tbuckley/cabot-search huggingface dataset:
Abstract 4305: FBXO31 functions as an oncoprotein by suppressing apoptosis via regulation of MAPK pathway in esophageal squamous cell carcinoma cell lines.
Authors: Jia Liu, Bin Li, George SW Tsao, Annie ML Cheung
Journal: Cancer Research (2013)

Abstract FBXO31 is a DNA-damage responsive F-box protein, found to be down-regulated in breast and hepatocellular carcinoma but up-regulated in esophageal squamous cell carcinoma. The role of FBXO31 in carcinogenesis is not fully determined. Mitogen activated protein kinases (MAPKs) play pivotal role in cellular response to diverse stresses, and are involved in regulating cell proliferation, differentiation and apoptosis. In this study, data from gain-of-function and loss-of-function experiments revealed that FBXO31 regulated cell apoptosis upon UV stress, as evidenced by changes in expressions of cleaved caspase 3 and PARP in FBXO31 modified cell lines compared to control cell lines, as well as regulation of sub-G1 population measured by flow cytometry analysis. The effects of FBXO31 on apoptosis were associated with changes in MAPK p38 and JNK phosphorylation. In order to verify the role of FBXO31 in cell apoptosis and MAPK regulation, shRNA rescue experiments were performed. The results showed that ectopic overexpression of wild type FBXO31 in stable cell line which expressed shRNA targeting the 3’ UTR of FBXO31 could reverse the effects of FBXO31-knockdown on apoptosis, and on MAPK p38 and JNK phosphorylation. Furthermore, we found that JNK was a dominant mediator of FBXO31 in regulating cell apoptosis upon UV stress since treatment with JNK inhibitor, but not p38 inhibitor, reversed apoptosis induced by FBXO31-knockdown. Consistent with this finding, soft agar assay and in vivo xenograft experiments showed that knockdown of FBXO31 reduced the tumorigenic potential of ESCC cells. In conclusion, our data suggest that FBXO31 functions as an oncogenic protein in ESCC by suppressing cell apoptosis via MAPK pathway. This mechanism may favor the survival of tumor cells in stringent environment and contribute to ESCC development. Citation Format: Jia Liu, Bin Li, George SW Tsao, Annie ML Cheung. FBXO31 functions as an oncoprotein by suppressing apoptosis via regulation of MAPK pathway in esophageal squamous cell carcinoma cell lines. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4305. doi:10.1158/1538-7445.AM2013-4305
Does theophylline really improve acute mountain sickness?
Authors: R. Fischer, S.M. Lang, R.M. Huber
Journal: European Respiratory Journal (2001)

From the authors: 

Roggla et al . 1 performed a double-blind, placebo-controlled crossover trial in eight subjects to investigate the effects of “nonretardized” theophylline on oxygen tension in arterial blood ( P a,O2) and carbon dioxide tension in arterial blood ( P a,CO2), 2 h after ingestion of 300 mg theophylline. They did not demonstrate a significant increase of P a,O2 or significant decrease of P a,CO2 in the theophylline group and questioned the evidence of our study indicating a positive effect of theophylline on acute mountain sickness (AMS). However, there were major differences between both studies. …
The Need for Psychiatry in a Municipal General Hospital
Authors: Merrill Moore
Journal: New England Journal of Medicine (1951)

AT THE Boston City Hospital, psychiatry labeled as such does not officially exist. Actually, about 1000 obviously psychotic patients are admitted to its wards each year. Most of these patients are also suffering from medical and surgical diseases. The hospital, furthermore, contains the usual large number of patients with psychoneuroses or psychosomatic disorders. This number has been variously estimated as 50 to 80 per cent of all admissions. Emotional disorders may be the main reasons for the admission of many patients, or they may constitute a burdensome complication in addition to whatever medical diseases affect them. The obviously psychotic patients . . .
Infections During Intensive Chemotherapy for Non-Hodgkin's Lymphoma
Authors: JAMES F. BISHOP
Journal: Annals of Internal Medicine (1981)

