bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutrophils launch monocyte extravasation by release of granule proteins
Authors: Zernecke Alma , Weber Christian , Soehnlein Oliver 
Published: April 2009

SummaryDuring their journey from the blood stream to sites of inflammation polymorphonuclear leukocytes (PMN) release a wide panoply of granule proteins. Shortly after the PMN efflux, the extravasation of monocytes sets in and recent research provides evidence that the release of PMN granule proteins and monocyte extravasation are causally interrelated. Granule proteins seeded on the endothelium by adherent PMN allow direct activation and subsequent adhesion of monocytes. In addition, PMN granule components enhance the endothelial expression of cell adhesion molecules, efficiently supporting the arrest of monocytes at inflamed vessels. Moreover, granule proteins contribute to the fine tuning of the local chemokine network. Proteolytic modification of chemokines as well as enhancement of local chemokine synthesis lead to increased monocyte extravasation. Finally, PMN granule proteins exert direct chemotactic effects, a mechanism which is of special importance in the early recruitment of inflammatory monocytes. Hence, granule proteins modify the monocyte extravasation cascade in a multifaceted manner ensuring the efficiency of these mechanisms.
Trends in prevalence of deep venous thrombosis among hospitalised patients in an Asian institution
Authors: Lee Lai Heng , Ng Heng Joo 
Published: April 2009

SummaryVenous thromboembolism (VTE) has long been considered a disease of secondary importance among Asians because of its perceived low prevalence. We studied the prevalence and patterns of deep venous thrombosis (DVT) among hospitalised patients in our tertiary referral centre. Primary and secondary DVT prevalence among hospitalised patients was 0.453%, a significant rise from reported rates of 0.079% and 0.158% in 1989–1990 and 1996–1997, respectively. Malignancies and orthopaedic surgery were the most common risk factors for DVT. Further comparisons with the two earlier Singaporean studies showed no changes in the gender and ethnic background of patients but a higher proportion of elderly patients (>80 years) was recorded in the current study (11.7% vs. 7.0%, p = 0.04). Statistically significant increases were found in all medical and surgical disciplines except among obstetrics and gynaecology patients. Orthopaedic patients had the highest increase in DVT rates between the 1989–1990 and 2002–2003 periods (0.082% vs. 0.96%, p<0.01). Doppler ultrasound scans performed increased from approximately one per 100 admissions in 1996–1997 to one per 30 admissions in 2002–2003. The significant increase in period prevalence of DVT among hospitalised patients in Singapore could be accounted by methodologic differences between comparative studies, an increase in proportion of elderly patients and most importantly, a possible shift in perception of the importance of VTE among Asians, resulting in a higher index of suspicion and lower threshold for performing diagnostic tests.
Fibrinogen gamma gene 3’-end polymorphisms and risk of venous thromboembolism in the African-American and Caucasian population
Authors: Willige Shirley Uitte de , Pyle Meridith , Vos Hans , de Visser Marieke , Lally Cathy , Dowling Nicole , Hooper W. Craig , Bertina Rogier , Austin Harland 
Published: April 2009

SummaryGenetic determinants of venous thromboembolism (VTE) in the African-American population are poorly characterised. It was recently shown that fibrinogen gamma gene (FGG) polymorphisms 10034C>T and 9340T>C influence VTE risk in the Caucasian population. In the African-American population these polymorphisms are common, with allele frequencies above 25%. Here we evaluated whether these and other FGG 3’-end polymorphisms were associated with VTE risk in the African-American population and aimed to replicate the association in the Caucasian population. We examined 557 Caucasian patients and 678 Caucasian controls, and 537 African-American patients and 586 African-American controls from the ‘Genetic Attributes and Thrombosis Epidemiology’ (GATE) study. In the African-American population, 10034C>T and 9340T>C marginally influenced VTE-risk, with a 20% increase in risk for 10034TT carriers and a 20% reduction in risk for 9340CC carriers. In the Caucasian population, 10034TT was associated with a 1.7-fold increase in risk, which increased to 2.1-fold for idiopathic VTE patients. 9340CC significantly reduced VTE risk approximately two-fold. In conclusion, both FGG polymorphisms 10034C>T and 9340T>C influence VTE-risk, with the strongest effects observed in the Caucasian population, confirming previous data on these polymorphisms in this population.
Venous thromboembolism in nonagenarians
Authors: Vasco Beatriz , Villalba Joan Carles , Lopez-Jimenez Luciano , Falga Conxita , Montes Julio , Trujillo-Santos Javier , Monreal Manuel ,   for the RIETE Investigators
Published: April 2009

