tbuckley/cabot-search huggingface dataset:
Ataxia Telangiectasia Mutated and Checkpoint Kinase 2 Regulate BRCA1 to Promote the Fidelity of DNA End-Joining
Authors: Hui-Chun Wang, Wen-Cheng Chou, Sheau-Yann Shieh, Chen-Yang Shen
Journal: Cancer Research (2006)

Homologous recombination (HR) and nonhomologous end-joining (NHEJ) are the two mechanisms responsible for repairing DNA double-strand breaks (DSBs) and act in either a collaborative or competitive manner in mammalian cells. DSB repaired by NHEJ may be more complicated than the simple joining of the ends of DSB, because, if nucleotides were lost, it would result in error-prone repair. This has led to the proposal that a subpathway of precise NHEJ exists that can repair DSBs with higher fidelity; this is supported by recent findings that the expression of the HR gene, BRCA1, is causally linked to in vitro and in vivo precise NHEJ activity. To further delineate this mechanism, the present study explored the connection between NHEJ and the cell-cycle checkpoint proteins, ataxia telangiectasia mutated (ATM) and checkpoint kinase 2 (Chk2), known to be involved in activating BRCA1, and tested the hypothesis that ATM and Chk2 promote precise end-joining by BRCA1. Support for this hypothesis came from the observations that (a) knockdown of ATM and Chk2 expression affected end-joining activity; (b) in BRCA1-defective cells, precise end-joining activity was not restored by a BRCA1 mutant lacking the site phosphorylated by Chk2 but was restored by wild-type BRCA1 or a mutant mimicking phosphorylation by Chk2; (c) Chk2 mutants lacking kinase activity or with a mutation at a site phosphorylated by ATM had a dominant negative effect on precise end-joining in BRCA1-expressing cells. These results suggest that the other two HR regulatory proteins, ATM and Chk2, act jointly to regulate the activity of BRCA1 in controlling the fidelity of DNA end-joining by precise NHEJ.
High LYVE-1–Positive Lymphatic Vessel Numbers Are Associated with Poor Outcome in Breast Cancer
Authors: Petri Bono, Veli-Matti Wasenius, Päivi Heikkilä, Johan Lundin, David G. Jackson, Heikki Joensuu
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The clinical significance of intratumoral or peritumoral lymph vessel density is not known. LYVE-1, a lymphatic endothelium-specific hyaluronan receptor, is a novel lymphatic vessel marker that is expressed on lymph vessel endothelial cells of both normal and neoplastic tissues. Experimental Design: We investigated expression of LYVE-1 by immunhistochemistry in 180 unilateral, invasive ductal breast carcinomas and assessed the presence and density of lymph vessels within the tumor and at the tumor periphery. Results: A minority (12%) of breast carcinomas had intratumoral lymph vessels, whereas peritumoral lymph vessels were identified in almost all cases (94%). No substantial association was found between the number of LYVE-1–positive vessels and the number of CD31 or vascular endothelial growth factor receptor-3–positive vessels, or vascular endothelial growth factor-C expression. The number of metastatic axillary lymph nodes increased in parallel with increasing lymph vessel counts (P = 0.033). A higher than the median lymph vessel count at the tumor periphery was significantly associated with unfavorable distant disease-free survival and overall survival. Women with high peritumoral lymph vessel density had only 58% (95% confidence interval, 46–70%) 5-year distant disease-free survival as compared with 74% (66–83%) among those with a low peritumoral lymph vessel density (P = 0.0088). In contrast, the presence of intratumoral lymph vessels was associated with neither axillary nodal status nor survival. Lymph vessel density was not an independent prognostic factor in a multivariate survival analysis. Conclusions: A high peritumoral lymph vessel density is associated with a poor outcome in ductal breast cancer.
Pharmacy beyond the dispensary: general practitioners' views.
Authors: J. A. Spencer, C. Edwards
Journal: BMJ (1992)

