tbuckley/cabot-search huggingface dataset:
Rapid in vivo transport and catabolism of human apolipoprotein A-IV-1 and slower catabolism of the apoA-IV-2 isoprotein.
Authors: D J Rader, J Schäfer, P Lohse, B Verges, M Kindt, L A Zech, A Steinmetz, H B Brewer
Journal: Journal of Clinical Investigation (1993)

Apolipoprotein (apo) A-IV is a polymorphic, intestinally derived apolipoprotein that is genetically linked to and similar in structure to apoA-I, the major apolipoprotein in high density lipoproteins (HDL). ApoA-IV plays a potentially important role in lipoprotein metabolism and reverse cholesterol transport, but its in vivo metabolism is poorly understood. In order to gain insight into factors modulating apoA-IV metabolism in humans, the in vivo kinetics of the two major human apoA-IV isoproteins apoA-IV-1 and apoA-IV-2 were investigated in normolipidemic human subjects. 131I-apoA-IV-1 and 125I-apoA-IV-2 were reassociated with autologous plasma and injected into study subjects. Analysis of the kinetic data revealed a rapid mean fractional catabolic rate (FCR) for apoA-IV-1 of 2.42 +/- 0.11 d-1. The mean production, or transport, rate of apoA-IV-1 was 16.3 +/- 1.4 mg/kg per d. Plasma apoA-IV concentrations were highly correlated with apoA-IV production rate (r = 0.84, P < 0.001) and not correlated with apoA-IV fractional catabolic rate (r = 0.25, P = NS). The mean FCR of apoA-IV-2 was 2.21 +/- 0.10 d-1. In the ten subjects in whom 131I-apoA-IV-1 and 125I-apoA-IV-2 were simultaneously injected, the FCR of apoA-IV-2 was significantly slower by paired t test (P = 0.003). The FCR of apoA-IV-2 in an apoA-IV-2/2 homozygote was only 1.49 d-1, substantially slower than in all other subjects. We conclude that: (a) apoA-IV is a rapidly catabolized apolipoprotein in humans, with a fractional catabolic rate more than 10 times greater than that of apoA-I; (b) apoA-IV has a high absolute transport rate similar to that of apoA-I; (c) plasma levels of apoA-IV are primarily determined by apoA-IV production rate in normolipidemic subjects; and (d) the fractional catabolic rate of the common variant apoA-IV-2 is slower than that of the wild-type apoA-IV-1.
Quantitation of exposure to benzo[a]pyrene with monoclonal antibodies.
Authors: R M Santella, L L Hsieh, C D Lin, S Viet, I B Weinstein
Journal: Environmental Health Perspectives (1985)

It is now possible to quantitate carcinogen adducts on DNA by highly sensitive immunoassays. These techniques are particularly useful for screening human populations for exposure to potential environmental carcinogens. We have developed a panel of monoclonal antibodies that react with benzo(a)pyrene (BP) modified DNA to be used in an enzyme linked immunoassay (ELISA) to quantitate adduct levels of both human and animal samples. BALBc/Cr mice were immunized with either DNA modified by 7 beta, 8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9, 10-tetrahydrobenzo(a)pyrene (BPDE-I-DNA) complexed electrostatically to methylated bovine serum albumin or with BPDE-I-modified guanosine conjugated with bovine serum albumin (BPDE-I-G-BSA). Four stable clones were produced from the spleen cells of animals immunized with BPDE-I-DNA and one from BPDE-I-G-BSA immunized animals. All antibodies were shown to be highly specific for BPDE-I-DNA and did not crossreact with nonmodified DNA or with N-2-acetylaminofluorene or 1-aminopyrene modified DNA. The antibodies differed in their sensitivity to BPDE-II-DNA, BPDE-I-poly G, BPDE-I-tetraols and BPDE-I-dG. In general, all the antibodies showed the greatest affinity for their original antigen. Those generated against modified DNA showed highest reactivity against modified DNA while the one antibody generated against the monoadduct showed highest reactivity with the monoadduct. These antibodies are currently being used in a highly sensitive competitive ELISA to quantitate levels of BP-DNA adducts in various animal and human tissue samples.
Factor V (Quebec): a bleeding diathesis associated with a qualitative platelet Factor V deficiency.
Authors: P B Tracy, A R Giles, K G Mann, L L Eide, H Hoogendoorn, G E Rivard
Journal: Journal of Clinical Investigation (1984)

