tbuckley/cabot-search huggingface dataset:
<i>In vivo</i> cell lineage analysis in cyproterone acetate-treated rat liver using genetic labeling of hepatocytes
Authors: Isabelle Auvigne, Virginie Pichard, Dominique Aubert, Nelly Robillard, Nicolas Ferry
Journal: Hepatology (2002)

Genetic labeling using recombinant retroviruses is a powerful strategy for the study of cell lineage in the liver. However, this type of vector is only able to infect dividing cells. The synthetic steroid cyproterone acetate (CPA) is mitogenic and carcinogenic in the adult rat liver. In this study, we used retroviral vectors carrying the nuclear targeted β-galactosidase gene to selectively label and follow the fate of hepatocytes dividing on administration of CPA. Labeled cells as well as those in mitosis were preferentially located around the portal tract, whereas apoptotic bodies were predominant in the pericentral area. Labeled hepatocytes did not disappear after apoptosis, suggesting a preferential elimination of nontransduced cells. The presence of labeled binucleated hepatocytes showed the persistence of a binucleation process. Finally, we performed long-term analysis of labeled cells in transgenic animals tolerant for β-galactosidase and treated with 2-acetylaminofluorene (2-AAF) to promote the growth of CPA-initiated hepatocytes. The presence of β-galactosidase-positive hepatocyte clones showed that hepatocytes divided during treatment with 2-AAF. Only 3% of β-galactosidase clones were positive for the placental form of glutathione S-transferase (GSTp), indicating the absence of a preferential appearance of preneoplastic foci in the population of β-galactosidase-labeled hepatocytes. In conclusion, our results show that the mitogenic and tumor-initiating activities of CPA are directed toward different hepatocyte populations.
The F word
Authors: A C Carr
Journal: BMJ (2010)

<b>Objectives:</b> To evaluate the mortality rates among patients with early rheumatoid arthritis (RA) treated actively according to the “sawtooth” strategy. <b>Methods:</b> The study included 150 early, disease modifying antirheumatic drug (DMARD) naive patients with RA from two patient cohorts. The first cohort was assembled between 1986 and 1989 (87 patients, aged 19–65 years at onset) and the second between 1991 and 1993 (63 patients, aged 27–83 years at onset). The mean duration of symptoms at the time of diagnosis was 7.1 months (range 2–24). The clinical data and the use of DMARDs were systematically recorded. The causes of death were obtained from death certificates and medical records, if available. The data were collected up to 1 November 2000. <b>Results:</b> During a follow up time of 7–14 years, 24 patients died. The standardised mortality ratio was not increased (0.93 in the first cohort and 1.62 in the second cohort). Age adjusted mortality rates did not differ statistically significantly between the two patient cohorts. The causes of death included malignancy (8 patients); cardiovascular diseases (10); respiratory disease (4), including two patients with pneumonia; sepsis (one); and RA (one). High inflammatory activity, disease activity, and poor functional ability at study entry, and the presence of extra-articular features during the follow up were more common among the patients who had died. <b>Conclusions:</b> No statistically significant increase in mortality rates was seen in these actively treated early RA cohorts during the follow up. High disease activity at the onset and the development of extra-articular features seem to be associated with mortality.
Ultramorphological sperm characteristics in the risk assessment of health effects after radiation exposure among salvage workers in Chernobyl.
Authors: A Fischbein, N Zabludovsky, F Eltes, V Grischenko, B Bartoov
Journal: Environmental Health Perspectives (1997)

We present a pilot study of individuals (liquidators) who were engaged in clean-up operations after the disaster at the nuclear power plant at Chernobyl in Ukraine. In the 10 years since the disaster, adverse health effects among exposed individuals have not been clearly defined. There is widespread fear of damage to the reproductive system, with implications for fertility problems and adverse effects on offspring. Bearing this in mind, methods to evaluate the potential for production of fertile semen have been applied using quantitative ultramorphological (QUM) analysis. QUM analysis examines the organization and integrity of sperm organelles by electron microscopy, using both transmission electron microscopy and scanning electron microscopy. Significant differences were observed between clean-up workers and controls of similar age regarding certain ultramorphological parameters of the sperm head. The results of this pilot study suggest that QUM analysis of human sperm is a feasible approach for evaluating the fertility potential of individuals who were exposed to ionizing radiation from the Chernobyl nuclear power plant accident.
Altered regulation of apolipoprotein A-IV gene expression in the liver of the genetically obese Zucker rat.
Authors: W Strobl, B Knerer, R Gratzl, K Arbeiter, Y C Lin-Lee, W Patsch
Journal: Journal of Clinical Investigation (1993)

