tbuckley/cabot-search huggingface dataset:
Pathogenesis of coronary artery spasm in miniature swine with regional intimal thickening after balloon denudation.
Authors: Y Yamamoto, H Tomoike, K Egashira, T Kobayashi, T Kawasaki, M Nakamura
Journal: Circulation Research (1987)

Pathogenesis of coronary artery spasm induced by histamine in miniature pigs was studied angiographically in in vivo and in vitro conditions. Endothelial balloon denudation was performed and the animals were fed laboratory chow for 3 months, after which coronary artery spasm was repeatedly provoked by histamine given intracoronarily. Regional hypercontraction of the coronary artery was documented by selective coronary arteriography, and the resulting myocardial ischemia was confirmed by ECG-ST changes. To evaluate coronary artery spasm without the influence of blood constituents and neural control and to quantitate the pharmacophysiological characteristics of histamine-induced coronary constriction in the coronary spasm, the same heart was isolated and perfused with Krebs-Henseleit solution under a constant perfusion pressure of 90 mm Hg. Histamine (10(-5) M) reduced the diameter of the coronary artery of the isolated heart by 29 +/- 4 and 67 +/- 3% (p less than 0.001) in nondenuded and denuded areas, respectively. These figures were similar to data obtained angiographically in vivo after the administration of histamine 10 micrograms/kg. The constriction of the denuded areas in response to histamine was topologically the same in vivo and in vitro. The degree of focal constriction induced by histamine, defined as a percent of stenoses from the mean diameter of the areas of proximal and distal to the spastic site, was similar in in vivo (10 micrograms/kg i.c.) and in vitro (10(-5) M) conditions. KCl (40 mM) reduced both the denuded and nondenuded coronary artery diameter by 67 +/- 3% and 68 +/- 3% (NS), respectively. The dose-response relation of the coronary diameter to histamine was not influenced by pretreatment with the nerve transmitter blockers guanethidine (3 X 10(-6) M), atropine (10(-6) M), and tetrodotoxin (3 X 10(-7) M). Phenylephrine (10(-5) M) did not potentiate constriction of the denuded areas.(ABSTRACT TRUNCATED AT 250 WORDS)
Dermatologic Manifestations of Infection in the Compromised Host
Authors: J S Wolfson, A J Sober, R H Rubin
Journal: Annual Review of Medicine (1983)

The skin occupies an important position in the prevention and evaluation of infection in patients who are immunocompromised. The skin can provide a portal of entry for both locally invasive and disseminated infection; and, not infrequently, skin lesions may be the first sign of disseminated infection from other primary sites. The first clinical principle in approaching this problem is that the skin must be protected from trauma, maceration, or alteration in its normal microbial flora. The second principle is that any lesion, no matter how innocuous, should be carefully evaluated in this patient population. Since the gross morphology of the lesion is so frequently modified by the altered inflammatory response of the immunocompromised patient, an aggressive biopsy approach is essential for diagnosis and therapy.
PEG-b-PPS-b-PEI micelles and PEG-b-PPS/PEG-b-PPS-b-PEI mixed micelles as non-viral vectors for plasmid DNA: Tumor immunotoxicity in B16F10 melanoma
Authors: Diana Velluto, Susan N. Thomas, Eleonora Simeoni, Melody A. Swartz, Jeffrey A. Hubbell
Journal: Biomaterials (2011)
The efficiency of acute infection of CD4+ T cells is markedly enhanced in the setting of antigen-specific immune activation.
Authors: D Weissman, T D Barker, A S Fauci
Journal: The Journal of Experimental Medicine (1996)

Human immunodeficiency virus (HIV) disease in sub-Saharan Africa generally differs from that observed in the United States and other developed countries in that the risk of seroconversion after exposure is greater and the rate of disease progression to AIDS and death is faster. One theory that could in part explain this difference is the increased state of immune activation associated with a relatively high rate of parasite infestation and other infections among inhabitants of these regions. Using a model based on the cellular microenvironment of lymphoid organs, the role of exposure to HIV during a state of antigen-specific immune activation was investigated. Dendritic cells and CD4+ T cells are the major cellular components of the paracortical region of lymphoid tissue, the primary site of HIV replication. We analyzed cocultures of HIV-pulsed dendritic cells that had matured in the presence of tetanus toxoid and CD4+ T cells before and after inducing an antigen-specific response by in vivo immunization with tetanus toxoid. During antigen-specific immune activation, 100 times less HIV was needed to initiate a productive infection. These findings provide a model system to further delineate the relationship between immune activation and the propagation of HIV infection and suggest a mechanism for the epidemiologic observations of an increased ease of developing HIV infection and faster progression for HIV disease in geographic areas where immune activation is prevalent.
Development of a Cancer-Targeted Tissue-Specific Promoter System
Authors: Takuya Fukazawa, Yutaka Maeda, Frances M. Sladek, Laurie B. Owen-Schaub
Journal: Cancer Research (2004)

