tbuckley/cabot-search huggingface dataset:
Heart Failure
Authors: David S.H. Bell
Journal: Diabetes Care (2003)

There is a high frequency of heart failure (HF) accompanied by an increased mortality risk for patients with diabetes. The poor prognosis of these patients has been explained by an underlying diabetic cardiomyopathy exacerbated by hypertension and ischemic heart disease. In these patients, activation of the sympathetic nervous system results in increased myocardial utilization of fatty acids and induction of fetal gene programs, decreasing myocardial function. Activation of the renin-angiotensin system results in myocardial remodeling. It is imperative for physicians to intercede early to stop the progression of HF, yet at least half of patients with left ventricular dysfunction remain undiagnosed and untreated until advanced disease causes disability. This delay is largely because of the asymptomatic nature of early HF, which necessitates more aggressive assessment of HF risk factors and early clinical signs. Utilization of β-blockade, ACE inhibitors, or possibly angiotensin receptor blockers is essential in preventing remodeling with its associated decline in ventricular function. β-Blockers not only prevent, but may also reverse, cardiac remodeling. Glycemic control may also play an important role in the therapy of diabetic HF. The adverse metabolic side effects that have been associated with β-adrenergic inhibitors in the diabetic patient may be circumvented by use of a third-generation β-blocker. Prophylactic utilization of ACE inhibitors and β-blockers to avoid, rather than await, the need to treat HF should be considered in high-risk diabetic patients.
Aetiology of hypospadias: a systematic review of genes and environment
Authors: L.F.M. van der Zanden, I.A.L.M. van Rooij, W.F.J. Feitz, B. Franke, N.V.A.M. Knoers, N. Roeleveld
Journal: Human Reproduction Update (2012)

Hypospadias is a common congenital malformation of the male external genitalia. Most cases have an unknown aetiology, which is probably a mix of monogenic and multifactorial forms, implicating both genes and environmental factors. This review summarizes current knowledge about the aetiology of hypospadias. Pubmed was used to identify studies on hypospadias aetiology published between January 1995 and February 2011. Reference lists of the selected manuscripts were also searched to identify additional studies, including those published before 1995. The search provided 922 articles and 169 articles were selected for this review. Studies screening groups of patients with hypospadias for single gene defects found mutations in WT1, SF1, BMP4, BMP7, HOXA4, HOXB6, FGF8, FGFR2, AR, HSD3B2, SRD5A2, ATF3, MAMLD1, MID1 and BNC2. However, most investigators are convinced that single mutations do not cause the majority of isolated hypospadias cases. Indeed, associations were found with polymorphisms in FGF8, FGFR2, AR, HSD17B3, SRD5A2, ESR1, ESR2, ATF3, MAMLD1, DGKK, MID1, CYP1A1, GSTM1 and GSTT1. In addition, gene expression studies indentified CTGF, CYR61 and EGF as candidate genes. Environmental factors consistently implicated in hypospadias are low birthweight, maternal hypertension and pre-eclampsia, suggesting that placental insufficiency may play an important role in hypospadias aetiology. Exogenous endocrine-disrupting chemicals have the potential to induce hypospadias but it is unclear whether human exposure is high enough to exert this effect. Other environmental factors have also been associated with hypospadias but, for most, the results are inconsistent. Although a number of contributors to the aetiology of hypospadias have been identified, the majority of risk factors remain unknown.
Lung Growth and Maturation after Tracheal Occlusion in Diaphragmatic Hernia
Authors: ALEXANDRA BENACHI, BERNADETTE CHAILLEY-HEU, ANNE-LISE DELEZOIDE, MARC DOMMERGUES, FRANCIS BRUNELLE, YVES DUMEZ, JACQUES R. BOURBON
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Tracheal occlusion (TO) was performed at 120 d of gestation by noninvasive endoscopic technique using a releasable latex balloon, in fetal lambs with diaphragmatic hernia (DH) established at 85 d. The lungs were studied at 139 d in five fetuses with DH + TO, five fetuses with DH only, and six control fetuses. Fluid retention consecutive to TO allowed fetal lungs to grow. Histological pulmonary structure was more mature in DH + TO than in DH alone. The growth-inducing effect of TO was however incomplete, with an increased protein/DNA ratio. Tissue phospholipids were increased, but this was not reflected in the surfactant compartment. The major surfactant component, disaturated phosphatidylcholine, was reduced to 58% of its control value in DH, and further reduced to 17.5% of its control value in DH + TO. The proportion of surfactant protein B immunoreactive cells, assumed to represent the proportion of type II cells, was increased in DH (27% of all parenchymal cells), and reduced in DH + TO (7.8%) as compared with control fetuses (15%). In conclusion, although noninvasive tracheal occlusion in utero is feasible and may partly compensate the adverse effects of DH on lung organogenesis, it reduces the number of type II cells and induces a dramatic surfactant deficit. Using this technique in human fetuses requires careful consideration until further evaluation of lung functional characteristics has been achieved in this experimental model.
Immunohistochemical Detection of 4-Hydroxyaminoquinoline 1-Oxide--DNA Adducts in Mouse Tissues In Vivo
Authors: K. Nakagawa, M. Tada, T. Morita, J. Utsunomiya, T. Ishikawa
Journal: JNCI Journal of the National Cancer Institute (1988)

