tbuckley/cabot-search huggingface dataset:
Accounting for Individual Differences in Risk of Alzheimer Disease
Authors: William Grant
Journal: PLoS Medicine (2005)

Gatz's statement, "At least half of the explanation for individual differences in susceptibility to Alzheimer disease is genetic" [1], is, in my opinion, incorrect.As the one who led the team debating Ashford and Mortimer, whose 2002 article [2] supports this statement, at the 2001 conference on Alzheimer disease (AD) in Cincinnati ("Challenging Views of Alzheimer's Disease") [3], I think that the evidence that dietary and lifestyle factors explain the majority of the individual risk for AD in the US is very strong.My original paper in 1997 [4] found that total dietary fat and energy intake were the most important dietary risk factors, while fi sh and cereal intake were the most important risk reduction factors.These fi ndings have been generally confi rmed by Drs.Luchsinger and Morris and others.The reason I did my study was that the Honolulu Heart Study reported that Japanese American men in Hawaii had 2.5 times the risk of AD of native Japanese.African-Americans have about four times the risk of AD of native Nigerians.If genetics were the primary risk factor, those living in the US would have a risk of developing AD very similar to that of individuals living in their ancestral home.The reason this is not the case is that the American diet provides too much food, which is a particular problem for those genetically predisposed to AD.
STUDIES ON HUMAN GROWTH HORMONE. II. THE PHYSIOLOGICAL DISPOSITION AND METABOLIC FATE OF HUMAN GROWTH HORMONE IN MAN*
Authors: Mary L. Parker, Robert D. Utiger, William H. Daughaday
Journal: Journal of Clinical Investigation (1962)

The metabolic effects of human growth hor- mone have received much attention, but little is known regarding the metabolism of the hormone itself in man.Studies of growth hormone metabolism carried out in experimental animals suggest that both bovine growth hormone and human growth hormone have rapid turnovers.Van Dyke, Simpson, Li and Evans (1) and Gemzell, Heijkenskjdld and Str6m (2) injected rats with large doses of bovine growth hormone and deter- mined plasma levels of growth hormone by the tibial cartilage width assay.The half-lives of disappearance were 26 and 40 minutes, respec- tively, in the two studies, and the volume of distribution of the hormone was roughly equivalent to the extracellular fluid space.Isotopic methods have also been applied to the study of growth hormone metabolism.Sonenberg and co-workers (3) injected rats with radioiodinated bovine growth hormone and, although their work was principally concerned with tissue localization, they published a graph depicting the disappearance of radioactivity from plasma after a single intra- venous injection.The half-life of disappearance was approximately 25 minutes.In the experi- ments of Salmon, Utiger, Parker and Reichlin (4), radioiodinated human growth hormone had a half-life of disappearance from plasma of 17 minutes when injected into rabbits.
Lung transplantation and coronary artery disease - a relative contraindication?
Authors: Julia Fresenius, Fabian Fohrer, Werner von Wulffen, Nikolaus Kneidinger, Rene Schramm, Hauke Winter, Lorenz Frey, Jürgen Behr, Claus Neurohr
Journal: European Respiratory Journal (2014)

Introduction   The diagnosis of coronary artery disease (CAD) is considered as a relative contraindication for lung transplantation.   Aims and Objectives   The aim of this study is to examine the mortality of patients with diagnosed CAD and normal left ventricular function and patients with excluded CAD before lung transplantation.   Methods   A retrospective analysis of all lung transplantations at LMU Munich between 1998 and 2012 was performed.   Results   328 coronary angiographies were performed before lung transplantation (127 patients with COPD, 174 patients with Interstitial Lung Disease and 27 patients with other diagnosis). All patients have a normal left ventricular function with an EF over 60%. 254 patients (77.4%) had coronary angiography without any pathological finding. In 74 patients (22.6%) a stenosis of 40 % or higher was found in at least one vessel with good left ventricular function. 54 of the 74 CAD-patients (73%) obtained a conservative therapy. The remaining 20 patients (27%) needed additional interventional therapy (PCI with stent implantation).  Patients with CAD had a significant higher mortality after 1, 3 and 5 years compared to patients without CAD (p= 0.07; 0.01; 0.02 respectively). There is no significant difference in the mortality between the conservative and the interventional treated CAD patients. Perioperative bleeding complications could be detected in 11.1% of the CAD patients and in 5.5 % of the patients without CAD. Multivariate regression analysis revealed, CAD is a risk factor for mortality independent of age and the type of transplantation.   Conclusions   Our data suggest, the coronary artery disease influence outcome after lung transplantation.
Axitinib versus sorafenib as first-line therapy in patients with metastatic renal-cell carcinoma: a randomised open-label phase 3 trial
Authors: Thomas E Hutson, Vladimir Lesovoy, Salman Al-Shukri, Viktor P Stus, Oleg N Lipatov, Angel H Bair, Brad Rosbrook, Connie Chen, Sinil Kim, Nicholas J Vogelzang
Journal: The Lancet Oncology (2013)
Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II
Authors: Morten Dahl, Alison K. Bauer, Mohamed Arredouani, Raija Soininen, Karl Tryggvason, Steven R. Kleeberger, Lester Kobzik
Journal: Journal of Clinical Investigation (2007)

