tbuckley/cabot-search huggingface dataset:
Abstract LB-003: Intracellular delivery of SOCS3 suppresses solid tumor progression
Authors: Seulmee Shin
Journal: Cancer Research (2019)

Abstract Introduction Suppressor of cytokine signaling 3 (SOCS3) functions as a negative-feedback regulator of JAK/STAT signaling that suppresses JAK kinase activity and promotes degradation of the activated cytokine receptor complex. Loss of SOCS3 enhances the growth and survival of some solid tumors; therefore, methods to replenish intracellular levels of the protein may provide an effective therapy against solid tumors dependent on JAK/STAT signaling for growth or survival. Objective The present study utilized advanced macromolecule transduction domain (aMTD) sequences to develop improved cell-permeable (iCP-) SOCS3 as a protein-based biotherapeutic against solid tumors including gastric-, colorectal, lung-, breast-cancer and glioblastoma. Methods Cell-permeable SOCS3 proteins, with (iCP-SOCS3) and without (Non-CP-SOCS3) a 12-amino acid aMTD sequence or containing an earlier generation of MTD based on the signal peptide of FGF4, termed membrane-translocating motif (MTM) were expressed and purified from E. coli. The proteins also contained a solubilization domain (SD) to enhance the solubility of the recombinant proteins in physiological buffers. The therapeutic potential of iCP-SOCS3 as anti-cancer agent for solid tumors was examined both in cultured cells and in human-mouse xenograft models. Results Compared to CP-SOCS3, iCP-SOCS3 fused to aMTD exhibited higher solubility and yield (25- and 300-folds higher, respectively) that are qualified to be developed for clinical use. Moreover, it exhibited cell-/tissue-permeability along with strong biological activity that was shown by significantly suppressed IFN-γ-induced phosphorylation of STAT1 and STAT3. In vitro study conducted with various cancer cell lines demonstrated that iCP-SOCS3 significantly suppresses cancer-associated phenotypes (e.g., &amp;gt;80% inhibition of proliferation in lung cancer and glioblastoma, &amp;gt;70% induction of apoptosis in gastric cancer, &amp;gt;65% inhibition of migration/invasion in gastric cancer) and induces changes in biomarker expression (e.g., p21, cleavage caspase-3 in breast cancer). In addition, iCP-SOCS3 significantly suppressed the tumor growth of human solid tumor xenografts (65% inhibition in gastric-, 79% in colorectal-, 69% in lung-, 63% in breast-cancer and 78% in glioblastoma CDXs, respectively). Conclusion In conclusion, these results provide further evidence that SOCS3 can function as a tumor suppressor and intracellular delivery of SOCS3 with iCP-SOCS3 may provide novel protein therapy against solid tumors. Citation Format: Seulmee Shin. Intracellular delivery of SOCS3 suppresses solid tumor progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-003.
Study indicates salt is an acquired taste
Authors: E. R. Gonzalez
Journal: JAMA (1983)

Which comes first to an infant born in this salt-loving culture? A taste<i>for</i>salt, or a taste<i>of</i>it? Probably the latter, according to David L. Yeung, PhD, who presented a report at the recent Chicago meeting of the Federation of American Societies for Experimental Biology: Children's taste for salt at the age of 4 years appears to be determined by the amount of salt their parents feed them in infancy. This finding is the most recent in a long-term, longitudinal study of nutrition in infants and children. The study, which has been under way since 1977, is sponsored by the H. J. Heinz Company of Canada, Ltd, Toronto—where Yeung, who is also associate professor of nutritional sciences at the University of Toronto Faculty of Medicine, serves as corporate nutrition coordinator. In the salt substudy, Yeung and colleagues first examined the sodium chloride intake of 403 infants, half of
Benign Bradycardia—A Pleasing Paradox
Journal: JAMA (1973)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Efficacy of combination tenofovir plus lamivudine versus tenofovir monotherapy in patients with chronic hepatitis B virus
Authors: F. Glyn, U. S. Gill, W. Alazawi, V. Ross, P. Kooner, R. Marley, G. R. Foster, P. T. F. Kennedy
Journal: Gut (2011)

