tbuckley/cabot-search huggingface dataset:
Induction of caspase-dependent, p53-mediated apoptosis by apigenin in human neuroblastoma.
Authors: Rijin Xiao, Thomas M Badger, Frank A Simmen
Journal: Molecular Cancer (2005)

We previously reported that lifetime consumption of soy proteins or whey proteins reduced the incidence of azoxymethane (AOM)-induced colon tumors in rats. To obtain insights into these effects, global gene expression profiles of colons from rats with lifetime ingestion of casein (CAS, control diet), soy protein isolate (SPI), and whey protein hydrolysate (WPH) diets were determined. Male Sprague Dawley rats, fed one of the three purified diets, were studied at 40 weeks after AOM injection and when tumors had developed in some animals of each group. Total RNA, purified from non-tumor tissue within the proximal half of each colon, was used to prepare biotinylated probes, which were hybridized to Affymetrix RG_U34A rat microarrays containing probes sets for 8799 rat genes. Microarray data were analyzed using DMT (Affymetrix), SAM (Stanford) and pair-wise comparisons. Differentially expressed genes (SPI and/or WPH vs. CAS) were found. We identified 31 induced and 49 repressed genes in the proximal colons of the SPI-fed group and 44 induced and 119 repressed genes in the proximal colons of the WPH-fed group, relative to CAS. Hierarchical clustering identified the co-induction or co-repression of multiple genes by SPI and WPH. The differential expression of I-FABP (2.92-, 3.97-fold down-regulated in SPI and WPH fed rats; P = 0.023, P = 0.01, respectively), cyclin D1 (1.61-, 2.42-fold down-regulated in SPI and WPH fed rats; P = 0.033, P = 0.001, respectively), and the c-neu proto-oncogene (2.46-, 4.10-fold down-regulated in SPI and WPH fed rats; P < 0.001, P < 0.001, respectively) mRNAs were confirmed by real-time quantitative RT-PCR. SPI and WPH affected colonic neuro-endocrine gene expression: peptide YY (PYY) and glucagon mRNAs were down-regulated in WPH fed rats, whereas somatostatin mRNA and corresponding circulating protein levels, were enhanced by SPI and WPH. The identification of transcripts co- or differentially-regulated by SPI and WPH diets suggests common as well as unique anti-tumorigenesis mechanisms of action which may involve growth factor, neuroendocrine and immune system genes. SPI and WPH induction of somatostatin, a known anti-proliferative agent for colon cancer cells, would inhibit tumorigenesis.
Added value of ovarian reserve testing on patient characteristics in the prediction of ovarian response and ongoing pregnancy: an individual patient data approach
Authors: Simone L. Broer, Jeroen van Disseldorp, Kimiko A. Broeze, Madeleine Dolleman, Brent C. Opmeer, Patrick Bossuyt, Marinus J.C. Eijkemans, Ben-Willem J. Mol, Frank J.M. Broekmans, S.L. Broer, J. van Disseldorp, K.A. Broeze, M. Dolleman, B.C. Opmeer, R.A. Anderson, M. Ashrafi, L. Bancsi, L. E. Caroppo, A. Copperman, T. Ebner, M. Eldar Geva, M. Erdem, E.M. Greenblatt, K. Jayaprakasan, Raine Fenning, E.R. Klinkert, J. Kwee, C.B. Lambalk, A. La Marca, M. McIlveen, L.T. Merce, S. Muttukrishna, S.M. Nelson, H.Y. Ng, B. Popovic-Todorovic, J.M.J. Smeenk, C. Tomás, P.J.Q. Van der Linden, I.A. van Rooij, I.K. Vladimirov, P.B. Bossuyt, M.J.C. Eijkemans, B.W. Mol, Broekmans Frank
Journal: Human Reproduction Update (2012)