Alveolar macrophages (AMs) express the class A scavenger receptors (SRAs) macrophage receptor with collagenous structure (MARCO) and scavenger receptor AI/II (SRA-I/II), which recognize oxidized lipids and provide innate defense against inhaled pathogens and particles. Increased MARCO expression in lungs of ozone-resistant mice suggested an additional role protecting against inhaled oxidants. After ozone exposure, MARCO–/– mice showed greater lung injury than did MARCO+/+ mice. Ozone is known to generate oxidized, proinflammatory lipids in lung lining fluid, such as 5β,6β-epoxycholesterol (β-epoxide) and 1-palmitoyl-2-(9′-oxo-nonanoyl)-glycerophosphocholine (PON-GPC). Intratracheal instillation of either lipid caused substantial neutrophil influx in MARCO–/– mice, but had no effect in MARCO+/+ mice. Normal AMs showed greater uptake in vitro of β-epoxide compared with MARCO–/– AMs, consistent with SRA function in binding oxidized lipids. SR-AI/II–/– mice showed similar enhanced acute lung inflammation after β-epoxide or another inhaled oxidant (aerosolized leachate of residual oil fly ash). In contrast, subacute ozone exposure did not enhance inflammation in SR-AI/II–/– versus SR-AI/II+/+ mice, reflecting increased AM expression of MARCO. These data identify what we believe to be a novel function for AM SRAs in decreasing pulmonary inflammation after oxidant inhalation by scavenging proinflammatory oxidized lipids from lung lining fluids.
microRNAs: Master Regulators as Potential Therapeutics in Cancer
Authors: Michela Garofalo, Carlo M. Croce
Journal: The Annual Review of Pharmacology and Toxicology (2011)

It has been demonstrated that all the known processes involved in cancer, including apoptosis, proliferation, survival, and metastasis, are regulated by small regulatory noncoding RNAs consisting of approximately 19-25 nucleotides; these are named microRNAs (miRNAs). Both loss and gain of miRNA function contribute to cancer development through the upregulation and silencing, respectively, of different target genes. Experimental evidence indicates that the use of miRNA mimics or anti-microRNAs may represent a powerful therapeutic strategy to interfere with key molecular pathways involved in cancer. This review provides insights about how micro- RNAs act as oncogenes and tumor suppressor genes and how these findings, along with our increasing understanding of miRNA regulation, can be applied to optimize recent miRNA-based technologies and make them suitable for clinical applications.
Binding of tissue plasminogen activator to cultured human endothelial cells.
Authors: K A Hajjar, N M Hamel, P C Harpel, R L Nachman
Journal: Journal of Clinical Investigation (1987)

