tbuckley/cabot-search huggingface dataset:
Claudin-low breast cancers: clinical, pathological, molecular and prognostic characterization
Authors: Renaud Sabatier, Pascal Finetti, Arnaud Guille, José Adelaide, Max Chaffanet, Patrice Viens, Daniel Birnbaum, François Bertucci
Journal: Molecular Cancer (2014)

The lastly identified claudin-low (CL) subtype of breast cancer (BC) remains poorly described as compared to the other molecular subtypes. We provide a comprehensive characterization of the largest series of CL samples reported so far. From a data set of 5447 invasive BC profiled using DNA microarrays, we identified 673 CL samples (12,4%) that we describe comparatively to the other molecular subtypes at several levels: clinicopathological, genomic, transcriptional, survival, and response to chemotherapy. CL samples display profiles different from other subtypes. For example, they differ from basal tumors regarding the hormone receptor status, with a lower frequency of triple negative (TN) tumors (52% vs 76% for basal cases). Like basal tumors, they show high genomic instability with many gains and losses. At the transcriptional level, CL tumors are the most undifferentiated tumors along the mammary epithelial hierarchy. Compared to basal tumors, they show enrichment for epithelial-to-mesenchymal transition markers, immune response genes, and cancer stem cell–like features, and higher activity of estrogen receptor (ER), progesterone receptor (PR), EGFR, SRC and TGFβ pathways, but lower activity of MYC and PI3K pathways. The 5-year disease-free survival of CL cases (67%) and the rate of pathological complete response (pCR) to primary chemotherapy (32%) are close to those of poor-prognosis and good responder subtypes (basal and ERBB2-enriched). However, the prognostic features of CL tumors are closer to those observed in the whole BC series and in the luminal A subtype, including proliferation-related gene expression signatures (GES). Immunity-related GES valuable in basal breast cancers are not significant in CL tumors. By contrast, the GES predictive for pCR in CL tumors resemble more to those of basal and HER2-enriched tumors than to those of luminal A tumors. Many differences exist between CL and the other subtypes, notably basal. An unexpected finding concerns the relatively high numbers of ER-positive and non-TN tumors within CL subtype, suggesting a larger heterogeneity than in basal and luminal A subtypes.
A comparative case study of two models of a clinical informaticist service
Authors: T. Greenhalgh
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objectives:</b> To describe and evaluate two different models of a clinical informaticist service. <b>Design:</b> A case study approach, using various qualitative methods to illuminate the complexity of the project groups9 experiences. <b>Setting:</b> UK primary health care. <b>Interventions:</b> Two informaticist projects to provide evidence based answers to questions arising in clinical practice and thereby support high quality clinical decision making by practitioners. <b>Results:</b> The projects took contrasting and complementary approaches to establishing the service. One was based in an academic department of primary health care. The service was academically highly rigorous, remained true to its original proposal, included a prominent research component, and involved relatively little personal contact with practitioners. This group achieved the aim of providing general information and detailed guidance to others intending to set up a similar service. The other group was based in a service general practice and took a much more pragmatic, flexible, and facilitative approach. They achieved the aim of a credible, acceptable, and sustainable service that engaged local practitioners beyond the innovators and enthusiasts and secured continued funding. <b>Conclusion:</b> An informaticist service should be judged on at least two aspects of quality—an academic dimension (the technical quality of the evidence based answers) and a service dimension (the facilitation of questioning behaviour and implementation). This study suggests that, while the former may be best achieved within an academic environment, the latter requires a developmental approach in which pragmatic service considerations are addressed.
Validation of the first treatment-specific questionnaire for the assessment of patient satisfaction with allergen-specific immunotherapy in allergic patients: The ESPIA questionnaire
Authors: José Luis Justicia, Victoria Cardona, Pedro Guardia, Pedro Ojeda, José María Olaguíbel, José María Vega, Carmen Vidal, Eva Baró, Mario Alberto García
Journal: Journal of Allergy and Clinical Immunology (2013)
Subunit structure of factor VIII antigen synthesized by cultured human endothelial cells.
Authors: E A Jaffe, R L Nachman
Journal: Journal of Clinical Investigation (1975)

