bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperhomocystinemia Impairs Endothelial Function and eNOS Activity via PKC Activation
Authors: Jiang Xiaohua , Yang Fan , Tan Hongmei , Liao Dan , Bryan Robert M. , Randhawa Jaspreet K. , Rumbaut Rolando E. , Durante William , Schafer Andrew I. , Yang Xiaofeng , Wang Hong 
Published: October 2005

Objective—A risk factor for cardiovascular disease, hyperhomocystinemia (HHcy), is associated with endothelial dysfunction. In this study, we examined the mechanistic role of HHcy in endothelial dysfunction.Methods and Results—Through the use of 2 functional models, aortic rings and intravital video microscopy of the cremaster, we found that arterial relaxation in response to the endothelium-dependent vessel relaxant, acetylcholine or the nitric oxide synthase (NOS) activator (A23187), was significantly impaired in cystathionine β-synthase null (CBS−/−) mice. However, the vascular smooth muscle cell (VSMC) response to the nitric oxide (NO) donor (SNAP) was preserved in CBS−/−mice. In addition, superoxide dismutase and catalase failed to restore endothelium-dependent vasodilatation. Endothelial nitric oxide synthase (eNOS) activity was significantly reduced in mouse aortic endothelial cells (MAECs) of CBS−/−mice, as well as in Hcy-treated mouse and human aortic endothelial cells (HAECs). Hcy-mediated eNOS inhibition—which was not rescued by adenoviral transduction of superoxide dismutase and glutathione peroxidase, or by tetrahydrobiopterin, sepiapterin, and arginine supplementations in MAEC—was associated with decreased protein expression and increased threonine 495 phosphorylation of eNOS in HAECs. Ultimately, a protein kinase C (PKC) inhibitor, GF109203X (GFX), reversed Hcy-mediated eNOS inactivation and threonine 495 phosphorylation in HAECs.Conclusions—These data suggest that HHcy impairs endothelial function and eNOS activity, primarily through PKC activation.
The Effects of Augmentation with Swine Small Intestine Submucosa on Tendon Healing under Tension
Authors: Schlegel Theodore F. , Hawkins Richard J. , Lewis Chad W. , Motta Tatiana , Turner A. Simon 
Published: October 2005

Background Rotator cuff failure after surgery may be attributed to inferior tissue healing properties that result from repetitive cyclic loading during early rehabilitation. Enhancing the biological healing process may reduce the incidence of failures after rotator cuff repairs. Hypothesis Augmentation of rotator cuff tissue using swine small intestine submucosa in a sheep model will improve the rate and quality of tissue repair. Study Design Controlled laboratory study. Methods We resected and reattached 26 sheep infraspinatus tendons under tension, with 13 animals receiving a small intestine submucosa patch (augmented group). Animals were sacrificed at 12 weeks, and biomechanical testing and histologic evaluation were performed. Biomechanical testing was completed in 10 tendons from each group. Specimens were loaded to failure at a constant displacement to obtain the load deformation curve used to calculate load to failure and stiffness of the healed bone-tendon interface. Histologic testing addressed tissue healing at the bone-tendon interface. Results The load-to-failure data did not indicate a significant difference between the augmented and nonaugmented groups (1252 ± 402 N vs 985 ± 459 N, respectively; P >. 05). However, the augmented group had significantly better stiffness than the nonaugmented group (215 ± 44 N/mm vs 154 ± 63 N/mm, respectively; P =. 03). Histologic data revealed that the infraspinatus tendon in all specimens inserted into the bone through a zone of fibrocartilage, although none of the patches were intact. Conclusion Although there were no differences in the load-to-failure data between the 2 groups, the statistically significant improvement in stiffness for the augmented group is clinically relevant. Stiffness is the biomechanical parameter representing the tissue response to subdestructive loads seen with early rehabilitation. Augmenting the repair with a collagen matrix improved the early healing characteristics of the repair construct. Clinical Relevance Enhancing the biological process of tendon healing under tension by using a collagen matrix patch may improve the ultimate success of rotator cuff repair.
Femoral Press-Fit Fixation Technique in Anterior Cruciate Ligament Reconstruction Using Bone-Patellar Tendon-Bone Graft
Authors: Pavlik Attila , Hidas Péter , Tállay András , Toman József , Berkes István 
Published: October 2005