Records of 133 infections occurring in 73 of 125 patients with late-stage non-Hodgkin's lymphoma on intensive chemotherapy programs for a median of 23 months were reviewed. Granulocytopenia, usually related to chemotherapy, was the major predisposing factor, associated with 51% of infections. The incidence of infection in chemotherapy courses associated with less than 500 granulocytes/µL was higher than those with 500 or more granulocytes/µL (p = 0.0004). Splenectomized patients tended to have a higher incidence of chemotherapy courses with an infection (p = 0.06); marrow involvement was not a significant predisposing factor to infection. The commonest sites of infection were lung, skin, and alimentary canal. Gram-negative organisms and Staphylococcus aureus caused 83% of documented infections; Pseudomonas aeruginosa was the major cause of pneumonia and bacteremia; and herpes zoster and fungi each caused only 3% of infections. Other infections associated with impaired cellular or humoral immunity were uncommon. Poor prognosis was associated with infections in granulocytopenic patients with stable or falling granulocyte counts, infection at multiple sites, and bacteremia, especially polymicrobial bacteremia.
Lionel Edward Tyler
Authors: Susan Collier
Journal: BMJ (2005)

Medical microbiologist who became a pioneer of hospital infection controlRobert Blowers had a lifelong interest in Staphylococcus aureus and hospital infection.From the mid-1950s onwards he produced a succession of publications on the prevention of hospital infections, particularly those following surgery.These ranged across the design of operating theatres, isolation rooms, and surgical clothing, and the prevention of the airborne spread of infection and clinical protocols for wound management.He co-produced the seminal textbook Hospital Infection: Causes and Prevention, which became the "bible" on infection control for nearly 20 years.In 1959 he was a key member of the Ministry of Health working group that produced a report on staphylococcal infections in hospitals.At a Department of Health workshop in December 2004, just a week before Robert's death, his major contribution was recalled by the department's inspector of microbiology and infection control, who had that week sent him a Christmas card with the message "you will be pleased to know that we are at last trying to implement your 1959 recommendations!"
Interleukin (IL) 4, in the absence of antigen stimulation, induces an anergy-like state in differentiated CD8+ TC1 cells: loss of IL-2 synthesis and autonomous proliferation but retention of cytotoxicity and synthesis of other cytokines.
Authors: S Sad, T R Mosmann
Journal: The Journal of Experimental Medicine (1995)

Naive T cells in the periphery mainly secrete interleukin (IL) 2 upon activation. After stimulation in the presence of appropriate costimulators, both CD4+ and CD8+ T cells differentiate into effector cells secreting distinct T helper (Th) 1- and Th2-like cytokine patterns. Subsequent to differentiation, both CD4+ (Th1 and Th2) and CD8+ (TC1 and TC2) cells are stable and cannot be induced to differentiate into the opposite pattern or revert to the naive cytokine secretion pattern. We now show that IL-4 caused committed TC1 bulk populations or clones to lose the ability to synthesize IL-2. The cells retained the ability to secrete interferon (IFN) gamma, granulocyte/macrophage colony-stimulating factor, and tumor necrosis factor, did not synthesize any Th2 cytokines, and did not alter cell surface marker expression. IL-4 rapidly inhibited IL-2-synthesizing ability in the absence or presence of antigen-presenting cells, thus demonstrating that IL-4 acted directly on TC1 cells. The defect in IL-2 synthesis could not be reversed by subsequent stimulation with potent antigen-presenting cells in the presence of IL-2 and anti-IL-4, or with anti-CD3 plus anti-CD28 antibodies. Both IL-2+ and IL-2- TC1 cells were strongly cytotoxic toward allogeneic but not syngeneic targets. However, IL-2- TC1 cells were unable to proliferate unless exogenous IL-2 was provided. TC1 cells that lose IL-2 synthesis but retain IFN-gamma synthesis and cytotoxicity may be similar to the "anergic" cells induced by stimulation of CD4+ or CD8+ cells in the absence of costimulators. These results suggest that during a mixed type 1/type 2 response in vivo, IL-4 may induce the IL-2+ TC1--&amp;gt;IL-2-TC1 conversion, and thus curtail the expansion of the TC1 response without impairing short-term effector function.
897. Na,K-ATPase β1-Mediated Selective Gene Transfer into Neurons
Authors: Keiji Ishii, Kiminori Nakamura, Satoshi Kawaguchi, Rong Li, Sachie Hirai, Naoya Sakuragi, Takuro Wada, Kazunori Kato, Toshihiko Yamashita, Hirofumi Hamada
Journal: Molecular Therapy (2006)

