tbuckley/cabot-search huggingface dataset:
Learning to cooperate: Reciprocity and self-control
Authors: Peter Danielson
Journal: Behavioral and Brain Sciences (2002)

Using a simple learning agent, we show that learning self-control in the primrose path experiment does parallel learning cooperation in the prisoner's dilemma. But Rachlin's claim that “there is no essential difference between self-control and altruism” is too strong. Only iterated prisoner's dilemmas played against reciprocators are reduced to self-control problems. There is more to cooperation than self-control and even altruism in a strong sense.
Calcium accumulation and enzymatic activities of subcellular fractions from aortas and ventricles of genetically hypertensive rats.
Authors: J W Wei, R A Janis, E E Daniel
Journal: Circulation Research (1976)

Subcellular fractions were obtained from aortas and ventricles of 6-month-old spontaneously hypertensive and normotensive Wistar rats by the use of differential and sucrose density gradient centrifugation. These preparations were studied to determine what alterations in calcium accumulation and enzymatic activities might be associated with hypertension. The total amount of calcium accumulation (in the presence of ATP and 17 muM free calcium) by the plasma membrane-enriched fraction from hypertensive rat aortas significantly less than that from normotensive rats (11.3 +/- 0.4 vs 16.2 +/- 1.6 mumol of calcium/g of protein, n = 8). In contrast the specific activities of the plasma membrane marker enzymes, 5'-nucleotidase and phosphodiesterase I, were 80% and 40% greater, respectively, in the hypertensive than in the normotensive fractions. On the other hand, various fractions from ventricles of the two types of rats were generally similar in enzyme activities and calcium accumulation. The decreased rate of relaxation of aortas from spontaneously hypertensive rats may be caused by the decreased rate of calcium transport demonstrated in this study.
A Small Molecule Polyamine Oxidase Inhibitor Blocks Androgen-Induced Oxidative Stress and Delays Prostate Cancer Progression in the Transgenic Adenocarcinoma of the Mouse Prostate Model
Authors: Hirak S. Basu, Todd A. Thompson, Dawn R. Church, Cynthia C. Clower, Farideh Mehraein-Ghomi, Corey A. Amlong, Christopher T. Martin, Patrick M. Woster, Mary J. Lindstrom, George Wilding
Journal: Cancer Research (2009)

Abstract High levels of reactive oxygen species (ROS) present in human prostate epithelia are an important etiologic factor in prostate cancer (CaP) occurrence, recurrence, and progression. Androgen induces ROS production in the prostate by a yet unknown mechanism. Here, to the best of our knowledge, we report for the first time that androgen induces an overexpression of spermidine/spermine N1-acetyltransferase, the rate-limiting enzyme in the polyamine oxidation pathway. As prostatic epithelia produce a large excess of polyamines, the androgen-induced polyamine oxidation that produces H2O2 could be a major reason for the high ROS levels in the prostate epithelia. A small molecule polyamine oxidase inhibitor N,N'-butanedienyl butanediamine (MDL 72,527 or CPC-200) effectively blocks androgen-induced ROS production in human CaP cells, as well as significantly delays CaP progression and death in animals developing spontaneous CaP. These data show that polyamine oxidation is not only a major pathway for ROS production in prostate, but inhibiting this pathway also successfully delays CaP progression. [Cancer Res 2009;69(19):7689–95]
Host-derived oxidized phospholipids and HDL regulate innate immunity in human leprosy
Authors: Daniel Cruz, Andrew D. Watson, Christopher S. Miller, Dennis Montoya, Maria-Teresa Ochoa, Peter A. Sieling, Miguel A. Gutierrez, Mohamad Navab, Srinivasa T. Reddy, Joseph L. Witztum, Alan M. Fogelman, Thomas H. Rea, David Eisenberg, Judith Berliner, Robert L. Modlin
Journal: Journal of Clinical Investigation (2008)

