tbuckley/cabot-search huggingface dataset:
Evolutionary Trajectories of Primate Genes Involved in HIV Pathogenesis
Authors: M. Ortiz, N. Guex, E. Patin, O. Martin, I. Xenarios, A. Ciuffi, L. Quintana-Murci, A. Telenti
Journal: Molecular Biology and Evolution (2009)

The current availability of five complete genomes of different primate species allows the analysis of genetic divergence over the last 40 million years of evolution. We hypothesized that the interspecies differences observed in susceptibility to HIV-1 would be influenced by the long-range selective pressures on host genes associated with HIV-1 pathogenesis. We established a list of human genes (n = 140) proposed to be involved in HIV-1 biology and pathogenesis and a control set of 100 random genes. We retrieved the orthologous genes from the genome of humans and of four nonhuman primates (Pan troglodytes, Pongo pygmaeus abeli, Macaca mulatta, and Callithrix jacchus) and analyzed the nucleotide substitution patterns of this data set using codon-based maximum likelihood procedures. In addition, we evaluated whether the candidate genes have been targets of recent positive selection in humans by analyzing HapMap Phase 2 single-nucleotide polymorphisms genotyped in a region centered on each candidate gene. A total of 1,064 sequences were used for the analyses. Similar median KA/KS values were estimated for the set of genes involved in HIV-1 pathogenesis and for control genes, 0.19 and 0.15, respectively. However, genes of the innate immunity had median values of 0.37 (P value = 0.0001, compared with control genes), and genes of intrinsic cellular defense had KA/KS values around or greater than 1.0 (P value = 0.0002). Detailed assessment allowed the identification of residues under positive selection in 13 proteins: AKT1, APOBEC3G, APOBEC3H, CD4, DEFB1, GML, IL4, IL8RA, L-SIGN/CLEC4M, PTPRC/CD45, Tetherin/BST2, TLR7, and TRIM5α. A number of those residues are relevant for HIV-1 biology. The set of 140 genes involved in HIV-1 pathogenesis did not show a significant enrichment in signals of recent positive selection in humans (intraspecies selection). However, we identified within or near these genes 24 polymorphisms showing strong signatures of recent positive selection. Interestingly, the DEFB1 gene presented signatures of both interspecies positive selection in primates and intraspecies recent positive selection in humans. The systematic assessment of long-acting selective pressures on primate genomes is a useful tool to extend our understanding of genetic variation influencing contemporary susceptibility to HIV-1.
Molecular targets on mast cells and basophils for novel therapies
Authors: Ilkka T. Harvima, Francesca Levi-Schaffer, Petr Draber, Sheli Friedman, Iva Polakovicova, Bernhard F. Gibbs, Ulrich Blank, Gunnar Nilsson, Marcus Maurer
Journal: Journal of Allergy and Clinical Immunology (2014)
1160 HCV GENOTYPE 1 PROTEASE INHIBITOR RESISTANCE MUTATIONS AT NS3 PROTEASE AMINO ACIDS 155 AND 156 CONFER RESISTANCE TO GENOTYPE 2A, 3A, 5A, AND 6A VIRUSES
Authors: S.B. Jensen, S. Serre, J. Bukh, J. Gottwein
Journal: Journal of Hepatology (2013)
Modified exhaled nitric oxide measurement in monocrotaline-exposed rats to monitor pulmonary hypertension
Authors: Magdalena Sophie Strobl, Catharina Schreiber, Stefan Hubmer, Helga Bergmeister, Irene M. Lang, Diana Bonderman
Journal: European Respiratory Journal (2012)

Background and aims. Rats exposed to monocrotaline (MCT) are broadly used as animal model for pulmonary arterial hypertension (PAH). In analogy to human disease, right heart catheter (RHC) is the established gold standard for pulmonary pressure monitoring. Although exhaled nitric oxide (ENO) levels have been shown to correlate with pulmonary pressures in humans with pulmonary vascular disease, no link between ENO and pulmonary pressures could be established in rats. The aim of the present study was to test whether a technical modification of the NO measurement process could help generate reliable ENO values that correlate with pulmonary pressures as assessed by simultaneous RHC.

