bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitric oxide synthase I mediates osteoclast activity in vitro and in vivo
Authors: Jung Jae Y. , Lin Aaron C. , Ramos Lisette M. , Faddis Brian T. , Chole Richard A. 
Published: May 2003

AbstractBone resorption is responsible for the morbidity associated with a number of inflammatory diseases such as rheumatoid arthritis, orthopedic implant osteolysis, periodontitis and aural cholesteatoma. Previous studies have established nitric oxide (NO) as a potentially important mediator of bone resorption. NO is a unique intercellular and intracellular signaling molecule involved in many physiologic and pathologic pathways. NO is generated from L‐arginine by the enzyme nitric oxide synthase (NOS). There are three known isoforms of NOS with distinct cellular distributions. In this study, we have used mice with targeted deletions in each of these isoforms to establish a role for these enzymes in the regulation of bone resorption in vivo and in vitro. In a murine model of particle induced osteolysis, NOS I‐/‐ mice demonstrated a significantly reduced osteoclast response. In vitro, osteoclasts derived from NOS I‐/‐ mice were larger than wild type controls but demonstrated decreased resorption. Although NOS I has been demonstrated in osteoblasts and osteocytes as a mediator of adaptive bone remodeling, it has not previously been identified in osteoclasts. These results demonstrate a critical role for NOS I in inflammatory bone resorption and osteoclast function in vitro. © 2003 Wiley‐Liss, Inc.
Expression of genes for certain enzymes of pyrimidine and purine salvage pathway in peripheral blood leukocytes collected from patients with Graves' or Hashimoto's disease
Authors: Karbownik Małgorzata , Brzeziańska Ewa , Zasada Krzysztof , Lewiński Andrzej 
Published: May 2003

AbstractIncreased activities of some enzymes, which participate in pyrimidine and purine salvage pathway, were found in blood fractions of patients suffering from different autoimmunological diseases, thyroid diseases included. The aim of the study was to estimate the expression of genes, specific for deoxycytidine kinase (dCK, EC 3.7.1.74), thymidine kinase 1 (TK1; EC 2.7.1.21), and adenosine deaminase (ADA, EC 3.5.4.4) in blood leukocytes, collected from patients with autoimmunological thyroid diseases (AITD), i.e., Graves' or Hashimoto's disease. The total mRNA was isolated from peripheral blood leukocytes and, afterwards, submitted to reverse transcription (RT), with the following amplification of genes encoding for particular examined enzymes and β‐actin, as a supervisory gene [RT‐polymerase chain reaction (RT‐PCR)]; ADA gene was amplified with the use of three different primer pairs (ADA3, ADA4, and ADA5). PCR products were electrophoresed in 8% polyacrylamide gel and then, submitted to densitometric analysis. The levels of expression of all the examined genes in leukocytes from patients with either Graves' or Hashimoto's disease were significantly increased when compared to those in controls; above a twofold elevation of expression of TK1, ADA4, and ADA5 genes was observed. In conclusion, the changes of activities of salvage enzymes in patients with AITD occur likely at transcription level; the measurement of gene expression for purine and pyrimidyne salvage enzymes may likely help explain the mechanism of autoimmune diseases, being also significant in the diagnostics and/or monitoring of AITD. J. Cell. Biochem. 89: 550–555, 2003. © 2003 Wiley‐Liss, Inc.
Fatal toxicity following radio‐ and chemotherapy of medulloblastoma in a child with unrecognized Nijmegen Breakage Syndrome
Authors: Distel Luitpold , Neubauer Susann , Varon Raymonda , Holter Wolfgang , Grabenbauer Gerhard 
Published: May 2003

