bluuebunny/crossref_metadata_2025 huggingface dataset:
Postnatal regulation of limb proprioception by muscle‐derived neurotrophin‐3
Authors: Taylor Michael D. , Vancura Ryan , Patterson Colleen L. , Williams Janelle M. , Riekhof John T. , Wright Douglas E.
Published: August 2002

To investigate the effects of neurotrophin‐3 (NT‐3) on postnatal proprioceptive neurons and their targets, transgenic mice were generated that use the myosin light chain 1 (mlc) promoter to overexpress NT‐3 in skeletal muscle. Ribonuclease protection assays revealed that NT‐3 overexpression in hindlimb skeletal muscle began at embryonic day 14 (E14) and continued throughout adulthood. Overexpression of NT‐3 during late embryogenesis resulted in increased numbers of large sensory and small fusimotor axons. Within a week of birth, mlc/NT‐3 mice retract their limbs to the torso when lifted by the tail. Footprint analysis revealed that mlc/NT‐3 mice had significant abnormalities in their gait compared with wild‐types. Beam walking and rotorod analysis confirmed the poor limb control by mlc/NT‐3 mice. These locomotive deficits progressively worsened with age and were likely related to the formation of morphologically abnormal muscle spindles. The most common spindle anomaly was the presence of excessive intrafusal bag fibers within individual muscle spindles. To assess the role of NT‐3 in recovery from nerve injury, sciatic nerve crushes were performed in young adult mice. Two days after injury, mlc/NT‐3 mice displayed significantly improved sciatic functional indexes and a significant increase in muscle spindles that remained associated with axons. The latter finding suggests that excess NT‐3 in muscle may retard the degeneration of proprioceptive axons after nerve crush. Long‐term survival after nerve injury in mlc/NT‐3 mice did not induce further changes in spindle number or morphology. These findings demonstrate that, in addition to promoting embryonic proprioceptive neuron survival, postnatal overexpression of NT‐3 in muscle leads to abnormal spindle formation and deficits in locomotive control. However, our results also show that NT‐3 may be therapeutic for proprioceptive axons immediately after nerve injury by delaying axon degeneration. J. Comp. Neurol. 432:244–258, 2001. © 2001 Wiley‐Liss, Inc.
Brevican in the developing hippocampal fimbria: Differential expression in myelinating oligodendrocytes and adult astrocytes suggests a dual role for brevican in central nervous system fiber tract development
Authors: Ogawa Tokiko , Hagihara Kazuki , Suzuki Mitsuru , Yamaguchi Yu
Published: August 2002

Brevican is one of the most abundant extracellular matrix proteoglycans in the mammalian brain. We have previously shown that brevican produced by gray matter astrocytes constitutes a major component of perineuronal extracellular matrix in the adult brain. In this paper, we investigate the expression of brevican in the postnatal hippocampal fimbria to explore the role of the proteoglycan in central nervous system fiber tract development. We demonstrate that brevican is expressed by both oligodendrocytes and white matter astrocytes in the fimbria, but the expression of brevican in these two glial cell types is differently regulated during development. At P14, brevican immunoreactivity was observed throughout the fimbria, with particularly strong immunoreactivity in the developing interfascicular glial rows. In situ hybridization showed that oligodendrocytes in the glial rows strongly express brevican during the second and third postnatal weeks. Expression in oligodendrocytes was then down‐regulated after P21. In the adult fimbria, no brevican expression was observed in oligodendrocytes. The time window of brevican expression coincides with the phase in which immature oligodendrocytes actively extend membrane processes and enwrap axon fibers. In contrast, the expression in astrocytes started around P21 as oligodendrocytes began to down‐regulate the expression. In the adult fimbria, brevican expression was restricted to astrocytes. In situ hybridization with isoform‐specific probes and RNase protection assays showed that the authentic, secreted form of brevican, not the glycosylphosphatidylinositol‐anchored variant, is the predominant species expressed in the developing fimbria. Our results suggest that brevican plays a dual role in developing and adult fiber tracts. J. Comp. Neurol. 432:285–295, 2001. © 2001 Wiley‐Liss, Inc.
Characterization of neuropeptide Y–expressing cells in the mouse retina using immunohistochemical and transgenic techniques
Authors: Sinclair John Robert , Nirenberg Sheila
Published: August 2002

The amacrine cells of the retina are a complex family of interneurons. They are made up of numerous subgroups, each with different morphologic and/or biochemical properties and each presumably serving a different function. In this study, we characterized one subgroup, defined by its expression of a peptide, neuropeptide Y (NPY). The cells were identified using antibodies to NPY and characterized using a transgenic mouse line that expressed the reporter enzyme, β‐galactosidase, in the NPY‐immunoreactive (NPY‐IR) cells. We found that NPY‐IR cells were present in two layers, the inner nuclear layer (INL) and the ganglion cell layer (GCL). The cells in both layers were densely distributed, with those in the INL having a mean density of 1452 ± 65 cells/mm2, and those in the GCL having a mean density of 644 ± 41 cells/mm2. The cells in the INL extended their processes in the sublamina of the inner plexiform layer (IPL) closest to the INL/IPL border, the presumptive OFF sublamina, and the cells in the GCL extended their processes in the sublamina near the GCL/IPL border, the presumptive ON sublamina. Both populations of cells were immunoreactive to a GABA transporter and, thus, likely GABAergic. The high density of these cells suggests that they play a prominent role in IPL processing. The location of their processes suggests that one population acts in the pathway that mediates OFF responses, and the other in the pathway that mediates ON responses, and their expression of a GABA marker indicates that their actions are likely inhibitory. J. Comp. Neurol. 432:296–306, 2001. © 2001 Wiley‐Liss, Inc.
Structure and projections of white matter neurons in the postnatal rat visual cortex
Authors: Clancy Barbara , Silva‐Filho Manoel , Friedlander Michael J.
Published: August 2002