Methods. 33 male Sprague-Dawley rats were studied 28 days after MCT-exposure and unilateral pneumonectomy. Hemodynamic parameters were monitored by an implantable telemetry system (DSI Datascience, St. Paul, MN U.S.A.). ENO was measured by means of chemiluminescence (CLD 66, Eco Physics, Duernten, Switzerland) in single, conscious, spontaneously breathing rats. ENO values measured by a standard accumulation method (ENO standard) and those obtained after process modification (ENO modified) were correlated with mean pulmonary arterial pressures (mPAP).

Results. After process modification, measuring errors were diminished and potential influencing factors eliminated. There was a clear correlation between ENO modified and mPAP (p=0.007; R=-.459), while no correlation was observed between ENO standard and mPAP (p=0.236; R=-.212).

Conclusion. Modified non-invasive ENO measurement may be used to monitor PAH in monocrotaline-exposed rats.
Predictors of Health Care Costs in Adults With Diabetes
Authors: Todd P. Gilmer, Patrick J. O’Connor, William A. Rush, A. Lauren Crain, Robin R. Whitebird, Ann M. Hanson, Leif I. Solberg
Journal: Diabetes Care (2005)

OBJECTIVE—The purpose of this study was to assess the impact of baseline A1c, cardiovascular disease, and depression on subsequent health care costs among adults with diabetes. RESEARCH DESIGN AND METHODS—A prospective analysis was performed of data from a patient survey and medical record review merged with 3 years of medical claims. Costs were estimated using detailed data on resource use and Medicare payment methodologies. Generalized linear models were used to analyze costs related to clinical predictors after adjusting for demographic and socioeconomic factors. RESULTS—In multivariate analysis of 1,694 adults with diabetes, 3-year costs in those with coronary heart disease (CHD) and hypertension were over 300% of those with diabetes only ($46,879 vs. $14,233; P &amp;lt; 0.05). Depression was associated with a 50% increase in costs ($31,967 vs. $21,609; P &amp;lt; 0.05). Relative to those with a baseline A1c of 6%, those with an A1c of 10% had 3-year costs that were 11% higher ($26,408 vs. $23,873; P &amp;lt; 0.05). Higher A1c predicted higher costs only for those with baseline A1c &amp;gt;7.5% (P = 0.015). CONCLUSIONS—In adults with diabetes, CHD, hypertension, and depression spectrum disorders more strongly predicted future costs than the A1c level. Concurrent with aggressive efforts to control glucose, greater efforts to prevent or control CHD, hypertension, and depression are necessary to control health care costs in adults with diabetes.
Induction of heat shock proteins in short-term cultured hepatocytes derived from normal and chronically griseofulvin-treated mice
Authors: Kurt Zatloukal, Ruth Sohar, Elisabeth Lackinger, Helmut Denk
Journal: Hepatology (1988)

Freshly isolated mouse hepatocytes were tested with respect to the induction of heat shock (stress) proteins by elevated temperature, sodium arsenite and ethanol treatment. With heat, arsenite and ethanol treatments, the synthesis of a protein with a molecular weight of 68 kD (heat shock protein 68) was predominantly elevated; arsenite and ethanol exerted their effects on heat shock protein synthesis in a dose-dependent manner. Hepatocytes derived from livers of chronically griseofulvin-pretreated mice differed in their response from normal hepatocytes in that ethanol was ineffective in these cells. These results indicate that different modes and pathways of the stress response exist, depending on the nature of the inducing agent but also on pretreatment conditions. In vivo , pathologic alterations of cells and organs (e.g., in the course of chronic diseases) can, therefore, be expected to modulate the stress response.
Reprogrammed Cells for Disease Modeling and Regenerative Medicine
Authors: Anne B.C. Cherry, George Q. Daley
Journal: Annual Review of Medicine (2013)

The conversion of somatic cells into pluripotent cells is transforming the way diseases are researched and treated. Induced pluripotent stem (iPS) cells' promise may soon be realized in the field of hematology, as hematopoietic stem cell transplants are already commonplace in clinics around the world. We provide a current comparison between induced pluripotent and embryonic stem cells, describe progress toward modeling hematological disorders using iPS cells, and illustrate the hurdles that must be overcome before iPS cell therapies will be available in clinics.
Tissue Factor in Cardiovascular Diseases
Authors: Jan Steffel, Thomas F. Lüscher, Felix C. Tanner
Journal: Circulation (2006)

