tbuckley/cabot-search huggingface dataset:
Constitutive ablation of dendritic cells breaks self-tolerance of CD4 T cells and results in spontaneous fatal autoimmunity
Authors: Caspar Ohnmacht, Andrea Pullner, Susan B.S. King, Ingo Drexler, Stefanie Meier, Thomas Brocker, David Voehringer
Journal: The Journal of Experimental Medicine (2009)

Lack of immunological tolerance against self-antigens results in autoimmune disorders. During onset of autoimmunity, dendritic cells (DCs) are thought to be critical for priming of self-reactive T cells that have escaped tolerance induction. However, because DCs can also induce T cell tolerance, it remains unclear whether DCs are required under steady-state conditions to prevent autoimmunity. To address this question, we crossed CD11c-Cre mice with mice that express diphtheria toxin A (DTA) under the control of a loxP-flanked neomycin resistance (neoR) cassette from the ROSA26 locus. Cre-mediated removal of the neoR cassette leads to DTA expression and constitutive loss of conventional DCs, plasmacytoid DCs, and Langerhans cells. These DC-depleted (ΔDC) mice showed increased frequencies of CD4 single-positive thymocytes and infiltration of CD4 T cells into peripheral tissues. They developed spontaneous autoimmunity characterized by reduced body weight, splenomegaly, autoantibody formation, neutrophilia, high numbers of Th1 and Th17 cells, and inflammatory bowel disease. Pathology could be induced by reconstitution of wild-type (WT) mice with bone marrow (BM) from ΔDC mice, whereas mixed BM chimeras that received BM from ΔDC and WT mice remained healthy. This demonstrates that DCs play an essential role to protect against fatal autoimmunity under steady-state conditions.
P127 CD4+ REGULATORY T CELLS (TREGS) MODULATE INTERACTIONS BETWEEN NK CELLS AND HEPATIC STELLATE CELLS (HSC) IN HEPATITIS C
Authors: B. Langhans, A.W. Alwan, E.-M. Althausen, B. Krämer, A. Glässner, M. Eisenhardt, J. Nattermann, C.P. Strassburg, U. Spengler
Journal: Journal of Hepatology (2014)
Expression of Base Excision DNA Repair Genes Is a Sensitive Biomarker for <b> <i>in Vivo</i> </b> Detection of Chemical-induced Chronic Oxidative Stress
Authors: Ivan Rusyn, Shoji Asakura, Brian Pachkowski, Blair U. Bradford, Mikhail F. Denissenko, Jeffrey M. Peters, Steven M. Holland, Janardan K. Reddy, Michael L. Cunningham, James A. Swenberg
Journal: Cancer Research (2004)

Abstract Oxidative stress to DNA is recognized as one of the mechanisms for the carcinogenic effects of some environmental agents. Numerous studies have been conducted in an attempt to document the fact that chemical carcinogens that are thought to induce production of oxidants also cause the formation of oxidative DNA lesions. Although many DNA adducts continue to be useful biomarkers of dose/effect, changes in gene expression have been proposed to be a practical novel tool for studying the role of chemically induced oxidative DNA damage. Here, we hypothesized that expression of base excision DNA repair genes is a sensitive biomarker for in vivo detection of chemically induced chronic oxidative stress. To test this hypothesis, mice were treated with a known rodent carcinogen and peroxisome proliferator, WY-14,643 (500 ppm, 1 month). A number of end points that are commonly used to assess oxidative DNA damage were considered. Our data demonstrate that no difference in 8-oxoguanine, the number of abasic sites, or single strand breaks can be detected in genomic DNA from livers of control or WY-treated animals. However, a concordant marked induction of genes specific for the long-patch base excision DNA repair, a predominant pathway that removes oxidized DNA lesions in vivo, was observed in livers of WY-treated mice. Kupffer cell NADPH oxidase, and peroxisomes in parenchymal cells have been proposed as the potential sources of peroxisome proliferator-induced oxidants. The analysis of expression of base excision DNA repair genes was used to assess whether this biomarker of oxidative stress can be used to determine the source of oxidants. The data suggest that DNA-damaging oxidants are generated by enzymes that are induced after activation of peroxisome proliferator activator receptor α, such as those involved in lipid metabolism in peroxisomes, and are not the result of activation of NADPH oxidase in Kupffer cells. We conclude that expression of base excision DNA repair genes is a sensitive in vivo biomarker for chemically induced oxidative stress to DNA that can be successfully used for the identification of the molecular source of radicals responsible for DNA damage in vivo.
When I use a word: Fortuitous---ambiguously inappropriate to describe maternal death?
Authors: G. Howarth
Journal: BMJ (2000)

