tbuckley/cabot-search huggingface dataset:
New Human Retroviruses Discovered
Authors: Bridget M Kuehn
Journal: JAMA (2005)

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
Diffuse cutaneous mastocytosis treated with psoralen photochemotherapy: case report and review of the literature
Authors: V.A. Kinsler, J.L.M. Hawk, D.J. Atherton
Journal: British Journal of Dermatology (2005)

Sir, A male infant aged 7 months was referred to Great Ormond Street Hospital for Children with a history of blistering and pruritus. His skin was normal until the age of 10 weeks, when he developed an erythematous rash over the back of his head, neck and shoulders. The primary symptom at this stage was pruritus, unalleviated by mild topical steroids, emollients and antihistamines from his general practitioner. He then developed blisters on his neck and groin, some of which became secondarily infected, and he began to have episodes of intense flushing, which would last for up to 2 h. His sleep was disturbed by pruritus, but he was otherwise well, gaining weight and developing normally. Examination revealed slightly thickened, granular‐looking skin with a yellow tinge, marked dermographism, and thin‐walled blisters. A clinical diagnosis of diffuse cutaneous mastocytosis was made, and was confirmed on punch biopsy. Initial therapy was with high‐dose nonsedative and sedative antihistamines during the day and night, respectively, and the application of beclometasone dipropionate ointment diluted 1 : 10 in white soft paraffin under wet wraps twice daily. Relief of symptoms was, however, minimal, and by 14 months of age he was unable to sleep for more than a few hours at a time, and the episodes of flushing were occurring every other day. There were no other identifiable systemic symptoms.
RAP‐011, an activin receptor ligand trap, increases hemoglobin concentration in hepcidin transgenic mice
Authors: Jacqueline M. Langdon, Sangjucta Barkataki, Alan E. Berger, Chris Cheadle, Qian‐Li Xue, Victoria Sung, Cindy N. Roy
Journal: American Journal of Hematology (2014)

Over expression of hepcidin antimicrobial peptide is a common feature of iron-restricted anemia in humans. We investigated the erythroid response to either erythropoietin or RAP-011, a "murinized" ortholog of sotatercept, in C57BL/6 mice and in hepcidin antimicrobial peptide 1 over expressing mice. Sotatercept, a soluble, activin receptor type IIA ligand trap, is currently being evaluated for the treatment of anemias associated with chronic renal disease, myelodysplastic syndrome, β-thalassemia, and Diamond Blackfan anemia and acts by inhibiting signaling downstream of activin and other Transforming Growth Factor-β superfamily members. We found that erythropoietin and RAP-011 increased hemoglobin concentration in C57BL/6 mice and in hepcidin antimicrobial peptide 1 over expressing mice. While erythropoietin treatment depleted splenic iron stores in C57BL/6 mice, RAP-011 treatment did not deplete splenic iron stores in mice of either genotype. Bone marrow erythroid progenitors from erythropoietin-treated mice exhibited iron-restricted erythropoiesis, as indicated by increased median fluorescence intensity of transferrin receptor immunostaining by flow cytometry. In contrast, RAP-011-treated mice did not exhibit the same degree of iron-restricted erythropoiesis. In conclusion, we have demonstrated that RAP-011 can improve hemoglobin concentration in hepcidin antimicrobial peptide 1 transgenic mice. Our data support the hypothesis that RAP-011 has unique biologic effects which prevent or circumvent depletion of mouse splenic iron stores. RAP-011 may, therefore, be an appropriate therapeutic for trials in human anemias characterized by increased expression of hepcidin antimicrobial peptide and iron-restricted erythropoiesis.
Functional rather than immunoreactive levels of IgG<sub>4</sub> correlate closely with clinical response to grass pollen immunotherapy
Authors: M. H. Shamji, C. Ljørring, J. N. Francis, M. A Calderon, M. Larché, I. Kimber, A. J. Frew, H. Ipsen, K. Lund, P. A. Würtzen, S. R. Durham
Journal: Allergy (2011)

