tbuckley/cabot-search huggingface dataset:
Epoxyeicosatrienoic Acids and Dihydroxyeicosatrienoic Acids Are Potent Vasodilators in the Canine Coronary Microcirculation
Authors: Christine L. Oltman, Neal L. Weintraub, Mike VanRollins, Kevin C. Dellsperger
Journal: Circulation Research (1998)

Abstract —Cytochrome P 450 epoxygenases convert arachidonic acid into 4 epoxyeicosatrienoic acid (EET) regioisomers, which were recently identified as endothelium-derived hyperpolarizing factors in coronary blood vessels. Both EETs and their dihydroxyeicosatrienoic acid (DHET) metabolites have been shown to relax conduit coronary arteries at micromolar concentrations, whereas the plasma concentrations of EETs are in the nanomolar range. However, the effects of EETs and DHETs on coronary resistance arterioles have not been examined. We administered EETs and DHETs to isolated canine coronary arterioles (diameter, 90.0±3.4 μm; distending pressure, 20 mm Hg) preconstricted by 30% to 60% of the resting diameter with endothelin. All 4 EET regioisomers produced potent, concentration-dependent vasodilation (EC 50 values ranging from −12.7 to −10.1 log [M]) and were approximately 1000 times more potent than reported in conduit coronary arteries. The vasodilation produced by 14,15-EET was not attenuated by removal of the endothelium and indicated a direct action of 14,15-EET on microvascular smooth muscle. Likewise, 14,15-DHET, 11,12-DHET, 8,9-DHET, and the δ-lactone of 5,6-EET produced extremely potent vasodilation (EC 50 values ranging from −15.8 to −13.1 log [M]). The vasodilation produced by these eicosanoids was highly potent in comparison to that produced by other vasodilators, including arachidonic acid (EC 50 =−7.5 log [M]). The epoxide hydrolase inhibitor, 4-phenylchalone oxide, which blocked the conversion of [ 3 H]14,15-EET to [ 3 H]14,15-DHET by canine coronary arteries, did not alter arteriolar dilation to 11,12-EET; thus, the potent vasodilation induced by EETs does not require formation of DHETs. In contrast, charybdotoxin (a K Ca channel inhibitor) and KCl (a depolarizing agent) blocked vasodilation by 11,12-EET and 11,12-DHET. We conclude that EETs and DHETs potently dilate canine coronary arterioles via activation of K Ca channels. The preferential ability of these compounds to dilate resistance blood vessels suggests that they may be important regulators of coronary circulation.
Mucin 5B promoter polymorphism is associated with idiopathic pulmonary fibrosis but not with development of lung fibrosis in systemic sclerosis or sarcoidosis
Authors: Carmel J Stock, Hiroe Sato, Carmen Fonseca, Winston A S Banya, Philip L Molyneaux, Huzaifa Adamali, Anne-Marie Russell, Christopher P Denton, David J Abraham, David M Hansell, Andrew G Nicholson, Toby M Maher, Athol U Wells, Gisela E Lindahl, Elisabetta A Renzoni
Journal: Thorax (2013)

<h3>Background</h3> A polymorphism (rs35705950) 3 kb upstream of <i>MUC5B</i>, the gene encoding Mucin 5 subtype B, has been shown to be associated with familial and sporadic idiopathic pulmonary fibrosis (IPF). We set out to verify whether this variant is also a risk factor for fibrotic lung disease in other settings and to confirm the published findings in a UK Caucasian IPF population. <h3>Methods</h3> Caucasian UK healthy controls (n=416) and patients with IPF (n=110), sarcoidosis (n=180) and systemic sclerosis (SSc) (n=440) were genotyped to test for association. The SSc and sarcoidosis cohorts were subdivided according to the presence or absence of fibrotic lung disease. To assess correlation with disease progression, time to decline in forced vital capacity and/or lung carbon monoxide transfer factor was used in the IPF and SSc groups, while a persistent decline at 4 years since baseline was evaluated in patients with sarcoidosis. <h3>Results</h3> A significant association of the <i>MUC5B</i> promoter single nucleotide polymorphism with IPF (p=2.04×10<sup>–17</sup>; OR 4.90, 95% CI 3.42 to 7.03) was confirmed in this UK population. The <i>MUC5B</i> variant was not a risk factor for lung fibrosis in patients with SSc or sarcoidosis and did not predict more rapidly progressive lung disease in any of the groups. Rather, a trend for a longer time to decline in forced vital capacity was observed in patients with IPF. <h3>Conclusions</h3> We confirm the <i>MUC5B</i> variant association with IPF. We did not observe an association with lung fibrosis in the context of SSc or sarcoidosis, potentially highlighting fundamental differences in genetic susceptibility, although the limited subgroup numbers do not allow a definitive exclusion of an association.
BONE MARROW AS SOURCE OF CELLS IN REACTIONS OF CELLULAR HYPERSENSITIVITY
Authors: David M. Lubaroff, Byron H. Waksman
Journal: The Journal of Experimental Medicine (1968)

