tbuckley/cabot-search huggingface dataset:
Effect of Recombinant Surfactant Protein C–Based Surfactant on the Acute Respiratory Distress Syndrome
Authors: Roger G. Spragg, James F. Lewis, Hans-Dieter Walmrath, Jay Johannigman, Geoff Bellingan, Pierre-Francois Laterre, Michael C. Witte, Guy A. Richards, Gerd Rippin, Frank Rathgeb, Dietrich Häfner, Friedemann J.H. Taut, Werner Seeger
Journal: New England Journal of Medicine (2004)

Preclinical studies suggest that exogenous surfactant may be of value in the treatment of the acute respiratory distress syndrome (ARDS), and two phase 2 clinical trials have shown a trend toward benefit. We conducted two phase 3 studies of a protein-containing surfactant in adults with ARDS.In two multicenter, randomized, double-blind trials involving 448 patients with ARDS from various causes, we compared standard therapy alone with standard therapy plus up to four intratracheal doses of a recombinant surfactant protein C-based surfactant given within a period of 24 hours.The overall survival rate was 66 percent 28 days after treatment, and the median number of ventilator-free days was 0 (68 percent range, 0 to 26); there was no significant difference between the groups in terms of mortality or the need for mechanical ventilation. Patients receiving surfactant had a significantly greater improvement in blood oxygenation during the initial 24 hours of treatment than patients receiving standard therapy, according to both univariate and multivariate analyses.The use of exogenous surfactant in a heterogeneous population of patients with ARDS did not improve survival. Patients who received surfactant had a greater improvement in gas exchange during the 24-hour treatment period than patients who received standard therapy alone, suggesting the potential benefit of a longer treatment course.
Activation of Akt Predicts Poor Outcome in Neuroblastoma
Authors: Daniela Opel, Christopher Poremba, Thorsten Simon, Klaus-Michael Debatin, Simone Fulda
Journal: Cancer Research (2007)

Abstract Whereas aberrant activation of the phosphatidylinositol 3′-kinase (PI3K)/Akt pathway, a key survival cascade, has previously been linked to poor prognosis in several human malignancies, its prognostic effect in neuroblastoma has not yet been explored. We therefore investigated the phosphorylation status of Akt, S6 ribosomal protein as target of mammalian target of rapamycin, and extracellular signal–regulated kinase (ERK) in 116 primary neuroblastoma samples by tissue microarray and its correlation with established prognostic markers and survival outcome. Here, we provide for the first time evidence that phosphorylation of Akt at serine 473 (S473) and/or threonine 308 (T308), S6 ribosomal protein, and ERK frequently occurs in primary neuroblastoma. Importantly, we identified Akt activation as a novel prognostic indicator of decreased event-free or overall survival in neuroblastoma, whereas phosphorylation of S6 ribosomal protein or ERK had no prognostic effect. In addition, Akt activation correlated with variables of aggressive disease, including MYCN amplification, 1p36 aberrations, advanced disease stage, age at diagnosis, and unfavorable histology. Monitoring Akt at T308 or both phosphorylation sites improved the prognostic significance of Akt activation in neuroblastoma specimens compared with S473 phosphorylation. Parallel experiments in neuroblastoma cell lines revealed that activation of Akt by insulin-like growth factor (IGF)-I significantly inhibited tumor necrosis factor–related apoptosis-inducing ligand– or chemotherapy-induced apoptosis in a PI3K-dependent manner because the PI3K inhibitor LY294002 completely reversed the IGF-I–mediated protection of neuroblastoma cells from apoptosis. By showing that activation of Akt correlates with poor prognosis in primary neuroblastoma in vivo and with apoptosis resistance in vitro, our findings indicate that Akt presents a clinically relevant target in neuroblastoma that warrants further investigation. [Cancer Res 2007;67(2):735–45]
Report of 33 Novel AVPR2 Mutations and Analysis of 117 Families with X-Linked Nephrogenic Diabetes Insipidus
Authors: MARIE-FRANC[COMBINING CEDILLA]OISE ARTHUS, MICHE[Combining Grave Accent]LE LONERGAN, M. JOYCE CRUMLEY, ANNA K. NAUMOVA, DENIS MORIN, LUIZ A. DE MARCO, BERNARD S. KAPLAN, GARY L. ROBERTSON, SEI SASAKI, KENNETH MORGAN, DANIEL G. BICHET, T. MARY FUJIWARA
Journal: Journal of the American Society of Nephrology (2000)