Abstract Present cancer gene therapy using proapoptotic genes has had limited success because the therapy is prone to cause side effects as a result of the lack of tissue and cancer specificity. To target cancer cells without damaging normal cells, we have designed a novel dual promoter system in which a tissue-specific transcription system under the control of a cancer-specific promoter drives expression of a therapeutic gene. The applicability of this system was demonstrated by adapting it to target lung cancer. We termed this lung cancer system TTS (TTF1 gene under the control of human telomerase reverse transcriptase promoter and human surfactant protein A1 promoter). The TTS system showed much higher promoter activity in lung cancer cells compared with other kinds of cancer and normal lung cells, including stem cells. Moreover, insertion of negative glucocorticoid responsive elements in the system allows it to be drug controllable. The approaches that we have used could be adapted to target other types of cancer. We report a novel cancer-targeted tissue-specific dual promoter system designed for gene therapy.
CD62L expression identifies a unique subset of polyfunctional CD56dim NK cells
Authors: Kerstin Juelke, Monica Killig, Merlin Luetke-Eversloh, Eliana Parente, Joachim Gruen, Barbara Morandi, Guido Ferlazzo, Andreas Thiel, Isabela Schmitt-Knosalla, Chiara Romagnani
Journal: Blood (2010)
Anaphylaxis in America - Results from a National Telephone Survey
Authors: J. Boyle, C.A. Camargo, P. Lieberman, H. Sampson, L.B. Schwartz, F.E.R. Simons, M. Zitt, M. Wilkinson, C. Collins, M. Tringale, R. Wood
Journal: Journal of Allergy and Clinical Immunology (2012)
Subcutaneuous injection of monoclonal antibody anti-DEC205 conjugated with ovalbumin atenuates allergic lung inflammation of animals previously sensitized to allergen
Authors: Ana Paula Ligeiro de Oliveira, Eline Rampazo, Eliane Gomes, Marcio Yamamoto, Silvia Boscardin, Momtchilo Russo
Journal: European Respiratory Journal (2012)

DEC205 (Dendritic Endothelial Cell 205) is an endocytic receptor abundant on DCs in lymphoid tissues. Ovalbumin (OVA) protein can be chemically coupled to monoclonal a-DEC-205 antibody. Here, we sought to study the effect of a-DEC205 monoclonal antibody conjugated to OVA after OVA sensitization in a model of allergic lung disease. BALB/c mice were sensitized twice with OVA/Alum on days 0 and 7 and challenged twice with intranasal OVA on days 14 and 21 (OVA/alum group). The animals received a-DEC-205-OVA treatment after OVA sensitization (OVA/DEC group). The treatment consisted of two injections of a-DEC205 a week apart. We found that treatment with a-DEC205 decreased significantly allergic inflammation as revealed by total cell numbers and eosinophils counts in bronchoalveolar lavage (BAL) fluid.  In the group treated with a-DEC 205, but not with the isotype control, we observed a reduction of total and OVA-specific IgE antibodies as well as IL-4 and IL-5 levels in BAL. Furthermore, treatment with a-DEC 205 decreased the methacholine-induced respiratory pattern associated with allergy.Our results indicate that treatment with anti-DEC205 monoclonal antibody conjugated to OVA is effective in reducing allergic responses in animals previously sensitized to OVA. These results suggest a potential therapeutic use of a-DEC 205 in allergic disorders.
Endogenous Estrogens Influence Endothelial Function in Young Men
Authors: Robert Lew, Paul Komesaroff, Maro Williams, Tye Dawood, Krishnankutty Sudhir
Journal: Circulation Research (2003)

