tbuckley/cabot-search huggingface dataset:
Gut mucosal granulocyte activation precedes nitric oxide production: studies in coeliac patients challenged with gluten and corn
Authors: G Kristjansson
Journal: Gut (2005)

<b>Background and aims:</b> To elucidate the dynamics of nitric oxide (NO) production induced by rectal gluten challenge and the relation between NO production and mucosal granulocyte activation. <b>Subjects and methods:</b> Release of rectal NO was measured in 13 patients with coeliac disease and in 18 controls before and after rectal wheat gluten challenge. Rectal gas was collected with a rectal balloon using a newly developed instrument/technique, the "mucosal patch technique". The instrument allows simultaneous measurements of concentrations of granulocyte mediators in the rectal mucosa. We measured myeloperoxidase (MPO), eosinophil cationic protein (ECP), and histamine. For comparison, we made similar measurements after corn (maize) gluten challenge. <b>Results:</b> In all coeliac patients rectal NO concentration increased after gluten challenge and reached a peak after 15 hours (mean 9464 (SEM 2393) parts per billion (ppb); range 250–24982). The maximum MPO and ECP increase occurred five hours after challenge. A correlation was found between mucosal MPO and NO production at 15 hours. Six of the patients showed an increase in NO production 15 hours after rectal corn gluten challenge but this was much smaller than after gluten challenge. No increases were seen in the control group after either challenge. <b>Conclusion:</b> Mucosal activation of neutrophils and eosinophils precedes pronounced enhancement of mucosal NO production after rectal wheat gluten challenge in patients with coeliac disease. Some of our coeliac patients displayed signs of an inflammatory reaction, as measured by NO and granulocyte markers, after rectal corn gluten challenge.
The Hereditary Renal Diseases
Authors: Gerald T. Perkoff
Journal: New England Journal of Medicine (1967)

Hereditary Functional Abnormalities of the KidneyIn contrast to the situation encountered with hereditary diffuse nephropathies, several of the hereditary functional abnormalities are relatively well understood, and their clinical features are widely known. In great measure this is so because abnormalities of renal function can be studied by quantitative technics and physiologic experiments have yielded much information. Indeed, as technical capabilities increase, understanding of the mechanisms involved in this group of hereditary renal diseases grows steadily.For the purposes of this discussion the functional renal disorders have been grouped arbitrarily according to the site in the renal tubule of the . . .
Prognostic significance of ventricular tachycardia and fibrillation induced at programmed stimulation and delayed potentials detected on the signal-averaged electrocardiograms of survivors of acute myocardial infarction.
Authors: A R Denniss, D A Richards, D V Cody, P A Russell, A A Young, M J Cooper, D L Ross, J B Uther
Journal: Circulation (1986)

The relative prognostic significance of ventricular tachycardia and ventricular fibrillation inducible at programmed stimulation within 1 month of acute myocardial infarction was compared in a prospective study of 403 clinically well survivors of transmural infarction who were 65 years old or younger. The prognostic significance of delayed potentials on the signal-averaged electrocardiogram was also examined in a subset of 306 patients without bundle branch block. Among the study patients, 20% had inducible ventricular tachycardia, 14% had inducible ventricular fibrillation, and 66% had no inducible arrhythmias. The 2 year probability of remaining free from cardiac death or nonfatal ventricular tachycardia or fibrillation was 0.73 for those with inducible ventricular tachycardia, 0.93 for those with inducible ventricular fibrillation, and 0.92 for those with no inducible arrhythmias. The cycle length of inducible ventricular tachycardia was 230 msec or more in 70% of the patients with inducible tachycardia who died. Of the patients studied by signal-averaged electrocardiography, 26% had delayed potentials. At 2 years, the probability of remaining free from cardiac death or nonfatal ventricular tachycardia or fibrillation was 0.73 for patients with delayed potentials and 0.95 for patients with no delayed potentials. There was a significant correlation (p less than .001) between the presence of delayed potentials and the ability to induce ventricular tachycardia. In conclusion, in survivors of recent infarction who have not had spontaneous ventricular tachycardia or fibrillation, inducible tachycardia (but not inducible fibrillation) at programmed stimulation predicts a significant risk of death or spontaneous tachycardia or fibrillation. A similar risk is found for patients with delayed potentials on the signal-averaged electrocardiogram.
Vascular effects of HMG CoA-reductase inhibitors (statins) unrelated to cholesterol lowering: new concepts for cardiovascular disease
Authors: Allan M Lefer, Rosario Scalia, David J Lefer
Journal: Cardiovascular Research (2001)

Time for primary review 18 days. 

