tbuckley/cabot-search huggingface dataset:
Carotid sinus baroreceptor reflex control of the circulation in medial sclerotic and renal hypertensive rabbits and its modification by the aortic baroreceptors.
Authors: J E Angell-James, M J George
Journal: Circulation Research (1980)

We studied the reflex control of blood pressure, heart rate, and hindlimb vascular resistance by the carotid sinus baroreceptors in normal (N), experimental renal hypertensive (RH, one kidney renal wrap model), and medial sclerotic (MS) rabbits under urethane anaesthesia using an isolated perfused carotid sinus preparation and auto-perfused hindlimb. The contralateral carotid sinus was denervated. Compared to N rabbits, the blood pressure and hindlimb vascular resistance of RH and MS rabbits were significantly elevated at all carotid sinus pressures 15 weeks after inducing the disease process. The maximum gains of the curves relating carotid sinus pressure to vascular resistance were significantly elevated in the MS and RH rabbits, but those relating carotid sinus pressure to heart rate were significantly reduced. The changes were greatest in the RH group in which the responses also were set to a higher carotid sinus pressure. In the three groups, division of the aortic nerves produced different changes in the sigmoid curves relating carotid sinus pressure to heart rate, blood pressure, and vascular resistance. There was a linear relationship between blood pressure and basal vascular resistance (correlation coefficient 0.88).
Carotid body inflammation and cardiorespiratory alterations in intermittent hypoxia
Authors: Rodrigo Del Rio, Esteban A. Moya, María J. Parga, Carlos Madrid, Rodrigo Iturriaga
Journal: European Respiratory Journal (2011)

Chronic intermittent hypoxia (CIH), a main feature of obstructive sleep apnoea (OSA), increases hypoxic ventilatory responses and elicits hypertension, partially attributed to an enhance carotid body (CB) responsiveness to hypoxia. As inflammation has been involved in CIH-induced hypertension and chemosensory potentiation, we tested whether ibuprofen may block CB chemosensory and cardiorespiratory alterations induced by CIH in a rat model of OSA. We studied the effects of ibuprofen (40 mg·kg −1 ·day −1 ) on immunohistochemical interleukin (IL)-1β and tumour necrosis factor (TNF)-α levels in the CB, the number of c-fos-positive neurons in the nucleus tractus solitarii (NTS), CB chemosensory and ventilatory responses to hypoxia, and arterial blood pressure in male rats either exposed for 21 days to 5% O 2 (12 episodes·h −1 , 8 h·day −1 ) or kept under sham condition. CIH increased CB TNF-α and IL-1β and c-fos-positive neurons in the NTS, enhanced carotid chemosensory and ventilatory hypoxic responses, and produced hypertension. Ibuprofen prevented CB cytokine overexpression and CIH-induced increases in c-fos-positive neurons in the NTS, the enhanced hypoxic ventilatory responses and hypertension, but failed to impede the CB chemosensory potentiation. Results suggest that pro-inflammatory cytokines may contribute to the CIH-induced cardiorespiratory alterations, acting at several levels of the hypoxic chemoreflex and cardiovascular control pathways.
A randomized, double-blind, multicentre study comparing daily 2 and 5 mg of tropisetron for the control of nausea and vomiting induced by low-dose cisplatin- or non-cisplatin-containing chemotherapy
Authors: A.N.M. Wymenga, W.T.A. van der Graaf, J.A. Wils, L. Siegenbeek van Heukelom, G.H.M. van der Linden, A.C. Dullemond-Westland, M. Nooy, C. van der Heul, K.M. de Bruijn, E.G.E. de Vries
Journal: Annals of Oncology (1996)
Acidosis Mediates the Upregulation of UT-A Protein in Livers from Uremic Rats
Authors: Janet D Klein, Patricia Rouillard, Brian R Roberts, Jeff M Sands
Journal: Journal of the American Society of Nephrology (2002)

