bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of Nonfinancial Performance Measures with the Financial Performance of a Lodging Chain
Authors: Banker Rajiv D. , Potter Gordon , Srinivasan Dhinu
Published: October 2005

A test of nonfinancial measures used as part of a management-incentive program by a U.S.-based, full-service hotel chain found that improvements in the nonfinancial measures were followed shortly by increases in revenue and profit. The two nonfinancial measures are customer satisfaction as measured by guests’ comment card indications of likelihood to return and level of complaints. The lag between the nonfinancial measures and changes in revenue and operating profit was six months in this case. While the test applies directly to that one chain, the lesson is important to the rest of the hotel industry.
The Use of Fixed-rate and Floating-rate Debt for Hotels
Authors: Corgel John B. (Jack) , Gibson Scott
Published: October 2005

A time-series simulation that compares hotel-industry revenue per available room (RevPAR) with London Interbank Offer Rate (LIBOR) indicates that hotel investors would fare more favorably with floating-rate loans than with the commonly used fixed-rate financing. Using data from 1987 through 2004, the study determined that LIBOR and RevPAR changes are strongly correlated, indicating a relationship of RevPAR and floating interest rates. Moreover, a simulation found that hotels using variable-rate mortgages would have been more likely to cover debt service in good times and bad than would hotels financed with fixed-rate loans. The correlation was strongest for midscale, limited-service properties but also operated for budget and resort deals. The relationship of RevPAR with floating rates suggests a reduction in the costs to borrowers and lenders arising from distressed loans.
Effects of Local Administration of Vascular Endothelial Growth Factor on Properties of the in Situ Frozen-Thawed Anterior Cruciate Ligament in Rabbits
Authors: Ju Young-Jin , Tohyama Harukazu , Kondo Eiji , Yoshikawa Toshikazu , Muneta Takeshi , Shinomiya Kenichi , Yasuda Kazunori
Published: October 2005

Background

In the autogenous tendon for anterior cruciate ligament reconstruction, intrinsic fibroblasts are necrotized immediately after surgery, and repopulation and revascularization occur. Vascular endothelial growth factor is considered to be a potent mediator of angiogenesis.

Hypothesis

An application of vascular endothelial growth factor significantly enhances angiogenesis in the in situ frozen anterior cruciate ligament, and the application significantly affects mechanical properties of the in situ frozen anterior cruciate ligament.

Study Design

Controlled laboratory study.

Methods

Right anterior cruciate ligaments from 66 rabbits underwent the freeze-thaw treatment, and animals were then divided into 3 groups. Group I served as a freeze-thaw but otherwise untreated control. In group II, 0.2 mL phosphate-buffered saline alone was applied. In group III, 30 µ g vascular endothelial growth factor was applied. The groups were compared on the basis of histologic revascularization examinations using the Chalkley score, an indicator of the microvessel density, and mechanical evaluations, which included the anterior-posterior translation of the tibia relative to the femur during ± 10 N of anterior-posterior load and the mechanical properties of the anteromedial bundle of the anterior cruciate ligament.

Results

Group III's Chalkley score was significantly greater than that of groups I and II. The tensile strength and the tangent modulus of anterior cruciate ligaments in groups I, II, and III were significantly lower than those of a normal anterior cruciate ligament, although there were no significant differences among groups I, II, and III.

Conclusion

Vascular endothelial growth factor, as administered in this study, significantly promoted angiogenesis in the devitalized anterior cruciate ligament with in situ freeze-thaw treatment, but it did not affect the mechanical properties of the in situ frozen-thawed anterior cruciate ligament in the rabbit model.

Clinical Relevance

An application of the recombinant anterior cruciate ligament is a potential future strategy to enhance revascularization of the autograft in anterior cruciate ligament reconstruction.
Arthroscopic Single-Row versus Double-Row Suture Anchor Rotator Cuff Repair
Authors: Mazzocca Augustus D. , Millett Peter J. , Guanche Carlos A. , Santangelo Stephen A. , Arciero Robert A.
Published: October 2005

Background

Recurrent defects after open and arthroscopic rotator cuff repair are common. Double-row repair techniques may improve initial fixation and quality of rotator cuff repair.

Purpose

To evaluate the load to failure, cyclic displacement, and anatomical footprint of 4 arthroscopic rotator cuff repair techniques.

Hypothesis

Double-row suture anchor repair would have superior structural properties and would create a larger footprint compared to single-row repair.

Study Design

Controlled laboratory study.

Methods

Twenty fresh-frozen cadaveric shoulders were randomly assigned to 4 arthroscopic repair techniques. The repair was performed as either a single-row technique or 1 of 3 double-row techniques: diamond, mattress double anchor, or modified mattress double anchor. Angle of loading, anchor type, bone mineral density, anchor distribution, angle of anchor insertion, arthroscopic technique, and suture type and size were all controlled. Footprint length and width were quantified before and after repair. Displacement with cyclic loading and load to failure were determined.

Results

There were no differences in load to failure and displacement with cyclic loading between the single-row repair and each double-row repair. All repair groups demonstrated load to failure greater than 250 N. A significantly greater supraspinatus footprint width was seen with double-row techniques compared to single-row repair.

Conclusions

The single-row repair technique was similar to the double-row techniques in load to failure, cyclic displacement, and gap formation. The double-row anchor repairs consistently restored a larger footprint than did the single-row method.