Cultured human endothelial cells were labeled with (3H)leucine, and the radioactive Factor VIII antigen present in the postculture medium was isolated by double anitbody immunoprecipitation and characterized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis after reduction with dithiothreitol. The Factor VIII antigen synthesized by cultured endothelial cells was found to contain the same single polypeptide subunit (mol wt 225,000) present in plasma Factor VIII antigen. These results suggest that in vivo, the endothelial cell is a major site of synthesis of circulating Factor VIII antigen.
Carbimazole in respiratory failure.
Authors: P F Jenkins, M S Knapp
Journal: BMJ (1979)

nutrition, by removing the arm, and by appropriate antibiotic treatment of septicaemia.Cellular and humoral immunity is improved by daily dialysis and feeding, and possibly humoral toxic factors due to a burn are removed across the artificial kidney membrane.5The close co-operation of all the units concerned and the mobile capability of the two RAF teams made the most comprehensive management possible.Despite the appalling prognosis in such cases, we believe that treatment should not be denied.
Evidence of a New Chimeric<i>bcr</i>/c-<i>abl</i>mRNA in Patients with Chronic Myelocytic Leukemia and the Philadelphia Chromosome
Authors: Kees Stam, Nora Heisterkamp, Gerard Grosveld, Annelies de Klein, Ram S. Verma, Morton Coleman, Harvey Dosik, John Groffen
Journal: New England Journal of Medicine (1985)

The hallmark of chronic myelocytic leukemia is the presence of the Philadelphia chromosome (Ph1). In recent studies, we obtained data that strongly suggested the involvement of an oncogene, c-abl, in this type of leukemia. This oncogene, normally located on chromosome 9, is translocated to chromosome 22 as a result of the Ph1 translocation. In addition, we identified a region on chromosome 22, the breakpoint cluster region (bcr), which contains the chromosomal breakpoint in all patients with chronic myelocytic leukemia who are positive for Ph1. Recent studies have suggested that the bcr is part of a gene that is truncated as a consequence of the Ph1 translocation. The deleted part of this gene could be replaced by c-abl sequences; to test this hypothesis we analyzed the RNA of five patients with chronic myelocytic leukemia. All five had chimeric bcr/c-abl messenger RNA, suggesting that the deleterious effects of this disease can be associated with an abnormal chimeric protein encoded by the bcr and the c-abl oncogene.
Hereditary Components in Epileptic Patients
Authors: Ernst Rodin
Journal: JAMA (1966)

The electroencephalograms of 80 families of epileptic patients were compared with those of 30 normal control families. Abnormal family EEGs were not only encountered in patients with centrencephalic seizures but also in patients with psychomotor epilepsy. One half of all patients with focal sharp wave or spike discharges were found to have another family member with an abnormal EEG. Abnormal family EEGs were more frequently encountered in female than in male patients. Mothers of epileptic patients had a significantly higher percentage of electroencephalographic abnormalities than fathers, regardless of the type of seizure the patient was experiencing. Patients whose seizures started between the ages of 6 and 15 years usually had a genetic component to their illness, as demonstrated by electroencephalographic abnormalities in one parent and at least one sibling.
Better science not less science
Authors: K Norcross
Journal: BMJ (1983)

