tbuckley/cabot-search huggingface dataset:
Caspase-1–mediated pathway promotes generation of thromboinflammatory microparticles
Authors: Andrea S. Rothmeier, Patrizia Marchese, Brian G. Petrich, Christian Furlan-Freguia, Mark H. Ginsberg, Zaverio M. Ruggeri, Wolfram Ruf
Journal: Journal of Clinical Investigation (2015)

Extracellular ATP is a signal of tissue damage and induces macrophage responses that amplify inflammation and coagulation. Here we demonstrate that ATP signaling through macrophage P2X7 receptors uncouples the thioredoxin (TRX)/TRX reductase (TRXR) system and activates the inflammasome through endosome-generated ROS. TRXR and inflammasome activity promoted filopodia formation, cellular release of reduced TRX, and generation of extracellular thiol pathway–dependent, procoagulant microparticles (MPs). Additionally, inflammasome-induced activation of an intracellular caspase-1/calpain cysteine protease cascade degraded filamin, thereby severing bonds between the cytoskeleton and tissue factor (TF), the cell surface receptor responsible for coagulation activation. This cascade enabled TF trafficking from rafts to filopodia and ultimately onto phosphatidylserine-positive, highly procoagulant MPs. Furthermore, caspase-1 specifically facilitated cell surface actin exposure, which was required for the final release of highly procoagulant MPs from filopodia. Together, the results of this study delineate a thromboinflammatory pathway and suggest that components of this pathway have potential as pharmacological targets to simultaneously attenuate inflammation and innate immune cell–induced thrombosis.
Tuberculin Hypersensitivity in Tuberculous Infants Treated with Isoniazid
Authors: Arthur Robinson, Maryethel Meyer, Gardner Middlebrook
Journal: New England Journal of Medicine (1955)

THE purpose of this paper is to record marked decrease of skin tuberculin hypersensitivity in 4 tuberculous infants during isoniazid therapy, and to discuss the possible implications of this phenomenon. Nine other cases are presented in which the hypersensitivity did not occur.ObservationsThe group of cases in which tuberculin hypersensitivity was greatly diminished is described in Table 1. All 4 of these patients were under two years of age, were found to have positive skin reactions to old tuberculin (definitely positive Mantoux reactions to 1:1000 dilution) on contact examination and had normal roentgenograms of the chest. They were all treated . . .
Clinical Neurosurgery: Proceedings of the Congress of Neurological Surgeons, Miami Beach, Fla., 1959
Authors: H. R. Oberhill
Journal: JAMA (1961)

The seventh volume of this series contains the edited proceedings of the Ninth Annual Meeting of the Congress of Neurological Surgeons (1959), and is dedicated to Dr. William J. German of Yale, this meeting's honored guest and speaker. As presented, the papers are devoted essentially to the study of brain tumors, including a long-term study, discussed by Dr. German, of some of Harvey Cushing's cases from the Brain Tumor Registry in New Haven. In addition to Dr. German's contributions, papers are presented by several authorities in both investigative and clinical neurological and neurosurgical fields. This volume, like those preceding it, is primarily of interest to the neurosurgeon or to the student in allied neurological fields. Dr. German's papers deal with the long-term follow-up of glioma cases, the longest survival reported being 43 years and 3 months. He observes that recurrence is unlikely after 10 years. Another paper is a longer-term
Chronic Arsenic Exposure and Cardiac Repolarization Abnormalities with QT Interval Prolongation in a Population-based Study
Authors: Judy L. Mumford, Kegong Wu, Yajuan Xia, Richard Kwok, Zhihui Yang, James Foster, William E. Sanders
Journal: Environmental Health Perspectives (2007)

