tbuckley/cabot-search huggingface dataset:
Molecular Mechanisms Regulating Hormone-Sensitive Lipase and Lipolysis
Authors: Cecilia Holm, Torben Østerlund, Henrik Laurell, Juan Antonio Contreras
Journal: Annual Review of Nutrition (2000)

Hormone-sensitive lipase, the rate-limiting enzyme of intracellular TG hydrolysis, is a major determinant of fatty acid mobilization in adipose tissue as well as other tissues. It plays a pivotal role in lipid metabolism, overall energy homeostasis, and, presumably, cellular events involving fatty acid signaling. Detailed knowledge about its structure and regulation may provide information regarding the pathogenesis of such human diseases as obesity and diabetes and may generate concepts for new treatments of these diseases. The current review summarizes the recent advances with regard to hormone-sensitive lipase structure and molecular mechanisms involved in regulating its activity and lipolysis in general. A summary of the current knowledge regarding regulation of expression, potential involvement in lipid disorders, and role in tissues other than adipose tissue is also provided.
The humoral immune response to p53 in patients with hepatocellular carcinoma is specific for malignancy and independent of the α-fetoprotein status
Authors: Martin Volkmann, Martina Müller, Walter J. Hofmann, Martina Meyer, Jens Hagelstein, Ulrich Räth, Burkhard Kommerell, Hanswalter Zentgraf, Peter R. Galle
Journal: Hepatology (1993)

Recently, p53 gene aberrations have been recognized as a relevant factor in hepatocarcinogenesis, in tumors from both high-risk and low-risk areas. Because p53 gene mutations typically result in increased p53 levels in tumor cells, this cellular protein might become immunogenic during tumor development. To test this hypothesis, we have analyzed sera from 80 European patients with hepatocellular carcinoma for the presence of p53 antibodies. For this purpose we developed an immunoblot assay using recombinant p53 as antigen. Sixty-seven sera from patients with different acute and chronic liver diseases were used as controls. In addition, serum alpha-fetoprotein assays were performed. Circulating antibodies against p53 were found in 25% (20 of 80) of the sera from patients with hepatocellular carcinoma but not in various nonmalignant liver diseases. The association of p53 antibodies with malignancy was highly significant (p < 0.00003). In 73.8% (59 of 80) of the hepatocellular carcinoma sera the alpha-fetoprotein levels were elevated. Among the 21 alpha-fetoprotein-negative hepatocellular carcinoma sera, 5 were found to contain p53 antibodies (23.8%). In conclusion, an antibody response against p53 developed in a significant proportion of patients with hepatocellular carcinoma but not in those with nonmalignant liver diseases. Serological testing for p53 antibodies gives the opportunity to identify a subgroup of patients with hepatocellular carcinoma not detected by conventional tests for serum alpha-fetoprotein.
Clinical interpretation of antineutrophil cytoplasmic antibodies: parvovirus B19 infection as a pitfall
Authors: J Hermann
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> While antibodies directed against proteinase 3 (PR3-ANCA) and myeloperoxidase (MPO-ANCA) have a high specificity for the diagnosis of systemic vasculitis, they may also be found as an epiphenomenon of acute viral infection. <b>Objective:</b> To investigate whether positive ANCA test results may be a common feature of acute parvovirus B19 infection. <b>Methods:</b> Sera were analysed from 1242 patients from a rheumatology outpatient clinic for reactivity with parvovirus B19 and EBV antibodies. They were tested for the presence of PR3-ANCA and MPO-ANCA, along with sera known to contain IgM antibodies to these viruses obtained from among 41 366 samples submitted for virological screening. <b>Results:</b> ANCA were found in 10% (5/50) of the sera positive for IgM antibodies to parvovirus and in 3/51 sera containing IgM antibodies to EBV. Three of six patients with arthritis and concomitant parvovirus infection were found positive for PR3-ANCA and two were found positive for MPO-ANCA. All six patients tested negative for ANCA after six months of follow up. <b>Conclusions:</b> PR3-ANCA and MPO-ANCA may occur transiently in patients with acute B19 infection or infectious mononucleosis, highlighting the importance of repeated antibody tests in oligosymptomatic clinical conditions in which systemic autoimmune disease is suspected.
Changes in Cardiac Biomarkers During Doxorubicin Treatment of Pediatric Patients With High-Risk Acute Lymphoblastic Leukemia: Associations With Long-Term Echocardiographic Outcomes
Authors: Steven E. Lipshultz, Tracie L. Miller, Rebecca E. Scully, Stuart R. Lipsitz, Nader Rifai, Lewis B. Silverman, Steven D. Colan, Donna S. Neuberg, Suzanne E. Dahlberg, Jacqueline M. Henkel, Barbara L. Asselin, Uma H. Athale, Luis A. Clavell, Caroline Laverdière, Bruno Michon, Marshall A. Schorin, Stephen E. Sallan
Journal: Journal of Clinical Oncology (2012)

