tbuckley/cabot-search huggingface dataset:
Energy-preserving effects of IGF-1 antagonize starvation-induced cardiac autophagy
Authors: Rodrigo Troncoso, Jose Miguel Vicencio, Valentina Parra, Andriy Nemchenko, Yuki Kawashima, Andrea del Campo, Barbra Toro, Pavan K. Battiprolu, Pablo Aranguiz, Mario Chiong, Shoshana Yakar, Thomas G. Gillette, Joseph A. Hill, Evan Dale Abel, Derek LeRoith, Sergio Lavandero
Journal: Cardiovascular Research (2011)

Insulin-like growth factor 1 (IGF-1) is known to exert cardioprotective actions. However, it remains unknown if autophagy, a major adaptive response to nutritional stress, contributes to IGF-1-mediated cardioprotection. We subjected cultured neonatal rat cardiomyocytes, as well as live mice, to nutritional stress and assessed cell death and autophagic rates. Nutritional stress induced by serum/glucose deprivation strongly induced autophagy and cell death, and both responses were inhibited by IGF-1. The Akt/mammalian target of rapamycin (mTOR) pathway mediated the effects of IGF-1 upon autophagy. Importantly, starvation also decreased intracellular ATP levels and oxygen consumption leading to AMP-activated protein kinase (AMPK) activation; IGF-1 increased mitochondrial Ca2+ uptake and mitochondrial respiration in nutrient-starved cells. IGF-1 also rescued ATP levels, reduced AMPK phosphorylation and increased p70S6K phosphorylation, which indicates that in addition to Akt/mTOR, IGF-1 inhibits autophagy by the AMPK/mTOR axis. In mice harbouring a liver-specific igf1 deletion, which dramatically reduces IGF-1 plasma levels, AMPK activity and autophagy were increased, and significant heart weight loss was observed in comparison with wild-type starved animals, revealing the importance of IGF-1 in maintaining cardiac adaptability to nutritional insults in vivo. Our data support the cardioprotective actions of IGF-1, which, by rescuing the mitochondrial metabolism and the energetic state of cells, reduces cell death and controls the potentially harmful autophagic response to nutritional challenges. IGF-1, therefore, may prove beneficial to mitigate damage induced by excessive nutrient-related stress, including ischaemic disease in multiple tissues.
Expression of protease activated receptor-2 (PAR-2) in central airways of smokers and non-smokers
Authors: D Miotto
Journal: Thorax (2002)

Background: Protease activated receptor-2 (PAR-2) is a transmembrane G protein coupled receptor preferentially activated by trypsin and tryptase. The protease activated receptors play an important role in most components of injury responses including cell proliferation, migration, matrix remodelling, and inflammation. Cigarette smoking causes an inflammatory process in the central airways, peripheral airways, lung parenchyma, and adventitia of pulmonary arteries. Methods: To quantify the expression of PAR-2 in the central airways of smokers and non-smokers, surgical specimens obtained from 30 subjects undergoing lung resection for localised pulmonary lesions (24 with a history of cigarette smoking and six non-smoking control subjects) were examined. Central airways were immunostained with an antiserum specific for PAR-2 and PAR-2 expression was quantified using light microscopy and image analysis. Results: PAR-2 expression was found in bronchial smooth muscle, epithelium, glands, and in the endothelium and smooth muscle of bronchial vessels. PAR-2 expression was similar in the central airways of smokers and non-smokers. When smokers were divided according to the presence of symptoms of chronic bronchitis and chronic airflow limitation, PAR-2 expression was increased in smooth muscle (median 3.8 (interquartile range 2.9–5.8) and 1.4 (1.07–3.4) respectively); glands (33.3 (18.2–43.8) and 16.2 (11.5–22.2), respectively); and bronchial vessels (54.2 (48.7–56.8) and 40.0 (36–40.4), respectively) of smokers with symptoms of chronic bronchitis with normal lung function compared with smokers with chronic airflow limitation (COPD), but the increase was statistically significant (p&lt;0.005) only for bronchial vessels. Conclusions: PAR-2 is present in bronchial smooth muscle, glands, and bronchial vessels of both smokers and non-smokers. An increased expression of PAR-2 was found in bronchial vessels of patients with bronchitis compared with those with COPD.
Ovarian cancer.
Authors: James A. Hall
Journal: CA A Cancer Journal for Clinicians (1995)

the algorithm on page 116 neglects the important role of fine-needle aspiration and/or core biopsy whether done by a radiologist or other physician before, if not sparing, the referral of the patient to a surgeon.In fact, a significant percentage of clinical and/or mammographically bothersome findings can be adequately evaluated by these means and many unnecessary surgical biopsies avoided.I would refer your readers to the excellent article "Stereotactic Breast Biopsy" by Robert A.
P-ANCA in monozygotic twins with inflammatory bowel disease.
Authors: P Yang, G Jarnerot, D Danielsson, C Tysk, E Lindberg
Journal: Gut (1995)

