tbuckley/cabot-search huggingface dataset:
T‐cell immunoglobulin and mucin domain 4 (TIM‐4) signaling in innate immune‐mediated liver ischemia‐reperfusion injury
Authors: Haofeng Ji, Yuanxing Liu, Yu Zhang, Xiu‐da Shen, Feng Gao, Ronald W. Busuttil, Vijay K. Kuchroo, Jerzy W. Kupiec‐Weglinski
Journal: Hepatology (2014)

Hepatic ischemia-reperfusion injury (IRI), an innate immunity-driven inflammation response, occurs in multiple clinical settings including liver resection, transplantation, trauma, and shock. T-cell immunoglobulin and mucin (TIM)-4, the only TIM protein not expressed on T cells, is found on macrophages and dendritic cells. The regulatory function of macrophage TIM-4 in the engulfment of apoptotic/necrotic bodies in innate immunity-mediated disease states remains unknown. This study focuses on the putative role of TIM-4 signaling in a model of liver warm ischemia (90 minutes) and reperfusion. The ischemia insult triggered TIM-4 expression by stressed hepatocellular phosphatidylserine (PS) presentation, peaking at 6 hours of reperfusion, and coinciding with the maximal hepatocellular damage. TIM-4-deficient or wild-type WT mice treated with antagonistic TIM-4 monoclonal antibody (mAb) were resistant against liver IRI, evidenced by diminished serum alanine aminotransferase (sALT) levels and well-preserved hepatic architecture. Liver hepatoprotection rendered by TIM-4 deficiency was accompanied by diminished macrophage infiltration/chemoattraction, phagocytosis, and activation of Toll-like receptor (TLR)2/4/9-dependent signaling. Correlating with in vivo kinetics, the peak of TIM-4 induction in lipopolysaccharide (LPS)-activated bone marrow derived-macrophages (BMM) was detected in 6-hour cultures. To mimic liver IRI, we employed hydrogen peroxide-necrotic hepatocytes, which readily present PS. Indeed, necrotic hepatocytes were efficiently captured/engulfed by WT (TIM-4+) but not by TIM-4-deficient BMM. Finally, in a newly established model of liver IRI, adoptive transfer of WT but not TIM-4-deficient BMM readily recreated local inflammation response/hepatocellular damage in the CD11b-DTR mouse system.These findings document the importance of macrophage-specific TIM-4 activation in the mechanism of hepatic IRI. Macrophage TIM-4 may represent a therapeutic target to minimize innate inflammatory responses in IR-stressed organs.
Abstract 13658: Identification of Two Native Nav1.5 Phosphorylation Sites as Potential Determinants of the Increased Late Na+ Current in Heart Failure
Authors: Fabien Coyan, Sophie Burel, Matthew R Meyer, Cheryl F Lichti, Joan H Brown, Flavien Charpentier, Jeanne M Nerbonne, Reid R Townsend, Lars S Maier, Céline Marionneau
Journal: Circulation (2014)

Voltage-gated Na+ (Nav) channels are key determinants of myocardial excitability and defects in Nav channel functioning or regulation, associated with inherited and acquired cardiac disease, increase the risk of life-threatening arrhythmias. In heart failure, the inactivation properties of Nav1.5 channels are altered, resulting in decreased channel availability and increased late Na+ current. Although previous studies have suggested roles for CaMKII and CaMKII-dependent Nav1.5 phosphorylation, the global native phosphorylation pattern of Nav1.5 channels associated with these alterations is unknown. Phosphoproteomic analyses were undertaken to identify and quantify in situ the native phosphorylation sites on the Nav1.5 proteins purified from wild-type and CaMKIIdc-overexpressing (CaMKIIdc-Tg) mouse ventricles. A total of 18 phosphosites were identified, 8 of which are novel compared with our previous MS analyses. Of these 18 phosphosites, the C-terminal phosphoserines pS1937/pS1938 are present in the CaMKIIdc-Tg IPs (n=3/4) and absent in the WT IPs (n=0/4). In addition, pS1989 is 9-fold more represented (p
Heroin Addiction Trends
Authors: MARK H. GREENE, ROBERT L. DUPONT
Journal: American Journal of Psychiatry (1974)