The precise origin of cells infiltrating tuberculin skin reactions was studied with the technique of immunofluorescence. Thymectomized, irradiated Lewis rats were restored with bone marrow from allogeneic or F(1) donors. They were passively sensitized to tuberculin by a subsequent transfer of Lewis lymph node cells and were given intradermal skin tests with tuberculoprotein. In 24 hr reactions the majority of cells were shown to be derived from the infused marrow. These results were the same regardless whether the lymphocyte transfer was performed on the day of irradiation and marrow injection or 7 days later. The cells in the tuberculin reactions, marrow, spleen, and lymph nodes not derived from the bone marrow were found to originate in the transferred lymph node cells. The relative percentages of marrow-derived and lymph node-derived cells in the tuberculin reactions remained the same during the 9-24 hr period following skin test.
Cryotherapy in Infants With Retinopathy of Prematurity
Authors: N. W. Hindle
Journal: JAMA (1990)

To the Editor.—  In the Multicentre Trial of Cryotherapy for Retinopathy of Prematurity (ROP), the avascular peripheral retina was treated in one of the impaired eyes with threshold ROP. 1 An  outcome was an eye that had a fold of retina through the macula or partial to complete retrolental membrane (grade III through V retrolental fibroplasia). 2 Twenty-two percent of the treated eyes had unfavorable results, compared with 43% of the untreated eyes. Not yet reported is the fact that some of the favorable eyes with grade II retrolental fibroplasia and grade III retrolental fibroplasia not through the macula will be visually disabled (acuity   Drs Phelps and Phelps 3 present a complex process for determining treatment of one or both eyes.
Hereditary angioedema - retrospective of the last 20 years*1
Authors: S.Lopes Silva, A.Spínola Santos, A.Lopes Pregal, M.Branco Ferreira, E. Alonso, T. Michelena, E. Pedro, G. Palma-Carlos, M.H. Clode, M.Pereira Barbosa, A.G. Palma-Carlos
Journal: Journal of Allergy and Clinical Immunology (2004)
Mast cells in COPD airways: relationship to bronchodilator responsiveness and angiogenesis
Authors: Amir Soltani, Yean Pin Ewe, Zhen Sheng Lim, Sukhwinder S. Sohal, David Reid, Steve Weston, Richard Wood-Baker, E. Haydn Walters
Journal: European Respiratory Journal (2011)

We have investigated whether mast cells are associated with bronchodilator responsiveness and airway vascular changes in chronic obstructive pulmonary disease (COPD) airways. We have previously shown that the reticular basement membrane is hypervascular and the lamina propria is hypovascular in COPD. Bronchial biopsies from 32 COPD subjects, 15 smokers with normal lung function and 17 controls, were immunostained for factor VIII, mast cell tryptase and chymase antibodies. Mast cells in the airway smooth muscle, the reticular basement membrane and the underlying lamina propria were quantitated. 41% of COPD subjects had significant bronchodilator responsiveness, but this was not related to smooth muscle mast cell numbers. The reticular basement membrane had greater mast cell density in all groups compared with controls (p<0.01). In this compartment, perivascular mast cell density was related to hypervascularity. Lamina propria mast cell density was increased only in COPD (p<0.05). Perivascular mast cell density in the lamina propria was not related to its decreased vessel density. Bronchodilator responsiveness in COPD is not related to large airway smooth muscle mast cells of either type; both reticular basement membrane and lamina propria mast cells are increased in COPD patients, and perivascular mast cells may be involved in increased angiogenesis in the reticular basement membrane.
The march from early life food sensitization to allergic disease: a systematic review and meta‐analyses of birth cohort studies
Authors: S. A. Alduraywish, C. J. Lodge, B. Campbell, K. J. Allen, B. Erbas, A. J. Lowe, S. C. Dharmage
Journal: Allergy (2015)