Background The security of the graft fixation is an important factor of anterior cruciate ligament reconstruction, especially in the early postoperative period. Hypothesis The femoral press-fit fixation technique is a safe, alternative technique for the fixation of the bone-patellar tendon-bone graft. Study Design Case series; Level of evidence, 4. Methods Between January 1, 1998, and June 30, 2002, 285 patients, with a mean age of 29.1 years, underwent operation and observation in our department. All patients had arthroscopic anterior cruciate ligament reconstruction using bone-patellar tendon-bone graft with femoral press-fit and tibial interference screw fixation. The mean follow-up period was 35.8 months (range, 24-77 months). During each patient's evaluation, a physical examination, a subjective evaluation, the International Knee Documentation Committee and Lysholm scores, KT-1000 arthrometer testing, and radiological evaluation were performed. The paired Student t test or X2 test was used for statistical analysis. Results According to the International Knee Documentation Committee score, 241 patients (85%) had good (46 normal and 195 nearly normal) results, whereas 39 patients had abnormal and 5 patients had severely abnormal overall results. The preoperative mean Lysholm score was 63.5 ± 12.7 points. At the final examination, the mean value was 93.5 ± 7.8 points (P <. 01). One hundred ninety-seven athletes could return to their previous sports activity level, whereas 13 patients gave up their sports career. The KT-1000 arthrometer results showed a side-to-side difference of 1.91 ± 2.1 mm at the maximum manual strength tests. Conclusion The femoral press-fit fixation is an alternative fixation method for the bone-patellar tendon-bone graft and provides good stability for the anterior cruciate ligament reconstruction. The use of press-fit fixation technique avoids most interference screw or other hardware-induced complications at the femoral side.
Modulation of STAT1 protein levels: a mechanism shaping CD8 T-cell responses in vivo
Authors: Gil M. Pilar , Salomon Rachelle , Louten Jennifer , Biron Christine A. 
Published: October 2005

AbstractType 1 interferons (IFNs) are induced in vivo, administered therapeutically, and potential targets for amelioration of autoimmune diseases. The cytokines mediate profound antiproliferative effects. Signal transducer and activator of transcription 1 (STAT1)-dependent signaling pathways are required for inhibition of proliferation, and viral infections can elicit high levels of type 1 IFNs as well as total STAT1 protein expression. Thus, a mechanism must be in place to help antigen-specific T cells overcome IFN-induced inhibition of proliferation. The studies reported here demonstrate that total CD8 T-cell proliferation in the presence of IFNs, ex vivo in response to cytokines and in vivo during viral infection, is inhibited through a STAT1-dependent mechanism. In contrast, major proportions of antigen-specific CD8, but not CD4, T cells are rendered less sensitive to this inhibition, express lower endogenous levels of total STAT1, and are selectively proliferating in the presence of type 1 IFN, at key times after viral challenge. Taken together, these novel results show that differential STAT1 expression is used by the immune system to modify cytokine-mediated effects on T-cell expansion and have implications for the consequences of therapeutic intervention in cytokine function.
Rapamycin, and not cyclosporin A, preserves the highly suppressive CD27+ subset of human CD4+CD25+ regulatory T cells
Authors: Coenen Jeroen J. A. , Koenen Hans J. P. M. , van Rijssen Esther , Hilbrands Luuk B. , Joosten Irma 
Published: October 2005

