tbuckley/cabot-search huggingface dataset:
Attenuation of cardiac dysfunction by HSPA12B in endotoxin-induced sepsis in mice through a PI3K-dependent mechanism
Authors: H. Zhou, J. Qian, C. Li, J. Li, X. Zhang, Z. Ding, X. Gao, Z. Han, Y. Cheng, L. Liu
Journal: Cardiovascular Research (2010)

AimsCardiac dysfunction is a critical manifestation of severe sepsis/septic shock and is responsible for high mortality due to sepsis. Recent evidence suggests that angiogenic factors have a protective effect on sepsis-induced organ damage. Heat shock protein A12B (HSPA12B) is a newly discovered gene that is essential for angiogenesis. We hypothesized that overexpression of HSPA12B would induce protection against endotoxin-induced cardiac dysfunction.
Effects of deferasirox-deferoxamine on myocardial and liver iron in patients with severe transfusional iron overload
Authors: Yesim Aydinok, Antonis Kattamis, M. Domenica Cappellini, Amal El-Beshlawy, Raffaella Origa, Mohsen Elalfy, Yurdanur Kilinç, Silverio Perrotta, Zeynep Karakas, Vip Viprakasit, Dany Habr, Niculae Constantinovici, Junwu Shen, John B. Porter
Journal: Blood (2015)
Expression of platelet-derived growth factor in a model of acute liver injury
Authors: Massimo Pinzani, Stefano Milani, Cecilia Grappone, Frederick L. Weber, Paolo Gentilini, Hanna E. Abboud
Journal: Hepatology (1994)

Platelet-derived growth factor has been shown to play an important role in the repair process after acute tissue injury and in the pathogenesis of several fibrogenic disorders. The aim of this study was to evaluate whether increased expression of platelet-derived growth factor and its β-receptor subunit occurs in a model of acute liver injury. Male Sprague-Dawley rats were given a single intragastric dose of carbon tetrachloride and killed at intervals of 24, 48 and 72 hr and 1 wk. Control animals were included in each group. Platelet-derived growth factor-B chain mRNA expression, analyzed by RNase protection assay, was not detectable in control samples or in samples obtained 24 hr or 1 wk after carbon tetrachloride. However, the presence of protected fragments of 130 kb was clearly detected after 48 hr and was still present, although less abundant, after 72 hr. The distribution of platelet-derived growth factor protein in liver tissue sections, evaluated by immunohistochemistry, was restricted to centrilobular veins and portal tracts in normal liver. In carbon tetrachloride-treated rats, prominent staining was observed in areas corresponding to hepatocellular necrosis and inflammatory infiltration. This feature, already present at 24 hr after carbon tetrachloride, became more marked at 48 hr with a gradual resolution after 72 hr. The expression of platelet-derived growth factor-receptor β-subunit mRNA, evaluated by in situ hybridization, was markedly increased after carbon tetrachloride with a peak at 24 hr and was mainly localized over mesenchymal cells in the hepatic sinusoids. The overall analysis of these results suggests that platelet-derived growth factor may play a positive role in the process of tissue repair after acute liver injury by promoting effective necrotic tissue removal and the reconstruction of an adequate extracellular matrix network. (Hepatology 1994;19:701-707).
Glucose turnover and insulin clearance after growth hormone treatment in girls with turner's syndrome
Authors: L.D. Monti, P. Brambilla, A. Caumo, F. Magni, S. Omati, G. Nizzoli, B. di Natale, M. Galli-Kienle, C. Cobelli, G. Chiumello, G. Pozza
Journal: Metabolism (1997)
REPORT OF RESEARCH AND EXPERIMENTATION IN EXERCISE AND RECREATIONAL THERAPY
Authors: D. D. CAMPBELL, JOHN EISELE DAVIS
Journal: American Journal of Psychiatry (1940)