Perinuclear antineutrophil cytoplasmic antibodies (P-ANCA) have been demonstrated in patients with ulcerative colitis and in a higher frequency than expected in their first degree relatives. A hypothesis was proposed that P-ANCA is genetically determined and may represent a subclinical marker of genetic susceptibility to ulcerative colitis. This study analysed P-ANCA in monozygotic twins with inflammatory bowel disease to evaluate this hypothesis further. P-ANCA was analysed with indirect immunofluorescence technique in 12 monozygotic twin pairs with ulcerative colitis and 14 twin pairs with Crohn9s disease. Furthermore, the study included 21 non-twin patients with ulcerative colitis, 18 non-twin patients with Crohn9s disease, and 52 healthy controls matched for sex and age. In ulcerative colitis P-ANCA occurred in nine of 14 (64.3%) monozygotic twins and in 13 of 21 (61.9%) non-twin cases, which was significantly different compared with healthy controls who were positive in three of 52 (5.8%) cases (p &lt; 0.0001). P-ANCA was found in two of 10 (20%) healthy twin siblings to twins with ulcerative colitis, which was not significantly different from healthy controls (p = 0.18). The results in Crohn9s disease did not differ from healthy controls. Previous findings of P-ANCA occurring in ulcerative colitis but not in Crohn9s disease are supported. This study does not support the hypothesis that P-ANCA is a subclinical marker of genetic susceptibility to ulcerative colitis.
Predicting Early Failure after Adjuvant Chemotherapy in High-Risk Breast Cancer Patients with Extensive Lymph Node Involvement
Authors: Ian F. Faneyte, Johannes L. Peterse, Harm van Tinteren, Corina Pronk, Elisabeth G. E. de Vries, Sjoerd Rodenhuis, Marc J. van de Vijver
Journal: Clinical Cancer Research (2004)

Abstract Purpose: There is limited knowledge of risk factors for breast cancer recurrence within 2 years. This study aimed to predict early failure and identify high-risk patients for prognostic and therapeutic purposes. Experimental Design: We studied 739 patients from a randomized trial who were &amp;lt;56 years of age and had ≥4 or more positive lymph nodes, no distant metastases, and no previous other malignancies. After complete surgical treatment, patients received conventional-dose anthracycline-based chemotherapy or a high-dose scheme of anthracycline-based plus alkylating chemotherapy. We assessed clinical and (immuno)histological parameters to predict recurrence within 2 years. Results: Early failure occurred in 19% (n = 137). Median survival after early failure was limited to 0.7 year. Estrogen and progesterone receptor negativity and visceral relapse predicted poor prognosis. Early failure was associated with young age, large tumors, high histological grade, angio-invasion, apical node metastasis, and ≥10 involved nodes. Estrogen receptor, progesterone receptor, and p27 negativity; HER2 overexpression; and p53 positivity also predicted early failure. The surgical or chemotherapy regimen and histological type did not. The same parameters except tumor size were associated with early death. Grade III, ≥10 involved nodes, and estrogen receptor negativity were independently associated with early failure and together identified a subset of patients (7%) with 3-fold increased early failure and 5-fold increased early death. Conclusions: Early failure is associated with poor survival. The combination of three commonly determined parameters constitutes a strong predictive model for early failure and death.
Increases in Mitochondrial Reactive Oxygen Species Trigger Hypoxia-Induced Calcium Responses in Pulmonary Artery Smooth Muscle Cells
Authors: Gregory B. Waypa, Robert Guzy, Paul T. Mungai, Mathew M. Mack, Jeremy D. Marks, Michael W. Roe, Paul T. Schumacker
Journal: Circulation Research (2006)

