tbuckley/cabot-search huggingface dataset:
Noninvasive Determination of Spatially Resolved and Time-Resolved Tissue Perfusion in Humans During Nitric Oxide Inhibition and Inhalation by Use of a Visible-Reflectance Hyperspectral Imaging Technique
Authors: Karel J. Zuzak, Michael D. Schaeberle, Mark T. Gladwin, Richard O. Cannon, Ira W. Levin
Journal: Circulation (2001)

Background — Vascular disease is commonly associated with reduced local synthesis of nitric oxide (NO) and impaired tissue perfusion. We introduce a novel noninvasive, visible-reflectance, hyperspectral imaging technique for quantifying the percentage of hemoglobin existing as oxyhemoglobin (HbO 2 ) as an index of skin tissue perfusion. Methods and Results — To simulate vascular endothelial dysfunction, N G -monomethyl- l -arginine (L-NMMA) was infused into the brachial arteries of 9 healthy subjects for 5 minutes to inhibit forearm NO synthesis, first with the subject breathing room air and subsequently during NO inhalation at 80 ppm for 1 hour. Blood flow was measured by venous occlusion plethysmography, and the percentage of HbO 2 perfusing skin tissue was imaged noninvasively with a visible-reflectance hyperspectral technique. L-NMMA reduced blood flow by 31.7±4.9% and percentage of HbO 2 by 6.5±0.1 ( P =0.002 and P &lt;0.001 versus baseline, respectively). With subjects inhaling NO, blood flow fell during L-NMMA infusion by only 10.9±7.3%, and the percentage of HbO 2 decreased by 3.6±0.1 ( P =0.007 and P &lt;0.001, respectively, versus room air L-NMMA responses). Conclusions — Visible-reflectance hyperspectral imaging demonstrates (1) a significant decline in the percentage of HbO 2 in skin tissue when blood flow is reduced after inhibition of forearm NO synthesis and (2) restoration of HbO 2 toward basal values with improved blood flow during inhalation of NO. This imaging method may provide an effective approach for time-resolved noninvasive monitoring of skin hemoglobin oxygen saturation and assessment of responses to therapeutic interventions in patients with vascular disease.
Large age and hospital-dependent variation in administration of adjuvant chemotherapy for stage III colon cancer in southern Netherlands
Authors: L.N. van Steenbergen, H.J.T. Rutten, G.J. Creemers, J.F.M. Pruijt, J.W.W. Coebergh, V.E.P.P. Lemmens
Journal: Annals of Oncology (2009)
Dietary Protein Restriction and the Progression of Chronic Renal Disease
Authors: ANDREW S. LEVEY, TOM GREENE, GERALD J. BECK, ARLENE W. CAGGIULA, JOHN W. KUSEK, LAWRENCE G. HUNSICKER, SAULO KLAHR
Journal: Journal of the American Society of Nephrology (1999)

Abstract. The Modification of Diet in Renal Disease (MDRD) Study was the largest randomized clinical trial to test the hypothesis that protein restriction slows the progression of chronic renal disease. However, the primary results published in 1994 were not conclusive with regard to the efficacy of this intervention. Many physicians interpreted the failure of the MDRD Study to demonstrate a beneficial effect of protein restriction over a 2- to 3-yr period as proving that this therapy does not slow disease progression. The authors believe that this viewpoint is incorrect, and is the result of misinterpretation of inconclusive evidence as evidence in favor of the null hypothesis. Since then, numerous secondary analyses of the MDRD Study have been undertaken to clarify the effect of protein restriction on the rate of decline in GFR, urine protein excretion, and onset of end-stage renal disease. This review describes some of the principles of secondary analyses of randomized clinical trials, presents the results of these analyses from the MDRD Study, and compares them with results from other randomized clinical trials. Although these secondary results cannot be regarded as definitive, the authors conclude that the balance of evidence is more consistent with the hypothesis of a beneficial effect of protein restriction than with the contrary hypothesis of no beneficial effect. Until additional data become available, physicians must continue to make recommendations in the absence of conclusive results. The authors suggest that physicians incorporate the results of these secondary analyses into their interpretation of the findings of the MDRD Study.
The long-term programming effect of maternal 25-hydroxyvitamin D in pregnancy on allergic airway disease and lung function in offspring after 20 to 25 years of follow-up
Authors: Susanne Hansen, Ekaterina Maslova, Marin Strøm, Allan Linneberg, Thorhallur I. Halldorsson, Charlotta Granström, Ronald Dahl, Hans Jürgen Hoffmann, Sjurdur F. Olsen
Journal: Journal of Allergy and Clinical Immunology (2015)
Specifically activated memory T cell subsets from cancer patients recognize and reject xenotransplanted autologous tumors
Authors: Philipp Beckhove, Markus Feuerer, Mathias Dolenc, Florian Schuetz, Carmen Choi, Nora Sommerfeldt, Jochen Schwendemann, Katrin Ehlert, Peter Altevogt, Gunther Bastert, Volker Schirrmacher, Viktor Umansky
Journal: Journal of Clinical Investigation (2004)

