bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inflammatory response in induced sputum mononuclear cells from patients with acute exacerbation of asthma
Authors: Hamzaoui A. , Ben Brahim M. , Zhioua A. , Ayed Kh. , Hamzaoui K. 
Published: July 2002

Examination of sputum provides a direct method to investigate airway inflam mation non‐invasively in particular Th1 (IL‐2, IFN–γ) and Th2 (IL–4, IL–10) cytokine production.IL–2, IL–4, IL–10 and IFN–γ cytokine were studied in induced sputum mononuclear cells of asthmatic patients.Sputum induction was performed on 10 patients and 10 normal controls. Basal and mitogen‐stimulated cytokine production was determined in induced sputum T‐cell culture. Supernatants were collected and assayed not only with specific ELISA but also with polymerase chain reaction (PCR) techniques.Data showed a significantly higher production of IL–10 by both the ELISA and the RT‐PCR techniques in asthmatic patients compared with sputum mononuclear cells from healthy controls. IL–4 production was detected at a low level using the ELISA method in asthmatic patients. The RT‐PCR analysis detected a significantly IL–4‐mRNA expression in all asthmatic patients, compared with controls. Results of IL–10 and IL–4 mRNA expression were reproducible. We did not find any alteration in the expression of the type 1 derived cytokines (IL–2 and IFN–γ) in asthmatic patients or in healthy controls.Our study showed a tendency of induced sputum mononuclear cells to express a Th2‐like cytokine pattern in acute exacerbation of asthmatic patients, where IL–10 and IL–4 are synthesized in larger amounts. The combination of sputum induction as a non‐invasive tool to explore the lung and the identification of disease‐associated cytokine expression and of specific cytokine mRNA should help elucidate mechanisms of the immunologically mediated inflammatory
responses in asthma.
Ethanol induces taurine release in the amygdala: an in vivo microdialysis study
Authors: QUERTEMONT ETIENNE , DAHCHOUR ABDELKADER , WARD ROBERTA J. , DE WITTE PHILIPPE 
Published: July 2002

AbstractThe effect of acute IP ethanol injections on the extracellular aspartate, glutamate, taurine and GABA content of the basolateral amygdala microdialysate was investigated in relationship with total brain ethanol. Each acute intraperitoneal injection of ethanol, 0.5, 1.0, 2.0 and 3.0 g/kg body weight, induced an immediate increase in microdialysate taurine; both 0.5 and 1.0 g/kg ethanol evoked an increase during the first 20 minutes following injection which returned to baseline value by 40 minutes, despite the fact that ethanol was detectable in the brain until 60 or 120 minutes, respectively. After either 2.0 or 3.0 g/kg ethanol there was an increase in taurine of gradual intensity which gradually declined to reach baseline values by 100 minutes. In contrast, the ethanol concentration for 2.0 g/kg remained elevated at the end of the 120 minutes; approximately 25 mg ethanol/mg protein. The stimulated release of taurine within the amygdala could participate in the regulation of ethanolinduced changes in osmolarity, since taurine is postulated to act as an osmoregulator in the brain. Taurine could also mediate or interact with ethanol‐induced central nervous system effects, as it exerts a modulatory action on cell excitability and neurotransmitter processes.
Outcome and Toxicity of an Ifosfamide‐Based Soft Tissue Sarcoma Treatment Protocol in Children. The Importance of Local Therapy
Authors: Yule S. Murray , Skinner Roderick , English Martin W. , Cole Mike , Pearson Andrew D. J. , Lucraft Helen H. , Craft Alan W. 
Published: July 2002

Background. Although the survival of children with soft tissue sarcoma (STS) has improved considerably, the outcome of patients with metastatic disease, and those with primary tumours of the extremities or parameningeal sites remains disappointing. We describe the clinical outcome of an ifosfamide‐based regimen with local therapy directed only to children who failed to achieve a complete response to initial chemotherapy.Patients and Methods. Twenty‐one children with STS (16 rhabdomyosarcoma) who presented with unresectable tumours were treated with five courses of ifosfamide (9 g/m2) and etoposide (600 mg/m2). Patients who did not achieve a complete response then received local therapy. Chemotherapy with ifosfamide combined with etoposide, vincristine (1.5 mg/m2 and doxorubicin (60 mg/m2) or vincristine and actinomycin D (1.5 mg/m2) was continued for one year.Results and Discussion. Objective responses to five courses of ifosfamide and etoposide were seen in all patients. Disease free survival (DFS) at a median follow up of 59 months was 57% (95% CI 29–75%). The DFS of children who received local therapy was 89% compared with 33% in those who received chemotherapy alone (p=0.027). Locoregional recurrences did not occur in children who received radiotherapy to the site of the primary tumour. Ifosfamide‐based chemotherapy does not reduce the incidence of loco‐regional recurrence in children who do not receive local therapy.
The Role of Insulin‐Like Growth Factor System in Soft Tissue Sarcomas: From Physiopathology to Targeted Therapeutic Approaches
Authors: Zumkeller Walter 
Published: July 2002

