tbuckley/cabot-search huggingface dataset:
Abstract B09: Liver-specific knockout of GRP94 in mice disrupts cell adhesion, activates liver progenitor cells, and accelerates liver tumorigenesis
Authors: Wan-Ting Chen, Chun-Chih Tseng, Kyle Pfaffenbach, Gary Kanel, Biquan Luo, Bangyan L. Stiles, Amy S. Lee
Journal: Cancer Research (2013)

Abstract Liver cancer is one of the most common solid tumors with poor prognosis and high mortality. Mutation or deletion of the tumor suppressor PTEN is strongly correlated with human liver cancer. Glucose-regulated protein 94 (GRP94) is a major endoplasmic reticulum (ER) chaperone protein, but its in vivo function is still emerging. To study the role of GRP94 in maintaining liver homeostasis and tumor development, we created two liver-specific knockout mouse models with the deletion of Grp94 alone, or in combination with Pten, using the albumin-cre system. We demonstrated that while deletion of GRP94 in the liver led to hyperproliferation of liver progenitor cells, deletion of both GRP94 and PTEN accelerated development of liver tumors, including both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC) suggestive of progenitor cell origin. Furthermore, at the premalignant stage, we observed disturbance of cell adhesion proteins but no detectable overt liver injury. We further discovered that when GRP94 was deleted in PTEN-null livers, ERK was selectively activated, suggesting that this could be a potential molecular mechanism for enhanced liver tumorigenesis in this mouse model. Conclusion: We identify GRP94 as a novel regulator of cell adhesion, liver homeostasis, and tumorigenesis. Citation Format: Wan-Ting Chen, Chun-Chih Tseng, Kyle Pfaffenbach, Gary Kanel, Biquan Luo, Bangyan L. Stiles, Amy S. Lee. Liver-specific knockout of GRP94 in mice disrupts cell adhesion, activates liver progenitor cells, and accelerates liver tumorigenesis. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr B09.
Correlation between heart rate variability and pulmonary function in adults
Authors: Evandro Sperandio, Mayara Silveira, Agatha Matheus, Vinícius Lauria, David Santos, Rodrigo Pareira, Flávio Almeida, Vítor Almeida, Marcelo Romiti, Antônio Gagliardi, Rodolfo Arantes, Victor Dourado
Journal: European Respiratory Journal (2014)

It is known that oxidative stress in lung disease is associated with a predominance of the sympathetic nervous system. This fact indicates a worse autonomic modulation, which is directly linked to heart rate variability (HRV). We aimed to investigate whether there is correlation between HRV and pulmonary function (PF) in healthy adults. One hundred and nineteen subjects aged 20-80 years were enrolled and performed spirometry. We assessed anthropometrics, fasting blood glucose, triglycerides and cholesterol, tobacco history, and time and frequency domains of short-term HRV analysis (10-min at rest). Physical activity in daily life was evaluated by 7 days of triaxial accelerometry. Significant (p  1  (R 2  = 0,12) and FVC (R 2  = 0,18). We may conclude that there is a moderate but determinant association between HRV and pulmonary function. Whether strategies to enhance the autonomic modulation could slow the decline in lung function should be investigated.
Association of diabetes and tuberculosis: impact on treatment and post-treatment outcomes
Authors: María Eugenia Jiménez-Corona, Luis Pablo Cruz-Hervert, Lourdes García-García, Leticia Ferreyra-Reyes, Guadalupe Delgado-Sánchez, Miriam Bobadilla-del-Valle, Sergio Canizales-Quintero, Elizabeth Ferreira-Guerrero, Renata Báez-Saldaña, Norma Téllez-Vázquez, Rogelio Montero-Campos, Norma Mongua-Rodriguez, Rosa Areli Martínez-Gamboa, José Sifuentes-Osornio, Alfredo Ponce-de-León
Journal: Thorax (2012)

