tbuckley/cabot-search huggingface dataset:
Microbial genomics: an increasingly revealing interface in human health and disease
Authors: Martin L Hibberd
Journal: Genome Medicine (2013)

Th e diverse microbial communities associated with humans are now beginning to be comprehensively interro gated and characterized, thanks to new genomic, metagenomic and other high-throughput approaches. However, there is a huge amount of work to be done that will require a large-scale eff ort from the scientifi c commu nity, particularly in the development and application of analysis tools and in achieving a biological understanding of the human-microbe interface. Th is endeavor has already begun with projects such as MetaHIT [1] and the Human Microbiome Project Consortium [2] taking advantage of the extensive advances made with the advent of highly parallel next-generation sequencing approaches. But I would call for one additional eff ort: in the midst of all the thousands of microbial genomes, the role of one additional genome the human genome - should also be fully evaluated. It is becoming increasingly clear that human genetic variants, particularly in microbial sensing genes, might infl uence the structure of the human-associated microbial communities and lead to diseases such as infl ammatory bowel disease [3]. Interestingly, the shaping of these microbial communities, infl uenced by the human genome, might occur during the early colonization following birth and might infl uence many of the subsequent microbiome interactions. Genome-scale methods allow us to move away from targeted investigations, which are necessarily limited to our knowledge of candidate genes, to population-based analyses that permit the full genomic repertoire to be interrogated, enabling the discovery of key mutations and mechanisms that drive host-microbe (and microbemicrobe) interactions in their natural environment. However, even when all the genes in a genome have been identifi ed, detailed studies at the molecular level are required to provide novel mechanistic insights. Without such understanding, the statistical associations between microbial genes and their products that are currently being linked to medical outcomes may not stand fi In this issue, we launch a new article series highlighting the application of genomic and other high-throughput approaches to investigate the role of microbes in human health and disease. Forthcoming articles will feature recent progress in characterizing, detecting, monitoring and understanding the underlying mechanisms involved in infectious diseases, the role of the microbiome, and how such information can be applied to medicine. Th ere is great potential in this fifrom basic and technological advances to their application and integration into clinical approaches for disease prediction, surveillance, diagnosis and treatment.
Dejerine Hand Phenomenon
Authors: Jordi Pérez-Bovet, Jordi Rimbau-Muñoz
Journal: JAMA Neurology (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
To feed or not to feed? Are nutritional supplements worthwhile in active Crohn's disease?
Authors: H Lochs
Journal: Gut (2006)

Partial enteral nutrition is unlikely to suppress inflammation and so treat active Crohn’s disease

Enteral nutrition is an effective therapy for active Crohn’s disease (CD) although less effective than steroids. This has been shown in a number of original studies and meta-analyses.1,2 Enteral nutrition leads to remission in approximately 60% of patients within 4–6 weeks. Unfortunately, enteral nutrition has never been compared with placebo or other medical therapies such as mesalamine or topical steroids. With the lack of such studies demonstrating that enteral nutrition is superior to placebo, the question has been raised if enteral nutrition has any therapeutic effect at all. However, remission rates with enteral nutrition range from 53% to 80%, which is higher than remission rates of placebo groups in most studies, which range from 18% to 40%. Therefore, a direct anti-inflammatory effect of enteral nutrition in active CD is generally accepted. The therapeutic efficacy of enteral nutrition in active CD is also suggested by results of recent studies demonstrating mucosal healing as well as a reduction in proinflammatory cytokines3,4 by enteral nutrition. The effect of enteral nutrition appears to be similar if the diet is drunk or applied via a tube and is also comparable with the effect of parenteral nutrition. Specific compositions of enteral diets—elemental diets or diets containing specific components—have no advantage over standard polymeric diets.1,5–7

In adults, enteral nutrition is rarely used as the sole therapy for active CD in clinical practice. This is partly due to its inferiority compared with steroids and partly to the inconvenience of enteral nutrition, resulting in low patient compliance—specifically if the mostly unpalatable diets are drunk. This appears to be different in children, who accept enteral nutrition much better, with compliance rates …
Deficiency of interleukin-18 in mice leads to hyperphagia, obesity and insulin resistance
Authors: Mihai G Netea, Leo A B Joosten, Eli Lewis, Dalan R Jensen, Peter J Voshol, Bart Jan Kullberg, Cees J Tack, Han van Krieken, Soo-Hyun Kim, Anton F Stalenhoef, Fons A van de Loo, Ineke Verschueren, Leslie Pulawa, Shizuo Akira, Robert H Eckel, Charles A Dinarello, Wim van den Berg, Jos W M van der Meer
Journal: Nature Medicine (2006)
GPs' role and recognition: No spare capacity
Authors: N J. Sharvill
Journal: BMJ (1993)

