tbuckley/cabot-search huggingface dataset:
ADP-Ribosylarginine Hydrolase Regulates Cell Proliferation and Tumorigenesis
Authors: Jiro Kato, Jianfeng Zhu, Chengyu Liu, Mario Stylianou, Victoria Hoffmann, Martin J. Lizak, Connie G. Glasgow, Joel Moss
Journal: Cancer Research (2011)

Protein ADP-ribosylation is a reversible posttranslational modification of uncertain significance in cancer. In this study, we evaluated the consequences for cancer susceptibility in the mouse of a genetic deletion of the enzyme responsible for removing mono-ADP-ribose moieties from arginines in cellular proteins. Specifically, we analyzed cancer susceptibility in animals lacking the ADP-ribosylarginine hydrolase (ARH1) that cleaves the ADP ribose-protein bond. ARH1(-/-) cells or ARH1(-/-) cells overexpressing an inactive mutant ARH1 protein (ARH1(-/-)+dm) had higher proliferation rates than either wild-type ARH1(+/+) cells or ARH1(-/-) cells engineered to express the wild-type ARH1 enzyme. More significantly, ARH1(-/-) and ARH1(+/-) mice spontaneously developed lymphomas, adenocarcinomas, and metastases more frequently than wild-type ARH1(+/+) mice. In ARH1(+/-) mice, we documented in all arising tumors mutation of the remaining wild-type allele (or loss of heterozygosity), illustrating the strict correlation that existed between tumor formation and absence of ARH1 gene function. Our findings show that proper control of protein ADP-ribosylation levels affected by ARH1 is essential for cancer suppression.
Drug Reactions and Your Duty
Authors: NORMAN DE NOSAQUO
Journal: Annals of Internal Medicine (1966)

Editorials1 June 1966Drug Reactions and Your DutyNORMAN DE NOSAQUO, M.D.NORMAN DE NOSAQUO, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-64-6-1360 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe Registry on Adverse Reactions sponsored by the Council on Drugs of the American Medical Association serves the primary function of alerting the profession to the potential for harm by drugs and other chemicals. An article on p. 1325 of this issue describes the procedures used for the handling, evaluation, and distribution of information on drug-associated reactions. Physicians are advised of the findings of the Registry's consultant panels by means of tabulations and resumés of the reports received, the publication of cautionary statements and special articles in JAMA, and through direct replies to inquiries on specific problems.Chief among the... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Registry on Adverse Reactions Chicago, Ill. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1966Volume 64, Issue 6Page: 1360-1361KeywordsAdverse reactionsDrug distributionDrug informationDrugs Issue Published: 1 June 1966 PDF downloadLoading ...
986. In Vivo Production of Anti-HIV-1 Neutralizing Antibody from Rhesus Macaque Muscle Using a Recombinant Adeno-Associated Virus Vector
Authors: K. Reed Clark, Jianchao Zhang, David C. Montefiori, Philip R. Johnson
Journal: Molecular Therapy (2005)

