bluuebunny/crossref_metadata_2025 huggingface dataset:
Adherence to repeat screening flexible sigmoidoscopy in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial
Authors: Weissfeld Joel L. , Ling Bruce S. , Schoen Robert E. , Bresalier Robert S. , Riley Thomas , Prorok Philip C. ,   PLCO Project Team
Published: August 2002

BACKGROUND

Acceptance of screening flexible sigmoidoscopy has been poor, in part because of providers' concerns regarding the acceptability of the procedure. In the current prospective study, the authors used adherence to repeat testing to assess the acceptability of screening flexible sigmoidoscopy.

METHODS

The current study was a prospective study of a randomized clinical trial drawing volunteers from the community. Subjects included 10,164 Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial participants who were available for follow‐up 3 years after undergoing a baseline screening flexible sigmoidoscopy examination. The authors measured adherence and identified those factors that appeared to affect adherence to repeat sigmoidoscopy.

RESULTS

Overall, 18.3% of women and 10.0% of men did not undergo a repeat sigmoidoscopy. Among individuals who attended the Year‐3 clinic, 10.4% of women and 5.1% of men specifically refused repeat sigmoidoscopy when it was offered (risk of refusal in women compared with men, 2.04; 95% confidence interval, 1.76–2.36). Another factor found to be associated with refusal included a technically inadequate baseline sigmoidoscopy.

CONCLUSIONS

Gender and past experiences with sigmoidoscopy may impact adherence to repeat screening. Nonetheless, among research volunteers in a randomized clinical trial of screening, excellent adherence to repeat screening flexible sigmoidoscopy could be achieved. Cancer 2002;94:2569–76. © 2002 American Cancer Society.

DOI 10.1002/cncr.10538
Ascending and descending projections of the lateral vestibular nucleus in the frog Rana esculenta
Authors: Matesz Clara , Kulik Akos , Bácskai Timea
Published: August 2002

The lectin Phaseolus vulgaris leucoagglutinin was injected into the frog lateral vestibular nucleus (LVN) to study its antero‐ and retrograde projections. The following new observations were made. 1) In the diencephalon, vestibular efferents innervate the thalamus in a manner similar to that of mammalian species. The projections show a preference for the anterior, central, and ventromedial thalamic nuclei. 2) In the mesencephalon, vestibular fibers terminate in the tegmental nuclei and the nucleus of medial longitudinal fascicle. 3) In the rhombencephalon, commissural and internuclear projections interconnect the vestibular nuclei. Some of the termination areas in the reticular formation can be homologized with the mammalian inferior olive and the nucleus prepositus hypoglossi. Another part of the vestibuloreticular projection may transmit vestibular impulses toward the vegetative centers of the brainstem. A relatively weak projection is detected in the spinal nucleus of the trigeminal nerve, dorsal column nuclei, and nucleus of the solitary tract. 4) In the spinal cord, vestibular terminals are most numerous in the ipsilateral ventral horn and in the triangular area of the dorsal horn. 5) The coincidence of retrogradely labeled cells with vestibular receptive areas suggests reciprocal interconnections between these structures and the LVN. 6) In seven places, the LVN projections overlap the receptive areas of proprioceptive fibers, suggesting a convergence of sensory modalities involved in the sense of balance. J. Comp. Neurol. 444:115–128, 2002. © 2002 Wiley‐Liss, Inc.
Ontogeny of NADPH diaphorase/nitric oxide synthase reactivity in the brain of Xenopus laevis
Authors: López Jesús M. , Gonźlez Agustín
Published: August 2002

The development of nitric oxide synthase (NOS) expression in the brain of Xenopus laevis tadpoles was studied by means of immunohistochemistry using specific antibodies against NOS and enzyme histochemistry for nicotinamide adenine dinucleotide phosphate (NADPH)‐diaphorase. Both techniques yielded identical results and were equally suitable for demonstrating the nitrergic system in the brain. The only mismatches were observed in the olfactory nerve and glomeruli and in the terminal nerve; they were intensely labeled with the NADPH‐diaphorase technique but failed to stain with NOS immunohistochemistry. As early as stage 33, nitrergic cells were observed in the caudal rhombencephalon within the developing inferior reticular nucleus. At later embryonic stages, different sets of reticular and tegmental neurons were labeled in the middle reticular nucleus and, more conspicuously, in the laterodorsal and pedunculopontine tegmental nuclei. As development proceeded, new nitrergic cell groups gradually appeared in the mesencephalon, diencephalon, and telencephalon. A general caudorostral temporal sequence was observed, both in the whole brain and within each main brain subdivision. The premetamorphic period was mainly characterized by the maturation of the cell populations developed in the embryonic period. During prometamorphosis, the nitrergic system reached an enormous development, and many new cell groups were observed for the first time, in particular in the telencephalon. By the climax of metamorphosis, the pattern of organization of nitrergic cells and fibers observed in the brain was similar to that present in the adult brain. Transient expression of NOS was not detected in any brain region. Our data suggest that nitric oxide plays an important role during brain development of Xenopus. Comparison with the developmental pattern of nitrergic systems in other vertebrates shows that amphibians possess more common features with amniotes than with anamniotes. J. Comp. Neurol. 445:59–77, 2002. © 2002 Wiley‐Liss, Inc.
Descending supraspinal pathways in amphibians: III. Development of descending projections to the spinal cord in Xenopus laevis with emphasis on the catecholaminergic inputs
Authors: Sánchez‐Camacho Cristina , Martín Oscar , Ten Donkelaar Hans J. , González Agustín
Published: August 2002