In conclusion, the writers do not wish to create the impression that physical therapy has been viewed as a panacea. Its many limitations, both as to content and methods have been apparent in attempts to utilize many and diversified activities nor has physical therapy been employed at this Facility as a purely independent adjuvant. The ideal therapeutic program advocated and carried out has represented a balanced regimen of work, rest and recreation. Attempts are constantly being made to impress patients with the importance of progressing from play activity to the more responsible role typified by work so that they may be assisted in their return to normal responsibility. The importance of utilizing play mechanisms as a distinctive means of elevating the patient's social respect in the direction of more easeful and confident social relationships, which will assist the individual to resume his place in normal society, is being constantly stressed. The physical program has been organized so as to fit most effectively and cooperatively into the regular hospital routine. It is hoped that these observations may lead to further study of the possibilities of this adjuvant in the promotion of more effective rehabilitative methods.
Genetic and Expression Profiles of Squamous Cell Carcinoma of the Head and Neck Correlate with Cisplatin Sensitivity and Resistance in Cell Lines and Patients
Authors: Jan Akervall, Xiang Guo, Chao-Nan Qian, Jacqueline Schoumans, Brandon Leeser, Eric Kort, Andrew Cole, James Resau, Carol Bradford, Thomas Carey, Johan Wennerberg, Harald Anderson, Jan Tennvall, Bin T. Teh
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The choice of treatment for squamous cell carcinoma of the head and neck (SCCHN) is still primarily based on the tumor-node-metastasis classification. However, it is reasonable to believe that biological profiles of SCCHN may be independently associated with response to therapy. The aim of the present study was to examine genetic changes and gene expression profiles that might correlate with sensitivity to cisplatin [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] in 10 SCCHN cell lines. Experimental Design: Five cisplatin-sensitive and five cisplatin-resistant cell lines [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay] were studied by comparative genomic hybridization, spectral karyotyping, and cDNA microarray analysis (21,632 sequence-validated human cDNA; confirmation by reverse transcriptase-PCR for selected genes). For the MET proto-oncogene, which showed low expression in the chemosensitive cell lines, we did immunohistochemical staining on SCCHN of 29 patients who received induction chemotherapy. Results: The five cisplatin-resistant cell lines showed significantly more genetic imbalances (regions of loss and amplification) and chromosomal abnormalities by comparative genomic hybridization and spectral karyotyping, respectively, than did the five cisplatin-sensitive cell lines. Microarray studies identified ∼60 genes that clearly distinguish between the two groups of cell lines. Some of these genes are known to be involved in tumor progression, metastasis, and drug resistance. We identified low expression of c-met (immunohistochemistry) as a predictive factor for complete response in nondiploid tumors (P = 0.026). Conclusions: We conclude that cisplatin sensitivity and resistance are related to distinctive differences in the genetic and expression profiles in individual SCCHN tumor cell lines and in SCCHN patients. The genes we have identified may serve as potential targets for novel treatment strategies.
BRCA1-IRIS Overexpression Promotes Cisplatin Resistance in Ovarian Cancer Cells
Authors: Kerri L. Chock, Jamie M.S. Allison, Yoshiko Shimizu, Wael M. ElShamy
Journal: Cancer Research (2010)