Intracellular pathogens survive by evading the host immune system and accessing host metabolic pathways to obtain nutrients for their growth. Mycobacterium leprae, the causative agent of leprosy, is thought to be the mycobacterium most dependent on host metabolic pathways, including host-derived lipids. Although fatty acids and phospholipids accumulate in the lesions of individuals with the lepromatous (also known as disseminated) form of human leprosy (L-lep), the origin and significance of these lipids remains unclear. Here we show that in human L-lep lesions, there was preferential expression of host lipid metabolism genes, including a group of phospholipases, and that these genes were virtually absent from the mycobacterial genome. Host-derived oxidized phospholipids were detected in macrophages within L-lep lesions, and 1 specific oxidized phospholipid, 1-palmitoyl-2-(5,6-epoxyisoprostane E2)-sn-glycero-3-phosphorylcholine (PEIPC), accumulated in macrophages infected with live mycobacteria. Mycobacterial infection and host-derived oxidized phospholipids both inhibited innate immune responses, and this inhibition was reversed by the addition of normal HDL, a scavenger of oxidized phospholipids, but not by HDL from patients with L-lep. The accumulation of host-derived oxidized phospholipids in L-lep lesions is strikingly similar to observations in atherosclerosis, which suggests that the link between host lipid metabolism and innate immunity contributes to the pathogenesis of both microbial infection and metabolic disease.
An Address ON SOME APPLICATIONS OF EXPERIENCE GAINED BY THE WAR TO THE PROBLEMS OF CIVIL MEDICAL PRACTICE: Read before the South Midland Branch of the British Medical Association
Authors: W. H. White
Journal: BMJ (1919)

WHILE much of our war experience will, we lhope, not be of civil use, in some medical diseases it will be of great value.May we this afterneon consideL the cllief of those which have come, under my own observation ?THE HEART.Tlle war hals not iiicreased our knowledge of organic valvular disease of the heart, but happily, thlanks to T. Lewis and hiis co.workers, it has-been more widely diffused.A large exaperience of Recruiting and Invaliding Boards has slhown me-thlat there has existed a considerable divergento of opinion as to the fitness of the heart for muscular work.Occasionally there was a failure to remember what has often been taight at the bedside for many years- namely, that what really matters is not so mudbh the noise we hear ou'auscultation, but wlhether the heart is doing its work efficiently.Often tllh louder a murmur is, the bette-rf or a loud murmur may mean that the cardiac muscle is-strong.A mandoing his work as a dock labourer lhad a valvular murmur which could be heard-with tlho naked ear ole yard from th'e fiOot of hiis bed; another man with a valrular -miurmur won a walking race from London to Brighton.Apart from instances of persons w'ith valvular disease who can do full muscalar work, there are numerous patients wlho get on very well and lead useful lives if tlleir work is -adjusted-to that whiclh tle heart can perform without further damaging itself.The doctor is of tlle greatest use, for he can prevent the patients with valvular disease from doina too little or too mueb; he can help them to find out the limit of.their power and see that they always keep just below it.Sometimes it was not recognized that a sytoIidi murmur is by itself often no evidence of valvulak disefise -for example, there are haemic murmurs-, mrnuls_ at the impulse which disappear when the patient lies'down or takes a deep bth, and p6blky Gtl8d varieties of functional murmurs.I have hfard sever lThousands of recruiting appeals.Many of the'appellants were in a low qade because, owing to a murmur, tlle hleart was con- sidered a bar to a hiigher category when really it Vas per- fectly healthy, and thie category, might have been higher, altbouglh tlle appellant, believing he had 'heart disease, wished to be rejected altogether.In many departments of medicine and surgery the carly recruiting boards varied so greatly in their standards that the Ministry of National Service issued "Geileral Directions for the Guidance of Medical Recruitinig Boards."Those of us wlho drew up the medical part of these had many helpers, and, with the aid of Dr. T. LOekis, it 'was -laid down that if the man's occupation did not prove his.capability, for -physical -exer- tion, and there was doub'about this, the board.should see how he responds to exertion, and the following test was reommended:1.The man's-pulse is taken while he stands at rest.
Transurethral surgery and twice-daily radiation plus paclitaxel-cisplatin or fluorouracil-cisplatin with selective bladder preservation and adjuvant chemotherapy for patients with muscle invasive bladder cancer (RTOG 0233): a randomised multicentre phase 2 trial
Authors: Timur Mitin, Daniel Hunt, William U Shipley, Donald S Kaufman, Robert Uzzo, Chin-Lee Wu, Mark K Buyyounouski, Howard Sandler, Anthony L Zietman
Journal: The Lancet Oncology (2013)
Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the β–amyloid precursor protein gene
Authors: Lydia Hendriks, Cornelia M. van Duijn, Patrick Cras, Marc Cruts, Wim Van Hul, Frans van Harskamp, Andrew Warren, Melvin G. McInnis, Stylianos E. Antonarakis, Jean-Jacques Martin, Albert Hofman, Christine Van Broeckhoven
Journal: Nature Genetics (1992)
Searching for Blood DNA Methylation Markers of Breast Cancer Risk and Early Detection
Authors: M. Garcia-Closas, M. H. Gail, K. T. Kelsey, R. G. Ziegler
Journal: JNCI Journal of the National Cancer Institute (2013)

