tbuckley/cabot-search huggingface dataset:
Effects of Bradykinin and Autonomic Nervous System Inhibition on Systemic and Regional Hemodynamics in the Unanesthetized Rhesus Monkey
Authors: Michael J. Reichgott, Ralph P. Forsyth, Kenneth L. Melmon
Journal: Circulation Research (1971)

Studies were performed in unanesthetized monkeys to determine if bradykinin infusions reproduce the circulatory events of early endotoxemia. Kinin infusions before and during autononiic ganglionic blockade with trimethaphan were significantly correlated (P &lt;0.05) with decreases in mean arterial pressure. Kinin infusion at 15-18, µg/kg min - produced 26 mm Hg fall in mean blood pressure at 3 min, due to fall in total peripheral resistance of 14 mm Hg/liter min -1 . Heart rate rose 23 beats/min. After 10 minutes of infusion, peripheral resistance had returned to base line, blood pressure remained low due to fall in cardiac output of 0.53 liters/min (P &lt;0.01). Ganglionic blockade prevented recovery of resistance. Plasma bradykinin levels at 3 and 10 minutes were 14 and 15 µg/ml, respectively. Regional and systemic hemodynamic effects of kinin (15-18 µg/kg min were determined in 10 monkeys. After 10 minutes of infusion, bradykinin produced systemic effects. Regional flow measurement (by radioactive microsphere technique) demonstrated a pattern similar to that seen during hemorrhage. Canglionic blockade lowered mean arterial pressure 33 mm Hg by generalized vasodilatation, Kinin infusion then resulted in further vasodilatation and fall in blood pressure of 12 mm Hg, and cardiac output of 0.74 liters/min. Regional flow distribution during combined infusion was similar to that seen during early endotoxemia.
Coexistent cutaneous T-cell lymphoma and B-cell malignancy
Authors: Florent Grange, Marie-Françoise Avril, Eric Esteve, Pascal Joly, Jacques Bosq, Anne de Murets, Elisabeth Thomine, Jean-Christophe Ortoli, Pierre Duvillard, Loïc Vaillant, Martine Bagot, Janine Wechsler
Journal: Journal of the American Academy of Dermatology (1994)
Unraveling a novel transcription factor code determining the human arterial-specific endothelial cell signature
Authors: Xabier L. Aranguren, Xabier Agirre, Manu Beerens, Giulia Coppiello, Maialen Uriz, Ine Vandersmissen, Mohammed Benkheil, Joaquin Panadero, Natalia Aguado, Alberto Pascual-Montano, Victor Segura, Felipe Prósper, Aernout Luttun
Journal: Blood (2013)

Endothelial cells (ECs) lining arteries and veins have distinct molecular/functional signatures. The underlying regulatory mechanisms are incompletely understood. Here, we established a specific fingerprint of freshly isolated arterial and venous ECs from human umbilical cord comprising 64 arterial and 12 venous genes, representing distinct functions/pathways. Among the arterial genes were 8 transcription factors (TFs), including Notch target HEY2, the current "gold standard" determinant for arterial EC (aEC) specification. Culture abrogated differential gene expression in part due to gradual loss of canonical Notch activity and HEY2 expression. Notably, restoring HEY2 expression or Delta-like4-induced Notch signaling in cultured ECs only partially reinstated the aEC gene signature, whereas combined overexpression of the 8 TFs restored this fingerprint more robustly. Whereas some TFs stimulated few genes, others boosted a large proportion of arterial genes. Although there was some overlap and cross-regulation, the TFs largely complemented each other in regulating the aEC gene profile. Finally, overexpression of the 8 TFs in human umbilical vein ECs conveyed an arterial-like behavior upon their implantation in a Matrigel plug in vivo. Thus, our study shows that Notch signaling determines only part of the aEC signature and identifies additional novel and complementary transcriptional players in the complex regulation of human arteriovenous EC identity.
Consolidating consolidation? Sleep stages, memory systems, and procedures
Authors: John A. Groeger, Derk-Jan Dijk
Journal: Behavioral and Brain Sciences (2005)

We argue that by neglecting the fact that procedural memory may also have episodic qualities, and by considering only a systems approach to memory, Walker's account of consolidation of learning during subsequent sleep ignores alternative accounts of how sleep stages may be interdependent. We also question the proposition that sleep-based consolidation largely bypasses hippocampal structures.
Cancer surveillance of patients with longstanding ulcerative colitis: a clinical, endoscopical, and histological study.
Authors: O Brostrom, R Lofberg, A Ost, H Reichard
Journal: Gut (1986)

