tbuckley/cabot-search huggingface dataset:
Effects of a novel cholecystokinin (CCK) receptor antagonist, MK-329, on gallbladder contraction and gastric emptying in humans. Implications for the physiology of CCK.
Authors: R A Liddle, B J Gertz, S Kanayama, L Beccaria, L D Coker, T A Turnbull, E T Morita
Journal: Journal of Clinical Investigation (1989)

To explore the physiology of cholecystokinin (CCK) in humans, we investigated the effect on gallbladder contraction and gastric emptying of a recently developed CCK receptor antagonist, MK-329. In a double-blind, four-period crossover study eight subjects received single doses of 0.5, 2, or 10 mg MK-329, or placebo, followed by an intravenous infusion of CCK-8 (30 pmol/kg.h). In placebo-treated subjects gallbladder volumes decreased on average to 43% of initial volumes after 2 h of CCK infusion. MK-329 caused a dose-dependent inhibition of CCK-stimulated gallbladder contraction with 10 mg producing complete blockade (P less than 0.01, cf. placebo). Gallbladder contraction and gastric emptying rates after a mixed meal were then measured in a two-period crossover study. Subjects received placebo or 10 mg of MK-329 2 h before eating. Gastric emptying of both solids and liquids was measured simultaneously by gamma scintigraphy. In placebo-treated subjects plasma CCK levels increased postprandially to 2.3 pM, gallbladder volumes decreased 68.4 +/- 3.8% (SE), and the times for 50% emptying of liquids and solids from the stomach were 58 +/- 10 and 128 +/- 8 min, respectively. In MK-329-treated subjects there was a marked elevation in peak CCK levels to 13.8 pM (P less than 0.01, cf. placebo), and gallbladder contraction was completely inhibited. Solid and liquid emptying rates were unaffected. These findings demonstrate that (a) MK-329 is a potent, orally active antagonist of CCK in humans, and (b) CCK is the major regulator of postprandial gallbladder contraction. These data also support the concept of negative feedback regulation of CCK secretion and suggest that mechanisms other than CCK play a dominant role in the regulation of postprandial gastric emptying rates.
Advantages of Concurrent Biochemotherapy Modified by Decrescendo Interleukin-2, Granulocyte Colony-Stimulating Factor, and Tamoxifen for Patients With Metastatic Melanoma
Authors: Steven J. O'Day, Guy Gammon, Peter D. Boasberg, Maureen A. Martin, Tim S. Kristedja, Matthew Guo, Stacey Stern, Shirley Edwards, Patricia Fournier, Monica Weisberg, Maureen Cannon, Nancy W. Fawzy, Timothy D. Johnson, Richard Essner, Leland J. Foshag, Donald L. Morton
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Concurrent biochemotherapy results in high response rates but also significant toxicity in patients with metastatic melanoma. We attempted to improve its efficacy and decrease its toxicity by using decrescendo dosing of interleukin-2 (IL-2), posttreatment granulocyte colony-stimulating factor (G-CSF), and low-dose tamoxifen. PATIENTS AND METHODS: Forty-five patients with poor prognosis metastatic melanoma were treated at a community hospital inpatient oncology unit affiliated with the John Wayne Cancer Institute (Santa Monica, CA) between July 1995 and September 1997. A 5-day modified concurrent biochemotherapy regimen of dacarbazine, vinblastine, cisplatin, decrescendo IL-2, interferon alfa-2b, and tamoxifen was repeated at 21-day intervals. G-CSF was administered beginning on day 6 for 7 to 10 days. RESULTS: The overall response