4–Hydroxyaminoquinoline 1-oxide (4HAQO)-DNA adducts were immunohistochemically demonstrated in the nuclei of various organs of mice with the use of an antibody directed against 4HAQO-modified DNA. Specificity of the immunostaining was confirmed by several tests, including preincubation of the antibody with 4HAQO-modified DNA or related molecules and digestion of the sections with DNase. 4HAQO dissolved in isotonic solution and injected sc into an isolated portion of the mouse skin clamped off with ring-shaped forceps resulted in dose-dependent generation of DNA adducts in the nuclei of epithelial cells, fibroblasts, and panniculus carnosus cells. Nuclear staining was absent in animals given injections of isotonic solution only, and the intensity of staining correlated well with the level of unscheduled DNA synthesis demonstrated autoradiographically. 4HAQO-DNA adducts were observed in all target organs of 4HAQO tumorigenesis (i.e., lung, trachea, pancreas, uterus, vagina, skin, and colon) after injection of the carcinogen. Nuclear staining was absent or low in nontarget organs, including the liver and brain. Considerable variation was found in staining levels between cell types and different anatomic locations of cells within each target organ. The intensity of immunohistochemical staining correlated well with numbers of 4HAQO-DNA adducts measured by the radiolabeling technique. [J Natl Cancer Inst 1988;80:419–425]
Underlying conditions in chronic pulmonary aspergillosis including simple aspergilloma
Authors: N.L. Smith, D.W. Denning
Journal: European Respiratory Journal (2010)

Chronic pulmonary aspergillosis (CPA) is a condition caused by the ubiquitous fungus Aspergillus fumigatus in non-immunocompromised individuals. Numerous underlying conditions have been associated with CPA. Details of the underlying conditions of 126 CPA patients attending our tertiary referral clinic from all over the UK were extracted from the clinical notes, and the distribution of these underlying conditions was analysed. For those with several underlying pulmonary conditions, one was nominated as the primary condition. Many patients presented with multiple underlying conditions, and a total of 232 underlying conditions were identified for the 126 patients. Previous classical tuberculosis and non-tuberculous mycobacterial infection were the most common primary underlying conditions (15.3% and 14.9%, respectively). Others included allergic bronchopulmonary aspergillosis (ABPA), chronic obstructive pulmonary condition (COPD) and/or emphysema, pneumothorax and prior treated lung cancer. Some conditions were found more often as one of multiple underlying conditions, while others were found only as secondary underlying conditions. Tuberculosis, non-tuberculous mycobacterial infection and ABPA remain the predominant risk factors for development of CPA, with COPD, prior pneumothorax or treated lung cancer also relatively common among our referrals. Many patients have multiple underlying pulmonary conditions. CPA should be considered when upper lobe cavitary or fibrotic disease and systemic symptoms are present in those with lung disease.
Protein Conformational Diversity Correlates with Evolutionary Rate
Authors: Diego Javier Zea, Alexander Miguel Monzon, Maria Silvina Fornasari, Cristina Marino-Buslje, Gustavo Parisi
Journal: Molecular Biology and Evolution (2013)

Native state of proteins is better represented by an ensemble of conformers in equilibrium than by only one structure. The extension of structural differences between conformers characterizes the conformational diversity of the protein. In this study, we found a negative correlation between conformational diversity and protein evolutionary rate. Conformational diversity was expressed as the maximum root mean square deviation (RMSD) between the available conformers in Conformational Diversity of Native State database. Evolutionary rate estimations were calculated using 16 different species compared with human sharing at least 700 orthologous proteins with known conformational diversity extension. The negative correlation found is independent of the protein expression level and comparable in magnitude and sign with the correlation between gene expression level and evolutionary rate. Our findings suggest that the structural constraints underlying protein dynamism, essential for protein function, could modulate protein divergence.
Genetic and biochemical characterization of human lymphocyte cell surface antigens. The A-1A5 and A-3A4 determinants.
Authors: P M Peters, M E Kamarck, M E Hemler, J L Strominger, F H Ruddle
Journal: The Journal of Experimental Medicine (1984)

