tbuckley/cabot-search huggingface dataset:
CD137 costimulatory T cell receptor engagement reverses acute disease in lupus-prone NZB × NZW F1 mice
Authors: Juergen Foell, Simona Strahotin, Shawn P. O’Neil, Megan M. McCausland, Carolyn Suwyn, Michael Haber, Praveen N. Chander, Abhijit S. Bapat, Xiao-Jie Yan, Nicholas Chiorazzi, Michael K. Hoffmann, Robert S. Mittler
Journal: Journal of Clinical Investigation (2003)

Systemic lupus erythematosus (SLE) is a CD4+ T cell–dependent, immune complex–mediated, autoimmune disease that primarily affects women of childbearing age. Generation of high-titer affinity-matured IgG autoantibodies, specific for double-stranded DNA and other nuclear antigens, coincides with disease progression. Current forms of treatment of SLE including glucocorticosteroids are often inadequate and induce severe side effects. Immunological approaches for treating SLE in mice using anti-CD4 mAb's or CTLA4-Ig and anti-CD154 mAb's have proven to be effective. However, like steroid treatment, these regimens induce global immunosuppression, and their withdrawal allows for disease progression. In this report we show that lupus-prone NZB × NZW F1 mice given three injections of anti-CD137 (4-1BB) mAb's between 26 and 35 weeks of age reversed acute disease, blocked chronic disease, and extended the mice's lifespan from 10 months to more than 2 years. Autoantibody production in recipients was rapidly suppressed without inducing immunosuppression. Successful treatment could be traced to the fact that NZB × NZW F1 mice, regardless of their age or disease status, could not maintain pathogenic IgG autoantibody production in the absence of continuous CD4+ T cell help. Our data support the hypothesis that CD137-mediated signaling anergized CD4+ T cells during priming at the DC interface.
Mechanisms of Mitotic Cell Death Induced by Chemotherapy-Mediated G2 Checkpoint Abrogation
Authors: Celia Vogel, Christian Hager, Holger Bastians
Journal: Cancer Research (2007)

Abstract The novel concept of anticancer treatment termed “G2 checkpoint abrogation” aims to target p53-deficient tumor cells and is currently explored in clinical trials. The anticancer drug UCN-01 is used to abrogate a DNA damage–induced G2 cell cycle arrest leading to mitotic entry and subsequent cell death, which is poorly defined as “mitotic cell death” or “mitotic catastrophe.” We show here that UCN-01 treatment results in a mitotic arrest that requires an active mitotic spindle checkpoint, involving the function of Mad2, Bub1, BubR1, Mps1, Aurora B, and survivin. During the mitotic arrest, hallmark parameters of the mitochondria-associated apoptosis pathway become activated. Interestingly, this apoptotic response requires the spindle checkpoint protein Mad2, suggesting a proapoptotic function for Mad2. However, although survivin and Aurora B are also required for the mitotic arrest, both proteins are part of an antiapoptotic pathway that restrains the UCN-01–induced apoptosis by promoting hyperphosphorylation of Bcl-2 and by inhibiting the activation of Bax. Consequently, inhibition of the antiapoptotic pathway by genetic ablation of survivin or by pharmacologic inhibitors of Aurora B or cyclin-dependent kinase 1 lead to a significant enhancement of apoptosis and therefore act synergistically with UCN-01. Thus, by defining the mechanism of cell death on G2 checkpoint abrogation we show a highly improved strategy for an anticancer treatment by the combined use of UCN-01 with abrogators of the survivin/Aurora B–dependent antiapoptotic pathway that retains the selectivity for p53-defective cancer cells. [Cancer Res 2007;67(1):339–45]
THE EFFECT OF INJURY BY TOXIC AGENTS UPON OSMOTIC PRESSURE MAINTAINED BY CELLS OF LIVER AND OF KIDNEY
Authors: Eugene L. Opie
Journal: The Journal of Experimental Medicine (1950)