Studies were performed on a French-Canadian family afflicted with a bleeding disorder exhibiting an autosomal dominant inheritance pattern and a severe bleeding diathesis after trauma. Clinical laboratory coagulation tests were unimpressive; the only persistent abnormalities include mild thrombocytopenia and moderately reduced Factor V clotting activities. Some individuals had prolonged Stypven times when platelet-rich plasma was used, suggesting that their platelets could not support functional prothrombinase complex assembly. Detailed studies were performed by use of plasma and isolated, washed platelets from a sister and brother. Bioassay data indicate that both individuals had Factor V activities of approximately 40 and 36% of normal, respectively. A comparison of the Factor V radioimmunoassay and bioassay data on the brother's plasma indicated that the circulating amount of Factor V functional activity was low relative to Factor V antigen concentration (approximately 65-75%). In both individuals, the platelet Factor V functional activities were extremely low (2-4%) relative to antigen levels present as determined by radioimmunoassay. These discrepancies between Factor V activities and antigen concentration do not appear to be due to an unstable Factor V molecule or to the presence of a Factor V or Factor Va inhibitor or inactivator. Kinetics of prothrombin activation by use of purified clotting factors indicated that thrombin-activated platelets from both individuals supported prothrombinase complex assembly identical to controls in the presence of added purified Factor Va. Consequently, their bleeding diathesis appears to reflect their platelet, rather than their plasma, Factor V activity. These results suggest that platelet Factor V is an essential component in maintaining stable and prolonged hemostasis after trauma.
Tumor promoting effects of CD95 signaling in chemoresistant cells
Authors: Elisabet Ametller, Susana García-Recio, Domizziana Costamagna, Cristina Mayordomo, Patricia Fernández-Nogueira, Neus Carbó, Eva María Pastor-Arroyo, Pedro Gascón, Vanessa Almendro
Journal: Molecular Cancer (2010)

CD95 is a death receptor controlling not only apoptotic pathways but also activating mechanisms promoting tumor growth. During the acquisition of chemoresistance to oxaliplatin there is a progressive loss of CD95 expression in colon cancer cells and a decreased ability of this receptor to induce cell death. The aim of this study was to characterize some key cellular responses controlled by CD95 signaling in oxaliplatin-resistant colon cancer cells.We show that CD95 triggering results in an increased metastatic ability in resistant cells. Moreover, oxaliplatin treatment itself stimulates cell migration and decreases cell adhesion through CD95 activation, since CD95 expression inhibition by siRNA blocks the promigratory effects of oxaliplatin. These promigratory effects are related to the epithelia-to-mesenchymal transition (EMT) phenomenon, as evidenced by the up-regulation of some transcription factors and mesenchymal markers both in vitro and in vivo.We conclude that oxaliplatin treatment in cells that have acquired resistance to oxaliplatin-induced apoptosis results in tumor-promoting effects through the activation of CD95 signaling and by inducing EMT, all these events jointly contributing to a metastatic phenotype.
Inhibition of contractile activation reduces reoxygenation-induced endothelial gap formation
Authors: C SCHAFER, S WALTHER, M SCHAFER, L DIETERICH, S KASSECKERT, Y ABDALLAH, H PIPER
Journal: Cardiovascular Research (2003)