Abstract. X-linked nephrogenic diabetes insipidus (NDI) is a rare disease caused by mutations in the arginine vasopressin receptor 2 gene ( AVPR2 ). Thirty-three novel AVPR2 mutations were identified in 62 families that were not included in our previous studies. This study describes the diversity of mutations observed in a total of 117 families, the number of affected people at the time of diagnosis, skewed X chromosome inactivation in severely affected females, the inferred parental origin of de novo mutations, and it provides estimates of incidence. Among 117 families, there were 82 different putative disease-causing mutations. Based on haplotype analysis, it can be inferred that when the same AVPR2 mutation is identified in different families that were not known to be related, the mutations most likely arose independently. More than half of the families had only one affected male; two families presented with a severely affected female and no family history of NDI. A de novo mutation arose during oogenesis in the mother in 20% of isolated cases. The estimate of about 8.8 per million male live births of the incidence of X-linked NDI in the province of Quebec, Canada may be representative of the general population except in Nova Scotia and New Brunswick, where the incidence is more than six times higher. Documentation of the diversity of mutations will assist in revealing the full spectrum of clinical variation. Discussion of genetic and population genetic aspects of X-linked NDI may contribute to early diagnosis and treatment.
FIXED DRUG ERUPTION: AN AUTORADIOGRAPHIC STUDY OF EXCHANGE GRAFTS†
Authors: DAVID PORTER, STANLEY COMAISH
Journal: British Journal of Dermatology (1969)

Journal Article FIXED DRUG ERUPTION: AN AUTORADIOGRAPHIC STUDY OF EXCHANGE GRAFTS Get access DAVID I PORTER, DAVID I PORTER University of Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne Search for other works by this author on: Oxford Academic Google Scholar STANLEY COMAISH STANLEY COMAISH University of Department of Dermatology, Royal Victoria Infirmary, Newcastle upon Tyne Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 81, Issue 3, 1 March 1969, Pages 171–174, https://doi.org/10.1111/j.1365-2133.1969.tb16001.x Published: 01 March 1969 Article history Accepted: 24 September 1968 Published: 01 March 1969
Molecular Characteristics Predict Clinical Outcomes: Prospective Trial Correlating Response to the EGFR Tyrosine Kinase Inhibitor Gefitinib with the Presence of Sensitizing Mutations in the Tyrosine Binding Domain of the <i>EGFR</i> Gene
Authors: Naiyer A. Rizvi, Valerie Rusch, William Pao, Jamie E. Chaft, Marc Ladanyi, Vincent A. Miller, Lee M. Krug, Christopher G. Azzoli, Manjit Bains, Robert Downey, Raja Flores, Bernard Park, Bhuvanesh Singh, Maureen Zakowski, Robert T. Heelan, Ronglai Shen, Mark G. Kris
Journal: Clinical Cancer Research (2011)