In 1976, Endo et al. [1] reported on the discovery of a specific competitive inhibitor of the enzyme 3-hydroxy-3-methylglutaryl (HMG) CoA reductase. This compound, isolated from fungi, was called mevastatin. In 1988, Alberts [2] described a more potent HMG CoA reductase inhibitor, lovastatin, isolated from Aspergillus terreus . These two compounds started the development of a series of cholesterol lowering agents, now commonly called ‘statins’. Statins block the conversion of HMG CoA to mevalonic acid and thus dramatically attenuate the biosynthesis of cholesterol. These effects occur largely in the liver, where the statins primarily distribute [2]. The major effect of these pharmacologic agents is a marked reduction in LDL-cholesterol levels in the blood.

On the basis of these and other findings, the statins have been widely prescribed in humans with elevated serum cholesterol levels. These statins are well tolerated, are very safe, and effectively lower serum LDL-cholesterol levels and maintain this effect over periods of many years [3]. In one clinical trial, 4444 patients were carefully studied and not only was simvastatin shown to be safe and effective in lowering circulating cholesterol, it also significantly improved survival in patients with coronary heart disease (CHD) [4], and carried a 37% reduction in the risk of treated patients undergoing myocardial vascularization procedures [4]. These findings speak eloquently to the clinical usefulness of the statins. For many years, all the beneficial effects of the statins were attributed to their cholesterol lowering effect. Nevertheless, quite recently, the statins were found to exert direct cardiovascular effects which clearly are independent of their cholesterol lowering effects, and are not directly attributable to a reduction in serum cholesterol levels.

The purpose of this review is to describe, evaluate, and discuss the major mechanisms underlying these non-lipid-lowering effects … 

* Corresponding author. Tel.: +1-215-503-7760; fax: +1-215-503-2073 allan.m.lefer{at}mail.tju.edu
Jerome, Patron of Books
Authors: Alister Brass
Journal: JAMA (1972)

The painting of St. Jerome by Caravaggio featured on this week's JAMA cover marks the third time in nine years that this extraordinary man has introduced the annual Book Number. Jerome's pre-eminent position in the history of Western writing and letters makes him an appropriate figure for this position, for almost alone among the early fathers of the Christian Church he is remembered as a man of great learning and scholarly achievement, a true lover of books.  That Jerome has appealed to so many artists as well as bibliophiles is hardly surprising, as he was a towering figure bestriding the Church and the crumbling Roman empire in the late 4th and early 5th centuries. As in the paintings shown here, he is usually portrayed in a contemporary setting, always at work on a book— appropriate to his achievement as the first man to translate the Hebrew Bible into Latin. In
A Clinical Technique Using Hg<sup>197</sup>for Determining the Blood-Cerebrospinal Fluid Barrier: A Preliminary Report
Authors: JAMES JANECEK, GLEN CRAMER, MERLE K. LOKEN, CARL D. KOUTSKY
Journal: American Journal of Psychiatry (1967)

Five psychiatric patients were given one millicurie of Hg197 intravenously; following this, lumbar and venous punctures were performed. The data suggest that Hg197 passes the blood-cerebrospinal fluid barrier. As indicated by this study and by the literature on the blood-cerebrospinal fluid barrier, radioisotope techniques may prove to be a valuable investigative method.
Visual Circuit Development Requires Patterned Activity Mediated by Retinal Acetylcholine Receptors
Authors: Timothy J. Burbridge, Hong-Ping Xu, James B. Ackman, Xinxin Ge, Yueyi Zhang, Mei-Jun Ye, Z. Jimmy Zhou, Jian Xu, Anis Contractor, Michael C. Crair
Journal: Neuron (2014)
Familial Aggregation of Factors Associated with Coronary Heart Disease
Authors: SIGISMOND DEUTSCHER, FREDERICK H. EPSTEIN, MARCUS O. KJELSBERG
Journal: Circulation (1966)