Purpose/Results. Although surgical, chemo‐ and radiotherapeutic treatment regimens in patients with soft tissue sarcomas have constantly been refined over the past two decades, the survival rate for these patients is rather low.Discussion. There is a great need to investigate the mechanisms for oncogenesis and to identify the factors involved in malignant transformation in sarcomas. Among these factors, IGFs are thought to play a pivotal role as progression factors in various types of sarcomas. The dysregulation of the IGF‐II synthesis, e.g. by loss of imprinting which occurs in most
types of sarcomas, is a permissive effect through the suppression of cell death. In addition, cells that overexpress the type I IGF receptors are more susceptible to transformation by oncogenes. As TP53 suppresses the activity of IGF‐II P3 and P4, as well as the type I IGF receptor promoter, mutations of TP53 in sarcomas may alternatively lead to the activation of these factors. Finally, the phenomenon of non‐islet cell tumour hypoglycaemia that occurs in patients with sarcomas, and which is related to the secretion of IGF‐II prohormones, is discussed. Future therapeutic strategies may be based upon the application of antibodies or antisense oligonucleotides directed against the type I IGF receptors, with the common goal of inducing apoptosis in sarcoma cells. Ultimately, these and other therapeutic approaches may lead to a better outcome in patients suffering from sarcoma.
Longitudinal Growth Following Treatment for Osteosarcoma
Authors: Cool W. Paul , Grimer Robert J. , Carter Simon R. , Tillman Roger M. , Davies A. Mark 
Published: July 2002

Purpose. The purpose of this study was to analyse the height at diagnosis and growth in 72 skeletally immature children who had been treated for osteosarcoma in the area of the knee.Subjects. Of the patients, the average age at diagnosis was 10 years in girls and 12 years in boys. All children received neo‐adjuvant chemotherapy, and had limb salvage by endoprosthetic replacement.Results and conclusion. The results of this study indicate that there is no evidence that children with osteosarcoma are taller at diagnosis than their normal counterparts. However, there was a marked retardation in growth in the year following the administration of cytotoxic chemotherapy. There were 19 children who reached skeletal maturity. The final height in
these children was not significantly different from the normal population.
Transferrin Promotes Endothelial Cell Migration and Invasion: Implication in Cartilage Neovascularization
Authors: Carlevaro Mariella F. , Albini Adriana , Ribatti Domenico , Gentili Chiara , Benelli Roberto , Cermelli Silvia , Cancedda Ranieri , Cancedda Fiorella Descalzi 
Published: July 2002

During endochondral bone formation, avascular cartilage differentiates to hypertrophic cartilage that then undergoes erosion and vascularization leading to bone deposition. Resting cartilage produces inhibitors of angiogenesis, shifting to production of angiogenic stimulators in hypertrophic cartilage. A major protein synthesized by hypertrophic cartilage both in vivo and in vitro is transferrin. Here we show that transferrin is a major angiogenic molecule released by hypertrophic cartilage. Endothelial cell migration and invasion is stimulated by transferrins from a number of different sources, including hypertrophic cartilage. Checkerboard analysis demonstrates that transferrin is a chemotactic and chemokinetic molecule. Chondrocyte-conditioned media show similar properties. Polyclonal anti-transferrin antibodies completely block endothelial cell migration and invasion induced by purified transferrin and inhibit the activity produced by hypertrophic chondrocytes by 50–70% as compared with controls. Function-blocking mAbs directed against the transferrin receptor similarly reduce the endothelial migratory response. Chondrocytes differentiating in the presence of serum produce transferrin, whereas those that differentiate in the absence of serum do not. Conditioned media from differentiated chondrocytes not producing transferrin have only 30% of the endothelial cell migratory activity of parallel cultures that synthesize transferrin.
The angiogenic activity of transferrins was confirmed by in vivo assays on chicken egg chorioallantoic membrane, showing promotion of neovascularization by transferrins purified from different sources including conditioned culture medium.
Based on the above results, we suggest that transferrin is a major angiogenic molecule produced by hypertrophic chondrocytes during endochondral bone formation.
Expression of a Truncated, Kinase-Defective TGF-β Type II Receptor in Mouse Skeletal Tissue Promotes Terminal Chondrocyte Differentiation and Osteoarthritis
Authors: Serra Rosa , Johnson Mahlon , Filvaroff Ellen H. , LaBorde James , Sheehan Daniel M. , Derynck Rik , Moses Harold L. 
Published: July 2002