<h3>Introduction</h3> Highly effective oral antivirals (OAV) have been licensed for use in Chronic Hepatitis B (CHB). Efficacy of Tenofovir (TDF) and Entecavir (ETV) monotherapy has been demonstrated in randomised controlled trials. However, there may be a role for de novo combination therapy to reduce the development of resistance. For this reason, the authors offer patients combination therapy with TDF and Lamivudine (LAM) irrespective of whether they are OAV-naïve or experienced. In this study the authors test the hypothesis that combination therapy is superior to TDF monotherapy as assessed by viral suppression and ALT normalisation. <h3>Methods</h3> A retrospective prospective study of 185 patients (male=135), from a single centre, was performed. Viral suppression, was defined as &lt;80 IU/ml and ALT normalisation &lt;40 IU/l. Our real life data was compared with a published meta-analysis on the use of all treatments for HBV, but which reports TDF as the most potent OAV.1 <h3>Results</h3> Median age of patients was 45 (range 18–81). 74% were eAg negative prior to starting TDF and LAM. Median ALT at baseline was 46 (range 12–1141). 86 patients were treatment naïve prior to commencing combination therapy. Of 99 patients previously exposed to OAV9s, 65 were partial responders and 34 virally suppressed when switching to TDF and LAM. 125/185 patients had completed 12 months and 84, 24 months of combination therapy. Overall viral suppression was recorded in 84% and 94% at 12 and 24 months respectively and ALT normalisation was seen in 67% and 74% at 12 and 24 months respectively. In the OAV-naïve group viral suppression was 81% compared with 84% in the OAV-experienced and ALT normalisation was 56% and 72% respectively in these groups at 12 months. In the published meta-analysis, viral suppression was 91% and ALT normalisation 67% at 12 months in a treatment naïve group. Comparing real life with published data showed no statistical significance for viral suppression and normalisation of ALT for combination versus monotherapy (p=0.12 and p=0.2 respectively). <h3>Conclusion</h3> These data highlight the efficacy of TDF in generating and sustaining viral suppression and ALT normalisation at 12 months and beyond. Combination OAV therapy versus TDF monotherapy does not show superiority. Furthermore, there is no reported resistance with TDF to date, but data are limited to 4-year follow-up. Given that OAV resistance may occur over many years, combination OAV may still have a role in the treatment of CHB, however larger randomised controlled trials are needed to determine this.
Psychoanalysis
Authors: George L. Engel
Journal: JAMA (1975)

ON THE occasion of Freud's death in 1939,The Journaleditorialized that "Psychoanalysis has become firmly established in psychology, education, and medicine."<sup>1</sup>Thirty-five years later,The Journalpublished a COMMENTARY by Jacob Conn entitled, "The Decline of Psychoanalysis."<sup>2</sup>Both express the wishes of their respective authors, for neither very accurately reflects the true state of affairs, not in 1939, not in 1974. By 1939 psychoanalysis had had considerable impact on psychology, relatively little on education other than in a popularized form, and virtually none at all on the mainstream of medicine, psychiatry included. It was not part of the educational experience of medical students, few analysts being members of medical school faculties in 1939. Nor did psychiatrists have any significant exposure to psychoanalysis as part of their formal education. In 1939 there were six psychoanalytic training institutes and the total membership of the American Psychoanalytic Association was less
President’s Message
Authors: Giovanni A. Fava, Nicoletta Sonino, Anna Bartak, Marieke D. Spreeuwenberg, Helene Andrea, Lot Holleman, Piet Rijnierse, Bert V. Rossum, Elisabeth F.M. Hamers, Anke M.M.A. Meerman, Janneke Aerts, Jan J.V. Busschbach, Roel Verheul, Theo Stijnen, Paul M.G. Emmelkamp, Peter Herschbach, Petra Berg, Sabine Waadt, Gabriele Duran, Ursula Engst-Hastreiter, Gerhard Henrich, Katrin Book, Andreas Dinkel, B. Metternich, D. Kosch, L. Kriston, M. Härter, M. Hüll, Yutaka Matsuoka, Daisuke Nishi, Naohiro Yonemoto, Satomi Nakajima, Yoshiharu Kim, Manfred E. Beutel, Franz Bleichner, Friedrich von Heymann, Karin Tritt, Jochen Hardt, Eric Bui, Lionel Cailhol, Jacques Puel, Philippe Birmes, Laurent Schmitt, Anna Ogliari, Kristian Tambs, Jennifer R. Harris, Simona Scaini, Cesare Maffei, Ted Reichborn-Kjennerud, Marco Battaglia, Luigi Grassi, Silvana Sabato, Elena Rossi, Luciana Marmai, Bruno Biancosino
Journal: Psychotherapy and Psychosomatics (2009)
Vascular reactivity in sepsis: importance of controls and role of nitric oxide.
Authors: A Yaghi, N A Paterson, D G McCormack
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

