tbuckley/cabot-search huggingface dataset:
The relation between reduced protein degradation and elevated adenosine 3',5'-monophosphate in isolated rat atria.
Authors: D S O'Hara, G D Curfman, C G Trumbull, S M Sandler, T W Smith
Journal: Circulation Research (1981)

We studied the effect on protein degradation of agents that alter intracellular adenosine 3',5'-monophophate (cyclic AMP) in isolated rat right atria.Protein degradation rate was determined by measurement of the rate of release of L-tyroslne from atria cultured in the presence of cycloheximide.Stimulation of adenylate cyclase activity by either L-isoproterenol, glucagon, prostaglandin Ei, prostaglandin E2 or cholera toxin produced a 23-43% decrease in tyrosine release rate.L-Isoproterenol (1 fiM) lowered the protein degradation rate both in the presence (27 ± 3%) or absence (25 ± 2%) of insulin.In constrast, the a-adrenergic agonist methoxamine (10 JIM) increased the rate of tyrosine efflux.The phosphodiesterase inhibitors papaverine (0.1 mM) and theophylline (1 mM) reduced tyrosine release rate by 62 ± 2% and 25 ± 2%, respectively.The cyclic nucleotide analog dibutyryl cyclic AMP produced a 23 ± 4% reduction in tyrosine efflux rate, an effect that may be in part due to butyrate released by hydrolysis.Both carbamylcholine and nitroprusside, agents which activate guanylate cyclase, had no apparent effect on the rate of overall protein degradation.In experiments with atria labeled in vitro with radioactive tyrosine, the degradation rate of soluble cell proteins fractionated by gel filtration was uniformly decreased by L-isoproterenol over a wide molecular weight range.Comparison of degradation rate to protein kinase activation, high energy phosphate levels and beating rate show that suppression of degradation is more closely correlated with mechanical activity or energy depletion than with cyclic AMP content.Therefore, these data do not establish whether cyclic AMP modifies protein degradation directly, or by effects secondary to increased contractile activity.Ore Res 49: 80S-617, 1981 CARDIAC hypertrophy is an important adaptive response to a variety of physiological and pathological stimuli.Even though this adaptive process is of considerable clinical and fundamental significance, the biochemical mechanisms controlling the balance between protein synthesis and degradation are poorly understood.The administration of catecholamines in vivo has been used widely as a model for the experimental induction of cardiac hypertrophy and is associated with increased rates of protein synthesis in adult and neonatal hearts (Mallov, 1973;Claycomb, 1976).Recently, it has been found that this enhancement of protein synthesis can be produced in vitro (Kaellfelt et al., 1976;Chua et al., 1978) using the isolated perfused heart and therefore may be due in part to a direct effect on the myocardium.In view of the pronounced stimulation of cardiac adenylate cyclase by /?-adrenergic agonists and the known modulation of protein turnover associated with adenosine 3',5'-monophosphate (cyclic AMP) in several systems (Woodside et al.,
Osteosarcoma metastasizing to pancreas confirmed by endoscopic ultrasound-guided fine-needle aspiration
Authors: Peng Jin, Wei Wang, Hui Su, Jian-qiu Sheng
Journal: Endoscopy (2014)

An 18-year-old male with a history of osteosarcoma of the proximal part of the left tibia presented complaining of upper abdominal pain and vomiting. Osteosarcoma had been diagnosed 4 years previously and been treated with amputation and chemotherapy. Laboratory tests revealed mild anemia (hemoglobin 114 g/L, reference range 120 – 150 g/L), and normal serum amylase and bilirubin. Abdominal computed tomography (CT) showed a cystic–solid mass measuring 4.3 × 4.5 cm on the head of the pancreas ([Fig. 1]). Thoracic CT revealed another mass in the inferior lobe of the left lung ([Fig. 2]). No calcification was seen in either lesion. Endoscopic ultrasound (EUS) was carried out using an electronic echoendoscope (GF-UE260-AL5 for radial scanning and GF-UCT240-AL5 for linear scanning; Olympus, Tokyo, Japan) and this showed more clearly a mass containing necrotic areas in the pancreatic head and neck and a dilated pancreatic duct ([Fig. 3] and [Fig. 4]). Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of the pancreatic mass using a 22-gauge needle (EchoTip Ultra; Cook Medical Inc., Winston-Salem, NC, USA) confirmed the diagnosis of metastatic osteosarcoma ([Fig. 5] and [Fig. 6]). Pancreatoduodenectomy and thoracotomy with resection of the left inferior lobe was then performed, followed by chemotherapy. At 7 months postoperatively the patient had recovered from the treatment and remained free of detectable disease.
BEYOND THE FONTAN: SURGICAL AND CATHETER BASED REINTERVENTIONS ARE COMMON IN LONG-TERM SINGLE VENTRICLE SURVIVORS
Authors: Tacy E. Downing, Kiona Allen, David Goldberg, Lindsay S. Rogers, Chitra Ravishankar, Jack Rychik, Stephanie Fuller, Lisa M. Montenegro, James Steven, Thomas Spray, Susan Nicolson, J. William Gaynor, Andrew Glatz
Journal: Journal of the American College of Cardiology (2016)
Abstract 2281: Host CXCR2 expression regulates mammary tumor growth, angiogenesis and progression
Authors: Kalyan C. Nannuru, Michelle L. Varney, Rakesh K. Singh
Journal: Cancer Research (2010)