To cite this article: Shamji MH, Ljørring C, Francis JN, Calderon MA, Larché M, Kimber I, Frew AJ, Ipsen H, Lund K, Würtzen PA, Durham SR. Functional rather than immunoreactive levels of IgG 4 correlate closely with clinical response to grass pollen immunotherapy. Allergy 2012; 67 : 217–226. Abstract Background: Induction of allergen‐specific IgG 4 antibodies is the most consistent immunological finding in immunotherapy trials. However, quantitative assessments of IgG 4 antibodies have not proven beneficial in evaluating clinical changes during or after immunotherapy. In the current study, we investigated the relationship between clinical outcome and allergen‐specific IgG 4 titres or functional antibody responses following immunotherapy. We hypothesized that functional assays of serum IgG–associated inhibitory activity such as inhibition of IgE–allergen interactions (IgE‐blocking factor) and inhibition of CD23‐dependent IgE‐facilitated allergen binding (IgE‐FAB) correlate more closely with clinical outcome and may be biomarkers of clinical response. Methods: In an 8‐month dose–response randomized double‐blind placebo‐controlled study, 221 polysensitized subjects with severe seasonal rhinitis received Alutard SQ, Phleum pratense 100 000 SQ‐U, 10 000 SQ‐U or placebo injections. Serum specimens were collected before treatment, after up‐dosing, during the peak season and at the end of the study. Allergen‐specific IgG 4 titres and IgG‐associated inhibitory activity were evaluated. Results: A time‐ and dose‐dependent increase in serum inhibitory activity for both the IgE‐blocking factor and IgE‐FAB was observed, which paralleled increases in grass pollen–specific IgG 4 antibodies. A modest but significant inverse relationship was demonstrated between postimmunotherapy serum inhibitory activity and combined symptom–rescue medication scores (IgE‐FAB: r = −0.25, P = 0.0002; IgE‐blocking factor: r = −0.28, P &lt; 0.0001), whereas this was not observed for immunoreactive IgG 4 levels ( r = −0.11, P = 0.12). Conclusions: Functional assays of inhibitory IgG 4 and IgE‐blocking factor may be more useful surrogates of clinical response than IgG 4 . Whether these antibody effects may serve as predictive biomarkers of clinical efficacy in individual patients requires further investigation.
380. Studies on the Mechanism of Gene Repair Using Saccharomyces cerevisae as a Model System
Authors: Katie Maguire, Hetal Parekh-Olmedo, Eric B. Kmiec
Journal: Molecular Therapy (2005)

Oligonucleotides are being used to direct base changes within genes and can be used as a gene therapy for human disease. While the entire mechanism of the targeted nucleotide exchange (TNE) reaction has yet to be elucidated, there is evidence that it may be separated into at least two phases: the pairing phase, which consists of the MSSO pairing to the target site within the gene, and the repair phase, in which the MSSO directs the repair of the targeted base. This repair phase could possibly be separated into two phases: the first repair event, which is the correction of the strand to which the oligonucleotide is complementary, and the second repair event, in which the corrected strand serves as a template to repair the non-targeted strand. While the proteins that are involved in the pairing phase of the reaction are known, it remains unclear as to which proteins are playing a role in the repair phase of the reaction. Yeast strains deficient in Rad1p and MMR proteins, Msh2p and Msh6p, were used to determine the ability of a modified single-stranded oligonucleotide to direct a base change within a mutant Hygromycin eGFP fusion gene. The data indicate that in the absence of these proteins, the oligonucleotide is incapable of directing the base change, as the targeting frequency is reduced 30 fold and shows very little targeting activity. Upon complementation of Rad1p, using the 2um based plasmid pNF1000, the ability to direct the base change is restored. These data indicate that proteins involved in MMR and NER are playing a role in the TNE reaction and future studies aim to elucidate this role.
Abstract 16630: Clinical Benefit of Chelation Therapy in Post-MI Patients With Diabetes and Peripheral Artery Disease
Authors: Gervasio A Lamas, Esteban Escolar, Robin Boineau, Richard Nahin, Christine Goertz, Daniel Mark, Patrick Golden, Dorothy Merritt, Yves Rosenberg, Lauren Lindblad, Kerry Lee
Journal: Circulation (2014)

Introduction:  The NIH-funded Trial to Assess Chelation Therapy (TACT) reported a clinical benefit of ethylene diamine tetraacetic acid (EDTA)-based chelation on cardiovascular (CV) outcomes in post-MI patients with diabetes (DM). Post-MI diabetic patients with peripheral artery disease (PAD) have particularly high risk.   Methods:  TACT, a multi-center, double-blind, placebo-controlled, trial of EDTA chelation, enrolled patients (pts) age > 50 years with an MI at least 6 weeks prior and creatinine    Results:  TACT enrolled 1708 pts, of which 303 (18%) had PAD. EDTA chelation reduced the primary endpoint by a similar extent in pts with (hazard ratio (HR) 0.7) and without PAD (HR 0.87, p for interaction 0.38). Among the 633 (37%) of patients with DM, 153 (24%) had PAD. There were 81 assigned to EDTA and 72 to placebo. Baseline characteristics including obesity, hypertension, hypercholesterolemia, heart failure, stroke and prior CABG were similar between treatment groups. Creatinine was higher in the placebo group (median 1.2 v 1.0; p=0.003). There were 80% on statins, 92% on antiplatelet or antithrombotic therapy, and 32% treated with insulin. EDTA chelation led to a reduction in the primary endpoint (46% vs. 22%; p=0.002, Figure), and total mortality (25% v. 11%, p=0.032). HR point estimates comparing chelation vs. placebo for each component of the composite endpoint were all    Conclusions:  In post-MI pts with DM and PAD treated with standard therapies, EDTA-based chelation therapy markedly reduced cardiovascular events.
Biographisches Lexikon der hervorragenden Ärzte der letzten fünfzig Jahre.
Authors: I. Fischer
Journal: JAMA (1933)

