tbuckley/cabot-search huggingface dataset:
Intrapericardial infusion of endothelin-1 induces ventricular arrhythmias in dogs
Authors: I Szokodi
Journal: Cardiovascular Research (1998)

Objectives: Recently, extremely high levels of endothelin-1 (ET-1) were detected in the pericardial fluid of patients with heart disease; however, the pathophysiological importance of this finding is not known. The present study was designed to characterize ET-1 levels in canine pericardial fluid and to investigate the effects of local high concentrations of exogenous ET-1 in vivo. Methods: In anesthetized, open-chest dogs ET-1 (Groups 1 and 2: 11 and 33 pmol·kg−1·min−1; n=6 and 6, respectively) or physiological saline (Group 3, n=5) were infused into the closed pericardial sac for 40 min. In serial pericardial fluid and aortic blood plasma samples, ET-1 levels were measured by radioimmunoassay, and analysed by high-performance liquid chromatography (HPLC). Systemic arterial blood pressure, heart rate, cardiac output (CO), standard ECG and right ventricular endocardial monophasic action potentials (MAPs) were recorded. Results: Basal pericardial fluid ET-1 levels were significantly higher than respective plasma levels (342±210 vs. 8.0±5.2 pmol·l−1, n=14, P<0.001). In HPLC analysis pericardial fluid ET-1 was indistinguishable from ET-11–21. Infusion of exogenous ET-1 into the pericardial space induced ventricular arrhythmias in all instances, which were associated with 9.7-fold increase in pericardial fluid ET-1 levels. Ventricular tachycardias developed in 9 of 12 animals. The arrhythmogenic effect of ET-1 was more apparent in dogs with the larger dose. Before the onset of arrhythmias, intrapericardial infusion of ET-1 increased QT time (Group 1: 207±18 to 230±23 ms, P<0.01; Group 2: 220±12 to 277±17 ms, P<0.01) and MAP duration at 90% repolarization (at 300 ms cycle length) (Group 1: 192±9 to 216±9 ms, P<0.01; Group 2: 205±9 to 255±9 ms, P<0.001). Hemodynamic variables did not change significantly prior to the onset of ventricular tachyarrhythmias. In Group 3, arrhythmias were not observed and all electrophysiological and hemodynamic parameters remained unchanged. Conclusions: Administration of exogenous ET-1 into the pericardial space induces ventricular arrhythmias associated with prolongation of QT time and MAP duration. Whether pericardial fluid ET-1 under pathophysiological conditions can ever reach sufficiently high levels to induce ventricular arrhythmias remains to be elucidated.
PRINCIPAL MINERAL ELEMENTS IN NUTRITION
Authors: ICIE G. MACY
Journal: JAMA (1942)

In a consideration of the mineral constituents of the body, one should bear in mind that, while these elements constitute only a small portion of the body weight, they enter into all the activities of the body to a much greater degree than their mere weight would indicate. For many years the important dietary components were stated to be protein, fat and carbohydrate, with slight emphasis placed on water and minerals; later, vitamins were added as necessary adjuncts. In the last few years, however, through voluminous records of physiologic investigations, the mineral elements have come into prominence and are now recognized as essential participants in practically every metabolic process carried on by the body. The brief summary permitted in this presentation forbids reference to many significant studies of mineral metabolism. For the most part, only studies which contain analyses of food, urine and feces for the seven principal minerals will
Lipopolysaccharide-induced Diaphragmatic Contractile Dysfunction and Sarcolemmal Injury in Mice Lacking the Neuronal Nitric Oxide Synthase
Authors: ALAIN S. COMTOIS, ESTHER BARREIRO, PAUL L. HUANG, ANDRÉ MARETTE, MYLÈNE PERRAULT, SABAH N. A. HUSSAIN
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