rate was 57% (95% confidence interval, 42% to 72%), the complete response rate was 23%, and the partial response rate was 34%. Complete remissions were achieved in an additional 11% of patients by surgical resection of residual disease after biochemotherapy. The median time to progression was 6.3 months and the median duration of survival was 11.4 months. At a maximum follow-up of 36 months (range, 10 to 36 months), 32% of patients are alive and 14% remain free of disease. Decrescendo IL-2 dosing and administration of G-CSF seemed to reduce toxicity, length of hospital stay, and readmission rates. No patient required intensive care unit monitoring, and there were no treatment-related deaths. CONCLUSION: The data from this study indicate that the modified concurrent biochemotherapy regimen reduces the toxicity of concurrent biochemotherapy with no apparent decrease in response rate in patients with poor prognosis metastatic melanoma.
Gambogic Acid Induces Apoptosis in Imatinib-Resistant Chronic Myeloid Leukemia Cells via Inducing Proteasome Inhibition and Caspase-Dependent Bcr-Abl Downregulation
Authors: Xianping Shi, Xin Chen, Xiaofen Li, Xiaoying Lan, Chong Zhao, Shouting Liu, Hongbiao Huang, Ningning Liu, Siyan Liao, Wenbin Song, Ping Zhou, Shunqing Wang, Li Xu, Xuejun Wang, Q. Ping Dou, Jinbao Liu
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Chronic myelogenous leukemia (CML) is characterized by the constitutive activation of Bcr-Abl tyrosine kinase. Bcr-Abl-T315I is the predominant mutation that causes resistance to imatinib, cytotoxic drugs, and the second-generation tyrosine kinase inhibitors. The emergence of imatinib resistance in patients with CML leads to searching for novel approaches to the treatment of CML. Gambogic acid, a small molecule derived from Chinese herb gamboges, has been approved for phase II clinical trial for cancer therapy by the Chinese Food and Drug Administration (FDA). In this study, we investigated the effect of gambogic acid on cell survival or apoptosis in CML cells bearing Bcr-Abl-T315I or wild-type Bcr-Abl. Experimental Design: CML cell lines (KBM5, KBM5-T315I, and K562), primary cells from patients with CML with clinical resistance to imatinib, and normal monocytes from healthy volunteers were treated with gambogic acid, imatinib, or their combination, followed by measuring the effects on cell growth, apoptosis, and signal pathways. The in vivo antitumor activity of gambogic acid and its combination with imatinib was also assessed with nude xenografts. Results: Gambogic acid induced apoptosis and cell proliferation inhibition in CML cells and inhibited the growth of imatinib-resistant Bcr-Abl-T315I xenografts in nude mice. Our data suggest that GA-induced proteasome inhibition is required for caspase activation in both imatinib-resistant and -sensitive CML cells, and caspase activation is required for gambogic acid–induced Bcr-Abl downregulation and apoptotic cell death. Conclusions: These findings suggest an alternative strategy to overcome imatinib resistance by enhancing Bcr-Abl downregulation with the medicinal compound gambogic acid, which may have great clinical significance in imatinib-resistant cancer therapy. Clin Cancer Res; 20(1); 151–63. ©2013 AACR.
Endothelial Dysfunction Is Correlated With Microalbuminuria in Children With Short-Duration Type 1 Diabetes
Authors: Ana M. Ladeia, Carol Ladeia-Frota, Luiz Pinho, Eridan Stefanelli, Luis Adan
Journal: Diabetes Care (2005)

