bluuebunny/crossref_metadata_2025_split huggingface dataset:
Posterior Thigh Muscle Injuries in Elite Track and Field Athletes
Authors: Malliaropoulos Nikolaos , Papacostas Emmanuel , Kiritsi Olga , Rad PGD-MSK , Papalada Agapi , Gougoulias Nikolaos , Maffulli Nicola 
Published: June 2010

Introduction: Posterior thigh muscle injuries in athletes are common, and prediction of recovery time would be of value. Hypothesis: Knee active range of motion deficit 48 hours after a unilateral posterior thigh muscle injury correlates with time to full recovery. Study Design: Cohort study (prognosis); Level of evidence, 2. Methods: One hundred sixty-five track and field athletes with acute, first-time, unilateral posterior thigh muscle injuries were prospectively evaluated regarding knee active range of motion deficit. This was compared with the uninjured side 48 hours after injury. A control group was also examined. Ultrasound was used to image the muscle lesion. All athletes were managed nonoperatively with the same rehabilitation protocol. The “full rehabilitation time” (interval from the injury to full athletic activities) was recorded. Results: Range of motion of the affected leg was decreased in the 165 injured athletes compared with the uninjured side and the control group. Sonography identified abnormalities in 55% (90 of 165) of the injured athletes. The biceps femoris was the most commonly affected muscle (68 of 90 [75%]). The musculotendinous junction (proximal or distal) was involved in 93% (85 of 90) of lesions. Eighty-one percent (133 of 165) of athletes had active range of motion deficit of less than 20°, and had returned to full performance at 2 weeks. In 6 of 165 athletes (3.6%), with active range of motion deficit of more than 30°, recovery time exceeded 6 weeks, with a significant correlation between full rehabilitation time and active range of motion deficit (χ2 = 152.560; P = .0001). Conclusion: Knee active range of motion deficit is an objective and accurate measurement, predicting recovery time in elite athletes.
SATB1 dictates expression of multiple genes including IL-5 involved in human T helper cell differentiation
Authors: Ahlfors Helena , Limaye Amita , Elo Laura L. , Tuomela Soile , Burute Mithila , Gottimukkala Kamal Vishnu P. , Notani Dimple , Rasool Omid , Galande Sanjeev , Lahesmaa Riitta 
Published: June 2010

AbstractSpecial AT-rich binding protein 1 (SATB1) is a global chromatin organizer and a transcription factor regulated by interleukin-4 (IL-4) during the early T helper 2 (Th2) cell differentiation. Here we show that SATB1 controls multiple IL-4 target genes involved in human Th cell polarization or function. Among the genes regulated by SATB1 is that encoding the cytokine IL-5, which is predominantly produced by Th2 cells and plays a key role in the development of eosinophilia in asthma. We demonstrate that, during the early Th2 cell differentiation, IL-5 expression is repressed through direct binding of SATB1 to the IL-5 promoter. Furthermore, SATB1 knockdown-induced up-regulation of IL-5 is partly counteracted by down-regulating GATA3 expression using RNAi in polarizing Th2 cells. Our results suggest that a competitive mechanism involving SATB1 and GATA3 regulates IL-5 transcription, and provide new mechanistic insights into the stringent regulation of IL-5 expression during human Th2 cell differentiation.
Phosphatidylinositol 3-kinase-δ inhibitor CAL-101 shows promising preclinical activity in chronic lymphocytic leukemia by antagonizing intrinsic and extrinsic cellular survival signals
Authors: Herman Sarah E. M. , Gordon Amber L. , Wagner Amy J. , Heerema Nyla A. , Zhao Weiqiang , Flynn Joseph M. , Jones Jeffrey , Andritsos Leslie , Puri Kamal D. , Lannutti Brian J. , Giese Neill A. , Zhang Xiaoli , Wei Lai , Byrd John C. , Johnson Amy J. 
Published: June 2010

