tbuckley/cabot-search huggingface dataset:
Balancing Punishment and Compassion for Seriously Ill Prisoners
Authors: Brie A. Williams, Rebecca L. Sudore, Robert Greifinger, R. Sean Morrison
Journal: Annals of Internal Medicine (2011)

Compassionate release is a program that allows some eligible, seriously ill prisoners to die outside of prison before sentence completion. It became a matter of federal statute in 1984 and has been adopted by most U.S. prison jurisdictions. Incarceration is justified on 4 principles: retribution, rehabilitation, deterrence, and incapacitation. Compassionate release derives from the theory that changes in health status may affect these principles and thus alter justification for incarceration and sentence completion. The medical profession is intricately involved in this process because eligibility for consideration for compassionate release is generally based on medical evidence. Many policy experts are calling for broader use of compassionate release because of many factors, such as an aging prison population, overcrowding, the increasing deaths in custody, and the soaring medical costs of the criminal justice system. Even so, the medical eligibility criteria of many compassionate-release guidelines—which often assume a definitive prognosis—are clinically flawed, and procedural barriers may further limit their rational application. We propose changes to address these flaws.
RIP1 Activates PI3K-Akt via a Dual Mechanism Involving NF-κB–Mediated Inhibition of the mTOR-S6K-IRS1 Negative Feedback Loop and Down-regulation of PTEN
Authors: Seongmi Park, Dawen Zhao, Kimmo J. Hatanpaa, Bruce E. Mickey, Debabrata Saha, David A. Boothman, Michael D. Story, Eric T. Wong, Sandeep Burma, Maria-Magdalena Georgescu, Vivek M. Rangnekar, Sandili S. Chauncey, Amyn A. Habib
Journal: Cancer Research (2009)

Therapeutic inhibition of mammalian target of rapamycin (mTOR) in cancer is complicated by the existence of a negative feedback loop linking mTOR to the phosphatidylinositol 3-kinase (PI3K)-Akt pathway. Thus, mTOR inhibition by rapamycin or TSC1/2 results in increased PI3K-Akt activation. The death domain kinase receptor interacting protein 1 (RIP1) plays a key role in nuclear factor-kappaB (NF-kappaB) activation and also activates the PI3K-Akt pathway through unknown mechanisms. RIP1 has recently been found to be overexpressed in glioblastoma multiforme, the most common adult primary malignant brain tumor, but not in grade II to III glioma. Our data suggest that RIP1 activates PI3K-Akt using dual mechanisms by removing the two major brakes on PI3K-Akt activity. First, increased expression of RIP1 activates PI3K-Akt by interrupting the mTOR negative feedback loop. However, unlike other signals that regulate mTOR activity without affecting its level, RIP1 negatively regulates mTOR transcription via a NF-kappaB-dependent mechanism. The second mechanism used by RIP1 to activate PI3K-Akt is down-regulation of cellular PTEN levels, which appears to be independent of NF-kappaB activation. The clinical relevance of these findings is highlighted by the demonstration that RIP1 levels correlate with activation of Akt in glioblastoma multiforme. Thus, our study shows that RIP1 regulates key components of the PTEN-PI3K-Akt-mTOR pathway and elucidates a novel negative regulation of mTOR signaling at the transcriptional level by the NF-kappaB pathway. Our data suggest that the RIP1-NF-kappaB status of tumors may influence response to treatments targeting the PTEN-PI3K-mTOR signaling axis.
Response of Established Human Breast Tumors to Vaccination with Mammaglobin-A cDNA
Authors: Kishore Narayanan, Andrés Jaramillo, Nicholas D Benshoff, Lacey G Campbell, Timothy P Fleming, Jill R Dietz, T Mohanakumar
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: A novel breast cancer–associated antigen, mammaglobin-A, is expressed in 80% of primary breast tumors. The characterization of immune responses against this highly expressed breast cancer–specific antigen would be of value in the development of new therapeutic strategies for breast cancer. Methods: We developed an in vivo model using human leukocyte antigen-A*0201/human CD8 + (HLA-A2 + /hCD8 + ) double-transgenic mice to define the epitopes and to study the level of protection acquired by mammaglobin-A cDNA vaccination toward mammaglobin-A + /HLA-A2 + breast cancer cell lines. Mammaglobin-A epitopes were identified using an HLA class I peptide binding prediction computer program, and their activity was verified using gamma interferon ELISPOT and cytotoxicity assays. Results: We identified seven mammaglobin-A–derived candidate epitopes that bind the HLA-A*0201 molecule (Mam-A2.1–7). CD8 + cytotoxic T lymphocytes (CTLs) from HLA-A2 + /hCD8 + mice reacted to the Mam-A2.1 (amino acids [aa] 83–92, LIYDSSLCDL), Mam-A2.2 (aa 2–10, KLLMVLMLA), Mam-A2.4 (aa 66–74, FLNQTDETL), and Mam-A2.6 (aa 32–40, MQLIYDSSL) epitopes. CD8 + CTLs from breast cancer patients also recognized a similar epitope pattern as did those in the HLA-A2 + /hCD8 mice and reacted to the Mam-A2.1, Mam-A2.2, Mam-A2.3, Mam-A2.4, and Mam-A2.7 epitopes. Passive transfer of mammaglobin-A–reactive CTLs into SCID (severe combined immunodeficient) beige mice with actively growing mammaglobin-A + tumors resulted in statistically significant regression ( P <.001) in the growth of the tumors. Conclusions: The HLA-A2 + /hCD8 + mouse represents a valuable animal model to characterize the HLA-A*0201–restricted CD8 + CTL immune response to mammaglobin-A in vivo , and the data reported here demonstrate the immunotherapeutic potential of mammaglobin-A for the treatment and/or prevention of breast cancer.
Clinical Characterization of Left Ventricular Noncompaction in Children
Authors: Ricardo H. Pignatelli, Colin J. McMahon, William J. Dreyer, Susan W. Denfield, Jack Price, John W. Belmont, William J. Craigen, Jen Wu, Howaida El Said, Louis I. Bezold, Sarah Clunie, Susan Fernbach, Neil E. Bowles, Jeffrey A. Towbin
Journal: Circulation (2003)

