tbuckley/cabot-search huggingface dataset:
Hemodialysis Vascular Access Modifies the Association between Dialysis Modality and Survival
Authors: Jeffrey Perl, Ron Wald, Philip McFarlane, Joanne M. Bargman, Edward Vonesh, Yingbo Na, S. Vanita Jassal, Louise Moist
Journal: Journal of the American Society of Nephrology (2011)

Several comparisons of peritoneal dialysis (PD) and hemodialysis (HD) in incident patients with ESRD demonstrate superior survival in PD-treated patients within the first 1 to 2 years. These survival differences may be due to higher HD-related mortality as a result of high rates of incident central venous catheter (CVC) use or due to an initial survival advantage conferred by PD. We compared the survival of incident PD patients with those who initiated HD with a CVC (HD-CVC) or with a functional arteriovenous fistula or arteriovenous graft (HD-AVF/AVG). We used multivariable piece-wise exponential nonproportional and proportional hazards models to evaluate early (1 year) mortality as well as overall mortality during the period of observation using an intention-to-treat approach. We identified 40,526 incident adult dialysis patients from the Canadian Organ Replacement Register (2001 to 2008). Compared with the 7412 PD patients, 1-year mortality was similar for the 6663 HD-AVF/AVG patients but was 80% higher for the 24,437 HD-CVC patients (adjusted HR, 1.8; 95% confidence intervals [CI], 1.6 to 1.9). During the entire period of follow-up, HD-AVF/AVG patients had a lower risk for death, and HD-CVC patients had a higher risk for death compared with patients on PD. In conclusion, the use of CVCs in incident HD patients largely accounts for the early survival benefit seen with PD.
XPC silencing in normal human keratinocytes triggers metabolic alterations that drive the formation of squamous cell carcinomas
Authors: Hamid Reza Rezvani, Arianna L. Kim, Rodrigue Rossignol, Nsrein Ali, Meaghan Daly, Walid Mahfouf, Nadège Bellance, Alain Taïeb, Hubert de Verneuil, Frédéric Mazurier, David R. Bickers
Journal: Journal of Clinical Investigation (2010)

DNA damage is a well-known initiator of tumorigenesis. Studies have shown that most cancer cells rely on aerobic glycolysis for their bioenergetics. We sought to identify a molecular link between genomic mutations and metabolic alterations in neoplastic transformation. We took advantage of the intrinsic genomic instability arising in xeroderma pigmentosum C (XPC). The XPC protein plays a key role in recognizing DNA damage in nucleotide excision repair, and patients with XPC deficiency have increased incidence of skin cancer and other malignancies. In cultured human keratinocytes, we showed that lentivirus-mediated knockdown of XPC reduced mitochondrial oxidative phosphorylation and increased glycolysis, recapitulating cancer cell metabolism. Accumulation of unrepaired DNA following XPC silencing increased DNA-dependent protein kinase activity, which subsequently activated AKT1 and NADPH oxidase-1 (NOX1), resulting in ROS production and accumulation of specific deletions in mitochondrial DNA (mtDNA) over time. Subcutaneous injection of XPC-deficient keratinocytes into immunodeficient mice led to squamous cell carcinoma formation, demonstrating the tumorigenic potential of transduced cells. Conversely, simultaneous knockdown of either NOX1 or AKT1 blocked the neoplastic transformation induced by XPC silencing. Our results demonstrate that genomic instability resulting from XPC silencing results in activation of AKT1 and subsequently NOX1 to induce ROS generation, mtDNA deletions, and neoplastic transformation in human keratinocytes.
Methylation mediated silencing of TMS1/ASC gene in prostate cancer
Authors: Partha M Das, Kavitha Ramachandran, Jane VanWert, Larry Ferdinand, Gopal Gopisetty, Isildinha M Reis, Rakesh Singal
Journal: Molecular Cancer (2006)