As shown in a previous paper the cells of the liver and of the kidney maintain an osmotic pressure approximately twice that of blood and of erythrocytes, exceeding this slightly in the case of liver and being slightly less in that of kidney. When liver cells are injured by chloroform or by carbon tetrachloride the osmotic pressure they maintain falls to the level of the medium that surrounds them but is promptly restored when recovery from the injury, with some regeneration of liver cells, occurs. When nephrosis is caused by potassium chromate or by chloroform the osmotic pressure maintained by parenchymatous cells of the renal cortex falls to that of the medium about them but returns to its normal level with recovery from the injury.
Food Faddism, Cultism, and Quackery
Authors: William T. Jarvis
Journal: Annual Review of Nutrition (1983)

INTRODUCTION . . . . .. . .. . . . . . . . . . .. .... .. . . . . . . . . .. . . . . . . .. . . . . . . . ... .... . .. . . . . . . . . . . . . .... . . . . . . . . 36 DEFINITIONS . . . . . . . . . . . . . . . . . . . . . . . ... . .... . . . ... . . . . . . . . . . . . . . . . . . ... . . ...... . .. . . . . . . . . . . .. .. . . . . . . 36 MAGICAL THINKING ABOUT FOOD . . . . .. . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . ... . . . . 37 WHY FOOD FADDISM PERSISTS . . .. . . .... . . . . . . . . . . . . . . . . . . . . . . ... .... . . . . . . . . . . . . . . . . . . . 38 Human Vulnerability   38 How Nutrition Education Unwittingly Aids Food Faddism...... . . . . . . . . . . . . . . . .... . . . . . 39 Food Symbolism  40 Basic Fallacies Persist  . . . . ..... .   . . . .   . . ...... 41 HARM DONE BY FOOD FADDISM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41 Fatalities Related to Food Faddism   42 Dangers From Herbs . . .. . . . . . . . . . . . . . . .. . . .. . . . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . 42 Malnutrition..   .....     ...... 43 Economic Harm  43 Distortion of Perspective  .   . . . . . 43 CURRENT PRACTICES . . . . . . . .. . . . . . . . . . . . . . . . . ... . . . . . ... . . . . . . . . . . . . . . . . . . . . . .. . . . .. . . . . . . . . . . . . 45 Pseudo-Nutrition Experts  45 Pyramid Sales Schemes... . . . . .. . . . . . . . . ... . . . . . . . . . . ........ . . . . .. . . . ....... . . . . . . . . . . . 45 Vitam!� and Mineral Supplement Promotion by Pharmaceutical Companies . . . . . . . . .. 46 Practitioners. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 Health Books. Magazines, and Pseudoscientific Journals  47 COPING WITH FOOD FADDISM . . .. .. . .. .. . . . . . ... . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . .. . . . . . . . . 48 Education. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Health Care Deliverers       49 The Law . ... . . . . . . . .. . . . .. . . . .. . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . .. 49 CONCLUSION . . . . . . .. . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . .. ... . . . . . . . . . . . . . . .. . . . 49
Congenital toxoplasmosis and TORCH
Authors: D.H.M Joynson, C Verhofstede, L Van Renterghem, J Plum, S Vanderschueren, P Vanhaesebrouck, AndréJ Nahmias, RichardW Blumberg, DavidR Jenkins, T.S Brand, D.O Ho-Yen, A.W.L Joss, J.M.W Chatterton, Jan Desmyter, Patrick Goubau, Gilbert Donders
Journal: The Lancet (1990)
The 2′-O-methylation status of a single guanosine controls transfer RNA–mediated Toll-like receptor 7 activation or inhibition
Authors: Stefanie Jöckel, Gernot Nees, Romy Sommer, Yang Zhao, Dmitry Cherkasov, Hiroyuki Hori, Gundi Ehm, Markus Schnare, Marianne Nain, Andreas Kaufmann, Stefan Bauer
Journal: The Journal of Experimental Medicine (2012)