Doxorubicin causes cardiac injury and cardiomyopathy in children with acute lymphoblastic leukemia (ALL). Measuring biomarkers during therapy might help individualize treatment by immediately identifying cardiac injury and cardiomyopathy.Children with high-risk ALL were randomly assigned to receive doxorubicin alone (n = 100; 75 analyzed) or doxorubicin with dexrazoxane (n = 105; 81 analyzed). Echocardiograms and serial serum measurements of cardiac troponin T (cTnT; cardiac injury biomarker), N-terminal pro-brain natriuretic peptide (NT-proBNP; cardiomyopathy biomarker), and high-sensitivity C-reactive protein (hsCRP; inflammatory biomarker) were obtained before, during, and after treatment.cTnT levels were increased in 12% of children in the doxorubicin group and in 13% of the doxorubicin-dexrazoxane group before treatment but in 47% and 13%, respectively, after treatment (P = .005). NT-proBNP levels were increased in 89% of children in the doxorubicin group and in 92% of children in the doxorubicin-dexrazoxane group before treatment but in only 48% and 20%, respectively, after treatment (P = .07). The percentage of children with increased hsCRP levels did not differ between groups at any time. In the first 90 days of treatment, detectable increases in cTnT were associated with abnormally reduced left ventricular (LV) mass and LV end-diastolic posterior wall thickness 4 years later (P < .01); increases in NT-proBNP were related to an abnormal LV thickness-to-dimension ratio, suggesting LV remodeling, 4 years later (P = .01). Increases in hsCRP were not associated with any echocardiographic variables.cTnT and NT-proBNP may hold promise as biomarkers of cardiotoxicity in children with high-risk ALL. Definitive validation studies are required to fully establish their range of clinical utility.
MIGRATION OF PARASITES AS THE CAUSE OF ANEMIA IN ÆSTIVO-AUTUMNAL MALARIAL INFECTIONS
Authors: Mary R. Lawson
Journal: The Journal of Experimental Medicine (1919)

The anemia in malarial infections is explained by the fact that each parasite destroys several red corpuscles. Reduction of hemoglobin out of proportion to the loss of red corpuscles is explained by the fact that there is always a partial loss of hemoglobin in certain of the surviving corpuscles due to parasitic action. Migration of parasites occurs in all aestivo-autumnal infections. If one wishes to observe, migrations, it will save time to study the heavy infections. Free parasites have been frequently noted by many observers, who have failed to interpret properly their presence in the blood.
Interleukin 18
Authors: Susan L. Swain
Journal: The Journal of Experimental Medicine (2001)

IL-18 was identified as a factor promoting IFN-γ production 1 and it was originally called IFN-γ–inducing factor (IGIF). Further study indicated IL-18 had a structure related to IL-1 2 and later it was found that the IL-18 receptor resembles that for IL-1 34. IL-18, like IL-1 and agents interacting with Toll receptors, signals via MyD88 which activates TNF receptor–associated factor and ultimately nuclear factor κB 5. Like IL-1, IL-18 is made as an inactive precursor that is cleaved by caspase-1 (interleukin-1–converting enzyme) to produce active cytokine 6. Many cell types have been reported to produce IL-18, including macrophages and dendritic cells 7; IL-18 mRNA or protein is also seen in Kupffer cells 8, astrocytes and microglia 9, intestinal and airway epithelial cells 10, and in kerotinocytes 11 and osteoblasts 12. What induces IL-18 has not been extensively studied, but IL-18 is found after bacterial 13 and viral 14 infection and, by inference, in many other infectious diseases. IL-18 production from many cells is constitutive or prolonged after induction 15. An important, but not well-explored, role for IL-18 can also be inferred from the fact that poxviruses make a homologue of IL-18–binding protein, a natural suppressor of IL-18 16 and also an inhibitor of interleukin-1–converting enzyme 17.
Slit1 and Slit2 Cooperate to Prevent Premature Midline Crossing of Retinal Axons in the Mouse Visual System
Authors: Andrew S. Plump, Lynda Erskine, Christelle Sabatier, Katja Brose, Charles J. Epstein, Corey S. Goodman, Carol A. Mason, Marc Tessier-Lavigne
Journal: Neuron (2002)
Aspirin and COX-2 Inhibitor Use in Patients With Stage III Colon Cancer
Authors: Kimmie Ng, Jeffrey A Meyerhardt, Andrew T Chan, Kaori Sato, Jennifer A Chan, Donna Niedzwiecki, Leonard B Saltz, Robert J Mayer, Al B Benson, Paul L Schaefer, Renaud Whittom, Alexander Hantel, Richard M Goldberg, Alan P Venook, Shuji Ogino, Edward L Giovannucci, Charles S Fuchs
Journal: JNCI Journal of the National Cancer Institute (2014)