Clinical Relevance

The arthroscopic techniques studied have strong structural properties that approached the reported performance of open repair techniques. Double-row techniques provide a larger footprint width; although not addressed by this study, such a factor may improve the biological quality of repair.
Effect of Gender and Maturity on Quadriceps-to-Hamstring Strength Ratio and Anterior Cruciate Ligament Laxity
Authors: Ahmad Christopher S. , Clark A. Martin , Heilmann Niels , Schoeb J. Scott , Gardner Thomas R. , Levine William N.
Published: October 2005

Background

Exercise programs have been introduced to reduce the ACL injury risk in female athletes. The most effective age at which to start these programs is not known.

Hypothesis

Age and gender affect ligament laxity and quadriceps-to-hamstring strength ratio.

Study Design

Cross-sectional study; Level of evidence, 3.

Methods

Fifty-three female and 70 male recreational soccer players, 10 to 18 years of age, were studied with physical examination, KT-1000 arthrometry, and manual maximum quadriceps and hamstring strength using a handheld dynamometer. The subjects were separated into 4 groups to examine maturity-related intergender differences: group G1, premenarchal girls (n = 24); group B1, boys 13 years and younger (n = 38); group G2, girls 2 or more years after menarche (n = 29); and group B2, boys 14 years and older (n = 32).

Results

Both knees of 123 soccer players were evaluated. The mean ages for groups G1, B1, G2, and B2 were 11.50 ± 1.69, 10.63 ± 1.85, 15.5 ± 1.43, and 15.59 ± 1.24 years, respectively, and the mean laxity measurements were 8.84 ± 2.12, 8.51 ± 1.61, 8.85 ± 1.86, and 7.33 ± 1.27 mm, respectively. Laxity was significantly less for the mature boys (P= .0015) than for the immature boys, mature girls, and immature girls. With increasing maturity, significant increases in both quadriceps and hamstring muscle strength were observed for both boys and girls (P< .05). Boys demonstrated a greater percentage increase in hamstring strength with maturity (179%) compared with girls (27%) (P< .05). Mature girls (2.06) had significantly greater quadriceps-tohamstring ratio when compared with immature girls (1.74), immature boys (1.58), and mature boys (1.48) (P< .05).

Conclusion

Female athletes after menarche increase their quadriceps strength greater than their hamstring strength, putting them at risk for anterior cruciate ligament injury. Anterior cruciate ligament–prevention programs based on improving dynamic control of the knee by emphasizing hamstring strengthening should be instituted for girls after menarche.
Antibody-induced neutrophil activation as a trigger for transfusion-related acute lung injury in an ex vivo rat lung model
Authors: Sachs Ulrich J. H. , Hattar Katja , Weissmann Norbert , Bohle Rainer M. , Weiss Timo , Sibelius Ulf , Bux Juergen
Published: October 2005

Transfusion-related acute lung injury (TRALI) is a hazardous complication of transfusion and has become the leading cause of transfusion-related death in the United States and United Kingdom. Although leukoagglutinating antibodies have been frequently shown to be associated with the syndrome, the mechanism by which they induce TRALI is poorly understood. Therefore, we reproduced TRALI in an ex vivo rat lung model. Our data demonstrate that TRALI induction by antileukocyte antibodies is dependent on the density of the cognate antigen but does not necessarily require leukoagglutinating properties of the antibody or the presence of complement proteins. Rather, antibody-mediated activation of neutrophils seems to initiate TRALI, a process that could be triggered by neutrophil stimulation with fMLP. Antibody-mediated neutrophil activation and subsequent release of reactive oxygen species may thus represent key events in the pathophysiologic cascade that leads to immune TRALI.
Developmental and functional significance of the CSF-1 proteoglycan chondroitin sulfate chain
Authors: Nandi Sayan , Akhter Mohammed P. , Seifert Mark F. , Dai Xu-Ming , Stanley E. Richard
Published: October 2005

The primary macrophage growth factor, colony-stimulating factor-1 (CSF-1), is homodimeric and exists in 3 biologically active isoforms: a membrane-spanning, cell-surface glycoprotein (csCSF-1) and secreted glycoprotein (sgCSF-1) and proteoglycan (spCSF-1) isoforms. To investigate the in vivo role of the chondroitin sulfate glycosaminoglycan (GAG) chain of spCSF-1, we created mice that exclusively express, in a normal tissue-specific and developmental manner, either the secreted precursor of spCSF-1 or the corresponding precursor in which the GAG addition site was mutated. The reproductive, hematopoietic tooth eruption and tissue macrophage defects of CSF-1-deficient, osteopetrotic Csf1op/Csf1op mice were corrected by transgenic expression of the precursors of either sgCSF-1 or spCSF-1. Furthermore, in contrast to the transgene encoding csCSF-1, both failed to completely correct growth retardation, suggesting a role for csCSF-1 in the regulation of body weight. However, spCSF-1, in contrast to sgCSF-1, completely resolved the osteopetrotic phenotype. Furthermore, in transgenic lines expressing different concentrations of sgCSF-1 or spCSF-1, spCSF-1 more efficiently corrected Csf1op/Csf1op defects of tooth eruption, eyelid opening, macrophage morphology, and B-cell deficiency than sgCSF-1. These results indicate an important role of the CSF-1 chondroitin sulfate proteoglycan in in vivo signaling by secreted CSF-1. (Blood. 2006;107:786-795)
A novel bispecific protein (ULBP2-BB4) targeting the NKG2D receptor on natural killer (NK) cells and CD138 activates NK cells and has potent antitumor activity against human multiple myeloma in vitro and in vivo
Authors: von Strandmann Elke Pogge , Hansen Hinrich P. , Reiners Katrin S. , Schnell Roland , Borchmann Peter , Merkert Sabine , Simhadri Venkateswara R. , Draube Andreas , Reiser Marcel , Purr Ingvill , Hallek Michael , Engert Andreas
Published: October 2005