BACKGROUND Although ovarian reserve tests (ORTs) are frequently used prior to IVF treatment for outcome prediction, their added predictive value is unclear. We assessed the added value of ORTs to patient characteristics in the prediction of IVF outcome. METHODS An individual patient data (IPD) meta-analysis from published studies was performed. Studies on FSH, anti-Müllerian hormone (AMH) or antral follicle count (AFC) in women undergoing IVF were identified and authors were contacted. Using random intercept logistic regression models, we estimated the added predictive value of ORTs for poor response and ongoing pregnancy after IVF, relative to patient characteristics. RESULTS We were able to collect 28 study databases, comprising 5705 women undergoing IVF. The area under the receiver-operating characteristic curve (AUC) for female age in predicting poor response was 0.61. AFC and AMH each significantly improved the model fit (P-value <0.001). Moreover, almost a similar accuracy was reached using AMH or AFC alone (AUC 0.78 and 0.76, respectively). Combining the two tests, however, did not improve prediction (AUC 0.80, P = 0.19) of poor response. In predicting ongoing pregnancy after IVF, age was the best single predictor (AUC 0.57), and none of the ORTs added any value. CONCLUSIONS This IPD meta-analysis demonstrates that AFC and AMH clearly add to age in predicting poor response. As single tests, AFC and AMH both fully cover the prediction of poor ovarian response. In contrast, none of the ORTs add any information to the limited capacity of female age to predict ongoing pregnancy after IVF. The clinical usefulness of ORTs prior to IVF will be limited to the prediction of ovarian response.
p53 protein accumulation in lung carcinomas of patients exposed to asbestos and tobacco smoke.
Authors: K Nuorva, R Mäkitaro, E Huhti, D Kamel, K Vähäkangas, R Bloigu, Y Soini, P Pääkkö
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Primary lung carcinomas often carry mutations in the p53 tumor suppressor gene. Most of these mutations alter the conformation of the p53 protein into a more stable phenotype that makes it immunohistochemically detectable. Asbestos is a carcinogen that can cause deletions in chromosomes and possibly also gene mutations. In this study we examined 70 primary lung carcinomas for p53 protein accumulation using a polyclonal antihuman p53 antibody, CM-1. Patients were interviewed about their occupational and smoking history and classified according to their anamnestical asbestos exposure. Presence of asbestos bodies (AB) was evaluated from histologic samples of peripheral nontumorous lung tissue using both 5-microns-thick sections stained with Perls' iron and 30-microns-thick unstained sections. Abnormal accumulation of p53 protein was found in 36 tumors (51%), more often in patients exposed to asbestos than in patients without exposure (67% versus 40%, p = 0.027). Significant association was also noticed between the accumulation of p53 and the asbestos content of lung tissue: 35% of the p53-positive patients had more than one AB/cm2 compared with 14% of p53-negative cases (p = 0.046). Patients with strongly p53-positive tumors were heavier smokers (57.2 +/- 38.2 pack-years) than patients with p53-negative or lightly positive tumors (38.9 +/- 19.9 pack-years) (p = 0.017). Our findings indicate that both asbestos exposure and heavy smoking can cause abnormal p53 protein accumulation suggestive of mutated p53.
HIF-1α expression regulates the bactericidal capacity of phagocytes
Authors: Carole Peyssonnaux, Vivekanand Datta, Thorsten Cramer, Andrew Doedens, Emmanuel A. Theodorakis, Richard L. Gallo, Nancy Hurtado-Ziola, Victor Nizet, Randall S. Johnson
Journal: Journal of Clinical Investigation (2005)

Hypoxia is a characteristic feature of the tissue microenvironment during bacterial infection. Here we report on our use of conditional gene targeting to examine the contribution of hypoxia-inducible factor 1, α subunit (HIF-1α) to myeloid cell innate immune function. HIF-1α was induced by bacterial infection, even under normoxia, and regulated the production of key immune effector molecules, including granule proteases, antimicrobial peptides, nitric oxide, and TNF-α. Mice lacking HIF-1α in their myeloid cell lineage showed decreased bactericidal activity and failed to restrict systemic spread of infection from an initial tissue focus. Conversely, activation of the HIF-1α pathway through deletion of von Hippel–Lindau tumor-suppressor protein or pharmacologic inducers supported myeloid cell production of defense factors and improved bactericidal capacity. HIF-1α control of myeloid cell activity in infected tissues could represent a novel therapeutic target for enhancing host defense.
Safeguarding the child athlete in sport: a review, a framework and recommendations for the IOC youth athlete development model
Authors: M Mountjoy, D J A Rhind, A Tiivas, M Leglise
Journal: British Journal of Sports Medicine (2015)

