tbuckley/cabot-search huggingface dataset:
Nitric Oxide and Nitrotyrosine in the Lungs of Patients with Acute Respiratory Distress Syndrome
Authors: CHANCHAI SITTIPUNT, KENNETH P. STEINBERG, JOHN T. RUZINSKI, CARPANTATO MYLES, SHA ZHU, RICHARD B. GOODMAN, LEONARD D. HUDSON, SADIS MATALON, THOMAS R. MARTIN
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Nitric oxide (NO) end-products (nitrate and nitrite) are present in bronchoalveolar lavage (BAL) fluid of patients with inflammatory lung diseases. Reactive oxygen-nitrogen intermediates damage macromolecules by oxidation or nitration of critical residues in proteins. The goal of this study was to measure NO end-products (nitrate + nitrite), in BAL fluid before and after the onset of acute respiratory distress syndrome (ARDS) and to determine if these products are associated with expression of inducible nitric oxide synthase enzyme (iNOS) in BAL cells and nitration of BAL proteins. We performed bronchoalveolar lavage (BAL) in patients at risk for ARDS (n = 19), or with ARDS (n = 41) on Days 1, 3, 7, 14, and 21 after onset, and measured total nitrite (after reducing nitrate to nitrite) and protein-associated nitrotyrosine concentration in each BAL fluid sample. Cytospin preparations of BAL cells were analyzed by immunocytochemistry for iNOS and nitrotyrosine. Nitrate + nitrite were detected in BAL fluid from patients at risk for ARDS, and for as long as 21 d after the onset of ARDS. Nitrotyrosine was detectable in all BAL fluid samples for as long as 14 d after the onset of ARDS (range, 38.8 to 278.5 pmol/mg of protein), but not in BAL of normal volunteers. Alveolar macrophages of patients with ARDS were positive for iNOS and nitrotyrosine, and remained positive for as long as 14 d after onset of ARDS. The BAL nitrate + nitrite did not predict the onset of ARDS, but the concentration was significantly higher on Days 3 and 7 of ARDS in patients who died. Thus, NO end products accumulate in the lungs before and after onset of ARDS; iNOS is expressed at high levels in AM during ARDS; and nitration of intracellular and extracellular proteins occurs in the lungs in ARDS. The data support the concept that NO-dependent pathways are important in the lungs of patients before and after the onset of ARDS.
The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study at 30 Years: The “Gift” That Keeps on Giving!
Authors: William T. Cefalu, Robert E. Ratner
Journal: Diabetes Care (2013)

There are events that occur during our lives that because of the significance or enormity of the event we vividly remember the time, place, and what we were doing at the time! Clearly, events related to our family life would be good examples as we all remember the time, place, and emotion surrounding the birth of a child, a marriage, or perhaps the untimely death of a parent or other loved one. We also seem to recall with uncanny details where we were and what we were doing when we first heard news of a remarkable achievement, a human tragedy, or natural disaster. For example, most people today will easily recall their circumstances on the morning of 11 September 2001. Those in our generation vividly remember when we first heard of the assassination of John F. Kennedy or watched the first lunar landing on our black-and-white televisions. With this in mind, we can vividly recall when the initial results of the Diabetes Control and Complications Trial (DCCT) were presented in Las Vegas in 1993 at the American Diabetes Association (ADA) Scientific Sessions. During the session, the significance of the findings was quite apparent. We realized there was no more guessing on what our standards of treatment were to be…now we had data! But, to be honest, we clearly did not appreciate the fact that 20 years later, we would be reflecting on that moment as just the beginning of a long and rewarding story. We agreed that the initial results at the time ushered in a new paradigm of treatment, but not one of us in attendance that day could have predicted what was to come of the DCCT and that the study would be as relevant today as it was then and continue to inform and provide new information …
1146 THE EFFECTS OF BROADLY NEUTRALIZING ANTIBODIES IN EXPERIMENTAL HCV INFECTION
Authors: Y.P. de Jong, M. Dorner, A.B. Balazs, J.B. Robbins, R.N. Labitt, B.M. Donovan, A. Krishnan, M. Charlton, L. Chiriboga, D.R. Burton, C.M. Rice, D. Baltimore, M. Law, A. Ploss
Journal: Journal of Hepatology (2013)
Unilateral Ablation of Pre-Bötzinger Complex Disrupts Breathing during Sleep but Not Wakefulness
Authors: Leanne C. McKay, Jack L. Feldman
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

