tbuckley/cabot-search huggingface dataset:
Overexpression of 5-Lipoxygenase in Colon Polyps and Cancer and the Effect of 5-LOX Inhibitors <i>In vitro</i> and in a Murine Model
Authors: Laleh G. Melstrom, David J. Bentrem, Mohammad R. Salabat, Timothy J. Kennedy, Xian-Zhong Ding, Matthew Strouch, Sambasiva M. Rao, Richard C. Witt, Charles A. Ternent, Mark S. Talamonti, Richard H. Bell, Thomas A. Adrian
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Arachidonic acid metabolism via the cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) pathways modulates cell growth and apoptosis. Many studies have examined the effects of COX inhibitors on human colorectal cancer, but the role of 5-LOX in colonic cancer development has not been well studied. The purpose of this study was to evaluate the expression of 5-LOX in colonic polyps and cancer and the effect of 5-LOX inhibition on colon cancer cell proliferation. Experimental Design: Colonic polyps, cancer, and normal mucosa were evaluated for 5-LOX expression by immunohistochemistry. Reverse transcription-PCR was used to establish 5-LOX expression in colon cancer cells. Thymidine incorporation and cell counts were used to determine the effect of the nonspecific LOX inhibitor Nordihydroguaiaretic Acid and the 5-LOX inhibitor Rev5901 on DNA synthesis. A heterotopic xenograft model in athymic mice using HT29 and LoVo human colon cancer cells was used to evaluate the effect of the 5-LOX inhibitor zileuton on tumor growth. Results: 5-LOX is overexpressed in adenomatous polyps and cancer compared with that of normal colonic mucosa. LOX inhibition and 5-LOX inhibition decreased DNA synthesis in a concentration- and time-dependent manner in the Lovo cell line (P &amp;lt; 0.05). Inhibition of 5-LOX in an in vivo colon cancer xenograft model inhibited tumor growth compared with that of controls (P &amp;lt; 0.05). Conclusions: This study showed that 5-LOX is up-regulated in adenomatous colon polyps and cancer compared with normal colonic mucosa. The blockade of 5-LOX inhibits colon cancer cell proliferation both in vitro and in vivo and may prove a beneficial chemopreventive therapy in colon cancer.
<i>Helicobacter pylori</i> specific nested PCR assay for the detection of 23S rRNA mutation associated with clarithromycin resistance
Authors: S Maeda, H Yoshida, K Ogura, F Kanai, Y Shiratori, M Omata
Journal: Gut (1998)

Clarithromycin is one of the most important antibiotics for Helicobacter pylori eradication. However, 5-10% of strains are reported to be resistant. It has been shown that one point mutation in the 23S rRNA gene is associated with resistance to clarithromycin.To establish a polymerase chain reaction (PCR) system which amplifies a segment of the 23S rRNA gene containing the mutation points with primers specific for H pylori, so that H pylori infection and the mutation associated with clarithromycin resistance can be examined simultaneously.To detect H pylori infection and the mutation simultaneously, primers specific for the H pylori 23S rRNA gene were designed based on sequence conservation among H pylori strains and sequence specificity as compared with other bacteria. DNA from 57 cultured strains and from 39 gastric juice samples was amplified in the seminested 23S rRNA PCR. Clinical applicability was evaluated in 85 patients.DNA samples from 57 cultured strains were all amplified. The novel assay and the urease A PCR agreed in 37/39 gastric juice samples with no false positives. The assay did not amplify the DNA of bacteria other than H pylori. Eight of 85 samples had the mutation before treatment. In clarithromycin based treatment, eradication was achieved in 2/5 (40%) with the mutation and 29/34 (85%) without the mutation.The assay using gastric juice is quick (within 12 hours) and non-invasive (endoscopy not required), enabling rapid initiation of appropriate antibiotic treatment.
Impact of the Conditioning Regimen in Patients With Multiple Myeloma Who Undergo Autologous Transplantation
Authors: Javier de la Rubia, Juan J. Lahuerta
Journal: Journal of Clinical Oncology (2011)