Participation in sport has many physical, psychological and social benefits for the child athlete. A growing body of evidence indicates, however, that sport participation may have inherent threats for the child’s well-being. The subject of safeguarding children in sport has seen an increase in scientific study in recent years. In particular, there is increasing emphasis on identifying who is involved in abuse, the context of where it occurs and the identification of the various forms of abuse that take place in the sporting domain. Safeguarding principles developed by the International Safeguarding Children in Sport Founders Group are presented along with 8 underlying pillars which underpin the successful adoption and implementation of safeguarding strategies. This safeguarding model is designed to assist sport organisations in the creation of a safe sporting environment to ensure that the child athlete can flourish and reach their athletic potential through an enjoyable experience. The aim of this narrative review is to (1) present a summary of the scientific literature on the threats to children in sport; (2) introduce a framework to categorise these threats; (3) identify research gaps in the field and (4) provide safeguarding recommendations for sport organisations.
Blood Coagulation Following Vasectomy
Authors: C. Thomas Kisker
Journal: JAMA (1979)

Concern that men may have an increased risk of the development of thrombophlebitis following vasectomy prompted the study of 58 vasectomized men and 37 age-matched controls. Eight patients undergoing total hip replacement also were studied, since they are known to have an increased risk of thrombotic complications. There were no changes in coagulation suggestive of a thrombotic tendency in the vasectomized population, though an increase in fibrinogen concentration was present preoperatively, and transient increases in factor V concentration, prothrombin time, and fibrinogen concentration were seen postoperatively in some cases. None of the vasectomized patients had clinical evidence suggestive of thrombosis.
Abstract #LB-292: Involvement of Thymidine Kinase1 in 5-FU-Enhanced [18F]FLT Uptake in Salvage Pathway-Dependent Cancer Cells
Authors: Seung-Jin Lee, Seog-Young Kim, Jin-Sook Ryu, Seung-Jun Oh, Dae-Hyuk Moon
Journal: Cancer Research (2009)