In adult rats, bilateral ablation of pre-Bötzinger complex (preBötC) neurokinin 1-expressing (NK1R) neurons leads to a progressive and irreversible disruption in breathing pattern, initially during sleep, eventually resulting in an ataxic breathing pattern during wakefulness.Here we determine whether ablation of fewer preBötC NK1R neurons leads to a persistent pattern of disordered breathing during sleep but not during wakefulness.Adult male Sprague-Dawley rats (n = 12) were instrumented to record diaphragmatic, abdominal, and neck EMG, and EEG. Fourteen days later, a second surgery was performed to stereotaxically microinject into the preBötC on one side the toxin saporin conjugated to substance P (SP-SAP), which selectively ablates NK1R neurons.Postinjection, rats were monitored within a plethysmograph until they were killed (Days 21-51). At Days 6-9 post-unilateral SP-SAP injection, respiratory pattern during sleep, particularly REM sleep, became increasingly disordered, characterized by an increase in frequency of central sleep apnea and hypopneas (36.8 +/- 7.4 episodes/h of REM vs. 6 +/- 2.0 episodes/h in preinjection controls; P < 0.05), whereas breathing during resting wakefulness remained stable. Unlike bilateral SP-SAP-injected rats, an ataxic breathing pattern did not develop during wakefulness. Rats that were monitored up to 51 days post-SP-SAP injection continued to have sleep-disordered breathing; breathing during wakefulness remained relatively stable. Histologic analysis of the ventrolateral medulla confirmed that NK1R neurons within the preBötC on the injected but not on the contralateral side of the medulla were ablated.Gradual loss of preBötC NK1R neurons may be an underlying factor of sleep-disordered breathing, in particular of central sleep apnea.
Monokines regulate glycosylation of acute-phase proteins.
Authors: A Mackiewicz, M K Ganapathi, D Schultz, I Kushner
Journal: The Journal of Experimental Medicine (1987)

The acute-phase response to inflammatory stimuli, characterized by increased synthesis of acute-phase proteins (APP), is often accompanied by changes in the glycosylation patterns of some of these proteins. While expression of APP genes in hepatocytes is regulated by monokines, mechanisms governing changes in glycosylation are not known. Exposure of human hepatoma cell line Hep 3B to conditioned medium from LPS-activated human monocytes and to medium from the keratocarcinoma cell line COLO-16 led to increased synthesis of alpha 1 proteinase-inhibitor and ceruloplasmin and to alterations of their glycosylation patterns similar to those seen in human serum in various inflammatory states. IL-1, tumor necrosis factor, and hepatocyte stimulating factor I increased synthesis of ceruloplasmin without alterations in the pattern of its glycosylation. These findings demonstrate that altered glycosylation seen in plasma in some inflammatory states can be explained by the effects of monokines on glycosylation in hepatocytes and that gene expression and glycosylation of some APP during the acute-phase response may be regulated by different mechanisms.
Intermediate hair follicles: a new more clinically relevant model for hair growth investigations
Authors: B.H. Miranda, D.J. Tobin, D.T. Sharpe, V.A. Randall
Journal: British Journal of Dermatology (2010)

