bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of apoptosis in rheumatoid synovial fibroblasts by celecoxib, but not by other selective cyclooxygenase 2 inhibitors
Authors: Kusunoki Natsuko , Yamazaki Ryuta , Kawai Shinichi
Published: December 2002

Objective

Selective cyclooxygenase 2 (COX‐2) inhibitors are now being used as antiinflammatory agents that cause fewer gastrointestinal complications, compared with other antiinflammatory drugs, in patients with rheumatoid arthritis (RA). This study was undertaken to investigate whether selective COX‐2 inhibitors could induce apoptosis of RA synovial fibroblasts (RASFs).

Methods

RASFs were exposed to selective COX‐2 inhibitors, i.e., celecoxib, etodolac, meloxicam, nimesulide, N‐[2‐(cyclohexyloxyl)‐4‐nitrophenyl]‐methanesulfonamide, and rofecoxib, under various conditions. Cell proliferation and cell viability were assessed by incorporation of 5‐bromo‐2′‐deoxyuridine and by the 2‐(4‐iodophenyl)‐3‐(4‐nitrophenyl)‐5‐(2,4‐disulfophenyl)‐2H‐tetrazolium monosodium salt assay, respectively. Apoptosis was detected by identifying DNA fragmentation. Activation of peroxisome proliferator–activated receptor γ (PPARγ) was measured by the luciferase reporter gene assay with a PPAR response element–driven luciferase reporter plasmid and a PPARγ expression plasmid.

Results

Celecoxib strongly inhibited the proliferation of RASFs, whereas other selective COX‐2 inhibitors had little or no effect. In addition, celecoxib reduced the viability of RASFs by induction of apoptosis, in a concentration‐dependent manner. This action was abolished by addition of caspase inhibitors. Interleukin‐1β had a weak enhancing effect on celecoxib‐induced apoptosis in RASFs. In contrast, other selective COX‐2 inhibitors at concentrations up to 100 μM did not induce apoptosis of RASFs. Indomethacin, a nonselective COX inhibitor, activated PPARγ transcription, while celecoxib did not.

Conclusion

Celecoxib suppressed the proliferation of RASFs by COX‐2–independent and PPARγ‐independent induction of apoptosis. Although the mechanism involved remains unclear, celecoxib may have not only antiinflammatory activity, but also a disease‐modifying effect on rheumatoid synovial proliferation.
Isolation and characterization of bone marrow multipotential mesenchymal progenitor cells
Authors: Jones Elena A. , Kinsey Sally E. , English Anne , Jones Richard A. , Straszynski Liz , Meredith David M. , Markham Alex F. , Jack Andrew , Emery Paul , McGonagle Dennis
Published: December 2002

Objective

There is an increased interest in rheumatology in mesenchymal progenitor/stem cells (MPCs) and their roles in rheumatic diseases, but little is known about the phenotype of these cells in vivo. The aim of this study was to isolate and characterize human bone marrow (BM) MPCs.

Methods

Fluorescence microscopy was used to identify putative MPCs among adherent BM cells. To purify them, a positive selection with antifibroblast microbeads was used, combined with fluorescence‐activated cell sorting (FACS) for microbead+,CD45low cells. A more detailed phenotype of these cells was determined using 4‐color flow cytometry, and standard chondrogenic, osteogenic, and adipogenic assays were used to investigate their differentiation potentials.

Results

Putative MPCs microscopically identified as large, fibroblast‐like, D7‐FIB+ cells were purified using positive selection with D7‐FIB–conjugated (antifibroblast) microbeads followed by FACS for specifically bound microbead+,CD45low cells. These cells represented 0.01% of mononuclear cells in the BM. They were uniformly positive for CD105, LNGFR, HLA–DR, CD10, CD13, CD90, STRO‐1, and bone morphogenetic protein receptor type IA (BMPRIA) and were negative for CD14, CD34, CD117, and CD133. Only cells with this phenotype could proliferate and produce adherent cell monolayers capable of chondrogenic, osteogenic, and adipogenic differentiation. D7‐FIB− cells in the BM lacked any MPC activity. Uncultured skin fibroblasts had a phenotype similar to that of BM MPCs, but were negative for LNGFR, STRO‐1, HLA–DR, and BMPRIA.

Conclusion

This study shows the distinct phenotype, morphology, and method of isolation of BM MPCs. The findings may have implications for defining the physiologic roles of MPCs in arthritis, bone diseases, and joint regeneration.
Linkage and association studies of single‐nucleotide polymorphism–tagged tumor necrosis factor haplotypes in juvenile oligoarthritis
Authors: Zeggini Eleftheria , Thomson Wendy , Kwiatkowski Dominic , Richardson Anna , Ollier William , Donn Rachelle ,   The British Paediatric Rheumatology Study Group
Published: December 2002

Objective

The presence of increased levels of tumor necrosis factor (TNF) in serum and synovial fluid of patients and the encouraging outcome of anti‐TNF therapy have implicated TNFα in the etiopathogenesis of juvenile oligoarthritis. Although the locus is polymorphic, no study has investigated all TNF single‐nucleotide polymorphisms (SNPs) with respect to disease. The aim of this study was to examine the association of multiple TNF SNPs with juvenile oligoarthritis and to construct and analyze SNP‐tagged TNF haplotypes.

Methods

A total of 144 simplex families consisting of parent and affected child, as well as 88 healthy, unrelated control subjects were available for study. In these individuals, 9 polymorphic positions of TNF were typed by a high‐throughput genotyping method based on the SNaPshot assay. The chi‐square and extended transmission disequilibrium tests were used to test for association and linkage, respectively. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were also calculated. Haplotype‐tagging SNPs (htSNPs) for the locus were identified by ordering the haplotypes according to their frequencies.

