tbuckley/cabot-search huggingface dataset:
Frequent loss of heterozygosity at the Hcr1 (hepatocarcinogenesis resistance) locus on chromosome 10 in primary hepatocellular carcinomas from LFF1 rat strain
Authors: Maria R. De Miglio, Maria R. Muroni, Maria M. Simile, Patrizia Virdis, Giuseppina Asara, Maddalena Frau, Diego F. Calvisi, Maria A. Seddaiu, Rosa M. Pascale, Francesco Feo
Journal: Hepatology (2001)

Hepatocarcinogenesis sensitivity ( Hcs1 , 2 ) and resistance ( Hcr1–3 ) loci have been identified by linkage analysis on rat chromosomes 7 and 1, and 10, 4, and 8, respectively. Cytogenetic studies documented deletions on chromosomes 3 and 6 of neoplastic rat hepatocytes. Hepatocellular carcinomas (HCCs) were produced in F1 hybrid rats between Long–Evans (LE) and Fisher 344 (F344) rats. Scanning of the above chromosomes for loss of heterozygosity (LOH) showed allelic imbalance (AI) at multiple regions on chromosomes 6, 7, and 10q. Detailed deletion mapping of chromosome 10 localized a putative suppressor Hcr1 gene to within a 3.2–cM interval flanked by D10Rat51 and D10Rat121 . Two other distinct regions with frequent AIs were found inside the Hcr1 locus, at marker loci including DNaseI and Mrp genes, and in a segment including 4 consecutive markers ( D10Rat64 , D10Rat182 , D10Rat113 , D10Rat216 ). In 40% of HCCs, AI was seen at the p53 locus. AI on chromosome 7 occurred at the Hcs1 locus, where is located c– myc , which is amplified in HCCs, suggesting allelic gain. Most AIs occurred in poorly/moderately differentiated carcinomas, and a few events were seen in well–differentiated tumors on chromosomes 7 and 10. These data suggest that alteration of a cluster of oncosuppressor genes on 10q is important for HCC progression. The existence of AI on segments of rat chromosomes 6, 7, and 10, syntenic to chromosomal segments of human HCCs where chromosomal gains or deletions occur, suggests a commonalty of some molecular events in the pathogenesis of HCCs in rats and humans. Our map provides information toward cloning putative oncosuppressor genes associated with this carcinoma. (Hepatology 2001;33:1110–1117.)
A king, a doctor, and a convenient death
Authors: J H R Ramsay
Journal: BMJ (1994)

Lord Dawson of Penn was the most admired and respected doctor of his generation. The skill with which he managed King George V's respiratory illness in 1928 undoubtedly saved the king's life and made Dawson a national celebrity. He was also respected within the medical profession. He was president of the Royal College of Physicians, elected twice president of the BMA, and honoured with a viscountcy.

His reputation would have been considerably diminished, however, had it been known that when the king was suffering from cardiorespiratory failure in January 1936 he administered a lethal combination of morphine and cocaine at a time when the king was already comatose and close to death. His action remained a well kept secret and the truth came to light only 50 years later when his private diary was opened, Dawson having died in 1945.

The king had been in failing health for several weeks when Queen Mary summoned Dawson to Sandringham on 17 January. Contemporary accounts of the king's last days given by the Archbishop of Canterbury and others tell of days that were tranquil and pain free with the king …
Use of Di(2-ethylhexyl) Phthalate–Containing Medical Products and Urinary Levels of Mono(2-ethylhexyl) Phthalate in Neonatal Intensive Care Unit Infants
Authors: Ronald Green, Russ Hauser, Antonia M. Calafat, Jennifer Weuve, Ted Schettler, Steven Ringer, Kenneth Huttner, Howard Hu
Journal: Environmental Health Perspectives (2005)