Mitochondria have been implicated as a potential site of O(2) sensing underlying hypoxic pulmonary vasoconstriction (HPV), but 2 disparate models have been proposed to explain their reaction to hypoxia. One model proposes that hypoxia-induced increases in mitochondrial reactive oxygen species (ROS) generation activate HPV through an oxidant-signaling pathway, whereas the other proposes that HPV is a result of decreased oxidant signaling. In an attempt to resolve this debate, we use a novel, ratiometric, redox-sensitive fluorescence resonance energy transfer (HSP-FRET) probe, in concert with measurements of reduced/oxidized glutathione (GSH/GSSG), to assess cytosolic redox responses in cultured pulmonary artery smooth muscle cells (PASMCs). Superfusion of PASMCs with hypoxic media increases the HSP-FRET ratio and decreases GSH/GSSG, indicating an increase in oxidant stress. The antioxidants pyrrolidinedithiocarbamate and N-acetyl-l-cysteine attenuated this response, as well as the hypoxia-induced increases in cytosolic calcium ([Ca(2+)](i)), assessed by the Ca(2+)-sensitive FRET sensor YC2.3. Adenoviral overexpression of glutathione peroxidase or cytosolic or mitochondrial catalase attenuated the hypoxia-induced increase in ROS signaling and [Ca(2+)](i). Adenoviral overexpression of cytosolic Cu, Zn-superoxide dismutase (SOD-I) had no effect on the hypoxia-induced increase in ROS signaling and [Ca(2+)](i), whereas mitochondrial matrix-targeted Mn-SOD (SOD-II) augmented [Ca(2+)](i). The mitochondrial inhibitor myxothiazol attenuated the hypoxia-induced changes in the ROS signaling and [Ca(2+)](i), whereas cyanide augmented the increase in [Ca(2+)](i). Finally, simultaneous measurement of ROS and Ca(2+) signaling in the same cell revealed that the initial increase in these 2 signals could not be distinguished temporally. These results demonstrate that hypoxia triggers increases in PASMC [Ca(2+)](i) by augmenting ROS signaling from the mitochondria.
Hospital admitted COPD patients treated at home using telemedicine technology - a randomized multicentre trial
Authors: Anna S Jakobsen, Lars C Laursen, Birte Østergaard, Susan Rydahl-Hansen, Klaus V Phanareth
Journal: European Respiratory Journal (2012)

Background:  COPD Patients with acute exacerbations are frequently admitted to emergency wards causing the patients to feel anxiety, loss of control and stress, and also causing considerable healthcare costs for the society.   Aim:  We investigated whether patients with COPD exacerbations admitted to a hospital could avoid further admittance and safely be treated at home by means of telemedicine technology (TT).   Methods:  Fifty-seven patients with severe COPD, who fulfilled the inclusion criteria and consented to participate within 24 hours of a hospital admission, were randomised to receive either standard treatment at the hospital or standard treatment at home using TT. The equipment consisted of a video conference system and a webcam, measuring equipment (spirometer, thermometer, and pulsoximeter), 24 hour online web-service, access to oxygen, nebulizer and medical therapy. Two university hospitals participated. Readmission within 30 days after discharge was selected as primary outcome.   Results:  Twenty-nine patients were allocated to the TT group and 28 patients received usual care in the hospital. There were 10 readmissions in each group involving eight patients in the TT group and six patients in the control group. Readmission rate was 27, 6% (95% CI 11, 3 to 43, 9) in the TT group and 21,4% (95% CI 6,2 to 36,6) in the conventional group. No statistically significant differences between groups in readmission rate, use of antibiotics or systemic steroids were seen. No deaths occurred during the study period.   Conclusion:  We propose that a considerable segment of patients with COPD exacerbations admitted to hospital can be safely treated at home using the TT solution.
Inhibition of aldosterone biosynthesis by atriopeptins in rat adrenal cells.
Authors: W B Campbell, M G Currie, P Needleman
Journal: Circulation Research (1985)