SummaryThe balance between the efficacy and safety of anticoagulant therapy in patients aged ≥90 years with venous thromboembolism (VTE) is uncertain. RIETE is an ongoing, prospective registry of consecutive patients with acute, objectively confirmed, symptomatic VTE. We evaluated the efficacy and safety of anticoagulant therapy during the first three months in all patients aged ≥90 years. In addition, we tried to identify those at a higher risk for VTE. Of 21,873 patients enrolled from March 2001 to February 2008, 610 (2.8%) were aged ≥90 years. Of these, 307 (50%) presented with pulmonary embolism (PE), 240 (39%) had immobility ≥4 days, and 271 (44%) had abnormal creatinine levels. During the first three months of therapy, 140 patients aged ≥90 years (23%) died. Of these, 45 (32%) died of PE (34 of the initial episode, 11 of recurrent PE), 18 (13%) had fatal bleeding. Recent im-mobility ≥4 days was the most common risk factor for VTE (240 of 610 patients, 39%), but only 54 of them (22%) had received thromboprophylaxis. The most frequent causes for immobility were senile dementia, acute infection, trauma or decompen-sated heart failure. The duration of immobility was <4 weeks in 126 patients (52%), and most of them were bedridden at home. In conclusion, one in every four VTE patients aged ≥90 years died during the first three months of therapy. Of these, one in every three died of PE, one in every eight had fatal bleeding. Identifying at-risk patients may help to prevent some of these deaths.
Novel aspects in the regulation of the leukocyte adhesion cascade
Authors: Chavakis Emmanouil , Choi Eun , Chavakis Triantafyllos 
Published: April 2009

SummaryLeukocyte recruitment plays a major role in the immune response to infectious pathogens and during inflammatory and autoimmune disorders. The process of leukocyte extravasation from the blood into the inflamed tissue requires a complex cascade of adhesive events between the leukocytes and the endothelium including leukocyte rolling, adhesion and transendothelial migration. Leukocyte-endothelial interactions are mediated by tightly regulated binding interactions between adhesion receptors on both cells. In this regard, leukocyte adhesion onto the endothelium is governed by leukocyte integrins and their endothelial counter-receptors of the immunoglobulin superfamily. The present review will focus on novel aspects with respect to the modulation of the leukocyte adhesion cascade.
Nutrition Evidence-Based Guidelines for Treating Hyperlipidemia in Children With Type 1 Diabetes
Authors: Robinson Megan Thomas 
Published: April 2009

Purpose The purpose of this case presentation is to review the current nutrition evidence-based guidelines and treatment goals for hyperlipidemia in children with type 1 diabetes. The American Heart Association (AHA) places children with type 1 diabetes in the highest tier for cardiovascular risk. Methods Early screening for hyperlipidemia in children with diabetes is recommended to identify those children at risk. If the fasting low-density lipoprotein cholesterol (LDL-C) level is ≥100 mg/dL (2.6 mmol/L), medical nutrition therapy is recommended as the first line of treatment to reach the desired goal (LDL-C <100 mg/dL). Medical nutrition therapy includes the following: decreasing saturated fat (<7% total calories), avoiding trans fatty acids, decreasing total cholesterol to <200 mg daily, increasing soluble fiber, and adding phytosterols daily. Results The patient discussed in this case presentation achieved a desired LDL-C level <100 mg/dL (2.6 mmol/L) by following the recommended heart-healthy guidelines. Statin therapy was not considered unless the LDL-C goal, <130 mg/dL (3.38 mmol/L), was not achieved by diet alone. Conclusions In this case study, evidence-based nutrition guidelines have been evaluated and reviewed to demonstrate heart-healthy eating for children with hyperlipidemia and type 1 diabetes. It is known that approximately 40% to 50% of children with elevated lipids will continue to have abnormal lipids into adolescence and early adulthood. Therefore, early screening is recommended by the AHA to track lipid changes during childhood and adolescence and to begin treating abnormal LDL-C levels to prevent the development of atherosclerosis.
What is the long-term benefit of constraint-induced movement therapy? A four-year follow-up
Authors: Brogårdh Christina , Flansbjer Ulla-Britt , Lexell Jan 
Published: April 2009