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer used in medical products made with polyvinyl chloride (PVC) plastic and may be toxic to humans. DEHP is lipophilic and binds noncovalently to PVC, allowing it to leach from these products. Medical devices containing DEHP are used extensively in neonatal intensive care units (NICUs). Among neonates in NICUs, we studied exposure to DEHP-containing medical devices in relation to urinary levels of mono(2-ethylhexyl) phthalate (MEHP), a metabolite of DEHP.We used a cross-sectional design for this study.We studied 54 neonates admitted to either of two level III hospital NICUs for at least 3 days between 1 March and 30 April 2003.A priori, we classified the infants' exposures to DEHP based on medical products used: The low-DEHP exposure group included infants receiving primarily bottle and/or gavage feedings; the medium exposure group included infants receiving enteral feedings, intravenous hyperalimentation, and/or nasal continuous positive airway pressure; and the high exposure group included infants receiving umbilical vessel catheterization, endotracheal intubation, intravenous hyperalimentation, and indwelling gavage tube. We measured MEHP in the infants' urine using automated solid-phase extraction/isotope dilution/high-performance liquid chromatography/tandem mass spectrometry.Urinary MEHP levels increased monotonically with DEHP exposure. For the low-, medium-, and high-DEHP exposure groups, median (interquartile range) MEHP levels were 4 (18), 28 (58), and 86 ng/mL (150), respectively (p = 0.004). After adjustment for institution and sex, urinary MEHP levels among infants in the high exposure group were 5.1 times those among infants in the low exposure group (p = 0.03).Intensive use of DEHP-containing medical devices in NICU infants results in higher exposure to DEHP as reflected by elevated urinary levels of MEHP.
Bcl-2 Orchestrates a Cross-talk between Endothelial and Tumor Cells that Promotes Tumor Growth
Authors: Tomoatsu Kaneko, Zhaocheng Zhang, Maria G. Mantellini, Elisabeta Karl, Benjamin Zeitlin, Monique Verhaegen, María S. Soengas, Mark Lingen, Robert M. Strieter, Gabriel Nunez, Jacques E. Nör
Journal: Cancer Research (2007)

Abstract The current understanding of the interaction between the endothelium and cancer cells is fundamentally based on the concept that endothelial cells are responsive to differentiation and survival signals originating from the tumor cells. Whereas the effect of tumor cell–secreted factors on angiogenesis is well established, little is known about the effect of factors secreted by endothelial cells on tumor cell gene expression and tumor progression. Here, we show that bcl-2 gene expression is significantly higher in the tumor-associated endothelial cells of patients with head and neck squamous cell carcinomas (HNSCC) as compared with endothelial cells from the normal oral mucosa. Bcl-2 induces vascular endothelial growth factor (VEGF) expression in neovascular endothelial cells through a signal transducer and activator of transcription 3 (STAT3)–mediated pathway. Endothelial cell–derived VEGF signals through VEGFR1 and induces expression of Bcl-2 and the proangiogenic chemokines CXCL1 and CXCL8 in HNSCC cells. Notably, inhibition of Bcl-2 expression in neovascular endothelial cells with RNA interference down-regulates expression of Bcl-2, CXCL8, and CXCL1 in HNSCC cells, and is sufficient to inhibit growth and decrease the microvessel density of xenografted HNSCC in immunodeficient mice. Together, these results show that Bcl-2 is the orchestrator of a cross-talk between neovascular endothelial cells and tumor cells, which has a direct effect on tumor growth. This work identifies a new function for Bcl-2 in cancer biology that is beyond its classic role in cell survival. [Cancer Res 2007;67(20):9685–93]
Serine protease inhibitors serpina1 and serpina3 are down-regulated in bone marrow during hematopoietic progenitor mobilization
Authors: Ingrid G. Winkler, Jean Hendy, Paul Coughlin, Anita Horvath, Jean-Pierre Lévesque
Journal: The Journal of Experimental Medicine (2005)