Abstract Background Transcriptional silencing associated with aberrant promoter methylation has been established as an alternate pathway for the development of cancer by inactivating tumor suppressor genes. TMS1 (Target of Methylation induced Silencing), also known as ASC (Apoptosis Speck like protein containing a CARD) is a tumor suppressor gene which encodes for a CARD (caspase recruitment domain) containing regulatory protein and has been shown to promote apoptosis directly and by activation of downstream caspases. This study describes the methylation induced silencing of TMS1/ASC gene in prostate cancer cell lines. We also examined the prevalence of TMS1/ASC gene methylation in prostate cancer tissue samples in an effort to correlate race and clinico-pathological features with TMS1/ASC gene methylation. Results Loss of TMS1/ASC gene expression associated with complete methylation of the promoter region was observed in LNCaP cells. Gene expression was restored by a demethylating agent, 5-aza-2'deoxycytidine, but not by a histone deacetylase inhibitor, Trichostatin A. Chromatin Immunoprecipitation (ChIP) assay showed enrichment of MBD3 (methyl binding domain protein 3) to a higher degree than commonly associated MBDs and MeCP2. We evaluated the methylation pattern in 66 prostate cancer and 34 benign prostatic hyperplasia tissue samples. TMS1/ASC gene methylation was more prevalent in prostate cancer cases than controls in White patients (OR 7.6, p 0.002) while no difference between the cases and controls was seen in Black patients (OR 1.1, p 0.91). Conclusion Our study demonstrates that methylation-mediated silencing of TMS1/ASC is a frequent event in prostate cancer, thus identifying a new potential diagnostic and prognostic marker for the treatment of the disease. Racial differences in TMS1/ASC methylation patterns implicate the probable role of molecular markers in determining in susceptibility to prostate cancer in different ethnic groups.
High Rate of Sustained Unresponsiveness with Early-Intervention Peanut Oral Immunotherapy
Authors: Brian P. Vickery, Ayeshia Beavers, Jelena Berglund, Jill P. French, Deanna K. Hamilton, Lauren Herlihy, Edwin H. Kim, Michael D. Kulis, Nicole Szczepanski, Pamela H. Steele, Yamini Virkud, Benjamin L. Wright, A. Wesley Burks
Journal: Journal of Allergy and Clinical Immunology (2015)
microRNA-451 Regulates Macrophage Migration Inhibitory Factor Production and Proliferation of Gastrointestinal Cancer Cells
Authors: Eva Bandres, Nerea Bitarte, Fernando Arias, Jackeline Agorreta, Puri Fortes, Xabi Agirre, Ruth Zarate, Juan A. Diaz-Gonzalez, Natalia Ramirez, Jesus J. Sola, Paula Jimenez, Javier Rodriguez, Jesus Garcia-Foncillas
Journal: Clinical Cancer Research (2009)

microRNAs (miRNA) are small RNAs that function as post-transcriptional regulators of gene expression. Recent evidence has shown that some miRNAs can act as oncogenes or tumor suppressors. This study was conducted to evaluate the potential association of miRNA expression with clinical outcome in patients with gastric cancer.Expression of 250 human mature miRNAs was measured by real-time PCR on paraffin-embedded tumor samples of 21 patients with gastric cancer stage III uniformly treated with surgical resection followed by chemoradiation. We identified the miRNAs correlated with disease-free and overall survival times, and the results were evaluated including 24 other patients. In vitro cell proliferation and radiosensitivity studies were done to support clinical data.The results revealed that down-regulation of miR-451 was associated with worse prognosis. miR-451 was detected by in situ hybridization in epithelial cells and showed decreased expression in gastric and colorectal cancer versus nontumoral tissues. Overexpression of miR-451 in gastric and colorectal cancer cells reduced cell proliferation and increased sensitivity to radiotherapy. Microarray and bioinformatic analysis identified the novel oncogene macrophage migration inhibitory factor (MIF) as a potential target of miR-451. In fact, overexpression of miR-451 down-regulated mRNA and protein levels of MIF and decreased expression of reporter genes with MIF target sequences. Moreover, we found a significant inverse correlation between miR-451 and MIF expression in tumoral gastric biopsies.These findings support the role of miR-451 as a regulator of cancer proliferation and open new perspectives for the development of effective therapies for chemoradioresistant cancers.
A METHOD FOR SUPRAVITAL STAINING OF ANIMALS WITH NEUTRAL RED AND ITS PRESERVATION IN PARAFFIN SECTIONS
Authors: Claude E. Forkner
Journal: The Journal of Experimental Medicine (1930)