Patients with diabetes have increased risk of developing atherosclerotic diseases (1). In type 1 diabetes, vascular complications are more frequently identified after the 5th year of the disease. Ultrasound assessment of endothelial function is a noninvasive method for detecting early structural and functional atherosclerotic process in the arterial wall. Impaired flow-mediated dilatation (FMD), an early marker of atherosclerosis, has been detected in children with family hypercholesterolemia (2) and diabetes (3). This study assessed the presence of endothelial dysfunction in children with type 1 diabetes and <5 years duration of the disease.

This cross-sectional study included 18 randomly selected type 1 diabetic patients (13 boys) followed up at a public health assistance center, with disease duration of 2.9 ± 1.2 years (0.7–4.9 years) and without clinical evidence of vascular complications, and 14 healthy control subjects (7 boys) without chronic diseases or hypercholesterolemia, matched by age (±2 years) and BMI. Patients with retinopathy, hypertension, obesity, thyroid disease, and history of smoking were excluded. Laboratory data included fasting blood glucose, plasma lipids, HbA1c (A1C), creatinine, TSH, and microalbuminuria.

After the subjects had been lying in supine position for 10 min in a stable- temperature room, the response to reactive hyperemia (FMD) was evaluated. The diameter of the brachial artery was measured in a longitudinal section (2–15 cm above the elbow) with a high-resolution vascular ultrasound. Reactive …
Three-Dimensional Cell Growth Confers Radioresistance by Chromatin Density Modification
Authors: Katja Storch, Iris Eke, Kerstin Borgmann, Mechthild Krause, Christian Richter, Kerstin Becker, Evelin Schröck, Nils Cordes
Journal: Cancer Research (2010)

Cell shape and architecture are determined by cell-extracellular matrix interactions and have profound effects on cellular behavior, chromatin condensation, and tumor cell resistance to radiotherapy and chemotherapy. To evaluate the role of chromatin condensation for radiation cell survival, tumor cells grown in three-dimensional (3D) cell cultures as xenografts and monolayer cell cultures were compared. Here, we show that increased levels of heterochromatin in 3D cell cultures characterized by histone H3 deacetylation and induced heterochromatin protein 1alpha expression result in increased radiation survival and reduced numbers of DNA double strand breaks (DSB) and lethal chromosome aberrations. Intriguingly, euchromatin to heterochromatin-associated DSBs were equally distributed in irradiated 3D cell cultures and xenograft tumors, whereas irradiated monolayer cultures showed a 2:1 euchromatin to heterochromatin DSB distribution. Depletion of histone deacetylase (HDAC) 1/2/4 or application of the class I/II pharmacologic HDAC inhibitor LBH589 induced moderate or strong chromatin decondensation, respectively, which was translated into cell line-dependent radiosensitization and, in case of LBH589, into an increased number of DSBs. Neither growth conditions nor HDAC modifications significantly affected the radiation-induced phosphorylation of the important DNA repair protein ataxia telangiectasia mutated. Our data show an interrelation between cell morphology and cellular radiosensitivity essentially based on chromatin organization. Understanding the molecular mechanisms by which chromatin structure influences the processing of radiation-induced DNA lesions is of high relevance for normal tissue protection and optimization of cancer therapy.
Long-term evaluation of the General Electric cardiac pacemaker
Authors: D. R. Kahn, M. M. Kirsh, S. Vathayanon, P. W. Willis, J. A. Walton, K. McIntosh, P. W. Ferguson, H. Sloan
Journal: Thorax (1970)

A review of General Electric (G.E.) electronic cardiac pacemakers for symptomatic complete A-V heart block in two sequential three-year periods at the University of Michigan Medical Center indicates that there has been no increase in the useful life of these units. With G.E. epicardial pacemakers failure occurred after an average of 12 months. In the early years the major cause of failure was wire breakage, and the later major cause was battery exhaustion or component failure. Exit block was a major complication. There was no improvement when G.E. catheter pacemakers were used instead of the epicardial type. The Medtronic catheter pacemakers lasted longer, with fewer battery and component failures and no instances of exit block. Although infection was more common with Medtronic pacemakers, secondary to erosion of the power unit or the catheter through the skin, it may be that this complication could be eliminated by locating the battery box beneath the latissimus dorsi muscle in the axilla and by careful catheter placement to avoid pressure necrosis and subsequent cutaneous perforation.
Government unveils new approach to emergency care
Authors: Rebecca Coombes
Journal: BMJ (2005)

Fewer people calling 999 in the United Kingdom will be taken to emergency departments for treatment in future, under government plans announced last week.