Mobilization of hematopoietic progenitor cells into the blood involves a massive release of neutrophil serine proteases in the bone marrow. We hypothesize that the activity of these neutrophil serine proteases is regulated by the expression of naturally occurring inhibitors (serpina1 and serpina3) produced locally within the bone marrow. We found that serpina1 and serpina3 were transcribed in the bone marrow by many different hematopoietic cell populations and that a strong reduction in expression occurred both at the protein and mRNA levels during mobilization induced by granulocyte colony-stimulating factor or chemotherapy. This decreased expression was restricted to the bone marrow as serpina1 expression was maintained in the liver, leading to no change in plasma concentrations during mobilization. The down-regulation of serpina1 and serpina3 during mobilization may contribute to a shift in the balance between serine proteases and their inhibitors, and an accumulation of active neutrophil serine proteases in bone marrow extravascular fluids that cleave and inactivate molecules essential to the retention of hematopoietic progenitor cells within the bone marrow. These data suggest an unexpected role for serpina1 and serpina3 in regulating the bone marrow hematopoietic microenvironment as well as influencing the migratory behavior of hematopoietic precursors.
Response to “Primary cervical cancer screening by self-sampling of human papillomavirus DNA in internal medicine outpatient clinics”, by Dannecker et al. (Ann Oncol 2004; 15: 863–869) and “Histopathological validation of the sentinel node concept in cervical cancer”, by Barranger et al. (Ann Oncol 2004; 15: 870–874): DNA microarrays will be instrumental in the future diagnosis of cervical dysplasia and neoplasia
Authors: P.K. Wright
Journal: Annals of Oncology (2005)
The Impact of Renal Dysfunction on Outcomes in the ExTRACT-TIMI 25 Trial
Authors: Keith A.A. Fox, Elliott M. Antman, Gilles Montalescot, Stefan Agewall, Bhupathi SomaRaju, Freek W.A. Verheugt, Jose Lopez-Sendon, Hanoch Hod, Sabina A. Murphy, Eugene Braunwald
Journal: Journal of the American College of Cardiology (2007)
Electrical Resynchronization
Authors: Anne M. Dubin, Jeffrey A. Feinstein, V. Mohan Reddy, Frank L. Hanley, George F. Van Hare, David N. Rosenthal
Journal: Circulation (2003)

Background— Many patients with congenital heart disease develop right ventricular (RV) failure due to anatomy and prior therapy. RV problems may include right bundle-branch block (RBBB), volume loading, and chamber enlargement. Because the failing RV may have regional dyskinesis, we hypothesized that resynchronization therapy might augment its performance. Methods and Results— We studied 7 patients with RV dysfunction and RBBB, using a predefined pacing protocol. QRS duration, cardiac index (CI), and RV dP/dt were measured in 4 different pacing states. Atrioventricular pacing improved CI and RV dP/dt max and decreased QRS duration as compared with atrial pacing or sinus rhythm. Conclusions— Atrioventricular pacing in patients with RBBB and RV dysfunction augments RV and systemic performance. RV resynchronization is a promising novel therapy for patients with RV failure.
Cancer Risk Prediction Models: A Workshop on Development, Evaluation, and Application
Authors: Andrew N. Freedman, Daniela Seminara, Mitchell H. Gail, Patricia Hartge, Graham A. Colditz, Rachel Ballard-Barbash, Ruth M. Pfeiffer
Journal: JNCI Journal of the National Cancer Institute (2005)