Transient contributions of subplate neurons to the initial development of the cortex are well‐characterized, yet little data are available on a subpopulation of subplate neurons that persist in the white matter (WM) of the cerebral cortex across development. To characterize the WM neurons, differential interference contrast and Nomarski optics were used to visualize individual cells in the WM in slices of rat visual cortex at postnatal ages 9–23. Soma‐dendritic morphology and local axonal projection patterns, including probable synaptic innervation sites of their axons, were identified by intracellular filling with biocytin during electrophysiologic recordings. Dendritic branches of all WM neurons, tripartitioned here into upper, middle, and deep divisions, extend throughout the WM and frequently into the overlying cortex. Axonal arborizations from most WM neurons, including apparent boutons, project into adjacent WM with many also innervating overlying cortical layers, whereas some project into the stratum oriens/alveus of the hippocampal formation. Processes of a subset of WM neurons appear to be confined to the WM itself. By using antimicrotubule associated protein (MAP2) immunostaining to quantify the density of WM neurons in rat visual cortex, we find that their overall numbers decrease to approximately 30% of initial levels during postnatal development. During this same developmental period, an increasing percentage of WM neurons contain the synthetic enzyme for nitric oxide, nitric oxide synthase (NOS), as evaluated by immunostaining. Thus, WM neurons that survive the initial perinatal period of cell death are positioned under the laminae of the maturing cortex to potentially modulate the integration of visual signals through either conventional synaptic or nonconventional (diffusible NO signaling) mechanisms. J. Comp. Neurol. 434:233–252, 2001. © 2001 Wiley‐Liss, Inc.
In vivo expression and localization of the fibroblast growth factor system in the intact and lesioned rat peripheral nerve and spinal ganglia
Authors: Grothe Claudia , Meisinger Christof , Claus Peter
Published: August 2002

Basic fibroblast growth factor (FGF‐2) is involved in several cellular processes of the nervous system during development, maintenance, and regeneration. In the central nervous system, FGF‐2 has been shown to be expressed in neurons and glial cells, depending on the developmental stage and brain area. In the present study, a comprehensive analysis was performed of the cellular distribution of the transcripts of FGF‐2 and of the FGF high‐affinity receptors (R) 1–4 in intact and lesioned sciatic nerve and spinal ganglia. In the adult rat sciatic nerve FGF‐2, FGFR1–3 were expressed at low levels as revealed by reverse transcriptase‐polymerase chain reaction (RT‐PCR). Sciatic nerve crush resulted in an increase of these transcript levels. FGFR4 expression was not detected in the intact and crushed nerve as revealed by RT‐PCR and RNase protection assay. In situ hybridization using riboprobes for FGF‐2, FGFR1–3 displayed staining in diverse cell types. Immunocytochemical staining of consecutive sections with cell markers for myelin, macrophages, and neurons revealed colocalization of the transcripts with Schwann cells and macrophages. In addition to FGF‐2 and FGFR1, the transcripts of FGFR2–4 were expressed in neurons of spinal ganglia. Crush lesion of the sciatic nerve resulted in no alterations of the FGFR1–4 transcripts, whereas FGF‐2 and FGFR3 mRNAs were up‐regulated in spinal ganglia. The expression of FGFRs and FGF‐2 in Schwann cells and macrophages at the lesion site of the sciatic nerve and in sensory neurons suggests that FGF‐2 is involved in specific functions of these cells during regeneration. J. Comp. Neurol. 434:342–357, 2001. © 2001 Wiley‐Liss, Inc.
Axonal topography of cortical basket cells in relation to orientation, direction, and ocular dominance maps
Authors: Buzás Péter , Eysel Ulf T. , Adorján Péter , Kisvárday Zoltán F.
Published: August 2002

The axonal (bouton) distributions of a layer 4 clutch cell (CC), two layer 3 medium‐sized basket cells (MBC), and a layer 3 large basket cell (LBC) to orientation, direction, and ocular dominance maps were studied quantitatively. 1) The CC provided exclusively local projections (<380 μm from the soma) and contacted a narrow “niche” of functional representations. 2) The two MBCs emitted local projections (75% and 79% of all boutons), which were engaged with isoorientations (61% and 48%) and isodirections, and long‐range projections (25% and 21%, >313 μm and >418 μm), which encountered cross‐orientation sites (14% and 12%) and isoorientation sites (7% and 5%). Their direction preferences were mainly perpendicular to or opposite those of local projections. 3) The LBC provided the majority (60%) of its boutons to long‐range distances (>437 μm). Locally, LBC boutons showed a rather balanced contribution to isoorientations (19%) and cross‐orientations (12%) and preferred isodirections. Remotely, however, cross‐orientation sites were preferred (31% vs. 23%) and the directional output was balanced. 4) Monte Carlo simulations revealed that the differences between the orientation specificity of local and long‐range projections cannot be explained by a homogeneous lateral distribution of the boutons. 5) There was a similar eye preference in the local and long‐range projection fields of the MBCs. The LBC contacted both contra‐ and ipsilateral eye domains. 6) The basket axons showed little laminar difference in orientation and direction topography. The results suggest that an individual basket cell can mediate a wide range of effects depending on the size and termination pattern of the axonal field. J. Comp. Neurol. 437:259–285, 2001. © 2001 Wiley‐Liss, Inc.
Suckling stimulus suppresses messenger RNA for tyrosine hydroxylase in arcuate neurons during lactation
Authors: Berghorn Kathie A. , Le Wei‐Wei , Sherman Thomas G. , Hoffman Gloria E.
Published: August 2002

