tbuckley/cabot-search huggingface dataset:
The Down syndrome critical region gene 1 short variant promoters direct vascular bed–specific gene expression during inflammation in mice
Authors: Takashi Minami, Kiichiro Yano, Mai Miura, Mika Kobayashi, Jun-ichi Suehiro, Patrick C. Reid, Takao Hamakubo, Sandra Ryeom, William C. Aird, Tatsuhiko Kodama
Journal: Journal of Clinical Investigation (2009)

Down syndrome critical region gene 1 (DSCR-1) short variant (DSCR-1s) is an inhibitor of calcineurin/NFAT signaling encoded by exons 4–7 of DSCR1. We previously reported that VEGF induces DSCR-1s expression in endothelial cells, which in turn negatively feeds back to attenuate endothelial cell activation. Here, in order to characterize the role of the promoter that drives DSCR-1s expression in mediating inducible expression in vivo and to determine the functional relevance of DSCR-1s in inflammation, we targeted a DNA construct containing 1.7 kb of the human DSCR1s promoter coupled to the lacZ reporter to the hypoxanthine guanine phosphoribosyl transferase (Hprt) locus of mice. We determined that lacZ was uniformly expressed in the endothelium of transgenic embryos but was markedly downregulated postnatally. Systemic administration of VEGF or LPS in adult mice resulted in cyclosporine A–sensitive reactivation of the DSCR1s promoter and endogenous gene expression in a subset of organs, including the heart and brain. The DSCR1s promoter was similarly induced in the endothelium of tumor xenografts. In a mouse model of endotoxemia, DSCR-1s–deficient mice demonstrated increased sepsis mortality, whereas adenovirus-mediated DSCR-1s overexpression protected against LPS-induced lethality. Collectively, these data suggest that the DSCR1s promoter directs vascular bed–specific expression in activated endothelium and that DSCR-1s serves to dampen the host response to infection.
Inorganic particles of agricultural origin
Authors: Kingsley Kay
Journal: Environmental Health Perspectives (1974)

Substantial quantities of mineral silicates are used as carriers for agricultural pest control agents. Most of this material is applied by air dissemination, either dry or as a droplet spray. Therefore, pulmonary and gastric deposition of the mineral carriers (and active agents) will occur among pesticide application personnel and some proportion of the general population in the vicinity of pest control operations-to the extent that particle size of the disseminated material is below the critical 5mum respirable diameter. Furthermore, ingestion of particulates deposited on food crops may be expected as well as mineral finding its way into drinking water supplies. It has been found that the silicates widely used in America can contain three forms of asbestos, anthophyllite, tremolite, and chrysolite. Of these, anthophyllite and chrysotile have been found associated with a neoplastic outcome after many years of exposure. It is therefore proposed that comprehensive mineralogical investigation of pesticide carriers is warranted, including epidemiological and clinical study of formulation and application personnel as well as exposed nonoccupational populations.
Molecular Mechanisms of the Diabetogenic Effects of Arsenic: Inhibition of Insulin Signaling by Arsenite and Methylarsonous Acid
Authors: David S. Paul, Anne W. Harmon, Vicenta Devesa, David J. Thomas, Miroslav Stýblo
Journal: Environmental Health Perspectives (2007)

Increased prevalences of diabetes mellitus have been reported among individuals chronically exposed to inorganic arsenic (iAs). However, the mechanisms underlying the diabetogenic effects of iAs have not been characterized. We have previously shown that trivalent metabolites of iAs, arsenite (iAs(III)) and methylarsonous acid (MAs(III)) inhibit insulin-stimulated glucose uptake (ISGU) in 3T3-L1 adipocytes by suppressing the insulin-dependent phosphorylation of protein kinase B (PKB/Akt).Our goal was to identify the molecular mechanisms responsible for the suppression of PKB/Akt phosphorylation by iAs(III) and MAs(III).The effects of iAs(III) and MAs(III) on components of the insulin-activated signal transduction pathway that regulate PKB/Akt phosphorylation were examined in 3T3-L1 adipocytes.Subtoxic concentrations of iAs(III) or MAs(III) had little or no effect on the activity of phosphatidylinositol 3-kinase (PI-3K), which synthesizes phosphatidylinositol-3,4,5-triphosphate (PIP(3)), or on phosphorylation of PTEN (phosphatase and tensin homolog deleted on chromosome ten), a PIP(3) phosphatase. Neither iAs(III) nor MAs(III) interfered with the phosphorylation of 3-phosphoinositide-dependent kinase-1 (PDK-1) located downstream from PI-3K. However, PDK-1 activity was inhibited by both iAs(III) and MAs(III). Consistent with these findings, PDK-1-catalyzed phosphorylation of PKB/Akt(Thr308) and PKB/Akt activity were suppressed in exposed cells. In addition, PKB/Akt(Ser473) phosphorylation, which is catalyzed by a putative PDK-2, was also suppressed. Notably, expression of constitutively active PKB/Akt restored the normal ISGU pattern in adipocytes treated with either iAs(III) or MAs(III).These results suggest that inhibition of the PDK-1/PKB/Akt-mediated transduction step is the key mechanism for the inhibition of ISGU in adipocytes exposed to iAs(III) or MAs(III), and possibly for impaired glucose tolerance associated with human exposures to iAs.
Radionuclide Shunt Patency Study for Suspected Ventriculoatrial Shunt Malfunction
Authors: Beril Gok, Sachin Batra, Hedieh Eslamy, Daniele Rigamonti, Harvey Ziessman
Journal: Clinical Nuclear Medicine (2013)

