tbuckley/cabot-search huggingface dataset:
Abstract B8: Targeting p21-activated kinases in human lung cancer
Authors: Christy C. Ong, Adrian M. Jubb, Peter M. Haverty, Wei Zhou, Adrian L. Harris, Marcia Belvin, Lori S. Friedman, Hartmut Koeppen, Klaus P. Hoeflich
Journal: Clinical Cancer Research (2012)

Abstract P21-activated kinases (PAKs) are important mediators of Rac and Cdc42 GTPase function as well as pathways required for Ras-driven tumorigenesis. PAKs have been implicated in signaling by growth factor receptors and morphogenetic processes that control cell polarity, invasion and actin cytoskeleton organization. To better understand the role of PAK1 in lung tumorigenesis, PAK1 genomic copy number and expression were determined for a panel of adenocarcinoma and squamous non-small cell lung cancers (NSCLC) and small cell lung cancers (SCLC). 64% of squamous NSCLC samples were positive for PAK1 expression and 52% of all cases showed staining of moderate (2+) or strong (3+) immunohistochemical intensity in the malignant cells. Nuclear localization of PAK1 was also evident in a significant proportion of squamous NSCLCs. Adjacent normal lung tissue did not express appreciable levels of PAK1. Selective PAK1 inhibition was associated with delayed cell cycle progression in vitro and in vivo. NSCLC cells were profiled using a library of pathway-targeted small molecule inhibitors and several synergistic combination therapies, including combination with antagonists of inhibitor of apoptosis (IAP) proteins, were revealed for PAK1. Dual inhibition of PAK1 and X chromosome-linked IAP (XIAP) efficiently increased effector caspase activation and apoptosis of NSCLC cells. Together, our results provide evidence for dysregulation of PAK1 in NSCLC and a role for PAK1 in cellular survival and proliferation in this indication.
Effect of Thymic Stromal Lymphopoietin (TSLP) on Cord Blood (CB) Progenitor Cell Hemopoietic Cytokine Receptors (HCR)
Authors: D. Heroux, I. Asher, J. Denburg, G. Delespesse, Z. Allakhverdi
Journal: Journal of Allergy and Clinical Immunology (2011)
Rheumatic fever and its management
Authors: Antoinette M Cilliers
Journal: BMJ (2006)

The diagnosis of acute rheumatic fever is a clinical challenge and depends on the possibility of the disease being borne in mind. Although the complete eradication of rheumatic fever from the Western world has not been achieved, the disease is often forgotten in the differential diagnosis of a patient with fever and polyarthralgia or arthritis. Rheumatic fever remains an important acquired cardiac disease in low and middle income countries and among poorly resourced communities in high income countries. Rheumatic heart disease places a heavy economic burden on the healthcare system in low and middle income countries because of the costs of medical treatment and heart valve surgery and also because it is a disease of young adults, who are the most economically active group of any population. Management is complex and involves different levels of care. The only new advances in the management of acute rheumatic fever to date are in the development of vaccines. #### Summary points #### Sources and search criteria
Estrogen Replacement Therapy and Risk of Breast Cancer-Reply
Authors: Graham A. Colditz
Journal: JAMA (1991)

In Reply.  —We appreciate the concern expressed by Drs Bush and Helzlsouer regarding the elevated risk of breast cancer among women currently using estrogen replacement therapy. They raise the question of differential rates of mammography among the women who are current users of postmenopausal hormones (64%) compared with nonusers (49%). Actually, this modest difference in rates initially concerned us as well. After a detailed examination, we concluded that it cannot explain the association between estrogen use and breast cancer incidence. As of 1988, among women in the Nurses' Health Study who reported having a mammogram, two thirds indicated that they had had more than one previous mammogram, suggesting that the population is approaching the steady state in which mammography increases lead time but not the total number of cases of breast cancer that are diagnosed. In the Health Insurance Plan on New York, 1 after 5 years, the excess incidence
The Influence of Hypertonic Saline Infusions Upon the Fractional Reabsorption of Urate and Other Ions in Normal and Hypertensive Man
Authors: PAUL J. CANNON, DAVID S. SVAHN, FELIX E. DEMARTINI
Journal: Circulation (1970)