Smoking related to clinical diagnosisNo of controls No (o/o) of smokers No of No (%) of Age in same age in aged marked patients smokers range range controls Periductal mastitis 68 60 (88) 19-48 10 397 3955 (38O0)* Non-lactating 39 34 (87) 23-46 8 944 3441 (38-5)* Mammaryduct 32 30(94) 26-48 9 321 3504(37.6)*Duct ectasia 186 52 (28) 42-85 9 093 2722 (29 9) * p < 0 0001, XI test, comparing numbers of smokers and controls.view of Bundred and colleagues that periductal mastitis and duct ectasia are separate conditions with different clinical syndromes, different pathological features, and different aetiologies.Clinicians and pathologists should be aware of this and use appropriate terminology.
Genetic loci influencing kidney function and chronic kidney disease
Authors: John C Chambers, Weihua Zhang, Graham M Lord, Pim van der Harst, Debbie A Lawlor, Joban S Sehmi, Daniel P Gale, Mark N Wass, Kourosh R Ahmadi, Stephan J L Bakker, Jacqui Beckmann, Henk J G Bilo, Murielle Bochud, Morris J Brown, Mark J Caulfield, John M C Connell, H Terence Cook, Ioana Cotlarciuc, George Davey Smith, Ranil de Silva, Guohong Deng, Olivier Devuyst, Lambert D Dikkeschei, Nada Dimkovic, Mark Dockrell, Anna Dominiczak, Shah Ebrahim, Thomas Eggermann, Martin Farrall, Luigi Ferrucci, Jurgen Floege, Nita G Forouhi, Ron T Gansevoort, Xijin Han, Bo Hedblad, Jaap J Homan van der Heide, Bouke G Hepkema, Maria Hernandez-Fuentes, Elina Hypponen, Toby Johnson, Paul E de Jong, Nanne Kleefstra, Vasiliki Lagou, Marta Lapsley, Yun Li, Ruth J F Loos, Jian'an Luan, Karin Luttropp, Céline Maréchal, Olle Melander, Patricia B Munroe, Louise Nordfors, Afshin Parsa, Leena Peltonen, Brenda W Penninx, Esperanza Perucha, Anneli Pouta, Inga Prokopenko, Paul J Roderick, Aimo Ruokonen, Nilesh J Samani, Serena Sanna, Martin Schalling, David Schlessinger, Georg Schlieper, Marc A J Seelen, Alan R Shuldiner, Marketa Sjögren, Johannes H Smit, Harold Snieder, Nicole Soranzo, Timothy D Spector, Peter Stenvinkel, Michael J E Sternberg, Ramasamyiyer Swaminathan, Toshiko Tanaka, Lielith J Ubink-Veltmaat, Manuela Uda, Peter Vollenweider, Chris Wallace, Dawn Waterworth, Klaus Zerres, Gerard Waeber, Nicholas J Wareham, Patrick H Maxwell, Mark I McCarthy, Marjo-Riitta Jarvelin, Vincent Mooser, Goncalo R Abecasis, Liz Lightstone, James Scott, Gerjan Navis, Paul Elliott, Jaspal S Kooner
Journal: Nature Genetics (2010)
EXPERIMENTAL ASCITES. STUDIES OF ELECTROLYTE BALANCE IN DOGS WITH PARTIAL AND COMPLETE OCCLUSION OF THE PORTAL VEIN AND OF THE VENA CAVA ABOVE AND BELOW THE LIVER
Authors: John A. Schilling, Augusta B. McCoord, Samuel W. Clausen, Stanley B. Troup, Frank W. McKee
Journal: Journal of Clinical Investigation (1952)

