tbuckley/cabot-search huggingface dataset:
Urine based detection of intestinal mucosal cell damage in neonates with suspected necrotising enterocolitis
Authors: J P M Derikx, N J Evennett, P L J Degraeuwe, T L Mulder, A A van Bijnen, L W E van Heurn, W A Buurman, E Heineman
Journal: Gut (2007)

Necrotising enterocolitis (NEC) is a severe gastrointestinal disease with a mortality of 20–40%, affecting predominantly premature neonates.1 In the early phase of the disease NEC continues to present a diagnostic challenge for the attending clinician. The signs and symptoms are often non-specific, including gastrointestinal problems such as abdominal distension and feeding intolerance, which are also among the most prevalent presenting features of neonatal sepsis.2 The diagnosis is further hampered by the limited diagnostic accuracy of the laboratory and radiological tests currently in use.3,4

Histopathologically, NEC is characterised by intestinal coagulative or ischaemic necrosis, starting at the mucosa and extending into the submucosa and muscularis externa.1 We sought a non-invasive test to find evidence of enterocyte cell death in infants with gastrointestinal symptoms suspicious of NEC, in order to differentiate NEC from other neonatal diseases that present with abdominal signs.

Intestinal fatty acid binding protein (I-FABP) has been reported to be a useful plasma marker for early enterocyte cell death.5,6 The small (14–15 kDa) cytosolic I-FABP is specifically present in mature enterocytes of small and large intestine and is released as soon as cell membrane integrity is compromised. I-FABP is present in very small amounts in the plasma of healthy individuals, probably representing the normal turnover of enterocytes, but levels …
Anti-TNFα Therapy of Rheumatoid Arthritis: What Have We Learned?
Authors: Marc Feldmann, Ravinder N. Maini
Journal: Annual Review of Immunology (2001)

Rheumatoid arthritis (RA), a systemic disease, is characterized by a chronic inflammatory reaction in the synovium of joints and is associated with degeneration of cartilage and erosion of juxta-articular bone. Many pro-inflammatory cytokines including TNF alpha, chemokines, and growth factors are expressed in diseased joints. The rationale that TNF alpha played a central role in regulating these molecules, and their pathophysiological potential, was initially provided by the demonstration that anti-TNF alpha antibodies added to in vitro cultures of a representative population of cells derived from diseased joints inhibited the spontaneous production of IL-1 and other pro-inflammatory cytokines. Systemic administration of anti-TNF alpha antibody or sTNFR fusion protein to mouse models of RA was shown to be anti-inflammatory and joint protective. Clinical investigations in which the activity of TNF alpha in RA patients was blocked with intravenously administered infliximab, a chimeric anti-TNF alpha monoclonal antibody (mAB), has provided evidence that TNF regulates IL-6, IL-8, MCP-1, and VEGF production, recruitment of immune and inflammatory cells into joints, angiogenesis, and reduction of blood levels of matrix metalloproteinases-1 and -3. Randomized, placebo-controlled, multi-center clinical trials of human TNF alpha inhibitors have demonstrated their consistent and remarkable efficacy in controlling signs and symptoms, with a favorable safety profile, in approximately two thirds of patients for up to 2 years, and their ability to retard joint damage. Infliximab (a mAB), and etanercept (a sTNF-R-Fc fusion protein) have been approved by regulatory authorities in the United States and Europe for treating RA, and they represent a significant new addition to available therapeutic options.
Timing the Origin of New World Monkeys
Authors: C. G. Schrago
Journal: Molecular Biology and Evolution (2003)

The origin of New World monkeys (Infraorder Platyrrhini) has been an extensively debated issue. In this study, we analyzed mitochondrial genomes from Cebus (Platyrrhini), Homo, Hylobates, Pan, Pongo (Hominoids), Macaca, Papio (Cercopithecoids), and Tarsius (outgroup) to investigate this matter. Two distinct methodologies were employed on mitochondrial genes to estimate divergence times: the traditional likelihood ratio test performed in ML analyses of individual and concatenated gene sequences and the recent multigene Bayesian approach. Using the Cercopithecoid-Hominoid split as calibration point (25 MYA), our results show consistently that Platyrrhines split from Catarrhines at around 35 MYA. Although the main focus of the study is New World monkey origins, we have also estimated other primate divergence times: Homo-Pan at 5–7 MYA; Pongo-(Homo/Pan) at 13–16 MYA; Hylobates-(Pongo/Homo/Pan) at 15–19 MYA; and Macaca-Papio at 10–12 MYA. Our estimate for the origin of New World monkeys is in agreement with the hypothesis of a transatlantic journey from Africa to South America, as suggested by the fossil record.
Irradiation in the Epidemiology of Leukemia Among Adults&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R Gibson, S Graham, A Lilienfeld, L Schuman, J E Dowd, M L Levin
Journal: JNCI Journal of the National Cancer Institute (1972)