In this issue of the Journal, Xu et al. (1) used prospectively collected blood samples to determine whether epigenome-wide methylation profiles in blood DNA differ between women who subsequently develop breast cancer and those who do not. Potentially, such a profile could predict the risk of developing breast cancer or detect this disease days to several years before it appears clinically. Existing breast cancer risk prediction models have limited discriminatory accuracy for this common disease (2), and improved methods for early detection are also needed (3,4). In this context, the findings of Xu et al. are promising and exemplify the potential value of epigenome-wide association studies (5,6). However, several important considerations temper the initial enthusiasm and highlight challenges for future studies.
Extracorporeal Tissue Engineered Liver-Assist Devices
Authors: Emmanouhl S. Tzanakakis, Donavon J. Hess, Timothy D. Sielaff, Wei-Shou Hu
Journal: Annual Review of Biomedical Engineering (2000)

▪ Abstract The treatment of acute liver failure has evolved to the current concept of hybrid bioartificial liver (BAL) support, because wholly artificial systems have not proved efficacious. BAL devices are still in their infancy. The properties that these devices must possess are unclear because of our lack of understanding of the pathophysiology of liver failure. The considerations that attend the development of BAL devices are herein reviewed. These considerations include choice of cellular component, choice of membrane component, and choice of BAL system configuration. Mass transfer efficiency plays a role in the design of BAL devices, but the complexity of the systems renders detailed mass transfer analysis difficult. BAL devices based on hollow-fiber bioreactors currently show the most promise, and available results are reviewed herein. BAL treatment is designed to support patients with acute liver failure until an organ becomes available for transplantation. The results obtained to date, in this relatively young field, point to a bright future. The risks of using xenogeneic treatments have yet to be defined. Finally, the experience gained from the past and current BAL systems can be used as a basis for improvement of future BAL technology.
Minimally Invasive Diagnosis of Acquired Immunodeficiency Syndrome-Related Primary Central Nervous System Lymphoma
Authors: Antonella Cingolani, Andrea De Luca, Adriana Ammassari, Andrea Antinori, Luigi Ortona, Luigi M. Larocca, Massimo Scerrati
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: The detection of Epstein-Barr virus (EBV)-DNA in cerebrospinal fluid (CSF) by means of the polymerase chain reaction (PCR) has been revealed, in retrospective studies, to be a good marker of primary central nervous system lymphoma (PCNSL) related to acquired immunodeficiency syndrome (AIDS); however, the technique's usefulness in the management of AIDS patients with focal brain lesions is still unknown. We studied the clinical usefulness of testing CSF obtained by lumbar puncture for the presence of EBV-DNA as a minimally invasive approach to the diagnosis of AIDS-PCNSL in patients with focal brain lesions. Methods: Human immunodeficiency virus (HIV)-infected patients with focal brain lesions, observed prospectively during a 30-month period, underwent lumbar puncture if not contraindicated; otherwise, ventricular CSF was obtained at brain biopsy. The presence of EBV-DNA was determined by means of PCR. Results: We evaluated 122 patients: 42 diagnosed with brain lymphoma and the remaining 80 diagnosed with other brain disorders. Cerebrospinal fluid was collected from 101 patients—by lumbar puncture in 95, including 40 patients with AIDS-PCNSL. The sensitivity and specificity of PCR for EBV-DNA detection in lumbar CSF were 80% (95% confidence interval [CI] = 60.9%–91.6%) and 100% (95% CI = 92.6%–100%), respectively. Lumbar puncture and subsequent assessment of EBV-DNA would have allowed a correct diagnosis in 63.2% (95% CI = 46.0%– 77.7%) of patients with AIDS-PCNSL and excluded this diagnosis in 76.3% (95% CI = 65.2%–84.8%) of patients without lymphoma (because EBV-DNA was not detected). Conclusions: The presence of EBV-DNA in lumbar CSF is a sensitive and highly specific diagnostic marker of AIDS-PCNSL, and EBV-DNA detection in this fluid may allow a minimally invasive diagnosis in a large percentage of patients with brain lymphomas.
Critical Update and Emerging Trends in Epidermal Growth Factor Receptor Targeting in Cancer
Authors: José Baselga, Carlos L. Arteaga
Journal: Journal of Clinical Oncology (2005)

The epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase of the ErbB receptor family that is abnormally activated in many epithelial tumors. The aberrant activation of the EGFR leads to enhanced proliferation and other tumor-promoting activities, which provide a strong rationale to target this receptor family. There are two classes of anti-EGFR agents: monoclonal antibodies (MAbs) directed at the extracellular domain of the receptor and small molecule, adenosine triphosphate–competitive inhibitors of the receptor's tyrosine kinase. Anti-EGFR MAbs have shown antitumor activity in advanced colorectal carcinoma, squamous cell carcinomas of the head and neck, non–small-cell lung cancer (NSCLC) and renal cell carcinomas. The tyrosine kinase inhibitors (TKIs) have a partially different activity profile. They are active against NSCLC, and a specific EGFR inhibitor has shown improvement in survival. Recently, mutations and amplifications of the EGFR gene have been identified in NSCLC and predict for enhanced sensitivity to anti-EGFR TKIs. In addition to specific anti-EGFR TKIs, there are broader acting inhibitors such as dual EGFR HER-2 inhibitors and combined anti-pan-ErbB and antivascular endothelial growth factor receptor inhibitors. Current research efforts are directed at selecting the optimal dose and schedule and identifying predictive factors of response and resistance beyond EGFR gene mutations and/or amplifications. Finally, there is a need for improved strategies to integrate anti-EGFR agents with conventional therapies and to explore combinations with other molecular targeted approaches including other antireceptor therapies, receptor-downstream signaling transduction inhibitors, and targeted approaches interfering with other essential drivers of cancer, such as angiogenesis.
Polymorphisms in DNA repair genes modulate survival in cisplatin/gemcitabine-treated non-small-cell lung cancer patients
Authors: R. de las Peñas, M. Sanchez-Ronco, V. Alberola, M. Taron, C. Camps, R. Garcia-Carbonero, B. Massuti, C. Queralt, M. Botia, R. Garcia-Gomez, D. Isla, M. Cobo, M. Santarpia, F. Cecere, P. Mendez, J.J. Sanchez, R. Rosell
Journal: Annals of Oncology (2006)
Fibreoptic bronchoscopy: effect of multiple bronchial biopsies on diagnostic yield in bronchial carcinoma.
Authors: A R Gellert, R M Rudd, G Sinha, D M Geddes
Journal: Thorax (1982)

The findings in bronchial biopsy specimens obtained at fibreoptic bronchoscopy in 271 patients with bronchial carcinoma were reviewed. Fifty-nine per cent of 703 specimens taken from the site of bronchoscopically visible tumours in 215 patients provided evidence of carcinoma. Unequivocal histological evidence of carcinoma was obtained in 78.6% of the 215 patients with visible tumours. When only one biopsy specimen was taken evidence of carcinoma was obtained in 65.2% of cases. At least five biopsy specimens were required to provide a greater than 90% probability of obtaining at least one positive sample. The anatomical site of the tumour had no significant effect on the proportion of biopsy specimens that were positive or the frequency of obtaining at least one positive sample. When extrinsic bronchial compression was the only visible abnormality evidence of carcinoma was obtained by bronchial biopsy in 26.8% of 56 cases.
Insect Cryptochromes: Gene Duplication and Loss Define Diverse Ways to Construct Insect Circadian Clocks
Authors: Q. Yuan, D. Metterville, A. D. Briscoe, S. M. Reppert
Journal: Molecular Biology and Evolution (2007)

Cryptochrome (CRY) proteins are components of the central circadian clockwork of metazoans. Phylogenetic analyses show at least 2 rounds of gene duplication at the base of the metazoan radiation, as well as several losses, gave rise to 2 cryptochrome (cry) gene families in insects, a Drosophila-like cry1 gene family and a vertebrate-like cry2 family. Previous studies have shown that insect CRY1 is photosensitive, whereas photo-insensitive CRY2 functions to potently inhibit clock-relevant CLOCK:CYCLE-mediated transcription. Here, we extended the transcriptional repressive function of insect CRY2 to 2 orders—Hymenoptera (the honeybee Apis mellifera and the bumblebee Bombus impatiens) and Coleoptera (the red flour beetle Tribolium castaneum). Importantly, the bee and beetle CRY2 proteins are not light sensitive in culture, in either degradation of protein levels or inhibitory transcriptional response, suggesting novel light input pathways into their circadian clocks as Apis and Tribolium do not have CRY1. By mapping the functional data onto a cryptochrome/6-4 photolyase gene tree, we find that the transcriptional repressive function of insect CRY2 descended from a light-sensitive photolyase-like ancestral gene, probably lacking the ability to repress CLOCK:CYCLE-mediated transcription. These data provide an evolutionary context for proposing novel circadian clock mechanisms in insects.
Insulin allergy: clinical manifestations and management strategies
Authors: L. Heinzerling, K. Raile, H. Rochlitz, T. Zuberbier, M. Worm
Journal: Allergy (2008)