investigations that are more readily available, which in combination yield a minimum posterior probability of 20%.Adding a test for brain natriuretic peptide to the determination of a patient's history of myocardial infarction in the diagnostic screening process reduces the posterior probability to 15%.We would like to thank Chris Teideman, Tim Lancaster and Alice Fuller for their help and support.Contributors:
The protective role of manganese superoxide dismutase against adriamycin-induced acute cardiac toxicity in transgenic mice.
Authors: H C Yen, T D Oberley, S Vichitbandha, Y S Ho, D K St Clair
Journal: Journal of Clinical Investigation (1996)

Adriamycin (ADR) is a potent anticancer drug known to cause severe cardiac toxicity. Although ADR generates free radicals, the role of free radicals in the development of cardiac toxicity and the intracellular target for ADR-induced cardiac toxicity are still not well understood. We produced three transgenic mice lines expressing increased levels of human manganese superoxide dismutase (MnSOD), a mitochondrial enzyme, as an animal model to investigate the role of ADR-mediated free radical generation in mitochondria. The human MnSOD was expressed, functionally active, and properly transported into mitochondria in the heart of transgenic mice. The levels of copper-zinc SOD, catalase, and glutathione peroxidase did not change in the transgenic mice. Electron microscopy revealed dose-dependent ultrastructural alterations with marked mitochondrial damage in nontransgenic mice treated with ADR, but not in the transgenic littermates. Biochemical analysis indicated that the levels of serum creatine kinase and lactate dehydrogenase in ADR-treated mice were significantly greater in nontransgenic than their transgenic littermates expressing a high level of human MnSOD after ADR treatment. These results support a major role for free radical generation in ADR toxicity as well as suggesting mitochondria as the critical site of cardiac injury.
BIOIMPEDANCE TOMOGRAPHY (ELECTRICAL IMPEDANCE TOMOGRAPHY)
Authors: R.H. Bayford
Journal: Annual Review of Biomedical Engineering (2006)

Electrical impedance tomography (EIT) is a relatively new imaging method that has evolved over the past 20 years. It has the potential to be of great value in clinical diagnosis; however, EIT is a technically difficult problem to solve in terms of developing hardware for data capture and the algorithms to reconstruct the images. This review looks at the development of EIT and how it has evolved. It focuses on its clinical applications, examining hardware for the collection of data and reconstruction algorithms to generate images. Finally, this review looks at future developments that are evolving from EIT. These new variations use mixed modalities that may produce interesting new clinical imaging tools.
Differentiation and Loss of Malignant Character of Spontaneous Pulmonary Metastases in Patient-Derived Breast Cancer Models
Authors: Jessica Bockhorn, Aleix Prat, Ya-Fang Chang, Xia Liu, Simo Huang, Meng Shang, Chika Nwachukwu, Maria J. Gomez-Vega, J. Chuck Harrell, Olufunmilayo I. Olopade, Charles M. Perou, Huiping Liu
Journal: Cancer Research (2014)

