐variance beamformer in practical situations. The effectiveness of the eigenspace‐based beamformer was validated in our numerical experiments and experiments using auditory responses. We further extended the eigenspace‐based beamformer so that it incorporates the information regarding the noise covariance matrix. Such a prewhitened eigenspace beamformer was experimentally demonstrated to be useful when large background activity exists. Hum. Brain Mapping 15:199–215, 2002. © 2002 Wiley‐Liss, Inc.
Event‐related changes in neuromagnetic activity associated with syncopation and synchronization timing tasks
Authors: Mayville Justine M. , Fuchs Armin , Ding Mingzhou , Cheyne Douglas , Deecke Lüder , Kelso J.A. Scott
Published: August 2002

For low rhythmic rates (1.0 to ∼2.0 Hz), subjects are able to successfully coordinate finger flexion with an external metronome in either a syncopated (between the beats) or synchronized (on each beat) fashion. Beyond this rate, however, syncopation becomes unstable and subjects spontaneously switch to synchronization to maintain a 1:1 stimulus/response relationship. We used a whole‐head magnetometer to investigate the spatiotemporal dynamics of neuromagnetic activity (MEG) associated with both coordinative patterns at eight different rates spanning the range 1.0–2.75 Hz. Timing changes in the event‐related fields accompanied transitions from syncopation to synchronization and followed the placement of the motor response within each stimulus/response cycle. Decomposition of event‐related fields into component auditory and motor brain responses revealed that the amplitude of the former decreased with increasing coordination rate whereas the motor contribution remained approximately constant across all rates. Such an interaction may contribute to changes in auditory‐motor integration that cause syncopation to become unstable. Examination of event‐related changes in high frequency bands revealed that MEG signal power in the beta band (15–30 Hz) was significantly lower during syncopated coordination in sensors covering the contralateral sensorimotor area suggesting a dependence of beta rhythm amplitude on task difficulty. Suppression of beta rhythms was also stronger during synchronization preceded by syncopation, e.g., after subjects had switched, when compared with a control condition in which subjects synchronized throughout the entire range of rates. Hum. Brain Mapping 14:65–80, 2001. © 2001 Wiley‐Liss, Inc.
A study on the selective phosphorylation and phosphinylation of hydroxyphenols
Authors: Marosi György , Toldy Andrea , Parlagh Gyula , Nagy Zoltán , Ludányi Krisztina , Anna Péter , Keglevich György
Published: August 2002

By choice of appropriate reaction conditions, the phosphorylation of hydroquinone by diethyl chlorophosphate gave predominantly the monophosphate (2). A similar reaction of phloroglucinol led to the mixture of the possible products (6, 7, and 8). The monophosphinylation of the above hydroxyphenols by diphenylphosphinyl chloride could be accomplished with a good selectivity to give product 4 or 9, the yields, however, being variable. © 2002 Wiley Periodicals, Inc. Heteroatom Chem 13:126–130, 2002; Published online in Wiley Interscience (www.interscience.wiley.com). DOI 10.1002/hc.10006
Synthesis of new calix[4]arene‐based phosphorus ligands and their application in the Rh(I) catalyzed hydroformylation of 1‐octene
Authors: Kunze C. , Selent D. , Neda I. , Schmutzler R. , Spannenberg A. , Börner A.
Published: August 2002

The synthesis of calix[4]arene‐based phosphorus diamides and phosphites is described. These oligocyclic ligands have been tested in the Rh(I)‐ catalyzed hydroformylation of 1‐octene. Depending on the reaction conditions, yields up to 99% and n/iso‐selectivities between 0.7 and 2.6 have been observed. tert‐Butyl groups on the upper rim of the calix[4]arene template had a beneficial effect on the catalytic reaction. In general biuret‐derived P‐ligands were superior. For comparison, the corresponding “monomeric” ligands have also been synthesized and were employed in the catalytic reaction. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:577–585, 2001
Competitive [4 + 2] cycloadditions in equimolar mixtures of 1‐arylphosphole oxides
Authors: Keglevich György , Chuluunbaatar Tungalag , Dajka Beáta , Namkhainyambuu Bat‐Amgalan , Ludányi Krisztina , Tőke László
Published: August 2002