Cancer researchers, clinicians, and the public are increasingly interested in statistical models designed to predict the occurrence of cancer. As the number and sophistication of cancer risk prediction models have grown, so too has interest in ensuring that they are appropriately applied, correctly developed, and rigorously evaluated. On May 20-21, 2004, the National Cancer Institute sponsored a workshop in which experts identified strengths and limitations of cancer and genetic susceptibility prediction models that were currently in use and under development and explored methodologic issues related to their development, evaluation, and validation. Participants also identified research priorities and resources in the areas of 1) revising existing breast cancer risk assessment models and developing new models, 2) encouraging the development of new risk models, 3) obtaining data to develop more accurate risk models, 4) supporting validation mechanisms and resources, 5) strengthening model development efforts and encouraging coordination, and 6) promoting effective cancer risk communication and decision-making.
A Low-Carbohydrate as Compared with a Low-Fat Diet in Severe Obesity
Authors: Frederick F. Samaha, Nayyar Iqbal, Prakash Seshadri, Kathryn L. Chicano, Denise A. Daily, Joyce McGrory, Terrence Williams, Monica Williams, Edward J. Gracely, Linda Stern
Journal: New England Journal of Medicine (2003)

The effects of a carbohydrate-restricted diet on weight loss and risk factors for atherosclerosis have been incompletely assessed.We randomly assigned 132 severely obese subjects (including 77 blacks and 23 women) with a mean body-mass index of 43 and a high prevalence of diabetes (39 percent) or the metabolic syndrome (43 percent) to a carbohydrate-restricted (low-carbohydrate) diet or a calorie- and fat-restricted (low-fat) diet.Seventy-nine subjects completed the six-month study. An analysis including all subjects, with the last observation carried forward for those who dropped out, showed that subjects on the low-carbohydrate diet lost more weight than those on the low-fat diet (mean [+/-SD], -5.8+/-8.6 kg vs. -1.9+/-4.2 kg; P=0.002) and had greater decreases in triglyceride levels (mean, -20+/-43 percent vs. -4+/-31 percent; P=0.001), irrespective of the use or nonuse of hypoglycemic or lipid-lowering medications. Insulin sensitivity, measured only in subjects without diabetes, also improved more among subjects on the low-carbohydrate diet (6+/-9 percent vs. -3+/-8 percent, P=0.01). The amount of weight lost (P<0.001) and assignment to the low-carbohydrate diet (P=0.01) were independent predictors of improvement in triglyceride levels and insulin sensitivity.Severely obese subjects with a high prevalence of diabetes or the metabolic syndrome lost more weight during six months on a carbohydrate-restricted diet than on a calorie- and fat-restricted diet, with a relative improvement in insulin sensitivity and triglyceride levels, even after adjustment for the amount of weight lost. This finding should be interpreted with caution, given the small magnitude of overall and between-group differences in weight loss in these markedly obese subjects and the short duration of the study. Future studies evaluating long-term cardiovascular outcomes are needed before a carbohydrate-restricted diet can be endorsed.
Identifying repeat domains in large genomes.
Authors: Degui Zhi, Benjamin J Raphael, Alkes L Price, Haixu Tang, Pavel A Pevzner
Journal: Genome biology (2006)

Abstract We present a graph-based method for the analysis of repeat families in a repeat library. We build a repeat domain graph that decomposes a repeat library into repeat domains, short subsequences shared by multiple repeat families, and reveals the mosaic structure of repeat families. Our method recovers documented mosaic repeat structures and suggests additional putative ones. Our method is useful for elucidating the evolutionary history of repeats and annotating de novo generated repeat libraries.
Uroporphyria in mice: Thresholds for hepatic CYP1A2 and iron
Authors: Nadia Gorman, Kerry L. Ross, Heidi S. Walton, William J. Bement, Juliana G. Szakacs, Glenn S. Gerhard, Timothy P. Dalton, Daniel W. Nebert, Richard S. Eisenstein, Jacqueline F. Sinclair, Peter R. Sinclair
Journal: Hepatology (2002)

