tbuckley/cabot-search huggingface dataset:
Gene Expression Profile Signatures Indicate a Role for Wnt Signaling in Endothelial Commitment From Embryonic Stem Cells
Authors: Hong Wang, Peter C. Charles, Yaxu Wu, Rongqin Ren, Xinchun Pi, Martin Moser, Michal Barshishat-Kupper, Jeffrey S. Rubin, Charles Perou, Victoria Bautch, Cam Patterson
Journal: Circulation Research (2006)

We have used global gene expression analysis to establish a comprehensive list of candidate genes in the developing vasculature during embryonic (ES) cell differentiation in vitro. A large set of genes, including growth factors, cell surface molecules, transcriptional factors, and members of several signal transduction pathways that are known to be involved in vasculogenesis or angiogenesis, were found to have expression patterns as expected. Some unknown or functionally uncharacterized genes were differentially regulated in flk1+ cells compared with flk1- cells, suggesting possible roles for these genes in vascular commitment. Particularly, multiple components of the Wnt signaling pathway were differentially regulated in flk1+ cells, including Wnt proteins, their receptors, downstream transcriptional factors, and other components belonging to this pathway. Activation of the Wnt signal was able to expand vascular progenitor populations whereas suppression of Wnt activity reduced flk1+ populations. Suppression of Wnt signaling also inhibited the formation of matured vascular capillary-like structures during late stages of embryoid body differentiation. These data indicate a requisite and ongoing role for Wnt activity during vascular development, and the gene expression profiles identify candidate components of this pathway that participate in vascular cell differentiation.
Analysis of Factors Influencing Outcome in Patients With In-Transit Malignant Melanoma Undergoing Isolated Limb Perfusion Using Modern Treatment Parameters
Authors: H. Richard Alexander, Douglas L. Fraker, David L. Bartlett, Steven K. Libutti, Seth M. Steinberg, Perry Soriano, Tatiana Beresnev
Journal: Journal of Clinical Oncology (2009)

PURPOSE In-transit disease afflicts approximately 10% of patients with extremity melanoma; no single treatment approach has been uniformly accepted as the most effective. We report long-term outcomes in patients with in-transit extremity melanoma who underwent isolated limb perfusion (ILP) in an era of increasingly accurate staging, uniform operative and treatment conditions, and regular long-term follow-up. PATIENTS AND METHODS Between May 1992 and February 2005, 91 patients (median age, 57 years; 50 women, 41 men) underwent a 90-minute hyperthermic ILP (melphalan, 10 to 13 mg/L limb volume, tumor necrosis factor [TNF; n = 44], or interferon [n = 38]) using uniform operative technique and intraoperative leak monitoring. Patients were prospectively followed for response, in-field progression-free survival (PFS), and overall survival (OS). Parameters associated with in-field PFS and OS were analyzed by standard statistical methods. Results There was one operative death (1.1%). There were 62 complete responses (69%) and 23 partial responses (26%) in 90 assessable patients. At a median potential follow-up of 11 years, median in-field PFS was 12.4 months and median OS was 47.4 months; 5 and 10-year actuarial OS probabilities were 43% and 34%, respectively. Female sex and low tumor burden (< or = 20 lesions) were associated with prolonged in-field PFS (male:female hazard ratio [HR], 2.07; 95% CI, 1.27 to 3.38; 21+ v < or = 20 tumors HR, 2.29; 95% CI, 1.21 to 4.34; P < .011 for both). Female sex was associated with improved OS (P = .027; male:female HR, 1.82; 95% CI, 1.07 to 3.09). CONCLUSION In appropriately selected patients, ILP has clinical benefit. The use of TNF was not associated with improved in-field PFS, while female sex was associated with better survival.
Anti-angiogenic Therapy Using Thalidomide Combined With Chemotherapy in Small Cell Lung Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial
Authors: Siow Ming Lee, Penella J. Woll, Robin Rudd, David Ferry, Mary O'Brien, Gary Middleton, Stephen Spiro, Lindsay James, Kulsam Ali, Mark Jitlal, Allan Hackshaw
Journal: JNCI Journal of the National Cancer Institute (2009)