Journal Article Irradiation in the Epidemiology of Leukemia Among Adults Get access R. Gibson, Ph.D., R. Gibson, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar S. Graham, Ph.D., S. Graham, Ph.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar A. Lilienfeld, M.D., M.P.H., A. Lilienfeld, M.D., M.P.H. Search for other works by this author on: Oxford Academic PubMed Google Scholar L. Schuman, M.D., M.P.H., L. Schuman, M.D., M.P.H. Search for other works by this author on: Oxford Academic PubMed Google Scholar J. E. Dowd, M.S., J. E. Dowd, M.S. Search for other works by this author on: Oxford Academic PubMed Google Scholar M. L. Levin, M.D., D.P.H. M. L. Levin, M.D., D.P.H. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 48, Issue 2, February 1972, Pages 301–311, https://doi.org/10.1093/jnci/48.2.301 Published: 01 February 1972 Article history Received: 26 July 1971 Revision received: 15 October 1971 Accepted: 10 November 1971 Published: 01 February 1972
Evidence for cholinergic regulation of microvessel hydraulic conductance during tissue hypoxia.
Authors: V L Tucker, V H Huxley
Journal: Circulation Research (1990)

Cholinergic regulation of single-vessel hydraulic conductivity (Lp) during normoxia and hypoxia was tested in single mesenteric vessels of pithed frogs (Rana pipiens). Capillaries were cannulated in situ and perfused with frog Ringer's solution containing 10 mg/ml albumin and human erythrocytes while the mesentery was continuously superfused with frog Ringer's solution (15 degrees C). Lp was first measured under normoxic (room air equilibrated) conditions by the modified Landis microocclusion method. Repeated measurements of filtration coefficient under control conditions, for periods up to 80 minutes, demonstrated that Lp did not change with time in normoxic vessels (n = 18). After initial control measurement (Lpo), perfusion with 1 microM acetylcholine increased Lp by 4.6 +/- 1.0-fold (mean +/- SEM, n = 6). The response to acetylcholine was antagonized by the addition of 10 microns atropine to the perfusate (Lp/Lpo = 1.8 +/- 0.4). Perfusion with atropine alone reduced Lp in three of six capillaries Lp/Lpo = 0.56 +/- 0.04); Lp in the remaining three vessels was unaffected. Tissue hypoxia was simulated by exposing the mesentery to deoxygenated superfusate Po2 less than or equal to 10 mm Hg) for 10-15 minutes. Tissue hypoxia had no effect on Lp in atropine-treated vessels (n = 8). Without atropine, tissue hypoxia increased Lp by 2.3 +/- 0.7-fold, whereas the addition of atropine completely antagonized this response (n = 5). In contrast to the inhibitory action of atropine during tissue hypoxia, Lp rose 5.2 +/- 1.6-fold (n = 4) in vessels simultaneously exposed to deoxygenated perfusate.(ABSTRACT TRUNCATED AT 250 WORDS)
Autologous blood and infections after colorectal surgery
Authors: OlivierR.C. Busch, WimC.J. Hop, RichardL. Marquet, Johannes Jeekel, J.G.A. Houbiers, L.M.G. van de Watering, C.J.H. van de Velde, A. Brand, F.W. Schildberg, K-W. Jauch, M.M. Heiss
Journal: The Lancet (1994)
HUMORAL ANTIBODIES AND RESISTANCE OF VACCINATED AND CONVALESCENT MONKEYS TO POLIOMYELITIS VIRUS
Authors: Albert B. Sabin, Peter K. Olitsky
Journal: The Journal of Experimental Medicine (1936)

