bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal expression and cellular origin of CC chemokine receptors CCR1, CCR2 and CCR5 in the central nervous system: insight into mechanisms of MOG-induced EAE
Authors: Eltayeb Sana , Berg Anna-Lena , Lassmann Hans , Wallström Erik , Nilsson Maria , Olsson Tomas , Ericsson-Dahlstrand Anders , Sunnemark Dan 
Published: May 2007

AbstractBackgroundThe CC chemokine receptors CCR1, CCR2 and CCR5 are critical for the recruitment of mononuclear phagocytes to the central nervous system (CNS) in multiple sclerosis (MS) and other neuroinflammatory diseases. Mononuclear phagocytes are effector cells capable of phagocytosing myelin and damaging axons. In this study, we characterize the regional, temporal and cellular expression of CCR1, CCR2 and CCR5 mRNA in the spinal cord of rats with myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE). While resembling human MS, this animal model allows unique access to CNS-tissue from various time-points of relapsing neuroinflammation and from various lesional stages: early active, late active, and inactive completely demyelinated lesions.MethodsThe expression of CCR1, CCR2 and CCR5 mRNA was studied within situhybridization using radio labelled cRNA probes in combination with immunohistochemical staining for phenotypic cell markers. Spinal cord sections from healthy rats and rats with MOG-EAE (acute phase, remission phase, relapse phase) were analysed. In defined lesion stages, the number of cells expressing CCR1, CCR2 and CCR5 mRNA was determined. Data were statistically analysed by the nonparametric Mann-Whitney U test.ResultsIn MOG-EAE rats, extensive up-regulation of CCR1 and CCR5 mRNA, and moderate up-regulation of CCR2 mRNA, was found in the spinal cord during episodes of active inflammation and demyelination. Double staining with phenotypic cell markers identified the chemokine receptor mRNA-expressing cells as macrophages/microglia. Expression of all three receptors was substantially reduced during clinical remission, coinciding with diminished inflammation and demyelination in the spinal cord. Healthy control rats did not show any detectable expression of CCR1, CCR2 or CCR5 mRNA in the spinal cord.ConclusionOur results demonstrate that the acute and chronic-relapsing phases of MOG-EAE are associated with distinct expression of CCR1, CCR2, and CCR5 mRNA by cells of the macrophage/microglia lineage within the CNS lesions. These data support the notion that CCR1, CCR2 and CCR5 mediate recruitment of both infiltrating macrophages and resident microglia to sites of CNS inflammation. Detailed knowledge of expression patterns is crucial for the understanding of therapeutic modulation and the validation of CCR1, CCR2 and CCR5 as feasible targets for therapeutic intervention in MS.
Surgical Complications Associated With Sentinel Lymph Node Dissection (SLND) Plus Axillary Lymph Node Dissection Compared With SLND Alone in the American College of Surgeons Oncology Group Trial Z0011
Authors: Lucci Anthony , McCall Linda Mackie , Beitsch Peter D. , Whitworth Patrick W. , Reintgen Douglas S. , Blumencranz Peter W. , Leitch A. Marilyn , Saha Sukumal , Hunt Kelly K. , Giuliano Armando E. 
Published: May 2007

PurposeThe American College of Surgeons Oncology Group trial Z0011 was a prospective, randomized, multicenter trial comparing overall survival between patients with positive sentinel lymph nodes (SLNs) who did and did not undergo axillary lymph node dissection (ALND). The current study compares complications associated with SLN dissection (SLND) plus ALND, versus SLND alone.Patients and MethodsFrom May 1999 to December 2004, 891 patients were randomly assigned to SLND + ALND (n = 445) or SLND alone (n = 446). Information on wound infection, axillary seroma, paresthesia, brachial plexus injury (BPI), and lymphedema was available for 821 patients.ResultsAdverse surgical effects were reported in 70% (278 of 399) of patients after SLND + ALND and 25% (103 of 411) after SLND alone (P ≤ .001). Patients in the SLND + ALND group had more wound infections (P ≤ .0016), seromas (P ≤ .0001), and paresthesias (P ≤ .0001) than those in the SLND-alone group. At 1 year, lymphedema was reported subjectively by 13% (37 of 288) of patients after SLND + ALND and 2% (six of 268) after SLND alone (P ≤ .0001). The difference between the two groups' lymphedema, assessed by arm measurements at 30 days (P = .36), 6 months (P = .22), and 1 year (P = .078), although close to the cutoff for significance at 1 year, was not significant. BPIs occurred in less than 1% of patients.ConclusionIn trial Z0011, the use of SLND + ALND resulted in more wound infections, axillary seromas, and paresthesias than SLND alone. Lymphedema was more common after SLND + ALND but was significantly different only by subjective report. The use of SLND alone resulted in fewer complications.
Evaluation of Cognitive Function Associated With Chemotherapy: A Review of Published Studies and Recommendations for Future Research
Authors: Vardy Janette , Rourke Sean , Tannock Ian F. 
Published: May 2007