Tissue plasminogen activator (t-PA) and urokinase (u-PA), the major activators of plasminogen, are synthesized and released from endothelial cells. We previously demonstrated specific and functional binding of plasminogen to cultured human umbilical vein endothelial cells (HUVEC). In the present study we found that t-PA could bind to HUVEC. Binding of t-PA to HUVEC was specific, saturable, plasminogen-independent, and did not require lysine binding sites. The t-PA bound in a rapid and reversible manner, involving binding sites of both high (Kd, 28.7 +/- 10.8 pM; Bmax, 3,700 +/- 300) and low (Kd, 18.1 +/- 3.8 nM; Bmax 815,000 +/- 146,000) affinity. t-PA binding was 70% inhibited by a 100-fold molar excess of u-PA. When t-PA was bound to HUVEC, its apparent catalytic efficiency increased by three- or fourfold as measured by plasminogen activation. HUVEC-bound t-PA was active site-protected from its rapidly acting inhibitor: plasminogen activator inhibitor. These results demonstrate that t-PA specifically binds to HUVEC and that such binding preserves catalytic efficiency with respect to plasminogen activation. Therefore, endothelial cells can modulate hemostatic and thrombotic events at the cell surface by providing specific binding sites for activation of plasminogen.
The two most common histological subtypes of malignant germ cell tumour are distinguished by global microRNA profiles, associated with differential transcription factor expression
Authors: Matthew J Murray, Harpreet K Saini, Stijn van Dongen, Roger D Palmer, Balaji Muralidhar, Mark R Pett, Matias Piipari, Claire M Thornton, James C Nicholson, Anton J Enright, Nicholas Coleman
Journal: Molecular Cancer (2010)

We hypothesised that differences in microRNA expression profiles contribute to the contrasting natural history and clinical outcome of the two most common types of malignant germ cell tumour (GCT), yolk sac tumours (YSTs) and germinomas. By direct comparison, using microarray data for paediatric GCT samples and published qRT-PCR data for adult samples, we identified microRNAs significantly up-regulated in YSTs (n = 29 paediatric, 26 adult, 11 overlapping) or germinomas (n = 37 paediatric). By Taqman qRT-PCR we confirmed differential expression of 15 of 16 selected microRNAs and further validated six of these (miR-302b, miR-375, miR-200b, miR-200c, miR-122, miR-205) in an independent sample set. Interestingly, the miR-302 cluster, which is over-expressed in all malignant GCTs, showed further over-expression in YSTs versus germinomas, representing six of the top eight microRNAs over-expressed in paediatric YSTs and seven of the top 11 in adult YSTs. To explain this observation, we used mRNA expression profiles of paediatric and adult malignant GCTs to identify 10 transcription factors (TFs) consistently over-expressed in YSTs versus germinomas, followed by linear regression to confirm associations between TF and miR-302 cluster expression levels. Using the sequence motif analysis environment iMotifs, we identified predicted binding sites for four of the 10 TFs (GATA6, GATA3, TCF7L2 and MAF) in the miR-302 cluster promoter region. Finally, we showed that miR-302 family over-expression in YST is likely to be functionally significant, as mRNAs down-regulated in YSTs were enriched for 3' untranslated region sequences complementary to the common seed of miR-302a~miR-302d. Such mRNAs included mediators of key cancer-associated processes, including tumour suppressor genes, apoptosis regulators and TFs. Differential microRNA expression is likely to contribute to the relatively aggressive behaviour of YSTs and may enable future improvements in clinical diagnosis and/or treatment.
Jumonji and Cardiac Fate
Authors: Erik Willems, Mark Mercola
Journal: Circulation Research (2013)

C onsiderable information is known about the extracellular signals that drive pluripotent stem cells (PSCs) through a stepwise program to become cardiomyocytes.An article by Ohtani et al in this issue links extrinsic signals to histone demethylation needed to form mesoderm, the first step in cardiogenesis.
Embodied Cognition and Mirror Neurons: A Critical Assessment
Authors: Alfonso Caramazza, Stefano Anzellotti, Lukas Strnad, Angelika Lingnau
Journal: Annual Review of Neuroscience (2014)

According to embodied cognition theories, higher cognitive abilities depend on the reenactment of sensory and motor representations. In the first part of this review, we critically analyze the central claims of embodied theories and argue that the existing behavioral and neuroimaging data do not allow investigators to discriminate between embodied cognition and classical cognitive accounts, which assume that conceptual representations are amodal and symbolic. In the second part, we review the main claims and the core electrophysiological findings typically cited in support of the mirror neuron theory of action understanding, one of the most influential examples of embodied cognition theories. In the final part, we analyze the claim that mirror neurons subserve action understanding by mapping visual representations of observed actions on motor representations, trying to clarify in what sense the representations carried by these neurons can be claimed motor.
Analysis of Prognostic Factors in Patients With Nonmetastatic Rhabdomyosarcoma Treated on Intergroup Rhabdomyosarcoma Studies III and IV: The Children's Oncology Group
Authors: Jane L. Meza, James Anderson, Alberto S. Pappo, William H. Meyer
Journal: Journal of Clinical Oncology (2006)