OBJECTIVES--To ascertain general practitioners9 attitudes to an extended role for community pharmacists. DESIGN--Postal questionnaire to a 1 in 6 sample of general practitioners in the Northern, West Midlands, and Oxford regions (total sample size 1087). MAIN OUTCOME MEASURES--Attitudes towards specific extended roles, pharmacist prescribing of particular drugs, the role of the pharmacist, and the relationship between the professions. RESULTS--744 questionnaires were returned in a usable form, an overall response rate of 68.4%. Attitudes varied, from a majority in favour of pharmacists reporting adverse drug reactions to a majority against their supervising repeat prescriptions (81% and 36% in agreement respectively). A similar range of attitudes was shown to pharmacist prescribing, from 84% in agreement with their prescribing nicotine chewing gum (deregulated since the survey) to 11% agreeing to their prescribing cimetidine. About half the respondents thought general practitioners should be allowed to dispense and a third that pharmacists "should stick to dispensing." 27% agreed that pharmacists were too influenced by commercial pressures to give unbiased advice. CONCLUSIONS--Most doctors would favour an extension of the activities of community pharmacists but worry about their role in screening and counselling patients and in prescribing. Despite relationships being generally felt to be good, there may be a need for better communication and cooperation locally and for proper evaluation of initiatives to extend the role of the pharmacist.
Rapid recovery of cardiac beta-adrenergic receptors after isoproterenol-induced "down"-regulation.
Authors: C J Limas, C Limas
Journal: Circulation Research (1984)

Desensitization of beta-receptor-linked adenylate cyclase occurs after prolonged occupancy of the beta-receptors by their agonists. We have followed the development and recovery from "down"-regulation of beta-receptors in enzymatically dissociated cardiac myocytes by using the hydrophilic antagonist [3H]-CGP-12177 to identify surface-bound beta-receptors. After in vitro incubation with (-)-isoproterenol, almost 50% of the beta-receptors are lost within 10 minutes. Isoproterenol-mediated cyclic adenosine monophosphate accumulation by isolated myocytes was also decreased after a 15-minute preincubation with isoproterenol. "Lost" beta-receptors can, however, be recovered when isoproterenol-pretreated, washed cardiac myocytes are incubated at 37 degrees C, 85 +/- 7% of the lost beta-receptors have returned to the cell surface after 20 minutes of incubation. The requirements for such recycling were investigated. Receptor recovery does not depend on de novo protein synthesis, since it is unaffected by prior exposure to cycloheximide. It is, however, dependent on cellular energy, because it is prevented by adenosine triphosphate depletion and involves a lysosomal step since it is inhibited by the lysomotropic agent, chloroquine. In addition, the Golgi apparatus and the microtubules are involved in the beta-receptor recycling to the cell surface, as evidenced by the inhibitory effects of monensin and colchicine, respectively. The mechanism of isoproterenol-induced down-regulation of cardiac beta-receptors involves a rapid, reversible cycling to and from the cytosol and the cell membrane. This intracellular receptor traffic is energy dependent, requires several structures, including lysosomes and microtubules, and may be modified by pathological processes involving the heart.
A CYST OF THE PANCREAS: OPERATION: RECOVERY.
Authors: JAMES B. EAGLESON
Journal: JAMA (1899)

Mrs. J. K., 34 years old and a native of Norway, was referred to me by Dr. Gibson of Seattle. Her family history was negative and she did not remember having received an injury of any kind in the abdomen. She has two children, aged 16 and 5 years, and has had two abortions, the last two years ago. Her general health had always been quite good, until 1896, when she began to have some indigestion and distress in the stomach, and this gradually increased. In May, 1897, she had a sudden attack of severe pain in the left side, in the region of the kidney, accompanied by severe nausea and vomiting. The attack was thought by some to be acute pleurisy, but no definite diagnosis was determined on. It lasted about five weeks. A second attack occurred in the latter part of July, diagnosed as some disease of the
Molecular analysis of G1B and G3A IFNγ mutants reveals that defects in CIITA or RFX result in defective class II MHC and li gene induction
Authors: Keh-Chuang Chin, Catherine Mao, Cheryl Skinner, James L. Riley, Kenneth L. Wright, Carlos S. Moreno, George R. Stark, Jeremy M. Boss, Jenny P.-Y. Tingt
Journal: Immunity (1994)
Hypoxic Stimulation of the Stress-activated Protein Kinases in Pulmonary Artery Fibroblasts
Authors: PAMELA H. SCOTT, ANDREW PAUL, CHRISTOPHER M. BELHAM, ANDREW J. PEACOCK, ROGER M. WADSWORTH, GWYN W. GOULD, DAVID WELSH, ROBIN PLEVIN
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Pulmonary hypertension in response to chronic hypoxia is invariably accompanied by remodeling of the pulmonary vessels but the mechanism by which hypoxia increases the replication of vascular cells is unknown. To investigate the hypothesis that hypoxia stimulates intracellular kinase cascades we measured the activity of “classic” mitogen-activated protein (MAP) kinase pathways and “stress- activated” MAP kinase pathways in bovine pulmonary artery fibroblasts subjected to hypoxia for up to 30 h. Hypoxia (1% O2) stimulated strongly the stress-activated protein kinases, c-Jun NH2-terminal kinase (JNK) and p38 MAP kinase. Two peaks of p38 MAP kinase activity at 6 and 24 h were associated with an increase in the activity of mitogen-activated protein kinase-activated protein (MAPKAP) kinase-2, the immediate downstream target of p38 MAP kinase. Furthermore, the second phase of p38 MAP kinase activity could be reversed if cells were reoxygenated after 12 h. These data suggest that hypoxic stimulation of pulmonary artery cells is mediated by activation of the stress-activated protein kinases.
Primary hepatocellular neoplasms in a MODY3 family with a novel HNF1A germline mutation
Authors: J.S.B. Willson, T.D. Godwin, G.A.R. Wiggins, P.J. Guilford, J.L. McCall
Journal: Journal of Hepatology (2013)