1. Monkeys convalescent from a paralytic attack of poliomyelitis develop humoral antibodies slowly; in the present series their first appearance in most was at 2 months and in some not until 3 months after the attack. 2. Convalescent monkeys display resistance to reinfection with the same strain by the nasal route long before antibodies become demonstrable in their serum, in this respect differing from many vaccinated monkeys whose serum neutralizes the virus, while they remain susceptible to nasal infection. 3. When antibodies appear in the serum of resistant convalescent monkeys, they are not quantitatively greater than in the serum of vaccinated monkeys which succumb to infection. As regards resistance to infection, humoral antibodies, therefore, do not have the same significance in vaccinated as in convalescent poliomyelitis monkeys.
Participation in Cognitively Stimulating Activities and Risk of Incident Alzheimer Disease
Authors: Robert S. Wilson
Journal: JAMA (2002)

ContextFrequent participation in cognitively stimulating activities has been hypothesized to reduce risk of Alzheimer disease (AD), but prospective data regarding an association are lacking.ObjectiveTo test the hypothesis that frequent participation in cognitive activities is associated with a reduced risk of AD.DesignLongitudinal cohort study with baseline evaluations performed between January 1994 and July 2001 and mean follow-up of 4.5 years.Participants and SettingA total of 801 older Catholic nuns, priests, and brothers without dementia at enrollment, recruited from 40 groups across the United States. At baseline, they rated frequency of participation in common cognitive activities (eg, reading a newspaper), from which a previously validated composite measure of cognitive activity frequency was derived.Main Outcome MeasuresClinical diagnosis of AD by a board-certified neurologist using National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria and change in global and specific measures of cognitive function, compared by cognitive activity score at baseline.ResultsBaseline scores on the composite measure of cognitive activity ranged from 1.57 to 4.71 (mean, 3.57; SD, 0.55), with higher scores indicating more frequent activity. During an average of 4.5 years of follow-up, 111 persons developed AD. In a proportional hazards model that controlled for age, sex, and education, a 1-point increase in cognitive activity score was associated with a 33% reduction in risk of AD (hazard ratio, 0.67; 95% confidence interval, 0.49-0.92). Results were comparable when persons with memory impairment at baseline were excluded and when terms for the apolipoprotein E ∊4 allele and other medical conditions were added. In random-effects models that controlled for age, sex, education, and baseline level of cognitive function, a 1-point increase in cognitive activity was associated with reduced decline in global cognition (by 47%), working memory (by 60%), and perceptual speed (by 30%).ConclusionThese results suggest that frequent participation in cognitively stimulating activities is associated with reduced risk of AD.
Familial aggregation of irritable bowel syndrome: a prospective study
Authors: J S Kalantar
Journal: Gut (2003)

<b>Background:</b> Patients with irritable bowel syndrome (IBS) often report family members with similar symptoms, but family studies are lacking. We hypothesised that if there is familial aggregation, there would be an increased frequency of IBS in first degree relatives of IBS patients compared with relatives of controls (the patient's spouse). <b>Methods:</b> A valid self report bowel disease questionnaire (BDQ) that recorded symptoms, the somatic symptom checklist (a measure of somatisation), and a family information form (FIF) to collect the names and addresses of all first degree relatives were mailed to two groups of patients and their spouses (patients attending an IBS educational programme and residents of Olmsted County, Minnesota, who had been coded as IBS on a database). A BDQ was then mailed to all first degree relatives of subjects identified from the FIF. IBS diagnosis in the relatives was based on the Manning criteria. <b>Results:</b> The BDQ was sent to a total of 355 eligible relatives; 71% responded (73% relatives of patients, 67% relatives of spouses). Relatives were comparable in mean age, sex distribution, and somatisation score. IBS prevalence was 17% in patients' relatives versus 7% in spouses' relatives (odds ratio adjusted for age and sex 2.7 (95% confidence interval (CI) 1.2, 6.3)). When also adjusted for somatisation score, the odds ratio was reduced to 2.5 (95% CI 0.9, 6.7). <b>Conclusions:</b> Familial aggregation of IBS occurs, supporting a genetic or intrafamilial environment component, but this may be explained in part by familial aggregation of somatisation.
Role of Angiotensin II in Activation of the JAK/STAT Pathway Induced by Acute Pressure Overload in the Rat Heart
Authors: Jing Pan, Keiichi Fukuda, Hiroaki Kodama, Shinji Makino, Toshiyuki Takahashi, Motoaki Sano, Shingo Hori, Satoshi Ogawa
Journal: Circulation Research (1997)