Members of the TGF-β superfamily are important regulators of skeletal development. TGF-βs signal through heteromeric type I and type II receptor serine/threonine kinases. When over-expressed, a cytoplasmically truncated type II receptor can compete with the endogenous receptors for complex formation, thereby acting as a dominant-negative mutant (DNIIR). To determine the role of TGF-βs in the development and maintenance of the skeleton, we have generated transgenic mice (MT-DNIIR-4 and -27) that express the DNIIR in skeletal tissue. DNIIR mRNA expression was localized to the periosteum/perichondrium, syno-vium, and articular cartilage. Lower levels of DNIIR mRNA were detected in growth plate cartilage. Transgenic mice frequently showed bifurcation of the xiphoid process and sternum. They also developed progressive skeletal degeneration, resulting by 4 to 8 mo of age in kyphoscoliosis and stiff and torqued joints. The histology of affected joints strongly resembled human osteo-arthritis. The articular surface was replaced by bone or hypertrophic cartilage as judged by the expression of type X collagen, a marker of hypertrophic cartilage normally absent from articular cartilage. The synovium was hyperplastic, and cartilaginous metaplasia was observed in the joint space.
We then tested the hypothesis that TGF-β is required for normal differentiation of cartilage in vivo. By 4 and 8 wk of age, the level of type X collagen was increased in growth plate cartilage of transgenic mice relative to wild-type controls. Less proteoglycan staining was detected in the growth plate and articular cartilage matrix of transgenic mice. Mice that express DNIIR in skeletal tissue also demonstrated increased Indian hedgehog (IHH) expression. IHH is a secreted protein that is expressed in chondrocytes that are committed to becoming hypertrophic. It is thought to be involved in a feedback loop that signals through the periosteum/ perichondrium to inhibit cartilage differentiation. The data suggest that TGF-β may be critical for multifaceted maintenance of synovial joints. Loss of responsiveness to TGF-β promotes chondrocyte terminal differentiation and results in development of degenerative joint disease resembling osteoarthritis in humans.
Classification of integral lattices with large class number
Authors: Scharlau Rudolf , Hemkemeier Boris 
Published: July 2002

A detailed exposition of Kneser’s neighbour method for quadratic lattices over totally real number fields, and of the sub-procedures needed for its implementation, is given. Using an actual computer program which automatically generates representatives for all isomorphism classes in one genus of rational lattices, various results about genera ofℓ\ell-elementary lattices, for small prime levelℓ,\ell ,are obtained. For instance, the class number of1212-dimensional77-elementary even lattices of determinant767^6is395395; no extremal lattice in the sense of Quebbemann exists. The implementation incorporates as essential parts previous programs of W. Plesken and B. Souvignier.
Gene selection for sample classification based on gene
expression data: study of sensitivity to choice of parameters of the
GA/KNN method
Authors: Li Leping , Weinberg Clarice R. , Darden Thomas A. , Pedersen Lee G. 
Published: July 2002

