bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of selective tolerance to interleukin‐1β by human chondrocytes in vitro*
Authors: Lee Greta M. , Tioran Marianne E. , Jansen Marilyn , Graff Ronald D. , Kelley Scott S. , Lin Peiyuan 
Published: October 2002

AbstractInterleukin‐1 induces release of NO and PGE2 and production of matrix degrading enzymes in chondrocytes. In osteoarthritis (OA), IL‐1 continually, or episodically, acts on chondrocytes in a paracrine and autocrine manner. Human chondrocytes in chondron pellet culture were treated chronically (up to 14 days) with IL‐1β. Chondrons from OA articular cartilage were cultured for 3 weeks before treatment with IL‐1β (0.05–10 ng/ml) for an additional 2 weeks. Spontaneous release of NO and IL‐1β declined over the pretreatment period. In response to IL‐1β (0.1 ng/ml), NO and PGE2 release was maximal on Day 2 or 3 and then declined to near basal level by Day 14. Synthesis was recovered by addition of 1 ng/ml IL‐1β on Day 11. Expression of inducible nitric oxide synthase (iNOS), detected by immunofluorescence, was elevated on Day 2 and declined through Day 14, which coordinated with the pattern of NO release. On the other hand, IL‐1β‐induced MMP‐13 synthesis was elevated on Day 3, declined on Day 5, and then increased again through Day 14. IL‐1β increased glucose consumption and lactate production throughout the treatment. IL‐1β stimulated proteoglycan degradation in the early days and inhibited proteoglycan synthesis through Day 14. Chondron pellet cultures from non‐OA cartilage released the same amount of NO but produced less PGE2 and MMP‐13 in response to IL‐1β than OA cultures. Like the OA, IL‐1β‐induced NO and PGE2 release decreased over time. In conclusion, with prolonged exposure to IL‐1β, human chondrocytes develop selective tolerance involving NO and PGE2 release but not MMP‐13 production, metabolic activity, or matrix metabolism. © 2002 Wiley‐Liss, Inc.
Structure–activity relationships of heparin‐mimicking compounds in induction of bFGF release from extracellular matrix and inhibition of smooth muscle cell proliferation and heparanase activity
Authors: Benezra Miriam , Ishai‐Michaeli Rivka , Ben‐Sasson Shmuel A. , Vlodavsky Israel 
Published: October 2002

AbstractA series of nine synthetic polyaromatic compounds were synthesized by polymerization of aromatic ring monomers with formaldehyde, which yield substantially ordered backbones with different functional anionic groups (hydroxyl and carboxyl) on the phenol ring. These compounds were tested for their heparin‐mimicking activity: (1) inhibition of heparanase activity; (2) inhibition of SMC proliferation; and (3) release of bFGF from the ECM. We demonstrate that compounds that have two hydroxyl groups para and ortho to the carboxylic group and a carboxylic group at a distance of two carbons from the phenol ring inhibit heparanase activity and SMC proliferation, as well as induced an almost complete release of bFGF from ECM. Addition of a methyl group next to the carboxylic group led to a preferential inhibition of heparanase activity. Similar results were obtained with a compound that contains one hydroxyl group para to the carboxylic group and an ether group near the carboxylic group on the phenol ring. Preferential inhibition of SMC proliferation was best achieved when the position of the hydroxyl group is para and ortho to the carboxylic group and the carboxylic group is at a distance of one carbon from the phenol ring. On the other hand, for maximal release of bFGF from ECM, the position of the carboxylic group should be three carbons away from the phenol ring. These new heparin‐mimicking compounds may have a potential use in inhibition of tumor metastasis, arteriosclerosis, and inflammation. © 2002 Wiley‐Liss, Inc.
Novel insulin/GIP co‐producing cell lines provide unexpected insights into Gut K‐cell function in vivo
Authors: Ramshur Erin B. , Rull Teena R. , Wice Burton M. 
Published: October 2002