Four different [4 + 2] cycloadditions were observed to take place in the equimolar mixtures of two different arylphosphole oxides 2a + 2b or 2b + 2c. In addition to the phosphole oxide dimers 3a‐a and 3b‐b, or 3b‐b and 3c‐c, the crossed cycloadducts 3a‐b and 3b‐a, or 3b‐c and 3c‐b were also formed in considerable portions. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:633–635, 2001
Transforming growth factor ß1 and ß2 (TGFβ2 / TGFβ2) profile changes in previously irradiated free flap beds
Authors: Schultze‐Mosgau Stefan , Wehrhan Falk , Grabenbauer Gerhard , Amann Kerstin , Radespiel‐Tröger Martin , Neukam Friedrich Wilhelm , Rodel Franz
Published: August 2002

Background

Following preoperative radiotherapy prior to ablative surgery of squamous epithelial carcinomas of the head and neck region, inflammatory changes and the expression of cytokines involved in wound healing could be observed. These processes lead to a delayed healing of free flaps in the graft bed. The aim of the present experimental study was to analyze the expression profiles of transforming growth factor (activated TGFβ1, TGFβ2) and latency‐associated peptide (LAP) in the irradiated graft beds and the transition area between grafts and irradiated graft beds.

Methods

In Wistar rats (male, weight 300–500 g) undergoing preoperative irradiation of the neck region with 30 Gy (30 animals) and non‐irradiated rats (42 animals), a free myocutaneous gracilis flap taken from the groin was transplanted to the irradiated region of the neck. The interval between irradiation and transplantation was 4 weeks. In each group on postoperative days 3, 7, 14, and 28, cytoplasmatic expression of activated TGFβ1, LAP, and TGFβ2 was analyzed by immunohistochemistry to determine labeling indices (positive stained cells/total cells).

Results

The success rate in graft beds irradiated with 30 Gy was 76% and in non‐irradiated graft beds was 86% (p = .02). In the graft beds irradiated with 30 Gy, there was an increased expression of activated TGFβ1 (range, 19.0–33.0), LAP (14.0–21.0), and TGFβ2 (3.0–19.5) together with obvious fibrosis. The expression was located in perivascular fibroblasts and endothelial cells. In contrast, a lower expression of activated TGFβ1 (11.0–21.0), LAP (1.0–8.0), and TGFβ2 (0.0–0.9) (p = .006) was observed in non‐irradiated graft beds. In the transition area between graft and irradiated graft bed, high expression of activated TGFβ1 (37.0), LAP (19.0), and TGFβ2 (16.7–33.4) was observed on the 3rd postoperative day in contrast to the transition area in non‐irradiated graft beds (activated TGFβ1 26.0, LAP 7.0, and TGFβ2 0.l).

Conclusion

The radiation induced, increased de novo synthesis of LAP, activation of TGFβ1, and increased expression of TGFβ2 may represent at least one mechanism for the increased fibrosis and wound healing disorders seen in irradiated tissues and in the transition area to graft tissue. The expression of TGFβ1, LAP, and TGFβ2 might possess prognostic value with regard to wound healing and fibrosis in previously irradiated graft beds. © 2002 John Wiley & Sons, Inc. Head Neck 24: 33–41, 2002.
Quality of life and oral function in patients treated with radiation therapy for head and neck cancer
Authors: Epstein Joel B. , Robertson Manuella , Emerton Sue , Phillips Norm , Stevenson‐Moore Peter
Published: August 2002

Background

Multiple oral complaints develop during radiation therapy for head and neck cancer, and quality of life is affected after treatment. The purpose of this investigation was to assess the quality of life, oral function, and oral symptoms in a cohort of patients during and after radiation therapy.