The genes that code for the human lymphocyte cell surface determinants defined by monoclonal antibodies A- 1A5 and A- 3A4 have been genetically mapped. All human chromosomes, except Y, were included in a series of human less than mouse lymphocyte hybrid populations that retained expression of lymphocyte-specific surface markers. Expression of the A- 1A5 and A- 3A4 antigens was quantitated by indirect immunofluorescence and fluorescence-activated cell sorter (FACS) analysis. Hybrid populations heterogeneous for antigen expression were sorted to yield antigenically homogeneous subpopulations. Isozyme analysis indicated concordant segregation of the A- 1A5 determinant with chromosome 10, and the A- 3A4 determinant with chromosome 4. In contrast to the unhybridized human parent cell line (MOLT-4), from which A- 1A5 immunoprecipitated two proteins (160,000 and 125,000 Mr), A- 1A5 only immunoprecipitated a single band (125,000 Mr) from an A- 1A5 -expressing human less than mouse hybrid. The genetic disassociation of these two proteins from the A- 1A5 -reactive complex suggests that the appearance of the 160,000 Mr protein requires a gene locus that is unlinked to the locus for the 125,000 Mr protein on chromosome 10. A third component of the A- 1A5 -reactive protein complex (210,000 Mr), which is recognized by the monoclonal antibody TS2/7, was not expressed on the parent MOLT-4 cells, but was weakly expressed on MOLT-4 less than mouse BW5147 hybrids. This allowed preliminary mapping of that determinant to either chromosome 10 or 15. The A- 3A4 antigen (approximately 45,000 Mr) is a novel cell surface structure expressed on all hematopoietic cell lines tested, and represents the first cell surface marker mapped to chromosome 4.
Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans
Authors: Troy D Querec, Rama S Akondy, Eva K Lee, Weiping Cao, Helder I Nakaya, Dirk Teuwen, Ali Pirani, Kim Gernert, Jiusheng Deng, Bruz Marzolf, Kathleen Kennedy, Haiyan Wu, Soumaya Bennouna, Herold Oluoch, Joseph Miller, Ricardo Z Vencio, Mark Mulligan, Alan Aderem, Rafi Ahmed, Bali Pulendran
Journal: Nature Immunology (2008)
Intraoperative Imaging-Guided Cancer Surgery: From Current Fluorescence Molecular Imaging Methods to Future Multi-Modality Imaging Technology
Authors: Chongwei Chi, Yang Du, Jinzuo Ye, Deqiang Kou, Jingdan Qiu, Jiandong Wang, Jie Tian, Xiaoyuan Chen
Journal: Theranostics (2014)

Cancer is a major threat to human health.Diagnosis and treatment using precision medicine is expected to be an effective method for preventing the initiation and progression of cancer.Although anatomical and functional imaging techniques such as radiography, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) have played an important role for accurate preoperative diagnostics, for the most part these techniques cannot be applied intraoperatively.Optical molecular imaging is a promising technique that provides a high degree of sensitivity and specificity in tumor margin detection.Furthermore, existing clinical applications have proven that optical molecular imaging is a powerful intraoperative tool for guiding surgeons performing precision procedures, thus enabling radical resection and improved survival rates.However, detection depth limitation exists in optical molecular imaging methods and further breakthroughs from optical to multi-modality intraoperative imaging methods are needed to develop more extensive and comprehensive intraoperative applications.Here, we review the current intraoperative optical molecular imaging technologies, focusing on contrast agents and surgical navigation systems, and then discuss the future prospects of multi-modality imaging technology for intraoperative imaging-guided cancer surgery.
Characteristics of daily arm activities in patients with COPD
Authors: Kenneth Meijer, Janneke Annegarn, Valéria Lima Passos, Hans H. Savelberg, Annemie M. Schols, Emiel F. Wouters, Martijn A. Spruit
Journal: European Respiratory Journal (2014)