Abstract Breast cancer is a devastating clinical condition affecting more than 100,000 women in a year and is responsible for more than 40,000 deaths every year. Chemokines and their receptors have been shown to regulate various aspects of tumor development and progression. Constitutive expression of pro-inflammatory chemokines, a hallmark of many human cancers, helps establish a supportive tumor stroma, and, in some cases, directly stimulates tumor proliferation and invasion via receptors on tumor cells. Evidence suggests that CXCR2 regulate multiple functions in leukocytes, endothelial cells (ECs), and/or tumor cells and their precursors and thus play important role in tumor angiogenesis, growth and metastasis. In this study, we investigated the role of host CXCR2 expression in mammary tumor growth, neovascularization and tumor induced osteolysis using a syngenic mouse mammary tumor model. Eight week old BALB/c mice either expressing CXCR2 (mCXCR2 WT) or genomic knock down of CXCR2 (mCXCR2 −/−) were used to study the functional role of host CXCR2 in mammary tumor growth and progression. Orthotopical implantation of mammary tumors in mouse mammary fat pad reveals a significant decrease in tumor growth in mCXCR2 −/− compared to wild type mice. Knock-down of host CXCR2 has significantly reduced tumor-induced neovascularization in orthotopical tumors. Bone is the most common site of metastasis in breast cancer. To access the role of host CXCR2 in tumor-induced osteolysis and tumor growth in bone microenvironment, mammary tumor cells were implanted on calvaria. Tumor-induced osteolysis and osteoclast homing at the tumor-bone interface was significantly reduced in CXCR2 knockout mice compared to wild type mice. These results suggest that host CXCR2 may play a critical role in tumor development and angiogenesis as well as tumor-induced osteolysis. These data demonstrate direct evidence of host CXCR2 in breast cancer progression and metastasis, and will allow development of CXCR2 targeting as a novel approach to breast cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2281.
PWE-266 Protective role of β blockers in SBP: myth or reality
Authors: M Mansoor, H Sherfi, Z Rahman, J Ramesh
Journal: Gut (2012)

<h3>Introduction</h3> β Blockers may have a protective effect on the development of spontaneous bacterial peritonitis by increasing the intestinal transit time and reducing portal pressure. The aim of this study is to evaluate the significant benefit of β blocker in prevention of spontaneous bacterial peritonitis in patients with chronic liver disease and ascites. <h3>Methods</h3> We retrospectively evaluated 332 patients with cirrhosis and ascites admitted over a period of 5 years (males 230, females 102). Diagnosis of spontaneous bacterial peritonitis was based on an ascitic fluid neutrophilic count of &gt;250/mm<sup>3</sup> and/or a positive culture without evidence of secondary peritonitis. <h3>Results</h3> Spontaneous bacterial peritonitis was diagnosed in 52 of 332 (15.66%) patients. Of the 92 on β-blockers, 6 (6.5%) had SBP and out of 240 patients who were not on β-blockers, 46 (19.2%) had SBP. The patients who were on β-blockers, had a significantly lower incidence of SBP (χ<sup>2</sup> test with continuity correction; p=0.008). <h3>Conclusion</h3> Our data indicate that spontaneous bacterial peritonitis significantly increases mortality in patients with cirrhosis. Propranolol therapy was found to be associated with a significantly lower risk for spontaneous bacterial peritonitis, but a Type II statistical error cannot be definitely excluded. The potential protective effect of propranolol on the incidence of spontaneous bacterial peritonitis might deserve evaluation in properly designed prospective studies. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Senzolo M</b>, Cholongitas E, Burra P, <i>et al.</i> β-Blockers protect against spontaneous bacterial peritonitis in cirrhotic patients: a meta-analysis. <i>Liver Int</i> 2009;<b>29</b>:1189–93.
P126 Breathlessness And Lung Function Predicts Future Work Disability In Older Workers: Detection, Intervention, Retention?
Authors: J. Szram, S. Schofield, A. Woods, P. Cullinan
Journal: Thorax (2014)