The effect of synthetic atriopeptins on basal and stimulated aldosterone secretion was determined in isolated adrenal glomerulosa cells of the rat. Neither atriopeptin I (1-21) or III (1-24, i.e., the Phe-Arg-Tyr carboxy-terminal extension of atriopeptin I) altered basal aldosterone release. However, if the cells were prepared from adrenals of sodium-depleted rats, the basal aldosterone release was increased by 9-fold, compared with cells from normal rats. This elevated release was inhibited by 32% by atriopeptin I and atriopeptin III. Atriopeptin III was more potent than atriopeptin I. Angiotensin II and adrenocorticotropin stimulated the release of aldosterone in a concentration-related manner. Both atriopeptin I and atriopeptin III inhibited the stimulation by the peptides. Atriopeptin I inhibited angiotensin II- and adrenocorticotropin-induced aldosterone production by 50% at concentrations of 12 and 11 nM, respectively, and 0.5 and 0.2 nM, respectively, for atriopeptin III. Potassium-stimulated aldosterone production was also inhibited by atriopeptin I and atriopeptin III with 50% inhibition at concentrations of 10 and 0.4 nM, respectively. Shorter peptides (1-20, 1-19, and 3-19) were equipotent to atriopeptin I (1-21) as inhibitors of angiotensin II-induced steroidogenesis. To determine the site at which atriopeptins inhibit aldosterone synthesis, we used cyanoketone to inhibit 3 beta-hydroxy-dehydrogenase and dissociate the early and late pathways. Angiotensin II (2 nM) increased the synthesis of pregnenolone (early pathway), as well as the conversion of [3H]corticosterone to [3H]aldosterone (late pathway). Atriopeptin III inhibited basal pregnenolone synthesis by 36% and completely blocked angiotensin II-stimulated synthesis. The peptide similarly inhibited the late pathway.(ABSTRACT TRUNCATED AT 250 WORDS)
Is physical activity anti-inflammatory on the airways?
Authors: D. A Mahler
Journal: Thorax (2007)

Further evidence that physical activity may prevent or modify airway inflammation

In this issue of Thorax ( see p 403 ), Shaaban and colleagues1 report an inverse relationship between weekly exercise and bronchial hyperresponsiveness (BHR) in 5518 adults. Participants answered questionnaires on whether “they usually exercised so much that they got out of breath or sweaty” in order to estimate weekly frequency and duration of physical activity. Although this methodology may be difficult to validate, self-report questionnaires are used routinely to obtain information in epidemiological studies. These findings are consistent with the results of two previous studies: Rasmussen and coworkers2 found that decreased physical fitness in childhood was significantly correlated with the development of adolescent asthma over a 10 year period, and Huovinen et al 3 showed in a 17 year study of 262 twins that the …
Cutaneous complications of intravenous drug abuse
Authors: P. Del Giudice
Journal: British Journal of Dermatology (2004)

Injection drug abuse is a world-wide problem responsible for numerous minor to life-threatening and fatal complications. The skin is the tissue most evidently affected by intravenous drug addiction. A wide spectrum of cutaneous complications may occur in intravenous drug users. These include acute or delayed local complications, hypersensitivity reactions, cutaneous manifestations of systemic infections or becoming the site of toxigenic infections. Between 1996 and 2001, in our institution in south-eastern France, we observed cutaneous complications after crushed buprenorphine tablet injections in 13 patients. This paper reviews and classifies adverse effects of parenteral drug abuse on the skin.
Plasma cholesteryl ester transfer protein is predominantly derived from Kupffer cells
Authors: Yanan Wang, Sam van der Tuin, Nathanja Tjeerdema, Andrea D. van Dam, Sander S. Rensen, Tim Hendrikx, Jimmy F.P. Berbée, Biljana Atanasovska, Jingyuan Fu, Menno Hoekstra, Siroon Bekkering, Niels P. Riksen, Wim A. Buurman, Jan Willem Greve, Marten H. Hofker, Ronit Shiri‐Sverdlov, Onno C. Meijer, Johannes W.A. Smit, Louis M. Havekes, Ko Willems van Dijk, Patrick C.N. Rensen
Journal: Hepatology (2015)

The role of Kupffer cells (KCs) in the pathophysiology of the liver has been firmly established. Nevertheless, KCs have been underexplored as a target for diagnosis and treatment of liver diseases owing to the lack of noninvasive diagnostic tests. We addressed the hypothesis that cholesteryl ester transfer protein (CETP) is mainly derived from KCs and may predict KC content. Microarray analysis of liver and adipose tissue biopsies, obtained from 93 obese subjects who underwent elective bariatric surgery, showed that expression of CETP is markedly higher in liver than adipose tissue. Hepatic expression of CETP correlated strongly with that of KC markers, and CETP messenger RNA and protein colocalized specifically with KCs in human liver sections. Hepatic KC content as well as hepatic CETP expression correlated strongly with plasma CETP concentration. Mechanistic and intervention studies on the role of KCs in determining the plasma CETP concentration were performed in a transgenic (Tg) mouse model expressing human CETP. Selective elimination of KCs from the liver in CETP Tg mice virtually abolished hepatic CETP expression and largely reduced plasma CETP concentration, consequently improving the lipoprotein profile. Conversely, augmentation of KCs after Bacille‐Calemette‐Guérin vaccination largely increased hepatic CETP expression and plasma CETP. Also, lipid‐lowering drugs fenofibrate and niacin reduced liver KC content, accompanied by reduced plasma CETP concentration. Conclusions : Plasma CETP is predominantly derived from KCs, and plasma CETP level predicts hepatic KC content in humans.(H epatology 2015;62:1710–1722)
Antigen-capturing Cells Can Masquerade as Memory B Cells
Authors: Jennifer Bell, David Gray
Journal: The Journal of Experimental Medicine (2003)