We have previously reported differential impairment of pulmonary and systemic vascular contractility in hyperdynamic sepsis. The objectives of this study were (1) to determine whether the magnitude of this phenomenon depends on the control group chosen for comparison, and (2) to examine the role of nitric oxide (NO) in this altered vascular contractility. Rats were randomized to sepsis induced by cecal ligation and perforation (CLP) or to one of two control procedures. The Sepsis group had a jugular venous line for fluid administration, laparotomy, and CLP. Control group 1 (Control) had only a jugular venous line inserted, while group 2 (Sham) had a jugular venous line inserted and an abdominal incision. All rats were killed 24 h after surgery. Vascular contractility of small pulmonary arterial and thoracic aortic rings was assessed in vitro by obtaining cumulative dose-response curves to the contractile agonists potassium chloride (KCl), phenylephrine (PE), and prostaglandin F2 alpha (PGF2 alpha). Pulmonary vessels from animals in the Sepsis and Sham groups exhibited significant attenuation of the contractile responses to KCl, PE, and PGF2 alpha compared with the Control group. In contrast, contractility of the aortic rings to KCl, PE, and PGF2 alpha was not significantly different in the three groups studied. Incubation of pulmonary and aortic vessels with NG-nitro-L-argine methyl ester (L-NAME, 10 microM) caused an increase in the response to KCl, PE, and PGF2 alpha in pulmonary vessels in Sepsis and Sham rats but not in Control rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Efficacy of eribulin in patients (pts) with metastatic breast cancer (MBC): A pooled analysis by HER2 and ER status.
Authors: Chris Twelves, Javier Cortes, Linda T. Vahdat, Martin S. Olivo, Yi He, Peter Andrew Kaufman, Ahmad Awada
Journal: Journal of Clinical Oncology (2014)

631^ Background: Eribulin (E) has been assessed in 2 phase 3, open-label trials in pts with locally recurrent or MBC progressing after an anthracycline (A) and taxane (T). E significantly increased overall survival (OS) compared with treatment of physician's choice (TPC) in 1 study and there was a non-significant trend for improved OS with E vs capecitabine (cape) in the other. We present an unplanned pooled analysis of these data. Methods: In the EMBRACE trial, women had received 2-5 lines of chemotherapy for advanced disease. In this ≥ third-line setting, pts were randomized 2:1 to E mesylate (1.4 mg/m2 iv on days 1 and 8 every 21 days) or TPC. In study 301, pts who had received 0–2 prior chemotherapies for advanced disease were randomized 1:1 to either E (as above) or cape (1.25 g/m2orally b.i.d. days 1–14 every 21 days). We analysed OS by 2-sided stratified log-rank tests and Cox regression in the overall intent-to-treat population and in the HER2–, triple negative (TNBC) and HER2+ subgroups. Results: In total 1,864 pts (median age 54 yrs) were included, most treated in the second (31.5%) or third-line (32.7%) MBC settings. Overall, E provided significantly improved OS vs control; this benefit was also significant in HER2− and TNBC, but not HER2+ pts (Table). E improved progression-free survival overall (4.0 vs 3.4 months, HR = 0.90, 95%CI = 0.81, 0.997, p = 0.046), in HER2– (3.7 vs 3.0 months, HR = 0.84, 95%CI = 0.74, 0.95, p = 0.006) and TNBC pts (2.8 vs 2.6 months, HR = 0.78, 95%CI = 0.63, 0.96, p= 0.018). As reported before, the E safety profile was similar in the studies. Conclusions: E significantly improved OS vs standard therapies in MBC pts with HER2− and TNBC in this pooled analysis; in pts with HER2+ disease the difference did not reach statistical significance but numbers were smaller. Clinical trial information: NCT00337103 and NCT00388726. Overall HER2− HER2+ TNBC E Con E Con E Con E Con n 1062 802 748 572 169 123 243 185 Median OSa, months 15.2 12.8 15.2 12.3 13.5 12.2 12.9 8.2 HR (95%CI)b 0.85 (0.77, 0.95) 0.82 (0.72, 0.93) 0.82 (0.62, 1.06) 0.74 (0.60, 0.92) pb 0.003 0.002 0.135 0.006 Abbreviations: Con, control; E, eribulin; HR, hazard ratio. aBased on survival curve adjusted by study. bStratified by geographic region, prior cape use and study (plus HER2 status for overall group only; plus TNBC for HER2– group only).
Autophagy gene polymorphisms influence the interaction of E coli and macrophages in Crohn's disease
Authors: T. Elliott, N. Prescott, B. Hudspith, N. Rayment, J. Hermon-Taylor, J. Brostoff, C. Mathew, J. D. Sanderson
Journal: Gut (2011)