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
A Pluronic® micelle formulation increases the anti-leukemic activity of the novel anti-cancer nitric oxide prodrug JS-K.
Authors: Paul Shami, Ken Kosak, Joseph Saavedra, Larry Keefer
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

3293 

We have developed a class of O 2-arylated diazeniumdiolate nitric oxide (NO) generators that release NO upon activation by the glutathione S-transferases (GST). This drug design exploits the upregulation of GST in malignant cells as compared to normal tissue and thus provides selective delivery of NO to targeted tumors. O2 -(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate or JS-K is a lead compound from this family. JS-K induces apoptosis and differentiation in human myeloid leukemia HL-60 cells, and inhibits HL-60 cell growth in NOD/SCID mice xenografts. JS-K also has potent anti-neoplastic activity in vitro and in vivo against multiple myeloma, prostate cancer and liver cancer. JS-K is sparingly soluble in aqueous media. Preliminary pharmacokinetic studies have shown that JS-K has a short in vivo half-life due to its reactivity with blood components. We therefore used polymers made of polyethylene oxide and polypropylene oxide (Pluronics®) in order to develop a nanoscale micelle formulation for the clinical development of JS-K. JS-K loading in Pluronics® P123 micelles did not affect micelle stability (particle size of 19.18 ± 5.64 and 19.75 ± 5.84 nm at 2 and 45 minutes, respectively). JS-K loaded in Pluronic® P123 micelles had increased in vitro cytoxicity against HL-60 cells (IC50 of 0.45 and 0.09 μM at 72 hours after JS-K addition for free JS-K and JS-K formulated in P123 micelles, respectively) while empty P123 micelles did not affect cell growth. Administration of free JS-K to NOD/SCID mice at a dose of 5 μmol/kg induced a sustained 25% drop in systolic blood pressure. Administration of JS-K formulated in P123 micelles to NOD/SCID IL2R γ null at the same dose did not induce hypotension. This suggests stabilization of JS-K in the bloodstream by the micelles and therefore slower intravascular release of NO. We then studied the anti-leukemic activity of JS-K formulated in P123 micelles in NOD/SCID IL2R γ null mice implanted subcutaneously with HL-60 cells. Loading of JS-K in P123 micelles led to significantly better anti-tumor activity than free unformulated JS-K administered at the same dose and schedule (4 μmol/kg IV thrice weekly). We fit a linear mixed model using SAS PROC MIXED to the data, using a random effect to account for correlation among measurements within the same animal. In this model, rate of tumor growth, as fit by a linear and quadratic effect of time, was found to be significantly higher (p=0.01 by F-test) among animals treated with free JS-K compared to animals treated with JS-K formulated in P123 micelles. Mice treated with empty P123 micelles had significantly greater tumor growth than mice treated with either free JS-K or JS-K formulated in P123 micelles. JS-K establishes a new class of cancer chemotherapeutic agents. Formulation of JS-K in Pluronic® micelles will speed its clinical development.
The Development of an Isogenic Subline of Mice (C57BL/6-&lt;italic&gt;H&lt;/italic&gt;-2&lt;sup&gt;&lt;italic&gt;d&lt;/italic&gt;&lt;/sup&gt;) Resistant to Transplantable Neoplasms Indigenous to Strain C57BL&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;
Authors: P R Borges, B J Kvedar, G E Foerster
Journal: JNCI Journal of the National Cancer Institute (1954)

Journal Article The Development of an Isogenic Subline of Mice (C57BL/6-H-2 d ) Resistant to Transplantable Neoplasms Indigenous to Strain C57BL Get access Paulo R. F. Borges, Paulo R. F. Borges Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar Barbara J. Kvedar, Barbara J. Kvedar Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Elizabeth Foerster G. Elizabeth Foerster Roscoe B. Jackson Memorial Laboratory, Bar Harbor, Maine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 15, Issue 2, October 1954, Pages 341–346, https://doi.org/10.1093/jnci/15.2.341 Published: 01 October 1954 Article history Received: 14 June 1954 Published: 01 October 1954
Abstract 698: Late Enhancement in Isolated Noncompaction Left Ventricle is Related to Repetitive Ventricular Arrhythmias
Authors: Ana G Almeida, João S Marques, Pereira Guilherme, Nuno C Dias, Manuel G varela, Luis M Sargento, Cláudio David, Mário G Lopes
Journal: Circulation (2008)