Apolipoprotein (apo) A-IV, a structural component of chylomicrons and high-density lipoproteins, may play a role in the catabolism of triglyceride-rich lipoproteins and in reverse cholesterol transport. To study the regulation of apoA-IV gene expression by genetic and nutritional factors, we determined the effect of a fish oil-rich and a sucrose-rich diet on apoA-IV gene transcription and nuclear and total cellular apoA-IV mRNA abundance in livers of genetically obese, hyperlipoproteinemic (fa/fa) Zucker rats and their lean (Fa/-) littermates. In obese rats fed chow, hepatic apoA-IV gene expression was more than twofold higher than in lean rats because of a post-transcriptional mechanism. apoA-I gene expression and apoC-III mRNA levels, studied as controls, were similar in both groups. The fish oil-rich diet reduced total cellular apoA-IV mRNA abundance transcriptionally to 34 +/- 4% of basal values in lean rats, but did not alter apoA-IV gene expression in obese rats. In contrast, this diet reduced apoA-I gene expression in both lean and obese animals. The sucrose-rich diet increased apoA-IV gene expression twofold in both lean and obese rats. Thus, genetic obesity alters the response of hepatic apoA-IV gene expression to a lipid-lowering diet rich in fish oil by a mechanism affecting transcriptional regulation.
Prolonged depersonalization after marijuana use
Authors: H V Szymanski
Journal: American Journal of Psychiatry (1981)

The author describes four cases of prolonged depersonalization that occurred months after marijuana use. Each occurred in the setting of a stressful life event. Depersonalization is a common experience during acute intoxication with marijuana, and these cases suggest that after the patients had experienced depersonalization, external stressors and intrapsychic factors may have contributed to its continued use as a defense mechanism.
STEM CELL MOBILIZATION BY GRANULOCYTE COLONY STIMULATING FACTOR POST MYOCARDIAL INFARCTION TO PROMOTE MYOCYTE REPAIR
Authors: Chris Glover, Rob Beanlands, Michel Le May, Derek So, Marino Labinaz, Edward O'Brien, Jean-Francois Marquis, Richard Davies, Rob de Kemp, Cathy Kelly, Harry Atkins
Journal: Journal of the American College of Cardiology (2011)
Infliximab Maintenance Therapy for Fistulizing Crohn's Disease
Authors: Bruce E. Sands, Frank H. Anderson, Charles N. Bernstein, William Y. Chey, Brian G. Feagan, Richard N. Fedorak, Michael A. Kamm, Joshua R. Korzenik, Bret A. Lashner, Jane E. Onken, Daniel Rachmilewitz, Paul Rutgeerts, Gary Wild, Douglas C. Wolf, Paul A. Marsters, Suzanne B. Travers, Marion A. Blank, Sander J. van Deventer
Journal: New England Journal of Medicine (2004)

Infliximab, a monoclonal antibody against tumor necrosis factor, is an effective maintenance therapy for patients with Crohn's disease without fistulas. It is not known whether infliximab is an effective maintenance therapy for patients with fistulas.
Localized Regulation of Axonal RanGTPase Controls Retrograde Injury Signaling in Peripheral Nerve
Authors: Dmitry Yudin, Shlomit Hanz, Soonmoon Yoo, Elena Iavnilovitch, Dianna Willis, Tal Gradus, Deepika Vuppalanchi, Yael Segal-Ruder, Keren Ben-Yaakov, Miki Hieda, Yoshihiro Yoneda, Jeffery L. Twiss, Mike Fainzilber
Journal: Neuron (2008)
Functional Prostaglandin-Endoperoxide Synthase 2 Polymorphism Predicts Poor Outcome in Sarcoidosis
Authors: Michael R. Hill, Anastasia Papafili, Helen Booth, Phillippa Lawson, Marianne Hubner, Huw Beynon, Catherine Read, Gisela Lindahl, Richard P. Marshall, Robin J. McAnulty, Geoffrey J. Laurent
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