To determine if tumor regression following treatment with gefitinib correlates with the presence of sensitizing mutations in epidermal growth factor receptor (EGFR).Patients with resectable stage I and II non-small cell lung cancer (NSCLC) enriched for the likelihood of EGFR mutation (≤ 15 pack-year cigarette smoking history and/or a component of bronchioloalveolar carcinoma) received preoperative gefitinib for 21 days. Tumor specimens were analyzed for EGFR and KRAS mutations and EGFR protein expression and amplification. Patients with 25% or more reduction in tumor size measured bidimensionally at 3 weeks and/or patients with an EGFR mutation received adjuvant gefitinib for 2 years postoperatively.Fifty patients with stage I/II NSCLC were treated. After 21 days of preoperative gefitinib a response of 25% or more was observed in 21 of 50 (42%) patients. Seventeen of 21 patients with a response had an EGFR mutation and 4 of 21 patients with a response did not (P = 0.0001). Twenty-five of 50 patients were eligible to receive adjuvant gefitinib. With a median follow-up of 44.1 months, 2-year disease free survival for EGFR mutant patients and for those who received adjuvant gefitinib was not statistically different than those who were EGFR wild-type and those who did not receive adjuvant gefitinib. The median disease free and overall survivals have not been reached.The presence of sensitizing EGFR mutations correlates with radiographic response. A short course of preoperative treatment serves a platform for evaluating activity of new agents and assures sufficient tumor availability for correlative analyses.
Inhibition of telomerase activity and human telomerase reverse transcriptase gene expression by histone deacetylase inhibitor in human brain cancer cells
Authors: Aik Kia Khaw, Miranti Silasudjana, Birendranath Banerjee, Masao Suzuki, Rajamanickam Baskar, Prakash Hande
Journal: Clinical Cancer Research (2007)

AACR Centennial Conference: Translational Cancer Medicine-- Nov 4-8, 2007; Singapore

C19 

The aim of the present study is to investigate the effect of histone deacetylase inhibitor, Trichostatin A (TSA) on the cell growth, apoptosis, genomic DNA damage and the expression of telomerase and associated factors in human normal and brain cancer cells. Here, human normal un-transformed fibroblasts (MRC-5), human normal hTERT-immortalised fibroblasts (hTERT-BJ1) and human brain cancer cell lines (glioblastoma cell line, A-172 and medulloblastoma cell line, ONS-76) were treated with 0.5 to 3.0 µM TSA for 24 h. Exposure to TSA resulted in apoptosis in a dose-dependent manner in the brain cancer cells. Glioblastoma cell line (A-172) displayed higher sensitivity to TSA-induced cell killing effect and apoptosis than the medulloblastoma cell line (ONS-76). The brain cancer cell lines and hTERT-BJ1 cell line displayed significant inhibition in telomerase activity and hTERT mRNA level after 2 µM TSA treatment. Elevated expressions of p53 and p21 with a decrease in cyclin-D level supported the observation on cell cycle arrest following TSA treatment. Upregulation of Bax and cytochrome C correlated with the apoptotic events in TSA-treated cells. This study suggests that telomerase and hTERT might be the primary targets of TSA which may have the potential to be used as a telomerase inhibitor in cancer therapy.    This study is supported by Academic Research Fund, Ministry of Education and NUS. International Union Against Cancer (UICC, Switzerland) is acknoweldged for Yamagiwa-Yoshida Memorial International Cancer Study Grant award to MPH in 2003.
Health-Related Quality Of Life (HRQoL) In Adult Patients With Hereditary Angioedema Due To C1 Inhibitor Deficiency (HAE-C1-INH) Assessed By SF-36v2
Authors: Teresa Caballero, Magdalena Julia Caminoa, Elia Pérez-Fernández, Carmen Gómez-Traseira, Anne Aabom, Werner Aberer, Stephen D. Betschel, Anette Bygum, Dorottya Csuka, Henriette Farkas, Maria Gomide, Adriane Groffik, Anete S. Grumach, Iris Leivobich, Alejandro Malbran, Eniko Mihaly, Dumitru Moldovan, Krystyna Obtulowicz, Gregor Porebski, Celina Rayonne, Avner Reshef, Petra Staubach, Michaela Wiednig, Maria Joao Forjaz, Nieves Prior
Journal: Journal of Allergy and Clinical Immunology (2014)
STK4 regulates TLR pathways and protects against chronic inflammation–related hepatocellular carcinoma
Authors: Weiyun Li, Jun Xiao, Xin Zhou, Ming Xu, Chaobo Hu, Xiaoyan Xu, Yao Lu, Chang Liu, Shengjie Xue, Lei Nie, Haibin Zhang, Zhiqi Li, Yanbo Zhang, Fu Ji, Lijian Hui, Wufan Tao, Bin Wei, Hongyan Wang
Journal: Journal of Clinical Investigation (2015)