AbstractTargeted therapy with imatinib in chronic myeloid leukemia (CML) prompted a new treatment paradigm. Unlike CML, chronic lymphocytic leukemia (CLL) lacks an aberrant fusion protein kinase but instead displays increased phosphatidylinositol 3-kinase (PI3K) activity. To date, PI3K inhibitor development has been limited because of the requirement of this pathway for many essential cellular functions. Identification of the hematopoietic-selective isoform PI3K-δ unlocks a new therapeutic potential for B-cell malignancies. Herein, we demonstrate that PI3K has increased enzymatic activity and that PI3K-δ is expressed in CLL cells. A PI3K-δ selective inhibitor CAL-101 promoted apoptosis in primary CLL cells ex vivo in a dose- and time-dependent fashion that was independent of common prognostic markers. CAL-101–mediated cytotoxicity was caspase dependent and was not diminished by coculture on stromal cells. In addition, CAL-101 abrogated protection from spontaneous apoptosis induced by B cell–activating factors CD40L, TNF-α, and fibronectin. In contrast to malignant cells, CAL-101 does not promote apoptosis in normal T cells or natural killer cells, nor does it diminish antibody-dependent cellular cytotoxicity. However, CAL-101 did decrease activated T-cell production of various inflammatory and antiapoptotic cytokines. Collectively, these studies provide rationale for the clinical development of CAL-101 as a first-in-class targeted therapy for CLL and related B-cell lymphoproliferative disorders.
A mutant allele of the Swi/Snf member BAF250a determines the pool size of fetal liver hemopoietic stem cell populations
Authors: Krosl Jana , Mamo Aline , Chagraoui Jalila , Wilhelm Brian T. , Girard Simon , Louis Isabelle , Lessard Julie , Perreault Claude , Sauvageau Guy 
Published: June 2010

Abstract
It is believed that hemopoietic stem cells (HSC), which colonize the fetal liver (FL) rapidly, expand to establish a supply of HSCs adequate for maintenance of hemopoiesis throughout life. Accordingly, FL HSCs are actively cycling as opposed to their predominantly quiescent bone marrow counterparts, suggesting that the FL microenvironment provides unique signals that support HSC proliferation and self-renewal. We now report the generation and characterization of mice with a mutant allele of Baf250a lacking exons 2 and 3. Baf250aE2E3/E2E3 mice are viable until E19.5, but do not survive beyond birth. Most interestingly, FL HSC numbers are markedly higher in these mice than in control littermates, thus raising the possibility that Baf250a determines the HSC pool size in vivo. Limit dilution experiments indicate that the activity of Baf250aE2E3/E2E3 HSC is equivalent to that of the wild-type counterparts. The Baf250aE2E3/E2E3 FL-derived stroma, in contrast, exhibits a hemopoiesis-supporting potential superior to the developmentally matched controls. To our knowledge, this demonstration is the first that a mechanism operating in a cell nonautonomous manner canexpand the pool size of the fetal HSC populations.
Intrinsic response of thoracic propriospinal neurons to axotomy
Authors: Siebert Justin R , Middelton Frank A , Stelzner Dennis J 
Published: June 2010

Abstract

Background
Central nervous system axons lack a robust regenerative response following spinal cord injury (SCI) and regeneration is usually abortive. Supraspinal pathways, which are the most commonly studied for their regenerative potential, demonstrate a limited regenerative ability. On the other hand, propriospinal (PS) neurons, with axons intrinsic to the spinal cord, have shown a greater regenerative response than their supraspinal counterparts, but remain relatively understudied in regards to spinal cord injury.

Results
Utilizing laser microdissection, gene-microarray, qRT-PCR, and immunohistochemistry, we focused on the intrinsic post-axotomy response of specifically labelled thoracic propriospinal neurons at periods from 3-days to 1-month following T9 spinal cord injury. We found a strong and early (3-days post injury, p.i) upregulation in the expression of genes involved in the immune/inflammatory response that returned towards normal by 1-week p.i. In addition, several regeneration associated and cell survival/neuroprotective genes were significantly up-regulated at the earliest p.i. period studied. Significant upregulation of several growth factor receptor genes (GFRa1, Ret, Lifr) also occurred only during the initial period examined. The expression of a number of pro-apoptotic genes up-regulated at 3-days p.i. suggest that changes in gene expression after this period may have resulted from analyzing surviving TPS neurons after the cell death of the remainder of the axotomized TPS neuronal population.

Conclusions
Taken collectively these data demonstrate that thoracic propriospinal (TPS) neurons mount a very dynamic response following low thoracic axotomy that includes a strong regenerative response, but also results in the cell death of many axotomized TPS neurons in the first week after spinal cord injury. These data also suggest that the immune/inflammatory response may have an important role in mediating the early strong regenerative response, as well as the apoptotic response, since expression of all of three classes of gene are up-regulated only during the initial period examined, 3-days post-SCI. The up-regulation in the expression of genes for several growth factor receptors during the first week post-SCI also suggest that administration of these factors may protect TPS neurons from cell death and maintain a regenerative response, but only if given during the early period after injury.
Prevalence of alternative splicing choices in Arabidopsis thaliana
Authors: English Adam C , Patel Ketan S , Loraine Ann E 
Published: June 2010

Abstract

Background
Around 14% of protein-coding genes of Arabidopsis thaliana genes from the TAIR9 genome release are annotated as producing multiple transcript variants through alternative splicing. However, for most alternatively spliced genes in Arabidopsis, the relative expression level of individual splicing variants is unknown.

Results
We investigated prevalence of alternative splicing (AS) events in Arabidopsis thaliana using ESTs. We found that for most AS events with ample EST coverage, the majority of overlapping ESTs strongly supported one major splicing choice, with less than 10% of ESTs supporting the minor form. Analysis of ESTs also revealed a small but noteworthy subset of genes for which alternative choices appeared with about equal prevalence, suggesting that for these genes the variant splicing forms co-occur in the same cell types. Of the AS events in which both forms were about equally prevalent, more than 80% affected untranslated regions or involved small changes to the encoded protein sequence.

Conclusions
Currently available evidence from ESTs indicates that alternative splicing in Arabidopsis occurs and affects many genes, but for most genes with documented alternative splicing, one AS choice predominates. To aid investigation of the role AS may play in modulating function of Arabidopsis genes, we provide an on-line resource (ArabiTag) that supports searching AS events by gene, by EST library keyword search, and by relative prevalence of minor and major forms.
No association between variation in the NR4A1 gene locus and metabolic traits in white subjects at increased risk for type 2 diabetes
Authors: Müssig Karsten , Machicao Fausto , Machann Jürgen , Schick Fritz , Claussen Claus D , Stefan Norbert , Fritsche Andreas , Häring Hans-Ulrich , Staiger Harald 
Published: June 2010

Abstract

Background
The nuclear receptor NR4A1 is implicated in metabolic regulation in insulin-sensitive tissues, such as liver, adipose tissue, and skeletal muscle. Functional loss of NR4A1 results in insulin resistance and enhanced intramuscular and hepatic lipid content. Therefore, we investigated in a cohort of white European subjects at increased risk for type 2 diabetes whether genetic variation within the NR4A1 gene locus contributes to prediabetic phenotypes, such as insulin resistance, ectopic fat distribution, or β-cell dysfunction.

Methods
We genotyped 1495 subjects (989 women, 506 men) for five single nucleotide polymorphisms (SNPs) tagging 100% of common variants (MAF = 0.05) within the NR4A1 gene locus with an r2 = 0.8. All subjects underwent an oral glucose tolerance test (OGTT), a subset additionally had a hyperinsulinemic-euglycemic clamp (n = 506). Ectopic hepatic (n = 296) and intramyocellular (n = 264) lipids were determined by magnetic resonance spectroscopy. Peak aerobic capacity, a surrogate parameter for oxidative capacity of skeletal muscle, was measured by an incremental exercise test on a motorized treadmill (n = 270).

Results
After appropriate adjustment and Bonferroni correction for multiple comparisons, none of the five SNPs was reliably associated with insulin sensitivity, ectopic fat distribution, peak aerobic capacity, or indices of insulin secretion (all p ≥ 0.05).

Conclusions
Our data suggest that common genetic variation within the NR4A1 gene locus may not play a major role in the development of prediabetic phenotypes in our white European population.
Hypoxia increases the metastatic ability of breast cancer cells via upregulation of CXCR4
Authors: Cronin Patricia A , Wang Jiang H , Redmond H Paul 
Published: June 2010

AbstractBackgroundChemokine SDF1α and its unique receptor CXCR4 have been implicated in organ-specific metastases of many cancers including breast cancer. Hypoxia is a common feature of solid tumors and is associated with their malignant phenotype. We hypothesized that hypoxia would upregulate CXCR4 expression and lead to increased chemotactic responsiveness to its specific ligand SDF1α.MethodsThree breast cancer cell lines MDA-MB-231, MCF7 and 4T1 were subjected to 48 hrs of hypoxia or normoxia. Cell surface receptor expression was evaluated using flow cytometry. An extracellular matrix invasion assay and microporous migration assay was used to assess chemotactic response and metastatic ability.ResultsCXCR4 surface expression was significantly increased in the two human breast cancer cell lines, MDA-MB-231 and MCF7, following exposure to hypoxia. This upregulation of CXCR4 cell surface expression corresponded to a significant increase in migration and invasion in response to SDF1-αin vitro. The increase in metastatic potential of both the normoxic and the hypoxic treated breast cancer cell lines was attenuated by neutralization of CXCR4 with a CXCR4 neutralizing mAb, MAB172 or a CXCR4 antagonist, AMD3100, showing the relationship between CXCR4 overexpression and increased chemotactic responsiveness.ConclusionsCXCR4 expression can be modulated by the tissue microenvironment such as hypoxia. Upregulation of CXCR4 is associated with increased migratory and invasive potential and this effect can be abrogated by CXCR4 inhibition. Chemokine receptor CXCR4 is a potential therapeutic target in the adjuvant treatment of breast cancer.
TRPM3 channel stimulated by pregnenolone sulphate in synovial fibroblasts and negatively coupled to hyaluronan
Authors: Ciurtin Coziana , Majeed Yasser , Naylor Jacqueline , Sukumar Piruthivi , English Anne A , Emery Paul , Beech David J 
Published: June 2010

Abstract

Background
Calcium-permeable channels are known to have roles in many mammalian cell types but the expression and contribution of such ion channels in synovial cells is mostly unknown. The objective of this study was to investigate the potential relevance of Transient Receptor Potential Melastatin 3 (TRPM3) channel to fibroblast-like synoviocytes (FLSs) of patients with rheumatoid arthritis.

Methods
The study used RT-PCR and immunofluorescence to detect mRNA and protein. Intracellular calcium measurement detected channel activity in a FLS cell-line and primary cultures of FLSs from patients with rheumatoid arthritis. Enzyme-linked immunosorbent assays measured hyaluronan.

Results
Endogenous expression of TRPM3 was detected. Previously reported stimulators of TRPM3 sphingosine and pregnenolone sulphate evoked sustained elevation of intracellular calcium in FLSs. The FLS cell-line showed an initial transient response to sphingosine which may be explained by TRPV4 channels but was not observed in FLSs from patients. Blocking antibody targeted to TRPM3 inhibited sustained sphingosine and pregnenolone sulphate responses. Secretion of hyaluronan, which contributes adversely in rheumatoid arthritis, was suppressed by pregnenolone sulphate in FLSs from patients and the effect was blocked by anti-TRPM3 antibody.

Conclusions
The data suggest that FLSs of patients with rheumatoid arthritis express TRPM3-containing ion channels that couple negatively to hyaluronan secretion and can be stimulated by pharmacological concentrations of pregnenolone sulphate.
Debate: Limitations on universality: the "right to health" and the necessity of legal nationality
Authors: Kingston Lindsey N , Cohen Elizabeth F , Morley Christopher P 
Published: June 2010

AbstractBackgroundThe "right to health," including access to basic healthcare, has been recognized as a universal human right through a number of international agreements. Attempts to protect this ideal, however, have relied on states as the guarantor of rights and have subsequently ignored stateless individuals, or those lacking legal nationality in any nation-state. While a legal nationality alone is not sufficient to guarantee that a right to healthcare is accessible, an absence of any legal nationality is almost certainly an obstacle in most cases. There are millions of so-called stateless individuals around the globe who are, in effect, denied medical citizenship in their countries of residence. A central motivating factor for this essay is the fact that statelessness as a concept is largely absent from the medical literature. The goal for this discussion, therefore, is primarily to illustrate the need for further monitoring of health access issues by the medical community, and for a great deal more research into the effects of statelessness upon access to healthcare. This is important both as a theoretical issue, in light of the recognition by many of healthcare as a universal right, as well as an empirical fact that requires further exploration and amelioration.DiscussionMost discussions of the human right to health assume that every human being has legal nationality, but in reality there are at least 11 to 12 million stateless individuals worldwide who are often unable to access basic healthcare. The examples of the Roma in Europe, the hill tribes of Thailand, and many Palestinians in Israel highlight the negative health impacts associated with statelessness.SummaryStateless individuals often face an inability to access the most basic healthcare, much less the "highest attainable standard of health" outlined by international agreements. Rather than presuming nationality, statelessness must be recognized by the medical community. Additionally, it is imperative that stateless populations be recognized, the health of these populations be tracked, and more research conducted to further elaborate upon the connection between statelessness and access to healthcare services, and hence a universal right to health.
Anti-angiogenic SPARC peptides inhibit progression of neuroblastoma tumors
Authors: Chlenski Alexandre , Guerrero Lisa J , Peddinti Radhika , Spitz Jared A , Leonhardt Payton T , Yang Qiwei , Tian Yufeng , Salwen Helen R , Cohn Susan L 
Published: June 2010

