tbuckley/cabot-search huggingface dataset:
PRODUCTION OF INFLAMMATORY CHANGES IN THE MICROCIRCULATION BY CATIONIC PROTEINS EXTRACTED FROM LYSOSOMES
Authors: Aaron Janoff, Benjamin W. Zweifach
Journal: The Journal of Experimental Medicine (1964)

Lysosomal granules of rabbit exudate polymorphonuclear (PMN) leucocytes were isolated and then lysed by freezing-thawing. Topical application of this material to rat and rabbit mesentery produced sticking and emigration of leucocytes, stasis of blood flow, and petechial hemorrhage. The granule-free, supernatant fraction of the homogenized leucocytes failed to produce any of these reactions. Cationic proteins extracted from these granules by weak acid and precipitated by ethanol at concentrations of 20 and 45 per cent, were also tested on heterologous, homologous, and autologous mesenteric vessels. The 20 per cent ethanol-precipitated fraction produced all of the aforementioned injury reactions, whereas the 45 per cent fraction was inactive. The intensity of inflammatory changes produced by the active cationic protein fraction was greater than that produced by lysed whole granules. Both the 20 per cent and 45 per cent ethanol fractions of cationic protein induced clumping of rabbit platelets, in vitro. The 20 per cent ethanol fraction also caused a slight acceleration in rate of swelling of isolated rabbit liver mitochondria. The active material proved to be non-pyrogenic in rabbits. This material exhibited no kinin-like effects when tested on isolated smooth muscle preparations (rabbit aorta and guinea pig ileum). In the rat, the protein produced a transient vasodepression which was inhibited by pretreatment of the animal with an antihistamine. Ultraviolet absorption data and ribose assays showed that the 20 per cent ethanol fraction contained only 4 per cent or less of ribonucleic acid. Upon electrophoresis in starch gel, using acid buffer, this fraction separated into at least three major components which migrated towards the cathode. Precipitation of one of the slowly migrating components by titration of the fraction to pH 10.5 greatly increased the inflammatory activity of the material. The inflammatory basic protein fraction was essentially devoid of acid phosphatase, beta glucuronidase, acid ribonuclease, lysozyme, and catalase activity. The non-inflammatory basic protein fraction contained appreciable quantities of acid ribonuclease and lysozyme. The foregoing data demonstrate that certain of the cationic proteins present in lysosomes of rabbit exudate PMN leucocytes can reproduce one of the cardinal features of the inflammatory response; namely, adhesion and emigration of leucocytes in the microcirculation. These findings offer fresh support for the role of lysosomes in the pathogenesis of tissue injury, and may help to account for the propagation of leucocyte emigration to peak numbers during inflammatory reactions.
Resistance and Venous Oxygen Dynamics during Sinusoidal Exercise of Dog Skeletal Muscle
Authors: DAVID E. MOHRMAN, HARVEY V. SPARKS
Journal: Circulation Research (1973)

We observed the response of vascular resistance and venous oxygen (O 2 ) saturation to sinusoidally modulated continuous exercise of the isolated dog calf. Stimulus frequency was varied sinusoidally between 0.5 Hz and 1 Hz with modulation frequencies ranging from 0.005 Hz to 0.05 Hz. Venous O 2 responses were corrected for dispersion due to vascular and catheter transit. As modulation frequency was increased, the amplitude of the response of both resistance and venous O 2 to changing stimulation frequency decreased. The dynamics of the resistance response depended on flow rate. At high constant flow (56 ±8 ml/100 g min -1 ) the resistance response followed higher modulation frequencies without loss of amplitude (Bode corner frequency = 0.016 ± 0.003 Hz) than it did at low constant flow (25 ± 7 ml/100 g min -1 ) (Bode corner frequency = 0.0049 ± 0.0006 Hz). The dynamics of the venous Osaturation response were not significantly altered by flow. In the low constant-flow range, vascular resistance and venous O 2 saturation had similar dynamics in response to sinusoidal modulation of exercise rate. This finding indicates that oxidative metabolism may be linked to the resistance changes at low flow. At high constant flow, however, the vascular resistance response followed higher modulation frequencies without loss of amplitude than did venous O 2 saturation in three of four dogs. Given certain assumptions, it is doubtful that changes in oxidative metabolism are linked to changes in vascular resistance at high constant flow. Vascular resistance, under the conditions of this experiment, appeared to be controlled by at least two mechanisms, the slower of which may be related to oxidative metabolism.
Histone acetyltransferase PCAF Up-regulated cell apoptosis in hepatocellular carcinoma via acetylating histone H4 and inactivating AKT signaling
Authors: Xin Zheng, Xiaohong Gai, Feihu Ding, Zhongtang Lu, Kangsheng Tu, Yingmin Yao, Qingguang Liu
Journal: Molecular Cancer (2013)