Maturity onset diabetes of the young type 3 (MODY3) and hepatocellular adenomas (HCAs) are associated with mutations in the HNF1A gene. HNF1A codes for the transcription factor HNF1α, which interacts with DNA as a homodimer or a heterodimer with HNF1β, to regulate multiple cellular functions including glucidic metabolism, lipidic transport, and detoxication. We report three members of one family with a novel germline in-frame deletion of HNF1A exons 2-3 identified initially using array CGH and direct sequence analysis. All three family members have MODY3 in association with primary liver cell tumours (HCA, liver adenomatosis (LA), and hepatocellular carcinoma (HCC)). Additionally, a high rate of infant mortality was observed in the family. The described family demonstrates a novel HNF1A mutation associated with both benign and malignant primary liver cell tumours and MODY3.
Equilibrium Studies of Amino Acid Transport: Intestinal Tissue-to-Lumen and Lumen-to-Tissue Fluxes.
Authors: Harold P. Schedl
Journal: Annals of Internal Medicine (1969)

s1 May 1969Equilibrium Studies of Amino Acid Transport: Intestinal Tissue-to-Lumen and Lumen-to-Tissue Fluxes.Harold P. Schedl, M.D., Duane L. Miller, B.A., Helen D. Wilson, B.S.Harold P. Schedl, M.D.Search for more papers by this author, Duane L. Miller, B.A.Search for more papers by this author, Helen D. Wilson, B.S.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-5-1070_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptFrom studies in man we obtained evidence that the transport mechanism for the neutral amino acid, L-methionine, varied with intestinal site SCHEDL, et al.:J. Clin. Invest. 47: 417, 1968). This was further explored in the rat using the model amino acid, alpha-aminoisobutyric acid (AIB). AIB participates in neutral amino acid transport mechanisms but is not metabolized, thus permitting dissociation of transport processes from metabolism. AIB given parenterally was allowed to equilibrate in the body, and its secretion into the intestinal lumen of proximal and midsegments was monitored during recirculation of isotonic saline through the lumen. Proximal segments began at... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Iowa City, Iowa PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1969Volume 70, Issue 5Page: 1070-1071KeywordsAmino acid metabolismAmino acidsIsotonicityMethionine Issue Published: 1 May 1969 PDF DownloadLoading ...
Review of F. G. Miller and R. D. Truog,<i>Death, Dying and Organ Transplantation: Reconstructing Medical Ethics at the End of Life</i>
Authors: Benjamin E. Hippen
Journal: The American Journal of Bioethics (2012)

This book is a model of quality scholarship in bioethics. The central arguments are detailed, carefully constructed, empirically well grounded, and are presented in cogent, clear prose with an econ...
Selective abrogation of the uPA-uPAR interaction in vivo reveals a novel role in suppression of fibrin-associated inflammation
Authors: Brian M. Connolly, Eun Young Choi, Henrik Gårdsvoll, Alexandra L. Bey, Brooke M. Currie, Triantafyllos Chavakis, Shihui Liu, Alfredo Molinolo, Michael Ploug, Stephen H. Leppla, Thomas H. Bugge
Journal: Blood (2010)
ABNORMAL T-LYMPHOCYTE SUBPOPULATIONS ASSOCIATED WITH TRANSFUSIONS OF BLOOD-DERIVED PRODUCTS
Authors: CraigM. Kessler, R.S. Schulof, AllanL. Goldstein, PaulH. Naylor, NaomiL.C. Luban, JackF. Kelleher, GregH. Reaman
Journal: The Lancet (1983)
France offers E800 reward for each new baby
Authors: A. Dorozynski
Journal: BMJ (2003)

The French prime minister, Jean-Pierre Raffarin, announced last week that a bonus of €800 (£560, $895) will be awarded mothers for each baby born after 1 January 2004. The bonus is part of a series of measures to encourage families to have more children. It is estimated that 90% of families will qualify for the childbirth bonus.