Results

The study detected association of several TNF SNPs and established linkage of the locus to juvenile oligoarthritis. The most significant association observed was between the intronic +851 TNF SNP and the persistent oligoarthritis subgroup (OR 3.86, 95% CI 1.6–9.2). Haplotype data mining showed that only 4 of the 9 SNPs need to be typed in order to capture the most frequent TNF haplotypes.

Conclusion

The TNF locus is linked and associated with juvenile oligoarthritis. Information on the htSNPs can be useful in genetic studies of diseases in which TNF may be of relevance.
Biophysical limits on athermal effects of RF and microwave radiation
Authors: Adair Robert K.
Published: December 2002

Using biophysical criteria, I show that continuous radiofrequency (RF) and microwave radiation with intensity less than 10 mW/cm2 are unlikely to affect physiology significantly through athermal mechanisms. Biological systems are fundamentally noisy on the molecular scale as a consequence of thermal agitation and are noisy macroscopically as a consequence of physiological functions and animal behavior. If electromagnetic fields are to significantly affect physiology, their direct physical effect must be greater than that from the ubiquitous endogenous noise. Using that criterion, I show that none of a set of interactions of weak fields, which I argue is nearly complete on dimensional grounds, can affect biology on the molecular scale. Moreover, I conclude that such weak fields are quite unlikely to generate significant effects in their interactions with larger biological elements such as cells. In the course of that analysis, I examine important special examples of electromagnetic interactions: “direct” interactions where biology is modified simply by the motion of charged elements generated by the electric field; resonance interactions; the effects of electrostrictive forces and induced dipole moments; and modifications of radical pair recombination probabilities. In each case, I show that it is unlikely that low intensity fields can generate significant physiological consequences. Bioelectromagnetics 24:39–48, 2003. © 2002 Wiley‐Liss, Inc.
No effects of extremely low frequency magnetic fields found on cytotoxic activities and cytokine production of human peripheral blood mononuclear cells in vitro
Authors: Ikeda Keiichi , Shinmura Yasushi , Mizoe Hiroki , Yoshizawa Hiroaki , Yoshida Atsuya , Kanao Seiichi , Sumitani Hiroyuki , Hasebe Setsu , Motomura Toshio , Yamakawa Taku , Mizuno Fumio , Otaka Yoshihisa , Hirose Hideki
Published: December 2002

Several epidemiologic studies have suggested an association between exposure to extremely low frequency (ELF) magnetic fields (MFs) and cancer in adults and children. A possible target of MFs is the immune system. The effects of the exposure to ELF MFs on the immunological functions of human peripheral blood mononuclear cells (PBMCs) obtained from healthy male volunteers were assessed by measuring the natural killer (NK) and lymphokine activated killer (LAK) activities and the production of interferon‐γ (IFN‐γ), tumor necrosis factor‐α (TNF‐α), interleukin‐2 (IL‐2), and interleukin‐10 (IL‐10). The PBMCs were exposed to three different MF: linearly polarized (vertical), circularly polarized, and elliptically polarized, at 50 and 60 Hz. Magnetic flux densities were set at 500, 100, 20, and 2 μT (rms) for vertical field and at 500 μT (rms) for the rotating fields. Using cytotoxicity assay and enzyme‐linked immunosorbent assay (ELISA) for cytokine production, we could not find any effects of ELF MFs on the cytotoxic activities and the cytokines production of human PBMCs. Bioelectromagnetics 24:21–31, 2003. © 2002 Wiley‐Liss, Inc.
Calmodulin‐dependent cyclic nucleotide phosphodiesterase activity is altered by 20 μT magnetostatic fields
Authors: Liboff A.R. , Cherng S. , Jenrow K.A. , Bull A.
Published: December 2002

Absorbance measurements at 660 nm of calmodulin (CaM) dependent cyclic nucleotide phosphodiesterase activity under cell free conditions indicate that 30‐min exposures to weak magnetostatic field intensities alters this activity, compared to zero magnetic field exposures. This effect depends nonlinearly on the concentration of free calcium, with maximum magnetic interaction apparently occurring at an optimal Ca2+ concentration corresponding to 50% activation (EC50). If one regards Ca2+/CaM activation as a switching process, then increasing the magnetic field at Ca2+ levels in excess of optimal acts to bias this switch towards lower calcium concentrations. A magnetic dependence has been previously reported by others in an homologous system, CaM dependent myosin light chain phosphorylation, implying that there may be an underlying magnetic interaction that involves the initial Ca2+/CaM binding process common to both enzymatic pathways. The level of magnetostatic intensity at which this effect is observed (∼20 μT) implies that CaM activation may be functionally sensitive to the geomagnetic field. Bioelectromagnetics 24:32–38, 2003. © 2002 Wiley‐Liss, Inc.
Effects of electromagnetic radiation of mobile phones on the central nervous system
Authors: Hossmann K.‐A. , Hermann D.M.
Published: December 2002

With the increasing use of mobile communication, concerns have been expressed about the possible interactions of electromagnetic radiation with the human organism and, in particular, the brain. The effects on neuronal electrical activity, energy metabolism, genomic responses, neurotransmitter balance, blood–brain barrier permeability, cognitive function, sleep, and various brain diseases including brain tumors are reviewed. Most of the reported effects are small as long as the radiation intensity remains in the nonthermal range, and none of the research reviewed gives an indication of the mechanisms involved at this range. However, health risks may evolve from indirect consequences of mobile telephony, such as the sharply increased incidence rate of traffic accidents caused by telephony during driving, and possibly also by stress reactions which annoyed bystanders may experience when cellular phones are used in public places. These indirect health effects presumably outweigh the direct biological perturbations and should be investigated in more detail in the future. Bioelectromagnetics 24:49–62, 2003. © 2002 Wiley‐Liss, Inc.
Testing the effectiveness of small radiation shields for mobile phones
Authors: Oliver J. Patrick , Chou C. K. , Balzano Quirino
Published: December 2002