AbstractBackgroundIn large‐scale pediatric chemo‐ and radiotherapy trials a proportion of patients as high as 10–15% is usually reported as having severe treatment related toxicity occasionally resulting in toxic death. Little is known on the underlying predisposition of the individual child. Several hereditary disorders including immunodeficiency (ID) syndromes or repair disorders, Ataxia Telangiectasia (AT), and Nijmegen breakage syndrome (NBS) were associated with an elevated risk for severe treatment related toxicity.ProcedureThis report involves the case of a 7‐year‐old boy with medulloblastoma who suffered from remarkably severe side effects during and after postoperative radio‐ and chemotherapy. Several months following craniospinal radiation with a total dose of 36 Gy, late normal tissue side effects were observed within the treated volume. Eighteen months after initiation of treatment the patient died due to protracted cardiopulmonary failure.ResultsTo quantify the intrinsic radiation sensitivity, lymphoblastoid cells were used to examine chromosomal aberrations by fluorescence in situ hybridization detecting between two to ninefold higher chromosomal breakage rates in comparison to cells of average cancer patients. Skin fibroblasts showed in the clonogenic survival assays a twofold increased sensitivity. Western blotting demonstrated a typical lack of Nbs1. PCR‐SSCP analysis followed by direct sequencing of positive samples revealed a homozygous truncating mutation of the NBS1 gene (657del5).ConclusionsThis case highlights that severe treatment related complications in pediatric cancer patients may be the result of increased intrinsic radio‐ and chemosensitivity due to NBS, AT, and other ID syndromes. It is suggested to exclude such conditions in all patients with anthropometric parameters below the 3rd centile and other signs suggestive for repair disorders or ID syndromes. Med Pediatr Oncol 2003;41:44–48. © 2003 Wiley‐Liss, Inc.
The role of mRNA 5′‐noncoding and 3′‐end sequences on 40S ribosomal subunit recruitment, and how RNA viruses successfully compete with cellular mRNAs to ensure their own protein synthesis
Authors: Kean Katherine M. 
Published: May 2003

AbstractSince the elaboration of the scanning model to explain eukaryotic translation initiation, alternative hypotheses have gained support. Cap and 5′ end‐independent recruitment of the 40S ribosomal subunit conferred by the presence of an internal ribosome entry segment (IRES) in the 5′UTR of the mRNA is widely accepted, and has been formally and definitively proven for a picornavirus. However, the mechanism of IRES function remains essentially a black box. Using the complex viral IRESes as model systems, approaches taken to shed light on the mystery include systematic comparisons and molecular genetic analyses. The hypothesis that actively translated mRNAs are circular, rather than linear, molecules is based on rather indirect evidence. This model has invoked a revision of the image of 40S ribosomal subunit recruitment, to include recycling from the mRNA 3′‐ to the 5′‐end in addition to true de novo 5′‐end directed entry. Biochemical and genetic studies are used to define the network of interactions necessary for efficient ribosome recruitment. This has lent weight to the concept of mRNA 5′–3′ cross‐talk and clarified the mechanics of how this enhances translation efficiency. These refinements and revisions to the model of translation initiation form the core of this review, with current knowledge being considered from the perspective on how host‐cell translation could yield to selective viral translation via the phenomenon of translational shut‐off.
Generation of protein isoform diversity by alternative initiation of translation at non‐AUG codons
Authors: Touriol Christian , Bornes Stéphanie , Bonnal Sophie , Audigier Sylvie , Prats Hervé , Prats Anne‐Catherine , Vagner Stéphan 
Published: May 2003

AbstractThe use of several translation initiation codons in a single mRNA, by expressing several proteins from a single gene, contributes to the generation of protein diversity. A small, yet growing, number of mammalian mRNAs initiate translation from a non‐AUG codon, in addition to initiating at a downstream in‐frame AUG codon. Translation initiation on such mRNAs results in the synthesis of proteins harbouring different amino terminal domains potentially conferring on these isoforms distinct functions. Use of non‐AUG codons appears to be governed by several features, including the sequence context and the secondary structure surrounding the codon. Selection of the downstream initiation codon can occur by leaky scanning of the 43S ribosomal subunit, internal entry of ribosome or ribosomal shunting. The biological significance of non‐AUG alternative initiation is demonstrated by the different subcellular localisations and/or distinct biological functions of the isoforms translated from the single mRNA as illustrated by the two main angiogenic factor genes encoding the fibroblast growth factor 2 (FGF2) and the vascular endothelial growth factor (VEGF). Consequently, the regulation of alternative initiation of translation might have a crucial role for the biological function of the gene product.
The puzzling lateral flexible stalk of the ribosome
Authors: Gonzalo Philippe , Reboud Jean‐Paul 
Published: May 2003