Males produce endogenous estrogen from testosterone via the enzyme aromatase. Previous studies have suggested a role for endogenous estrogens in cardiovascular function in men. We examined the effects of endogenous estrogen suppression via aromatase inhibition on endothelial function, systemic arterial compliance, and lipoprotein levels in healthy young men. Using a placebo-controlled double-blind randomized design, 20 healthy men, aged 18 to 32 years, were randomized to receive either the aromatase inhibitor anastrozole (1 mg) or matching placebo. Hormone, lipid levels, C-reactive protein (CRP), and homocysteine were measured. Endothelial function, determined by flow-mediated dilation of the brachial artery, and systemic arterial compliance were assessed at baseline and after 6 weeks of treatment. There was a significant decrease in 17β-estradiol concentrations with aromatase inhibition, from 85.4±4.2 to 64.3±8.1 pmol/L (mean±SD, P =0.042). Compared with baseline, a significant decrease in flow-mediated dilation was observed in subjects taking anastrozole [median, 6.1% (range, 5.2 to 13.4) to 3.5% (2.0 to 5.7), P =0.034] but not in the placebo group. No changes were observed in nitroglycerin-induced endothelium-independent dilation in either group. There was no change in systemic arterial compliance with either aromatase therapy or placebo. There were no significant changes in lipoproteins, testosterone, DHEA, CRP, or homocysteine levels in either the anastrozole or placebo group. We conclude that suppression of endogenous estrogens with an aromatase inhibitor resulted in impairment of flow-mediated dilation without significant changes in lipoproteins, homocysteine, or CRP. Our results suggest that endogenous estrogens play a direct regulatory role in endothelial function in young healthy men.
Functional Evidence for a Novel Suramin-Insensitive Pyrimidine Receptor in Rat Small Pulmonary Arteries
Authors: S. Anthony Hartley, Kenichi Kato, Katie J. Salter, Roland Z. Kozlowski
Journal: Circulation Research (1998)

Abstract —Uridine nucleotides are known to cause constriction of pulmonary arterial smooth muscle. However, the P2 receptor subtypes underlying the contractile effects of these nucleotides in the pulmonary circulation have not been determined. We have used myography and the patch-clamp recording technique to compare the effects of UTP and UDP in isolated small pulmonary arteries (diameter 100 to 400 μm) and their constituent smooth muscle cells. In endothelium-denuded arteries, both UTP and UDP (0.01 to 3 mmol/L) induced concentration-dependent increases in tension that were independent of P2X receptor stimulation. The UDP-mediated increase in tension was significantly less sensitive to the nonselective P2 receptor blocker suramin than the UTP-mediated increase in tension. In single isolated arterial myocytes, voltage-clamped at −50 mV (close to the resting membrane potential of these cells), application of both UTP and UDP evoked periodic oscillations of inward current primarily because of a Ca 2+ -activated Cl − current ( I Cl,Ca ). Oscillations of I Cl,Ca evoked by UTP were reversibly inhibited by suramin, although those evoked by UDP were insensitive to the antagonist. In addition to confirming the presence of classical P2Y 2 receptors, these results also provide functional evidence for the existence of a novel UDP receptor in pulmonary arterial myocytes, which may contribute to pyrimidine-evoked vasoconstriction. This notion is supported by molecular evidence that demonstrates the presence of P2Y 6 receptor transcripts in rat pulmonary arterial smooth muscle.
Effects of cardiac sympathetic stimulation and ablation of canine ventricular anodal strength-interval curves.
Authors: M J Burgess, H J Levine
Journal: Circulation Research (1976)

We studied the effects of cardiac sympathetic stimulation and ablation on characteristics of the anodal-strength interval curve in 10 pentobarbital-anesthetized open-chest dogs. We gave special attention to the form and particularly the depth of early dips of the anodal strength-interval curve. When the central connections of the cardiac sympathetic nerves were intact, left stellate stimulation decreased threshold for excitation during the dip only slightly (from 883 +/- 442 muA to 774 +/- 326 muA P less than 0.1). However, after left stellectomy and upper thoracic ganglionectomy, stimulation of the cut ends the ansa subclavia decreased the dip threshold from an average of 952 +/- 321 muA to 707 +/- 210 muA, A less than 0.01. Dip thresholds in strength-interval curves determined 1-1.5 hours after ganglionectomy average 1164 +/- 296 muA compared to an average dip threshold of 791 +/- 269 muA in strength-interval curves measured immediately prior to stellectomy. This increase is statistically significant (P less than 0.005). In addition to the effects of sympathetic tone on disparity of refractory period and ventricular fibrillation threshold, the effects of sympathetic tone on the form of the strength-interval curve may be another factor influencing vulnerability to arrhythmias and particularly in patients with abnormal autonomic tone.
Lymphomagenicity of recombinant mink cell focus-inducing murine leukemia viruses.
Authors: M W Cloyd, J W Hartley, W P Rowe
Journal: The Journal of Experimental Medicine (1980)

