tbuckley/cabot-search huggingface dataset:
Increased uptake of liposomal–dna complexes by lung metastases following intravenous administration
Authors: Isao Ito, Gopalan Began, Imran Mohiuddin, Tomoyuki Saeki, Yuji Saito, Cynthia D Branch, Ara Vaporciyan, L Clifton Stephens, Nancy Yen, Jack A Roth, Rajagopal Ramesh
Journal: Molecular Therapy (2003)

We have investigated the effects of an improved liposomal formulation (extruded DOTAP:cholesterol (DOTAP:Chol)-DNA complex) on transgene expression in tumor cells and normal cells of murine and human origin both in vitro and in vivo. In vitro, transgene expression was significantly increased (P = 0.01) in human tumor cells compared to normal human cells. The increased transgene expression was due to increased uptake of the liposome-DNA complex by tumor cell phagocytosis. Furthermore, immunohistochemical analysis demonstrated a greater transgene expression in lung tumors than in surrounding normal tissues. Increased transgene expression due to enhanced uptake of the liposome-DNA complexes by tumor cells in vivo was also demonstrated using fluorescently labeled DOTAP:Chol liposomes. Finally, evaluation of lung tissue explants obtained from patients undergoing pulmonary resection demonstrated significantly higher (P = 0.001) transgene expression in tumor cells than in normal cells. Thus, we demonstrated that intravenous injection of DOTAP:Chol-DNA complex results in increased transgene expression in tumor and is due to increased phagocytosis of the complexes by tumor cells.
The Biology of Thrombosis
Authors: Y Nemerson, H L Nossel
Journal: Annual Review of Medicine (1982)

For the past decade the concept of a primary role for platelets in the pathogenesis of thrombosis, especially arterial thrombosis, has been a domi­ nant force in research on thrombosis. Several large-scale studies were de­ signed to determine if agents that inhibit platelet aggregation affect clinical arterial ischemic disease. Some of the results were positive, but not as dramatic as might have been anticipated (1, 2). It is possible that agents with a more powerful inhibitory effect and that are directed at platelet adhesion rather than aggregation would have greater therapeutic efficiency. Mean­ while data have been accumulating to indicate that methods for controlling the coagulation system have not been optimally exploited. A prospective study on hemostatic function and cardiovascular death showed that men who subsequently died of cardiovascular causes showed at recruitment significantly higher plasma levels of factors VII and VIII as well as fibrino­ gen and cholesterol. There were no differences in platelet count or adhesive­ ness (3). A recent Dutch trial suggested that dicumarol might reduce mortality by considerably more than the 20% established by earlier trials (4). Several pilot studies of patients with acute myocardial infarction showed that acutely occluded coronary arteries can be recanalized by the intra-coronary injection of streptokinase. This technique has great potential
Changes in bilirubin pigments secreted in bile after liver transplantation
Authors: Carl A. Goresky, Ellen R. Gordon, Juan-Ramon Sanabria, Steven M. Strasberg, Wayne M. Flye
Journal: Hepatology (1992)

ABSTRPlCT The species of bile pigments secreted in T–tube fistula bile after liver transplantation were ascertained by high–performance liquid chromatography in 15 patients for 10 days after liver transplant. Nine glycosidic conjugates and unconjugated bilirubin were resolved by the analytical procedure. The principal pigments in bile and their proportions in normal patients were the following: bilirubin diglucuronide = 83.0% ± bilirubin monoglucuronide = 9.7% ± 1.4% (S.D.); bilirubin monoglucuronide monoglucoside = 4.0% 2.8% (S.D.); and bilirubin monoglucuronide monoxyloside = 1.5% ± 1.8% (S.D.). All of the other possible glucuronide, glucose and xylose monoconjugates and diconjugates and unconjugated bilirubin were also found, but each was normally less than 1% of the total. In 13 of the 15 transplant patients, a significant depression in proportions of bilirubin diglucuronide and elevation in proportions of bilirubin monoglucuronide were found after the transplant, with an accompanying but generally small increase in the proportions of the minor conjugates. In two patients with rejection of the transplant, the changes were of larger magnitude, with improvement occurring only with recovery from the rejection. In one of these patients, kidney failure was present, and in addition to the diglucuronide and monoglucuronide conjugates diglucoside and monoglucoside monoxyloside conjugates were found in plasma. The underlying metabolic abnormalities are not clear but likely reflect underlying abnormal intracellular cofactor levels for conjugation. Glycogen depletion with reduction of UDP–glucuronate levels or reduced UDP–glucuronate formation from UDP–glucose, secondary to elevation of UDP–xylose, could potentially account for the changes in pigment excretion. (Hepatology 1992;15:849-857).
Lapatinib Versus Hormone Therapy in Patients With Advanced Renal Cell Carcinoma: A Randomized Phase III Clinical Trial
Authors: Alain Ravaud, Robert Hawkins, Jason P. Gardner, Hans von der Maase, Niko Zantl, Peter Harper, Frédéric Rolland, Bruno Audhuy, Jean-Pascal Machiels, Frank Pétavy, Martin Gore, Patrick Schöffski, Iman El-Hariry
Journal: Journal of Clinical Oncology (2008)

