tbuckley/cabot-search huggingface dataset:
<i>In Vivo</i> Quantification of Hypoxic and Metabolic Status of NSCLC Tumors Using [18F]HX4 and [18F]FDG-PET/CT Imaging
Authors: Catharina M.L. Zegers, Wouter van Elmpt, Bart Reymen, Aniek J.G. Even, Esther G.C. Troost, Michel C. Öllers, Frank J.P. Hoebers, Ruud M.A. Houben, Jonas Eriksson, Albert D. Windhorst, Felix M. Mottaghy, Dirk De Ruysscher, Philippe Lambin
Journal: Clinical Cancer Research (2014)

Abstract Purpose: Increased tumor metabolism and hypoxia are related to poor prognosis in solid tumors, including non–small cell lung cancer (NSCLC). PET imaging is a noninvasive technique that is frequently used to visualize and quantify tumor metabolism and hypoxia. The aim of this study was to perform an extensive comparison of tumor metabolism using 2[18F]fluoro-2-deoxy-d-glucose (FDG)-PET and hypoxia using HX4-PET imaging. Experimental Design: FDG- and HX4-PET/CT images of 25 patients with NSCLC were coregistered. At a global tumor level, HX4 and FDG parameters were extracted from the gross tumor volume (GTV). The HX4 high-fraction (HX4-HF) and HX4 high-volume (HX4-HV) were defined using a tumor-to-blood ratio &amp;gt; 1.4. For FDG high-fraction (FDG-HF) and FDG high-volume (FDG-HV), a standardized uptake value (SUV) &amp;gt; 50% of SUVmax was used. We evaluated the spatial correlation between HX4 and FDG uptake within the tumor, to quantify the (mis)match between volumes with a high FDG and high HX4 uptake. Results: At a tumor level, significant correlations were observed between FDG and HX4 parameters. For the primary GTV, the HX4-HF was three times smaller compared with the FDG-HF. In 53% of the primary lesions, less than 1 cm3 of the HX4-HV was outside the FDG–HV; for 37%, this volume was 1.9 to 12 cm3. Remarkably, a distinct uptake pattern was observed in 11%, with large hypoxic volumes localized outside the FDG-HV. Conclusion: Hypoxic tumor volumes are smaller than metabolic active volumes. Approximately half of the lesions showed a good spatial correlation between the PET tracers. In the other cases, a (partial) mismatch was observed. The addition of HX4-PET imaging has the potential to individualize patient treatment. Clin Cancer Res; 20(24); 6389–97. ©2014 AACR.
Mains-powered hypoxic gas generation: a cost-effective and safe method to evaluate patients at risk from hypoxia during air travel
Authors: K. J. Spurling, C. Zammit, S. Lozewicz
Journal: Thorax (2010)

However, the principal finding remains: while we agree that the presence of airway eosinophilia is a reliable predictor of steroid responsiveness, the absence of eosinophilia does not accurately predict steroid unresponsiveness.Whether intentionally or not, these authors imply that only patients with demonstrable sputum eosinophilia are steroid responsive.This is not the case.
Prognostic factors in primary diffuse large B-cell lymphoma of adrenal gland treated with rituximab-CHOP chemotherapy from the Consortium for Improving Survival of Lymphoma (CISL)
Authors: Yu Ri Kim, Jin Seok Kim, Yoo Hong Min, Dok Hyun Yoon, Ho-Jin Shin, Yeung-Chul Mun, Yong Park, Young Rok Do, Seong Hyun Jeong, Joon Seong Park, Sung Yong Oh, Suee Lee, Eun Kyung Park, Joung-Soon Jang, Won-Sik Lee, Hwe-Won Lee, HyeonSeok Eom, Jae-sook Ahn, Jae-Heon Jeong, Sun Kyung Baek, Seok Jin Kim, Won Seog Kim, Cheolwon Suh
Journal: Journal of Hematology & Oncology (2012)