Bone marrow of breast cancer patients was found to contain CD8+ T cells specific for peptides derived from breast cancer–associated proteins MUC1 and Her-2/neu. Most of these cells had a central or effector memory phenotype (CD45RA–CD62L+ or CD45RA–CD62L–, respectively). To test their in vivo function, we separated bone marrow–derived CD45RA+ naive or CD45RA–CD45RO+ memory T cells, stimulated them with autologous dendritic cells pulsed with tumor lysate, and transferred them into NOD/SCID mice bearing autologous breast tumors and normal skin transplants. CD45RA– memory but not CD45RA+ naive T cells infiltrated autologous tumor but not skin tissues after the transfer. These tumor-infiltrating cells had a central or effector memory phenotype and produced perforin. Many of them expressed the P-selectin glycoprotein ligand 1 and were found around P-selectin+ tumor endothelium. Tumor infiltration included cluster formation in tumor tissue by memory T cells with cotransferred dendritic cells. It was associated with the induction of tumor cell apoptosis and significant tumor reduction. We thus demonstrate selective homing of memory T cells to human tumors and suggest that tumor rejection is based on the recognition of tumor-associated antigens on tumor cells and dendritic cells by autologous specifically activated central and effector memory T cells.
Faithful Markers of Circulating Cancer Stem Cells: Is CD133 Sufficient for Validation in Clinics?
Authors: Francesco Crea, Lorenzo Fornaro, Gianluca Masi, Alfredo Falcone, Romano Danesi, William Farrar
Journal: Journal of Clinical Oncology (2011)

TO THE EDITOR: We read with great interest the recent article by Iinuma et al published in Journal of Clinical Oncology. The authors describe an innovative strategy to identify circulating cancer stem cells (C-CSCs) from blood samples in patients with radically resected nonmetastatic colorectal cancer (CRC). In particular, the study suggests a prognostic value for the identification of CD133, cytokeratins (CKs) and carcinoembryonicm antigen (CEA) mRNA in selected patients with Dukes’ stage B and C. This large study (which included a validation cohort) could pave the way to better prognostic stratification, ultimately optimizing the use of adjuvant chemotherapy. In addition, similar assays may be more accurate than classical response evaluation criteria when testing cancer stem cell (CSC) –specific therapies in the advanced disease setting, as underlined in the accompanying editorial. As we have recently suggested, CSCspecific assays may constitute the backbone of next-generation pharmacogenomics.
BMP-6 in Renal Cell Carcinoma Promotes Tumor Proliferation through IL-10–Dependent M2 Polarization of Tumor-Associated Macrophages
Authors: Jae-Ho Lee, Geun Taek Lee, Seung Hyo Woo, Yun-Sok Ha, Seok Joo Kwon, Wun-Jae Kim, Isaac Yi Kim
Journal: Cancer Research (2013)

Dysregulated bone morphogenetic proteins (BMP) may contribute to the development and progression of renal cell carcinoma (RCC). Herein, we report that BMP-6 promotes the growth of RCC by interleukin (IL)-10-mediated M2 polarization of tumor-associated macrophages (TAM). BMP-6-mediated IL-10 expression in macrophages required Smad5 and STAT3. In human RCC specimens, the three-marker signature BMP-6/IL-10/CD68 was associated with a poor prognosis. Furthermore, patients with elevated IL-10 serum levels had worse outcome after surgery. Together, our results suggest that BMP-6/macrophage/IL-10 regulates M2 polarization of TAMs in RCC.
Hypoxia-Induced Pulmonary Vascular Remodeling
Authors: Kurt R. Stenmark, Karen A. Fagan, Maria G. Frid
Journal: Circulation Research (2006)