Background— Left ventricular noncompaction (LVNC) is a reportedly uncommon genetic disorder of endocardial morphogenesis with a reportedly high mortality rate. The purpose of this study was to identify the clinical characteristics of children with LVNC. Methods and Results— We retrospectively reviewed 36 children with LVNC evaluated at Texas Children’s Hospital (TCH) from January 1997 to December 2002. Five children had associated cardiac lesions. There were 16 girls and 20 boys. The median age at presentation was 90 days (range, 1 day to 17 years). The median duration of follow-up was 3.2 years (range, 0.5 to 12 years). Twenty-seven patients (75%) had ECG abnormalities, most commonly biventricular hypertrophy (10 patients, 28%). Both ventricles were involved in 8 patients (22%) and only the left ventricle in 28 patients (78%). Left ventricular systolic function was depressed in 30 patients (83%), with a median ejection fraction of 30% (range, 15% to 66%) at diagnosis. Nine patients presenting in the first year of life with depressed left ventricular contractility had a transient recovery of function; however, ejection fraction deteriorated later in life, at a median interval of 6.3years (range, 3 to 12 years). Two patients had an “undulating” phenotype from dilated to hypertrophic cardiomyopathy. Two patients (6%) were identified with an underlying G4.5 gene mutation. Five patients (14%) died during the study. Conclusions— LVNC does not have an invariably fatal course when diagnosed in the neonatal period. A significant number of patients have transient recovery of function followed by later deterioration, which may account for many patients presenting as adults, some manifesting an “undulating” phenotype.
Treatment strategy, disease activity, and outcome in four cohorts of patients with early rheumatoid arthritis
Authors: J M C Albers, L Paimela, P Kurki, K B Eberhardt, P Emery, M A van 't Hof, F H J M Schreuder, M Leirisalo-Repo, P L C M van Riel
Journal: Annals of the Rheumatic Diseases (2001)