Recently, Regelink et al 1 reported the long-term results of a series of 90 patients with multiple myeloma (MM) who underwent either single or tandem autologous stem-cell transplantation.Conditioning regimens that were administered for the first and second transplantation were high-dose melphalan (MEL) and the combination of busulfan (BU) and cyclophosphamide, respectively.The authors reported a significantly higher 10-year overall survival and event-free survival for patients in the tandem transplantation group.According to their hypothesis, the better outcomes that were observed in patients who underwent tandem transplantation were only a result of the greater amount of chemotherapy administered in this group of patients; this suggests that these results would have been achieved regardless of the conditioning regimen that was administered in the second transplantation.However, and in contrast to the opinion of Regelink et al, we believe that the use of a preparative regimen that combined two alkylating agents in the second transplantation could have played a key role in the encouraging long-term results that were reported by the authors.In this regard, when two conditioning regimens (MEL v BU ϩ MEL, or BUMEL) were prospectively compared by the Programa Espan ˜ol de Tratamientos en Hematología (PETHEMA)/Grupo Espan ˜ol de Mieloma (GEM), a higher response rate was found with BUMEL than with MEL alone.Furthermore, median progression-free survival favored BUMEL. 2 These results have been recently updated, and after a median follow-up of 72 and 47 months in the BUMEL and MEL groups, respectively, the median progression-free survival was 41 months for patients who received BUMEL and 31 months for those who received MEL 200 mg/m 2 .At 5 years, progression-free survival was 39% (95% CI, 34% to 44%) for patients in the BUMEL group compared with 21% (95% CI, 18% to 24%) for patients in the MEL 200 mg/m 2 group (P ϭ .009). 3 Thus, our results strongly suggest that the conditioning regimen that is administered before transplantation may be of the utmost importance in the long-term results of these patients.Despite many advances in the field of MM, there are still challenges ahead.Today, relapse is the main cause of failure for patients with MM who undergo autologous stem-cell transplantation.Therefore, from our point of view, the development of new preparative regimens is a logical approach to try to improve current results.In this regard, our results as well as those reported by Regelink et al 1 suggest that the administration of alternative conditioning regimens, such as the combination of BU and MEL, may offer an improved response compared with the standard high-dose MEL, and this deserves additional investigation.
Apolipoprotein E Suppresses the Type I Inflammatory Response In Vivo
Authors: Kamilah Ali, Melissa Middleton, Ellen Puré, Daniel J. Rader
Journal: Circulation Research (2005)

Apolipoprotein E (apoE) is synthesized in the liver and in macrophages, and it has antiatherogenic properties that are mediated, at least in part, through the regulation of plasma cholesterol homeostasis. Previous data suggest that apoE also has antiinflammatory properties that may contribute to protection against atherosclerosis independent of its role in lipid metabolism. In this study, apoE knockout and C57BL/6 mice were stimulated with low-dose lipopolysaccharide (LPS) and other Toll-like receptor (TLR) agonists. We show that apoE modulates the systemic type I inflammatory response in vivo. The proinflammatory cytokines tumor necrosis factor α, interleukin (IL)-6, IL-12, and interferon-γ were upregulated to a significantly greater extent in apoE-deficient mice than in wild-type mice at both the mRNA and protein levels following administration of LPS. In contrast, hypercholesterolemic low-density lipoprotein receptor/apobec-1 double knockout mice had a similar cytokine response as wild-type mice, eliminating hypercholesterolemia as a cause for the exaggerated cytokine response. Importantly, reconstitution of apoE expression in the liver of apoE-deficient mice normalized the LPS-induced plasma protein levels of IL-12p40. Furthermore, there was selective upregulation of plasma IL-12 in apoE knockout mice by a TLR3 agonist, poly I:C, but not by other TLR agonists, CpG oligonucleotide or Toxoplasma gondii antigen. This implies that apoE selectively regulates TLR4- and TLR3-mediated signaling of IL-12 production. These results indicate that apoE modulates the T helper-1–type immune response in vivo by modulating IL-12 production.
A Spectrophotometric Study of Actomyosin
Authors: JANE S. ROBB, MARLIN GRUBB, HELENA BRAUNFELDS
Journal: Circulation Research (1955)

It is known that when actomyosin and adenosine triphosphate (ATP) interact, the ultraviolet absorption is no longer that characteristic either of actomyosin or of ATP. This report deals with a spectrophotometric study of interactions of various chemicals and/or drugs with actomyosin. The intention was to discover whether these agents alter the absorption, i.e., optical density (O.D.) of actomyosin solutions and if so, whether all the agents produce similar changes.
Interleukin 4 reverses T cell proliferative unresponsiveness and prevents the onset of diabetes in nonobese diabetic mice.
Authors: M J Rapoport, A Jaramillo, D Zipris, A H Lazarus, D V Serreze, E H Leiter, P Cyopick, J S Danska, T L Delovitch
Journal: The Journal of Experimental Medicine (1993)