AbstractEnteroendocrine (EE) cells represent complex, rare, and diffusely‐distributed intestinal epithelial cells making them difficult to study in vivo. A specific sub‐population of EE cells called Gut K‐cells produces and secretes glucose‐dependent insulinotropic peptide (GIP), a hormone important for glucose homeostasis. The factors that regulate hormone production and secretion, as well as the timing of peptide release, are remarkably similar for K‐cells and islet β‐cells suggesting engineering insulin production by K‐cells is a potential gene therapeutic strategy to treat diabetes. K‐cell lines could be used to study the feasibility of this potential therapy and to understand Gut K‐cell physiology in general. Heterogeneous STC‐1 cells were transfected with a plasmid (pGIP/Neo) encoding neomycin phosphotransferase, driven by the GIP promoter‐only cells in which the GIP promoter was active survived genetic selection. Additional clones expressing pGIP/Neo plus a GIP promoter/insulin transgene were isolated—only doubly transfected cells produced preproinsulin mRNA. Bioactive insulin was stored and then released following stimulation with arginine, peptones, and bombesin—physiological GIP secretagogues. Like K‐cells in vivo, the GIP/insulin‐producing cells express the critical glucose sensing enzyme, glucokinase. However, glucose did not regulate insulin or GIP secretion or mRNA levels. Conversely, glyceraldehyde and methyl‐pyruvate were secretagogues, indicating cells depolarized in response to changes in intracellular metabolite levels. Potassium channel opening drugs and sulphonylureas had little effect on insulin secretion by K‐cells. The K‐cell lines also express relatively low levels of Kir 6.1, Kir 6.2, SUR1, and SUR2 suggesting secretion is independent of KATPchannels. These results provided unexpected insights into K‐cell physiology and our experimental strategy could be easily modified to isolate/characterize additional EE cell populations. © 2002 Wiley‐Liss, Inc.
Response of the donor and recipient cells in mesenchymal cell transplantation to cartilage defect
Authors: Wakitani Shigeyuki , Yamamoto Tetsuya 
Published: October 2002

AbstractTo facilitate the repair of articular cartilage defects, autologous mesenchymal cells from bone marrow or periosteum were transplanted in a rabbit model. Two weeks after the transplantation of the mesenchymal cells, the whole area of the original defect was occupied by cartilage. From the deep area of the reparative cartilage, which contacted with host bone, chondrocytes became hypertrophic and the invasion of bone with vasculature started, until the replacement reached the natural junction of the host cartilage and the subchondral bone about 4 weeks after transplantation. Twelve weeks after the transplantation, the repair cartilage in the defect became a little thinner than the adjacent normal cartilage, which became a little thinner 24 weeks after the transplantation (the longest observation period in the study). Large, full‐thickness defects of the weight‐bearing region of the articular cartilage were repaired with hyaline‐like cartilage after implantation of autologous mesenchymal cells. The repair process by mesenchymal cell transplantation was explained as follows: The donor transplanted cell differentiated into cartilage and the defects were completely filled with cartilage. Then, mesenchymal cells that entered the chondrogenic lineage rapidly progressed through this lineage to the hypertrophic state, which was then the target for erosion and vascular invasion. Although this vasculature and the newly formed bone were considered to be host‐derived, there was no evidence to that effect. To prove this, suitable experimental marking of these donor cells is needed. In the case of chondrocyte transplantation, the repair cartilage maintained its thickness to the full depth of the original defect; the tissue derived from the implanted chondrocytes was not invaded by vessels or replaced by subchondral bone. Microsc. Res. Tech. 58:14–18, 2002. © 2002 Wiley‐Liss, Inc.
Odor discrimination by G protein‐coupled olfactory receptors
Authors: Touhara Kazushige 
Published: October 2002

AbstractThe vertebrate olfactory system possesses a remarkable capacity to recognize and discriminate a variety of odorants by sending the coding information from peripheral olfactory sensory neurons in the olfactory epithelium to the olfactory bulb of the brain. The recognition of odorants appear to be mediated by a G protein‐coupled receptor superfamily that consists of ∼1% of total genes in vertebrates. Since the first discovery of the olfactory receptor gene superfamily in the rat, similar chemosensory receptors have been found in various species across different phyla. The functions of these receptors, however, had been uncharacterized until the recently successful functional expression and ligand screening of some olfactory receptors in various cell expression systems. The functional cloning of odorant receptors from single olfactory neurons allowed for the identification of multiple receptors that recognized a particular odorant of interest. Reconstitution of the odorant responses demonstrated that odorant receptors recognized various structurally‐related odorant molecules with a specific molecular receptive range, and that odor discrimination is established based on a combinatorial receptor code model in which the identities of different odorants are encoded by a combination of odorant receptors. The receptor code for an odorant changes at different odorant concentrations, consistent with our experience that perceived quality of an odorant changes at different concentrations. The molecular bases of odor discrimination at the level of olfactory receptors appear to correlate well with the receptive field in the olfactory bulb where the input signal is further processed to create the specific odor maps. Microsc. Res. Tech. 58:135–141, 2002. © 2002 Wiley‐Liss, Inc.
Impulse conduction of olfactory receptor neuron axons
Authors: Phillips Shayne , Griff Edwin R. 
Published: October 2002