PurposeThere is evidence that some cancer survivors suffer cognitive impairment after chemotherapy. Determining if a patient has cognitive impairment is challenging, especially because impairment is usually subtle.Patients and MethodsWe assessed the design of studies evaluating cognitive function during or after chemotherapy in adult patients with solid tumors. We also reviewed methods used to evaluate cognitive function in subjects with other diseases and make recommendations for future studies.ResultsWe identified 22 studies that met our criteria: 82% included women with breast cancer. Eight studies were longitudinal, 12 were cross-sectional, and two were follow-ups of cross-sectional studies. Sixteen studies used a battery of neuropsychological (NP) tests to assess subjects, and 13 included a control group. Ten studies (45%) had no explicit definition of cognitive impairment; most others used z scores or T scores and defined impairment based on standard deviations below the mean, but there was no consistency in for the cutoff point used or the number of tests required.ConclusionThere is no consistency in defining cognitive impairment, in the NP batteries used, or in statistical methods in studies of cognitive function of cancer patients. We suggest guidelines to define criteria for cognitive impairment. Use of summary scores and control groups is recommended. Practice effect should be adjusted for in longitudinal studies. A balance is needed between comprehensive batteries and briefer tests, which still need to be sensitive to mild impairment.
Risk and Clinical Implications of Transformation of Follicular Lymphoma to Diffuse Large B-Cell Lymphoma
Authors: Montoto Silvia , Davies Andrew John , Matthews Janet , Calaminici Maria , Norton Andrew J. , Amess John , Vinnicombe Sarah , Waters Rachel , Rohatiner Ama Z.S. , Lister T. Andrew 
Published: May 2007

Purpose To study the clinical significance of transformation to diffuse large B-cell lymphoma (DLBCL) in patients with follicular lymphoma (FL). Patients and Methods From 1972 to 1999, 325 patients were diagnosed with FL at St Bartholomew's Hospital (London, United Kingdom). With a median follow-up of 15 years, progression occurred in 186 patients and biopsy-proven transformation in 88 of the 325. The overall repeat biopsy rate was 70%. Results The risk of histologic transformation (HT) by 10 years was 28%, HT not yet having been observed after 16.2 years. The risk was higher in patients with advanced stage (P = .02), high-risk Follicular Lymphoma International Prognostic Index (FLIPI; P = .01), and International Prognostic Index (IPI; P = .04) scores at diagnosis. Expectant management (as opposed to treatment being initiated at diagnosis) also predicted for a higher risk of HT (P = .008). Older age (P = .005), low hemoglobin level (P = .03), high lactate dehydrogenase (P < .0001), and high-risk FLIPI (P = .01) or IPI (P = .003) score at the time of first recurrence were associated with the diagnosis of HT in a biopsy performed at that time. The median survival from transformation was 1.2 years. Patients with HT had a shorter overall survival (P < .0001) and a shorter survival from progression (P < .0001) than did those in whom it was not diagnosed. Conclusion Advanced stage and high-risk FLIPI and IPI scores at diagnosis correlate with an increased risk of HT. This event strongly influences the outcome of patients with FL by shortening their survival. There may be a subgroup of patients in whom HT does not occur.
Prospective, Randomized Study of Single Compared With Double Autologous Stem-Cell Transplantation for Multiple Myeloma: Bologna 96 Clinical Study
Authors: Cavo Michele , Tosi Patrizia , Zamagni Elena , Cellini Claudia , Tacchetti Paola , Patriarca Francesca , Di Raimondo Francesco , Volpe Ettore , Ronconi Sonia , Cangini Delia , Narni Franco , Carubelli Affra , Masini Luciano , Catalano Lucio , Fiacchini Mauro , de Vivo Antonio , Gozzetti Alessandro , Lazzaro Antonio , Tura Sante , Baccarani Michele 
Published: May 2007