Chronic hypoxic exposure induces changes in the structure of pulmonary arteries, as well as in the biochemical and functional phenotypes of each of the vascular cell types, from the hilum of the lung to the most peripheral vessels in the alveolar wall. The magnitude and the specific profile of the changes depend on the species, sex, and the developmental stage at which the exposure to hypoxia occurred. Further, hypoxia-induced changes are site specific, such that the remodeling process in the large vessels differs from that in the smallest vessels. The cellular and molecular mechanisms vary and depend on the cellular composition of vessels at particular sites along the longitudinal axis of the pulmonary vasculature, as well as on local environmental factors. Each of the resident vascular cell types (ie, endothelial, smooth muscle, adventitial fibroblast) undergo site- and time-dependent alterations in proliferation, matrix protein production, expression of growth factors, cytokines, and receptors, and each resident cell type plays a specific role in the overall remodeling response. In addition, hypoxic exposure induces an inflammatory response within the vessel wall, and the recruited circulating progenitor cells contribute significantly to the structural remodeling and persistent vasoconstriction of the pulmonary circulation. The possibility exists that the lung or lung vessels also contain resident progenitor cells that participate in the remodeling process. Thus the hypoxia-induced remodeling of the pulmonary circulation is a highly complex process where numerous interactive events must be taken into account as we search for newer, more effective therapeutic interventions. This review provides perspectives on each of the aforementioned areas.
Transplacental passage and fetal secretion of aldosterone
Authors: Francis Bayard, Isadore G. Ances, Alan J. Tapper, Virginia V. Weldon, Avinoam Kowarski, Claude J. Migeon
Journal: Journal of Clinical Investigation (1970)

The transplacental passage and the production of aldosterone were studied in late pregnancy during a constant infusion of 1,2-aldosterone-(3)H to mothers at the time of elective cesarean section. It was found that, while maternal aldosterone crossed the placenta, there was a significant secretion of aldosterone by the fetus. The aldosterone concentration in fetal plasma was 2-12 times higher than that of the corresponding mothers. Pregnancy had no effect on the metabolic clearance rate of aldosterone, but it increased the rate of production of this steroid. However, the increments that we observed were smaller than those reported in previous reports. The discrepancy was probably due to differences in body posture, our subjects being supine for at least 10 hr at the time of study.
Did my wife elope with someone else?
Authors: W. Misaki
Journal: BMJ (2004)

Mienwa, leader of the senior clerks clerking obstetrics and gynaecology, after watching Senegal triumph over France in their group opening match of the 2002 World Cup, reluctantly strolls back to the ward in an exuberant mood he just cannot conceal. Being the extrovert that he is makes it even more plain to all the staff on the ward.

“You cut [dodged] the ward round this morning just because you were watching football,” comments the SIC (sister in charge), “You men are just too obsessed with that game.”

“Oh yeah, I just couldn't miss seeing Diouf do his thing in this opener,” retorts Mienwa, lifting his leg as though he were hitting a ball. “Who is the SHO on call tonight?”

“It's Dr Wange; he is in the evacuation room,” answers sister.

In the evacuation room Mienwa …
Chromatin Contributions to the Regulation of Innate Immunity
Authors: Stephen T. Smale, Alexander Tarakhovsky, Gioacchino Natoli
Journal: Annual Review of Immunology (2014)

A fundamental property of cells of the innate immune system is their ability to elicit a transcriptional response to a microbial stimulus or danger signal with a high degree of cell type and stimulus specificity. The selective response activates effector pathways to control the insult and plays a central role in regulating adaptive immunity through the differential regulation of cytokine genes. Selectivity is dictated by signaling pathways and their transcription factor targets. However, a growing body of evidence supports models in which different subsets of genes exhibit distinct chromatin features that play active roles in shaping the response. Chromatin also participates in innate memory mechanisms that can promote tolerance to a stimulus or prime cells for a more robust response. These findings have generated interest in the capacity to modulate chromatin regulators with small-molecule compounds for the treatment of diseases associated with innate or adaptive immunity.
Safety and efficacy of longer-term lower-dose cyclosporin A therapy
Authors: D.W. Pryce, L.E. Rhodes, N. Hardwick, P.S. Friedmann
Journal: British Journal of Dermatology (1994)