The inability of the immune system to recognize and kill malignant plasma cells in patients with multiple myeloma (MM) has been attributed in part to the ineffective activation of natural killer (NK) cells. In order to activate and target NK cells to the malignant cells in MM we designed a novel recombinant bispecific protein (ULBP2-BB4). While ULBP2 binds the activating NK receptor NKG2D, the BB4 moiety binds to CD138, which is overexpressed on a variety of malignancies, including MM. ULBP2-BB4 strongly activated primary NK cells as demonstrated by a significant increase in interferon-γ (IFN-γ) secretion. In vitro, ULBP2-BB4 enhanced the NK-mediated lysis of 2 CD138+ human MM cell lines, U-266 and RPMI-8226, and of primary malignant plasma cells in the allogenic and autologous setting. Moreover, in a nude mouse model with subcutaneously growing RPMI-8226 cells, the cotherapy with ULBP-BB4 and human peripheral blood lymphocytes abrogated the tumor growth. These data suggest potential clinical use of this novel construct in patients with MM. The use of recombinant NK receptor ligands that target NK cells to tumor cells might offer new approaches for other malignancies provided a tumor antigen-specific antibody is available.
Von Hippel-Lindau–dependent polycythemia is endemic on the island of Ischia: identification of a novel cluster
Authors: Perrotta Silverio , Nobili Bruno , Ferraro Marcella , Migliaccio Carmela , Borriello Adriana , Cucciolla Valeria , Martinelli Vincenzo , Rossi Francesca , Punzo Francesca , Cirillo Paola , Parisi Giuseppe , Zappia Vincenzo , Rotoli Bruno , Ragione Fulvio Della
Published: October 2005

Chuvash polycythemia (MIM 263400) is an autosomal recessive disorder characterized by a high hemoglobin level, relatively high serum erythropoietin, and early death. It results from a Von Hippel-Lindau (VHL) gene mutation (C598T) that causes increased HIF-1α activity and erythrocyte production in the face of normoxia. This polycythemia is endemic in Chuvashia, whereas its worldwide frequency is very low. We investigated the incidence of the Chuvash-type VHL mutation in Campania (South Italy) and identified 14 affected subjects (5 families). Twelve live on the island of Ischia (Bay of Naples). From analysis of the mutated allele, we found that the disease was more frequent on Ischia (0.070) than in Chuvashia (0.057). The haplotype of all patients matched that identified in the Chuvash cluster, thereby supporting the single-founder hypothesis. We also found that nonaffected heterozygotes had increased HIF-1α activity, which might confer a biochemical advantage for mutation maintenance. In conclusion, we have identified the first large cluster of Chuvash erythrocytosis outside Chuvashia, which suggests that this familial polycythemia might be endemic in other regions of the world.
l-arginine import via cationic amino acid transporter CAT1 is essential for both differentiation and proliferation of erythrocytes
Authors: Shima Yoichiro , Maeda Tomoji , Aizawa Shin , Tsuboi Isao , Kobayashi Daisuke , Kato Ryo , Tamai Ikumi
Published: October 2005

In the present study, we examined the role in hematopoiesis of cationic amino acid transporter 1 (CAT1), which transports l-arginine, l-lysine, l-ornithine, and l-histidine. The expression level of human CAT1 (hCAT1) mRNA in mononuclear cells (MNCs) fractionated according to lineage-selective markers was examined by reverse transcriptase-polymerase chain reaction. The expression of CAT1 in glycophorin A-positive erythroid cells was 8 times higher than in nonfractionated MNC (control) cells. Characteristics of l-arginine uptake by K562 cells, an established leukemic cell line used as an erythroid model, were similar to those of CAT1 in regards to saturation kinetics, sodium independence, and substantial inhibition of l-arginine uptake by N-ethylmaleimide, which is a specific inhibitor of system y+ amino acid transporter. Removal of l-arginine from the culture medium prevented both proliferation and differentiation of K562 cells, while removal of l-lysine or l-histidine had little effect on differentiation, though proliferation was blocked. Hematopoietic stem cells obtained from human cord blood failed to develop into erythroid cells in the absence of l-arginine in the culture medium. These findings indicate that hCAT1 is involved in erythroid hematopoiesis through its role in importing l-arginine, which appears to be essential for the differentiation of red blood cells.
ASPIC: a novel method to predict the exon-intron structure of a gene that is optimally compatible to a set of transcript sequences
Authors: Bonizzoni Paola , Rizzi Raffaella , Pesole Graziano
Published: October 2005

Background:

Currently available methods to predict splice sites are mainly based on the independent and progressive alignment of transcript data (mostly ESTs) to the genomic sequence. Apart from often being computationally expensive, this approach is vulnerable to several problems – hence the need to develop novel strategies.