Abstract Patient-derived human-in-mouse xenograft models of breast cancer (PDX models) that exhibit spontaneous lung metastases offer a potentially powerful model of cancer metastasis. In this study, we evaluated the malignant character of lung micrometastases that emerge in such models after orthotopic implantation of human breast tumor cells into the mouse mammary fat pad. Interestingly, relative to the parental primary breast tumors, the lung metastasis (met)–derived mammary tumors exhibited a slower growth rate and a reduced metastatic potential with a more differentiated epithelial status. Epigenetic correlates were determined by gene array analyses. Lung met–derived tumors displayed differential expression of negative regulators of cell proliferation and metabolism and positive regulators of mammary epithelial differentiation. Clinically, this signature correlated with breast tumor subtypes. We identified hsa-miR-138 (miR-138) as a novel regulator of invasion and epithelial–mesenchymal transition in breast cancer cells, acting by directly targeting the polycomb epigenetic regulator EZH2. Mechanistic investigations showed that GATA3 transcriptionally controlled miR-138 levels in lung metastases. Notably, the miR-138 activity signature served as a novel independent prognostic marker for patient survival beyond traditional pathologic variables, intrinsic subtypes, or a proliferation gene signature. Our results highlight the loss of malignant character in some lung micrometastatic lesions and the epigenetic regulation of this phenotype. Cancer Res; 74(24); 7406–17. ©2014 AACR.
RNAi Screen Identifies a Synthetic Lethal Interaction between PIM1 Overexpression and PLK1 Inhibition
Authors: Riet van der Meer, Ha Yong Song, Seong-Hoon Park, Sarki A. Abdulkadir, Meejeon Roh
Journal: Clinical Cancer Research (2014)

To identify genes whose depletion is detrimental to Pim1-overexpressing prostate cancer cells and to validate this finding in vitro and in vivo.RNAi screening was used to identify genes whose depletion is detrimental to Pim1-overexpressing cells. Our finding was validated using shRNA or PLK1-specific inhibitor BI 2536. Xenograft studies were performed using both PLK1-knockdown cells and BI 2536 to investigate the effects of PLK1 inhibition on tumorigenesis in Pim1-overexpressing cells. Finally, PLK1 and PIM1 expression patterns in human prostate tumors were examined by immunohistochemistry using tissue microarrays.We identified the mitotic regulator polo-like kinase (PLK1) as a gene whose depletion is particularly detrimental to the viability of Pim1-overexpressing prostate cancer. Inhibition of PLK1 by shRNA or BI 2536 in Pim1-overexpressing prostate cancer xenograft models resulted in a dramatic inhibition of tumor progression. Notably, Pim1-overexpressing cells were more prone to mitotic arrest followed by apoptosis due to PLK1 inhibition than control cells. Furthermore, inhibition of PLK1 led to the reduction of MYC protein levels both in vitro and in vivo. Our data also suggest that PIM1 and PLK1 physically interact and PIM1 might phosphorylate PLK1. Finally, PLK1 and PIM1 are frequently co-expressed in human prostate tumors, and co-expression of PLK1 and PIM1 was significantly correlated to higher Gleason grades.Our findings demonstrate that PIM1-overexpressing cancer cells are particularly sensitive to PLK1 inhibition, suggesting that PIM1 might be used as a marker for identifying patients who will benefit from PLK1 inhibitor treatment.
A proportion of patients with lymphoma may harbor mutations of the perforin gene
Authors: Rita Clementi, Franco Locatelli, Loïc Dupré, Alberto Garaventa, Lorenzo Emmi, Marco Bregni, Graziella Cefalo, Antonia Moretta, Cesare Danesino, Margherita Comis, Andrea Pession, Ugo Ramenghi, Rita Maccario, Maurizio Aricò, Maria Grazia Roncarolo
Journal: Blood (2005)
Value of Rectal Biopsies in the Diagnosis and Treatment of<i>Schistosoma mansoni</i>Infections
Authors: Clifford L. Spingarn, Morton H. Edelman, Theodore Gold, Harry Yarnis, Robert Turell
Journal: New England Journal of Medicine (1957)