To determine the clinical consequences of pulmonary tuberculosis (TB) among patients with diabetes mellitus (DM).We conducted a prospective study of patients with TB in Southern Mexico. From 1995 to 2010, patients with acid-fast bacilli or Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and microbiological evaluation. Annual follow-ups were performed to ascertain treatment outcome, recurrence, relapse and reinfection.The prevalence of DM among 1262 patients with pulmonary TB was 29.63% (n=374). Patients with DM and pulmonary TB had more severe clinical manifestations (cavities of any size on the chest x-ray, adjusted OR (aOR) 1.80, 95% CI 1.35 to 2.41), delayed sputum conversion (aOR 1.51, 95% CI 1.09 to 2.10), a higher probability of treatment failure (aOR 2.93, 95% CI 1.18 to 7.23), recurrence (adjusted HR (aHR) 1.76, 95% CI 1.11 to 2.79) and relapse (aHR 1.83, 95% CI 1.04 to 3.23). Most of the second episodes among patients with DM were caused by bacteria with the same genotype but, in 5/26 instances (19.23%), reinfection with a different strain occurred.Given the growing epidemic of DM worldwide, it is necessary to add DM prevention and control strategies to TB control programmes and vice versa and to evaluate their effectiveness. The concurrence of both diseases potentially carries a risk of global spreading, with serious implications for TB control and the achievement of the United Nations Millennium Development Goals.
Radiation and Transforming Growth Factor-β Cooperate in Transcriptional Activation of the Profibrotic <i>Plasminogen Activator Inhibitor-1</i> Gene
Authors: Jurre Hageman, Bart J. Eggen, Tom Rozema, Kevin Damman, Harm H. Kampinga, Robert P. Coppes
Journal: Clinical Cancer Research (2005)

Abstract Radiation-induced fibrosis is an important side effect in the treatment of cancer. Profibrotic proteins, such as plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-β (TGF-β), and tissue type inhibitor of metalloproteinases-1 (Timp-1), are thought to play major roles in the development of fibrosis via the modulation of extracellular matrix integrity. We did a detailed analysis of transcriptional activation of these profibrotic genes by radiation and TGF-β. Irradiation of HepG2 cells led to a high increase in PAI-1 mRNA levels and a mild increase in Timp-1 mRNA levels. In contrast, TGF-β1 and Smad7 were not increased. Radiation and TGF-β showed strong cooperative effects in transcription of the PAI-1 gene. The TGF-β1 gene showed a mild cooperative activation, whereas Timp-1 and Smad7 were not cooperatively activated by radiation and TGF-β. Analysis using the proximal 800 bp of the human PAI-1 promoter revealed a dose-dependent increase of PAI-1 levels between 2 and 32 Gy γ-rays that was independent of latent TGF-β activation. Subsequent site-directed mutagenesis of the PAI-1 promoter revealed that mutation of a p53-binding element abolished radiation-induced PAI-1 transcription. In line with this, PAI-1 was not activated in p53-null Hep3B cells, indicating that p53 underlies the radiation-induced PAI-1 activation and the cooperativity with the TGF-β/Smad pathway. Together, these data show that radiation and TGF-β activate PAI-1 via partially nonoverlapping signaling cascades that in concert synergize on PAI-1 transcription. This may play a role in patient-to-patient variations in susceptibility toward fibrosis after radiotherapy.
Human Macrophage–derived Chemokine (MDC), a Novel Chemoattractant for Monocytes, Monocyte-derived Dendritic Cells, and Natural Killer Cells
Authors: Ronald Godiska, David Chantry, Carol J. Raport, Silvano Sozzani, Paola Allavena, Dina Leviten, Alberto Mantovani, Patrick W. Gray
Journal: The Journal of Experimental Medicine (1997)

A cDNA encoding a novel human chemokine was isolated by random sequencing of cDNA clones from human monocyte-derived macrophages. This protein has been termed macrophagederived chemokine (MDC) because it appears to be synthesized specifically by cells of the macrophage lineage. MDC has the four-cysteine motif and other highly conserved residues characteristic of CC chemokines, but it shares &amp;lt;35% identity with any of the known chemokines. Recombinant MDC was expressed in Chinese hamster ovary cells and purified by heparin– Sepharose chromatography. NH2-terminal sequencing and mass spectrophotometry were used to verify the NH2 terminus and molecular mass of recombinant MDC (8,081 dalton). In microchamber migration assays, monocyte-derived dendritic cells and IL-2–activated natural killer cells migrated to MDC in a dose-dependent manner, with a maximal chemotactic response at 1 ng/ml. Freshly isolated monocytes also migrated toward MDC, but with a peak response at 100 ng/ml MDC. Northern analyses indicated MDC is highly expressed in macrophages and in monocyte-derived dendritic cells, but not in monocytes, natural killer cells, or several cell lines of epithelial, endothelial, or fibroblast origin. High expression was also detected in normal thymus and less expression in lung and spleen. Unlike most other CC chemokines, MDC is encoded on human chromosome 16. MDC is thus a unique member of the CC chemokine family that may play a fundamental role in the function of dendritic cells, natural killer cells, and monocytes.
Weighing up risk factors for pneumonia: the role of mental illness and benzodiazepine use
Authors: Jennifer K Quint, Jeremy Stuart Brown
Journal: Thorax (2012)