Objective: To evaluate the long-term benefits of constraint-induced movement therapy in chronic stroke. Design: A four-year follow-up after constraint-induced group therapy assessing arm and hand function and self-reported daily hand use. Subjects: Fourteen post-stroke individuals (six women and eight men; mean age 59.6 ± 12.7 years, range 23—75 years) with mild to moderate impairments of hand function. Outcome measures: The Sollerman hand function test and the Motor Activity Log test. Results: Four years after constraint-induced group therapy the participants had maintained their hand function, as measured by the Sollerman hand function test. The self-reported use and quality of movements of the more affected hand, as measured by the Motor Activity Log test, had decreased compared to post-treatment and three months follow-up (P<0.01), but was still significantly higher than pre-treatment (P<0.05). Conclusion: There seems to be a long-term benefit of constraint-induced group therapy. Hand function was maintained over time and daily hand use had increased compared to pre-treatment. To provide guidelines about the clinical use of constraint-induced movement therapy further, larger and controlled studies are needed.
Changes in gene expression of granulocytes during in vivo granulocyte colony-stimulating factor/dexamethasone mobilization for transfusion purposes
Authors: Drewniak Agata , van Raam Bram J. , Geissler Judy , Tool Anton T.J. , Mook Olaf R.F. , van den Berg Timo K. , Baas Frank , Kuijpers Taco W. 
Published: April 2009

AbstractThe treatment of healthy donors with granulocyte colony-stimulating factor (G-CSF) and dexamethasone results in sufficient numbers of circulating granulocytes to prepare granulocyte concentrates for clinical purposes. Granulocytes obtained in this way demonstrate relatively normal functional behavior combined with a prolonged life span. To study the influence of mobilizing agents on granulocytes, we used oligonucleotide microarrays to identify genes that are differentially expressed in mobilized granulocytes compared with control granulocytes. More than 1000 genes displayed a differential expression pattern, with at least a 3-fold difference. Among these, a large number of genes was induced that encode proteins involved in inflammation and the immune response, such as C-type lectins and leukocyte immunoglobulin-like receptors. Because mobilized granulocytes have a prolonged life span, we focused on genes involved in the regulation of apoptosis. One of the most prominent among these was CAST, the gene encoding calpastatin. Calpastatins are the endogenous inhibitors of calpains, a family of calcium-dependent cysteine proteases recently shown to be involved in neutrophil apoptosis. Transcriptional activity of the CAST gene was induced by G-CSF/dexamethasone treatment both in vivo and in vitro, whereas the protein expression of CAST was stabilized during culture. These studies provide new insight in the genotypic changes as well as in the regulation of the immunologic functions and viability of mobilized granulocytes used for clinical transfusion purposes.
Pattern recognition scavenger receptor SRA/CD204 down-regulates Toll-like receptor 4 signaling–dependent CD8 T-cell activation
Authors: Yi Huanfa , Yu Xiaofei , Gao Ping , Wang Yanping , Baek Sun-Hee , Chen Xing , Kim Hyung L. , Subjeck John R. , Wang Xiang-Yang 
Published: April 2009