Journal Article Safety and efficacy of longer‐term lower‐dose cyclosporin A therapy Get access D.W. Pryce, D.W. Pryce Dermatology Unit, the University of Liverpool. PO Box 147, Liverpool L69 3 BX. U.K. Search for other works by this author on: Oxford Academic Google Scholar L.E. Rhodes, L.E. Rhodes Dermatology Unit, the University of Liverpool. PO Box 147, Liverpool L69 3 BX. U.K. Search for other works by this author on: Oxford Academic Google Scholar N. Hardwick, N. Hardwick Dermatology Unit, the University of Liverpool. PO Box 147, Liverpool L69 3 BX. U.K. Search for other works by this author on: Oxford Academic Google Scholar P.S. Friedmann P.S. Friedmann Dermatology Unit, the University of Liverpool. PO Box 147, Liverpool L69 3 BX. U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 130, Issue 5, 1 May 1994, Pages 681–689, https://doi.org/10.1111/j.1365-2133.1994.tb13123.x Published: 01 May 1994
Apoptotic Vesicles Crossprime CD8 T Cells and Protect against Tuberculosis
Authors: Florian Winau, Stephan Weber, Subash Sad, Juana de Diego, Silvia Locatelli Hoops, Bernadette Breiden, Konrad Sandhoff, Volker Brinkmann, Stefan H.E. Kaufmann, Ulrich E. Schaible
Journal: Immunity (2006)
Silica: A lung carcinogen
Authors: Kyle Steenland, Elizabeth Ward
Journal: CA A Cancer Journal for Clinicians (2013)

Abstract Silica has been known to cause silicosis for centuries, and evidence that silica causes lung cancer has accumulated over the last several decades. This article highlights 3 important developments in understanding the health effects of silica and preventing illness and death from silica exposure at work. First, recent epidemiologic studies have provided new information about silica and lung cancer. This includes detailed exposure‐response data, thereby enabling the quantitative risk assessment needed for regulation. New studies have also shown that excess lung mortality occurs in silica‐exposed workers who do not have silicosis and who do not smoke. Second, the US Occupational Safety and Health Administration has recently proposed a new rule lowering the permissible occupational limit for silica. There are approximately 2 million US workers currently exposed to silica. Risk assessments estimate that lowering occupational exposure limits from the current to the proposed standard will reduce silicosis and lung cancer mortality to approximately one‐half of the rates predicted under the current standard. Third, low‐dose computed tomography scanning has now been proven to be an effective screening method for lung cancer. For clinicians, asking about occupational history to determine if silica exposure has occurred is recommended. If such exposure has occurred, extra attention might be given to the early detection of silicosis and lung cancer, as well as extra emphasis on quitting smoking. CA Cancer J Clin 2014;64:63–69. © 2013 American Cancer Society, Inc.
Estimating exome genotyping accuracy by comparing to data from large scale sequencing projects
Authors: Verena Heinrich, Tom Kamphans, Jens Stange, Dmitri Parkhomchuk, Jochen Hecht, Thorsten Dickhaus, Peter N Robinson, Peter M Krawitz
Journal: Genome Medicine (2013)

With exome sequencing becoming a tool for mutation detection in routine diagnostics there is an increasing need for platform-independent methods of quality control. We present a genotype-weighted metric that allows comparison of all the variant calls of an exome to a high-quality reference dataset of an ethnically matched population. The exome-wide genotyping accuracy is estimated from the distance to this reference set, and does not require any further knowledge about data generation or the bioinformatics involved. The distances of our metric are visualized by non-metric multidimensional scaling and serve as an intuitive, standardizable score for the quality assessment of exome data.
Cancer statistics, 2012
Authors: Rebecca Siegel, Deepa Naishadham, Ahmedin Jemal
Journal: CA A Cancer Journal for Clinicians (2012)