As well as classically defined switched immunoglobulin isotype-expressing B cells, memory B cells are now thought to include IgM-expressing cells and memory cells that lack B cell lineage markers, such as B220 or CD19. We set out to compare the relative importance of memory B cell subsets with an established flow cytometry method to identify antigen-specific cells. After immunization with PE, we could detect B220+ and, as reported previously, B220− antigen-binding cells (McHeyzer-Williams, L.J., M. Cool, and M.G. McHeyzer-Williams. 2001. J. Immunol. 167:1393–1405). The B220−PE+ cells bore few markers typical of B cells, but resembled myeloid cells. Further analysis of the antigen-binding characteristics of these cells showed that, upon immunization with two fluorescent proteins, the B220− cells could bind both. Furthermore, this subpopulation was detected in RAG1−/− mice after transfer of anti-PE mouse serum. These data strongly suggest that these cells capture serum Ig, via Fc receptors, and thus appear antigen-specific. Investigation of these antigen-capturing cells in a variety of knockout mice indicates that they bind monomeric IgG in an FcγR1 (CD64)–dependent manner. We find no evidence of a B220− memory B cell population that is not explicable by antigen-capturing cells, and warn that care must be taken when using antigen-specificity or surface IgG as an indicator of B cell memory.
High plasma concentrations of human urotensin II do not alter local or systemic hemodynamics in man
Authors: I Wilkinson
Journal: Cardiovascular Research (2002)

Objective: Human urotensin II (hUII) is an endocrine hormone that acts as a potent arterial vasoconstrictor in both in vitro and in vivo studies in animals. We examined, for the first time, the local and systemic hemodynamic response to hUII in man in vivo. Methods: Four healthy male volunteers took part in pilot studies and 11 in definitive studies. Forearm blood flow (FBF) was measured in response to intra-arterial infusion of authentic, biologically active hUII (incremental rates of 0.001–300 pmol min−1) and saline placebo using venous occlusion plethysmography. Blood pressure, heart rate, cardiac output and hUII plasma concentrations were also measured. Forearm studies were repeated in five subjects with inhibition of endothelial mediators using aspirin and a "nitric oxide clamp". Dorsal hand vein diameter was determined by a standard displacement technique in response to local administration of hUII (3–300 pmol min−1) with and without nitric oxide synthase inhibition. Results: There was no significant change in FBF during brachial infusion of saline or hUII (dose range, 0.001 to 300 pmol min−1). A nitric oxide clamp did not unmask vasoactive effects of hUII. Human UII infusions (100 and 300 pmol min−1) significantly increased plasma hUII concentrations from baseline (12±3 pmol l−1) to 106±15 and 307±98 pmol l−1, respectively. Despite high circulating hUII concentrations, no change was seen in systemic hemodynamics and ECGs were unchanged. Human UII had no effect on hand vein diameter (n=6). Conclusions: In contrast to our hypothesised role of hUII, we found no vasoactive responses to hUII in vivo, consistent with recent in vitro studies in human blood vessels, but in contrast to non-human primate studies in vivo. Our data do not support a key role for hUII in the regulation of vascular tone and resting blood pressure in man. However, studies with hUII receptor antagonists are also needed before firm conclusions can be drawn.
Addiction Circuitry in the Human Brain
Authors: Nora D. Volkow, Gene-Jack Wang, Joanna S. Fowler, Dardo Tomasi
Journal: The Annual Review of Pharmacology and Toxicology (2011)

A major challenge in understanding substance-use disorders lies in uncovering why some individuals become addicted when exposed to drugs, whereas others do not. Although genetic, developmental, and environmental factors are recognized as major contributors to a person's risk of becoming addicted, the neurobiological processes that underlie this vulnerability are still poorly understood. Imaging studies suggest that individual variations in key dopamine-modulated brain circuits, including circuits involved in reward, memory, executive function, and motivation, contribute to some of the differences in addiction vulnerability. A better understanding of the main circuits affected by chronic drug use and the influence of social stressors, developmental trajectories, and genetic background on these circuits is bound to lead to a better understanding of addiction and to more effective strategies for the prevention and treatment of substance-use disorders.