Abstract Background PCAF is an important intrinsic histone acetyltransferases. This study tried to establish the effect of PCAF on HCC cell apoptosis. Method Both in vitro and in vivo experiments including IHC, DAPI staining, caspase 3/7 activity assay, BrdU assay, MTT assay, western immunoblotting and co-immunoprecipitation were used here. Results PCAF was found to be expressed at the low level in most of HCC cell lines. PCAF overexpression induced cell apoptosis and growth arrest with increased Histone H4 acetylation and inactivation of AKT signaling in Huh7 and HepG2 cells. The opposite results were obtained by silencing PCAF in Hep3B cells. The co-immunoprecipitation assay confirmed that PCAF protein was bound with histone H4 protein in the nucleus of Hep3B cells. Finally, the in vivo experiment confirmed the findings mentioned-above. Conclusion These data identified PCAF promotes cell apoptosis and functions as a HCC repressor through acetylating histone H4 and inactivating AKT signaling.
Behaviour of IgG antibody avidity for the antigen and of IgA antibody in active cytomegalovirus, Epstein-Barr virus, herpes simplex virus and human herpes virus 6 infections. Adaptation of a commercial test
Authors: J. Gutiérrez, M. Rodríguez, M.C. Maroto, G. Piédrola, J. Peirón
Journal: Journal of Infection (1997)
International Union of Pharmacology. XXXV. The Glucagon Receptor Family
Authors: Kelly E. Mayo, Laurence J. Miller, Dominique Bataille, Stéphane Dalle, Burkhard Göke, Bernard Thorens, Daniel J. Drucker
Journal: Pharmacological Reviews (2003)

Peptide hormones within the secretin-glucagon family are expressed in endocrine cells of the pancreas and gastrointestinal epithelium and in specialized neurons in the brain, and subserve multiple biological functions, including regulation of growth, nutrient intake, and transit within the gut, and digestion, energy absorption, and energy assimilation. Glucagon, glucagon-like peptide-1, glucagon-like peptide-2, glucose-dependent insulinotropic peptide, growth hormone-releasing hormone and secretin are structurally related peptides that exert their actions through unique members of a structurally related G protein-coupled receptor class 2 family. This review discusses advances in our understanding of how these peptides exert their biological activities, with a focus on the biological actions and structural features of the cognate receptors. The receptors have been named after their parent and only physiologically relevant ligand, in line with the recommendations of the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR).
Harnessing the Power of the Placebo Effect and Renaming It “Remembered Wellness”
Authors: Herbert Benson, M.D, Richard Friedman, Ph.D
Journal: Annual Review of Medicine (1996)

▪ Abstract The placebo effect yields beneficial clinical results in 60–90% of diseases that include angina pectoris, bronchial asthma, herpes simplex, and duodenal ulcer. Three components bring forth the placebo effect: (a) positive beliefs and expectations on the part of the patient; (b) positive beliefs and expectations on the part of the physician or health care professional; and (c) a good relationship between the two parties. Because of the heavily negative connotations of the very words “placebo effect,” the term should be replaced by “remembered wellness.” Remembered wellness has been one of medicine's most potent assets and it should not be belittled or ridiculed. Unlike most other treatments, it is safe and inexpensive and has withstood the test of time.
Thrombocytogenesis in Surgical Patients
Authors: JOHN A. WILLIAMS, JOHN S. BELKO, RICHAHD WARREN
Journal: Circulation Research (1955)

Comparative studies of peripheral blood and bone marrow have shown that the postoperative marked and sustained reduction of blood platelets is accompanied by a block in the mechanism of delivery of platelets into the blood stream and a delay in maturation of blast cells of the megakaryocyte lineage.
Bltr Mediates Leukotriene B4–Induced Chemotaxis and Adhesion and Plays a Dominant Role in Eosinophil Accumulation in a Murine Model of Peritonitis
Authors: Andrew M. Tager, Jennifer H. Dufour, Katayoon Goodarzi, Scott D. Bercury, Ulrich H. von Andrian, Andrew D. Luster
Journal: The Journal of Experimental Medicine (2000)