An eight year endoscopical and histological cancer surveillance programme comprising 71 patients with ulcerative colitis is presented. Forty one patients had total colitis and 30 substantial colitis. Mean duration of the disease was 19.7 years (range 9-46 years). An average of 2.6 colonoscopies per patient in the total colitis group were carried out, and at least two biopsies were taken at 10 locations in the colon. In the total colitis group, seven had either low (four), or high grade dysplasia (two), or Dukes9 A cancer (one). In the group with substantial colitis two patients with low grade dysplasia were found. Dysplasia or cancer leading to operation was found above the rectum in four of five operated patients, all having had total colitis for 25 to 44 years. The dysplasia and cancer findings at the colonoscopy preceding surgery corresponded well with the surgical specimens. In three operated patients a sequence of dysplasia development was recorded. With the exception of long duration and dysplasia, nothing in the clinical course distinguished the operated cases. Using this surveillance programme prophylactic colectomy can be limited to patients in a high risk group developing dysplasia. The risk of missing a cancer before it becomes incurable seems to be low.
QUANTITATIVE CHEMICAL STUDIES ON COMPLEMENT OR ALEXIN
Authors: Michael Heidelberger, M. Rocha e Silva, Manfred Mayer
Journal: The Journal of Experimental Medicine (1941)

1. Quantitative data are given on the effect of variations in the time of contact and the proportions of the reactants on the quantity of complement combining component nitrogen (C'1 N) found in active guinea pig serum. 2. C'1 N was the same when determined with precipitates containing excess antibody or excess antigen. 3. Finely divided specific precipitates took up the complement combining component (C'1) from subsequently added guinea pig serum almost as well as specific precipitates formed in the presence of complement.
T cell regulation of B cell activation. T cells independently regulate the responses mediated by distinct B cell subpopulations.
Authors: Y Asano, R J Hodes
Journal: The Journal of Experimental Medicine (1982)

The present studies have been carried out to characterize the regulatory influences acting upon defined pathways of T cell-dependent B cell activation. In these studies, it was demonstrated that high concentrations of free carrier strongly inhibited the MHC-restricted in vitro T cell-dependent antibody responses of primed Lyb-5- B cells to the corresponding carrier-hapten conjugate. In contrast, these same concentrations of free carrier failed to inhibit the T cell dependent responses of Lyb-5+ B cells to the same antigen. The inhibition of Lyb-5- B cell responses by free carrier was shown to result from active suppression mediated by carrier-specific primed Lyt-1+2- T cells and to require the additional participation of unprimed Lyt-1-2+ T cells. The activation of this suppression was antigen-specific, but suppression once activated was antigen nonspecific in its effect. These findings thus demonstrate that distinct pathways of B cell activation can be independently regulated by T suppressor network influences, and that these pathways therefore constitute potentially independent components of the immune response to a given antigenic stimulus.
Hormones and Endocrine-Disrupting Chemicals: Low-Dose Effects and Nonmonotonic Dose Responses
Authors: Laura N. Vandenberg, Theo Colborn, Tyrone B. Hayes, Jerrold J. Heindel, David R. Jacobs, Duk-Hee Lee, Toshi Shioda, Ana M. Soto, Frederick S. vom Saal, Wade V. Welshons, R. Thomas Zoeller, John Peterson Myers
Journal: Endocrine Reviews (2012)

For decades, studies of endocrine-disrupting chemicals (EDCs) have challenged traditional concepts in toxicology, in particular the dogma of “the dose makes the poison,” because EDCs can have effects at low doses that are not predicted by effects at higher doses. Here, we review two major concepts in EDC studies: low dose and nonmonotonicity. Low-dose effects were defined by the National Toxicology Program as those that occur in the range of human exposures or effects observed at doses below those used for traditional toxicological studies. We review the mechanistic data for low-dose effects and use a weight-of-evidence approach to analyze five examples from the EDC literature. Additionally, we explore nonmonotonic dose-response curves, defined as a nonlinear relationship between dose and effect where the slope of the curve changes sign somewhere within the range of doses examined. We provide a detailed discussion of the mechanisms responsible for generating these phenomena, plus hundreds of examples from the cell culture, animal, and epidemiology literature. We illustrate that nonmonotonic responses and low-dose effects are remarkably common in studies of natural hormones and EDCs. Whether low doses of EDCs influence certain human disorders is no longer conjecture, because epidemiological studies show that environmental exposures to EDCs are associated with human diseases and disabilities. We conclude that when nonmonotonic dose-response curves occur, the effects of low doses cannot be predicted by the effects observed at high doses. Thus, fundamental changes in chemical testing and safety determination are needed to protect human health.
Mechanisms of augmented segment shortening in nonischemic areas during acute ischemia of the canine left ventricle.
Authors: W Y Lew, Z Y Chen, B Guth, J W Covell
Journal: Circulation Research (1985)

