tbuckley/cabot-search huggingface dataset:
NO-cGMP pathway increases the hyperpolarisation-activated current, If, and heart rate during adrenergic stimulation
Authors: N Herring
Journal: Cardiovascular Research (2001)

Objectives: The role of the nitric oxide (NO)-cGMP pathway in the autonomic modulation of cardiac pacemaking is controversial and may involve an interplay between the L-type calcium current, ICaL, and the hyperpolarisation activated current, If. We tested the hypothesis that following adrenergic stimulation, the NO-cGMP pathway stimulates phosphodiesterase 2 (PDE2) to reduce cAMP dependent stimulation of If and heart rate (HR). Methods: In the presence of norepinephrine (NE, 1 μM), the effects of the NO donor sodium nitroprusside (SNP) were evaluated in sinoatrial node (SAN)/atria preparations and isolated SAN cells from adult guinea pigs. Results: Contrary to our hypothesis, SNP (10 and 100 μM, n=5) or the membrane permeable cGMP analogue, 8Br-cGMP (0.5 mM, n=6) transiently increased HR by 5±1, 12±1 and 12±2 beats/min, respectively. The guanylyl cyclase inhibitor 1H-(1,2,4)-oxadiazolo-(4,3-a)-quinoxalin-1-one (ODQ, 10 μM, n=5) abolished the increase in HR to SNP (100 μM) as did the If blockers caesium chloride (2 mM, n=7) and 4-(N-ethyl-N-phenylamino)-1,2-dimethyl-6-(methylamino)-pyrimidinium chloride (ZD7288, 1 μM, n=7). Addition of SNP (10 μM) also transiently increased If in SAN cells (n=5). After inhibition of PDE2 with erythro-9-(2-hydroxy-3-nonyl)-adenine (EHNA, 10 μM, n=5), the increase in HR to SNP in the presence of NE was significantly augmented and maintained. RT-PCR analysis confirmed the presence of PDE2 in addition to cGMP inhibited PDE3 mRNA in central SAN tissue. Conclusions: These results suggest that during adrenergic stimulation, activation of the NO-cGMP pathway does not decrease HR, but has a transient stimulatory effect that is If dependent, and is limited in magnitude and duration by stimulation of PDE2.
Memory CD8+ T Cells Provide Innate Immune Protection against <i>Listeria monocytogenes</i> in the Absence of Cognate Antigen
Authors: Rance E. Berg, Emily Crossley, Sean Murray, James Forman
Journal: The Journal of Experimental Medicine (2003)

Interferon (IFN)-γ plays an important role in the innate immune response against intracellular bacterial pathogens. It is commonly thought that natural killer cells are the primary source of this cytokine that is involved in activating antibacterial effects in infected cells and polarizing CD4+ T cells toward the Th1 subset. However, here we show that both effector and memory CD8+ T cells have the potential to secrete IFN-γ in response to interleukin (IL)-12 and IL-18 in the absence of cognate antigen. We demonstrate that memory CD8+ T cells specific for the ovalbumin protein secrete IFN-γ rapidly after infection with wild-type Listeria monocytogenes (LM). Furthermore, small numbers of ovalbumin-specific, memory CD8+ T cells can reduce spleen and liver bacterial counts in IFN-γ–deficient mice 3 d after LM infection. Up-regulation of the receptors for IL-12 and IL-18 provides a mechanism for the ability of memory CD8+ T cells to respond in this antigen nonspecific manner. Thus, CD8+ T cells play an important role in the innate immune response against intracellular pathogens by rapidly secreting IFN-γ in response to IL-12 and IL-18.
Abstract 1147: Expression of <i>ERO1L</i> gene is poor prognostic factor for gastric cancer.
Authors: So-Young Seol, Jae Yun Lim, Sun Och Yoon, Soon Won Hong, Jong Won Kim, Seung Ho Choi, Jae Yong Cho
Journal: Cancer Research (2013)