Cancer cells rely on angiogenesis for growth and dissemination, and small cell lung cancer (SCLC) is a highly angiogenic tumor. We evaluated thalidomide, an anti-angiogenic agent, when combined with chemotherapy and as maintenance treatment. A total of 724 patients (51% with limited and 49% with extensive disease) were randomly assigned to receive placebo or thalidomide capsules, 100–200 mg daily for up to 2 years. All patients received etoposide and carboplatin every 3 weeks for up to six cycles. Endpoints were overall survival, progression-free survival, tumor response rate, toxicity, and quality of life (QoL). Hazard ratios (HRs) for comparing thalidomide against placebo were estimated using Cox regression modeling. Statistical tests were two-sided. The median overall survival was 10.5 months (placebo) and 10.1 months (thalidomide) (HR for death = 1.09, 95% confidence interval [CI] = 0.93 to 1.27; P = .28). Among patients with limited-stage disease, there was no evidence of a survival difference (HR for death = 0.91, 95% CI = 0.73 to 1.15), but among patients with extensive disease, survival was worse in the thalidomide group (HR for death = 1.36, 95% CI = 1.10 to 1.68). Progression-free survival rates were also similar in the two groups (HR = 1.07, 95% CI = 0.92 to 1.24). Thalidomide was associated with an increased risk of having a thrombotic event, mainly pulmonary embolus and deep vein thrombosis (19% thalidomide vs 10% placebo; HR = 2.13, 95% CI = 1.41 to 3.20; P < .001). There were no statistically significant differences between treatments in hematological and nonhematological toxic effects, except more patients in the thalidomide group had rash, constipation, or neuropathy. Overall, QoL scores were similar in the two treatment groups, but thalidomide was associated with less insomnia and diarrhea and more constipation and peripheral neuropathy. In this large randomized trial, thalidomide in combination with chemotherapy did not improve survival of patients with SCLC but was associated with an increased risk of thrombotic events.
First Study of the Safety, Tolerability, and Pharmacokinetics of CP-724,714 in Patients with Advanced Malignant Solid HER2-Expressing Tumors
Authors: Pamela N. Munster, Carolyn D. Britten, Monica Mita, Karen Gelmon, Susan E. Minton, Stacy Moulder, Dennis J. Slamon, Feng Guo, Stephen P. Letrent, Louis Denis, Anthony W. Tolcher
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To test the tolerability, safety, and recommended phase II dose of CP-724,714, a reversible, highly selective, oral HER2 tyrosine kinase inhibitor in patients with advanced solid tumor malignancies that express HER2. Experimental Design: A phase I trial evaluated escalating doses of CP-724,714, administered daily in 21-day cycles. Pharmacokinetics/pharmacodynamics were evaluated in serial blood samples and in pretreatment and posttreatment tumor and skin biopsies. Results: Thirty female patients [median age, 51 years (range, 37-71); median performance status, 1 (range, 0-1)] received CP-724,714 at four dose levels: 250 mg once daily (4 patients), 250 mg twice daily (15 patients), 250 mg thrice daily (6 patients), and 400 mg twice daily (5 patients). Dosing at 400 mg twice daily and 250 mg thrice daily was not feasible due to reversible, cholestatic liver dysfunction. Treatment-related adverse events were nausea (58%), asthenia (23%), hyperbilirubinemia (27%), elevated transaminases (30%), and skin rash (30%); neither diarrhea nor cardiomyopathy was observed. No objective responses were observed in 28 evaluable patients; 8 (29%) patients had stable disease. Twenty-seven (96%) patients received prior trastuzumab and were heavily pretreated (median prior chemotherapy, 6; range, 1-11). Systemic exposure exceeded the in vivo efficacy threshold required in preclinical studies. Conclusions: Dose-limiting toxicities included hyperbilirubinemia, elevated alanine aminotransferase, thrombocytopenia and pulmonary embolus. Although the protocol-specified maximum tolerated dose of CP-724,714 was 250 mg thrice daily, the recommended phase II dose was 250 mg twice daily due to excessive late-cycle hepatotoxicity. Despite extensive prior treatment, 29% of patients had stable disease. A phase II trial has been initiated in patients with breast cancer.
A 13-yr-old male with fever, malaise, body pains and dry cough
Authors: A.C. Defilippi, P. Tomà, U.G. Rossi, O. Sacco, B. Ciravegna, C. Gambini, G.A. Rossi
Journal: European Respiratory Journal (2004)