Previous studies (1-6) of experimental ascites primarily concerned with protein metabolism and exchange have emphasized the importance of so- dium in ascitic fluid production.Recently, the importance of sodium retention in several forms of effusions and edema has been described by nu- merous observers (7-15) who have all directly or indirectly implicated the kidney in the causal re- lationships of this abnormality of sodium' metabo- lism.This report concerns sodium, potassium, and chloride balance studies in dogs with experimentally produced ascites.Following the administra- tion of large amounts of sodium, these ascitic ani- mals, in contrast to the normal dog, do not ex- crete the excess sodium in their urine.Whereas normally in the dog there is a slightly delayed ex- cretion of sodium with temporary retention of so- dium in extracellular and intracellular spaces, these ascitic animals produce predictable amounts of ascites following an increased salt load.Potas- sium is promptly excreted by the kidneys and chloride is retained only when there is sodium re- tention.The ascites of these animals seems to resemble in some ways that of the human cirrhotic and the patient with right sided heart fail- ure or chronic constrictive pericarditis.The liver seems implicated in this abnormality of sodium metabolism.
Intramyocardial delivery of human CD133+ cells in a SCID mouse cryoinjury model: Bone marrow vs. cord blood-derived cells☆
Authors: N MA, Y LADILOV, J MOEBIUS, L ONG, C PIECHACZEK, A DAVID, A KAMINSKI, Y CHOI, W LI, D EGGER
Journal: Cardiovascular Research (2006)

The regenerative potential of endothelial and hematopoietic progenitor cells in the heart may vary according to their origin. This study was designed to compare the functional effects of CD133+ cells from human cord blood and bone marrow in a mouse model of myocardial injury.5 x 10(5) CD133+ cells from bone marrow (BM(CD133)) or cord blood (UCB(CD133)) were injected in the necrosis border zone of NOD/SCID (non-obese diabetic/severe combined immunodeficiency) mice with left ventricular cryoinjury (CI+). Transplanted cells were tracked by immunostaining for hNuclear antigen and by PCR for hDNA. Echocardiography was used to measure contractility. Scar size, capillary density, and cardiomyocyte apoptosis were evaluated by histology. In addition, the myogenic and endothelial differentiation capacity of BM(CD133) and UCB(CD133) was compared in vitro.DNA was detected 4 weeks after cell injection by PCR, but hNuc+ cells were found by immunostaining only after 48 h. Capillary density in both BM(CD133) and UCB(CD133) cell-treated CI+ mice was higher than in control CI+ mice, but not different between BM(CD133) and UCB(CD133) cell-treated hearts. There were no differences in scar size and myocardial mass among BM(CD133), UCB(CD133) and control CI+ mice, but cardiomyocyte apoptosis was reduced by both BM(CD133) and UCB(CD133) cells. The post-injury deterioration of shortening fraction (46.2+/-1% in sham-operated mice and 41.3+/-0.8% in control CI+ mice) was prevented by BM(CD133) cells (45.4+/-0.9%), but not by UCB(CD133) cells (40.8+/-0.7%). On the other hand, both BM(CD133) and UCB(CD133) cells abolished post-injury mortality. In vitro, neither cultivated BM(CD133) or UCB(CD133) cells developed into myocytes, but both readily differentiated towards an endothelial cell phenotype.While both cord blood and marrow CD133+ cells have some beneficial effects on post-injury angiogenesis and survival, only marrow cells appear to improve myocardial contractility.
Structure and function of “metalloantibiotics”
Authors: Li‐June Ming
Journal: Medicinal Research Reviews (2003)

Although most antibiotics do not need metal ions for their biological activities, there are a number of antibiotics that require metal ions to function properly, such as bleomycin (BLM), streptonigrin (SN), and bacitracin. The coordinated metal ions in these antibiotics play an important role in maintaining proper structure and/or function of these antibiotics. Removal of the metal ions from these antibiotics can cause changes in structure and/or function of these antibiotics. Similar to the case of "metalloproteins," these antibiotics are dubbed "metalloantibiotics" which are the title subjects of this review. Metalloantibiotics can interact with several different kinds of biomolecules, including DNA, RNA, proteins, receptors, and lipids, rendering their unique and specific bioactivities. In addition to the microbial-originated metalloantibiotics, many metalloantibiotic derivatives and metal complexes of synthetic ligands also show antibacterial, antiviral, and anti-neoplastic activities which are also briefly discussed to provide a broad sense of the term "metalloantibiotics."
Ciprofloxacin prevents the inhibitory effects of acute ethanol exposure on hepatic regeneration in the rat
Authors: Gerald Y. Minuk, Tony Gauthier, Xin K. Zhang, Gu Qi Wang, Norman M. Pettigrew, Frank J. Burczynski
Journal: Hepatology (1995)

