bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell-Cell Signaling Through NOTCH Regulates Human Embryonic Stem Cell Proliferation
Authors: Fox Victoria , Gokhale Paul J. , Walsh James R. , Matin Maryam , Jones Mark , Andrews Peter W. 
Published: December 2007

Abstract
Unlike pluripotent mouse embryonic stem (ES) cells, human ES cells and their malignant equivalents, embryonal carcinoma (EC) cells, require close cell-cell contact for efficient growth. Signaling through the NOTCH receptor, initiated by interaction with ligands of the DELTA/JAGGED family expressed on neighboring cells, plays a role in regulating the self-renewal of several stem cell systems. Members of the NOTCH and DELTA/JAGGED families are expressed by human EC and ES cells, and we have therefore investigated the possible role of NOTCH in the maintenance of these cells. Cleavage of both NOTCH1 and NOTCH2 to yield the intracellular domain responsible for the canonical signaling pathway of NOTCH was detected in several human EC and ES cell lines, suggesting that NOTCH signaling is active. Furthermore, the proliferation of human EC cells, as well as the expression of several downstream NOTCH target genes, was markedly reduced after small interfering RNA knockdown of NOTCH1, NOTCH2, and the canonical effector CBF-1 or after blocking NOTCH signaling with the γ-secretase inhibitor L-685,458. The inhibitor also caused a reduction in the growth of human ES cells, although without evidence of differentiation. The results indicate that cell-cell signaling through the NOTCH system provides a critical cue for the proliferation of human EC and ES cell in vitro.
Disclosure of potential conflicts of interest is found at the end of this article.
Assessment of three automated assays for C-reactive protein determination in dogs
Authors: Fransson Boel A. , Bergström Annika , Wardrop K. Jane , Hagman Ragnvi 
Published: December 2007

Abstract
Objective—To determine the characteristics of an automated canine C-reactive protein (CRP) assay and evaluate 2 human CRP assays for use in dogs.
Animals—56 client-owned dogs with pyometra and 11 healthy control dogs.
Procedures—Samples from 11 dogs with high (> 100 mg/L) or low (< 10 mg/L) CRP concentrations (determined by use of a canine ELISA) were evaluated by use of the automated canine CRP assay. Intra- and interassay imprecision was determined (by use of those 2 plasma pools), and assay inaccuracy was assessed by use of logistic regression analysis of results obtained via ELISA and the automated canine CRP assay. Two automated human CRP assays were used to measure plasma CRP concentration in 10 dogs.
Results—By use of the ELISA, mean ± SD plasma CRP concentration was 96.1 ± 38.5 mg/L and 10.1 ± 23.2 mg/L in dogs with pyometra and control dogs, respectively. The automated canine assay had intra-assay coefficients of variation (CVs) of 7.8% and 7.9%, respectively, and interassay CVs of 11.1% and 13.1%, respectively. Results from the automated assay were highly correlated with results obtained via ELISA. The human assay results did not exceed 0.4 mg/L in any dog.
Conclusions and Clinical Relevance—The automated canine CRP assay had less interassay imprecision, compared with the ELISA. The 2 human CRP assays were not suitable for analysis of canine plasma samples. The automated canine CRP assay was more precise than the ELISA for serial evaluations of plasma CRP concentration in dogs.
Effects of perzinfotel on the minimum alveolar concentration of isoflurane in dogs
Authors: Kushiro Tokiko , Wiese Ashley J. , Eppler Mark C. , Muir William W. 
Published: December 2007

Abstract
Objective—To determine the effect of IV administration of perzinfotel on the minimum alveolar concentration (MAC) of isoflurane in dogs.
Animals—6 healthy sexually intact male Beagles.
Procedures—Dogs were instrumented with a telemetry device that permitted continuous monitoring of heart rate, arterial blood pressure, and body temperature. Dogs were anesthetized with propofol (4 to 6 mg/kg, IV) and isoflurane for 30 minutes before determination of MAC of isoflurane. Isoflurane MAC values were determined 4 times, separated by a minimum of 7 days, before and after IV administration of perzinfotel (0 [control], 5, 10, and 20 mg/kg). Bispectral index and percentage hemoglobin saturation with oxygen (SpO2) were monitored throughout anesthesia.
Results—Isoflurane MAC was 1.32 ± 0.14%. Intravenous administration of perzinfotel at 0, 5, 10, and 20 mg/kg decreased isoflurane MAC by 0%, 24%, 30%, and 47%, respectively. Perzinfotel significantly decreased isoflurane MAC values, compared with baseline and control values. The bispectral index typically increased with higher doses of perzinfotel and lower isoflurane concentrations, but not significantly. Heart rate, body temperature, and SpO2 did not change, but systolic, mean, and diastolic arterial blood pressures significantly increased with decreases in isoflurane MAC after administration of perzinfotel at 10 and 20 mg/kg, compared with 0 and 5 mg/kg.
Conclusions and Clinical Relevance—IV administration of perzinfotel decreased isoflurane MAC values. Improved hemodynamics were associated with decreases in isoflurane concentration.
Use of bispectral index to monitor depth of anesthesia in isoflurane-anesthetized dogs
Authors: Campagnol Daniela , Teixeira Neto Francisco J. , Monteiro Eduardo R. , Beier Suzane L. , Aguiar Antônio J. A. 
Published: December 2007