In this study we evaluated the role of the neuronal nitric oxide synthase (nNOS) in lipopolysaccharide (LPS)-induced diaphragmatic contractile dysfunction and sarcolemmal injury. Wild-type (WT) mice or mice deficient in the nNOS gene (nNOS− / −) were injected with either saline (control) or Escherichia coli LPS (LPS groups) and sacrificed 12 h later. The diaphragm was then examined for NOS expression, NOS activity, and in-vitro contractility. We also assessed sarcolemmal injury in isolated muscle strips under resting condition and after 3 min of artificial stimulations. In WT mice, LPS injection reduced maximum force to about 75% of that of control animals and raised total NOS activity significantly due to the induction of the iNOS isoform. Although muscle fiber injury was minimal under resting condition, the percentage of injured fibers in control and LPS-injected mice approached 27% and 40% of total fibers, respectively, in response to artificial stimulation. By comparison, LPS injection in nNOS− / − mice elicited a worsening of muscle contractility (maximum force < 60% of control animals) but elicited degrees of sarcolemmal injury similar to those observed in the WT animals. In addition, muscle NOS activity and iNOS protein level in nNOS− / − mice injected with LPS reached about 10% and 60% of that of WT animals, respectively (p < 0.05 compared with WT animals). Protein level of endothelial NOS isoform in the diaphragm was not altered by LPS injection in either WT or nNOS− / − animals. We conclude that nNOS plays a protective role in attenuating the negative influence of sepsis on diaphragmatic contractility but is not involved in the pathogenesis of sepsis-induced sarcolemmal injury.
Fetal Cystic Hygroma
Authors: Frank A. Chervenak, Glenn Isaacson, Karin J. Blakemore, W. Roy Breg, John C. Hobbins, Richard L. Berkowitz, Marge Tortora, Kara Mayden, Maurice J. Mahoney
Journal: New England Journal of Medicine (1983)

Fetal cystic hygromas are congenital malformations of the lymphatic system appearing as single or multiloculated fluid-filled cavities, most often about the neck. They are thought to arise from failure of the lymphatic system to communicate with the venous system in the neck. They often progress to hydrops and cause fetal death. In an effort to delineate the cause and natural history of this disorder, we studied 15 consecutive cases of nuchal hygroma detected prenatally by ultrasound. None of the 15 fetuses ultimately survived. Thirteen fetuses were hydropic at the time of diagnosis; nine either died or were bradycardic in utero before abortion; one died a few hours after birth. Eleven fetuses (73 per cent) had karyotypes consistent with Turner's syndrome, and an additional fetus with female genitalia had a 46,XY karyotype. Three fetuses had 46,XX karyotypes, and two of these had multiple malformations. When a hygroma is detected during fetal life, careful sonographic examination of the entire fetus, determination of the fetal karyotype, and an evaluation of the family history are indicated.
Bile Acid Exposure Up-regulates Tuberous Sclerosis Complex 1/Mammalian Target of Rapamycin Pathway in Barrett's-Associated Esophageal Adenocarcinoma
Authors: Chia-Jui Yen, Julie G. Izzo, Dung-Fang Lee, Sushovan Guha, Yongkun Wei, Tsung-Teh Wu, Chun-Te Chen, Hsu-Ping Kuo, Jung-Mao Hsu, Hui-Lung Sun, Chao-Kai Chou, Navtej S. Buttar, Kenneth K. Wang, Peng Huang, Jaffer Ajani, Mien-Chie Hung
Journal: Cancer Research (2008)

Barrett's esophagus, a columnar metaplasia of the lower esophagus epithelium related to gastroesophageal reflux disease, is the strongest known risk factor for the development of esophageal adenocarcinoma (EAC). Understanding the signal transduction events involved in esophageal epithelium carcinogenesis may provide insights into the origins of EAC and may suggest new therapies. To elucidate the molecular pathways of bile acid-induced tumorigenesis, the newly identified inflammation-associated signaling pathway involving I kappaB kinases beta (IKK beta), tuberous sclerosis complex 1 (TSC1), and mammalian target of rapamycin (mTOR) downstream effector S6 kinase (S6K1) was confirmed to be activated in immortalized Barrett's CPC-A and CPC-C cells and esophageal cancer SEG-1 and BE3 cells. Phosphorylation of TSC1 and S6K1 was induced in response to bile acid stimulation. Treatment of these cells with the mTOR inhibitor rapamycin or the IKK beta inhibitor Bay 11-7082 suppressed bile acid-induced cell proliferation and anchorage-independent growth. We next used an orthotopic rat model to evaluate the role of bile acid in the progression of Barrett's esophagus to EAC. Of interest, we found high expression of phosphorylated IKK beta (pIKK beta) and phosphorylated S6K1 (pS6K1) in tumor tissues and the Barrett's epithelium compared with normal epithelium. Furthermore, immunostaining of clinical EAC tissue specimens revealed that pIKK beta expression was strongly correlated with pS6K1 level. Together, these results show that bile acid can deregulate TSC1/mTOR through IKK beta signaling, which may play a critical role in EAC progression. In addition, Bay 11-7082 and rapamycin may potentially be chemopreventive drugs against Barrett's esophagus-associated EAC.
Ventricular Septal Defect of Atrioventricular Canal Type with Straddling Right Atrioventricular Valve and Mitral Valve Deformity
Authors: G. C. RASTELLI, PATRICK A. ONGLEY, JACK L. TITUS
Journal: Circulation (1968)