Liver expresses a 49-kD UT-A protein whose abundance is increased by uremia. Chronic renal failure causes acidosis; therefore, the role of acidosis in increasing UT-A abundance was tested. Rats underwent 5/6 nephrectomy, and half were given bicarbonate mixed in their food. Bicarbonate administration significantly increased blood pH. Compared with sham-operated rats, UT-A protein abundance was significantly increased by 50% in livers from uremic, acidotic rats; bicarbonate administration prevented the increase in UT-A protein. To determine whether acidosis alone would increase UT-A protein in liver, rats were made acidotic, but not uremic, by feeding them HCl. HCl-feeding significantly lowered blood pH, increased urea excretion, and increased the abundance of the 49-kD liver UT-A protein by 36% compared with pair-fed nonacidotic rats. HCl-feeding significantly increased the abundance of the 117-kD UT-A1 protein in kidney inner medulla but did not change aquaporin-2 protein. Next, rats were fed urea to determine whether elevated blood urea would increase UT-A protein. However, urea feeding had no effect on UT-A in liver or kidney inner medulla. It was, therefore, concluded that acidosis, either directly or through a change in ammonium concentration, rather than other dietary components, stimulates the upregulation of UT-A protein in liver and kidney inner medulla.
Gleason Score and Lethal Prostate Cancer: Does 3 + 4 = 4 + 3?
Authors: Jennifer R. Stark, Sven Perner, Meir J. Stampfer, Jennifer A. Sinnott, Stephen Finn, Anna S. Eisenstein, Jing Ma, Michelangelo Fiorentino, Tobias Kurth, Massimo Loda, Edward L. Giovannucci, Mark A. Rubin, Lorelei A. Mucci
Journal: Journal of Clinical Oncology (2009)

Purpose Gleason grading is an important predictor of prostate cancer (PCa) outcomes. Studies using surrogate PCa end points suggest outcomes for Gleason score (GS) 7 cancers vary according to the predominance of pattern 4. These studies have influenced clinical practice, but it is unclear if rates of PCa mortality differ for 3 + 4 and 4 + 3 tumors. Using PCa mortality as the primary end point, we compared outcomes in Gleason 3 + 4 and 4 + 3 cancers, and the predictive ability of GS from a standardized review versus original scoring. Patients and Methods Three study pathologists conducted a blinded standardized review of 693 prostatectomy and 119 biopsy specimens to assign primary and secondary Gleason patterns. Tumor specimens were from PCa patients diagnosed between 1984 and 2004 from the Physicians' Health Study and Health Professionals Follow-Up Study. Lethal PCa (n = 53) was defined as development of bony metastases or PCa death. Hazard ratios (HR) were estimated according to original GS and standardized GS. We compared the discrimination of standardized and original grading with C-statistics from models of 10-year survival. Results For prostatectomy specimens, 4 + 3 cancers were associated with a three-fold increase in lethal PCa compared with 3 + 4 cancers (95% CI, 1.1 to 8.6). The discrimination of models of standardized scores from prostatectomy (C-statistic, 0.86) and biopsy (C-statistic, 0.85) were improved compared to models of original scores (prostatectomy C-statistic, 0.82; biopsy C-statistic, 0.72). Conclusion Ignoring the predominance of Gleason pattern 4 in GS 7 cancers may conceal important prognostic information. A standardized review of GS can improve prediction of PCa survival.
Developing MicroRNA Therapeutics
Authors: Eva van Rooij, Angela L. Purcell, Arthur A. Levin
Journal: Circulation Research (2012)

Rarely a new research area has gotten such an overwhelming amount of attention as have microRNAs. Although several basic questions regarding their biological principles still remain to be answered, many specific characteristics of microRNAs in combination with compelling therapeutic efficacy data and a clear involvement in human disease have triggered the biotechnology community to start exploring the possibilities of viewing microRNAs as therapeutic entities. This review serves to provide some general insight into some of the current microRNAs targets, how one goes from the initial bench discovery to actually developing a therapeutically useful modality, and will briefly summarize the current patent landscape and the companies that have started to explore microRNAs as the next drug target.
Different Patterns Of IgE Recognition To Amoxicillin In Patients With Immediate Hypersensitivity Reactions
Authors: A. Ariza, C. Mayorga, I. Doña, F. Gomez, E. Perez-Inestrosa, M.I. Montañez, J.L. Rodriguez-Bada, M.A. Guerrero, M. Blanca, M.J. Torres
Journal: Journal of Allergy and Clinical Immunology (2011)
Arteriosclerotic Vascular Disease and Testicular Fibrosis
Authors: FREDERIC G. DALLDORF
Journal: Circulation (1961)