Objective: Barrier function of coronary endothelium becomes disturbed by ischemia–reperfusion. We investigated the mechanism of reperfusion-induced endothelial gap formation in monolayers of cultured endothelial cells (CEC) of the rat, exposed to simulated ischemia (40 min anoxia, pHo 6.4) and reperfusion (30 min reoxygenation, pHo 7.4). Methods: Cytosolic Ca2+ (fura-2) and intercellular gap formation (planimetrical analysis) were determined. Reoxygenation conditions were varied: (a) continuing perfusion at pHo 6.4, (b) with or without glucose (2.5 mM), (c) in presence of NaCN (2 mM), (d) with Ca2+ (10 mM) or BAPTA/AM (25 μM), (e) in the presence of myosin light chain kinase inhibitors ML-7 (5 μM) or wortmannin (1 μM). Results: During anoxia, CEC developed cytosolic Ca2+ overload which was not reversed during 30 min reoxygenation. Intercellular gap formation started during anoxia, but was increased during reoxygenation. Reoxygenation-related gap formation was largest in presence of glucose, lower when glucose was withdrawn or NaCN was added. Presence of ML-7 or wortmannin also reduced gap formation during reoxygenation. Conclusions: Reoxygenation induces gap formation. This is dependent on (i) Ca2+ overload during reoxygenation, (ii) energy production and (iii) activation of myosin light chain kinase. Together these results indicate that activation of the endothelial contractile machinery is the underlying cause.
Trends in the Treatment of Bipolar Disorder by Outpatient Psychiatrists
Authors: Carlos Blanco, Gonzalo Laje, Mark Olfson, Steven C. Marcus, Harold Alan Pincus
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: This study examined recent changes in the prescribing patterns for medications to treat bipolar disorder in office-based psychiatric practice. METHOD: The authors analyzed physician-reported data from the National Ambulatory Medical Care Survey for 1992–1995 and 1996–1999, focusing on physicians specializing in psychiatry. Demographic, clinical, and medication prescription characteristics of patients' visits were compared to identify changes between the periods. Logistic regression models were used to identify predictors of medication prescription, with adjustment for the presence of other covariates. RESULTS: In both survey periods, over one-third of the total psychiatrist visits by patients with bipolar disorder did not include prescription of a mood stabilizer. There was a decrease in the use of lithium over time, accompanied by an increase in the use of valproic acid. Antipsychotic medication was prescribed more frequently for the bipolar manic and mixed subtypes, and there was a secular increase in the use of the newer antipsychotics. During each time period, prescription of antidepressants was common, often in the absence of a mood stabilizer. CONCLUSIONS: Despite important advances in the range of mood stabilizers available, the pharmacological treatment of bipolar disorder continues to be an area with substantial opportunity for quality improvement.
THE INFLUENCE OF CONSANGUINITY ON THE ORGANS OF SPECIAL SENSE.
Authors: LEE WALLACE DEAN
Journal: JAMA (1903)

In treating this subject I have found that I am compelled to confine myself almost entirely to the eye. It presents to us such possibilities for exact investigation that the results secured overshadow those gained from a study of the other organs of special sense.  We have here blood vessels and a nerve with its end organ exposed to view. We can look on mesoblastic and epiblastic tissue. We can observe embryonic conditions if they exist. With the exception of the nervous system, more degenerate conditions are found in the eye than in any other part of the body. As most of the deleterious results of consanguinity are degenerative conditions, we ought to expect this to be a good field for research. You will readily observe that this paper is not a complete treatise on this subject. It has been almost impossible to find literature relating to it.
Uterine DCs are essential for pregnancy
Authors: Jeffrey W. Pollard
Journal: Journal of Clinical Investigation (2008)

Successful embryo implantation requires complex interactions between the uterus and embryo, including the establishment of maternal immunologic tolerance of fetal material. The maternal-fetal interface is dynamically populated by a wide variety of innate immune cells; however, the relevance of uterine DCs (uDCs) within the decidua to the success of implantation has remained unclear. In this issue of the JCI, Plaks et al. show, in a transgenic mouse model, that uDCs are essential for pregnancy, as their ablation results in a failure of decidualization, impaired implantation, and embryonic resorption (see the related article beginning on page 3954). Depletion of uDCs altered decidual angiogenesis, suggesting that uDCs contribute to successful implantation via their effects on decidual tissue remodeling, including angiogenesis, and independent of their anticipated role in the establishment of maternal-fetal tolerance.
Examining the Joint Effect of Multiple Risk Factors Using Exposure Risk Profiles: Lung Cancer in Nonsmokers
Authors: Michail Papathomas, John Molitor, Sylvia Richardson, Elio Riboli, Paolo Vineis
Journal: Environmental Health Perspectives (2010)