A simple, rapid method for staining all the supravitally stainable cells in the body, as in supravital preparations with neutral red, is described, together with a method for faithful preservation of the dye in paraffin sections. The essential points of the technique are, first, to secure the reaction of cells to neutral red which corresponds to the so-called supravital technique, involving the reaction of only those substances which respond to the dye while the cell is living; and second, to preserve the stain through the processes of fixation, embedding, and counterstaining.
Antiplatelet drugs for prevention of pre-eclampsia and its consequences: systematic review
Authors: L. Duley
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To assess the effectiveness and safety of antiplatelet drugs for prevention of pre-eclampsia and its consequences. <b>Design:</b> Systematic review. <b>Data sources:</b> Register of trials maintained by Cochrane Pregnancy and Childbirth Group, Cochrane Controlled Trials Register, and Embase. <b>Included studies:</b> Randomised trials involving women at risk of pre-eclampsia, and its complications, allocated to antiplatelet drug(s) versus placebo or no antiplatelet drug. <b>Main outcomes measures:</b> Pre-eclampsia, preterm birth, fetal or neonatal death, and small for gestational age baby. Studies were assessed for quality of concealment of allocation and losses to follow up. <b>Results:</b> 39 trials (30 563 women) were included, and 45 trials (&gt;3000 women) excluded. Use of antiplatelet drugs was associated with a 15% reduction in the risk of pre-eclampsia (32 trials, 29 331 women; relative risk 0.85, 95% confidence interval 0.78 to 0.92; number needed to treat 100, 59 to 167). There was also an 8% reduction in the risk of preterm birth (23 trials, 28 268 women; 0.92, 0.88 to 0.97; 72, 44 to 200), and a 14% reduction in the risk of fetal or neonatal death (30 trials, 30 093 women; 0.86, 0.75 to 0.98; 250, 125 to &gt;10 000) for women allocated antiplatelet drugs. Small for gestational age babies were reported in 25 trials (20 349 women), with no overall difference between the groups (relative risk 0.92, 0.84 to 1.01). There were no significant differences in other measures of outcome. <b>Conclusions:</b> Antiplatelet drugs, largely low dose aspirin, have small to moderate benefits when used for prevention of pre-eclampsia.
Detection of Myobacterium tuberculosis in nasopharyngeal aspirate samples in children
Authors: Luis Miguel Franchi, Rosa I Cama, Robert H Gilman, Sonia Montenegro-James, Patricia Sheen
Journal: The Lancet (1998)

At the Institute de Salud del Niño in Lima, Peru, most cases of pulmonary tuberculosis are diagnosed and referred to peripheral health centres for treatment. Tuberculosis, however, caused 137 admissions in 1996, of whom 45% were children younger than 5 years. 1 Health Children's InstituteStatistic Office. Year report. 1996; 96: 20-30 Google Scholar Paediatric tuberculosis is difficult to diagnose, and is generally made on the basis of clinical and epidemiological criteria, including signs and symptoms, chest radiography, percussion and postural drainage, and, most importantly, history of close contact with a patient with pulmonary tuberculosis. 2 Vallejo JG Ong LT Starke JR Clinical features, diagnosis, and treatment of tuberculosis in infants. Pediatrics. 1994; 94: 1-7 PubMed Google Scholar Bacteriological confirmation, however, is more difficult. Children are commonly infected with a small load of Mycobacterium tuberculosis and generally they cannot produce an adequate sputum sample. For this reason, 50–60% of children may be diagnosed with pulmonary tuberculosis in the absence of a positive culture or sensitivity testing. Because there is no efficient way to confirm the diagnosis, uninfected children may be treated unnecessarily, especially in areas with a low prevalence. Alternative ways of obtaining bronchial secretions are used to improve the yield of culture results; gastric aspiration is the most common, in which a nasogastric tube is used to aspirate the bronchial secretions that have pooled in the stomach overnight. Overnight fasting is needed and it must be done immediately after the patient awakes in the morning. The yield of gastric aspiration is adequate and is similar to bronchoalveolar lavage. 3 Abdaco D Steiner P Gastric lavage is better than bronchoalveolar lavage for isolation of Myobacterium tuberculosis. Pediatric Infec Dis J. 1992; 11: 735-738 Crossref PubMed Scopus (172) Google Scholar
Acid-Sensing Ion Channels Contribute to Transduction of Extracellular Acidosis in Rat Carotid Body Glomus Cells
Authors: Zhi-Yong Tan, Yongjun Lu, Carol A. Whiteis, Christopher J. Benson, Mark W. Chapleau, Francois M. Abboud
Journal: Circulation Research (2007)