Arm activities are required for maintenance of self-care and independent living. This study aimed to investigate whether and to what extent arm activities of daily living (ADL) in chronic obstructive pulmonary disease (COPD) patients differ compared to healthy controls and the extent to which they perform arm ADL at a relatively higher upper limb muscle effort. Daily arm and leg activities were assessed using accelerometers in the home environment (COPD: n=21, healthy: n=24; part 1). The relative efforts of the trapezius, deltoid and biceps muscles were studied using electromyography during domestic arm ADL in a laboratory setting (COPD: n=17, healthy: n=15; part 2). After correction for walking time, the time spent on arm ADL was similar between COPD patients and healthy control subjects (p=0.52), while the intensity of arm activities was lower in COPD patients (p=0.041). In the laboratory setting, arm ADL were performed at a lower intensity by COPD patients, while the trapezius muscle effort was significantly higher during several arm ADL compared to healthy control subjects (p&lt;0.05). COPD patients have a similar duration of arm ADL compared to healthy subjects after correction for walking time, but perform arm activities at a lower intensity. Moreover, patients perform some arm ADL at a relatively higher muscle effort.
A phase II trial of riluzole, an antagonist of metabotropic glutamate receptor 1 (GRM1) signaling, in metastatic melanoma.
Authors: J. M. Mehnert, J. H. Lee, J. Shirk, D. Bhavsar, O. Anosike, J. L. Chan, W. Shih, S. Chen, J. S. Goydos
Journal: Journal of Clinical Oncology (2010)

TPS309 Background: Our group made the novel discovery that ectopic expression of GRM1 in murine melanocytes results in transformation to melanoma (Pollock, Nat Genet. 2003). Indeed, aberrant GRM1 expression is detected in >60% of human melanoma cell lines and biopsies, and in vitro human melanoma cells respond to stimulators or inhibitors of GRM1, which modulate cell growth and signaling cascades including extracellular signal-regulated kinase (ERK). In a xenograft model of melanoma treated with riluzole, an oral agent that blocks glutamate release, tumor growth was decreased compared with controls (Namkoong, Cancer Res. 2007). To explore mechanistic and pharmacodynamic effects of riluzole in human melanomas, a phase 0 trial was performed. 12 patients with stage III/IV resectable melanoma received riluzole 200 mg qd X 14 days prior to surgery. 4 (34%) showed significant post-treatment decreases in a) tumor levels of pAKT and/or pERK and b) FDG-PET intensity (Yip, Clin Cancer Res. 2009). These data show that glutamate blockade with riluzole inhibits signaling through the MAPK and PI3K/AKT pathways and suppresses the metabolic activity of melanoma, indicating that GRM1 may be important in melanoma pathogenesis. We thus sought to explore, for the first time to our knowledge, the antitumor activity of riluzole in melanoma patients. Methods: Patients with stage III unresectable or stage IV melanoma, ECOG PS ≤ 2, and adequate organ function will be given rilzuole 200 mg qd X 6 weeks before restaging, with the primary endpoint of tumor response. Using a Simon two stage minimax design to test the response rate of 5% vs. 20% at alpha=0.05 and power=80%, 13 will accrue in stage 1. If 0 responses are seen the trial will terminate; otherwise, 14 patients will accrue (total 27). If ≤ 3 responses are noted, no further investigation as a single agent is warranted. For the secondary aim of overall survival measurement, cumulative event rate and confidence interval will be calculated by the Kaplan-Meier method. Pre/post treatment levels of pERK, pAKT, and activated caspase 3 will be compared using appropriate parametric or nonparametric methods. 6 patients have been enrolled with paired tumor samples obtained from most to date. No significant financial relationships to disclose.
Kinetics of Rubidium Uptake in the Working Dog Heart
Authors: Wilfred H. Ziegler, Carl A. Goresky
Journal: Circulation Research (1971)

More than 50% of tracer rubidium entering the coronary circulation is actively taken up by the heart muscle cells during a single passage. Rubidium ions must traverse the capillary wall, the interstitial space, and the muscle cell membrane to enter the very large potential rubidium pool within the cells. The aim of this investigation was to determine which, if any, of these steps are rate limiting. The anterior descending branch of the left common coronary artery was perfused at its origin. Pulse injections containing 86 Rb + , 22 Na + or 14 C-sucrose, and 125 I-albumin were made into the perfusion line and timed serial samples of coronary sinus blood were collected and analyzed. A model was designed which incorporates rate constants describing both the exchange of 80 Rb + at the capillary wall and its entry at the muscle cell membrane. Labeled sucrose or 22 Na + was used to determine flow per interstitial fluid volume, a parameter necessary for the application of the model. It was assumed that the interstitial fluid volume available for labeled sucrose or 22 Na + was identical to that available for 86 Rb + . The rate constant describing exchange at the capillary wall (the permeability surface product per unit accessible interstitial fluid volume) increased with perfusion, whereas that for uptake by the myocardial cells was relatively constant and independent of flow.
Relative Sensitivity of Postpartum Gestational Diabetic Women to Oral Contraceptive Agents and Other Metabolic Stress
Authors: Ronald K Kalkhoff
Journal: Diabetes Care (1980)

