bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional replacement of oxygen by other oxidants in articular cartilage
Authors: Lee Robert B. , Urban Jill P. G. 
Published: December 2002

AbstractObjectiveArticular cartilage chondrocytes consume remarkably little O2 in comparison with most other animal cells; glycolysis forms the principal source of ATP in this cartilage. Although not lethal for many days, imposition of anoxia immediately lowers intracellular ATP, inhibits rates of glycolysis, and prevents articular chondrocytes from producing extracellular matrix macromolecules. This study was undertaken to investigate the role of O2 in articular chondrocyte metabolism.MethodsWe examined the effects of oxygen and of several other classes of exogenous oxidants, i.e., 1) the dyes methylene blue and 2,6‐dichlorophenol‐indophenol, 2) the iron (III) complex ferricyanide, and 3) the keto‐acids oxaloacetate and pyruvate (and phosphoenolpyruvate, a metabolic precursor of pyruvate), on rates of glycolysis and of sulfate incorporation by bovine articular cartilage in vitro.ResultsLactate production was lowest under conditions of anoxia and was stimulated severalfold by addition of O2 (air‐saturated medium). Under strict anoxia, other oxidants restored lactate production to rates at least comparable with those seen in aerobic controls; under aerobic conditions, they had little effect. Oxygen and all of the other oxidants examined stimulated sulfate incorporation more strongly than lactate production. The compounds that promoted glycolysis and hence sulfate incorporation in cartilage under anoxia were themselves reduced; that is, they functioned as oxidants in lieu of O2.ConclusionFor normal function, articular cartilage appears to require exogenous oxidants to stimulate glycolysis and produce ATP and extracellular matrix. Under physiologic conditions, oxygen acts as this oxidant, but its role can be adequately assumed by other agents.
Peptide‐induced suppression of collagen‐induced arthritis in HLA–DR1 transgenic mice
Authors: Myers Linda K. , Sakurai Yoshihiko , Tang B. , He Xiaowen , Rosloniec Edward F. , Stuart John M. , Kang Andrew H. 
Published: December 2002

AbstractObjectiveTo identify peptides capable of altering the immune response to type II collagen (CII) in the context of HLA–DR.MethodsImmunizing mice transgenic for the human HLA–DRB1*0101 immune response gene with CII elicits an arthritis (collagen‐induced arthritis [CIA]) that resembles rheumatoid arthritis. We have previously identified an immunodominant determinant of CII, CII (263–270), recognized by T cells in the context of DR1. To produce synthetic peptides with the potential of disrupting the DR1‐restricted immune response, synthetic analog peptides were developed that contain site‐directed substitutions in critical positions. These peptides were used to treat CIA in DR1 transgenic mice.ResultsAn analog peptide, CII (256–276, N263, D266), that inhibited T cell responses in vitro, was identified. When DR1 mice were coimmunized with CII and CII (256–276, N263, D266), the incidence and severity of arthritis were greatly reduced, as was the antibody response to CII. Moreover, CII (256–276, N263, D266) was effective in down‐regulating the immune responses to CII and arthritis, even when administered 2 weeks following immunization with CII. Spleen and lymph node cells from CII‐immunized mice cultured with CII (256–276, N263, D266) in vitro produced increased amounts of interleukin‐4 (IL‐4) compared with cells cultured with the wild‐type peptide, CII (256–276). Furthermore, CII (256–276, N263, D266) was incapable of preventing arthritis in DR1 IL‐4−/− mice (genetically deficient in IL‐4).ConclusionThese data establish that CII (256–276, N263, D266) is a potent suppressor of the DR‐mediated immune response to CII. Its effect is mediated, at least in part, by IL‐4. These experiments represent the first description of an analog peptide of CII recognized by T cells in the context of a human major histocompatibility complex molecule that can suppress autoimmune arthritis.
De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal‐onset multisystem inflammatory disease (NOMID): A new member of the expanding family of pyrin‐associated autoinflammatory diseases
Authors: Aksentijevich Ivona , Nowak Miroslawa , Mallah Mustapha , Chae Jae Jin , Watford Wendy T. , Hofmann Sigrun R. , Stein Leonard , Russo Ricardo , Goldsmith Donald , Dent Peter , Rosenberg Helene F. , Austin Frances , Remmers Elaine F. , Balow James E. , Rosenzweig Sergio , Komarow Hirsh , Shoham Nitza G. , Wood Geryl , Jones Janet , Mangra Nadira , Carrero Hector , Adams Barbara S. , Moore Terry L. , Schikler Kenneth , Hoffman Hal , Lovell Daniel J. , Lipnick Robert , Barron Karyl , O'Shea John J. , Kastner Daniel L. , Goldbach‐Mansky Raphaela 
Published: December 2002