Carotid body chemoreceptors sense hypoxemia, hypercapnia, and acidosis and play an important role in cardiorespiratory regulation. The molecular mechanism of pH sensing by chemoreceptors is not clear, although it has been proposed to be mediated by a drop in intracellular pH of carotid body glomus cells, which inhibits a K + current. Recently, pH-sensitive ion channels have been described in glomus cells that respond directly to extracellular acidosis. In this study, we investigated the possible molecular mechanisms of carotid body pH sensing by recording the responses of glomus cells isolated from rat carotid body to rapid changes in extracellular pH using the whole-cell patch-clamping technique. Extracellular acidosis evoked transient inward current in glomus cells that was inhibited by the acid-sensing ion channel (ASIC) blocker amiloride, absent in Na + -free bathing solution, and enhanced by either Ca 2+ -free buffer or addition of lactate. In addition, ASIC1 and ASIC3 were shown to be expressed in rat carotid body by quantitative PCR and immunohistochemistry. In the current-clamp mode, extracellular acidosis evoked both a transient and sustained depolarizations. The initial transient component of depolarization was blocked by amiloride, whereas the sustained component was eliminated by removal of K + from the pipette solution and partially blocked by the TASK (tandem-p-domain, acid-sensitive K + channel) blockers anandamide and quinidine. The results provide the first evidence that ASICs may contribute to chemotransduction of low pH by carotid body chemoreceptors and that extracellular acidosis directly activates carotid body chemoreceptors through both ASIC and TASK channels.
Sources of Error in the Erythrocyte Sedimentation Rate
Authors: J. S. Lawrence
Journal: Annals of the Rheumatic Diseases (1953)

The combination of environmental chamber exposure and bronchoalveolar lavage (BAL) was used to study the time-course of the cell response in the human lung to nitrogen dioxide (NO2). Healthy subjects were exposed for 20 min to 7 mg NO2.m-3 (4 ppm), a concentration which occurs indoors in industries and is below the peak exposure limit for work places in most countries, 10 mg.m-3 (5.5 ppm). BAL was performed in all subjects several weeks before exposure and 4, 8, 24 and 72 h after exposure, in eight subjects at each time. Mastocytosis and lymphocytosis were found in BAL fluid 4-24 h after exposure, with normalization after 72 h. A mild increase in lysozyme positive macrophages was found 24-72 h after exposure. The time-course of the human pulmonary cell response to NO2, demonstrated in BAL fluid, represents a new and previously not reported finding after exposure to this common air pollutant. Our findings are diverging from results obtained in animal studies, using approximately the same NO2 concentrations, indicating that the results from the animal studies may not be transferable to man.
<i>GNAS1</i> T393C Polymorphism and Survival in Patients with Sporadic Colorectal Cancer
Authors: Ulrich H. Frey, Hakan Alakus, Jeremias Wohlschlaeger, Klaus J. Schmitz, Günther Winde, Hans G. van Calker, Karl-Heinz Jöckel, Winfried Siffert, Kurt W. Schmid
Journal: Clinical Cancer Research (2005)

Signaling via the G protein Galpha s pathway is linked to proapoptotic processes in cancer cell lines. We have recently shown an association between the GNAS1 T393C polymorphism and disease progression in patients with bladder cancer with homozygous TT genotypes displaying increased transcription of Galpha s and a more favorable clinical course compared with C-allele carriers.In the present study, 151 patients with sporadic colorectal cancer were retrospectively genotyped to examine a potential association between T393C genotypes and survival. Moreover, two other single-nucleotide polymorphisms in common haplotype blocks within the gene GNAS1 and their interaction with the T393C polymorphism were investigated.The allele frequency in the patients group was not significantly different from that of healthy blood donors. Kaplan-Meier curves for overall survival (mean follow-up, 43 months) showed that in International Union Against Cancer (UICC) stages I to II, the 5-year survival rate was significantly higher in TT genotypes (87.8%) compared with TC (71.0%) and CC genotypes (50.0%; P = 0.009), whereas no genotype effect could be observed for UICC stages III to IV. In multivariate Cox proportional analysis the T393C polymorphism was an independent prognostic factor for survival. Homozygous CC patients were at highest risk for death (hazard ratio, 12.1; P = 0.006) compared with TT genotypes. Heterozygous patients had an intermediate risk compatible with a gene-dose effect. The two haplotype blocks investigated were not associated with clinical outcome.The results support the role of the T393C polymorphism as a marker for survival in patients with colorectal cancer stages I to II and in the identification of patients who may benefit from adjuvant chemotherapy.
Leveling With Young People About Sex
Authors: E. James Lieberman
Journal: JAMA (1969)

