tbuckley/cabot-search huggingface dataset:
Ancestry and Pathology in King Tutankhamun's Family
Authors: Zahi Hawass
Journal: JAMA (2010)

The New Kingdom in ancient Egypt, comprising the 18th, 19th, and 20th dynasties, spanned the mid-16th to the early 11th centuries bc. The late 18th dynasty, which included the reigns of pharaohs Akhenaten and Tutankhamun, was an extraordinary time. The identification of a number of royal mummies from this era, the exact relationships between some members of the royal family, and possible illnesses and causes of death have been matters of debate.To introduce a new approach to molecular and medical Egyptology, to determine familial relationships among 11 royal mummies of the New Kingdom, and to search for pathological features attributable to possible murder, consanguinity, inherited disorders, and infectious diseases.From September 2007 to October 2009, royal mummies underwent detailed anthropological, radiological, and genetic studies as part of the King Tutankhamun Family Project. Mummies distinct from Tutankhamun's immediate lineage served as the genetic and morphological reference. To authenticate DNA results, analytical steps were repeated and independently replicated in a second ancient DNA laboratory staffed by a separate group of personnel. Eleven royal mummies dating from circa 1410-1324 bc and suspected of being kindred of Tutankhamun and 5 royal mummies dating to an earlier period, circa 1550-1479 bc, were examined.Microsatellite-based haplotypes in the mummies, generational segregation of alleles within possible pedigree variants, and correlation of identified diseases with individual age, archeological evidence, and the written historical record.Genetic fingerprinting allowed the construction of a 5-generation pedigree of Tutankhamun's immediate lineage. The KV55 mummy and KV35YL were identified as the parents of Tutankhamun. No signs of gynecomastia and craniosynostoses (eg, Antley-Bixler syndrome) or Marfan syndrome were found, but an accumulation of malformations in Tutankhamun's family was evident. Several pathologies including Köhler disease II were diagnosed in Tutankhamun; none alone would have caused death. Genetic testing for STEVOR, AMA1, or MSP1 genes specific for Plasmodium falciparum revealed indications of malaria tropica in 4 mummies, including Tutankhamun's. These results suggest avascular bone necrosis in conjunction with the malarial infection as the most likely cause of death in Tutankhamun. Walking impairment and malarial disease sustained by Tutankhamun is supported by the discovery of canes and an afterlife pharmacy in his tomb.Using a multidisciplinary scientific approach, we showed the feasibility of gathering data on Pharaonic kinship and diseases and speculated about individual causes of death.
Depressive Symptoms and Risk of Type 2 Diabetes in a National Sample of Middle-Aged and Older Adults
Authors: Panayotes Demakakos, Mary B. Pierce, Rebecca Hardy
Journal: Diabetes Care (2010)

To examine the association between baseline elevated depressive symptoms and incident type 2 diabetes in a national sample of people aged > or =50 years.The sample consisted of 6,111 individuals free from self-reported doctor-diagnosed diabetes at baseline in 2002-2003. The eight-item Center for Epidemiological Studies-Depression (CES-D) scale was the measurement of depressive symptoms. Cox proportional hazards regression models were used to assess whether baseline elevated (> or =4) depressive symptoms were associated with a higher risk of type 2 diabetes over 45.8 months of follow-up.The hazard ratio (HR) for diabetes was 1.62 (95% CI 1.15-2.29) in a model adjusted for age, sex, marital status, education, total net household wealth, cardiovascular and psychiatric and other noncardiovascular comorbidities, BMI, and health behaviors for participants with elevated CES-D symptoms compared with those without. Complementary analysis performed for a subsample (n = 5,090) showed that additional adjustment of this model for use of antidepressants did not explain the association (HR 1.58, 95% CI 1.09-2.29).Elevated depressive symptoms were associated with a higher risk of developing type 2 diabetes after accounting for sociodemographic, lifestyle, and clinical factors in a national sample of people aged > or =50 years.
Microbial Flora Drives Interleukin 22 Production in Intestinal NKp46+ Cells that Provide Innate Mucosal Immune Defense
Authors: Naoko Satoh-Takayama, Christian A.J. Vosshenrich, Sarah Lesjean-Pottier, Shinichiro Sawa, Matthias Lochner, Frederique Rattis, Jean-Jacques Mention, Kader Thiam, Nadine Cerf-Bensussan, Ofer Mandelboim, Gerard Eberl, James P. Di Santo
Journal: Immunity (2008)
Tolerogenic dendritic cells inhibit antiphospholipid syndrome derived effector/memory CD4<sup>+</sup> T cell response to β2GPI
Authors: Honorio Torres-Aguilar, Miri Blank, Shaye Kivity, Mudi Misgav, Jacob Luboshitz, Silvia S Pierangeli, Yehuda Shoenfeld
Journal: Annals of the Rheumatic Diseases (2011)