Objective  Study participants can differ from the target population they are taken to represent. We sought to investigate whether older age magnifies such differences, examining age-trends, among study participants, in self-rated level of activity compared to others of the same age.  Design  Cross-sectional examination of the relation of participant age to reported ‘relative activity’ (ie, compared to others of the same age), a bidirectionally correlated proxy for relative vitality, in exemplars of randomised and observational studies.  Setting  University of California, San Diego (UCSD)  Participants  2404 adults aged 40–79 including employees of UCSD, and their partners (San Diego Population Study, observational study). 1016 adults (aged 20-85) not on lipid medications and without known heart disease, diabetes, cancer or HIV (UCSD Statin Study, randomised trial).  Measurements  Self-rated activity relative to others’ age, 5-point Likert Scale, was evaluated by age decade, and related via correlation and regression to a suite of health-relevant subjective and objective outcomes.  Results  Successively older participants reported successively greater activity relative to others of their age (greater departure from the norm for their age), p  Conclusions  Study participants may not be representative of the population they are intended to reflect. Our results suggest that departures from representativeness may be amplified with increasing age. Consequently, the older the age, the greater the disparity may be between what is recommended based on ‘evidence, ’ and what is best for the patient.  Trial Registration  UCSD Statin Study—Clinicaltrials.gov # NCT00330980 (http://ClinicalTrials.gov)
IFN-γ Regulation in Anti-CD4 Antibody–Induced T Cell Unresponsiveness
Authors: Birgit Sawitzki, Brit Kieselbach, Marion Fisser, Christian Meisel, Katrin Vogt, Matthias Gaestel, Manfred Lehmann, Kirsten Risch, Gerald Grütz, Hans-Dieter Volk
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. The anti-rat CD4 mAb RIB5/2 is very potent in inducing allospecific tolerance in vivo. It is interesting that the unresponsiveness is breakable by exogenous IL-2 applied during the induction phase of tolerance. The molecular mechanisms underlying anti-CD4 antibody–mediated inhibition of allospecific T cell activation and how this is antagonized by exogenous IL-2 were investigated. Anti-CD4 treatment, in vivo and in vitro, completely abrogated IL-2 production by alloreactive T cells. In contrast, anti-CD4–treated alloactivated T cells showed similar IFN-γ mRNA expression as untreated alloactivated T cells but did not secrete any protein. Thus, the anti-CD4 antibody cannot prevent IFN-γ mRNA expression but is interfering with posttranscriptional mechanisms that control IFN-γ production during alloactivation of T cells. Addition of IL-2 but not IL-15 to anti-CD4–treated alloactivated T cells restored IFN-γ protein production without leading to enhanced IFN-γ mRNA expression. Further investigations revealed a diminished activation of translation initiation factor eIF2α in anti-CD4–treated T cells, which was restored by exogenous IL-2. As activated eIF2α is essential for the translation of IFN-γ mRNA, the results may explain the reversibility of anti-CD4–induced unresponsiveness by exogenous IL-2. Furthermore, these results not only shed further light onto the molecular mechanisms of tolerance induction but also reveal the possible weaknesses of anti-CD4 antibody–induced unresponsiveness.
Textbook of Psychiatry
Authors: Thomas A. Loftus
Journal: JAMA (1964)

This is really two books in one. Part I with 262 pages is a lucid account of the more common problems of psychiatry, with emphasis on the etiological role of disturbed growth and development. The frame of reference is largely Freudian, although the authors have not hesitated to add from their experience. Defense mechanisms are considered from the standpoints of both development and symptom formation. Problems of children are discussed and there is an interesting (although brief) aside on the recent advances in neurophysiological and neurochemical concepts of behavior. The common psychiatric disorders are reviewed, following the standard APA classification with emendations for treatment from the authors' experience. Techniques of examination are not elaborated upon. Although Part I is eminently practical and well recommended for both medical students and the practitioner—it is in the section on social psychiatry (Part II, pp 265-368) that the book really distinguishes itself. This section
Biphasic forearm vascular responses to intraarterial arginine vasopressin.
Authors: S Suzuki, A Takeshita, T Imaizumi, Y Hirooka, M Yoshida, S Ando, M Nakamura
Journal: Journal of Clinical Investigation (1989)

Forearm vascular responses to arginine vasopressin (AVP) infused into a brachial artery in a wide range of infusion rates (0.05-2.0 ng/kg per min) were examined in 20 young healthy volunteers. Intraarterial AVP at lower doses (0.05 and 0.1 ng/kg per min) caused forearm vasoconstriction, whereas AVP at a dose of 0.2 ng/kg per min or higher caused forearm vasodilatation. The maximal forearm vasoconstriction was induced at the venous plasma AVP level of 76.3 +/- 8.8 pg/ml. Forearm vasodilatation was associated with the venous plasma AVP level of 369 +/- 43 pg/ml or higher. Forearm vasodilatation was the result of the direct effect of AVP since forearm blood flow and vascular resistance in the contralateral arm did not change. We attempted to explore the mechanisms involved in AVP-induced direct vasodilatation. The treatment with indomethacin, 75 mg/d for 3 d, did not alter AVP-induced forearm vasodilatation. In contrast, intraarterial infusion of isoosmolar CaCl2 totally prevented AVP-induced forearm vasodilatation. Intra-arterial CaCl2 also markedly attenuated forearm vasodilatation induced by intraarterial sodium nitroprusside, but did not alter forearm vasodilatation induced by intraarterial isoproterenol. These results indicate that the direct vascular effects of intra-arterial AVP on the forearm vessels are biphasic, causing vasoconstriction at lower doses and vasodilatation at higher doses. The direct vasodilatation induced by intraarterial AVP at higher doses is not mediated by prostaglandins but may involve cGMP-related mechanisms.
L'échoendoscopie peut-elle se substituer à la radiologie interventionnelle dans le traitement des hémorragies digestives d'origine artérielle ou veineuse?
Authors: C Giacino, S Ezzedine, S Brardjanian, JM Gonzales, P Ah-Soune, M Gasmi, V Vitton, JC Grimaud, M Barthet
Journal: Endoscopy (2010)