Tyrosine hydroxylase (TH) mRNA in tuberoinfundibular dopamine (TIDA) neurons is suppressed during lactation but rebounds upon pup removal. A time course of TH mRNA changes after pup removal revealed three phases: (1) a nuclear phase (evident 1.5 hours after pup removal, maximal at 3 hours) with TH mRNA appearing in 1 or 2 nuclear loci with little or no change in cytoplasmic mRNA; (2) a cytoplasmic phase (noted 6 hours after pup removal, peaked 12–24 hours) with a significant increase in total TH mRNA levels mainly in the cytoplasm; and (3) a stabilization phase (24–48 hours after pup removal) when nuclear signals were low and cytoplasmic RNA showed a slight decline with extension of RNA clusters into the cell dendrites. In rats whose pups could suckle only on one side, TH was up‐regulated only on the side contralateral to nipple blockade. These data indicate that after suckling terminates, TH up‐regulation is evident at 1.5 hours, but 6 hours is needed before the cells transport sufficient mRNA into the cytoplasm. The rapid signaling of TH up‐regulation stems from the fact that the TIDA neurons respond to neural signals from termination of suckling. J. Comp. Neurol. 438:423–432, 2001. © 2001 Wiley‐Liss, Inc.
Selective Purkinje cell ectopia in the cerebellum of the Weaver mouse
Authors: Armstrong Carol , Hawkes Richard
Published: August 2002

The adult mouse cerebellar vermis consists of four transverse zones, each of which is further subdivided into parasagittal stripes. In the adult weaver (wv/wv) mouse, the zebrin II expression pattern in the cerebellar vermis is abnormal, consistent with the absence of a central zone (∼lobules VI/VII). Because the small, heat shock protein HSP25 is a constitutive marker of parasagittal bands of Purkinje cells in the caudal central zone and the nodular zone (∼lobules IX/X), we used HSP25 immunocytochemistry to show that the patterning abnormalities in wv/wv reflect selective Purkinje cell ectopia rather than the absence of the central zone. A specific HSP25‐immunopositive Purkinje cell ectopia within the central zone was identified. Symmetrical clusters of HSP25‐immunopositive Purkinje cells, which presumably would have formed the parasagittal stripes in the wild type, are present ectopically on either side of the midline in wv/wv. In contrast, in the nodular zone, HSP25‐immunopositive Purkinje cells form a near‐monolayer and are organized into parasagittal stripes. We therefore conclude that specific Purkinje cell clusters in the wv/wv cerebellum fail to disperse and that this ectopia contributes to the topographical abnormalities. J. Comp. Neurol. 439:151–161, 2001. © 2001 Wiley‐Liss, Inc.
Granule cells migrate within raphes in the developing cerebellum: An evolutionarily conserved morphogenic event
Authors: Karam Sana D. , Kim Yun S. , Bothwell Mark
Published: August 2002

The early phase of granule cell migration in the developing chick cerebellum occurs within ribbons of cells moving through parasagittally arrayed gaps between Purkinje cell clusters. These parasagittal arrays of migrating granule cells, termed “granule cell raphes,” also have been reported in rabbit and cat, but recent publications variously report that granule cell raphes are absent or present in rodents. By using Nissl counterstaining and Pax6 immunohistochemistry, we confirm that granule cells do migrate in raphes in the developing mouse cerebellum, and also in the primate cerebellum during a period of development that coincides with Purkinje cell compartmentation. In mouse and primate cerebellum, as in chick cerebellum, granule cell migratory streams occur at the borders of Purkinje cell clusters. GFAP immunostaining of Bergmann glial fibers shows no parasagittally localized pattern of distribution, indicating that the formation of granule cell ribbons is not prepatterned by heterogeneous distribution of radial glia. The conservation of the ribboned pattern of granule cell migration from bird to primate and the timing of this event suggest a possible role for granule cell raphes in parasagittal compartmentation of Purkinje cells. A potential mechanism for such an interaction is discussed. J. Comp. Neurol. 440:127–135, 2001. © 2001 Wiley‐Liss, Inc.
Activation of prostanoid EP3 and EP4 receptor mRNA‐expressing neurons in the rat parabrachial nucleus by intravenous injection of bacterial wall lipopolysaccharide
Authors: Engblom David , Ek Monica , Ericsson‐Dahlstrand Anders , Blomqvist Anders
Published: August 2002