The objective of this study was to identify prognostic factors for survival in patients with primary diffuse large B-cell lymphoma (DLBCL) of the adrenal gland. Thirty one patients diagnosed with primary adrenal DLBCL from 14 Korean institutions and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) were analyzed. Complete remission (CR) and overall response rate after R-CHOP chemotherapy were 54.8% and 87.0%. The 2-year estimates of overall survival (OS) and progression-free survival (PFS) were 68.3% and 51.1%. In patients achieving CR, significant prolongations of OS (P = 0.029) and PFS (P = 0.005) were observed. Ann Arbor stage had no influence on OS. There was no significant difference in OS between patients with unilateral involvement of adrenal gland and those with bilateral involvement. When staging was modified to include bilateral adrenal involvement as one extranodal site, early stage (I or II) significantly correlated with longer OS (P = 0.021) and PFS (P < 0.001). Contrary to prior reports, our data suggests that outcomes of primary adrenal DLBCL are encouraging using a regimen of R-CHOP, and that achieving CR after R-CHOP is predictive of survival. Likewise, our modified staging system may have prognostic value.
<i>Mist1-KrasG12D</i> Knock-In Mice Develop Mixed Differentiation Metastatic Exocrine Pancreatic Carcinoma and Hepatocellular Carcinoma
Authors: David A. Tuveson, Liqin Zhu, Aarthi Gopinathan, Nicholas A. Willis, Leili Kachatrian, Rebecca Grochow, Christopher L. Pin, Natalia Y. Mitin, Elizabeth J. Taparowsky, Phyllis A. Gimotty, Ralph H. Hruban, Tyler Jacks, Stephen F. Konieczny
Journal: Cancer Research (2006)

Abstract Despite the prevalence of oncogenic Kras mutations in the earliest stages of pancreatic ductal adenocarcinoma, the cellular compartment in which oncogenic Kras initiates tumorigenesis remains unknown. To address this, we have gene targeted KrasG12D into the open reading frame of Mist1, a basic helix-loop-helix transcription factor that is expressed during pancreatic development and required for proper pancreatic acinar organization. Although the pancreata of Mist1KrasG12D/+ mutant mice predictably exhibited acinar metaplasia and dysplasia, the frequent death of these mice from invasive and metastatic pancreatic cancer with mixed histologic characteristics, including acinar, cystic, and ductal features, was unexpected and in contrast to previously described mutant mice that ectopically expressed the Kras oncogene in either acinar or ductal compartments. Interestingly, many of the mutant mice developed hepatocellular carcinoma, implicating Mist1KrasG12D/+ cells in both pancreatic and hepatic neoplasia. Concomitant Trp53+/− mutation cooperated with Mist1KrasG12D/+ to accelerate lethality and was associated with advanced histopathologic findings, including parenchymal liver metastasis. These findings suggest that Mist1-expressing cells represent a permissive compartment for transformation by oncogenic Kras in pancreatic tumorigenesis. (Cancer Res 2006; 66(1): 242-7)
Tumor Imaging and Interferon-γ–Inducible Protein-10 Gene Transfer Using a Highly Efficient Transferrin-Conjugated Liposome System in Mice
Authors: Huiqin Zhuo, Yi Peng, Qin Yao, Nuo Zhou, Sufang Zhou, Jian He, Yuan Fang, Xi Li, Hongwei Jin, Xiaoling Lu, Yongxiang Zhao
Journal: Clinical Cancer Research (2013)