“In the coming years, the nation may labour,” said Christian Jacob, minister delegate for the family. He added that one out of two couples wanted an additional child and “must be helped to realise that wish.”

In 2002 in France the average number …
1224 TIMING AND CHARACTERISTICS OF DRUG RESISTANCE MUTATIONS (DRMS) IN CHRONIC HEPATITIS C PATIENTS DURING AND AFTER TREATMENT WITH PROTEASE INHIBITOR THERAPY AT A SINGLE CENTRE
Authors: C. Velazquez, Malcolm Macartney, Dianne Irish, Sudeep Tanwar, Paul Trembling, Brian John Hogan, J. Catt, S. Glasgow, M. Ju, M.T. Moore, M. Hains, B. Smith, D. Suri, M. G. Jacobs, Jude A. Oben, P. Smith, C. Booth, Simon Bridge, Andre Garcia, Adele McCormick, Eleni Nastouli, Geoffrey Dusheiko, William Rosenberg, Tanzina Haque
Journal: Journal of Hepatology (2013)
Shared idiotypic determinants on antibodies and T-cell-derived suppressor factor specific for the random terpolymer L-glutamic acid60-L-alanine30-L-tyrosine10.
Authors: R N Germain, S T Ju, T J Kipps, B Benacerraf, M E Dorf
Journal: The Journal of Experimental Medicine (1979)

T-cell derived suppressor factors (TsF) specific for the random copolymers L-glutamic acid60-L-alanine30-Ltyrosine10 and L-glutamic acid60-L-alanine40, referred to as GAT and GA, respectively, were prepared and partially purified on the approprate antigen immunoadsorbents. GAT-TsF obtained from nonresponder DBA/1 (H-2q) and SJL (H-2s) mice were passed over immunoadsorbents prepared from normal guinea pig serum (NGPS) or guinea pig anti-idiotype antiserum (anti-CGAT) specific for a common cross-reactive idiotype found on most anti-GAT antibodies in all mouse strains tested. Both the directly suppressive activity of the GAT-TsF and the ability of GAT-TsF to induce new suppressor T cells (Ts2) in vitro were adsorbed to and fully recoverable from the guinea pig anti-CGAT-Sepharose immunoadsorbent, while the TsF passed through the control NGPS-Sepharose without appreciable binding. The SJL GAT-TsF specifically eluted from anti-CGAT-immunoadsrobents was shown to still posses I-J determinants. These data provide evidence suggesting a sharing of V region structures between B-cell antibody and T-cell suppressor factor specific for an antigen (GAT) under Ir gene control, in agreement with earlier studies on T and B-cell alloreceptors, T-cell helper factors, and T and B-cell receptors for conventional antigens.
Effect of heel-raising exercise upon collateral resistance in patients with occlusion of the superficial femoral artery
Authors: K AGERSKOV, O HENRIKSEN
Journal: Cardiovascular Research (1983)

Invasive blood pressure measurements were performed in the common femoral- and popliteal artery of six limbs with occlusion of the superficial femoral artery during upright exercise (heel raising) and intraarterial alpha-receptor blockade. Femoral blood flow was obtained by an indicator dilution method injecting 131 RISA into the femoral artery and sampling from the popliteal artery. Exercise increased femoral blood flow from an average of 184 (SE +/- 27) cm3 . min-1 at rest to 531 (SE +/- 61) cm3 . min-1 during a 40 degrees head up tilt. Intraarterially induced alpha-receptor blockade caused a further increase in blood flow to 685 (SE +/- 86) cm3 . min-1 during exercise. Changes in collateral arterial resistance was calculated relative to the supine resting value. During exercise a decrease of 24% (SE +/- 13) was observed. After alpha-receptor blockade and exercise collateral resistance decreased by 46% (SE +/- 12). The results indicate that the passive head-up tilt induced a constriction of the collateral arteries which is abolished by heel raising exercise (ie standing on tip toe). It seems, however, that during these circumstances there still remains some alpha-receptor mediated constriction of the collateral arteries which is blocked by intraarterially injected alpha-receptor blocking agents.
Targeted tumor therapy: turning the genome on its head
Authors: Matthew M Lawler, Ian S Dunn, Estelle E Newton, Lenora B Rose, James T Kurnick
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts TriBiotica has combined molecular biology of cancer and proprietary chemistry to implement an innovative therapeutic approach to cancer treatment. Instead of developing immunological reagents (such as cells, antibodies or chimeric receptors) targeting antigens already present on
Users' Guides to the Medical Literature
Authors: Gordon H. Guyatt, R. Brian Haynes, Roman Z. Jaeschke, Deborah J. Cook, Lee Green, C. David Naylor, Mark C. Wilson, W. Scott Richardson, None for the Evidence-Based Medicine Working Group
Journal: JAMA (2000)