Systemic inflammation activates central autonomic circuits, such as neurons in the pontine parabrachial nucleus. This activation may be the result of afferent signaling through the vagus nerve, but it may also depend on central prostaglandin‐mediated mechanisms. Recently, we have shown that neurons in the parts of the parabrachial nucleus that are activated by immune challenge express prostaglandin receptors of the EP3 and EP4 subtypes, but it remains to be determined if the prostaglandin receptor‐expressing neurons are identical to those that respond to immune stimuli. In the present study, bacterial wall lipopolysaccharide was injected intravenously in adult male rats and the expression of c‐fos mRNA and of EP3 and EP4 receptor mRNA was examined with complementary RNA probes labeled with digoxigenin and radioisotopes, respectively. Large numbers of neurons in the external lateral parabrachial subnucleus, a major target of vagal‐solitary tract efferents, expressed c‐fos mRNA. Quantitative analysis showed that about 60% (range 40%–79%) of these neurons also expressed EP3 receptor mRNA. Conversely, slightly more than 50% (range 48%–63%) of the EP3 receptor‐expressing neurons in the same subnucleus coexpressed c‐fos mRNA. In contrast, few EP4 receptor‐expressing neurons were c‐fos positive, with the exception of a small population located in the superior lateral and dorsal lateral subnuclei. These findings show that immune challenge activates central autonomic neurons that could be the target of centrally produced prostaglandin E2, suggesting that synaptic signaling and paracrine mechanisms may interact on these neurons. J. Comp. Neurol. 440:378–386, 2001. © 2001 Wiley‐Liss, Inc.
The completed second kind integral equation formulation for Stokes flow with mixed boundary conditions
Authors: Power H. , Gómez J. E.
Published: August 2002

In this article, we develop a novel indirect second kind integral equation formulation for the solution of the mixed boundary value problem for Stokes flow between two closed surfaces (multiple‐connected domain). At the exterior surface the fluid velocity is specified (boundary condition of the first kind) and at the interior surface the fluid surface traction is given (boundary condition of the second kind). The theoretical background to the proposed technique is explained in detail, including mathematical proofs of existence and uniqueness of solution. Numerical results of test examples are included to validate the formulation. As expected, the numerical solution of the proposed approach is very stable under iterative solvers requiring few numbers of iteration to achieve a desirable accuracy, even for very large number of surface nodes. Copyright © 2001 John Wiley & Sons, Ltd.
Computational modelling of the surface fatigue crack growth on gear teeth flanks
Authors: Glodež S. , Ren Z. , Fajdiga G.
Published: August 2002

The paper describes a 2‐dimensional computational model for simulation of the surface initiated fatigue crack growth in the contact area of gear teeth flanks that leads to surface pitting. The discretized model of a gear tooth with the assumed initial crack is subjected to normal contact pressure, which takes into account the EHD‐lubrication conditions and tangential loading due to friction between gear teeth flanks. The model accounts also for the influence of a fluid driven into the crack by hydraulic mechanism on crack propagation. The J‐integral method in the framework of the finite element analysis is used for simulation of the fatigue crack propagation from the initial to the critical crack length, when the surface material layer breaks away and pit appears on the surface. The model is applied to a real pitting problem of a gear and corresponding computational results in terms of pit sizes correlate well to the development of micropits observed in experimental testing. Copyright © 2001 John Wiley & Sons, Ltd.
Simulation of damage–permeability coupling in hygro‐thermo‐mechanical analysis of concrete at high temperature
Authors: Gawin D. , Pesavento F. , Schrefler B. A.
Published: August 2002

This paper presents the numerical procedure used and the results obtained for full coupling between damage and intrinsic permeability in a recently developed model for heat and mass transfer and damage analysis of concrete at high temperature. A formula describing effects of damage on intrinsic permeability is numerically tested. A numerical example concerning high temperature behaviour of high performance concrete structure is presented, showing a considerable effect of damage–intrinsic permeability coupling on concrete hygrothermal performance. Copyright © 2002 John Wiley & Sons, Ltd.
Colour‐appearance modeling using feedforward networks with Bayesian regularization method. Part II: Reverse model
Authors: Xin John H. , Sijie Shao , Chung Korris
Published: August 2002

In Part I of this article, the development of a multilayer perceptrons feedforward artificial neural network model to predict colour appearance from colorimetric values was reported. Bayesian regularization was employed for the training of the network. In this part of the article, the reverse model, that is, the perdition of colorimetric values from the colour appearance attributes is reported using the same neural network design methodology developed in Part I. This study should contribute to the building of an artificial neural network–based colour appearance prediction, both forward and reverse, using the most comprehensive LUTCHI colour appearance data sets for training and testing. Good prediction accuracy and generalization ability were obtained using the neural networks built in the study. Because the neural network approach is of a black‐box type, colour appearance prediction using this method should be easier to apply in practice. © 2002 Wiley Periodicals, Inc. Col Res Appl, 27, 116–121, 2002; DOI 10.1002/col.10030
Guidelines for dynamics‐based parameterization of one‐dimensional cellular automata rule spaces
Authors: de Oliveira Gina Maira Barbosa , de Oliveira Pedro P.B. , Omar Nizam
Published: August 2002

As paradigmatic complex systems, various studies have been done in the context of one‐dimensional cellular automata (CA) on the definition of parameters directly obtained from their transition rule, aiming at the help they might provide to forecasting CA dynamic behavior. Out of the analysis of the most important parameters available for this end, as well as others evaluated by us, a set of guidelines is proposed that should be followed when defining a parameter of that kind. Based upon the guidelines, a critique of those parameters is made, which leads to a set of five that jointly provide a good forecasting set; two of them were drawn from the literature and three are new ones defined according to the guidelines. By using them as a heuristic in the evolutionary search for CA of a predefined computational behavior, good results have been obtained, exemplified herein by the evolutionary search for CA that perform the Synchronization Task. © 2001 John Wiley & Sons, Inc.
Noise induced transitions in some socio‐economic systems
Authors: Gligor Mircea
Published: August 2002