Nine small radiation shields made to adhere to the case of mobile phones were tested at 914 and 1880 MHz. Five popular products were tested because advertisements typically claim they are up to 99% effective in blocking radio frequency (RF) radiation emitted from mobile phones. Also, four other conceptually unusual products were tested because advertisements typically claim they emit oscillations that counteract the RF radiation from mobile phones. Each shield was tested on the same mobile phone, and measurements were made to compare the absorption of RF energy in the head with and without each shield attached to the phone. The phone was positioned against a head model, and an automated measurement process was used to determine specific absorption rate (SAR) in the same way it is used at Motorola to test the compliance of mobile phones with respect to human exposure limits. The location of the peak SAR was not observed to change with any of the shields attached to the phone, and the 1 g, peak spatial average SAR did not change by any statistically significant amount. These results indicate the small shields are ineffective in reducing the exposure of the head to RF energy emitted by a mobile phone. Bioelectromagnetics 24:66–69, 2003. © 2002 Wiley‐Liss, Inc.
Acute exposure to 50 Hz magnetic fields with harmonics and transient components: Lack of effects on nighttime hormonal secretion in men
Authors: Kurokawa Yoshika , Nitta Hiroshi , Imai Hideki , Kabuto Michinori
Published: December 2002

The purpose of this study was to examine whether low frequency magnetic field (MF) influences nighttime secretion of hormones, particularly melatonin. Ten healthy males stayed in the experimental room (2.7 m cube with 3 axis Merritt coils) on two separate nights. On one night, subjects were exposed to linearly polarized 50 Hz, 20 μT sinusoidal MF with the third (30%) and the fifth (10%) harmonics and repetitive transient waves (1 burst/s of 1 kHz waves, exponentially attenuated with a duration of 50 ms; initially 100 μT peak), and the other night was for blind control. During the nights (2000–0800 h, including sleeping time, 2300–0700 h), blood samples were collected from the subjects at 1 h intervals for determining the levels of plasma hormones (melatonin, growth hormone (GH), cortisol, prolactin) and at 10 min intervals from 2200 to 0200 h for observing the GH surge induced by sleep. Statistical analyses revealed no significant difference between the 2 nights in the profiles of the four hormones, and the result suggested that extremely low frequency (ELF) or intermediate frequency (IF) MF to which humans are exposed residentially has no acute effect on nighttime secretion of hormones, particularly melatonin. Bioelectromagnetics 24:12–20, 2003. © 2002 Wiley‐Liss, Inc.
Human exposure by mobile phones in enclosed areas
Authors: Toropainen Anssi
Published: December 2002

Human exposure by mobile phones in enclosed areas such as train carriages, elevators, and cars is considered. Equivalent power density and whole body specific absorption rate (SAR) are estimated by applying multimode resonant cavity theory and a straight forward worst case approach. The results show that exceeding the International Commission on Non‐Ionizing Radiation Protection (ICNIRP) guidelines due to simultaneous use of several mobile phones in enclosed areas is highly improbable. Bioelectromagnetics 24:63–65, 2003. © 2002 Wiley‐Liss, Inc.
The wonders of magnetism
Authors: Tenforde Thomas S.
Published: December 2002

In this acceptance address for the Bioelectromagnetics Society's 2001 d'Arsonval Award, Dr. Tenforde reviews the highlights of the nonionizing field aspects of his research and scientific service career. These are focused in four areas: (a) development and application of microelectrophoretic methods to probe the surface chemistry of normal and cancerous cells; (b) research on the biophysical mechanisms of interaction and the dosimetry of static and extremely low frequency magnetic fields; (c) application of extremely high intensity magnetic fields in several spectroscopic methods for probing the detailed structures of large biological macromolecules; and (d) development of national and international guidelines for the exposure of workers and members of the general public to electromagnetic fields with frequencies spanning the entire nonionizing electromagnetic spectrum. Bioelectromagnetics 24:3–11, 2003. © 2002 Wiley‐Liss, Inc.
Chemistry and biology of the ramoplanin family of peptide antibiotics
Authors: McCafferty Dewey G. , Cudic Predrag , Frankel Brenda A. , Barkallah Salim , Kruger Ryan G. , Li Wenkai
Published: December 2002

The peptide antibiotic ramoplanin factor A2 is a promising clinical candidate for treatment of Gram‐positive bacterial infections that are resistant to antibiotics such as glycopeptides, macrolides, and penicillins. Since its discovery in 1984, no clinical or laboratory‐generated resistance to this antibiotic has been reported. The mechanism of action of ramoplanin involves sequestration of peptidoglycan biosynthesis Lipid intermediates, thus physically occluding these substrates from proper utilization by the late‐stage peptidoglycan biosynthesis enzymes MurG and the transglycosylases (TGases). Ramoplanin is structurally related to two cell wall active lipodepsipeptide antibiotics, janiemycin, and enduracidin, and is functionally related to members of the lantibiotic class of antimicrobial peptides (mersacidin, actagardine, nisin, and epidermin) and glycopeptide antibiotics (vancomycin and teicoplanin). Peptidomimetic chemotherapeutics derived from the ramoplanin sequence may find future use as antibiotics against vancomycin‐resistant Enterococcus faecium (VRE), methicillin‐resistant Staphylococcus aureus (MRSA), and related pathogens. Here we review the chemistry and biology of the ramoplanins including its discovery, structure elucidation, biosynthesis, antimicrobial activity, mechanism of action, and total synthesis. © 2002 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 66: 261–284, 2002
A combinatorial biocatalysis approach to an array of cholic acid derivatives
Authors: Secundo Francesco , Carrea Giacomo , De Amici Marco , Joppolo di Ventimiglia Samuele , Dordick Jonathan S.
Published: December 2002