Chronic arsenic exposure is associated with cardiovascular abnormalities. Prolongation of the QT (time between initial deflection of QRS complex to the end of T wave) interval and profound repolarization changes on electrocardiogram (ECG) have been reported in patients with acute promyelocytic leukemia treated with arsenic trioxide. This acquired form of long QT syndrome can result in life-threatening arrhythmias.The objective of this study was to assess the cardiac effects of arsenic by investigating QT interval alterations in a human population chronically exposed to arsenic.Residents in Ba Men, Inner Mongolia, have been chronically exposed to arsenic via consumption of water from artesian wells. A total of 313 Ba Men residents with the mean arsenic exposure of 15 years were divided into three arsenic exposure groups: low (< or = 21 microg/L), medium (100-300 microg/L), and high (430-690 microg/L). ECGs were obtained on all study subjects. The normal range for QTc (corrected QT) interval is 0.33-0.44 sec, and QTc > or = 0.45 sec was considered to be prolonged.The prevalence rates of QT prolongation and water arsenic concentrations showed a dose-dependent relationship (p = 0.001). The prevalence rates of QTc prolongation were 3.9, 11.1, 20.6% for low, medium, and high arsenic exposure, respectively. QTc prolongation was also associated with sex (p < 0.0001) but not age (p = 0.486) or smoking (p = 0.1018). Females were more susceptible to QT prolongation than males.We found significant association between chronic arsenic exposure and QT interval prolongation in a human population. QT interval may potentially be useful in the detection of early cardiac arsenic toxicity.
Effect of interferon-γ on hepatitis B viral antigen expression in primary hepatocyte culture
Authors: Johnson Y. N. Lau, Vincent G. Bain, Nikolai V. Naoumov, Heather M. Smith, Graeme J. M. Alexander, Roger Williams
Journal: Hepatology (1991)

Interferon-alpha has been shown recently to selectively enhance hepatocyte expression of HBsAg/pre-S2 in chronic hepatitis B virus infection in a way that may enhance immune recognition. To determine the effect of interferon-gamma on hepatitis B virus antigen expression, hepatocytes isolated from patients with chronic hepatitis B virus infection were incubated in the absence or presence of interferon-gamma and viral antigen expression was assessed by both radioimmunoassay and immunocytochemistry using appropriate monoclonal antibodies. Interferon-gamma inhibited the expression of all hepatitis B virus antigens tested. Intracellular HBsAg measured by radioimmunoassay of sonicated hepatocytes fell by 29% with 1 U/ml (p less than 0.01) and 36% with 10 U/ml of interferon-gamma (p less than 0.001) compared with control treatment. Secreted HBsAg was reduced by 19% with 10 U/ml of interferon-gamma (p less than 0.01). Intracellular HBeAg was also decreased by 29% with 1 U/ml (p less than 0.05) and 42% with 10 U/ml of interferon-gamma (p less than 0.05), but no significant change was found in the amount of secreted HBeAg. The proportion of hepatocytes containing various hepatitis B virus antigens and the intracellular viral antigen staining densities also fell significantly with interferon-gamma incubation. Interestingly, the addition of interferon-gamma abolished the augmenting effect of interferon-alpha on intracellular HBsAg. These data indicate that interferon-gamma, in contrast to interferon-alpha, has an inhibitory effect on hepatocyte expression of all hepatitis B virus antigens including HBsAg/pre-S2, suggesting that this may be one factor that accounts for their difference in clinical activity in patients with chronic hepatitis B virus infection.
THE TECHNIQUE OF TRANSLUMBAR ARTERIOGRAPHY
Authors: Parke G. Smith
Journal: JAMA (1952)

By translumbar arteriography is meant the roentgenographic visualization of the abdominal aorta and its branches at that instant when they have been rendered radiopaque by the injection into the aorta of a roentgenopaque fluid. The technique, which will be described below, provides valuable information that is otherwise unobtainable by the present routinely utilized methods of urologic diagnosis. By the procedure, the renal arterial supply is visualized and abnormalities from its normal pattern are detected.  DIAGNOSTIC VALUE OF ARTERIOGRAPHY  It is possible to differentiate between renal tumors and cysts because of the obvious difference in arterial patterns of these two conditions, the former showing an irregular pattern in the area of the tumor as well as the characteristic pooling and puddling of the contrast medium in that area. As would be expected, the presence of a cyst is determined by demonstrating an avascular area and, in contrast to tumor, a lack
Cruelty: A dispositional or a situational behavior in man?
Authors: Mika Haritos-Fatouros
Journal: Behavioral and Brain Sciences (2006)