To further potentiate HIV-1 vaccine strategies, we are developing a novel approach to provide protective host humoral immune responses against HIV-1, which to date have been difficult to elicit using conventional vaccine approaches. In concept, |[ldquo]|reverse immunization|[rdquo]| is predicated on the delivery antibody genes that code for pre-selected, broadly neutralizing HIV-1 antibodies. Following in vivo antibody gene transfer and expression from a source depot (such as skeletal muscle), the individual would be supplied with a constant source of potent anti-HIV-1 antibodies prior to pathogen exposure. Towards that goal, we report sustained circulating levels of the human anti-HIV-1 neutralizing single-chain (scFv) antibody X5 in two rhesus macaques following rAAV mediated delivery into skeletal muscle. X5 recognizes a conserved, discontinous CD4 binding induced (CD4i) epitope on the gp160 surface and has been shown to possess potent in vitro neutralization activity against multiple primary HIV-1 isolates. X5 scFv gene expression was mediated by a self-complementary, rAAV1 vector at a dose of 3.5|[times]|1013 DRP per animal. Animals were bled at 0, 2, 4, 6, 8, 10, and 12 weeks post-injection and levels of human X5 in sera determined by a HIV-1 gp120/sCD4 binding ELISA. Both animals had peak serum concentrations at 4 weeks (3-5 ug/ml) that leveled off to 0.5-1 ug/ml by the 12 week timepoint. One animal appears to have produced low levels of anti-X5 antibodies by 6 weeks post-injection based on the animal's serum reactivity to purified X5 (western strip blot). Significantly, both animal's sera, at multiple timepoints, possessed robust in vitro neutralization activity (titers ranged between 1:500 |[ndash]| 1:1,400) against a CD4 independent HIV-1 isolate (NL-ADArs), which is consistent with the CD4i binding properties of X5. We are currently evaluating whether expression of the human X5 scFv induced an antigen specific cellular immune response in the non-human primates. These proof-of-concept data suggest that antibody gene transfer may be a powerful vaccination strategy to provide individuals with protective humoral immune responses against HIV-1 prior to virus exposure.
A systematic analysis of global anemia burden from 1990 to 2010
Authors: Nicholas J. Kassebaum, Rashmi Jasrasaria, Mohsen Naghavi, Sarah K. Wulf, Nicole Johns, Rafael Lozano, Mathilda Regan, David Weatherall, David P. Chou, Thomas P. Eisele, Seth R. Flaxman, Rachel L. Pullan, Simon J. Brooker, Christopher J. L. Murray
Journal: Blood (2013)
Value of Detection of Formiminoglutamic Acid in Urine for the Diagnosis of Malabsorption States
Authors: D. P. Rose
Journal: BMJ (1965)

Aplastic Anaemia-Lewis BDICALJOURNAL 1031 with acquired aplastic anaemia.Since then three other adult patients apparently suffering from aplastic anaemia have developed P.N.H.: in two the P.N.H. defect became severe and dominated the picture, while the fourth patient had a mild P.N.H. defect and died while the aplastic phase was still dominant.These cases have not been included in the series analysed above, although in their initial presentation they were indistinguishable from acquired aplastic anaemia.They are recorded here to draw attention to the fact that the possibility of the development of P.N.H. should perhaps be considered when the prognosis in aplastic anaemia is assessed.Summary In a 12-year period 60 patients suffering from chronic acquired aplastic anaemia have been investigated.In some cases the disease has run an acute course with death in weeks.Half the patients died within 15 months of onset.Eighteen are still alive but only six are in full remission, while another three are in partial remission with normal haemoglobin, with or without neutropenia, but with persistence of'thrombocytopenia.Invariably platelets have been the last component to return to normal, usually after a prolonged period.Both sexes were equally affected, but the outlook may be more serious in patients over the age of 40 ; it was especially grave in a group of 16 patients who had profound neutropenia (fewer than 100/c.mm.) and severe thrombocytopenia (fewer than 20,000/c.mm.), but on the whole neutropenia did not materially affect prognosis to the same extent as did thrombo- cytopenia; death was usually due to haemorrhage rather than infection.In 22 cases bone-marrow aspiration showed normal or hyperplastic foci, but prognosis was little affected by this.Evaluation of treatment is difficult, as spontaneous remissions may occur, but testosterone and corticosteroids in moderate doses can induce remissions in children near puberty.In adults prognosis and median survival seemed little influenced.Fresh blood or platelet transfusions were valuable during haemor- rhagic episodes.Splenectomy was carried out in four patients with equivocal results.I wish to thank Professor J. V. Dacie for his guidance and encouragement, and the physicians of Hammersmith
A Remarkable Lesion of the Nerve-Centres in Leucocythaemia
Authors: B. Bramwell
Journal: BMJ (1886)

PHYSICIANS have long been familiar with the fact that haemorrhage into the substance, or on to the surface, of the brain, may occur in the cQurse9f splenic leucocythaemia ; and pathologists have shown that in tbt disease the capillary blood-vessels of the viscera (liver, kidneys, die.), are often enormously dilated snd distended with white blobd- oorpuscles; but, so far as I have been able to ascertain, no case has hitherto been reported in which such a remarkable lesion of the nerve- cqnures, as was present in this case, has been demonstrated.My old master, the late Professor Hughes ~Bennett, tdWd, it is true, in his onal account of the disease, describe and figure a dilated and ds- d condition of the blood-vessels and capilaris of the pia mater.
IMMUNOGLOBULINS ON THE SURFACE OF LYMPHOCYTES
Authors: Emil R. Unanue, Howard M. Grey, Enrique Rabellino, Priscilla Campbell, Jon Schmidtke
Journal: The Journal of Experimental Medicine (1971)