Profile regression is a Bayesian statistical approach designed for investigating the joint effect of multiple risk factors. It reduces dimensionality by using as its main unit of inference the exposure profiles of the subjects that is, the sequence of covariate values that correspond to each subject.We applied profile regression to a case-control study of lung cancer in nonsmokers, nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, to estimate the combined effect of environmental carcinogens and to explore possible gene-environment interactions.We tailored and extended the profile regression approach to the analysis of case-control studies, allowing for the analysis of ordinal data and the computation of posterior odds ratios. We compared and contrasted our results with those obtained using standard logistic regression and classification tree methods, including multifactor dimensionality reduction.Profile regression strengthened previous observations in other study populations on the role of air pollutants, particularly particulate matter ≤ 10 μm in aerodynamic diameter (PM10), in lung cancer for nonsmokers. Covariates including living on a main road, exposure to PM10 and nitrogen dioxide, and carrying out manual work characterized high-risk subject profiles. Such combinations of risk factors were consistent with a priori expectations. In contrast, other methods gave less interpretable results.We conclude that profile regression is a powerful tool for identifying risk profiles that express the joint effect of etiologically relevant variables in multifactorial diseases.
Abstract 358: Nf1 inactivation in NG2-cells is not sufficient for murine optic glioma formation.
Authors: Anne C. Solga, Scott M. Gianino, David H. Gutmann
Journal: Cancer Research (2013)

Abstract Individuals with the tumor predisposition syndrome, neurofibromatosis 1 (NF1), are prone to development of low-grade astrocytomas (gliomas). These tumors frequently include optic pathway gliomas predominantly arising in young children. We have previously developed several Nf1 genetically-engineered mouse (GEM) strains that form optic gliomas similar to those that occur in children with NF1. However, in the optic nerve, there are two types of potential neuroglial progenitors, GFAP+ and NG2+ cells. This latter population has been shown to represent a potential cell of origin for rat malignant gliomas, suggesting that NG2+ progenitors may represent the initiating cell for Nf1 optic glioma. In this study, we employed a complementary series of in vitro and in vivo approaches to determine whether NG2+ cells could give rise to Nf1 optic glioma. First, we demonstrate that Nf1 loss in NG2+ cells does not increase glial cell proliferation in vitro. Second, NG2-Cre-expressing cells give rise to all three macroglial lineages (astrocytes, NG2+ cells, and oligodendrocytes) in vivo, similar to GFAP-Cre-expressing cells that drive Nf1 optic glioma formation. Third, in striking contrast to the GFAP-Cre strain, Nf1 loss in NG2+ progenitor cells in vivo is insufficient for optic gliomagenesis. Together, these data exclude NG2+ cells as the likely cell of origin for NF1-associated optic glioma and establish a model of gliomagenesis in which Nf1 loss occurs in specific neuroglial progenitors during embryonic development. Citation Format: Anne C. Solga, Scott M. Gianino, David H. Gutmann. Nf1 inactivation in NG2-cells is not sufficient for murine optic glioma formation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 358. doi:10.1158/1538-7445.AM2013-358
Corot's 'Gout' and a 'Gipsy' Girl
Authors: Rachel B. Panush
Journal: JAMA (1990)

Representations of rheumatic disease in art provide insight into artistic expression, help us understand the evolution and perhaps the etiology of rheumatic diseases, and remind us of great contributions by artists in adverse circumstances. We noted hand deformities characteristic of inflammatory arthritis in Jean-Baptiste-Camille Corot's<i>Gipsy Girl With Mandolin</i>(1870 to 1875), National Gallery of Art, Washington, DC. Corot suffered with what probably was gout beginning in 1866. We are unaware that arthritis has been observed in Corot's subjects or that Corot's depiction of arthritis has been appreciated from the perspective of his own rheumatic disease. Examination of other Corot portraits identifies some with blurred hand details consistent with the artist's style and the remainder with normal hands. These observations suggest that the artist portrayed specific anatomic abnormalities in the "Gipsy Girl's" hand, indicating familiarity with inflammatory arthritis. It is speculative whether this was Corot's own or the model's arthritis; we favor the interpretation that Corot's gout was reflected in this particular work. We thus add a new perspective to Corot's<i>Gipsy Girl With Mandolin</i>—a subject with arthritis, a painter knowledgeable about arthritis, and a painting that therefore might be understood at least in part from an appreciation of the artist's specific illness. (<i>JAMA</i>. 1990;264:1136-1138)
Use of drugs by children.
Authors: G. W. Rylance, C. G. Woods, R. E. Cullen, M. E. Rylance
Journal: BMJ (1988)