Foreign RNA serves as pathogen-associated molecular pattern (PAMP) and is a potent immune stimulator for innate immune receptors. However, the role of single bacterial RNA species in immune activation has not been characterized in detail. We analyzed the immunostimulatory potential of transfer RNA (tRNA) from different bacteria. Interestingly, bacterial tRNA induced type I interferon (IFN) and inflammatory cytokines in mouse dendritic cells (DCs) and human peripheral blood mononuclear cells (PBMCs). Cytokine production was TLR7 dependent because TLR7-deficient mouse DCs did not respond and TLR7 inhibitory oligonucleotides inhibited tRNA-mediated activation. However, not all bacterial tRNA induced IFN-α because tRNA from Escherichia coli Nissle 1917 and Thermus thermophilus were non-immunostimulatory. Of note, tRNA from an E. coli knockout strain for tRNA (Gm18)-2'-O-methyltransferase (trmH) regained immunostimulatory potential. Additionally, in vitro methylation of this immunostimulatory Gm18-negative tRNA with recombinant trmH from T. thermophilus abolished its IFN-α inducing potential. More importantly, Gm18-modified tRNA acted as TLR7 antagonist and blocked IFN-α induction of influenza A virus-infected PBMCs.
CtIP-mediated resection is essential for viability and can operate independently of BRCA1
Authors: Federica Polato, Elsa Callen, Nancy Wong, Robert Faryabi, Samuel Bunting, Hua-Tang Chen, Marina Kozak, Michael J. Kruhlak, Colleen R. Reczek, Wen-Hwa Lee, Thomas Ludwig, Richard Baer, Lionel Feigenbaum, Stephen Jackson, André Nussenzweig
Journal: The Journal of Experimental Medicine (2014)

Homologous recombination (HR) is initiated by DNA end resection, a process in which stretches of single-strand DNA (ssDNA) are generated and used for homology search. Factors implicated in resection include nucleases MRE11, EXO1, and DNA2, which process DNA ends into 3′ ssDNA overhangs; helicases such as BLM, which unwind DNA; and other proteins such as BRCA1 and CtIP whose functions remain unclear. CDK-mediated phosphorylation of CtIP on T847 is required to promote resection, whereas CDK-dependent phosphorylation of CtIP-S327 is required for interaction with BRCA1. Here, we provide evidence that CtIP functions independently of BRCA1 in promoting DSB end resection. First, using mouse models expressing S327A or T847A mutant CtIP as a sole species, and B cells deficient in CtIP, we show that loss of the CtIP-BRCA1 interaction does not detectably affect resection, maintenance of genomic stability or viability, whereas T847 is essential for these functions. Second, although loss of 53BP1 rescues the embryonic lethality and HR defects in BRCA1-deficient mice, it does not restore viability or genome integrity in CtIP−/− mice. Third, the increased resection afforded by loss of 53BP1 and the rescue of BRCA1-deficiency depend on CtIP but not EXO1. Finally, the sensitivity of BRCA1-deficient cells to poly ADP ribose polymerase (PARP) inhibition is partially rescued by the phospho-mimicking mutant CtIP (CtIP-T847E). Thus, in contrast to BRCA1, CtIP has indispensable roles in promoting resection and embryonic development.
Transcardiac increase in tumor necrosis factor‐α and left ventricular end‐diastolic volume in patients with dilated cardiomyopathy
Authors: Takayoshi Tsutamoto, Atsuyuki Wada, Masato Ohnishi, Takashi Tsutsui, Chitose Ishii, Keijin Ohno, Masanori Fujii, Takehiro Matsumoto, Takashi Yamamoto, Tomoyuki Takayama, Tomohiro Dohke, Minoru Horie
Journal: European Journal of Heart Failure (2003)
Impact of Dietary Patterns and Interventions on Cardiovascular Health
Authors: Ignatius G.E. Zarraga, Ernst R. Schwarz
Journal: Circulation (2006)