Neuron-selective gene transfer is an attractive therapeutic strategy for neurological disorders. Selective gene transfer requires high efficiency as well as tissue specificity of the target molecule employed. Selection of an optimal target molecule is critical. Here, we contrived the hybridoma library screening to identify optimal target molecules for neuron selective gene transfer using fiber mutant adenoviruses as targeting tools. We generated genetically modified adenoviruses incorporating Z33, an IgG Fc-binding motif from Staphylococcus protein A, at the fiber (Adv-FZ33 and Adv-FdZ). The Z33 vectors were capable of infecting cells through use of linked antibodies against surface antigen molecules. In this report, we established hybridoma clone 6E3 and mouse monoclonal antibody (mAb6E3) by this screening technique and identified the target antigen as Na,K-ATPase β1. Flow cytometry, chemiluminescent β-Gal reporter gene assays and immunocytochemistry using mAb6E3 and fiber mutant adenovirus documented efficient gene transfer into PC12 cells. This showed Na,K-ATPase β1 functions as the effective receptor for gene transfer into neurons. Immunohistochemistry images of rat spinal cord tissue showed that Na,K-ATPase β1 was expressed in neurons but not in oligodendrocytes or astrocytes. Experiments to transduce genes into neuron-glia cocultures using mAb6E3 and fiber mutant adenovirus resulted in neuron-selective gene transfer. These data indicate that Na,K-ATPase β1 is a good candidate molecule for neuron-selective gene transfer. Gene transfer via Na,K-ATPase β1 may be a useful strategy for treating neurological disorders, especially local disorders.
Resistance to adenovirally induced hyperleptinemia in rats. Comparison of ventromedial hypothalamic lesions and mutated leptin receptors.
Authors: K Koyama, M Shimabukuro, G Chen, M Y Wang, Y Lee, P S Kalra, M G Dube, S P Kalra, C B Newgard, R H Unger
Journal: Journal of Clinical Investigation (1998)

Leptin regulates appetite and body weight via hypothalamic targets, but it can act directly on cultured pancreatic islets to regulate their fat metabolism. To obtain in vivo evidence that leptin may act peripherally as well as centrally, we compared the effect of adenovirally induced hyperleptinemia on food intake, body weight, and islet fat content in ventromedial hypothalamic-lesioned (VMHL) rats, sham-lesioned (SL) controls, and Zucker Diabetic Fatty (ZDF) rats in which the leptin receptor is mutated. Infusion with recombinant adenovirus containing the rat leptin cDNA increased plasma leptin by approximately 20 ng/ml in VMHL and ZDF rats but had no effect on their food intake, body weight, or fat tissue weight. Caloric matching of hyperphagic VMHL rats to SL controls did not reduce their resistance to hyperleptinemia. Whereas prediabetic ZDF rats had a fourfold elevation in islet fat, in VMHL rats islet fat was normal and none of them became diabetic. Isolated islets from ZDF rats were completely resistant to the lipopenic action of leptin, while VMHL islets exhibited 50% of the normal response; caloric matching of VMHL rats to SL controls increased leptin responsiveness of their islets to 92% of controls. We conclude that leptin regulation of adipocyte fat requires an intact VMH but that islet fat content is regulated independently of the VMH.
Effects of NO on mitochondrial function in cardiomyocytes: Pathophysiological relevance
Authors: S DAVIDSON, M DUCHEN
Journal: Cardiovascular Research (2006)

Although the specific roles of nitric oxide (NO) in the heart in general and on cardiac mitochondria in particular remain controversial, it is now clear that both endogenous and exogenous sources of NO exert important modulatory effects on mitochondrial function. There is also growing evidence that NO can be produced within the mitochondria themselves. NO can influence respiratory activity, both through direct effects on the respiratory chain or indirectly via modulation of mitochondrial calcium accumulation. At pathological concentrations, NO can cause irreversible alterations in respiratory function and can also interact with reactive oxygen species (ROS) to form reactive nitrogen species, which may further impair mitochondrial respiration and can even lead to opening of the mitochondrial permeability transition pore and cell death. Diabetes, aging, myocardial ischemia, and heart failure have all been associated with altered ROS generation, which can alter the delicate regulatory balance of effects of NO in the mitochondria. As NO competes with oxygen at cytochrome oxidase, it can be argued that experiments exploring the roles of NO on mitochondrial respiration should be performed at physiological (i.e. relatively low) oxygen tensions. Improvements in techniques, and a gradual appreciation of the many potential pitfalls in studying mitochondrial NO, are leading to a recognition of the role of NO in the regulation of mitochondrial function in the heart in health and disease.
Dapsone: modes of action, toxicity and possible strategies for increasing patient tolerance
Authors: M. D. COLEMAN
Journal: British Journal of Dermatology (1993)