Abstract Each year, the American Cancer Society estimates the numbers of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. A total of 1,638,910 new cancer cases and 577,190 deaths from cancer are projected to occur in the United States in 2012. During the most recent 5 years for which there are data (2004‐2008), overall cancer incidence rates declined slightly in men (by 0.6% per year) and were stable in women, while cancer death rates decreased by 1.8% per year in men and by 1.6% per year in women. Over the past 10 years of available data (1999‐2008), cancer death rates have declined by more than 1% per year in men and women of every racial/ethnic group with the exception of American Indians/Alaska Natives, among whom rates have remained stable. The most rapid declines in death rates occurred among African American and Hispanic men (2.4% and 2.3% per year, respectively). Death rates continue to decline for all 4 major cancer sites (lung, colorectum, breast, and prostate), with lung cancer accounting for almost 40% of the total decline in men and breast cancer accounting for 34% of the total decline in women. The reduction in overall cancer death rates since 1990 in men and 1991 in women translates to the avoidance of about 1,024,400 deaths from cancer. Further progress can be accelerated by applying existing cancer control knowledge across all segments of the population, with an emphasis on those groups in the lowest socioeconomic bracket. CA Cancer J Clin 2012. © 2012 American Cancer Society.
Nitrite-Derived Nitric Oxide Protects the Rat Kidney against Ischemia/Reperfusion Injury In Vivo
Authors: Pinpat Tripatara, Nimesh S A Patel, Andrew Webb, Krishnaraj Rathod, Florence M J Lecomte, Emanuela Mazzon, Salvatore Cuzzocrea, Mohammed M Yaqoob, Amrita Ahluwalia, Christoph Thiemermann
Journal: Journal of the American Society of Nephrology (2007)

In normal conditions, nitric oxide (NO) is oxidized to the anion nitrite, but in hypoxia, this nitrite may be reduced back to NO by the nitrite reductase action of deoxygenated hemoglobin, acidic disproportionation, or xanthine oxidoreductase (XOR). Herein, is investigated the effects of topical sodium nitrite administration in a rat model of renal ischemia/reperfusion (I/R) injury. Rats were subjected to 60 min of bilateral renal ischemia and 6 h of reperfusion in the absence or presence of sodium nitrite (30 nmol) administered topically 1 min before reperfusion. Serum creatinine, serum aspartate aminotransferase, creatinine clearance, fractional excretion of Na(+), and plasma nitrite/nitrate concentrations were measured. The nitrite-derived NO-generating capacity of renal tissue was determined under acidic and hypoxic conditions by ozone chemiluminescence in homogenates of kidneys that were subjected to sham, ischemia-only, and I/R conditions. Nitrite significantly attenuated renal dysfunction and injury, an effect that was abolished by previous treatment of rats with the NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazole-1-oxyl-3-oxide (2.5 mumol intravenously 5 min before ischemia and 50 nmol topically 6 min before reperfusion). Renal tissue homogenates produced significant amounts of NO from nitrite, an effect that was attenuated significantly by the xanthine oxidoreductase inhibitor allopurinol. Taken together, these findings demonstrate that topically administered sodium nitrite protects the rat kidney against I/R injury and dysfunction in vivo via the generation, in part, of xanthine oxidoreductase-catalyzed NO production. These observations suggest that nitrite therapy might prove beneficial in protecting kidney function and integrity during periods of I/R such as those encountered in renal transplantation.
Tailoring neurophysiological strategies with clinical context enhances resection and safety and expands indications in gliomas involving motor pathways
Authors: Lorenzo Bello, Marco Riva, Enrica Fava, Valentina Ferpozzi, Antonella Castellano, Fabio Raneri, Federico Pessina, Alberto Bizzi, Andrea Falini, Gabriella Cerri
Journal: Neuro-Oncology (2014)

BackgroundResection of motor pathway gliomas requires the intraoperative recognition of essential cortical-subcortical motor structures. The degree of involvement of motor structures is variable, and increases as result of treatments patients are submitted to. Intraoperative neurophysiology offers various stimulation modalities, which efficiency is based on the ability to recognize essential sites with the highest possible resolution in most clinical conditions. Two stimulation paradigms evolved for intraoperative guidance of motor tumors removal: the 60 Hz-technique [low frequency (LF)] and the pulse-technique [high frequency-(HF)], delivered by bipolar or monopolar probe respectively. Most surgical teams rely on to either of the 2 techniques. The key point is the integration of the choice of the stimulation modality with the clinical context.