To examine the interaction between normal and nonischemic areas of the left ventricle during acute ischemia, we implanted midwall ultrasonic segment length gauges in the ischemic zone and in nonischemic areas of the canine left ventricle. During acute ischemia, end-diastolic pressure and segment length in the nonischemic areas increased. There was no change from control in the segment length at the time of aortic valve opening and closure. Thus, in nonischemic areas, total segment shortening, as measured by the percent change in segment length from the time of end-diastole to aortic valve closure, increased. This was due to an increase in isovolumic shortening (end-diastole to aortic valve opening) with no change in ejection shortening (aortic valve opening to closure). The progressive increase in isovolumic shortening in nonischemic areas over time was directly paralleled by the progressive development of the isovolumic lengthening or bulge in the ischemic zone. Nonischemic areas, whether adjacent, on the opposite wall, or distant to the ischemic zone, all behaved similarly. Adrenergic blockade did not qualitatively alter these findings. We conclude that acute ischemia induces a mechanical disadvantage which is greater than just the loss of contractile function by the ischemic segment. Despite the apparent hyperfunction of nonischemic areas, the increased total segment shortening is expended in stretching the ischemic zone during isovolumic systole. As a result, there is no significant "compensatory" increase in ejection shortening in nonischemic areas.(ABSTRACT TRUNCATED AT 250 WORDS)
Summary and agreement statement of the 2nd International Conference on Concussion in Sport, Prague 2004
Authors: P McCrory, K Johnston, W Meeuwisse, M Aubry, R Cantu, J Dvorak, T Graf-Baumann, J Kelly, M Lovell, P Schamasch
Journal: British Journal of Sports Medicine (2005)

In November 2001, the 1st International Symposium on Concussion in Sport was held in Vienna, Austria to provide recommendations for the improvement of safety and health of athletes who suffer concussive injuries in ice hockey, football (soccer), and other sports. The 2nd International Symposium on Concussion in Sport was organised by the same group and held in Prague, Czech Republic in November 2004. It resulted in a revision and update of the Vienna consensus recommendations, which are presented here.
Efficacy of Sertraline in the Long-Term Treatment of Obsessive-Compulsive Disorder
Authors: Lorrin M. Koran, Elizabeth Hackett, Arkady Rubin, Robert Wolkow, Delbert Robinson
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Obsessive-compulsive disorder (OCD) typically begins early in life and has a chronic course. Despite the need for long-term treatment, the authors found no placebo-controlled studies that have examined the relapse-prevention efficacy of maintenance therapy. METHOD: Patients who met criteria for response after 16 and 52 weeks of a single-blind trial of sertraline were randomly assigned to a 28-week double-blind trial of 50–200 mg/day of sertraline or placebo. Primary outcomes after the double-blind trial were full relapse, dropout due to relapse or insufficient response, or acute exacerbation of OCD symptoms. RESULTS: Of 649 patients at baseline, 232 completed 52 weeks of the single-blind trial and met response criteria. Among the 223 patients in the double-blind phase of the study, sertraline had significantly greater efficacy than placebo on two of three primary outcomes: dropout due to relapse or insufficient clinical response (9% versus 24%, respectively) and acute exacerbation of symptoms (12% versus 35%). Sertraline resulted in improvement in quality of life during the initial 52-week trial and continued improvement, significantly superior to placebo, during the subsequent 28-week double-blind trial. Long-term treatment with sertraline was well tolerated. Over the entire study period, less than 20% of the patients stopped treatment because of adverse events. CONCLUSIONS: Sertraline demonstrated sustained efficacy among patients responding to treatment and was generally well tolerated during the 80-week study. During the study's last 28 weeks, sertraline demonstrated greater efficacy than placebo in preventing dropout due to relapse or insufficient clinical response and acute exacerbation of OCD symptoms.
Delayed presentation of a pseudoaneurysm of the subclavian and axillary artery – the importance of vigilance
Authors: Nemandra Sandiford, Kostantinos Tsitskaris, Matthew Erritty
Journal: Journal of the Royal Society of Medicine (2010)