Introduction: La prise en charge des hémorragies digestives en cas d'impossibilité ou d'échec du traitement endoscopique conventionnel requiert habituellement un abord vasculaire chirurgical ou radiologique sans délai. Très récemment, le développement de l'échoendoscopie couplée au doppler a amené de nouvelles possibilités thérapeutiques par sclérose et embolisation vasculaire écho-guidée. De très rares cas isolés ont seulement été rapportés dans la littérature.
Effect of New Oral Antidiabetic Agent CS-045 on Glucose Tolerance and Insulin Secretion in Patients with NIDDM
Authors: Yasuhiko Iwamoto, Takeshi Kuzuya, Ayako Matsuda, Takuya Awata, Shinobu Kumakura, Gen Inooka, Ikuo Shiraishi
Journal: Diabetes Care (1991)

Objective To study the effects of CS-045, a newly developed thiazolidine analogue, on glucose tolerance and insulin response to oral glucose load in patients with non-insulin-dependent diabetes mellitus (NIDDM). Research Design and Methods Nineteen NIDDM patients (mean ± SD age 48.9 ± 9.4 yr) whose previous glycemic control on diet and/or sulfonylurea (SU) therapy was judged stable but unsatisfactory (&amp;gt; 7.8 mM) were selected for this study. CS-045 (400 mg/day p.o.) was given alone or together with the previous SU drugs for 12 wk. A 75-g oral glucose tolerance test (OGTT) was performed before and after CS-045 treatment. Results The following results were found after CS-045 treatment. 1) Fasting plasma glucose (FPG) and HbA1c decreased (n = 19, FPG, 11.0 ± 2.4 vs. 8.4 ± 2.7 mM [before vs. after], P &amp;lt; 0.001; HbA1c, 8.0 ± 1.1 vs. 7.4 ± 1.3%, P &amp;lt; 0.005), and glucose tolerance markedly improved. 2) Fasting insulin (immunoreactive insulin [IRI]) and insulin response during OGTT decreased (n = 19, fasting IRI, 77.4 ± 49.8 vs. 56.5 ± 24.6 pM [before vs. after], P &amp;lt; 0.05; area under the curve of IRI, 540.3 ± 350.5 vs. 426.4 ± 216.3 pM.h, P &amp;lt; 0.05). Conclusions CS-045 is effective in improving glucose tolerance without stimulation of insulin secretion in NIDDM, suggesting an effect in improving insulin sensitivity.
SERUM TOXICITY IN VARIOUS PSYCHIATRIC DISORDERS
Authors: JOSEPH WORTIS
Journal: American Journal of Psychiatry (1959)

The serum of schizophrenic, alcoholic, and mongoloid patients had no inhibiting effect on the respiratory activity of surviving rat brain. The serum of patients treated with chlorpromazine enhanced the respiratory activity. A slight tendency to elevated values found in recently admitted schizophrenic adults who were not taking chlorpromazine may be due to prior medication before admission. Phenylketonuric serum depressed brain oxidations, though a similar effect was induced by racemic phenylalanine in concentrations above 40 mg.% as well as by other essential amino acids. It has been suggested that the depressant action of various amino acids may be due not to a direct effect of the amino acids, but to aldehyde formation. It has also been known for a long time that a number of toxic amines such as tyramine, phenylethylamine, mescalin, indole and skatol, all inhibit brain oxidations. The observed phenomenon may explain the general depression of brain oxidations found in vivo in phenylketonuria by Himwich and Fazekas. The low cerebral matabolic rate found in mongoloid children in vivo by these authors may be due to the brain pathology associated with the condition.
Under the Influence: A History of Nitrous Oxide and Oxygen Anaesthesia
Authors: Deryck Duncalf
Journal: JAMA (1983)