Leukotriene B4 (LTB4) is a potent chemoattractant active on multiple leukocytes, including neutrophils, macrophages, and eosinophils, and is implicated in the pathogenesis of a variety of inflammatory processes. A seven transmembrane–spanning, G protein–coupled receptor, called BLTR (LTB4 receptor), has recently been identified as an LTB4 receptor. To determine if BLTR is the sole receptor mediating LTB4-induced leukocyte activation and to determine the role of LTB4 and BLTR in regulating leukocyte function in inflammation in vivo, we generated a BLTR-deficient mouse by targeted gene disruption. This mouse reveals that BLTR alone is responsible for LTB4-mediated leukocyte calcium flux, chemotaxis, and firm adhesion to endothelium in vivo. Furthermore, despite the apparent functional redundancy with other chemoattractant–receptor pairs in vitro, LTB4 and BLTR play an important role in the recruitment and/or retention of leukocytes, particularly eosinophils, to the inflamed peritoneum in vivo. These studies demonstrate that BLTR is the key receptor that mediates LTB4-induced leukocyte activation and establishes a model to decipher the functional roles of BLTR and LTB4 in vivo.
Assessment of acute spinal inflammation in patients with ankylosing spondylitis by magnetic resonance imaging: a comparison between contrast enhanced T1 and short tau inversion recovery (STIR) sequences
Authors: X Baraliakos
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objectives:</b> To compare the performance of two different MRI sequences—T<sub>1</sub> weighted, fat saturated, spin echo after application of contrast medium, and short τ inversion recovery (STIR) sequences—to detect spinal inflammation in patients with ankylosing spondylitis (AS). <b>Methods:</b> Both MRI sequences were performed in 38 patients with active AS and compared using the MRI activity scoring system, ASspiMRI-a. One vertebral unit (VU) was defined as the region between two virtual lines drawn through the middle of each vertebral body. <b>Results:</b> Intraclass correlation coefficients were excellent—0.91 and 0.86 for the Gd-DTPA and STIR sequences, respectively. The overall correlation of the single MRI scores for both sequences was also good (<i>r</i> = 0.84, p = 0.01). The intrarater variance was 6.71 and 9.41 and the interrater variance was 13.16 and 19.04 for the Gd-DTPA and STIR sequences, respectively. The smallest detectable distance was 4.7 and 5.6 for the Gd-DTPA and STIR sequences, respectively. The concordance rate for both sequences was 83.5% (range 80.5–87.7% in the three spinal segments). Inflammatory spinal lesions were found in 10.1% of the VUs in the STIR sequence but not in the T<sub>1</sub>/Gd-DTPA sequence, while the T<sub>1</sub>/Gd-DTPA sequence showed inflammatory lesions in 6.4% of the VUs that were found normal by STIR. <b>Conclusions:</b> Both MRI techniques can evaluate active spinal lesions in patients with AS. More spinal lesions are detected by the STIR sequence, but the reliability between readings and readers is better for the Gd-DTPA sequence. The ASspiMRI-a is a reliable instrument for evaluating acute spinal changes in AS.
Challenges in initiating and conducting personalized cancer therapy trials: perspectives from WINTHER, a Worldwide Innovative Network (WIN) Consortium trial
Authors: J. Rodon, J.C. Soria, R. Berger, G. Batist, A. Tsimberidou, C. Bresson, J.J. Lee, E. Rubin, A. Onn, R.L. Schilsky, W.H. Miller, A.M. Eggermont, J. Mendelsohn, V. Lazar, R. Kurzrock
Journal: Annals of Oncology (2015)
Efficacy of sulfasalazine in patients with inflammatory back pain due to undifferentiated spondyloarthritis and early ankylosing spondylitis: a multicentre randomised controlled trial
Authors: J Braun, J Zochling, X Baraliakos, R Alten, G Burmester, K Grasedyck, J Brandt, H Haibel, M Hammer, A Krause, F Mielke, H-P Tony, W Ebner, B Gomor, J Hermann, H Zeidler, E Beck, M Baumgaertner, J Sieper
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objectives:</b> To assess the effect of sulfasalazine (SSZ) on inflammatory back pain (IBP) due to active undifferentiated spondyloarthritis (uSpA) or ankylosing spondylitis in patients with symptom duration &lt;5 years. <b>Methods:</b> Patients with IBP and a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) &gt;3 from 12 centres were randomly assigned to 24 weeks' treatment with SSZ 2 g/day or placebo. The primary outcome variable was the change in BASDAI over 6 months. Secondary outcomes included measures of spinal pain, physical function and inflammation. <b>Results:</b> 230 patients (50% men, age range 18–64 years, 67% human leucocyte antigen B27 positive) were treated with either SSZ 2×1 g/day or placebo for 6 months. Enthesitis was found in 50%, and peripheral arthritis in 47% of the patients. The mean (SD) BASDAI dropped markedly in both groups: by 3.7 (2.7) and 3.8 (2.4), respectively, as did most secondary outcome measures. No noticeable difference in treatment was observed between groups. Patients with IBP and no peripheral arthritis had significantly (p = 0.03) more benefit with SSZ (BASDAI 5.1 (1.3) to 2.8 (2.3)) than with placebo (5.2 (1.6) to 3.8 (2.4)). Spinal pain (p = 0.03) and morning stiffness (p = 0.05) improved with SSZ in these patients, but other secondary outcomes were not markedly different. <b>Conclusion:</b> SSZ was no better than placebo for the treatment of the signs and symptoms of uSpA; however, SSZ was more effective than placebo in the subgroup of patients with IBP and no peripheral arthritis.
Glucose metabolism and diet-based prevention of liver dysfunction in MPV17 mutant patients
Authors: Rossella Parini, Francesca Furlan, Luigi Notarangelo, Antonella Spinazzola, Graziella Uziel, Pietro Strisciuglio, Daniela Concolino, Carlo Corbetta, Gabriella Nebbia, Francesca Menni, Giorgio Rossi, Marco Maggioni, Massimo Zeviani
Journal: Journal of Hepatology (2008)