Tissue factor (TF), formerly known as thromboplastin, is the key initiator of the coagulation cascade; it binds factor VIIa resulting in activation of factor IX and factor X, ultimately leading to fibrin formation. TF expression and activity can be induced in endothelial cells, vascular smooth muscle cells, and monocytes by various stimuli such as cytokines, growth factors, and biogenic amines. These mediators act through diverse signal transduction mechanisms including MAP kinases, PI3-kinase, and protein kinase C. Cellular TF is present in three pools as surface, encrypted, and intracellular protein. TF can also be detected in the bloodstream, referred to as circulating or blood-borne TF. Elevated levels of TF are observed in patients with cardiovascular risk factors such as hypertension, diabetes, dyslipidemia, and smoking as well as in those with acute coronary syndromes. TF may indeed be involved in the pathogenesis of atherosclerosis by promoting thrombus formation; in addition, it can induce migration and proliferation of vascular smooth muscle cells. As a consequence, therapeutic strategies have been developed to specifically interfere with the action of TF such as antibodies against TF, site-inactivated factor VIIa, or recombinant TF pathway inhibitor. Inhibition of TF action appears to be an attractive target for the treatment of cardiovascular diseases.
Clinical and angiographic outcome after sirolimus-eluting stent implantation in aorto-ostial lesions
Authors: Ioannis Iakovou, Lei Ge, Iassen Michev, Giuseppe M. Sangiorgi, Matteo Montorfano, Flavio Airoldi, Alaide Chieffo, Goran Stankovic, Giancarlo Vitrella, Mauro Carlino, Nicola Corvaja, Carlo Briguori, Antonio Colombo
Journal: Journal of the American College of Cardiology (2004)
Maternal Suicidality and Risk of Suicidality in Offspring: Findings From a Community Study
Authors: Roselind Lieb, Thomas Bronisch, Michael Höfler, Andrea Schreier, Hans-Ulrich Wittchen
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: This study evaluated the associations between suicidal ideation and suicide attempts in mothers and various aspects of suicidality in their offspring in a representative community sample. METHOD: Baseline and 4-year follow-up data were used from the Early Developmental Stages of Psychopathology study, a prospective, longitudinal community study of adolescents and young adults. Results are based on 933 adolescents who completed follow-up and for whom direct diagnostic information for the biological mother was available. Suicidal ideation and suicide attempts were assessed in adolescents and mothers with the Munich-Composite International Diagnostic Interview. RESULTS: Compared to offspring of mothers without suicidality, offspring of mothers reporting suicide attempts showed a remarkably higher risk for suicidal thoughts and suicide attempts and a tendency toward suicide attempts at an earlier age. Associations were comparable for male and female offspring. Transmission of maternal suicidality was roughly stable with control for maternal comorbid psychopathology. CONCLUSIONS: The offspring of mothers with suicide attempts are at a markedly increased risk for suicidality themselves and tend to manifest suicide attempts earlier than offspring of mothers without suicidality. Suicidality seems to run in families, independent of depression and other psychopathology.
BLOOD DESTRUCTION DURING EXERCISE
Authors: G. O. Broun
Journal: The Journal of Experimental Medicine (1923)