Pneumonia causes a significant public health burden in the UK in terms of morbidity and mortality. Historically, the annual incidence of community acquired pneumonia has been reported to be between 5 and 11 per 1000 adult population,1–3 estimated more recently to be between 207 and 233 per 100 000 in England.4 In 2010, influenza and pneumonia were responsible for 4.5% of all male deaths, and 5.8% of all female deaths ranking them 5th and 4th in terms of causes of mortality in men and women respectively in England and Wales.5 With such a huge mortality burden, it is important to identify modifiable risk factors to help decrease the incidence of the disease. The commonest cause of community acquired pneumonia, accounting for over a third of cases, is Streptococcus pneumoniae .6 ,7 S pneumoniae is also an important cause of septicaemia, meningitis, infective exacerbations of chronic obstructive pulmonary disease and bronchiectasis. Vaccination against S pneumoniae is recommended in many countries for high risk groups. In the UK, these groups include all children, all those over 65 years, as well as subjects with chronic medical conditions that are associated with a higher risk of pneumococcal disease including COPD, renal impairment and cardiovascular disease.8

Several factors that are associated with an increased risk of pneumonia and pneumococcal disease, including being underweight, excessive alcohol intake and smoking,8–10 are also commoner in patients with mental illnesses such as psychosis and depression. So, is mental illness also a modifiable and important risk factor for pneumonia and pneumococcal disease? In this issue of the journal, two papers are published suggesting it is. Seminog and Goldacre11 investigated the risk of pneumococcal disease in people with severe mental illness. Using two electronic databases, the English national dataset of linked Hospital Episode Statistics and …
Statistical methods and software for the analysis of highthroughput reverse genetic assays using flow cytometry readouts.
Authors: Florian Hahne, Dorit Arlt, Mamatha Sauermann, Meher Majety, Annemarie Poustka, Stefan Wiemann, Wolfgang Huber
Journal: Genome biology (2006)

Highthroughput cell-based assays with flow cytometric readout provide a powerful technique for identifying components of biologic pathways and their interactors. Interpretation of these large datasets requires effective computational methods. We present a new approach that includes data pre-processing, visualization, quality assessment, and statistical inference. The software is freely available in the Bioconductor package prada. The method permits analysis of large screens to detect the effects of molecular interventions in cellular systems.
The effects of isoprenaline on epicardial ST-segment elevation, lactate production, and myocardial blood flow following coronary artery ligation
Authors: R. M. NORRIS, H. J. SMITH, B. N. SINGH, H. NISBET, M. B. JOHN, P. J. HURLEY
Journal: Cardiovascular Research (1975)