Hepatocellular carcinoma (HCC) is frequently associated with pathogen infection–induced chronic inflammation. Large numbers of innate immune cells are present in HCCs and can influence disease outcome. Here, we demonstrated that the tumor suppressor serine/threonine-protein kinase 4 (STK4) differentially regulates TLR3/4/9-mediated inflammatory responses in macrophages and thereby is protective against chronic inflammation–associated HCC. STK4 dampened TLR4/9-induced proinflammatory cytokine secretion but enhanced TLR3/4-triggered IFN-β production via binding to and phosphorylating IL-1 receptor–associated kinase 1 (IRAK1), leading to IRAK1 degradation. Notably, macrophage-specific Stk4 deletion resulted in chronic inflammation, liver fibrosis, and HCC in mice treated with a combination of diethylnitrosamine (DEN) and CCl4, along with either LPS or E. coli infection. STK4 expression was markedly reduced in macrophages isolated from human HCC patients and was inversely associated with the levels of IRAK1, IL-6, and phospho-p65 or phospho-STAT3. Moreover, serum STK4 levels were specifically decreased in HCC patients with high levels of IL-6. In STK4-deficient mice, treatment with an IRAK1/4 inhibitor after DEN administration reduced serum IL-6 levels and liver tumor numbers to levels similar to those observed in the control mice. Together, our results suggest that STK4 has potential as a diagnostic biomarker and therapeutic target for inflammation-induced HCC.
Change of breathing pattern after breathing assist technique and pursed-lip breathing intervention
Authors: Aya Sato, Kei Kondo, Shinya Nakamura, Kenji Yazaki, Toshihiko Kikuchi, Mitsuko Sato, Tazuko Sato, Kenji Kikuchi, Masahiko Wakasa
Journal: European Respiratory Journal (2012)

Background: The general pattern of breathing after breathing assist technique (BAT) and pursed-lip breathing (PLB) has never been reported.  Aim: The aim of this study was to evaluate the pattern of breathing after BAT and PLB using a portable sleep recorder (PSR: SAS2100 by NIHON KOHDEN).  Methods: Five patients with pulmonary disease (2 females and 3 males, mean ± SD age 81.8 ± 1.8) participated in this research. BAT assists during expiration. Participants performed BAT for 10 min and training PLB for 10 min, 5 times a week for 8 to 56 days. We evaluated the breathing pattern by PSR, respiratory rate(RR), 6-minute distance (6MD), and oxygen saturation (SpO 2 ) before and after these programs.  Case A: Vital Capacity (VC) 0.94L (%VC 44.8%), Forced Expiratory Volume in one second (FEV 1.0 ) 0.52L (%FEV 1.0  37.4%).  Case B: VC 2.34L (%VC 80.1%), FEV 1.0  0.65L (%FEV 1.0  37.4%).  Case C: VC 1.73L (%VC 60.1%), FEV 1.0  0.57L (%FEV 1.0  34.3%).  Case D: VC 2.17L (%VC 75.9%), FEV 1.0  0.58L (%FEV 1.0  35.6%).  Case E: VC 1.37L (%VC 61.6%), FEV 1.0  0.96L (%FEV 1.0  73.2%).  Results: The average height of waveforms of the breathing pattern increased about 3 times. 6MD in 2cases and SpO 2  in 3cases increased in this study; however, the 3 other cases of 6MD and 2 other cases of SpO 2  remained unchanged. Additionally, RR decreased in 4 cases. Since the start of the program, changes in the breathing pattern from mouth to nose breathing were observed in a case.  Conclusions: This study revealed that BAT and PLB resulted in a decrease of RR and a change in the breathing pattern; furthermore, after this program, changes from mouth to nose breathing were observed.
The Interrelationships of Serum Lipids in Men and Women Past Sixty-Five Years of Age and Their Bearing on Atherosclerosis
Authors: MENARD M. GERTLER, BERNARD S. OPPENHEIMER
Journal: Circulation (1953)