A review of the ambulance service recommends instead that more patients be treated at home by new “super paramedics” who will be trained to the same level as nurses. More patients should also be dealt with over the phone and referred to appropriate services such as GP services, both in and out of hours, or an emergency nurse service.

The health minister Norman Warner said the changes could prevent at least one million attendances at emergency departments each year: “People, by and …
Activation of innate immune defense mechanisms contributes to polyomavirus BK-associated nephropathy
Authors: Andrea Ribeiro, Markus Wörnle, Nasim Motamedi, Hans J. Anders, Elisabeth F. Gröne, Hans Nitschko, Peter Kurktschiev, Hanna Debiec, Matthias Kretzler, Clemens D. Cohen, Hermann J. Gröne, Detlef Schlöndorff, Holger Schmid
Journal: Kidney International (2011)
Weight Reduction May Be Beneficial for Japanese Men With Cardiometabolic Risk Factors Even if They Are Not Abdominally Obese
Authors: Eiji Oda
Journal: Diabetes Care (2010)

A consensus statement (1) for the criteria of metabolic syndrome (MetS) where abdominal obesity is not a necessary component was jointly issued by the International Diabetes Federation Task Force on Epidemiology and Prevention; the National Heart, Lung, and Blood Institute; the American Heart Association; the World Heart Federation; the International Atherosclerosis Society; and the International Association for the Study of Obesity. However, abdominal or visceral fat obesity is a necessary component in Japanese criteria of MetS (2), and some Japanese investigators insist that weight reduction is ineffective to reduce cardiovascular risk factors in subjects without abdominal obesity. Therefore, I investigated whether …
Cefotetan‐induced hemolytic anemia causing severe hypophosphatemia
Authors: Suneel Mohammed, Sandra Knoll, Albert Van Amburg, Paul A. Mennes
Journal: American Journal of Hematology (1994)

Phosphorus is a major component of proteins, phospholipids, and nucleotides. The increased uptake of phosphorus by cells during erythropoiesis can result in severe hypophosphatemia. A case of severe hypophosphatemia due to accelerated erythropoiesis in response to Cefotetan-induced hemolytic anemia is described. The hypophosphatemia seen during hemolysis may be the result, rather than the cause, of the hemolysis.
New-Onset Diabetes in Elderly Subjects
Authors: Orit Twito, Ella Ahron, Anat Jaffe, Shani Afek, Efrat Cohen, Martine Granek-Catarivas, Pinchas Klein, Doron Hermoni
Journal: Diabetes Care (2013)

New-onset diabetes mellitus (DM) in elderly patients is associated with increased risk of diabetes complications and mortality. It is unknown whether glycemic control in this population influences the mortality risk.The current study was conducted using the computerized database of the Sharon-Shomron District of Clalit Health Services in Israel. Included in the study were subjects 65 years of age and above with new-onset DM. The primary outcome measures were all-cause mortality and coronary revascularization procedures with either percutaneous coronary intervention or coronary artery bypass grafting.Participants (n = 2,994) were stratified into four groups according to their mean HbA1c levels during the follow-up period (<6.5% [48 mmol/mol], 6.5-6.99% [48-52 mmol/mol], 7-7.49% [53-57 mmol/mol], and ≥7.5% [58 mmol/mol]). During a mean follow-up of 5.54 ± 2.1 years, 1,173 (39.17%) participants died and 285 (9.51%) underwent coronary revascularization. An HbA1c level >7.5% (58 mmol/mol) was associated with a significantly increased all-cause mortality rate (hazard ratio [HR] 1.74 [95% CI 1.2-1.8], P < 0.0001). This difference remained statistically significant after a multivariate model adjusted for the conventional cardiovascular risk factors and for the use of hypoglycemic agents and statins. Kaplan-Meier survival plots revealed lower survival rates in this group of patients. Coronary revascularization rates were highest among subjects with HbA1c 6.5-6.99% (48-52 mmol/mol) (HR 1.6 [1.01-2.4], P < 0.05) and lowest in patients with HbA1c ≥7.5% (58 mmol/mol).An HbA1c level >7.5% (58 mmol/mol) is associated with increased risk for all-cause mortality and with a lower revascularization rate in elderly patients with new-onset DM.
Clinical Advances in the Diagnosis and Therapy of the Interstitial Lung Diseases
Authors: Talmadge E. King
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Section:ChooseTop of pageAbstract <<EPIDEMIOLOGY OF ILDsDIAGNOSIS OF ILDsIIPsTHERAPY FOR IIPsSARCOIDOSISLAMOCCUPATIONAL AND ENVIRONM...CONCLUSIONSReferencesCITING ARTICLES
ET-01 * IL-13 CONJUGATED QUANTUM DOTS FOR THE IDENTIFICATION AND CHARACTERIZATION OF GLIOMA STEM CELLS, SOLUBLE RECEPTORS AND EXOSOMES RELEASED BY GBM TUMORS
Authors: M. Achutha, C. Siedlecki, M. Glantz, L. Xu, J. Connor
Journal: Neuro-Oncology (2014)