Background Alopecia causes widespread psychological distress, but is relatively poorly controlled. The development of new treatments is hampered by the lack of suitable human hair follicle models. Although intermediate and vellus hair follicles are the main clinical targets for pharmacological therapy, terminal hair follicles are more frequently studied as smaller hair follicles are more difficult to obtain. Objectives This investigation was designed to quantify in vivo morphological and in vitro behavioural differences in organ culture between matched intermediate and terminal hair follicles, in order to develop a new clinically relevant model system. Methods Microdissected terminal and intermediate hair follicles, from the same individuals, were analysed morphometrically (250 follicles; five individuals), or observed and measured over 9 days of organ culture (210 follicles; six individuals). Results Intermediate hair follicles were less pigmented and smaller, penetrating less below the skin surface (mean ± SEM) (2·59 ± 0·07 vs. 3·52 ± 0·10 mm; P = 0·02), with smaller fibre (0·03 ± 0·002 vs. 0·07 ± 0·002 mm), connective tissue sheath (0·24 ± 0·01 mm vs. 0·33 ± 0·01 mm), bulb (0·19 ± 0·01 vs. 0·31 ± 0·01 mm) and dermal papilla (0·06 ± 0·002 vs. 0·12 ± 0·01 mm) diameters (P < 0·001). Intermediate hair follicle bulbs appeared 'tubular', unlike their 'bulbous' terminal follicle counterparts. In organ culture they also grew more slowly (0·044 ± 0·002 vs. 0·067 ± 0·003 mm per day; P < 0·001), remained in anagen longer (84 ± 0·03% vs. 74 ± 0·03% at day 9; P = 0·012) and produced less hair fibre (0·36 ± 0·02 vs. 0·50 ± 0·03 mm; P < 0·001) than terminal follicles. Conclusions Smaller intermediate hair follicles showed major morphological differences from terminal follicles in vivo and retained significant, biologically relevant differences in vitro in organ culture. Therefore, intermediate hair follicles offer a novel, exciting, more clinically relevant, albeit technically difficult, model for future investigations into hair growth. This should be particularly important for developing new therapies.
Three colleagues with sarcoidosis?
Authors: A. Sibille, P. Van Bleyenbergh, K. Lagrou, A. Verstraeten, W. Wuyts
Journal: European Respiratory Journal (2011)

To the Editors:

Bilateral pulmonary nodules are a relatively common finding in thoracic radiology and hence are an important problem that chest physicians often face. Aetiology can be diverse, ranging from neoplastic conditions to infectious lesions. An accurate and prompt diagnosis is needed in order to target the most appropriate and least harmful treatment. We report the case of a 49-yr-old, Caucasian, otherwise healthy male patient with bilateral lung nodules and an unusual diagnosis.

The patient had an unremarkable history and was referred due to asymptomatic bilateral lung nodules. He had stopped smoking 6 months earlier and had a normal chest radiograph a year before referral, taken for follow-up of benign colon polyps. At the time of presentation he was not on any medication.

The patient was an engineer working in a Belgian high-tech facility. His job mainly consisted of office work with occasional visits to production sites where coating of medical material was performed. When visiting these sites, he did not systematically wear a protective mask. The problems occurred after a business trip to the USA where he met with three colleagues. He first visited his general practitioner with a flu-like syndrome. Other symptoms included a productive cough, night sweats and loss of weight (5 kg in 2 weeks). He was treated symptomatically with paracetamol. Two of his colleagues developed the same complaints. One never visited a doctor but the other did and was diagnosed with sarcoidosis based on the finding of non-necrotising granulomatous lesions in transbronchial biopsies. He was put on steroids and his condition improved. Oddly, the third colleague who did not visit the doctor had an existing diagnosis of sarcoidosis but remained asymptomatic.