In developmental stages of the clawed toad, Xenopus laevis, we describe the ontogeny of descending supraspinal connections, catecholaminergic projections in particular, by means of retrograde tracing techniques with dextran amines. Already at embryonic stages (stage 40), spinal projections from the reticular formation, raphe nuclei, Mauthner neurons, vestibular nuclei, the locus coeruleus, the interstitial nucleus of the medial longitudinal fasciculus, the posterior tubercle, and the periventricular nucleus of the zona incerta are well developed. At the beginning of the premetamorphic period (stage 46), spinal projections arise from the suprachiasmatic nucleus, the torus semicircularis, the pretectal region, and the ventral telencephalon. After stage 48, tectospinal and cerebellospinal projections develop, with spinal projections from the preoptic area following at stage 51. Rubrospinal projections are present at stage 50. During the prometamorphic period, spinal projections arise in the nucleus of the solitary tract, the lateral line nucleus, and the mesencephalic trigeminal nucleus. With in vitro double‐labeling methods, based on retrograde tracing of dextran amines in combination with tyrosine hydroxylase (TH) immunohistochemistry, we show that at stage 40/41, catecholaminergic (CA) neurons in the posterior tubercle are the first to project to the spinal cord. Subsequently, at stage 43, new projections arise in the periventricular nucleus of the zona incerta and the locus coeruleus. The last CA projection to the spinal cord originates from neurons in the nucleus of the solitary tract at the beginning of prometamorphosis (stage 53). Our data show a temporal, rostrocaudal sequence in the development of the CA cell groups projecting to the spinal cord. Moreover, the early appearance of CA fibers, preterminals and terminal‐like structures in dorsal, intermediate, and ventral zones of the embryonic spinal cord, suggests an important role for catecholamines during development in nociception, autonomic functions, and motor control at the spinal level. J. Comp. Neurol. 446:11–24, 2002. © 2002 Wiley‐Liss, Inc.
Plastic reaction of the rat visual corticocollicular connection after contralateral retinal deafferentiation at the neonatal or adult stage: Axonal growth versus reactive synaptogenesis
Authors: García Del Caño Gontzal , Gerrikagoitia Inmaculada , Martínez‐Millán Luis
Published: August 2002

The effects of neonatal or adult enucleation on the final adult pattern of the rat visual corticocollicular (C‐Co) connection were studied using the anterograde tracer biotinylated dextranamine 10,000 (BDA) iontophoretically injected in the primary visual cortex. In control animals, column‐shaped terminal fields limited to a small portion of the collicular surface were observed. Synaptic boutons were present in all superficial strata of the superior colliculus (SC), with the highest density in the ventral part of the stratum griseum superficiale (SGS). Neonatal enucleation caused a considerable expansion of the contralateral visual C‐Co terminal fields, which occupied almost the entire collicular surface, suggesting that axonal sprouting had occurred. In addition, terminal boutons tended to localize more dorsally in these cases compared with controls. Following enucleation in adult animals, no changes were observed with respect to the extension of the terminal fields, although a plastic reaction leading to an increase in the bouton density in the stratum zonale (SZ) and upper SGS was found, reflecting a process of reactive synaptogenesis at these levels. These results show that both neonatal and adult visual C‐Co fibers react in response to retinal ablation, although this reaction shows distinct characteristics. Molecular factors, such as growth‐associated cytoskeletal proteins operating in the cortical origin, and extracellular matrix components and myelin‐associated axonal growth inhibitors acting on the collicular target very likely account for these differences. J. Comp. Neurol. 446:166–178, 2002. © 2002 Wiley‐Liss, Inc.
Synaptic distribution of ionotropic glutamate receptors in the inner plexiform layer of the primate retina
Authors: Grünert Ulrike , Haverkamp Silke , Fletcher Erica L. , Wässle Heinz
Published: August 2002

The distribution and synaptic clustering of glutamate receptors (GluRs) were studied in the inner plexiform layer (IPL) of the macaque monkey retina by using subunit specific antisera. A punctate immunofluorescence pattern was observed in the IPL for all subunits tested, and electron microscopy confirmed that the immunoreactive puncta represent clustering of receptors at sites postsynaptic to the bipolar cell ribbon synapses (dyads). Usually only one of the two postsynaptic processes at the dyads expressed a given subunit. Immunoreactive GluR2, GluR2/3, and GluR4 puncta were found at high density throughout the IPL and are probably expressed at every dyad. The GluR1 subunit was expressed at lower density. The N‐methyl‐D‐aspartate (NMDA) receptor subunits NR2A and NR1C2′ were restricted to synapses localized in two broad bands in the center of the IPL. They were often colocalized with GluR2/3 and GluR4 subunits. The orphan receptor subunits δ1/2 predominated in three horizontal bands. The kainate receptor subunits GluR6/7 were clustered in large postsynaptic densities adjacent to bipolar cell axon terminals but lacking a synaptic ribbon on the presynaptic side. This might represent a conventional synapse made by a bipolar axon terminal. The results suggest that GluR2/3 and GluR4, together with NMDA receptors, are preferentially expressed on ganglion cell dendrites, whereas kainate receptors and the δ1/2 subunits are mostly localized on amacrine cell processes. J. Comp. Neurol. 447:138–151, 2002. © 2002 Wiley‐Liss, Inc.
Localization of kainate receptors at the cone pedicles of the primate retina
Authors: Haverkamp Silke , Grünert Ulrike , Wässle Heinz
Published: August 2002