Animals recently caged do not show as large a decrease in cell volume after exercise as those which have been confined several months. When a dog kept for a long time under sedentary conditions is exercised continuously for several weeks, a decrease in cell volume occurs in the 1st or 2nd week of exercise, but usually by the end of the 3rd week the loss has been made up. Apparently by this time the hematopoietic tissues have adapted themselves to the increased demands made upon them by the hastened rate of destruction. There is, furthermore, some anatomical evidence that such is the case.
Association between Smoking and Chronic Renal Failure in a Nationwide Population-Based Case-Control Study
Authors: Elisabeth Ejerblad, C. Michael Fored, Per Lindblad, Jon Fryzek, Paul W. Dickman, Carl-Gustaf Elinder, Joseph K. McLaughlin, Olof Nyrén
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. For determining whether smoking is associated with an increased risk for chronic renal failure (CRF) overall and by type of renal disease, smoking data were analyzed from a nationwide population-based case-control study. Eligible as cases were native 18- to 74-yr-old Swedes whose serum creatinine for the first time and permanently exceeded 3.4 mg/dl (men) or 2.8 mg/dl (women). A total of 926 cases (78% of all eligible) and 998 control subjects (75% of 1330 randomly selected subjects from the source population), frequency matched to the cases by gender and age within 10 yr, were included. A face-to-face interview and a self-administered questionnaire provided information about smoking habits and other lifestyle factors. Logistic regression models estimated odds ratios (OR) as measures of relative risk for disease-specific types of CRF among smokers compared with never-smokers. Despite a modest and nonsignificant overall association, the risk increased with high daily doses (OR among smokers of >20 cigarettes/d, 1.51; 95% confidence interval [CI], 1.06 to 2.15), long duration (OR among smokers for >40 yr, 1.45; 95% CI, 1.00 to 2.09), and a high cumulative dose (OR among smokers with >30 pack-years, 1.52; 95% CI, 1.08 to 2.14). Smoking increased risk most strongly for CRF classified as nephrosclerosis (OR among smokers with >20 pack-years, 2.2; 95% CI, 1.3 to 3.8), but significant positive associations were also noted with glomerulonephritis. This study thus suggests that heavy cigarette smoking increases the risk of CRF for both men and women, at least CRF classified as nephrosclerosis and glomerulonephritis.
Gastric Acidity and Levodopa in Parkinsonism
Authors: Ramon Jenkins
Journal: JAMA (1973)

To the Editor.—  About 20% of patients with Parkinson's disease have a poor therapeutic response to levodopa taken by mouth. It has been suggested that the pH of gastric juice modifies absorption. Rivera-Calimlin and co-workers showed that parkinsonian patients with alkaline gastric juice achieve a peak serum level of levodopa more rapidly, 1 and they reported such a patient whose failure to improve when given levodopa was corrected by alkalinization of the stomach contents. 2 Conversely, Cotzias has shown that the action of levodopa in mice is enhanced when it is delivered intragastrically with molar concentrations of hydrochloric acid. 3   We used the azuresin (Diagnex Blue) diagnostic test to test the secretion of gastric hydrochloric acid in 93 consecutive, unselected, parkinsonian patients. Levodopa was given in therapeutic doses and postural stability,bradykinesia, finger dexterity, tremor, and rigidity were each scored at intervals on a 0- to 4-point scale. 4 Their
Phase II Trial of Chronomodulated Infusion of High-Dose Fluorouracil and l-Folinic Acid in Previously Untreated Patients With Metastatic Colorectal Cancer
Authors: H. Cure
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To study tolerability and efficacy of an intensified chronomodulated schedule of fluorouracil (5-FU) and l-folinic acid (l-FA) as first-line treatment of metastatic colorectal cancer, 5-FU was given near individually determined dose-limiting toxicity in a multicenter phase II trial. PATIENTS AND METHODS: One hundred patients (68 men and 32 women, median age 62 years, World Health Organization performance status ≤ 2) with previously untreated and inoperable metastases received chronomodulated daily infusion of 5-FU/l-FA (from 10:00 pm to 10:00 am with peak at 4:00 am). 5-FU dose was escalated from 900 to 1,100 mg/m2/d with fixed dose of l-FA at 150 mg/m2/d for 4 days every 14 days. RESULTS: 5-FU dose escalation was achieved in 66% of the patients. Grade 3 to 4 toxicities mainly consisted of nausea or vomiting (14% of patients and 1.5% of courses), hand-foot syndrome (38% of patients and 8% of courses), mucositis (26% of patients and 4% of courses), and diarrhea (21% of patients and 2.3% of courses...
Phase I Study of Sequential Vaccinations With Fowlpox-CEA(6D)-TRICOM Alone and Sequentially With Vaccinia-CEA(6D)-TRICOM, With and Without Granulocyte-Macrophage Colony-Stimulating Factor, in Patients With Carcinoembryonic Antigen–Expressing Carcinomas
Authors: John L. Marshall, James L. Gulley, Philip M. Arlen, Patricia K. Beetham, Kwong-Yok Tsang, Rebecca Slack, James W. Hodge, Sandra Doren, Douglas W. Grosenbach, Jimmy Hwang, Evelyn Fox, Lauretta Odogwu, Susie Park, Dennis Panicali, Jeffrey Schlom
Journal: Journal of Clinical Oncology (2004)