In mice treated with 5-aminolevulinic acid (ALA) and polyhalogenated aromatic compounds, the levels of both hepatic cytochrome P450 (CYP)1A2 and iron—which can be quite different among inbred strains—are critical in causing experimental uroporphyria. Here we investigate the development of uroporphyria as a function of CYP1A2 and iron levels in the liver of mice having a common C57BL/6 genetic background. We compared Cyp1a2(−/−) knockout mice, Cyp1a2(+/−) heterozygotes, Cyp1a2(+/+) wild type, and Cyp1a2(+/+) mice pretreated with a low dose of 3,3',4,4',5-pentachlorobiphenyl (PCB126) (4 μg/kg). Cyp1a2(+/−) mice contain about 60% of the hepatic CYP1A2 content of Cyp1a2(+/+) mice, and the PCB126-pretreated Cyp1a2(+/+) mice have about twice the wild-type levels of CYP1A2. ALA- and iron-treated Cyp1a2(+/+) mice are known to accumulate hepatic uroporphyrin; this accumulation was increased 7-fold by pretreatment with the low dose of PCB126. ALA- and iron-treated Cyp1a2(+/−) heterozygote mice accumulated no uroporphyrin in 4 weeks, but by 8 weeks accumulated significant amounts of uroporphyrin. As previously reported, the ALA- and iron-treated Cyp1a2(−/−) knockout mouse has no CYP1A2 and exhibits no detectable uroporphyrin accumulation. Iron dose-response curves in ALA- and PCB126-treated Cyp1a2(+/+) mice showed that hepatic iron levels greater than 850 μg/g liver were required to produce significant uroporphyrin accumulation in the liver. Other measures of hepatic effects of iron (iron-response element-binding protein [IRP]-iron response element [IRE] binding activity and accumulation of protoporphyrin from ALA) decreased when the level of iron was considerably lower than 850 μg/g liver. At low iron doses, accumulation of iron was principally in Kupffer cells, whereas at the higher doses (required to stimulate uroporphyrin accumulation), more iron was found in parenchymal cells. We conclude that small changes in hepatic CYP1A2 levels can dramatically affect uroporphyria in C57BL/6 mice, providing the animals have been sufficiently loaded with iron; these data might be clinically relevant to acquired (sporadic) porphyria cutanea tarda, because humans show greater than 60-fold genetic differences in hepatic basal CYP1A2.
Ovarian Cancer and Antiangiogenic Therapy: Caveat Emptor
Authors: Kate E. Oliver, William P. McGuire
Journal: Journal of Clinical Oncology (2014)

14,101; (2) Paid in-county subscriptions stated on Form 3541 (include advertiser's proof and exchange copies): N/A; (3) Sales through dealers and carriers, street vendors, counter sales, and other non-USPS paid distribution: 6,797; (4) Other classes mailed through the USPS: N/A.(c) Total paid and/or requested circulation (sum of 15b (1), (2), (3), and (4)): 20,898.(d) Free distribution by mail (samples, complimentary, and other free): (1) Outsidecounty as stated on form 3541: 177; (2) In-county as stated on form 3541: N/A; (3) Other classes mailed through the USPS: N/A; (4) Free distribution outside the mail (carriers or other means): 171.(e) Total free distribution (sum of 15d (1), (2), (3), and (4)): 348.(f) Total distribution (sum of 15c and 15e): 21,246.(g) Copies not distributed: 1,905.(h) Total (sum of 15f and 15g): 23,151.(i) Percent paid and/or requested circulation (15c/15f x 100): 98.36%.Actual no.
Efficacy and safety of sublingual tablets of house dust mite allergen extracts in adults with allergic rhinitis
Authors: Karl-Christian Bergmann, Pascal Demoly, Margitta Worm, Wytske J. Fokkens, Teresa Carrillo, Ana I. Tabar, Hélène Nguyen, Armelle Montagut, Robert K. Zeldin
Journal: Journal of Allergy and Clinical Immunology (2014)
p53-Induced miR-15a/16-1 and AP4 Form a Double-Negative Feedback Loop to Regulate Epithelial–Mesenchymal Transition and Metastasis in Colorectal Cancer
Authors: Lei Shi, Rene Jackstadt, Helge Siemens, Huihui Li, Thomas Kirchner, Heiko Hermeking
Journal: Cancer Research (2013)