We conducted a prospective, observational study of aspirin and COX-2 inhibitor use and survival in stage III colon cancer patients enrolled in an adjuvant chemotherapy trial. Among 799 eligible patients, aspirin use was associated with improved recurrence-free survival (RFS) (multivariable hazard ratio [HR] = 0.51, 95% confidence interval [CI] = 0.28 to 0.95), disease-free survival (DFS) (HR = 0.68, 95% CI = 0.42 to 1.11), and overall survival (OS) (HR = 0.63, 95% CI = 0.35 to 1.12). Adjusted HRs for DFS and OS censored at five years (in an attempt to minimize misclassification from noncancer death) were 0.61 (95% CI = 0.36 to 1.04) and 0.48 (95% CI = 0.23 to 0.99). Among 843 eligible patients, those who used COX-2 inhibitors had multivariable HRs for RFS, DFS, and OS of 0.53 (95% CI = 0.27 to 1.04), 0.60 (95% CI = 0.33 to 1.08), and 0.50 (95% CI = 0.23 to 1.07), and HRs of 0.47 (95% CI = 0.24 to 0.91) and 0.26 (95% CI = 0.08 to 0.81) for DFS and OS censored at five years. Aspirin and COX-2 inhibitor use may be associated with improved outcomes in stage III colon cancer patients.
Effect of Margin Status on Local Recurrence After Breast Conservation and Radiation Therapy for Ductal Carcinoma In Situ
Authors: Clive Dunne, John P. Burke, Monica Morrow, Malcolm R. Kell
Journal: Journal of Clinical Oncology (2009)

There is no consensus on what constitutes an adequate surgical margin in patients receiving breast-conserving surgery (BCS) and postoperative radiation therapy (RT) for ductal carcinoma in situ (DCIS). Inadequate margins may result in high local recurrence, and excessively large resections may lead to poor cosmetic outcome without oncologic benefit.A comprehensive search for published trials that examined outcomes after adjuvant RT after BCS for DCIS was performed using MEDLINE and cross referencing available data. Reviews of each study were conducted, and data were extracted. Primary outcome was ipsilateral breast tumor recurrence (IBTR) related to surgical margins.A total of 4,660 patients were identified from trials examining BCS and RT for DCIS. Patients with negative margins were significantly less likely to experience recurrence than patients with positive margins after RT (odds ratio [OR] = 0.36; 95% CI, 0.27 to 0.47). A negative margin significantly reduced the risk of IBTR when compared with a close (OR = 0.59; 95% CI, 0.42 to 0.83) or unknown margin (OR = 0.56; 95% CI, 0.36 to 0.87). When specific margin thresholds were examined, a 2-mm margin was superior to a margin less than 2 mm (OR = 0.53; 95% CI, 0.26 to 0.96); however, we saw no significant difference in the rate of IBTR with margins between 2 mm and more than 5 mm (OR = 1.51; 95% CI, 0.51 to 5.0; P > .05).Surgical margins negative for DCIS should be obtained after BCS for DCIS. A margin threshold of 2 mm seems to be as good as a larger margin when BCS for DCIS is combined with RT.
Activation-Induced Cytidine Deaminase Contributes to Pancreatic Tumorigenesis by Inducing Tumor-Related Gene Mutations
Authors: Yugo Sawai, Yuzo Kodama, Takahiro Shimizu, Yuji Ota, Takahisa Maruno, Yuji Eso, Akira Kurita, Masahiro Shiokawa, Yoshihisa Tsuji, Norimitsu Uza, Yuko Matsumoto, Toshihiko Masui, Shinji Uemoto, Hiroyuki Marusawa, Tsutomu Chiba
Journal: Cancer Research (2015)