Abstract
Objective—To evaluate the correlation between the bispectral index (BIS) and end-tidal isoflurane (ETISO) concentration and compare the use of 3 BIS sensor positions in dogs.
Animals—6 adult dogs.
Procedures—Mechanically ventilated dogs received pancuronium, and depth of anesthesia was altered by increasing ETISO concentration from 1.5% to 2.3% and 3.0%. The BIS, suppression ratio (relative percentage of isoelectric electroencephalographic waveforms), and signal quality index (SQI) were recorded at each ETISO concentration for each of 3 BIS sensor positions (frontal-occipital, bifrontal, and frontal-temporal positions).
Results—The BIS and ETISO concentration were poorly correlated; regardless of sensor positioning, mean BIS values did not change significantly as ETISO was increased. At 3% isoflurane, regardless of sensor positioning, there was an increase in suppression ratio coincident with BIS < 40 in some dogs, whereas paradoxic increases in BIS (> 60) were recorded in others. Furthermore, at 3.0% isoflurane, the SQI was significantly lower for the bifrontal sensor position (compared with values for the other positions), but low SQI values prevented recording of BIS values from the frontal-occipital sensor position in 2 dogs. Overall, BIS values derived from the 3 sensor positions did not differ.
Conclusions and Clinical Relevance—In dogs, BIS values may not reflect changes in depth of isoflurane anesthesia in the absence of noxious stimulation. Of the 3 sensor positions, frontal-temporal positioning provided better correlation with changes in depth of anesthesia induced via changes in isoflurane concentrations. However, the sensor placements yielded similar results at SQI values > 50.
Evaluation of the influences of exercise, birth date, and osteochondrosis on plasma bone marker concentrations in Hanoverian Warmblood foals
Authors: Vervuert Ingrid , Winkelsett Sarah , Christmann Ludwig , Bruns Erich , Hoppen Hans-Otto , Distl Ottmar , Hertsch Bodo , Coenen Manfred 
Published: December 2007

Abstract
Objective—To determine whether plasma concentrations of bone turnover markers in growing Hanoverian foals are influenced by age, housing conditions, or osteochondrosis.
Animals—165 healthy foals and 119 foals with osteochondrosis.
Procedures—Foals were allocated according to birth date and housing management into groups of early-born (born before March 31, 2001; n = 154 foals, 88 of which were healthy and 66 of which had osteochondrosis) and late-born (born after March 31, 2001; 130 foals, 77 of which were healthy and 53 of which had osteochondrosis) foals. Plasma osteocalcin and carboxyterminal propeptide of type I collagen concentrations were analyzed as markers of bone formation, and carboxyterminal telopeptide of type I collagen concentration was analyzed as a marker of bone resorption. Foals underwent radiographic evaluation to screen for osteochondrosis.
Results—Plasma concentrations of osteocalcin, carboxyterminal propeptide of type I collagen, and carboxyterminal telopeptide of type I collagen decreased with age, but these changes were more distinct in late-born foals than in early-born foals. Neither sex nor predisposition to develop osteochondrosis affected the pattern of bone marker changes in either group.
Conclusions and Clinical Relevance—An age-related decrease in concentrations of bone markers was seen during the first 200 days of life. Changes in bone marker concentrations were similar for foals with osteochondrosis and healthy foals. The correlation between the decrease in bone marker concentration and date of birth indicates that there are differences in skeletal development between early- and late-born foals.
Effect of conformation of the distal portion of the femur and proximal portion of the tibia on the pathogenesis of cranial cruciate ligament disease in dogs
Authors: Guerrero Tomás G. , Geyer Hans , Hässig Michael , Montavon Pierre M. 
Published: December 2007