Glioblastoma Multiforme is an aggressive brain tumor combining high infiltrative properties with a heterogenous nature making it challenging to identify and remove them by surgery and increasing their resistance to other conventional therapies. GBM tumors are known to express the IL-13Rα2 receptors which we have used to target nanoliposomes for enhancing theranostic efficacy. In our present investigation we utilized interleukin-13 ( IL-13) conjugated quantum dots (IL-13QD) to selectively bind the glioma stem cells in culture and the soluble receptor in a medium and the exosomes released in a biological fluid. The binding phenomenon was characterized by various techniques like atomic force microscopy, dynamic light scattering method, electron microscopy and fluorescent microscopy. Investigation was also performed to determine the release of soluble IL-13Rα2 receptor and IL-13Rα2 expressing exosomes from the glioma stem cells in the culture media and in the cerebrospinal fluid. After confirming the presence of soluble receptor by immunoblots and ELISA and exosomes by electron microscopy and dynamic light scattering method, in vitro studies were performed with the IL-13QD in a media containing the exosomes and soluble receptors to investigate the binding and aggregation properties of the IL-13QD. Our investigation revealed the aggregation properties of the IL-13QD in the presence of soluble receptor and exosomes indicating a correlation between the receptor expression and aggregation and dissociation of quantum dots. Further studies are in progress with patient samples that would lead to a development of a biomarker and a therapeutic agent for the highly malignant brain tumors.
Novel Genes for Airway Wall Thickness Identified with Combined Genome-Wide Association and Expression Analyses
Authors: Akkelies E. Dijkstra, Dirkje S. Postma, Bram van Ginneken, Mark O. Wielpütz, Michael Schmidt, Nikolaus Becker, Michael Owsijewitsch, Hans-Ulrich Kauczor, Harry J. de Koning, Jan W. Lammers, Matthijs Oudkerk, Corry-Anke Brandsma, Yohan Bossé, David C. Nickle, Don D. Sin, Pieter S. Hiemstra, Ciska Wijmenga, Joanna Smolonska, Pieter Zanen, Judith M. Vonk, Maarten van den Berge, H. Marike Boezen, Harry J. M. Groen
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Airway wall thickness (AWT) is affected by both environmental and genetic factors and is strongly associated with airflow limitation in smaller airways.To investigate the genetic component of AWT.AWT was measured on low-dose computed tomography scans in male heavy smokers participating in a lung cancer screening study (n = 2,640). Genome-wide association studies on AWT were performed under an additive model using linear regression (adjusted for pack-years, lung volume), followed by metaanalysis. An independent cohort was used for validation of the most strongly associated single-nucleotide polymorphisms (SNPs). The functional relevance of significant SNPs was evaluated.Three significant loci on chromosomes 2q (rs734556; P = 6.2 × 10(-7)) and 10q (rs10794108, P = 8.6 × 10(-8); rs7078439, P = 2.3 × 10(-7)) were associated with AWT and confirmed in the metaanalysis in cohorts with comparable lung function: P values = 4.6 × 10(-8), 7.4 × 10(-8), and 7.5 × 10(-8), respectively. SNP rs734556 was associated with decreased lung tissue expression of SERPINE2, a susceptibility gene for emphysema. Two nominally significant SNPs showed effects with similar direction: rs10251504 in MAGI2 (P = 5.8 × 10(-7)) and rs4796712 in NT5C3B (P = 3.1 × 10(-6)). Higher MAGI2 expression in bronchial biopsies of patients with chronic obstructive pulmonary disease was significantly associated with fewer inflammatory cells. The presence of the NT5C3B risk allele was associated with higher lung tissue expression (P = 1.09 × 10(-41)).Genetic variants contribute to AWT. Among others, the identified genes are also involved in emphysema, airway obstruction, and bronchial inflammation.
Tissue factors on acute promyelocytic leukemia and endothelial cells are differently regulated by retinoic acid, arsenic trioxide and chemotherapeutic agents
Authors: J Zhu, W-M Guo, Y-Y Yao, W-L Zhao, L Pan, X Cai, B Ju, G-L Sun, H-L Wang, S-J Chen, G-Q Chen, J Caen, Z Chen, Z-Y Wang
Journal: Leukemia (1999)
Are the Platyhelminthes a monophyletic primitive group? An assessment using 18S rDNA sequences
Authors: S. Carranza, J. Baguna, M. Riutort
Journal: Molecular Biology and Evolution (1997)