AbstractThe lateral flexible stalk of the large ribosomal subunit is made of several interacting proteins anchored to a conserved region of the 28S (26S) rRNA termed the GTPase‐associated domain or thiostrepton loop. This structure is demonstrated to adopt puzzling changes of conformation following the different steps of the elongation cycle. Some of these proteins termed the P‐proteins in eukaryotes and L10 and L7/L12 in bacteria, present little structural similarities between Eubacteria on one side and Archae and Eukaryotes on the other side. However, up to now, these proteins seem to present a similar macromolecular organisation and they have been involved in the same functions. Convincing evidence attests that these proteins participate in elongation factor binding to the ribosome, and it has been suggested that these proteins might be evolved in a GTP hydrolysis activating protein activity. Involvement of these proteins in the translational mechanism is discussed. Moreover, in eukaryotes, small P‐proteins are also found as isolated proteins in a cytoplasmic pool that exchanges with the ribosome‐associated P‐proteins. Moreover, a part of the ribosomal proteins is phosphorylated (hence their P‐protein names). The biological signification of these particularities is discussed.
East of EDEN was a poly(A) tail
Authors: Paillard Luc , Osborne H. Beverley 
Published: May 2003

AbstractPost‐transcriptional regulations of gene expression (control of mRNA stability and translation) play a central role in achieving cellular functions. In a large number of cases, post‐transcriptional regulations are dependent on mRNA poly(A) tails, as mRNAs with a long poly(A) tail are generally much more stable and actively translated than deadenylated mRNAs. In this review, we will discuss the activities that modify poly(A) tail lengths in Xenopus oocytes and embryos. We will particularly focus on one activity, the “EDEN” mechanism, that provokes specific poly(A) tail shortening rapidly after fertilization. EDEN‐dependent deadenylation is mediated by the specific binding of a protein, EDEN‐BP. The EDEN mechanism will be compared with several other mechanisms that provoke deadenylation in a large variety of species. The proposal that the EDEN mechanism is probably a mechanism of widespread importance in the metazoan world will be discussed.
Transaction cost framework in operations and supply chain management research: theory and measurement
Authors: Grover Varun , Malhotra Manoj K. 
Published: May 2003

AbstractOver the past decade, transaction cost theory (TCT) has received considerable attention from researchers in various disciplines of business. Unfortunately, the rich theoretical base of TCT has seen limited application in the operations and supply chain management research. This article seeks to change that by providing a cogent synthesis of TCT, its assumptions, constructs, and propositions. It also summarizes existing empirical work in management and other disciplines that draws from the TCT perspective and examines relationships in manufacturing organizations. A measurement model of transaction costs is subsequently presented using data from 203 manufacturing firms in the OEM electronics industry. Guidelines and recommendations for researchers are then presented regarding both the uses of the theory and its measurement. It is hoped that this study will stimulate work in the important areas of inter‐firm relationships that draw from this rich but underutilized theoretical lens, and thereby add another perspective to the knowledge base in related areas of the operations and supply chain management fields.
Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein‐7
Authors: Hidaka Chisa , Goodrich Laurie R. , Chen Chih‐Tung , Warren Russell F. , Crystal Ronald G. , Nixon Alan J. 
Published: May 2003

AbstractBackground: Cartilage has a limited capacity to heal. Although chondrocyte transplantation is a useful therapeutic strategy, the repair process can be lengthy. Previously we have shown that over expression of bone morphogenetic protein‐7 (BMP‐7) in chondrocytes by adenovirus‐mediated gene transfer leads to increased matrix synthesis and cartilage‐like tissue formation in vitro. In this context we hypothesized that implantation of genetically modified chondrocytes expressing BMP‐7 would accelerate the formation of hyaline‐like repair tissue in an equine model of cartilage defect repair.Methods: Chondrocytes treated with adenovirus vector encoding BMP‐7 (AdBMP‐7) or as control, an adenovirus vector encoding an irrelevant gene (Escherichia coli cytosine deaminase, AdCD) were implanted into extensive (15 mm diameter) articular cartilage defects in the patellofemoral joints of 10 horses. Biopsies were performed to evaluate early healing at 4 weeks. At the terminal time point of 8 months, repairs were assessed for morphology, MRI appearance, compressive strength, biochemical composition and persistence of implanted cells.Results: Four weeks after surgery AdBMP‐7‐treated repairs showed an increased level of BMP‐7 expression and accelerated healing, with markedly more hyaline‐like morphology than control. Quantitative real‐time polymerase chain reaction (PCR) analysis of the repair tissue 8 months after surgery showed that few implanted cells persisted. By this time, the controls had healed similarly to the AdBMP‐7‐treated defects, and no difference was detected in the morphologic, biochemical or biomechanical properties of the repair tissues from the two treatment groups.Conclusions: Implantation of genetically modified chondrocytes expressing BMP‐7 accelerates the appearance of hyaline‐like repair tissue in experimental cartilage defects.Clinical relevance: Rehabilitation after cell‐based cartilage repair can be prolonged, leading to decreased patient productivity and quality of life. This study shows the feasibility of using genetically modified chondrocytes to accelerate cartilage healing. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Shear movement at the fracture site delays healing in a diaphyseal fracture model
Authors: Augat Peter , Burger Johannes , Schorlemmer Sandra , Henke Thomas , Peraus Manfred , Claes Lutz 
Published: May 2003

