tbuckley/cabot-search huggingface dataset:
O46 BARCELONA CLINIC LIVER CANCER STAGING AND THE NET BENEFIT OF LIVER RESECTION FOR PATIENTS WITH HEPATOCELLULAR CARCINOMA: A MULTICENTRE, COHORT STUDY
Authors: A. Vitale, T.-L. Huo, F. Trevisani, M. Volk, Y.-H. Lee, F. Farinati, U. Cillo
Journal: Journal of Hepatology (2014)
Neurotensin polyplex as an efficient carrier for delivering the human GDNF gene into nigral dopamine neurons of hemiparkinsonian rats
Authors: Juan A. Gonzalez-Barrios, Maria Lindahl, Michael J. Bannon, Veronica Anaya-Martínez, Gonzalo Flores, Ivan Navarro-Quiroga, Louis E. Trudeau, Jorge Aceves, Daniel B. Martinez-Arguelles, Refugio Garcia-Villegas, Ismael Jiménez, Jose Segovia, Daniel Martinez-Fong
Journal: Molecular Therapy (2006)

Recently we showed that the neurotensin polyplex is a nanoparticle carrier system that targets reporter genes in nigral dopamine neurons in vivo. Herein, we report its first practical application in experimental parkinsonism, which consisted of transfecting dopamine neurons with the gene coding for human glial cell line-derived neurotrophic factor (hGDNF). Hemiparkinsonism was induced in rats by a single dose of 6-hydroxydopamine (30 microg) into the ventrolateral part of the striatum. We showed that transfection of the hGDNF gene into the substantia nigra of rats 1 week after the neurotoxin injection produced biochemical, anatomical, and functional recovery from hemiparkinsonism. RT-PCR analysis showed mRNA expression of exogenous hGDNF in the transfected substantia nigra. Western blot analysis verified transgene expression by recognizing the flag epitope added at the C-terminus of the hGDNF polypeptide, which was found mainly in dopamine neurons by double immunofluorescence techniques. These data indicate that the neurotensin polyplex holds great promise for the neuroprotective therapy of Parkinson disease.
Mitochondrial energetic and AKT status mediate metabolic effects and apoptosis of metformin in human leukemic cells
Authors: S Scotland, E Saland, N Skuli, F de Toni, H Boutzen, E Micklow, I Sénégas, R Peyraud, L Peyriga, F Théodoro, E Dumon, Y Martineau, G Danet-Desnoyers, F Bono, C Rocher, T Levade, S Manenti, C Junot, J-C Portais, N Alet, C Récher, M A Selak, M Carroll, J-E Sarry
Journal: Leukemia (2013)
Renal cell carcinoma in autosomal dominant polycystic kidney disease.
Authors: D S Keith, V E Torres, B F King, H Zincki, G M Farrow
Journal: Journal of the American Society of Nephrology (1994)

To provide information on the clinical presentation, diagnosis, pathology, and biologic behavior of renal cell carcinoma in patients with autosomal dominant polycystic kidney disease (ADPKD), three cases seen at this institution between 1955 and 1992, as well as the cases reported in the literature, were reviewed in detail. No male predominance was observed (12 men, 13 women) in the 25 patients who met the inclusion criteria. The age of presentation was earlier than that seen in the general population (45 versus 61 yr). Fever, night sweats, and weight loss were prominent at presentation. Fever is a more common presenting symptom of renal cell carcinoma in ADPKD (32%) than in the general population (7%). Twenty percent of the patients had metastatic disease at presentation. Even with computed tomography and magnetic resonance, the diagnosis was difficult and often delayed, and the accumulation of 111In-labeled white blood cells can wrongly suggest a cyst infection. Renal cell carcinoma in ADPKD is more often concurrently bilateral (12 versus 1 to 5%), multicentric (28 versus 6%), and sarcomatoid in type (33 versus 1 to 5%) than in the general population. Because previous studies have failed to demonstrate a higher prevalence of renal cell carcinoma in ADPKD, this information suggests either a malignant potential restricted to a small subset of patients with this disease or an alteration in the biologic behavior of renal cell carcinoma when it develops in the setting of ADPKD.
Future of Cholesteryl Ester Transfer Protein Inhibitors
Authors: Daniel J. Rader, Emil M. deGoma
Journal: Annual Review of Medicine (2014)