There is growing evidence for an increase in food allergies. The question of whether early life food sensitization, a primary step in food allergies, leads to other allergic disease is a controversial but important issue. Birth cohorts are an ideal design to answer this question.We aimed to systematically investigate and meta-analyse the evidence for associations between early food sensitization and allergic disease in birth cohorts.MEDLINE and SCOPUS databases were searched for birth cohorts that have investigated the association between food sensitization in the first 2 years and subsequent wheeze/asthma, eczema and/or allergic rhinitis. We performed meta-analyses using random-effects models to obtain pooled estimates, stratified by age group.The search yielded fifteen original articles representing thirteen cohorts. Early life food sensitization was associated with an increased risk of infantile eczema, childhood wheeze/asthma, eczema and allergic rhinitis and young adult asthma. Meta-analyses demonstrated that early life food sensitization is related to an increased risk of wheeze/asthma (pooled OR 2.9; 95% CI 2.0-4.0), eczema (pooled OR 2.7; 95% CI 1.7-4.4) and allergic rhinitis (pooled OR 3.1; 95% CI 1.9-4.9) from 4 to 8 years.Food sensitization in the first 2 years of life can identify children at high risk of subsequent allergic disease who may benefit from early life preventive strategies. However, due to potential residual confounding in the majority of studies combined with lack of follow-up into adolescence and adulthood, further research is needed.
Crypt dysplasia on Barrett's oesophagus
Authors: Francisco Baldaque-Silva, Margarida Marques, Joanne Lopes, Fatima Carneiro, Michael Vieth, Guilherme Macedo
Journal: Gut (2013)

In a study by Sharma et al 1 recently published in Gut, high-definition endoscopy and narrow band imaging (NBI) enabled detection of more areas of dysplasia than Seattle protocol. In addition, regular mucosa did not harbour high-grade dysplasia (HGD)/cancer, leading to the suggestion that biopsies could be avoided in those areas.

However, authors stated in the discussion that the routine use of NBI targeted biopsies for detection of HGD/cancer should not be recommended. To highlight this point, we would like report a case of a C10M12 Barrett's oesophagus (BO) patient with two previous macroscopic lesions with HGD and adenocarcinoma resected using multiband mucosectomy (figure 1). In a careful follow-up using the same endoscope as in the reported study,1 no macroscopic lesions were detected and biopsies were performed according to Seattle …
A Pilot Study of CTLA-4 Blockade after Cancer Vaccine Failure in Patients with Advanced Malignancy
Authors: Deirdre O'Mahony, John C. Morris, Cate Quinn, Wendy Gao, Wyndham H. Wilson, Barry Gause, Stefania Pittaluga, Sattva Neelapu, Margaret Brown, Thomas A. Fleisher, James L. Gulley, Jeffrey Schlom, Robert Nussenblatt, Paul Albert, Thomas A. Davis, Israel Lowy, Mike Petrus, Thomas A. Waldmann, John E. Janik
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Eleven patients with progressive advanced malignancy after administration of a cancer vaccine received a fully human anti-CTLA-4 monoclonal antibody (ipilimumab). The primary end point was to determine drug toxicity. Tumor response, tumor-specific CD8+ T-cell immune responses, and modulation of CD4+ CD25+ FoxP3+ regulatory T-cell (Treg) numbers were secondary end points. Experimental Design: Three patients with colon cancer, four with non–Hodgkin's lymphoma, and four with prostate cancer were treated. The first dose was given at 3 mg/kg and subsequent doses were administered monthly at 1.5 mg/kg for a total of four cycles. Results: Tumor regression was observed in two patients with lymphoma; one of which obtained a partial response of 14-month duration. Ipilimumab was well tolerated with predominantly grade 1/2 toxicities. One drug-related grade 3 toxicity was observed. One patient died within 30 days of treatment due to progressive colon cancer. No increase in vaccine-specific T-cell responses was observed after therapy. Tregs as detected by expression of CD4+CD25 +CD62L + declined at early time points but rebounded to levels at or above baseline values at the time of the next infusion. Conclusions: Ipilimumab treatment depressed Treg numbers at early time points in the treatment cycle but was not accompanied by an increase in vaccine-specific CD8+ T-cell responses in these patients previously treated with a variety of investigational anticancer vaccines. A partial response was observed in one patient with follicular lymphoma. A phase I/II trial evaluating ipilimumab in patients with follicular lymphoma is currently ongoing.
A baby with cough and poor feeding
Authors: S. Sonnappa, G. Cohen, A. Ramsay, R. Dinwiddie, A. Jaffé
Journal: European Respiratory Journal (2003)