Isoprenaline was infused at low and high rates into anaesthetized dogs after ligation of the left anterior descending coronary artery, the resultant changes in epicardial ST-segment elevation being compared with lactate production and myocardial blood flow in the infarcting myocardium. Although ST elevation was increased at both infusion rates, there was no change in the arterial-local coronary venous difference of lactate concentration nor in myocardial blood flow at the centre of the infarct. The results suggest that the relationship between epicardial ST-segment elevation and other indices of ischaemic myocardial injury is complex and requires further evaluation.
Brain Structural Abnormalities in Psychotropic Drug-Naive Pediatric Patients With Obsessive-Compulsive Disorder
Authors: Philip R. Szeszko, Shauna MacMillan, Marjorie McMeniman, Steven Chen, Keith Baribault, Kelvin O. Lim, Jennifer Ivey, Michelle Rose, S. Preeya Banerjee, Rashmi Bhandari, Gregory J. Moore, David R. Rosenberg
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The authors investigated structural abnormalities in brain regions comprising cortical-striatal-thalamic-cortical loops in pediatric patients with obsessive-compulsive disorder (OCD). METHOD: Volumes of the caudate nucleus, putamen, and globus pallidus and gray and white matter volumes of the anterior cingulate gyrus and superior frontal gyrus were computed from contiguous 1.5-mm magnetic resonance images from 23 psychotropic drug-naive pediatric patients with OCD (seven male patients and 16 female patients) and 27 healthy volunteers (12 male subjects and 15 female subjects). RESULTS: Patients had smaller globus pallidus volumes than healthy volunteers, but the two groups did not differ in volumes of the caudate nucleus, putamen, or frontal white matter regions. Compared to healthy volunteers, patients had more total gray matter in the anterior cingulate gyrus but not the superior frontal gyrus. Total anterior cingulate gyrus volume correlated significantly and positively with globus pallidus volume in the healthy volunteers but not in patients. CONCLUSIONS: These findings provide evidence of smaller globus pallidus volume in patients with OCD without the potentially confounding effects of prior psychotropic drug exposure. Volumetric abnormalities in the anterior cingulate gyrus appear specific to the gray matter in OCD, at least at the gross anatomic level, and are consistent with findings of functional neuroimaging studies that have reported anterior cingulate hypermetabolism in the disorder.
Increased Synthesis and Release of Endothelin-1 during the Initial Phase of Airway Inflammation
Authors: FINN FINSNES, GEIR CHRISTENSEN, TORSTEIN LYBERG, OLE M. SEJERSTED, OLE H. SKJØNSBERG
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Recently, we have shown a substantial increase in the endothelin-1 (ET-1) concentration in bronchoalveolar fluid (BALF) during an experimental eosinophilic airway inflammation. Moreover, we observed a significant inhibition of the inflammatory response after treatment with an endothelin receptor antagonist. This indicates that ET-1 may have proinflammatory properties and play a key role in eosinophilic inflammations, such as bronchial asthma. Accordingly, we hypothesized that the synthesis and release of ET-1 precedes the inflammatory response, and that the bronchial epithelium is the site of ET-1 synthesis in the lungs. An eosinophilic airway inflammation was induced by intratracheal Sephadex instillation in rats, and the animals were evaluated after 15 min, 30 min, 1, 2, 3, 6, 12, and 48 h. The ET-1 mRNA synthesis, assessed by Northern and slot blot analyses, was significantly increased 15 min after Sephadex challenge, peaking at 30 min with a 4.7-fold increase, before any signs of inflammation in the BALF could be observed. The increased synthesis was mainly located to the bronchial epithelium and macrophages at sites of inflammation as determined by in situ hybridization. A significant increase in tissue ET-1 was observed 3 h after provocation, and the recruitment of eosinophils followed a substantial release of ET-1 peptide in BALF peaking at 24 h with a 13-fold increase. Therefore, the rapid ET-1 mRNA synthesis and the considerable increase in the level of ET-1 indicate that this peptide plays an important role in the initiation of an eosinophilic airway inflammation.
Experimental Pinta in the Chimpanzee
Authors: U. S. Grant Kuhn
Journal: JAMA (1968)

Pinta is a dermatrophic treponemal disease with immunologic similarities to syphilis but without its generalized and serious consequences. Workers in treponemal immunology have long been intrigued with the possible use of<i>Treponema carateum</i>, the causative agent of pinta, to confer immunity to syphilis.<sup>1</sup>Failure in attempts to establish the disease in experimental animals has impeded the laboratory study of the organism. However, chimpanzees have not heretofore been studied under controlled conditions for their susceptibility to inoculation with<i>T carateum</i>from humans with pinta. The susceptibility of chimpanzees to human syphilis, as reflected in current studies at the Venereal Disease Research Laboratory, and the close immunologic relationship of chimpanzees to man, prompted exploration of the premise that<i>T carateum</i>might also be transferable to these animals. Because pinta does not occur in the United States but can be found to occur to a limited extent in Mexico, a collaborative effort
Azithromycin Blocks Neutrophil Recruitment in<i>Pseudomonas</i>Endobronchial Infection
Authors: Wan C. Tsai, Michael L. Rodriguez, Katherine S. Young, Jane C. Deng, Victor J. Thannickal, Kazuhiro Tateda, Marc B. Hershenson, Theodore J. Standiford
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Macrolides exert their effects on the host by modulation of immune responses. In this study, we assessed the therapeutic efficacy of azithromycin in a murine model of mucoid Pseudomonas aeruginosa endobronchial infection. The clearance of Pseudomonas from the airway of mice treated with the macrolide azithromycin was not different than untreated mice challenged with Pseudomonas beads. However, the azithromycin-treated mice showed a remarkable reduction in lung cellular infiltrate in response to Pseudomonas beads, as compared with untreated mice. This effect was associated with significant decreases in lung levels of tumor necrosis factor-alpha and keratinocyte-derived chemokine in azithromycin-treated mice compared with untreated mice. Furthermore, there was a significant reduction in the response of both mouse and human neutrophils to chemokine-dependent and -independent chemoattractants when studied in vitro. Inhibition of chemotaxis correlated with azithromycin-mediated inhibition of extracellular signal-regulated kinase-1 and -2 activation. This study indicates that the azithromycin treatment in vivo results in significant reduction in airway-specific inflammation, which occurs in part by inhibition of neutrophil recruitment to the lung through reduction in proinflammatory cytokine expression and inhibition of neutrophil migration via the extracellular signal-regulated kinase-1 and -2 signal transduction pathway.
Opportunistic fungal and bacterial infection in the renal transplant recipient.
Authors: N E Tolkoff-Rubin, R H Rubin
Journal: Journal of the American Society of Nephrology (1992)