This book is essentially a compilation of articles by the author, originally published over the years since 1965 in the<i>British Journal of Anaesthesia</i>. A preface summarizes both the highlights and the author's own personal experience with nitrous oxide including autoexperimentation. The opening chapter is about Joseph Priestley and his discovery of oxygen. Here we are treated to a glimpse into the life of a one-time 18th-century minister and later tutor—always a well-to-do gentleman and scholar. The chapters continue in the same intimate style through Sir Humphrey Davy's researches in relation to inhalation anesthesia and go on to the gradual acceptance of nitrous oxide anesthesia in Great Britain, its manufacture and storage, ending with experience in ambulatory patients. The text is interspersed with quotes from contemporary writings along with the author's interpretations of the events described. The end result is a colorful, fascinating exposé of the history of the most
ω-3 vs. ω-6 lipid emulsions exert differential influence on neutrophils in septic shock patients: impact on plasma fatty acids and lipid mediator generation
Authors: Konstantin Mayer, Christine Fegbeutel, Katja Hattar, Ulf Sibelius, Hans-Joachim Krämer, Kai-Uwe Heuer, Bettina Temmesfeld-Wollbrück, Stephanie Gokorsch, Friedrich Grimminger, Werner Seeger
Journal: Intensive Care Medicine (2003)
Abstract 3428: Validation and utilization of next generation sequencing in the clinical assessment of gliomas
Authors: MacLean P. Nasrallah, Maria Martinez-Lage, Alan Fox, Shrey Sukhadia, Arati Desai, Donald M. O'Rourke, Steven Brem, David Roth, Jennifer J.D. Morrissette, Robert D. Daber
Journal: Cancer Research (2014)

Abstract Background. Identifying prognostic and potentially therapeutic genetic alterations in gliomas is crucial to improve clinical outcome and guide future targeted therapies in this devastating disease. Here, we establish the feasibility of next generation sequencing (NGS) profiling of glioma samples in a clinical setting. Methods. We optimized and validated a 47 gene panel for use on both fresh and Formalin Fixed Paraffin embedded (FFPE) tissue specimens in a CLIA-certified laboratory. Validation was performed in 27 samples by comparing mutation detection on two different NGS platforms, and we have since incorporated routine molecular tumor profiling into the standard workup of glioma patients seen at our institution. Results. From analysis of 120 clinical samples, we found disease-associated changes in 90 patients (75%). Overall 184 changes including disease-associated point mutations and variants of unclear significance were identified across 98 samples, resulting in an average of 1.85 mutations per sample and a range of 1- 6 mutations. This included 49 amplifications across several genes (EGFR, PDGFRA and KIT). Conclusions. The final validated assay allows for a cost effective and efficient analysis of a spectrum of clinically relevant and actionable biomarkers including point mutations, insertions, deletions and gene amplifications. Given the high fraction of tumors presenting with known disease associated changes, routine genomic profiling has the promise of improving patient outcomes and allow for access to targeted therapies. Citation Format: MacLean P. Nasrallah, Maria Martinez-Lage, Alan Fox, Shrey Sukhadia, Arati Desai, Donald M. O'Rourke, Steven Brem, David Roth, Jennifer J.D. Morrissette, Robert D. Daber. Validation and utilization of next generation sequencing in the clinical assessment of gliomas. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3428. doi:10.1158/1538-7445.AM2014-3428
Bacterial flora in psoriasis
Authors: RAZA ALY, HOWARD I. MAIBACH, ADRIAN MANDEL
Journal: British Journal of Dermatology (1976)

Journal Article Bacterial flora in psoriasis Get access RAZA ALY, RAZA ALY Department of Dermatology, University of California, San Francisco, CA 94143, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar HOWARD I. MAIBACH, HOWARD I. MAIBACH Department of Dermatology, University of California, San Francisco, CA 94143, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar ADRIAN MANDEL ADRIAN MANDEL Department of Dermatology, University of California, San Francisco, CA 94143, U.S.A. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 95, Issue 6, 1 December 1976, Pages 603–606, https://doi.org/10.1111/j.1365-2133.1976.tb07031.x Published: 01 December 1976