Presentation of evidence from multiple disciplines is the most impressive feature of Nell's article. I have observations and objections, however, about the following issues: (1) violence as a by-product of cruelty; (2) the equation of animal and human cruelty; (3) social psychological evidence contrary to the biological model; (4) whether prevention of cruelty best arises from predispositional or situational factors.
WEIL'S DISEASE (LEPTOSPIROSIS): A CLINICAL AND BACTERIOLOGICAL STUDY OF NINETEEN CASES OCCURRING CHIEFLY AMONG FISH WORKERS
Authors: L. S. P. Davidson, R. M. Campbell, H. J. Rae, J. Smith
Journal: BMJ (1934)

The occurrence in Minorca of an epideinic of jaundice was first described by Cleghorn in 1745.The publication by Weil in 1886 of an account of four cases of infectious jaundice led to the recognition of a symptom-complex of fever, jaundice, enlargement of the liver and spleen, the occurrence of haemorrhages, and, occasionally, febrile relapses under the designation of Weil's disease.Following the discovery of the L. icterohaemorrhagiae in the blood of a patient suffering from the Japanese form of the disease, and the proof of its specificity by Inada and Ido in 1915, the name " spirochaetosis icterohaemor- rhagica" was suggested as a substitute for the many titles applied to this disease.Stokes and Rylel in 1916 obtained bacteriological evidence of the existence of the disease among the British soldiers in Flanders; similar outbreaks were-reported and confirmed among the German, French, and Italian troops on the Westem Front.The occurrence of spirochaetosis in the form of an acute febrile illness, without jaundice, was recognized.2In consequence it has been the practice of European workers to revert to the non-descriptive title of " Weil's disease," in preference to its synonyms laying emphasis on jaundice.Interest in the disease has increased in recent years in Holland, where in the past decade 452 cases have been observed, with a mortality of 10.2 per cent.3Infection occurs by bathing and by accidental or suicidal immer- sion in the canals; a highler occupational incidence is reported among bargemen and workers in abattoirs and other rat-infested premises. Leptospiral Infection in BritainPotential sources of infection irn Britain are known to exist, the carrier rate in rats varying from four out of 101 rats in London4 to thirty out of 100 in different parts of England.5 Buchanan6 found sixty-one infected rats out of a total of 166 from various parts of Scotland.In the light of these figures the reports of leptospiral infection in man are surprisingly' few, and their authenticity-is undoubted only in three outbreaks.Manson-Bahr7 in 1922 described a case in a seaman four days after immer- sion in the Thames, the L. icterohaemarrhagiae being isolated from the blood.An outbreak of epidemic jaundice in 1923, among miners in certain wet pits in East Lothian, was described by Gulland and Buchanan,8 the diagnosis in eighteen cases being based on the clinical features.Investigations by Buchanan resulted in proof * Since this paper -was submitted to the British Medical Joutrnzal four more cases of proved Weil's disease in fish workers have been investigated, making a total of twenty-three.
Identification of Minimal Neuronal Networks Involved in Flexor-Extensor Alternation in the Mammalian Spinal Cord
Authors: Adolfo E. Talpalar, Toshiaki Endo, Peter Löw, Lotta Borgius, Martin Hägglund, Kimberly J. Dougherty, Jesper Ryge, Thomas S. Hnasko, Ole Kiehn
Journal: Neuron (2011)
Tracking Patterns of Enteric Illnesses in Populations and Communities
Authors: Terry Peace, Asit Mazumder
Journal: Environmental Health Perspectives (2006)

