tbuckley/cabot-search huggingface dataset:
Fluorescent Cardiac Imaging
Authors: Christian Detter, Sabine Wipper, Detlef Russ, Andre Iffland, Lars Burdorf, Eckart Thein, Karl Wegscheider, Hermann Reichenspurner, Bruno Reichart
Journal: Circulation (2007)

The purpose of the present study was to examine whether the effect of coronary stenoses of variable severity on myocardial perfusion can be quantitatively assessed in vivo by analysis of fluorescent cardiac imaging (FCI) compared with the gold standard, the fluorescent microsphere method. FCI is a novel technology to visualize coronary vessels and myocardial perfusion intraoperatively using the indocyanine green dye with an infrared-sensitive imaging device.Graded stenoses and total vessel occlusion of the left anterior descending coronary artery were created in 11 open-chest pigs. Stenoses were graded to reduce resting left anterior descending coronary artery flow by 25%, 50%, 75%, and 100% of baseline flow measured by transit-time flowmeter. FCI images were analyzed with a digital image processing system. The impairment of myocardial perfusion was quantified by background-subtracted peak fluorescence intensity and slope of fluorescence intensity obtained with FCI and compared with myocardial blood flow assessed by fluorescent microsphere. All stenoses resulted in an impairment of myocardial perfusion visualized by FCI. Occlusion of the left anterior descending coronary artery resulted in a total perfusion defect (no fluorescence intensity) of the corresponding anterior myocardial wall. During graded stenosis and total vessel occlusion, normalized background-subtracted peak fluorescence intensity and slope of fluorescence intensity decreased significantly (P<0.0001). Both background-subtracted peak fluorescence intensity (r=0.92, P<0.0001) and slope of fluorescence intensity (r=0.93, P<0.0001) analyzed by FCI demonstrated good linear correlation with fluorescent microsphere-derived myocardial blood flow.The impairment of myocardial perfusion in response to increased coronary stenosis severity and total vessel occlusion can be quantitatively assessed by FCI and correlates well with results obtained by fluorescent microsphere.
Psychiatric Status After Hysterectomy-Reply
Authors: Ronald L. Martin
Journal: JAMA (1981)

<h3>In Reply.—</h3> As Dr Poma points out, there were some indications of new psychiatric symptoms in the 44 women followed up—two (not three) new cases of treatment, three with a new psychiatric diagnosis, and the worsening of symptoms in a few. It is still argued, however, that this is not necessarily an excess, nor does it necessarily implicate the hysterectomy procedure. These occurrences were mild. The two women newly given psychotropics received only diazepam, not a remarkable event in this era. One of these women also received psychiatric counseling for the first time (briefly during divorce proceedings). Thus, there were only two new cases of treatment and one concurrent with an event (divorce) often associated with psychiatric symptoms.<sup>1</sup>Of the three women with new psychiatric diagnoses at followup, one had simply denied symptoms at the prehysterectomy evaluation that were reported at follow-up to have been present for years before
The risk of Borrelia burgdorferi infection is not increased in pet owners
Authors: M. A. Cimmino
Journal: JAMA (1989)

<h3>To the Editor. —</h3> The possibility that cat owners may be at risk of infection by the spirochete<i>Borrelia burgdorferi</i>, the etiologic agent of Lyme disease, has been suggested by Steere and coworkers<sup>1</sup>in their early studies on the disease. They have reported that significantly more patients are cat owners than unaffected neighbors.<sup>1</sup>More recently, the association between dog ownership and risk of human Lyme disease has been denied by Eng and coworkers<sup>2</sup>in a small pilot study. Although pets may represent a spirochete reservoir,<sup>3</sup>it is unlikely that human beings can be infected directly by them. However, in areas of endemic Lyme disease, both adult and nymphal ticks, carried into the household by dogs and cats, may infest humans.<sup>4</sup> <h3>Study. —</h3> We have evaluated the relationship between pet ownership and<i>B burgdorferi</i>infection in 238 subjects living in north Italy, in a rural area endemic
POLYPI OF THE APPENDIX.
Authors: GEO. W. PRESSLY
Journal: JAMA (1906)