To determine whether the inhibitory effects of ethanol on hepatic regeneration could be prevented by ciprofloxacin, a fluroquinolone antibiotic with gammaaminobutyric acid (GABAA), receptor antagonist properties, adult, male Sprague-Dawley rats (n = 6-8/group) received intraperitoneal injections of saline, putrescine (a hepatic growth promotor, 50 mg/kg), or ciprofloxacin (100 mg/kg), followed 1 hour later by gastric gavage with saline or ethanol (5 g/kg). One hour post-gavage, all rats underwent a 70% partial hepatectomy (PHx). Hepatic regenerative activity was documented 24 hours post-PHx by 3H-thymidine incorporation into hepatic DNA (DNA synthesis), proliferating cell nuclear antigen staining, and hepatic tissue putrescine levels. Compared with healthy controls, DNA synthesis rates were significantly lower in ethanol-gavaged/saline-treated rats (22.7 ± 4.4 × 103 vs. 12.3 ± 6.9 × 103 DPM/mg DNA, respectively, P < .001) but unaltered in putrescine-(18.8 ± 3.4 × 103 DPM/ mg DNA) and ciprofloxacin-treated (18.3 ± 2.6 × 103 DPM/mg DNA) rats. Hepatic proliferating cell nuclear antigen staining supported these findings. Hepatic putrescine levels also correlated with DNA synthesis data, being decreased in ethanol-gavaged/saline-treated rats (86 ± 14 pmoles/mg tissue) compared with healthy controls (120 ± 12 pmoles/mg, P < .01), ethanol-gavaged/putrescine-treated (112 ± 14 pmoles/mg, P < .05) and ethanol-gavaged/ciprofloxacin-treated (125 ± 17 pmoles/mg, P < .05) rats. To determine whether these effects resulted from GABAA receptor-mediated changes in liver membrane potentials, intracellular membrane potentials were recorded before and 1 hour after PHx in healthy control, ethanol-gavaged/saline-treated and ethanol-gavaged/ciprofloxacin-treated rats. In these studies, ciprofloxacin prevented ethanol-induced depolarization of the liver (change in membrane potential of healthy controls, ethanol-gavaged/saline-treated, and ethanol-gavaged/ciprofloxacin-treated rats were −9 ± 1, −15 ± 2, and −3 ± 1 mV, respectively). In conclusion, the results of this study indicate that the inhibitory effects of acute ethanol exposure on hepatic regenerative activity in rats can be prevented by exogenous ciprofloxacin. (Hepatology 1995; 22:1797-1800).
Lysosomal Sequestration of Sunitinib: A Novel Mechanism of Drug Resistance
Authors: Kristy J. Gotink, Henk J. Broxterman, Mariette Labots, Richard R. de Haas, Henk Dekker, Richard J. Honeywell, Michelle A. Rudek, Laurens V. Beerepoot, René J. Musters, Gerrit Jansen, Arjan W. Griffioen, Yehuda G. Assaraf, Roberto Pili, Godefridus J. Peters, Henk M.W. Verheul
Journal: Clinical Cancer Research (2011)

Resistance to antiangiogenic tyrosine kinase inhibitors such as sunitinib is an important clinical problem, but its underlying mechanisms are largely unknown. We analyzed tumor sunitinib levels in mice and patients and studied sensitivity and resistance mechanisms to sunitinib.Intratumoral and plasma sunitinib concentrations in mice and patients were determined. Sunitinib exposure on tumor cell proliferation was examined. Resistant tumor cells were derived by continuous exposure and studied for alterations in intracellular sunitinib accumulation and activity.Intratumoral concentrations of sunitinib in mice and patients were 10.9 ± 0.5 and 9.5 ± 2.4 μmol/L, respectively, whereas plasma concentrations were 10-fold lower, 1.0 ± 0.1 and 0.3 ± 0.1 μmol/L, respectively. Sunitinib inhibited tumor cell growth at clinically relevant concentrations in vitro, with IC(50) values of 1.4 to 2.3 μmol/L. Continuous exposure to sunitinib resulted in resistance of 786-O renal and HT-29 colon cancer cells. Fluorescent microscopy revealed intracellular sunitinib distribution to acidic lysosomes, which were significantly higher expressed in resistant cells. A 1.7- to 2.5-fold higher sunitinib concentration in resistant cells was measured because of increased lysosomal sequestration. Despite the higher intracellular sunitinib accumulation, levels of the key signaling p-Akt and p-ERK 1/2 were unaffected and comparable with untreated parental cells, indicating reduced effectiveness of sunitinib.We report that sunitinib inhibits tumor cell proliferation at clinically relevant concentrations and found lysosomal sequestration to be a novel mechanism of sunitinib resistance. This finding warrants clinical evaluation whether targeting lysosomal function will overcome sunitinib resistance.
Lung cancer in never-smokers: radon exposure and environmental tobacco smoke
Authors: Boris B.M. Melloni
Journal: European Respiratory Journal (2014)