Enteric illness arising from contaminated water and food is a major health concern worldwide, and tracking the incidences and severity of outbreaks is still a challenging task. Most developed and developing countries have administrative databases for medical visits and services maintained by the government and/or health insurance authorities. Although these databases could be extremely valuable resources to track patterns of environmental and other health issues, test hypotheses, and develop epidemiologic models and predictions, very little research has been done to develop methods to ensure the robustness of such databases and to demonstrate their utility as a research tool.We used the Medical Services Plan (MSP) database of British Columbia, Canada, to develop innovative ways to use medical billing and fee-for-services data to track long-term patterns of enteric illness at the level of populations and communities.To illustrate the power and robustness of the method, we provided several examples covering 8 years of data from each of four communities covering a large range of population size. Not only could this method generalize to other diseases for which specific fee item markers can be found, but also it gives results consistent with a known outbreak and yields data patterns, which could not be revealed by the currently used methods. Because diagnostic code and fee item data for medical services are collected by most medical insurance agencies, our method can have global applications for tracking enteric and other illnesses at the level of populations and communities.
Anorexia and resting energy-expenditure (REE) in cirrhotic patients:Role of plasma concentrations of leptin and tumor necrosisfactor-α (TNF-α)
Authors: A. Buda, M. Varnier, C. Pasini, P. Burra, S. Fagiuoli, F. Farinati, A. Graziotto, P. Englaro, R. Naccarato, D. Martines
Journal: Journal of Hepatology (2000)
THE DIFFERENTIATION OF THE CARDIAC INCOMPETENCY OF INTRINSIC HEART DISEASE AND OF CHRONIC NEPHRITIS.
Authors: FRANK BILLINGS
Journal: JAMA (1898)

The recognition of an incompetent heart is usually not difficult. The dyspnea of exertion, the sense of post-sternal weight and constriction of the chest, the cough of exertion, and upon assuming the recumbent position, the enlarged liver with tenderness and often with pain or a feeling of weight in the epigastrium, the indigestion of portal congestion, the usually scant urine, the edema of the feet, or all of the above named conditions much aggravated until constant dyspnea with orthopnea, general anasarca, excessive physical weakness, marked palor, or palor and cyanosis give unmistakable evidence of cardiac weakness. The local signs of valvular disease may be absent or present. Signs of cardiac enlargement with dilatation of the chambers of the heart are present and may usually be recognized.  These phenomena are usually present in varying degrees of severity, in an incompetent heart. When due to intrinsic heart disease a valvular lesion or
Quality of life of patients with severe chronic neutropenia receiving long-term treatment with granulocyte colony-stimulating factor
Authors: E. A. Jones
Journal: JAMA (1993)

To evaluate the impact of long-term granulocyte colony-stimulating factor (GCSF) treatment on quality of life of patients with congenital, cyclic, or idiopathic neutropenia. STUDY DESIGN, INTERVENTION, AND OUTCOME MEASURES: Twenty-one patients receiving daily subcutaneous GCSF responded to retrospective questions about disease-related symptoms and physical, psychological, and social functioning before and with GCSF therapy.Statistically significant improvement occurred in energy, emotional reactions, social isolation, functional ability, life satisfaction, decreased hospital admissions, and school attendance.GCSF greatly improves quality of life in patients with severe chronic neutropenia.
Hepatic stem cell niches
Authors: Claus Kordes, Dieter Häussinger
Journal: Journal of Clinical Investigation (2013)

Stem cell niches are special microenvironments that maintain stem cells and control their behavior to ensure tissue homeostasis and regeneration throughout life. The liver has a high regenerative capacity that involves stem/progenitor cells when the proliferation of hepatocytes is impaired. In recent years progress has been made in the identification of potential hepatic stem cell niches. There is evidence that hepatic progenitor cells can originate from niches in the canals of Hering; in addition, the space of Disse may also serve as a stem cell niche during fetal hematopoiesis and constitute a niche for stellate cells in adults.
Of mentors, mentoring, and extracellular matrix
Authors: D. Montgomery Bissell
Journal: Hepatology (2009)

D. Montgomery Bissell briefly describes the way he came to a career in academic medicine, how he found mentors, initial projects, and finally a focus on matrix biology and hepatic fibrosis. He draws some lessons from the experience, which should have relevance for physician-scientist trainees, those considering that path, anyone with responsibility for training the next generation, institutional leaders, and the National Institutes of Health. (HEPATOLOGY 2009;50:1330–1338.)
A Double-blind Trial of Oral Progesterone, Alprazolam, and Placebo in Treatment of Severe Premenstrual Syndrome
Authors: Ellen W. Freeman
Journal: JAMA (1995)