AbstractThis study tested the hypothesis that interfragmentary axial movement of transverse diaphyseal osteotomies would result in improved fracture healing compared to interfragmentary shear movement. Ten skeletally mature merino sheep underwent a mid‐diaphyseal osteotomy of the right tibia, stabilized by external fixation with an interfragmentary gap of 3 mm. A custom made external fixator allowed either pure axial (n = 5) or pure shear movement (n = 5) of 1.5 mm amplitude during locomotion by the animals. The movement of the osteotomy gap was monitored weekly in two sheep by an extensometer temporarily attached to the fixator. After 8 weeks the sheep were killed, and healing of the osteotomies was evaluated by radiography, biomechanical testing, and undecalcified histology. Shear movement considerably delayed the healing of diaphyseal osteotomies. Bridging of the osteotomy fragments occurred in all osteotomies in the axial group (100%), while in the shear group only three osteotomies (60%) were partially bridged. Peripheral callus formation in the shear group was reduced by 36% compared to the axial group (p < 0.05). In the axial group bone formation was considerably larger at the peripheral callus and in between the osteotomy gaps but not in the intramedullary area. The larger peripheral callus and excess in bone tissue at the level of the gap resulted in a more than three times larger mechanical rigidity for the axial than for the shear group (p < 0.05). In summary, fixation that allows excessive shear movement significantly delayed the healing of diaphyseal osteotomies compared to healing under axial movement of the same magnitude. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved.
Caution regarding the combined effects of extracellular matrices and nutrient media on cultured endothelial cells
Authors: Bareille R. , Villars F. , Rémy M. , Fernandez Ph. , Bordenave L. 
Published: May 2003

AbstractTo study the influence of smooth muscle cells (SMC) on endothelial cells (EC), different co‐culture designs are available, including EC seeding on SMC extracellular matrix (ECM). We explored human umbilical vein endothelial cell (HUVEC) adhesion and proliferation on either in situ or coated ECM, elaborated by HUVECs or human arterial smooth muscle cells (HUASMCs), in the presence of different nutrient media containing varying amounts of fetal calf serum. Coating wells with HUVEC or HUASMC ECMs did not improve HUVEC adhesion 1 h after cell seeding, compared with uncoated wells. HUVEC adhesion on in situ HUVEC—ECM and HUASMC—ECM was significantly increased compared with uncoated wells. The substratum upon which cells are maintained was found to play a crucial role, in conjunction with the medium to which HUVECs are exposed for their proliferative response. These results stress the importance of selecting media in relation to the particular substratum, in order to avoid misinterpretation of data.
Hydrotherapy—a new approach to improve function in the older patient with chronic heart failure
Authors: Cider Åsa , Schaufelberger Maria , Sunnerhagen Katharina Stibrant , Andersson Bert 
Published: May 2003

AbstractAims:Hydrotherapy, i.e. exercise in warm water, as a rehabilitation program has been considered potentially dangerous in patients with chronic heart failure (CHF) due to the increased venous return caused by the hydrostatic pressure. However, hydrotherapy has advantages compared to conventional training. We studied the applicability of an exercise programme in a temperature‐controlled swimming pool, with specific reference to exercise capacity, muscle function, quality of life and safety.Methods and results:Twenty‐five patients with CHF (NYHA II–III, age 72.1±6.1) were randomised into either 8 weeks of hydrotherapy (n=15), or into a control group (n=10). The training program was well tolerated with no adverse events. Patients in the hydrotherapy group improved their maximal exercise capacity (+6.5 vs.−5.9 W,P=0.001), isometric endurance in knee extension (+4 vs.−9 s,P=0.01) together with an improvement in the performance of heel‐lift (+4 vs. −3 n.o.,P=<0.01), shoulder abduction (+12 vs. −8 s,P=0.01) and shoulder flexion (+6 vs. +4,P=0.01) in comparison to patients in the control group.Conclusion:Physical training in warm water was well tolerated and seems to improve exercise capacity as well as muscle function in small muscle groups in patients with CHF. This new approach broadens the variety of training regimes for older patients with CHF.
High‐resolution comparative genomic hybridisation yields a high detection rate of chromosomal aberrations in childhood acute lymphoblastic leukaemia
Authors: Kristensen Tim D. , Wesenberg Finn , Jonsson Olafur G. , Carlsen Niels T. , Forestier Erik , Kirchhoff Maria , Lundsteen Claes , Schmiegelow Kjeld 
Published: May 2003