Results:

We propose a method, based on a novel multiple genome-EST alignment algorithm, for the detection of splice sites. To avoid limitations of splice sites prediction (mainly, over-predictions) due to independent single EST alignments to the genomic sequence our approach performs a multiple alignment of transcript data to the genomic sequence based on the combined analysis of all available data. We recast the problem of predicting constitutive and alternative splicing as an optimization problem, where the optimal multiple transcript alignment minimizes the number of exons and hence of splice site observations.

We have implemented a splice site predictor based on this algorithm in the software tool ASPIC (Alternative Splicing PredICtion). It is distinguished from other methods based on BLAST-like tools by the incorporation of entirely new ad hoc procedures for accurate and computationally efficient transcript alignment and adopts dynamic programming for the refinement of intron boundaries. ASPIC also provides the minimal set of non-mergeable transcript isoforms compatible with the detected splicing events. The ASPIC web resource is dynamically interconnected with the Ensembl and Unigene databases and also implements an upload facility.

Conclusion:

Extensive bench marking shows that ASPIC outperforms other existing methods in the detection of novel splicing isoforms and in the minimization of over-predictions. ASPIC also requires a lower computation time for processing a single gene and an EST cluster. The ASPIC web resource is available at http://aspic.algo.disco.unimib.it/aspic-devel/.
The stress response against denatured proteins in the deletion of cytosolic chaperones SSA1/2 is different from heat-shock response in Saccharomyces cerevisiae
Authors: Matsumoto Rena , Akama Kuniko , Rakwal Randeep , Iwahashi Hitoshi
Published: October 2005

Background

A yeast strain lacking the two genes SSA1 and SSA2, which encode cytosolic molecular chaperones, acquires thermotolerance as well as the mild heat-shocked wild-type yeast strain. We investigated the genomic response at the level of mRNA expression to the deletion of SSA1/2 in comparison with the mild heat-shocked wild-type using cDNA microarray.

Results

Yeast cDNA microarray analysis revealed that genes involved in the stress response, including molecular chaperones, were up-regulated in a similar manner in both the ssa1/2 deletion mutant and the mild heat-shocked wild-type. Genes involved in protein synthesis were up-regulated in the ssa1/2 deletion mutant, but were markedly suppressed in the mild heat-shocked wild-type. The genes involved in ubiquitin-proteasome protein degradation were also up-regulated in the ssa1/2 deletion mutant, whereas the unfolded protein response (UPR) genes were highly expressed in the mild heat-shocked wild-type. RT-PCR confirmed that the genes regulating protein synthesis and cytosolic protein degradation were up-regulated in the ssa1/2 deletion mutant. At the translational level, more ubiquitinated proteins and proteasomes were detected in the ssa1/2 deletion mutant, than in the wild-type, confirming that ubiquitin-proteasome protein degradation was up-regulated by the deletion of SSA1/2.

Conclusion

These results suggest that the mechanism for rescue of denatured proteins in the ssa1/2 deletion mutant is different from that in the mild heat-shocked wild-type: Activated protein synthesis in the ssa1/2 deletion mutant supplies a deficiency of proteins by their degradation, whereas mild heat-shock induces UPR.
The two authentic methionine aminopeptidase genes are differentially expressed in Bacillus subtilis
Authors: You CongHui , Lu HongYan , Sekowska Agnieszka , Fang Gang , Wang YiPing , Gilles Anne-Marie , Danchin Antoine
Published: October 2005

Background

Two putative methionine aminopeptidase genes, map (essential) and yflG (non-essential), were identified in the genome sequence of Bacillus subtilis. We investigated whether they can function as methionine aminopeptidases and further explored possible reasons for their essentiality or dispensability in B. subtilis.

Results

In silico analysis of MAP evolution uncovered a coordinated pattern of MAP and deformylase that did not correlate with the pattern of 16S RNA evolution. Biochemical assays showed that both MAP (MAP_Bs) and YflG (YflG_Bs) from B. subtilis overproduced in Escherichia coli and obtained as pure proteins exhibited a methionine aminopeptidase activity in vitro. Compared with MAP_Bs, YflG_Bs was approximately two orders of magnitude more efficient when assayed on synthetic peptide substrates. Both map and yflG genes expressed in multi-copy plasmids could complement the function of a defective map gene in the chromosomes of both E. coli and B. subtilis. In contrast, lacZ gene transcriptional fusions showed that the promoter activity of map was 50 to 100-fold higher than that of yflG. Primer extension analysis detected the transcription start site of the yflG promoter. Further work identified that YvoA acted as a possible weak repressor of yflG expression in B. subtilis in vivo.

Conclusion

Both MAP_Bs and YflG_Bs are functional methionine aminopeptidases in vitro and in vivo. The high expression level of map and low expression level of yflG may account for their essentiality and dispensality in B. subtilis, respectively, when cells are grown under laboratory conditions. Their difference in activity on synthetic substrates suggests that they have different protein targets in vivo.
PineappleDB: An online pineapple bioinformatics resource
Authors: Moyle Richard L , Crowe Mark L , Ripi-Koia Jonni , Fairbairn David J , Botella José R
Published: October 2005

Background

A world first pineapple EST sequencing program has been undertaken to investigate genes expressed during non-climacteric fruit ripening and the nematode-plant interaction during root infection. Very little is known of how non-climacteric fruit ripening is controlled or of the molecular basis of the nematode-plant interaction. PineappleDB was developed to provide the research community with access to a curated bioinformatics resource housing the fruit, root and nematode infected gall expressed sequences.