AbstractCompound action potentials were recorded from rat olfactory receptor neuron axons at measured distances from the stimulation electrode along the lateral surface of the main olfactory bulb. Distances were plotted as a function of the latencies measured from stimulus onset to the prominent negative trough of the triphasic compound action potential. A straight line was fitted to these data to calculate impulse conduction velocity, 0.42 ± 0.01 m/s (n = 25). Two procedures were used to investigate whether those axons that project to caudal regions of the bulb had faster conduction velocities than axons projecting to rostral bulb. First, the stimulating electrode was moved to mid‐bulb and the recording electrode was placed on the caudal bulb. Alternatively, axons were stimulated antidromically at the caudal bulb. These two procedures stimulate those axons projecting to caudal bulb and bypass olfactory receptor neuron axons that synapse in the rostral bulb. The mean impulse conduction velocities from these caudal and antidromic recordings were 0.58 ± 0.19 m/s (n = 8) and 0.57 ± 0.19 m/s (n = 9), respectively. Though both of these means are higher than the impulse conduction velocity calculated for stimulation at the rostral bulb, the differences were not statistically significant. Microsc. Res. Tech. 58:161–167, 2002. © 2002 Wiley‐Liss, Inc.
Grouping and representation of odorant receptors in domains of the olfactory bulb sensory map
Authors: Nagao Hiroshi , Yamaguchi Masahiro , Takahash Yuji , Mori Kensaku 
Published: October 2002

AbstractIndividual glomeruli in the mammalian main olfactory bulb represent a single or at most a few types of odorant receptors. Thus the physical arrangement of glomeruli at the surface of the olfactory bulb can be viewed as a sensory map representing ∼1,000 types of odorant receptors. This review summarizes the recent advance of the knowledge regarding the spatial organization of the sensory map in the main olfactory bulb. Recent studies show that individual olfactory bulbs contain dual sensory maps, one in the lateral hemisphere and the other in the medial hemisphere of the bulb. The tracings of selective subsets of olfactory axons to their target glomeruli in the olfactory bulb show that glomeruli are parceled into large zones or bands. The spatial arrangement of these zones and bands are stereotypical and conserved across individual mice. Optical imaging studies show that glomeruli in the most rostrodosal zone, zone I, are further parceled into smaller functional domains, and suggest that odorant receptors having a common or similar molecular feature receptive site are grouped together and represented by glomeruli within the functional domain. The possible relation between the functional domain organization and the subjectively perceived odor quality (olfactory submodality) is reviewed. Microsc. Res. Tech. 58:168–175, 2002. © 2002 Wiley‐Liss, Inc.
Pentadactyl pattern of the avian wing autopodium and pyramid reduction hypothesis
Authors: KundráT Martin , Seichert Václav , Russell Anthony P. , Smetana Karel 
Published: October 2002

AbstractWe report herein that a pentadactyl developmental pattern is evident in early wing morphogenesis of Gallus (chicken) and Struthio (ostrich). Five avascular zones (spatially predestined locations of contiguous metacarpal and phalangeal aggregation) and four interdigital vascular spaces are established by the regression patterns of autopodial vasculature. Transient vestiges of the first and fifth metacarpals are confirmed histologically and histochemically. They lie within the preaxial‐most and postaxial‐most avascular zones, respectively. These observations reveal conservative patterning of the avian hand and corroborate a II‐III‐IV metacarpal interpretation, argue for II‐III‐IV identity of ossified digits in birds, and favour a simple reduction rather than a homeotic shift in terms of the phenotype expressed by Hox genes in the phylogeny of the avian manus. We suggest that gradual, bilateral reduction of phalanges and metacarpals, via apoptosis mediated by BMP, occurred during the evolution of birds (Pyramid Reduction Hypothesis). This is congruent with the establishment of a central wing axis that became co‐opted for coordinated movements. On the basis of evidence presented here, the direct avian ancestor is predicted to have been five‐fingered with dominant digits (+ metacarpals) as follow: II, III, IV. J. Exp. Zool. (Mol. Dev. Evol.) 294:152–159, 2002. © 2002 Wiley‐Liss, Inc.
Neonatal rotavirus infection in Belém, Northern Brazil: Nosocomial transmission of a P[6] G2 strain
Authors: Linhares Alexandre C. , Mascarenhas Joana D'Arc P. , Gusmão Rosa Helena P. , Gabbay Yvone B. , Fialho Alexandre M. , Leite José Paulo G. 
Published: October 2002