To determine the effectiveness of oral micronized progesterone, alprazolam, and placebo in premenstrual syndrome (PMS) treatment and the effect of clinical contact on treatment responses.Randomized, double-blind, placebo-controlled 3-month parallel treatment arms with flexible dosage and with the length of clinical contact randomized within each treatment group.University hospital PMS medical treatment outpatient program in obstetrics/gynecology department.Among volunteers for PMS treatment, 444 were evaluated and 185 meeting defined PMS criteria were randomized to treatment; treatment data are available for 170. There were no medical withdrawals for adverse events.A double-blinded protocol in which 300 mg of oral micronized progesterone, 0.25 mg of alprazolam, or placebo was administered four times a day from day 18 of the menstrual cycle through day 2 of the next cycle, including taper. The mean daily dose at the third treatment was 1760 mg of progesterone or 1.5 mg of alprazolam. Subjects were randomized to brief (< 20 minutes) or extended (50 minutes) visits.Daily symptom report (DSR) scored for total DSR symptoms, four DSR factors.Alprazolam was significantly better than placebo or progesterone for total premenstrual symptoms and DSR factors of mental function, pain, and mood. Thirty-seven percent of the alprazolam group experienced a 50% reduction in total DSR scores. There were no clinically significant withdrawal symptoms when alprazolam administration was restricted to the luteal phase. Oral micronized progesterone therapy was no better than placebo. Brief vs extended visits had no effect on treatment outcome. Treatment response was associated with severity of premenstrual symptoms at baseline but with no other diagnostic variables.Alprazolam has a role in PMS treatment and offers a therapy limited to the luteal phase. Oral micronized progesterone is ineffective for PMS.
656. Development of Viral Vectors To Mediate Neuron-Specific Gene Silencing
Authors: Colin P. Glover, Alison S. Bienemann, Beverly L. Davidson, James B. Uney
Journal: Molecular Therapy (2005)

Top of pageAbstract
The ability to manipulate gene expression in specific cell types within the brain is a fundamental requirement for successful gene therapy and studies of gene function. Adenovirus, Adeno-associated virus and Lentivirus based vectors have all proved to be excellent tools for the targeted overexpression of genes in neurons. The targeted knockdown of gene expression however, is more complicated and historically the elucidation of gene function has principally been achieved by the use of transgenic knockout mice. It has recently been shown that RNA interference (RNAi) can be used for the efficient knockdown of specific genes. Furthermore, gene silencing by RNAi can be achieved by the viral mediated expression of short hairpin RNAs (shRNAs). Most studies of this sort have used powerful RNA polymerase III promoters (U6 and H1) to drive shRNA expression. These promoters are ubiquitous and would silence a gene in all cell types and possibly produce undesirable effects in non-target cells. Therefore, the targeting of shRNA expression to specific cell types will be of significant importance for studies of gene function and also for the potential uses of RNAi in therapeutic paradigms.

We have investigated the potential of a number of different strategies to restrict shRNA expression solely to neurons. We have constructed composite promoters consisting of neuron restrictive silencer elements (NRSE) in combination with the polIII U6 promoter. Our data demonstrates that the combination of NRSEs and the U6 promoter does not restrict shRNA expression specifically to neurons. We have also constructed alternative expression systems based on RNA polII to drive shRNA expression, including a second composite promoter consisting of NRSE sequences and the minimal CMV promoter, and a truncated human SynapsinI promoter. Finally, it has recently been demonstrated that microRNAs (miRNAs) are transcribed from a polII promoter and that miRNAs can be used as shRNA shuttles. We have therefore designed shRNA shuttles based on mir30. These shRNA shuttles have been expressed from the human Synapsin I promoter alone, or in combination with the woodchuck post-transcriptional element (WPRE). To evaluate these strategies we have initially used shRNA targeted to EGFP and hence have assessed and compared the effectiveness of shRNA gene knockdown.