Abstract Gastric cancer is the second cause of cancer-related deaths worldwide. Even though within same stage, gastric cancer patients present diverse clinical manifestations and prognosis. Molecular markers will be important in predicting patients’ outcomes and tailoring personalized treatments according to individual biology. In this study, we analyzed the gene expression profile of human gastric cancer (published on CCR) to identify potential biomarkers. We found that TXN family genes and ERO1L were significantly overexpressed and related to prognosis. We evaluated ERO1L significantly overexpressed in gastric cancer and ERO1L was very highly expressed in hypoxic condition. The other study has identified ERO1L as included in the small group of eight genes predicting poor survival of patients with pulmonary adenocarcinoma. To investigate the function of ERO1L gene in gastric cancer cell line (AGS, MKN1 and NCI-N87), we tested the effect of shRNA inhibition of ERO1L on gastric cancer cells. To determine the biologic role of ERO1L in regulating cancer cell proliferation, stable transfection of shRNA for ERO1L in gastric cancer cells. Our results showed that shERO1L decrease cell proliferation. Furthermore, Knock down expression by shERO1L have effects on regulating gastric cancer cell apoptosis. Next, we tested whether or not the ERO1L gene is involved in progression to metastatic disease in gastric cancer,especially in late tumorigenesis, including migration and invasion. As a results, Knock down expression for ERO1L significantly decreased the migration and invasiveness of gastric cancer cells. In conclusion, our findings show that a prognostic molecular signature that can predict the poor progression of gastric cancer tumors. Furthermore, unequal distribution of expression patterns reflecting activation of ERO1L with different survival rates supports a personalized target therapy in gastric cancer with biomarker gene signature driven patient selection. While further work is needed to elucidate the biological contributions of these markers in. in vivo, the results presented here provide a basis for future investigations of the functional and clinical effect of new target genes in gastric cancer. Citation Format: So-Young Seol, Jae Yun Lim, Sun Och Yoon, Soon Won Hong, Jong Won Kim, Seung Ho Choi, Jae Yong Cho. Expression of ERO1L gene is poor prognostic factor for gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1147. doi:10.1158/1538-7445.AM2013-1147
[547] A SYSTEMATIC REVIEW OF TRANSJUGULAR LIVER BIOPSY SERIES PUBLISHED BETWEEN 1978-2006: QUALITY OF SPECIMENS FOR EVALUATION OF CHRONIC HEPATITIS C AND COMPLICATIONS
Authors: G. Kalambokis, P. Manousou, L. Marelli, S. Vibhakorn, E. Cholongitas, M. Senzolo, D. Patch, A.K. Burroughs
Journal: Journal of Hepatology (2007)
Bedside Rounds Revisited
Authors: George E. Thibault
Journal: New England Journal of Medicine (1997)

Nearly 40 years after William Osler advocated “radical reform” at Johns Hopkins to bring medical education to the bedside,1 Romano reported the observations of 100 patients at Peter Bent Brigham Hospital whose physicians had made case presentations during ward rounds.2 He concluded: “Ward round teaching, when conducted tactfully and sympathetically . . . is not a traumatic emotional experience to patients but educates and reassures them.”2 In the five decades since Romano's report, there has been a progressive decline in the practice of bedside teaching.3,4 The perception that patients are uncomfortable during rounds at the bedside is often cited . . .
RECOVERY FROM SUBACUTE INFECTIVE ENDOCARDITIS FOLLOWING GENTIAN VIOLET THERAPY
Authors: RALPH H. MAJOR
Journal: JAMA (1925)

The prognosis in subacute infective endocarditis has in the past been regarded as extremely gloomy. Lenhartz,<sup>1</sup>after an experience of many years, found only one patient who recovered. Libman<sup>2</sup>has repeatedly emphasized the great seriousness of this disease, and Barker<sup>3</sup>states that every one of his thirty patients died. A patient with subacute infective endocarditis made such a prompt recovery following the intravenous use of gentian violet that the case seemed worthy of record. A colored woman, aged 25, admitted to the Bell Memorial Hospital, March 6, 1924, complained of shortness of breath and pain in the chest. Her family history was negative. The patient had had much trouble with her teeth and also frequent attacks of tonsillitis. Her history otherwise was negative. Five months before admission, the patient had a profuse menorrhagia and went to bed on the advice of her physician. There was some flow
Abstract 332: Establishment of animal model for metastasis of human lung cancers using NOJ/SCID mice.
Authors: Naoko Aragane, Akemi Sato, Naomi Kobayashi, Masaru Ide, Eisaburo Sueoka, Seiji Okada, Shinya Kimura
Journal: Cancer Research (2013)

