tbuckley/cabot-search huggingface dataset:
Pyridone 6, A Pan-Janus–Activated Kinase Inhibitor, Induces Growth Inhibition of Multiple Myeloma Cells
Authors: Laura Pedranzini, Tobias Dechow, Marjan Berishaj, Raymond Comenzo, Ping Zhou, Janeen Azare, William Bornmann, Jacqueline Bromberg
Journal: Cancer Research (2006)

Abstract Interleukin-6 (IL-6) and the subsequent Janus-activated kinase (JAK)-dependent signaling pathways play a critical role in the pathogenesis of multiple myeloma. Here, we compared the sensitivity and specificity of a novel pan-JAK inhibitor, tetracyclic pyridone 6 (P6), with that of AG490 in a panel of myeloma-derived cell lines. P6 induced growth arrest and subsequent apoptosis of the IL-6-dependent hybridoma and myeloma-derived cell lines (B9 and INA-6) grown either in IL-6-containing medium or in the presence of bone marrow–derived stromal cells (BMSC) using much lower concentrations of drug and with significantly faster kinetics than AG490. Myeloma-derived cell lines, which either express constitutively activated JAK/signal transducers and activators of transcription (STAT) 3 (U266) or are IL-6 growth stimulated (KMS11), are partially growth inhibited by P6. However, P6 does not inhibit the growth of myeloma-derived cell lines lacking activated JAKs/STATs nor does it inhibit mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase activity compared with AG490, which led to activation of ERK and induced robust apoptosis of all the examined cell lines. Finally, P6 inhibited the growth of primary myeloma patient samples grown in the presence of BMSCs. Thus, P6 is a more sensitive and specific inhibitor of JAK-STAT3 activity compared with AG490 and potently inhibited the growth of primary myeloma cells and myeloma-derived cell lines grown on BMSCs. (Cancer Res 2006; 66(19): 9714-21)
Versatile and open software for comparing large genomes.
Authors: Stefan Kurtz, Adam Phillippy, Arthur L Delcher, Michael Smoot, Martin Shumway, Corina Antonescu, Steven L Salzberg
Journal: Genome biology (2004)

Abstract The newest version of MUMmer easily handles comparisons of large eukaryotic genomes at varying evolutionary distances, as demonstrated by applications to multiple genomes. Two new graphical viewing tools provide alternative ways to analyze genome alignments. The new system is the first version of MUMmer to be released as open-source software. This allows other developers to contribute to the code base and freely redistribute the code. The MUMmer sources are available at http://www.tigr.org/software/mummer .
Cardiopulmonary exercise testing for the selection of patients undergoing surgery for lung cancer: friend or foe?
Authors: E. Lim, M. Beckles, C. Warburton, D. Baldwin
Journal: Thorax (2010)

<h3>SUMMARY:</h3> Most dementias begin insidiously, developing slowly and generally occurring in the elderly age group. The so-called rapidly progressive dementias constitute a different, diverse collection of conditions, many of which are reversible or treatable. For this reason, prompt identification and assessment of acute and subacute forms of dementia are critical to effective treatment. Numerous other entities within this category of presenile rapid-onset dementias are untreatable such as the prion-related diseases. Neuroimaging aids in the diagnosis and evaluation of many of these rapidly progressive dementias, which include myriad conditions ranging from variations of more common neurodegenerative dementias, such as Alzheimer disease, dementia with Lewy bodies, and frontotemporal dementia; infectious-related dementias such as acquired immune deficiency syndrome dementia; autoimmune and malignancy-related conditions; to toxic and metabolic forms of encephalopathy. This first of a 2-part review will specifically address the ability of MR imaging and ancillary neuroimaging strategies to support the diagnostic evaluation of rapidly progressive dementias due to neurodegenerative causes.
Exponential Decay of GC Content Detected by Strand-Symmetric Substitution Rates Influences the Evolution of Isochore Structure
Authors: J. E. Karro, M. Peifer, R. C. Hardison, M. Kollmann, H. H. von Grünberg
Journal: Molecular Biology and Evolution (2007)