Evasion of apoptosis plays a key role in cancer development, drug resistance, and recurrence. The BRCA1 locus product protein BRCA1-IRIS is overexpressed in several cisplatin-resistant ovarian cancer cell lines, but its relationship to resistance is uncertain. Here, we show that in human ovarian surface epithelial (HOSE) cells, overexpression of BRCA1-IRIS triggers expression of the antiapoptotic protein survivin. Negative modulation of phosphatidylinositol 3-kinase (PI3K) signaling or AKT silencing reduced survivin expression in this setting. Conversely, silencing BRCA1-IRIS in ovarian cancer cell lines derepressed PTEN expression along with the antiapoptotic AKT targets FOXO1 and FOXO3a, suppressing survivin expression. Cisplatin (≤50 μmol/L) exposure was sufficient to activate expression of the BRCA1-IRIS-AKT-survivin cascade in HOSE cells, whereas under similar conditions cisplatin failed to induce apoptosis in ovarian cancer cell lines expressing this regulatory cascade. Mechanistic investigations indicated that BRCA1-IRIS triggers survivin expression through a PI3K/AKT-dependent pathway involving NF-κB, but also through a PI3K/AKT-independent pathway involving PTEN, FOXO1, and FOXO3a. Our findings indicate how BRCA1-IRIS overexpression prevents chemotherapy-induced cell death by upregulating expression of survivin, and they highlight this regulatory cascade as a candidate focus to improve treatment of advanced drug-resistant ovarian cancers.
Allelic Imbalance at the HER2/TOP2A Locus in Breast Cancer
Authors: C.J.J. Huijsmans, H. Rigter, A.J. van den Brule, J. Poodt, J.C. van der Linden, P.H.M. Savelkoul, M. Hilbink-Smolders, M.H.A. Hermans
Journal: Annals of Oncology (2013)
Epac-Rap Signaling Reduces Cellular Stress and Ischemia-induced Kidney Failure
Authors: Geurt Stokman, Yu Qin, Hans-Gottfried Genieser, Frank Schwede, Emile de Heer, Johannes L. Bos, Ingeborg M. Bajema, Bob van de Water, Leo S. Price
Journal: Journal of the American Society of Nephrology (2011)

Renal ischemia-reperfusion injury is associated with the loss of tubular epithelial cell-cell and cell-matrix interactions which contribute to renal failure. The Epac-Rap signaling pathway is a potent regulator of cell-cell and cell-matrix adhesion. The cyclic AMP analogue 8-pCPT-2'-O-Me-cAMP has been shown to selectively activate Epac, whereas the addition of an acetoxymethyl (AM) ester to 8-pCPT-2'-O-Me-cAMP enhanced in vitro cellular uptake. Here we demonstrate that pharmacological activation of Epac-Rap signaling using acetoxymethyl-8-pCPT-2'-O-Me-cAMP preserves cell adhesions during hypoxia in vitro, maintaining the barrier function of the epithelial monolayer. Intrarenal administration in vivo of 8-pCPT-2'-O-Me-cAMP also reduced renal failure in a mouse model for ischemia-reperfusion injury. This was accompanied by decreased expression of the tubular cell stress marker clusterin-α, and lateral expression of β-catenin after ischemia indicative of sustained tubular barrier function. Our study emphasizes the undervalued importance of maintaining tubular epithelial cell adhesion in renal ischemia and demonstrates the potential of pharmacological modulation of cell adhesion as a new therapeutic strategy to reduce the extent of injury in kidney disease and transplantation.
PET Imaging of Inflammation Biomarkers
Authors: Chenxi Wu, Fang Li, Gang Niu, Xiaoyuan Chen
Journal: Theranostics (2013)

Inflammation plays a significant role in many disease processes.Development in molecular imaging in recent years provides new insight into the diagnosis and treatment evaluation of various inflammatory diseases and diseases involving inflammatory process.Positron emission tomography using 18 F-FDG has been successfully applied in clinical oncology and neurology and in the inflammation realm.In addition to glucose metabolism, a variety of targets for inflammation imaging are being discovered and utilized, some of which are considered superior to FDG for imaging inflammation.This review summarizes the potential inflammation imaging targets and corresponding PET tracers, and the applications of PET in major inflammatory diseases and tumor associated inflammation.Also, the current attempt in differentiating inflammation from tumor using PET is also discussed.
P129 Skeletal muscle weakness, not arterial stiffness, differs according to GOLD group in COPD: Abstract P129 Table 1.
Authors: M Fisk, N Gale, D Mohan, MN Marchong, J Forman, DA Lomas, JR Cockcroft, CE Bolton, W MacNee, J Fuld, CM Calverley, CM McEniery, R Tal-Singer, IB Wilkinson, MI Polkey
Journal: Thorax (2013)