Description

PineappleDB is an online, curated database providing integrated access to annotated expressed sequence tag (EST) data for cDNA clones isolated from pineapple fruit, root, and nematode infected root gall vascular cylinder tissues. The database currently houses over 5600 EST sequences, 3383 contig consensus sequences, and associated bioinformatic data including splice variants, Arabidopsis homologues, both MIPS based and Gene Ontology functional classifications, and clone distributions. The online resource can be searched by text or by BLAST sequence homology. The data outputs provide comprehensive sequence, bioinformatic and functional classification information.

Conclusion

The online pineapple bioinformatic resource provides the research community with access to pineapple fruit and root/gall sequence and bioinformatic data in a user-friendly format. The search tools enable efficient data mining and present a wide spectrum of bioinformatic and functional classification information. PineappleDB will be of broad appeal to researchers investigating pineapple genetics, non-climacteric fruit ripening, root-knot nematode infection, crassulacean acid metabolism and alternative RNA splicing in plants.
The design of the Dutch EASYcare study: a randomised controlled trial on the effectiveness of a problem-based community intervention model for frail elderly people [NCT00105378]
Authors: Melis René JF , van Eijken Monique IJ , Borm George F , Wensing Michel , Adang Eddy , van de Lisdonk Eloy H , van Achterberg Theo , Olde Rikkert Marcel GM
Published: October 2005

Background

Because of their complex clinical presentations and needs frail elderly people require another approach than people who age without many complications. Several inpatient geriatric health services have proven effectiveness in frail persons. However, the wish to live independently and policies that promote independent living as an answer to population aging call for community intervention models for frail elderly people. Maybe models such as preventive home visits, comprehensive geriatric assessment, and intermediate care qualify, but their efficacy is controversial, especially in frail elderly persons living in the community. With the Dutch EASYcare Study Geriatric Intervention Programme (DGIP) we developed a model to study effectiveness of problem based community intervention models in frail elderly people.

Methods/Design

DGIP is a community intervention model for frail elderly persons where the GP refers elderly patients with a problem in cognition, mood, behaviour, mobility, and nutrition. A geriatric specialist nurse applies a guideline-based intervention with a limited number of follow up visits. The intervention starts with the application of the EASYcare instrument for geriatric screening. The EASYcare instrument assesses (instrumental) activities of daily life, cognition, mood, and includes a goal setting item. During the intervention the nurse regularly consults the referring GP and a geriatrician. Effects on functional performance (Groningen Activity Restriction Scale), health related quality of life (MOS-20), and carer burden (Zarit Burden Interview) are studied in an observer blinded randomised controlled trial. 151 participants were randomised over two treatment arms – DGIP and regular care – using pseudo cluster randomisation. We are currently performing the follow up visits. These visits are planned three and six months after inclusion. Process measures and cost measures will be recorded. Intention to treat analyses will focus on post intervention differences between treatment groups.

Discussion

The design of a trial evaluating the effects of a community intervention model for frail elderly people was presented. The problem-based participant selection procedure satisfied; few patients that the GP referred did not meet our eligibility criteria. The use of standard terminology makes detailed insight into the contents of our intervention possible using terminology others can understand well.
Distinct effects of glucose and glucosamine on vascular endothelial and smooth muscle cells: Evidence for a protective role for glucosamine in atherosclerosis
Authors: Duan Wenlan , Paka Latha , Pillarisetti Sivaram
Published: October 2005

Accelerated atherosclerosis is one of the major vascular complications of diabetes. Factors including hyperglycemia and hyperinsulinemia may contribute to accelerated vascular disease. Among the several mechanisms proposed to explain the link between hyperglycemia and vascular dysfunction is the hexosamine pathway, where glucose is converted to glucosamine. Although some animal experiments suggest that glucosamine may mediate insulin resistance, it is not clear whether glucosamine is the mediator of vascular complications associated with hyperglycemia. Several processes may contribute to diabetic atherosclerosis including decreased vascular heparin sulfate proteoglycans (HSPG), increased endothelial permeability and increased smooth muscle cell (SMC) proliferation. In this study, we determined the effects of glucose and glucosamine on endothelial cells and SMCs in vitro and on atherosclerosis in apoE null mice. Incubation of endothelial cells with glucosamine, but not glucose, significantly increased matrix HSPG (perlecan) containing heparin-like sequences. Increased HSPG in endothelial cells was associated with decreased protein transport across endothelial cell monolayers and decreased monocyte binding to subendothelial matrix. Glucose increased SMC proliferation, whereas glucosamine significantly inhibited SMC growth. The antiproliferative effect of glucosamine was mediated via induction of perlecan HSPG. We tested if glucosamine affects atherosclerosis development in apoE-null mice. Glucosamine significantly reduced the atherosclerotic lesion in aortic root. (P < 0.05) These data suggest that macrovascular disease associated with hyperglycemia is unlikely due to glucosamine. In fact, glucosamine by increasing HSPG showed atheroprotective effects.
Ultrasound imaging versus morphopathology in cardiovascular diseases. Myocardial cell damage
Authors: Baroldi Giorgio , Bigi Riccardo , Cortigiani Lauro
Published: October 2005