Abstract Lung cancer is the leading cause of cancer death among malignant tumors. Lymphogenic and distant metastases were found approximately 70% at the diagnosis, and most of recurrence after surgery occurs as distant metastasis. Therefore, it is important to establish the new strategy for control of metastatic lung cancers. Since metastasis consists of several steps such as loss of cell adhesion, intravasation, survival in circulation, exit into new tissues, and colonization in a distant site, a suitable animal model is indispensable for investigation of metastasis. In addition, recent investigations revealed that biological and molecular characteristics of cancer cells were different between primary and metastatic lesions, as well as among each metastatic site. To establish the animal model reflecting human metastatic lung cancers, we used NOD/Scid/Jak3null (NOJ) mice, which exhibit deficiencies in NK cell activity, macrophage and DC function, and complement activation as well as T and B cell deficiencies. This animal model enabled us to engraft various human cells more easily than previous immunodeficiency mouse models. At first, twenty kinds of human lung cancer cell lines were screened by expression pattern of E-cadherin and vimentin using western blot analysis, and two cell lines with high expression of vimentin and low expression of E-cadherin were selected. The cells (1×107/mouse) were injected into the dorsal flanks, and one cell line, H1975 showed lymphogenic metastasis to axillary and abdominal lymph nodes, resulting dissemination to pleura and diaphragm with ascites. Since H1975 cells carry epidermal growth factor receptor (EGFR) mutation, L858R and T790M, we can monitor the existence of cancer cells using a sensitive detection system, mutation-biased PCR and quenched probe system (MBP-QP), which were established in our laboratory. We have also tried to establish the animal model which lung cancer cells are inoculated into lung to mimic metastasis of human lung cancers. Using these model systems, we have been performing comprehensive analysis including mRNA expression, the mutation status of lung cancer related genes in each metastatic site, and compared the phosphorylation status of 38 kinds of molecules. Our goal of this study is to establish the animal model to reproduce phenotypes of metastasis of human lung cancers for screening of anti-metastatic agents. Citation Format: Naoko Aragane, Akemi Sato, Naomi Kobayashi, Masaru Ide, Eisaburo Sueoka, Seiji Okada, Shinya Kimura. Establishment of animal model for metastasis of human lung cancers using NOJ/SCID mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 332. doi:10.1158/1538-7445.AM2013-332
MATERNAL DEATHS FROM COCCIDIOIDOMYCOSIS
Authors: LEROY E. SMALE
Journal: JAMA (1949)

Disseminated coccidioidomycosis as a cause of maternal deaths has not been reported previously. We are reporting 4 fatal cases, while a fifth case is still being observed. Unquestionably, other fatal and unrecognized cases have occurred in this endemic area, or the subjects have migrated to other areas, with a final diagnosis of maternal death due to meningitis of unspecified cause. In Kern General Hospital for the year 1948, there were 4 maternal deaths in 2,410 deliveries; of these deaths, 3 were due to disseminated coccidioidomycosis. It is interesting to note that during the same year no mothers died of tuberculosis, either in this hospital or in Kern County. We feel that other cases will be discovered and reported and that the pathogenesis of disseminated coccidioidomycosis as a fatal complication of pregnancy and as a cause of maternal death will become well known. <h3>REVIEW OF LITERATURE</h3> An exhaustive search of the
The nature of antioxidant defense mechanisms: a lesson from transgenic studies.
Authors: Y S Ho, J L Magnenat, M Gargano, J Cao
Journal: Environmental Health Perspectives (1998)

Reactive oxygen species (ROS) have been implicated in the pathogenesis of many clinical disorders such as adult respiratory distress syndrome, ischemia-reperfusion injury, atherosclerosis, neurodegenerative diseases, and cancer. Genetically engineered animal models have been used as a tool for understanding the function of various antioxidant enzymes in cellular defense mechanisms against various types of oxidant tissue injury. Transgenic mice overexpressing three isoforms of superoxide dismutase, catalase, and the cellular glutathione peroxidase (GSHPx-1) in various tissues show an increased tolerance to ischemia-reperfusion heart and brain injury, hyperoxia, cold-induced brain edema, adriamycin, and paraquat toxicity. These results have provided for the first time direct evidence demonstrating the importance of each of these antioxidant enzymes in protecting the animals against the injury resulting from these insults, as well as the effect of an enhanced level of antioxidant in ameliorating the oxidant tissue injury. To evaluate further the nature of these enzymes in antioxidant defense, gene knockout mice deficient in copper-zinc superoxide dismutase (CuZnSOD) and GSHPx-1 have also been generated in our laboratory. These mice developed normally and showed no marked pathologic changes under normal physiologic conditions. In addition, a deficiency in these genes had no effects on animal survival under hyperoxida. However, these knockout mice exhibited a pronounced susceptibility to paraquat toxicity and myocardial ischemia-reperfusion injury. Furthermore, female mice lacking CuZnSOD also displayed a marked increase in postimplantation embryonic lethality. These animals should provide a useful model for uncovering the identity of ROS that participate in the pathogenesis of various clinical disorders and for defining the role of each antioxidant enzyme in cellular defense against oxidant-mediated tissue injury.
Outdoor air pollution, low birth weight, and prematurity.
Authors: M Bobak
Journal: Environmental Health Perspectives (2000)