AbstractThe immunosuppressive drugs rapamycin and cyclosporin A (CsA) are widely used to prevent allograft rejection. Moreover, they were shown to be instrumental in experimental models of tolerance induction. However, it remains to be elucidated whether these drugs have an effect on the CD4+CD25+ regulatory T-cell (TREG) population, which plays an important role in allograft tolerance. Recently, we reported that alloantigen-driven expansion of human CD4+CD25+ TREGs gives rise to a distinct highly suppressive CD27+TREG subset next to a moderately suppressive CD27-TREG subset. In the current study we found that rapamycin and CsA do not interfere with the suppressive activity of human naturally occurring CD4+CD25+ T cells. However, in contrast to CsA, rapamycin preserved the dominance of the potent CD27+TREG subset over the CD27-TREG subset after alloantigen-driven expansion of CD4+CD25+ TREGs in vitro. Accordingly, CD4+CD25+ TREGs cultured in the presence of rapamycin displayed much stronger suppressive capacity than CD4+CD25+ TREGs cultured in the presence of CsA. In addition, CD4+CD25+ TREG cells cultured in the presence of rapamycin, but not CsA, were able to suppress ongoing alloimmune responses. This differential effect of rapamycin and CsA on the CD27+TREG subset dominance may favor the use of rapamycin in tolerance-inducing strategies.
Sequential heart and autologous stem cell transplantation for systemic AL amyloidosis
Authors: Gillmore Julian D. , Goodman Hugh J. , Lachmann Helen J. , Offer Mark , Wechalekar Ashutosh D. , Joshi Jayshree , Pepys Mark B. , Hawkins Philip N. 
Published: October 2005

AbstractExtensive cardiac amyloid deposition in systemic AL amyloidosis is associated with a grave prognosis. Heart transplantation is rarely performed because of the systemic and progressive nature of the disease. Patients with severe cardiac amyloid infiltration are ineligible for the preferred treatment of melphalan chemotherapy with stem cell transplantation (SCT) rescue because of the high risk for treatment-related mortality. Heart transplantation followed by SCT was performed in 5 patients with AL amyloidosis and predominant cardiomyopathy. Patients were followed up for a median of 95 months (range, 37-118 months) from diagnosis. At censor, 3 of 5 patients were well without evidence of intracardiac or extracardiac amyloid accumulation, and median overall survival by Kaplan-Meier estimate was not reached. Two patients died of progressive amyloidosis 33 and 90 months after heart transplantation after relapse of their underlying plasma cell dyscrasia. Heart transplantation followed by SCT is feasible in selected patients with cardiac AL amyloidosis and may confer substantial survival benefit.
Risk of monoclonal gammopathy of undetermined significance (MGUS) and subsequent multiple myeloma among African American and white veterans in the United States
Authors: Landgren Ola , Gridley Gloria , Turesson Ingemar , Caporaso Neil E. , Goldin Lynn R. , Baris Dalsu , Fears Thomas R. , Hoover Robert N. , Linet Martha S. 
Published: October 2005

Abstract
The age-adjusted incidence of multiple myeloma (MM) is 2-fold higher in African Americans than in whites. A few small studies have reported a higher prevalence of monoclonal gammopathy of undetermined significance (MGUS) in African Americans versus whites. Etiologic factors for MGUS and determinants for transformation of MGUS to MM are unknown. We quantified the prevalence of MGUS and subsequent risk of MM among 4 million African American and white male veterans admitted to Veterans Affairs (VA) hospitals. The age-adjusted prevalence ratio of MGUS in African Americans compared with whites was 3.0 (2.7-3.3 95% confidence interval). Among 2046 MGUS cases, the estimated cumulative risk of MM during the first 10 years of follow-up was similar (P = .37) for African Americans (17%) and whites (15%). In the largest study to date, we suggest that the excess risk of MM in African Americans results from an increase in risk of MGUS rather than an increased risk of progression from MGUS to MM.
Severe malarial anemia of low parasite burden in rodent models results from accelerated clearance of uninfected erythrocytes
Authors: Evans Krystal J. , Hansen Diana S. , van Rooijen Nico , Buckingham Lynn A. , Schofield Louis 
Published: October 2005