This review article summarizes the results of histopathological and clinical imaging studies to assess myocardial necrosis in humans. Different histopathological features of myocardial cell necrosis are reviewed. In addition, the present role of echocardiographic techniques in assessing irreversible myocardial damage is briefly summarized.
Regulation of IκBα expression involves both NF-κB and the MAP kinase signaling pathways
Authors: Zhang Ning , Ahsan Muhammad H , Zhu Lingyun , Sambucetti Lidia C , Purchio Anthony F , West David B
Published: October 2005

IκBα is an inhibitor of the nuclear transcription factor NF-κB. Binding of IκBα to NF-κB inactivates the transcriptional activity of NF-κB. Expression of IκBα itself is regulated by NF-κB, which provides auto-regulation of this signaling pathway. Here we present a mouse model for monitoring in vivo IκBα expression by imaging I κB α-luc transgenic mice for IκBα promoter driven luciferase activity. We demonstrated a rapid and systemic induction of IκBα expression in the transgenic mice following treatment with LPS. The induction was high in liver, spleen, lung and intestine and lower in the kidney, heart and brain. The luciferase induction in the liver correlated with increased IκBα mRNA level. Pre-treatment with proteasome inhibitor bortezomib dramatically suppressed LPS-induced luciferase activity. The p38 kinase inhibitor SB203580 also showed moderate inhibition of LPS-induced luciferase activity. Analysis of IκBα mRNA in the liver tissue showed a surprising increase of the IκBα mRNA after bortezomib and SB203580 treatments, which could be due to increased IκBα mRNA stability. Our data demonstrate that regulation of IκBα expression involves both the NF-κB and the p38 signaling pathways. The I κB α-luc transgenic mice are useful for analyzing IκBα expression and the NF-κB transcriptional activity in vivo.
Ethnic differential item functioning in the assessment of quality of life in cancer patients
Authors: Pagano Ian S , Gotay Carolyn C
Published: October 2005

Background

Past research has shown that Filipino cancer patients report lower levels of quality of life (QoL) than other ethnic groups. One possible explanation for this is that Filipinos do not define QoL in the same manner as others, resulting in bias in their assessments. Hence, Filipinos would not necessarily have lower QoL.

Methods

Item response theory methods were used to assess differential item functioning (DIF) in the quality of life (measured by the EORTC QLQ-C30) of cancer patients across four ethnic groups (Caucasian, Filipino, Hawaiian, and Japanese). The sample consisted of 359 cancer patients.

Results

Results showed the presence of DIF on several items, indicating ethnic differences in the assessment of quality of life. Relative to the Caucasian and Japanese groups, items related to physical functioning, cognitive functioning, social functioning, nausea and vomiting, and financial difficulties exhibited DIF for Filipinos. On these items Filipinos exhibited either higher or lower QoL scores, even though their overall QoL was the same.

Conclusion

This evidence may explain why Filipinos have previously been found to have lower overall QoL. Although Filipinos score lower on QoL than other groups, this may not reflect lower QoL, but rather differences in how QoL is defined. The presence of DIF did not appear, however, to alter the psychometric properties of the QLQ-C30.
Heparin-induced thrombocytopenia: an update
Authors: Franchini Massimo
Published: October 2005

Heparin-induced thrombocytopenia (HIT) is the most important and most frequent drug-induced, immune-mediated type of thrombocytopenia. It is associated with significant morbidity and mortality if unrecognized. In this review, we briefly discuss the main features of heparin-induced thrombocytopenia, particularly analyzing the most recent advances in the pathophysiology, diagnosis and treatment of this syndrome.
Effect of connective tissue growth factor (CCN2/CTGF) on proliferation and differentiation of mouse periodontal ligament-derived cells
Authors: Asano Masahiro , Kubota Satoshi , Nakanishi Tohru , Nishida Takashi , Yamaai Tomoichiro , Yosimichi Gen , Ohyama Kazumi , Sugimoto Tomosada , Murayama Yoji , Takigawa Masaharu
Published: October 2005

Background

CCN2/CTGF is known to be involved in tooth germ development and periodontal tissue remodeling, as well as in mesenchymal tissue development and regeneration. In this present study, we investigated the roles of CCN2/CTGF in the proliferation and differentiation of periodontal ligament cells (murine periodontal ligament-derived cell line: MPL)in vitro.

Results

In cell cultures of MPL, the mRNA expression of the CCN2/CTGF gene was stronger in sparse cultures than in confluent ones and was significantly enhanced by TGF-β. The addition of recombinant CCN2/CTGF (rCCN2) to MPL cultures stimulated DNA synthesis and cell growth in a dose-dependent manner. Moreover, rCCN2 addition also enhanced the mRNA expression of alkaline phosphatase (ALPase), type I collagen, and periostin, the latter of which is considered to be a specific marker of the periosteum and periodontium; whereas it showed little effect on the mRNA expression of typical osteoblastic markers, e.g., osteopontin and osteocalcin. Finally, rCCN2/CTGF also stimulated ALPase activity and collagen synthesis.