Lapatinib is an orally reversible inhibitor of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER-2) tyrosine kinases with demonstrated activity in patients with HER-2-positive breast cancer. In the current phase III open-label trial, lapatinib was compared with hormone therapy (HT) in patients with advanced renal cell carcinoma (RCC) that express EGFR and/or HER-2.Patients with advanced RCC who had experienced disease progression through first-line cytokine therapy--stratified by Karnofsky performance status and number of metastatic sites--were randomly assigned to lapatinib 1,250 mg daily or HT. The primary end point was time to progression (TTP); secondary end points included overall survival (OS), safety, and biomarker analyses.Four hundred sixteen patients were enrolled onto the study. Median TTP was 15.3 weeks for lapatinib versus 15.4 weeks for HT (hazard ratio [HR] = 0.94; P = .60), and median OS was 46.9 weeks for lapatinib versus 43.1 weeks for HT (HR = 0.88; P = .29). In a biomarker analysis of patients with EGFR-overexpressed tumors (3+ by immunohistochemistry [IHC]; n = 241) median TTP was 15.1 weeks for lapatinib versus 10.9 weeks for HT (HR = 0.76; P = .06), and median OS was 46.0 weeks for lapatinib versus 37.9 weeks for HT (HR = 0.69; P = .02). These results were confirmed by Cox regression analysis. No unexpected toxicities were observed; the most commonly reported drug-related adverse events (all grades) for lapatinib were rash (44%) and diarrhea (40%).Lapatinib was well tolerated with equivalent overall efficacy to HT in advanced RCC patients who had experienced disease progression while receiving cytokines, and the study supports that lapatinib prolonged OS relative to HT in patients with 3+ EGFR status determined by IHC.
How Sudden Is Sudden Cardiac Death?
Authors: Dirk Müller, Rahul Agrawal, Hans-Richard Arntz
Journal: Circulation (2006)

Out-of-hospital sudden cardiac death (SCD) is a frequent cause of death. Survival rates remain low despite increasing efforts in medical care. Better understanding of the circumstances of SCD could be helpful in developing preventive measures and facilitating proper reactions to such a pending event.Information on cases of out-of-hospital SCD was collected in the Berlin, Germany, emergency medical system via a questionnaire. Bystander interviews were performed by the emergency physician on scene immediately after declaration of death or return of circulation. Of 5831 rescue missions, 406 involved patients with presumed cardiac arrest. Sixty-six percent had a known cardiac disease. In 72%, the arrest occurred at home, and in 67%, it occurred in the presence of an eyewitness. Information on symptoms immediately preceding the arrest was available in 80% (n = 323) of all 406 patients and in 274 of those with witnessed arrest. Symptoms were identical in the 2 groups. Typical angina was present for a median of 120 minutes in 25% of the 274 patients with witnessed arrest and in 33% with a symptom duration of less than 1 hour.SCD occurs most often at home in the presence of relatives and after a longer period of typical warning symptoms. Although the much-hailed use of public access defibrillation is supported by several studies, the present results raise the question of whether educational measures and targeted educational programs tailored for patients at risk and their relatives should have a higher priority.
Lower Oesophagus Lined with Intestinal and Gastric Epithelia
Authors: L. Abrams, D. Heath
Journal: Thorax (1965)

The patient first had symptoms at the age of 14 years when he began to suffer from heartburn.This came on when he was lying down and was relieved when he sat up.Indigestion was also caused by eating pickles.The symptoms recurred intermittently and
Pro-atrial natriuretic peptide and pro-vasopressin for predicting short-term and long-term survival in community-acquired pneumonia: results from the German Competence Network CAPNETZ
Authors: S. Kruger, S. Ewig, J. Kunde, O. Hartmann, N. Suttorp, T. Welte
Journal: Thorax (2010)