Dapsone is useful in the treatment of a number of inflammatory conditions which are characterized by neutrophil infiltration. It is the drug of choice for suppression of the symptoms of dermatitis herpetiformis, as it inhibits the process by which neutrophils leave the circulation and migrate to lesional sites. It also prevents the tissue destruction normally caused by the neutrophils' respiratory burst. Although dapsone can cause a number of serious idiosyncratic reactions, such as agranulocytosis, tolerance of the drug at higher doses is more usually determined by its haematological side‐effects of methaemoglobinaemia and haemolysis. These effects are due entirely to the hepatic N‐hydroxylation of dapsone to a hydroxylamine metabolite, some of which escapes from the liver and rapidly enters red cells. Attempts have been made to counteract the haemotoxic effects of the metabolite by the use of antioxidants such as vitamins E and C. Recently, the co‐administration of a metabolic inhibitor such as cimetidine has been shown to reduce significantly dapsone‐dependent methaemoglobinaemia, without any change in drug efficacy. It remains to be seen if this approach will be adopted clinically, to improve patient tolerance of high dapsone dosage.
β1 Integrin Adhesion Enhances IL-6–Mediated STAT3 Signaling in Myeloma Cells: Implications for Microenvironment Influence on Tumor Survival and Proliferation
Authors: Kenneth H. Shain, Danielle N. Yarde, Mark B. Meads, Mei Huang, Richard Jove, Lori A. Hazlehurst, William S. Dalton
Journal: Cancer Research (2009)

The bone marrow microenvironmental components interleukin (IL)-6 and fibronectin (FN) individually influence the proliferation and survival of multiple myeloma (MM) cells; however, in vivo, these effectors most likely work together. We examined signaling events, cell cycle progression, and levels of drug response in MM cells either adhered to FN via beta1 integrins, stimulated with IL-6, or treated with the two combined. Although G(1)-S cell cycle arrest associated with FN adhesion was overcome when IL-6 was added, the cell adhesion-mediated drug resistance (CAM-DR) was maintained in the presence of IL-6. Concomitant exposure of MM cells to IL-6 and FN adhesion revealed a dramatic increase in signal transducers and activators of transcription 3 (STAT3) phosphorylation, nuclear translocation, and DNA binding, compared with either IL-6 or FN adhesion alone in four MM cell lines. Importantly, this increase in STAT3 activation correlated with a novel association between STAT3 and gp130 in cells adhered to FN before stimulation with IL-6, relative to nonadherent cells. Taken together, these results suggest a mechanism by which collaborative signaling by beta1 integrin and gp130 confers an increased survival advantage to MM cells.
CLINICAL EVALUATION OF A NEW TOPICAL CORTICOSTEROID BECLOMETHASONE DIPROPIONATE
Authors: I. W. CALDWELL, S. P. HALL-SMITH, R. A. MAIN, P. J. ASHURST, V. KIRTON, W. T. SIMPSON, G. W. WILLIAMS
Journal: British Journal of Dermatology (1968)

SUMMARY. —Beclomethasone dipropionate is a new topical steroid with marked vasoconstrictor and anti‐inflammatory activity. At a concentration of 0·025% in a simple, oil‐in‐water emulsion “cream” base beclomethasone dipropionate is significantly more effective clinically than is fluocinolone acetonide 0·025%) in an apparently similar base. The effectiveness of beclomethasone dipropionate 0·025% in an ointment base is significantly increased by dissolving the steroid in propylene glycol before incorporating it into the ointment. Beclomethasone dipropionate 0·025% in a propylene glycol/ointment base is clinically indistinguishable from fluocinolone acetonide 0·025% ointment. Further investigation of the influence of cream and ointment bases on the clinical effectiveness of topical steroids might prove interesting.
Why does the human brain need to be a nonlinear system?
Authors: Zbigniew J. Kowalik, Andrzej Wrobel, Andrzej Rydz
Journal: Behavioral and Brain Sciences (1996)

Abstract We focus on one aspect of Wright &amp; Liley's target article: the linearity of the EEG. According to the authors, some nonlinear models of the cortex can be reduced (approximated) to the linear case at the millimetric scale. We argue here that the statement about the linear character of EEG is too strong and that EEG exhibits nonlinear features which cannot be ignored.
Prediction of Transition to Chronic Atrial Fibrillation in Patients With Paroxysmal Atrial Fibrillation by Signal- Averaged Electrocardiography
Authors: Yasushi Abe, Masatake Fukunami, Takahisa Yamada, Masaharu Ohmori, Tsuyoshi Shimonagata, Kazuaki Kumagai, Jiyoong Kim, Shoji Sanada, Masatsugu Hori, Noritake Hoki
Journal: Circulation (1997)