Objective Radionuclide shunt studies have been used for decades to evaluate intracranial shunt patency (SP); however, the methodology is neither standardized nor well validated. The purpose of this study was to determine the clinical utility of radionuclide ventriculoatrial (VA) SP study for diagnosis of suspected shunt malfunction. Methods A retrospective review was undertaken of all patients who had a VA radionuclide SP study between 2001 and 2009. All had a 20-minute gamma camera acquisition (1 min/frame) immediately following injection of 99mTc DTPA into the shunt reservoir. Time-activity curves were generated and a half-time (T½) of emptying quantified. The results were correlated with the final clinical diagnoses. Results Forty-nine studies in 40 adult patients with a minimum of 6 months’ follow-up were analyzed. Thirteen shunt studies had a T½ of 3.9 to 8.0 minutes, had final diagnosis of normal functioning shunt, and did not need revision surgery for a mean follow-up of 15.1 months. Fourteen patient studies had a T½ of less than 3.9 minutes; 13 had final diagnosis of overdraining shunts, and 1 required revision surgery. Twenty-two had a T½ longer than 8 minutes: 13 had final diagnosis of shunt obstruction, 4 had overdrainage, and 5 had underdrainage. Conclusions The radionuclide SP study is valuable for evaluation of VA SP. Results can be interpreted using a single variable (T½). T½ of 3.9 to 8 minutes indicates a patent shunt; T½ less than 3.9 minutes is consistent with overdrainage. T½ of >8 requires further evaluation to differentiate between obstruction and overdrainage/underdrainage.
Antigens, Lymphoid Cells, and the Immune Response
Authors: Max Samter
Journal: JAMA (1971)

It is a pleasure to welcome this new venture by the seasoned editors of<i>Advances in Immunology</i>. It is apparent—and should be considered a compliment—that the organization of the chapters of<i>Advances</i>has served as a model for the organization of this text. The monograph is a provocative and scholarly review of research on the interaction between antigen and lymphocyte. The "confrontation" between antigen and cell has been one of the major efforts of the Walter and Eliza Hall Institute, and the book is properly dedicated to F. M. Burnet "to whom we both owe so much." The past decade has contributed a large variety of studies on lymphocytes—some in vitro, some in vivo—which, at times, seem to contradict each other. It is the objective of this monograph to place the findings into proper perspective: it is an excellent, critical, near-definite review, but not merely a summing-up. There are still
Baked Proteins In The Management Of Cow'S Milk And Egg Allergic Children, Less Than 2 Years Of Age: Are Infants At Increased Risk Of Breakthrough Reactions?
Authors: M.I. Kidon, M. Deutch, M. Yaron, A. Goren, A. Siedletzki, S. Steinberg, A. Reshef
Journal: Journal of Allergy and Clinical Immunology (2012)
Treatment of Angina Pectoris
Authors: Joseph F. Uricchio, Daniel G. Calenda
Journal: New England Journal of Medicine (1953)

MORGAGNI,1 in the middle of the eighteenth century, described patients who were no doubt suffering from angina pectoris; however, it remained for Heberden,2 in 1768, to present his classic description of the disorder:But there is a disorder of the breast marked with strong, peculiar symptoms, considerable for the kind of danger belonging to it, and not extremely rare which deserves to be mentioned here at length. The seat of it, and the sense of strangling and anxiety with which it is attended, may make it improperly called angina pectoris.... They who are afflicted with it are seized while they . . .
Active cytomegalovirus infection of arterial smooth muscle cells in immunocompromised rats. A clue to herpesvirus-associated atherogenesis?
Authors: M C Persoons, M J Daemen, J H Bruning, C A Bruggeman
Journal: Circulation Research (1994)