In the macaque monkey retina cone pedicles, the output synapses of cone photoreceptors, contain between 20 and 45 ribbon synapses (triads), which are the release sites for glutamate, the cone transmitter. Several hundred postsynaptic dendrites contact individual cone pedicles, and we studied the glutamate receptors expressed and clustered at these contacts, particularly the kainate receptor subunits GluR5, GluR6/7, and KA2. Pre‐ and postembedding immunocytochemistry and electron microscopy were used to localize GluR5 and GluR6/7 to specific synaptic contacts at the cone pedicle base. The GluR5 subunit was aggregated at bipolar cell flat contacts. The GluR6/7 subunit was aggregated at bipolar cell flat contacts and at the desmosome‐like junctions formed by horizontal cell processes underneath the cone pedicles. KA2 immunoreactivity was observed at the invaginating dendritic tips of ON‐cone and rod bipolar cells, which we interpret as a cross‐reactivity of the KA2 antiserum with some other, unknown protein of the monkey retina. Kainate receptors are preferentially expressed by OFF‐cone bipolar cells and to a lesser extent by horizontal cells. We also performed double‐labeling experiments with the ribbon‐specific marker bassoon and with antibodies against GluR5 and GluR6/7 in order to define the position of the flat bipolar cell contacts with respect to the triads. There was a tendency of GluR6/7 clusters to represent triad‐associated contacts, whereas GluR5 clusters represented non‐triad‐associated contacts. The GluR5 and GluR6/7 subunits were clustered at different bipolar cell contacts. We studied a possible cone‐selective expression of the kainate receptor subunits by double labeling cone pedicles for the S‐cone opsin and for the different receptor subunits. We observed a reduced expression of both GluR5 and GluR6/7 at the S‐cone pedicles. The reduced expression of GluR6/7 was analyzed in more detail and it appears to be a consequence of a horizontal cell‐specific expression: H1 horizontal cells express GluR6/7, whereas H2 horizontal cells, which preferentially innervate S‐cones, show no expression of GluR6/7. J. Comp. Neurol. 436:471–486, 2001. © 2001 Wiley‐Liss, Inc.
Colocalization of GABA and glycine in the ventral nucleus of the lateral lemniscus in rat: An in situ hybridization and semiquantitative immunocytochemical study
Authors: Riquelme Raquel , Saldaña Enrique , Osen Kirsten K. , Ottersen Ole P. , Merchán Miguel A.
Published: August 2002

We have studied by in situ hybridization for GAD65 mRNA in thick sections and by semiquantitative postembedding immunocytochemistry in consecutive semithin sections, the expression of γ‐aminobutyric acid (GABA) and glycine in cell bodies and axosomatic puncta of the rat ventral nucleus of the lateral lemniscus (VNLL), a prominent monaural brainstem auditory structure. The in situ hybridization and the densitometric analysis of the immunostaining suggest that the rat VNLL contains two main populations of neurons. Approximately one‐third of neurons are unstained with either technique and are presumably excitatory; their cell bodies are enveloped by a large number of glycine‐immunoreactive puncta. Most if not all of the remaining two‐thirds colocalize GABA and glycine and are assumed to be inhibitory. These two populations show a complementary distribution within the VNLL, with inhibitory neurons located mainly ventrally and excitatory neurons dorsally. In scatterplots of gray values measured from cell bodies, the double‐labeled cells appear to form a single cluster in terms of their staining intensities for the two transmitter candidates. However, this cluster may have to be further subdivided because cells with extreme GABA/glycine ratios differ from those with average ratios with respect to location or size. The VNLL seems unique among auditory structures by its large number of neurons that colocalize GABA and glycine. Although the functional significance of this colocalization remains unknown, our results suggest that the VNLL exerts convergent excitatory and inhibitory influences over the inferior colliculus, which may underlie the timing processing in the auditory midbrain. J. Comp. Neurol. 432:409–424, 2001. © 2001 Wiley‐Liss, Inc.
Descending supraspinal pathways in amphibians. I. A dextran amine tracing study of their cells of origin
Authors: Sánchez‐Camacho Cristina , Marín Oscar , Ten Donkelaar Hans J. , González Agustín
Published: August 2002

The present study is the first of a series on descending supraspinal pathways in amphibians in which hodologic and developmental aspects are studied. Representative species of anurans (the green frog, Rana perezi, and the clawed toad, Xenopus laevis), urodeles (the Iberian ribbed newt, Pleurodeles waltl), and gymnophionans (the Mexican caecilian, Dermophis mexicanus) have been used. By means of retrograde tracing with dextran amines, previous data in anurans were largely confirmed and extended, but the studies in P. waltl and D. mexicanus present the first detailed data on descending pathways to the spinal cord in urodeles and gymnophionans. In all three orders, extensive brainstem‐spinal pathways were present with only minor representation of spinal projections originating in forebrain regions. In the rhombencephalon, spinal projections arise from the reticular formation, several parts of the octavolateral area, the locus coeruleus, the laterodorsal tegmental nucleus, the raphe nucleus, sensory nuclei (trigeminal sensory nuclei and the dorsal column nucleus), and the nucleus of the solitary tract. In all species studied, the cerebellar nucleus and scattered cerebellar cells innervate the spinal cord, predominantly contralaterally. Mesencephalic projections include modest tectospinal projections, torospinal projections, and extensive tegmentospinal projections. The tegmentospinal projections include projections from the nucleus of Edinger‐Westphal, the red nucleus, and from anterodorsal, anteroventral, and posteroventral tegmental nuclei. In the forebrain, diencephalospinal projections originate in the ventral thalamus, posterior tubercle, the pretectal region, and the interstitial nucleus of the fasciculus longitudinalis medialis. The most rostrally located cells of origin of descending spinal pathways were found in the suprachiasmatic nucleus, the preoptic area and a subpallial region in the caudal telencephalic hemisphere, probably belonging to the amygdaloid complex. Our data are discussed in an evolutionary perspective. J. Comp. Neurol. 434:186–208, 2001. © 2001 Wiley‐Liss, Inc.
Co‐expression of estrogen and thyroid hormone receptors in individual hypothalamic neurons
Authors: Kia Hosein Kami , Krebs Christopher J. , Koibuchi Noriyuki , Chin William W. , Pfaff Donald W.
Published: August 2002