Abstract:Background:Cytogenetic aberrations are of prognostic significance in childhood acute lymphoblastic leukaemias and a high detection rate could improve the biological understanding and classification of these diseases.Methods:Bone‐marrow samples from 92 children with acute lymphoblastic leukaemia were studied by high‐resolution comparative genomic hybridisation (HRCGH) using dynamic standard reference intervals that enhance both specificity and sensitivity in the detection of aberrations.Results:In 80 patients (87%) HRCGH revealed a total of 405 aberrations, mostly whole chromosome gains (n = 265) and partial losses (n = 80). The 25 leukaemias with a gain of more than five whole chromosomes by HRCGH harboured only 7% of all losses. With G‐band karyotyping 59 patients (64%) had aberrations. HRCGH revealed more aberrations per patient than did G‐band karyotyping (median: 3 vs. 1,P = 0.005), revealed aberrations in 27 of the 34 patients for whom the G‐band karyotyping failed or was found to be normal, and specifically revealed more 9p losses (21% vs. 5%,P < 0.005), 12p losses (12% vs. 2%,P < 0.05) and 17q gains (11% vs. 1%,P < 0.01). Compared to the present study, the frequency of patients with aberrant karyotypes was significantly lower in previous conventional CGH studies (64% vs. 87%,P < 0.0001), as was the rate of partial aberrations per patient (1.1% vs. 1.7,P < 0.001), particularly with fewer 6q losses, 9p losses and 17q gains detected.Conclusion:HRCGH is superior to conventional CGH as an adjunct to G‐band karyotyping as it detects recurrent aberrations at a significantly higher rate than both these techniques.
Serum levels of cytokines correlate to donor chimerism and acute graft‐vs.‐host disease after haematopoietic stem cell transplantation
Authors: Remberger Mats , Jaksch Marie , Uzunel Mehmet , Mattsson Jonas 
Published: May 2003

Abstract:Background: Some patients become full donor chimeras (DC) early after stem‐cell transplantation (SCT), while others remain mixed chimeras for a longer time. Little is known about the mechanism behind these phenomena.Methods: Serum cytokine levels during conditioning and during the first month after SCT were analysed in 30 patients. Of the 21 patients who became full T‐cell DC from the first analysed sample, 12 developed grade II–IV acute graft‐vs.‐host disease (GVHD) and the other nine, mild or no acute GVHD. Another nine patients were T‐cell mixed chimeras (MC). All MC patients had no or mild acute GVHD.Results: During the pretransplant conditioning, DC patients had higher levels of tumour necrosis factor (TNF)‐α and lower levels of transforming growth factor (TGF)‐β and interleukin (IL)‐10, compared with MC patients. During the first week after SCT, lower levels of TGF‐β and IL‐10 and higher levels of soluble Fas (sFas) were found in DC patients compared with MC patients. During the second and third weeks after SCT, increased levels of TNF‐α, interferon (IFN)‐γ and sFas were found among DC patients compared with MC patients. Patients who developed moderate‐to‐severe acute GVHD had higher levels of TNF‐α, IFN‐γ, IL‐10 and sFas at 2 weeks post‐SCT than in those with less GVHD. Patients homozygous for the TNFd microsatellite alleles 3 or 4 had significantly higher TNF‐α levels during conditioning and more often developed acute GVHD grades II–IV.Conclusion: These results indicate that an imbalance between pro‐inflammatory and immune‐ modulating cytokines are involved in the development of chimerism and acute GVHD after allo‐SCT. The Fas/FasL pathway is probably involved in the elimination of recipient cells leading to full donor chimerism.