Abstract
Objective—To evaluate mediolateral radiographic views of stifle joints to identify conforma-tional differences between athletically sound dogs and dogs with cranial cruciate ligament disease (CCLD).
Sample Population—Radiographic images of 50 stifle joints of 43 dogs with surgically confirmed CCLD and 50 stifle joints of 38 dogs without clinical signs of stifle joint disease.
Procedures—Mediolateral radiographic views of stifle joints were obtained, and long axes of the femur, tibia, and femoral condyles were measured. Angles between long axes of the femur and femoral condyle and between long axes of the femur and tibia were measured. Circles were drawn representing the joint surface of femoral condyles (circle 1), area of contact on the tibial plateau (circle 2), and femoral trochlea (circle 3). Radii of circles 1, 2 (line F), and 3 were measured. Distances between midpoints of circles 1 and 2 (line K) and between midpoint of circle 2 and most cranial aspect of the tibial tuberosity (line G) were measured. To evaluate differences in conformation that could lead to CCLD, quotients derived from measurements were created for comparison; angles were compared between dog groups.
Results—Significant differences were found in the quotients created by the lengths of lines G and F and lines G and K between dogs with and without CCLD.
Conclusions and Clinical Relevance—No anatomic differences were detected in the distal portion of the femur between dogs with and without CCLD. Development of the tibial tuberosity and shape (convexity) of tibial condyles may be relevant in the pathogenesis of CCLD.
Alteration of release and role of adenosine diphosphate and thromboxane A2 during collagen-induced aggregation of platelets from cattle with Chediak-Higashi syndrome
Authors: Honda Naofumi , Ohnishi Katsuyuki , Fujishiro Tsuyoshi , Ikeda Masahiro , Ito Katsuaki 
Published: December 2007

Abstract
Objective—To compare the interaction of endogenous ADP with collagen and thromboxane A2 (TXA2) during collagen-induced platelet aggregation between platelets from healthy cattle and those with Chediak-Higashi syndrome (CHS).
Population Sample—Platelets harvested from blood samples from healthy Japanese Black cattle and those with CHS.
Procedures—Aggregation of gel-filtered platelets; release of ATP-ADP; and generation of thromboxane B2 (TXB2), a metabolite of TXA2, were measured.
Results—The potency of collagen to induce aggregation in platelets of cattle with CHS (ie, CHS platelets) was less than a tenth of that in platelets of healthy cattle (ie, control platelets). Platelet aggregation induced by collagen at an intermediate concentration depended on the coexistence of ADP and TXA2, suggesting that released ADP cannot cause platelet aggregation by itself. Collagen-induced ADP release was markedly decreased, whereas TXB2 production was slightly low in CHS platelets, compared with that in control platelets. A combination of subthreshold amounts of ADP and 9,11-dideoxy-9α, 11α-methano-epoxy-prostaglandin F2α (U46619), a TXA2 analogue, caused platelet aggregation. Similarly, a combination of subthreshold amounts of collagen and ADP caused platelet aggregation, whereas collagen and U46619 were not synergistic.
Conclusions and Clinical Relevance—Deficient ADP release ensuing from the δ-storage pool deficiency in platelets from cattle with CHS resulted in reduction of collagen-induced platelet aggregation, through attenuation of synergism between TXA2 and ADP and between ADP and collagen. Furthermore, results of the study reported here indicated that TXA2 was important for aggregation of bovine platelets.
Inside Front Cover: Polymer–Silicon Flexible Structures for Fast Chemical Vapor Detection (Adv. Mater. 23/2007)
Authors: Singamaneni S. , McConney M. E. , LeMieux M. C. , Jiang H. , Enlow J. O. , Bunning T. J. , Naik R. R. , Tsukruk V. V. 
Published: November 2007

AbstractVladimir Tsukruk and co‐workers demonstrate on p. 4248 the application of plasma‐polymerized organic/silicon bimaterial structures as highly sensitive and agile chemical sensors. Owing to their unique nanoscale topology, highly crosslinked structure, and precise choice of the precursors, polymer films coated on microcantilevers exhibited record sensitivity to water vapor and other volatile organic compounds in conjunction with fast response times. The inside cover image by Brian Schrank shows the bimaterial structure deflection in the presence of a stimuli vapor.
Involvement of protein kinase Cζ in interleukin‐1β induction of ADAMTS‐4 and type 2 nitric oxide synthase via NF‐κB signaling in primary human osteoarthritic chondrocytes
Authors: Chockalingam Priya S. , Varadarajan Usha , Sheldon Richard , Fortier Eric , LaVallie Edward R. , Morris Elisabeth A. , Yaworsky Paul J. , Majumdar Manas K. 
Published: November 2007