Renal hemodynamics and the excretion rates of six ions were studied in a group of 24 normotensive and hypertensive subjects during expansion of extracellular fluid volume (ECF) with intravenous infusions of hypertonic saline. In response to the 2.5% saline infusions arterial blood pressure did not change from control values, but glomerular filtration rate increased, and renal vascular resistance decreased. Accompanying these hemodynamic alterations the urinary excretion rates of sodium, calcium, magnesium, potassium, chloride, and urate increased significantly. Net fractional reabsorption of the six ions fell significantly below control values. The induced changes in net Ca, Mg, K, Cl, and urate reabsorption in all the subjects were directly and significantly related to the simultaneous depression of Na reabsorption. The data indicate that increased excretion and net tubular rejection of urate accompany depression of tubular sodium reabsorption during hypertonic saline infusions in normal and hypertensive man. The nonspecificity of depressed fractional ion reabsorption during the infusions is compatible with the hypothesis that physical forces which alter fluid uptake by peritubular capillaries determine to a significant extent the natriuretic response of the human nephron to hypertonic saline infusions. Alternatively, if a natriuretic hormone elicited by ECF volume expansion in man accounts for the depressed fractional Na reabsorption, the data imply that directly or indirectly this substance inhibits net fractional reabsorption of a variety of other ions.
Stepwise Screening of Atrial Fibrillation in a 75-Year-Old Population
Authors: Johan Engdahl, Lisbeth Andersson, Maria Mirskaya, Mårten Rosenqvist
Journal: Circulation (2013)

Background— Atrial fibrillation (AF) is a frequent source of cardiac emboli in patients with ischemic stroke. AF may be asymptomatic and therefore undiagnosed. Screening for silent AF seems suitable in risk populations, however little is known on the yield and cost-effectiveness of such screening. Methods and Results— All inhabitants in the municipality of Halmstad, Sweden aged 75 to 76 years were invited to a stepwise screening program for AF. As a first step, participants recorded a 12-lead ECG and reported their relevant medical history. Those with sinus rhythm on 12-lead ECG, no history of AF, and ≥2 risk factors according to CHADS 2 were invited to a 2-week recording period using a hand-held ECG and asked to record 20 or 30 seconds twice daily and if palpitations occurred. One thousand, three hundred thirty inhabitants were invited, of whom 848 (64%) participated. Previously undiagnosed silent AF was found in 10 (1%) among 848 individuals who recorded 12-lead ECG. Among 81 patients with known AF, 35 (43%) were not on oral anticoagulation treatment. Among 403 persons with ≥2 risk factors for stroke, who completed the hand-held ECG event recording, 30 (7.4%) were diagnosed with paroxysmal AF. Thus 75/848 (9%) of the screened population were candidates for new oral anticoagulation treatment, of those 57 actually started oral anticoagulation treatment. Conclusions— Stepwise risk factor–stratified AF screening in a 75-year-old population yields a large share of candidates for oral anticoagulation treatment on AF indication.
Protection afforded by cycle helmets
Authors: F McDermott, J Lane
Journal: BMJ (1994)

EDITOR, - The foreword to British Standard 6863, amended 1991, for cyclists' helmets reads in part: “The requirements of this Standard are intended for helmets that give protection in the kind of accident in which the rider falls onto the ground without other vehicles being involved.”1 This implies that helmets are of little value when the cyclist collides with a motor vehicle. This view has …
Pregnancy Hormone Levels Signal Trisomy 21, Improved Screening, Lower Costs Possible
Authors: Teri Randall
Journal: JAMA (1991)

ADVANCES in biochemistry are helping scientists identify pregnant women who are at high risk for carrying a fetus with Down's syndrome. Scientists now recognize three substances in the mother's serum—human chorionic gonadotropin, unconjugated estriol, and α-fetoprotein (AFP)—the concentrations of which, when coupled with the woman's age-associated risk, allow a more accurate calculation of the likelihood that she is carrying an affected fetus. The prenatal blood test, administered during the second trimester and followed by amniocentesis and chromosome analysis on those mothers who are at risk, detects about 67% of all affected fetuses in the general pregnant population—a twofold to threefold improvement from the standard screening method that employs only AFP serum levels and age-associated risk. <h3>Identifying Younger Patients</h3> The new method helps to identify younger patients who are at high risk and should have amniocentesis performed but may not be offered the procedure under standard screening methods. It can also
Genomic Instability in Mice Is Greater in Fanconi Anemia Caused by Deficiency of <i>Fancd2</i> than <i>Fancg</i>
Authors: Ramune Reliene, Mitsuko L. Yamamoto, P. Nagesh Rao, Robert H. Schiestl
Journal: Cancer Research (2010)