Positron emission tomography (PET) imaging with [18F]fluorothymidine ([18F]FLT) is a potential noninvasive marker for early monitoring of therapeutic response. [18F]FLT, a thymidine analogue, is trapped in cells after phosphorylation by thymidine kinase 1 (TK1), which is expressed in late G1 and S phase of cell cycle, but still there is limited information for the effect of relative expression of TK1 of tumors on the prediction of [18F]FLT-PET. Recent studies showed that 5-fluorouracil (5-FU) exceptionally increased [18F]FLT uptake of tumor in early time point irrespective of cytotoxicity, which provoked further experiments for the appropriate imaging endpoint and the molecular mechanism(s) for [18F]FLT flare. In this study, we examined 5-FU-induced [18F]FLT uptake in cells differentially expressing TK1 and in xenograft mice with dynamic imaging for the validation of quantitative prediction of 5-FU response by [18F]FLT-PET. We selected 4 representative cell lines, which have similar responsibility to 5-FU as evidenced by MTS assay and differential salvage pathway dependency by TK1 expression and activity in exponentially growing phase (A431>HT29>>HCT8>SCC7). 5-FU gradually increased [18F]FLT uptake from 4 hr and sustained to 24 hr by 2.0-, 3.3-, and 2.2-fold in A431, HT29, and HCT8 cells, respectively, while transiently increased by 2.3-fold in SCC7 cells. In A431 and HT29 cells, TK1 activity was also enhanced about 1.6 and 2.0-fold with the induction of [18F]FLT uptake and 5-FU-induced [18F]FLT uptake were abolished by cycloheximide treatment. However, HCT8 and SCC7 cells failed to increase in TK1 activity gradually. 5-FU dose-dependently increased [18F]FLT uptake in A431 and HT29 cells, suggesting that TK1 dependent-[18F]FLT flare by 5-FU could reflect therapeutic response of 5-FU in salvage pathway-dependent cells. The increase of TK1 activity by 5-FU were correlated with the induction of TK1 protein and mRNA levels, and the G1S phase cell cycle progression (cyclin D1, E, and A). Next, we demonstrated the TK1 dependent-[18F]FLT flare by 5-FU in A431 and HT29 xenograft mice with dynamic imaging. In A431 tumors, the changes of k3/k4 before and 24 hr after 5-FU treatment were valued as 1.2130±3.1765 and 11.5738±4.9342 in vehicle- and 5-FU treated mice (p=0.0397), while SUVmean showed no difference. In HT29 tumors, the k3, k3/k4, SUVmean were significantly different between vehicle- and 5-FU treated mice. These studies showed that 5-FU sustained the increase of TK1 activity in salvage dependent cells with the G1S phase cell cycle arrest, which could quantitatively reflect therapeutic response of 5-FU as [18F]FLT flare. The kinetic analysis by dynamic imaging would gives a help to the prediction of 5-FU response within salvage pathway-dependent tumors  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-292.
Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Jin Li, Shukui Qin, Ruihua Xu, Thomas C C Yau, Brigette Ma, Hongming Pan, Jianming Xu, Yuxian Bai, Yihebali Chi, Liwei Wang, Kun-Huei Yeh, Feng Bi, Ying Cheng, Anh Tuan Le, Jen-Kou Lin, Tianshu Liu, Dong Ma, Christian Kappeler, Joachim Kalmus, Tae Won Kim
Journal: The Lancet Oncology (2015)
Power injector associated iatrogenic air embolism to the right heart
Authors: Sunny Jhamnani, Julio A Panza
Journal: Thorax (2013)

Air embolism is the entry of air into the vascular system and is usually associated with surgeries, trauma and central lines.1

A patient presented to the clinic with new onset atrial flutter and lower extremity oedema. The patient was admitted and within 24 h, the course became complicated by respiratory failure, requiring intubation and admission to the intensive care unit. A …
Kidney Transplant and Shifts in Family Dynamics
Authors: JOHN P. KEMPH, ERIC A. BERMANN, HENRY P. COPPOLILLO
Journal: American Journal of Psychiatry (1969)

The authors studied the reactions of patients provided with renal homotransplantations and their families. Usually when the family learned of the imminent death of one of its members, one or more relatives offered to donate a kidney. The family then gave much support to the donor. However, shortly after the transplant the major investments of the family returned to the recipient. Some of the intrapsychic and interpersonal shifts—immediate fantasies and alterations in role structure, feelings, and attitudes—within these families are discussed.
Effect of Door-to-Balloon Time on Mortality in Patients With ST-Segment Elevation Myocardial Infarction
Authors: Robert L. McNamara, Yongfei Wang, Jeph Herrin, Jeptha P. Curtis, Elizabeth H. Bradley, David J. Magid, Eric D. Peterson, Martha Blaney, Paul D. Frederick, Harlan M. Krumholz
Journal: Journal of the American College of Cardiology (2006)
Sputum inflammatory phenotypes are not stable in children with asthma
Authors: Louise Fleming, Lemonia Tsartsali, Nicola Wilson, Nicolas Regamey, Andrew Bush
Journal: Thorax (2012)