Abstract Pancreatic ductal adenocarcinoma (PDAC) develops via an accumulation of various gene mutations. The mechanism underlying the mutations in PDAC development, however, is not fully understood. Recent insight into the close association between the mutation pattern of various cancers and specific mutagens led us to investigate the possible involvement of activation-induced cytidine deaminase (AID), a DNA editing enzyme, in pancreatic tumorigenesis. Our immunohistochemical findings revealed AID protein expression in human acinar ductal metaplasia, pancreatic intraepithelial neoplasia, and PDAC. Both the amount and intensity of the AID protein expression increased with the progression from precancerous to cancerous lesions in human PDAC tissues. To further assess the significance of ectopic epithelial AID expression in pancreatic tumorigenesis, we analyzed the phenotype of AID transgenic (AID Tg) mice. Consistent with our hypothesis that AID is involved in the mechanism of the mutations underlying pancreatic tumorigenesis, we found precancerous lesions developing in the pancreas of AID Tg mice. Using deep sequencing, we also detected Kras and c-Myc mutations in our analysis of the whole pancreas of AID Tg mice. In addition, Sanger sequencing confirmed the presence of Kras, c-Myc, and Smad4 mutations, with the typical mutational footprint of AID in precancerous lesions in AID Tg mice separated by laser capture microdissection. Taken together, our findings suggest that AID contributes to the development of pancreatic precancerous lesions by inducing tumor-related gene mutations. Our new mouse model without intentional manipulation of specific tumor-related genes provides a powerful system for analyzing the mutations involved in PDAC. Cancer Res; 75(16); 3292–301. ©2015 AACR.
MiR-320a acts as a prognostic factor and Inhibits metastasis of salivary adenoid cystic carcinoma by targeting ITGB3
Authors: Lijuan Sun, Bodu Liu, Zhaoyu Lin, Yandan Yao, Yanyang Chen, Yang Li, Jianing Chen, Dongsheng Yu, Zhangui Tang, Bosheng Wang, Shuguang Zeng, Song Fan, Youyuan Wang, Yilin Li, Erwei Song, Jinsong Li
Journal: Molecular Cancer (2015)

Salivary Adenoid cystic carcinoma (SACC) patients with local invasion and lung metastasis are often resistant to conventional therapy such as operation, chemotherapy and radiotherapy. To explore the underling mechanisms, we studied the roles of miRNA in regulating invasiveness of SACC cells.MicroRNA profiling was done in SACC cells with microarray. MiRNA mimics or antisense oligonucleotide was transfected and invasiveness of SACC cells was evaluated by adhesion assay and transwell assay. The target gene of miRNA was identified by luciferase reporter assay and "rescue" experiment. Tumor metastasis was evaluated by BALB/c-nu mice xenografts. MiRNA and its target gene expression were identified by in-situ hybridization and immunohistochemistry respectively, in 302 patients from affiliated hospitals of Sun Yat-sen University and in 148 patients from affiliated hospitals of Central South University, and correlated to the clinicopathological status of the patients.MiR-320a was down-regulated in high lung metastatic ACCM and SACC-LM cells compared with the corresponding low metastatic ACC2 and SACC-83 cells, and inhibited adhesion, invasion and migration of SACC cells by targeting integrin beta 3 (ITGB3). In vivo, enforced miR-320a expression suppressed metastasis of SACC xenografts. In the two independent sets, miR-320a was downregulated in primary SACCs with metastasis compared to those without metastasis, and low expression of this miRNA predicts poor patient survival and rapid metastasis. Multivariate analysis showed that miR-320a expression was an independent indicator of lung metastasis.MiR-320a inhibits metastasis in SACCs by targeting ITGB3 and may serve as a therapeutic target and prognostic marker in salivary cancers.
Mental Health Problems of Homeless Women and Differences Across Subgroups
Authors: Marjorie J. Robertson, Marilyn A. Winkleby
Journal: Annual Review of Public Health (1996)

Homeless women are a large and diverse group, constituting one fifth of the US homeless adult population. Although most homeless women do not have major mental illness, homeless women exhibit disproportionately high rates of major mental disorders and other mental problems. Rates of mental disorders are highest among whites and women without children, and important variations by subgroups of homeless women reinforce the need for disaggregated analysis. Many homeless women with serious mental illness are not receiving needed care, apparently due in part to the lack of perception of a mental health problem and the lack of services designed to meet the special needs of homeless women.
Survival and differentiation of porcine hepatocytes encapsulated by semiautomatic device and allotransplanted in large number without immunosuppression
Authors: Stéphane Benoist, Riad Sarkis, Najim Chafaı̈, Véronique Barbu, Jiri Honiger, Fatima Lakehal, Laurent Becquemont, Marielle Baudrimont, Jacqueline Capeau, Chantal Housset, Bernard Nordlinger
Journal: Journal of Hepatology (2001)
Thrombin and NAD(P)H Oxidase–Mediated Regulation of CD44 and BMP4-Id Pathway in VSMC, Restenosis, and Atherosclerosis
Authors: Aleksandr E. Vendrov, Nageswara R. Madamanchi, Zeenat S. Hakim, Mauricio Rojas, Marschall S. Runge
Journal: Circulation Research (2006)