<h3>OBJECTIVE</h3> To compare four different inception cohorts of patients with early rheumatoid arthritis (RA) with respect to treatment strategies, disease activity, and outcome during a five year follow up period. <h3>METHOD</h3> Data from cohorts of patients with early RA, with a standardised assessment at least every six months for five years from four different centres, were included in one database. Owing to slight differences in the individual study designs, linearly interpolated values were calculated to complete the standard follow up schedule. <h3>RESULTS</h3> Despite similar inclusion criteria, significant differences in demographic factors and baseline disease activity were found between the different cohorts. During the follow up an aggressive treatment strategy was followed in the Dutch and Finnish cohort, an intermediate strategy in the British cohort, and a conservative strategy in the Swedish cohort. A significant improvement in disease activity was seen in all cohorts, though the most rapid and striking improvement was seen in those receiving aggressive treatment. This resulted in less radiographic destruction in the long run. <h3>CONCLUSION</h3> This observational study of cohorts of patients with early RA confirms that early aggressive treatment results not only in a more rapid reduction of disease activity but also in less radiographic progression in the long term.
Combined inhibition of morphogen pathways demonstrates additive antifibrotic effects and improved tolerability
Authors: Alfiya Distler, Veronika Lang, Tina Del Vecchio, Jingang Huang, Yun Zhang, Christian Beyer, Neng-Yu Lin, Katrin Palumbo-Zerr, Oliver Distler, Georg Schett, Jörg HW Distler
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> The morphogen pathways Hedgehog, Wnt and Notch are attractive targets for antifibrotic therapies in systemic sclerosis. Interference with stem cell regeneration, however, may complicate the use of morphogen pathway inhibitors. We therefore tested the hypothesis that combination therapies with low doses of Hedgehog, Wnt and Notch inhibitors maybe safe and effective for the treatment of fibrosis. <h3>Methods</h3> Skin fibrosis was induced by bleomycin and by overexpression of a constitutively active TGF-β receptor type I. Adverse events were assessed by clinical monitoring, pathological evaluation and quantification of Lgr5-positive intestinal stem cells. <h3>Results</h3> Inhibition of Hedgehog, Wnt and Notch signalling dose-dependently ameliorated bleomycin-induced and active TGF-β receptor type I-induced fibrosis. Combination therapies with low doses of Hedgehog/Wnt inhibitors or Hedgehog/Notch inhibitors demonstrated additive antifibrotic effects in preventive as well as in therapeutic regimes. Combination therapies were well tolerated. In contrast with high dose monotherapies, combination therapies did not reduce the number of Lgr5 positive intestinal stem cells. <h3>Conclusions</h3> Combined inhibition of morphogen pathways exerts additive antifibrotic effects. Combination therapies are well tolerated and, in contrast to high dose monotherapies, may not impair stem cell renewal. Combined targeting of morphogen pathways may thus help to overcome dose-limiting toxicity of Hedgehog, Wnt and Notch signalling.
Sales of food aid as sign of distress, not excess
Authors: Barbara A Reed, Jean-Pierre Habicht
Journal: The Lancet (1998)

In 1996 the sale and export of food aid from refugee camps near Uvira, Zaire, prompted a reduction in donated rations. However, research has revealed that the sales did not reflect an excess of food in the camps. They were provoked by the absence of important components of the food basket, by cultural aversion to the staple (maize) and oil provided, by difficulties in food preparation, and by the refugees' limited ability to diversify their diet and cover pressing non-food needs. Food sales improved the micronutrient content of diets but at the expense of energy lost from an already energy-deficient diet. At most 23% of the refugee households were eating sufficient and adequate diets; the poorest one-fifth of households were twice as likely to sell or exchange food as were other households and their diets were the worst. These findings demonstrate the perils of the gap between policy and practice in food-aid distribution.
The human genome project: big science transforms biology and medicine
Authors: Leroy Hood, Lee Rowen
Journal: Genome Medicine (2013)

The Human Genome Project has transformed biology through its integrated big science approach to deciphering a reference human genome sequence along with the complete sequences of key model organisms. The project exemplifies the power, necessity and success of large, integrated, cross-disciplinary efforts - so-called ‘big science’ - directed towards complex major objectives. In this article, we discuss the ways in which this ambitious endeavor led to the development of novel technologies and analytical tools, and how it brought the expertise of engineers, computer scientists and mathematicians together with biologists. It established an open approach to data sharing and open-source software, thereby making the data resulting from the project accessible to all. The genome sequences of microbes, plants and animals have revolutionized many fields of science, including microbiology, virology, infectious disease and plant biology. Moreover, deeper knowledge of human sequence variation has begun to alter the practice of medicine. The Human Genome Project has inspired subsequent large-scale data acquisition initiatives such as the International HapMap Project, 1000 Genomes, and The Cancer Genome Atlas, as well as the recently announced Human Brain Project and the emerging Human Proteome Project.
Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tract
Authors: Alexander M. Owyang, Colby Zaph, Emma H. Wilson, Katherine J. Guild, Terrill McClanahan, Hugh R. P. Miller, Daniel J. Cua, Michael Goldschmidt, Christopher A. Hunter, Robert A. Kastelein, David Artis
Journal: The Journal of Experimental Medicine (2006)