Systematic observations made in Washington. D.C., documented the epidemic spread of heroin use and its subsequent decline. Major indicators supporting the contention of reduced heroin use include: 1) a stable year of peak heroin use among all treatment cohorts admitted since January 1971; 2) a marked reduction in deaths due to heroin overdose; 3) a steady decline in the number of urine tests positive for heroin among arrestees tested; 4) a sharp reduction in the annual number of narcotics arrests; 5) a sustained reduction in the demand for heroin addiction treatment; and 6) a significant increase in the mean age of identified heroin users.
Methodological aspects of nuclear magnetic resonance spectroscopy of exhaled breath condensate
Authors: Paolo Montuschi, Debora Paris, Dominique Melck, Vincenzina Lucidi, Giovanni Ciabattoni, Andrea Motta
Journal: European Respiratory Journal (2011)

We investigated the following methodological aspects of nuclear magnetic resonance (NMR) spectroscopy-based metabolomics of exhaled breath condensate (EBC): 1) within-day, between-day and technical repeatability; 2) detection limit; 3) possible EBC contamination with saliva or cleaning solution for disinfection of EBC collection setup. A 600 MHz Bruker Avance spectrometer (Bruker BioSpin, Rheinstetten, Germany) was used. EBC was collected with a condenser (Ecoscreen, Jaeger, Hoechberg, Germany). Within-day repeatability of NMR spectroscopy, expressed according to Bland-Altman, was assessed in 5 healthy and 11 cystic fibrosis subjects collecting separate samples twice within the same day. All values were within the 2SD range. Between-day repeatability was assessed in the same subjects collecting 3 samples on day 1,3,7. Technical repeatability was assessed measuring 3 different samples 10 times. Between-day and technical repeatability were expressed as intraclass correlation coefficient which was 0.93 and 0.96, respectively. Detection limit was 0.14 μM. EBC and salivary metabolomic spectra were different as signals in 3.3-4.5 ppm region in saliva were absent in EBC. Apart from reference TSP, no peak was observed in the cleaning solution (sodium hypochlorite, 3.55 mM) spectrum.  This technique has a low detection limit for NMR spectroscopy, is reproducible and not affected by contamination with saliva or cleaning solution.
Stimulation of One Particular Subset of Natural Killer Cells by Peptidoglycans Extracted From Gram-Positive Bacteria&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A F Goguel, B Payelle, P C Quan, G Lespinats
Journal: JNCI Journal of the National Cancer Institute (1984)

Peritoneal nonspecific cytotoxicity was stimulated by ip injection into C57BL/6 or (C57BL/6 X C3H/He)F1 mice of Staphylococcus aureus peptidoglycan (PGS), which possessed an antitumor effect, and of Micrococcus lysodeikticus peptidoglycan (PGM), which was ineffective against tumors. The natural killer (NK) cell populations elicited by both peptidoglycans had the same phenotype: Thy 1.2+, T200+, Ly 5.1+, Qa5+, and Ly 2.2-. In vivo treatment with sheep anti-mouse beta interferon serum abrogated this effect. The fluids from phorbol myristate acetate-stimulated murine EL 4 thymoma cells enhanced this particular NK activity, and thus PGM-induced effector cells became able to kill solid tumor cells. In conclusion, both PGS and PGM elicited the same particular subset of NK cell populations, and the peptidoglycan structure can play an important role in the intensity of this response.
Abstract 19959: Ultrasound-Facilitated Nitric Oxide Delivery Enhances in vivo Inflammatory Atheroma Detection Using Targeted Echogenic Immunoliposomes
Authors: Hyunggun Kim, Melanie R Moody, Melvin E Klegerman, Patrick Kee, Shaoling Huang, David D McPherson
Journal: Circulation (2010)

Background: We have previously demonstrated that antibody-conjugated echogenic immunoliposomes (ELIP) can detect early inflammatory atheroma. We have developed nitric oxide (NO)-containing ELIP that can enhance endothelial permeability and allow enhanced uptake of different sized molecules into the arterial wall. We hypothesize that pretreatment of NO-ELIP with ultrasound activation will enhance uptake of rhodamine-labeled targeted ELIP into atheroma in an in-vivo model, allowing for improved component highlighting. Methods: ELIP were prepared by hydration, sonication, freezing and lyophilization. Targeted ELIP were prepared by conjugating anti-intercellular adhesion molecule-1 (ICAM-1) antibodies. New Zealand white rabbits (N=12) were fed an atherogenic diet, followed by balloon denudation of the abdominal aorta. Following atheroma formation, rhodamine-labeled anti-ICAM-1-ELIP were injected with or without pretreatment with NO-ELIP 5 minutes prior to anti-ICAM-1-ELIP administration. Aortas were imaged wi...
Multicenter clinical trial of mitoxantrone in non-Hodgkin's lymphoma and Hodgkin's disease.
Authors: R T Silver, D C Case, R H Wheeler, T P Miller, R S Stein, J J Stuart, B A Peterson, S E Rivkin, H M Golomb, None Costanzi
Journal: Journal of Clinical Oncology (1991)

In this phase II multicenter trial, the efficacy and safety of mitoxantrone (Novantrone; Lederle Laboratories, Wayne, NJ) were evaluated in the treatment of 206 patients with relapsed non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD) previously treated with other agents. Sixty-nine percent of the patients had received prior therapy with doxorubicin. The patients received 14 mg/m2 of mitoxantrone every 3 weeks. Nineteen (12%) of the NHL patients and two (7%) of the HD patients had complete responses (CRs). The combined CR and partial response (PR) rates were 37% (60 of 163) for NHL patients and 36% (10 of 28) for HD patients; the median duration of response was 323 days for NHL patients and 209 days for HD patients. The median survival times were 337 days for patients with NHL and 469 days for patients with HD. The median survival time for patients with low-grade NHL was 589 days compared with 298 days for patients with intermediate-grade NHL and 167 days for patients with high-grade NHL. The median time to treatment failure was 73 days for NHL patients and 98 days for HD patients. The major toxicity was myelosuppression, which was moderate and reversible. Nausea, vomiting, and alopecia were mild. There were two cases of congestive heart failure (CHF) considered related to treatment; both patients had received prior treatment with doxorubicin. In this group of heavily pretreated patients, mitoxantrone was effective and well tolerated. Responses were seen with mitoxantrone in patients who had relapsed after prior therapy with doxorubicin and in patients who had failed to respond to prior therapy with doxorubicin. Mitoxantrone should be evaluated in less heavily pretreated patients and should be considered for incorporation into combination chemotherapeutic regimens for the treatment of malignant lymphoma.
Scleroderma lung disease: A scleroderma physiologic index (SPI) derived from lung physiology and oxygen saturation
Authors: Katerina Antoniou, David Hansell, Nicole Goh, Katerina Samara, Elizabeth Renzoni, Maher Toby, Nikos Siafakas, Athol Wells
Journal: European Respiratory Journal (2013)

The quantitation of disease severity in Scleroderma Lung (SSc-ILD) using pulmonary function tests is often confounded by emphysema. We identified the scleroderma physiologic index (SPI) with readily available measures (spirometry, diffusion capacity and oxygen saturation).Consecutive patients with a clinical/computed tomography diagnosis of scleroderma lung (n = 292) were divided into group I (n = 146) and group II (n = 146). Cohort 1 (derive cohort) and 2 (test cohort) did not differ in outcome, PFTs, age, gender, smoking status at baseline. There were 55 /146 deaths in cohort 1 and 50/146 deaths in cohort 2. The formula has been derived in cohort 1 and then calculated in test cohort 2. The SPI was derived in group I (by fitting pulmonary function tests against disease extent on CT) and was tested in Group II (test cohort). The formula for the SPI was as follows: 384.0 – (0.37x percent predicted diffusing capacity for carbon monoxide [DLCO]) – (0.59x percent predicted FVC) + 0.72x percent predicted FEV1) = (3.46 x saturation). In the test cohort, the SPI (median 40.9, range 9.2 to 82) was strongly predictive of mortality (HR 1.07, CI 1.04 -1.10, p
Evidence for local platelet activation in pulmonary vessels in patients with pulmonary hypertension secondary to chronic obstructive pulmonary disease
Authors: C Rostagno, D Prisco, M Boddi, L Poggesi
Journal: European Respiratory Journal (1991)