Purpose We performed a prospective, randomized study of single (arm A) versus double (arm B) autologous stem-cell transplantation (ASCT) for younger patients with newly diagnosed multiple myeloma (MM). Patients and Methods A total of 321 patients were enrolled onto the study and were randomly assigned to receive either a single course of high-dose melphalan at 200 mg/m2 (arm A) or melphalan at 200 mg/m2 followed, after 3 to 6 months, by melphalan at 120 mg/m2 and busulfan at 12 mg/kilogram (arm B). Results As compared with assignment to the single-transplantation group (n = 163 patients), random assignment to receive double ASCT (n = 158 patients) significantly increased the probability to attain at least a near complete response (nCR; 33% v 47%, respectively; P = .008), prolonged relapse-free survival (RFS) duration of 18 months (median, 24 v 42 months, respectively; P < .001), and significantly extended event-free survival (EFS; median, 23 v 35 months, respectively; P = .001). Administration of a second transplantation and of novel agents for treating sequential relapses in up to 50% of patients randomly assigned to receive a single ASCT likely contributed to prolong the survival duration of the whole group, whose 7-year rate (46%) was similar to that of the double-transplantation group (43%; P = .90). Transplantation-related mortality was 3% in arm A and 4% in arm B (P = .70). Conclusion In comparison with a single ASCT as up-front therapy for newly diagnosed MM, double ASCT effected superior CR or nCR rate, RFS, and EFS, but failed to significantly prolong overall survival. Benefits offered by double ASCT were particularly evident among patients who failed at least nCR after one autotransplantation.
Effects of temperature on tuning of the auditory pathway in the cicadaTettigetta josei(Hemiptera, Tibicinidae)
Authors: Fonseca P. J. , Correia T. 
Published: May 2007

SUMMARYThe effects of temperature on hearing in the cicada Tettigetta josei were studied. The activity of the auditory nerve and the responses of auditory interneurons to stimuli of different frequencies and intensities were recorded at different temperatures ranging from 16°C to 29°C.Firstly, in order to investigate the temperature dependence of hearing processes, we analyzed its effects on auditory tuning, sensitivity, latency and Q10dB. Increasing temperature led to an upward shift of the characteristic hearing frequency, to an increase in sensitivity and to a decrease in the latency of the auditory response both in the auditory nerve recordings (periphery) and in some interneurons at the metathoracic–abdominal ganglionic complex (MAC). Characteristic frequency shifts were only observed at low frequency (3–8 kHz). No changes were seen in Q10dB. Different tuning mechanisms underlying frequency selectivity may explain the results observed.Secondly, we investigated the role of the mechanical sensory structures that participate in the transduction process. Laser vibrometry measurements revealed that the vibrations of the tympanum and tympanal apodeme are temperature independent in the biologically relevant range(18–35°C). Since the above mentioned effects of temperature are present in the auditory nerve recordings, the observed shifts in frequency tuning must be performed by mechanisms intrinsic to the receptor cells.Finally, the role of potassium channels in the response of the auditory system was investigated using a specific inhibitor of these channels,tetraethylammonium (TEA). TEA caused shifts on tuning and sensitivity of the summed response of the receptors similar to the effects of temperature. Thus,potassium channels are implicated in the tuning of the receptor cells.
Chemosensory reception, behavioral expression, and ecological interactions at multiple trophic levels
Authors: Ferrer Ryan P. , Zimmer Richard K. 
Published: May 2007