AbstractObjectiveProtein kinase Cζ (PKCζ), an atypical PKC, has been found to be transcriptionally up‐regulated in human osteoarthritic (OA) articular cartilage. This study was undertaken to examine the role of PKCζ in interleukin‐1β (IL‐1β)–induced NF‐κB signaling in human OA chondrocytes, and ultimately to better understand its function in the regulation of downstream mediators of cartilage matrix degradation.MethodsPharmacologic inhibitors or genetic knockdown techniques were used to investigate the role of PKCζ. Western blot analysis was used to evaluate phosphorylation of PKCζ and NF‐κB. Quantitative polymerase chain reaction (PCR) and activity assays were used to evaluate ADAMTS‐4 expression and aggrecanase activity, respectively. Quantitative PCR, biochemical identification, and Western blot analysis were used to evaluate type 2 nitric oxide synthase (NOS2) and NO production.ResultsPhosphorylation of PKCζ and NF‐κB was induced by IL‐1β treatment in a time‐dependent manner, and was specifically inhibited by inhibitors of atypical PKCs. Inhibition of PKCζ suppressed IL‐1β–induced up‐regulation of ADAMTS‐4 messenger RNA (mRNA) and aggrecanase activity. Inhibitors of atypical PKCs also inhibited IL‐1β–induced NO production and NOS2 mRNA expression, demonstrating a novel link between PKCζ and NO production. Furthermore, small interfering RNA– or short hairpin RNA–mediated knockdown of PKCζ mRNA resulted in significant repression of both ADAMTS‐4 and NOS2 mRNA expression.ConclusionOur results show that PKCζ is involved in the regulation of IL‐1β–induced NF‐κB signaling in human OA chondrocytes, which in turn regulates downstream expression of ADAMTS‐4 and NOS2. Therefore, inhibition of PKCζ could potentially regulate the production of matrix‐degrading enzymes as well as NO production and have a profound effect on disease progression in OA.
Adalimumab significantly reduces both spinal and sacroiliac joint inflammation in patients with ankylosing spondylitis: A multicenter, randomized, double‐blind, placebo‐controlled study
Authors: Lambert Robert G. W. , Salonen David , Rahman Proton , Inman Robert D. , Wong Robert L. , Einstein Steven G. , Thomson Glen T. D. , Beaulieu Andre , Choquette Denis , Maksymowych Walter P. 
Published: November 2007

AbstractObjectiveTo compare the efficacy of adalimumab versus placebo in reducing spinal and sacroiliac (SI) joint inflammation, by magnetic resonance imaging (MRI) in patients with active ankylosing spondylitis (AS).MethodsThis was a randomized, multicenter, double‐blind, placebo‐controlled study. Patients (n = 82) received 40 mg adalimumab or placebo every other week during an initial 24‐week double‐blind period. MRIs of both the spine and SI joints were obtained at baseline, week 12, and week 52. Spinal and SI joint inflammation were measured using the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index.ResultsThe spine SPARCC score in placebo‐treated patients increased by a mean of 9.4% from baseline, compared with a mean decrease of 53.6% in adalimumab‐treated patients (P < 0.001); the SI joint SPARCC score decreased by a mean of 12.7% from baseline in placebo‐treated patients and by 52.9% in adalimumab‐treated patients (P = 0.017). The response in adalimumab‐treated patients was maintained at week 52. Placebo‐treated patients were switched to open‐label adalimumab treatment at week 24 and experienced similar reductions in spinal and SI joint inflammation by week 52. Similar large reductions in the spine and SI joint SPARCC scores were noted, even in patients who failed to meet the ASsessment in Ankylosing Spondylitis (International Working Group) criteria (nonresponders) at 12 weeks. In adalimumab‐treated patients, a reduced C‐reactive protein concentration at week 12 was significantly associated with improvement in the spine SPARCC score (P = 0.018).ConclusionAdalimumab significantly reduced both spinal and SI joint inflammation in patients with active AS after 12 weeks of treatment, and these improvements were maintained for up to 52 weeks.
Treatment of early rheumatoid arthritis: A randomized magnetic resonance imaging study comparing the effects of methotrexate alone, methotrexate in combination with infliximab, and methotrexate in combination with intravenous pulse methylprednisolone
Authors: Durez Patrick , Malghem Jacques , Toukap Adrien Nzeusseu , Depresseux Geneviève , Lauwerys Bernard R. , Westhovens René , Luyten Frank P. , Corluy Luc , Houssiau Frédéric A. , Verschueren Patrick 
Published: November 2007