Rationale: The majority of patients with sarcoidosis resolve their condition; however 5–10% of patients with sarcoidosis develop pulmonary fibrosis with poor prognosis. Prostaglandin-endoperoxide synthase 2 (PTGS2) is a key regulatory enzyme in the synthesis of the antifibrotic agent prostaglandin E2 and is reduced in sarcoidosis lung. A promoter polymorphism in PTGS2, −765G>C, is reported to reduce its expression.Objectives: To investigate if −765G>C is associated with susceptibility to, and poorer outcome within, sarcoidosis and to examine a possible mechanism by which −765G>C reduces PTGS2 expression.Methods: We used a case-control design study and genotyped −765G>C in a white British population of 198 patients with sarcoidosis and 166 control subjects. Patients with sarcoidosis were classified before genotyping as having persistent or nonpersistent disease using clinical criteria that included chest radiography staging, need for treatment, lung function, and longitudinal follow-up. Electrophoretic mobility shift assays were used to identify changes in transcription factor binding caused by the −765G>C polymorphism.Results: Carriage of the –765C allele was strongly associated with susceptibility to sarcoidosis (odds ratio, 2.50; 95% confidence interval, 1.51–4.13; p = 0.006) and, within this disease, with poorer outcome (odds ratio, 3.11; 95% confidence interval, 1.35–7.13; p = 0.008). The association with sarcoidosis was replicated in a second Austrian population. Electrophoretic mobility shift assays revealed that the −765C allele causes a loss of Sp1/Sp3 transcription factor binding and an increase in Egr-1 binding to the region.Conclusion: Our data suggest that the −765G>C polymorphism identifies individuals who are susceptible to sarcoidosis and, more importantly, at risk of pulmonary fibrotic disease. An altered Sp1/Sp3 binding to the −765 region may contribute to the mechanism by which −765G>C reduces PTGS2 expression.
Glutathione Synthetase Deficiency as a Cause of Hereditary Hemolytic Disease
Authors: Daniel N. Mohler, Philip W. Majerus, Virginia Minnich, Charles E. Hess, Michael D. Garrick
Journal: New England Journal of Medicine (1970)

Two enzymes are required for de novo glutathione synthesis: glutamyl-cysteine synthetase and glutathione synthetase. In a 32-year-old man with a well compensated hemolytic disorder, the erythrocytes were devoid of glutathione synthetase activity, whereas erythrocytes from his parents and four children had levels that were half those of normal control erythrocytes. These heterozygotes had no other detectable hematologic abnormalities. Both the patient and his heterozygous relatives had normal levels of erythrocyte glutamyl-cysteine synthetase. Glutathione synthetase deficiency is an autosomally inherited trait that, in a homozygous subject, produces a mild hemolytic disorder.
THE PATHOLOGY OF ACTIVE TUBERCULOSIS OF THE PERICARDIUM.
Authors: H. GIDEON WELLS
Journal: JAMA (1901)

A number of cases of tuberculosis of the pericardium having been observed in the autopsies studied in the pathological laboratory of Rush Medical College, during the past six years, at the suggesion of Professor Hektoen I have collected the reports and specimens for study, including among them the cases observed at autopsy at the Cook County Hospital during the past 3½ years. Altogether the material has been drawn from 1048 autopsies on the bodies of adults. Tuberculosis may produce in the pericardium distinctly tuberculous processes, with miliary tubercles or caseous masses, which may be shown by microscopic and bacteriologic investigation to be positively tuberculous; again it produces simply a fibroplastic process in which the adhesions and the pericardial membranes contain no anatomical evidences of tuberculosis. This latter form is often difficult to distinguish from any fibrous pericardial synechia of other origin, and will not come into consideration in this paper,
The Use of Immunoglobulin G4 Immunostaining in Diagnosing Pancreatic and Extrapancreatic Involvement in Autoimmune Pancreatitis
Authors: Maesha G. Deheragoda, Nicholas I. Church, Manuel Rodriguez–Justo, Philippa Munson, Neomal Sandanayake, Edward W. Seward, Keith Miller, Marco Novelli, Adrian R.W. Hatfield, Stephen P. Pereira, George J.M. Webster
Journal: Clinical Gastroenterology and Hepatology (2007)
Extracellular deposition of beta-amyloid upon p53-dependent neuronal cell death in transgenic mice.
Authors: F M LaFerla, C K Hall, L Ngo, G Jay
Journal: Journal of Clinical Investigation (1996)