At the Mayo Clinic, four patients were seen in whom a ventricular septal defect (VSD) of the atrioventricular (A-V) canal type was associated with an angle of nearly 90° between the intact atrial septum and the ventricular septum. The right atrium overrode the ventricular septum and communicated with both ventricles. A complex, straddling right A-V valve had some attachments in the left ventricle and resembled the common A-V valve of persistent common A-V canal. In three of the patients, a congenital mitral valve deformity also existed. Mild cyanosis probably is not a contraindication to surgical repair in such patients because right atrial blood may enter the left ventricle directly.
Benign Spontaneous Pneumothorax
Authors: LEROY HYDE
Journal: Annals of Internal Medicine (1962)

Excerpt The term "pneumothorax" is thought to have been used first by Itard in 1803, when he recognized five cases at autopsy (1). Kjaergaard (2) reported that McDowell in 1856 was the first, apparently, to describe spontaneous pneumothorax occurring in a healthy person. Although at first believed to be related to pulmonary tuberculosis, spontaneous pneumothorax was recognized to be a benign entity by Kjaergaard; this was emphasized subsequently by other studies (1, 3, 4). The present report is based on 200 consecutive cases of benign, non-traumatic, non-tuberculous pneumothorax, not associated with other pulmonary disease as pneumonia or tumor. MATERIALS AND METHODS
Student elective in Papua New Guinea
Authors: B A P Karunaratne
Journal: BMJ (1982)

prenatal life.Psalm 139 speaks of God's care and concern for the developing embryo.5It is clear that the unborn child is regarded in scripture as a unique and specific individual from the earliest days of pregnancy.6-There are no grounds, biological or biblical, for a careless or shallow view of the value of human life or the contention that the zygote is not a human being.A leading article in a recent Christian Medical Fellowship quarterly newsletter con- cludes: "We should be constantly affirming God's abiding principles for man as stewards of His creation.Christians are rightly in the forefront of science.Man was ordained to control and replenish the earth.We can adequately discharge this responsibility only through constant reference to the Creator's objectives and His principles by which man is to relate to man....The ability to perform is not license to do.Each test-tube test must itself be tested by those laws which on Judgment Day will inexorably test every man." 9
Dysplastic changes in the peripheral blood of children with microdeletion 22q11.2
Authors: Namık Özbek, Murat Derbent, Lale Olcay, Zerrin Yılmaz, Kürşat Tokel
Journal: American Journal of Hematology (2004)

Abstract Myelodysplasia refers to abnormal morphology of the bone marrow and/or peripheral blood. This condition is frequently due to myelodysplastic syndrome; however, myelodysplasia is caused by a variety of factors and is not always a sign of pre‐malignant disease. We observed myelodysplastic changes in peripheral blood smears and bone marrow specimens from a patient who had chromosomal microdeletion 22q11.2 (del22q11.2). We then investigated such changes in several other patients who were newly diagnosed with del22q11.2 ( n = 5 total, including the index case) and compared the findings to those in four sets of controls without this chromosomal abnormality. Specifically, the controls were children with conotruncal heart defects ( n = 3); otherwise healthy children with bacterial ( n = 4) or viral infection ( n = 4); and healthy children ( n = 4). The myelodysplasia scores in the myeloid cells and eosinophils of the children with del22q11 were higher than those in all four of the control groups. Myelodysplastic changes in the peripheral blood of children with del22q11.2 have not been reported previously. We believe that certain gene(s) in the deleted region may be responsible for the myelodysplastic changes that we observed in our patients with this chromosomal abnormality. Am. J. Hematol. 77:126–131, 2004. © 2004 Wiley‐Liss, Inc.
Inward sodium current at resting potentials in single cardiac myocytes induced by the ischemic metabolite lysophosphatidylcholine.
Authors: A I Undrovinas, I A Fleidervish, J C Makielski
Journal: Circulation Research (1992)