INFECTIONS with the trematode worm, Schistosoma mansoni, have frequently been encountered among the large group of native-born Puerto Ricans now residing in New York City.1 As part of a study of this disease, we endeavored to determine the value of the examination of biopsied fragments of rectal mucosa in diagnosis and as a guide to treatment. This report deals with our observations in 106 cases.The use of a rectal biopsy for the diagnosis of schistosomiasis was first suggested in 1942 by Ottolina and Atencio2 after a study of post-mortem material. By digesting various tissues with caustic potash and . . .
Increased circulating pro-brain natriuretic peptide (proBNP) and brain natriuretic peptide (BNP) in patients with cirrhosis: relation to cardiovascular dysfunction and severity of disease
Authors: J H Henriksen
Journal: Gut (2003)

<b>Magnetic resonance imaging of the lung using sequences with ultrashort echo times is a radiation-free alternative to computed tomography to assess bronchial thickness in asthma, and will help improve the management of severe asthma</b>https://bit.ly/3fGLE4B
Myocardial contraction velocity measured by ultrasound echocardiography-differentiation and evaluated by left ventricular pressures in pigs
Authors: P.-E. PAULEV, J. F. PEDERSEN, F. NEUMANN
Journal: Cardiovascular Research (1973)

Journal Article Myocardial contraction velocity measured by ultrasound echocardiography-differentiation and evaluated by left ventricular pressures in pigs Get access POUL-ERIK PAULEV, POUL-ERIK PAULEV From the Institute of Medical Physiology B, University of Copenhagen, and The Ultrasonic Laboratory, Department of Surgery H, Gentofte Hospital, Copenhagen, Denmark Search for other works by this author on: Oxford Academic PubMed Google Scholar JAN FOG PEDERSEN, JAN FOG PEDERSEN From the Institute of Medical Physiology B, University of Copenhagen, and The Ultrasonic Laboratory, Department of Surgery H, Gentofte Hospital, Copenhagen, Denmark Search for other works by this author on: Oxford Academic PubMed Google Scholar FLEMMING NEUMANN FLEMMING NEUMANN From the Institute of Medical Physiology B, University of Copenhagen, and The Ultrasonic Laboratory, Department of Surgery H, Gentofte Hospital, Copenhagen, Denmark Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 7, Issue 2, March 1973, Pages 277–281, https://doi.org/10.1093/cvr/7.2.277 Published: 01 March 1973
The effect of warming on adrenergic neurotransmission in canine cutaneous vein.
Authors: J P Cooke, J T Shepherd, P M Vanhoutte
Journal: Circulation Research (1984)

The effect of warming on adrenergic neurotransmission was examined in canine cutaneous veins. Isometric tension was recorded from rings of saphenous veins of the dog in organ chambers filled with physiological salt solution. During contractions caused by potassium or prostaglandin F2 alpha, warming from 37 to 41 degrees C caused an augmentation. During contractions caused by stimulation of the adrenergic nerves, and by exogenous norepinephrine, warming caused a relaxation. The relaxation with warming was not altered by the beta-adrenergic antagonist, propranolol, or by inhibitors of extraneuronal and neuronal uptake of norepinephrine. During contractions evoked by the alpha 2-adrenergic agonists, alpha-methyl norepinephrine and B-HT 920, warming caused a relaxation, whereas during contractions due to the alpha 1-adrenergic agonists, cirazoline , methoxamine, ST 587, and phenylephrine, it caused an augmentation. The relaxation caused by warming during norepinephrine-induced contractions was prevented by the preferential alpha 2-antagonists yohimbine and rauwolscine, but not by the preferential alpha 1-antagonist, prazosin. In strips of saphenous vein incubated with [3H] norepinephrine , warming did not affect the release of labeled transmitter evoked by nerve stimulation. These experiments indicate that warming directly enhances contractility of vascular smooth muscle, while depressing the responsiveness of cutaneous vessels to sympathetic nerve activation by a selective inhibitory effect on postjunctional alpha 2-adrenoceptors. Relaxation with warming is greater during nerve stimulation than during administration of exogenous norepinephrine, which may be due to a predominance of postjunctional alpha 2-adrenoceptors in the neuromuscular junction.
SERUM BUTYRYLCHOLINESTERASE PREDICTS SURVIVAL FOLLOWING EXTRACORPOREAL MEMBRANE OXYGENATION AFTER CARDIOVASCULAR SURGERY
Authors: Georg Goliasch, Max-Paul Winter, Kurt Ruetzler, Gottfried Heinz, Irene Lang, Gerald Maurer, Herbert Koinig, Barbara Steinlechner, Alexander Niessner, Klaus Distelmaier
Journal: Journal of the American College of Cardiology (2014)
Follistatin Gene Delivery Enhances Muscle Growth and Strength in Nonhuman Primates
Authors: Janaiah Kota, Chalonda R. Handy, Amanda M. Haidet, Chrystal L. Montgomery, Amy Eagle, Louise R. Rodino-Klapac, Danielle Tucker, Christopher J. Shilling, Walter R. Therlfall, Christopher M. Walker, Steven E. Weisbrode, Paul M. L. Janssen, K. Reed Clark, Zarife Sahenk, Jerry R. Mendell, Brian K. Kaspar
Journal: Science Translational Medicine (2009)