Proximal humeral fractures are common injuries, especially in the elderly population. Palvanen et al.1 found an increase in the incidence of these injuries of 13.7% per year with an overall five times increase in their incidence between 1970 and 2002. These injuries are generally caused by falls and more than 70% of these patients are over 60 years of age. Seventy-five percent of these injuries occur in women. Most fractures of the humerus in the elderly are treated conservatively. Most of these patients are either discharged from the Emergency Department and followed up as outpatients or admitted to a rehabilitation ward without further surgical review or reassessment of the neurovascular status of the affected limb.

Vascular complications of these injuries are rare, and tend to present acutely. We discuss a case of delayed presentation of a pseudoaneurysm of the subclavian and axillary arteries after a proximal humerus fracture which was treated conservatively. The pseudoaneurysm evolved over a period of two days and required emergency vascular surgical intervention upon diagnosis. This case highlights why these injuries should be managed with a high degree of vigilance, reviewed regularly and referred early for specialist input. It emphasizes the absolute necessity of thorough neurovascular examination when assessing these patients.
Vimentin, carcinoembryonic antigen and keratin in the diagnosis of mesothelioma, adenocarcinoma and reactive pleural lesions
Authors: N al-Saffar, PS Hasleton
Journal: European Respiratory Journal (1990)

An immunohistochemical study of reactive pleural lesions, adenocarcinomas and mesotheliomas using carcinoembryonic antigen (CEA), cytokeratin and vimentin was carried out. All the specimens were obtained at surgery except for 11 mesotheliomas found at necropsy. Vimentin was positive in 23 of 27 mesotheliomas and negative in all the adenocarcinomas and 4 of 17 reactive mesothelial lesions. Conversely, CEA was positive in all the adenocarcinomas but negative in all mesotheliomas. Immunoreactivity for vimentin was seen in only 3 of 11 post-mortem mesotheliomas. Vimentin is a useful adjunct to the tissue diagnosis of mesothelioma especially when CEA is negative and cytokeratin positive. Its use appears largely confirmed to well fixed surgically derived tissues.
Molecular mechanism for feedback regulation of C4 biosynthesis in guinea pig peritoneal macrophage.
Authors: H S Auerbach, R D Baker, W J Matthews, H R Colten
Journal: The Journal of Experimental Medicine (1984)

Previous reports have shown that regulation of local extrahepatic production of complement may not reflect the regulation of plasma concentrations of the corresponding proteins and, further, that alteration of the tissue microenvironment can affect local macrophage protein synthesis. This report describes the molecular basis for control of the biosynthesis and secretion of a class III major histocompatibility complex gene product, the fourth component of complement (C4), from guinea pig macrophages by extracellular native C4 protein. The effect is specific for C4 synthesis, since production of C2 and total secreted protein was unaffected by fluid phase C4. C4 synthesis by extracellular C4 is regulated at a pretranslational level, without an effect on posttranslational proteolytic cleavage, glycosylation, or secretion. Specific C4 and factor B cDNA probes were used to demonstrate, by dot hybridization and Northern blot analysis, a decrease in messenger RNA coding for C4 that paralleled the inhibition of C4 biosynthesis, while the amount of total RNA and mRNA specific for factor B remained constant. Inhibition of C4 biosynthesis and the disappearance of mRNA encoding C4 occurred between 4 and 6 h after exposure of the macrophages to biologically active or methylamine-inactivated C4 protein. These data demonstrate that regulation of C4 biosynthesis by guinea pig macrophages serves as a model for the study of the molecular mechanisms of macrophage activation as well as the control of production of a component of the inflammatory response.
Biomarkers for risk of developing active tuberculosis in contacts of TB patients: a prospective cohort study
Authors: Niaina Rakotosamimanana, Vincent Richard, Vaomalala Raharimanga, Brigitte Gicquel, T. Mark Doherty, Alimuddin Zumla, Voahangy Rasolofo Razanamparany
Journal: European Respiratory Journal (2015)