Immunofluorescent studies using live cells from antibody-forming organs and anti-immunoglobulin antibodies demonstrate two populations of small lymphocytes which are differentiated by the presence or absence of Ig on their surface membranes. Most of the lymphocytes with detectable surface Ig appear to derive from cells of the bone marrow, while most of the Ig-negative lymphocytes derive from the thymus. Thus, adult mice thymectomized, lethally irradiated, and transplanted with bone marrow cells showed a normal number of lymphocytes with surface Ig but were depleted of the Ig-negative lymphocytes. Injection of thymocytes into these mice did not result in an increase in the number of lymphocytes with surface Ig in spleen and lymph nodes. Most of the injected thymocytes could be identified by means of histocompatibility markers. Also, the spleen and lymph nodes of neonatally thymectomized mice contained lymphocytes with surface Ig but were depleted of the Ig-negative lymphocytes. Attempts were made to identify light chains on thymocytes by a sensitive radioimmunoassay. In some experiments no light chains were detected and in others a small amount, i.e. no more than 2.6% of the amount present on spleen lymphocytes, could be detected. Whether these low figures are significant or represent a small amount of serum contamination is not clear as yet.
Abstract 2077: Interactions between sulfiredoxin, S100A4 and non-muscle myosin IIA regulate cancer cell adhesion and motility
Authors: Robert R. Bowers, Yefim Manevich, Danyelle M. Townsend, Kenneth D. Tew
Journal: Cancer Research (2011)

Abstract Sulfiredoxin (Srx) is an antioxidant protein that reduces over-oxidized catalytic cysteine residues of peroxiredoxins I-IV and catalyzes reduction of some S-glutathionylated proteins. We previously showed that Srx plays a role in cell migration and interacts with non-muscle myosin IIA (NM IIA; Bowers et al AACR 2010). The purpose of the present study was to extend our knowledge of the effect of Srx on cell adhesion and migration. Immunoprecipitation of Srx from non-small lung cancer (A549 cells) revealed a number of Srx-interacting proteins including NM IIA and S100A4. NM IIA plays a central role in the control of cell adhesion and migration, and S100A4 is a key regulator of NM IIA activity that is linked to cancer metastases. Adhesion assays showed that A549 cells over-expressing Srx have reduced adhesion to fibronectin-coated dishes and decreased levels of Tyr397-phosphorylated focal adhesion kinase (p-FAK). Conversely, Srx knockdown by shRNA increased A549 cell adhesion to fibronectin and p-FAK levels. Srx over-expression in A549 cells increased actin stress fiber formation and altered focal adhesion formation. Depletion of Srx in A549 cells resulted in decreased actin stress fiber formation and also altered sites of cell:extracellular matrix adhesion. In silico molecular modeling of an Srx-S100A4 homodimer complex showed close proximity (∼13Å) of the single Cys99 of Srx to the Cys85 of S100A4. The calculated binding constant for the Srx-S100A4 interaction indicated reasonable affinity (KD∼ 62 nM). This affinity was not dependent upon disulfide bonding, since mutation of Srx residue Cys99 to Ser resulted in increased affinity (KD ∼22 nM). In vitro S-glutathionylation of Cys85 of S100A4 markedly increased its affinity to Srx (KD∼4 nM), but had no effect with the inactive Srx C99S mutant. Srx over-expression produced a doubling of the basal cellular level of free Ca2+ suggesting that the protein:protein interactions altered the capacity of S100A4 to bind Ca2+. Our data show that Srx may play important role in S100A4-mediated cancer cell cytoskeletal remodeling and motility and could potentially be a target for development of specific anticancer therapies. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2077. doi:10.1158/1538-7445.AM2011-2077
Xenoandrogenic Activity in Serum Differs across European and Inuit Populations
Authors: Tanja Krüger, Philip S. Hjelmborg, Bo A.G. Jönsson, Lars Hagmar, Aleksander Giwercman, Gian-Carlo Manicardi, Davide Bizzaro, Marcello Spanò, Anna Rignell-Hydbom, Henning S. Pedersen, Gunnar Toft, Jens Peter Bonde, Eva C. Bonefeld-Jørgensen
Journal: Environmental Health Perspectives (2007)