<h3>Background</h3> Community-acquired pneumonia (CAP) is the most important clinical infection with a high long-term mortality rate. The aim of this study was to evaluate the value of biomarkers for the prediction of short-term and long-term mortality in CAP. <h3>Methods</h3> A total of 1740 patients of mean±SD age 60±18 years (45% female) with proven CAP were enrolled in the study. Mid-regional pro-atrial natriuretic peptide (MR-proANP), C-terminal pro-atrial vasopressin (CT-proAVP), procalcitonin, C-reactive protein, leucocyte count (WBC) and CRB-65 score were determined on admission. Patients were followed up for 180 days. <h3>Results</h3> MR-proANP and CT-proAVP levels increased with increasing severity of CAP, classified according to CRB-65 score. In patients who died within 28 and 180 days, median MR-proANP (313.9 vs 80.0 and 277.8 vs 76.0 pmol/l, each p&lt;0.0001) and CT-proAVP (42.6 vs 11.2 and 33.2 vs 10.7 pmol/l, each p&lt;0.0001) levels were significantly higher than the levels in survivors. In receiver operating characteristics analysis for survival at 28 and 180 days, the areas under the curves (AUCs) for CT-proAVP (0.84, 95% CI 0.82 to 0.86 and 0.78, 95% CI 0.76 to 0.80) and MR-proANP (0.81, 95% CI 0.79 to 0.83 and 0.81, 95% CI 0.79 to 0.83) were superior to the AUC of CRB-65 (0.74, 95% CI 0.71 to 0.76 and 0.71, 95% CI 0.69 to 0.74, p&lt;0.05), procalcitonin, C-reactive protein and WBC. In multivariable Cox proportional hazards regression analyses adjusted for comorbidity and pneumonia severity, MR-proANP and CT-proAVP were independent and the strongest predictors of short-term and long-term mortality. <h3>Conclusions</h3> MR-proANP and CT-proAVP are powerful tools for the prediction of short-term and long-term risk stratification of patients with CAP.
Distinction between epidermal antigens binding pemphigus vulgaris and pemphigus foliaceus autoantibodies.
Authors: J R Stanley, L Koulu, C Thivolet
Journal: Journal of Clinical Investigation (1984)

Pemphigus vulgaris (PV) and pemphigus foliaceus (PF) are autoimmune blistering diseases in which antibodies develop to the cell surface of epidermal cells. In this study we sought to determine the antigenic specificity of antibodies in the sera of patients with PV and PF. Sera from 12 patients with PV were used to immunoprecipitate extracts of cultured human epidermal cells that were radiolabeled with 14C-amino acids. Immunoprecipitates were identified by SDS polyacrylamide gel electrophoresis (PAGE) and fluorography. All 12 PV sera precipitated a protein which, when reduced, displayed chains of 130,000 and 80,000 mol wt on SDS-PAGE. Electrophoresis under nonreducing conditions identified a 210,000-mol wt molecule, which was presumably formed by disulfide crosslinking of the 130,000 and 80,000-mol wt chains. Immunoprecipitates of epidermal cell extracts that were labeled with 14C-glucosamine indicated that the 130,000-mol wt chain. Seven of eight PF sera, which were run concurrently with the PV sera in this immunoprecipitation assay, did not precipitate this glycoprotein, nor did they specifically precipitate any protein. To determine if a specific molecule which reacted with antibodies in PF sera could be identified, we used immunoblot analysis of extracts of normal human epidermis. The proteins in these extracts were reduced, separated by SDS-PAGE, and electrophoretically transferred to nitrocellulose sheets or to 2-aminophenylthioether paper. Immunoperoxidase staining of the transferred proteins with PF sera indicated that four of eight PF sera contained antibodies that stained a protein band of 160,000 mol wt. Indirect immunofluorescence, using normal human skin as the substrate, indicated that IgG that was eluted from this protein band stained the epidermis in a cell surface pattern. PV sera did not specifically recognize any bands by immunoblot analysis. Immunoblots performed with PV antigen that was immunoprecipitated from cell culture extracts suggested that, once denatured for SDS-PAGE, PV antigen is no longer immunoreactive. Taken together, these data indicate that: autoantibodies contained in PV sera from various patients have a unique molecular specificity; autoantibodies from most PF sera have a specificity different from that of PV autoantibodies; and autoantibodies from various PF patients may not have identical antigenic specificities. These differences in antigenic specificity between PV and PF sera may account for the clinical and histologic differences between these diseases.
HuR Contributes to Cyclin E1 Deregulation in MCF-7 Breast Cancer Cells
Authors: Xun Guo, Rebecca S. Hartley
Journal: Cancer Research (2006)