The cholesteryl ester transfer protein (CETP) plays an integral role in the metabolism of plasma lipoproteins. Despite two failures, CETP inhibitors are still in clinical development. We review the genetics of CETP and coronary disease, preclinical data on CETP inhibition and atherosclerosis, and the effects of CETP inhibition on cholesterol efflux and reverse cholesterol transport. We discuss the two failed CETP inhibitors, torcetrapib and dalcetrapib, and attempt to extract lessons learned. Two CETP inhibitors, anacetrapib and evacetrapib, are in phase III development, and we attempt to differentiate them from the failed drugs. Whether pharmacologic CETP inhibition will reduce the risk of cardiovascular disease is one of the most fascinating and important questions in the field of cardiovascular medicine.
T Helper 1 Cells and Interferon γ Regulate Allergic Airway Inflammation and Mucus Production
Authors: Lauren Cohn, Robert J. Homer, Naiqian Niu, Kim Bottomly
Journal: The Journal of Experimental Medicine (1999)

CD4 T helper (Th) type 1 and Th2 cells have been identified in the airways of asthmatic patients. Th2 cells are believed to contribute to pathogenesis of the disease, but the role of Th1 cells is not well defined. In a mouse model, we previously reported that transferred T cell receptor-transgenic Th2 cells activated in the respiratory tract led to airway inflammation with many of the pathologic features of asthma, including airway eosinophilia and mucus production. Th1 cells caused inflammation with none of the pathology associated with asthma. In this report, we investigate the role of Th1 cells in regulating airway inflammation. When Th1 and Th2 cells are transferred together into recipient mice, there is a marked reduction in airway eosinophilia and mucus staining. To address the precise role of Th1 cells, we asked (i), Are Th2-induced responses inhibited by interferon (IFN)-gamma? and (ii) Can Th1 cells induce eosinophilia and mucus in the absence of IFN-gamma? In IFN-gamma receptor(-/-) recipient mice exposed to inhaled antigen, the inhibitory effects of Th1 cells on both airway eosinophilia and mucus production were abolished. In the absence of IFN-gamma receptor signaling, Th1 cells induced mucus but not eosinophilia. Thus, we have identified new regulatory pathways for mucus production; mucus can be induced by Th2 and non-Th2 inflammatory responses in the lung, both of which are inhibited by IFN-gamma. The blockade of eosinophilia and mucus production by IFN-gamma likely occurs through different inhibitory pathways that are activated downstream of Th2 cytokine secretion and require IFN-gamma signaling in tissue of recipient mice.
Role of Chemokines in Endocrine Autoimmune Diseases
Authors: Mario Rotondi, Luca Chiovato, Sergio Romagnani, Mario Serio, Paola Romagnani
Journal: Endocrine Reviews (2007)

Chemokines are a group of peptides of low molecular weight that induce the chemotaxis of different leukocyte subtypes. The major function of chemokines is the recruitment of leukocytes to inflammation sites, but they also play a role in tumoral growth, angiogenesis, and organ sclerosis. In the last few years, experimental evidence accumulated supporting the concept that interferon-γ (IFN-γ) inducible chemokines (CXCL9, CXCL10, and CXCL11) and their receptor, CXCR3, play an important role in the initial stage of autoimmune disorders involving endocrine glands. The fact that, after IFN-γ stimulation, endocrine epithelial cells secrete CXCL10, which in turn recruits type 1 T helper lymphocytes expressing CXCR3 and secreting IFN-γ, thus perpetuating autoimmune inflammation, strongly supports the concept that chemokines play an important role in endocrine autoimmunity. This article reviews the recent literature including basic science, animal models, and clinical studies, regarding the role of these chemokines in autoimmune endocrine diseases. The potential clinical applications of assaying the serum levels of CXCL10 and the value of such measurements are reviewed. Clinical studies addressing the issue of a role for serum CXCL10 measurement in Graves’ disease, Graves’ ophthalmopathy, chronic autoimmune thyroiditis, type 1 diabetes mellitus, and Addison’s disease have been considered. The principal aim was to propose that chemokines, and in particular CXCL10, should no longer be considered as belonging exclusively to basic science, but rather should be used for providing new insights in the clinical management of patients with endocrine autoimmune diseases.
ASCO/SSO Review of Current Role of Risk-Reducing Surgery in Common Hereditary Cancer Syndromes
Authors: José G. Guillem, William C. Wood, Jeffrey F. Moley, Andrew Berchuck, Beth Y. Karlan, David G. Mutch, Robert F. Gagel, Jeffrey Weitzel, Monica Morrow, Barbara L. Weber, Francis Giardiello, Miguel A. Rodriguez-Bigas, James Church, Stephen Gruber, Kenneth Offit
Journal: Journal of Clinical Oncology (2006)