Kelly, in his exhaustive work on the appendix, reports the first four cases of polypi of the appendix; before this no mention of such eases can be found in the literature. The following case is reported as the fifth of its kind. <h3>Patient.</h3> —L. B., male, aged 19, has had four attacks of colic in the past year. <h3>History.</h3> —The first two were very light and were speedily relieved with morphin and salines. The third attack lasted for twelve hours and some soreness persisted for two days. The fourth attack was much more severe, the pain lasting for thirty-six hours and the tenderness was troublesome for more than a week. <h3>Operation.</h3> —Two months after the last attack he was operated on and the appendix was found much distended, with liquid feces which was thought to be pus, but on eversion the two polypi shown in the illustration were found, the
Clinical Genetics and Genetic Counseling in Alzheimer Disease
Authors: John C. S. Breitner
Journal: Annals of Internal Medicine (1991)

Because of growing evidence for genetic causes of Alzheimer disease, clinicians are often asked about risks for this disorder among relatives of patients. This paper briefly reviews the evidence for genetic and other causes of Alzheimer disease, including specifically its typical late-onset variant. Several recent developments in the molecular genetics of early-onset Alzheimer disease are described briefly. These findings, however, may not apply to more typical, late-onset Alzheimer disease. Genetic studies of the latter disorder are complicated by the censorship of any inherited predisposition to disease by death from other causes. Hence, heritable disease may be apparent only in families with large numbers of elderly relatives at risk. Relying on empiric observations of risk among relatives from several recent studies of pooled Alzheimer families, curves are presented describing theoretic age-specific risks in relatives of patients and unaffected controls. Real (current) lifetime risks of Alzheimer disease are then estimated by modification of the theoretic figures with corresponding current age-specific mortality characteristics of the U.S. population. The lifetime incidence among relatives of patients with Alzheimer disease is estimated to be 19%, or three to four times the risk among control relatives. Because both mortality of and risk for Alzheimer disease change rapidly with advancing age, it may be possible to reduce the current morbidity from Alzheimer disease by 50% if onset can be postponed by only 5 years.
Underreporting of AIDS Cases in South Carolina, 1986 and 1987
Authors: George A. Conway
Journal: JAMA (1989)

An evaluation of the completeness and accuracy of case reporting of the acquired immunodeficiency syndrome (AIDS) for the 18-month period from January 1, 1986, through June 30, 1987, was conducted for South Carolina. A total of 596,585 hospital discharge billing records were searched by computer for conditions defining AIDS. The resulting 1513 records were manually reviewed. Of these, 349 discharges for 163 individuals were classified as being definitely AIDS related, the clinical features of these cases meeting Centers for Disease Control criteria for AIDS diagnosis. Of these cases, 153 were reportable to the South Carolina AIDS registry at the time of their diagnosis. Comparison of this case list with registry records revealed that only 91 (59.5%) had been reported. Reporting was significantly poorer for cases among blacks (53.1%) than for cases among whites (71.6%). These findings may have important implications for the interpretation of AIDS surveillance data and for planning activities in which awareness of complete case counts may be critical.
DR-06 * REACTIVE OXYGEN SPECIES MEDIATE THERAPEUTIC RESPONSE AND RESISTANCE IN GLIOBLASTOMA
Authors: E. Singer, J. Judkins, N. Salomonis, P. Soteropoulos, S. McAllister, L. Soroceanu
Journal: Neuro-Oncology (2014)