The risk of opportunistic infection in the renal transplant recipient is determined by the interaction between two factors: the epidemiologic exposures the individual encounters within the community and the hospital and a complex function termed the net state of immunosuppression. There are two general categories of opportunistic fungal infection in this patient population: (1) disseminated primary or reactivation infection with one of the geographically restricted systemic mycoses (histoplasmosis, coccidioidomycosis, blastomycosis, and paracoccidioidomycosis) and (2) opportunistic infection with fungal species that rarely cause invasive infection in the normal host (Aspergillus species, Candida species, Cryptococcus neoformans, and the Mucoraceae), with these last usually being acquired within the hospital environment. Newly available azole compounds, fluconazole and itraconazole, are exciting new alternatives to amphotericin in the treatment of at least some of these infections. The three most important forms of opportunistic bacterial infections are those due to Listeria monocytogenes, Nocardia asteroides, and a variety of mycobacterial species. Clinical diseases with these first two are effectively prevented by low-dose trimethoprim-sulfamethoxazole prophylaxis. There are two cardinal therapeutic rules to be followed by clinicians in dealing with these infections: prevention is better than treatment; when treatment is required, however, the major determinant of the success of therapy is the rapidity with which the diagnosis is made and effective therapy is initiated.
Use of mental health services for anxiety, mood, and substance disorders in 17 countries in the WHO world mental health surveys
Authors: Philip S Wang, Sergio Aguilar-Gaxiola, Jordi Alonso, Matthias C Angermeyer, Guilherme Borges, Evelyn J Bromet, Ronny Bruffaerts, Giovanni de Girolamo, Ron de Graaf, Oye Gureje, Josep Maria Haro, Elie G Karam, Ronald C Kessler, Viviane Kovess, Michael C Lane, Sing Lee, Daphna Levinson, Yutaka Ono, Maria Petukhova, José Posada-Villa, Soraya Seedat, J Elisabeth Wells
Journal: The Lancet (2007)
Natural History of Clinically Compensated Hepatitis C Virus–Related Graft Cirrhosis After Liver Transplantation
Authors: Marina Berenguer, Martín Prieto, José M. Rayón, Julio Mora, Miguel Pastor, Vicente Ortiz, Domingo Carrasco, Fernando San Juan, Manuel-de-Juan Burgueño, José Mir, Joaquín Berenguer
Journal: Hepatology (2000)

The natural history of clinically compensated hepatitis C virus (HCV) cirrhosis after liver transplantation is unknown. This information is relevant to transplant centers to improve the management of these patients and decide the optimal timing for retransplantation. The aims of the study were (1) to describe the natural history of patients with HCV-cirrhosis transplants in a center with annual liver biopsies, and (2) to determine predictors for clinical decompensation, retransplantation, and mortality rates. A total of 49 patients with HCV-graft cirrhosis, 39 clinically compensated at histologic diagnosis of cirrhosis (post-liver transplantation cirrhosis) were included and followed up for 1 year (15 days-3.5 years). All patients tested were infected with genotype 1b. Predictive variables included histologic activity index (HAI) at post-liver transplantation cirrhosis, liver function tests, age, sex, and maintenance immunosuppression. Eighteen of 39 patients developed at least 1 episode of decompensation after a median of 7.8 months (4 days-2.6 years; 93% ascites). The cumulative probability of decompensation was 8%, 17%, and 42% at 1, 6, and 12 months, respectively. Graft and patient survival rates were 100%, 85%, and 71% and 100%, 92%, and 74% at 1, 6, and 12 months, respectively. Patient survival rates dropped significantly once decompensation developed (93%, 61%, and 41% at 1, 6, and 12 months, respectively). Variables associated with decompensation, retransplantation, and mortality rate included a high Child-Pugh score (&gt;A), low levels of albumin at post-liver transplantation cirrhosis, and a short interval between liver transplantation and post-liver transplantation cirrhosis. The natural history of clinically compensated HCV-graft cirrhosis is shortened when compared with immunocompetent patients. If retransplantation is considered, it should be performed promptly once decompensation develops.