The paper proposes the use of some stochastic methods in order to explain the presence of the critical points in macroeconomic time series, starting from the classical linear model input‐output elaborated by W. Leontief. The development of the model (N. Georgescu‐Roegen, 1971) yields the set of the linear differential equations describing the dynamics of a system containing two or more interdependent production processes. In order to describe the nonlinear economic growth, a feed‐back mechanism is introduced, improving in this way the one‐dimensional variant of the model. We study further the influence of the noise on a control parameter and the conditions in which noise induced transitions arise. The economic data illustrating such transition refer to a country evolving to the market economy (Romania), whose evolution proves a lot of instabilities that are interesting to study from physical point of view. © 2001 John Wiley & Sons, Inc.
Lack of correlation between AT frequency and genome size in higher plants and the effect of nonrandomness of base sequences on dye binding
Authors: Barow Martin , Meister Armin
Published: August 2002

Background

Different plant species vary as to the ratio of nucleotide base pairs of genomic DNA. A correlation between genome size and base pair ratio has been claimed. Base composition can be analyzed by base‐specific dyes.

Methods

Genome size is determined by flow cytometry of suspensions of nuclei stained by the base independent dye, PI. For estimation of the AT frequency, the AT‐specific dyes 4,6‐diamidino‐2‐phenylindole, dihydrochloride (DAPI) and Hoechst 33342 (HO) were used. We define a dye factor (DF) as the ratio of the two estimates (peak ratios) of nuclear fluorescence intensities of sample relative to reference plant nuclei using a given dye and an intercalating fluorochrome.

Results

No significant correlation between genome size and the DF for DAPI was found when 54 plant species were investigated. However, similarities within and differences among the plant families were shown. The comparison of DAPI and HO DFs gave no consistent differences as would be predicted from the model of different binding site length of dyes. This result may be explained by the nonrandom distribution of base pairs.

Conclusions

There is no general correlation between genome size and AT/GC ratio in higher plants. Similar AT/GC ratios within a plant family result from the general similarity of the DNA sequences within a family. The fluorescence of base‐specific dyes is influenced by the nonrandom distribution of bases in the DNA molecule. Cytometry 47:1–7, 2002. © 2001 Wiley‐Liss, Inc.
Use of SYTOX green dye in the flow cytometric analysis of bacterial phagocytosis
Authors: Gaforio J.J. , Serrano M.J. , Ortega E. , Algarra I. , Alvarez de Cienfuegos G.
Published: August 2002

Background

Fluorescein isothiocyanate (FITC) is used widely to label the targets used in flow cytometric phagocytosis assays. Unfortunately, the fluorescence intensity of phagocytosed FITC‐labeled targets is influenced by changes in intracellular pH level, making quantitative measurements with this fluorophore problematic. We describe the use of SYTOX green nucleic acid stain to measure phagocytosis by flow cytometry.

Methods

Suspensions of isopropyl alcohol‐permeabilized Escherichia coli DH5α were stained with the SYTOX green dye and then incubated with resident peritoneal macrophages. The samples were analyzed by flow cytometry and phagocytosis was determined by gating the cells.

Results

Results are expressed as percentage of phagocyte‐associated green fluorescent cells. The validity of the method was shown by the effects of a phagocytosis inhibitor (incubation at 4°C) or enhancer (gamma interferon [IFN‐ γ] treatment) being accurately assessed with this assay.

Conclusions

The method described was reproducible and provides an advantageous alternative to the use of FITC to label bacteria for the flow cytometric measurement of target uptake by phagocytic cells. Cytometry 48:93–96, 2002. © 2002 Wiley‐Liss, Inc.
Fibroadenomas with atypia: Causes of under‐ and overdiagnosis by aspiration biopsy
Authors: Simsir Aylin , Waisman Jerry , Cangiarella Joan
Published: August 2002

Fibroadenoma (FA) is a common benign breast lesion frequently sampled by fine‐needle aspiration biopsy (FNAB). Although the cytologic diagnosis is straightforward in most cases, cellular discohesion and atypia in FAs may lead to falsely atypical or positive FNAB diagnoses. Conversely, some adenocarcinomas mimic a fibroadenomatous pattern on FNAB, resulting in a false‐negative diagnosis. We reviewed the cytologic and histologic findings in 25 cases with a preoperative FNAB diagnosis of FA, wherein excision was recommended based on atypia. Our aim was to analyze the spectrum of changes causing under‐ or overdiagnosis in such cases. The smears were assessed for cellularity, cellular discohesion, presence of dissociated intact cells and nucleoli, nuclear pleomorphism, oval bare nuclei, and stromal fragments. The histologic findings were correlated with FNAB features. At excision, 88% of FAs classified as atypical on FNAB were benign (FA with ductal hyperplasia and lactational change, myxoid FA, and other fibroepithelial lesions). Differentiating myxoid FA from colloid carcinoma was difficult due to the abundance of extracellular mucin in which the dissociated epithelial cells were floating. Two (8%) cases were carcinomas on excision; the reasons for underdiagnosis in one case reflected sampling, and in the other, interpretative error. There was one (4%) benign phyllodes tumor which lacked stromal fragments and single stromal cells on FNAB smears. The lesion was called atypical, based on the epithelial discohesion on the smears. We conclude that the majority of FAs with atypia on FNAB are benign lesions. Considering the grave consequences of a false‐positive cytologic diagnosis, we recommend a conservative approach in interpreting FNAB smears which overall display a fibroadenomatous pattern. Diagn. Cytopathol. 25:278–284, 2001. © 2001 Wiley‐Liss, Inc.
Bioisosterism, enantioselectivity, and molecular modeling of new effective N6‐ and/or N(9)‐substituted 2‐phenyl adenines and 8‐aza analogs: Different binding modes to A1 adenosine receptors
Authors: Bianucci A. Maria , Biagi Giuliana , Coi Alessio , Giorgi Irene , Oreste Livi , Pacchini Federica , Scartoni Valerio , Lucacchini Antonio , Costa Barbara
Published: August 2002