It is well known that paroxysmal atrial fibrillation (PAF) often precedes the establishment of chronic atrial fibrillation (CAF). However, there have been no definite methods to predict the transition from PAF to CAF. The purpose of this report was to determine prospectively whether P-wave-triggered signal-averaged ECG (P-SAE) is useful for the prediction of the transition to CAF in patients with PAF.One hundred twenty-two consecutive patients with PAF were prospectively followed after P-SAE, echocardiography, and 24-hour Holter monitoring at study entry. The duration (Ad) and root-mean-square voltage for the last 30 ms (LP30) of the filtered P wave were measured in P-SAE. The abnormality of P-SAE for the prediction of transition to CAF was defined as Ad > or = 145 ms and LP30 < 3.0 microV. Twenty-three (19%; group 1) of the patients had the abnormality of P-SAE, whereas the others (group 2) did not. During the follow-up period (mean, 26+/-12 months), 10 patients (43%) in group 1 acquired CAF, whereas the transition to CAF was observed in only 4 patients (4%) in group 2. Kaplan-Meier analysis revealed that the transition to CAF was significantly observed more often in group 1 than in group 2 (log-rank test, P<.0001). The Cox proportional hazards regression model identified that the variables most significantly associated with the transition to CAF were Ad (chi2=8.6, P=.003) and LP30 (chi2=5.1, P=.02), although significant differences in the left atrial dimension (40.8+/-5.3 versus 37.3+/-5.5 mm, P<.01) and the number of atrial premature contractions (3641+/-4524 versus 1489+/-2895 beats/d, P<.05) were observed between groups 1 and 2.These results indicate that P-SAE could be useful to identify patients at risk for the transition from PAF to CAF.
Optimal Time for Early Laparoscopic Cholecystectomy for Acute Cholecystitis
Authors: Syed Nabeel Zafar, Augustine Obirieze, Babawande Adesibikan, Edward E. Cornwell, Terrence M. Fullum, Daniel D. Tran
Journal: JAMA Surgery (2014)

<h3>Importance</h3> There is growing evidence in support of performing early laparoscopic cholecystectomy (LC) for acute cholecystitis. However, the definition of<i>early</i>LC varies from 0 through 10 days depending on the research protocol. The optimum time to perform early LC is still unclear. <h3>Objectives</h3> To determine whether outcomes after early LC for acute cholecystitis vary depending on time from presentation to surgery and to determine the optimum time to perform LC for acute cholecystitis. <h3>Design, Setting, and Participants</h3> We performed a retrospective review of prospectively collected data from the Nationwide Inpatient Sample (NIS) for 2005 through 2009. The population-based sample included 95 523 adults (18 years and older) who underwent LC within 10 days of presentation for acute cholecystitis. <h3>Interventions</h3> Patients were categorized and analyzed in 2 ways based on length of time from presentation to surgery. First, patients were categorized into 3 groups: 0 through 1 day, 2 through 5 days, and 6 through 10 days. Second, we compared outcomes for each incremental preoperative day (days 0-5). <h3>Main Outcomes and Measures</h3> Outcomes of interest were mortality, length of stay, complications, and cost. Propensity score matching and generalized linear modeling were used. The hypothesis being tested was formulated after data collection was complete. <h3>Results</h3> A total of 95 523 patients were selected. After matching the 3 groups based on propensity scores, patients who underwent surgery during days 2 through 5 and days 6 through 10 had increasingly worse outcomes when compared with those undergoing surgery on days 0 through 1. The odds of mortality were 1.26 (95% CI, 1.00-1.58) and 1.93 (95% CI, 1.38-2.68), and the odds of postoperative infections were 0.88 (95% CI, 0.69-1.12) and 1.53 (95% CI, 1.05-2.23) for days 2 through 5 and days 6 through 10, respectively. Adjusted mean hospital cost increased from $8974 (days 0-1) to $17 745 (days 6-10). Analysis by each incremental day revealed the optimal time of surgery to be within the first 48 hours of presentation. <h3>Conclusions and Relevance</h3> Laparoscopic cholecystectomy performed within 2 days of presentation of acute cholecystitis yielded the best outcomes and lowest costs. Although causality could not be established, delaying LC was associated with more complications, higher mortality, and higher costs.