Objectives The importance of β 2 -glycoprotein I (β 2 GPI)-specific CD4 + T cells in the development of pathogenic processes in patients with antiphospholipid syndrome (APS) and APS mouse models is well established. Therefore, our objective is to manipulate the β2GPI specific CD4 + T cells using tolerogenic dendritic cells (tDCs) to induce tolerance. We aim to evaluate the capability of tDCs to induce antigen-specific tolerance in effector/memory T cells from patients with APS and to elucidate the involved mechanism. Methods DCs and tDCs were produced from patients with APS peripheral-blood-monocytes, using specific cytokines. β 2 GPI-specific tolerance induction was investigated by coculturing control DC (cDC) or tDC, β 2 GPI-loaded, with autologous effector/memory T cells, evaluating the proliferative response, phenotype, cytokines secretion, viability and regulatory T cells. Results Human monocyte-derived DCs treated with interleukin (IL)-10 and transforming growth factor β-1 (10/TGF-DC) induced β 2 GPI-specific-unresponsiveness in effector/memory CD4 + T cells (46.5%±26.0 less proliferation) in 16 of 20 analysed patients with APS, without affecting the proliferative response to an unrelated candidin. In five analysed patients, 10/TGF-DC-stimulated T cells acquired an IL-2 low interferon γ low IL-10 high cytokine profile, with just a propensity to express higher numbers of Foxp3 + CTLA-4 + cells, but with an evident suppressive ability. In four of 10 analysed patients, 10/TGF-DC-stimulated T cell hyporesponsiveness could not be reverted and showed higher percentages of late apoptosis, p&lt;0.02. Conclusions The inherent tolerance induction resistance of activated T cells present during the development of autoimmune diseases has delayed the application of tDC as an alternative therapy. This study highlights the 10/TGF-DC feasibility to induce antigen-specific unresponsiveness in autoreactive T cells generated in patients with APS by inducing apoptosis or T cells with regulatory abilities.
A Multiparametric Serum Kallikrein Panel for Diagnosis of Non–Small Cell Lung Carcinoma
Authors: Chris Planque, Lin Li, Yingye Zheng, Antoninus Soosaipillai, Karen Reckamp, David Chia, Eleftherios P. Diamandis, Lee Goodglick
Journal: Clinical Cancer Research (2008)

Human tissue kallikreins are a family of 15 secreted serine proteases. We have previously shown that the expression of several tissue kallikreins is significantly altered at the transcriptional level in lung cancer. Here, we examined the clinical value of 11 members of the tissue kallikrein family as potential biomarkers for lung cancer diagnosis.Serum specimens from 51 patients with non-small cell lung cancer (NSCLC) and from 50 healthy volunteers were collected. Samples were analyzed for 11 kallikreins (KLK1, KLK4-8, and KLK10-14) by specific ELISA. Data were statistically compared and receiver operating characteristic curves were constructed for each kallikrein and for various combinations.Compared with sera from normal subjects, sera of patients with NSCLC had lower levels of KLK5, KLK7, KLK8, KLK10, and KLK12, and higher levels of KLK11, KLK13, and KLK14. Expression of KLK11 and KLK12 was positively correlated with stage. With the exception of KLK5, expression of kallikreins was independent of smoking status and gender. KLK11, KLK12, KLK13, and KLK14 were associated with higher risk of NSCLC as determined by univariate analysis and confirmed by multivariate analysis. The receiver operating characteristic curve of KLK4, KLK8, KLK10, KLK11, KLK12, KLK13, and KLK14 combined exhibited an area under the curve of 0.90 (95% confidence interval, 0.87-0.97).We propose a multiparametric panel of kallikrein markers for lung cancer diagnosis with relatively good accuracy. This model requires validation with a larger series and may be further improved by addition of other biomarkers.
Social cognition of religion
Authors: William Sims Bainbridge
Journal: Behavioral and Brain Sciences (2006)

Research on religion can advance understanding of social cognition by building connections to sociology, a field in which much cognitively oriented work has been done. Among the schools of sociological thought that address religious cognition are: structural functionalism, symbolic interactionism, conflict theory, phenomenology, and, most recently, exchange theory. The gulf between sociology and cognitive science is an unfortunate historical accident.
Metachronous tumour development in the pancreas
Authors: N Ueno, N Kobayashi, H Kawamura, M Ueda, I Endo, S Togo, H Shimada
Journal: Gut (2006)

