tbuckley/cabot-search huggingface dataset:
The roles of fractalkine signaling in neurodegenerative disease
Authors: Bruce Lamb
Journal: Molecular Neurodegeneration (2012)

Background The primary neuropathological characteristics of AD include intracellular, filamentous inclusions of hyperphosphorylated microtubule associated protein tau (MAPT) in neurons (neurofibrillary tangles, NFTs) and extracellular deposits of the beta-amyloid peptide (A-Beta) in senile plaques. While A-Beta plaques are unique to AD, NFTs are observed in a wide variety of neurodegenerative diseases, including AD, frontotemporal dementia, cortical basal degeneration and other disorders, collectively termed tauopathies. Microglia, the primary immune effector cells in the brain, continually monitor the tissue parenchyma for pathological alterations and become activated in AD and other tauopathies. Increasing evidence suggests that microglia contribute to the pathopysiology of AD including; correlational studies in human AD and mouse models, retrospective epidemiological studies demonstrating that use of nonsteroidal anti-inflammatory drugs (NSAIDs) substantially reduces AD risk, genome-wide association studies of human AD and studies utilizing genetically modified mouse models. Neuronal-microglial communication through the chemokine fractalkine (CX3CL1) and its cognate receptor, CX3CR1, plays a critical role in neuroinflammation and neuroprotection. First, CX3CL1 is highly expressed by neurons while CX3CR1 is only expressed by microglia within the CNS. Second, CX3CL1 is neuroprotective in models of neuroinflammation. Finally, studies of Cx3cr1 knockout mice revealed enhanced neurodegeneration in mouse models of amyotrophic lateral sclerosis (ALS) and Parkinson’s Disease (PD).
Triple Antiviral Therapy as a New Option for Patients With Interferon Nonresponsive Chronic Hepatitis C
Authors: Stefano Brillanti, Fabio Levantesi, Livia Masi, Mauro Foli, Luigi Bolondi
Journal: Hepatology (2000)

The aim of the study was to evaluate the efficacy of triple antiviral therapy with interferon, ribavirin, and amantadine in comparison with interferon and ribavirin combination treatment in patients with interferon-nonresponsive chronic hepatitis C. We performed an open-label, prospective randomized controlled trial at a secondary referral center. We used a 2:1 ratio, patients received interferon, ribavirin, and amantadine, or interferon and ribavirin for 12 months, and were followed up for an additional 6 months. Ninety-four consecutive adult interferon nonresponders with chronic hepatitis C were screened. Sixty consecutive elected patients entered the study. No patients withdrew because of adverse effects. Forty patients received interferon alfa (5 megaunits on alternate days), ribavirin (800-1,000 mg daily), and amantadine (200 mg daily) for 12 months, and 20 patients received the same treatment without amantadine. At the end of follow-up, alanine transaminase (ALT) level normalization was maintained in 23 of 40 patients (57%) after triple therapy, but in 2 of 20 patients (10%) after double therapy (P <.001, RR = 2.11, 95% CI, 1.43-3.12), whereas disappearance of serum HCV RNA persisted in 19 of 40 patients (48%) and in 1 of 20 patients (5%), respectively (P <.001, RR = 1.81, 95% CI, 1.32-2.47). The safety profile was similar in the 2 groups. In conclusion, in patients with interferon-nonresponsive chronic hepatitis C, triple antiviral therapy for 1 year results in a high rate of sustained biochemical and virologic responses.
MicroRNAs as Oncogenes and Tumor Suppressors
Authors: Chang-Zheng Chen
Journal: New England Journal of Medicine (2005)

Recent discoveries related to microRNAs, RNA interference, small interfering RNAs (siRNAs), and small modulatory RNAs have revealed a new class of mechanisms of gene regulation that are mediated by small, noncoding RNAs. Among these small RNAs are the microRNAs. These are thought to control gene expression at the post-transcriptional level by degrading or repressing target messenger RNAs (mRNAs). Surprisingly simple and elegant, microRNA-mediated gene regulation is guided by the base-pairing rules of Watson and Crick.MicroRNAs are individually encoded by their own set of genes and are an integral component of the genetic program. Some are located in noncoding regions . . .
Fulminant Hepatic Failure due to Genital Herpes in a Healthy Woman: Was She Healthy?
Authors: David T. Purtilo
Journal: JAMA (1985)