<h3></h3> Economic pressures and the ageing population have increased the importance of maintaining fitness to work in older adults. Dyspnoea and airflow limitation are associated with disability particularly in individuals with diagnosed disease. A cross-sectional general population survey of 51–60 year olds demonstrated significant associations between breathlessness, airflow obstruction and work performance; a follow-up survey was completed 18 months later to examine changes in work. Participants from the first study were sent a postal questionnaire asking about job and employment changes. Questionnaire and spirometry results from the initial study were used to define breathlessness (modified MRC scale) and airflow obstruction (GOLD stage) respectively. Information from the follow up questionnaire was also used to identify cases, defined as those who had experienced a change in employment, and frequency matched controls of the same gender, who reported no change in work circumstances (with a ratio of two controls per case). Results from respondents to the follow up questionnaire (1663/1773 (94%)), all of whom had been in full time work at the time of the first study) showed that the majority (78.5%) continued in full time employment; however 10.6% were working part time and 10.9% were no longer in paid employment at follow up. Of the participants still in employment who reported changing their hours or activity at work, 9.3% stated that this change had been to their health. Prevalence of economic inactivity rose with increasing breathlessness and with increasing airflow obstruction in workers of both sexes; these relationships were statistically significant in all cases except for airflow obstruction in women (Figure). The odds of GOLD stage 1 or greater airflow obstruction was significantly higher in cases than in controls (unadjusted OR 1.71, 95% CI 1.10–2.77, p = 0.02). These findings suggest that breathlessness and airflow obstruction are associated with subsequent job instability and premature loss from the workforce in older workers. A focused surveillance programme could identify those at higher risk of employment problems with the intention of ameliorating them – providing that there are suitable interventions available to support continuing workforce activity in adults in their sixth decade of life and beyond.
AB0105 Effects of Etanercept on the Selected Parameters of Rat Placenta
Authors: A. Korobowicz-Markiewicz, F. Burdan, J. Szumił o, J. Dudka, V. Opoka-Winiarska, A. Korga, R. Klepacz
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Etanercept interferes with the tumor necrosis factor (TNF) and is widely used in various autoimmune diseases. However, its developmental toxicity has not been fully established. <h3>Objectives</h3> To analyze the effects of etanercept, new generation biological agent used in the therapy of rheumatoid arthritis, on the selected parameters of rat placenta – both in healthy females and in animals with experimentally induced arthritis. <h3>Methods</h3> This study included seven groups of Wistar rats: 1) with experimentally induced arthritis (group R), 2-3) with the arthritis treated with etanercept (0.4 or 4.0 mg/kg b.w.; groups RE1 and RE2), 4-5) receiving etanercept despite the lack of arthritis (E1, E2), and 6-7) controls receiving placebo (C1, C2). Female rats were immunized according to the Trentham9s method. The drug (0.4 and 4.0 mg/kg) was subcutaneously injected to animals that exhibited one or higher severity score in the visual system for evaluation of CIA rodent model. After the last injection all the females were inseminated and pregnant animals were kept without any xenobiotics until gestational day 21 when cesarean section was performed. Parallel CIA, etanercept-exposed animals without CIA and untreated (sham operated) females were also examined. Morphological and histological structure of placenta, immunohistochemical reaction of placental homogenates to genes encoding tumor necrosis factor (TNF), cyclooxygenase 1 (COX-1), and proliferating cells nuclear antigen (PCNA), concentration of TNF in placental homogenates, placental expression of interleukin encoding genes: IL1α, IL1β, LTβ, IL6, COX-1, and TNF. <h3>Results</h3> Concentrations of TNF were significantly higher in placental homogenates from females with experimentally induced arthritis (groups R, RE1, and RE2). On detailed analysis of these three groups, the concentration of examined cytokine proved significantly higher in animals that did not receive etanercept (group R). The only significant intergroup difference in qualitative expression of examined genes pertained to <i>IL1α</i> gene, the presence of which could be observed solely in placentas of rats from group R. <h3>Conclusions</h3> Experimentally induced arthritis causes inflammatory response within the placenta. This effect is partially reversed by etanercept administration; the application of this agent does not negatively affect placental function and morphology. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5644
Trends in Medicare Payments in the Last Year of Life
Authors: James D. Lubitz, Gerald F. Riley
Journal: New England Journal of Medicine (1993)