The autopsy protocols and sections of the testes were examined in a group of 199 men over the age of 35 years who were free of known causes of either vascular disease or testicular fibrosis. In 44 (22 per cent) of the cases, testicular sections showed marked fibrosis of the peritubular membranes or complete hyalinization. Testes of the remaining men showed minimal or no signs of testicular fibrosis. Of these 155 patients with normal or minimally fibrotic testes, 47 (30.7 per cent) had complications of arteriosclerotic vascular disease (i.e., myocardial or cerebral infarcts, arteriosclerotic aneurysms, etc.) and in 36 cases (23.5 per cent) those complications were considered to be the cause of death. Of the 44 cases with advanced testicular fibrosis, four (9.1 per cent) had complications of arteriosclerotic vascular disease and only one patient (2.2 per cent) died of the disease. An interpretation of these findings is presented.
Familial Aggregation of Common Sequence Variants on 15q24-25.1 in Lung Cancer
Authors: Pengyuan Liu, Haris G. Vikis, Daolong Wang, Yan Lu, Yian Wang, Ann G. Schwartz, Susan M. Pinney, Ping Yang, Mariza de Andrade, Gloria M. Petersen, Jonathan S. Wiest, Pamela R. Fain, Adi Gazdar, Colette Gaba, Henry Rothschild, Diptasri Mandal, Teresa Coons, Juwon Lee, Elena Kupert, Daniela Seminara, John Minna, Joan E. Bailey-Wilson, Xifeng Wu, Margaret R. Spitz, Timothy Eisen, Richard S. Houlston, Christopher I. Amos, Marshall W. Anderson, Ming You
Journal: JNCI Journal of the National Cancer Institute (2008)

Three recent genome-wide association studies identified associations between markers in the chromosomal region 15q24-25.1 and the risk of lung cancer. We conducted a genome-wide association analysis to investigate associations between single-nucleotide polymorphisms (SNPs) and the risk of lung cancer, in which we used blood DNA from 194 case patients with familial lung cancer and 219 cancer-free control subjects. We identified associations between common sequence variants at 15q24-25.1 (that spanned LOC123688 [a hypothetical gene], PSMA4 , CHRNA3 , CHRNA5 , and CHRNB4 ) and lung cancer. The risk of lung cancer was more than fivefold higher among those subjects who had both a family history of lung cancer and two copies of high-risk alleles rs8034191 (odds ratio [OR] = 7.20, 95% confidence interval [CI] = 2.21 to 23.37) or rs1051730 (OR = 5.67, CI = 2.21 to 14.60, both of which were located in the 15q24-25.1 locus, than among control subjects. Thus, further research to elucidate causal variants in the 15q24-25.1 locus that are associated with lung cancer is warranted.
Leptomeningeal metastases: a RANO proposal for response criteria
Authors: Marc Chamberlain, Larry Junck, Dieta Brandsma, Riccardo Soffietti, Roberta Rudà, Jeffrey Raizer, Willem Boogerd, Sophie Taillibert, Morris D Groves, Emilie Le Rhun, Julie Walker, Martin van den Bent, Patrick Y Wen, Kurt A Jaeckle
Journal: Neuro-Oncology (2016)

Leptomeningeal metastases (LM) currently lack standardization with respect to response assessment. A Response Assessment in Neuro-Oncology (RANO) working group with expertise in LM developed a consensus proposal for evaluating patients treated for this disease. Three basic elements in assessing response in LM are proposed: a standardized neurological examination, cerebral spinal fluid (CSF) cytology or flow cytometry, and radiographic evaluation. The group recommends that all patients enrolling in clinical trials undergo CSF analysis (cytology in all cancers; flow cytometry in hematologic cancers), complete contrast-enhanced neuraxis MRI, and in instances of planned intra-CSF therapy, radioisotope CSF flow studies. In conjunction with the RANO Neurological Assessment working group, a standardized instrument was created for assessing the neurological exam in patients with LM. Considering that most lesions in LM are nonmeasurable and that assessment of neuroimaging in LM is subjective, neuroimaging is graded as stable, progressive, or improved using a novel radiological LM response scorecard. Radiographic disease progression in isolation (ie, negative CSF cytology/flow cytometry and stable neurological assessment) would be defined as LM disease progression. The RANO LM working group has proposed a method of response evaluation for patients with LM that will require further testing, validation, and likely refinement with use.
Localisation of a low-molecular-weight bronchial protease inhibitor in the peripheral human lung.
Authors: H W Mooren, J A Kramps, C Franken, C J Meijer, J A Dijkman
Journal: Thorax (1983)

The localisation of a low-molecular-weight bronchial protease inhibitor (LMI) in human peripheral lung tissue was studied by an immunohistochemical method. This inhibitor was found exclusively in a part of the non-ciliated cell population of the bronchiolar epithelium. An inverse relationship was observed between the number of LMI-positive non-ciliated cells per millimetre of basement membrane and the bronchiolar diameter. These findings may have a bearing on the protease-antiprotease theory of the development of pulmonary emphysema, LMI possibly playing a part in the protection of peripheral lung tissue against proteolytic destruction by enzymes liberated from granulocytes or migrating alveolar macrophages.
ANTIGEN-BINDING CELLS IN MICE IMMUNE OR TOLERANT TO ESCHERICHIA COLI POLYSACCHARIDE
Authors: Olof Sjöberg
Journal: The Journal of Experimental Medicine (1971)