<h3>Introduction</h3> A well established expression of the proposed defect in innate immunity in Crohn9s disease (CD) is the prolonged survival of strains of <i>Escherichia coli</i> in peripheral blood monocytes/macrophages (PBM) from patients with CD compared to those from healthy controls (HC). Altered handling of <i>E coli</i> in CD has been demonstrated in PBM and in-situ in CD by laser dissection of <i>E coli</i> infected macrophages. Several of the gene polymorphisms conferring an increased risk of CD occur in genes involved in bacteria-immune cell interactions. The aim of this study was to determine the influence of these polymorphisms on the interaction of <i>E coli</i> with CD-derived monocyte / macrophages. <h3>Methods</h3> PBM9s and lamina propria macrophages were obtained from 43 and 17 CD patients respectively (mean age 39 years / range 20–70 years). PBM9s were challenged with <i>E coli</i> and then the response of these PBM9s measured by levels of bacterial killing, using the gentamicin protection assay. Phagocytosis and reactive oxygen radicals (ROR9s) production were measured by flow cytometry using the phagotest and phagoburst assays. Cytokine (TNFα, IL10, IL23) production was measured by ELISA. In parallel experiments, TNFα, IL10 and CD163 expression was measured by qRT-PCR in laser dissected <i>E coli</i> laden and unladen lamina proprial macrophages. All patients were genotyped for the three common NOD-2 SNP9s (G908R, L1007fs and R702W), and the autophagy related SNP9s (ATG16L1 and IRGM). Genotypes and monocyte/macrophage markers were compared. <h3>Results</h3> Presence of the ATG16L1 risk variant was strongly associated with a reduced <i>E coli</i> induced TNFα expression in CD PBM9s (p=0.0017) and increased levels of ROR9s on uptake of CD derived <i>E coli</i> (p=0.0027). Presences of IRGM risk variant was associated with increased IL10 expression from PBM9s. NOD-2 mutations were not associated with a difference in any variable studied. No genotype altered survival of <i>E coli</i> in PBM at 2 or 4 h after infection or <i>in-situ</i> lamina propria macrophage cytokine expression. <h3>Conclusion</h3> These results show that defective autophagy modifies the handling of intracellular bacteria in CD but appears unlikely to be the main cause of prolonged bacterial survival. Further studies are needed to elucidate the nature of this innate defect and it9s role in CD pathogenesis.
Journal of Investigative Dermatology, Baltimore
Journal: JAMA (1965)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Oral high‐dose methylprednisolone and intravenous immunoglobulin treatments in adult chronic idiopathic thrombocytopenic purpura
Authors: Levent Altintop, Davut Albayrak
Journal: American Journal of Hematology (1997)

Ten adult patient of chronic idiopathic thrombocytopenic purpura (CITP) used oral prednisone and were treated with seven doses of oral high-dose methylprednisolone (30 mg/kg). Nine of ten patients responded after HDMP treatment (plt > 150 × 109/L). Two patients having 8 and 10 years of history achieved long-term remission after first HDMP treatment. One unresponsive and one responsive patients did not accept IVIG treatment as second therapy and lost the follow-up. The remaining six patients received IVIG (0.5 mg/kg for 5 days) as second therapy after 3 months. Platelet count increased above 150 × 109/L in 4 patients and between 60–80 × 109/L in 2 patients. The peak platelet counts of both therapy users were higher under HDMP than IVIG therapy (252 ± 110.4 vs 174.2 ± 83.7 × 109/L), but the difference was not significant. Responses were transient and returned to pretreatment values at 14–30 days, excluding long-term remission of 2 (2/10) patients after HDMP treatment. No side effect was observed. Thus, oral HDMP appears a good initial therapy for continuous remission in a small ratio of patients and a good security for emergency situations and prior to surgery in adult CITP patients. Am. J. Hematol. 56:191–192, 1997. © 1997 Wiley-Liss, Inc.
Book reviews
Journal: Allergy (1988)

Rother, K. &amp; Till, G. O. (eds.): The complement system. Ohshiro, T. &amp; Calderhead, R. G. : Low level laser therapy. Sitges‐Serra, A., Sitges‐Creus, A. &amp; Schwartz‐Riera, S. (eds.): Clinical progress in nutrition research. Braquet, P. (ed.): Platelet‐activating factor and cell immunology. Braquet, P. (ed.): The role of platelet‐activating factor in immune disorders. Becker, E. L. (ed.): Membrane activation in immunologically relevant cells. Veldman, J. E. (ed.): Immunology, histophysiology, tumour immunology in otorhinolaryngology.
SECTION ON BENEVOLENCE.
Journal: JAMA (1895)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Health in Colleges and Universities
Authors: Dana L. Farnsworth, Augustus Thorndike
Journal: New England Journal of Medicine (1956)

Emergency and Elective SurgeryAny college-health administration has other surgical conditions to contend with than those of trauma. To be sure, most of these pertain to superficial and minor surgical infections. In our experience less than 2 per cent of the enrolled students require hospitalization16 for all causes: medical, surgical and psychiatric. It is of interest, however, that two thirds of the hospital admissions outside the infirmary are for surgical conditions and that among such admissions, in our experience, are appendicitis, acute pancreatitis, intestinal obstruction, renal calculus, perforated gastric and duodenal ulcers and spontaneously ruptured spleen — truly surgical emergencies. . . .
Neurology
Journal: JAMA (1999)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal