tbuckley/cabot-search huggingface dataset:
Stress fracture of the femoral neck in a marathon runner.
Authors: S. Baer, D. Shakespeare
Journal: British Journal of Sports Medicine (1984)

severe right thigh pain, present since attempting a marathon 5 days previously. The patient began training one year prior to the race and gradually increased his activities to 50 miles per week; mostly on hard road surfaces and wearing purpose built shoes. Two weeks before the race he developed exercise-related pain localised to the medial aspect of the right thigh. He restricted his training, in the week prior to the race, to a 60-mile cycle ride and brisk walks. During the marathon attempt the initial 5 miles were accompanied by only minimal pain; but over the next 3 miles the pain increased to such a level that he was forced to retire. Medical advice was sought but no X-rays were taken and the injury was not diagnosed. After a further 5 days, medical advice was again sought and at this time examination revealed tenderness in the right groin and pain at the extremes of hip movement, passive flexion was accompanied by an audible click.
Molecular Biology of Gonadotropin-Releasing Hormone (GnRH)-I, GnRH-II, and Their Receptors in Humans
Authors: Chi Keung Cheng, Peter C. K. Leung
Journal: Endocrine Reviews (2005)

In human beings, two forms of GnRH, termed GnRH-I and GnRH-II, encoded by separate genes have been identified. Although these hormones share comparable cDNA and genomic structures, their tissue distribution and regulation of gene expression are significantly dissimilar. The actions of GnRH are mediated by the GnRH receptor, which belongs to a member of the rhodopsin-like G protein-coupled receptor superfamily. However, to date, only one conventional GnRH receptor subtype (type I GnRH receptor) uniquely lacking a carboxyl-terminal tail has been found in the human body. Studies on the transcriptional regulation of the human GnRH receptor gene have indicated that tissue-specific gene expression is mediated by differential promoter usage in various cell types. Functionally, there is growing evidence showing that both GnRH-I and GnRH-II are potentially important autocrine and/or paracrine regulators in some extrapituitary compartments. Recent cloning of a second GnRH receptor subtype (type II GnRH receptor) in nonhuman primates revealed that it is structurally and functionally distinct from the mammalian type I receptor. However, the human type II receptor gene homolog carries a frameshift and a premature stop codon, suggesting that a full-length type II receptor does not exist in humans.
Progression of idiopathic pulmonary fibrosis: lessons from asymmetrical disease
Authors: C. Tcherakian, V. Cottin, P.-Y. Brillet, O. Freynet, N. Naggara, Z. Carton, J.-F. Cordier, M. Brauner, D. Valeyre, H. Nunes
Journal: Thorax (2010)

<h3>Background</h3> In idiopathic pulmonary fibrosis (IPF) the distribution and spatial-temporal progression of fibrotic changes may be influenced by general or locoregional conditions. From this perspective, patients with asymmetrical disease (AIPF) may be unique. <h3>Methods</h3> This retrospective study included 32 patients (26 men, mean±SD age 69±7 years) with AIPF, as defined by an asymmetry ratio (most affected – least affected fibrosis score)/(most affected + least affected fibrosis score) &gt;0.2. The global fibrosis score was the average of the right and left scores. Patients with AIPF were compared with 64 matched controls with symmetrical IPF. <h3>Results</h3> Patients with AIPF did not differ from controls in global fibrosis score and forced vital capacity, but carbon monoxide transfer factor was less decreased (52±19% vs 43±13%, p=0.009). The rate of gastro-oesophageal reflux and acute exacerbations was significantly higher in patients with AIPF (62.5% vs 31.3%, p=0.006 and 46.9% vs 17.2%, p=0.004, respectively). In patients with AIPF the right side was more likely to be involved (62.5%); the median asymmetry ratio was 0.5 (range 0.24–1). Although the global fibrosis score worsened significantly in all 23 patients with AIPF with serial high-resolution CT scans (p&lt;0.0001), pulmonary fibrosis remained asymmetrical in all except three. During follow-up, 15 patients with AIPF experienced 18 acute exacerbations. The first episode was virtually unilateral, occurring in the most affected lung in 10 patients (66.7%). Survival was similar between patients with AIPF and controls. <h3>Conclusion</h3> AIPF may be related to locoregional factors including gastro-oesophageal reflux which may be responsible for both disease expansion and the occurrence of acute exacerbations.
Smad7 Gene Therapy Ameliorates an Autoimmune Crescentic Glomerulonephritis in Mice
Authors: Shuk-Man Ka, Xiao-Ru Huang, Hui-Yao Lan, Pei-Yi Tsai, Shun-Min Yang, Hao-Ai Shui, Ann Chen
Journal: Journal of the American Society of Nephrology (2007)

Autoimmune crescentic glomerulonephritis is characterized by severe immune response with glomerular crescentic formation and fibrosis in the kidney. Recent studies indicate that overexpression of renal Smad7 attenuates both renal fibrosis and inflammation in rat remnant kidney. However, little attention has been paid to the potential role of TGF-β/Smad signaling in autoimmune kidney disease. This study tested the hypothesis that blocking TGF-β signaling by overexpression of Smad7 may have a therapeutic effect in a mouse model of autoimmune crescentic glomerulonephritis that was induced in C57BL/6 × DBA/2J F1 hybrid mice by giving DBA/2J donor lymphocytes. Smad7 gene was transfected into the kidney using the ultrasound-microbubble–mediated system. Results showed that overexpression of Smad7 blocked both renal fibrosis and inflammatory pathways in terms of Smad2/3 and NF-κB activation (P < 0.01), thereby inhibiting α-smooth muscle actin; collagen I, III, and IV accumulation; and expression of inflammatory cytokines (IL-1β and IL-6), adhesion molecule/chemokine (intercellular adhesion molecule-1, monocyte chemoattractant protein-1), and inducible nitric oxide synthase (all P < 0.01). Leukocyte infiltration (CD4+ cells and macrophages) was also suppressed (P < 0.005). Severe histologic damage (glomerular crescent formation and tubulointerstitial injury) and functional injury including proteinuria were significantly improved (all P < 0.05). This study provides important evidence that overexpression of Smad7 may have therapeutic potential for autoimmune kidney disease.
Identification and Functional Characterization of Cardiac Troponin I As a Novel Disease Gene in Autosomal Dominant Dilated Cardiomyopathy
Authors: Sebastian Carballo, Paul Robinson, Robyn Otway, Diane Fatkin, Jan D.H. Jongbloed, Nicolaas de Jonge, Edward Blair, J. Peter van Tintelen, Charles Redwood, Hugh Watkins
Journal: Circulation Research (2009)

Idiopathic dilated cardiomyopathy (DCM) is inherited in approximately one third of cases, usually as an autosomal dominant trait. More than 30 loci have been identified, several of which encode sarcomeric proteins which can also be mutated to cause hypertrophic cardiomyopathy. One contractile protein gene well known as a hypertrophic cardiomyopathy disease gene, but with no reported mutation in autosomal dominant DCM, is TNNI3 which encodes cardiac troponin I.To test TNNI3 as a candidate gene, a panel of 96 probands with DCM was analyzed.Genomic DNA was isolated and TNNI3 exons screened by heteroduplex analysis. Exons with aberrant profiles were sequenced and variants evaluated by segregation analysis and study of normal controls. We report 2 novel TNNI3 missense mutations, Lys36Gln and Asn185Lys, each associated with severe and early onset familial DCM. Of the 5 mutation carriers, cardiac transplantation was required in 3, at ages 6, 15, and 24 years. Analysis of Ca(2+) regulation of actin-tropomyosin-activated myosin ATPase by troponin revealed that troponin reconstituted with either mutant troponin I gave lower maximum ATPase rates and lower Ca(2+) sensitivity than wild type. Furthermore, mutant thin filaments had reduced Ca(2+) affinity compared with normal.The functional alterations mirror closely a consistent phenotype found in proven DCM mutations in other thin filament proteins, thus supporting the interpretation that these mutations are disease-causing. These are the first reported autosomal dominant DCM-causing mutations in TNNI3, and so the findings expand the spectrum of disease-causing genes that lead to either hypertrophic cardiomyopathy or DCM depending on the specific mutation.
Human leukocyte antigen F (HLA-F). An expressed HLA gene composed of a class I coding sequence linked to a novel transcribed repetitive element.
Authors: D E Geraghty, X H Wei, H T Orr, B H Koller
Journal: The Journal of Experimental Medicine (1990)

We describe here the isolation and sequencing of a previously uncharacterized HLA class I gene. This gene, HLA-5.4, is the third non-HLA-A,B,C gene characterized whose sequence shows it encodes an intact class I protein. RNase protection assays with a probe specific for this gene demonstrated its expression in B lymphoblastoid cell lines, in resting T cells, and skin cells, while no mRNA could be detected in the T cell line Molt 4. Consistent with a pattern of expression different from that of other class I genes, DNA sequence comparisons identified potential regulator motifs unique to HLA-5.4 and possibly essential for tissue-specific expression. Protein sequence analysis of human and murine class I antigens has identified 10 highly conserved residues believed to be involved in antigen binding. Five of these are altered in HLA-5.4, and of these, three are nonconservative. In addition, examination of the HLA-5.4 DNA sequence predicts that the cytoplasmic segment of this protein is shorter than that of the classical transplantation antigens. The 3' untranslated region of the HLA-5.4 gene contains one member of a previously undescribed multigene family consisting of at least 30 members. Northern analysis showed that several of these sequences were transcribed, and the most ubiquitous transcript, a 600-nucleotide polyadenylated mRNA, was found in all tissues and cells examined. This sequence is conserved in the mouse genome, where a similar number of copies were found, and one of these sequences was also transcribed, yielding a 600-nucleotide mRNA. The characterization of this unique HLA class I gene and the demonstration of its tissue-specific expression have prompted us to propose that HLA-5.4 be designated HLA-F.
The JAK2/STAT3 signaling pathway is required for growth of CD44+CD24– stem cell–like breast cancer cells in human tumors
Authors: Lauren L.C. Marotta, Vanessa Almendro, Andriy Marusyk, Michail Shipitsin, Janina Schemme, Sarah R. Walker, Noga Bloushtain-Qimron, Jessica J. Kim, Sibgat A. Choudhury, Reo Maruyama, Zhenhua Wu, Mithat Gönen, Laura A. Mulvey, Marina O. Bessarabova, Sung Jin Huh, Serena J. Silver, So Young Kim, So Yeon Park, Hee Eun Lee, Karen S. Anderson, Andrea L. Richardson, Tatiana Nikolskaya, Yuri Nikolsky, X. Shirley Liu, David E. Root, William C. Hahn, David A. Frank, Kornelia Polyak
Journal: Journal of Clinical Investigation (2011)

Intratumor heterogeneity is a major clinical problem because tumor cell subtypes display variable sensitivity to therapeutics and may play different roles in progression. We previously characterized 2 cell populations in human breast tumors with distinct properties: CD44+CD24- cells that have stem cell-like characteristics, and CD44-CD24+ cells that resemble more differentiated breast cancer cells. Here we identified 15 genes required for cell growth or proliferation in CD44+CD24- human breast cancer cells in a large-scale loss-of-function screen and found that inhibition of several of these (IL6, PTGIS, HAS1, CXCL3, and PFKFB3) reduced Stat3 activation. We found that the IL-6/JAK2/Stat3 pathway was preferentially active in CD44+CD24- breast cancer cells compared with other tumor cell types, and inhibition of JAK2 decreased their number and blocked growth of xenografts. Our results highlight the differences between distinct breast cancer cell types and identify targets such as JAK2 and Stat3 that may lead to more specific and effective breast cancer therapies.
Skin Cancers and Non-Hodgkin Lymphoma Among Users of Systemic Glucocorticoids: A Population-Based Cohort Study
Authors: H. T. Sorensen, L. Mellemkjaer, G. L. Nielsen, J. A. Baron, J. H. Olsen, M. R. Karagas
Journal: JNCI Journal of the National Cancer Institute (2004)

Patients treated with glucocorticoids may have an increased risk of skin cancer. Using data from the population-based North Jutland Prescription Database and the Danish Cancer Registry, we compared observed and expected numbers of cases of skin cancer and non-Hodgkin lymphoma among 59 043 individuals who received prescriptions for glucocorticoids, a common immunosuppressive therapy, during an 8-year period from January 1, 1989, through December 31, 1996. The overall risks for squamous cell carcinomas and basal cell carcinomas of the skin were increased, particularly among persons who had 15 or more prescriptions (standardized incidence ratio [SIR] for squamous cell carcinomas = 2.45, 95% confidence interval [CI] = 1.37 to 4.04; SIR for basal cell carcinomas = 1.52, 95% CI = 1.09 to 2.07). An elevated risk was also found for non-Hodgkin lymphoma among those with 10–14 prescriptions (SIR = 2.68, 95% CI = 1.16 to 5.29). Our data suggest that use of glucocorticoids may be a shared risk factor for certain skin cancers and lymphomas.
Lack of efficacy of long‐term, low‐dose azithromycin in chronic rhinosinusitis: a randomized controlled trial
Authors: W. J. Videler, L. Badia, R. J. Harvey, S. Gane, C. Georgalas, F. W. van der Meulen, D. J. Menger, M. T. Lehtonen, S. K. Toppila‐Salmi, S. I. Vento, M. Hytönen, P. W. Hellings, L. Kalogjera, V. J. Lund, G. Scadding, J. Mullol, W. J. Fokkens
Journal: Allergy (2011)

To cite this article: Videler WJ, Badia L, Harvey RJ, Gane S, Georgalas C, van der Meulen FW, Menger DJ, Lehtonen MT, Toppila‐Salmi SK, Vento SI, Hytönen M, Hellings PW, Kalogjera L, Lund VJ, Scadding G, Mullol J, Fokkens WJ. Lack of Efficacy of long‐term, low‐dose azithromycin in chronic rhinosinusitis: a randomized controlled trial. Allergy 2011; 66 : 1457–1468. Abstract Background: In persistent chronic rhinosinusitis (CRS), conventional treatment is often insufficient. Long‐term, low‐dose administration of macrolides has been suggested as a treatment option. The MACS (Macrolides in chronic rhinosinusitis) study is a randomized placebo‐controlled trial evaluating the efficacy of azithromycin (AZM) in CRS. Methods: We describe a group of patients with recalcitrant CRS with and without nasal polyps unresponsive to optimal medical and (in 92% also) surgical treatment. Patients were treated with AZM or placebo. AZM was given for 3 days at 500 mg during the first week, followed by 500 mg per week for the next 11 weeks. Patients were monitored until 3 months post‐therapy. The assessments included Sino‐Nasal Outcome Test‐22 (SNOT‐22), a Patient Response Rating Scale, Visual Analogue Scale (VAS), Short Form‐36 (SF‐36), rigid nasal endoscopy, peak nasal inspiratory flow (PNIF), Sniffin’ Sticks smell tests and endoscopically guided middle meatus cultures. Results: Sixty patients with a median age of 49 years were included. Fifty per cent had asthma and 58% had undergone revision sinus surgery. In the SNOT‐22, Patient Response Rating Scale, VAS scores and SF‐36, no significant difference between the AZM and the placebo groups was demonstrated. Nasal endoscopic findings, PNIF results, smell tests and microbiology showed no relevant significant differences between the groups either. Conclusion: At the investigated dose of AZM over 3 months, no significant benefit was found over placebo. Possible reasons could be disease severity in the investigated group, under‐dosage of AZM and under‐powering of the study. Therefore, more research is urgently required.
Abstract 585: WIF1 re-expression in glioblastoma impairs migration through downregulation of the lncRNA MALAT1
Authors: Irene Vassallo, Marie-France Hamou, Monika E. Hegi
Journal: Cancer Research (2014)

Abstract Glioblastoma is the most aggressive form of human glioma. Despite progress in brain tumor therapy the prognosis remains dismal with a median survival of 15 months. We have recently shown that WIF1, an inhibitor of the WNT pathway, is downregulated in glioblastoma where it functions as strong tumor suppressor gene. Indeed, WIF1 re-expression impairs cell growth, cell migration, induces a senescence-like phenotype, and inhibits tumorigenicity in several orthotopic xenograft models. To analyse the molecular mechanisms underlying the tumor suppressive functions of WIF1 we developed a TET-on inducible system. Gene expression profiling following WIF1 induction revealed several interesting candidate genes validated in additional cell lines. The gene with strongest downregulation in WIF1-induced cells was MALAT1. MALAT1 is a long non-coding RNA that has been associated with tumor aggressiveness and invasion. Hence, MALAT1 is a plausible candidate, and its downregulation may contribute to the attenuation of malignancy seen in WIF1 expressing cells. Preliminary results show that the expression of a MALAT1 specific short-hairpin drastically reduces the infiltrative capability of glioblastoma cells. Analysis of gene xpression profiles revealed that MALAT1 is overexpressed in glioblastoma as compared to non-tumoral brain. These observations suggest that MALAT1 may contribute to the aggressive phenotype of glioblastoma. Experiments to test the effect of downregulation of MALAT1 in vivo are now ongoing. The poor prognosis is partially due to the extremely high capability of glioblastoma cells to migrate and to invade the surrounding brain structures, impairing complete surgical resection, hence leading inevitably to recurrence. This provides the rational to further investigate implications of MALAT1 in migration. Understanding the mechanisms of high invasive properties may indeed lead to the identification of new targets for therapy. Citation Format: Irene Vassallo, Marie-France Hamou, Monika E. Hegi. WIF1 re-expression in glioblastoma impairs migration through downregulation of the lncRNA MALAT1. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 585. doi:10.1158/1538-7445.AM2014-585
A biological model of commotio cordis: sudden death from low energy cheat wall impact
Authors: M.S. Link, P.J. Wang, N. Pandian, J.E. Udelson, M.Y. Lee, M.A. Vecchiotti, B. Vanderbrink, G. Mirra, S. Bharali, B.J. Maron, N.A.M. Estes
Journal: Journal of the American College of Cardiology (1998)
Dual effects of TGF-β on ERα-mediated estrogenic transcriptional activity in breast cancer
Authors: Yongsheng Ren, Liyu Wu, Andra R Frost, William Grizzle, Xu Cao, Mei Wan
Journal: Molecular Cancer (2009)

Abstract Background TGF-β resistance often develops in breast cancer cells that in turn overproduce this cytokine to create a local immunosuppressive environment that fosters tumor growth and exacerbates the invasive and metastatic behavior of the tumor cells themselves. Smads-mediated cross-talk with the estrogen receptor has been implied to play an important role in development and/or progression of breast cancer. We investigated how TGF-β regulates ERα-induced gene transcription and potential mechanisms of frequent TGF-β resistance in breast cancer. Methods Effect of TGF-β on ERα-mediated gene transcription was investigated in breast cancer cell lines using transient transfection, real-time PCR, sequential DNA precipitation, and small interfering RNA assays. The expression of Smads on both human breast cancer cell lines and ERα-positive human breast cancer tissue was evaluated by immunofluorescence and immunohistochemical assays. Results A complex of Smad3/4 mediates TGF-β inhibition of ERα-mediated estrogenic activity of gene transcription in breast cancer cells, and Smad4 is essential and sufficient for such repression. Either overexpression of Smad3 or inhibition of Smad4 leads to the "switch" of TGF-β from a repressor to an activator. Down-regulation and abnormal cellular distribution of Smad4 were associated with some ERα-positive infiltrating human breast carcinoma. There appears a dynamic change of Smad4 expression from benign breast ductal tissue to infiltrating ductal carcinoma. Conclusion These results suggest that aberrant expression of Smad4 or disruption of Smad4 activity lead to the loss of TGF-β suppression of ERα transactivity in breast cancer cells.
Ambulatory short-course high-dose oral amoxicillin for treatment of severe pneumonia in children: a randomised equivalency trial
Authors: Tabish Hazir, LeAnne M Fox, Yasir Bin Nisar, Matthew P Fox, Yusra Pervaiz Ashraf, William B MacLeod, Afroze Ramzan, Sajid Maqbool, Tahir Masood, Waqar Hussain, Asifa Murtaza, Nadeem Khawar, Parveen Tariq, Rai Asghar, Jonathon L Simon, Donald M Thea, Shamim A Qazi
Journal: The Lancet (2008)
Bioenergetic constraints on tactical decision making in middle distance running
Authors: A M Jones, B J Whipp
Journal: British Journal of Sports Medicine (2002)

The highest velocity that a runner can sustain during middle distance races is defined by the intersection of the runner's individual velocity-time curve and the distance-time curve. The velocity-time curve is presumably fixed at the onset of a race; however, whereas the race distance is ostensibly fixed, the actual distance-time curve is not. That is, it is possible for a runner to run further than the race distance if he or she runs wide on bends in track races. In this instance, the point of intersection of the individual velocity-time curve and the distance-time curve will move downwards and to the right, reducing the best average velocity that can be sustained for the distance.To illustrate this point, the race tactics used by the gold and silver medallists at 800 m and 5000 m in the Sydney Olympics were analysed. The paths taken by the runners were carefully tracked and the total distance they covered during the races and the average velocity they sustained over the distances they actually covered were calculated.In both the Olympic 800 m and 5000 m finals, for example, the winner was not the runner who ran at the highest average velocity in the race. Rather, the winners of these races were able to husband their metabolic resources to better effect by running closer to the actual race distance.Race results in middle distance running events are dependent not just on the energetic potential of the runners at the start of the race and their strategy for pace allocation, but also on the effect of their tactical approach to positioning on the total distance covered in the race. Middle distance runners should be conscious of minimising the distance covered in races if they wish to optimise their performance.