The interrelationships of serum lipids, that is, free cholesterol, esterified cholesterol, total cholesterol, lipid phosphorus, total lipids, neutral fats and S f 10-20 molecules were determined in 91 women and 38 men past the age of 65 years. It was observed that all the serum lipids with the exception of neutral fats were statistically higher in the women. Furthermore, it was shown that the serum total cholesterol and serum S f 10-20 molecules were correlated to a significant degree in the men, 0.59 ± .15, but to an insignificant degree in the women, 0.21 ± .12. It was also shown that the levels of serum total cholesterol and S f 10-20 molecules increase with age within the age range 65 to 85 in the women but remain stationary or actually decrease in the men. The bearing of these findings on atherosclerogenesis is discussed.
Ventricular Arrhythmias Induced by Sympathomimetic Amines in Unanesthetized Dogs Following Coronary Artery Occlusion
Authors: HARRIET M. MALING, NEIL C. MORAN, Martha A. Williams
Journal: Circulation Research (1957)

Epinephrine and norepinephrine, in doses which cause little ectopic activity in unanesthetized normal dogs, produce exaggerated ectopic responses about the fourth day after coronary ligation, when the arrhythmias caused by the ligation per se have subsided. These responses persist for approximately 12 days after ligation and suggest reactivation of latent ectopic foci. Observations with methoxamine, isoproterenol, and atropine indicate that ventricular tachycardia is easily induced after occlusion by drugs which simultaneously stimulate the myocardium and slow the sinus node rate.
Variants of <i>GCKR</i> Affect Both β-Cell and Kidney Function in Patients With Newly Diagnosed Type 2 Diabetes
Authors: Sara Bonetti, Maddalena Trombetta, Maria Linda Boselli, Fabiola Turrini, Giovanni Malerba, Elisabetta Trabetti, Pier Franco Pignatti, Enzo Bonora, Riccardo C. Bonadonna
Journal: Diabetes Care (2011)

In genome-wide association studies, performed mostly in nondiabetic individuals, genetic variability of glucokinase regulatory protein (GCKR) affects type 2 diabetes-related phenotypes, kidney function, and risk of chronic kidney disease (CKD). We tested whether GCKR variability affects type 2 diabetes or kidney-related phenotypes in newly diagnosed type 2 diabetes.In 509 GAD-negative patients with newly diagnosed type 2 diabetes, we 1) genotyped six single nucleotide polymorphisms in GCKR genomic region: rs6717980, rs1049817, rs6547626, rs780094, rs2384628, and rs8731; 2) assessed clinical phenotypes, insulin sensitivity by the euglycemic insulin clamp, and β-cell function by state-of-the-art modeling of glucose/C-peptide curves during an oral glucose tolerance test; and 3) estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease formula.The major alleles of rs6717980 and rs2384628 were associated with reduced β-cell function (P < 0.05), with mutual additive effects of each variant (P < 0.01). The minor alleles of rs1049817 and rs6547626 and the major allele of rs780094 were associated with reduced eGFR according to a recessive model (P < 0.03), but with no mutual additive effects of the variants. Additional associations were found between rs780094 and 2-h plasma glucose (P < 0.05) and rs8731 and insulin sensitivity (P < 0.05) and triglycerides (P < 0.05).Our findings are compatible with the idea that GCKR variability may play a pathogenetic role in both type 2 diabetes and CKD. Genotyping GCKR in patients with newly diagnosed type 2 diabetes might help in identifying patients at high risk for metabolic derangements or CKD.
Optical Imaging with Her2-Targeted Affibody Molecules Can Monitor Hsp90 Treatment Response in a Breast Cancer Xenograft Mouse Model
Authors: Stephanie M.W.Y. van de Ven, Sjoerd G. Elias, Carmel T. Chan, Zheng Miao, Zhen Cheng, Abhijit De, Sanjiv S. Gambhir
Journal: Clinical Cancer Research (2012)