The number of PFC and of RFC was studied in mice which were unimmunized, immunized, or tolerant against lipopolysaccharide of E. coli 055:B5 origin. The number of PFC/10(6) spleen cells increased from 0.5 in normal to 209 in immunized mice. The corresponding figures for RFC were 93 and 513 RFC/10(6) spleen cells. In tolerant animals, which contained few or no PFC, the number of RFC was increased as compared to that found in unimmunized mice. The formation of rosettes was specific, since their formation was inhibited by soluble coli polysaccharide and by rabbit antisera against mouse immunoglobulins. The antigen-binding cells were not derived from thymus, neither in immune or tolerant mice, because they did not carry the theta antigen. It is suggested that the majority of antigen-binding cells present in tolerant animals are cells having receptors for the antigen of rather low affinity. The relevance of these findings for the induction of high and low zone tolerance is discussed.
Prescription Drug Abuse
Authors: J. Walden Retan
Journal: Annals of Internal Medicine (2014)

Letters19 August 2014Prescription Drug AbuseJ. Walden Retan, MDJ. Walden Retan, MDFrom The Pain Clinic, Cooper Green/Mercy Health Services, Birmingham, Alabama.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L14-5016-4 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:Many persons who receive narcotics to treat chronic pain take them responsibly. Some don't. Kirschner and colleagues' (1) position paper deals with the irresponsible ones and raises questions.The authors support random urine drug testing. What should be done with the results? Results of urine testing that are negative for prescribed narcotics might indicate that a prescription was diverted from its intended use. They might also indicate that a patient took more than the prescribed amount of a narcotic near the beginning of a prescription to try to improve pain control and ran out of the drug ...References1. Kirschner N, Ginsburg J, Sulmasy LS; Health and Public Policy Committee of the American College of Physicians.. Prescription drug abuse: executive summary of a policy position paper from the American College of Physicians. Ann Intern Med. 2014;160:198. [PMID: 24323199] doi:10.7326/M13-2209 LinkGoogle Scholar2. Coffin P, Banta-Green C. The dueling obligations of opioid stewardship [Editorial]. Ann Intern Med. 2014;160:207. [PMID: 24322334] doi:10.7326/M13-2781 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From The Pain Clinic, Cooper Green/Mercy Health Services, Birmingham, Alabama.Disclosures: Authors have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L14-0178. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoPrescription Drug Abuse: Executive Summary of a Policy Position Paper From the American College of Physicians Neil Kirschner , Jack Ginsburg , Lois Snyder Sulmasy , and The Dueling Obligations of Opioid Stewardship Phillip Coffin and Caleb Banta-Green Prescription Drug Abuse Robert Newman Prescription Drug Abuse Neil Kirschner and Thomas G. Tape Prescription Drug Abuse Robert Newman Prescription Drug Abuse Neil Kirschner and Thomas G. Tape Metrics 19 August 2014Volume 161, Issue 4Page: 305-306KeywordsCannabisCocaineDrugsHeart failureLower back painLungsMetabolitesOpioidsUrine ePublished: 19 August 2014 Issue Published: 19 August 2014 CopyrightCopyright © 2014 by American College of Physicians. All Rights Reserved.PDF DownloadLoading ...
Preferential decrease in IgG4 anti-citrullinated protein antibodies during treatment with tumour necrosis factor blocking agents in patients with rheumatoid arthritis
Authors: W H Bos, G M Bartelds, M Vis, A R van der Horst, G J Wolbink, R J van de Stadt, D van Schaardenburg, B A C Dijkmans, W F Lems, M T Nurmohamed, L Aarden, D Hamann
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To investigate the dynamics of IgG1 and IgG4 anti-citrullinated protein antibody (ACPA) subclasses during anti-tumour necrosis factor (TNF) treatment in patients with rheumatoid arthritis (RA). <h3>Methods:</h3> IgG, IgG1 and IgG4 ACPA levels were determined by ELISA on anti-citrullinated fibrinogen (ACF) and IgG1 : IgG4 ACPA ratios were calculated. A pilot study was performed in 28 ACF-positive patients treated with infliximab for one year. Confirmation of the results was obtained using a cohort of 180 consecutive patients treated with adalimumab for 28 weeks. <h3>Results:</h3> The median reduction in ACF levels was 31% for total IgG, 29% for IgG1, 40% for IgG4 and 22% for the IgG4 : IgG1 ACF ratio in the infliximab cohort. In adalimumab-treated patients, ACF levels declined 14% for total IgG and IgG1, and 36% for IgG4 ACF; the IgG4 : IgG1 ratio was reduced by 24% (all percentage values p&lt;0.05). The decrease in antibody levels was correlated with the clinical response; European League Against Rheumatism good responders had the greatest decline in antibody levels and this effect was most pronounced for IgG4 (48% reduction). The IgG4 : IgG1 ACF ratio preferentially decreased in patients with adequate therapeutic adalimumab levels. <h3>Conclusion:</h3> ACPA subclass distribution is modulated by effective anti-inflammatory treatment. The preferential decline of IgG4 ACPA, reflected by the decreased IgG4 : IgG1 ratio, suggests a beneficial effect of anti-TNF treatment on chronic antigenic stimulation by citrullinated proteins. This effect may be directly anti-TNF mediated or the result of effective dampening of the inflammation in the rheumatoid joint.
Increased Serum Free Light Chains Precede the Presentation of Immunoglobulin Light Chain Amyloidosis
Authors: Brendan M. Weiss, Joseph Hebreo, Daniel V. Cordaro, Mark J. Roschewski, Thomas P. Baker, Kevin C. Abbott, Stephen W. Olson
Journal: Journal of Clinical Oncology (2014)