The distribution of guanine and cytosine nucleotides throughout a genome, or the GC content, is associated with numerous features in mammals; understanding the pattern and evolutionary history of GC content is crucial to our efforts to annotate the genome. The local GC content is decaying toward an equilibrium point, but the causes and rates of this decay, as well as the value of the equilibrium point, remain topics of debate. By comparing the results of 2 methods for estimating local substitution rates, we identify 620 Mb of the human genome in which the rates of the various types of nucleotide substitutions are the same on both strands. These strand-symmetric regions show an exponential decay of local GC content at a pace determined by local substitution rates. DNA segments subjected to higher rates experience disproportionately accelerated decay and are AT rich, whereas segments subjected to lower rates decay more slowly and are GC rich. Although we are unable to draw any conclusions about causal factors, the results support the hypothesis proposed by Khelifi A, Meunier J, Duret L, and Mouchiroud D (2006. GC content evolution of the human and mouse genomes: insights from the study of processed pseudogenes in regions of different recombination rates. J Mol Evol. 62:745–752.) that the isochore structure has been reshaped over time. If rate variation were a determining factor, then the current isochore structure of mammalian genomes could result from the local differences in substitution rates. We predict that under current conditions strand-symmetric portions of the human genome will stabilize at an average GC content of 30% (considerably less than the current 42%), thus confirming that the human genome has not yet reached equilibrium.
PAR-CLIP data indicate that Nrd1-Nab3-dependent transcription termination regulates expression of hundreds of protein coding genes in yeast
Authors: Shaun Webb, Ralph D Hector, Grzegorz Kudla, Sander Granneman
Journal: Genome biology (2014)

Abstract Background Nrd1 and Nab3 are essential sequence-specific yeast RNA binding proteins that function as a heterodimer in the processing and degradation of diverse classes of RNAs. These proteins also regulate several mRNA coding genes; however, it remains unclear exactly what percentage of the mRNA component of the transcriptome these proteins control. To address this question, we used the pyCRAC software package developed in our laboratory to analyze CRAC and PAR-CLIP data for Nrd1-Nab3-RNA interactions. Results We generated high-resolution maps of Nrd1-Nab3-RNA interactions, from which we have uncovered hundreds of new Nrd1-Nab3 mRNA targets, representing between 20 and 30% of protein-coding transcripts. Although Nrd1 and Nab3 showed a preference for binding near 5′ ends of relatively short transcripts, they bound transcripts throughout coding sequences and 3′ UTRs. Moreover, our data for Nrd1-Nab3 binding to 3′ UTRs was consistent with a role for these proteins in the termination of transcription. Our data also support a tight integration of Nrd1-Nab3 with the nutrient response pathway. Finally, we provide experimental evidence for some of our predictions, using northern blot and RT-PCR assays. Conclusions Collectively, our data support the notion that Nrd1 and Nab3 function is tightly integrated with the nutrient response and indicate a role for these proteins in the regulation of many mRNA coding genes. Further, we provide evidence to support the hypothesis that Nrd1-Nab3 represents a failsafe termination mechanism in instances of readthrough transcription.
Central Amino Acid Neurotransmitters and the Hypoxic Ventilatory Response
Authors: Ivan Soto-Arape, Melvin D. Burton, Homayoun Kazemi
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Acute sustained hypoxia causes an early rise in ventilation, followed by a reduction in ventilation (“roll off”) after several minutes to levels below the peak but above baseline. The underlying mechanism(s) of this biphasic response is unclear. Hypoxia induces changes in the release and metabolic turnover of glutamate and gamma aminobutyric acid (GABA). These endogenous neuroactive agents may play a role in mediating the biphasic hypoxic ventilatory response. Therefore, their role was studied in anesthetized (isoflurane), isocapnic, mechanically ventilated rats. Hypoxia alone (FiO2 = 0.1) produced the characteristic biphasic response in the phrenic neurogram (n = 6). When the glutamate receptor was blocked with application of two different N-methyl-D-aspartate (NMDA) antagonists, MK-801 or AP-5, to the ventrolateral medullary surface (VMS), the phrenic output fell by 90% during normoxia and demonstrated no response to hypoxia (n = 6 for each group). There was a rise of 60% in phrenic nerve output during normoxia when GABA antagonist bicuculline was applied to the VMS, and with hypoxia it rose another 15%, and no fall off was seen during hypoxia (n = 6). These findings suggest that during hypoxia the initial hyperventilation has a glutamatergic component and the subsequent fall off is mediated by GABAergic mechanisms.
Worldwide Trends in Incidence Rates for Oral Cavity and Oropharyngeal Cancers
Authors: Anil K. Chaturvedi, William F. Anderson, Joannie Lortet-Tieulent, Maria Paula Curado, Jacques Ferlay, Silvia Franceschi, Philip S. Rosenberg, Freddie Bray, Maura L. Gillison
Journal: Journal of Clinical Oncology (2013)