Abstract The transcription factor AP4 mediates epithelial–mesenchymal transition (EMT) in colorectal cancer but its control in this setting is not fully understood. Here, we report the definition of a double-negative feedback loop involving AP4 and miR-15a/16-1 that regulates EMT and metastatic progression. In colorectal cancer cells, AP4 was downregulated by DNA damage in a p53-dependent manner. AP4 downregulation by p53 was mediated indirectly by the tumor-suppressive microRNAs miR-15a and miR-16-1, which targeted the 3′ untranslated region (3′-UTR) of AP4 mRNA, induced mesenchymal–epithelial transition (MET), and inhibited colorectal cancer cell migration and invasion. The downregulation of AP4 was necessary for induction of MET and cell cycle arrest by miR-15a/16-1. In tumor xenoplants, ectopic miR-15a/16-1 suppressed formation of lung metastases. Furthermore, AP4 directly suppressed expression of miR-15a/16-1. In clinical specimens of colorectal cancer, miR-15a levels inversely correlated with AP4 protein levels shown previously to correlate with distant metastasis and poor survival. In summary, our results define a double-negative feedback loop involving miR-15a/16-1 and AP4 that stabilizes epithelial and mesenchymal states, respectively, which may determine metastatic prowess. Cancer Res; 74(2); 532–42. ©2013 AACR.
Cost-Effectiveness of Contralateral Prophylactic Mastectomy Versus Routine Surveillance in Patients With Unilateral Breast Cancer
Authors: Benjamin Zendejas, James P. Moriarty, Jamie O'Byrne, Amy C. Degnim, David R. Farley, Judy C. Boughey
Journal: Journal of Clinical Oncology (2011)

Contralateral prophylactic mastectomy (CPM) rates in women with unilateral breast cancer are increasing despite controversy regarding survival advantage. Current scrutiny of the medical costs led us to evaluate the cost-effectiveness of CPM versus routine surveillance as an alternative contralateral breast cancer (CBC) risk management strategy.Using a Markov model, we simulated patients with breast cancer from mastectomy to death. Model parameters were gathered from published literature or national databases. Base-case analysis focused on patients with average-risk breast cancer, 45 years of age at treatment. Outcomes were valued in quality-adjusted life-years (QALYs). Patients' age, risk level of breast cancer, and quality of life (QOL) were varied to assess their impact on results.Mean costs of treatment for women age 45 years are comparable: $36,594 for the CPM and $35,182 for surveillance. CPM provides 21.22 mean QALYs compared with 20.93 for surveillance, resulting in an incremental cost-effectiveness ratio (ICER) of $4,869/QALY gained for CPM. To prevent one CBC, six CPMs would be needed. CPM is no longer cost-effective for patients older than 70 years (ICER $62,750/QALY). For BRCA-positive patients, CPM is clearly cost-effective, providing more QALYs while being less costly. In non-BRCA patients, cost-effectiveness of CPM is highly dependent on assumptions regarding QOL for CPM versus surveillance strategy.CPM is cost-effective compared with surveillance for patients with breast cancer who are younger than 70 years. Results are sensitive to BRCA-positive status and assumptions of QOL differences between CPM and surveillance patients. This highlights the importance of tailoring treatment for individual patients.
Hypertension Following Bilateral Nephrectomy of the Dog
Authors: E. E. MUIRHEAD, F. JONES, P. GRAHAM
Journal: Circulation Research (1953)

Hypertension following bilateral nephrectomy of dogs has been obtained consistently in association with sodium balance and in the absence of expansion of the extracellular fluid volume as ordinarily measured. An enhanced dietary protein intake appears to be involved in the genesis of the hypertension under these conditions. Alterations in protein and potassium metabolism are described. The present, as well as former studies on the hypertension following nephrectomy, suggest that multiple factors may be involved in the pathogenesis of the hypertension. These factors are discussed.