To describe in detail the specific clinical and biological characteristics of three patients with MPV17 gene mutations, a rare hepatocerebral mitochondrial DNA depletion syndrome (MDS) and the positive effects of a novel dietetic treatment based on avoidance of fasting.We describe the case histories of three members of the same family with MPV17 mutations.Two patients had a very severe and progressive liver disease: 1 died in the first year of life and the other underwent liver transplantation. The third patient, now 13 years of age, had a milder form of liver disease and developed progressive ataxia. Psychomotor involvement at onset of disease was mild or absent. No patient had severe hyperlactataemia. In vivo functional studies on two patients showed no hyperlactataemia even after intravenous and oral glucose loading, regular fasting hypoglycemia 3-4h after meals and no response to glucagon. Liver function tests improved when patients received continuous iv glucose infusion or were regularly fed every 3h.These clinical and biochemical features allow us to differentiate patients with MPV17 mutations from other liver MDS and suggest that regular glucose intake at short intervals may be beneficial in slowing the progression of the disease.
Sarcolemmal K <sub>ATP</sub> Channel Triggers Opioid-Induced Delayed Cardioprotection in the Rat
Authors: Hemal H. Patel, Anna K. Hsu, Jason N. Peart, Garrett J. Gross
Journal: Circulation Research (2002)

Recently, the involvement of sarcolemmal K ATP (sarcK ATP ) channels in ischemic and pharmacological preconditioning (IPC and PPC) has been minimized by numerous studies suggesting a primary role for mitochondrial K ATP (mitoK ATP ) channels in early and delayed cardioprotection. Although the mitoK ATP channel has clearly been shown to be a distal effector of delayed IPC and PPC, studies implicating it as a trigger of protection in delayed IPC are lacking. Accordingly, we characterized the role of cardiac K ATP channels as triggers or distal effectors of delayed cardioprotection induced by opioids in rats, and the data suggest that the sarcK ATP channel triggers and that the mitoK ATP channel is a distal effector of opioid-induced delayed cardioprotection.
Reflex Hemodynamic Responses Initiated from the Thoracic Aorta
Authors: FRANCO LIOY, ALBERTO MALLIANI, MASSIMO PAGANI, GIORGIO RECORDATI, PETER J. SCHWARTZ
Journal: Circulation Research (1974)