AbstractSevere malarial anemia (SMA) is the most frequent life-threatening complication of malaria and may contribute to the majority of malarial deaths worldwide. To explore the mechanisms of pathogenesis, we developed a novel murine model of SMA in which parasitemias peaked around 1.0% of circulating red blood cells (RBCs) and yet hemoglobin levels fell to 47% to 56% of baseline. The severity of anemia was independent of the level of peak or cumulative parasitemia, but was linked kinetically to the duration of patent infection. In vivo biotinylation analysis of the circulating blood compartment revealed that anemia arose from accelerated RBC turnover. Labeled RBCs were reduced to 1% of circulating cells by 8 days after labeling, indicating that the entire blood compartment had been turned over in approximately one week. The survival rate of freshly transfused RBCs was also markedly reduced in SMA animals, but was not altered when RBCs from SMA donors were transferred into naive recipients, suggesting few functional modifications to target RBCs. Anemia was significantly alleviated by depletion of either phagocytic cells or CD4+ T lymphocytes. This study demonstrates that immunologic mechanisms may contribute to SMA by promoting the accelerated turnover of uninfected RBCs.
Comparison of the gene expression profile of undifferentiated human embryonic stem cell lines and differentiating embryoid bodies
Authors: Bhattacharya Bhaskar , Cai Jingli , Luo Youngquan , Miura Takumi , Mejido Josef , Brimble Sandii N , Zeng Xianmin , Schulz Thomas C , Rao Mahendra S , Puri Raj K 
Published: October 2005

Abstract

Background
The identification of molecular pathways of differentiation of embryonic stem cells (hESC) is critical for the development of stem cell based medical therapies. In order to identify biomarkers and potential regulators of the process of differentiation, a high quality microarray containing 16,659 seventy base pair oligonucleotides was used to compare gene expression profiles of undifferentiated hESC lines and differentiating embryoid bodies.

Results
Previously identified "stemness" genes in undifferentiated hESC lines showed down modulation in differentiated cells while expression of several genes was induced as cells differentiated. In addition, a subset of 194 genes showed overexpression of greater than ≥ 3 folds in human embryoid bodies (hEB). These included 37 novel and 157 known genes. Gene expression was validated by a variety of techniques including another large scale array, reverse transcription polymerase chain reaction, focused cDNA microarrays, massively parallel signature sequencing (MPSS) analysis and immunocytochemisty. Several novel hEB specific expressed sequence tags (ESTs) were mapped to the human genome database and their expression profile characterized. A hierarchical clustering analysis clearly depicted a distinct difference in gene expression profile among undifferentiated and differentiated hESC and confirmed that microarray analysis could readily distinguish them.

Conclusion
These results present a detailed characterization of a unique set of genes, which can be used to assess the hESC differentiation.
Evidence of recombination among early-vaccination era measles virus strains
Authors: Schierup Mikkel H , Mordhorst Carl H , Muller Claude P , Christensen Laurids S 
Published: October 2005

Abstract

Background
The advent of live-attenuated vaccines against measles virus during the 1960'ies changed the circulation dynamics of the virus. Earlier the virus was indigenous to countries worldwide, but now it is mediated by a limited number of evolutionary lineages causing sporadic outbreaks/epidemics of measles or circulating in geographically restricted endemic areas of Africa, Asia and Europe. We expect that the evolutionary dynamics of measles virus has changed from a situation where a variety of genomic variants co-circulates in an epidemic with relatively high probabilities of co-infection of the individual to a situation where a co-infection with strains from evolutionary different lineages is unlikely.