Human papillomavirus (HPV) has been identified as the cause of the increasing oropharyngeal cancer (OPC) incidence in some countries. To investigate whether this represents a global phenomenon, we evaluated incidence trends for OPCs and oral cavity cancers (OCCs) in 23 countries across four continents.We used data from the Cancer Incidence in Five Continents database Volumes VI to IX (years 1983 to 2002). Using age-period-cohort modeling, incidence trends for OPCs were compared with those of OCCs and lung cancers to delineate the potential role of HPV vis-à-vis smoking on incidence trends. Analyses were country specific and sex specific.OPC incidence significantly increased during 1983 to 2002 predominantly in economically developed countries. Among men, OPC incidence significantly increased in the United States, Australia, Canada, Japan, and Slovakia, despite nonsignificant or significantly decreasing incidence of OCCs. In contrast, among women, in all countries with increasing OPC incidence (Denmark, Estonia, France, the Netherlands, Poland, Slovakia, Switzerland, and United Kingdom), there was a concomitant increase in incidence of OCCs. Although increasing OPC incidence among men was accompanied by decreasing lung cancer incidence, increasing incidence among women was generally accompanied by increasing lung cancer incidence. The magnitude of increase in OPC incidence among men was significantly higher at younger ages (< 60 years) than older ages in the United States, Australia, Canada, Slovakia, Denmark, and United Kingdom.OPC incidence significantly increased during 1983 to 2002 predominantly in developed countries and at younger ages. These results underscore a potential role for HPV infection on increasing OPC incidence, particularly among men.
Reversible, strokelike migraine attacks in patients with previous radiation therapy
Authors: J. D. Bartleson, Karl N. Krecke, Brian P. O'Neill, Paul D. Brown
Journal: Neuro-Oncology (2003)

We report 2 adults with a past history of radiation therapy to the head for malignancy (one with primary B-cell lymphoma confined to the skull and the other with multiple hemangioendotheliomas) who developed episodes consistent with migraine with and without aura. In addition to more typical migraine attacks and beginning many years after their radiation therapy, both patients have experienced infrequent, stereotyped, prolonged, reversible neurologic deficits associated with headache, occasional seizures, and striking, transient, cortical gadolinium enhancement of the posterior cerebral gyri on MRI. Interictal MRI brain scans show stable abnormalities consistent with the patients' previous radiation therapy. The neurologic deficits often progressed over a few days, sometimes lasted weeks, and completely resolved. Electroencephalograms did not show epileptiform activity. Thorough investigation showed no residual or recurrent tumor and no recognized cause for the patients' attacks.
Mesenchymal Stem Cells in Acute Kidney Injury
Authors: Benjamin D. Humphreys, Joseph V. Bonventre
Journal: Annual Review of Medicine (2007)

The potential role of mesenchymal stem cells (MSCs, also called mesenchymal stromal cells) in endogenous repair and cell-based therapies for acute kidney injury (AKI) is under intensive investigation. Preclinical studies indicate that administered MSCs both ameliorate renal injury and accelerate repair. These versatile cells home to sites of injury, where they modulate the repair process. The mechanisms responsible for their protective and regenerative effects are incompletely understood. Some have reported that MSCs are capable of direct engraftment into injured nephrons under certain circumstances. This is highly controversial, however, and even those who argue there is engraftment acknowledge that the primary means of repair by these cells most likely involves paracrine and endocrine effects, including mitogenic, antiapoptotic, anti-inflammatory, and angiogenic influences. There is a good deal of interest in MSC-based approaches for the treatment of human kidney injury, thanks to positive preclinical results, the strong clinical need for novel therapies to treat AKI, the ease of isolation and expansion of MSCs, and encouraging preliminary clinical trial results in other fields. This review summarizes current knowledge and identifies gaps in our understanding of MSC biology that will need to be filled in order to translate recent discoveries into therapies for AKI in humans.
Overexpression of complement inhibitor Crry does not prevent cryoglobulin-associated membranoproliferative glomerulonephritis
Authors: Anja S. Mühlfeld, Stephan Segerer, Kelly Hudkins, Andrew G. Farr, Lihua Bao, Damian Kraus, V. Michael Holers, Richard J. Quigg, Charles E. Alpers
Journal: Kidney International (2004)
A Call for an End to the Diet Debates
Authors: Sherry L. Pagoto, Bradley M. Appelhans
Journal: JAMA (2013)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Effect of 7-Year Infancy-Onset Dietary Intervention on Serum Lipoproteins and Lipoprotein Subclasses in Healthy Children in the Prospective, Randomized Special Turku Coronary Risk Factor Intervention Project for Children (STRIP) Study
Authors: Tuuli Kaitosaari, Tapani Rönnemaa, Olli Raitakari, Sanna Talvia, Katariina Kallio, Iina Volanen, Aila Leino, Eero Jokinen, Ilkka Välimäki, Jorma Viikari, Olli Simell
Journal: Circulation (2003)