Bioisosterism of the adenine and 8‐azaadenine nuclei was demonstrated by comparison of A1 adenosine receptor binding affinity of 2‐phenyl N6‐substituted adenines and the corresponding 8‐azaadenines. Some of these new compounds are very potent A1 adenosine receptor antagonists. This work also describes the synthesis and A1 adenosine receptor binding of the enantiomers of some 2‐phenyladenines substituted with a 1‐phenylethyl chiral group in N6 and N(9) positions. Biological results, showing the same stereoselectivity for all the couples of enantiomers, may supply proof for the hypothesis of a possible double arrangement of 2‐phenylsubstituted adenines inside A1 adenosine receptors. Theoretical studies, based on an improved A1 adenosine receptor model and consisting of evaluation and comparison of interaction energies in complexes involving some selected chiral ligands, support the above hypothesis. Drug Dev. Res. 54:52–65, 2001. © 2001 Wiley‐Liss, Inc.
Fetal responsiveness to maternal passive swinging in low heart rate variability state: Effects of stimulation direction and duration
Authors: Lecanuet Jean‐Pierre , Jacquet Anne‐Yvonne
Published: August 2002

Pregnant women, carrying end of gestation fetuses (38–41 weeks gestational age) were either gently rocked in an anterior posterior plane in a rocking chair or gently swayed laterally in a garden glider. Stimulation lasted for either 5 or 26 s (R5 & R26, SW5 & SW26). Fetal heart rate (HR) (bpm) and ultrasonically detected fetal movements were recorded 26 s before and during stimulation. Heart rate data were processed two ways: (a) ANOVAs performed on average values for each group and (b) comparisons of the proportion of subjects in each group showing HR accelerative change (AC), HR decelerative change (DC), or no change (NC) using χ2 statistics. HR direction and amplitude of changes were determined with the help of a conservative procedure previously developed and fitted to multidirectional HR responses (Lecanuet, Granier‐Deferre, Jacquet, & Busnel, 1992). Results of ANOVAs indicated that a 26‐s rocking stimulation induced a significant average HR acceleration (4.53 bpm) compared to a nonstimulated (control) group. Five seconds of rocking had a weaker, but still significant, effect on HR acceleration, but the two swaying conditions did not reliably affect either the HR or behavioral measures. Processing data nonparametrically confirmed that R26 stimulation evoked mostly AC (72%) and identified a gradual decrement of AC and DC percentage responses from Group R5, SW26 to Group SW5 while NC percentages raised. Hypotheses concerning the target sense activated by this stimulation were considered in relation to responses to auditory stimuli. © 2002 John Wiley & Sons, Inc. Dev Psychobiol 40: 57–67, 2002
Gastric saline infusion reduces ultrasonic vocalizations and brown fat activity in suckling rat pups
Authors: Nelson Eric E. , Alberts Jeffrey R.
Published: August 2002

Under standard conditions involving isolation and cooling, it has been documented that intraoral infusion of milk and injection of the intestinal peptide cholecystokinin (CCK) result in an attenuation in ultrasonic vocalizations (USV) emitted by infant rat pups. One of the most effective stimuli in inhibiting ingestion in suckling rat pups is gastric distension, but the effect of gastric distension on USV production has not been reported. In this experiment, we subjected infant rats to intragastric infusion of isotonic saline (2% body weight) to produce a natural level of gastric distension and hydration. We found that this stimulus resulted in a powerful reduction in USV emissions in isolated 10‐day‐old rats. In a subsequent experiment, we found that gastric saline infusion also diminished brown adipose tissue (BAT) thermogenesis. There were different time courses of the gastric saline infusion effects on BAT thermogenesis and on USV emissions, however, suggesting that these processes may be independently regulated. We hypothesize that this stimulus induces a transient activation of the parasympathetic nervous system, which overrides the sympathetic control of BAT and USV production. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 40: 160–167, 2002. DOI 10.1002/dev.10019
Language, gesture, and the developing brain
Authors: Bates Elizabeth , Dick Frederic
Published: August 2002

Do language abilities develop in isolation? Are they mediated by a unique neural substrate, a “mental organ” devoted exclusively to language? Or is language built upon more general abilities, shared with other cognitive domains, and mediated by common neural systems? Here, we review results suggesting that language and gesture are “close family”, then turn to evidence that raises questions about how real those “family resemblances” are, summarizing dissociations from our developmental studies of several different child populations. We then examine both these veins of evidence in light of some new findings from the adult neuroimaging literature and suggest a possible reinterpretation of these dissociations as well as new directions for research with both children and adults. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 40: 293–310, 2002. DOI 10.1002/dev.10034
Role of amylin in insulin secretion and action in humans: antagonist studies across the spectrum of insulin sensitivity
Authors: Mather Kieren J. , Paradisi Giancarlo , Leaming Rosalind , Hook Ginger , Steinberg Helmut O. , Fineberg Naomi , Hanley Rochelle , Baron Alain D.
Published: August 2002

Background

Amylin is a peptide co‐secreted with insulin by pancreatic β‐cells. A role for amylin in the pathogenesis of type 2 diabetes mellitus (DM2) has been suggested by in vitro and in vivo studies indicating an effect of amylin to cause insulin resistance and/or inhibit insulin secretion.