Methods

A general quality of life survey (the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ‐C30), with an added oral symptom and function scale was administered to a consecutive series of patients who received radiation therapy for head and neck malignant disease. Patients completed surveys at the beginning of radiation therapy, immediately after, and 6 months after treatment.

Results and Discussion

The questionnaire used in this study provides increased information regarding the oral and dental function that is frequently affected by radiation therapy. Results of this study indicate the need to determine oral dysfunction after head and neck cancer therapy, so that the most predictable cure or best palliation of the malignancy with the least impact on oral function and quality of life is chosen.

Oral complications during and after radiation therapy for head and neck cancer are common and affect quality of life. Oral QOL does not return to pretreatment levels by 6 months after radiation therapy. This study supports the use of a general function scale such as the EORTC questionnaire with the addition of disease/site‐specific scales to provide data on outcomes of therapy and on the complications associated with therapy. The EORTC QLQ 30 questionnaire with the oral assessment addendum provides a measure of the quality of life and oral function in head and neck cancer patients and may provide useful outcome measures for assessment of oral care prevention and management strategies in these patient populations. The results show that the questionnaire is responsive to change throughout the course of radiation therapy for head and neck cancer. © 2001 John Wiley & Sons, Inc. Head Neck 23: 389–398, 2001.
Significance and management of thyroid lesions in lymph nodes as an incidental finding during neck dissection
Authors: Fliegelman Lawrence J. , Genden Eric M. , Brandwein Margaret , Mechanick Jeffrey , Urken Mark L.
Published: August 2002

Background

The incidental discovery of thyroid lesions in lymph nodes during a lymph node dissection performed for a separate primary head and neck tumor is an unusual clinical entity. Its discovery has led to controversy regarding its significance and management.

Methods

We identified five patients over the years 1991–1999 with this finding. All five patients were subsequently treated with a total thyroidectomy and a level VI lymph node dissection.

Results

Pathological examination revealed three papillary carcinomas and level VI lymph node metastases in the two patients who had carcinoma in their thyroid glands. All five patients are presently free of their primary and thyroid disease on follow‐up examinations.

Conclusions

These patients should be addressed with additional work‐up and surgery if metastatic thyroid cancer is documented in the lymph node. We offer a diagnostic algorithm that may aid in further work‐up and treatment in these unusual cases. © 2001 John Wiley & Sons, Inc. Head Neck 23: 885–891, 2001.
Differential mechanisms of Ca2+ responses in glial cells evoked by exogenous and endogenous glutamate in rat hippocampus
Authors: Latour Isabelle , Gee Christine E. , Robitaille Richard , Lacaille Jean‐Claude
Published: August 2002