We have developed a PEGylated transferrin-conjugated liposomes (PTf-Ls) system for the combined tumor imaging and targeted delivery of the IFN-γ-inducible protein-10 (IP-10) gene in a single macromolecular construct. Here, we characterize and analyze the use of this system in a mouse model of breast cancer.The biophysical and cell transfection properties of PTf-Ls were determined through a series of in vitro experiments. A nude mouse/breast cancer cell line xenograft model (mouse xenograft model) was used to image the tumor internalization of fluorescently labeled PTf-Ls. The clinical use of the system was tested by treating tumor-bearing mice with PTf-Ls loaded with IP-10 plasmid DNA or fluorescent lipoplexes.The resulting 165-nm liposomes (zeta potential = -10.6 mV) displayed serum resistance, low cytotoxicity (<5%), and high transfection efficiency (≤82.8%) in cultured cells. Systemic intravenous administration of fluorescent PTf-Ls in the mouse xenograft model resulted in nanoparticle circulation for 72 hours, as well as selective and efficient internalization in tumor cells, according to in vivo fluorescence and bioluminescence analyses. Tumor fluorescence increased gradually up to 26 hours, whereas background fluorescence decreased to near-baseline levels. Treatment of mice with PTf-Ls entrapped pcDNA3.1-IP-10 suppressed tumor growth in mice by 79% on day 50 and increased the mean survival time of mice. Fluorescent pcDNA-IP-10-entrapped PTf-Ls showed good properties for simultaneous tumor-targeted imaging and gene-specific delivery in an animal tumor model.Our developed transferrin-conjugated liposome system possesses promising characteristics for tumor-targeting, imaging, and gene therapy applications.
TV: The Day I Died
Authors: M. O'Brien
Journal: BMJ (2003)

![Graphic][1]</img>![Graphic][2]</img> Does the whole of your life really flash across your mind in an instant as you lose consciousness while drowning? Most of us must have wondered what it is like to die since death is one of the two certainties in life, along with taxation. It might be supposed that we can never know. However, there are many people who have recovered after losing consciousness in situations in which most others would have continued to death, and it is reasonable to suppose that their last thoughts might be the same as those of patients in similar situations who do not recover. These are commonly described as “near death experiences.” Some of these, which are recalled subsequently, are surprisingly clear and detailed. This programme is based on a number of anecdotal accounts of … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif
THE FUNCTION OF THE SPLEEN IN THE EXPERIMENTAL INFECTION OF ALBINO MICE WITH BACILLUS TUBERCULOSIS
Authors: Paul A. Lewis, Arthur Georges Margot
Journal: The Journal of Experimental Medicine (1915)

The resistance to an infection with the tubercle bacillus which can be given to mice by the removal of the spleen is lost when fresh spleen, either of mouse or sheep, is added to the diet. The logical conclusion that splenic function in its relation to the specific infection is restored by feeding spleen cannot, however, be drawn; because, in the first place, the character of the disease in the splenectomized spleen-fed animals differs somewhat from that in intact animals; and, secondly, because fresh spleen when fed to splenectomized animals apparently gives rise to an acute intoxication. This intoxication occurs quite regularly in mice. It is manifested in the infected animals and in those not inoculated. It has been seen in one of two splenectomized dogs experimented upon. Up to the present it can hardly be definitely characterized, but it seems to be best marked out by the specific anorexia associated with it.
Catecholaminergic polymorphic ventricular tachycardia: Recent mechanistic insights
Authors: K KONTULA, P LAITINEN, A LEHTONEN, L TOIVONEN, M VIITASALO, H SWAN
Journal: Cardiovascular Research (2005)