Estrogen receptors (ER) and thyroid hormone receptors (TR) are members of the nuclear receptor family of transcription factors that induce or repress the expression of target genes. Previous behavioral studies in female rodents have demonstrated that thyroid hormones can antagonize the effects of estrogen in the central nervous system (CNS), particularly by attenuating estrogen’s ability to facilitate reproductive behaviors. Additional molecular studies have suggested a mechanism for this antagonism by showing that ligand‐activated ERα and TRs have the potential to interact in their transcriptional controls. Although the expression patterns of ERα and TRs in the rodent brain appear to overlap in behaviorally relevant areas, it remained to be determined whether these two classes of proteins coexist in vivo at the level of single neurons. To address this possibility, we employed a highly sensitive double‐label in situ hybridization technique using digoxigenin and 35S‐labeled cRNA probes to analyze, in detail, the expression of ERα mRNA with TRα1 and TRα2 mRNAs in the same neurons of the ovariectomized (OVX) adult mouse brain. Our results demonstrate that a large majority of the ERα‐positive neurons also expresses TRα1 and TRα2 mRNAs. Quantitative examination of the cellular expression in the ventromedial and arcuate nuclei of the hypothalamus (VMH and Arc) showed that 81.5% and 80.5% of the neurons endowed with ERα mRNA also contain TRα1 and TRα2 mRNAs, respectively. In the amygdala, more than 60.5% and 67% of ERα‐positive cells also contain TRα1 and TRα2 mRNAs, respectively. These findings provide the first anatomical evidence that ER and TR can be found in the same neurons, including hypothalamic neurons. This coexpression of ERα and TR provides the cellular basis for a new level of neuronal integration in a brain region where estrogens control female reproductive behaviors. J. Comp. Neurol. 437:286–295, 2001. © 2001 Wiley‐Liss, Inc.
Development of three distinct GnRH neuron populations expressing two different GnRH forms in the brain of the African catfish (Clarias gariepinus)
Authors: Dubois Eline A. , Zandbergen Matthijs A. , Peute Jan , Bogerd Jan , Goos Henk J. Th.
Published: August 2002

The early development of both the catfish gonadotropin‐releasing hormone (cfGnRH)‐ and the chicken GnRH‐II (cGnRH‐II) system was investigated in African catfish by immunocytochemistry by using antibodies against the GnRH‐associated peptide (GAP) of the respective preprohormones. Weakly cfGnRH‐immunoreactive (ir) neurons and fibers were present at 2 weeks after hatching (ph) but only in the ventral telencephalon and pituitary. Two weeks later, cfGnRH fibers and neurons were also observed in more rostral and in more caudal brain areas, mainly in the preoptic area and hypothalamus. Based on differences in temporal, spatial, and morphologic appearance, two distinct cfGnRH populations were identified in the ventral forebrain: a population innervating the pituitary (ventral forebrain system) and a so‐called terminal nerve (TN) population. DiI tracing studies revealed that the TN population has no neuronal connections with the pituitary. The cGnRH‐II system is present from 2 weeks ph onward in the midbrain tegmentum and only their size and staining intensity increased during development. Based on the comparison of GnRH systems amongst vertebrates, we hypothesize that during fish evolution, three different GnRH systems evolved, each expressing their own molecular form: the cGnRH‐II system in the midbrain, a hypophysiotropic GnRH system in the hypothalamus with a species‐specific GnRH form, and a salmon GnRH‐expressing TN population. This hypothesis is supported by phylogenetic analysis of known GnRH precursor amino acid sequences. We hypothesize, because the African catfish is a less advanced teleost species, that it contains the cfGnRH form both in the ventral forebrain system and in the TN population.J. Comp. Neurol. 437:308–320, 2001. © 2001 Wiley‐Liss, Inc.
Relationship between insult intensity and mode of hair cell loss in the vestibular system of rats exposed to 3,3′‐iminodipropionitrile
Authors: Seoane Ana , Demêmes Danielle , Llorens Jordi
Published: August 2002