Our previous clinical experience with vaccinia and replication-defective avipox recombinant carcinoembryonic antigen (CEA) vaccines has demonstrated safety and clinical activity with a correlation between CEA-specific immune response and survival. Preclinical evidence demonstrated that the addition of the transgenes for three T-cell costimulatory molecules (B7-1, ICAM-1, LFA-3, designated TRICOM) results in a significant improvement in antigen-specific T-cell responses and antitumor activity. We describe here the first trial in humans of the CEA-TRICOM vaccines (also including an enhancer agonist epitope within the CEA gene).Fifty-eight patients with advanced CEA-expressing cancers were accrued to eight cohorts that involved vaccinations with the following: replication-defective fowlpox recombinant (rF)-CEA(6D)-TRICOM; primary vaccination with recombinant vaccinia (rV)-CEA(6D)-TRICOM plus rF-CEA(6D)-TRICOM booster vaccinations; and rV-CEA(6D)-TRICOM and then rF-CEA(6D)-TRICOM, plus granulocyte-macrophage colony-stimulating factor (GM-CSF) with vaccines, or with divided doses of vaccine with GM-CSF. Vaccines were administered every 28 days for six doses and then once every 3 months. Reverting to treatments every 28 days was allowed if patients progressed on the 3-month schedule.In this phase I study, no significant toxicity was observed. Twenty-three patients (40%) had stable disease for at least 4 months, with 14 of these patients having prolonged stable disease (> 6 months). Eleven patients had decreasing or stable serum CEA, and one patient had a pathologic complete response. Enhanced CEA-specific T-cell responses were observed in the majority of patients tested.We demonstrated that the CEA-TRICOM vaccines are safe and can generate significant CEA-specific immune responses, and they seem to have clinical benefit in some patients with advanced cancer.
Abstract A28: Analyses of FOXM1 isoforms in ovarian cancer
Authors: Tatiana Altadill, Marina Rigau, Blanca Majem, Lucia Lanau, Josep Castellví, Ángel García, Assumpció Pérez-Benavente, José Luis Sánchez, Silvia Cabrera, Jordi Xercavins, Josep Maria del Campo, Antonio Gil-Moreno, Marta Llauradó, Jaume Reventós
Journal: Clinical Cancer Research (2013)

Abstract Introduction &amp; Objectives: Epithelial ovarian cancer (OC) is the most lethal gynaecological malignancy and the fifth leading cause of cancer death in women in the Western world. Forkhead box M1 (FOXM1) transcription factor was already been described to be overexpressed in various malignancies, playing a key role in cell-cycle progression, chromosomal segregation and genomic stability, and oxidative stress. Moreover, it can also promote drug resistance to herceptin, paclitaxel and cisplatin in breast cancer cells. A recent report from our group has shown, for the first time, that FOXM1 is also overexpressed in OC, being associated with tumor grade. This result seem to indicate an interesting role of this molecule in the progression and resistance to therapy in OC. Our aim is to characterize FOXM1 isoforms in OC through the use of human tissue samples. Material &amp; Methods: Fresh ovarian primary tumors, ascites and peritoneal metastases from patients suffering advanced serous OC were collected from surgery room and processed for microarray analysis to detect FOXM1 expression levels. FOXM1 isoforms were analysed at mRNA expression level by using RTqPCR in a set of new frozen tissue samples. Results: We found that FOXM1 overexpression is increased in OC peritoneal metastases. Now, we are characterizing the isoforms of FOXM1 in primary, ascites and metastatic tumors. Nevertheless, more samples need to be analysed in order to have conclusive results. Conclusions: The present study highlights the role of FOXM1 isoforms in OC dissemination and pursues the idea to elucidate the biologic role of FOXM1 in OC tumorigenesis. Citation Format: Tatiana Altadill, Marina Rigau, Blanca Majem, Lucia Lanau, Josep Castellví, Ángel García, Assumpció Pérez-Benavente, José Luis Sánchez, Silvia Cabrera, Jordi Xercavins, Josep Maria del Campo, Antonio Gil-Moreno, Marta Llauradó, Jaume Reventós. Analyses of FOXM1 isoforms in ovarian cancer. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: From Concept to Clinic; Sep 18-21, 2013; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2013;19(19 Suppl):Abstract nr A28.