bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of MOI ratio on the composition and yield of chimeric infectious bursal disease virus‐like particles by baculovirus co‐infection: Deterministic predictions and experimental results
Authors: Hu Yu‐Chen , Bentley William E.
Published: August 2002

Virus‐like particles (VLPs) are empty particles consisting of virus capsid proteins that closely resemble native virus but are devoid of the native viral nucleic acids and therefore have attracted significant attention as noninfectious vaccines. A recombinant baculovirus, vIBD‐7, which encodes the structural proteins (VP2, VP3, and VP4) of infectious bursal disease virus (IBDV), produces native IBD VLPs in infected Spodoptera frugiperda insect cells. Another baculovirus, vEDLH‐22, encodes VP2 that is fused with a histidine affinity‐tag (VP2H) at the C‐terminus. By co‐infection with these two baculoviruses, hybrid VLPs with histidine tags were formed and purified by immobilized metal affinity chromatography (Hu et al., 1999). Also, we demonstrated that varying the MOI ratio of these infecting viruses altered the extent of VP2H incorporated into the particles. A dynamic mathematical model that described baculovirus infection and VLP synthesis (Hu and Bentley, 2000) was adapted here for co‐infection and validated by immunofluorescence labeling. It was shown to predict the VLP composition as a dynamic function of MOI. A constraint in the VP2H content incorporated into the particles was predicted and shown by experiments. Also, the MOI ratio of both infecting viruses was shown to be the major factor influencing the composition of the hybrid particles and an important factor in determining the overall yield. ELISA results confirmed that VP2H was exhibited to a varied extent on the outer surface of the particles. This model provides insight on the use of virus co‐infection in virus‐mediated recombinant protein expression systems and aids in the optimization of chimeric VLP synthesis. © 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 75: 104–119, 2001.
Cardiac troponin I for risk stratification following percutaneous coronary artery intervention in acute coronary syndromes
Authors: Nageh Thuraia , Sherwood Roy A. , Harris Beverley M. , Thomas Martyn R.
Published: August 2002

The cardiac troponins have been shown to provide prognostic information allowing risk stratification of patients with acute coronary syndromes (ACS). The benefit of early percutaneous coronary intervention (PCI) in this setting has been highlighted by the FRISC II study. We assessed the pattern of release of cardiac troponin I (cTnI) following PCI in patients with ACS and evaluated its prognostic value for major adverse cardiac events (MACE): death, Q‐wave myocardial infarction (QWMI), and repeat revascularization at follow‐up. cTnI was sampled at baseline and 6, 14, and 24 hr following PCI in 73 patients presenting with unstable and post‐MI angina. Clinical follow‐up was obtained in all 73 patients at a mean period of 43 ± 19.9 weeks (range, 11–68 weeks). Patients were stratified into two groups according to whether cTnI remained unchanged or fell below baseline 24 hr post‐PCI (group 1, n = 47) or increased above baseline 24 hr following PCI (group 2, n = 26). MACE occurred in 4 (8.5%) of patients in group 1 (QWMI = 1, CABG = 1, re‐PCI = 2) and in 19 (73%) of patients in group 2 (death = 1, QWMI = 2, CABG = 2, re‐PCI = 14; chi‐square = 32.34, P < 0.0001). The positive predictive value of rising cTnI within 24 hr following PCI for MACE at follow‐up was 0.73 and the negative predictive value was 0.92 (specificity = 83%, sensitivity = 86%; odds ratio = 29.18, 95% CI = 7.62–110.64, P < 0.0001). cTnI is an inexpensive and widely applicable tool that offers reliable prognostic information for the risk stratification of patients undergoing coronary revascularization in the setting of acute coronary syndromes and may identify a group of patients at particular risk of repeat PCI. Cathet Cardiovasc Intervent 2002;55:37–42. © 2002 Wiley‐Liss, Inc.
Clopidogrel therapy in patients undergoing coronary stenting: Value of a high‐loading‐dose regimen
Authors: Pache Jürgen , Kastrati Adnan , Mehilli Julinda , Gawaz Meinrad , Neumann Franz‐Josef , Seyfarth Melchior , Hall Donald , Braun Siegmund , Dirschinger Josef , Schömig Albert
Published: August 2002

The objective of this study was to assess the value of a clopidogrel regimen based on a high loading dose initiated before the stent placement procedure. A consecutive series of 864 patients treated with a high‐loading‐dose clopidogrel regimen (600 mg given 2–4 hr prior to intervention) was compared with 870 patients treated with conventional ticlopidine therapy. Abciximab was given periprocedurally in 62% of the patients. The composite endpoint of death, myocardial infarction, or urgent revascularization was reached by 39 (4.5%) clopidogrel patients and 59 (6.8%) ticlopidine patients. Clopidogrel therapy was associated with a 35% reduction of the risk for early adverse events (odds ratio 0.65; 95% confidence interval, 0.43–0.98). Thus, a high‐loading‐dose clopidogrel regimen in patients undergoing coronary artery stenting was safe and led to a more favorable clinical outcome than conventional therapy with ticlopidine regardless of concomitant treatment with abciximab. Cathet Cardiovasc Intervent 2002;55:436–441. © 2002 Wiley‐Liss, Inc.
Combined glycoprotein IIb/IIIa receptor inhibition and low‐dose fibrinolysis for peripheral arterial thrombosis
Authors: Rocha‐Singh Krishna J. , Trokey Janiece
Published: August 2002

This feasibility study evaluated the therapeutic potential of combined GP IIb/IIIa receptor inhibition with abciximab and low‐dose fibrinolysis with reteplase for treatment of acute femoropopliteal thrombosis. The simultaneous intra‐arterial administration of abciximab in conjunction with low‐dose reteplase (≤ 0.5 U/hr) was safe in 13 patients; 2 patients experienced major hemorrhagic complication at a reteplase dose of 1 U/hr. The primary success rate was 100%; all patients experienced an excellent clinical response with no clinical evidence of distal embolization. No patient required repeat endovascular or surgical revascularization during mean follow‐up of 9.3 months. This promising new thrombolytic strategy for the treatment of peripheral arterial occlusive disease requires further study. Cathet Cardiovasc Intervent 2002;55:457–460. © 2002 Wiley‐Liss, Inc.
Right heart catheterization in the presence of an inferior vena cava filter
Authors: Kussmaul William G. , Secaira Roberto , McCormick Daniel J. , Cohen Marc
Published: August 2002

Inferior vena cava filters are being inserted with increasing frequency. When such patients later require right heart catheterization, brachial or jugular vein access is usually attempted. We describe our experience in 10 consecutive patients using the standard femoral approach, first assessing filter patency and then carefully crossing the filter using a straight guidewire. The right heart chambers were successfully accessed in every case. There were no complications, and in no case did the filter migrate or become dislodged. This technique may prove useful when right heart catheterization is indicated in a patient who has a Greenfield inferior vena cava filter. Cathet Cardiovasc Intervent 2001;52:476–478. © 2001 Wiley‐Liss, Inc.
Late acute thrombosis after coronary brachytherapy: When is the risk over?
Authors: Liistro Francesco , Gimelli Giorgio , Di Mario Carlo , Nishida Takahiro , Montorfano Matteo , Carlino Mauro , Colombo Antonio
Published: August 2002

Late total occlusion (LTO) after simultaneous coronary stenting and brachytherapy has been described in recent randomized trials. We report a case of LTO presenting with an acute clinical event 15 months after the index procedure, suggesting that the risk is not confined to the first 6‐month to 1‐year period. Cathet Cardiovasc Intervent 2001;54:216–218. © 2001 Wiley‐Liss, Inc.
Sequential implantation of two helex septal occluder devices in a patient with complex atrial septal anatomy
Authors: Dobrolet Nancy C. , Iskowitz Steven , Lopez Leo , Whalen Ruby , Zahn Evan M.
Published: August 2002

We report the first implantation of two Helex septal occluder devices in a 10‐year‐old boy with complex atrial septal anatomy. The unique characteristics of this new device are discussed in the following case report. Cathet Cardiovasc Intervent 2001;54:242–246. © 2001 Wiley‐Liss, Inc.
R2PI Study of intermolecular hydrogen bond in solvent‐free chiral complexes
Authors: Giardini Guidoni A. , Piccirillo S. , Scuderi D. , Satta M. , Di Palma T.M. , Speranza M. , Filippi A. , Paladini A.
Published: August 2002

One‐ and two‐color, mass selected R2PI spectra of the S1←S0 transitions in the bare (+)‐(R)‐1‐phenyl‐1‐ethanol (ER) and its complexes with different solvent molecules (solv) (−)‐(R)‐2‐butanol (BR) or (+)‐(S)‐2‐butanol (BS) and (−)‐(R)‐2‐butylamine (AR) or (+)‐(S)‐2‐butylamine (AS), have been recorded after a supersonic molecular beam expansion. The one‐color R2PI excitation spectra of the diastereomeric complexes are characterized by significant shifts of their band origin relative to that of bare ER. The extent and the direction of these spectral shifts are found to depend on the structure and the configuration of solv and are attributed to different short‐range interactions in the ground and excited states of the complexes. In analogy with other diastereomeric complexes, the phenomenological binding energy of the homochiral cluster is found to be greater than that of the heterochiral one. Chirality 13:727–730, 2001. © 2001 Wiley‐Liss, Inc.
Molecular mechanics (MM4) force field development for phosphine and its alkyl derivatives
Authors: Todebush Patricia Metthe , Liang Guyan , Bowen J. Phillip
Published: August 2002

Based on the experimental structures and vibrational spectra of eight alkylphosphines, as well as ten ab initio calculated (MP2/6−31+g*) structures and five potential energy profiles, the MM4 force field has been extended to include this important functional group. The results are comparable to experimental values for phosphorus‐containing compounds. The addition of various cross‐terms significantly improved the MM4 calculated structures relative to its predecessor, MM3. The overall root mean square error in moments of inertia have been reduced from 1.65% in MM3 to 0.26% in MM4. MM4 was also successful in reducing the previously impressive root mean square error in vibrational frequencies from 35 cm−1 to 31 cm−1 for the eight compounds studied. Chirality 14:220–231, 2002. © 2002 Wiley‐Liss, Inc.
Regulation of focal adhesion targeting and inhibitory functions of the FAK related protein FRNK using a novel estrogen receptor “switch”
Authors: Martin Karen H. , Boerner Scott A. , Parsons J. Thomas
Published: August 2002

Focal adhesion kinase (FAK) is a regulator of numerous adhesion‐dependent processes including cell migration, cell proliferation, and cell survival. The C‐terminal domain of FAK, FAK‐related nonkinase (FRNK), is autonomously expressed and functions as an inhibitor of FAK signaling. Previous attempts to use FRNK as a tool to dissect FAK signaling have been limited because of an inability to temporally regulate the inhibitory functions of FRNK. In this report, we describe and characterize a conditionally targeted form of FRNK that was created by fusing the hormone‐binding domain of the estrogen receptor (ER*) to the C‐terminus of FRNK. In the absence of added hormone, FRNK‐ER* was diffusely distributed throughout the cytoplasm of cells. Upon addition of hormone, the cytoplasmic pool of FRNK‐ER* was rapidly redistributed to focal adhesions. We demonstrate that cells expressing FRNK‐ER* show a hormone‐dependent decrease in FAK tyrosine phosphorylation and cell migration. Furthermore, when cells expressing of FRNK‐ER* were treated with hormone, the cells responded with a dramatic change in cell morphology, suggesting a role for FAK in the regulation of the adhesive properties of focal adhesions. Cell Motil. Cytoskeleton 51:76–88, 2002. © 2002 Wiley‐Liss, Inc.
Intra‐tumoral interleukin‐6 down‐regulation system and genetic mutations of tumor suppressor genes in colorectal carcinoma
Authors: Miki Chikao , Tonouchi Hitoshi , Wakuda Reiko , Hatada Tsuyoshi , Inoue Yasuhiro , Minato Eiji , Kobayashi Minàko , Kusunoki Masato
Published: August 2002

BACKGROUND

The interleukin (IL)‐1‐IL‐6 network, the most potent cascade of pro‐inflammatory cytokines, plays an autocrine role in tumor growth. The IL‐1‐IL‐6 network is down‐regulated by a phased cytokine inhibitor IL‐1 receptor antagonist (ra) and an anti‐inflammatory cytokine IL‐10. The current study evaluated this down‐regulation system in colorectal carcinoma and its relation to the genetic alteration of tumor suppressor genes.

METHODS

Seventy‐four specimens of primary colorectal carcinoma and normal mucosa were collected to measure tissue concentrations of cytokines. Polymerase chain reaction amplification was performed to investigate the loss of heterozygosity of the microsatellite markers on chromosomes 17p and 18q.

RESULTS

The IL‐1ra/IL‐6 ratio in the carcinoma specimens was lower than ratios in adenomas and normal mucosae and decreased with disease progression. The IL‐1ra/IL‐6 ratio in early cancers tended to be lower than that in adenomas and normal mucosae. However, the tissue concentrations of IL‐1β and IL‐10 were not associated with any clinicopathologic parameters. The tissue IL‐1ra concentration correlated with that of IL‐6 only in adenomas and early cancers. Immunohistochemically, IL‐1ra and IL‐6 were localized in the tumor cytoplasm. A reduced tissue IL‐1ra/IL‐6 ratio in the carcinomas correlated with poor prognosis and was associated with the loss of heterozygosity of the microsatellite markers on chromosomes 18q.

CONCLUSIONS

There is an IL‐6‐IL‐1ra network system in colorectal tumors, but this system deteriorates with carcinogenesis and tumor growth. The deterioration of this network system was associated with the allelic loss of a portion of chromosome 18q, reflecting the genetic alteration of tumor suppressor genes. Cancer 2002;94:1584–92. © 2002 American Cancer Society.

DOI 10.1002/cncr.10324
Neonatal development of projections from the basolateral amygdala to prefrontal, striatal, and thalamic structures in the rat
Authors: Bouwmeester Hans , Wolterink Gerrit , Van Ree Jan M.
Published: August 2002

Recently, an animal model for neurodevelopmental disorders has been developed. In this model, the effects of an early neonatal (postnatal day 7 [Pd 7]) basolateral amygdala lesion are compared with the effects of a lesion later in life (Pd 21). The reported data indicate that amygdala damage at a specific point early in life results in enduring behavioral disturbances that become more manifest after puberty, for example, only an early lesion resulted in a disruption of the prepulse inhibition, which is also observed in people suffering from schizophrenia. Accordingly, it was postulated that the early damage may affect the neuroanatomic and neurochemical organization and functioning of other brain structures. This was studied by use of the anterograde tracers biotinylated dextran amine and Phaseolus vulgaris‐leucoagglutinin. At neonatal days 7, 9, 11, 13, and 26, amygdaloid fibers were in particular present in the mediodorsal thalamus (MDT), nucleus accumbens (Acb), and prefrontal cortex (PFC). The development of the topography of the amygdaloid innervation, however, differed markedly for the MDT and Acb compared with the PFC. For the MDT and Acb, no major changes in innervation were observed between Pd 7 and Pd 26, whereas the innervation of the PFC reorganized from a neonatal diffuse (Pd 7 and 9) to a restricted pattern (Pd 11, 13, and 26). In addition, the innervation changed to an adult‐like bilaminar pattern. These data provide information on the circuitry that may be involved in the aberrant neurodevelopment of neonatally amygdala‐lesioned rats, which have been proposed as an animal model for neurodevelopmental psychopathological disorders. J. Comp. Neurol. 442:239–249, 2002. © 2001 Wiley‐Liss, Inc.
Differential expression of nm23 genes in adult mouse dorsal root ganglia
Authors: Barraud Perrine , Amrein Lilian , Dobremez Eric , Dabernat Sandrine , Masse Karine , Larou Monique , Daniel Jean‐Yves , Landry Marc
Published: August 2002

Nm23 has been identified as a gene family encoding different isoforms of nucleoside diphosphate kinase (NDPK). This protein is a key enzyme in nucleotide metabolism and has been shown to play important roles in various cellular functions. In the present study, we have investigated the expression of three isotypes in mouse dorsal root ganglia. In situ hybridization and reverse transcriptase‐polymerase chain reaction analysis demonstrated high levels of nm23‐M1, ‐M2, and ‐M3 mRNA expression in peripheral nervous tissue. Moreover, in situ hybridization also displayed a specific nuclear localization for nm23‐M2 mRNA. Immunohistochemistry with light and electron microscopy on isoform‐specific antibodies revealed a differential subcellular distribution of NDPK isoforms. Isoform A was mainly cytosolic, showing only partial association with organelles. In contrast, isoform B was also found in the nucleus, which is in agreement with its proposed role as a transcription factor. The results also indicate a preferential association of isoform C with endoplasmic reticulum and plasma membranes in neuronal cells. Furthermore, isoform C appeared to combine with other NDPK isoforms as demonstrated by double‐labeling evidence by electron microscopy and might be responsible for binding NDPK oligomers to membranes. Thus, isoform C may be considered as a protein of importance for maintaining intracellular pools of GTP in the vicinity of membranes and, hence, for transmembrane signaling. The results indicate a high expression of NDPK isoforms, not only in the central but also in the peripheral nervous system. Their different subcellular compartmentalization suggests that they have isoform‐specific roles in neuronal cell physiology. J. Comp. Neurol. 444:306–323, 2002. © 2002 Wiley‐Liss, Inc.
Selective distribution of μ‐opioid receptors in C1 adrenergic neurons and their afferents
Authors: Aicher Sue A. , Kraus James A. , Sharma Sarita , Patel Aarti , Milner Teresa A.
Published: August 2002

Agonists of the μ‐opioid receptor (MOR) have profound effects on blood pressure, heart rate, and respiration that may be mediated by C1 adrenergic neurons in the rostral ventrolateral medulla (RVL). C1 neurons are sympathoexcitatory and are involved in both tonic and reflex regulation of sympathetic outflow. This study was designed to determine whether C1 neurons, or their afferents, contain MOR. C1 neurons were identified by using an antibody against the epinephrine synthesizing enzyme phenylethanolamine‐N‐methyl transferase (PNMT), whereas MOR was localized by using an antipeptide antibody that recognizes the cloned MOR, MOR1. Combined immunoperoxidase and immunogold methods were used to examine the cellular distribution of MOR1 relative to PNMT‐containing neurons in the RVL. MOR1 was found in 22% of PNMT‐containing dendrites (n = 392), whereas MOR1‐containing axons or axon terminals contacted 14% of PNMT‐containing dendrites. This distribution was heterogenous with regard to dendritic size: PNMT‐labeled dendrites containing MOR1 were usually large (60% were >1.2 μm), whereas PNMT‐containing dendrites that received MOR1‐labeled afferents were usually small (79% were <1.2 μm). Individual dendrites rarely contained MOR1 at both pre‐ and postsynaptic sites. Together these results suggest that MOR agonists may directly influence the activity of C1 neurons, as well as the activity of select afferents to these cells. Plasmalemmal membrane labeling for MOR1 was more frequent in smaller PNMT‐containing dendrites, suggesting that postsynaptic receptors are more readily available for ligand binding in small dendrites, although the receptor was more frequently detected in larger PNMT dendrites. The selective distribution of MORs to specific pre‐ and postsynaptic sites suggests the receptor may be selectively trafficked to positions where it may regulate afferent activity that is heterogeneously distributed along the dendritic tree of C1 neurons. J. Comp. Neurol. 433:23–33, 2001. © 2001 Wiley‐Liss, Inc.
Hypoglossal and reticular interneurons involved in oro‐facial coordination in the rat
Authors: Popratiloff Anastas S. , Streppel Michael , Gruart Agnés , Guntinas‐Lichius Orlando , Angelov Doychin N. , Stennert Eberhard , Delgado‐García José M. , Neiss Wolfram F.
Published: August 2002

Chewing, swallowing, breathing, and vocalization in mammals require precise coordination of tongue movements with concomitant activities of the mimetic muscles. The neuroanatomic basis for this oro‐facial coordination is not yet fully understood. After the stereotaxic microinjection of retrograde and anterograde neuronal tracers (biotin‐dextran, Fluoro‐Ruby, Fluoro‐Emerald, and Fluoro‐Gold) into the facial and hypoglossal nuclei of the rat, we report here a direct bilateral projection of hypoglossal internuclear interneurons onto facial motoneurons. We also confirm the existence of a small pool of neurons in the dorsal part of the brainstem reticular formation that project ipsilaterally to both facial and hypoglossal nuclei. For precise tracer injections, both motor nuclei were located and identified by the electrical antidromic activation of their constituent motoneurons. Injections of retrograde tracers into the facial nucleus consistently labeled neurons in the hypoglossal nucleus. These neurons prevalently lay in the ipsilateral side, were small in size, and, like classic intrinsic hypoglossal local‐circuit interneurons, had several thin dendrites. Reverse experiments — injections of anterograde tracers into the hypoglossal nucleus — labeled fine varicose nerve fiber terminals in the facial nucleus. These fiber terminals were concentrated in the intermediate subdivision of the facial nucleus, with a strong ipsilateral prevalence. Double injections of different tracers into the facial and the hypoglossal nuclei revealed a small, but constant, number of double‐labeled neurons located predominantly ipsilateral in the caudal brainstem reticular formation. Hypoglossal internuclear interneurons projecting to the facial nucleus, as well as those neurons of the parvocellular reticular formation that project to both facial and hypoglossal nuclei, could be involved in oro‐facial coordination. J. Comp. Neurol. 433:364–379, 2001. © 2001 Wiley‐Liss, Inc.
Axo‐axonic synapses formed by somatostatin‐expressing GABAergic neurons in rat and monkey visual cortex
Authors: Gonchar Yuri , Turney Stephen , Price Joseph L. , Burkhalter Andreas
Published: August 2002

In cerebral cortex of rat and monkey, the neuropeptide somatostatin (SOM) marks a population of nonpyramidal cells (McDonald et al. [1982] J. Neurocytol. 11:809–824; Hendry et al. [1984] J. Neurosci. 4:2497:2517; Laemle and Feldman [1985] J. Comp. Neurol. 233:452–462; Meineke and Peters [1986] J. Neurocytol. 15:121–136; DeLima and Morrison [1989] J. Comp. Neurol. 283:212–227) that represent a distinct type of γ‐aminobutyric acid (GABA) ‐ergic neuron (Gonchar and Burkhalter [1997] Cereb. Cortex 7:347–358; Kawaguchi and Kubota [1997] Cereb. Cortex 7:476–486) whose synaptic connections are incompletely understood. The organization of inhibitory inputs to the axon initial segment are of particular interest because of their role in the suppression of action potentials (Miles et al. [1996] Neuron 16:815:823). Synapses on axon initial segments are morphologically heterogeneous (Peters and Harriman [1990] J. Neurocytol. 19:154–174), and some terminals lack parvalbumin (PV) and contain calbindin (Del Rio and DeFelipe [1997] J. Comp. Neurol. 342:389–408), that is also expressed by many SOM‐immunoreactive neurons (Kubota et al. [1994] Brain Res. 649:159–173; Gonchar and Burkhalter [1997] Cereb. Cortex 7:347–358). We studied the innervation of pyramidal neurons by SOM neurons in rat and monkey visual cortex and examined putative contacts by confocal microscopy and determined synaptic connections in the electron microscope. Through the confocal microscope, SOM‐positive boutons were observed to form close appositions with somata, dendrites, and spines of intracortically projecting pyramidal neurons of rat area 17 and pyramidal cells in monkey striate cortex. In addition, in rat and monkey, SOM boutons were found to be associated with axon initial segments of pyramidal neurons. SOM axon terminals that were apposed to axon initial segments of pyramidal neurons lacked PV, which was shown previously to label axo‐axonic terminals provided by chandelier cells (DeFelipe et al. [1989] Proc. Natl. Acad. Sci. USA 86:2093–2097; Gonchar and Burkhalter [1999a] J. Comp. Neurol. 406:346:360). Electron microscopic examination directly demonstrated that SOM axon terminals form symmetric synapses with the initial segments of pyramidal cells in supragranular layers of rat and monkey primary visual cortex. These SOM synapses differed ultrastructurally from the more numerous unlabeled symmetric synapses found on initial segments. Postembedding immunostaining revealed that all SOM axon terminals contained GABA. Unlike PV‐expressing chandelier cell axons that innervate exclusively initial segments of pyramidal cell axons, SOM‐immunoreactive neurons innervate somata, dendrites, spines, and initial segments, that are just one of their targets. Thus, SOM neurons may influence synaptic excitation of pyramidal neurons at the level of synaptic inputs to dendrites as well as at the initiation site of action potential output. J. Comp. Neurol. 443:1–14, 2002. © 2002 Wiley‐Liss, Inc.
Analysis of shear locking in Timoshenko beam elements using the function space approach
Authors: Mukherjee Somenath , Prathap Gangan
Published: August 2002

Elements based purely on completeness and continuity requirements perform erroneously in a certain class of problems. These are called the locking situations, and a variety of phenomena like shear locking, membrane locking, volumetric locking, etc., have been identified. Locking has been eliminated by many techniques, e.g. reduced integration, addition of bubble functions, use of assumed strain approaches, mixed and hybrid approaches, etc. In this paper, we review the field consistency paradigm using a function space model, and propose a method to identify field‐inconsistent spaces for projections that show locking behaviour. The case of the Timoshenko beam serves as an illustrative example. Copyright © 2001 John Wiley & Sons, Ltd.
Shape identification for natural convection problems
Authors: Park H. M. , Ku J. H.
Published: August 2002

We consider an inverse problem of identifying the boundary shape of a domain, where the temperature field is dominated by natural convection, from temperature measurements on the other boundary. The potential applications of the present investigations are the determination of a phase change isotherm in the Bridgman crystal growth or the thermal tomography which detects flaws in materials non‐destructively. After mapping the irregular domains into a reference one employing a set of parameters, the inverse problem is formulated as a parameter optimization problem which is solved by a conjugate gradient method. The present method is found to identify the domains reasonably accurately even with noisy temperature measurements. Copyright © 2001 John Wiley & Sons, Ltd.
Type safety in the JVM: some problems in Java 2 SDK 1.2 and proposed solutions
Authors: Coglio Alessandro , Goldberg Allen
Published: August 2002

In the course of our work in developing formal specifications for components of the Java Virtual Machine (JVM), we have uncovered subtle bugs in the bytecode verifier of Sun's Java 2 SDK 1.2. These bugs, which lead to type safety violations, relate to the naming of reference types. Under certain circumstances, these names can be spoofed through delegating class loaders. These flaws expose some inaccuracies and ambiguities in the JVM specification.

We propose several solutions to all of these bugs. In particular, we propose a general solution that makes use of subtype loading constraints. Such constraints complement the equality loading constraints introduced in the Java 2 Platform, and are posted by the bytecode verifier when checking assignment compatibility of class types. By posting constraints instead of resolving and loading classes, the bytecode verifier in our solution has a cleaner interface with the rest of the JVM, and allows lazier loading. We sketch some excerpts of our mathematical formalization of this approach and of its type safety results. Copyright © 2001 John Wiley & Sons, Ltd.
Utility of urinary cytology for diagnosing human polyoma virus infection in transplant recipients: A study of 37 cases with electron microscopic analysis
Authors: De Las Casas Luis E. , Hoerl H. Daniel , Bardales Ricardo H. , Pirsch John D. , Sempf Joan M. , Wetzel Donna J. , Stewart Jimmie , Oberley Terry D. , Kurtycz Daniel F.I.
Published: August 2002

Human polyoma virus (HPOV) infection is associated with hemorrhagic cystitis, tubulointerstitial nephritis, and renal transplant dysfunction/allograft loss. We evaluated the utility of cytologic examination to detect HPOV infection in 37 urinary cytology (UC) samples (3 bladder washings, and 34 voided samples) from 29 transplant patients, compared to electron microscopic studies (EMS). Evidence of viral infection was found in 11 specimens (30%). Five cases were diagnosed as HPOV by both UC and EMS. One was positive for HPOV by EMS only. Two cases diagnosed as HPOV by UC were demonstrated to be adenovirus (AV) with EMS. Two cases diagnosed as cytomegalovirus (CMV) by EMS had negative UC. One was called HPOV by UC; EMS in this case was negative. Compared to EMS, the sensitivity and specificity of UC for detecting HPOV were 83% and 90%, respectively, with a positive predictive value of 63% and a negative predictive value of 96%. We conclude that UC is a relatively sensitive and specific method for detecting active HPOV infection in transplant patients, and is important in light of the clinical significance of HPOV infection in transplant recipients. The sensitivity and accuracy of UC for diagnosing HPOV can be increased by adding EMS. Diagn. Cytopathol. 25:376–381, 2001. © 2001 Wiley‐Liss, Inc.
Aspiration biopsy of osseous metastasis of occult hepatocellular carcinoma: Case report, literature review, and differential diagnosis
Authors: Suterwala Smita , Volk Emily E. , Danforth Robert D.
Published: August 2002

Fine‐needle aspiration (FNA) cytology is a reliable technique for rapid diagnosis in virtually every organ of the body, including bone lesions. We report on the FNA findings in a 61‐yr‐old male of an osteolytic sacral lesion, which determined the diagnosis of an unsuspected metastatic hepatocellular carcinoma. In this case, the diagnosis was confirmed by FNA biopsy without resorting to surgical biopsy. Diagn. Cytopathol. 25:63–67, 2001. © 2001 Wiley‐Liss, Inc.
Follicular variant of papillary carcinoma: Cytologic findings on FNAB samples—experience with 16 cases
Authors: Fulciniti Franco , Benincasa Giulio , Vetrani Antonio , Palombini Lucio
Published: August 2002

Between January 1, 1992 and December 31, 1997, a cytopathological diagnosis of follicular variant of papillary thyroid carcinoma (FVPC) was made on a series of 16 out of 18 patients with palpable nodules who underwent fine‐needle aspiration biopsy (FNAB) in our Department. The results of aspiration biopsy were followed by histopathological examination of the surgically excised tissues. There were three false‐negative aspirations (16.6%), of which two were probably bound to fine‐needle sampling and one due to a mixture of benign and malignant cells which had originally gone unrecognized. The accuracy of the cytopathologic diagnosis in this variant was 88.8%.

An analysis of the diagnostic cytopathological criteria was performed, which demonstrated the importance of both architectural features (monolayered and branching sheets, microacinar structures, and their combinations) and nuclear features (presence of nuclear grooves). Background ‐bound features were mainly represented by dense, nonfilamentous colloid.

The cytopathologic findings in FVPC were compared to those found in a series of 10 usual papillary carcinomas (UPC) and 10 follicular neoplasms (FN). These latter had originally been diagnosed by FNAB and were subsequently classified histologically as follicular adenoma (n = 6), follicular carcinoma (n = 3), or adenomatoid colloid nodule (n = 1).

Statistical evaluation was performed on the cytopathological findings in the three classes of lesions (FVPC, UPC, and FN) as to their presence and relative frequency or absence by using a nonparametric one‐way ANOVA (Kruskall‐Wallis) and, where necessary, a Mann‐Whitney U test.

Papillary cellular fragments and multinucleated giant cells (P < 0.005), nonfilamentous dense colloid, squamoid cells, and syncytia were significantly more represented in UPC than in FVPC (P < 0.05), while histiocytes were significantly more frequent in FVPC (P < 0.005). Other nuclear and/or background features were significant only in the distinction between papillary carcinomas as a group and FN.

The cytological differential diagnosis of the FVPC is briefly discussed with relevance to the possible pitfalls caused by its peculiar cyto‐ and histomorphology. Diagn. Cytopathol. 2001;25:86–93. © 2001 Wiley‐Liss, Inc.
Malignant melanoma with a myxoid stroma: A diagnostic pitfall on fine‐needle aspiration biopsy
Authors: Elliott Danielle , Pitman Martha Bishop
Published: August 2002

Malignant melanoma (MM), both primary and metastatic, may be associated with a prominent myxoid stromal reaction causing diagnostic confusion on fine‐needle aspiration biopsy (FNAB), most often with sarcomas that demonstrate a myxoid stroma, particularly malignant peripheral nerve sheath tumor (MPNST). We present a case of a 32‐yr‐old man with no past medical history who presented with a unilateral neck mass clinically suspicious for lymphoma. FNAB produced a specimen composed of large sheets of anaplastic cells encased in a myxoid stroma that was S100 and vimentin‐positive but HMB‐45‐negative. A diagnosis of MPNST was made. Excision demonstrated a metastatic MM of unknown primary, with a prominent myxoid stromal reaction. A repeat HMB‐45 was again negative. Electron microscopy demonstrated intracytoplasmic melanasomes and cisternae of rough endoplasmic reticulum with intracisternal parallel tubules, confirming the diagnosis. Although HMB‐45 is typically negative in both tumors, S100 should be strongly positive in myxoid MM and only focal in MPNST. Diagn. Cytopathol. 25:185–190, 2001. © 2001 Wiley‐Liss, Inc.
Hantzsch 1,4‐dihydropyridines containing a nitrooxyalkyl ester moiety to study calcium channel antagonist structure–activity relationships and nitric oxide release
Authors: Nguyen Jeffrey‐Tri , McEwen Carol‐Anne , Knaus Edward E.
Published: August 2002

A group of 3‐nitrooxyalkyl 5‐alkyl 1,4‐dihydro‐2,6‐dimethyl‐4‐(pyridyl)‐3,5‐pyridinedicarboxylates were prepared using a modified Hantzsch reaction that involved the condensation of a nitrooxyalkyl acetoacetate with an alkyl 3‐aminocrotonate and a pyridinecarboxaldehyde. 1H NMR nuclear Overhauser enhancement (nOe) studies for 3‐(3‐nitrooxypropyl) 5‐isopropyl 1,4‐dihydro‐2,6‐dimethyl‐4‐(2‐pyridyl)‐3,5‐pyridinedicarboxylate (17) indicates a predominant rotamer exists in solution where the pyridyl nitrogen atom is orientated above the 1,4‐DHP ring system, and the pyridyl nitrogen atom is antiperiplanar to the 1,4‐DHP ring H‐4 proton. Variable temperature 1H NMR studies (–30 to +60°C) showed the 1,4‐DHP NH proton in 17 is H‐bonded in CHCl3 solution. This interaction is believed to be due to intermolecular H‐bonding between the pyridyl nitrogen free electron pair and the 1,4‐DHP NH proton. In vitro calcium channel antagonist (CCA) activities were determined using a muscarinic‐receptor‐mediated Ca+2‐dependent contraction of guinea pig ileal longitudinal smooth muscle assay. This class of compounds exhibited lower CCA activity (IC50 = 5.3 × 10–6 to 3.5 × 10–8 M range) than the reference drug nifedipine (IC50 = 1.4 × 10–8 M). For compounds having C‐3 –CH2CH2ONO2 and C‐4 pyridyl substituents, the C‐5 alkyl was a determinant of CCA (i‐Pr > the approximately equipotent i‐Bu, t‐Bu, and Et analogs). The point of attachment of the isomeric C‐4 pyridyl substituent was a determinant of CCA when C‐3 –CH2CH2ONO2 and C‐5 i‐Pr substituents were present providing the potency profile 2‐pyridyl ≥ 3‐pyridyl > 4‐pyridyl. CCA with respect to the C‐3 nitrooxyalkyl substituent was inversely dependent on the length of the alkyl spacer. The percent nitric oxide (·NO) released in vitro by this group of compounds (range of 0.03–0.43%/ONO2 group), quantified as nitrite by reaction with the Griess reagent, was lower than that for the reference drug glycerol trinitrate (3.81%/ONO2 group). Nitric oxide release studies showed that the %·NO released was dependent on the number of ONO2 groups/molecule. A QSAR study for this group of compounds showed a correlation between the specific polarizability descriptor (SpPol) and %·NO release. Drug Dev. Res. 51:233–243, 2000. © 2001 Wiley‐Liss, Inc.
N‐methyl,N‐propargyl‐2‐phenylethylamine (MPPE), an analog of deprenyl, increases neuronal cell survival in thiamin deficiency encephalopathy
Authors: Kwan E. , Baker G.B. , Shuaib A. , Ling L. , Todd K.G.
Published: August 2002

Wernicke encephalopathy (WE) is a neurological disorder attributable to thiamin deficiency (TD). Severe TD, in humans and animals, results in highly selective lesions with a symmetrical distribution in brain regions including the mammillary bodies, thalamus, inferior colliculi, periaqueductal and periventricular regions, and inferior olivary nuclei. Experimental TD in the rat provides a robust and reproducible model that allows investigations of mechanisms underlying both apoptotic and necrotic neuronal death. (‐)‐Deprenyl (DEP), a selective monoamine oxidase B (MAO‐B) inhibitor, has been reported to be clinically effective in the treatment of neurodegenerative disorders and to have neuroprotective and/or neurorescue properties in a variety of ex vivo and in vitro paradigms, including experimental TD. Because the metabolites of DEP, amphetamine, and methamphetamine may have adverse behavioral effects, a DEP analog, N‐methyl,N‐propargyl‐2‐phenylethylamine (MPPE) that is not metabolized to amphetamine or methamphetamine was examined in the present studies. Results showed that TD rats treated with MPPE had significantly increased neuronal cell counts compared to vehicle‐treated TD rats. MPPE, like DEP, also significantly decreased the density of reactive astrocytes and the infiltration of microglia/macrophages. Chronic treatment with DEP or MPPE resulted in significant inhibition of MAO‐A and MAO‐B activity compared to VEH‐treated animals. Thus, MPPE, an inhibitor of MAO activity, was shown to be neuroprotective in the TD model of neuronal cell death. Drug Dev. Res. 51:244–252, 2000. © 2001 Wiley‐Liss, Inc.
A converging‐methods approach to fragile X syndrome
Authors: Churchill James D. , Grossman Aaron W. , Irwin Scott A. , Galvez Roberto , Klintsova Anna Y. , Weiler Ivan Jeanne , Greenough William T.
Published: August 2002

Converging approaches across domains of brain anatomy, cell biology, and behavior indicate that Fragile X syndrome, arising from impaired expression of a single gene and protein, appears to involve an aberration of normal developmental processes. Synapse overproduction and selective elimination, or pruning, characterize normal brain development. In autopsy tissue from Fragile X patients and in a knockout mouse model of the disease, synapse overproduction appears to occur unaccompanied by synapse pruning and maturation, leaving an excess of immature spine synapses in place. The absence of the Fragile X protein seems to impair the synthesis of important proteins at synapses. The developmental outcome in Fragile X is a nervous system that is relatively disorganized, resulting in disrupted perceptual, and cognitive social, behavior. © 2002 Wiley Periodicals, Inc. Dev Psychobiol 40: 323–338, 2002. DOI 10.1002/dev.10036
Differential response of Shh expression between chick forelimb and hindlimb buds by FGF‐4
Authors: Wada Naoyuki , Nohno Tsutomu
Published: August 2002

The interactions of Sonic hedgehog (Shh) and fibroblast growth factor (FGF) play important roles in vertebrate limb pattern formation. In the posterior region of the chick limb bud, Shh and FGF‐4 each maintain expression in a positive feedback loop. In the anterior region, Shh can also induce Fgf‐4 expression in the anterior apical ectodermal ridge. However, the possibility of Shh induction by FGF protein is unclear. Because many experiments to analyze gene expression have been carried out by using the forelimb bud of the chick embryo, we investigated gene expression of the cells in the anterior region of the chick hindlimb bud after FGF‐4 application and compared the results with those for the forelimb bud. When an FGF‐4–containing bead was implanted into the anterior region of a stage 20 hindlimb bud, ectopic expression of Shh was induced in the mesenchyme beneath the anterior end of the apical ectodermal ridge at 36 hr after implantation. Subsequent to Shh activation, Hoxd13 was also observed in the anterior‐distal region of the limb bud. Furthermore, FGF‐4 implantation to the hindlimb bud caused additional digit formation accompanying respecification of positional value in the anterior tissue. Ectopic Shh was induced in cells located distal to the FGF‐4 bead, and the cells of the flank region did not contribute to ectopic Shh induction. On the other hand, no ectopic Shh and Hoxd13 expression was detected by grafting an FGF‐4 bead into the forelimb bud. Although FGF‐4 implantation to the forelimb bud occasionally induced extra digit 2 formation, no embryos had an extra digit 3 or digit 4, and many specimens exhibited normal skeletal pattern. These results demonstrate the difference between the fore‐ and hindlimb buds in the cell competence of Shh induction in response to FGF‐4, suggesting the possibility that the responsiveness of mesenchymal cells in signaling molecules is not the same in the fore‐ and hindlimb buds. © 2001 Wiley‐Liss, Inc.
Expression and regulation of the retinoic acid synthetic enzyme RALDH‐2 in the embryonic chicken wing
Authors: Berggren Kirsten , Ezerman Elizabeth B. , Mccaffery Peter , Forehand Cynthia J.
Published: August 2002

Retinaldehyde dehydrogenase type 2 (RALDH‐2) is a major retinoic acid (RA) generating enzyme in the embryo. Here, we report immunolocalization of this enzyme (RALDH‐2‐IR) in the developing wings of stage 17–30 chicken embryos. RALDH‐2‐IR is located in the area of the presumptive muscle masses, although it is not colocalized with developing muscle cells. RALDH‐2‐IR is located in tendon precursor cells and may be present in muscular connective tissue. We show that motor neurons and blood vessels, tissues showing RALDH‐2‐IR as they enter the limb, are capable of synthesizing and releasing RA in culture. RALDH‐2‐IR in the limb mesenchyme is under the control of both the vasculature and the motor innervation; it is decreased with denervation and increased with hypervascularization. RALDH‐2‐IR is present in the motor neuron pool of the brachial spinal cord, but this expression pattern is apparently not under the control of limb target tissues, RA in the periphery, or somitic factors. RA is known to be a potent inducer of cellular differentiation; we propose that locally synthesized RA may be involved in aspects of wing tissue specification, including cartilage condensation and outgrowth, skeletal muscle differentiation, and recruitment of smooth muscle cells to the vasculature. © 2001 Wiley‐Liss, Inc.
α1 connexin (connexin43) gap junctions and activities of cAMP‐dependent protein kinase and protein kinase C in developing mouse heart
Authors: Duncan John C. , Fletcher William H.
Published: August 2002

α1 connexin (connexin43) is the dominant gap junction protein of the developing and mature heart where it forms channels that mediate intercellular electrical and metabolic coupling events that are critical for heart function. α1 connexin channels are rapidly and reversibly gated by actions of cAMP‐dependent protein kinase (PKA) and protein kinase C (PKC), and disruption of consensus sites for these phosphorylations are associated with severe heart malformations. However, there have been no reports on the relative activities of PKA or PKC in early heart formation. Nor has the presence and phosphorylation state of α1 connexin been documented in these same developmental stages. To begin these studies, we used hearts from 8.5–18.5 dpc (days postcoitus) mouse embryos, postpartum pups, and adults. Membrane or supernatant fractions were used for immunoblots to assess the amounts and distribution of α1 connexin protein and each protein kinase. Phosphotransferase assays were done to document the endogenous activities of PKA and PKC. Three species of α1 connexin at 44, 46, and 49 kDa were evident in 8.5‐ and 9.5‐dpc embryos and adult hearts, but the 49‐kDa band was not consistently found in 10.5 dpc or embryos through 18.5 dpc, although it was robust in adult heart. The amount of PKA was minimal in 8.5‐dpc hearts but rose thereafter and was maximal by 10.5 dpc and remained stable throughout development. Catalytic activity of this enzyme was minimal in 8.5‐dpc hearts then rose thereafter and was maximal by 10.5 dpc of development. PKCδ was confined mainly to membrane fractions, whereas PKCϵ had supernatant‐ and membrane‐associated forms. Both enzyme isoforms showed large fluctuations throughout development. In 8.5‐ and 9.5‐dpc hearts, PKC catalytic activity was maximal but, by 10.5 dpc, activity dramatically declined and remained low thereafter. The results demonstrate that α1 connexin is present at the heart tube stage (8.5 dpc) of development onward and provide evidence suggesting that channels formed by this protein are dynamically regulated by PKA and PKC, especially in 8.5‐ and 9.5‐day embryonic hearts, which are crucial times for heart formation and left/right patterning in general. © 2001 Wiley‐Liss, Inc.
Season of birth in females with anorexia nervosa in Northeast Scotland
Authors: Eagles John M. , Andrew Jane E. , Johnston Maureen I. , Easton Euan A. , Millar Harry R.
Published: August 2002

Objective

To determine whether patients with anorexia nervosa exhibit an abnormal pattern in their season of birth.

Method

Case records of female patients presenting to secondary services in Northeast Scotland from 1965 to 1997 who received a clinical diagnosis of anorexia nervosa were examined. The months of birth of the 446 anorexic patients with a confirmed diagnosis were compared with 5,766 female control subjects born locally in 1951, 1961, 1971, and 1981.

Results

Patients with anorexia nervosa had an excess of births in the first 6 months of the year (p = .013). The greatest excess was from March to June.

Discussion

This provides further evidence that birth dates of anorexics peak in the late spring and early summer. There are parallels with the epidemiology of schizophrenia. The evidence suggests that a seasonally fluctuating factor, most plausibly an intrauterine effect of common infectious agents during the winter months, is of etiological significance. © 2001 by John Wiley & Sons, Inc. Int J Eat Disord 30: 167–175, 2001.