To investigate possible ionic current mechanisms underlying ischemic arrhythmias, we studied single Na+ channel currents in rat and rabbit cardiac myocytes treated with the ischemic metabolite lysophosphatidylcholine (LPC) using the cell-attached and excised inside-out patch-clamp technique at 22 degrees C. LPC has been reported previously to reduce open probability and to induce sustained open channel activity at depolarized potentials. We now report two new observations for Na+ currents in LPC-treated patches: 1) The activation-voltage relation of the peak of the ensemble currents is shifted in the negative (hyperpolarizing) direction by approximately 20 mV compared with control currents. This effect was observed in all patches for depolarizations from a holding potential of -150 mV to different test potentials. 2) In some LPC-treated patches, Na+ channels exhibited sustained bursting activity at potentials as negative as -150 mV, giving a nondecaying inward current. This bursting activity was accompanied by double and triple simultaneous openings and closings, suggesting tight cooperativity in channel gating. These LPC-modified channels were identified as Na+ channels, because their unitary conductance was the same as Na+ channels in control solutions, because the single channel current-voltage relation was extrapolated to reverse at the Na+ Nernst potential, and because the current was blocked by the local anesthetic QX-222. This novel depolarizing current may play a role in the electrophysiological abnormalities in ischemia, including abnormal automaticity and reentrant arrhythmias, and could be a target for antiarrhythmic drugs.
SynDIG1: An Activity-Regulated, AMPA- Receptor-Interacting Transmembrane Protein that Regulates Excitatory Synapse Development
Authors: Evgenia Kalashnikova, Ramón A. Lorca, Inderpreet Kaur, Gustavo A. Barisone, Bonnie Li, Tatsuto Ishimaru, James S. Trimmer, Durga P. Mohapatra, Elva Díaz
Journal: Neuron (2010)
Newly Recognized Foreign Body in the Esophagus
Authors: Gilbert Mandel
Journal: JAMA (1975)

To the Editor.—  Foreign bodies in the esophagus are well-recognized and dreaded occurrences. A variety of objects can be swallowed, most frequently by infants and children. These include open safety pins, coins, small toys, buttons, and marbles. Pieces of meat or fish bones are frequently swallowed by adults.  A new and dangerous foreign body has emerged for due concern— namely, the pull-tab top from soda and beer cans.  We have treated a 16-year-old boy who put the pull-tab top from a soda can into the can prior to drinking and inadvertently swallowed the object. It then became lodged in his esophagus.  Our case represents the swallowing of an object that has arisen from technological advances. With the advent of metal soda and beer cans comes the convenient pull-tab top ring for opening the can. As in the case of our patient, people apparently have the habit of putting the pull
RADIOLOGY OF BONE DISEASES
Authors: J. W. D. Bull
Journal: BMJ (1954)

Preterm birth remains a major challenge in modern obstetrics and is increasing, even among low-risk primiparous women. Very few interventions have made a positive impact on outcome although cervical cerclage appears to benefit some women. Transabdominal cervical cerclage can be highly successful and should be considered in women with previous failed transvaginal cerclage, but requires operative abdominal delivery as it cannot be removed. The authors report the first case they are aware of, where a spontaneous abortion occurred with a transabdominal cerclage in situ and a mid-trimester dilation and evacuation was performed through the cerclage at 18 weeks gestation, instead of a hysterotomy. A subsequent pregnancy was successful and it was the first to go full term.
Activation of cellular oncogenes by chemical carcinogens in Syrian hamster embryo fibroblasts.
Authors: R Ebert, J C Barrett, R W Wiseman, R Pechan, E Reiss, G Röllich, D Schiffmann
Journal: Environmental Health Perspectives (1990)