Women who develop diabetes mellitus during pregnancy very often revert to normal carbohydrate metabolism after parturition. During this quiescent period, however, increased sensitivity to adverse metabolic stress is evident. Recurrence of impaired carbohydrate tolerance with greater frequency than in normal populations is observed following the administration of oral contraceptive agents, glucocorticoids, and certain placental hormones such as human chorionic somatomammotropin. Factors responsible for this vulnerability to adverse stress are unknown but, in part, may reside in subclinical defects in beta-cell function. Ultimately, the great majority of these individuals develop permanent disease, suggesting that diabetes initially manifested only during pregnancy is not transient but progresses to more severe forms later in life.
Human Bone Marrow–Derived MSCs Can Home to Orthotopic Breast Cancer Tumors and Promote Bone Metastasis
Authors: Robert H. Goldstein, Michaela R. Reagan, Kristen Anderson, David L. Kaplan, Michael Rosenblatt
Journal: Cancer Research (2010)

American women have a nearly 25% lifetime risk of developing breast cancer, with 20% to 40% of these patients developing life-threatening metastases. More than 70% of patients presenting with metastases have skeletal involvement, which signals progression to an incurable stage. Tumor-stroma cell interactions are only superficially understood, specifically regarding the ability of stromal cells to affect metastasis. In vivo models show that exogenously supplied human bone marrow-derived stem cells (hBMSC) migrate to breast cancer tumors, but no reports have shown endogenous hBMSC migration from the bone to primary tumors. Here, we present a model of in vivo hBMSC migration from a physiologic human bone environment to human breast tumors. Furthermore, hBMSCs alter tumor growth and bone metastasis frequency. These may home to certain breast tumors based on tumor-derived TGF-β1. Moreover, at the primary tumor level, interleukin 17B (IL-17B)/IL-17BR signaling may mediate interactions between hBMSCs and breast cancer cells.
Risk of Selected Subsequent Carcinomas in Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Mylène Bassal, Ann C. Mertens, Leslie Taylor, Joseph P. Neglia, Brian S. Greffe, Sue Hammond, Cécile M. Ronckers, Debra L. Friedman, Marilyn Stovall, Yutaka Y. Yasui, Leslie L. Robison, Anna T. Meadows, Nina S. Kadan-Lottick
Journal: Journal of Clinical Oncology (2006)

To determine the risk of subsequent carcinomas other than breast, thyroid, and skin, and to identify factors that influence the risk among survivors of childhood cancer.Subsequent malignant neoplasm history was determined in 13,136 participants (surviving > or = 5 years postmalignancy, diagnosed from 1970 to 1986 at age < 21 years) of the Childhood Cancer Survivor Study to calculate standardized incidence ratios (SIRs), using Surveillance, Epidemiology, and End Results data.In 71 individuals, 71 carcinomas were diagnosed at a median age of 27 years and a median elapsed time of 15 years in the genitourinary system (35%), head and neck area (32%), gastrointestinal tract (23%), and other sites (10%). Fifty-nine patients (83%) had received radiotherapy, and 42 (59%) developed a second malignant neoplasm in a previous radiotherapy field. Risk was significantly elevated following all childhood diagnoses except CNS neoplasms, and was highest following neuroblastoma (SIR = 24.2) and soft tissue sarcoma (SIR = 6.2). Survivors of neuroblastoma had a 329-fold increased risk of renal cell carcinomas; survivors of Hodgkin's lymphoma had a 4.5-fold increased risk of gastrointestinal carcinomas. Significantly elevated risk of head and neck carcinoma occurred in survivors of soft tissue sarcoma (SIR = 22.6), neuroblastoma (SIR = 20.9), and leukemia (SIR = 20.9).Young survivors of childhood cancers are at increased risk of developing subsequent carcinomas typical of later adulthood, underscoring the importance of long-term follow-up and risk-based screening. Follow-up of the cohort is ongoing to determine lifetime risk and delineate individual characteristics that contribute to risk.