To investigate the relationships between local platelet activation in pulmonary vessels and pulmonary artery pressure circulating platelet aggregates and plasma beta-thromboglobulin (beta-TG) levels were evaluated in peripheral venous blood and blood from different sites of pulmonary circulation (right ventricle, pulmonary artery and arteriolo-capillary bed) in 29 patients with COPD. Fifteen had pulmonary hypertension and 14 normal pulmonary artery pressure. In normotensive COPD no significant differences could be found in platelet aggregation and beta-TG levels among different sampling sites. On the contrary in patients with pulmonary hypertension a significant increase of platelet aggregates and beta-TG levels was found in blood withdrawn from the arteriolo-capillary bed. A significant correlation was demonstrated between platelet aggregation and both mean pulmonary artery pressure and pulmonary vascular resistance. These results indicate that in patients with pulmonary hypertension secondary to COPD a local platelet activation in pulmonary vessels does occur and may contribute to the maintainance of elevated pulmonary vascular resistance.
Patterns of lung function abnormalities in smokers as possible manifestation of "early" COPD phenotypes
Authors: Angelo Corsico, Laura Carrozzi, Francesco Pistelli, Erica Gini, Federica Albicini, Amelia Grosso, Ferruccio Aquilini, Rosanna Niniano, Federica Imberti, Eric Tsana Tegomo, Marta Agnesi, Antonio Foresi, Isa Cerveri
Journal: European Respiratory Journal (2012)

The notion that the earliest manifestation of COPD is an increase in gas trapping, with a decreasing VC that forces the FEV1 to decline with it, has been recently re-evaluated [1]. To assess the prevalent patterns of lung function abnormalities in smokers at the onset of COPD, we evaluate cross-sectional data of a longitudinal study on 321 non-outpatient smokers (mean age 55±10 years; 60% males) belonging in part to a smoking cessation program and in part to a lung cancer screening study. Smoking history and chronic respiratory symptoms were collected, and spirometry and lung volumes were determined, according to standardized protocols. Mean pack-years were 38±22 and 38% of the smokers reported chronic cough and/or phlegm and/or dyspnea; they were significantly older and smoked more pack-years than those without symptoms (for both p 115% predicted, 19% had only airflow obstruction and 9% had an isolated increase in FRC without airflow obstruction. A similar pattern of increase in gas volume was found regardless the presence of respiratory symptoms or by considering either RV or RV/TLC. In conclusion, air trapping is not the prevalent pattern of lung function abnormalities in these two groups of non-outpatient smokers. Isolated airflow obstruction or isolated increase in air trapping could be an “early” expression of two different phenotypes of COPD.

[1] P.T. Macklen. Therapeutic implications of the pathophysiology of COPD. Eur Resp J 2010; 35: 676-680.
Prevalence of sleep apnea - Hypopnea syndrome among lung transplantation candidates
Authors: Ana Hernández Voth, Pedro Benavides Mañas, María Dolores Hisado Díaz, Soraya Jodrá Sánchez, Alicia De Pablo Gafas, Jesus Muñoz Méndez, María Josefa Díaz De Atauri Rodríguez
Journal: European Respiratory Journal (2012)

Aim : To analyze the prevalence and possible associated factors with the Sleep Apnea – Hypopnea Syndrome (SAHS) among patients evaluated for Lung Transplantation (LT)   Methods:  Transversal descriptive study of a cohort of patients evaluated for LT, with a standard polysomnography (PSG), from September 2008 to February 2012. SAHS was defined as the presence of Apnea Hypopnea Index (AHI) ≥ 10 and excessive daytime sleepiness symptoms. Severity of these symptoms was evaluated by Epworth sleepiness scale. Anthropometric, clinical and blood test measurements were also analyzed in all patients   Results:  During this period a number of 52 patients were studied, 50% of them were man, average age was 54,8 years (SD ± 9.96). Principal LT indication pathologies were due to COPD (46.2%), Pulmonary Idiopathic Fibrosis (15.4%) and Usual Interstitial Pneumonitis (11.5%). PSG were performed with supplementary oxygen in 96.2% of the cases. AHI average was 8,26 (SD±1.4). SAHS was diagnosed in 13 patients (25%). Among these, 8 (61.5%) had COPD. Next table shows relationships between groups and principal analyzed variables.   Conclusions:  In this serie of LT candidate patients, prevalence of SAHS is high. We have not found anthropometric, clinical nor blood test data significantly associated with the diagnoses of SAHS which can contribute to make a clinical pretest suspect. Performance of a standard polysomnography in LT candidates is probably recommendable.
The effect of rosiglitazone on novel atherosclerotic risk factors in patients with type 2 diabetes mellitus and hypertension
Authors: Panteleimon A. Sarafidis, Anastasios N. Lasaridis, Peter M. Nilsson, Tzant F. Mouslech, Areti D. Hitoglou-Makedou, Panagiotis C. Stafylas, Kiriakos A. Kazakos, John G. Yovos, Achilleas A. Tourkantonis
Journal: Metabolism (2005)
Lung Cancer in Coastal Georgia: A Death Certificate Analysis of Occupation: Brief Communication
Authors: J. Malcolm Harrington, William J. Blot, Robert N. Hoover, W. Jere Housworth, Clark W. Heath, Joseph F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (1978)