Glioblastoma (GBM) resistance to therapy is the most common cause of tumor recurrence, which is ultimately fatal in 90 percent of the patients five years after initial diagnosis. A subpopulation of tumor cells with stem like properties are specifically endowed to resist or adapt to the standard therapies (e.g, radiation, chemotherapy) and lead to tumor resistance. We investigated the mechanisms underlying GBM response to treatment using the non-toxic, non-psychoactive cannabinoid derivative cannabidiol (CBD), in primary glioma stem-like cells in culture and in vivo. In culture, CBD induced an increase in reactive oxygen species (ROS) in GSC which lead to inhibition of proneural markers, cell survival, p-AKT, and self-renewal, concomitant with upregulation of anti-oxidant response gene products and mesenchymal markers. These phenotypic changes were also measured in GSC-derived xenografts from CBD-treated animals, suggesting this molecular adaptive response contributes to therapeutic response and resistance in vivo. CBD-induced mesenchymal shift was reversible by pretreatment with Tocopherol (vit E), indicating that it is ROS mediated. CBD- induced inhibition of self-renewal was mediated by activation of the AMPK-phosphor-p38-Bmi1 pathway. The anti-oxidant response cellular program was mediated by transcriptional activation of NFE2L2 and resulted in upregulation of its target genes, such as xCT. xCT is the enzymatic component of system Xc which regulates GSH levels, the main CNS redox buffering system, and plays a critical role in GBM cell survival. We hypothesized that combining CBD with xCT inhibition will exhibit an enhanced anti-tumor effect. Using genetic knockdown and the pharmacological agents Sulfasalazine and Erastin, we demonstrate that CBD and xCT inhibitors work synergistically to inhibit survival, self renewal and invasion of primary GSC. Taken together our data suggest that combination of CBD and non-toxic small molecules which regulate ROS levels constitute a promising therapeutic approach for glioblastoma.
RNA and protein synthesis in human peripheral blood polymorphonuclear leukocytes.
Authors: A Granelli-Piperno, J D Vassalli, E Reich
Journal: The Journal of Experimental Medicine (1979)

Polymorphonuclear leukocytes purified from human peripheral blood synthesized RNA and proteins when placed in cell culture. Autoradiography of the cultured cells revealed that a majority of mature PMNs were engaged in macromolecule synthesis, and an analysis of newly synthesized proteins by SDS-polyacrylamide gel electrophoresis showed that many different polypeptide chains were synthesized by these cells. The rate of [3H]uridine incorporation and the pattern of newly synthesized proteins were modulated by Con A and glucocorticoids. These results suggest that in spite of their short lifetime and a large performed enzymatic apparatus, mature PMNs retain a substantial capacity for RNA and protein synthesis; and, further, that modulation of macromolecule synthesis forms part of the mechanism by which PMNs respond to inflammatory and anti-flammatory stimuli.
Dermoscopic features of congenital acral melanocytic naevi in children: a prospective comparative and follow-up study
Authors: S.Y. Chuah, K. Tsilika, C. Chiaverini, E. Fontas, J.P. Ortonne, J.P. Lacour, P. Bahadoran
Journal: British Journal of Dermatology (2014)

Journal Article Dermoscopic features of congenital acral melanocytic naevi in children: a prospective comparative and follow‐up study Get access S.Y. Chuah, S.Y. Chuah Department of Dermatology National Skin Centre 1 Mandalay Road Singapore 308205 Search for other works by this author on: Oxford Academic Google Scholar K. Tsilika, K. Tsilika Service de Dermatologie Hôpital Archet 2, 151 Route Saint Antoine de Ginestière 06202 Nice CEDEX 3 France Search for other works by this author on: Oxford Academic Google Scholar C. Chiaverini, C. Chiaverini Service de Dermatologie Hôpital Archet 2, 151 Route Saint Antoine de Ginestière 06202 Nice CEDEX 3 France Search for other works by this author on: Oxford Academic Google Scholar E. Fontas, E. Fontas CHU NICE Department of Clinical Research University of Nice F‐06202 Nice CEDEX 3 France Search for other works by this author on: Oxford Academic Google Scholar J.P. Ortonne, J.P. Ortonne Service de Dermatologie Hôpital Archet 2, 151 Route Saint Antoine de Ginestière 06202 Nice CEDEX 3 France Search for other works by this author on: Oxford Academic Google Scholar J.P. Lacour, J.P. Lacour Service de Dermatologie Hôpital Archet 2, 151 Route Saint Antoine de Ginestière 06202 Nice CEDEX 3 France Search for other works by this author on: Oxford Academic Google Scholar P. Bahadoran P. Bahadoran Service de Dermatologie Hôpital Archet 2, 151 Route Saint Antoine de Ginestière 06202 Nice CEDEX 3 FranceCentre de Recherche Clinique Nice FranceINSERM U 1065, Team 1, CHU de Nice Nice France Correspondence Philippe Bahadoran. E‐mail: bahadoran.p@chu-nice.fr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 172, Issue 1, 1 January 2015, Pages 88–93, https://doi.org/10.1111/bjd.13187 Published: 01 January 2015
Quantitative analysis of IgE antibodies to food and inhalant allergens in 4‐year‐old children reflects their likelihood of allergic disease
Authors: M. Wickman, G. Lilja, L. Söderström, M. v. H. Hamsten, S. Ahlstedt
Journal: Allergy (2005)