D ietary recommendations are a key element in the man- agement of cardiovascular disease.Evidence is mounting that certain dietary patterns can influence cardiovascular health by modifying risk factors such as obesity, dyslipidemia, and hypertension, as well as factors involved in systemic inflammation, insulin sensitivity, oxidative stress, endothelial function, thrombosis, and cardiac rhythm. 1,2In recent years, numerous dietary fads have emerged, in part as a response to the rising prevalence of obesity in the United States. 3In the present study, we review the various dietary portfolios that have emerged in the literature and the major studies that investigated their effectiveness in modifying cardiovascular risk.
Concordance of the management of chronic gout in a UK primary-care population with the EULAR gout recommendations
Authors: E. Roddy, W. Zhang, M. Doherty
Journal: Annals of the Rheumatic Diseases (2007)

To assess concordance of the management of chronic gout in UK primary care with the European League Against Rheumatism (EULAR) gout recommendations.A postal questionnaire was sent to all adults aged >30 years registered with two general practices. Patients with possible gout attended for clinical assessment, at which the diagnosis was verified clinically. Aspects of chronic gout management, including provision of lifestyle modification advice, use of urate-lowering therapies (ULT) including dose titration to serum urate (SUA) level, prophylaxis against acute attacks, and diuretic cessation were assessed in accordance with the EULAR recommendations.Of 4249 (32%) completed questionnaires returned, 488 reported gout or acute attacks and were invited for clinical assessment. Of 359 attendees, 164 clinically confirmed cases of gout were identified. Advice regarding alcohol consumption was recalled by 59 (41%), weight loss by 36 (25%) and diet by 42 (29%). Allopurinol was the only ULT used and was taken by 44 (30%); 31 (70%) were taking 300 mg daily. Mean SUA was lower in allopurinol users than non-users (318 vs 434 micromol/l) and was less often >360 micromol/l in allopurinol users (23% vs 75%). Eight patients had recently commenced allopurinol; two of these also were taking prophylactic colchicine or non-steroidal anti-inflammatory drugs. Of 25 patients with diuretic-induced gout, 16 (64%) were still taking a diuretic.Treatment of chronic gout is often suboptimal and poorly concordant with EULAR recommendations. Lifestyle advice is infrequently offered, and allopurinol is restricted to a minority. Persistent hyperuricaemia was often seen in allopurinol non-users, but was also in allopurinol users, suggesting that doses >300 mg are often necessary.
A 12-Month Follow-Up Study of the Course of Body Dysmorphic Disorder
Authors: Katharine Phillips
Journal: American Journal of Psychiatry (2006)

Objective: This study investigated the course of body dysmorphic disorder (BDD), a relatively common and severe disorder, in the first prospective follow-up study, to the authors’ knowledge. Method: In this study, the authors obtained data with the Longitudinal Interval Follow-Up Evaluation on weekly BDD symptom status and treatment received over 1 year for 183 broadly ascertained subjects. Probabilities of full remission, partial remission, and relapse during this year were examined. Full remission was defined as minimal or no BDD symptoms and partial remission, as meeting less than full DSM-IV criteria for at least 8 consecutive weeks. Relapse was defined as meeting full BDD criteria for at least 2 consecutive weeks after attaining partial or full remission from BDD. Results: Over 1 year, the probability of full remission from BDD was only 0.09, and the probability of partial remission was 0.21. Although 84.2% of the subjects received mental health treatment during the 1-year period, mean BDD severity scores during the year reflected full DSM-IV criteria for BDD, and the mean proportion of time that the subjects met full BDD criteria was 80%. Gender and ethnicity did not significantly predict remission from BDD. Among the subjects whose BDD symptoms partially or fully remitted, the probability of relapse was 0.15. Conclusions: These findings indicate that BDD tends to be chronic. Remission probabilities were lower than reported for mood disorders, most anxiety disorders, and personality disorders in studies with similar methods.
Doppler ultrasonography of the anterior knee tendons in elite badminton players: colour fraction before and after match
Authors: M J Koenig, S Torp-Pedersen, M I Boesen, C C Holm, H Bliddal
Journal: British Journal of Sports Medicine (2008)