The mechanisms of Ca2+ responses evoked in hippocampal glial cells in situ, by local application of glutamate and by synaptic activation, were studied in slices from juvenile rats using the membrane permeant fluorescent Ca2+ indicator fluo‐3AM and confocal microscopy. Ca2+ responses induced by local application of glutamate were unaffected by the sodium channel blocker tetrodotoxin and were therefore due to direct actions on glial cells. Glutamate‐evoked responses were significantly reduced by the L‐type Ca2+ channel blocker nimodipine, the group I/II metabotropic glutamate receptor antagonist (S)‐α‐methyl‐4‐carboxyphenylglycine (MCPG), and the N‐methyl‐D‐aspartate (NMDA) receptor antagonist (±)2‐amino‐5‐phosphonopentanoic acid (APV). However, glutamate‐induced Ca2+ responses were not significantly reduced by the non‐NMDA receptor antagonist 6‐cyano‐7‐nitro‐quinoxaline‐2,3‐dione (CNQX). These results indicate that local application of glutamate increases intracellular Ca2+ levels in glial cells via the activation of L‐type Ca2+ channels, NMDA receptors, and metabotropic glutamate receptors. Brief (1 s) tetanization of Schaffer collaterals produced increases in intracellular Ca2+ levels in glial cells that were dependent on the frequency of stimulation (≥50 Hz) and on synaptic transmission (abolished by tetrodotoxin). These Ca2+ responses were also antagonized by the L‐type Ca2+ channel blocker nimodipine and the metabotropic glutamate receptor antagonist MCPG. However, the non‐NMDA receptor antagonist CNQX significantly reduced the Schaffer collateral‐evoked Ca2+ responses, while the NMDA antagonist APV did not. Thus, these synaptically mediated Ca2+ responses in glial cells involve the activation of L‐type Ca2+ channels, group I/II metabotropic glutamate receptors, and non‐NMDA receptors. These findings indicate that increases in intracellular Ca2+ levels induced in glial cells by local glutamate application and by synaptic activity share similar mechanisms (activation of L‐type Ca2+ channels and group I/II metabotropic glutamate receptors) but also have distinct components (NMDA vs. non‐NMDA receptor activation, respectively). Therefore, neuron‐glia interactions in rat hippocampus in situ involve multiple, complex Ca2+‐mediated processes that may not be mimicked by local glutamate application. Hippocampus 2001;11:132–145. © 2001 Wiley‐Liss, Inc.
Fluid flow and heat transfer in the transition process of natural convection over an inclined plate
Authors: Komori Katsuo , Kito Shunsuke , Nakamura Toshihisa , Inaguma Yoshiaki , Inagaki Terumi
Published: August 2002

The present study deals with fluid flow and heat transfer in the transition process of natural convection over an inclined plate. In order to examine the mechanism of the transition process, experiments on the flow and heat transfer were performed for various plate inclination angles in the range of 20 to 75°. The wall temperature and fluid flow fields were visualized using a liquid crystal sheet and fluorescent paint, respectively. The visualization confirmed that separation of a boundary layer flow took place, and the onset point of streaks appeared over the plate wall when the modified Rayleigh number exceeded a characteristic value for each inclination angle. The local Nusselt number in the transition range was proportional to the one‐third power of the local modified Rayleigh number. By introducing a nondimensional parameter, a new correlation between visualizations of the flow and temperature fields and heat transfer was proposed. © 2001 Scripta Technica, Heat Trans Asian Res, 30(8): 648–659, 2001
Forced convective heat transfer for fluid flowing through a porous medium with internal heat generation
Authors: Du Hua , Wang Xuan
Published: August 2002

Forced convection in channels filled with packed beads with internal heat source was numerically analyzed by using the extended Darcy model for the flow and energy conservation equations with nonthermal equilibrium (NTE). The temperature difference between the matrix and fluid phases was discussed with three dimensionless parameters (Rep, H/dp, and ks/kf). It is concluded that the thermal equilibrium assumption may be adopted for the situation when the solid conduction dominated over the convection or when the heat transfer coefficient between the two phases is large at large Rep. The Nusselt number at the wall with the variation of Rep for different ks/kf was also investigated. © 2001 Scripta Technica, Heat Trans Asian Res, 30(3): 213–221, 2001
Spectral albedo/reflectance of littered forest snow during the melt season
Authors: Melloh Rae A. , Hardy Janet P. , Davis Robert E. , Robinson Peggy B.
Published: August 2002