Background: It is well established that early diagnosis of allergic disease is warranted. Methods: In a prospective birth cohort study (BAMSE) 3743 children at 4 years of age were included. Children were classified as having any allergic disease, e.g. asthma, suspected allergic rhinitis (suspAR), eczema or oro‐gastro‐intestinal symptoms with questionnaire. Blood was obtained from 2612 of these children and analysed for IgE antibodies (ab) towards 14 common food and airborne allergens. Results: Positive IgE ab results were found in 38% of the children with any allergic disease, whereas such IgE ab results were found in 17% among those without any allergic disease. Furthermore, among children with any allergic disease the median summated IgE ab levels were 10.7 kU A /l compared with 1.5 kU A /l among those without such symptoms. The highest IgE ab levels were found to birch, peanut, cat and horse. When the sum of the IgE‐ab levels towards the selected allergens was at least 34 kU A /l, or, alternatively, more than four allergen tests were positive, there was a 75% likelihood of identifying the individual with any allergic disease. To identify those with asthma, as well as those with suspAR, a significant interaction was found for the combination of the sum of IgE‐ab levels and number of allergens positive at test. For eczema only, the number of positive allergens at test was associated to the likelihood of such disease. Conclusions: In children, 4 years of age, allergic disease was frequently not associated with the presence of single positive IgE antibody results, whereas increased IgE ab levels were significantly more prevalent among those with allergic disease. Thus, testing a certain profile of airborne and food allergens, and utilizing the sum of the IgE‐ab levels in combination with the number of allergens positive at tests, may represent a more efficient diagnostic tool then to use just single positive IgE‐ab results.
988. Repeat Administration of Lentiviral Vector to Mouse Nasal Epithelia
Authors: Patrick L. Sinn, Paul B. McCray
Journal: Molecular Therapy (2006)

Adverse immune responses to vector-encoded proteins may hinder the practical application of gene therapy. To date, little effort has been devoted to determining the immunological consequences of topical delivery of lentiviral vectors to respiratory epithelia. Previously, we demonstrated that an integrating feline immunodeficiency virus-based lentiviral vector pseudotyped with a baculoviral envelope glycoprotein (GP64-FIV) readily transduced differentiated airway epithelia in vitro when applied to the apical surface. Furthermore, using a luciferase reporter gene and bioluminescence imaging, we observed in vivo gene transfer to the mouse nasal epithelia following a single application of GP64-FIV. Longitudinal bioluminescence analysis documented persistent expression in nasal epithelia for greater than 11 months without significant decline. By histological analysis, surface epithelial cells were transduced following a single nasal application of GP64-FIV expressing beta-galactosidase. Importantly, we observed that 7 consecutive doses of GP64-FIV delivered over 7 consecutive days led to greatly increased number of beta-galactosidase positive epithelial cells. However, using quantitative bioluminescent imaging, we observed that repeated doses given over consecutive days did not result in a linear increase in gene expression. We have now initiated studies investigating gene transfer efficacy and immune responses following lentiviral vector readministration with greater intervening time periods. In control mice, we observed that giving 2 nasal instilled doses (2 weeks apart) of an E1/E3 deleted Ad5 vector resulted in significantly attenuated expression of the second dose. In contrast, using the same delivery protocol, 2 doses of GP64-FIV did not result in loss of expression of the second dose. Ongoing studies are investigating the impact of lentiviral vector readministration on marker gene expression, as well as how gene transfer efficiency correlates with the production of neutralizing antibodies. GP64-FIV efficiently transduces and persistently expresses a transgene in nasal epithelia and has the potential for repeat administration without eliciting adverse immune responses. These data have important implications for lentiviral gene therapy.
Repository needed to improve access to drug company documents, conference hears
Authors: L. Banham
Journal: BMJ (2013)

Internal documents from drug companies are harder to access than those from tobacco companies, delegates heard this week at the Seventh International Congress on Peer Review and Biomedical Publication in Chicago.