<h3>Introduction</h3> In the GOLD 2011 COPD classification, patients in Group D are considered to be at highest risk of mortality, due to airflow limitation and exacerbations and also to be most symptomatic. Skeletal muscle weakness and cardiovascular disease are associated with mortality in patients with COPD and elderly people <i>per se</i> .We hypothesised that GOLD D patients would have more severe extra-pulmonary manifestations of COPD than A-C. <h3>Objectives</h3> To measure skeletal muscle weakness and arterial stiffness (an independent predictor of cardiovascular risk) in the ERICA (Evaluating the Role of Inflammation in Chronic Airways Disease) consortium (work package 1) cohort categorised by GOLD Group (ABCD). <h3>Methods</h3> ERICA is a multicentre UK study investigating the role of inflammation and the prevalence and significance of cardiovascular and skeletal muscle manifestations in COPD. This interim analysis was conducted on 395 (49%) of 800 planned participants. Measurements include aortic pulse wave velocity (APWV) to measure arterial stiffness, quadriceps maximal voluntary contraction force (QMVC), plasma fibrinogen and 6-minute walk distance (6MWD). We defined arterial stiffness as APWV &gt;10m/s, and skeletal muscle weakness as QMVC/BMI (Body Mass Index) ratio &gt;1.2. <h3>Results</h3> 395 subjects were classified according to GOLD groups using the mMRC (modified Medical Research Council) dyspnoea scale to evaluate symptoms, (<b>Table 1</b>). The majority of subjects were in groups D (57%) and B (33%), with low numbers observed in groups A (6%) and C (4%). Higher levels of airflow limitation were observed in groups C &amp; D (p = 0.012). Fibrinogen was higher in groups C &amp; D (p = 0.001), consistent with COPD severity. Group D had reduced 6MWD and quadriceps strength consistent with the hypothesis that they have more severe extra-pulmonary manifestations of COPD and increased risk of mortality. Of note, Group B (‘high symptom, low risk’) also had reduced quadriceps strength and 6MWD, although for 6MWD this reduction (p = 0.06 compared to group A) was not as profound as Group D (p &lt; 0.001). No difference between groups was observed for APWV. <h3>Conclusion</h3> The GOLD group classification captures risk related to skeletal muscle weakness but not arterial stiffness and indicates groups B &amp; D may benefit from intensive exercise therapy.
A Phase I and Pharmacokinetic Study of VNP40101M, a Novel Sulfonylhydrazine Alkylating Agent, in Patients with Refractory Leukemia
Authors: Francis Giles, Deborah Thomas, Guillermo Garcia-Manero, Stefan Faderl, Jorge Cortes, Srdan Verstovsek, Alessandra Ferrajoli, Sima Jeha, Miloslav Beran, Charles Koller, Michael Andreeff, Ann Cahill, Caroline Clairmont, Mario Sznol, Hagop Kantarjian
Journal: Clinical Cancer Research (2004)