Carcinogen-induced point mutations resulting in activation of ras oncogenes have been demonstrated in various experimental systems such as skin carcinogenesis, mammary, and liver carcinogenesis. In many cases, the data support the conclusion that these point mutations are critical changes in the initiation of these tumors. The Syrian hamster embryo (SHE) cell transformation model system has been widely used to study the multistep process of chemically induced neoplastic transformation. Recent data suggest that activation of the Ha-ras gene via point mutation is one of the crucial events in the transformation of these cells. We have now cloned the c-Ha-ras proto-oncogene from SHE cDNA-libraries, and we have performed polymerase chain reaction and direct sequencing to analyze tumor cell lines induced by different chemical carcinogens for the presence of point mutations. No changes were detectable at codons 12, 13, 59, 61, and 117 or adjacent regions in tumor cell lines induced by diethylstilbestrol, asbestos, benzo(a)pyrene, trenbolone, or aflatoxin B1. Thus, it is not known whether point mutations in the Ha-ras proto-oncogene are essential for the acquisition of the neoplastic phenotype of SHE cells. Activation of other oncogenes or inactivation of tumor suppressor genes may be responsible for the neoplastic progression of these cells. However, in SHE cells neoplastically transformed by diethylstilbestrol or trenbolone, a significant elevation of the c-Ha-ras expression was observed. Enhanced expression of c-myc was detected in SHE cells transformed by benzo(a)pyrene or trenbolone.
Pemphigus controlled by sulphapyridine
Authors: P.P. SEAH, LIONEL FRY, R.J. CAIRNS, M. FEIWEL
Journal: British Journal of Dermatology (1973)

Journal Article Pemphigus controlled by sulphapyridine Get access P.P. SEAH, P.P. SEAH St Mary's Hospital, London, W.2 Search for other works by this author on: Oxford Academic Google Scholar LIONEL FRY, LIONEL FRY St Mary's Hospital, London, W.2 Search for other works by this author on: Oxford Academic Google Scholar R.J. CAIRNS, R.J. CAIRNS St Bartholomew's Hospital, Rochester, Kent Search for other works by this author on: Oxford Academic Google Scholar M. FEIWEL M. FEIWEL St Mary's Hospital, London, W.2 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 89, Issue 1, 1 July 1973, Page 77, https://doi.org/10.1111/j.1365-2133.1973.tb01920.x Published: 01 July 1973 Article history Accepted: 08 January 1973 Published: 01 July 1973
CXCR3+ T Regulatory Cells Selectively Accumulate in Human Ovarian Carcinomas to Limit Type I Immunity
Authors: Nassima Redjimi, Caroline Raffin, Isabelle Raimbaud, Pascale Pignon, Junko Matsuzaki, Kunle Odunsi, Danila Valmori, Maha Ayyoub
Journal: Cancer Research (2012)

Abstract Antitumor type I T-cell responses involving IFN-γ production are critical to control cancer, but the efficacy of this response is limited by a variety of immunosuppressive mechanisms that promote tumoral immune escape. One critical mechanism involves the accumulation of FOXP3+ T regulatory cells (Treg), a class of suppressive T cells that prevent excessive tissue destruction caused by unchecked immune responses. Recent studies have revealed that FOXP3+ Treg include distinct subsets specifically controlling over the corresponding effector subset. In particular, CXCR3+ Treg have been described as a subset specialized in the control of type I T-cell responses in vivo. Here, we show that CXCR3+ Treg are highly enriched in human ovarian carcinomas, particularly in solid tumor masses, where they represent the majority of Treg. Tumor-associated CXCR3+. Treg coexpress T-bet but do not secrete IFN-γ ex vivo and suppress proliferation and IFN-γ secretion of T effectors. In addition, they coexpress Helios, suggesting that they originate from natural Treg. Finally, we show that the proportion of CXCR3+ Treg at tumor sites is directly correlated with that of CXCR3+ T effectors, consistent with expression of CXCR3 ligands. Together, our findings support the concept that natural CXCR3+ T-bet+ Treg selectively accumulate in ovarian tumors to control type I T-cell responses, resulting in the collateral limitation of efficient antitumor immunity. Cancer Res; 72(17); 4351–60. ©2012 AACR.
Denial of the AMA-Endorsed Disability Insurance Program Owing to Marriage Counseling-Reply
Authors: D. Gregory Miller
Journal: JAMA (1989)

<h3>In Reply.—</h3> Dr Komrad's concerns regarding the handling of mental and nervous disorders by the insurance industry are very legitimate. The insurance industry can be accused in many instances of being insensitive and extraordinarily cautious on the issue of mental and nervous disorders. However, prudent underwriting practices are essential to the financial viability of the insurer and ultimately the offered program, whether on an individual or group basis. The American Medical Association (AMA) and its newly formed subsidiary, AMA Insurance Agency, Inc, are concerned with underwriting and coverage issues associated with mental and nervous disorders. For over 20 years, the AMA has sponsored various high-quality, competitively priced insurance plans, designed to fit the personal and business needs of its member physicians. Included within every health and disability plan sponsored by the AMA is coverage for mental and nervous conditions. However, the two sponsored disability insurance plans (Long-term Disability and Office