The cytokine interleukin (IL) 25 has been implicated in the initiation of type 2 immunity by driving the expression of type 2 cytokines such as IL-5 and IL-13, although its role in the regulation of immunity and infection-induced inflammation is unknown. Here, we identify a dual function for IL-25: first, in promoting type 2 cytokine-dependent immunity to gastrointestinal helminth infection and, second, in limiting proinflammatory cytokine production and chronic intestinal inflammation. Treatment of genetically susceptible mice with exogenous IL-25 promoted type 2 cytokine responses and immunity to Trichuris. IL-25 was constitutively expressed by CD4+ and CD8+ T cells in the gut of mouse strains that are resistant to Trichuris, and IL-25-deficient mice on a genetically resistant background failed to develop a type 2 immune response or eradicate infection. Furthermore, chronically infected IL-25(-/-) mice developed severe infection-induced intestinal inflammation associated with heightened expression of interferon-gamma and IL-17, identifying a role for IL-25 in limiting pathologic inflammation at mucosal sites. Therefore, IL-25 is not only a critical mediator of type 2 immunity, but is also required for the regulation of inflammation in the gastrointestinal tract.
Is the cerebellum essentially a precise pattern matching device?
Authors: Franz Mechsner, Günther Palm
Journal: Behavioral and Brain Sciences (1997)

(1) The “timing idea” is not the only interpretation of cerebellar histology worth considering. Therefore, it is not imperative to strive for a theory of cerebellar function which gives it a prominent rôle. (2) The experiments with “moving stimuli” cannot support the tidal wave theory. (3) The notion that only “moving stimuli” can excite the cerebellar cortex is burdened with many intrinsic difficulties. (4) The common theoretical claim that the accuracy of skilled movements is due to exact pattern-matching processes in the cerebellum may be most misleading.
Cyclic strain upregulates nitric oxide synthase in cultured bovine aortic endothelial cells.
Authors: M A Awolesi, W C Sessa, B E Sumpio
Journal: Journal of Clinical Investigation (1995)

In vivo, endothelial cells (EC) are subjected to hemodynamic forces which may influence the production of nitric oxide. This study was designed to examine the effect of cyclic strain on the expression of endothelial nitric oxide synthase (eNOS) in cultured bovine aortic EC. EC were grown on flexible membranes which were subjected to deformation at 60 cycles/min with -5 or -20 kPa of vacuum. This results in an average strain of 6 and 10%, respectively, which is transmitted to the attached cells. Northern blot analysis of total cytosolic RNA demonstrated an increase in eNOS gene expression with both strain regimens but the increase with 10% average strain was greater than that at 6%. Nuclear runoff transcription assays confirmed the induction of eNOS transcripts. Western blot analysis showed an increase in eNOS level after 24 h of cyclic 10% average strain compared with controls or 6% average strain. Immunohistochemical staining of EC for eNOS was increased in the high strain periphery (7-24% strain) of membranes deformed with -20 kPa vacuum. These results demonstrate that cyclic strain upregulates the expression of eNOS transcripts and protein levels in bovine aortic EC thus emphasizing the importance of hemodynamic forces in the regulation of eNOS in vivo.
Regeneration of the pancreatic β cell
Authors: Massimo Trucco
Journal: Journal of Clinical Investigation (2005)

Type 1 diabetes is the result of an autoimmune attack against the insulin-producing β cells of the endocrine pancreas. Current treatment for patients with type 1 diabetes typically involves a rigorous and invasive regimen of testing blood glucose levels many times a day along with subcutaneous injections of recombinant DNA–derived insulin. Islet transplantation, even with its substantially improved outcome in recent years, is still not indicated for pediatric patients. However, in light of the fact that some regenerative capabilities of the endocrine pancreas have been documented and recent research has shown that human ES cell lines can be derived in vitro, this review discusses whether it is practical or even possible to combine these lines of research to more effectively treat young diabetic patients.
Evaluation of patients with acute myocardial infarction by magnetic resonance imaging: A mid term follow-up
Authors: Ibraim Pinto, Ricardo Pavanello, Rodrigo Barretto, Alexandre Abizaid, Leopoldo Piegas, Enilton Egito, Marcos Barbosa, auEdson Romano, Amanda Sousa, J.Eduardo Sousa
Journal: Journal of the American College of Cardiology (1996)
Origin on the electrocardiogram of U-waves and abnormal U-wave inversion
Authors: D di Bernardo
Journal: Cardiovascular Research (2002)