AbstractObjectiveTo compare the effects of methotrexate (MTX), alone or in combination with intravenous (IV) methylprednisolone (MP) or infliximab, on magnetic resonance imaging (MRI)–detected synovitis, bone edema, and erosive changes in patients with early rheumatoid arthritis (RA).MethodsForty‐four patients with early RA were randomized to receive MTX alone (MTX group), MTX plus IV MP (IV MP group), or MTX plus infliximab (infliximab group), infused on day 0 and weeks 2, 6, 14, 22, 30, 38, and 46. Gadolinium‐enhanced MRI scans of the metacarpophalangeal joints, wrists, and metatarsophalangeal joints were performed at baseline, week 18, and week 52.ResultsScores for MRI‐detected synovitis and bone edema improved over time in the 3 groups, with significantly lower synovitis scores in the infliximab group compared with the MTX group and significantly lower bone edema scores in the infliximab group compared with the MTX and the IV MP groups. Scores for MRI‐detected erosion significantly increased over time in all groups. There were no differences in erosion scores between the MTX group and the other groups. It is of note that patients treated with IV MP showed more significant progression in MRI‐detected erosions compared with patients treated with infliximab. At week 22, response rates according to the American College of Rheumatology 20% improvement criteria (ACR20), the ACR50, and the ACR70 were significantly higher in both the IV MP group and the infliximab group compared with the MTX group. At week 52, remission was achieved in 40% of patients in the MTX group and in 70% of patients in the IV MP and infliximab groups. Health Assessment Questionnaire scores improved significantly over time in all groups, with patients receiving IV MP experiencing significantly more improvement compared with patients treated with MTX alone. No severe side effects were observed, except 1 case of MTX‐related pneumonitis.ConclusionThe combination of MTX and infliximab is superior to MTX alone for reducing MRI‐detected signs of synovitis and bone edema in patients with early RA. Progression of MRI‐detected erosion was greater in patients treated with MTX plus IV MP compared with that in patients who received MTX plus infliximab.
Role of hypoxia and cAMP in the transdifferentiation of human fetal cardiac fibroblasts: Implications for progression to scarring in autoimmune‐associated congenital heart block
Authors: Clancy Robert M. , Zheng Ping , O'Mahony Marguerita , Izmirly Peter , Zavadil Jiri , Gardner Lawrence , Buyon Jill P. 
Published: November 2007

AbstractObjectiveIdentification of isolated congenital heart block (CHB) predicts, with near certainty, the presence of maternal anti‐SSA/Ro antibodies; however, the 2% incidence of CHB in first offspring of anti‐SSA/Ro+ mothers, 20% recurrence in subsequent pregnancies, and discordance in identical twins suggest that an environmental factor amplifies the effect of the antibody. Accordingly, this study was carried out to explore the hypothesis that hypoxia potentiates a profibrosing phenotype of the fetal cardiac fibroblast.MethodsEvidence of an effect of hypoxia was sought by immunohistologic evaluation of CHB‐affected fetal heart tissue and by determination of erythropoietin levels in cord blood. The in vitro effect of hypoxia on gene expression and phenotype in fibroblasts derived from fetal hearts and lungs was investigated by Affymetrix arrays, quantitative polymerase chain reaction (PCR), immunofluorescence, and immunoblotting.ResultsIn vivo hypoxic exposure was supported by the prominent intracellular fibroblast expression of hypoxia‐inducible factor 1α in conduction tissue from 2 fetuses in whom CHB led to death. The possibility that hypoxia was sustained was suggested by significantly elevated erythropoietin levels in cord blood from CHB‐affected, as compared with unaffected, anti‐SSA/Ro–exposed neonates. In vitro exposure of cardiac fibroblasts to hypoxia resulted in transdifferentiation to myofibroblasts (a scarring phenotype), as demonstrated on immunoblots and immunofluorescence by increased expression of smooth muscle actin (SMA), an effect not seen in lung fibroblasts. Hypoxia‐exposed cardiac fibroblasts expressed adrenomedullin at 4‐fold increased levels, as determined by Affymetrix array, quantitative PCR, and immunofluorescence, thus focusing attention on cAMP as a modulator of fibrosis. MDL12,330A, an adenylate cyclase inhibitor that lowers the levels of cAMP, increased expression of fibrosis‐related proteins (mammalian target of rapamycin, SMA, plasminogen activator inhibitor type 1, and type I collagen), while the cAMP activator forskolin attenuated transforming growth factor β–elicited fibrosing end points in the cardiac fibroblasts.ConclusionThese findings provide evidence that hypoxia may amplify the injurious effects of anti‐SSA/Ro antibodies. Modulation of cAMP may be a key component in the scarring phenotype. Further assessment of the susceptibility of cardiac fibroblasts to cAMP modulation offers a new research direction in CHB.