Abstract Purpose: VNP40101M is a novel sulfonylhydrazine alkylating agent with broad antitumor activity in animal models. As alkylating agents are important antileukemia drugs, a Phase I and pharmacokinetic study of VNP40101M was conducted in patients with refractory or relapsed leukemias or poor-risk myelodysplastic syndromes (MDS). Experimental Design: VNP40101M was given as a single i.v. infusion over 15–70 min on day 1. Courses were repeated every 4 weeks according to antileukemic activity. The starting dose of 220 mg/m2 was escalated by ∼33% in cohorts of 3–6 patients until a maximum-tolerated dose was established. One additional cohort was treated with the maximum-tolerated dose divided over days 1 and 8. Results: Thirty-eight patients, including 28 with acute myeloid leukemia and 5 with MDS, received 52 courses of treatment. Nondose-limiting, reversible infusion-related toxicities were the most frequent adverse event, occurring in 24 (63%) patients on the first course. Dose escalation was terminated at 708 mg/m2 for prolonged myelosuppression in 1 of 7 patients, and 600 mg/m2 was selected as the recommended Phase II dose, with no significant extramedullary toxicity at this dose level. Two patients, 1 with MDS treated with 300 mg/m2 and 1 with acute myeloid leukemia treated with 600 mg/m2, achieved complete remission. Conclusions: VNP40101M had significant antileukemic activity and minimal extramedullary toxicity in patients with relapsed or refractory disease.
The Th17 immune response is controlled by the Rel–RORγ–RORγT transcriptional axis
Authors: Qingguo Ruan, Vasumathi Kameswaran, Yan Zhang, Shijun Zheng, Jing Sun, Junmei Wang, Jennifer DeVirgiliis, Hsiou-Chi Liou, Amer A. Beg, Youhai H. Chen
Journal: The Journal of Experimental Medicine (2011)

The Th17 cells use the retinoid-related orphan receptor-γ (Rorg or Rorc) to specify their differentiation and lineage-specific function. However, how Rorg is switched on during Th17 differentiation is unknown. We report here that c-Rel and RelA/p65 transcription factors drive Th17 differentiation by binding to and activating two distinct Rorg promoters that control RORγT and RORγ expression, respectively. Similar to RORγT, RORγ is selectively expressed in Th17 cells and is effective in specifying the Th17 phenotype. T cells deficient in c-Rel or RelA are significantly compromised in Th17 differentiation, and c-Rel–deficient mice are defective in Th17 responses. Thus, Th17 immunity is controlled by a Rel–RORγ–RORγT axis, and strategies targeting Rel/NF-κB can be effective for controlling Th17 cell–mediated diseases.
Population Genomic Analysis of ALMS1 in Humans Reveals a Surprisingly Complex Evolutionary History
Authors: Laura B. Scheinfeldt, Shameek Biswas, Jennifer Madeoy, Caitlin F. Connelly, Eric E. Schadt, Joshua M. Akey
Journal: Molecular Biology and Evolution (2009)

Mutations in the human gene ALMS1 result in Alström Syndrome, which presents with early childhood obesity and insulin resistance leading to Type 2 diabetes. Previous genomewide scans for selection in the HapMap data based on linkage disequilibrium and population structure suggest that ALMS1 was subject to recent positive selection. Through a detailed population genomic analysis of existing genomewide data sets and new resequencing data obtained in geographically diverse populations, we find that the signature of selection at ALMS1 is considerably more complex than what would be expected for an idealized model of a selective sweep acting on a newly arisen advantageous mutation. Specifically, we observed three highly divergent and globally dispersed haplogroups, two of which carry a set of seven derived nonsynonymous single nucleotide polymorphisms that are nearly fixed in Asian populations. Our data suggest that the interaction of human demographic history and positive selection on standing variation in Eurasian populations approximately 15 thousand years ago parsimoniously explains the spectrum of extant ALMS1 variation. These results provide new insights into the evolutionary history of ALMS1 in humans and suggest that selective events identified in genomewide scans may be more complex than currently appreciated.
Preventing ACL injuries, turning research into practice and avoiding media ambush
Authors: Karim M Khan
Journal: British Journal of Sports Medicine (2008)

Finland is famous for many things including its haunting national anthem (creatively called 'Finlandia') and a universal love of lakes and saunas. I'll stay away from memorable Eurovision winners Lordii!