Purpose The outcome for localized rhabdomyosarcoma (RMS) or undifferentiated sarcoma (UDS) is affected by age, histology, primary anatomic site, extent of disease, and therapy. Patients and Methods We evaluated patient and disease characteristics for their ability to predict outcome for patients with nonmetastatic RMS or UDS treated on Intergroup Rhabdomyosarcoma Study (IRS) -III (1984 to 1991) or IRS-IV (1991 to 1997). Results The estimated 5-year failure-free survival (FFS) rate was 90% for patients with embryonal RMS (ERMS) stage 1, group I or IIa; stage 2, group I; or group III orbit. The estimated 5-year FFS rate was 87% for patients with ERMS stage 1, group IIb or IIc; stage 1, group III nonorbit; stage 2, group II; and stage 3, group I or II; and 73% for patients with ERMS stage 2 or 3, group III. The estimated 5-year FFS rate was poor for patients with stage 2 or 3, group III ERMS with invasive (T2) tumors who were age younger than 1 year or 10 years or older (56%) and patients with stage 2 or 3, group III extremity primary tumors (43%). Overall, outcomes for patients with alveolar RMS (ARMS) or UDS were worse than for patients with ERMS. However, the 5-year FFS rate was good for patients with ARMS/UDS at favorable sites with group I or II (80%) or group III (76%) disease. The FFS rate was poorer for patients with ARMS/UDS at unfavorable sites with group I or II (66%) or group III (45%) disease. The estimated 5-year FFS rate was 31% for patients with group III ARMS/UDS at unfavorable sites with regional lymph node disease, which is similar to metastatic RMS. Conclusion Patient and disease characteristics identify distinct subsets with different outcomes, allowing the Soft Tissue Sarcoma Committee of the Children's Oncology Group to refine risk-adapted therapy assignment.
FURTHER OBSERVATIONS ON THE CULTIVATION OF VACCINE VIRUS FOR JENNERIAN PROPHYLAXIS IN MAN
Authors: Thomas M. Rivers, S. M. Ward
Journal: The Journal of Experimental Medicine (1933)

A dermal strain of vaccine virus has been passed through 99 successive culture passages. This procedure led to a diminution in the pathogenicity of the active agent for the rabbit. By repeated testicular passages in rabbits, however, the virus regained its pathogenicity for that host. New cultures were initiated with the revived virus. A culture strain of virus that has been twice revived in this manner has remained fairly stable for the rabbit through 60 culture passages and it produces mild, yet effective vaccinal reactions in man. Virus in early cultures was not attenuated for man, but later cultures of the original strain and cultures of the 2nd and 3rd revived strains produced mild reactions without fever and discomfort to the patients. Intradermal vaccinations with the culture virus are safe and satisfactory. With the culture virus 118 infants and children have been inoculated and in 100 of them a positive reaction occurred. The culture virus produced a refractory state to a standard dermal strain of calf lymph and vice versa. Culture virus stored in 50 per cent neutral glycerol at –10°C. or at +3°C. maintained a considerable amount of its activity for at least 1 year. Desiccated culture virus sealed in tubes maintained some of its activity when stored at 37°C. for 5 weeks. Fresh cultures can be initiated without difficulty from desiccated virus or from virus that has been stored with or without glycerol.
ISL-1 is overexpressed in non-Hodgkin lymphoma and promotes lymphoma cell proliferation by forming a p-STAT3/p-c-Jun/ISL-1 complex
Authors: Qiao Zhang, Zhe Yang, Zhuqing Jia, Cuiling Liu, Chen Guo, Huafei Lu, Ping Chen, Kangtao Ma, Weiping Wang, Chunyan Zhou
Journal: Molecular Cancer (2014)