The finding that intracellular expression of the beta-amyloid protein (Abeta) under a neuron-specific promoter led progressively to degeneration and death of neurons in the brains of transgenic mice provides a unique opportunity to utilize this animal model to both understand the mechanism that underlies neuronal cell death and define the complexity of events which may ensue. We observed a correlation between Abeta accumulation in selective neurons and activation of p53, a protein that has been implicated in the induction of apoptosis. Histological and immunohistochemical evaluations of adjacent brain sections suggest that expression of p53 is accompanied by nuclear DNA fragmentation. In certain regions with marked neuronal cell death, extracellular deposition of A(beta) became evident, together with the local activation of astrocytes. Interestingly, the neuritic structures underlying the Abeta deposits showed altered synaptophysin immunoreactivity and morphologic evidence for damage. This transgenic mouse model suggests that intracellular generation of the Abeta protein not only leads to the death of the neuron but may also functionally impair neighboring neurons as well. It further offers a mechanism whereby neuritic plaques may be derived.
Primary Amebic Meningoencephalitis
Authors: John F. Rothrock
Journal: JAMA (1980)

PRIMARY amebic meningoencephalitis is an acute, fulminating, purulent meningoencephalitis caused by free-living amebas of the genus<i>Naegleria</i>. It chiefly afflicts children and young adults in otherwise good health. Mortality approaches 100%. Although in this country most cases have been from the southeastern states, notably Virginia, the following case report helps to emphasize that no region is geographically immune. <h3>Report of a Case</h3> An 18-year-old man was admitted to the Tucson Medical Center, Tucson, Ariz, after a two-day history of headache, stiff neck, and fever. The patient had been in excellent health until two days before admission. He gave a history of swimming in a desert lake near Las Vegas several days before admission. The patient appeared healthy, alert, and fully oriented, although complaining of headache. His temperature was 38.2 c orally, and he had moderate nuchal rigidity. There were no other abnormal signs. The initial peripheral WBC count was 15,800/cu
599. Development of EIAV-Based Vectors for the Treatment of Haemophilia A
Authors: Emily J. Custard, Fraser J. Wilkes, Susan M. Kingsman, Kyriacos A. Mitrophanous, Pippa A. Radcliffe
Journal: Molecular Therapy (2005)

We have developed minimal vectors based on the non-primate lentivirus Equine Infectious Anaemia Virus (EIAV) for use in the clinic. This vector system fulfils a number of the requirements necessary for effective gene therapy for haemophilia A including: adequate coding capacity, long term expression, absence of a pre-existing immune response and the ability to transduce non-dividing cells.
Behavioural medicine: changing our behaviour
Authors: Theresa Marteau, Paul Dieppe, Robbie Foy, Ann-Louise Kinmonth, Neil Schneiderman
Journal: BMJ (2006)

Behavioural medicine: changing our behaviourA growing body of evidence shows how to make behavioural interventions effective H uman behaviour is a major determinant of health.Factors that influence health related behaviours and people's adaptive responses to disease and illness are becoming better understood.This understanding is leading to behaviourally based interventions targeted at the level of the individual and at service delivery, with impacts on both.Yet there is much more to do.In the United Kingdom the Society of Behavioural Medicine has been set up to promote research into and the use of well founded behavioural interventions.An example of behavioural interventions working at the individual level is that of psychological preparation of patients facing surgery: procedural information and behavioural instructions reliably reduce the use of analgesia and length of hospital stay. 1 Similarly, psychological treatments based on the principles of cognitive behavioural therapy, when compared with alternative active treatments, reduce the experience and expression of chronic pain. 2 Behavioural interventions can also trump prescribing in preventing disease: in a rare design comparing behavioural interventions head to head with medication, intensive promotion of physical activity and weight loss reduced the incidence of biochemical diabetes in a high risk group by 58%, 3 a greater reduction than that achieved by metformin.
Identification and treatment of a duodenal diverticular hemorrhage: an illustration of the usefulness of the jumbo-channel therapeutic endoscope
Authors: M. Moyer, D. Bethards
Journal: Endoscopy (2009)