Methods

We have determined the effect of endogenous amylin on insulin secretion and insulin action in humans by performing 4‐h hyperglycemic clamps during infusion of placebo or a specific amylin receptor antagonist (ARA) in paired, double‐blinded, crossover studies. We studied nine healthy lean, ten healthy obese (BMI>27) and ten obesity‐matched DM2 subjects.

Results

Infusion of ARA alone had no effect on basal insulin, glucose or glucose turnover in any group. Under combined hyperglycemia and ARA infusion, lean subjects displayed a 32% augmentation in insulin levels [AUC 33 565±3556 (placebo) to 44 562±1379 (ARA) pmol/l/min, p<0.01]. The concomitant increase in glucose disposal rate (GDR) was proportionate, indicating no change in insulin sensitivity (ISI 27.7±2.7 vs 27.3±2.1, p=NS). In obese subjects, basal insulin and the rise in insulin during the clamp were greater (AUC I 44% increase from 82 054±15 407 to 117 922±27 085, p<0.01), and also accompanied by a proportionate rise in GDR reflecting an unchanged insulin sensitivity (ISI 12.1±2.9 vs 10.8±3.0, p=NS). In lean and obese subjects, the C‐peptide response to hyperglycemia was also augmented by ARA (p=0.007). No effect of ARA on insulin secretion or action was observed in diabetic subjects.

Conclusions

The present data are consistent with an effect of endogenous amylin on the β‐cell to modulate and/or restrain insulin secretion, and indicate that endogenous amylin does not affect insulin action. These observations provide the first human evidence that amylin plays a role in the modulation of insulin secretion. Copyright © 2002 John Wiley & Sons, Ltd.
Initiation of apoptosis in the developing avian outflow tract myocardium
Authors: Rothenberg Florence , Hitomi Midori , Fisher Steven A. , Watanabe Michiko
Published: August 2002

Apoptosis occurs within the cardiac outflow tract (OFT) myocardium during normal development of chick hearts. This peak of apoptosis occurs at stage 30–31 and coincides with dramatic remodeling of the OFT, suggesting that apoptosis occurs to allow proper alignment of the great vessels over their respective ventricles. The signals that initiate apoptosis in this setting are unknown. The aim of this study was to characterize the cells undergoing apoptosis in the cardiac OFT myocardium and the cells that may influence this process. Two cell populations that may initiate apoptosis of the cardiomyocytes are the cardiac neural crest (CNC) cells and epicardial cells. We examined stage 30–31 chick embryos that had undergone removal of the CNC cells or had delayed epicardial growth for alterations of apoptosis. Removal of the CNC cells did not reduce the levels or pattern of apoptosis in the OFT myocardium. In contrast, impeding the growth of the epicardium over the OFT resulted in a 57% reduction in apoptotic cells in the OFT myocardium. Analysis of the apoptotic cells within the OFT myocardium showed that as many as 92% of them expressed cardiomyocyte markers. In the quail, the endothelial marker QH1 identified a component from the epicardium, endothelial cells, in regions where apoptosis is elevated in the OFT myocardium. These results suggest that a component from the epicardium, possibly endothelial cells, is required for the initiation of apoptosis in OFT cardiomyocytes. © 2002 Wiley‐Liss, Inc.
MLC3F transgene expression in iv mutant mice reveals the importance of left‐right signalling pathways for the acquisition of left and right atrial but not ventricular compartment identity
Authors: Franco Diego , Kelly Robert , Moorman Antoon F.M. , Lamers Wouter H. , Buckingham Margaret , Brown Nigel A.
Published: August 2002

Abstract

Transcriptional differences between left and right cardiac chambers are revealed by an nlacZ reporter transgene controlled by regulatory sequences of the MLC3F gene, which is expressed in the left ventricle (LV), atrioventricular canal (AVC), and right atrium (RA). To examine the role of left‐right signalling in the acquisition of left and right chamber identity, we have investigated MLC3F transgene expression in iv mutant mice. iv/iv mice exhibit randomised direction of heart looping and an elevated frequency of associated laterality defects, including atrial isomerism. At fetal stages, 3F‐nlacZ‐2E transgene expression remains confined to the morphological LV, AVC, and RA in L‐loop hearts, although these appear on the opposite side of the body. In cases of morphologically distinguishable right atrial appendage isomerism, both atrial appendages show strong transgene expression. Conversely, specimens with morphological left atrial appendage isomerism show only weak expression in both atrial appendages. The earliest left‐right atrial differences in the expression of the 3F‐nlacZ‐2E transgene are observed at E8.5. DiI labelling experiments confirmed that transcriptional regionalisation of the 3F‐nlacZ‐2E transgene at this stage reflects future atrial chamber identity. In some iv/iv embryos at E8.5, the asymmetry of 3F‐nlacZ‐2E expression was lost, suggesting atrial isomerism at the transcriptional level prior to chamber formation. These data suggest that molecular specification of left and right atrial but not ventricular chambers is dependent on left‐right axial cues. © 2001 Wiley‐Liss, Inc.
Rod contributions to the electroretinogram of the dark‐adapted developing zebrafish
Authors: Bilotta Joseph , Saszik Shannon , Sutherland Sarah E.
Published: August 2002