A variety of stimuli cause sensory hair cell loss in the mammalian inner ear. This loss occurs by several differing processes, the significance of which remains undetermined. This study examines the relationship between the intensity of the damaging stimulus and the mode of hair cell loss found in the vestibular sensory epithelia of the rat. The ototoxin 3,3′‐iminodipropionitrile (IDPN) was administered to rats at three different intoxication rates: acute exposure to high doses, repeated exposure to intermediate doses, and subchronic exposure to low doses. The morphology of the vestibular epithelia was examined by light microscopy and by scanning and transmission electron microscopy (SEM and TEM). In addition, DNA fragmentation in the epithelia was assessed by terminal deoxynucleotidyl transferase (tdt)‐dUTP‐nick‐end‐label (TUNEL). One day after acute IDPN, necrosis of hair cells was observed. However, at day 4 with this dose, and 1 and 4 days after repeated exposure, apoptotic figures and positive TUNEL labeling predominated. Subchronic IDPN resulted in a slowly evolving extrusion of basically intact hair cells in the crista and utricle. The data demonstrate that extrusion is a major mechanism of hair cell demise in mammals, that necrosis, apoptosis, and extrusion form a continuum of modes of hair cell loss, and that the intensity of the damaging stimulus determines the prevalence of each mode: Necrosis was most evident when the intensity was at its highest, whereas extrusion predominated when the intensity was at the lowest end of the scale. J. Comp. Neurol. 439:385–399, 2001. © 2001 Wiley‐Liss, Inc.
Differential expression of connexin26 and connexin32 in the pre‐Bötzinger complex of neonatal and adult rat
Authors: Solomon Irene C. , Halat Tami J. , El‐Maghrabi Raafat , O'Neal Marvin H.
Published: August 2002

The pre‐Bötzinger complex (pre‐BötC) is hypothesized to be the site for respiratory rhythm generation in mammals. Studies examining the cellular mechanisms mediating rhythm generation have focused on the role of chemically mediated synaptic interactions; however, electrotonic synaptic interactions (i.e., electrotonic coupling), which occur by means of gap junctions, may also play a role. Here, we used immunoblot and immunohistochemical analyses to determine whether the pre‐BötC contains the gap junction proteins necessary for electrotonic communication and whether the presence and distribution of these gap junction proteins show a developmental change in expression. We found that both connexin26 (Cx26) and connexin32 (Cx32) were expressed in pre‐BötC neurons of neonatal and adult rats; however, the relative amounts and their distribution varied by age. Cx26 labeling was seen in a high proportion of pre‐BötC neurons in neonatal rats ≤ 7 days postnatal (P7) but declined with increasing age. In contrast, Cx32 labeling was sparse in pre‐BötC neurons of neonatal rats ≤ P7, but increased with increasing age; the highest proportion was seen in adult rats. These data suggest the potential for gap junctional communication in the pre‐BötC of both neonatal and adult rats, and we propose that the gap junction proteins Cx26 and Cx32 form the neuroanatomic substrate for this gap junctional communication, which may be important in the synchronization of neural activity generating respiratory rhythm.J. Comp. Neurol. 440:12–19, 2001. © 2001 Wiley‐Liss, Inc.
An approximate method for the standard interval eigenvalue problem of real non‐symmetric interval matrices
Authors: Qiu Zhiping , Müller Peter C. , Frommer Andreas
Published: August 2002

In this study, we discuss an approximate method for estimating the upper and lower bounds on the set of all possible eigenvalues of the standard interval eigenvalue problem of the real non‐symmetric interval matrix. This kind of eigenvalue problem involves non‐probabilistic uncertainties. The favourable bound estimate is actually a set in eigenvalue space rather than a single vector. The obtained estimate is the calculable set which contains the true eigenvalues of the interval uncertain systems. In this study, first of all, we give a review of Deif's solution theorem for the standard interval eigenvalue problem in real non‐symmetric interval matrices, then we present the interval perturbation method for estimating the set of all possible eigenvalues of the real non‐symmetric interval matrix. Very weak condition of solution and inexpensive computational effort are the characteristics of the present interval perturbation method. The comparison example shows that the interval eigenvalues produced by the interval perturbation method show good agreement with those obtained by Deif's solution theorem. A numerical example of the Automobile Suspension System illustrates the application of the proposed method. Copyright © 2001 John Wiley & Sons, Ltd.
Parallel static and dynamic multi‐constraint graph partitioning
Authors: Schloegel Kirk , Karypis George , Kumar Vipin
Published: August 2002

Sequential multi‐constraint graph partitioners have been developed to address the static load balancing requirements of multi‐phase simulations. These work well when (i) the graph that models the computation fits into the memory of a single processor, and (ii) the simulation does not require dynamic load balancing. The efficient execution of very large or dynamically adapting multi‐phase simulations on high‐performance parallel computers requires that the multi‐constraint partitionings are computed in parallel. This paper presents a parallel formulation of a multi‐constraint graph‐partitioning algorithm, as well as a new partitioning algorithm for dynamic multi‐phase simulations. We describe these algorithms and give experimental results conducted on a 128‐processor Cray T3E. These results show that our parallel algorithms are able to efficiently compute partitionings of similar edge‐cuts as serial multi‐constraint algorithms, and can scale to very large graphs. Our dynamic multi‐constraint algorithm is also able to minimize the data redistribution required to balance the load better than a naive scratch‐remap approach. We have shown that both of our parallel multi‐constraint graph partitioners are as scalable as the widely‐used parallel graph partitioner implemented in PARMETIS. Both of our parallel multi‐constraint graph partitioners are very fast, as they are able to compute three‐constraint 128‐way partitionings of a 7.5 million vertex graph in under 7 s on 128 processors of a Cray T3E. Copyright © 2002 John Wiley & Sons, Ltd.
Long wavelength fluorophores and cell‐by‐cell correction for autofluorescence significantly improves the accuracy of flow cytometric energy transfer measurements on a dual‐laser benchtop flow cytometer
Authors: Sebestyén Zsolt , Nagy Péter , Horváth Gábor , Vámosi György , Debets Reno , Gratama Jan W. , Alexander Denis R. , Szöllősi János
Published: August 2002

Background

Flow cytometric fluorescence resonance energy transfer (FCET) is an efficient method to map associations between biomolecules because of its high sensitivity to changes in molecular distances in the range of 1–10 nm. However, the requirement for a dual‐laser instrument and the need for a relatively high signal‐to‐noise system (i.e., high expression level of the molecules) pose limitations to a wide application of the method.