Conclusion

These results taken together suggest important roles of CCN2/CTGF in the development and regeneration of periodontal tissue including the periodontal ligament.
Assessing the impact of the Australia-United States Free Trade Agreement on Australian and global medicines policy
Authors: Faunce Thomas , Doran Evan , Henry David , Drahos Peter , Searles Andrew , Pekarsky Brita , Neville Warwick
Published: October 2005

On 1 January 2005, a controversial trade agreement entered into force between Australia and the United States. Though heralded by the parties as facilitating the removal of barriers to free trade (in ways not achievable in multilateral fora), it also contained many trade-restricting intellectual property provisions and others uniquely related to altering pharmaceutical regulation and public health policy in Australia. The latter appear to have particularly focused on the world-respected process of federal government reimbursement after expert cost-effectiveness evaluation, popularly known as the Pharmaceutical Benefits Scheme ('PBS'). It remains uncertain what sort of impacts – if any – the Australia-United States Free Trade Agreement ('AUSFTA') will have on PBS processes such as reference pricing and their important role in facilitating equitable and affordable access to essential medicines.

This is now the field of inquiry for a major three year Australian Research Council ('ARC')-funded study bringing together a team of senior researchers in regulatory theory from the Australian National University and pharmacoeconomics from the University of Newcastle. The project proposes to monitor, assess and analyse the real and potential impacts of the AUSFTA in this area, providing Australian policy-makers with continuing expertise and options.

To the extent that the AUSFTA medicines provisions may represent animportant precedent in a global strategy by industry oncost-effectiveness evaluation of pharmaceuticals, the study will also beof great interest to policy makers in other jurisdictions.
Trends and characteristics of oral and maxillofacial injuries in Nigeria: a review of the literature
Authors: Adeyemo Wasiu Lanre , Ladeinde Akinola Ladipo , Ogunlewe Mobolanle Olugbemiga , James Olutayo
Published: October 2005

Background

The etiology of maxillofacial injuries varies from one country to another and even within the same country depending on the prevailing socioeconomic, cultural and environmental factors. Periodic verification of the etiology of maxillofacial injuries helps to recommend ways in which maxillofacial injuries can be averted. The aim of the present study is therefore to analyse the characteristics and trends of maxillofacial injuries in Nigeria based on a systematic review of the literature.

Methods

A literature search using MEDLINE was conducted for publications on maxillofacial injuries in Nigeria. The relevant references in these publications were manually searched for additional non-Medline articles or abstracts. Forty-two studies met the inclusion criteria and the full-texts of these articles were thoroughly examined. Due to lack of uniformity and consistency in assessment and measurement variables, and treatment modalities in most of the studies, it was impossible to apply the traditional methods of a systematic review. Therefore, a narrative approach was conducted to report the findings of the included studies.

Results

Although, other causes like assaults, sport injuries, and industrial accidents increased in numbers, throughout the period between 1965 and 2003, road traffic crashes remained the major etiological factor of maxillofacial injuries in all regions, except northeastern region where assault was the major cause. A significant increase in motorcycles related maxillofacial injuries was observed in most urban and suburban centres of the country. Animal attacks were not an unusual cause of maxillofacial injuries in most parts of northern Nigeria. Patients in the age group of 21–30 years were mostly involved. A strong tendency toward an equal male-to-female ratio was observed between earlier and later periods.

Conclusion

Road traffic crashes remain the major cause of maxillofacial injuries in Nigeria, unlike in most developed countries where assaults/interpersonal violence has replaced road traffic crashes as the major cause of the injuries. There is a need to reinforce legislation aimed to prevent road traffic crashes and the total enforcement of existing laws to reduce maxillofacial injuries among children and adults. Special attention should also be paid by the authority to improve the socioeconomic conditions of Nigerian populace.
A streamlined method for systematic, high resolution in situ analysis of mRNA distribution in plants
Authors: Drea Sinéad , Corsar Julia , Crawford Brian , Shaw Peter , Dolan Liam , Doonan John H
Published: October 2005

Background

In situ hybridisation can provide cellular, and in some cases sub-cellular, resolution of mRNA levels within multicellular organisms and is widely used to provide spatial and temporal information on gene expression. However, standard protocols are complex and laborious to implement, restricting analysis to one or a few genes at any one time. Whole-mount and reverse transcriptase-PCR (RT-PCR) based protocols increase throughput, but can compromise both specificity and resolution. With the advent of genome-wide analysis of gene expression, there is an urgent need to develop high-throughput in situ methods that also provide high resolution.

Results

Here we describe the development of a method for performing high-throughput in situ hybridisations that retains both the high resolution and the specificity of the best manual versions. This refined semi-automated protocol has the potential for determining the spatial and temporal expression patterns of hundreds of genes in parallel on a variety of tissues. We show how tissue sections can be organized on microscope slides in a manner that allows the screening of multiple probes on each slide. Slide handling, hybridisation and processing steps have been streamlined providing a capacity of at least 200 probes per week (depending on the tissue type). The technique can be applied easily to different species and tissue types, and we illustrate this with wheat seed and Arabidopsis floral meristems, siliques and seedlings.