Abstract Fanconi anemia (FA) results from mutations in the FANC genes and is characterized by bone marrow failure, birth defects, and a high incidence of cancer. FANCG is a part of the FA core complex that is responsible for monoubiquitination of FANCD2 and FANCI. The precise role of the FA pathway is not well understood, although it may be involved in homologous recombination (HR), nonhomologous end joining, and translesion synthesis (TLS). Fancd2−/– mice have a more severe phenotype than Fancg−/–, and other FA core complex–deficient mice, although both Fancg and Fancd2 belong to the same FA pathway. We hypothesized that Fancd2 deficiency results in a more severe phenotype because Fancd2 also has a FA pathway-independent function in the maintenance of genomic integrity. To test this hypothesis, we determined the level of DNA damage and genomic instability in Fancd2−/−, Fancg−/–, and wild-type controls. Fancd2−/− mice displayed a higher magnitude of chromosomal breakage and micronucleus formation than the wild-type or Fancg−/− mice. Also, DNA strand breaks were increased in Fancd2−/− but not in Fancg−/− mice. In addition, Fancd2−/– mice displayed an elevated frequency of DNA deletions, resulting from HR at the endogenous pun locus. In contrast, in Fancg−/– mice, the frequency of DNA deletions was decreased. Thus, Fancd2 but not Fancg deficiency results in elevated chromosomal/DNA breakage and permanent genome rearrangements. This provides evidence that Fancd2 plays an additional role in the maintenance of genomic stability than Fancg, which might explain the higher predisposition to cancer seen in the Fancd2−/− mice. Cancer Res; 70(23); 9703–10. ©2010 AACR.
Determinants of cord‐blood IgE concentrations in 6401 German neonates
Authors: R. L Bergmann, J. Schulz, S. Günther, J. W. Dudenhausen, K. E. Bergmann, C. P. Bauer, W. Dorsch, E. Schmidt, W. Luck, S. Lau, Th. Graß, U. Wahn
Journal: Allergy (1995)

For screening atopy risk in 6401 (84%) of all infants born during the year 1990 in six obstetric departments of five German cities, cord-blood IgE values were determined with CAP-RAST-FEIA. After cases with elevated IgA values had been excluded, 25% of the values were above the detection limit of 0.35 kU/l, and 8.5% were above 0.9 kU/l. Boys had significantly higher values than girls (P < 0.001). The distribution of values was significantly different for different nationalities of mothers (P < 0.001). The percentage of elevated values (> 0.9 kU/l) increased significantly with the number of close family members with atopic history (P < 0.001). Regarding the atopic history of the father, siblings, and mother separately, only the mother's history had a significant association with the cord-blood IgE class (P < 0.001). The IgE values of 81 twin pairs correlated significantly with a coefficient of r = 0.4909 (P < 0.001). The smoking history of the parents during pregnancy showed an association with cord-blood IgE values (P < 0.02). No significant association could be shown between cord-blood IgE distribution and other variables, i.e., gestational age, birth size, birth modus, Apgar score, cord-blood pH value, neonatal problems, parity, age of the mother, medication during pregnancy, educational level of mother or father, time of year, or obstetric department. It is hypothesized that, in addition to some postpartum contamination or placental transfer of maternal IgE, cord-blood IgE values are also determined by the fetal immunologic reaction to intrauterine exposure to allergens and trigger factors, and by genetic influences.
Tips on… Improving one to one interactions
Authors: Kallur Suresh
Journal: BMJ (2002)

One to one skills are important in many of our day to day interactions--both professional and personal. These may be in the context of an appraisal, supervision, therapy, dissemination of information, giving feedback, or simply talking to another person. Improving our one to one skills can appreciably improve the quality of the interaction.

Think of what areas you will cover …
AN APPROACH TO THE PROBLEM OF HOMOSEXUALITY IN THE MILITARY SERVICE
Authors: LOUIS JOLYON WEST, WILLIAM T. DOIDGE, ROBERT L. WILLIAMS
Journal: American Journal of Psychiatry (1958)

The problem of homosexuality in the Armed Forces is briefly discussed. A critique of the present approach to the problem is offered. In the light of observations made in a controlled clinical study, and a review of four years' experience with 458 cases, a number of suggestions are offered for a new approach. These include: 1. Modification of punitive official attitudes; 2. Elimination of routine extensive investigations; 3. Establishment of the primary disorder as the basis for discharge; 4. Elimination of the special stigma; 5. Utilization of benign investigation procedures; and 6. Fulfillment of present potentially liberal retention policies.
Haploidentical hematopoietic stem cell transplantation can lead to viral clearance in severe combined immunodeficiency
Authors: Mary Slatter, Zohreh Nademi, Sanjay Patel, Dawn Barge, Manoj Valappil, Ken Brigham, Sophie Hambleton, Julia Clark, Terence Flood, Andrew Cant, Mario Abinun, Andrew Gennery
Journal: Journal of Allergy and Clinical Immunology (2013)
Tool innovation may be a critical limiting step for the establishment of a rich tool-using culture: A perspective from child development
Authors: Sarah R. Beck, Jackie Chappell, Ian A. Apperly, Nicola Cutting
Journal: Behavioral and Brain Sciences (2012)