To the Editor.—  The report by Rubin et al 1 failed to address an important issue: underlying immunodeficiency that may have permitted the viral-induced death. This report resembles that of Auch Moedy et al, 2 who had alleged that a healthy infant had also died of disseminated herpes simplex infection.  I criticize these reports because the authors failed to perform any immune function studies on the two patients. At the time of necropsy, serum samples can be obtained for quantitative immunoglobulins and other determinations. Death due to a ubiquitous viral agent is probably caused by inherited or acquired immune surveillance defects to specific viral agents, and it is likely that under Darwinian pressures immune-response genes have evolved in concert with ubiquitous viral agents to prevent life-threatening diseases.  Our clinical studies on the Epstein-Barr virus (EBV) support the hypothesis articulated above. Supporting this notion is the report of Britton et al,
Combination of ribavirin and interferon-alfa surpasses high doses of interferon-alfa alone in patients with genotype-1b-related chronic hepatitis C
Authors: Stanislas Pol, Bertrand Nalpas, Marc Bourlière, Patrice Couzigou, Albert Tran, Armand Abergel, Jean-Pierre Zarski, Pierre Berthelot, Christian Bréchot
Journal: Hepatology (2000)

The purpose of this study was to compare interferon-alfa alone (12-month course with high initial doses) with a combination of interferon-alfa and ribavirin in patients infected with genotype 1b. Three hundred and seven patients were randomized into 3 groups to receive 6 mega units (MU) of interferon-alfa-2b subcutaneously 3 times weekly for 6 months followed by 3 MU for 6 months (n = 95, group A); 10 MU for 3 months followed by 6 MU for 3 months, followed by 3 MU for 6 months (n = 83, group B); or the group-A schedule in combination with ribavirin (n = 129, group C) for 4 (n = 46), 6 (n = 44), or 12 months (n = 39). Negative polymerase chain reaction (PCR) was more frequent in group C than in groups A or B after 3 months of treatment ( P &lt; .006), at the end of treatment ( P = .017), and at the end of follow-up (32.8%, 16.9%, and 14.1%, respectively, P &lt; .003). A complete response (negative PCR and normal alanine transaminase) was higher in group C than in the other groups and when comparing 12- to 4- and 6-month combination therapy at the end of treatment ( P = .05) and of follow-up (45.2% vs. 25.4%, respectively, P = .05). The greater efficacy of the combination was related to the higher rate of primary virological response and also to a decrease in the percentage of breakthrough and of relapse. In 1b-infected patients, the combination of high doses of interferon-alfa (6 MU) and ribavirin for 12 months appears to be the best therapy, with a high rate of sustained response.
THE RELATIONSHIP OF THE CHEMOTACTIC BEHAVIOR OF THE COMPLEMENT-DERIVED FACTORS, C3a, C5a, AND C567, AND A BACTERIAL CHEMOTACTIC FACTOR TO THEIR ABILITY TO ACTIVATE THE PROESTERASE 1 OF RABBIT POLYMORPHONUCLEAR LEUKOCYTES
Authors: Elmer L. Becker
Journal: The Journal of Experimental Medicine (1972)

The inhibition profiles obtained when a series of p-nitrophenyl ethyl alkylphosphonates and of p-nitrophenyl ethyl chloroalkylphosphonates were used to interfere with the chemotactic activity of polymorphonuclear leukocytes stimulated by C3a, C5a, and bacterial factor were the same as found previously when C567 was the chemotactic agent. This indicates that as in the chemotactic activity induced by C567, an obligatory step in the chemotaxis caused by C3a, C5a, and bacterial factor is the activation of proesterase 1 of the rabbit polymorphonuclear leukocyte. C5a and C3a activate proesterase 1 of peripheral blood polymophonuclear leukocytes as measured by the increase of acetyl DL-phenylalanine beta-naphthyl esterase activity. Attempts to detect in a like manner the proesterase 1 of the same leukocytes using bacterial factor under varying circumstances have consistently failed. It is concluded that bacterial factor, for unknown reasons, is unable to activate proesterase 1 to the same extent as the complement-derived chemotactic factors. The hypothesis of there being a quantitative difference in the ability of bacterial factor to activate proesterase 1 compared with the complement-derived factors explains the previous observations that bacterial factor can not deactivate to itself or to the complement-derived factors, although these latter factors can deactivate to themselves, to each other, and to the bacterial factor. The quantitative difference in the ability of bacterial factor to activate proesterase 1 compared to the complement-derived factors is also associated with and explains the finding that the maximal chemotactic activity attainable when bacterial factor is the chemotactic agent is distinctly less than that obtained using either C3a, C5a, or C567. These results indicate that the activation of proesterase 1 is a general requirement for the chemotactic activity of rabbit polymorphonuclear leukocytes with known macromolecular chemotactic agents and suggest that under several different circumstances the level of chemotactic activity attained is related to the degree of such activation.
The modular microarchitecture of human liver
Authors: Harald F. Teutsch
Journal: Hepatology (2005)