A 66-year-old man presented to our institution for evaluation of the pancreatic system. His medical history showed that he had undergone distal pancreatectomy to treat intraductal papillary mucinous neoplasm 44 months earlier. His condition took an uneventful postoperative …
Attitudes towards reproduction in Latin America. Teachings from the use of modern reproductive technologies
Authors: F Zegers-Hochschild
Journal: Human Reproduction Update (1999)

The use of modern reproductive technology, such as in-vitro fertilization and its related procedures, has opened new areas of legal, religious and public concern. Thirty years ago, the development of effective methods to control procreation generated a debate on whether couples had the right to enjoy sex in the absence of its procreative effect. Today, assisted reproductive technology (ART) allows couples to have their own children in the absence of a direct intermediation of sex. The Catholic Church has reacted against both contraception and ART, and specific instructions have been directed to the public, the medical profession and legislators. In a recent survey, 88.4% of the population in Latin America claims to be Catholic; therefore, bioethical considerations and legal implications concerning intervention in reproduction are strongly permeated by the moral teachings of Catholicism. In 1996, 83 medical doctors and scientists, participating in the Latin American Network of Assisted Reproduction, produced a consensus document on ethical aspects and legal implications of ART. The document contains minimal ethical guidelines that Latin American professionals have decided to adhere to, even in the absence of legal regulations. This article examines how the medical profession, legislators and the public react to religious influence when confronted by difficult bioethical decisions such as the right to procreate.
Control of vascular cell proliferation and migration by cyclin-dependent kinase signalling: new perspectives and therapeutic potential
Authors: V ANDRES
Journal: Cardiovascular Research (2004)

Neointimal lesion development is a chronic inflammatory process that involves excessive cell proliferation and migration within the artery wall. Progression through the mammalian cell cycle requires the sequential activation of holoenzymes composed of a catalytic cyclin-dependent protein kinase (CDK) and a regulatory subunit named cyclin. Members of the family of CDK inhibitory proteins (CKIs) interact with and inhibit the activity of CDK/cyclins. Cell migration occurs predominantly at the G1/S phase of the cell cycle, and both CDKs and CKIs are among the molecular machines that coordinately regulate the cycling events that control cell proliferation and locomotion. The purpose of this review is to discuss the role of CDK/cyclins and CKIs in the regulation of vascular cell proliferation and migration and in the control of neointimal thickening. Pharmacological and gene therapy strategies targeting these cell cycle regulators for the treatment of cardiovascular disease will also be discussed.
Hydroxyethyl Starch for Intravenous Volume Replacement
Authors: Massimo Antonelli, Claudio Sandroni
Journal: JAMA (2013)

Hydroxyethyl starches are synthetic fluid products used commonly in clinical practice worldwide. Synthetic colloids received market approval in the 1960s without evaluation of their efficacy and safety in large phase 3 clinical trials. Subsequent studies reported mixed evidence on their benefits and harms. Adding to the controversy, a number of studies reporting benefit were conducted by Dr Joachim Boldt, an investigator who had a large number of studies retracted for ethical or scientific misconduct.1 Two recent large randomized controlled trials2- 3 have fueled further debate over the safety of hydroxyethyl starch for routine clinical use.
Plasma metallothionein concentration in patients with liver disorders: Special emphasis on the relation with primary biliary cirrhosis
Authors: Theo P. J. Mulder, Roelof A. Janssens, Hein W. Verspaget, Cornelis B. H. W. Lamers
Journal: Hepatology (1991)