Presenting research at the conference, Kay Dickersin, of Johns Hopkins Bloomberg School of Public Health and the Cochrane Collaboration, said that a public repository was needed to improve access to internal company documents that may be relevant to healthcare.

Internal company documents are of interest because they …
Reactions of oxidatively activated arylamines with thiols: reaction mechanisms and biologic implications. An overview.
Authors: P Eyer
Journal: Environmental Health Perspectives (1994)

Aromatic amines belong to a group of compounds that exert their toxic effects usually after oxidative biotransformation, primarily in the liver. In addition, aromatic amines also undergo extrahepatic activation to yield free arylaminyl radicals. The reactive intermediates are potential promutagens and procarcinogens, and responsible for target tissue toxicity. Since thiols react with these intermediates at high rates, it is of interest to know the underlying reaction mechanisms and the toxicologic implications. Phenoxyl radicals from aminophenols and aminyl radicals from phenylenediamines quickly disproportionate to quinone imines and quinone diimines. Depending on the structure, Michael addition or reduction reactions with thiols may prevail. Products of sequential oxidation/addition reactions (e.g., S-conjugates of aminophenols) are occasionally more toxic than the parent compounds because of their higher autoxidizability and their accumulation in the kidney. Even after covalent binding of quinone imines to protein SH groups, the resulting thioethers are able to autoxidize. The quinoid thioethers can then cross-link the protein by addition to neighboring nucleophiles. The reactions of nitrosoarenes with thiols yield a so-called "semimercaptal" from which various branching reactions detach, depending on substituents. Compounds with strong pi-donors, like 4-nitrosophenetol, give a resonance-stabilized N-(thiol-S-yl)-arylamine cation that may lead to bicyclic products, thioethers, and DNA adducts. Examples of toxicologic implications of the interactions of nitroso compounds with thiols are given for nitrosoimidazoles, heterocyclic nitroso compounds from protein pyrolysates, and nitrosoarenes. These data indicate that interactions of activated arylamines with thiols may not be regarded exclusively as detoxication reactions.
Predicting Advanced Proximal Colonic Neoplasia With Screening Sigmoidoscopy
Authors: Theodore R. Levin
Journal: JAMA (1999)

ContextIndications are not well defined for follow-up colonoscopy for all patients with distal colonic tubular adenomas (TAs) found at screening sigmoidoscopy.Objective To determine whether distal adenoma size, number, and villous histology, along with family history and age, are predictors of advanced proximal colonic neoplasia.Design Cross-sectional analysis conducted between January 1, 1994, and December 31, 1995.Setting Large group-model health maintenance organization in northern California.Patients A total of 2972 asymptomatic subjects aged 50 years or older undergoing colonoscopy as follow-up to a screening sigmoidoscopy.Main Outcome Measure Based on sigmoidoscopy, colonoscopy, and pathology reports, occurrence of advanced proximal neoplasia, defined as adenocarcinoma or TAs 1 cm or larger or with villous features or severe dysplasia located beyond sigmoidoscopic view. ResultsThe prevalence of advanced proximal neoplasia was similar among patients with no TAs at sigmoidoscopy, those with TAs less than 1 cm in diameter, and those with TAs 1 cm in diameter or larger (prevalence, 5.3%, 5.5%, and 5.6%, respectively).Of patients with a distal tubulovillous or villous adenoma, 12.1% had advanced proximal neoplasia.In multivariate analyses, having a distal tubulovillous adenoma or villous adenoma was the strongest predictor of advanced proximal neoplasia (odds ratio, 2.30; 95% confidence interval, 1.69-3.14).Age of 65 years or older, having more than 1 adenoma, and a positive family history of colorectal cancer were also significant predictors.Distal adenoma size was not a significant predictor in any multivariate analyses.Conclusions Advanced proximal neoplasia is not uncommon in subjects with or without distal TAs, but subjects with advanced distal histology and those older than 65 years are at increased risk.Age-specific screening using sigmoidoscopy starting at ages 50 to 55 years and colonoscopy after age 65 years may be justified.