Cardiac excitation-contraction coupling occurs by a calcium ion-mediated mechanism in which the signal of action potential is converted into Ca2+ influx into the cardiomyocytes through the sarcolemmal L-type calcium channels. This is followed by Ca2+-induced release of additional Ca2+ ions from the lumen of the sarcoplasmic reticulum into the cytosol via type 2 ryanodine receptors (RyR2). RyR2 channels form large complexes with additional regulatory proteins, including FKBP12.6 and calsequestrin 2 (CASQ2). Catecholamines, released into the body fluids during emotional or physical stress, activate Ca2+-induced Ca2+ release by protein kinase A-mediated phosphorylation of RyR2. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an insidious, early-onset and highly malignant, inherited disorder characterized by effort-induced ventricular arrhythmias in the absence of structural alterations of the heart. At least some cases of sudden, unexplained death in young individuals may be ascribed to CPVT. Mutations of the RyR2 gene cause autosomal dominant CPVT, while mutations of the CASQ2 gene may cause an autosomal recessive or dominant form of CPVT. The steps of the molecular pathogenesis of CPVT are not entirely clear, but inappropriate "leakiness" of RyR2 channels is thought to play a role; the underlying mechanisms may involve an increase in the basal activity of the RyR2 channel, alterations in its phosphorylation status, a defective interaction of RyR2 with other molecules or ions, such as FKBP12.6, CASQ2, or Mg2+, or its abnormal activation by extra- or intraluminal Ca2+ ions. Beta-adrenergic antagonists have proven to be of value in prevention of arrhythmias in CPVT patients, but occasional treatment failures call for alternative measures. There is great interest at present for the development of novel antiarrhythmic drugs for CPVT, as the same approaches may be applied for treatment of more common forms of life-threatening arrhythmias, such as those arising during ischemia and heart failure.
A placebo controlled study of albendazole in the treatment of pulmonary echinococcosis
Authors: M. Keshmiri, H. Baharvahdat, S.h Fattahi, B Davachi, R.h. Dabiri, H. Baradaran, T. Ghiasi, M.t. Rajabimashhadi, F. Rajabzadeh
Journal: European Respiratory Journal (1999)

Infection with Echinococcus granulosus is endemic in Middle Eastern countries. Some patients are noted to undergo spontaneous resolution, but many require surgical removal with its associated risks. Although, there are studies showing favourable responses to medical treatment, there is no controlled study on the effect of albendazole. In this study, 20 patients with 179 E. granulosus cysts affecting the lungs were entered into a triple blind parallel randomized clinical trial comparing the effects of albendazole versus placebo. Fifteen patients (150 cysts) completed 6 months of treatment; four patients (26 cysts) were in the placebo group and 11 patients (124 cysts) in the treatment group receiving 800 mg albendazole daily in three cycles of 6 weeks with 2 weeks between cycles. Ten of 11 patients (91%) in the treatment group showed either cure (five patients) or improvement (five patients); in the placebo group, only one of four (25%) showed spontaneous improvement but no cure. In the treatment group, 88 of 124 cysts (71%) showed improvement compared to four of 26 (15.4%) in the placebo group (p=0.000). Complication from therapy was insignificant; one case had recurrent disease, which responded to further therapy. It is suggested that patients suffering from uncomplicated hydatid disease should be given a trial of albendazole before surgery is considered.
Cardiovascular Characteristics in Subjects With Increasing Levels of Abnormal Glucose Regulation
Authors: Brunella Capaldo, Procolo Di Bonito, Michele Iaccarino, Mary J. Roman, Elisa T. Lee, Richard B. Devereux, Gabriele Riccardi, Barbara V. Howard, Giovanni de Simone
Journal: Diabetes Care (2012)