The plasma metallothionein concentration was evaluated in healthy subjects and in patients with several types of liver disorders. Plasma metallothionein concentrations in controls varied between 2.4 and 4.8 ng/ml. Patients with disorders associated with increased liver copper concentrations (i.e., primary biliary cirrhosis and primary sclerosing cholangitis) had significantly (both p less than 0.002) elevated plasma metallothionein concentrations (range = 1.8 to 52.2 ng/ml), and a considerable number of these were above the maximum control level (21 of 41 patients). In contrast, patients with liver disorders not associated with increased liver copper concentrations (alcoholic and cryptogenic cirrhosis, and acute viral and chronic active hepatitis) generally had normal plasma metallothionein concentrations and only a few were above the maximum control level (11 of 64 patients, maximum = 8.8 ng/ml). The metallothionein concentrations in plasma samples from patients in stage I or II primary biliary cirrhosis were within or slightly above the control range, whereas most patients in stage III had elevated levels (p less than 0.002), and almost all patients in stage IV had clearly elevated (p less than 0.0001) concentrations. In primary biliary cirrhosis the plasma metallothionein concentration tended to increase during the evolution of the disorder, and the concentration correlated significantly with the serum total bilirubin concentration. In conclusion, the plasma metallothionein concentration is significantly elevated in patients with primary biliary cirrhosis and in patients with primary sclerosing cholangitis. Although related to the histological stage of primary biliary cirrhosis, the measurement of plasma metallothionein concentrations contributes little to the diagnosis or the evaluation of the severity of these disorders.(ABSTRACT TRUNCATED AT 250 WORDS)
Food anaphylaxis in schools: evaluation of the management plan and the efficiency of the emergency kit
Authors: D. A. Moneret‐Vautrin, G. Kanny, M. Morisset, J. Flabbee, L. Guénard, E. Beaudouin, L. Parisot
Journal: Allergy (2001)

Background: Children with severe food allergies can benefit from a personalized care project (PCP) in schools. The usefulness of the PCP and the residual risk of allergic emergencies are poorly appreciated. The objective was to evaluate the efficiency of the management plan and the training in the use of the emergency kit. Methods: A telephone survey using a detailed questionnaire was performed in 45 families whose children had been previously referred to the department. The distribution of disorders was as follows: asthma, 37.7%; atopic dermatitis and asthma, 28.8%; atopic dermatitis, 15.5%; angioedema and urticaria, 13.3%; and anaphylactic shock, 4.2%. Food allergy had been diagnosed in the 45 children by past history, and double‐blind or single‐blind, placebo‐controlled food challenges (DBPCFCs, or SBPCFCs) with evidence of specific IgE. Exactly 75.5% of the children had peanut allergy. Multiple food allergies characterized 46.8% of the subjects. They had benefited from a strict elimination diet and a protocol for emergency care including a ready‐to‐use intramuscular epinephrine injection. A PCP had been requested by the School Public Health Service. Results: Thirty‐nine PCPs were implemented (86.5% of the requests). They represented 63% of the PCPs for food allergy in the eastern region of France: one per 5800 school‐age children. The retrospective period of evaluation was 25 months on average. The types of meals were very diverse, and medically acceptable in 83% of cases. The place where the emergency kit was stored in the school varied. Forty reactions occurred in 33% of the children (5/6 times in the absence of a PCP), asthma in 28%, shock in 1%, and immediate skin reactions in 11%. Reactions occurred at home in 78% of the subjects, and in school in 22% of the subjects. The cause of the reactions was not specifically known in 63% of cases. Twenty‐seven percent of the reactions were linked to the ingestion of food allergens. In 10% of subjects, the reaction was due to a modification of ingredients by the food industry. Conclusions: The frequency of respiratory symptoms during oral challenge tests was confirmed by the frequency of asthmatic reactions within the follow‐up period. The role of hidden allergens and of misleading labeling validates the need for PCPs in the case of peanut and tree nut allergies, past history of severe reactions, multiple food allergies, reactions to a low dose in DBPCFCs, and asthmatic reactions to foods. This study provides encouraging data on the usefulness of PCPs and confirms the need for thorough instruction and training of the school staff in dealing with allergic emergencies. Addition of a β‐agonist spray to the emergency kit is suggested.
Identification of a second class of IgG Fc receptors on human neutrophils. A 40 kilodalton molecule also found on eosinophils.
Authors: R J Looney, D H Ryan, K Takahashi, H B Fleit, H J Cohen, G N Abraham, C L Anderson
Journal: The Journal of Experimental Medicine (1986)

We describe a newly recognized 40 kD FcR for IgG on human neutrophilic granulocytes. An mAb (IV3) developed against the IgG FcR of K562 cells, and specific as well for a 40 kD FcR on human monocytes and platelets, was found to purify by affinity adsorption a 40 kD protein from detergent lysates of surface-radioiodinated neutrophils. This protein, proteolytically degraded to 33 kD when purified in the absence of diisopropylfluorophosphate, is distinct from the 51-73 kD protein precipitated by the anti-neutrophil FcR mAb, 3G8, previously described by others. Complete inhibition of binding of rabbit IgG-coated erythrocytes to neutrophils was achieved only when both antibodies, IV3 and 3G8, were used. Fab fragments of IV3 were as effective inhibitors as the intact molecule. IV3 IgG or Fab fragments completely and selectively inhibited immune complex-mediated generation of superoxide by human neutrophils; superoxide generation by other stimulants was not abrogated by IV3. This antibody (IV3) bound also to human eosinophils and completely inhibited the binding of IgG-coated erythrocytes to eosinophils. IV3 appears to define the human homolog of the murine macrophage FcRII identified initially by mAb 2.4G2 and present in the mouse on both neutrophils and eosinophils.
Embryonic Heart Failure in <i>NFATc1</i> <sup>−/−</sup> Mice
Authors: Colin K.L. Phoon, Rui Ping Ji, Orlando Aristizábal, Diane M. Worrad, Bin Zhou, H. Scott Baldwin, Daniel H. Turnbull
Journal: Circulation Research (2004)