We previously showed that low-saturated-fat dietary intervention from infancy until 5 years of age safely and effectively reduced serum cholesterol concentration. We now report how such intervention influenced serum lipids, LDL particle size, and HDL subfractions in children when they reached the age of 7 years.Healthy 7-month-old infants (n=1062) were randomized to the intervention (n=540) and control (n=522) groups. Each year, two individualized counseling sessions were organized to the intervention families. Serum lipid values were measured annually. The intervention boys had 0.20 to 0.39 mmol/L lower serum cholesterol values than the control boys throughout the follow-up (always P<0.05), but the values of the intervention and control girls did not differ. The LDL particle sizes and HDL subfractions were determined in a random subgroup of 96 intervention and 101 control children at the age of 7 years. The mean particle diameter of major LDL peak was 262.6 A in the intervention boys and 258.5 A in the control boys (P=0.05), and 259.2 A in the intervention girls and 261.3 A in the control girls (P=0.30). HDL2 and HDL3 cholesterol concentrations did not differ between the intervention and control children or between the two genders.The 7-year intervention favorably influenced not only the serum total and LDL cholesterol concentrations but also the LDL particle size in boys. LDL particle size remained unchanged in girls, as did HDL2 and HDL3 concentrations in both genders.
Same-admission versus interval cholecystectomy for mild gallstone pancreatitis (PONCHO): a multicentre randomised controlled trial
Authors: David W da Costa, Stefan A Bouwense, Nicolien J Schepers, Marc G Besselink, Hjalmar C van Santvoort, Sandra van Brunschot, Olaf J Bakker, Thomas L Bollen, Cornelis H Dejong, Harry van Goor, Marja A Boermeester, Marco J Bruno, Casper H van Eijck, Robin Timmer, Bas L Weusten, Esther C Consten, Menno A Brink, B W Marcel Spanier, Ernst Jan Spillenaar Bilgen, Vincent B Nieuwenhuijs, H Sijbrand Hofker, Camiel Rosman, Annet M Voorburg, Koop Bosscha, Peter van Duijvendijk, Jos J Gerritsen, Joos Heisterkamp, Ignace H de Hingh, Ben J Witteman, Philip M Kruyt, Joris J Scheepers, I Quintus Molenaar, Alexander F Schaapherder, Eric R Manusama, Laurens A van der Waaij, Jacco van Unen, Marcel G Dijkgraaf, Bert van Ramshorst, Hein G Gooszen, Djamila Boerma
Journal: The Lancet (2015)
MECHANISM AND DYNAMICS OF CADHERIN ADHESION
Authors: Deborah Leckband, Anil Prakasam
Journal: Annual Review of Biomedical Engineering (2006)