Hemorrhage from small-bowel diverticula is rare and requires a high degree of clinical suspicion and an adequate endoscopic view for the diagnosis [1] [2]. Effective endoscopic therapy in this setting, as with most types of upper gastrointestinal bleeding, requires first that the lesion be adequately identified. Unfortunately, blood clot and particulate matter frequently obscure the field of view and prevent identification and treatment of the bleeding source. Conventional upper endoscopes with 2.8- and 3.7-mm working channels are often underpowered to effectively suction and clear blood clots and retained food material. Although repositioning of the patient, use of large-bore lavage tubes, and second look endoscopy after erythromycin infusion are useful adjunctive measures, endoscopically directed clearing of the field with simultaneous viewing would be ideal [3] [4]. Recently, a “jumbo-channel” gastroscope (GIF-XTQ160, Olympus Corporation, Tokyo, Japan) has become widely available and boasts a 6-mm working channel for increased effectiveness in evacuating blood clots and debris ([Fig. 1]).
Colorectal cancer: detection, treatment, and rehabilitation
Authors: J. J. DeCosse, G. J. Tsioulias, J. S. Jacobson
Journal: CA A Cancer Journal for Clinicians (1994)

In the United States, colorectal cancer is the second most common cause of cancer mortality after lung cancer. However, incidence and mortality rates have been falling, reflecting improvements in primary prevention, early detection, and treatment. This article reviews the major advances in the understanding and management of colorectal cancer.
Synoptic weather modeling and estimates of the exposure-response relationship between daily mortality and particulate air pollution.
Authors: C A Pope, L S Kalkstein
Journal: Environmental Health Perspectives (1996)

This study estimated the association between particulate air pollution and daily mortality in Utah Valley using the synoptic climatological approach to control for potential weather effects. This approach was compared with alternative weather modeling approaches. Although seasonality explained a significant amount of variability in mortality, other weather variables explained only a very small amount of additional variability in mortality. The synoptic climatological approach performed as well or slightly better than alternative approaches to controlling for weather. However, the estimated effect of particulate pollution on mortality was mostly unchanged or slightly larger when synoptic categories were used to control for weather. Furthermore, the shape of the estimated dose-response relationship was similar when alternative approaches to controlling for weather were used. The associations between particulate pollution and daily mortality were not significantly different from a linear exposure-response relationship that extends throughout the full observed range of pollution.
Purkinje neuron Ca2+ influx reduction rescues ataxia in SCA28 model
Authors: Francesca Maltecca, Elisa Baseggio, Francesco Consolato, Davide Mazza, Paola Podini, Samuel M. Young, Ilaria Drago, Ben A. Bahr, Aldamaria Puliti, Franca Codazzi, Angelo Quattrini, Giorgio Casari
Journal: Journal of Clinical Investigation (2014)

Spinocerebellar ataxia type 28 (SCA28) is a neurodegenerative disease caused by mutations of the mitochondrial protease AFG3L2. The SCA28 mouse model, which is haploinsufficient for Afg3l2, exhibits a progressive decline in motor function and displays dark degeneration of Purkinje cells (PC-DCD) of mitochondrial origin. Here, we determined that mitochondria in cultured Afg3l2-deficient PCs ineffectively buffer evoked Ca2+ peaks, resulting in enhanced cytoplasmic Ca2+ concentrations, which subsequently triggers PC-DCD. This Ca2+-handling defect is the result of negative synergism between mitochondrial depolarization and altered organelle trafficking to PC dendrites in Afg3l2-mutant cells. In SCA28 mice, partial genetic silencing of the metabotropic glutamate receptor mGluR1 decreased Ca2+ influx in PCs and reversed the ataxic phenotype. Moreover, administration of the β-lactam antibiotic ceftriaxone, which promotes synaptic glutamate clearance, thereby reducing Ca2+ influx, improved ataxia-associated phenotypes in SCA28 mice when given either prior to or after symptom onset. Together, the results of this study indicate that ineffective mitochondrial Ca2+ handling in PCs underlies SCA28 pathogenesis and suggest that strategies that lower glutamate stimulation of PCs should be further explored as a potential treatment for SCA28 patients.
Targeting Syk-activated B cells in murine and human chronic graft-versus-host disease
Authors: Ryan Flynn, Jessica L. Allen, Leo Luznik, Kelli P. MacDonald, Katelyn Paz, Kylie A. Alexander, Ante Vulic, Jing Du, Angela Panoskaltsis-Mortari, Patricia A. Taylor, Jonathan C. Poe, Jonathan S. Serody, William J. Murphy, Geoffrey R. Hill, Ivan Maillard, John Koreth, Corey S. Cutler, Robert J. Soiffer, Joseph H. Antin, Jerome Ritz, Nelson J. Chao, Raphael A. Clynes, Stefanie Sarantopoulos, Bruce R. Blazar
Journal: Blood (2015)