Although the etiology of solid cancers is multifactorial, with environmental and genetic factors playing a variable role, a significant portion of the burden of cancer is accounted for by a heritable component. Increasingly, the heritable component of cancer predispositions has been linked to mutations in specific genes, and clinical interventions have been formulated for mutation carriers within affected families. The primary interventions for mutations carriers for highly penetrant syndromes such as multiple endocrine neoplasias, familial adenomatous polyposis, hereditary nonpolyposis colon cancer, and hereditary breast and ovarian cancer syndromes are primarily surgical. For that reason, the American Society of Clinical Oncology (ASCO) and the Society of Surgical Oncology (SSO) have undertaken an educational effort within the oncology community. A joint ASCO/SSO Task Force was charged with presenting an educational symposium on the surgical management of hereditary cancer syndromes at the annual ASCO and SSO meetings, resulting in an educational position article on this topic. Both the content of the symposium and the article were developed as a consensus statement by the Task Force, with the intent of summarizing the current standard of care. This article is divided into four sections addressing breast, colorectal, ovarian and endometrial cancers, and multiple endocrine neoplasia. For each, a brief introduction on the genetics and natural history of the disease is provided, followed by a detailed description of modern surgical approaches, including a description of the clinical and genetic indications and timing of prophylactic surgery, and the efficacy of prophylactic surgery when known. Although a number of recent reviews have addressed the role of genetic testing for cancer susceptibility, including the richly illustrated Cancer Genetics and Cancer Predisposition Testing curriculum by the ASCO Cancer Genetics Working Group (available through http://www.asco.org), this article focuses on the issues surrounding the why, how, and when of surgical prophylaxis for inherited forms of cancer. This is a complex process, which requires a clear understanding of the natural history of the disease and variance of penetrance, a realistic appreciation of the potential benefit and risk of a risk-reducing procedure in a potentially otherwise healthy individual, the long-term sequelae of such surgical intervention, as well as the individual patient and family's perception of surgical risk and anticipated benefit.
Can mannose-binding lectin explain the course and outcome of pregnancy in rheumatoid arthritis?
Authors: F. E. van de Geijn, Y. A. de Man, M. Wuhrer, S. P. Willemsen, A. M. Deelder, J. M. W. Hazes, R. J. E. M. Dolhain
Journal: Annals of the Rheumatic Diseases (2010)

Rheumatoid arthritis (RA) improves during pregnancy and flares after delivery. It has been hypothesised that high levels of the complement factor mannose binding lectin (MBL) are associated with a favourable disease course of R A by facilitating the clearance of pathogenic immunoglobulin G (IgG) lacking galactose sugar moieties. During pregnancy, …
PSYCHODYNAMIC PATTERNS IN THE HOMOSEXUAL SEX OFFENDER
Authors: BERNARD C. GLUECK
Journal: American Journal of Psychiatry (1956)

In this paper an attempt has been made to describe some of the psychodynamic factors in the homosexual pedophile. A description of the general research setting is followed by a discussion of 4 general formulations of the psychodynamics of the sexual offender. These are: 1. A consideration of the serious nature of the psychopathology present in the men studied, with indications that 76% of the homosexual pedophiles are using some type of schizophrenic adaptation. 2. The existence of marked fears of approaching an adult female sex object, with corresponding genital diminution fears. 3. Serious impairment of the capacity for abstract thinking, with impaired ability to utilize fantasy or other mechanisms involving abstractive capacity as an outlet for sexual conflicts and tensions. 4. Serious impairment of conscience formation, and resultant impairment of the restraining effects of conscience on overt behavior. The serious character of the psychopathology in the sexual offenders makes therapeutic approaches, based on the formulation that these are primarily psychoneurotic disturbances, quite ineffective. Some of the therapeutic efforts utilizing organic therapies, particularly electroshock, are described.
Sympathomimetic Agents in the Treatment of Shock
Authors: ROBERT C. TARAZI
Journal: Annals of Internal Medicine (1974)