Identifying those Mycobacterium tuberculosis latent-infected individuals most at risk of developing active tuberculosis (TB) using routine clinical and laboratory tests remains a huge challenge in TB control efforts. We conducted a prospective longitudinal study of clinical and laboratory markers associated with the risk of developing active TB in contacts with latent M. tuberculosis infection. HIV-negative household contacts (n=296) of pulmonary TB patients underwent monitoring of clinical features, full blood cell counts, tuberculin skin text (TST) and chest radiography performed regularly during 18 months of follow-up. Paired statistical tests, a Kaplan–Meier analysis and Cox proportional hazard modelling were performed on variables between contacts progressing or not progressing to active TB. The appearance of TB disease symptoms in contacts was significantly associated with an elevated peripheral percentage of blood monocytes (adjusted hazard ratio (aHR) 6.25, 95% CI 1.63–23.95; p&lt;0.01), a ≥14 mm TST response (aHR 5.72, 95% CI 1.22–26.80; p=0.03) and an increased monocyte:lymphocyte ratio (aHR 4.97, 95% CI 1.3–18.99; p=0.03). Among contacts having TST ≥14 mm, a strong association with risk of progression to TB was found with an elevated blood monocyte percentage (aHR 8.46, 95% CI 1.74–41.22; p&lt;0.01). Elevated percentage of peripheral blood monocytes plus an elevated TST response are potential biomarkers for identifying contacts of TB patients at highest risk of developing active TB.
Bufale Spotting, part 6: Assessing a lecture
Authors: Tom Jefferson, Lucia Zarra
Journal: Journal of the Royal Society of Medicine (2007)

Listen carefully to what is said. After the lecture do a random check on some the evidence presented to sustain a view. Honest lecturers should represent evidence fairly, only giving their opinion at the end (very much like an original paper). If you think the lecturer is twisting the evidence to suit his purpose, challenge him. Either way, be wary of the lecturer in future. Beware of amateurs who clearly have not rehearsed their presentations or who use their position and prestige to ram home a message. Here too, beware of immaculate presentations, especially if they have lots of special effects (sound, music, film clips, logos etc). Big pharma has taken to providing speakers at ‘key’ conferences with ready-made presentations. Quality is very high. The message is commercial.
Lung sounds during allergen-induced asthmatic responses in patients with asthma.
Authors: H J Schreur, Z Diamant, J Vanderschoot, A H Zwinderman, J H Dijkman, P J Sterk
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

We postulated that the distinct pathophysiologic mechanisms of airway narrowing during the early (EAR) and the late (LAR) asthmatic responses to inhaled allergens are reflected by the generation or transmission of lung sounds in asthma. Therefore, we measured FEV1 and recorded lung sounds in eight mildly asthmatic subjects before a standardized allergen challenge (PRE), during the EAR, during the recovery phase at 2 h (MID), during the LAR at 7 h, and after inhalation of a bronchodilator (POST). The recordings were made during flow- and volume-standardized quiet breathing, and during maximal forced breathing maneuvers. Airflow-dependent power spectra were analyzed for lung sound intensity (LSI), quartile power points (Q25, Q50, Q75), and extent of wheezing (W). These sound characteristics were compared among the various stages of the challenge in the presence (EAR, LAR) and absence (PRE, MID, POST) of acute airway obstruction using ANOVA. LSI, Q25 - Q75, and W were all elevated during airway obstruction. When matched for percent fall in FEV1, during the EAR and the LAR (mean +/- SD: 26.7 +/- 4.0, and 28.9 +/- 5.7, respectively; p = 0.385), the increase in Q25, and Q50 with airflow during quiet expiration, as well as the extent of wheezing, were higher during the LAR than during the EAR (p < or = 0.042 and p < or = 0.012, respectively). At similar levels of FEV1 (p > or = 0.156), LSI on expiration was higher at POST than at PRE or MID (p < or = 0.067), whereas Q25 (p < or = 0.047) and Q50 (p < or = 0.064) were lower at POST than at PRE. During forced expiration W was higher at MID and POST than at PRE (p < or = 0.014). We conclude that LSI, frequency content, and the extent of wheezing vary during the subsequent stages of allergen-induced bronchoconstriction in asthma despite matched values of FEV1. This suggests that airflow-standardized phonopneumography is a sensitive method for detecting differences in the pathophysiology of airway narrowing in asthma.