SUMMARYChemoreception may function throughout an entire animal lifetime, with independent, stage-specific selection pressures leading to changes in physiological properties, behavioral expression, and hence, trophic interactions. When the California newt (Taricha torosa) metamorphoses from an entirely aquatic larva to a semi-terrestrial juvenile/adult form, its chemosensory organs undergo dramatic reorganization. The relationship between newt life-history stage and chemosensory-mediated behavior was established by comparing responses of adults (as determined here) to those of conspecific larvae (as studied previously). Bioassays were performed in mountain streams,testing responses of free-ranging adults to 13 individual l-amino acids. Relative to stream water (controls), adults turned immediately upcurrent and moved to the source of arginine, glycine or alanine release. These responses were indicative of predatory search. Arginine was the strongest attractant tested, with a response threshold (median effective dose)of 8.3×10–7 mol l–1 (uncorrected for dilution associated with chemical release and delivery). In contrast to adult behavior, arginine suppressed cannibal-avoidance and failed to evoke search reactions in larvae. For a common set of arginine analogs, the magnitudes of adult attraction and larval suppression were not positively correlated. Suppression of cannibal-avoidance behavior in larvae was unaffected by most structural modifications of the arginine molecule. Adult behavior, on the other hand, was strongly influenced by even subtle alterations in the parent compound. Reactions to arginine in both adults and larvae were eliminated by blocking the external openings of the nasal cavity.Stimulating adult predatory search in one case and inhibiting larval cannibal avoidance in the other, arginine is a chemical signal with opposing behavioral effects and varying ecological consequences. Significant differences between responses of adults and larvae to changes in arginine structure suggest alternative, chemosensory receptor targets. Although arginine reception functions throughout an entire newt lifetime, an ontogenetic shift in larval and adult chemoreceptive ability changes behavioral expression, and thus, reflects the unique selection pressures that act at each life-history stage.
Human locomotion on ice: the evolution of ice-skating energetics through history
Authors: Formenti Federico , Minetti Alberto E. 
Published: May 2007

SUMMARYMore than 3000 years ago, peoples living in the cold North European regions started developing tools such as ice skates that allowed them to travel on frozen lakes. We show here which technical and technological changes determined the main steps in the evolution of ice-skating performance over its long history. An in-depth historical research helped identify the skates displaying significantly different features from previous models and that could consequently determine a better performance in terms of speed and energy demand. Five pairs of ice skates were tested, from the bone-skates, dated about 1800 BC, to modern ones.This paper provides evidence for the fact that the metabolic cost of locomotion on ice decreased dramatically through history, the metabolic cost of modern ice-skating being only 25% of that associated with the use of bone-skates. Moreover, for the same metabolic power, nowadays skaters can achieve speeds four times higher than their ancestors could. In the range of speeds considered, the cost of travelling on ice was speed independent for each skate model, as for running. This latter finding, combined with the accepted relationship between time of exhaustion and the sustainable fraction of metabolic power, gives the opportunity to estimate the maximum skating speed according to the distance travelled.Ice skates were probably the first human powered locomotion tools to take the maximum advantage from the biomechanical properties of the muscular system: even when travelling at relatively high speeds, the skating movement pattern required muscles to shorten slowly so that they could also develop a considerable amount of force.
Effective limb length and the scaling of locomotor cost in terrestrial animals
Authors: Pontzer Herman 
Published: May 2007

SUMMARYRelative to body size, smaller animals use more energy to travel a given distance than larger animals, but the anatomical variable driving this negative allometry remains the subject of debate. Here, I report a simple inverse relationship between effective limb length (i.e. hip height) and the energy cost of transport (COT; J kg–1 m–1)for terrestrial animals. Using published data for a diverse set of terrestrial species including birds, mammals, reptiles and arthropods, I show that between-species differences in locomotor cost are driven by differences in limb length. Notably, there is no independent effect of body mass on cost. Remarkably, effective limb length explains 98% of the observed variance in locomotor cost across a wide range of terrestrial species including mammals,birds, reptiles and arthropods. Variation about the limb-length/COT scaling relationship is attributable to taxonomic differences in limb design, with birds and arthropods exhibiting greater residuals than mammals. Differences in COT between semi-aquatic, generalist and cursorial species also corresponds to differences in leg length between these groups. These results are discussed in light of previous investigations of the limb length and locomotor cost.
Toll-Like Receptor 9 Ligand Blocks Osteoclast Differentiation Through Induction of Phosphatase
Authors: Amcheslavsky Alla , Bar-Shavit Zvi 
Published: May 2007