Abstract Many cancers overexpress cyclin E1 and its tumor-specific low molecular weight (LMW) isoforms. However, the mechanism of cyclin E1 deregulation in cancers is still not well understood. We show here that the mRNA-binding protein HuR increases cyclin E1 mRNA stability in MCF-7 breast carcinoma cells. Thus, mRNA stabilization may be a key event in the deregulation of cyclin E1 in MCF-7 cells. Compared with MCF10A immortalized breast epithelial cells, MCF-7 cells overexpress full-length cyclin E1 and its LMW isoforms and exhibit increased cyclin E1 mRNA stability. Increased mRNA stability is associated with a stable adenylation state and an increased ratio of cytoplasmic versus nuclear HuR. UV cross-link competition and UV cross-link immunoprecipitation assays verified that HuR specifically bound to the cyclin E1 3′-untranslated region. Knockdown of HuR with small interfering RNA (siRNA) in MCF-7 cells decreased cyclin E1 mRNA half-life (t1/2) and its protein level: a 22% decrease for the full-length isoforms and 80% decrease for the LMW isoforms. HuR siRNA also delayed G1-S phase transition and inhibited MCF-7 cell proliferation, which was partially recovered by overexpression of a LMW isoform of cyclin E1. Overexpression of HuR in MCF10A cells increased cyclin E1 mRNA t1/2 and its protein level. Taken together, our data show that HuR critically contributes to cyclin E1 overexpression and its growth-promoting function, at least in part by increasing cyclin E1 mRNA stability, which provides a new mechanism of cyclin E1 deregulation in breast cancer. (Cancer Res 2006; 66(16): 7948-56)
Titration of continuous positive airway pressure in Chinese patients with obstructive sleep apnea
Authors: JiaYing Luo, ZhiHui Qiu, YingXin Wu, Y.M. Luo
Journal: European Respiratory Journal (2012)

Objective Whether CPAP pressure derived from manual titration is the same as the pressure from automatic titrations is controversial. The purpose of this study was to compare the pressure derived from manual titration with the pressure from automatic titration. We also attempted to establish a formula to determine the appropriate CPAP pressure for Chinese individuals.

Methods Fifty-one patients with OSA (mean apnea/hypopnea index [AHI]=50.6 ±18.6 events/hour) who were newly diagnosed after an overnight full polysomnography and who were willing to accept CPAP as a long-term treatment were recruited for the study. Manual titration under the full polysomnography monitoring and unattended automatic titration with an automatic CPAP device (REMstar-auto, Respironics Inc. USA) were performed. We also performed a separate cohort study of one hundred patients with OSA (AHI= 54.3±18.9 events/h) by observing the efficacy and safety of CPAP pressure derived from manual titration.

Results The treatment pressure derived from automatic titration (9.8 ± 2.2 cmH2O) was significantly higher than that derived from manual titration (7.3± 1.5 cmH2O; p<0.001) in 51 patients. A cohort study of 100 patients showed that AHI was satisfactorily decreased after CPAP treatment using a pressure derived from manual titration (54.3±18.9 events/hour before treatment and 3.3±1.7 events/hour after treatment; P<0.001).

Conclusion Our results suggest that automatic titration pressure derived from REMstar-auto, is usually higher than the pressure derived from manual titration.

This work was funded by National Natural Science Foundation of China (Grant No.81120108001).
ABC of psychological medicine: Cancer
Authors: C. A White
Journal: BMJ (2002)