Abstract Purpose: To determine whether optical imaging can be used for in vivo therapy response monitoring as an alternative to radionuclide techniques. For this, we evaluated the known Her2 response to 17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride (17-DMAG) treatment, an Hsp90 inhibitor. Experimental Design: After in vitro 17-DMAG treatment response evaluation of MCF7 parental cells and 2 HER2-transfected clones (clone A medium, B high Her2 expression), we established human breast cancer xenografts in nude mice (only parental and clone B) for in vivo evaluation. Mice received 120 mg/kg of 17-DMAG in 4 doses at 12-hour intervals intraperitonially (n = 14) or PBS as carrier control (n = 9). Optical images were obtained both pretreatment (day 0) and posttreatment (day 3, 6, and 9), always 5 hours postinjection of 500 pmol of anti-Her2 Affibody-AlexaFluor680 via tail vein (with preinjection background subtraction). Days 3 and 9 in vivo optical imaging signal was further correlated with ex vivo Her2 levels by Western blot after sacrifice. Results: Her2 expression decreased with 17-DMAG dose in vitro. In vivo optical imaging signal was reduced by 22.5% in clone B (P = 0.003) and by 9% in MCF7 parental tumors (P = 0.23) 3 days after 17-DMAG treatment; optical imaging signal recovered in both tumor types at days 6 to 9. In the carrier group, no signal reduction was observed. Pearson correlation of in vivo optical imaging signal with ex vivo Her2 levels ranged from 0.73 to 0.89. Conclusions: Optical imaging with an affibody can be used to noninvasively monitor changes in Her2 expression in vivo as a response to treatment with an Hsp90 inhibitor, with results similar to response measurements in positron emission tomography imaging studies. Clin Cancer Res; 18(4); 1073–81. ©2012 AACR.
Increased expression of the Wilms tumor gene (WT1) at relapse in acute leukemia [letter]
Authors: H Tamaki, H Ogawa, K Inoue, T Soma, T Yamagami, S Miyake, Y Oka, Y Oji, T Tatekawa, A Tsuboi, S Tagawa, T Kitani, K Aozasa, T Kishimoto, H Sugiyama, H Miwa, K Kita
Journal: Blood (1996)
30 A COMBINATION OF BASELINE VARIABLES INCLUDING IL28B POLYMORPHISM CAN ACCURATELY PREDICT RESPONSE TO ANTIVIRAL TREATMENT IN HEPATITIS C RECURRENCE AFTER LIVER TRANSPLANTATION
Authors: G. Crespo, J.A. Carrión, M. Coto-Llerena, S. Pérez del Pulgar, M. García-Retortillo, M. Navasa, X. Forns
Journal: Journal of Hepatology (2011)
Plasmacytoid precursor dendritic cells facilitate allogeneic hematopoietic stem cell engraftment
Authors: Isabelle J. Fugier-Vivier, Francine Rezzoug, Yiming Huang, Amanda J. Graul-Layman, Carrie L. Schanie, Hong Xu, Paula M. Chilton, Suzanne T. Ildstad
Journal: The Journal of Experimental Medicine (2005)

Bone marrow transplantation offers great promise for treating a number of disease states. However, the widespread application of this approach is dependent upon the development of less toxic methods to establish chimerism and avoid graft-versus-host disease (GVHD). CD8+/TCR− facilitating cells (FCs) have been shown to enhance engraftment of hematopoietic stem cells (HSCs) in allogeneic recipients without causing GVHD. In the present studies, we have identified the main subpopulation of FCs as plasmacytoid precursor dendritic cells (p-preDCs). FCs and p-preDCs share many phenotypic, morphological, and functional features: both produce IFN-α and TNF-α, both are activated by toll-like receptor (TLR)-9 ligand (CpG ODN) stimulation, and both expand and mature after Flt3 ligand (FL) treatment. FL-mobilized FCs, most of which express a preDC phenotype, significantly enhance engraftment of HSCs and induce donor-specific tolerance to skin allografts. However, p-preDCs alone or p-preDCs from the FC population facilitate HSC engraftment less efficiently than total FCs. Moreover, FCs depleted of preDCs completely fail to facilitate HSC engraftment. These results are the first to define a direct functional role for p-preDCs in HSC engraftment, and also suggest that p-preDCs need to be in a certain state of maturation/activation to be fully functional.