AbstractClass A scavenger receptor (SRA), also known as CD204, has been shown to participate in the pathogenesis of atherosclerosis and the pattern recognition of pathogen infection. However, its role in adaptive immune responses has not been well defined. In this study, we report that the lack of SRA/CD204 promotes Toll-like receptor (TLR)4 agonist–augmented tumor-protective immunity, which is associated with enhanced activation of CD8+ effector T cell and improved inhibition of tumor growth. Dendritic cells (DCs) deficient in SRA/CD204 display more effective immunostimulatory activities upon TLR4 engagement than those from wild-type counterparts. Silencing of SRA/CD204 by RNA interference improves the ability of DCs to prime antigen-specific CD8+ T cells, suggesting that antigen-presenting cells, for example, DCs, play a major role in SRA/CD204-mediated immune modulation. Our findings reveal a previously unrecognized role for SRA/CD204, a non-TLR pattern recognition receptor, as a physiologic negative regulator of TLR4-mediated immune consequences, which has important clinical implications for development of TLR-targeted immunotherapeutic intervention.
Therapeutic effects of ablative radiation on local tumor require CD8+ T cells: changing strategies for cancer treatment
Authors: Lee Youjin , Auh Sogyong L. , Wang Yugang , Burnette Byron , Wang Yang , Meng Yuru , Beckett Michael , Sharma Rohit , Chin Robert , Tu Tony , Weichselbaum Ralph R. , Fu Yang-Xin 
Published: April 2009

AbstractPatients with locally advanced cancer or distant metastasis frequently receive prolonged treatment with chemotherapy and/or fractionated radiotherapy (RT). Despite the initial clinical response, treatment resistance frequently develops and cure in these patients is uncommon. Developments in RT technology allow for the use of high-dose (or ablative) RT to target local tumors, with limited damage to the surrounding normal tissue. We report that reduction of tumor burden after ablative RT depends largely on T-cell responses. Ablative RT dramatically increases T-cell priming in draining lymphoid tissues, leading to reduction/eradication of the primary tumor or distant metastasis in a CD8+ T cell–dependent fashion. We further demonstrate that ablative RT-initiated immune responses and tumor reduction are abrogated by conventional fractionated RT or adjuvant chemotherapy but greatly amplified by local immunotherapy. Our study challenges the rationale for current RT/chemotherapy strategies and highlights the importance of immune activation in preventing tumor relapse. Our findings emphasize the need for new strategies that not only reduce tumor burden but also enhance the role of antitumor immunity.
Early iron-deficiency-induced transcriptional changes in Arabidopsis roots as revealed by microarray analyses
Authors: Buckhout Thomas J , Yang Thomas JW , Schmidt Wolfgang 
Published: April 2009

AbstractBackgroundIron (Fe) is an essential nutrient in plants and animals, and Fe deficiency results in decreased vitality and performance. Due to limited bio-availability of Fe, plants have evolved sophisticated adaptive alterations in development, biochemistry and metabolism that are mainly regulated at the transcriptional level. We have investigated the early transcriptional response to Fe deficiency in roots of the model plant Arabidopsis, using a hydroponic system that permitted removal of Fe from the nutrient solution within seconds and transferring large numbers of plants with little or no mechanical damage to the root systems. We feel that this experimental approach offers significant advantages over previous and recent DNA microarray investigations of the Fe-deficiency response by increasing the resolution of the temporal response and by decreasing non-Fe deficiency-induced transcriptional changes, which are common in microarray analyses.ResultsThe expression of sixty genes were changed after 6 h of Fe deficiency and 65% of these were found to overlap with a group of seventy-nine genes that were altered after 24 h. A disproportionally high number of transcripts encoding ion transport proteins were found, which function to increase the Fe concentration and decrease the zinc (Zn) concentration in the cytosol. Analysis of global changes in gene expression revealed that changes in Fe availability were associated with the differential expression of genes that encode transporters with presumed function in uptake and distribution of transition metals other than Fe. It appeared that under conditions of Fe deficiency, the capacity for Zn uptake increased, most probably the result of low specificity of the Fe transporter IRT1 that was induced upon Fe deficiency. The transcriptional regulation of several Zn transports under Fe deficiency led presumably to the homeostatic regulation of the cytosolic concentration of Zn and of other transition metal ions such as Mn to avoid toxicity.ConclusionThe genomic information obtained from this study gives insights into the rapid transcriptional responses to Fe shortage in plants, and is important for understanding how changes in nutrient availability are translated into responses that help to avoid imbalances in ion distribution. We further identified rapidly induced or repressed genes with potential roles in perception and signaling during Fe deficiency which may aid in the elucidation of these processes.
Identification and characterization of new miRNAs cloned from normal mouse mammary gland
Authors: Sdassi Nezha , Silveri Licia , Laubier Johann , Tilly Gaëlle , Costa José , Layani Sarah , Vilotte Jean-Luc , Le Provost Fabienne 
Published: April 2009