Anatomical studies of the developing zebrafish retina have shown that rods approach maturity at about 15 days postfertilization (dpf). Past work has examined the photopic spectral sensitivity function of the developing zebrafish, but not spectral sensitivity under dark‐adapted conditions. This study examined rod contributions to the dark‐adapted spectral sensitivity function of the ERG b‐wave component in developing zebrafish. ERG responses to stimuli of various wavelengths and irradiances were obtained from dark‐adapted fish at 6–8, 13–15, 21–24, and 27–29 dpf. The results show that dark‐adapted spectral sensitivity varied with age. Spectral sensitivity functions of the 6–8 and 13–15 dpf groups appeared to be cone dominated and contained little or no rod contributions. Spectral sensitivity functions of the 21–24 and 27–29 dpf groups appeared to have both rod and cone contributions. Even at the oldest age group tested, the dark‐adapted spectral sensitivity function did not match the adult function. Thus, consistent with anatomical findings, the rod contributions to the ERG spectral sensitivity function appear to develop with age; however, these contributions are still not adult‐like by 29 dpf, which is contrary to anatomical work. These results illustrate that the zebrafish is an excellent model for visual development. © 2001 Wiley‐Liss, Inc.
From language to reading and dyslexia1
Authors: Snowling Margaret J.
Published: August 2002

This paper reviews evidence in support of the phonological deficit hypothesis of dyslexia. Findings from two experimental studies suggest that the phonological deficits of dyslexic children and adults cannot be explained in terms of impairments in low‐level auditory mechanisms, but reflect higher‐level language weaknesses. A study of individual differences in the pattern of reading skills in dyslexic children rejects the notion of ‘sub‐types’. Instead, the findings suggest that the variation seen in reading processes can be accounted for by differences in the severity of individual children's phonological deficits, modified by compensatory factors including visual memory, perceptual speed and print exposure. Children at genetic risk who go on to be dyslexic come to the task of reading with poorly specified phonological representations in the context of a more general delay in oral language development. Their prognosis (and that of their unaffected siblings) depends upon the balance of strengths and difficulties they show, with better language skills being a protective factor. Taken together, these findings suggest that current challenges to the phonological deficit theory can be met. Copyright © 2001 John Wiley & Sons, Ltd.
Effect of inositol on bulimia nervosa and binge eating
Authors: Gelber Diana , Levine Joseph , Belmaker R. H.
Published: August 2002

Objectives

This study aimed to determine whether inositol has therapeutic value in patients with bulimia nervosa and binge eating.

Method

A double‐blind crossover trial using 18 g inositol versus placebo was performed in 12 patients for 6 weeks in each arm.

Results

Inositol was significantly better than placebo on the Global Clinical Impression, the Visual Analogue Scale, and the Eating Disorders Inventory.

Discussion

Inositol is as therapeutic in patients with bulimia nervosa and binge eating as it is in patients with depression and panic and obsessive‐compulsive disorders. This increases its parallelism with serotonin selective reuptake inhibitors. © 2001 by John Wiley & Sons, Inc. Int J Eat Disord 29: 345–348, 2001.
Childhood trauma has dose‐effect relationship with dropping out from psychotherapeutic treatment for bulimia nervosa: A replication
Authors: Mahon Jennifer , Bradley S. Nicole , Harvey Peter K. , Winston Anthony P. , Palmer Robert L.
Published: August 2002

Objective

The primary goal of this study was to replicate the finding that experiences of childhood trauma have a dose‐effect relationship with dropping out from psychotherapeutic treatment for bulimia nervosa. It also aimed to replicate logistic regression findings that parental break‐up predicts dropping out.

Method

The cohort consisted of 114 women consecutively presenting to an outpatient eating disorders clinic with bulimia nervosa or atypical bulimia nervosa. Data were gathered using a retrospective, case‐note approach and were analysed using logistic regression (LR). A correlation technique was employed to assess the presence of a dose‐effect relationship between experiences of trauma in childhood and dropping out. LR models were double cross‐validated between this and an earlier cohort.

Results

The dose‐effect relationship between experiences of childhood trauma and dropping out was confirmed. Witnessing parental break‐up in childhood again predicted dropping out of treatment in adulthood. Cross‐validation of LR equations was unsuccessful.

Discussion

These results strongly suggest that experiences of childhood trauma have a dose‐effect relationship with dropping out. Parental break‐up is a stable predictor of dropping out. It is possible that these experiences influence attachment style, particularly the ability to make and maintain a trusting relationship with a psychotherapist. Clinical implications are discussed. © 2001 by John Wiley & Sons, Inc. Int J Eat Disord 30: 138–148, 2001.
Barriers to treatment for eating disorders among ethnically diverse women
Authors: Cachelin Fary M. , Rebeck Ramona , Veisel Catherine , Striegel‐Moore Ruth H.
Published: August 2002

Objective

This study examined barriers to treatment in an ethnically diverse community sample of women with eating disorders.

Method

Participants were 61 women (22 Hispanics, 8 Asians, 12 Blacks, 19 Whites) with eating disorders. Diagnosis was determined using the Eating Disorder Examination. Treatment‐seeking history, barriers to treatment seeking, ethnic identity, and acculturation were assessed.

Results

Although 85% of the sample reported wanting help for an eating problem, only 57% had ever sought treatment for an eating or weight problem. Individuals who had sought treatment reported being significantly more distressed about their binge eating than those who had not sought treatment and having begun overeating at a younger age. Of those who had sought help, 86% had not received any treatment for their eating problems. The main barriers to treatment seeking were financial reasons.

Conclusion

Women from minority groups who have eating disorders are underdiagnosed and typically not treated. © 2001 by John Wiley & Sons, Inc. Int J Eat Disord 30: 269–278, 2001.