Methods

Antibodies conjugated to cyanines 3 and 5 (Cy3 and Cy5) were used to label membrane proteins on the cell surface. FCET measurements were made on a widely used benchtop dual‐laser flow cytometer, the FACSCalibur, by using cell‐by‐cell analysis of energy transfer efficiency.

Results

To increase the accuracy of FCET measurements, we applied a long wavelength donor–acceptor pair, Cy3 and Cy5, which beneficially affected the signal‐to‐noise ratio in comparison with the classic pair of fluorescein and rhodamine. A new algorithm for cell‐by‐cell correction of autofluorescence further improved the sensitivity of the technique; cell subpopulations with only slightly different FCET efficiencies could be identified. The new FCET technique was tested on various direct and indirect immunofluorescent labeling strategies. The highest FCET values could be measured when applying direct labeling on both (donor and acceptor) sides. Upon increasing the complexity of the labeling scheme by introducing secondary antibodies, we detected a decrease in the energy transfer efficiency.

Conclusions

We developed a new FCET protocol by applying long wavelength excitation and detection of fluorescence and by refining autofluorescence correction. The increased accuracy of the new method makes cells with low receptor expression amenable to FCET investigation, and the new approach can be implemented easily on a commercially available dual‐laser flow cytometer, such as a FACSCalibur. Cytometry 48:124–135, 2002. © 2002 Wiley‐Liss, Inc.
Fine‐needle aspiration cytology of pleuropulmonary blastoma: A case report with unusual features
Authors: Shin Bong Kyung , Kim Min Kyung , Park Seong Hwan , Kim Chung Yeul , Cho Seong Jin , Lee Kwang Chul , Kim Kwang Taik , Oh Yu Hwan , Kim Insun , Kim Han Kyeom
Published: August 2002

Pleuropulmonary blastoma (PPB) is a rare and aggressive intrathoracic neoplasm of childhood, typically presenting as a pulmonary and/or pleural‐based mass with cystic, solid, or combined features. Histologically, the tumor is well characterized with a mixture of primitive mesenchymal and variably differentiated sarcomatous components, and the cytologic features described in the three previous reports are also compatible to the histologic ones. Now, we present another case of PPB showing unusual features. A 3‐yr‐old boy presented with a pleural‐ or chest wall‐based tumor. The fine‐needle aspiration cytologic smears were highly cellular with poorly differentiated cells showing variable size and shape rather than those of typical blastemal cells. The histologic findings were also distinctive, exhibiting diffuse sheets of poorly differentiated cells without typical blastemal cell component. Diagnosis was confirmed by the support of immunohistochemical and ultrastructural features. The patient underwent a typical aggressive clinical course to death within 8 mo after diagnosis. Diagn. Cytopathol. 25:397–402, 2001. © 2001 Wiley‐Liss, Inc.
Fine‐needle aspiration cytology of Kikuchi's lymphadenitis: A report of ten cases
Authors: Viguer José M. , Jiménez‐Heffernan José A. , Pérez Pablo , López‐Ferrer Pilar , Gónzalez‐Peramato Pilar , Vicandi Blanca
Published: August 2002

The purpose of this study was to evaluate the cytologic features of Kikuchi's lymphadenitis (KL). Smears from 10 patients with histologically proven KL were reviewed. In all cases, fine‐needle aspiration (FNA) was performed prior to biopsy. To assess the validity of morphologic recognition, a blinded study, including smears from non‐Hodgkin's lymphomas, nonspecific, and mycobacterial lymphadenitis was performed. At least 5 cases showed characteristic cytologic findings that permitted their specific recognition. A polymorphous lymphoid population with abundant karyorrhectic debris and histiocytes, many of which showed a small size and eccentrically placed, crescent nuclei, were characteristic features of KL. The remaining 5 cases failed to show typical findings and were indistinguishable from other nonspecific, reactive lymphadenopathies. When typical cytologic findings are present in an adequate clinical context (cervical nodes in young patients), a precise diagnosis is possible, avoiding unnecessary biopsies. Diagn. Cytopathol. 25:220–224, 2001. © 2001 Wiley‐Liss, Inc.
Presynaptic diadenosine polyphosphate receptors: Interaction with other neurotransmitter systems
Authors: Miras‐Portugal M. Teresa , Pintor Jesús , Gualix Javier , Giraldez Lisandro , Castro Enrique , Díaz‐Hernández Miguel , Gómez‐Villafuertes Rosa
Published: August 2002