The susceptibility of medial and neointimal arterial smooth muscle cells (SMCs) to acute cytomegalovirus (CMV) infection was investigated in immunocompetent and immunocompromised rats. The left common carotid artery of all the rats was injured by balloon catheterization. On days 14 and 17 after injury, rats were either intravenously infected with a rat CMV (RCMV) or mock-infected. Active RCMV infection was shown in the neointima of the injured arteries of immunosuppressed rats, characterized by specific cytopathological changes in hematoxylin-eosin-stained sections and by the presence of early viral antigens and the presence of the virus at different stages of maturation at the electron-microscopic level. Viral genome was shown as well by use of in situ hybridization procedures. However, medial cells were hardly ever infected, and RCMV did not infect neointimal parts that were recovered by endothelial cells. No infection was seen in control right carotid arteries or in the injured arteries of immunocompetent rats. Acute intimal RCMV infection was accompanied by infiltration of inflammatory cells, predominantly mononuclear cells that stained positive with an ED-1 monoclonal antibody. The majority of infected neointimal cells were SMCs containing smooth muscle actin. No changes were found in medial or neointimal cross-sectional areas of the infected arteries. In the present study, an active RCMV infection of arterial SMCs was established in vivo, and it was concluded that neointimal SMCs are far more susceptible than are medial SMCs and that the absence of endothelium and immunosuppression are necessary conditions for arterial RCMV infection.
AI-29 * ANGIOGENIC SWITCH FROM VEGFR2/HIF1 IN NEWLY DIAGNOSED GLIOBLASTOMA (GB) TO CXCR4-SDF1 PATHWAY IN RECURRENT PAIRED TUMOR AFTER RADIOTHERAPY (RT)-TEMOZOLOMIDE (TMZ)
Authors: E. Tabouret, A. Tchoghandjian, E. Denicolai, C. Delfino, P. Metellus, L. Padovani, I. Nanni, M. Barrie, C. Boucard, L. Ouafik, D. Figarella-Branger, O. Chinot
Journal: Neuro-Oncology (2014)

BACKGROUND: Angiogenesis is one of the key features of GB. Our objective was to explore the potential changes of angiogenic factors expression between initial diagnosis of GB and recurrence after RT/TMZ. METHODS: Paired frozen tumor tissues from both initial and recurrent surgery were available for 29 patients with GB treated with RT/TMZ without bevacizumab upfront. Screening of over 150 genes expressions related to angiogenesis was performed on first 10 paired samples, using RT- PCR arrays (Qiagen®). Comparative expressions were determined using Qiagen® software. In a second step, RNA expressions of the selected identified genes were analyzed on all samples (29 paired tumors) using quantitative RT-PCR (qRT-PCR). Protein expression was examined by immunohistochemistry (IHC) with a semi-quantitative measure. Anti-tumoral effect of an anti-CXCR4 (AMD3100) in addition to TMZ and RT was tested in GB explants. RESULTS: In the screening step performed by RT-PCR arrays the initial-recurrence expression changes contributed to a selection of seven genes for which expression was then quantified by qRT-PCR: VEGFA, VEGFR2, VEGFR1, SDF1, CXCR4, uPA and HIF1α. From initial diagnosis to recurrence RNA expressions of CXCR4 (p = 0.029) and SDF1 (p = 0.107) were increased while expressions of HIF1α (p = 0.009) and VEGFR2 (p = 0.081) were decreased. Similarly, SDF1 protein expression (IHC) tended to increased (p = 0.096) while VEGFR2 staining was significantly decreased (p = 0.004) at recurrence. The role of CXCL4 was further supported by an increase of anti-tumoral effect observed with the combination of AMD3100 and RT/TMZ versus RT/TMZ alone in GB explants. By multivariate analysis, VEGFR2 RNA initial and recurrence expression levels were significantly correlated respectively to initial overall survival (p = 0.019, Hazard ratio (HR) =3.650) and recurrent overall survival (p = 0.024, HR = 2.536). CONCLUSION: Recurrence of GB after chemo-radiation could be associated with a switch of angiogenic pattern from VEGFR2-HIF1α to SDF1-CXCR4 pathway, leading to new perspectives in angiogenic modulation and GB treatment.
Pulmonary Aspergillosis in a Child with Leukemia
Authors: I. Berkel, B. Say, B. Tinaztepe
Journal: New England Journal of Medicine (1963)