Beginning at the time of insulitis (7 wk of age), CD4+ and CD8+ mature thymocytes from nonobese diabetic (NOD) mice exhibit a proliferative unresponsiveness in vitro after T cell receptor (TCR) crosslinking. This unresponsiveness does not result from either insulitis or thymic involution and is long lasting, i.e., persists until diabetes onset (24 wk of age). We previously proposed that it represents a form of thymic T cell anergy that predisposes to diabetes onset. This hypothesis was tested in the present study by further investigating the mechanism responsible for NOD thymic T cell proliferative unresponsiveness and determining whether reversal of this unresponsiveness protects NOD mice from diabetes. Interleukin 4 (IL-4) secretion by thymocytes from &amp;gt; 7-wk-old NOD mice was virtually undetectable after treatment with either anti-TCR alpha/beta, anti-CD3, or Concanavalin A (Con A) compared with those by thymocytes from age- and sex-matched control BALB/c mice stimulated under identical conditions. NOD thymocytes stimulated by anti-TCR alpha/beta or anti-CD3 secreted less IL-2 than did similarly activated BALB/c thymocytes. However, since equivalent levels of IL-3 were secreted by Con A-activated NOD and BALB/c thymocytes, the unresponsiveness of NOD thymic T cells does not appear to be dependent on reduced IL-2 secretion. The surface density and dissociation constant of the high affinity IL-2 receptor of Con A-activated thymocytes from both strains are also similar. The patterns of unresponsiveness and lymphokine secretion seen in anti-TCR/CD3-activated NOD thymic T cells were also observed in activated NOD peripheral spleen T cells. Exogenous recombinant (r)IL-2 only partially reverses NOD thymocyte proliferative unresponsiveness to anti-CD3, and this is mediated by the inability of IL-2 to stimulate a complete IL-4 secretion response. In contrast, exogenous IL-4 reverses the unresponsiveness of both NOD thymic and peripheral T cells completely, and this is associated with the complete restoration of an IL-2 secretion response. Furthermore, the in vivo administration of rIL-4 to prediabetic NOD mice protects them from diabetes. Thus, the ability of rIL-4 to reverse completely the NOD thymic and peripheral T cell proliferative defect in vitro and protect against diabetes in vivo provides further support for a causal relationship between this T cell proliferative unresponsiveness and susceptibility to diabetes in NOD mice.
Autoantibodies against type XVII collagen C-terminal domain in a patient with bullous pemphigoid associated with psoriasis vulgaris
Authors: D. Inokuma, K. Kodama, K. Natsuga, M. Kasai, M. Abe, W. Nishie, R. Abe, T. Hashimoto, H. Shimizu
Journal: British Journal of Dermatology (2008)

Journal Article Autoantibodies against type XVII collagen C‐terminal domain in a patient with bullous pemphigoid associated with psoriasis vulgaris Get access D. Inokuma, D. Inokuma Department of Dermatology, Hokkaido University Graduate School of Medicine, N 15 W 7, Kita‐ku, Sapporo 060‐8638, Japan Search for other works by this author on: Oxford Academic Google Scholar K. Kodama, K. Kodama Sapporo Railway Hospital, Sapporo, Japan Search for other works by this author on: Oxford Academic Google Scholar K. Natsuga, K. Natsuga Department of Dermatology, Hokkaido University Graduate School of Medicine, N 15 W 7, Kita‐ku, Sapporo 060‐8638, Japan Search for other works by this author on: Oxford Academic Google Scholar M. Kasai, M. Kasai Sapporo Railway Hospital, Sapporo, Japan Search for other works by this author on: Oxford Academic Google Scholar M. Abe, M. Abe Sapporo Railway Hospital, Sapporo, Japan Search for other works by this author on: Oxford Academic Google Scholar W. Nishie, W. Nishie Department of Dermatology, Hokkaido University Graduate School of Medicine, N 15 W 7, Kita‐ku, Sapporo 060‐8638, Japan Search for other works by this author on: Oxford Academic Google Scholar R. Abe, R. Abe Department of Dermatology, Hokkaido University Graduate School of Medicine, N 15 W 7, Kita‐ku, Sapporo 060‐8638, Japan Search for other works by this author on: Oxford Academic Google Scholar T. Hashimoto, T. Hashimoto Department of Dermatology, Kurume University School of Medicine, Kurume, Japan E‐mail: inokuma@med.hokudai.ac.jp Search for other works by this author on: Oxford Academic Google Scholar H. Shimizu H. Shimizu Department of Dermatology, Hokkaido University Graduate School of Medicine, N 15 W 7, Kita‐ku, Sapporo 060‐8638, Japan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 160, Issue 2, 1 February 2009, Pages 451–454, https://doi.org/10.1111/j.1365-2133.2008.08961.x Published: 01 February 2009
Lung cancer practice guidelines: lessons learned and issues addressed by the Ontario Lung Cancer Disease Site Group.
Authors: W K Evans, T Newman, I Graham, J J Rusthoven, D Logan, F A Shepherd, D Chamberlain
Journal: Journal of Clinical Oncology (1997)