Diadenosine polyphosphates (ApnA n = 2–6) are natural compounds that can play a neurotransmitter role in the synaptic terminals of the central nervous system. Microfluorimetric studies of [Ca2+]i in single synaptic terminals have shown the presence of specific ionotropic receptors for nucleotides and dinucleotides. These dinucleotide receptors may or may not coexist at the same terminal. Aminergic terminals from rat basal ganglia have been immunologically characterised by the presence of the vesicular monoamine transporter 2 after the functional studies. Fifty‐eight percent of these terminals respond to nucleotides, and of these, 17% respond only to Ap5A.
Cholinergic terminals from rat midbrain were immunologically characterised by the vesicular acetylcholine transporter. Sixty‐three percent of these terminals responded to nucleotides, and of these, 22% responded only to Ap5A. The presynaptic ionotropic dinucleotide receptors can coexist not only with the ATP receptors, but also with various subtypes of nicotinic receptors. GABAergic terminals from rat midbrain were immunologically characterised by the vesicular inhibitory amino acid transporter. Fifty‐nine percent of these terminals responded to nucleotides, and of these, 17% responded only to Ap5A. The presynaptic dinucleotide receptors, when stimulated, are able to induce the GABA release from synaptosomal preparations. These data clearly show the broad interaction of nucleotides and dinucleotides with other neurotransmitter systems. Drug Dev. Res. 52:239–248, 2001. © 2001 Wiley‐Liss, Inc.
P2 receptors on macroglial cells: Functional implications for gliosis
Authors: Franke Heike , Bringmann Andreas , Pannicke Thomas , Krügel Ute , Grosche Jens , Reichenbach Andreas , Illes Peter
Published: August 2002

The present review summarizes data about the expression of P2 receptors in two types of macroglial cells, i.e., in astrocytes of the nucleus accumbens (NAc) and Müller glial cells of the retina. Changes in the expression of these receptors during pathological conditions may indicate an involvement in the induction and/or maintenance of reactive astrogliosis. In fact, astrocytic proliferation was induced in the NAc by the application of different P2X and P2Y receptor agonists, such as 2‐methylthio ATP (2‐MeSATP), α,β‐methylene adenosine 5′‐triphosphate (α,β‐meATP) and adenosine 5′‐O‐(2‐thiodiphosphate (ADP‐β‐S). An increased content of glial fibrillary acidic protein, astrocytic hypertrophy, and proliferation as indicated by enhanced incorporation of 5‐bromo‐2′‐deoxyuridine (BrdU) was found under these conditions; an enhanced BrdU incorporation signalizes a higher rate of DNA synthesis. Müller glial cells of the human retina express both metabotropic P2Y and ionotropic P2X7 receptors. Application of the P2X7 receptor agonist benzoyl‐benzoyl ATP (BzATP) evoked a cationic conductance increase that led to the depolarization of cells and to Ca2+ entry from the extracellular space. Long‐lasting application of BzATP, however, did not cause the formation of pores permeable for large molecules, excluding the presence of classic P2X7 receptors. Müller glial cells of the human retina show increased P2X7 receptor‐mediated cationic currents during proliferative gliosis. A role of P2X7 receptors in glial proliferation is also indicated by the observation that the DNA synthesis rate of cultured Müller cells is enhanced in the presence of BzATP, as shown by the measurement of BrdU incorporation. The data indicate that activation of P2 receptors may exert both short‐ and long‐term effects in macroglial cells, and that these receptors may be involved in glial responses to pathological conditions. Drug Dev. Res. 53:140–147, 2001. © 2001 Wiley‐Liss, Inc.
Prevalence and fate of type 1 diabetes‐associated autoantibodies in cord blood samples from newborn infants of non‐diabetic mothers
Authors: Hämäläinen Anu‐Maaria , Ilonen Jorma , Simell Olli , Savola Kaisa , Kulmala Petri , Kupila Antti , Simell Tuula , Erkkola Risto , Koskela Pentti , Knip Mikael
Published: August 2002

Background

Cord blood samples were collected from 1002 consecutive births at Turku University Hospital to study the prevalence and fate of type 1 diabetes‐associated autoantibodies in newborn infants of unaffected mothers.

Methods

The samples were analysed for cytoplasmic islet cell antibodies (ICA), autoantibodies to the 65 kD isoform of glutamic acid decarboxylase (GADA), autoantibodies to the protein tyrosine phosphatase related IA‐2 antigen (IA‐2A), insulin autoantibodies (IAA) and HLA DQB1 genotypes.

Results

ICA were detected in 27 cord blood samples (2.7%), with a median of 6 (range 4–34) JDF units. GADA were found to be positive (≥6.6 RU) in six samples (0.6%), with a median of 66 (range 19–125) RU. IA–2A (≥0.43 RU) were observed in three samples (0.3%), with a median of 1.3 (range 0.8–57) RU, while only one cord blood sample (0.1%) tested positive for IAA (≥1.56 nU/ml) with a value of 5.4 RU. Maternal or gestational age, sex and birth weight of the infant were not related to antibody prevalence or titres. Altogether there were 29 infants with antibody positivity in their cord blood (2.9%). Five of these (0.5%) tested positive for two antibodies (ICA and GADA), and one was positive for all four antibodies measured. All nine infants from whom follow‐up samples were available became antibody negative by the age of 15 months, and in all but one case inverse seroconversion occurred by the age of 9 months.

Conclusions

Around 3% of infants of non‐diabetic mothers in Finland have diabetes‐associated autoantibodies at birth, and these antibodies disappear at the latest by the age of 15 months. Copyright © 2001 John Wiley & Sons, Ltd.
The search for type 2 diabetes susceptibility genes using whole‐genome scans: an epidemiologist's perspective
Authors: Stern Michael P.
Published: August 2002

Most whole‐genome scan studies of type 2 diabetes have ascertained families on affected sibpairs. Although assuring enrollment of multiplex families, this strategy may lead to the enrollment of unrepresentative families, particularly in low‐risk populations where relatively few diabetics have an affected sibling. In high‐risk populations such as Hispanics and Native Americans, population‐based ascertainment is often possible, since the high frequency of the disease favors enrollment of multiplex families even when they are not specifically sought.