A 9‐week-old female baby presented at her local hospital with a 10‐day history of cough and poor feeding. The pregnancy had been uneventful with normal antenatal scans. The baby was born at term by normal vaginal delivery weighing 3.23 kg with good American Paediatric Gross Assessment Record scores and was sent home on the second day after birth. Prior to this presentation, she had exhibited no respiratory symptoms and was maintaining good growth.

On review, the baby was afebrile with no respiratory distress. Chest auscultation revealed reduced breath sounds on the left side. The rest of the physical examination results were unremarkable. Arterial oxygen saturation was 97% in air.

Initial chest computed tomography (CT) results are shown in figure 1⇓. Unfortunately, the initial chest radiograph was “lost”.



Fig. 1.— 
Initial computed tomography of the chest showing: a) upper and b) lower lung lobes.



One week later, the baby underwent thoracotomy and resection. A chest radiograph taken the day prior to surgery is shown in figure 2⇓.



Fig. 2.— 
Preoperative chest radiograph.



The histopathology of the lesion is shown in figure 3⇓.



Fig. 3.— 
Histopathology of lung lesion (haematoxylin and eosin stain). Scale bars a) 200 µm and b) 100 µm.



BEFORE TURNING THE PAGE, INTERPRET THE RADIOGRAPHS, COMPUTED TOMOGRAM OF THE CHEST AND HISTOPATHOLOGICAL RESULTS AND SUGGEST DIAGNOSIS AND …
Renomedullary Vasodepressor Substance, Medullin
Authors: JAMES B. LEE, BENJAMIN G. COVINO, BERTIL H. TAKMAN, EMIL R. SMITH, Marilyn Mazzeo
Journal: Circulation Research (1965)

The chemical and physiological properties of renomedullary depressor substances were investigated utilizing the normotensive, vagotomized, pentolinium-treated rat for assay. By a combination of solvent extraction, column chromatography, and thin-layer chromatography, three biologically active acidic lipids were isolated from rabbit renal medulla. The first compound, called medullin, is an acidic lipid with potent vasodepressor and relatively weak nonvascular smooth muscle-stimulating properties. Ultraviolet analysis revealed spectra closely resembling that of prostaglandin E-1 (PGE-1). Infrared analysis showed the presence of carbonyl, methylene, and hydroxyl groups in addition to trans ethylene bonds. Although closely resembling PGE-1, medullin appears to be a more unsaturated carboxylic lipid with less polar (hydroxyl) groups. The hypotensive action of medullin is attributable to a direct effect on peripheral arteriolar beds without cardiac depression, because intra-arterial and intravenous injections of medullin reduced peripheral resistance markedly and increased cardiac output simultaneously. In addition, no effect on cardiac rate or contractility was observed in the isolated rabbit heart preparation. Comparative studies of medullin and PGE-1 indicated that the hypotensive activity of these compounds is similar with respect to potency and mechanism of action. The only biological difference between crystalline PGE-1 and medullin was a fiftyfold greater stimulation of nonvascular smooth muscle by PGE-1 in comparison to medullin. A second biologically active acidic lipid isolated from rabbit medulla was tentatively identified as PGE-1, and was found to possess both vasodepressor and nonvascular smooth muscle-stimulating properties. The third isolate from rabbit medulla possessed potent intestinal stimulating activity but weak to absent vasodepressor effects, properties similar to those of prostaglandin F compounds.
Early Age at Smoking Initiation and Tobacco Carcinogen DNA Damage in the Lung
Authors: J. K. Wiencke, S. W. Thurston, K. T. Kelsey, A. Varkonyi, J. C. Wain, E. J. Mark, D. C. Christiani
Journal: JNCI Journal of the National Cancer Institute (1999)