AbstractObjectiveNeonatal‐onset multisystem inflammatory disease (NOMID; also known as chronic infantile neurologic, cutaneous, articular [CINCA] syndrome) is characterized by fever, chronic meningitis, uveitis, sensorineural hearing loss, urticarial skin rash, and a characteristic deforming arthropathy. We investigated whether patients with this disorder have mutations in CIAS1, the gene which causes Muckle‐Wells syndrome and familial cold autoinflammatory syndrome, two dominantly inherited disorders with some similarities to NOMID/CINCA syndrome.MethodsGenomic DNA from 13 patients with classic manifestations of NOMID/CINCA syndrome and their available parents was screened for CIAS1 mutations by automated DNA sequencing. Cytokine messenger RNA (mRNA) levels were assessed by real‐time polymerase chain reaction on peripheral blood leukocyte mRNA, and serum cytokine levels were assayed by enzyme‐linked immunosorbent assay. Protein expression was assessed by Western blotting of lysates from plastic‐adherent peripheral blood mononuclear cells.ResultsIn 6 of the 13 patients, we found 6 heterozygous missense substitutions in CIAS1. Five of the 6 mutations are novel. None of these sequence changes was observed in a panel of >900 chromosomes from healthy controls. Two distinct nucleotide changes in a single codon in unrelated patients resulted in the same amino acid change. In 4 mutation‐positive children whose parental DNA was available, no mutation was found in the parental DNA, supporting the conclusion that the mutations arose de novo. Consistent with the recently discovered role of CIAS1 in the regulation of interleukin‐1 (IL‐1), we found evidence of increased IL‐1β, as well as tumor necrosis factor, IL‐3, IL‐5, and IL‐6, but not transforming growth factor β, in a mutation‐positive patient compared with normal controls.ConclusionOur data increase the total number of known germline mutations in CIAS1 to 20, causing a spectrum of diseases ranging from familial cold autoinflammatory syndrome to Muckle‐Wells syndrome to NOMID/CINCA syndrome. Mutations in CIAS1 were only found in ∼50% of the cases identified clinically as NOMID/CINCA syndrome, which raises the possibility of genetic heterogeneity. IL‐1 regulation by CIAS1 suggests that IL‐1 receptor blockade may constitute a rational approach to the treatment of NOMID/CINCA syndrome.
Expression of matrix metalloproteinases in articular cartilage of temporomandibular and knee joints of mice during growth, maturation, and aging
Authors: Gepstein Amira , Shapiro Sarah , Arbel Gil , Lahat Nitza , Livne Erella 
Published: December 2002

AbstractObjectiveThis study examined the involvement of different matrix metalloproteinases (MMPs) in articular cartilage in the process of growth, maturation, and aging of mice, and compared the temporal changes in the expression of MMPs between temporomandibular joints (TMJ) and knee joints.MethodsHomogenates of intact tibial plateau, femoral condyle, and TMJ condyle cartilages from animals of different ages were assessed for gelatinase (MMP‐2 and MMP‐9) activity by zymography. The messenger RNA (mRNA) expression of MMPs 1, 2, 3, 9, and 13 in tibial plateau cartilage was determined by semiquantitative reverse transcription–polymerase chain reaction, and immunohistochemistry was used to localize MMPs 2, 3, 9, and 13 in the knee joints and TMJ from mice of different ages.ResultsThe pattern of gelatinase (MMP‐2 and MMP‐9) activity and their protein expression as well as that of MMPs 3 and 13 varied with the age of the mouse, and differences in expression were observed between the knee and TMJ cartilage. The expression of mRNA for the MMPs in the tibial plateau was also age related.ConclusionThis study demonstrated changes in the protein and mRNA expression of MMPs 2, 9, 3, and 13 during growth, maturation, and aging in mice. The temporal changes were characteristic of the joint, and distinct differences were observed between the TMJ and knee cartilage. The differences in temporospatial expression of MMPs between the knee joint and TMJ may be the result of differences in load and function of these joints. The information provided in this study contributes to a better understanding of the role of these MMPs in the maintenance and integrity of cartilage tissue.
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

AbstractObjectiveSelective 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).MethodsRASFs 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.ResultsCelecoxib 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.ConclusionCelecoxib 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

AbstractObjectiveThere 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.MethodsFluorescence 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.ResultsPutative 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.ConclusionThis 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

AbstractObjectiveThe 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.MethodsA 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.ResultsThe 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.ConclusionThe 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

AbstractUsing 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

AbstractSeveral 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

AbstractAbsorbance 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

AbstractWith 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

AbstractNine 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

AbstractThe 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.