In the course of an epidemiological study covering an entire community, Tecumseh, Michigan, the familial aggregation of various levels of four variables associated with coronary heart disease-serum cholesterol, systolic blood pressure, relative weight, and blood glucose after a standard load-was assessed quantitatively by determining the relative frequencies of high, intermediate, and low levels of the variables for several familial combinations. High, intermediate, and low levels for each variable were defined in terms of quintiles (highest, middle three, lowest, respectively) of the distribution of the variable specific for age and sex. Parents and their children and siblings were compared. There was a striking resemblance between children and their fathers and mothers for all the four variables under study, as well as for height which was used as a frame of reference. The degree of resemblance between parents and children was approximately the same at the three levels-"low," "intermediate," and "high"-of the variables, pointing to a multifactorial mode of determination. In an attempt to assess the relative role of environmental and genetic factors with respect to the determination of the variables under study, degrees of aggregation by age were compared. An appreciable degree of resemblance was found among siblings below the age of 16 who may be presumed to share the same environment to a great extent. Aggregation was less marked for siblings between the ages of 16 and 40, a time when less of the same environment is shared, but it rose again after age 40. It is postulated that the observed rise after age 40 is due to an increase in the penetrance of the genes involved, at middle age and beyond. In addition, this pattern of aggregation suggests that environmental factors may play a stronger role prior to middle age. A similar subdivision by age, was used to study relationships between parents and children; although no corresponding differences between age groups were found, this apparent inconsistency with the sibship data could be explained, in part, by differences in age composition of the groups involved. The practical implication of the foregoing pattern of familial aggregation lies in the possibility of specifying for an individual the risk of developing high values of a variable predisposing to coronary heart disease in the future on the basis of the values shown by his parents and siblings.
Retaliation and antisocial punishment are overlooked in many theoretical models as well as behavioral experiments
Authors: Anna Dreber, David G. Rand
Journal: Behavioral and Brain Sciences (2012)

Guala argues that there is a mismatch between most laboratory experiments on costly punishment and behavior in the field. In the lab, experimental designs typically suppress retaliation. The same is true for most theoretical models of the co-evolution of costly punishment and cooperation, which a priori exclude the possibility of defectors punishing cooperators.
Role of Nitric Oxide in Thermoregulation and Hypoxic Ventilatory Response in Obese Zucker Rats
Authors: HITOSHI NAKANO, SHIN-DA LEE, ANDREW D. RAY, JOHN A. KRASNEY, GASPAR A. FARKAS
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

To examine the role of nitric oxide (NO) on thermoregulation and control of breathing in obesity, awake obese and age-matched lean Zucker (Z) rats underwent a sustained hypoxic challenge. Body temperature (Tb), oxygen consumption (V˙ o 2) and ventilation (V˙ e) were measured during room air and during 30-min of hypoxia (10% O2) after intraperitoneal administration of either 100 mg/kg of NG-nitro-l-arginine methyl ester (l-NAME), a nonspecific NOS inhibitor, 25 mg/kg of 7-nitroindazole (7-NI), a selective neuronal NOS inhibitor, or equal volume of vehicle (dimethyl sulfoxide: DMSO) as control. Tb in obese rats during room air was significantly lower than that of lean rats. Hypoxia induced a more pronounced drop in Tb and V˙ o 2 in lean rats than in obese rats. Tb in lean Z rats dropped significantly by ∼ 0.2 ° C after l-NAME and, more markedly, by ∼ 1.1 ° C after 7-NI compared with control during room air, whereas Tb in obese Z rats was unaffected. l-NAME and 7-NI attenuated hypoxia-induced hypothermia or hypometabolism in lean rats, but not in obese rats. Lean rats exhibited an abrupt increase in V˙ e in response to hypoxia followed by a gradual decline in V˙ e. In contrast, obese rats displayed an initial increase in V˙ e that plateaued during sustained hypoxia. Both l-NAME and 7-NI induced marked decreases in V˙ e during room air and hypoxia compared with control lean rats, whereas V˙ e was virtually unaffected by either agent in obese rats. The present results suggest that the blunted thermoregulatory and ventilatory responses to hypoxia in obese Z rats may be attributed to reduced activity of NOS in the central nervous system.Keywords: obesity; control of breathing; metabolism; nitric oxide synthase
IODINE KINETICS DURING I-131 SCANNING IN PATIENTS WITH THYROID CANCER
Authors: S-G Park, J C Reynolds, F Brucker-Davis, M Whatley, K McEllin, D Maxted, J Robbins, B D Weintraub
Journal: Clinical Nuclear Medicine (1997)