The results of the first generation of genome scan studies caused concern because of a perceived lack of reproducibility. More recently, however, a number of replications have emerged, specifically on chromosomes 1q, 2q, 3q, 9p, 10q, and 11q. The MODY 1 and 3 regions on chromosome 12q and 20q have also been replicated in multiple studies. The clinical features of diabetes in these latter families, however, suggest the common form of type 2 diabetes, rather than maturity‐onset diabetes of the young (MODY). Also, diabetes in these families does not appear to be caused by the classical MODY mutations. Interestingly, functional variants of the MODY 4 gene (insulin promoter factor‐1) have been associated with both MODY and the common form of type 2 diabetes.

Currently available linkage studies implicate relatively broad chromosomal regions, and the challenge of narrowing these regions to facilitate gene discovery remains formidable. The linkages that have been replicated thus far provide good starting points to search for functional variants in type 2 diabetes susceptibility genes. Copyright © 2002 John Wiley & Sons, Ltd.
Cell–matrix interactions during development and apoptosis of the mouse mammary gland in vivo
Authors: Prince Janine M. , Klinowska Teresa C.M. , Marshman Emma , Lowe Emma T. , Mayer Ulrike , Miner Jeff , Aberdam Daniel , Vestweber Dietmar , Gusterson Barry , Streuli Charles H.
Published: August 2002

Epithelial cell survival is dependent on extracellular signals provided by both soluble factors and by adhesion. In the mammary gland, extensive apoptosis of epithelial cells occurs rapidly when lactation ceases, but the mechanism of apoptosis induction is not known. In tissue culture, mammary epithelial cells require laminin as a survival ligand and specific β1 integrins are necessary to suppress apoptosis. To explore the possibility that dynamic changes in cell–matrix interactions contribute to the onset of apoptosis during mammary involution in vivo, a detailed immunohistochemical analysis of the expression of integrin subunits and their extracellular matrix ligands during mouse mammary gland development has been performed. The kinetics of apoptosis were determined by using tissue samples obtained from virgin, pregnant, lactating, and involuting gland. The maximal elevation of apoptosis occurred within 24 hr of weaning as determined by histologic analysis and caspase‐3 staining. A wide variety of laminin subunits, together with nidogen‐1 and ‐2, and perlecan were identified within the basement membrane region of epithelial ducts, lobules, and alveoli in both human and mouse mammary gland. However, no change in the distribution of any of the basement membrane proteins or their cognate integrin receptors was observed during the transition from lactation to apoptosis. Instead, we discovered that altered ligand‐binding conformation of the β1 integrin to a nonbinding state coincided with the immediate onset of mammary apoptosis. This finding may provide a novel dynamic mechanism for inhibiting the transduction of extracellular matrix survival signals, thereby contributing to the onset of apoptosis in a developmental context in vivo. © 2002 Wiley‐Liss, Inc.
Xiro‐1 controls mesoderm patterning by repressing bmp‐4 expression in the spemann organizer
Authors: Glavic Alvaro , Gómez‐Skarmeta Jose Luis , Mayor Roberto
Published: August 2002

The Iroquois genes code for homeodomain proteins that have been implicated in the neural development of Drosophila and vertebrates. We show here for the first time that Xiro‐1, one of the Xenopus Iroquois genes, is expressed in the Spemann organizer from the start of gastrulation and that its overexpression induces a secondary axis as well as the ectopic expression of several organizer genes, such as chordin, goosecoid, and Xlim‐1. Our results also indicate that Xiro‐1 normally functions as a transcriptional repressor in the mesoderm. Overexpression of Xiro‐1 or a chimeric form fused to the repressor domain of Engrailed cause similar phenotypes while overexpression of functional derivatives of Xiro‐1 fused with transactivation domains (VP16 or E1A) produce the opposite effects. Finally, we show that Xiro‐1 works as a repressor of bmp‐4 transcription and that its effect on organizer development is dependent on BMP‐4 activity. We propose that the previously observed down regulation of bmp‐4 in the dorsal mesoderm during gastrulation can be explained by the repressor activity of Xiro‐1 described here. Thus, Xiro‐1 seems to have at least two different functions: control of neural plate and organizer development, both of which could be mediated by repression of bmp‐4 transcription. © 2001 Wiley‐Liss, Inc.
Phonological spelling errors among dyslexic children learning a transparent orthography: the case of Czech
Authors: Caravolas Markéta , Volín Jan
Published: August 2002

Substantial evidence from studies of English‐speaking dyslexic children's spelling suggests that these individuals have a persistent impairment in representing the phonological structure and content of words in writing. In contrast, several studies of German dyslexic children (Landerl & Wimmer, 2000) suggest that, among learners of transparent orthographies, the above impairment is transient and resolves by the end of grade 2; instead dyslexic spelling is characterised by a persistent impairment in learning inconsistent spelling patterns. In order to determine whether phonological spelling difficulties are transient among dyslexic spellers of other transparent orthographies, we analysed phonological accuracy in the spellings of 43 dyslexic children, 43 age‐matched control and 43 spelling‐matched control children attending primary schools in Prague. Czech dyslexic children presented an interesting test case because Czech has a transparent orthography. Czech dyslexics as old as 11 years (grade 5) continued to produce high rates of phonologically inaccurate spellings relative to their age peers; thus their difficulties with phonological representation in spelling had not resolved. This pattern is consistent with findings from studies of English‐speaking dyslexics, and it suggests that orthographic depth may impact less dramatically on the manifestation of dyslexia than has been proposed previously. Copyright © 2001 John Wiley & Sons, Ltd.