To evaluate whether impaired fasting glucose (IFG) or the combination of IFG and impaired glucose tolerance (IGT) is associated with progressive abnormalities of cardiac geometry and function.We studied 562 nondiabetic (311 women), nonhypertensive participants of the second Strong Heart Study exam, without prevalent cardiovascular (CV) disease and with estimated glomerular filtration rate ≥60 mL/min/1.73 m(2) (age 46-65 years, 198 with isolated IFG [35%], and 132 with combined IFG and IGT [23%]). Anthropometric parameters, insulin resistance, fibrinogen, C-reactive protein (CRP), lipid profile, blood pressure (BP), and echocardiographic parameters were compared with 232 participants with normal glucose tolerance (NGT).BMI, prevalence of central obesity, homeostatic model assessment index of insulin resistance, plasma triglycerides, fibrinogen, and CRP increased progressively across categories of glucose intolerance (P < 0.0001), with the IFG+IGT group having higher values than those with isolated IFG (0.05 < P < 0.0001). Compared with NGT, both IFG and IFG+IGT exhibited greater left ventricular (LV) mass (P < 0.0001) and lower Doppler early peak rapid filling velocity to peak atrial filling velocity ratio (P < 0.005), without differences in LV systolic function. The odds of LV hypertrophy (LV mass index >46.7 in women or >49.2 g/m(2.7) in men) was 3.5 in IFG participants (95% CI 0.68-17.76; P = NS) and 9.76 (2.03-46.79; P = 0.004) in IFG+IGT, compared with NGT, after adjustment for age, sex, heart rate, systolic BP, and waist circumference (WC). In the overall sample, LV mass index was associated with WC (P = 0.033), CRP (P = 0.027), and 2-h oral glucose tolerance test (P = 0.001) independently of confounders.Cardiometabolic profile and markers of inflammation are more severely altered in men and women with both IFG and IGT compared with those with IFG alone. These individuals, in the absence of hypertension, have a 10-fold greater probability of preclinical CV disease (LV hypertrophy).
PROPERTIES OF THE CAUSATIVE AGENT OF A CHICKEN TUMOR
Authors: Albert Claude
Journal: The Journal of Experimental Medicine (1935)

The fractionation of active chicken tumor extracts has been continued. 1. By a rapid method of dialysis the diffusible fraction of the treated extract, representing about 75 per cent of the solids, has been eliminated without reducing the tumor-producing activity. 2. Combined methods of fractionation have resulted in the elimination of as much as 95 per cent of the total solids of the extract as inactive constituents. Since there was some concomitant enhancement of the activity of the agent the results were equivalent to a 25-fold concentration of it in terms of dry weight. 3. The chemical content of the undiffusible fraction has been determined in terms of total nitrogen, reducing substances, sulfur, phosphorus, and lipoids. 4. The evidence points to a protein and a phospholipoid as the principal constituents of the active residue. Further fractionation is being attempted with a view to connecting the tumor-producing activity with one of its remaining constituents.
Dynamic Tuning of T Cell Reactivity by Self-Peptide–Major Histocompatibility Complex Ligands
Authors: Phillip Wong, Gregory M. Barton, Katherine A. Forbush, Alexander Y. Rudensky
Journal: The Journal of Experimental Medicine (2001)

Intrathymic self-peptide-major histocompatibility complex class II (MHC) molecules shape the T cell repertoire through positive and negative selection of immature CD4(+)CD8(+) thymocytes. By analyzing the development of MHC class II-restricted T cell receptor (TCR) transgenic T cells under conditions in which the endogenous peptide repertoire is altered, we show that self-peptide-MHC complexes are also involved in setting T cell activation thresholds. This occurs through changes in the expression level of molecules on thymocytes that influence the sensitivity of TCR signaling. Our results suggest that the endogenous peptide repertoire modulates T cell responsiveness in the thymus in order to enforce tolerance to self-antigens.
Induction of differentiation in cultured rat and human podocytes.
Authors: P Mundel, J Reiser, W Kriz
Journal: Journal of the American Society of Nephrology (1997)