Background Anterior knee tendon problems are seldom reported in badminton players although the game is obviously stressful to the lower extremities. Hypotheses Painful anterior knee tendons are common among elite badminton players. The anterior knee tendons exhibit colour Doppler activity. This activity increases after a match. Painful tendons have more Doppler activity than tendons without pain. Study design Cohort study. Methods 72 elite badminton players were interviewed about training, pain and injuries. The participants were scanned with high-end ultrasound equipment. Colour Doppler was used to examine the tendons of 64 players before a match and 46 players after a match. Intratendinous colour Doppler flow was measured as colour fraction (CF). The tendon complex was divided into three loci: the quadriceps tendon, the proximal patellar tendon and the insertion on the tibial tuberosity. Results Interview: Of the 72 players, 62 players had problems with 86 tendons in the lower extremity. Of these 86 tendons, 48 were the anterior knee tendons. Ultrasound: At baseline, the majority of players (87%) had colour Doppler flow in at least one scanning position. After a match, the percentage of the knee complexes involved did not change. CF increased significantly in the dominant leg at the tibial tuberosity; single players had a significantly higher CF after a match at the tibial tuberosity and in the patellar tendon both before and after a match. Painful tendons had the highest colour Doppler activity. Conclusions Most elite badminton players had pain in the anterior knee tendons and intratendinous Doppler activity both before and after match. High levels of Doppler activity were associated with self-reported ongoing pain.
Protein Acetylation and Histone Deacetylase Expression Associated with Malignant Breast Cancer Progression
Authors: Junko Suzuki, Yunn-Yi Chen, Gary K. Scott, Sandy DeVries, Koei Chin, Christopher C. Benz, Frederic M. Waldman, E. Shelley Hwang
Journal: Clinical Cancer Research (2009)

Excess histone deacetylase (HDAC) activity can induce hypoacetylation of histone and nonhistone protein substrates, altering gene expression patterns and cell behavior potentially associated with malignant transformation. However, HDAC expression and protein acetylation have not been studied in the context of breast cancer progression.We assessed expression levels of acetylated histone H4 (ac-H4), ac-H4K12, ac-tubulin, HDAC1, HDAC2, and HDAC6 in 22 reduction mammoplasties and in 58 specimens with synchronous normal epithelium, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) components. Differences among groups were tested for significance using nonparametric tests.From normal epithelium to DCIS, there was a marked reduction in histone acetylation (P < 0.0001). Most cases showed similar levels of acetylation in DCIS and IDC, although some showed further reduction of ac-H4 and ac-H4K12 from DCIS to IDC. Expression of HDAC1, HDAC2, and HDAC6 was also significantly reduced but by a smaller magnitude. Greater reductions of H4 acetylation and HDAC1 levels were observed from normal to DCIS in estrogen receptor-negative compared with estrogen receptor-positive, and in high-grade compared with non-high-grade tumors.Overall, there was a global pattern of hypoacetylation associated with progression from normal to DCIS to IDC. These findings suggest that the reversal of this hypoacetylation in DCIS and IDC could be an early measure of HDAC inhibitor activity.
Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis
Authors: Vijay K Yadav, Santhanam Balaji, Padmanaban S Suresh, X Sherry Liu, Xin Lu, Zhishan Li, X Edward Guo, J John Mann, Anil K Balapure, Michael D Gershon, Rudraiah Medhamurthy, Marc Vidal, Gerard Karsenty, Patricia Ducy
Journal: Nature Medicine (2010)
The natural history of nonalcoholic fatty liver: A follow-up study
Authors: Mohd R. Teli, Oliver F. W. James, Alastair D. Burt, Mark K. Bennett, Christopher P. Day
Journal: Hepatology (1995)