Park, S-G; Reynolds, J C; Brucker-Davis, F; Whatley, M; McEllin, K; Maxted, D; Robbins, J; Weintraub, B D Author Information
Ménétrier disease with antrum polyposis and gastritis cystica profunda
Authors: J. Soares, P. Bastos, R. Gonçalves
Journal: Endoscopy (2012)

A 46-year-old man was admitted with epigastric pain, weight loss, and hypoalbuminemia. He had no history of gastric surgery. A gastroscopy revealed giant polypoid gastric folds within the gastric body and fundus ([Fig. 1]) and several polyps with central erosion in the gastric antrum ([Fig. 2]). Biopsies of the gastric body and antral lesions revealed chronic gastritis. Endoscopic ultrasound showed a thickened mucosal layer, with multiple anechogenic areas, indicative of cysts, in the mucosal and submucosal layers ([Fig. 3]). Snare biopsy of gastric corpus and antral lesions showed elongated foveolar epithelium with foveolar mucous cell hyperplasia and cystic dilation of the foveolar glands in the basal portion of mucosa, extending to the submucosa ([Fig. 4]). No dysplasia was observed, and tests for cytomegalovirus and Helicobacter pylori were negative. These findings were consistent with Ménétrier disease (MD) with coexisting gastritis cystica profunda (GCP). After discussing the cancer risk and treatment options with the patient, we initiated treatment with a proton pump inhibitor (PPI).
New complications associated with the Angelchik prosthesis.
Authors: C Ubhi, D L Morris
Journal: Thorax (1986)

Exogenous particles in lymph nodes in patients with shrinking pleuritis with atelectasis SIR,-I am rather surprised that Dr Dernevik (December 1985;40:948-51) uses the term shrinking pleuritis with atelectasis in preference to the more descriptive term of round atelectasis.This interesting form of lung collapse has been well described by Hanke and Kretzschmar, who advo- cate the term round atelectasis.In 1980 they reported experi- ence with 80 cases of this condition and pointed out its specific radiological features.'This benign condition is often mistaken for a bronchial carcinoma.In view of this, its recognition is of prime importance to avoid unnecessary invasive tests and tho- racotomies.Since I became aware of the condition I have accumulated 10 cases over the last three years.Thoracotomy was avoided in eight patients.The remaining two each had bronchial carcinoma with pleural effusion, which resulted in the formation of the round atelectasis.In this very small series only one case was related to asbestos exposure.All except two of the others had pleural effusions.It is advisable to consider the possibility of round atelectasis when assessing subpleural opacities, especially those seen in the lower zones of the lung fields.Awareness of this condition will prove to be beneficial.
242 The role of long acting octreotide in treating patients with advanced hepatocellular cancer (HCC). A randomized placebo-controlled trial
Authors: D. Dimitroulopoulos, D. Xinopoulos, K. Tsamakidis, A. Zisimopoulos, E. Andriotis, D. Panagiotakos, A. Fotopoulou, C. Chrysohoou, A. Bazinis, S. Markidou, E. Paraskevas
Journal: Journal of Hepatology (2004)
Functional genomics in zebrafish permits rapid characterization of novel platelet membrane proteins
Authors: Marie N. O'Connor, Isabelle I. Salles, Ana Cvejic, Nicholas A. Watkins, Adam Walker, Stephen F. Garner, Chris I. Jones, Iain C. Macaulay, Michael Steward, Jaap-Jan Zwaginga, Sarah L. Bray, Frank Dudbridge, Bernard de Bono, Alison H. Goodall, Hans Deckmyn, Derek L. Stemple, Willem H. Ouwehand
Journal: Blood (2008)