Case historyA previously healthy 13-yr-old male was evaluated at La Spezia Hospital, La Spezia, Italy, because of a 15-day history of fever, malaise, body aches and dry cough, which were not modified by treatment with amoxicillin.A summary of the first admission blood tests is shown in table 1.The chest radiograph and the high-resolution computed tomography (HRCT) scans performed at that time are shown in figure 1a-c.Treatment with ampicillin, teicoplanin and netilmycin was administered for 7 days followed (as a result of no significant clinical response) by 12 days i.v.therapy with ciprofloxacine and imipenemcilastatine.The apyretic patient was discharged on oral ciprofloxacin.However, 2 weeks later, he was referred to the Giannina Gaslini Institute, Genoa, Italy, for further evaluations due to the recurrence of fever and dry cough.On second admission, the patient9s body temperature was 37.8uC, his respiratory rate was 28 breaths?min -1 and transcutaneous O 2 saturation in room air was 98%.Blood test results are shown in table 1. Chest radiograph and HRCT scans are shown in figure 2a-c.Fibreoptic bronchoscopy did not demonstrate any airway abnormality.Bronchoalveolar lavage (BAL) analysis showed as follows: 1) increased neutrophil percentage (35%); b) no acid-fast bacilli, viruses, fungi or malignant cells; and 3) positive cultures for Streptococcus mitis and S. milleri.Microscopic examination of transbronchial-biopsy specimens obtained from the right lower lobe showed interstitial nonspecific lymphocyte infiltration.Treatment with ampicillin-tazobactam and vancomycin was prescribed for 10 days, with only slight improvement of the clinical and laboratory parameters but no further changes in the chest radiographs.A diagnostic surgical procedure was performed and specimens from the right lower lung lobe were sent to the pathologist for evaluation (fig.3a-d).
Different Effects of Inhaled Aspirinlike Drugs on Allergen-Induced Early and Late Asthmatic Responses
Authors: PIERSANTE SESTINI, ROSA METELLA REFINI, MARIA GRAZIA PIERONI, ADRIANO VAGHI, MARIA ROBUSCHI, SEBASTIANO BIANCO
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Little is known about the anti-asthmatic effects of powerful anti-inflammatory agents such as aspirin-like drugs. We compared the effects of two aspirin-like drugs with different pharmacologic activities, sodium salicylate (SSA) and indomethacin, with the effect of lysine acetylsalicylate (LASA), inhaled 30 min before challenge, on the early and the late asthmatic response induced by a single dose of allergen causing a 25% decrease in FEV1 in a preliminary challenge. Inhaled SSA partially prevented both the early and late response, providing a protection with respect to placebo of 22 ± 6% in the early phase and 23 ± 9% in the late phase of the response. These values were lower (but not significantly) than those of LASA (41 ± 9% and 39 ± 11%, respectively). In a second group of patients, indomethacin failed to affect the early response, while LASA provided a protection of 31 ± 7%. However, these two drugs were equally effective in reducing the late response (44 ± 18% and 39 ± 17% protection for LASA and indomethacin, respectively). In subjects with an early response, despite being ineffective in preventing allergen-induced bronchoconstriction, indomethacin blocked the allergen-induced increase in bronchial hyperresponsiveness measured 2 h after challenge. We conclude that inhaled salicylates, but not indomethacin, exert a protective activity against the early allergic response. This difference is not explained by the different pattern of cyclooxygenase inhibitory activity of these drugs.
3D Porous Calcium-Alginate Scaffolds Cell Culture System Improved Human Osteoblast Cell Clusters for Cell Therapy
Authors: Ching-Yun Chen, Cherng-Jyh Ke, Ko-Chung Yen, Hui-Chen Hsieh, Jui-Sheng Sun, Feng-Huei Lin
Journal: Theranostics (2015)

Age-related orthopedic disorders and bone defects have become a critical public health issue, and cell-based therapy is potentially a novel solution for issues surrounding bone tissue engineering and regenerative medicine.Long-term cultures of primary bone cells exhibit phenotypic and functional degeneration; therefore, culturing cells or tissues suitable for clinical use remain a challenge.A platform consisting of human osteoblasts (hOBs), calcium-alginate (Ca-Alginate) scaffolds, and a self-made bioreactor system was established for autologous transplantation of human osteoblast cell clusters.The Ca-Alginate scaffold facilitated the growth and differentiation of human bone cell clusters, and the functionally-closed process bioreactor system supplied the soluble nutrients and osteogenic signals required to maintain the cell viability.This system preserved the proliferative ability of cells and cell viability and up-regulated bone-related gene expression and biological apatite crystals formation.The bone-like tissue generated could be extracted by removal of calcium ions via ethylenediaminetetraacetic acid (EDTA) chelation, and exhibited a size suitable for injection.The described strategy could be used in therapeutic application and opens new avenues for surgical interventions to correct skeletal defects.
Selective Screening for Gestational Diabetes in Chinese Women
Authors: Xilin Yang, Bridget Hsu-Hage, Lichun Yu, David Simmons
Journal: Diabetes Care (2002)

The American Diabetes Association (ADA) has recommended selective screening for gestational diabetes mellitus (GDM) (1). Pregnant women aged <25 years, who have normal body weight, no family history of diabetes, and are not members of an ethnic/racial group with a high prevalence of diabetes, are regarded as a low-risk group for GDM and need not be screened. The effect of selective screening guidelines has been investigated in Caucasian populations using a 100-g 3-h oral glucose tolerance test (OGTT) (2,3). We report here the effect of the selective screening protocol.