AbstractA total of 614 fecal specimens were obtained during a survey for rotavirus infection conducted between May 1996 and May 1998 among 437 newborns admitted to special care nurseries at a public hospital in the urban area of Belém, Brazil. Routine stool samples were taken weekly from all babies up to the age of 28 days. Overall, 51 (11.7%) of the neonates excreted rotaviruses while in hospital, of whom 42 (82.3%) developed asymptomatic nosocomial infection; nosocomial infection was also proved in five of the nine patients with diarrhea. Three distinct RNA profiles were detected, of which one short electropherotyping pattern was far more frequent (≃90% of the strains). Using monoclonal antibody‐based enzyme immunoassays, 32 (62.7%) of the rotavirus‐positive strains were classified as G2, and 1 (1.9%) as mixed G1 and G2. A G serotype could not be assigned to 18 (35.3%) of the isolates. A reverse transcription‐polymerase chain reaction was used for determining the VP4 type‐specificity of a subset of 28 rotavirus‐positive samples. Characterization of the VP7‐genotype specificity was also sought for 18 of these latter strains. Overall, P[6] and G2 genotypes were identified in 93% and 94% of tested samples respectively, with results being further confirmed by Southern hybridization. Although surveillance was conducted during a 25‐month period, 50 (98%) of 51 rotavirus isolates clustered between January and December 1997. The earliest [P6]G2 rotavirus infections were detected by late January 1997, involving two (13‐ and 14‐day‐old) babies admitted with acute diarrhea. Thereafter, strains bearing these genotype specificities were identified among five infants with hospital‐acquired gastroenteritis, followed by 16 others who were infected asymptomatically. This is the first report from Brazil describing nosocomial transmission of P[6]G2 rotavirus strains among neonates. J. Med. Virol. 67:418–426, 2002. © 2002 Wiley‐Liss, Inc.
Molecular analysis of measles virus genome derived from SSPE and acute measles patients in Papua, New Guinea
Authors: Miki Kenji , Komase Katsuhiro , Mgone Charles S. , Kawanishi Ryuta , Iijima Masumi , Mgone Joyce M. , Asuo Peter G. , Alpers Michael P. , Takasu Toshiaki , Mizutani Tomohiko 
Published: October 2002

AbstractA very high annual incidence of 56 per million population below the age of 20 years for subacute sclerosing panencephalitis (SSPE) has been reported from Papua New Guinea (PNG). In a more recent study, we have confirmed this unusual high incidence for Eastern Highlands Province (EHP) of PNG. In the study, it was observed that the vaccination rate among SSPE patients registered at Goroka Base General Hospital (GBGH) in EHP was higher than that of other infants in the province in recent years. To identify the measles virus (MV) responsible for SSPE in EHP, sequence analysis of hypervariable region of the N gene was performed from 13 MV genomes: 2 amplified from clinical specimens of SSPE patients and 11 from acute measles patients. In 2 cases among the 11 with acute measles, nucleotide sequence of the entire H gene derived from isolated viruses was determined. Both nucleotide sequence and phylogenetic tree analyses showed that the amplified MV cDNAs were closely related to one another and belonged to the D3 genotype though they were different from any previously reported MV sequences. No genome sequences of vaccine strains were detected. These findings suggest that the MV strains prevailing in the highlands of PNG belong to genotype D3 of the MV and this wild‐type MV rather than the vaccine strains was likely to be responsible for SSPE in these patients. J. Med. Virol. 68:105–112, 2002. © 2002 Wiley‐Liss, Inc.
Transient CD4/CD8 ratio inversion and aberrant immune activation during dengue virus infection
Authors: Liu Ching‐Chuan , Huang Kao‐Jean , Lin Yee‐Shin , Yeh Trai‐Ming , Liu Hsiao‐Sheng , Lei Huan‐Yao 
Published: October 2002