To characterize novel signaling pathways that underlie NAD(P)H oxidase-mediated signaling in atherosclerosis, we first examined differences in thrombin-induced gene expression between wild-type and p47phox(-/-) (NAD[P]H oxidase-deficient) VSMC. Of the 9000 genes analyzed by cDNA microarray method at the G1/S transition point, 76 genes were similarly and significantly modulated in both the cell types, whereas another 22 genes that encompass various functional groups were regulated in NAD(P)H oxidase-dependent manner. Among these 22 genes, thrombin-induced NAD(P)H oxidase-mediated regulation of Klf15, Igbp1, Ak4, Adamts5, Ech1, Serp1, Sec61a2, Aox1, Aoh1, Fxyd5, Rai14, and Serpinh1 was shown for the first time in VSMC. The role of NAD(P)H oxidase in the regulation of a subset of these genes (CD44, BMP4, Id1, and Id3) was confirmed using modulators of reactive oxygen species (ROS) generation, a ROS scavenger and in gain-of-function experiments. We then characterized regulation of these genes in restenosis and atherosclerosis. In both apoE(-/-) mice and in a mouse vascular injury model, these genes are regulated in NAD(P)H oxidase-dependent manner during vascular lesion formation. Based on these findings, we propose that NAD(P)H oxidase-dependent gene expression in general, and the CD44 and BMP4-Id signaling pathway in particular, is important in restenosis and atherosclerosis.
Etrolizumab as induction therapy for ulcerative colitis: a randomised, controlled, phase 2 trial
Authors: Séverine Vermeire, Sharon O'Byrne, Mary Keir, Marna Williams, Timothy T Lu, John C Mansfield, Christopher A Lamb, Brian G Feagan, Julian Panes, Azucena Salas, Daniel C Baumgart, Stefan Schreiber, Iris Dotan, William J Sandborn, Gaik W Tew, Diana Luca, Meina T Tang, Lauri Diehl, Jeffrey Eastham-Anderson, Gert De Hertogh, Clementine Perrier, Jackson G Egen, John A Kirby, Gert van Assche, Paul Rutgeerts
Journal: The Lancet (2014)

Etrolizumab is a humanised monoclonal antibody that selectively binds the β7 subunit of the heterodimeric integrins α4β7 and αEβ7. We aimed to assess etrolizumab in patients with moderately-to-severely active ulcerative colitis.In this double-blind, placebo-controlled, randomised, phase 2 study, patients with moderately-to-severely active ulcerative colitis who had not responded to conventional therapy were recruited from 40 referral centres in 11 countries. Eligible patients (aged 18-75 years; Mayo Clinic Score [MCS] of 5 of higher [or ≥6 in USA]; and disease extending 25 cm or more from anal verge) were randomised (1:1:1) to one of two dose levels of subcutaneous etrolizumab (100 mg at weeks 0, 4, and 8, with placebo at week 2; or 420 mg loading dose [LD] at week 0 followed by 300 mg at weeks 2, 4, and 8), or matching placebo. The primary endpoint was clinical remission at week 10, defined as MCS of 2 or less (with no individual subscore of >1), analysed in the modified intention-to-treat population (mITT; all randomly assigned patients who had received at least one dose of study drug, had at least one post-baseline disease-activity assessment, and had a centrally read screening endoscopic subscore of ≥2). This study is registered with ClinicalTrials.gov, number NCT01336465.Between Sept 2, 2011, and July 11, 2012, 124 patients were randomly assigned, of whom five had a endoscopic subscore of 0 or 1 and were excluded from the mITT population, leaving 39 patients in the etrolizumab 100 mg group, 39 in the etrolizumab 300 mg plus LD group, and 41 in the placebo group for the primary analyses. No patients in the placebo group had clinical remission at week 10, compared with eight (21% [95% CI 7-36]) patients in the etrolizumab 100 mg group (p=0·0040) and four (10% [0·2-24]) patients in the 300 mg plus LD group (p=0·048). Adverse events occurred in 25 (61%) of 41 patients in the etrolizumab 100 mg group (five [12%] of which were regarded as serious), 19 (48%) of 40 patients in the etrolizumab 300 mg plus LD group (two [5%] serious), and 31 (72%) of 43 patients in the placebo group (five [12%] serious).Etrolizumab was more likely to lead to clinical remission at week 10 than was placebo. Therefore, blockade of both α4β7 and αEβ7 might provide a unique therapeutic approach for the treatment of ulcerative colitis, and phase 3 studies have been planned.Genentech.