A comparison of death certificate statements on occupation for 858 white males who lived in coastal Georgia counties and who died of lung cancer during 1961--74, and for 858 controls who were of the same age and county of residence revealed a twofold excess risk of lung cancer associated with the construction industry. No elevated risk of lung cancer was found for workers in the wood and paper industries in the urban areas of Savannah, Brunswick, or Waycross, but a threefold increase was uncovered for the remaining coastal counties where the wood and paper industry was the largest employer.
Effects of Various Oncogenic Agents on Tumor-Producing Capabilities of Series D BALB/c Mammary Nodule Outgrowth Lines&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Daniel Medina, K. B. DeOme
Journal: JNCI Journal of the National Cancer Institute (1970)

In previous papers, we reported the effects of viral, chemical, and physical carcinogens on the tumor-producing capabilities of the nodule outgrowth line D1. The present paper describes the tumor-producing capabilities of a series of nodule outgrowth lines in BALB/c mice negative for mammary tumor virus (MTV) and in BALB/c f. C3H mice positive for MTV. Of 7 outgrowth lines tested for their responsiveness to MTV, 6 showed increased tumor-producing capabilities. The responsiveness of any outgrowth line to MTV was not correlated with its background tumor potential. Also described are the effects of MTV, nodule-inducing virus (NIV), 3-methylcholanthrene (MCA), and prolonged hormone stimulation, applied singly and combined, on the tumor-producing capabilities of nodule outgrowth line D2. Single application of prolonged hormone stimulation, MTV, or MCA increased the tumor-producing capabilities of line D2; however, NIV had no measurable effect. Combined applications of MTV and MCA, MTV and hormone stimulation, and MCA and hormone stimulation had additive effects. The D series of nodule outgrowth lines is a good system to study the effects of MTV's and chemical carcinogens, applied individually or combined. The present studies and the previously reported ones indicate that different outgrowth lines respond differently to various oncogenic agents and that the response of an outgrowth line to a combination of several carcinogens cannot be predicted by its response to a single application of the agents.
Consideration of palivizumab not justified.
Authors: R D Clifford
Journal: Thorax (2006)

Broughton and colleagues1 state that consideration should be given to the use of prophylactic palivizumab to infants born at less than 32 weeks in the case of maternal smoking or even if they have siblings. However, the authors present no data from their own or other studies to indicate that this would be in any way cost effective or justified. Certainly the word “consider” is fortunate, given the stated funding provided to one author by the manufacturer.

The study demonstrated a relationship between lower respiratory morbidity from respiratory syncytial virus (RSV) and smoking which has been widely shown elsewhere. The numbers of …
Local Therapies for Hepatic Metastases
Authors: Fabian M. Johnston, Michael N. Mavros, Joseph M. Herman, Timothy M. Pawlik
Journal: Journal of the National Comprehensive Cancer Network (2013)

The liver is one of the most common sites for metastatic disease, and optimal management of hepatic metastases often requires a multidisciplinary approach. Most commonly, liver metastases are derived from a colorectal or neuroendocrine primary tumor. Liver resection with curative intent is standard for resectable cases, but unfortunately most patients are not initially resectable because of the size, location, and/or extent of disease; inadequate remnant liver volume; or comorbidities. For patients with liver-limited or liver-dominant colorectal liver metastases (CRLM), the current challenges are to use different locoregional treatments to convert some borderline unresectable cases to resectable, and improve local control and overall survival. Although neuroendocrine liver metastases (NELM) may behave in a relatively indolent manner from an oncologic perspective, significant morbidity may be caused by excess hormone production when compared with metastatic liver disease from other primaries, and liver-directed treatment may be beneficial in reducing symptoms and perhaps extending survival. In the multidisciplinary management of patients with liver metastases, local therapies are especially important. Local approaches may be complementary (ie, portal vein embolization) or an alternative (ie, ablation, hepatic arterial infusion, selective radioembolization, and stereotactic body radiotherapy) to surgical resection. This article evaluates the available evidence on current regional strategies for managing patients with liver metastases, with an emphasis on CRLM and NELM, highlighting the clinical usefulness and limitations of each modality.