Sympathomimetic drugs can be very useful in the treatment of shock but only when used as part of an overall therapeutic plan to improve tissue perfusion and deal with the pathophysiological abnormalities in each situation. They can be classified according to [1] the target organ, [2] the type of action (direct or indirect), and [3] the specific adrenergic receptor stimulated. In addition, secondary effects, such as the influence of increased arterial pressure on cardiac function, must be taken into account. Vasodilatation or vasoconstriction might not be equal in all vascular beds, and the effect of either can be markedly influenced by local vascular lesions. The choice of the most effective agent, therefore, entails careful balance between its effects and the hemodynamic disorder—hence, the need for careful, continuous monitoring for diagnosis, follow-up, and readjustment of treatment. Occasionally, a combination of drugs can help achieve a proper balance between cardiac and peripheral effects.
Increased Visceral Fat and Serum Levels of Triglyceride Are Associated With Insulin Resistance in Japanese Metabolically Obese, Normal Weight Subjects With Normal Glucose Tolerance
Authors: Akira Katsuki, Yasuhiro Sumida, Hideki Urakawa, Esteban C. Gabazza, Shuichi Murashima, Noriko Maruyama, Kohei Morioka, Kaname Nakatani, Yutaka Yano, Yukihiko Adachi
Journal: Diabetes Care (2003)

The purpose of this study was to investigate the association between visceral adiposity or triglyceride (TG) metabolism and insulin resistance in metabolically obese, normal weight (MONW) Japanese individuals with normal glucose tolerance.We evaluated body fat areas, lipid profiles, and the glucose infusion rate (GIR) during a euglycemic-hyperinsulinemic clamp study in 20 MONW subjects (BMI <25 kg/m(2)and visceral fat areas 100 cm(2)) with normal glucose tolerance. Body fat areas were measured by computed tomography scans. Control data were obtained from 20 normal subjects (BMI <25 kg/m(2) and visceral fat areas <100 cm(2)).MONW subjects showed a significant increase in fasting serum levels of TG (P < 0.01) and a decrease in GIR (P < 0.01) compared with normal subjects. There were significant correlations between visceral fat areas (r = -0.563, P < 0.01) or serum levels of TG (r = -0.474, P < 0.05) and GIR in MONW subjects. Multiple regression analyses showed that visceral fat areas (F = 7.702, P < 0.02) and serum levels of TG (F = 7.114, P < 0.05) were significantly associated with GIR in all (MONW and normal) subjects.Increased visceral fat and serum levels of TG are associated with insulin resistance in Japanese MONW subjects with normal glucose tolerance. Excess visceral fat and elevated TG levels may play important roles in the development of insulin resistance in Japanese MONW subjects with normal glucose tolerance.
Accumulation of p53 Tumor Suppressor Gene Protein: An Independent Marker of Prognosis in Breast Cancers
Authors: A. D. Thor, D. H. Moore, S. M. Edgerton, E. S. Kawasaki, E. Reihsaus, H. T. Lynch, J. N. Marcus, L. Schwartz, L.-C. Chen, B. H. Mayall, H. S. Smith
Journal: JNCI Journal of the National Cancer Institute (1992)

Journal Article Accumulation of p53 Tumor Suppressor Gene Protein: An Independent Marker of Prognosis in Breast Cancers Get access Ann D. Thor, Ann D. Thor * Department of Pathology, Massachusetts General Hospital and Harvard Medical SchoolBoston, Mass *Correspondence to : Ann D. Thor, M.D., Department of Pathology, Warren 2, Massachusetts General Hospital, Fruit St., Boston, MA 02114. Search for other works by this author on: Oxford Academic PubMed Google Scholar Dan H. Moore, II, Dan H. Moore, II Biomedical Sciences Division, Lawrence Livermore National LaboratoriesLivermore, Calif Search for other works by this author on: Oxford Academic PubMed Google Scholar Susan M. Edgerton, Susan M. Edgerton Department of Pathology, Massachusetts General Hospital and Harvard Medical SchoolBoston, Mass Search for other works by this author on: Oxford Academic PubMed Google Scholar Ernest S. Kawasaki, Ernest S. Kawasaki Department of Human Genetics, Cetus Corp.Emeryville, Calif Search for other works by this author on: Oxford Academic PubMed Google Scholar Ellen Reihsaus, Ellen Reihsaus Department of Human Genetics, Cetus Corp.Emeryville, Calif Search for other works by this author on: Oxford Academic PubMed Google Scholar Henry T. Lynch, Henry T. Lynch Department of Preventive Medicine and Pathology, Creighton UniversityOmaha, Neb Search for other works by this author on: Oxford Academic PubMed Google Scholar Joseph N. Marcus, Joseph N. Marcus Department of Preventive Medicine and Pathology, Creighton UniversityOmaha, Neb Search for other works by this author on: Oxford Academic PubMed Google Scholar Laurent Schwartz, Laurent Schwartz Department of Radiation Medicine, Massachusetts General Hospital and Harvard Medical SchoolBoston, Mass Search for other works by this author on: Oxford Academic PubMed Google Scholar Ling-Chun Chen, Ling-Chun Chen Geraldine Brush Cancer Research Institute at the California Pacific Medical CenterSan Francisco Search for other works by this author on: Oxford Academic PubMed Google Scholar Brian H. Mayall, Brian H. Mayall Department of Laboratory Medicine, University of CaliforniaSan Francisco Search for other works by this author on: Oxford Academic PubMed Google Scholar ... Show more Helene S. Smith Helene S. Smith Geraldine Brush Cancer Research Institute at the California Pacific Medical CenterSan Francisco Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 11, 3 June 1992, Pages 845–855, https://doi.org/10.1093/jnci/84.11.845 Published: 03 June 1992 Article history Received: 09 August 1991 Revision received: 31 December 1991 Accepted: 19 February 1992 Published: 03 June 1992
Prohibitin Is a Novel Target Gene of Vitamin D Involved in Its Antiproliferative Action in Breast Cancer Cells
Authors: Xinjian Peng, Rajeshwari Mehta, Sheng Wang, Srikumar Chellappan, Rajendra G. Mehta
Journal: Cancer Research (2006)