Mature podocytes are highly differentiated cells that are unable to divide in vivo. During glomerulogenesis, podocytes develop from simple cuboidal cells into their adult phenotype, which is characterized by a complex pattern of processes. Cultivation of podocytes under standard conditions leads to dedifferentiation, including the loss of processes and of pp44, a marker of differentiated podocytes. In this study, the cell culture conditions for rat and human podocytes were modified by avoiding repeated subcultivation. This led to profound phenotypic changes in podocytes in vitro. The conversion of cobblestones into arborized cells was directly observed, and a series of intermediate phenotypes was documented. The cells converted within 3 wk from typical cobblestone appearance into individual arborized cells more closely resembling in vivo podocytes. Arborized cells were frequently binucleated and reached a size of up to 500 microns. Both cobblestone and arborized cells originated from podocytes, as evidenced by the expression of a podocyte-specific O-acetylated ganglioside and of the WT-1 protein. In contrast to primary cultures and early passages of cobblestones, a cloned rat podocyte cell line did not express WT-1 and could not be induced to differentiate into arborized cells. This finding indicates a role for WT-1 in maintaining differentiation of adult podocytes. The differentiation of arborized cells led to growth arrest and was reflected by the formation of processes and the expression of pp44 and desmin, which were never detected in cobblestones. It was concluded that partial differentiation of cultured podocytes can be achieved simply by avoiding repeated subcultivation, resulting in an arborized phenotype more closely reflecting in vivo podocytes.
SIDS and idiopathic ALTE: Genetic similarities
Authors: L. Nosetti, L. Filonzi, C. Magnani, V. Mongiardi, C. Borghi, V. Milan, L. Nespoli, F. Nonnis Marzano
Journal: European Respiratory Journal (2012)

Backgtround: Recent advances in molecular genetics have opened new perspectives in the definition of pathogenic mechanisms of SIDS. Several studies, during the past decade, identified polymorphisms in the serotonin transporter ( 5HTT ) ( SLC6A4  encoding 5HTT) as a predisposing factor in infant death. Aim of the study: This project represents a significant step to add knowledge on the involvement of the serotonin polymorphisms of two different  5HTT  regions (5-HTTLPR, hydroxytryptamine transporter-linked polymorphic region, and Stin2, intron 2 VNTR), the promoter region of MAOA (monoamine oxidase A), and DAT in an Italian SIDS population, ALTE patients, IALTE (idiopathic ALTE) and controls. Methods: We enrolled 76 infants with an history of Apparent Life Threatening Event, distingued in Idiopathic ALTE (IALTE) and Non Idiopathic ALTE (ALTE) by clinical, diagnostic and therapeutic data (12 channels polysomnography E-Series Compumedics). Genotypes and allelic frequencies of DAT, MAOA and 5HTT were determined in ALTE and IALTE infants compared with data obtained from 150 healthy controls. Results: No association was found between DAT polmorphysm and ALTE/IALTE groups either in the genotype (p=0.25; p=0.112) nor in the allelic frequence (p=0.94;P=0.88). The comparison of MAOA genotypes and allelic frequence between ALTE and control group was not significant, on the opposite the comparison between IALTE and control group was statistically significant for the genotypes (P=0.09) and a tendency for allele (p=0.036). Analisys of 5HTT polymorphisms in IALTE remarked the pathogenetic role of L/L genotype (P
A quantitative method for detecting deposits of amyloid A protein in aspirated fat tissue of patients with arthritis
Authors: B. P C Hazenberg, P. C Limburg, J. Bijzet, M. H van Rijswijk
Journal: Annals of the Rheumatic Diseases (1999)

<h3>OBJECTIVE</h3> To describe a new, quantitative, and reproducible method for detecting deposits of amyloid A protein in aspirated fat tissue and to compare it with smears stained with Congo red. <h3>METHODS</h3> After extraction of at least 30 mg of abdominal fat tissue in guanidine, the amyloid A protein concentration was measured by a monoclonal antibody-based sandwich ELISA. <h3>RESULTS</h3> The concentrations in 24 patients with arthritis and AA amyloidosis (median 236, range 1.1–8530 ng/mg tissue) were higher (p&lt;0.001) than in non-arthritic controls, uncomplicated rheumatoid arthritis, and other types of systemic amyloidosis (median 1.1, range 1.1–11.6 ng/mg tissue). Patients with extensive deposits, according to Congo red staining, had higher concentrations than patients with minute deposits. <h3>CONCLUSION</h3> This is a new, quantitative, and reproducible method for detecting deposits of amyloid A protein in aspirated fat tissue of patients with arthritis, even when minute deposits are present as detected in smears stained with Congo red.