Cadherins are essential cell adhesion molecules involved in tissue morphogenesis and the maintenance of tissue architecture in adults. The adhesion and selectivity functions of cadherins are located in their extracellular regions. Biophysical studies show that the adhesive activity is not confined to a single interface. Instead, multiple cadherin domains contribute to binding. By contrast, the specificity-determining site maps to the N-terminal domains, which adhere by the reciprocal binding of Trp2 residues from opposing proteins. Structural cooperativity can transmit the effects of subtle structural changes or ligand binding over large distances in the protein. Increasingly, studies show that differential cadherin-mediated adhesion, rather than exclusive homophilic binding between identical cadherins, direct cell segregation and the organization of tissue interfaces during morphogenesis. Force measurements quantified both kinetic and strength differences between different classical cadherins that may underlie cell sorting behavior. Despite the complex adhesion mechanisms and differences in binding properties, cadherin-mediated cell adhesion is also regulated by many other biochemical processes. Elucidating the mechanisms by which cadherins organize cell junctions and tissue architecture requires not only quantitative, mechanistic investigations of cadherin function but also investigations of the biochemical and cellular processes that can modulate those functions.
Factors predicting progression of gastric intestinal metaplasia: results of a randomised trial on Helicobacter pylori eradication
Authors: W K Leung
Journal: Gut (2004)

<b>Background and aim:</b> Gastric intestinal metaplasia (IM) is generally considered to be a precancerous lesion in the gastric carcinogenesis cascade. This study identified the risk factors associated with progression of IM in a randomised control study. <b>Subjects and methods:</b> A total of 587 <i>Helicobacter pylori</i> infected subjects were randomised to receive a one week course of anti-<i>Helicobacter</i> therapy (omeprazole, amoxicillin, and clarithromycin (OAC)) or placebo. Subjects underwent endoscopy with biopsy at baseline and at five years. Severity of IM was graded according to the updated Sydney classification and progression was defined as worsening of IM scores at five years in either the antrum or corpus, or development of neoplasia. Backward stepwise multiple logistic regression was used to identify independent risk factors associated with IM progression. <b>Results:</b> Of 435 subjects (220 in the OAC and 215 in the placebo group) available for analysis, 10 developed gastric cancer and three had dysplasia. Overall progression of IM was noted in 52.9% of subjects. Univariate analysis showed that persistent <i>H pylori</i> infection, age &gt;45 years, male subjects, alcohol use, and drinking water from a well were significantly associated with IM progression. Duodenal ulcer and OAC treatment were associated with a reduced risk of histological progression. Progression of IM was more frequent in those with more extensive and more severe IM at baseline. With multiple logistic regression, duodenal ulcer (odds ratio (OR) 0.23 (95% confidence interval (CI) 0.09–0.58)) was found to be an independent protective factor against IM progression. Conversely, persistent <i>H pylori</i> infection (OR 2.13 (95% CI 1.41–3.24)), age &gt;45 years (OR 1.92 (95% CI 1.18–3.11)), alcohol use (OR 1.67 (95% CI 1.07–2.62)), and drinking water from a well (OR 1.74 (95% CI 1.13–2.67)) were independent risk factors associated with IM progression. <b>Conclusion:</b> Eradication of <i>H pylori</i> is protective against progression of premalignant gastric lesions.
Transient bullous dermolysis of the newborn in three generations
Authors: H. Fassihi, V.C. Diba, V. Wessagowit, P.J.C. Dopping-Hepenstal, C.A. Jones, N.P. Burrows, J.A. McGrath
Journal: British Journal of Dermatology (2005)

Transient bullous dermolysis of the newborn (TBDN) is a rare form of dystrophic epidermolysis bullosa (DEB) that presents with neonatal skin blistering but which usually improves markedly during early life or even remits completely. Skin biopsies reveal abnormal intraepidermal accumulation of type VII collagen which results in poorly constructed anchoring fibrils and a sublamina densa plane of blister formation. The reason for the spontaneous clinical improvement is not known, but there is a gradual recovery in type VII collagen secretion from basal keratinocytes to the dermal-epidermal junction, with subsequent improvement or correction of anchoring fibril morphology. In this report, we describe TBDN occurring in three generations of the same family. Blistering occurred only during the first few months after birth, and all affected individuals were found to have a heterozygous glycine substitution mutation in exon 45 of the type VII collagen gene, COL7A1, designated G1522E. This mutation represents the third report of a pathogenic COL7A1 mutation in TBDN. Despite limited understanding of the disease mechanism in TBDN, this distinct form of DEB is important to recognize as it typically has a benign and self-limiting course. However, not all cases of DEB associated with intraepidermal type VII collagen are 'transient'. Genetic counselling in such patients therefore should be guarded until the pathophysiology of TBDN is better understood.