PULMONARY aspergillosis is a fungous infection usually caused by Aspergillus fumigatus although other species of aspergilli occasionally are encountered. This fungus was described and named by Micheli1 in 1729. Bennett2 was probably the first to report its presence in human beings, and later investigators discovered that aspergilli, under certain conditions, may invade many different parts of the body. The most commonly affected organ is the lung, but other sites, such as the brain, meninges, heart, spleen, liver, kidneys, aorta and smaller vessels, thyroid gland, duodenum, bones, lymph nodes and the skin can also be involved, particularly in disseminated forms of . . .
Antiphospholipid Antibodies in Predicting Adverse Pregnancy Outcome: A Prospective Study
Authors: Anne Lynch
Journal: Annals of Internal Medicine (1994)

Objective: To determine if the presence of antiphospholipid antibody (aPL) in healthy pregnant women is associated with adverse pregnancy outcome, including 1) intrauterine fetal loss, 2) maternal pregnancy complications, 3) low birth weight, and 4) low 5-minute Apgar scores. Design: Prospective cohort study in women with normal pregnancies. Setting: Obstetrics clinic at the University of Colorado Health Sciences Center. Patients: Eligible patients included 451 low-risk, nulliparous pregnant women who came to the obstetrics clinic before 25 weeks gestation; 408 were enrolled and 389 had blood drawn at the first prenatal visit and completed clinical follow-up. Measurements: Blood for six aPL measures was drawn at the first prenatal visit and for 239 patients at delivery. Results: Ninety-five patients (24.4%) had elevated aPL levels by one or more measures at the first prenatal visit: 15.8% of the aPL-positive and 6.5% of the aPL-negative patients experienced fetal loss (relative risk, 2.44; 95% CI, 1.29 to 4.62). However, an elevated IgG anticardiolipin antibody level at the first prenatal visit was the only aPL measurement that was significantly associated with fetal loss (relative risk, 3.5; CI, 1.56 to 8.07). Adjustment for confounding variables decreased the relative risk of aPL for fetal loss slightly, but the difference remained statistically significant. Neither a positive aPL result at the initial visit nor a positive result at delivery was associated with maternal complications of pregnancy, low birth weight, or low Apgar scores. Conclusions: Patients with elevated aPL levels at their initial prenatal visit had an increase in fetal loss but no increase in maternal pregnancy complications, low birth weight, or low Apgar scores. Immunoglobulin G anticardiolipin antibody was the only single test of aPL significantly associated with fetal loss.
Taskforce rejects system of presumed consent for organ donation in UK
Authors: Z. Kmietowicz
Journal: BMJ (2008)

The government is to launch a major publicity campaign on the importance of organ donation, with the aim of getting many more people in the United Kingdom to join the organ donor register.

A report from the Organ Donation Taskforce has rejected introducing a system of presumed consent to increase the number of organ donations, saying that there is insufficient evidence that such an opt-out system would increase numbers of donations and that it risked breaking the trust between patients and doctors that is essential in an effective transplantation service. 

The government, which has accepted recommendations from the taskforce in full, has opted instead to put £4.5m (€5.3m; $6.7m) into a campaign that it hopes will see the number of people on the register rise from the more than 15 million currently to 20 million by 2010 and 25 million by 2013. 

Work is already under way to implement recommendations made in the taskforce’s first report, published in January ( BMJ 2008;336:111; doi:10.1136/bmj.39462.489132.DB). These recommendations include recruiting 63 new donor transplant coordinators, reimbursing trusts for managing organ donations, and establishing a UK-wide network of dedicated organ retrieval teams ( BMJ  January 19 2008;336:111). 

However, if …
Atherosclerosis or lipoprotein-induced endothelial dysfunction. Potential mechanisms underlying reduction in EDRF/nitric oxide activity.
Authors: N A Flavahan
Journal: Circulation (1992)