Animal and in vitro studies have indicated that human male reproductive disorders can arise as a result of disrupted androgen receptor (AR) signalling by persistent organic pollutants (POPs). Our aim in the present study was to compare serum xenoandrogenic activity between study groups with different POP exposures and to evaluate correlations to the POP proxy markers 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE).We determined xenoandrogenic activity in the serum fraction containing the lipophilic POPs but free of endogenous hormones. Adult male serum (n = 261) from Greenland, Sweden, Warsaw (Poland), and Kharkiv (Ukraine) was analyzed. Xenoandrogenic activity was determined as the effect of serum extract alone (XAR) and in the presence of the synthetic AR agonist R1881 (XARcomp) on AR transactivated luciferase activity.The study groups differed significantly with respect to XARcomp activity, which was increased in the Inuits and decreased in the European study groups; we observed no difference for XAR activity. We found the highest level of the AR antagonist p,p'-DDE in Kharkiv, and accordingly, this study group showed the highest percent of serum samples with decreased XARcomp activities. Furthermore, the percentage of serum samples with decreased XARcomp activities followed the p,p'-DDE serum level for the European study groups. No correlations between serum XAR or XARcomp activities and the two POP markers were revealed.The differences in XARcomp serum activity between the study groups suggest differences in chemical exposure profiles, genetics, and/or lifestyle factors.
Abiodun (“Abi”) Akande (née Alonge)
Authors: J O Ajala
Journal: BMJ (2006)

​GeneralGeneral practitioner Greater Manchester (b 1971; q University College Hospital Ibadan, Nigeria, 1998), died from complications of chemotherapy on 1 September 2006.



Figure 1



Shortly after qualifying, Abiodun Akande (“Abi”) came to the United Kingdom for postgraduate training. After completing house jobs in 1999, she became a general practitioner in Greater Manchester in 2005. Her career as a general practitioner was short but she considered it more a vocation than a job. Her Christian faith and love for her family were the bedrock of her life. Abi was in complete remission after treatment for acute leukaemia. She developed complications from chemotherapy while undergoing stem cell harvesting. She leaves a husband and two children.
Implementation of a Composite Score System for Evaluation of Circulating Tumor Cells in Blood of Breast Cancer Patients.
Authors: A. de Albuquerque, S. Kaul, G. Breier, P. Krabisch, N. Stryzhevska, G. Bastert, N. Fersis
Journal: Cancer Research (2009)

Abstract Background: We present a highly specific immunomagnetic separation technique in combination with an improved multimarker gene panel for molecular identification and characterization of circulating breast tumor cells in blood. Here we describe the creation of a new composite score in order to manage results and avoid false positives. Methods: Blood from breast cancer patients with primary or metastatic disease was drawn into two 10mL EDTA-tubes. The high affinity antibodies BM7 (MUC1) and VU1D9 (EpCAM) were used for immunomagnetic tumor cell enrichment. Separated cells were lysed and used for mRNA isolation and c-DNA synthesis (Qiagen®). A real-time quantitative RT-PCR approach using MESA FAST SYBR Assay (Eurogentec®) and primers selected from the UniversalProbeLibrary system (Roche AG®) for the epithelial markers cytokeratin 19 (CK19), mammaglobin 1 (MG1), epithelial cell adhesion molecule (EpCAM), baculoviral IAP repeat-containing 5 (Sur), immunosuppressive CD276 (CD276), carcinoembryonic antigen-related cell adhesion molecule 5 (CEA), HER-2, aldehyde dehydrogenase 1 family, member A1 (ALDH1), hypoxia inducible factor (HIF-1alpha) and CD44 molecule (CD44) was used for tumor cell identification and characterization. The ß-actin transcript was used for internal control and matched calibrator probes containing 2 or 10 tumor cells were used for quantitative expression analysis of tumor associated genes present in blood.Results: Positivity rate was based on a score that consists of 2 different characteristics: Marker detection (ranking according to the number of positive markers, varies from 0 – negative - to 1 – positive - for each marker) in combination with the marker expression level (ranking according to the C(t) values and varies from 0 – less then 2 tumor cells – to 1 – more then 2 tumor cells). This composite score is based on the expression of CK19, MG1, EpCAM, Sur and CD276 and has a ranking from 0 to 10. Negative cases are classified with score 0 and 1, cases ranked with score 2 need retesting and finally scores above 2 indicate clearly positive patients. The additional surrogate markers CEA, HER-2, ALDH, HIF and CD44 are analysed in positive patients in order to obtain further information. In our group of metastatic breast cancer patients, 53% were classified as positive, 42% of the patients were negative and in 5% a retesting is needed. Conclusion: The results of the composite score clearly show an increase of sensitivity and specificity for this assay. The implementation of this test in the routine monitoring of patients should help us to evaluate treatment response and create individualized treatment schedules. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3015.
Treatment of Graves' Ophthalmopathy
Authors: Robert D. Utiger
Journal: New England Journal of Medicine (1989)