Abstract This study was designed to determine whether the JAK/STAT (indicating just another kinase/signal transducer and activator of transcription) pathway is activated in cardiac hypertrophy induced in vivo by pressure overload in rats and to demonstrate whether angiotensin II is involved in the activation of the JAK/STAT pathway. Acute pressure overload was produced by constricting the abdominal aorta of Wistar rats. Immunoprecipitation–Western blot analysis revealed that pressure overload activated JAK1, JAK2, and Tyk2 as early as 5 minutes and that STAT1, STAT2, and STAT3 were tyrosine-phosphorylated rapidly after exposure to the pressure overload. Phosphorylation of STAT1 and STAT2 peaked in the early stage at 5 to 15 minutes, whereas that of STAT3 peaked in the late stage at 60 minutes. Gel mobility shift of the interferon gamma activation site/interferon alpha–stimulating response element was observed immediately after the aortic banding, whereas the band of sis -inducing element was shifted in the late stage at 60 minutes. Both cilazapril (angiotensin II–converting enzyme inhibitor) and E4177 (angiotensin II type 1 [AT 1 ] receptor antagonist) significantly suppressed the phosphorylation of Tyk2 and partially inhibited the phosphorylation of JAK2, but neither affected JAK1. Coimmunoprecipitation of the AT 1 receptor with JAK2 or Tyk2 was clearly observed at 5 minutes and peaked at 15 minutes (20-fold the control value). These results indicate that the JAK/STAT pathway is activated by acute pressure overload in rats and that angiotensin II is involved in activating Tyk2, and partially activating JAK2, via the AT 1 receptor. Both angiotensin II–dependent and –independent pathways take part in activating the JAK/STAT pathway in the pressure-overloaded rat heart.
Integrative Genomics Analysis Identifies Candidate Drivers at 3q26-29 Amplicon in Squamous Cell Carcinoma of the Lung
Authors: Jing Wang, Jun Qian, Megan D. Hoeksema, Yong Zou, Allan V. Espinosa, S.M. Jamshedur Rahman, Bing Zhang, Pierre P. Massion
Journal: Clinical Cancer Research (2013)

Chromosome 3q26-29 is a critical region of genomic amplification in lung squamous cell carcinomas (SCC). Identification of candidate drivers in this region could help uncover new mechanisms in the pathogenesis and potentially new targets in SCC of the lung.We conducted a meta-analysis of seven independent datasets containing a total of 593 human primary SCC samples to identify consensus candidate drivers in 3q26-29 amplicon. Through integrating protein-protein interaction network information, we further filtered for candidates that may function together in a network. Computationally predicted candidates were validated using RNA interference (RNAi) knockdown and cell viability assays. Clinical relevance of the experimentally supported drivers was evaluated in an independent cohort of 52 lung SCC patients using survival analysis.The meta-analysis identified 20 consensus candidates, among which four (SENP2, DCUN1D1, DVL3, and UBXN7) are involved in a small protein-protein interaction network. Knocking down any of the four proteins led to cell growth inhibition of the 3q26-29-amplified SCC. Moreover, knocking down of SENP2 resulted in the most significant cell growth inhibition and downregulation of DCUN1D1 and DVL3. Importantly, a gene expression signature composed of SENP2, DCUN1D1, and DVL3 stratified patients into subgroups with different response to adjuvant chemotherapy.Together, our findings show that SENP2, DCUN1D1, and DVL3 are candidate driver genes in the 3q26-29 amplicon of SCC, providing novel insights into the molecular mechanisms of disease progression and may have significant implication in the management of SCC of the lung.
Biochemical, Cellular, and <i>In vivo</i> Activity of Novel ATP-Competitive and Selective Inhibitors of the Mammalian Target of Rapamycin
Authors: Ker Yu, Lourdes Toral-Barza, Celine Shi, Wei-Guo Zhang, Judy Lucas, Boris Shor, Jamie Kim, Jeroen Verheijen, Kevin Curran, David J. Malwitz, Derek C. Cole, John Ellingboe, Semiramis Ayral-Kaloustian, Tarek S. Mansour, James J. Gibbons, Robert T. Abraham, Pawel Nowak, Arie Zask
Journal: Cancer Research (2009)