This study tested the hypothesis, suggested by several recent reports, that air pollution may increase the risk of adverse birth outcomes. This study analyzed all singleton live births registered by the Czech national birth register in 1991 in 67 districts where at least one pollutant was monitored in 1990-1991 (n = 108,173). Maternal exposures to sulfur dioxide (SO(2)), total suspended particles (TSP), and nitrous oxides (NO(x)) in each trimester of pregnancy were estimated as the arithmetic means of all daily measurements taken by all monitors in the district of birth of each infant. Odds ratios of low birth weight (< 2,500 g), prematurity (< 37 weeks of gestation), and intrauterine growth retardation (IUGR; < 10th percentile of birth weight for gestational age and sex) were estimated by robust logistic regression. The median (and 25th and 75th percentile) trimester exposures were 32 (18, 56) microg/m(3) for SO(2); 72 (55, 87) microg/m(3) for TSP; and 38 (23, 59) microg/m(3) for NO(x). Low birth weight (prevalence 5.2%) and prematurity (prevalence 4.8%) were associated with SO(2) and somewhat less strongly with TSP. IUGR was not associated with any pollutant. The effects on low birth weight and prematurity were marginally stronger for exposures in the first trimester, and were not attenuated at all by adjustment for socioeconomic factors or the month of birth. Adjusted odds ratios of low birth weight were 1.20 [95% confidence interval (CI), 1.11-1.30] and 1.15 (CI, 1.07-1.24) for a 50 microg/m(3) increase in SO(2) and TSP, respectively, in the first trimester; adjusted odds ratios of prematurity were 1.27 (CI, 1.16-1.39) and 1.18 (CI, 1.05-1.31) for a 50 microg/m(3) increase in SO(2) and TSP, respectively, in the first trimester. Low gestational age accounted for the association between SO(2) and low birth weight. These findings provide further support for the hypothesis that air pollution can affect the outcome of pregnancy.
Production of IgM rheumatoid factor by normal lymphocytes after stimulation with preparations containing IgM rheumatoid factor from patients with juvenile arthritis.
Authors: G Nesher, T.L Moore, T.G Osborn, R.W Dorner
Journal: Annals of the Rheumatic Diseases (1991)

Preparations containing IgM rheumatoid factor (RF) and hidden IgM RF were isolated from the serum samples of nine patients with juvenile rheumatoid arthritis. Six of these preparations stimulated lymphocytes from normal donors to produce IgG and IgM, of which up to 11% had IgM RF activity. In contrast, the polyclonal activator pokeweed mitogen also stimulated IgM production, but only 1% had IgM RF activity. A relation between the activator and IgM RF or hidden IgM RF is suggested. This is based on the positive correlation between IgM RF concentration in these preparations and their ability to stimulate lymphocytes to produce IgG, IgM, and IgM RF. These data indicate that preparations from patients with juvenile rheumatoid arthritis containing IgM RF and hidden IgM RF are potent stimulants of lymphocytes from normal donors, with specific production of IgM RF.
Oxygen Saturation of Hepatic Blood During Hemorrhagic Shock in the Dog
Authors: JAMES J. SMITH, DONALD A. ROTH, ROBERT A. GRACE
Journal: Circulation Research (1955)

During experimental hemorrhagic shock there was a large fall in oxygen saturation of portal, hepatic venous and inferior vena caval blood. Saturation levels were restored to about 90 per cent of the control values after reinfusion of the drawn blood.
Terminal Transferase and Leukemia
Authors: Robert C. Gallo
Journal: New England Journal of Medicine (1975)

Terminal deoxynucleotidyl transferase (TdT) is an enzyme that catalyzes the elongation of preformed oligomeric or polymeric DNA chains by adding deoxyribonucleoside monophosphates to the 3′-OH ends of these chains.1 It was discovered independently by Bollum and his colleagues2 , 3 and by Krakow et al.4 Two features of TdT make it a unique and interesting enzyme. The first is that, unlike any other DNA-synthesizing enzyme (DNA polymerase), it does not use nucleic acid templates for instruction. Consequently, it has no apparent biologic role in DNA replication or repair. Secondly, in a survey of many tissues, Chang showed that appreciable levels of TdT . . .
Progressive activation of TH2/TH22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis
Authors: Julia K. Gittler, Avner Shemer, Mayte Suárez-Fariñas, Judilyn Fuentes-Duculan, Kara J. Gulewicz, Claire Q.F. Wang, Hiroshi Mitsui, Irma Cardinale, Cristina de Guzman Strong, James G. Krueger, Emma Guttman-Yassky
Journal: Journal of Allergy and Clinical Immunology (2012)
Outbreak of chronic arsenic poisoning among retired workers from an arsenic mine in Japan.
Authors: N Ishinishi, Y Kodama, K Nobutomo, T Inamasu, E Kunitake, Y Suenaga
Journal: Environmental Health Perspectives (1977)