<h3>Background</h3> Two distinct, stable inflammatory phenotypes have been described in adults with asthma: eosinophilic and non-eosinophilic. Treatment strategies based on these phenotypes have been successful. This study evaluated sputum cytology in children with asthma to classify sputum inflammatory phenotypes and to assess their stability over time. <h3>Methods</h3> Sputum induction was performed in 51 children with severe asthma and 28 with mild to moderate asthma. Samples were classified as eosinophilic (&gt;2.5% eosinophils), neutrophilic (&gt;54% neutrophils); mixed granulocytic (&gt;2.5% eosinophils, &gt;54% neutrophils); or paucigranulocytic (≤2.5% eosinophils, ≤54% neutrophils). Sputum induction was repeated every 3 months in children with severe asthma (n=42) over a 1-year period and twice in mild to moderate asthma (n=17) over 3–6 months. <h3>Results</h3> 62 children (78%) had raised levels of inflammatory cells in at least one sputum sample. In the longitudinal analysis 37 of 59 children (63%) demonstrated two or more phenotypes. Variability in sputum inflammatory phenotype was observed in both the severe and the mild to moderate asthma groups. Change in phenotype was not related to change in inhaled corticosteroid (ICS) dose or asthma control, nor was it reflected in a change in exhaled nitric oxide (FE<sub>NO</sub>). 24 children (41%) fulfilled the criteria for non-eosinophilic asthma on one occasion and eosinophilic on another. There were no differences in severity, asthma control, atopy, ICS dose or forced expiratory volume in 1 s between those who were always non-eosinophilic and those always eosinophilic. <h3>Conclusion</h3> Raised levels of inflammatory cells were frequently found in children with asthma of all severities. Sputum inflammatory phenotype was not stable in children with asthma.
Methylation of<i>TFPI2</i>in Stool DNA: A Potential Novel Biomarker for the Detection of Colorectal Cancer
Authors: Sabine C. Glöckner, Mashaal Dhir, Joo Mi Yi, Kelly E. McGarvey, Leander Van Neste, Joost Louwagie, Timothy A. Chan, Wolfram Kleeberger, Adriaan P. de Bruïne, Kim M. Smits, Carolina A.J. Khalid-de Bakker, Daisy M.A.E. Jonkers, Reinhold W. Stockbrügger, Gerrit A. Meijer, Frank A. Oort, Christine Iacobuzio-Donahue, Katja Bierau, James G. Herman, Stephen B. Baylin, Manon Van Engeland, Kornel E. Schuebel, Nita Ahuja
Journal: Cancer Research (2009)

We have used a gene expression array-based strategy to identify the methylation of tissue factor pathway inhibitor 2 (TFPI2), a potential tumor suppressor gene, as a frequent event in human colorectal cancers (CRC). TFPI2 belongs to the recently described group of embryonic cell Polycomb group (PcG)-marked genes that may be predisposed to aberrant DNA methylation in early stages of colorectal carcinogenesis. Aberrant methylation of TFPI2 was detected in almost all CRC adenomas (97%, n = 56) and stages I to IV CRCs (99%, n = 115). We further explored the potential of TFPI2 as a biomarker for the early detection of CRC using stool DNA-based assays in patients with nonmetastatic CRC and average-risk noncancer controls who were candidates for screening. TFPI2 methylation was detected in stool DNA from stage I to III CRC patients with a sensitivity of 76% to 89% and a specificity of 79% to 93%. Detection of TFPI2 methylation in stool DNA may act as a useful adjunct to the noninvasive strategies for screening of CRCs in the future.
Nuclear thyroid hormone receptors in rabbit heart: reduced triiodothyronine binding in atrium compared with ventricle.
Authors: S K Banerjee, J M Ulrich, G J Kaldor
Journal: Circulation Research (1988)

Radiolabeled triiodothyronine (T3) binding to isolated nuclei was measured to compare the binding characteristics of the nuclear receptors in rabbit ventricular and atrial muscle cells. Scatchard analysis of the binding data yielded a maximum binding capacity of 170 +/- 20 fmol per mg DNA and apparent dissociation constant of 525 +/- 100 pM for ventricular nuclei. The binding capacity and the dissociation constant for the atrial muscle cell nuclei were 55 +/- 10 fmol per mg DNA and 500 +/- 75 pM, respectively. The results suggest that the binding capacity for T3 receptor in the atrium is considerably lower than that found in the ventricle. The reduced binding capacity of the T3 receptor in the atrium might reflect differences in the nuclear T3 receptors between ventricle and atrium.
Overexpression of Cyclooxygenase-2 Predisposes to Podocyte Injury
Authors: Huifang Cheng, Suwan Wang, Young-Il Jo, Chuan-Ming Hao, Mingzhi Zhang, Xiaofeng Fan, Chris Kennedy, Matthew D. Breyer, Gilbert W. Moeckel, Raymond C. Harris
Journal: Journal of the American Society of Nephrology (2007)