The mammalian target of rapamycin (mTOR) is centrally involved in cell growth, metabolism, and angiogenesis. While showing clinical efficacy in a subset of tumors, rapamycin and rapalogs are specific and allosteric inhibitors of mTOR complex 1 (mTORC1), but they do not directly inhibit mTOR complex 2 (mTORC2), an emerging player in cancer. Here, we report chemical structure and biological characterization of three pyrazolopyrimidine ATP-competitive mTOR inhibitors, WAY-600, WYE-687, and WYE-354 (IC(50), 5-9 nmol/L), with significant selectivity over phosphatidylinositol 3-kinase (PI3K) isofoms (>100-fold). Unlike the rapalogs, these inhibitors acutely blocked substrate phosphorylation by mTORC1 and mTORC2 in vitro and in cells in response to growth factor, amino acids, and hyperactive PI3K/AKT. Unlike the inhibitors of PI3K or dual-pan PI3K/mTOR, cellular inhibition of P-S6K1(T389) and P-AKT(S473) by the pyrazolopyrimidines occurred at significantly lower inhibitor concentrations than those of P-AKT(T308) (PI3K-PDK1 readout), showing mTOR selectivity in cellular setting. mTOR kinase inhibitors reduced AKT downstream function and inhibited proliferation of diverse cancer cell lines. These effects correlated with a strong G(1) cell cycle arrest in both the rapamycin-sensitive and rapamycin-resistant cells, selective induction of apoptosis, repression of global protein synthesis, and down-regulation of angiogenic factors. When injected into tumor-bearing mice, WYE-354 inhibited mTORC1 and mTORC2 and displayed robust antitumor activity in PTEN-null tumors. Together, our results highlight mechanistic differentiation between rapalogs and mTOR kinase inhibitors in targeting cancer cell growth and survival and provide support for clinical development of mTOR kinase inhibitors as new cancer therapy.
Early versus late alternating chemotherapy in small-cell lung cancer
Authors: R.A. Joss, M. Bacchi, C. Hürny, J. Bernhard, T. Cerny, G. Martinelli, S. Leyvraz, H.J. Senn, R. Stahel, P. Siegenthaler, C. Ludwig, P. Alberto
Journal: Annals of Oncology (1995)
Come dance with me in Ireland
Authors: L. Farrell
Journal: BMJ (2009)

Admit it. You know it. I know it, we all know it: a doctor’s most secret and unholy joy is making another doctor look like a klutz. It can be subtle: the almost imperceptible raising of an eyebrow, the almost inaudible in-drawing of breath. Or it can be a custard pie in the face.

“Perhaps you could take this call,” said my partner, poker faced. I was young, keen as a puppy, and I bounced beamishly out the door. I didn’t know the …
Idiotypic and subgroup analysis of human monoclonal rheumatoid factors. Implications for structural and genetic basis of autoantibodies in humans.
Authors: G J Silverman, R D Goldfien, P Chen, R A Mageed, R Jefferis, F Goñi, B Frangione, S Fong, D A Carson
Journal: Journal of Clinical Investigation (1988)

Rheumatoid factors (RFs) in humans have been studied intensively because of their association with autoimmune and lymphoproliferative diseases. Many human IgM-RFs express cross-reactive idiotypes (CRIs) and have homologous light chains, some of which are encoded by a single V kappa gene, termed V kappa 325. However, although antibody activity generally requires the interaction between heavy and light chain variable regions, much less is known about structural relationships among RF heavy chains. To delineate further the structural and genetic basis of RF autoantibody synthesis, we generated "sequence-dependent" reagents specific for the human heavy and kappa light chain subgroups, and used them to analyze a panel of 27 monoclonal RFs. In addition, these proteins were tested for the expression of a heavy chain-associated CRI (G6), and a light chain-associated CRI (17.109). The results showed that most 17.109-reactive RFs contain heavy chains of the VHI subgroup, which bear the G6 idiotypic marker. However, among the 14 17.109-reactive RFs, two have heavy chains of the VHII subgroup, and another two contain heavy chains of the VHIII subgroup. Previously, we have shown that 17.109 is a phenotypic marker of the human V kappa 325 gene. Accordingly, these results demonstrate that the same human V kappa gene can combine with several VH genes from different VH gene subgroups to generate RF activity.
A-Z of nutritional supplements: dietary supplements, sports nutrition foods and ergogenic aids for health and performance--Part 23
Authors: M K Ranchordas, E Blomstrand, P C Calder, L M Burke, S J Stear, L M Castell
Journal: British Journal of Sports Medicine (2011)

A-z of nutritional supplements : dietary supplements, sports nutrition foods and ergogenic aids for health and performance--part 23.