A total of 9,471 pregnant women in Tianjin, China, took part in a universal screening program …
Significant prevalence of antibodies reacting with simian virus 40 mimotopes in sera from patients affected by glioblastoma multiforme
Authors: E. Mazzoni, M. Gerosa, F. Lupidi, A. Corallini, A. P. Taronna, A. D'Agostino, M. Bovenzi, G. Ruggeri, F. Casali, J. C. Rotondo, G. Rezza, G. Barbanti-Brodano, M. Tognon, F. Martini
Journal: Neuro-Oncology (2013)

Glioblastoma multiforme (GBM) is a rare tumor, which affects 1/100 000 individuals, but it represents 30% of central nervous system malignancies. GBM is a severe tumor responsible for 2% of all cancer-related deaths. Although characterized by genotypic and phenotypic heterogeneities, GBM invariably resists conventional chemo- and radiotherapies. Several chromosome alterations and gene mutations were detected in GBM. Simian virus 40 (SV40), a small DNA tumor virus, has been found in GBM specimens by some studies, while other investigations have not confirmed the association. An indirect enzyme-linked immunosorbent assay with 2 synthetic peptides mimicking SV40 antigens of viral capsid proteins 1–3 was employed to detect specific antibodies against SV40 in serum samples from GBM-affected patients, together with controls represented by patients affected by breast cancer and normal subjects of the same median age. Our data indicate that in serum samples from GBM-affected patients (n = 44), the prevalence of antibodies against SV40 viral capsid protein antigens is statistically significantly higher (34%, P = .016 and P = .03) than in the control groups (15%), represented by healthy subjects (n = 101) and patients affected by breast cancer (n = 78), respectively. Our data indicate that SV40, or a closely related yet undiscovered human polyomavirus, is associated with a subset of GBM and circulates in humans. Our study can be transferred to the clinical oncology application to discriminate different types of heterogeneous GBM, which in turn may address an innovative therapeutic approach to this fatal cancer.
Status Epilepticus Treated with D-Tubocurarine and Controlled Respiration
Authors: H. I. A. Nisbet
Journal: BMJ (1959)

TREATMENT OF TRICHURIASIS BRDITAISH 95_to provide statistically valid conclusions at this stage.We are conducting a comprehensive trial with dithiazanine, and hope to publish a further report in due course.Our thanks are due to the nursing staff at Coldharbour Hospital for their care and observation of the patients under treatment.We are indebted to Mr. H.J. Attryde, chief technician, County Laboratory, Dorchester, who personally carried out all the egg counts in the trial.We also thank Eli Lilly
Primate and Rodent Specific Intron Gains and the Origin of Retrogenes with Splice Variants
Authors: Michał W Szcześniak, Joanna Ciomborowska, Witold Nowak, Igor B Rogozin, Izabela Makałowska
Journal: Molecular Biology and Evolution (2010)

Retroposition, a leading mechanism for gene duplication, is an important process shaping the evolution of genomes. Retrogenes are also involved in the gene structure evolution as a major player in the process of intron deletion. Here, we demonstrate the role of retrogenes in intron gain in mammals. We identified one case of "intronization," the transformation of exonic sequences into an intron, in the primate specific retrogene RNF113B and two independent "intronization" events in the retrogene DCAF12L2, one in the common ancestor of primates and rodents and another one in the rodent lineage. Intron gain resulted from the origin of new splice variants, and both genes have two transcript forms, one with retained intron and one with the intron spliced out. Evolution of these genes, especially RNF113B, has been very dynamic and has been accompanied by several additional events including parental gene loss, secondary retroposition, and exaptation of transposable elements.
CTGF Promotes Inflammatory Cell Infiltration of the Renal Interstitium by Activating NF-κB
Authors: Elsa Sánchez-López, Sandra Rayego, Raquel Rodrigues-Díez, Javier Sánchez Rodriguez, Raúl Rodrigues-Díez, Juan Rodríguez-Vita, Gisselle Carvajal, Luiz Stark Aroeira, Rafael Selgas, Sergio A. Mezzano, Alberto Ortiz, Jesús Egido, Marta Ruiz-Ortega
Journal: Journal of the American Society of Nephrology (2009)