Abstract Recent data show that human children (up to 8 years old) perform poorly when required to innovate tools. Our tool-rich culture may be more reliant on social learning and more limited by domain-general constraints such as ill-structured problem solving than otherwise thought.
Recovery-phase patterns of ST segment depression in the heart rate domain. Identification of coronary artery disease by the rate-recovery loop.
Authors: P M Okin, O Ameisen, P Kligfield
Journal: Circulation (1989)

Although the time course of ST segment depression after exercise has been related to the presence and severity of coronary artery disease, recovery-phase patterns of ST segment depression with reference to changing heart rate have not been quantified. We have found distinct recovery loop patterns of ST segment depression that distinguish subjects without coronary disease from patients with coronary artery disease when ST segment depression is examined in the heart rate domain. Continuous plots of ST segment depression and heart rate were constructed throughout treadmill exercise and recovery in 100 clinically normal subjects, in 124 patients with coronary artery disease proven by catheterization, and in 17 patients with no significant coronary disease at catheterization. Among clinically normal subjects, 95% (95 of 100) had normal (clockwise) rate-recovery loops, and 5% (five of 100) had abnormal (counterclockwise) rate-recovery loops. In these normal subjects, the resulting 95% specificity of a normal rate-recovery loop was similar to the 93% (93 of 100) specificity of standard end-exercise ST segment depression criteria. Among patients with coronary disease proven by angiography, 93% (115 of 124) had abnormal (counterclockwise) rate-recovery loops, and 7% (nine of 124) had normal rate-recovery loops. In contrast was the significantly lower 74% (92 of 124) sensitivity of standard ST segment criteria (p less than 0.001 vs. the rate-recovery loop). Specificity of a normal rate-recovery loop (71%, 12 of 17) and standard ST segment depression criteria (71%, 12 of 17) were similar in the patients with normal coronary arteries at angiography.(ABSTRACT TRUNCATED AT 250 WORDS)
1281 Matrix compliance determines hepatic stellate cell phenotype
Authors: M GACA, P GEORGES, P JANMEY, R WELLS
Journal: Hepatology (2003)

The mechanisms linking hepatocellular death, hepatic stellate cell (HSC) activation, and liver fibrosis are largely unknown. Here, we investigate whether acidic sphingomyelinase (ASMase), a known regulator of death receptor and stress-induced hepatocyte apoptosis, plays a role in liver fibrogenesis. We show that selective stimulation of ASMase (up to sixfold), but not neutral sphingomyelinase, occurs during the transdifferentiation/activation of primary mouse HSCs into myofibroblast-like cells, coinciding with cathepsin B (CtsB) and D (CtsD) processing. ASMase inhibition or genetic down-regulation by small interfering RNA blunted CtsB/D processing, preventing the activation and proliferation of mouse and human HSCs (LX2 cells). In accordance, HSCs from heterozygous ASMase mice exhibited decreased CtsB/D processing, as well as lower levels of α-smooth muscle actin expression and proliferation. Moreover, pharmacological CtsB inhibition reproduced the antagonism of ASMase in preventing the fibrogenic properties of HSCs, without affecting ASMase activity. Interestingly, liver fibrosis induced by bile duct ligation or carbon tetrachloride administration was reduced in heterozygous ASMase mice compared with that in wild-type animals, regardless of their sensitivity to liver injury in either model. To provide further evidence for the ASMase-CtsB pathway in hepatic fibrosis, liver samples from patients with nonalcoholic steatohepatitis were studied. CtsB and ASMase mRNA levels increased eight- and threefold, respectively, in patients compared with healthy controls. These findings illustrate a novel role of ASMase in HSC biology and liver fibrogenesis by regulating its downstream effectors CtsB/D.
Efficacy and safety of subcutaneous allergen-specific immunotherapy with depigmented polymerized mite extract in atopic dermatitis
Authors: Natalija Novak, Thomas Bieber, Matthias Hoffmann, Regina Fölster-Holst, Bernhard Homey, Thomas Werfel, Angelika Sager, Torsten Zuberbier
Journal: Journal of Allergy and Clinical Immunology (2012)
CANCER OF THE THROAT
Authors: Robt. Hy. S. Spicer
Journal: BMJ (1910)