The primary objective was to identify the lessons learned and issues addressed by the Disease Site Group (DSG) developing guidelines on lung cancer for practitioners in the province of Ontario.The minutes of the Ontario Lung Cancer Disease Site Group (LCDSG) and the meeting notes of a medical sociologist who attended all LCDSG meetings were reviewed to identify the disease-specific and generic issues addressed by the LCDSG during guideline development.The Ontario LCDSG has completed three practice guidelines and has five evidence-based recommendations (EBRs) in production. Topics for guideline development were selected on the basis of known practice variability (eg, advanced-stage non-small-cell lung cancer [NSCLC]); the size of the patient population that could potentially be affected by the guideline; results of phase II trials of new and potentially expensive agents (vinorelbine, paclitaxel, and docetaxel); and randomized controlled clinical trials that support new practice standards (combined modality therapy for unresectable stage III NSCLC). The wording of each EBR reflects the strength and quality of the evidence in support of the treatment option, the primary outcome(s), and the individual physician and discipline values concerning treatment outcomes in the absence of known patient values.
P55 Identifying Potential Predictors of Mortality and Morbidity in Tuberculous Meningitis (TBM)
Authors: C Petridou, C Petridou, A Jayaratnam
Journal: Thorax (2012)

<h3>Introduction</h3> The early and prompt diagnosis of TBM is essential to improve outcomes. Delayed treatment leads to increased morbidity and mortality. Cerebrospinal fluid (CSF) findings may assist in early diagnosis as well as potentially identifying patients at high-risk of death. <h3>Methods</h3> A retrospective analysis of patients treated for TBM from 2000–2010 was undertaken using the London TB Register. Data was collected from medical records and pathology results. <h3>Results</h3> Mortality was 20% (8/41) and 12% (5/41) were left with permanent neurological deficits. Mycobacterium tuberculosis (MTB) was cultured from CSF in 37% (14/38). Mortality in patients in whom CSF was culture positive was higher than those whose CSF culture was negative (33% vs 16%). The mean value of CSF protein was higher in patients with poorer outcomes than those who recovered fully (2.72 vs 1.92 g/L). Corticosteroids were given to 92% of patients (35/38). Of the three patients who did not receive steroids, one was left with a permanent disability. <h3>Conclusions</h3> In our population, we observed high mortality and morbidity rates for patients diagnosed with TBM. A large proportion of diagnoses were not confirmed microbiologically. Higher mortality rates were observed in those whose CSF cultured MTB A possible explanation for this finding is that those patients for whom microbiological confirmation was not obtained, the presumptive diagnosis of TBM was not correct. There is a trend towards higher mortality and morbidity in those with higher CSF protein values. This may be an indicator of increased bacterial load with an associated increase in inflammatory cytokines.
Chimerism of the Renal Glomerulus Revisited
Authors: Yashpal S. Kanwar, Farhad R. Danesh, Sumant S. Chugh
Journal: Journal of the American Society of Nephrology (2007)

Since the early descriptions of Alport syndrome, when the glomerular basement membrane (GBM) was found split into multiple laminar strands, investigators have wondered about the contribution of various cell types in the differential synthesis of these strands[1][1]; podocytes and endothelia flanking
Childhood Sleepwalking and Sleep Terrors
Authors: Dominique Petit, Marie-Hélène Pennestri, Jean Paquet, Alex Desautels, Antonio Zadra, Frank Vitaro, Richard E. Tremblay, Michel Boivin, Jacques Montplaisir
Journal: JAMA Pediatrics (2015)