Connective tissue growth factor (CTGF) is an important profibrotic factor in kidney diseases. Blockade of endogenous CTGF ameliorates experimental renal damage and inhibits synthesis of extracellular matrix in cultured renal cells. CTGF regulates several cellular responses, including adhesion, migration, proliferation, and synthesis of proinflammatory factors. Here, we investigated whether CTGF participates in the inflammatory process in the kidney by evaluating the nuclear factor-kappa B (NF-kappaB) pathway, a key signaling system that controls inflammation and immune responses. Systemic administration of CTGF to mice for 24 h induced marked infiltration of inflammatory cells in the renal interstitium (T lymphocytes and monocytes/macrophages) and led to elevated renal NF-kappaB activity. Administration of CTGF increased renal expression of chemokines (MCP-1 and RANTES) and cytokines (INF-gamma, IL-6, and IL-4) that recruit immune cells and promote inflammation. Treatment with a NF-kappaB inhibitor, parthenolide, inhibited CTGF-induced renal inflammatory responses, including the up-regulation of chemokines and cytokines. In cultured murine tubuloepithelial cells, CTGF rapidly activated the NF-kappaB pathway and the cascade of mitogen-activated protein kinases, demonstrating crosstalk between these signaling pathways. CTGF, via mitogen-activated protein kinase and NF-kappaB activation, increased proinflammatory gene expression. These data show that in addition to its profibrotic properties, CTGF contributes to the recruitment of inflammatory cells in the kidney by activating the NF-kappaB pathway.
A dynamic model of the cardiac ventricular action potential. I. Simulations of ionic currents and concentration changes.
Authors: C H Luo, Y Rudy
Journal: Circulation Research (1994)

A mathematical model of the cardiac ventricular action potential is presented. In our previous work, the membrane Na+ current and K+ currents were formulated. The present article focuses on processes that regulate intracellular Ca2+ and depend on its concentration. The model presented here for the mammalian ventricular action potential is based mostly on the guinea pig ventricular cell. However, it provides the framework for modeling other types of ventricular cells with appropriate modifications made to account for species differences. The following processes are formulated: Ca2+ current through the L-type channel (ICa), the Na(+)-Ca2+ exchanger, Ca2+ release and uptake by the sarcoplasmic reticulum (SR), buffering of Ca2+ in the SR and in the myoplasm, a Ca2+ pump in the sarcolemma, the Na(+)-K+ pump, and a nonspecific Ca(2+)-activated membrane current. Activation of ICa is an order of magnitude faster than in previous models. Inactivation of ICa depends on both the membrane voltage and [Ca2+]i. SR is divided into two subcompartments, a network SR (NSR) and a junctional SR (JSR). Functionally, Ca2+ enters the NSR and translocates to the JSR following a monoexponential function. Release of Ca2+ occurs at JSR and can be triggered by two different mechanisms, Ca(2+)-induced Ca2+ release and spontaneous release. The model provides the basis for the study of arrhythmogenic activity of the single myocyte including afterdepolarizations and triggered activity. It can simulate cellular responses under different degrees of Ca2+ overload. Such simulations are presented in our accompanying article in this issue of Circulation Research.
Adult mouse epicardium modulates myocardial injury by secreting paracrine factors
Authors: Bin Zhou, Leah B. Honor, Huamei He, Qing Ma, Jin-Hee Oh, Catherine Butterfield, Ruei-Zeng Lin, Juan M. Melero-Martin, Elena Dolmatova, Heather S. Duffy, Alexander von Gise, Pingzhu Zhou, Yong Wu Hu, Gang Wang, Bing Zhang, Lianchun Wang, Jennifer L. Hall, Marsha A. Moses, Francis X. McGowan, William T. Pu
Journal: Journal of Clinical Investigation (2011)

The epicardium makes essential cellular and paracrine contributions to the growth of the fetal myocardium and the formation of the coronary vasculature. However, whether the epicardium has similar roles postnatally in the normal and injured heart remains enigmatic. Here, we have investigated this question using genetic fate-mapping approaches in mice. In uninjured postnatal heart, epicardial cells were quiescent. Myocardial infarction increased epicardial cell proliferation and stimulated formation of epicardium-derived cells (EPDCs), which remained in a thickened layer on the surface of the heart. EPDCs did not adopt cardiomyocyte or coronary EC fates, but rather differentiated into mesenchymal cells expressing fibroblast and smooth muscle cell markers. In vitro and in vivo assays demonstrated that EPDCs secreted paracrine factors that strongly promoted angiogenesis. In a myocardial infarction model, EPDC-conditioned medium reduced infarct size and improved heart function. Our findings indicate that epicardium modulates the cardiac injury response by conditioning the subepicardial environment, potentially offering a new therapeutic strategy for cardiac protection.