This week's Journal contains reports of two prospective studies that provide new information concerning not only the treatment but also the natural history of Graves' ophthalmopathy.1 , 2 Ophthalmopathy is but one of the several seemingly unrelated and mysterious components of Graves' disease. The others are hyperthyroidism, localized myxedema, and thyroid acropachy.Nearly all patients with Graves' disease have hyperthyroidism at some time. The clinical manifestations of hyperthyroidism are well known, its presence can be confirmed readily by measurements of serum thyroxine and thyrotropin, and it can be treated effectively. Likewise, nearly all patients with Graves' disease have some ophthalmopathy — that . . .
Health promotion in general practice. It's useful in those at high risk.
Authors: P J Taylor
Journal: BMJ (1993)

be fully funded and must therefore address only the most limited and primitive expectations of both the patients and the professionals.The persistent clinical poverty of most NHS general practice cannot be cured or palliated by bolting on such token luxuries as well person clinics.Unless the BMA finds the courage and imagination to insist on resources for a labour intensive rather than a technology intensive public service, aiming at comprehensive anticipatory care for our whole population, even the best practices will continue to report failure.
The Treatment of Raoul Dufy's Arthritis
Authors: F. Homburger, Charles D. Bonner
Journal: New England Journal of Medicine (1979)

The medical story of Raoul Dufy represents one of those rare instances in which a medical advance is made at exactly the right time to salvage creative functioning in an important person and thereby enrich our heritage. For this and many other reasons we believe that Raoul Dufy's medical history should be published. One of the early patients treated for rheumatoid arthritis with adrenocorticotropic pituitary hormone (ACTH) and cortisone, Dufy had many of the complications that later deterred physicians from using these effective and powerful therapeutic agents. The benefits of the treatment were measurable through the quality and the amount . . .
Defibrillation efficacy. Comparison of defibrillation threshold versus dose-response curve determination.
Authors: D L Jones, W D Irish, G J Klein
Journal: Circulation Research (1991)

When an automatic defibrillator is implanted, it is essential to determine the efficacy of the defibrillating system accurately, while balancing the need to keep the number of fibrillation episodes to a minimum. Two methods have evolved to assess defibrillation efficacy: 1) the "defibrillation threshold," which requires few ventricular fibrillation episodes, and 2) the "dose-response curve," which requires many ventricular fibrillation episodes and relates percent success to energy. The purpose of this study was to compare these two methods directly. Twenty open-chest anesthetized pigs had triplicate defibrillation threshold determinations. To produce a dose-response curve, six shocks then were delivered at 0.5, 0.75, 1.0, 1.25, 1.5, and 2.0 times the mean defibrillation threshold, in a balanced randomized order, during separate episodes of ventricular fibrillation. The data were fitted by logistic regression, conversions of the logistic regression, and a saturable exponential and nonsaturable growth exponential. A comparison was made of the mean defibrillation threshold and the 50% point on the dose-response curve (ED50) for each model, for each animal. In addition, the reliability of each measure was assessed by comparing the coefficients of variation. There was no statistical difference between the group defibrillation threshold (6.6 +/- 0.5 J) and group ED50 values (ED50 range of the models, 5.7 +/- 1.9 to 7.0 +/- 0.9 J). However, the variability about the defibrillation threshold was less than that of the ED50 values for all mathematical models except the true logistic equation, which was virtually the same.(ABSTRACT TRUNCATED AT 250 WORDS)