A vector delivered into muscles of monkeys generates a natural regulatory molecule, which increases muscle size and strength and may be useful therapeutically.
Fatty acid uptake by isolated rat heart myocytes represents a carrier-mediated transport process.
Authors: W Stremmel
Journal: Journal of Clinical Investigation (1988)

The mechanism by which fatty acids enter cardiomyocytes is unclear. Therefore, the influx kinetics of [3H]oleate into isolated rat heart myocytes were examined. Cells were incubated at 37 degrees C with [3H]oleate bound to albumin in various molar ratios and the initial rate of uptake (V0) was determined as a function of the unbound oleate concentration in the medium. V0 was saturable with increasing oleate concentrations incubated (Km 78 nM; Vmax 1.9 nmol X min-1 per 10(6) cells) and temperature dependent with an optimum at 37 degrees C. Furthermore, binding of [3H]oleate to isolated plasma membranes of cardiomyocytes was saturable, revealing a KD of 42 nM, and was inhibited by heat denaturation or trypsin pretreatment of the membranes. From these membranes a single 40-kD protein with high affinity for a variety of long chain fatty acids was isolated. With a monospecific antibody to this membrane protein, binding as well as cellular influx of [3H]oleate was selectively inhibited. These data indicate that at least a portion of myocardial fatty acid uptake is mediated by a specific membrane protein.
Impaired renal Na+ retention in the sgk1-knockout mouse
Authors: Peer Wulff, Volker Vallon, Dan Yang Huang, Harald Völkl, Fang Yu, Kerstin Richter, Martina Jansen, Michaela Schlünz, Karin Klingel, Johannes Loffing, Gunther Kauselmann, Michael R. Bösl, Florian Lang, Dietmar Kuhl
Journal: Journal of Clinical Investigation (2002)

The serum- and glucocorticoid-regulated kinase (sgk1) is induced by mineralocorticoids and, in turn, upregulates heterologously expressed renal epithelial Na+ channel (ENaC) activity in Xenopus oocytes. Accordingly, Sgk1 is considered to mediate the mineralocorticoid stimulation of renal ENaC activity and antinatriuresis. Here we show that at standard NaCl intake, renal water and electrolyte excretion is indistinguishable in sgk1-knockout (sgk1–/–) mice and wild-type (sgk1+/+) mice. In contrast, dietary NaCl restriction reveals an impaired ability of sgk1–/– mice to adequately decrease Na+ excretion despite increases in plasma aldosterone levels and proximal-tubular Na+ and fluid reabsorption, as well as decreases in blood pressure and glomerular filtration rate.
Ontogeny of CpG island methylation and specificity of DNMT3 methyltransferases during embryonic development in the mouse
Authors: Ghislain Auclair, Sylvain Guibert, Ambre Bender, Michael Weber
Journal: Genome biology (2014)