Abstract Previously, we showed that N-methyl-N-nitrosourea–transformed MCF12F breast epithelial cells exhibited differential expression of several genes, including up-regulation of prohibitin and elevated sensitivity to a relatively noncalcemic vitamin D analogue, 1α-hydroxyvitamin D5 [1α(OH)D5]. In this report, we evaluated the functional significance of prohibitin in relation to the cellular response to vitamin D. The in silico screening for putative transcription factor binding sites identified two vitamin D receptor (VDR)/retinoid X receptor binding sites in the 1-kb promoter region of prohibitin. Prohibitin up-regulation by 1α(OH)D5 treatment at both transcriptional and translational levels was confirmed by real-time reverse transcription-PCR and Western blot analysis in breast cancer cells, identifying prohibitin as a vitamin D target gene. Confocal microscopic analysis showed that prohibitin was localized in the nuclei of MCF-7 cells and a portion of prohibitin was colocalized with VDR, but direct physical interaction between VDR and prohibitin in cell lysates was not detectable. In MCF-7 cells expressing tetracycline-inducible prohibitin (Tet-On model), the overexpression of prohibitin inhibited cell proliferation and enhanced vitamin D–induced antiproliferative activity. Knockdown of prohibitin was accompanied by increased number of cells incorporating bromodeoxyuridine in the whole population and increased cell distribution in the S phase of cell cycle. In addition, prohibitin level had no significant effect on the vitamin D–induced transactivation of CYP24, a VDR target gene. This is the first report to suggest that prohibitin serves as a novel vitamin D target gene, which is involved in the antiproliferative action of vitamin D without affecting CYP24 transactivation in breast cancer cells. (Cancer Res 2006; 66(14): 7361-9)
Posttranslational modifications of α-tubulin in alzheimer disease
Authors: Fan Zhang, Bo Su, Chunyu Wang, Sandra L Siedlak, Siddhartha Mondragon-Rodriguez, Hyoung-Gon Lee, Xinglong Wang, George Perry, Xiongwei Zhu
Journal: Translational Neurodegeneration (2015)

In Alzheimer disease (AD), hyperphosphorylation of tau proteins results in microtubule destabilization and cytoskeletal abnormalities. Our prior ultra-morphometric studies documented a clear reduction in microtubules in pyramidal neurons in AD compared to controls, however, this reduction did not coincide with the presence of paired helical filaments. The latter suggests the presence of compensatory mechanism(s) that stabilize microtubule dynamics despite the loss of tau binding and stabilization. Microtubules are composed of tubulin dimers which are subject to posttranslational modifications that affect the stability and function of microtubules.In this study, we performed a detailed analysis on changes in the posttranslational modifications in tubulin in postmortem human brain tissues from AD patients and age-matched controls by immunoblot and immunocytochemistry.Consistent with our previous study, we found decreased levels of α-tubulin in AD brain. Levels of tubulin with various posttranslational modifications such as polyglutamylation, tyrosination, and detyrosination were also proportionally reduced in AD brain, but, interestingly, there was an increase in the proportion of the acetylated α-tubulin in the remaining α-tubulin. Tubulin distribution was changed from predominantly in the processes to be more accumulated in the cell body. The number of processes containing polyglutamylated tubulin was well preserved in AD neurons. While there was a cell autonomous detrimental effect of NFTs on tubulin, this is likely a gradual and slow process, and there was no selective loss of acetylated or polyglutamylated tubulin in NFT-bearing neurons.Overall, we suggest that the specific changes in tubulin modification in AD brain likely represent a compensatory response.