Insulin enhancer binding protein-1 (ISL-1), a LIM-homeodomain transcription factor, is essential for the heart, motor neuron and pancreas development. Recently, ISL-1 has been found in some types of human cancers. However, how ISL-1 exerts the role in tumor development is not clear. The expression of ISL-1 was assessed in 211 human lymphoma samples and 23 normal lymph node samples. Immunohistochemistry results demonstrated a markedly higher expression of ISL-1 in 75% of non-Hodgkin lymphoma (NHL) samples compared with that in normal lymph nodes or Hodgkin lymphoma (HL) samples. CCK-8 analysis, cell cycle assay and xenograft model were performed to characterize the association between ISL-1 expression level and biological functions in NHL. The results showed that ISL-1 overexpression obviously promoted NHL cells proliferation, changed the cell cycle distribution in vitro and significantly enhanced xenografted lymphoma development in vivo. Real-time PCR, Western blot, luciferase assay and ChIP assay were used to explore the potential regulatory targets of ISL-1 and the results demonstrated that ISL-1 activated the c-Myc expression in NHL by direct binding to a conserved binding site on the c-Myc enhancer. Further results revealed that ISL-1 could be positively regulated by the c-Jun N-terminal kinase (JNK) and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways. Both the JNK and JAK/STAT signaling inhibitors could significantly suppressed the growth of NHL cells through the down-regulation of ISL-1 as demonstrated by CCK-8 and Western blot assays. Bioinformatic analysis and luciferase assay exhibited that ISL-1 was a novel target of p-STAT3 and p-c-jun. ChIP, Co-IP and ChIP-re-IP analysis revealed that ISL-1 could participate with p-STAT3 and p-c-Jun to form a p-STAT3/p-c-Jun/ISL-1 transcriptional complex that binds directly on the ISL-1 promoter, demonstrating a positive feedback regulatory mechanism for ISL-1 expression in NHL. Our results provide the first evidence that ISL-1 is tightly linked to NHL proliferation and development by promoting c-Myc transcription, and its aberrant expression was regulated by p-STAT3/p-c-Jun/ISL-1 complex activation.
Use of outpatient mental health services over time in a health maintenance organization and fee-for-service plans
Authors: W G Manning, K B Wells, B Benjamin
Journal: American Journal of Psychiatry (1987)

The authors compared the use of outpatient mental health services in a health maintenance organization (HMO) and fee-for-service plans over a 5-year period, using data from a randomized controlled trial. In any given year, enrollees in the HMO and a fee-for-service plan with identical benefits were equally likely to visit a mental health specialist. Over several years, the HMO enrollees were about 50% more likely ever to visit a mental health specialist; fee-for-service enrollees were more likely to receive mental health care in more than 1 study year.
Cortical and Subcortical Gray Matter Abnormalities in Schizophrenia Determined Through Structural Magnetic Resonance Imaging With Optimized Volumetric Voxel-Based Morphometry
Authors: Hema Ananth, Ioana Popescu, Hugo D. Critchley, Catriona D. Good, Richard S.J. Frackowiak, Raymond J. Dolan
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Structural neuroimaging studies have suggested an association between schizophrenia and abnormalities in brain morphology such as ventricular enlargement and differences in gray matter distribution. Less consistently reported are findings of regional abnormalities such as selective differences in thalamic volume. The authors applied an unbiased technique to test for differences in cerebral morphometry between patients with schizophrenia and matched comparison subjects. METHOD: T1-weighted images from 20 schizophrenic patients and matched comparison subjects were processed by using optimized automated voxel-based morphometry within multiple linear regression analyses. RESULTS: Global differences in gray matter volume were seen between the schizophrenic and comparison subjects, with selective regional gray matter differences noted in the mediodorsal thalamus and across cortical regions, including the ventral and medial prefrontal cortices. Within the schizophrenic subjects, a relationship was observed between gray matter volume loss in the medial prefrontal cortex and a positive family history of schizophrenia. There was no significant difference between patients and comparison subjects in rates of proportional gray matter reduction with age. CONCLUSIONS: These observations confirm an association between thalamocortical morphometric abnormalities and schizophrenia, consistent with theoretical models of primary pathoetiological dysfunction in filtering, integration, and information transfer processes in patients with schizophrenia.