In the mouse, the patterns of DNA methylation are established during early embryonic development in the epiblast. We quantified the targets and kinetics of DNA methylation acquisition in epiblast cells, and determined the contribution of the de novo methyltransferases DNMT3A and DNMT3B to this process.We generated single-base maps of DNA methylation from the blastocyst to post-implantation stages and in embryos lacking DNMT3A or DNMT3B activity. DNA methylation is established within two days of implantation between embryonic days 4.5 and 6.5. The kinetics of de novo methylation are uniform throughout the genome, suggesting a random mechanism of deposition. In contrast, many CpG islands acquire methylation slowly in late epiblast cells. Five percent of CpG islands gain methylation and are found in the promoters of germline genes and in exons of important developmental genes. The onset of global methylation correlates with the upregulation of Dnmt3a/b genes in the early epiblast. DNMT3A and DNMT3B act redundantly to methylate the bulk genome and repetitive elements, whereas DNMT3B has a prominent role in the methylation of CpG islands on autosomes and the X chromosome. Reduced CpG island methylation in Dnmt3b-deficient embryos correlates with gene reactivation in promoters but reduced transcript abundance in gene bodies. Finally, DNMT3B establishes secondary methylation marks at imprinted loci, which distinguishes bona fide germline from somatic methylation imprints.We reveal that the DNMT3 de novo methyltransferases play both redundant and specific functions in the establishment of DNA methylation in the mouse embryo.
MALE SEX DETERMINATION: Current Concepts of Male Sexual Differentiation
Authors: Michael L. Gustafson, M.D, Patricia K. Donahoe, M.D
Journal: Annual Review of Medicine (1994)

▪ Abstract In order for an infant to develop as a phenotypically complete male or female, a cascade of complex molecular and morphological events must occur at the appropriate time and in the correct sequence during ontogeny. The male embryo's genetic sex is determined by its chromosomal constituents, the most important of which is the sex-determining gene, or testis-determining factor (TDF), on the Y chromosome. Male gonadal sex, or testis formation, is subsequently thought to be determined by this gene and by other secondary pathways. The male gonad, in turn, normally produces hormones such as testosterone and Mullerian inhibiting substance (MIS) that regulate differentiation of the internal and external genitalia, thus determining phenotypic sex. When an abnormality develops in any of the above three processes, an intersex infant with ambiguous genitalia results from the incongruent genetic, gonadal, and phenotypic sex. Clinically, such 46XY males with intersex abnormalities present challenges for gender assignment, timely surgical intervention, and appropriate hormonal therapy.
A memorable patient: Clinical and communication skills conquer all
Authors: A F Dinah
Journal: BMJ (2001)

I had just started as a casualty officer in a rural part of England. My next patient was an 11 year old boy with a fishing hook in his finger. As I drew back the curtains and entered the cubicle, the child and his parents were slightly taken aback by my appearance. It was probably the first time that they were so close to a brown person. I am an Irish born UK graduate of Indian descent, but my skullcap and …
National Hospital Board
Authors: S. A. S. Malkin
Journal: BMJ (1940)

vegetables and gave them lime-juice to drink. In one month's time I had their blood re-examined and myself tested their eyes, but no appreciable difference in either the blood or vision was found.  In speaking of this subject before some Australian officers one of them told me that in the islands to the north of Aus tralia some of the natives could not see at all at night when they were suffering from intestinal worms. Soon after the cure of the intestinal condition their night vision returned as before.  It is interesting in this connexion to relate that in all my three and a half years' active service I only saw three cases of xerosis conjunctivae, and none of these cases complained of night blindness.-I am, etc., W. A. ANDERSON, Belfast, Feb. 27. Officer in Charge, Ophthalmic Centre, 2nd Army, B.E.F. (1914-18).