Increased podocyte cyclooxygenase-2 (COX-2) expression is seen in rats after renal ablation and Thy-1 nephritis and in cultured murine podocytes in response to mechanical stress. For investigation of whether COX-2 overexpression plays a role in podocyte injury, transgenic B6/D2 mice in which COX-2 expression was driven by a nephrin promoter were established. Selective upregulation of COX-2 expression in podocytes of transgenic mouse kidneys was confirmed by immunoblotting and immunohistochemistry. Whether upregulation of podocyte-specific COX-2 expression enhanced sensitivity to the development of Adriamycin nephropathy was examined. Adriamycin administration induced dramatically more albuminuria and foot process effacement and reduced glomerular nephrin mRNA and immunoreactivity in transgenic mice compared with wild-type littermates. Adriamycin also markedly increased immunoreactive COX-2 expression in podocytes from transgenic mice compared with the wild-type mice. Reverse transcriptase-PCR indicated that this increase represented a stimulation of endogenous COX-2 mRNA expression rather than COX-2 mRNA driven by the nephrin promoter. Balb/C mice, which are susceptible to renal injury by Adriamycin, also increased podocyte COX-2 expression and reduced nephrin expression in response to administration of the drug. Long-term treatment with the COX-2-specific inhibitor SC58236 ameliorated the albuminuria that was induced by Adriamycin in the transgenic mice. SC58236 also reduced Adriamycin-induced foot process effacement in both the COX-2 transgenic mice and Balb/C mice. Therefore, overexpression of COX-2 may predispose podocytes to further injury.
Whole-genome DNA/RNA sequencing identifies truncating mutations in RBCK1 in a novel Mendelian disease with neuromuscular and cardiac involvement
Authors: Kai Wang, Cecilia Kim, Jonathan Bradfield, Yunfei Guo, Elina Toskala, Frederick G Otieno, Cuiping Hou, Kelly Thomas, Christopher Cardinale, Gholson J Lyon, Ryan Golhar, Hakon Hakonarson
Journal: Genome Medicine (2013)

Whole-exome sequencing has identified the causes of several Mendelian diseases by analyzing multiple unrelated cases, but it is more challenging to resolve the cause of extremely rare and suspected Mendelian diseases from individual families. We identified a family quartet with two children, both affected with a previously unreported disease, characterized by progressive muscular weakness and cardiomyopathy, with normal intelligence. During the course of the study, we identified one additional unrelated patient with a comparable phenotype.We performed whole-genome sequencing (Complete Genomics platform), whole-exome sequencing (Agilent SureSelect exon capture and Illumina Genome Analyzer II platform), SNP genotyping (Illumina HumanHap550 SNP array) and Sanger sequencing on blood samples, as well as RNA-Seq (Illumina HiSeq platform) on transformed lymphoblastoid cell lines.From whole-genome sequence data, we identified RBCK1, a gene encoding an E3 ubiquitin-protein ligase, as the most likely candidate gene, with two protein-truncating mutations in probands in the first family. However, exome data failed to nominate RBCK1 as a candidate gene, due to poor regional coverage. Sanger sequencing identified a private homozygous splice variant in RBCK1 in the proband in the second family, yet SNP genotyping revealed a 1.2Mb copy-neutral region of homozygosity covering RBCK1. RNA-Seq confirmed aberrant splicing of RBCK1 transcripts, resulting in truncated protein products.While the exact mechanism by which these mutations cause disease is unknown, our study represents an example of how the combined use of whole-genome DNA and RNA sequencing can identify a disease-predisposing gene for a novel and extremely rare Mendelian disease.