Increased attention is being paid to the amount and types of medical services rendered in the period before death. There is a popular impression that a greater share of resources is being devoted to dying patients than in the past. We examined trends in the proportion of Medicare expenditures for persons 65 years old or older in their last year of life to determine whether there were any changes from 1976 to 1988.Using Medicare program data for 1976, 1980, 1985, and 1988, we classified Medicare payments according to whether they were made for people in their last year of life (decedents) or for survivors. We also assigned expenses for care in the last year of life according to intervals of 30 days before the person's death and examined trends according to age.Reflecting the large overall increase in Medicare spending, Medicare costs for decedents rose from $3,488 per person-year in 1976 to $13,316 in 1988. However, Medicare payments for decedents as a percentage of the total Medicare budget changed little, fluctuating between 27.2 and 30.6 percent during the study period. Payments for care during the last 60 days of life expressed as a percentage of payments for the last year also held steady at about 52 percent. Furthermore, the pattern of lower payments for older as compared with younger decedents also prevailed throughout the study period.The same forces that have acted to increase overall Medicare expenditures have affected care for both decedents and survivors. There is no evidence that persons in the last year of life account for a larger share of Medicare expenditures than in earlier years.
Further studies are needed on urgent ERCP with pancreatic stent placement or replacement for salvage of post-ERCP pancreatitis
Authors: Limei Ma, Li Liu, Zhining Fan
Journal: Endoscopy (2015)

We read with great interest the article by Kerdsirichairat et al. on urgent endoscopic retrograde cholangiopancreatography (ERCP) with pancreatic stent placement or replacement for salvage of post-ERCP pancreatitis (PEP) [1]. The authors presented their experience of treating or preventing early PEP by using urgent salvage ERCP with de novo pancreatic stent placement or replacement. However, we have some comments as follows.
Abstract 5366: NAD(P)H-Quinone oxidoreductase (NQO1): Potential role in the prevention of estrogen-induced breast cancer
Authors: Bhupendra Singh, Hari K. Bhat
Journal: Cancer Research (2010)

Abstract The importance of estrogens in the etiology of breast cancer is widely recognized. However, the exact mechanisms underlying the initiation and progression of estrogen-related cancers are not clear. Literature evidence and our studies strongly support the role of estrogen metabolism-mediated oxidative stress in estrogen-induced breast carcinogenesis. The objective of the current study was to characterize the role of NQO1 in the prevention of estrogen-induced mammary tumorigenesis by antioxidants vitamin C or butylated hydroxyanisole (BHA). NQO1 converts 17β-estradiol (E2)-quinones back to E2-catechols, thus making E2-quinones unavailable for oxidant damage. Female ACI rats were treated with E2 (3 mg); vitamin C (1% in drinking water); E2 + vitamin C; BHA (0.7% in diet); and E2 + BHA for up to 8 months. The female ACI rat is an established animal model to study the mechanisms of E2-induced breast cancer. The protein isolated from breast tissue and breast tumor tissue of rats treated with E2 and antioxidants was analyzed for NQO1 expression. NQO1 was suppressed in E2-exposed mammary tissue after treatment of rats with E2 for 8 months and in mammary tumors. This suppression was overcome by co-treatment of rats with E2 and vitamin C or BHA. Co-treatment of rats with E2 and vitamin C resulted in a 4-fold induction of NQO1 compared to control mammary tissue. Similarly, co-treatment of rats with E2 and BHA induced NQO1 4.4-fold compared to control mammary tissue. There was no change in NQO1 expression during early time points of E2 exposure (7 and 15 days). The up-regulation of NQO1 by vitamin C or BHA was evident after 4 months of treatment. There was no effect of BHA or vitamin C treatment on NQO1 expression on other non-target organs like liver, lung and heart except kidney. These studies suggest a protective role of NQO1 in E2-induced breast carcinogenesis. NQO1 may thus have a great potential in the development of therapeutic strategies for the prevention of estrogen-induced neoplasia. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5366.
BM-38 * THE PREFERRED ANATOMIC DISTRIBUTION OF 1172 BRAIN METASTASES BASED ON BRAIN VOLUME AND REGIONAL BLOOD FLOW
Authors: Z. Zhang, J. Johnson, Y. Watanabe, S. Jackson, P. Sperduto, C. Watts
Journal: Neuro-Oncology (2014)