t B 1821 of the more civilized races who shelter themselves from rain and cold.Damp, according to my belief, is what we have especially to guard against.For the treatment of phthisis the warm, damp climates, such as Torquay, Hastings, Mentone, etc., have almost entirely passed out of favour, and I do not think any one would recommend for this disease a cold, damp one.The places now con- sidered most favourably are the cold and dry, such as Davos, Wiesen, etc. Warm, damp climates tend to increase rather than lessen germ life.It is wonderful how in the treatment of whooping-cough protection from cola, north-east winter winds and damp saves children from bronchitis and pneumonia.By changing them from room to room, having the windows open as soon as they leave, then closed, and the room thoroughly warmed before they return, there is no difficulty about the matter of fresh air.In my opinion the present routine mgthod of suggesting fresh air under, all conditions will be very materially modified in the near fature.It is now admitted that the open-air treatment will not do everything in cases of phthisis.-Iam, etc.,
Perfusion and ventilation of isolated canine lungs
Authors: T. J. Otto, M. Trenkner, A. Stopczyk, M. Gawdzinski, B. Chelstowska
Journal: Thorax (1968)

In order to evaluate methods of preserving lungs for use in transplantation, experiments on 28 mongrel dogs were carried out. Two methods were tried—first, mechanical respiration of isolated lungs under deep hypothermia, with the vascular bed filled with blood; and, secondly, the perfusion of isolated lungs with the aid of a modified DeWall9s apparatus. Allogenic transplantations of lungs preserved in both ways were carried out. Gasometric and histological examinations of preserved lungs, before and after transplantation, were performed. The best results were obtained with perfusion under hypothermic conditions; ventilation without perfusion resulted in failure. Lung transplantation was successful when, after being preserved, the lung remained unchanged. Major discrepancies between the macroscopic and microscopic findings in preserved lungs were observed. An original classification of the changes occurring in preserved lungs is proposed.
A Novel Approach to Antigen-Specific Deletion of CTL with Minimal Cellular Activation Using α3 Domain Mutants of MHC Class I/Peptide Complex
Authors: Xiao-Ning Xu, Marco A Purbhoo, Nan Chen, Juthathip Mongkolsapaya, Jennifer H Cox, Ute-Christiane Meier, Sabrina Tafuro, P.Rod Dunbar, Andy K Sewell, Christopher S Hourigan, Victor Appay, Vincenzo Cerundolo, Scott R Burrows, Andrew J McMichael, Gavin R Screaton
Journal: Immunity (2001)
The Scientific Basis of Drug Therapy in Psychiatry
Authors: P. Dally
Journal: BMJ (1965)

MEDICJOUH 1481 suffering, and premature death.However, the great need in medical education and medical care to-day is for deeds, not words, for experiment and not disputation, and it is greatly to be hoped that Professor McKeown will be able to bring to rapid completion the plans prepared by himself and his colleagues for a balanced teaching hospital in Birmingham.
The effect of anti-IgE treatment on in vitro leukotriene release in children with seasonal allergic rhinitis
Authors: Matthias Volkmar Kopp, Jens Brauburger, Frank Riedinger, Dorothee Beischer a, Gabriele Ihorst, Wolfgang Kamin, Stefan Zielen, Christina Bez, Frank Friedrichs, Andrea von Berg, Kerstin Gerhold, Eckard Hamelmann, Thomas Hultsch, Joachim Kuehr
Journal: Journal of Allergy and Clinical Immunology (2002)
Exophytic combined hepatocellular carcinoma and cholangiocarcinoma
Authors: Sang Jae Noh, Hyun Kyung Lee, Hee Chul Yu, Woo Sung Moon
Journal: Clinical and Molecular Hepatology (2012)

Copyright © 2012 by The Korean Association for the Study of the LiverThis is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
148 LIVER TRANSPLANTATION IN CIRRHOTIC PATIENTS WITH MELD SCORE 18: A NEW PROGNOSTIC MODEL TO PREDICT DROP-OUT FROM THE WAITING LIST
Authors: M. Dall'Agata, M. Biselli, A. Gramenzi, S. Gitto, C. Liberati, M. Ravaioli, M. Gambato, R. Montalti, P. Burra, U. Cillo, G.E. Gerunda, A.D. Pinna, P. Andreone, M. Bernardi
Journal: Journal of Hepatology (2013)