In anesthetized vagotomized cats with both carotid arteries occluded, stretch of the walls of the thoracic aorta performed without obstructing aortic blood flow induced reflex increases in arterial blood pressure (systolic: 136 ± 4 [ SE ] to 170 ± 7 mm Hg), heart rate (230 ± 10 to 236 ± 11 beats/min), and maximum rate of rise of left ventricular pressure (dP/dt max) (2,337 ± 256 to 3,155 ± 302 mm Hg/sec). In cats with spinal transection (C 1 ), similar increases were observed. These responses were abolished by infiltrating the walls of the thoracic aorta with xylocaine. In adrenalectomized cats with intact central nervous systems, reflex responses were reduced but were still statistically significant. Phenoxybenzamine abolished the pressor response but not the increases in heart rate and dP/dt max. Propranolol drastically reduced the increases in heart rate and dP/dt max but not the pressor response. It is concluded that stretch of the thoracic aorta induced an increase in sympathetic activity affecting the heart, the peripheral vessels, and, probably, the adrenal glands through a spinal reflex.
PROSTATECTOMY IX GENERALESPECIALLY BY THE PERINEAL ROUTE.
Authors: GEORGE GOODFELLOW
Journal: JAMA (1904)

servatism.I admire conservatism, but when a gynecologist is sent for in 'a case requiring cesarean section he is beUer prepared to do that operation and save the life of both mother and child than by the old-fashioned way of bringing down a leg.With regard to the question of election in surgery: The time was when in a case of appendicitis three-fourihs of the profession advocated conservatism.Now we operate in every case.
Stability in community-acquired pneumonia: one step forward with markers?
Authors: R Menendez, R Martinez, S Reyes, J Mensa, E Polverino, X Filella, C Esquinas, A Martinez, P Ramirez, A Torres
Journal: Thorax (2009)

Biological markers as an expression of systemic inflammation have been recognised as useful for evaluating the host response in community-acquired pneumonia (CAP). The objective of this study was to evaluate whether the biological markers procalcitonin (PCT) and C-reactive protein (CRP) might reflect stability after 72 h of treatment and the absence of subsequent severe complications.A prospective cohort study was performed in 394 hospitalised patients with CAP. Clinical stability was evaluated using modified Halm's criteria: temperature <or=37.2 degrees C; heart rate <or=100 beats/min; respiratory rate <or=24 breaths/min; systolic blood pressure >or=90 mm Hg; oxygen saturation >or=90%; or arterial oxygen tension >or=60 mm Hg. PCT and CRP levels were measured on day 1 and after 72 h. Severe complications were defined as mechanical ventilation, shock and/or intensive care unit (ICU) admission, or death after 72 h of treatment.220 patients achieved clinical stability at 72 h and had significantly lower levels of CRP (4.2 vs 7 mg/dl) and of PCT (0.33 vs 0.48 ng/ml). Regression logistic analyses were performed to calculate several areas under the ROC curve (AUC) to predict severe complications. The AUC for clinical stability was 0.77, 0.84 when CRP was added (p = 0.059) and 0.77 when PCT was added (p = 0.45). When clinical stability was achieved within 72 h and marker levels were below the cut-off points (0.25 ng/ml for PCT and 3 mg/dl for CRP), no severe complications occurred.Low levels of CRP and PCT at 72 h in addition to clinical criteria might improve the prediction of absence of severe complications.
PPARα activation is essential for HCV core protein–induced hepatic steatosis and hepatocellular carcinoma in mice
Authors: Naoki Tanaka, Kyoji Moriya, Kendo Kiyosawa, Kazuhiko Koike, Frank J. Gonzalez, Toshifumi Aoyama
Journal: Journal of Clinical Investigation (2008)

Transgenic mice expressing HCV core protein develop hepatic steatosis and hepatocellular carcinoma (HCC), but the mechanism underlying this process remains unclear. Because PPARalpha is a central regulator of triglyceride homeostasis and mediates hepatocarcinogenesis in rodents, we determined whether PPARalpha contributes to HCV core protein-induced diseases. We generated PPARalpha-homozygous, -heterozygous, and -null mice with liver-specific transgenic expression of the core protein gene (Ppara(+/+):HCVcpTg, Ppara(+/-):HCVcpTg, and Ppara(-/-):HCVcpTg mice. Severe steatosis was unexpectedly observed only in Ppara(+/+):HCVcpTg mice, which resulted from enhanced fatty acid uptake and decreased mitochondrial beta-oxidation due to breakdown of mitochondrial outer membranes. Interestingly, HCC developed in approximately 35% of 24-month-old Ppara(+/+):HCVcpTg mice, but tumors were not observed in the other genotypes. These phenomena were found to be closely associated with sustained PPARalpha activation. In Ppara(+/-):HCVcpTg mice, PPARalpha activation and the related changes did not occur despite the presence of a functional Ppara allele. However, long-term treatment of these mice with clofibrate, a PPARalpha activator, induced HCC with mitochondrial abnormalities and hepatic steatosis. Thus, our results indicate that persistent activation of PPARalpha is essential for the pathogenesis of hepatic steatosis and HCC induced by HCV infection.