Abstract
CpG-ODN, in addition to stimulation of osteoclastogenic signals in early osteoclast precursors, also induces phosphatase, shifting the pattern of ERK phosphorylation from sustained to transient. This shift results in the degradation of c-fos, an essential molecule for osteoclast differentiation. Therefore, CpG-ODN blocks osteoclast differentiation.
Introduction: Activation of either Toll-like receptor 9 (TLR9) or RANK induces similar responses in osteoclast precursors. Paradoxically, activation of TLR9 results in inhibition of RANKL-induced osteoclastogenesis.
Materials and Methods: We used bone marrow—derived osteoclast precursors. Analyses of signaling molecules phosphorylation were performed using Western blotting. Different levels of gene expression analyses were performed using RT-PCR, Northern, and run-on analyses (for RNA), and EMSA, Western, and pulse-chase experiments (for protein). Phosphatase activity was measured spectrophotometrically.
Results: We found that RANKL and TLR9 ligand, oligodeoxynucleotides containing unmethylated CpG dinucleotides (CpG-ODN), induce sustained and transient extracellular signal-regulated kinase (ERK) phosphorylation, respectively. Furthermore, together they induce a transient phosphorylation of ERK. The duration of ERK phosphorylation is a key factor in determining induction of c-fos, a protein critical for osteoclastogenesis. Indeed, we found that CpG-ODN does not induce c-fos and inhibits its induction by RANKL by enhancing c-fos mRNA and protein degradation. Our observation that CpG-ODN, but not RANKL, induces the expression of the phosphatase PP2A suggests that CpG-ODN exerts its inhibitory activity by induction of ERK dephosphorylation. Moreover, together with the phosphatase inhibitor okadaic acid, CpG-ODN induces sustained ERK phosphorylation and c-fos expression.
Conclusions: Our findings suggest that the increased rate of c-fos degradation by the TLR9 ligand mediates the inhibition of RANKL-induced osteoclast differentiation. The TLR9 ligand, through induction of dephosphorylation, prevents the sustained ERK phosphorylation needed for maintaining high c-fos levels that are essential for osteoclast differentiation.
Krüppel-Like Zinc Finger Protein Glis3 Promotes Osteoblast Differentiation by Regulating FGF18 Expression
Authors: Beak Ju Youn , Kang Hong Soon , Kim Yong-Sik , Jetten Anton M 
Published: May 2007

Abstract
The zinc finger protein Glis3 is highly expressed in human osteoblasts and acts synergistically with BMP2 and Shh in enhancing osteoblast differentiation in multipotent C3H10T1/2 cells. This induction of osteoblast differentiation is at least in part caused by the induction of FGF18 expression. This study supports a regulatory role for Glis3 in osteoblast differentiation.
Introduction: Gli-similar 3 (Glis3) is closely related to members of the Gli subfamily of Krüppel-like zinc finger proteins, transcription factors that act downstream of sonic hedgehog (Shh). In this study, we analyzed the expression of Glis3 in human osteoblasts and mesenchymal stem cells (MSCs). Moreover, we examined the regulatory role of Glis3 in the differentiation of multipotent C3H10T1/2 cells into osteoblasts and adipocytes.
Materials and Methods: Microarray analysis was performed to identify genes regulated by Glis3 in multipotent C3H10T1/2 cells. Reporter and electrophoretic mobility shift assays were performed to analyze the regulation of fibroblast growth factor 18 (FGF18) by Glis3.
Results: Glis3 promotes osteoblast differentiation in C3H10T1/2 cells as indicated by the induction of alkaline phosphatase activity and increased expression of osteopontin, osteocalcin, and Runx2. In contrast, Glis3 expression inhibits adipocyte differentiation. Glis3 acts synergistically with BMP2 and Shh in inducing osteoblast differentiation. Deletion analysis indicated that the carboxyl-terminal activation function of Glis3 is needed for its stimulation of osteoblast differentiation. Glis3 is highly expressed in human osteoblasts and induced in MSCs during differentiation along the osteoblast lineage. Microarray analysis identified FGF18 as one of the genes induced by Glis3 in C3H10T1/2 cells. Promoter analysis and electrophoretic mobility shift assays indicated that a Glis3 binding site in the FGF18 promoter flanking region is important in its regulation by Glis3.
Conclusions: Our study showed that Glis3 positively regulates differentiation of C3H10T1/2 cells into osteoblasts and inhibits adipocyte differentiation. Glis3 acts synergistically with BMP2 and Shh in inducing osteoblast differentiation. The promotion of osteoblast differentiation by Glis3 involves increased expression of FGF18, a positive regulator of osteogenesis. This, in conjunction with the induction of Glis3 expression during osteoblast differentiation in MSCs and its expression in osteoblasts, suggests that Glis3 is an important modulator of MSC differentiation.