<h3>Importance</h3> Childhood sleepwalking and sleep terrors are 2 parasomnias with a risk of serious injury for which familial aggregation has been shown. <h3>Objectives</h3> To assess the prevalence of sleepwalking and sleep terrors during childhood; to investigate the link between early sleep terrors and sleepwalking later in childhood; and to evaluate the degree of association between parental history of sleepwalking and presence of somnambulism and sleep terrors in children. <h3>Design, Setting, and Participants</h3> Sleep data from a large prospective longitudinal cohort (the Quebec Longitudinal Study of Child Development) of 1940 children born in 1997 and 1998 in the province were studied from March 1999 to March 2011. <h3>Main Outcomes and Measures</h3> Prevalence of sleep terrors and sleepwalking was assessed yearly from ages 1<sup>1</sup>/<sub>2</sub>and 2<sup>1</sup>/<sub>2</sub>years, respectively, to age 13 years through a questionnaire completed by the mother. Parental history of sleepwalking was also queried. <h3>Results</h3> The peak of prevalence was observed at 1<sup>1</sup>/<sub>2</sub>years for sleep terrors (34.4% of children; 95% CI, 32.3%-36.5%) and at age 10 years for sleepwalking (13.4%; 95% CI, 11.3%-15.5%). As many as one-third of the children who had early childhood sleep terrors developed sleepwalking later in childhood. The prevalence of childhood sleepwalking increases with the degree of parental history of sleepwalking: 22.5% (95% CI, 19.2%-25.8%) for children without a parental history of sleepwalking, 47.4% (95% CI, 38.9%-55.9%) for children who had 1 parent with a history of sleepwalking, and 61.5% (95% CI, 42.8%-80.2%) for children whose mother and father had a history of sleepwalking. Moreover, parental history of sleepwalking predicted the incidence of sleep terrors in children as well as the persistent nature of sleep terrors. <h3>Conclusions and Relevance</h3> These findings substantiate the strong familial aggregation for the 2 parasomnias and lend support to the notion that sleepwalking and sleep terrors represent 2 manifestations of the same underlying pathophysiological entity.
Intensified insulin-based glycaemic control after myocardial infarction: mortality during 20 year follow-up of the randomised Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI 1) trial
Authors: Viveca Ritsinger, Klas Malmberg, Anton Mårtensson, Lars Rydén, Hans Wedel, Anna Norhammar
Journal: The Lancet Diabetes & Endocrinology (2014)
Bone marrow Th17 TNFα cells induce osteoclast differentiation, and link bone destruction to IBD
Authors: Thomas Ciucci, Lidia Ibáñez, Agathe Boucoiran, Eléonore Birgy-Barelli, Jérôme Pène, Grazia Abou-Ezzi, Nadia Arab, Matthieu Rouleau, Xavier Hébuterne, Hans Yssel, Claudine Blin-Wakkach, Abdelilah Wakkach
Journal: Gut (2014)

<h3>Objective</h3> Under both physiological and pathological conditions, bone volume is determined by the rate of bone formation by osteoblasts and bone resorption by osteoclasts. Excessive bone loss is a common complication of human IBD whose mechanisms are not yet completely understood. Despite the role of activated CD4<sup>+</sup> T cells in inflammatory bone loss, the nature of the T cell subsets involved in this process <i>in vivo</i> remains unknown. The aim of the present study was to identify the CD4<sup>+</sup> T cell subsets involved in the process of osteoclastogenesis <i>in vivo</i>, as well as their mechanism of action. <h3>Design</h3> CD4<sup>+</sup> T cells were studied in IL10−/− mice and Rag1−/− mice adoptively transferred with naive CD4<sup>+</sup>CD45RB<sup>high</sup> T cells, representing two well-characterised animal models of IBD and in patients with Crohn9s disease. They were phenotypically and functionally characterised by flow cytometric and gene expression analysis, as well as in <i>in vitro</i> cocultures with osteoclast precursors. <h3>Results</h3> In mice, we identified bone marrow (BM) CD4<sup>+</sup> T cells producing interleukin (IL)-17 and tumour necrosis factor (TNF)-α as an osteoclastogenic T cell subset referred to as Th17 TNF-α<sup>+</sup> cells. During chronic inflammation, these cells migrate to the BM where they survive in an IL-7-dependent manner and where they promote the recruitment of inflammatory monocytes, the main osteoclast progenitors. A population equivalent to the Th17 TNF-α<sup>+</sup> cells was also detected in patients with Crohn9s disease. <h3>Conclusions</h3> Our results highlight the osteoclastogenic function of the Th17 TNF-α<sup>+</sup> cells that contribute to bone loss <i>in vivo</i> in IBD.