Recombinant mink cell focus-inducing (MCF) murine leukemic viruses, as well as ecotropic and xenotropic viruses, were tested for ability to accelerate or cause development of lymphoma in AKR and other strains of mice. Of the three classes of virus isolated from AKR, only the MCF viruses were able to accelerate development of AKR lymphoma. This fully supports the idea that the MCF viruses are the proximal cause of spontaneous AKR lymphoma. MCF lymphomagenicity was strain specific, however, in that AKR MCF viruses did not induce lymphomas in many murine strains; they were moderately lymphomagenic in C3H/Bi mice and in National Institutes of Health Swiss partially congenic for Akv-1 or Akv-2. In contrast, MCF viruses from nonthymic hematopoietic neoplasms of C3H/Fg, BALB/c, or mice partially congenic for ecotropic virus loci (Akv-1, Akv-2, Fgv-1, C58v-1, and C58v-2) were not able to accelerate or cause lymphomia in AKR or any other mouse strain tested, including some of the strains of origin. MCF lymphomagenicity correlated with thymic origin in the virus and with ability to replicate in the thymus.
Genomic analysis of the relationship between gene expression variation and DNA polymorphism in Drosophila simulans
Authors: Mara KN Lawniczak, Alisha K Holloway, David J Begun, Corbin D Jones
Journal: Genome biology (2008)

Abstract Background Understanding how DNA sequence polymorphism relates to variation in gene expression is essential to connecting genotypic differences with phenotypic differences among individuals. Addressing this question requires linking population genomic data with gene expression variation. Results Using whole genome expression data and recent light shotgun genome sequencing of six Drosophila simulans genotypes, we assessed the relationship between expression variation in males and females and nucleotide polymorphism across thousands of loci. By examining sequence polymorphism in gene features, such as untranslated regions and introns, we find that genes showing greater variation in gene expression between genotypes also have higher levels of sequence polymorphism in many gene features. Accordingly, X-linked genes, which have lower sequence polymorphism levels than autosomal genes, also show less expression variation than autosomal genes. We also find that sex-specifically expressed genes show higher local levels of polymorphism and divergence than both sex-biased and unbiased genes, and that they appear to have simpler regulatory regions. Conclusion The gene-feature-based analyses and the X-to-autosome comparisons suggest that sequence polymorphism in cis -acting elements is an important determinant of expression variation. However, this relationship varies among the different categories of sex-biased expression, and trans factors might contribute more to male-specific gene expression than cis effects. Our analysis of sex-specific gene expression also shows that female-specific genes have been overlooked in analyses that only point to male-biased genes as having unusual patterns of evolution and that studies of sexually dimorphic traits need to recognize that the relationship between genetic and expression variation at these traits is different from the genome as a whole.
Reactive airways dysfunction syndrome following exposure to a fluorocarbon
Authors: R E de la Hoz
Journal: European Respiratory Journal (1999)

This report describes the case of a 43-yr-old male who developed reactive airways dysfunction syndrome after exposure to a high level of bromotrifluoromethane (CF3Br, Halon 1301), a fluorocarbon widely used in automatic fire extinguishing systems. The patient was a previously healthy, nonatopic male, who developed wheezing and intermittent and reversible obstructive ventilatory impairment starting immediately after a large accidental nonfire-related release of CF3Br in a confined space.
Management of treatment-emergent peripheral neuropathy in multiple myeloma
Authors: P G Richardson, M Delforge, M Beksac, P Wen, J L Jongen, O Sezer, E Terpos, N Munshi, A Palumbo, S V Rajkumar, J L Harousseau, P Moreau, H Avet-Loiseau, J H Lee, M Cavo, G Merlini, P Voorhees, W J Chng, A Mazumder, S Usmani, H Einsele, R Comenzo, R Orlowski, D Vesole, J J Lahuerta, R Niesvizky, D Siegel, M-V Mateos, M Dimopoulos, S Lonial, S Jagannath, J Bladé, J San Miguel, G Morgan, K C Anderson, B G M Durie, P Sonneveld
Journal: Leukemia (2011)
5-Methyltetrahydrofolate Rapidly Improves Endothelial Function and Decreases Superoxide Production in Human Vessels
Authors: Charalambos Antoniades, Cheerag Shirodaria, Nicholas Warrick, Shijie Cai, Joseph de Bono, Justin Lee, Paul Leeson, Stefan Neubauer, Chandi Ratnatunga, Ravi Pillai, Helga Refsum, Keith M. Channon
Journal: Circulation (2006)