Insulin allergy in patients with diabetes mellitus on insulin treatment is a rare condition. It is suspected upon noticing immediate symptoms following insulin injections. The immediate vital implications for the patient call for prompt diagnosis and management of insulin allergy. We review current knowledge and procedures based on four diabetic patients who presented in our clinic. Insulin allergy was suspected as they showed immediate symptoms after insulin injection (urticaria, rash, angioedema, hypotension, dyspnea). A detailed allergologic work‐up was performed and adequate therapy was initiated. In three of the four patients, a specific immunotherapy was started whereas in one patient a switch to oral antidiabetics was possible and consequently initiated. By standard prick testing and measurement of specific IgE antibodies, a type 1 IgE‐mediated allergy was confirmed. After initiation of insulin immunotherapy, the symptoms completely resolved in two out three of patients and significantly improved in the third patient. The fourth patient was successfully switched to oral antidiabetics. Insulin allergy is a rare but severe condition that calls for immediate allergological work‐up. It can be managed well in close cooperation between the diabetologist and the allergologist. Specific immunotherapy is efficient and should be considered.
Serrated adenoma in familial adenomatous polyposis: relation to germline APC gene mutation
Authors: T Matsumoto
Journal: Gut (2002)

Background: Serrated adenoma is a precursor of colorectal cancer. Aim: To clarify possible genotype-phenotype correlations of serrated adenomas in familial adenomatous polyposis (FAP). Patients: Eleven patients from eight families with FAP. Methods: We performed total colonoscopy with multiple biopsies in patients. Neoplasia with a serrated glandular structure was regarded as a serrated adenoma. In each patient, germline mutations of the APC gene were determined. Colonic phenotype was compared with germline mutations of the APC gene. Results: Serrated adenomas were found in three patients. These patients had macroscopic polyps <100 in number. Pedigrees with serrated adenomas had the truncating germline APC mutation at codon 161, 332, or 1556 while in the other pedigrees mutations were found between codons 554 and 1324. Conclusions: In FAP, serrated adenoma may be a phenotype characteristic of the attenuated form.
Cardiovascular Outcomes With Atrial-Based Pacing Compared With Ventricular Pacing
Authors: Jeffrey S. Healey, William D. Toff, Gervasio A. Lamas, Henning R. Andersen, Kevin E. Thorpe, Kenneth A. Ellenbogen, Kerry L. Lee, Allan M. Skene, Eleanor B. Schron, J. Douglas Skehan, Lee Goldman, Robin S. Roberts, A. John Camm, Salim Yusuf, Stuart J. Connolly
Journal: Circulation (2006)

Background— Several randomized trials have compared atrial-based (dual-chamber or atrial) pacing with ventricular pacing in patients with bradycardia. No trial has shown a mortality reduction, and only 1 small trial suggested a reduction in stroke. The goal of this review was to determine whether atrial-based pacing prevents major cardiovascular events. Methods and Results— A systematic review was performed of publications since 1980. For inclusion, trials had to compare an atrial-based with a ventricular-based pacing mode; use a randomized, controlled, parallel design; and have data on mortality, stroke, heart failure, or atrial fibrillation. Individual patient data were obtained from 5 of the 8 identified studies, representing 95% of patients in the 8 trials, and a total of 35 000 patient-years of follow-up. There was no significant heterogeneity among the results of the individual trials. There was no significant reduction in mortality (hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.87 to 1.03; P =0.19) or heart failure (HR, 0.89; 95% CI, 0.77 to 1.03; P =0.15) with atrial-based pacing. There was a significant reduction in atrial fibrillation (HR, 0.80; 95% CI, 0.72 to 0.89; P =0.00003) and a reduction in stroke that was of borderline significance (HR, 0.81; 95% CI, 0.67 to 0.99; P =0.035). There was no convincing evidence that any patient subgroup received special benefit from atrial-based pacing. Conclusions— Compared with ventricular pacing, the use of atrial-based pacing does not improve survival or reduce heart failure or cardiovascular death. However, atrial-based pacing reduces the incidence of atrial fibrillation and may modestly reduce stroke.