Abstract In this study, we demonstrate the suitability of the vertebrate Danio rerio (zebrafish) for functional screening of novel platelet genes in vivo by reverse genetics. Comparative transcript analysis of platelets and their precursor cell, the megakaryocyte, together with nucleated blood cell elements, endothelial cells, and erythroblasts, identified novel platelet membrane proteins with hitherto unknown roles in thrombus formation. We determined the phenotype induced by antisense morpholino oligonucleotide (MO)–based knockdown of 5 of these genes in a laser-induced arterial thrombosis model. To validate the model, the genes for platelet glycoprotein (GP) IIb and the coagulation protein factor VIII were targeted. MO-injected fish showed normal thrombus initiation but severely impaired thrombus growth, consistent with the mouse knockout phenotypes, and concomitant knockdown of both resulted in spontaneous bleeding. Knockdown of 4 of the 5 novel platelet proteins altered arterial thrombosis, as demonstrated by modified kinetics of thrombus initiation and/or development. We identified a putative role for BAMBI and LRRC32 in promotion and DCBLD2 and ESAM in inhibition of thrombus formation. We conclude that phenotypic analysis of MO-injected zebrafish is a fast and powerful method for initial screening of novel platelet proteins for function in thrombosis.
Learning to Tie My Shoes
Authors: Patrick L. Clary
Journal: JAMA (2009)

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Abstract LB-120: Site of origin of basal cell carcinoma stromal cells
Authors: Grace Y. Wang, Joy Wang, Lynn Wang, Ervin Epstein
Journal: Cancer Research (2012)

Abstract We have adapted a transgenic tetracycline-regulatable mouse model to identify slow dividing cells in murine basal cell carcinomas (BCCs). This system consists of 2 transgenes: histone H2B-green fluorescence protein (GFP) controlled by a tetracycline-responsive element (TRE) upstream of a CMV promoter; and a tissue specific promoter-driven tetracycline-regulatable activator protein (rTA). In the absence of rTA, the H2B-GFP expression should be silent. However, we and other labs have found that mice carrying the H2B-GFP transgene with or without the K5-rTA transgene showed significant numbers of GFP-expressing bone marrow cells, which are not regulated by doxycycline. To study BCCs, we crossed these leaky mice with our Ptch1+/− mouse and treated the offspring with ionizing radiation. Although the mice with the H2B-GFP transgene developed microscopically detectable BCCs in a manner similar to Ptch+/− parental mice, the presence of the H2B-GFP transgene significantly delayed the microscopic-to-macroscopic transition of tumors (i.e. mice develop their first macroscopic tumor at age 9-13 month for Ptch+/− vs. 13-18 months for Ptch1+/− K5rTA H2B-GFP). Moreover, approximately one third of the Ptch1+/− K5rTA H2B-GFP mice died with unknown causes before 9-month of age, the time point when we collected skin biopsies for evaluating microscopic tumors, in comparison to 10-15% mouse death in Ptch1+/− mice by this age. Studying the limited number of visible BCCs arising in Ptch1+/− H2B-GFP (no K5-rTA transgene), we found that all the tumor cells were GFP-negative; however, the stromal cells nearly uniformly expressed GFP. By contrast, microscopic BCCs had no GFP+ stromal cells. As expected, both tumor cells and stromal cells were GFP-positive in unchased Ptch1+/− K5rTA H2B-GFP mice. By immunostaining, the GFP-expressing stromal cells, unlike the tumor cells, did not express keratins 5 and 14 but were vimentin-positive, Ki67-negative and frequently located in proximity to blood vessels. Using flow cytometry analysis with a panel of cell surface markers, we further characterized the GFP-expressing tumor stromal cells and the bone marrow cells. However further assessment is needed to confirm that the BCC stromal cells are derived from the GFP-expressing bone marrow cells and to determine their potential role in the microscopic to visible tumor transition. Our findings suggest that bone marrow cells may be the cells of origin of tumor stromal cells in BCCs perhaps in other cancers in general. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-120. doi:1538-7445.AM2012-LB-120