BACKGROUND : Airway smooth muscle cells (ASMCs) of patients with COPD exhibit abnormal metabolism of hyaluronic acid (HA), contributing to inflammation and remodeling of the lung.   AIM:  To investigate if the abnormal metabolism of HA in ASMC is mediated by muscarinic receptors.   METHODS : HA was measured in the BAL of COPD patients at a stable state (n=53) and at exacerbation (n=44). ASMC were established from endobronchial biopsies of COPD and control. Cells were treated with carbachol and secretion of HA was measured by ELISA. Gene expression of HA synthases (HAS), hyaluronidases and HA receptors was investigated by qPCR.   RESULTS:  HA was significantly increased in the BAL of exacerbated patients as compared to stable COPD patients (pl0.005). HA secretion by ASMC was significantly stimulated by carbachol by 350% in COPD (pl0.001) and by 60% in controls (pl0.005). Carbachol also resulted in a significant increase of HAS-2 gene expression by 3 fold in COPD (pl0.005) and by 2 fold in controls.   CONCLUSIONS : Increased levels of HA in BAL are associated with acute exacerbations in COPD. This may be attributed to stimulation of muscarinic receptor in ASMC, apparently mediated by increased gene expression of HAS-2. Our results strengthen the concept for the pathologic HA turnover in COPD and the beneficial effect of targeting muscarinic receptors in the treatment of the disease.
DNA priming and influenza vaccine immunogenicity: two phase 1 open label randomised clinical trials
Authors: Julie E Ledgerwood, Chih-Jen Wei, Zonghui Hu, Ingelise J Gordon, Mary E Enama, Cynthia S Hendel, Patrick M McTamney, Melissa B Pearce, Hadi M Yassine, Jeffrey C Boyington, Robert Bailer, Terrence M Tumpey, Richard A Koup, John R Mascola, Gary J Nabel, Barney S Graham
Journal: The Lancet Infectious Diseases (2011)
LIM only 4 is overexpressed in late stage pancreas cancer
Authors: Jun Yu, Kenoki Ohuchida, Kohei Nakata, Kazuhiro Mizumoto, Lin Cui, Hayato Fujita, Hiroshi Yamaguchi, Takuya Egami, Hidehisa Kitada, Masao Tanaka
Journal: Molecular Cancer (2008)

Abstract Background LIM-only 4 (LMO4), a member of the LIM-only (LMO) subfamily of LIM domain-containing transcription factors, was initially reported to have an oncogenic role in breast cancer. We hypothesized that LMO4 may be related to pancreatic carcinogenesis as it is in breast carcinogenesis. If so, this could result in a better understanding of tumorigenesis in pancreatic cancer. Methods We measured LMO4 mRNA levels in cultured cells, pancreatic bulk tissues and microdissected target cells (normal ductal cells; pancreatic intraepithelial neoplasia-1B [PanIN-1B] cells; PanIN-2 cells; invasive ductal carcinoma [IDC] cells; intraductal papillary-mucinous adenoma [IPMA] cells; IPM borderline [IPMB] cells; and invasive and non-invasive IPM carcinoma [IPMC]) by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Results 9 of 14 pancreatic cancer cell lines expressed higher levels of LMO4 mRNA than did the human pancreatic ductal epithelial cell line (HPDE). In bulk tissue samples, expression of LMO4 was higher in pancreatic carcinoma than in intraductal papillary-mucinous neoplasm (IPMN) or non-neoplastic pancreas ( p &lt; 0.0001 for both). We carried out microdissection-based analyses. IDC cells expressed significantly higher levels of LMO4 than did normal ductal epithelia or PanIN-1B cells ( p &lt; 0.001 for both) or PanIN-2 cells ( p = 0.014). IPMC cells expressed significantly higher levels of LMO4 than did normal ductal epithelia ( p &lt; 0.001), IPMA ( p &lt; 0.001) and IPMB cells ( p = 0.003). Conclusion Pancreatic carcinomas (both IDC and IPMC) expressed significantly higher levels of LMO4 mRNA than did normal ductal epithelia, PanIN-1B, PanIN-2, IPMA and IPMB. These results suggested that LMO4 is overexpressed at late stages in carcinogenesis of pancreatic cancer.