Results
We performed an analysis of the partial sequences of the hemagglutinin gene of 18 measles virus strains collected in Denmark between 1965 and 1983 where vaccination was first initiated in 1987. The results were compared with those obtained with strains collected from other parts of the world after the initiation of vaccination in the given place. Intergenomic recombination among pre-/early-vaccination strains is suggested by 1) estimations of linkage disequilibrium between informative sites, 2) the decay of linkage disequilibrium with distance between informative sites and 3) a comparison of the expected number of homoplasies to the number of apparent homoplasies in the most parsimonious tree. No significant evidence of recombination could be demonstrated among strains circulating at present.

Conclusion
We provide evidence that recombination can occur in measles virus and that it has had a detectable impact on sequence evolution of pre-vaccination samples. We were not able to detect recombination from present-day sequence surveys. We believe that the decreased rate of visible recombination may be explained by changed dynamics, since divergent strains do not meet very often in current epidemics that are often spawned by a single sequence type. Signs of pre-vaccination recombination events in the present-day sequences are not strong enough to be detectable.
Non-classical protein secretion in bacteria
Authors: Bendtsen Jannick D , Kiemer Lars , Fausbøll Anders , Brunak Søren 
Published: October 2005

Abstract

Background
We present an overview of bacterial non-classical secretion and a prediction method for identification of proteins following signal peptide independent secretion pathways. We have compiled a list of proteins found extracellularly despite the absence of a signal peptide. Some of these proteins also have known roles in the cytoplasm, which means they could be so-called "moon-lightning" proteins having more than one function.

Results
A thorough literature search was conducted to compile a list of currently known bacterial non-classically secreted proteins. Pattern finding methods were applied to the sequences in order to identify putative signal sequences or motifs responsible for their secretion. We have found no signal or motif characteristic to any majority of the proteins in the compiled list of non-classically secreted proteins, and conclude that these proteins, indeed, seem to be secreted in a novel fashion. However, we also show that the apparently non-classically secreted proteins are still distinguished from cellular proteins by properties such as amino acid composition, secondary structure and disordered regions. Specifically, prediction of disorder reveals that bacterial secretory proteins are more structurally disordered than their cytoplasmic counterparts. Finally, artificial neural networks were used to construct protein feature based methods for identification of non-classically secreted proteins in both Gram-positive and Gram-negative bacteria.

Conclusion
We present a publicly available prediction method capable of discriminating between this group of proteins and other proteins, thus allowing for the identification of novel non-classically secreted proteins. We suggest candidates for non-classically secreted proteins in Escherichia coli and Bacillus subtilis. The prediction method is available online.
Mindboggle: Automated brain labeling with multiple atlases
Authors: Klein Arno , Mensh Brett , Ghosh Satrajit , Tourville Jason , Hirsch Joy 
Published: October 2005

Abstract

Background
To make inferences about brain structures or activity across multiple individuals, one first needs to determine the structural correspondences across their image data. We have recently developed Mindboggle as a fully automated, feature-matching approach to assign anatomical labels to cortical structures and activity in human brain MRI data. Label assignment is based on structural correspondences between labeled atlases and unlabeled image data, where an atlas consists of a set of labels manually assigned to a single brain image. In the present work, we study the influence of using variable numbers of individual atlases to nonlinearly label human brain image data.

Methods
Each brain image voxel of each of 20 human subjects is assigned a label by each of the remaining 19 atlases using Mindboggle. The most common label is selected and is given a confidence rating based on the number of atlases that assigned that label. The automatically assigned labels for each subject brain are compared with the manual labels for that subject (its atlas). Unlike recent approaches that transform subject data to a labeled, probabilistic atlas space (constructed from a database of atlases), Mindboggle labels a subject by each atlas in a database independently.

Results
When Mindboggle labels a human subject's brain image with at least four atlases, the resulting label agreement with coregistered manual labels is significantly higher than when only a single atlas is used. Different numbers of atlases provide significantly higher label agreements for individual brain regions.

Conclusion
Increasing the number of reference brains used to automatically label a human subject brain improves labeling accuracy with respect to manually assigned labels. Mindboggle software can provide confidence measures for labels based on probabilistic assignment of labels and could be applied to large databases of brain images.