Abstract

Background
MicroRNAs (miRNAs) are small non-coding RNAs that have been found to play important roles in silencing target genes and that are involved in the regulation of various normal cellular processes. Until now their implication in the mammary gland biology was suggested by few studies mainly focusing on pathological situations allowing the characterization of miRNAs as markers of breast cancer tumour classes. If in the normal mammary gland, the expression of known miRNAs has been studied in human and mice but the full repertoire of miRNAs expressed in this tissue is not yet available.

Results
To extend the repertoire of mouse mammary gland expressed miRNAs, we have constructed several libraries of small miRNAs allowing the cloning of 455 sequences. After bioinformatics' analysis, 3 known miRNA (present in miRbase) and 33 new miRNAs were identified. Expression of 24 out of the 33 has been confirmed by RT-PCR. Expression of none of them was found to be mammary specific, despite a tissue-restricted distribution of some of them. No correlation could be established between their expression pattern and evolutionary conservation. Six of them appear to be mouse specific. In several cases, multiple potential precursors of miRNA were present in the genome and we have developed a strategy to determine which of them was able to mature the miRNA.

Conclusion
The cloning approach has allowed improving the repertoire of miRNAs in the mammary gland, an evolutionary recent organ. This tissue is a good candidate to find tissue-specific miRNAs and to detect miRNA specific to mammals. We provide evidence for 24 new miRNA. If none of them is mammary gland specific, a few of them are not ubiquitously expressed. For the first time 6 mouse specific miRNA have been identified.
Chromosome Y variants from different inbred mouse strains are linked to differences in the morphologic and molecular responses of cardiac cells to postpubertal testosterone
Authors: Llamas Bastien , Verdugo Ricardo A , Churchill Gary A , Deschepper Christian F 
Published: April 2009

Abstract

Background
We have reported previously that when chromosome Y (chrY) from the mouse strain C57BL/6J (ChrYC57) was substituted for that of A/J mice (ChrYA), cardiomyocytes from the resulting "chromosome substitution" C57BL/6J-chrYA strain were smaller than that of their C57BL/6J counterparts. In reverse, when chrYA from A/J mice was substituted for that of chrYC57, cardiomyocytes from the resulting A/J-chrYC57 strain were larger than in their A/J counterparts. We further used these strains to test whether: 1) the origin of chrY could also be linked to differences in the profile of gene expression in the hearts of adult male mice, and 2) post-pubertal testosterone could play a role in the differential morphologic and/or molecular effects of chrYC57 and chrYA.

Results
The increased size of cardiomyocytes from adult male C57BL/6J mice compared to C57BL/6J-chrYA resulted from the absence of hypertrophic effects of post-pubertal testosterone on cells from the latter strain. However, gene profiling revealed that the latter effect could not be explained on the basis of an insensitivity of cells from C57BL/6J-chrYA to androgens, since even more cardiac genes were affected by post-pubertal testosterone in C57BL/6J-chrYA hearts than in C57BL/6J. By testing for interaction between the effects of surgery and strain, we identified 249 "interaction genes" whose expression was affected by post-pubertal testosterone differentially according to the genetic origin of chrY. These interaction genes were found to be enriched within a limited number of signaling pathways, including: 1) p53 signaling, which comprises the interacting genes Ccnd1, Pten and Cdkn1a that are also potential co-regulators of the androgen receptors, and 2) circadian rhythm, which comprises Arntl/Bmal1, which may in turn regulate cell growth via the control of Cdkn1a.

Conclusion
Although post-pubertal testosterone increased the size of cardiomyocytes from male C56BL/6J mice but not that from their C57BL/6J-chrYA counterparts, it affected gene expression in the hearts from both strains. However, several cardiac genes responded to post-pubertal testosterone in a strict strain-selective manner, which provides possible mechanisms explaining how chrY may, in part via interference with androgen regulatory events, be linked to morphologic differences of cardiac cells of adult male mice.