BACKGROUND: DNA adducts formed as a consequence of exposure to tobacco smoke may be involved in carcinogenesis, and their presence may indicate a high risk of lung cancer. To determine whether DNA adducts can be used as a "dosimeter" for cancer risk, we measured the adduct levels in nontumorous lung tissue and blood mononuclear cells from patients with lung cancer, and we collected data from the patients on their history of smoking. METHODS: We used the 32 P-postlabeling assay to measure aromatic hydrophobic DNA adducts in nontumorous lung tissue from 143 patients and in blood mononuclear cells from 54 of these patients. From the smoking histories, we identified exposure variables associated with increased DNA adduct levels by use of multivariate analyses with negative binomial regression models. RESULTS/CONCLUSIONS: We found statistically significant interactions for variables of current and former smoking and for other smoking variables (e.g., pack-years [ number of packs smoked per day × years of smoking] or years smoked), indicating that the impact of smoking variables on DNA adduct levels may be different in current and former smokers. Consequently, our analyses indicate that models for current and former smokers should be considered separately. In current smokers, recent smoking intensity (cigarettes smoked per day) was the most important variable. In former smokers, age at smoking initiation was inversely associated with DNA adduct levels. A highly statistically significant correlation ( r = .77 [Spearman's correlation]; two sided P <.001) was observed between DNA adduct levels in blood mononuclear cells and lung tissue. IMPLICATIONS: Our results in former smokers suggest that smoking during adolescence may produce physiologic changes that lead to increased DNA adduct persistence or that young smokers may be markedly susceptible to DNA adduct formation and have higher adduct burdens after they quit smoking than those who started smoking later in life.
<i>Plasmodium falciparum</i> Associated with Severe Childhood Malaria Preferentially Expresses PfEMP1 Encoded by Group A <i>var</i> Genes
Authors: Anja T.R. Jensen, Pamela Magistrado, Sarah Sharp, Louise Joergensen, Thomas Lavstsen, Antonella Chiucchiuini, Ali Salanti, Lasse S. Vestergaard, John P. Lusingu, Rob Hermsen, Robert Sauerwein, Jesper Christensen, Morten A. Nielsen, Lars Hviid, Colin Sutherland, Trine Staalsoe, Thor G. Theander
Journal: The Journal of Experimental Medicine (2004)

Parasite-encoded variant surface antigens (VSAs) like the var gene–encoded Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family are responsible for antigenic variation and infected red blood cell (RBC) cytoadhesion in P. falciparum malaria. Parasites causing severe malaria in nonimmune patients tend to express a restricted subset of VSA (VSASM) that differs from VSA associated with uncomplicated malaria and asymptomatic infection (VSAUM). We compared var gene transcription in unselected P. falciparum clone 3D7 expressing VSAUM to in vitro–selected sublines expressing VSASM to identify PfEMP1 responsible for the VSASM phenotype. Expression of VSASM was accompanied by up-regulation of Group A var genes. The most prominently up-regulated Group A gene (PFD1235w/MAL7P1.1) was translated into a protein expressed on the infected RBC surface. The proteins encoded by Group A var genes, such as PFD1235w/MAL7P1.1, appear to be involved in the pathogenesis of severe disease and are thus attractive candidates for a vaccine against life-threatening P. falciparum malaria.
THE USE OF SPECIFIC "LYMPHOCYTE" ANTISERA TO INHIBIT HYPERSENSITIVE REACTIONS OF THE "DELAYED" TYPE
Authors: Byron H. Waksman, Simone Arbouys, Barry G. Arnason
Journal: The Journal of Experimental Medicine (1961)

Rabbit antisera against normal guinea pig lymph node, when injected into guinea pigs, produced transient depression of the level of blood lymphocytes. It had no effect on other circulating cellular elements. Repeated injection over several days produced lymphopenia, which became progressively less marked with continued treatment, and clear-cut depletion of small lymphocytes in lymph nodes, whether draining an inoculation site or remote. In guinea pigs treated with lymphocyte antiserum, there was marked suppression of the tuberculin and contact allergic reactions and the "delayed" skin reaction to purified diphtheria toxoid, and a relative suppression of allergic encephalomyelitis and the rejection of first set skin homografts. There was a slight effect on second set graft rejection and no effect on PCA or the reversed passive Arthus reaction. Non-specific reactions to intradermal turpentine or to concentrated dinitrochlorobenzene placed on the skin were moderately reduced. The suppression of these reactions (except allergic encephalomyelitis) was closely correlated with the degree of lymphopenia. Lymphocyte antiserum absorbed with normal blood white cells lost both its lymphopenic effect and its ability to suppress the tuberculin reaction. It is tentatively concluded that a circulating mononuclear cell, probably the small lymphocyte, is the primary reactant in the various types of delayed hypersensitive reactions.