Retired former workers of Matsuo Arsenic Mine of Miyazaki prefecture in Japan were subjected to extensive medical examination. The number of retired workers subjected to examination were 61 of 208 workers who were engaged in the works of the mine and were tracked down by the work rolls. These workers left the mine more than 15 years prior to the time of the examination. The main works in the mine were classified as mining, dressing of ores, refining, and clerical work. Several findings such as arsenodermatitis, depigmentation, performation of nasal septum, hyposmia, anosmia, and peripheral nervous disturbance attributed to exposure to arsenic were observed in 9 of 21 roasters who often worked in the arsenic kitchen. No characteristic findings of arsenic poisoning, that is, gastrointestinal disturbance, disorder of the cardiovascular system, hematopoietic disorders, or liver disturbance were observed in the retired workers. Another notable finding was that 8 cases diagnosed as pneumoconiosis were found in 18 miners.
A CASE OF DIAPHRAGMAIC HERNIA
Authors: A. BAMBERGER
Journal: JAMA (1910)

I report this case not only because of the rarity of diaphragmatic hernia, but also because of the abstruse and puzzling symptoms it presented. <h3>Past History.—</h3> The patient, W. W., a negro butler, aged 23, had had the diseases of childhood; gonorrhea several times, but denied syphilis. He used alcohol and tobacco in moderation, but denied coming in contact with lead in any form. He had never had a similar illness and was well up to the onset of the present trouble. Ten years previously he had been stabbed in the left seventh intercostal space just lateral to the anterior axillary line. The cut was about 2 inches long, through which a mass looking like fat (as he described it) protruded. The wound was sutured under general anesthesia and an uneventful recovery followed. <h3>Present Trouble.—</h3> About 12:30 a. m., July 24, 1910, he entered my service at the Cook County
Surveillance of antimicrobial resistance---an international perspective
Authors: R J Williams, M J Ryan
Journal: BMJ (1998)

Surveillance is essential for containing antimicrobial resistance.1 Information on resistance is needed at local, national, and international levels to guide decision making and responses. Local information should be used in clinical management and to update treatment guidelines, educate prescribers, and guide infection control policies. At national level, information is required to guide policy, update lists of essential drugs and national guidelines for treatment, and evaluate the effect of intervention strategies. There is an added value to gathering surveillance data internationally for sharing of information on the emergence of resistance in key pathogens, analysis of the impact of resistance and of policies for control, stimulating dialogue and engaging policy makers, developing advocacy and educational programmes, and stimulating research.

Surveillance of antimicrobial resistance requires laboratory facilities organised in a network within which data on patterns of resistance can be shared for analysis and …
CD15-expressing phagocytic plasma cells in a patient with multiple myeloma
Authors: Reyhan Diz Kucukkaya, Abdullah Hacihanefioglu, Mustafa Nuri Yenerel, Mehmet Turgut, Meliha Nalcaci, Huseyin Keskin, Seyhun Solakoglu, Gulderen Yanikkaya Demirel
Journal: Blood (2001)
Race-ethnicity, crime, and other factors associated with adherence to inhaled corticosteroids
Authors: L. Keoki Williams, Christine L. Joseph, Edward L. Peterson, Christina Moon, Hugo Xi, Richard Krajenta, Reba Johnson, Karen Wells, Jason C. Booza, Kaan Tunceli, Jennifer E. Lafata, Christine C. Johnson, Dennis R. Ownby, Robert Enberg, Manel Pladevall
Journal: Journal of Allergy and Clinical Immunology (2006)
Intraindividual Comparison of 123I-mIBG SPECT/MRI, 123I-mIBG SPECT/CT, and MRI for the Detection of Adrenal Pheochromocytoma in Patients with Elevated Urine or Plasma Catecholamines
Authors: Ioannis Ilias, Georgios Meristoudis
Journal: Clinical Nuclear Medicine (2013)

Department of Endocrinology, E Venizelou Hospital, Athens, Greece Department of Nuclear Medicine, Henri Dunant Hospital, Athens, Greece [email protected] Conflicts of interest and sources of funding: none declared.