To obtain information on the use of prescribed and non-prescribed drugs in the general population of children 1590 children were surveyed in 1984-5 by weekly questionnaires filled out by parents. Drugs were taken in 13% of the 26 weeks studied and on 9% of the 182 days. Use in the summer and winter was similar. More than half (56%) of all drugs were taken on Saturdays and Sundays. Boys took drugs on 11% of days and girls on 8% of days. Almost half (45%) of drugs taken were not prescribed. Drugs acting on the respiratory tract and on coughs accounted for 42.2% of the drugs used. Analgesics were taken on 14.0% of days and antimicrobials on 12.5%. Aspirin accounted for 14.9% of all drugs used in any one week and for 31.7% of drugs obtained without prescription. Aspirin, paracetamol, triprolidine-pseudoephedrine (Actifed), ampicillin or amoxycillin, and salbutamol were the drugs most frequently used. The widespread use of drugs obtained without prescription suggests that community pharmacists and parents would benefit from further education on the choice of treatment in relation to symptoms. Doctors should be aware of the extent of treatment with non-prescription drugs and consider playing a greater part in advising on its indications.
Imaging of Head and Neck Tumors with Technetium(V)-99m DMSA A New Tumor-Seeking Agent
Authors: HITOYA OHTA, KEIGO ENDO, TORU FUJITA, TETSUO NAKASHIMA, HARUMI SAKAHARA, KANJI TORIZUKA, YASUTOMO SHIMIZU, YASUO ISHII, KAZUO MAKIMOTO, NAOTAKA HATA, KAZUKO HORIUCH, AKIRA YOKOYAMA, MASAO ISHII
Journal: Clinical Nuclear Medicine (1985)

Tumor scintigraphy, using Tc(V)-99m DMSA was performed on 76 patients with head and neck tumors. In 32 cases, SPECT also was performed. Tc(V)-99m DMSA was found to have a sensitivity of 75% (56 cases), a specificity of 85% (20 cases) and an accuracy of 78% on planar imaging. ECT studies showed accumulation of Tc(V)-99m DMSA in all 25 malignant cases studied. However, in benign tumors, four of seven cases (57%) showed radionuclide uptake. Tc(V)-99m DMSA has superior physical properties to Ga-67 and could be of use in the diagnosis of head and neck tumors.
LABORATORY AS AID IN CONTAGIOUS DISEASE ADMISSIONS IN CANTONMENT HOSPITALS
Authors: A. B. MORRILL
Journal: JAMA (1918)

Early last winter it was found at Camp Grant that the receiving officer, who admitted all patients, could not give time for the necessary examination of contagious cases, and measles and scarlet fever patients were occasionally put into clean wards, tying up these wards for long periods of time with quarantine regulations. For this reason the contagious disease department took over the admission of all contagious cases. All patients were stripped to the waist and examined. In the definite cases, patients were sent to the proper wards, and in doubtful cases to the observation wards. Difficulty soon developed in properly grouping the following types of cases: (1) infections in the incubation period of a second infection; (2) double infections, in which, for instance, a measles eruption masked a scarlet fever efflorescence; (3) cases that were apparently one infection but in reality were another. It was found that the leukocyte count
Erratum: Corrigendum: The gene encoding phosphodiesterase 4D confers risk of ischemic stroke
Authors: S Gretarsdottir, G Thorleifsson, S Th Reynisdottir, A Manolescu, S Jonsdottir, T Jonsdottir, T Gudmundsdottir, S M Bjarnadottir, O B Einarsson, H M Gudjonsdottir, M Hawkins, G Gudmundsson, H Gudmundsdottir, H Andrason, A S Gudmundsdottir, M Sigurdardottir, T T Chou, J Nahmias, S Goss, S Sveinbjörnsdottir, E M Valdimarsson, F Jakobsson, U Agnarsson, V Gudnason, G Thorgeirsson, J Fingerle, M Gurney, D Gudbjartsson, M L Frigge, A Kong, K Stefansson, J R Gulcher
Journal: Nature Genetics (2005)