Due to persistent cough and low-grade fever, our patient was subsequently referred …
Gender and variation in activity rates of hospital consultants
Authors: Karen Bloor, Nick Freemantle, Alan Maynard
Journal: Journal of the Royal Society of Medicine (2008)

To explore whether or not gender predicts consultant activity rates.Using data from the Hospital Episode Statistics for England 2004/2005, we explored inpatient activity rates of male and female hospital consultants, with and without adjustment for case-mix differences. As a sensitivity analysis we also explored outpatient attendances for male and female hospital consultants.Data from the Hospital Episode Statistics for England.Finished consultant episodes per year, with and without adjustment for case-mix differences, age and gender of consultant, contract held, hospital trust, specialty of practice, and clinical excellence awards, discretionary points and distinction awards.Including only consultants on full-time or maximum part-time contracts, men have significantly higher activity rates than women, after accounting for age, specialty and hospital trust.The reasons for the different activity rates of male and female consultants are unclear, but the implications of these results for the planning of the medical workforce are important.
The relationship between diabetes and pancreatic cancer.
Authors: Feng Wang, Margery Herrington, Jörgen Larsson, Johan Permert
Journal: Molecular Cancer (2003)

About 80% of pancreatic cancer patients have glucose intolerance or frank diabetes. This observation has led to the following two hypotheses: i. pancreatic cancer causes the associated diabetes and ii. the conditions associated with diabetes promote the development of pancreatic cancer. Evidence supporting both hypotheses has been accumulated in previous studies. This article reviews these studies, especially those that have been conducted recently.
Control of Carotid Vasomotor Tone by Local Renin–Angiotensin System in Normotensive and Spontaneously Hypertensive Rats
Authors: Lidia Caputo, Alain Tedgui, Bernard I. Lévy
Journal: Circulation Research (1995)

Abstract To investigate the relation between the tissue renin–angiotensin system (RAS) and the local vasomotor tone of large arteries, we used in vitro isolated carotid arteries from 14-week-old Wistar-Kyoto rats (WKY; n=80) and spontaneously hypertensive rats (SHR; n=80). Diameters were measured with the use of an ultrasonic echo-tracking system (12 MHz) under flow (2 mL/min) (F+) or no-flow (Fo) conditions, with intact endothelium (Endo+) or after endothelium removal (Endo−). The role of tissue RAS was assessed by incubating isolated carotid arteries with an angiotensin-converting enzyme inhibitor (ACE I; lisinopril, 10 −6 mol/L) or with a specific antagonist of angiotensin II AT 1 receptors (AT 1A ; losartan, 10 −6 mol/L). In addition, maximal dilation of carotid arteries was measured after poisoning with KCN (100 mg/L). In all experiments, KCN significantly increased carotid diameters (WKY, 23±0.9%; SHR, 19±0.8%; P &lt;.001 versus control conditions). In intact carotid arteries, flow caused significant dilation in WKY (7±0.5%, P &lt;.001) but had no effect in SHR. In the presence or absence of flow, ACE I and AT 1A induced similar dilations in both strains, and a specific antagonist of bradykinin B 2 receptors (Hoe 140, 10 −7 mol/L) had no effect on ACE I–induced dilation. After endothelium removal, carotid artery diameters were significantly increased ( P &lt;.001) in both strains, although more in SHR (13±0.8%) than in WKY (8±1.1%) ( P &lt;.001). Also, flow did not modify the diameter of deendothelialized vessels and ACE I had no effect in either strain. In contrast, AT 1A increased diameters further (WKY, 4±0.4%; SHR, 3±0.6%; P &lt;.01). The results of the present study suggest that in in vitro isolated intact carotid artery, (1) the endothelium exerts a basal vasoconstrictor effect that is larger in SHR than in WKY, which could participate in the relative insensitivity to flow in SHR; (2) in the absence of exogenous substrate the vessel wall is able to produce angiotensin II, which is active locally on the vascular tone; and (3) inhibition of angiotensin II formation, not degradation of bradykinin, appears to be responsible for the local relaxing effect of ACE inhibition.
Genetic susceptibility to Hodgkin's disease and secondary neoplasias: FISH analysis reveals patients at high risk of developing secondary neoplasia
Authors: D.M. Lillington, I.N.M. Micallef, E. Carpenter, M.J. Neat, J.A.L. Amess, J. Matthews, N.J. Foot, T.A. Lister, B.D. Young, A.Z.S. Rohatiner
Journal: Annals of Oncology (2002)
An Aptamer-siRNA Chimera Suppresses HIV-1 Viral Loads and Protects from Helper CD4 <sup>+</sup> T Cell Decline in Humanized Mice
Authors: Charles Preston Neff, Jiehua Zhou, Leila Remling, Jes Kuruvilla, Jane Zhang, Haitang Li, David D. Smith, Piotr Swiderski, John J. Rossi, Ramesh Akkina
Journal: Science Translational Medicine (2011)

A dual-function aptamer that targets both a HIV-1 surface protein and a critical messenger RNA can inhibit HIV infection in humanized mice.
Nucleolin involved in myocardial ischaemic preconditioning via post-transcriptional control of HSPA1A expression
Authors: Bimei Jiang, Pengfei Liang, Kangkai Wang, Chunliu Lv, Li Sun, Zhongyi Tong, Yanjuan Liu, Xianzhong Xiao
Journal: Cardiovascular Research (2014)

Recent studies have identified the critical roles of nucleolin in a variety of cellular processes, including regulation of viral replication and tumour formation. However, the possible roles of nucleolin in myocardial preconditioning remain undefined. We used an in vivo rat myocardial ischaemic preconditioning (IP) model (four cycles of 5 min ischaemia and 10 min reperfusion) and cellular hydrogen peroxide preconditioning (H2O2-PC) models. We found that nucleolin mRNA and protein expression showed a time-dependent increase during the recovery of myocardial ischaemic preconditioning in rats and H2O2-PC in neonatal rat cardiomyocytes. Nucleolin overexpression enhanced the protective effects of H2O2-PC, whereas nucleolin ablation abrogated the H2O2-PC-mediated protection in cardiomyocytes. On the other hand, nucleolin overexpression increased the stabilization of the HSPA1A mRNA and the expression of HSPA1A protein in cardiomyocytes, whereas nucleolin ablation abrogated the up-regulation of HSPA1A induced by H2O2-PC in cardiomyocytes. An interaction between nucleolin and HSPA1A mRNA was further identified using the RNA–protein interaction studies. Reporter gene assays, which depended on the untranslated regions (UTR) of HSPA1A mRNA, revealed that the post-transcriptional regulation was mainly attributed to the 3′ UTR. Finally, HSPA1A anti-sense oligonucleotides (asODNs) attenuated the protective effect of nucleolin in cardiomyocytes. These results indicate that nucleolin is up-regulated and involved in myocardial protection of ischaemic preconditioning via a post-transcriptional control of HSPA1A expression.
Antiproteinase 3 Antineutrophil Cytoplasmic Antibodies and Disease Activity in Wegener Granulomatosis
Authors: Javier D. Finkielman, Peter A. Merkel, Darrell Schroeder, Gary S. Hoffman, Robert Spiera, E. William St. Clair, John C. Davis, W. Joseph McCune, Andrea K. Lears, Steven R. Ytterberg, Amber M. Hummel, Margaret A. Viss, Tobias Peikert, John H. Stone, Ulrich Specks
Journal: Annals of Internal Medicine (2007)

Background: The utility of antineutrophil cytoplasmic antibody (ANCA) levels to guide the management of patients with Wegener granulomatosis remains controversial. Objective: To determine whether pro-proteinase 3 (PR3)–ANCA levels are a better measure of disease activity than mature-PR3–ANCA levels, whether decreases in either level are associated with shorter time to remission, and whether increases are followed by relapse. Design: Prospective, observational cohort study. Setting: 8 United States medical centers that participated in a treatment trial for Wegener granulomatosis. Patients: 156 patients with Wegener granulomatosis enrolled during periods of active disease. Measurements: PR3-ANCA levels (by capture enzyme-linked immunosorbent assay) and disease activity (by the Birmingham Vasculitis Activity Score for Wegener granulomatosis). Results: The ANCA levels were only weakly associated with disease activity across patients. The longitudinal association within patients was stronger, but changes in ANCA levels explained less than 10% of the variation in disease activity. Decreases in mature- and pro-PR3–ANCA levels were not statistically significantly associated with shorter time to remission, and increases in mature-PR3–ANCA levels (adjusted hazard ratio, 0.8 [95% CI, 0.4 to 1.9]; P = 0.67) and pro-PR3–ANCA levels (adjusted hazard ratio, 1.0 [CI, 0.5 to 2.1]; P = 0.99) were not associated with relapse. The proportion of patients who had relapse within 1 year of an increase in PR3-ANCA levels was 40% for mature-PR3 (CI, 18% to 56%) and 43% for pro-PR3 (CI, 22% to 58%). Limitations: Samples were collected approximately every 3 months. Sensitivity and specificity of ANCA levels for detecting remission and relapse could not be calculated because each patient had different follow-up times. Conclusion: Pro-PR3–ANCA is no better than mature-PR3–ANCA as a measure of Wegener granulomatosis activity. Decreases in PR3-ANCA levels are not associated with shorter time to remission, and increases are not associated with relapse. These findings suggest that ANCA levels cannot be used to guide immunosuppressive therapy.
Normal rabbit alveolar macrophages. I. The phagocytosis of tubular myelin.
Authors: B A Nichols
Journal: The Journal of Experimental Medicine (1976)

Normal rabbit alveolar macrophages are engorged with large, dense inclusions which contain whorls of myelin figures, suggesting an exogenous source of polar lipids in their diet. One contributory source of such lipids is surfactant, since macrophages were seen ingesting tubular myelin and vacuoles containing remnants of it were found in the cytoplasm. Thus, as indicated previously in kinetic studies, it appears that alveolar macrophages participate in the turnover of surfactant. However, the relative importance of the macrophage in comparison to other pathways of surfactant removal remains to be determined. It is also noteworthy that although tubular myelin and myelin figures were abundant in the fixative used to wash out the lungs, bacteria were not found in it or in the macrophages. Thus, removal of obsolete surfactant may prove to be one of the mojor endocytic functions of alveolar macrophages.
Activation of inflammasome signaling mediates pathology of acute P. aeruginosa pneumonia
Authors: Taylor S. Cohen, Alice S. Prince
Journal: Journal of Clinical Investigation (2013)

The respiratory tract is exceptionally well defended against infection from inhaled bacteria, with multiple proinflammatory signaling cascades recruiting phagocytes to clear airway pathogens. However, organisms that efficiently activate damaging innate immune responses, such as those mediated by the inflammasome and caspase-1, may cause pulmonary damage and interfere with bacterial clearance. The extracellular, opportunistic pathogen Pseudomonas aeruginosa expresses not only pathogen-associated molecular patterns that activate NF-κB signaling in epithelial and immune cells, but also flagella that activate the NLRC4 inflammasome. We demonstrate that induction of inflammasome signaling, ascribed primarily to the alveolar macrophage, impaired P. aeruginosa clearance and was associated with increased apoptosis/pyroptosis and mortality in a murine model of acute pneumonia. Strategies that limited inflammasome activation, including infection by fliC mutants, depletion of macrophages, deletion of NLRC4, reduction of IL-1β and IL-18 production, inhibition of caspase-1, and inhibition of downstream signaling in IL-1R– or IL-18R–null mice, all resulted in enhanced bacterial clearance and diminished pathology. These results demonstrate that the inflammasome provides a potential target to limit the pathological consequences of acute P. aeruginosa pulmonary infection.