Aims: Soon after the initial development of electrocardiography, U-waves were discovered in many normal subjects following the T-wave repolarisation waveform on the electrocardiogram. Various explanations have been offered for their origin, but none is universally accepted. We used our model of left ventricular repolarisation to explore the most common hypotheses for the genesis of U-waves. Methods: Recently, we have shown that a computer model of left ventricular repolarisation was able to explain the formation of the characteristic shape of the T-wave, and we have now used this model to explore the most common hypotheses for the genesis of U-waves. The repolarisation phase of the action potentials in the model exhibited an after-potential. We investigated separately the effect on the 12-lead electrocardiogram of three different features of the model: the amplitude of the after-potential; dispersion of repolarisation in the left ventricle ranging from 20 to 100 ms; the timing of the after-potential, relative to the end of the principal action potential component, ranging from −100 to 100 ms. Results: We show that delaying repolarisation in different regions of the heart cannot explain the U-wave, but show that the presence of after-potentials on the cardiac action potential do explain the U-wave polarity and other characteristic U-wave features. We also show that abnormal after-potential timing corresponds with abnormal U-wave inversion. Conclusion: Our model provides a realistic and simple solution to the problem of U-wave genesis.
Using Health Information Technology to Engage Communities in Health, Education, and Research
Authors: Lisa K. Marriott, David A. Nelson, Shauntice Allen, Karen Calhoun, Christina E. Eldredge, Kim S. Kimminau, Robert J. Lucero, Fernando Pineda-Reyes, Bernice B. Rumala, Arti P. Varanasi, June S. Wasser, Jackilen Shannon
Journal: Science Translational Medicine (2012)

The August 2011 Clinical and Translational Science Awards conference "Using IT to Improve Community Health: How Health Care Reform Supports Innovation" convened four "Think Tank" sessions. Thirty individuals, representing various perspectives on community engagement, attended the "Health information technology (HIT) as a resource to improve community health and education" session, which focused on using HIT to improve patient health, education, and research involvement. Participants discussed a range of topics using a semistructured format. This article describes themes and lessons that emerged from that session, with a particular focus on using HIT to engage communities to improve health and reduce health disparities in populations.
The Systemic Capillary Leak Syndrome
Authors: Laurent Arnaud, Marie Gouseff, Zahir Amoura
Journal: Annals of Internal Medicine (2011)

Letters6 September 2011The Systemic Capillary Leak SyndromeLaurent Arnaud, MD, Marie Gouseff, MD, and Zahir Amoura, MDLaurent Arnaud, MDFrom Groupe Hospitalier Pitié-Salpêtrière, 75013 Paris, France.Search for more papers by this author, Marie Gouseff, MDFrom Groupe Hospitalier Pitié-Salpêtrière, 75013 Paris, France.Search for more papers by this author, and Zahir Amoura, MDFrom Groupe Hospitalier Pitié-Salpêtrière, 75013 Paris, France.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-155-5-201109060-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We thank Dr. Pecker and colleagues for their comments on our recent SCLS study. On the basis of previously published data, a careful review of our study, and at least 2 personal cases, they contend that β2-agonists and IVIG do not provide equivalent prophylaxis and that IVIG should be the initial choice to prevent episodes of SCLS.In the past, many treatments have been claimed to be effective in treating SCLS. However, because SCLS is rare and has an unpredictable course, drawing clear conclusions is often difficult, and many of these treatments are not used anymore. To circumvent ... Author, Article, and Disclosure InformationAffiliations: From Groupe Hospitalier Pitié-Salpêtrière, 75013 Paris, France.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M10-2267. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Systemic Capillary Leak Syndrome: A Case Series of 28 Patients From a European Registry Marie Gousseff , Laurent Arnaud , Marc Lambert , Arnaud Hot , Mohamed Hamidou , Pierre Duhaut , Thomas Papo , Martin Soubrier , Marc Ruivard , Giuseppe Malizia , Nathalie Tieulié , Sophie Rivière , Jacques Ninet , Pierre-Yves Hatron , Zahir Amoura , and The Systemic Capillary Leak Syndrome Mark Pecker , Michael Adams , and Walter Graham Metrics 6 September 2011Volume 155, Issue 5Page: 335-336KeywordsCapillariesConflicts of interestDisclosureProphylaxisSurvival analysis ePublished: 6 September 2011 Issue Published: 6 September 2011 CopyrightCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...