Abstract

Background
New, more effective strategies are needed to treat highly aggressive neuroblastoma. Our laboratory has previously shown that full-length Secreted Protein Acidic and Rich in Cysteine (SPARC) and a SPARC peptide corresponding to the follistatin domain of the protein (FS-E) potently block angiogenesis and inhibit the growth of neuroblastoma tumors in preclinical models. Peptide FS-E is structurally complex and difficult to produce, limiting its potential as a therapeutic in the clinic.

Results
In this study, we synthesized two smaller and structurally more simple SPARC peptides, FSEN and FSEC, that respectively correspond to the N-and C-terminal loops of peptide FS-E. We show that both peptides FSEN and FSEC have anti-angiogenic activity in vitro and in vivo, although FSEC is more potent. Peptide FSEC also significantly inhibited the growth of neuroblastoma xenografts. Histologic examination demonstrated characteristic features of tumor angiogenesis with structurally abnormal, tortuous blood vessels in control neuroblastoma xenografts. In contrast, the blood vessels observed in tumors, treated with SPARC peptides, were thin walled and structurally more normal. Using a novel method to quantitatively assess blood vessel abnormality we demonstrated that both SPARC peptides induced changes in blood vessel architecture that are consistent with blood vessel normalization.

Conclusion
Our results demonstrate that SPARC peptide FSEC has potent anti-angiogenic and anti-tumorigenic effects in neuroblastoma. Its simple structure and ease of production indicate that it may have clinical utility in the treatment of high-risk neuroblastoma and other types of pediatric and adult cancers, which depend on angiogenesis.
Primary appendiceal mucinous adenocarcinoma alongside with situs inversus totalis: a unique clinical case
Authors: Petrou Athanasios , Papalambros Alexandros , Katsoulas Nikolaos , Bramis Konstantinos , Evangelou Konstantinos , Felekouras Evaggelos 
Published: June 2010

AbstractIntroductionMucinous adenocarcinoma is a rare neoplasm of the gastrointestinal tract and one of the three major histological subtypes of the primary appendiceal adenocarcinoma. The most common type of presentation is that of acute appendicitis and the diagnosis is usually occurred after appendectomy. The accurate preoperative diagnosis and management of the above condition represents a real challenge when uncommon anatomic anomalies such intestinal malrotation and situs inversus take place. Situs inversus totalis with an incidence of 0.01% is an uncommon condition caused by a single autosomal recessive gene of incomplete penetration in which the major visceral organs are mirrored from their normal positions.Case presentationWe present an unusual case of a 59 years old, previously healthy man presented with a left lower quadrant abdominal pain, accompanied with low fever, leukocytosis, anorexia and constipation. A chest radiograph demonstrated dextrocardia with a right side positioned stomach bubble. Both preoperative US and CT scan of the abdomen and pelvis declared situs inversus, with a characteristic thickening in its wall, appendix situated in the left lower quadrant of the abdomen. These findings reached to the diagnosis of acute appendicitis with situs inversus and a standard appendicectomy was performed. Pathologic evaluation established primary mucinous adenocarcinoma of the appendix and three months afterwards the patient underwent a subsequent extended left hemicolectomy.ConclusionIn conclusion, the occurrence of primary appendiceal mucinous adenocarcinoma along with situs inversus, definitely accounts as a unique clinical case. Even synchronous manifestation of primary mucinous adenocarcinoma of the appendix and situs inversus totalis represents an unusual anatomo-pathological entity, all physicians should be familiar having the knowledge to make an appropriate and accurate diagnosis that will lead to prompt and correct treatment.