Gene targeting in the mouse has become a standard approach, yielding important new insights into the genetic factors underlying cardiovascular development and disease. However, we still have very limited understanding of how mutations affect developing cardiovascular function, and few studies have been performed to measure altered physiological parameters in mouse mutant embryos. Indeed, although in utero lethality due to embryonic heart failure is one of the most common results of gene targeting experiments in the mouse, the underlying physiological mechanisms responsible for embryonic demise remain elusive. Using in utero ultrasound biomicroscopy (UBM), we studied embryonic day (E) 10.5 to 14.5 NFATc1-/- embryos and control littermates. NFATc1-/- mice, which lack outflow valves, die at mid-late gestation from presumed defects in forward blood flow with resultant heart failure. UBM showed increasing abnormal regurgitant flow in the aorta and extending into the embryonal-placental circulation, which was evident after E12.5 when outflow valves normally first develop. Reduced NFATc1-/- net volume flow and diastolic dysfunction contributed to heart failure, but contractile function remained unexpectedly normal. Among 107 NFATc1-/- embryos imaged, only 2 were observed to be in acute decline with progressive bradyarrhythmia, indicating that heart failure occurs rapidly in individual NFATc1-/- embryos. This study is among the first linking a specific physiological phenotype with a defined genotype, and demonstrates that NFATc1-/- embryonic heart failure is a complex phenomenon not simply attributable to contractile dysfunction.
Mechanisms of BRCA1 Tumor Suppression
Authors: Daniel P. Silver, David M. Livingston
Journal: Cancer Discovery (2012)

The p220 BRCA1 tumor suppressor protein has been implicated in multiple biochemical and biologic functions since its molecular cloning 18 years ago. Here, we discuss those functions most relevant for its tumor-suppressing activities with an emphasis on new findings. In particular, this review focuses on what is known of the activities of those BRCA1-binding partners that have tumor suppressor functions, on the reversion of mutant BRCA1 alleles concomitant with therapy resistance, on insights gained from studies of BRCA1 structure-function relationships, recent findings from animal models, and the potential role of BRCA1 in some nonhereditary tumors. From this information, a more detailed and refined picture of BRCA1 tumor suppression is beginning to emerge. Although key mysteries remain--such as why BRCA1 tumor suppression is focused on carcinomas of the breast and ovary--the pace of discovery is increasing.BRCA1 functions as a clinically important classical tumor suppressor in hereditary breast and ovarian cancer; here, we review progress in understanding how BRCA1 operates to suppress tumor formation.
Increased LIS1 expression affects human and mouse brain development
Authors: Weimin Bi, Tamar Sapir, Oleg A Shchelochkov, Feng Zhang, Marjorie A Withers, Jill V Hunter, Talia Levy, Vera Shinder, Daniel A Peiffer, Kevin L Gunderson, Marjan M Nezarati, Vern Ann Shotts, Stephen S Amato, Sarah K Savage, David J Harris, Debra-Lynn Day-Salvatore, Michele Horner, Xin-Yan Lu, Trilochan Sahoo, Yuchio Yanagawa, Arthur L Beaudet, Sau Wai Cheung, Salvador Martinez, James R Lupski, Orly Reiner
Journal: Nature Genetics (2009)
Factor VII levels as a guide to prognosis in fulminant hepatic failure.
Authors: B G Gazzard, J M Henderson, R Williams
Journal: Gut (1976)

Levels of clotting factors II, V, and VII were measured on admission and then daily in 12 patients with grade IV hepatic coma due to fulminant hepatic failure. Factor VII levels obtained within 36 hours of the development of grade IV coma were not of value in predicting which patients would subsequently recover consciousness. Four of the latter group had levels below 9% at this time while the levels in three of the seven fatal cases were higher. Serial determinations were of more value and levels rose rapidly in those patients who ultimately made a complete recovery.