In most zoological textbooks, Platyhelminthes are depicted as an early-emerging clade forming the likely sister group of all the other Bilateria. Other phylogenetic proposals see them either as the sister group of most of the Protostomia or as a group derived from protostome coelomate ancestors by progenesis. The main difficulty in their correct phylogenetic placing is the lack of convincing synapomorphies for all Platyhelminthes, which may indicate that they are polyphyletic. Moreover, their internal phylogenetic relationships are still uncertain. To test these hypotheses, new complete 18S rDNA sequences from 13 species of "Turbellaria" have been obtained and compared to published sequences of 2 other "Turbellaria," 3 species of parasitic Platyhelminthes, and several diploblastic and deuterostome and protostome triploblastics. Maximum-parsimony, maximum-likelihood, and neighbor-joining methods were used to infer their phylogeny. The results show the order Catenulida to form an independent early-branching clade and emerge as a potential sister group of the rest of the Bilateria, while the rest of Platyhelminthes (Rhabditophora), which includes the parasites, form a clear monophyletic group closely related to the protostomes. The order Acoela, morphologically considered as candidates to be ancestral, are shown to be fast-clock organisms for the 18S rDNA gene. Hence, long-branching of acoels and insufficient sampling of catenulids and acoels leave their position still unresolved and call for further studies. Within the Rhabditophora, our analyses suggest (1) a close relationship between orders Macrostomida and Polycladida, forming a clear sister group to the rest of orders; (2) that parasitic platyhelminthes appeared early in the evolution of the group and form a sister group to a still-unresolved clade made by Nemertodermatida, Lecithoepitheliata, Prolecithophora, Proseriata, Tricladida, and Rhabdocoela; and (3) that Seriata is paraphyletic.
Cholestatic liver disease modulates susceptibility to ischemia/reperfusion-induced arrhythmia, but not necrosis and hemodynamic instability: The role of endogenous opioid peptides
Authors: Amir Reza Hajrasouliha, Sina Tavakoli, Pejman Jabehdar-Maralani, Farzad Ebrahimi, Hamed Shafaroodi, Seyyed Hamid Mirkhani, Saied Amanpour, Ahmad Reza Dehpour
Journal: Journal of Hepatology (2005)