Regional based epidemiology of brain metastases was studied through the patients that were treated by gamma knife at the University of Minnesota. We reviewed 1903 procedures using Gamma Knife during the period from April 26, 2005 to June 29, 2010. Among them, 1172 (62%) cases were metastases. The most common types of metastases at our center, in descending order were lung, breast, skin and kidney. This matched well with medical data nationwide with the exception of breast metastases in women, which made up 44.5% in our group, higher than the national average. Taking into account the high accuracy of anatomical location required for stereotactic radiosurgery, we try to answer the question of whether metastatic lesions from specific sources are distributed according to the tissue volume of the region or by blood flow to the region. We use indices to represent the preference of certain tumors to metastasize to certain regions of the brain. An index of 1 signifies that the location of a metastasis strictly corresponds to the brain volume or the volume of regional blood flow. The bigger the brain volume, the more blood flow there is to the region. This increases the metastatic incidence, but not the index. Hence, a higher index indicates metastatic preference. The highest indices, >2 were found for small cell lung cancer (SCLC) in the cerebellum and brainstem, breast cancer in the cerebellum and renal carcinoma in the occipital lobe. These epidemiological data may help us to track the factors associated with lifestyle or the genomics involved in particular metastases. Understanding the metastatic preference may also give us further insight into the mechanisms of certain tumor proliferation and homing based on the different environments present in various parts of the brain.
Accelerated conformal radiotherapy for stage I non-small cell lung cancer (NSCLC) in patients with pulmonary dysfunction: A CALGB phase I study
Authors: J. Bogart, D. Watson, S. Seagren, A. W. Blackstock, X. Wang, R. Lenox, E. Vokes, A. T. Turrisi, M. R. Green
Journal: Journal of Clinical Oncology (2007)

7556 Background: The optimal treatment for medically inoperable stage I NSCLC has not been defined. Methods: CALGB 39904 is a prospective phase I study assessing accelerated once-daily radiotherapy for early stage NSCLC. The primary objectives were to define the maximally accelerated course of conformal radiotherapy; and to describe the short-term and long-term toxicity of therapy. Entry was limited to patients with clinical stage T1N0 and T2N0 NSCLC (&lt; 4 cm) with pulmonary dysfunction (FEV1 &lt;40% predicted, DLCO 45mmHg, V02 max &lt;15m1/kg/min, O2 requirement). The nominal total radiotherapy dose was held constant at 70 Gy, while the number of daily fractions in each successive cohort was reduced (table). Results: The study was activated on 12/15/2000, and closed on 7/29/2005. Forty patients were accrued with 8 on each cohort. One patient on cohort 5 declined protocol treatment leaving 39 eligible patients. Patients were generally female (53%), white (83%), and ECOG performance status = 1 (67%). The median age was 74 (range 48 to 87), and the majority of the patients (73%) had T1N0M0 disease. Treatment was well tolerated without grade 4+ toxicity. There was one hematologic toxicity (lymphopenia) in cohort 2, and one non-hematologic toxicity each in cohort 3 (dyspnea) and cohort 4 (pain).The major repsonse rate was 74% (31% complete response, 43 % partial response), and 26% of patients had stable disease. After a median follow-up of 38.1 months, 21 patients remain alive. The actuarial median survival of all eligible patients is 38.5 months (95% confidence interval= 19.45 to NE). Conclusion: Accelerated conformal radiotherapy was well tolerated in a high-risk population with clinical stage I NSCLC. Outcomes are comparable to prospective reports of alternative therapies, including stereotactic body radiosurgery and limited resection,with less apparent severe toxicity. Further investigation of this approach is warranted. No significant financial relationships to disclose. [Table: see text]