Patients with immunoglobulin light chain amyloidosis (AL amyloidosis) generally present with advanced organ dysfunction and have a high risk of early death. We sought to characterize monoclonal immunoglobulin (M-Ig) light chains before clinical presentation of AL amyloidosis.We obtained prediagnostic sera from 20 cases with AL amyloidosis and 20 healthy controls matched for age, sex, race, and age of serum sample from the Department of Defense Serum Repository. Serum protein electrophoresis with immunofixation and serum free light chain (FLC) analysis were performed on all samples.An M-Ig was detected in 100% of cases and 0% of controls (P < .001). The M-Ig was present in 100%, 80%, and 42% of cases at less than 4 years, 4 to 11 years, and more than 11 years before diagnosis, respectively. The median FLC differential (FLC-diff) was higher in cases compared with controls at all time periods, less than 4 years (174.8 v 0.3 mg/L; P < .001), 4 to 11 years (65.1 v 2.2 mg/L; P < .001), and more than 11 years (4.5 v 0.4 mg/L; P = .03) before diagnosis. The FLC-diff was greater than 23 mg/L in 85% of cases and 0% of controls (P < .001). The FLC-diff level increased more than 10% per year in 84% of cases compared with 16% of controls (P < .001).Increase of FLCs, including within the accepted normal range, precedes the development of AL amyloidosis for many years.
Cell-Type-Specific Sensorimotor Processing in Striatal Projection Neurons during Goal-Directed Behavior
Authors: Tanya Sippy, Damien Lapray, Sylvain Crochet, Carl C.H. Petersen
Journal: Neuron (2015)

Goal-directed sensorimotor transformation drives important aspects of mammalian behavior. The striatum is thought to play a key role in reward-based learning and action selection, receiving glutamatergic sensorimotor signals and dopaminergic reward signals. Here, we obtain whole-cell membrane potential recordings from the dorsolateral striatum of mice trained to lick a reward spout after a whisker deflection. Striatal projection neurons showed strong task-related modulation, with more depolarization and action potential firing on hit trials compared to misses. Direct pathway striatonigral neurons, but not indirect pathway striatopallidal neurons, exhibited a prominent early sensory response. Optogenetic stimulation of direct pathway striatonigral neurons, but not indirect pathway striatopallidal neurons, readily substituted for whisker stimulation evoking a licking response. Our data are consistent with direct pathway striatonigral neurons contributing a "go" signal for goal-directed sensorimotor transformation leading to action initiation.Video AbstracteyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiJlMDkyMWU0NTZkMzAwZWIxZDg0NzcwOTI0ZjBmYmFlYyIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc4ODcwMDkyfQ.V0nNQYw_CBplXgI3lku5QHuExFRn3QAk3_oy9tsaS-cow7y4xMU6YgzeK9aAkVoUZ3QkNSWXvKImeBJQpmZXfYWeGFKO7sMCfFSsXtVzrhZ1KN82gpZrE1uTH6sHaqUrZB9M5axOv2jKRJM-cDq6J2IzarxAmZcQPtbis_Q-wyTuMgMXD5SyDtmZcZFD65upJ2GGBoJ08j9P24JzhUvEbEa2-DamAyCXAThBsCcwi-QX_swf0maCWwJUrIj8gStP9TkbVnER6o1HUTRPgyLiuuJmRnKIO1rqbxyPoXVnoPxgaUlkc4X-w1pYjbtLYmYThmzlCC659CoJ4daWMRdvGw(mp4, (46.05 MB) Download video