Activation of endothelial cells by physical, chemi- cal, and hormonal stimuli can result in the release of a number of vasoactive mediators.1Under physiological conditions, mediator release ap- pears to be balanced in favor of inhibitory factors such as endothelium-derived relaxing factor (EDRF, identified as nitric oxide) and prostacyclin (PGI2) (Figure 1).'-3EDRF-NO and PGI have important protective actions in the vascular wall: They are potent inhibitors of smooth muscle contraction and smooth muscle proliferation,14 and they also inhibit platelet aggregation, stimulate platelet disaggregation, and inhibit platelet or monocyte adhesion to the endothelial surface.25,6The endothelial cells located at sites that are prone to atherosclerosis appear to be morphologically and functionally different from normal endothelial cells.7-10These endothelial cells have a diminished protective role in the blood vessel wall and may actively promote the atherosclerotic process.8Numerous studies have demonstrated that a dysfunction in the release of EDRF-NO appears to occur at an early stage in the atherosclerotic process in animals and hu- mans.'1-23This impairment in EDRF-NO release may be associated with an increased release of endotheliumderived contracting factors (EDCFs),18'24 which are func- tional and chemical antagonists of 1).The shift in the balance of endothelial mediators might contribute in part to the diminution in the protec- tive role of the endothelium and could predispose the blood vessel to vasospasm or to a further progression of the disease process.Previous studies have demonstrated that the impairment in endothelial dilator activity that occurs in ath- erosclerotic or hypercholesterolemic blood vessels re- flects an impairment in the ability of the cells to respond to specific stimuli.Thus, in a number of different arterial preparations (Table 1), hypercholesterolemia did not affect the endothelium-dependent relaxations evoked by certain stimuli, e.g., A23187, but caused
Preferential Impairment of Nitric Oxide–Mediated Endothelium-Dependent Relaxation in Human Cervical Arteries After Irradiation
Authors: Tsuneki Sugihara, Yuichi Hattori, Yuhei Yamamoto, Fazhi Qi, Ryoichi Ichikawa, Atsushi Sato, Ming-Yue Liu, Kazuhiro Abe, Morio Kanno
Journal: Circulation (1999)

Vascular abnormalities are a major cause of postoperative complications in irradiated tissues. Endothelial cell dysfunction characterized by diminished endothelium-dependent relaxation may be involved. We examined the endothelium-dependent relaxation and morphology of the endothelium in irradiated human cervical arteries.Irradiated arteries were taken from the neck region of patients who had radiation therapy. Arteries from patients who did not receive radiation therapy were used as controls. Endothelium-dependent relaxation to acetylcholine and A23187 was impaired in irradiated arteries. Norepinephrine-induced contraction and sodium nitroprusside-induced relaxation were unchanged. In control arteries, N(omega)-nitro-L-arginine and indomethacin each caused a partial inhibition of endothelium-dependent relaxation. In irradiated arteries, the impaired endothelium-dependent relaxation was unaffected by these agents, but it was abolished by high K(+). Acetylcholine produced similar degrees of hyperpolarization in control and irradiated arteries. Immunohistochemical examination for endothelial nitric oxide synthase indicated no expression in the endothelium of irradiated arteries. Electron scanning microscopy showed morphologically intact endothelial cells in irradiated arteries.In irradiated human cervical arteries, the nitric oxide- and prostacyclin-mediated endothelium-dependent relaxation, but not endothelium-derived hyperpolarizing factor-mediated relaxation, are specifically impaired, without significant morphological damage of the endothelium. The impaired nitric oxide-mediated relaxation was associated with a lack of endothelial nitric oxide synthase expression. Our results suggest the importance of impaired endothelial function in irradiated human blood vessels, which may partly explain the development of vascular stenosis and poor surgical wound healing in irradiated tissues.
External-Beam Radiotherapy for Localized Prostate Cancer
Authors: Thomas M. Pisansky
Journal: New England Journal of Medicine (2006)

External-beam radiotherapy is recommended for a 69-year-old man with localized prostate cancer. This therapy has evolved rapidly owing to the development of sophisticated techniques for focusing the radiation beam precisely on its target. Important adverse effects include radiation proctitis, cystitis, urethritis, and erectile dysfunction.
Evolutionary and biomedical implications of a Schistosoma japonicum complementary DNA resource
Authors: Wei Hu, Qing Yan, Da-Kang Shen, Feng Liu, Zhi-Dong Zhu, Huai-Dong Song, Xiang-Ru Xu, Zhao-Jun Wang, Yi-Ping Rong, Ling-Chun Zeng, Jian Wu, Xin Zhang, Ju-Jun Wang, Xue-Nian Xu, Sheng-Yue Wang, Gang Fu, Xiang-Lin Zhang, Zhi-Qin Wang, Paul J Brindley, Donald P McManus, Chun-Liang Xue, Zheng Feng, Zhu Chen, Ze-Guang Han
Journal: Nature Genetics (2003)