Conclusion

The approach has the high specificity and high resolution of previous in situ methods while allowing for the analysis of several genes expression patterns in parallel. This method has the potential to provide an analysis of gene expression patterns at the genome level.
Reproducibility and sensitivity to change of various methods to measure joint space width in osteoarthritis of the hip: a double reading of three different radiographic views taken with a three-year interval
Authors: Maheu Emmanuel , Cadet Christian , Marty Marc , Dougados Maxime , Ghabri Salah , Kerloch Isabelle , Mazières Bernard , Spector Tim D , Vignon Eric , Lequesne Michel G
Published: October 2005

Joint space width (JSW) and narrowing (JSN) measurements on radiographs are currently the best way to assess disease severity or progression in hip osteoarthritis, yet we lack data regarding the most accurate and sensitive measurement technique. This study was conducted to determine the optimal radiograph and number of readers for measuring JSW and JSN. Fifty pairs of radiographs taken three years apart were obtained from patients included in a structure modification trial in hip osteoarthritis. Three radiographs were taken with the patient standing: pelvis, target hip anteroposterior (AP) and oblique views. Two trained readers, blinded to each other's findings, time sequence and treatment, each read the six radiographs gathered for each patient twice (time interval ≥15 days), using a 0.1 mm graduated magnifying glass. Radiographs were randomly coded for each reading. The interobserver and intraobserver cross-sectional (M0 and M36) and longitudinal (M0–M36) reproducibilities were assessed using the intraclass coefficient (ICC) and Bland–Altman method for readers 1 and 2 and their mean. Sensitivity to change was estimated using the standardized response mean (SRM = change/standard deviation of change) for M0–M36 changes. For interobserver reliability on M0–M36 changes, the ICCs (95% confidence interval [CI]) were 0.79 (0.65–0.88) for pelvic view, 0.87 (0.78–0.93) for hip AP view and 0.86 (0.76–0.92) for oblique view. Intraobserver reliability ICCs were 0.81 (0.69–0.89) for observer 1 and 0.97 (0.95–0.98) for observer 2 for the pelvic view; 0.87 (0.78–0.92) and 0.97 (0.96–0.99) for the hip AP view; and 0.73 (0.57–0.84) and 0.93 (0.88–0.96) for the oblique view. SRMs were 0.61 (observer 1) and 0.82 (observer 2) for pelvic view; 0.64 and 0.75 for hip AP view; and 0.77 and 0.70 for oblique view. All three views yielded accurate JSW and JSN. According to the best reader, the pelvic view performed slightly better. Both readers exhibited high precision, with SRMs of 0.6 or greater for assessing JSN over three years. Selecting a single reader was the most accurate method, with 0.3 mm precision. Using this cutoff, 50% of patients were classified as 'progressors'.
Tyrosine Kinase and Mitogen-Activated Protein Kinase/Extracellularly Regulated Kinase Differentially Regulate Intracellular Calcium Concentration Responses to Angiotensin II/III and Bradykinin in Rat Cortical Thick Ascending Limb
Authors: Hus-Citharel Annette , Iturrioz Xavier , Corvol Pierre , Marchetti Jeannine , Llorens-Cortes Catherine
Published: October 2005

The cortical thick ascending limb (CTAL) coexpresses angiotensin (Ang) II/Ang III receptor type 1A (AT1A-R) and bradykinin (BK) receptor type 2 (B2-R). In several cell types, these two receptors share the same signaling pathways, although their physiological functions are often opposite. In CTAL, little is known about the intracellular transduction events leading to the final physiological response induced by these two peptides. We investigated and compared in this segment the action of Ang II/III and BK on intracellular calcium concentration ([Ca2+]i) response and metabolic CO2 production, an index of Na+ transport, by using inhibitors of protein kinase C (bisindolylmaleimide), Src tyrosine kinase (herbimycin A and PP2), and MAPK/ERK (PD98059 and UO126). Ang II/III and BK (10−7 mol/liter) released Ca2+ from the same intracellular pools but activated different Ca2+ entry pathways. Ang II/III- or BK-induced [Ca2+]i increases were similarly potentiated by bisindolylmaleimide. Herbimycin A and PP2 decreased similarly the [Ca2+]i responses induced by Ang II/III and BK. In contrast, PD98059 and UO126 affected the effects of BK to a larger extent than those of Ang II/III. Especially, the Ca2+ influx induced by BK was more strongly inhibited than that induced by Ang II/III in the presence of both compounds. The Na+ transport was inhibited by BK and stimulated by Ang II/III. The inhibitory action of BK on Na+ transport was blocked by UO126, whereas the stimulatory response of Ang II/III was potentiated by UO126 but blocked by bisindolylmaleimide. These data suggest that the inhibitory effect of BK on Na+ transport seems to be directly mediated by an increase in Ca2+ influx dependent on MAPK/ERK pathway activation. In contrast, the stimulatory effect of Ang II/III on Na+ transport is more complex and involves PKC and MAPK/ERK pathways.
The Leu34Phe ProCART Mutation Leads to Cocaine- and Amphetamine-Regulated Transcript (CART) Deficiency: A Possible Cause for Obesity in Humans
Authors: Yanik Tulin , Dominguez Geraldina , Kuhar Michael J. , Del Giudice Emanuele M. , Loh Y. Peng
Published: October 2005

Cocaine- and amphetamine-regulated transcript (CART) is an anorexigenic neuropeptide synthesized in the hypothalamus. A Leu34Phe missense mutation in proCART has been found in an obese family in humans. Here we show that humans bearing the Leu34Phe mutation in proCART have severely diminished levels of bioactive CART, but elevated amounts of partially processed proCART in their serum. Expression of wild-type proCART in AtT-20 cells showed that it was sorted to the regulated secretory pathway, a necessity for proper processing to bioactive CART. However, expressed Leu34Phe proCART was missorted, poorly processed, and secreted constitutively. The defective intracellular sorting of Leu34Phe proCART would account for the reduced levels of bioactive CART in affected humans. These results suggest that the obesity observed in humans bearing the Leu34Phe mutation could be due to a putative deficiency in hypothalamic bioactive CART.