Nonalcohol-induced fatty liver is widely believed to be a benign condition with little or no risk of disease progression. There have been occasional reports of progression to cirrhosis but none in the absence of preexisting fibrosis on the index biopsy specimen even when co-existing hepatitis was present (steatohepatitis). From our histological database (1978 to 1985), we identified 161 patients with fatty liver seen at our institution and traced the case notes of 156. One hundred five patients were initially excluded as having an alcohol-induced cause, and the remaining 51 either were seen in the clinic (37) or had died, in which cases copies of their death certificates were obtained (14). A further 7 patients were excluded after clinic attendance gave evidence of alcohol excess and another 4 after review of their initial biopsy showed the presence of fibrosis or steatohepatitis. The apparent cause of the steatosis in the 40 included patients with strictly nonalcohol-induced pure fatty liver was obesity in 12, diabetes in 4 (1 obese patient), and cachexia associated with extrahepatic malignancy in 6. Four of the remaining 19 had serological evidence of an autoimmune disorder, but none of these had any clinical or histological features of autoimmune liver disease. Nine patients had evidence of hyperlipidemia, 3 of whom were also obese. At a median follow-up of 11 years (7 to 16), 12 of 26 living patients had abnormal results of liver blood tests and had repeat liver biopsies performed. None had progressed to steatohepatitis or cirrhosis; 1 obese patient had developed mild fibrosis 9.8 years after her index biopsy.(ABSTRACT TRUNCATED AT 250 WORDS)
Loss of miR-638 in vitro promotes cell invasion and a mesenchymal-like transition by influencing SOX2 expression in colorectal carcinoma cells
Authors: Kelong Ma, Xiaorong Pan, Pingsheng Fan, Yinghua He, Jun Gu, Wei Wang, Tengyue Zhang, Zonghai Li, Xiaoying Luo
Journal: Molecular Cancer (2014)

Colorectal carcinoma (CRC) is a major cause of cancer mortality. The aberrant expression of several microRNAs is associated with CRC progression; however, the molecular mechanisms underlying this phenomenon are unclear. miR-638 and SRY-box 2 (SOX2) expression levels were detected in 36 tumor samples and their adjacent, non-tumor tissues from patients with CRC, as well as in 4 CRC cell lines, using real-time quantitative RT-PCR (qRT-PCR). SOX2 expression levels were detected in 90 tumor samples and their adjacent tissue using immunohistochemistry. Luciferase reporter and Western blot assays were used to validate SOX2 as a target gene of miR-638. The regulation of SOX2 expression by miR-638 was assessed using qRT-PCR and Western blot assays, and the effects of exogenous miR-638 and SOX2 on cell invasion and migration were evaluated in vitro using the HCT-116 and SW1116 CRC cell lines. We found that miR-638 expression was differentially impaired in CRC specimens and dependent on tumor grade. The inhibition of miR-638 by an antagomiR promoted cell invasion and a mesenchymal-like transition (lamellipodium stretching increased and cell-cell contacts decreased, which was accompanied by the suppression of the epithelial cell marker ZO-1/E-cadherin and the upregulation of the mesenchymal cell marker vimentin). A reporter assay revealed that miR-638 repressed the luciferase activity of a reporter gene coupled to the 3′-untranslated region of SOX2. miR-638 overexpression downregulated SOX2 expression, and miR-638 inhibition upregulated SOX2 expression. Moreover, miR-638 expression levels were correlated inversely with SOX2 mRNA levels in human CRC tissues. The RNAi-mediated knockdown of SOX2 phenocopied the invasion-inhibiting effect of miR-638; furthermore, SOX2 overexpression blocked the miR-638-induced CRC cell transition to epithelial-like cells. These results demonstrate that the loss of miR-638 promotes invasion and a mesenchymal-like transition by directly targeting SOX2 in vitro. These findings define miR-638 as a new, invasion-associated tumor suppressor of CRC.