Abstract
Motivation: We recently introduced a multivariate approach that selects a subset of predictive genes jointly for sample classification based on expression data. We tested the algorithm on colon and leukemia data sets. As an extension to our earlier work, we systematically examine the sensitivity, reproducibility and stability of gene selection/sample classification to the choice of parameters of the algorithm.
Methods: Our approach combines a Genetic Algorithm (GA) and the k-Nearest Neighbor (KNN) method to identify genes that can jointly discriminate between different classes of samples (e.g. normal versus tumor). The GA/KNN method is a stochastic supervised pattern recognition method. The genes identified are subsequently used to classify independent test set samples.
Results: The GA/KNN method is capable of selecting a subset of predictive genes from a large noisy data set for sample classification. It is a multivariate approach that can capture the correlated structure in the data. We find that for a given data set gene selection is highly repeatable in independent runs using the GA/KNN method. In general, however, gene selection may be less robust than classification.
Availability: The method is available at http://dir.niehs.nih.gov/microarray/datamining
Contact: LI3@niehs.nih.gov
* To whom correspondence should be addressed.
An information-based sequence distance and its application to
whole mitochondrial genome phylogeny
Authors: Li Ming , Badger Jonathan H. , Chen Xin , Kwong Sam , Kearney Paul , Zhang Haoyong 
Published: July 2002

Abstract
Motivation: Traditional sequence distances require an alignment and therefore are not directly applicable to the problem of whole genome phylogeny where events such as rearrangements make full length alignments impossible. We present a sequence distance that works on unaligned sequences using the information theoretical concept of Kolmogorov complexity and a program to estimate this distance.
Results: We establish the mathematical foundations of our distance and illustrate its use by constructing a phylogeny of the Eutherian orders using complete unaligned mitochondrial genomes. This phylogeny is consistent with the commonly accepted one for the Eutherians. A second, larger mammalian dataset is also analyzed, yielding a phylogeny generally consistent with the commonly accepted one for the mammals.
Availability: The program to estimate our sequence distance, is available at http://www.cs.cityu.edu.hk/~cssamk/gencomp/GenCompress1.htm. The distance matrices used to generate our phylogenies are available at http://www.math.uwaterloo.ca/~mli/distance.html
Contact: mli@wh.math.uwaterloo.ca
* To whom correspondence should be addressed.
The developing dorsal ganglion of the salp Thalia democratica, and the nature of the ancestral chordate brain
Authors: Lacalli T. C. , Holland L. Z. 
Published: July 2002

The development of the dorsal ganglion of the salp,Thalia democratica, is described from electron microscope reconstructions up to the stage of central neuropile formation. The central nervous system (CNS) rudiment is initially tubular with an open central canal. Early developmental events include: (i) the formation of a thick dorsal mantle of neuroblasts from which paired dorsal paraxial neuropiles arise; (ii) the differentiation of clusters of primary motor neurons along the ventral margin of the mantle; and (iii) the development from the latter of a series of peripheral nerves. The dorsal paraxial neuropiles ultimately connect to the large central neuropile, which develops later. Direct contact between neuroblasts and muscle appears to be involved in the development of some anterior nerves. The caudal nerves responsible for innervating more distant targets in the posterior part of the body develop without such contacts, which suggests that a different patterning mechanism may be employed in this part of the neuromuscular system.The results are compared with patterns of brain organization in other chordates. Because the salp CNS is symmetrical and generally less reduced than that of ascidian larvae, it is more easily compared with the CNS of amphioxus and vertebrates. The dorsal paraxial centres in the salp resemble the dorsolateral tectal centres in amphioxus in both position and organization; the central neuropile in salps likewise resembles the translumenal system in amphioxus. The neurons themselves are similar in that many of their neurites appear to be derived from the apical surface instead of the basal surface of the cell. Such neurons, with extensively developed apical neurites, may represent a new cell type that evolved in the earliest chordates in conjunction with the formation of translumenal or intralumenal integrative centres. In comparing the salp ganglion with vertebrates, we suggest that the main core of the ganglion is most like the mes–etencephalic region of the vertebrate brain, i.e. the zone occupied by the midbrain, isthmus, and anterior hindbrain. Counterparts of more anterior regions (forebrain) and posterior ones (segmented hindbrain) appear to be absent in salps, but are found in other tunicates, suggesting that evolution has acted quite differently on the main subdivisions of the CNS in different types of tunicates.
The radular apparatus of cephalopods
Authors: Messenger J. B. , Young J. Z. 
Published: July 2002