Cancer is the most feared of diseases.Unsurprisingly, it causes considerable psychological distress in patients, families, carers, and often those health professionals who care for them.Only a minority of cancer patients develop psychiatric illness, but other psychologically and socially determined problems are common.These include unpleasant symptoms such as pain, nausea, and fatigue; problems with finances, employment, housing, and childcare; family worries; and existential and spiritual doubts.Well planned care that fully involves patients and their families can minimise these problems. Psychological consequencesThough often dismissed as "understandable," distress is a treatable cause of reduced quality of life and poorer clinical outcome.Some patients delay seeking help because they fear or deny their symptoms of distress.Presentation can be obvious, as depressed or anxious mood can manifest as increased severity of somatic complaints such as breathlessness, pain, or fatigue.Adjustment disorder is the commonest psychiatric diagnosis, and neuropsychiatric complications may occur.The risk of suicide is increased in the early stages of coping with cancer. DepressionDepression is a response to perceived loss.A diagnosis of cancer and awareness of associated losses may precipitate feelings similar to bereavement.The loss may be of parts of the body (such as a breast or hair), the role in family or society, or impending loss of life.Severe and persistent depressive disorder is up to four times more common in cancer patients than in the general population, occurring in 10-20% during the disease. Anxiety, fear, and panicAnxiety is the response to a perceived threat.It manifests as apprehension, uncontrollable worry, restlessness, panic attacks, and avoidance of people and of reminders of cancer, together with signs of autonomic arousal.Patients may overestimate the risks associated with treatment and the likelihood of a poor outcome.Anxiety may also exacerbate or heighten perceptions of physical symptoms (such as breathlessness in lung cancer), and post-traumatic stress symptoms (with intrusive thoughts and avoidance of reminders of cancer) occasionally follow diagnosis or treatment that has been particularly frightening.Certain cancers and treatments are associated with specific fears.Thus, patients with head and neck cancers may worry about being able to breathe and swallow.Patients may develop phobias and conditioned vomiting in relation to unpleasant treatments such as chemotherapy.
Clinical relevance of cancer stem cells in bone marrow of early breast cancer patients
Authors: A. Giordano, H. Gao, E.N. Cohen, S. Anfossi, J. Khoury, K. Hess, S. Krishnamurthy, S. Tin, M. Cristofanilli, G.N. Hortobagyi, W.A. Woodward, A. Lucci, J.M. Reuben
Journal: Annals of Oncology (2013)
First-line response-adapted treatment with the combination of bendamustine and rituximab in patients with mucosa-associated lymphoid tissue lymphoma (MALT2008-01): a multicentre, single-arm, phase 2 trial
Authors: Antonio Salar, Eva Domingo-Domenech, Carlos Panizo, Concepción Nicolás, Joan Bargay, Ana Muntañola, Miguel Canales, José Luis Bello, Juan Manuel Sancho, José Francisco Tomás, María José Rodríguez, Francisco Javier Peñalver, Carlos Grande, José Javier Sánchez-Blanco, Luis Palomera, Reyes Arranz, Eulogio Conde, Mar García, Juan Fernando García, Dolores Caballero, Carlos Montalbán
Journal: The Lancet Haematology (2014)
Expression of the Tpl2/Cot oncogene in human T-cell neoplasias.
Authors: Anna V Christoforidou, Helen A Papadaki, Andrew N Margioris, George D Eliopoulos, Christos Tsatsanis
Journal: Molecular Cancer (2004)

Tpl2/Cot oncogene has been identified in murine T-cell lymphomas as a target of MoMuLV insertion. Animal and tissue culture studies have shown that Tpl2/Cot is involved in interleukin-2 (IL-2) and tumor necrosis factor-alpha (TNF-alpha) production by T-cells contributing to T-cell proliferation. In the present report we examined a series of 12 adult patients with various T-cell malignancies, all with predominant leukemic expression in the periphery, for the expression of Tpl2/Cot oncogene in order to determine a possible involvement of Tpl2/Cot in the pathogenesis of these neoplasms.Our results showed that Tpl2/Cot was overexpressed in all four patients with Large Granular Lymphocyte proliferative disorders (LGL-PDs) but in none of the remaining eight patients with other T-cell neoplasias. Interestingly, three of the LGL-PD patients displayed neutropenia, one in association with sarcoidosis. Serum TNF-alpha levels were increased in all Tpl2/Cot overexpressing patients while serum IL-2 was undetectable in all subjects studied. Genomic DNA analysis revealed no DNA amplification at the Tpl2/Cot locus in any of the samples analyzed.We conclude that Tpl2/Cot, a gene extensively studied in animal and tissue culture T-cell models may be also involved in the development of human LGL-PD and may have a role in the pathogenesis of immune manifestations associated with these diseases. This is the first report implicating Tpl2/Cot in human T-cell neoplasias and provides a novel molecular event in the development of LGL-PDs.
Functional receptor for C3a anaphylatoxin is expressed by normal hematopoietic stem/progenitor cells, and C3a enhances their homing-related responses to SDF-1
Authors: Ryan Reca, Dimitrios Mastellos, Marcin Majka, Leah Marquez, Janina Ratajczak, Silvia Franchini, Aleksandra Glodek, Marek Honczarenko, Lynn A. Spruce, Anna Janowska-Wieczorek, John D. Lambris, Mariusz Z. Ratajczak
Journal: Blood (2003)