The morphological homogeneity of the liver parenchyma has represented a major obstacle in finding an acceptable definition of the structural/functional units of the liver. Concepts such as the "lobule," the "portal unit" and the "acinus" remain debatable. This study investigates the modular microarchitecture on the basis of the lobular concept. Using alkaline phosphatase activity as a histochemical marker, modules could be recognized clearly. In autopsy specimens of human liver, modules were traced through sequential cryosections, and a "secondary" module having a height of 1.9 mm, a surface of 14.7 mm2, and a volume of 5.1 mm3 was reconstructed three-dimensionally. It was subdivided into 14 "primary" modules by portal tracts and vascular septa and by a common draining central venular tree. Primary modules were polyhedral, with seven to nine facets, having heights from 0.3 to 0.9 mm, surface areas from 1.7 to 5.0 mm2, and volumes from 0.1 to 0.9 mm3. Such variation in shape and size is considered an important part of the modular organization of the human liver. In conclusion, the findings on the three-dimensionality and microcirculation of liver modules support and extend the lobular concept and, at the same time, make apparent the shortcomings of the concepts of acinar and portal units. The results of this study should permit a better interpretation of histological sections of normal and pathological liver and provide a basis for understanding the metabolic heterogeneity of liver cells and their functional integration into parenchymal units. (HEPATOLOGY 2005.)
William Halstead Taylor
Authors: C Williams, A Khaleeli
Journal: BMJ (2009)

William Halstead Taylor (“Bill”) died peacefully at home on 23 February 2008. From 1959 he developed the chemical pathology laboratory services at the Liverpool Royal Infirmary and established the Metabolic Unit, an innovative single roomed ward suited to metabolic “balance” studies. As gauge of his remarkable journey, one of his first jobs was the then audacious move of stopping the practice of “capping” urine collection containers with twists of hemp rope.

Initially there was a very small number of staff, and, as those familiar with the deeper labyrinths of the old Royal Infirmary in Liverpool will remember, competition from literally thousands of cockroaches, which mercifully were photophobic. Test procedures, though sophisticated, depended predominantly on manual manipulation, and it took more than an hour of careful calibration before blood gas could be measured (approximated) on the apparatus of the day. Modern students of clinical chemistry will have limited familiarity with the noise of flames routinely used at that time to measure analytes such as sodium, potassium, and calcium. In those early days immunological techniques for measuring hormones and steroids were emerging, and radioactive tracers to that end where just entering the general laboratory domain. Bill was instrumental in taking the great step of ending gonadotrophin estimation techniques based on the weight of mouse ovary—a whole live mouse per patient being injected with human urine. This was not a popular move with some clinical staff, but Bill was not a man to court popularity. Thus it was that rabbits took over the animal house from mice and in return for being treated considerately generated a supply of antibodies for analytical use. Unfortunately this friendly transaction was unpredictable in outcome initially and …
The diagnosis and management of anaphylaxis: An updated practice parameter
Authors: Phillip Lieberman, Stephen F. Kemp, John Oppenheimer, David M. Lang, I. Leonard Bernstein, Richard A. Nicklas, John A. Anderson, David I. Bernstein, Jonathan A. Bernstein, Jordan N. Fink, Paul A. Greenberger, Dennis K. Ledford, James Li, Albert L. Sheffer, Roland Solensky, Bruce L. Wolf, Joann Blessing-Moore, David A. Khan, Rufus E. Lee, Jay M. Portnoy, Diane E. Schuller, Sheldon L. Spector, Stephen A. Tilles
Journal: Journal of Allergy and Clinical Immunology (2005)
454 PREDICTORS OF HEPATITIS B VIRUS RECURRENCE WITH EMERGENCE OF YMDD MOTIF MUTANT FOLLOWING ORTHOTOPIC LIVER TRANSPLANTATION
Authors: J. Chun, W. Kim, J.H. Kim, M.S. Kwak, S.W. Hwang, Y.J. Jung, J.B. Jeong, B.G. Kim, K.L. Lee, D.H. Kim, K.-S. Suh, N.-J. Yi, Y.J. Kim, J.-H. Yoon, H.S. Lee
Journal: Journal of Hepatology (2009)
Psychiatric Employment Evaluations and the Health Insurance Portability and Accountability Act
Authors: Liza H. Gold, Jeffrey L. Metzner
Journal: American Journal of Psychiatry (2006)