This paper describes the ontogeny, breakdown and absorption of the radular teeth of cephalopods and, for the first time, considers the function of the ‘bolsters’ or radular support muscles.The radular ribbon, which bears many regularly arranged transverse rows of teeth one behind the other, lies in a radular canal that emerges from the radular sac. Here the radular teeth are formed by a set of elongate cells with microvilli, the odontoblasts. These are organized into two layers, the outer producing the radular membrane and the bases of the teeth, the inner producing the cusps. The odontoblasts also secrete the hyaline shield and the teeth on the lateral buccal palps, when these are present. At the front end of the radular ribbon the teeth become worn in feeding and are replaced from behind by new ones formed continuously in the radular sac, so that the whole ribbon moves forward during ontogeny. Removal of the old teeth is achieved by cells in the radular organs; these cells, which are formed from modified odontoblasts (‘odontoclasts’), dissolve the teeth and membranes and absorb them. There is a subradular organ in all cephalopods. InOctopus vulgaris, which bores into mollusc shells and crustacean carapaces, it is especially well–developed and there is also a supraradular organ.A characteristic feature of the cephalopod radular apparatus is the pair of large radular support muscles or ‘bolsters’. Their function seems never to have been investigated, but experiments reported here show that when they elongate, the radular teeth become erect at the bending plane and splayed, presumably enhancing their ability to rake food particles into the pharynx. The bolsters ofOctopusfunction as muscular hydrostats: because their volume is fixed, contraction of their powerful transverse muscles causes them to elongate. In decapods and in nautiloids each bolster contains a ‘support rod’ of semi–fluid material, as well as massive transverse musculature. This rod may elongate to erect the radular teeth. At the extreme front end of the bolsters inOctopusthere are many nerve fibres that may constitute a receptor organ signalling the movements of the radula against hard material. Such nerves are absent from decapods and from octopods that do not bore holes.The buccal mass ofNautilusis massive, with heavily calcified tips to the beaks and a wide radular ribbon, with 13 rather than nine elements in each row. Nevertheless all the usual coleoid features are present in the radular apparatus and the teeth are formed and broken down in the same way. However,Nautilushas a unique structure, the radular appendage. This comprises a papillate mass extending over the palate in the mid–line and forming paired lateral masses that are in part secretory. The organ is attached to the front of the radula by muscles and connective tissue. Its function is unknown.
Detecting equilibrium cytochrome c folding intermediates by electrospray ionisation mass spectrometry: Two partially folded forms populate the molten‐globule state
Authors: Grandori Rita 
Published: July 2002

AbstractNanoelectrospray ionization mass spectrometry (nano‐ESI‐MS) is applied to the characterization of ferric cytochromec (cytc) conformational states under different solvent conditions. The methanol‐induced molten‐globule state in the pH range 2.6–3.0 is found to be populated by two distinct, partially folded conformers IA and IB. The more compact intermediate IB resembles that induced by glycerol in acid‐unfolded cytc. The less compact one, IA, also can be induced by destabilization of the native structure by trifluoroethanol. IA and IB can be detected, in the absence of additives, around the midpoint of the acid‐induced unfolding transition, providing direct evidence for involvement of equilibrium folding intermediates in cytc conformational transitions at low pH. This study shows that mass spectrometry can contribute to the characterization of molten‐globule states of proteins by detection of distinct, although poorly populated, conformations involved in a dynamic equilibrium.
Effects of turn residues in directing the formation of the β‐sheet and in the stability of the β‐sheet
Authors: Chen Pei‐Yeh , Lin Chih‐Kai , Lee Chung‐Tien , Jan Howard , Chan Sunney I. 
Published: July 2002

AbstractThe designed peptide (denoted 20‐mer, sequence VFITSDPGKTYTEVDPGOKILQ) has been shown to form a three‐strand antiparallel β‐sheet. It is generally believed that the DPro‐Gly segment has the propensity to adopt a type II′ β‐turn, thereby promoting the formation of this β‐sheet. Here, we replaced DPro‐Gly with Asp‐Gly, which should favor a type I′ turn, to examine the influence of different type of turns on the stability of the β‐sheet. Contrary to our expectation, the mutant peptide, denoted P6D, forms a five‐residue type I turn plus a β‐bulge between the first two strands due to a one amino‐acid frameshift in the hydrogen bonding network and side‐chain inversion of the first β‐strand. In contrast, the same kind of substitution at DPro‐14 in the double mutant, denoted P6DP14D, does not yield the same effect. These observations suggest that the SDGK sequence disfavors the type I′ conformation while the VDGO sequence favors a type I′ turn, and that the frameshift in the first strand provides a way for the peptide to accommodate a disfavored turn sequence by protruding a bulge in the formation of the β‐hairpin. Thus, different types of turns can affect the stability of a β‐structure.