Despite the importance of litter on forest floor albedo and brightness, previous studies have not documented forest floor albedo or litter cover in any detail. Our objective was to describe the seasonal influence of litter on spectral albedos and nadir reflectances of a forest snowpack in a mixed‐hardwood stand in the Sleepers River Research Watershed (SRRW) in Danville, Vermont (37°39′ N, 119°2′ W). Experimental measurements in a nearby open area at the Snow Research Station of the SRRW nearly duplicated the spectral trend observed in the forest. Spectral albedo and nadir reflectance measurements in the visible and near infrared (350–2500 nm) transitioned from a gently curved shape through the visible range (for finer‐grained, lightly littered snow) to one having a peak in the red/near‐infrared (near 760 nm) as the snowmelt season progressed (for coarser‐grained, more heavily littered snow). The snowpack became optically thin as surface litter reached high percentages. A point‐in‐time digital photographic survey of the late‐lying snowpacks of three forest stands and the open showed that median litter cover percentages in the coniferous, deciduous, mixed‐forest, and an open area were 17·5, 6·1, 1·2, and 0·04 respectively. A Kruskal–Wallis ANOVA on ranks and pairwise comparisons using Dunn's test indicated that the litter covers of the three forest stands were significantly different with >95% confidence. The snowpack was relatively shallow (<1 m), as is typical for this area of Vermont. From a remote‐sensing standpoint, and since shallow snow and increased grain size also lower the visible albedo, we can expect that snowpack litter will cause decreased albedo earlier in the snowmelt season, at deeper snow depths, and will tend to shift the maximum albedo peak to the red/NIR range as the melt season progresses. Published in 2001 by John Wiley & Sons, Ltd.
Radio‐tracking gravel particles in a large braided river in New Zealand: a field test of the stochastic theory of bed load transport proposed by Einstein
Authors: Habersack H. M.
Published: August 2002

Hans A. Einstein initiated a probabilistic approach to modelling sediment transport in rivers. His formulae were based on theory and were stimulated by laboratory investigations. The theory assumes that bed load movement occurs in individual steps of rolling, sliding or saltation and rest periods. So far very few attempts have been made to measure stochastic elements in nature. For the first time this paper presents results of radio‐tracing the travel path of individual particles in a large braided gravel bed river: the Waimakariri River of New Zealand. As proposed by Einstein, it was found that rest periods can be modelled by an exponential distribution, but particle step lengths are better represented by a gamma distribution. Einstein assumed an average travel distance of 100 grain‐diameters for any bed load particle between consecutive points of deposition, but larger values of 6·7 m or 150 grain‐diameters and 6·1 m or 120 grain‐diameters were measured for two test particle sizes. Together with other available large scale field data, a dependence of the mean step length on particle diameter relative to the D50 of the bed surface was found. During small floods the time used for movement represents only 2·7% of the total time from erosion to deposition. The increase in percentage of time being used for transport means that it then has to be regarded in stochastic transport models. Tracing the flow path of bed load particles between erosion and deposition sites is a step towards explaining the interactions between sediment transport and river morphology. Copyright © 2001 John Wiley & Sons, Ltd.
Short‐term discharge and suspended sediment fluctuations in the proglacial Skeldal River, north‐east Greenland
Authors: Stott T. A. , Grove J. R.
Published: August 2002

The summer discharge pattern of the Skeldal River, which drains a 560 km2 partly glacierized catchment in north‐east Greenland, is dominated by diurnal oscillations reflecting variations in the melt rate of snow and ice in the basin. Superimposed on this diurnal pattern are numerous short‐lived discharge fluctuations of irregular periodicity and magnitude. The larger fluctuations are described and attributed to both rainfall events and periodic collapse of the glacier margin damming flow from beneath the Skelbrae glacier. Other minor fluctuations are less readily explained but are associated with changes in the channelized and distributed reservoirs and possibly temporary blockage of subglacial conduits caused by ice melt with subsequent damming.

Fluctuations in suspended sediment concentration (SSC) are normally associated with discharge fluctuations, although examples of ‘transient flushes’ were observed where marked increases in SSC occurred in the absence of corresponding discharge variations. A strong relationship between the event discharge increase and event SSC increase for rainfall‐induced events was established, but no such relationship existed for non‐rainfall‐induced events. There is some evidence for an exhaustion effect in the SSC patterns both at the event time‐scale and as the month proceeds. A mean suspended sediment load of 1765 ± 0·26 t day−1 was estimated for the study period, which would be equivalent to a suspended sediment yield of 732 ± 4 t km−2 year−1. Copyright © 2001 John Wiley & Sons, Ltd.