This review was intended to familiarize psychiatrists with the implications of the Health Insurance Portability and Accountability Act of 1996 on the provision of third-party employment evaluations. Understanding the provisions of the act relative to third-party evaluations can assist psychiatrists in avoiding some of the conflicts that arise in performing such evaluations.
Alcohol consumption and ultrasonographically assessed carotid artery wall thickness and distensibility. The Atherosclerosis Risk in Communities (ARIC) Study Investigators.
Authors: J Demirovic, A Nabulsi, A R Folsom, M A Carpenter, M Szklo, P D Sorlie, R W Barnes
Journal: Circulation (1993)

BACKGROUND Although much has been written in recent years about the relation between alcohol and atherosclerotic disease, controversy exists as to whether and how alcohol exerts an effect on atherosclerosis in different sites. METHODS AND RESULTS We tested the hypothesis that alcohol consumption is associated inversely with carotid atherosclerosis in a population sample of 45- to 64-year-old men and women who participated in the Atherosclerosis Risk in Communities (ARIC) Study and were free of cardiovascular disease at a baseline examination in 1987 to 1989. B-mode ultrasonography was used to determine carotid artery intimal-medial wall thickness and distensibility as indices of the degree of atherosclerosis. The level of alcohol consumption in the ARIC sample was generally low. Age-adjusted mean values of alcohol consumed (grams per week) were 72.0 for white and 74.3 for nonwhite men and 24.8 for white and 11.2 for nonwhite women. After adjustments for age, artery depth, education, body mass index, sport index, cigarette-years of smoking, low-density lipoprotein cholesterol, and diabetes mellitus, there was no significant cross-sectional association of reported current alcohol intake with either carotid artery wall thickness (among white and nonwhite men and nonwhite women) or distensibility (in any of the four sex-race groups). Among white women, the adjusted mean value of carotid artery wall thickness tended to be higher in light to moderate drinkers than in never or rare drinkers, but the difference across drinking status categories was of borderline statistical significance (P = .04) and may be of little biological importance. CONCLUSIONS The ARIC Study found no material cross-sectional association between current alcohol intake and carotid atherosclerosis but provides an opportunity in the future to study atherosclerosis progression and incident events in relation to alcohol consumption in a large population sample of men and women.
P325Surfactant protein C genetic polymorphism in patients with occupational COPD is associated with right ventricle changes
Authors: O Kalmykov
Journal: Cardiovascular Research (2014)

Background: Chronic obstructive pulmonary disease (COPD) is characterized by steadily increasing morbidity and mortality, the last one is associated with mostly cardiovascular complications of COPD. The role of individual peculiarities of organism is taken into account in development of COPD. The role of surfactant, particularly surfactant protein C (SFTP-C) genetic polymorphism is known in development of irreversible bronchial obstruction component as most typical feature of COPD. While relation of SFTP-C to cardiological consequences of COPD was not studied enough. Aims and objectives: Investigation of relation of SFTP-C genetic polymorphism with development of chronic pulmonary hypertension, right heart hypertrophy with dysfunction and estimation of prophylactic potential of clinical-genetic investigation in workers exposed to dust. Methods: In 42 male Caucasian workers from machine-building industry 51,3±14,42 years old COPD of 2nd stage according to GOLD (2011) standards was diagnosed. Genotypes of SFTP-C: A138C (AA, AC, CC) and A186G (AA, AG, GG) were investigated in polymerase chain reaction with following mass spectrometry analysis. Morphofunctional state of heart was defined using echocardiography. Results: It was stated that A138G and A186G polymorphisms of SFTP-C gene are connected with more intensive changes of right heart. E.g., CC genotype is associated with right ventricle hypertrophy, GG genotype - with decrease of right ventricle pre-expulsion (p<0,01). This may be explained by determinant role of certain SFTP-C phenotypes in formation of fibrosis, pulmonary emphysema, further disturbances of pulmonary circulation and increased right ventricle pre-load. Conclusions: Evaluation of surfactant protein C genetic polymorphism in workers of dust-related occupations has a perspective of introduction as a prognostic marker in prophylaxis of COPD cardiovascular complications by formation of risk groups.
Cytotoxic T-Cell Activity and Progression of HIV Disease
Authors: Michael M. Lederman, Hernan Valdez
Journal: JAMA (1998)