This series provides clinicians with strategies and tools to interpret and integrate evidence from published research in their care of patients. The 2 key principles for applying all the articles in this series to patient care relate to the value-laden nature of clinical decisions and to the hierarchy of evidence postulated by evidence-based medicine. Clinicians need to be able to distinguish high from low quality in primary studies, systematic reviews, practice guidelines, and other integrative research focused on management recommendations. An evidence-based practitioner must also understand the patient's circumstances or predicament; identify knowledge gaps and frame questions to fill those gaps; conduct an efficient literature search; critically appraise the research evidence; and apply that evidence to patient care. However, treatment judgments often reflect clinician or societal values concerning whether intervention benefits are worth the cost. Many unanswered questions concerning how to elicit preferences and how to incorporate them in clinical encounters constitute an enormously challenging frontier for evidence-based medicine. Time limitation remains the biggest obstacle to evidence-based practice but clinicians should seek evidence from as high in the appropriate hierarchy of evidence as possible, and every clinical decision should be geared toward the particular circumstances of the patient.
Tumor-Specific Immune Mechanisms
Authors: Richard T. Smith
Journal: New England Journal of Medicine (1968)

Components of Host Responsiveness to Tumor-Specific AntigensA congeries of evidence indicates that a host does not treat neoplastic transformation, whether induced by virus or chemical oncogen as "self." The same cellular and humoral elements of the immune response are stimulated, and the same consequences of immunologic recognition are possible toward tumor-specific transplantation antigens (TSTA) as toward other transplantation antigens. The response to TSTA shows immunologic memory, since the animal that has marshaled a specific response once will display a changed reactivity against the same TSTA when reinoculated.Less is known regarding responsiveness of the primary host to the TSTA . . .
Birth weight and cognitive function in young adult life: historical cohort study
Authors: H. T. Sorensen, S. Sabroe, J. Olsen, K. J Rothman, M. W Gillman, P. Fischer
Journal: BMJ (1997)

<h3>Abstract</h3> <b>Objective:</b> To examine the relation between birth weight and cognitive function in young adult life. <b>Design:</b> Retrospective cohort study based on birth registry data and cognitive function measured during evaluation for military service. <b>Subjects:</b> 4300 Danish conscripts born between 1973 and 1975. <b>Main outcome measures:</b> Mean score in the Boerge Prien test of cognitive function; score is the number of correct answers to 78 questions and correlates with full scale intelligence quotient (IQ). <b>Results:</b> Mean score in the Boerge Prien test increased from 39.9 at a birth weight of ≤2500 g to 44.6 at a birth weight of 4200 g even after adjustment for gestational age and length at birth, maternal age and parity, and other variables. Above a birth weight of 4200 g the test score decreased slightly. <b>Conclusion:</b> Birth weight is associated with cognitive performance in young adult life. Interference with fetal growth may influence adult cognitive performance. <h3>Key messages</h3> Low birth weight and proportionate smallness at birth have been associated with poorer cognitive function in early childhood Only a few studies have examined whether this association persists into adult life This study found that the mean cognitive test score in 4300 Danish conscripts increased up to a birth weight of 4200 g after adjustment for confounders; there was a slight decrease above a birth weight of 4200 g Fetal growth seems to influence adult cognitive performance If fetal growth has an impact on mental development it has important consequences from the perspective of maternal care
A More Appropriate Name for the Antidiuretic Hormone
Authors: Antonio Boba
Journal: JAMA (1980)

<h3>To the Editor.—</h3> Albert Liebman's (241:2141, 1979) choice of a better name for the antidiuretic hormone, the "water-retaining hormone," still leaves much to be desired. In truth, the hormone acts in a general nonspecific manner on the size of the submicroscopic pores that exist in biological membranes; it is also true that, in general, this action results in an "economy" of water. However, it should be understood that this is not accomplished through a "retention" mechanism, but through an "absorption" mechanism, which can be shown to vary from resorption of bladder water to absorption of water via the skin to reabsorption of water at the level of the collecting tubule. What is essential to realize is that the effect of the hormone is so nonspecific that, through appropriate manipulations of the body's water load and partition, and through the manipulation of the renal blood flow pattern, the administration of the