A 39‐member library of bile acid derivatives was prepared starting from 3α,7α,12α‐trihydroxy‐5β‐cholan‐24‐oic acid methyl ester using a combinatorial biocatalytic approach. A regioselective oxidation step, catalyzed by hydroxysteroid dehydrogenases, followed by an acylation step with a series of different acyl donors catalyzed by Candida antarctica lipase B, led to the modification of the bile acid scaffold. Each member of the library was obtained in high purity and good yield. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 81: 391–396, 2003.
Messverfahren zur Bestimmung des Staubungsvermögens von dispersen Pulvern
Authors: Hamelmann F. , Schmidt E.
Published: December 2002

Disperse Feststoffsysteme setzen bei ihrer Handhabung, z. B. beim Lagern, Fördern, Mischen, Abfüllen usw., oft Staub frei. Freigesetzte Stäube können die Gesundheit von Menschen gefährden bzw. schädigen, nehmen Einfluss auf die Umwelt und können zu Bränden und Explosionen führen. Das Staubungsverhalten von Pulvern ist dabei von einer Vielzahl von Parametern abhängig, die sowohl das Pulver selbst als auch die Art und Intensität der Beanspruchung kennzeichnen. Dieser Beitrag gibt eine Übersicht über Verfahren, die zur Bestimmung des Staubungsverhaltens entwickelt bzw. verwendet wurden. Die verwendeten Partikelmesstechniken werden vorgestellt und die Verfahren in einer Systematik zusammengefasst.
Hybridverfahren zur Abluftreinigung
Authors: Ohlrogge K. , Herbst M. , Scheel H. , Wind J. , Peinemann K.‐V.
Published: December 2002

Membranverfahren haben bei verschiedenen Anwendungen in der Gastrennung einen anerkannten Stand der Technik erreicht. Hierzu gehören die Luftzerlegung zur Inertgasherstellung oder Sauerstoffanreicherung, die Wasserdampfabtrennung aus Druckluft, die Wasserstoff/Kohlenmonoxidtrennung und Wasserstoff/Stickstofftrennung bei der Ammoniaksynthese, die Kohlendioxid/Methantrennung bei der tertiären Ölgewinnung und die Abtrennung organischer Dämpfe aus Abluft oder Prozessgasen in der chemischen Industrie und beim Benzinumschlag. Ein großes Potential für die Anwendung von Membranverfahren liegt in der Abluftreinigung. Durch die Kombination von Membrantrennung und Adsorption können unter wirtschaftlichen und betriebssicheren Bedingungen niedrige Restemissionen erreicht werden.
Monitoring‐System mit adaptiven Wärmebilanzen für Batch‐Reaktoren
Authors: Hessel G. , Kryk H. , Schmitt W. , Seiler T. , Weiß F.‐P. , Hilpert R. , Roth M. , Deerberg G.
Published: December 2002

No abstracts.
Stationärer Betrieb von Adsorptionsanlagen
Authors: von Gemmingen U.
Published: December 2002

No abstracts.
Stoffübergang fest/flüssig bei oszillierender Relativbewegung zwischen Partikel und Flüssigkeit
Authors: Forner A. , Großer A. , Baumann K.‐H.
Published: December 2002

No abstracts.
Mikroverkapselung feiner Partikel in einer überkritischen Wirbelschicht
Authors: Kröber H. , Teipel U.
Published: December 2002

No abstracts.
Erhöhung der mikrobiellen katabolischen Aktivität durch das Phänomen der „Biologischen Resonanz“
Authors: Schmid A.
Published: December 2002

No abstracts.
Parallele Reaktorsysteme zur Bioprozessentwicklung
Authors: Weuster‐Botz D.
Published: December 2002

No abstracts.
Mikrobielle Textilveredlung mit anaeroben Mischkulturen: Integration von Abwasserreinigung und Produktion
Authors: Feitkenhauer H.
Published: December 2002

No abstracts.
Neue Ansätze in der Aufreinigung von Plasmid‐DNA im großen Maßstab
Authors: Costioli M. , Giovannini R. , Hilbrig F. , O’Mahony K. , Müller P. , Schumacher I. , Freitag R.
Published: December 2002

No abstracts.
Die chemische Bindung — Lernhindernisse und mögliche Lernhilfen
Authors: Reiners Christiane S.
Published: December 2002

THE CHEMICAL BOND There is an often‐quoted parable about a group of blind men who are taken to examine an elephant. Each comes in contact with a different part of the elephant and, therefore, draws a different conclusion about its nature: the man examining the trunk thinks, it is some kind of snake, the one touching its leg thinks it is a tree, and so on. The lesson of this story is, of course, that we can have many different views of the same reality, depending on where we are standing and what data we use for our conclusions. The chemical bond is the chemist's “elephant”. Unable to see this construct that they use to explain the aggregation of atoms into molecules, the chemists interpret its existence in terms of their own views of chemistry… To each of these chemists the chemical bond has different descriptors, although they may all be investigating the same molecule. Thus, the chemist concerned with quantum mechanics regards the chemical bond as an interaction of wave functions, the more classical physical chemist sees a balancing of energies and charges among the component atoms, and the organic or inorganic chemist interested in the three‐dimensional structure of the molecule interprets the bonds in terms of the geometry of the overlapping orbitals. [1, S. 190]
Zur Organischen Chemie im Chemieunterricht der höheren Schulen Preußens im 19. Jahrhundert
Authors: Brückmann Jutta
Published: December 2002

DIE BEZEICHNUNG „ORGANISCHE CHEMIE”︁ wird zu Beginn des 19. Jahrhunderts erstmals von J. J. Berzelius erwähnt (1806); mit der Umwandlung von Ammoniumcyanat in Harnstoff gelingt F. Wöhler (1828) die Darstellung eines Naturstoffes auf künstlichem Wege. Um 1860 fasst u.a. A. Kekulé die Organische Chemie als Chemie der Kohlenstoffverbindungen nach unserem heutigen Verständnis zusammen. Noch während des gleichen Jahrhunderts entwickelt sie sich zum Hauptwirtschaftszweig der Chemie. Auch auf theoretischem Gebiet übernimmt die Organische Chemie um 1860 durch die Einführung der Wertigkeit und der Strukturformeln die Vorreiterrolle vor der Anorganischen Chemie.
Synaptic density, convergence, and dendritic complexity of prevertebral sympathetic neurons
Authors: Gibbins Ian L. , Teo Ee Hiok , Jobling Phillip , Morris Judy L.
Published: December 2002

Prevertebral sympathetic ganglia contain a unique population of final motor neurons receiving convergent synaptic inputs not only from spinal preganglionic neurons, but also from peripheral intestinofugal neurons projecting from the gut. We used quantitative confocal and ultrastructural immunohistochemistry to determine how this increased synaptic convergence is accommodated by sympathetic final motor neurons in the celiac ganglion of guinea pigs. Terminals of intestinofugal neurons were identified by their immunoreactivity to vasoactive intestinal peptide. Stereologic analyses were based on transects and point counts at confocal and ultrastructural levels. The relative amount of dendritic neuropil in the medial regions of the ganglion was approximately 2.5 times greater than in the lateral regions of the ganglion, consistent with the 2 to 3 times difference in average dendritic field size of neurons in these regions. The total numbers of boutons and synaptic profiles showed significant positive correlations with the relative amount of neuropil in a region. However, the overall density of synaptic boutons was twice as high in the medial region of the ganglion compared with the lateral regions. Because the relative density of preganglionic synapses was similar in each region, this difference was due to the selective projection of intestinofugal inputs to neurons in the medial celiac ganglion, where they provided 45% of synaptic contacts. These results show that, compared with vasoconstrictor neurons, sympathetic neurons regulating gastrointestinal activity support a higher number of convergent inputs in two ways: in addition to having larger dendritic fields, they also have a twofold higher density of synapses. J. Comp. Neurol. 455:285–298, 2003. © 2002 Wiley‐Liss, Inc.
Neuronal development in larval polychaete Phyllodoce maculata (Phyllodocidae)
Authors: Voronezhskaya Elena E. , Tsitrin Eugeni B. , Nezlin Leonid P.
Published: December 2002

The existing view on neuronal development in polychaetes, as undergoing neurogenesis beginning in the rudiments of central ganglia and then extending peripherally, has been contrasted with the latest findings in molluscs, their sister trochozoan group, which show a peripheral to central mode of neurogenesis. The current study addresses this issue by examining early neuronal development in the polychaete Phyllodoce maculata using immunolabeling against acetylated α‐tubulin, serotonin, and the FMRFamide. The first nervous cell was detected 20 hours before hatching, at the early trochophore stage. A solitary serotonergic neuron was located at the posterior‐dorsal extreme of the larva and issued anterior projecting fibers, which outline the future ventral nerve cords and prototroch nerve. Two more serotonergic dorsal peripheral cells and three peripheral FMRFamidergic cells appeared soon thereafter. The fibers of these early cells formed a scaffolding, which prefigured the future adult nervous system (cerebral ganglion, ventral cords, prototroch and esophageal nerve rings) in prehatched trochophores. Shortly before hatching, the larval nervous system developed, including the apical organ, meridianal nerves in the episphere, and posttrochal nerves that innervate the feeding apparatus. After hatching, the rudiments of the adult nervous system started to develop along the paths already established by the earliest peripheral neurons. Thus, the general strategy of neurogenesis in a representative polychaete trochophore appears to resemble that of molluscs. The first neuronal cells to appear are peripheral in origin, located near the posterior margins of the embryo. Their similar anatomical appearance suggests that they share a similar functional role in trochophore development and behavior. J. Comp. Neurol. 455:299–309, 2003. © 2002 Wiley‐Liss, Inc.
Olivocochlear innervation in the mouse: Immunocytochemical maps, crossed versus uncrossed contributions, and transmitter colocalization
Authors: Maison Stéphane F. , Adams Joe C. , Liberman M. Charles
Published: December 2002

To further understand the roles and origins of γ‐aminobutyric acid (GABA) and calcitonin gene‐related peptide (CGRP) in the efferent innervation of the cochlea, we first produced in the mouse an immunocytochemical map of the efferent terminals that contain acetylcholine (ACh), CGRP, and GABA. Olivocochlear (OC) terminals in inner and outer hair cell (IHC and OHC) regions were analyzed quantitatively along the cochlear spiral via light‐microscopic observation of cochlear wholemounts immunostained with antibodies to glutamic acid decarboxylase (GAD), vesicular acetylcholine transporter (VAT), or the peptide CGRP. Further immunochemical characterization was performed in mice with chronic OC transection at the floor of the fourth ventricle to distinguish crossed from uncrossed contributions and, indirectly, the contributions of lateral versus medial components of the OC system. The results in mouse showed that (1) there are prominent GABAergic, cholinergic, and CGRPergic innervations in the OHC and IHC regions, (2) GABA and CGRP are extensively colocalized with ACh in all OC terminals in the IHC and OHC areas, (3) the longitudinal gradient of OC innervation peaks roughly at the 10‐kHz region in the OHC area and is more uniform along the cochlear spiral in the IHC area, (4) in contrast to other mammalian species there is no radial gradient of OC innervation of the OHCs, and (5) all OHC efferent terminals arise from the medial OC system and terminals in the IHC area arise from the lateral OC system. J. Comp. Neurol. 455:406–416, 2003. © 2002 Wiley‐Liss, Inc.
Palmitoyl protein thioesterase 1 is targeted to the axons in neurons
Authors: Ahtiainen Laura , Van Diggelen Otto P. , Jalanko Anu , Kopra Outi
Published: December 2002

Palmitoyl protein thioesterase 1 (PPT1) is a depalmitoylating enzyme whose deficiency leads to infantile neuronal ceroid lipofuscinosis. The disease is characterized by early loss of vision and massive neuronal death. Although PPT1 is expressed in many tissues, a deficiency of PPT1 damages neurons only in the cerebral and cerebellar cortexes and retina; other cell types remain relatively unaffected. We previously demonstrated that PPT1 is present in the synaptosomes and synaptic vesicles of neurons. To understand the crucial role of PPT1 for neuronal cells, we further investigated the expression and targeting of PPT1 in retinal, hippocampal, and cortical neurons during their maturation in culture. We found that PPT1 activity increases by neuronal maturation and is highest in retinal neuron cultures. In retinal neurons the expression of PPT1 precedes that of the synaptic vesicle protein 2 and synaptophysin, indicating a significant role for PPT1 in the early development of neuronal cells. We also found by quantitative confocal immunofluorescence microscopy that PPT1 is targeted preferably to axons in mature neurons, as indicated by its colocalization with the axonal marker microtubule‐associated protein 1. In axons PPT1 is targeted specifically to axonal varicosities and presynaptic terminals, as indicated by its significant colocalization with growth‐associated protein 43 and synaptophysin. Axonal localization of PPT1 was confirmed by double labeling with synaptophysin and postembedding immunoelectron microscopy. The polarized axonal targeting of PPT1 may well indicate a role for PPT1 in the exocytotic pathway of neurons. J. Comp. Neurol. 455:368–377, 2003. © 2002 Wiley‐Liss, Inc.
Temporal and spatial profiles of ABCA2‐expressing oligodendrocytes in the developing rat brain
Authors: Tanaka Yukiko , Yamada Katsuya , Zhou Cheng‐Ji , Ban Nobuhiro , Shioda Seiji , Inagaki Nobuya
Published: December 2002

ABCA2 protein belongs to the ABCA subclass of ATP‐binding cassette (ABC) transporters proposed to exert critical functions in transmembrane transport of endogenous lipids. In this study, we found by immunoblot analyses that approximately 260 kDa of ABCA2 protein is expressed predominantly in oligodendrocytes, and that the expression of the protein is upregulated in the brain during maturation, especially between postnatal days 6 and 19. Parallel to the changes in expression of ABCA2, immunohistochemical analyses showed rapid spatial spread of ABCA2‐immunolabeled oligodendrocytes in the brain during this period. These temporal and spatial changes in ABCA2 expression were in good agreement with findings in myeloarchitectonics reported previously. Further, double immunolabeling with ABCA2 and a major structural protein of myelin, myelin basic protein, demonstrated that onset of ABCA2 expression in oligodendrocytes coincides with the appearance of thick myelin segments immunolabeled with myelin basic protein. Because ABCA2 was abundantly expressed in adult cortex in white matter and gray matter, coexpression of ABCA2 and a marker for the oligodendroglial progenitors NG2 or platelet‐derived growth factor α receptor was investigated. No cells coexpressing ABCA2 and the marker were observed, suggesting that ABCA2 is expressed predominantly in myelin‐forming oligodendrocytes distinct from the adult oligodendroglial progenitors tested. These results suggested a role for ABCA2 in membrane transport of substrates such as the lipids that are closely linked to myelination processes. J. Comp. Neurol. 455:353–367, 2003. © 2002 Wiley‐Liss, Inc.
Developmental changes in the expression of growth hormone‐releasing hormone and pituitary adenylate cyclase‐activating polypeptide in zebrafish
Authors: Krueckl Sandra L. , Fradinger Erica A. , Sherwood Nancy M.
Published: December 2002

Growth hormone‐releasing hormone (GHRH) and pituitary adenylate cyclase‐activating polypeptide (PACAP) are structurally and functionally related members of the glucagon superfamily, a group of hormones important in development, growth, and metabolism. Our objectives were to determine the developmental expression pattern of the ghrh‐pacap1 gene using the zebrafish model. The temporal and spatial expression pattern of the ghrh‐pacap1 gene was examined by RT‐PCR and in situ hybridization. In zebrafish, the ghrh‐pacap1 mRNA transcript was expressed throughout development beginning at the transition between the blastula and gastrula periods. During midgastrulation, alternative splicing resulted in the generation of a novel transcript lacking the cryptic peptide. During the segmentation period, expression was localized to the neural tube, developing eye, and neural crest; strong expression was found in the developing cerebellum. Later in development, expression was localized in the hatching gland and developing pharyngeal arches. The temporal and spatial expression pattern of the ghrh‐pacap1 transcript suggests that these hormones may modulate patterning during development. J. Comp. Neurol. 455:396–405, 2003. © 2002 Wiley‐Liss, Inc.
Saccadic omnipause and burst neurons in monkey and human are ensheathed by perineuronal nets but differ in their expression of calcium‐binding proteins
Authors: Horn Anja K. , Brückner Gert , Härtig Wolfgang , Messoudi Ahmed
Published: December 2002

The extracellular matrix of the brain contains large aggregates of chondroitin sulfate proteoglycans (CSPG), which form lattice‐like cell coatings around distinct neuron populations and are termed perineuronal nets. The function of perineuronal nets is not fully understood, but they are often found around neurons containing the calcium‐binding protein parvalbumin, suggesting a function in primarily highly active neurons. In the present paper the distribution of perineuronal nets was studied in two functional cell groups of the primate oculomotor system with well‐known firing properties: 1) the saccadic omnipause neurons in the nucleus raphe interpositus (RIP) exhibit a high tonic firing rate, which is only interrupted during saccades; they are inhibitory and use glycine as a transmitter; and 2) premotor burst neurons for vertical saccades in the rostral interstitial nucleus of the medial longitudinal fascicle (RiMLF) fire with high‐frequency bursts during saccades; they are excitatory and use glutamate and/or aspartate as a transmitter. In the macaque monkey, both cell populations were identified by their parvalbumin immunoreactivity and were studied for the presence of perineuronal nets using CSPG antibodies or lectin binding with Wisteria floribunda agglutinin. In addition, the expression of another calcium‐binding protein, calretinin, was studied in both cell groups. Double‐ and triple‐immunofluorescence methods revealed that both omnipause and burst neurons are selectively ensheathed with strongly labeled perineuronal nets. Calretinin was coexpressed in at least 70% of the saccadic burst neurons, but not in the omnipause neurons. Parallel staining of human tissue revealed strongly labeled perineuronal nets around the saccadic omnipause and burst neurons, in corresponding brainstem regions, which specifically highlighted these neurons within the poorly structured reticular formation. These findings support the hypothesis that perineuronal nets may provide a specialized microenvironment for highly active neurons to maintain their fast‐spiking activity and are not related to the transmitter or the postsynaptic action of the ensheathed neurons. J. Comp. Neurol. 455:341–352, 2003. © 2002 Wiley‐Liss, Inc.
Fractones and other basal laminae in the hypothalamus
Authors: Mercier Frederic , Kitasako John T. , Hatton Glenn I.
Published: December 2002

The physiological role of basal laminae (BL) and connective tissue (meninges and their projections) in the adult brain is unknown. We recently described novel forms of BL, termed fractones, in the most neurogenic zone of the adult brain, the subependymal layer (SEL) of the lateral ventricle. Here, we investigated the organization of BL throughout the hypothalamus, using confocal and electron microscopy. New types of BL were identified. First, fractones, similar to those found in the lateral ventricle wall, were regularly arranged along the walls of the third ventricle. Fractones consisted of labyrinthine BL projecting from SEL blood vessels to terminate immediately beneath the ependyma. Numerous processes of astrocytes and of microglial cells directly contacted fractones. Second, another form of BL projection, termed anastomotic BL, was found between capillaries in dense capillary beds. The anastomotic BL enclosed extraparenchymal cells that networked with the perivascular cells coursing in the sheaths of adjacent blood vessels. Vimentin immunoreactivity was often detected in the anastomotic BL. In addition, the anastomotic BL overlying macrophages contained numerous fibrils of collagen. We also found that the BL located at the pial surface formed labyrinthine tube‐like structures enclosing numerous fibroblast and astrocyte endfeet, with pouches of collagen fibrils at the interface between the two cell types. We suggest that cytokines and growth factors produced by connective tissue cells might concentrate in BL, where their interactions with extracellular matrix proteins might contribute to their effects on the overlying neural tissue, promoting cytogenesis and morphological changes and participating in neuroendocrine regulation. J. Comp. Neurol. 455:324–340, 2003. © 2002 Wiley‐Liss, Inc.
Somatosensory input to the ventrolateral thalamic region in the macaque monkey: A potential substrate for parkinsonian tremor
Authors: Stepniewska Iwona , Sakai Sharleen T. , Qi Hui‐Xin , Kaas Jon H.
Published: December 2002

In the present study, we determined the anatomic relationships between somatosensory and motor pathways within ventrolateral (VL) thalamic nuclei of the motor thalamus of macaque monkeys. In labeling experiments, four macaque monkeys (Macaca mulatta) received injections of biotinylated dextran amine and wheat germ agglutinin conjugated to horseradish peroxidase into the cerebellar nuclei or internal segment of the globus pallidus and cervical segments of the spinal cord, respectively. Each tracer was visualized in brain sections by sequentially using a different chromogen. Labeled terminals were plotted and superimposed on adjacent brain sections processed for Nissl substance, acetylcholinesterase, and the antigens for calbindin and Cat‐301 to reveal thalamic nuclei. The labeled cerebellar terminals were distributed throughout the posterior VL (VLp), whereas the labeled pallidothalamic terminals were concentrated in the anterior VL and the ventral anterior nucleus. The spinothalamic input was directed mostly to the ventral posterior complex and cells just caudal to it. In addition, the patches of spinothalamic terminations intermingled and partly overlapped with the cerebellothalamic, but not with the pallidothalamic terminations within VLp. The regions of overlap of somatosensory and cerebellar inputs within the VLp of the present study appear to correspond to the reported locations of the tremor‐related cells in parkinsonian patients. Thus, the overlapping spinothalamic and cerebellar inputs may provide a substrate for the altered activity of motor thalamic neurons in such patients. J. Comp. Neurol. 455:378–395, 2003. © 2002 Wiley‐Liss, Inc.
Catecholaminergic innervation of the septum in the frog: A combined immunohistochemical and tract‐tracing study
Authors: Sánchez‐Camacho Cristina , Peña Juan J. , González Agustín
Published: December 2002

In the present study, we have investigated the distribution and the origin of the catecholaminergic innervation of the septal region in the frog Rana perezi. Immunohistochemistry for dopamine and two enzymes required for the synthesis of catecholamines, tyrosine hydroxylase (TH) and dopamine β‐hydroxylase (DBH) revealed a complex pattern of catecholaminergic (CA) innervation in the anuran septum. Dopaminergic fibers were primarily present in the dorsal portion of the lateral septum, whereas noradrenergic (DBH immunoreactive) fibers predominated in the medial septum/diagonal band complex. Catecholaminergic cell bodies were never observed within the septum. To determine the origin of this innervation, applications of dextran amines, both under in vivo and in vitro conditions, into the septum were combined with immunohistochemistry for TH. Results from these experiments demonstrated that four catecholaminergic cell groups project to the septum: (1) the group related to the zona incerta in the ventral thalamus, (2) the posterior tubercle/mesencephalic group, (3) the locus coeruleus, and (4) the nucleus of the solitary tract. While the two first groups provide dopaminergic innervation to the septum, the locus coeruleus provides the major noradrenergic projection. Noradrenergic fibers most likely arise also in the nucleus of the solitary tract. The results obtained in Rana
perezi are readily comparable to those in mammals suggesting that the role of catecholamines in the septum is well conserved through phylogeny and that the CA innervation of the amphibian septum may be involved in functional circuits similar to those in mammals. J. Comp. Neurol. 455:310–323, 2003. © 2002 Wiley‐Liss, Inc.
A Λ‐type neuron model using enhancement‐mode MOSFETs
Authors: Sekine Yoshifumi , Sumiyama Masami , Saeki Katsutoshi , Aihara Kazuyuki
Published: December 2002

Recently, research has been actively pursued to implement a neuron, which is the basic unit for building neural networks, in hardware with engineering applications as the objective. Specifically, pulse‐type hardware neuron models, which approximately replicate pulse signals, have been examined as the information transmission stage in the brain. However, a pulse‐type hardware neuron model is a complex circuit and includes inductors. Consequently, there are few practical models. In this paper, we present the Λ‐type neuron model, which is a pulse‐type hardware neuron model built from only enhancement‐mode MOSFETs (E‐MOSFETs), which can be handled in a standard CMOS process, and capacitors, and is useful as a hardware neuron model intended for large‐scale neural networks. First, we show that a Λ‐type negative resistance circuit having a negative resistance that varies over time can be fabricated from E‐MOSFETs, and explain its principle. Next, we show that this negative resistance circuit can be used to fabricate a Λ‐type neuron model from E‐MOSFETs, which can be handled in a standard CMOS process. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 86(1): 18–25, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10020
Interchip optical interconnection using planar‐type photonic circuit and optoelectronic integrated devices
Authors: Takamori Takeshi , Wada Hiroshi , Sasaki Hironori , Kamijoh Takeshi
Published: December 2002

Electrical interconnection on printed circuit boards and other peripheral technologies cannot keep up with decreasing interconnection dimensions and increasing driving clock speed in LSI technology, so that system performance is degraded. This “I/O bottleneck problem” has been recognized as a serious threat in the near future. Optical interconnection has drawn attention as a breakthrough technology to resolve this problem. The authors have been engaged in development of optical interconnection technologies that are capable of providing high‐speed and large‐capacity bus lines connecting spatially separated LSI chips on a printed circuit board. This paper explains the photonic circuit configuration and element technologies for interchip optical interconnection by means of a planar photonic substrate with diffractive optical devices and LSI chips integrated with optical devices. The experimental results obtained to date are introduced. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 86(1): 9–17, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10024
Large‐tolerant “OptoBump” interface for interchip optical interconnections
Authors: Ishii Yuzo , Arai Yoshimitsu
Published: December 2002

Optical interconnection technology for optical interboard and interchip connections will be an important technology in the next‐generation communication equipment seeking a high‐capacity throughput at the terabit per second level. With the objective of establishing an economical optical packaging technology, we propose an “optical I/O chip package,” which is an optical package for the hybrid integration of optoelectric (O/E) devices and LSI chips that can be mounted on a printed‐circuit board by standard surface mount technology (SMT). In this paper, we propose the OptoBump interface as the optical interconnection between the optical package and the board that connects these two elements by forming the microlens on both and using collimated light. Accommodating the fibers on the board and connecting the connectors become unnecessary because the connections having large beam diameters are able to tolerate offsets in the SMT mounting position. First, we calculated the required collimated beam diameter of 104 µm under the assumption of an SMT accuracy of ±50 µm. Next, we applied ray tracing to estimate the optical losses of the 45° mirror at the polymer optical waveguide facet integrated into the printed‐circuit substrate and clearly exhibited the incident beam conditions with both improved losses and tolerances. And we integrated the polymer microlens into the polymer optical waveguide and the surface‐emitting laser (VCSEL) and experimentally evaluated the optical coupling performance between them. The results verified a 1‐dB tolerance at ±50 µm and demonstrated the effectiveness of this proposal. © 2002 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 86(1): 1–8, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10025