Background— The circulating form of folic acid, 5-methyltetrahydrofolate (5-MTHF), may have beneficial effects on endothelial function; however, its mechanisms of action remain uncertain. Decreased nitric oxide (NO) bioavailability and increased vascular superoxide production in vascular disease states are due in part to endothelial NO synthase (eNOS) uncoupling related to deficiency of the eNOS cofactor tetrahydrobiopterin (BH 4 ), but whether this mechanism is important in human atherosclerosis and represents a rational therapeutic target remains unclear. We hypothesized that 5-MTHF would improve endothelial function by decreasing superoxide and peroxynitrite production and by improving eNOS coupling, mediated by BH 4 availability. Methods and Results— Vascular superoxide/peroxynitrite production and vasomotor responses to acetylcholine and bradykinin were determined in saphenous veins and internal mammary arteries from 117 patients undergoing CABG. The effects of 5-MTHF were examined ex vivo (n=61) by incubating vessels with 5-MTHF (1 to 100 μmol/L) and in vivo by intravenous infusion of 5-MTHF or placebo before vessel harvest (n=56). 5-MTHF improved NO-mediated endothelium-dependent vasomotor responses and reduced vascular superoxide, both ex vivo and in vivo. These changes were not explained by direct superoxide scavenging by 5-MTHF in vitro or by changes in plasma total homocysteine in vivo. Rather, 5-MTHF was a strong peroxynitrite scavenger and increased vascular BH 4 and the BH 4 /total biopterin ratio. Furthermore, 5-MTHF reversed eNOS uncoupling, as assessed by N G -nitro- l -arginine methyl ester–inhibitable superoxide production, increased the eNOS dimer:monomer ratio, and enhanced eNOS activity. Conclusions— 5-MTHF has beneficial effects on endothelial function and vascular superoxide production in human atherosclerosis, by preventing peroxynitrite-mediated BH 4 oxidation and improving eNOS coupling.
Selective Binding and Presentation of CCL5 by Discrete Tissue Microenvironments during Renal Inflammation
Authors: Stephan Segerer, Roghieh Djafarzadeh, Hermann-Josef Gröne, Christian Weingart, Dontscho Kerjaschki, Christian Weber, Andreas J. Kungl, Heinz Regele, Amanda E.I. Proudfoot, Peter J. Nelson
Journal: Journal of the American Society of Nephrology (2007)

T cells are differentially recruited to the tubulointerstitium during renal inflammation. The selective presentation of chemokines by surface structures may in part underlie this phenomenon. In an attempt to better characterize the presentation of chemokines by tissue environments an exemplary chemokine with a well-defined structure was selected, and a binding assay for the protein on fixed archival tissue sections was developed. This article describes the selective binding of the chemokine CCL5 to renal structures. CCL5 was shown to bind to endothelial regions, interstitial extracellular matrix, tubular epithelial cells, and tubular basement membranes but rarely to glomerular structures in well-preserved kidneys. In contrast, binding of CCL5 to glomerular components was seen in renal biopsies with acute allograft glomerulitis (in which T cells accumulate in glomeruli). The N terminus mediates receptor binding, whereas two clusters of basic amino acid residues ((44)RKNR(47) and (55)KKWVR(59)) are involved in the presentation of CCL5 by extracellular structures. Mutation of either loop abrogated CCL5 binding to tissue sections. Variations of the N terminus and a mutation that prevents higher order oligomerization did not change the binding pattern. The data suggest that renal compartments differ in their capacity to present chemokines, which may help explain the differential recruitment of leukocytes during allograft injury. Both clusters of basic residues in CCL5 are necessary for sufficient binding of CCL5 to tissue sections.