In this issue of BJSM, you can read the report of the Finnish randomised controlled trial (RCT) that showed a tremendous reduction of lower limb injuries with a simple warm-up programme (see page 802) .1 Although not powered for that holy grail of sports medicine research — reduced anterior cruciate ligament injuries – the study provides a very clear message. If you have a daughter who is playing basketball, soccer, handball or floorball, then it is crazy if her team isn’t undertaking one of the evidence-based warm-ups targeting lower limb injury prevention. You’ll find exercises illustrated in the links here as well as in papers previously published in Europe and the US. There is now incontrovertible evidence that a series of warm-up programmes that encourage neuromuscular training and balance activities have more benefits than risks. We owe a great deal to pioneers including Caraffa, Myklebust, Maendelbaum and Silvers.2 If you missed the special IOC knee consensus statement in June,3 you can download it from the BJSM home page (click on “Browse by Issues” on the right-hand side).

How can we “interface” …
Matrix metalloproteases: a role in overuse tendinopathies
Authors: M Magra, N Maffulli
Journal: British Journal of Sports Medicine (2005)

Sixty-nine patients who had neurosurgical treatment for acoustic neuroma by one of two different techniques were studied with a view to determining the incidence of postoperative epilepsy. Fourty-five patients who had larger tumours underwent a combined translabyrinthine and transtentorial neurosurgical approach. For the others with smaller neuromas a translabyrinthine method was used. Only the combined approach was associated with postoperative epilepsy, and it occurred in 22% of the patients. Epilepsy was associated with temporal love trauma during surgery.
Acute gastritis with hypochlorhydria: report of 35 cases with long term follow up
Authors: W V Harford, C Barnett, E Lee, G Perez-Perez, M J Blaser, W L Peterson
Journal: Gut (2000)

Between 1976 and 1987, 35 cases of acute gastritis with hypochlorhydria (AGH) were seen in our research laboratory. The aims of this study were to determine the natural history of AGH and the role of Helicobacter pylori in its pathogenesis.Archived serum and gastric biopsy samples obtained from AGH subjects were examined for evidence of H pylori colonisation. Twenty eight of 33 (85%) surviving AGH subjects returned a mean of 12 years after AGH for follow up studies, including determination of H pylori antibodies, basal and peak acid output, endoscopy, and gastric biopsies. A matched control group underwent the same studies.Archived material provided strong evidence of new H pylori acquisition in a total of 14 subjects within two months, in 18 within four months, and in 22 within 12 months of recognition of AGH. Prevalence of H pylori colonisation at follow up was 82% (23 of 28) in AGH subjects, significantly (p<0.05) higher than in matched controls (29%). Basal and peak acid output returned to pre-AGH levels in all but two subjects.One of several possible initial manifestations of H pylori acquisition in adults may be AGH. While H pylori colonisation usually persists, hypochlorhydria resolves in most subjects.
Influence of Recombinant Human Relaxin on Renal Hemodynamics in Healthy Volunteers
Authors: Marie C. Smith, Lee. A. Danielson, Kirk. P. Conrad, John M. Davison
Journal: Journal of the American Society of Nephrology (2006)

Maternal renal hemodynamic adaptation to human pregnancy is one of the most dramatic of all physiologic changes, but the factors that are responsible have remained elusive. In rat pregnancy, there are comparable renal hemodynamic changes, and in this species there is comprehensive evidence that the ovarian hormone relaxin (RLX) is responsible. This study investigated the renal effects of recombinant human RLX (rhRLX) in humans. Eleven volunteers (six male, five female) received intravenous infusions of rhRLX over 5 h at an infusion rate that was chosen to sustain serum concentrations that are comparable to early pregnancy. The renal clearances of inulin and para-aminohippurate were used to measure GFR and renal plasma flow, respectively. Irrespective of gender, renal plasma flow was increased by 47% compared with baseline levels (P < 0.0001), but no significant change was observed in GFR. There were no side effects or adverse reactions of rhRLX given as an intravenous infusion, and the data suggest that RLX indeed may be one of the elusive renal vasodilatory factors in human pregnancy. Further work is necessary to elucidate the complimentary factors that permit the concomitant increase in GFR during pregnancy.