In the minds of most parents the family physician qualifies as one of the few available experts on sex. As Harold Lief, MD, has pointed out (<i>Harper</i><b>229</b>:92 [Dec] 1964), this is one area where physicians are given too much credit. Most physicians are not adequately prepared to handle sex education with individuals or groups; but no one else is either, and the interested physician is in a good position to remedy the situation. <h3>Why Don't Parents Do It?</h3> It is a mistake to think that physicians, teachers, ministers, and others must handle sex education simply because too many parents have fallen down on the job. Even when parents do a good job, children will get information from other sources, and it is part of our responsibility to see that some of this is of good quality. If you ask parents who<i>have</i>done a good job, you will
Serum‐free culture of human hemopoietic progenitors in attenuated culture media
Authors: Yoshiaki Sonoda, Makio Ogawa
Journal: American Journal of Hematology (1988)

Abstract To elucidate the precise mechanisms of molecular and cellular regulation of hemopoiesis, it is necessary to develop a chemically defined culture assay for purified hemopoietic progenitors. To approach this long‐term goal, we attempted to develop a serum‐free culture system for enriched human progenitors that permits expression of all hemopoietic lineages and stages of development. Preliminary studies indicated that α‐medium was superior to iscove's modified Dulbecco's medium (IMDM) and that culture under low (5%) oxygen condition was better than an ambient level of oxygen. We developed an attenuated (modified quarter‐strength) α‐medium and compared the colony‐supporting ability of the three media by plating 1,000 bone marrow null cells per dish in the presence of a combination of recombinant human colony‐stimulating factors (CSFs). The numbers of colonies supported in α‐medium and attenuated α‐medium were approximately 70% of those in serum‐containing cultures. IMDM failed to support colony formation. While, in general, the colony sizes were smaller in the serum‐free cultures than in the serum‐containing cultures, a variety of types of single lineage and multilineage colonies were seen in serum‐free culture. A linear relationship between cell number and colony formation was seen in 100‐2,000 cells per dish. Serum‐free cultures of enriched human progenitors should be an important tool for analysis of the mechanisms of recombinant CSFs.
Adipose Tissue, Inflammation, and Cardiovascular Disease
Authors: Anders H. Berg, Philipp E. Scherer
Journal: Circulation Research (2005)

Mounting evidence highlights the role of adipose tissue in the development of a systemic inflammatory state that contributes to obesity-associated vasculopathy and cardiovascular risk. Circulating mediators of inflammation participate in the mechanisms of vascular insult and atheromatous change, and many of these inflammatory proteins are secreted directly from adipocytes and adipose tissue–derived macrophages. Several factors linking obesity with an increased cardiovascular risk have been identified. The adipocyte-specific secretory protein adiponectin is a particularly promising candidate in this context. Its levels are decreased in obesity. Adiponectin may mediate some of its demonstrated cardioprotective effects through its anti-inflammatory properties. In addition to decreased expression of beneficial adipokines, secretion of a host of inflammatory factors from visceral adipose tissue may contribute to the increased cardiovascular risk associated with obesity. The cardioprotective effects of many of the most popular drug regimens corroborate these conclusions, demonstrating that along with improvements in other therapeutic end points, they mediate improvements in systemic inflammation. In some cases, these improvements are attributable to direct suppression of inflammatory signaling in adipocytes. The targeted suppression of various proinflammatory cascades in adipocytes specifically represents an exciting new therapeutic opportunity for the cardiovascular disease area.