BackgroundEarly in human immunodeficiency virus type 1 (HIV-1) infection there is a decline in viral replication that has been attributed to host immunity, but the components of this response, particularly the ability of cytotoxic T lymphocytes to control viral burden and influence the outcome of disease, are poorly understood.MethodsWe prospectively studied 33 patients with primary HIV-1 infection for HIV-specific activated cytotoxic T lymphocytes and memory cytotoxic T lymphocytes and compared these lymphocyte responses with changes in viral load and clinical status over the subsequent 18 to 24 months.ResultsSoon after infection, activated HIV-specific cytotoxic T lymphocytes, mediated primarily by CD8+ cells, were detected in 17 of 23 patients (74 percent). Memory cytotoxic T lymphocytes were found in 6 of 6 patients tested (100 percent) during the first three months of infection and in 17 of 21 patients (81 percent) tested during the first six months. The frequencies of memory cytotoxic T lymphocytes varied markedly over time, but overall they declined over the first 6 to 8 months and then stabilized over the next 12 to 18 months. The patients with higher frequencies of Env-specific memory cytotoxic T lymphocytes had a median level of plasma HIV-1 RNA about one third that of the patients with lower frequencies (median number of RNA copies per milliliter, 22,000 vs. 62,000; P = 0.006). Patients with low frequencies of Env-specific memory cytotoxic T lymphocytes (or none) in early infection had a more rapid decline to less than 300 CD4+ cells per cubic millimeter (P = 0.05).ConclusionsIn early HIV-1 infection, the induction of memory cytotoxic T lymphocytes, particularly those specific for Env, helps control viral replication and is associated with slower declines in CD4+ cell counts. Host cytolytic effector responses appear to delay the progression of HIV-1 disease.
Predicting early and intermediate-term outcome of coronary angioplasty in the elderly.
Authors: R C Thompson, D R Holmes, B J Gersh, K R Bailey
Journal: Circulation (1993)

Although the technical success rate of coronary angioplasty in the elderly in high, very old patients have increased risk of procedure-related death and late recurrence of severe angina. We proposed to determine baseline variables that predict early and intermediate-term failure of percutaneous transluminal coronary angioplasty (PTCA) in patients more than 65 so we could effectively stratify risk.We studied 982 patients at least 65 years old who had urgent or elective PTCA (1980 through 1990). Follow-up (mean, 25 months) was obtained for all patients. Multiple baseline variables were analyzed with univariate and multivariate logistic regression to select independent ones to fit predictive models for in-hospital death or myocardial infarction (overall rate, 6.3%), total in-hospital adverse outcome (overall rate, 18.7%), cumulative survival free of myocardial infarction (overall rate, 15% at 3 years), and cumulative survival free of late nonfatal myocardial infarction, bypass surgery, repeat PTCA, or recurrent severe angina (overall rate, 47% at 3 years). The most heavily weighted parameter in the probability regression equation for each end point was the number of diseased coronary artery segments with at least 70% stenosis. Advanced age was less important. The number of concomitant medical illnesses was predictive of late outcome but not early in-hospital events. Lowest risk quintile versus highest risk quintile event rate was 2.9% versus 14% for acute myocardial infarction or death and 17.2% versus 29% for cumulative in-hospital events. For posthospital events at 3 years' follow-up, lowest risk quintile death or myocardial infarction rate was 4% versus 33% for highest risk quintile. For cumulative late adverse events at 3 years, the event rate was 28% versus 63% for the highest risk quintile.These results stratify patients at high and low risk of early and intermediate-term success after PTCA and identify elderly patients in whom PTCA is most appropriate.
Endocardial Electrograms from Pacemaker Catheters
Authors: ALVIN J. GORDON, MARIA CELESTE VAGUEIRO, S. SERGE BAROLD
Journal: Circulation (1968)

Proper placement of pacemaker catheters can be facilitated by recording endocardial electrograms from the catheters. These electrograms are also helpful in the investigation of pacemaker failure. Endocardial contact is indicated by S-T segment elevation. When bipolar catheters are used, these "contact currents" may be visible in electrograms from the tip or ring electrodes, or both. Right ventricular cavity electrograms are characterized by their high voltage and are influenced by intraventricular conduction defects and acute myocardial infarction. Serial changes have been described indicating myocardial injury, infarction, and healing in the area underlying the catheter tip.