AbstractThe immune status after dengue virus infection was studied in dengue patients from an outbreak of serotype 3 dengue virus infection in the southern part of Taiwan during November and December 1998. Consecutive blood samples from 29 dengue patients, of whom 21 had dengue fever and 8 had dengue hemorrhagic fever/dengue shock syndrome, were collected, and the immunophenotypes of the peripheral blood mononuclear cells were determined by flow cytometry. The early activation marker CD69 appeared on lymphocytes and monocytes at day 4 after the onset of fever, and declined afterward. However, a transient reverse in the CD4/CD8 ratio occurred at days 6–10 after the onset of fever. The CD4/CD8 ratio inversion was manifested in 10 of 29 dengue patients and was encountered more frequently in dengue hemorrhagic fever/dengue shock syndrome than in dengue fever patients. Analysis of the clinical blood cell count of these 10 cases showed that increase of immature neutrophils developed at fever days 5–6, CD4dim or CD8dim monocytosis at days 6–7, and atypical lymphocytosis at days 8–10 after the onset of fever. Serum IL‐6 was found at either day 7 or day 9–11. The PHA‐stimulated T‐cell response was depressed as well. These changes in immune parameters indicate aberrant immune activation during dengue virus infection and might be involved in the pathogenesis of dengue virus infection. J. Med. Virol. 68: 241–252, 2002. © 2002 Wiley‐Liss, Inc.
Attenuated plasticity in neurons and astrocytes in the mouse model of Sanfilippo syndrome type B
Authors: Li Hong Hua , Zhao Hui‐Zhi , Neufeld Elizabeth F. , Cai Yan , Gómez‐Pinilla Fernando 
Published: October 2002

AbstractSanfilippo syndrome type B (MPS III B) is a neurodegenerative disorder characterized by profound mental retardation and early death. It is caused by deficiency of a lysosomal enzyme involved in heparan sulfate (HS) degradation. Because HS accumulation can be a major feature of this disease, we have examined crucial molecular systems associated with HS function. Using a knockout mouse with disruption of the gene responsible for HS degradation, we evaluated the effects of possible HS accumulation on neuroplasticity that are within the spectrum of action of fibroblast growth factors (FGFs) and their receptor (FGFR). We found that levels of mRNA for the FGFR‐1 were attenuated in the mutant mice by the age of 6 months, whereas the mRNAs for FGF‐1 and FGF‐2 were reduced or unchanged in the brain regions tested. Neurogenesis, in which FGF‐2 is involved, was inhibited in the MPS III B mouse brain at both young and adult ages. We also examined the expression of the glial fibrillary acidic protein (GFAP) gene and GFAP‐positive cell density in both normal and injured conditions to study the functional response of astrocytes to insult. We found that, although the mutation alone caused drastic induction of reactive astrocytes, acute injury to the mutant brains failed to induce additional reactive astrocytes. Our results showed important alterations in the expression of several genes involved in the maintenance of neuroplasticity in the MPS III B. This in turn may result in reduction of neuronal health and brain function. © 2002 Wiley‐Liss, Inc.
Transgenic expression of the protein‐L‐isoaspartyl methyltransferase (PIMT) gene in the brain rescues mice from the fatal epilepsy of PIMT deficiency
Authors: Shimizu Takahiko , Ikegami Takashi , Ogawara Midori , Suzuki Yo‐ichi , Takahashi Mayumi , Morio Hidenori , Shirasawa Takuji 
Published: October 2002

AbstractProtein‐L‐isoaspartyl methyltransfearase (PIMT) plays a physiological role in the repair of damaged proteins containing isoaspartyl residues. In previous studies, we showed that PIMT‐deficient mice developed a fatal epileptic seizure associated with the accumulation of damaged proteins in the brain. The mutant mice also showed a neurodegenerative pathology in hippocampi and impaired spatial memory. Still undefined, however, is how the accumulation of isoaspartates leads to the death of PIMT‐deficient mice. In the present study, we generated PIMT transgenic (Tg) mice to investigate whether the exogenous expression of PIMT could improve the symptoms associated with PIMT deficiency. Rescue experiments showed that Tg expression of PIMT driven by a prion promoter effectively cured the PIMT‐deficient mice. Biochemically, a higher expression level of transgene led to the effective repair of damaged proteins in vivo. Although a lower level of expression caused an accumulation of damaged proteins in a partially rescued line, the mice survived. Interestingly, synapsin I, which was extensively modified posttranslationally in PIMT‐deficient mice, was specifically repaired in a partially rescued, but symptom‐improved, Tg line. Our results suggest that an overall accumulation of damaged proteins does not necessarily lead to a fatal epileptic seizure, whereas certain modifications, such as changes in synapsin I, may play a pivotal pathological role in epilepsy. © 2002 Wiley‐Liss, Inc.