Isolated noncompaction left ventricle (INLV), an unclassified cardiomyopathy, is associated to an ominous prognosis due to arrhythmias, embolism and heart failure. We hypothesized that, in patients with INLV, the presence of late enhancement (LE), assessed by cardiovascular magnetic resonance (CMR) could be related to repetitive ventricular arrhythmias, which are determinants of sudden death. Methods: 22 consecutive patients (pts), aged 35±11 years-old, 11 men) with INLV, were included. Diagnosis was established by echocardiography and CMR using accepted criteria. All underwent complete CMR LV assessment using a 17-segments model: SSFP short-axis LV volumes and ejection fraction; SSFP 2, 3, 4-chambers for noncompaction segmental distribution; LV segmental LE (segmented inversion-recovery fast gradient-echo sequence, 10–15 mn after 0.2mmol/kg of Gd-DTP); the number of segments with LE was assessed. A 24 hours-Holter monitoring was obtained in less than two-weeks interval and the number of repetitive ventricular arrhythmias was assessed (pairs, triplets, ventricular tachycardia). Results: Non-compaction was present in 212 segments, involving mainly the inferior, posterior and lateral walls, but all walls were involved in different patients. LE was detected in 242 segments (8±2 per patient), present in all non-compaction segments and in 30 morphologically normal segments. Fibrosis was visible in the non-compacted layer (all segments) and in the more internal layer of the compacted myocardium (161 segments, 67%). LV end-diastolic volume was 128±22ml/m2) and there was LV dilatation and reduced ejection fraction in 14 patients. Repetitive ventricular arrhythmias were present in all patients, varying from 3 to 155 episodes in the Holter monitoring. There was a correlation between the number of ventricular arrhythmias the number of non-compaction segments (r=0.43, 0,04) and the number of LE present segments (r=0.65, p=0.001). No correlation was found with LV end-diastolic volumes or ejection fraction. Conclusions: CMR late enhancement is a frequent finding in isolated non-compaction LV and is significantly associated to complex ventricular arrhythmias. Further study should address the prognostic meaning of LE in this condition
Exercise and Cancer Risk—How Much Is Enough?
Authors: Kerri Winters-Stone
Journal: JAMA Oncology (2015)

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 Oncology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Oncology journal
In vitro screening for putative psoriasis-specific antigens among wheat proteins and peptides
Authors: J. Skavland, P.R. Shewry, J. Marsh, B. Geisner, J.A. Marcusson
Journal: British Journal of Dermatology (2011)

Background Patients with psoriasis who had raised IgG and/or IgA antigliadin antibodies showed clinical improvement in a trial with a gluten‐free diet. The selection of patients for the diet treatment was based on the presence of specific antibodies, i.e. the result of humoral immunity. Objectives As psoriasis is now considered to be a T cell‐mediated disease we decided to challenge peripheral blood mononuclear cells (PBMCs) in vitro from randomly selected patients with well‐defined wheat proteins/peptides to explore the possibility of identifying a specific antigen with T cell activating properties in a subgroup of patients. Methods PBMCs from 37 patients (20 female and 17 male; mean age 49 years) and 37 healthy controls (12 female and 25 male; mean age 57 years) were included. Not all patients participated in all experiments. The PBMCs were exposed in vitro with the following wheat proteins/peptides in various concentrations: total albumins, 0·28 α‐amylase inhibitor and the synthetic peptides, p31–43, p57–68 and p62–75, based on coeliac‐active sequences of α‐gliadin. The proliferative response was measured as counts per minute after the cells had been pulsed with methyl‐3H‐thymidine. Results Albumin, α‐amylase inhibitor, p31–43 and p57–68 elicited a significant response in both patients and controls but showed no differences between the groups. The response induced by the α‐amylase inhibitor was higher than that induced by the albumin fraction and the p31–43 and p57–68 peptides. At a concentration of 25 μg mL−1, five of 36 patients with psoriasis responded positively to the p62–75 peptide and none of the 33 controls, using a stimulation index of 2·4 as the cut‐off level (P <0·05). These five patients did not show clinical features that differed from the remaining patients. Among the responding patients the relative number of CD4+ cells increased in some but not all after in vitro challenge with the albumins, 0·28 α‐amylase inhibitor, and p62–75. These antigens could also induce in vitro the expression of the homing antigen cutaneous lymphocyte antigen (CLA) in a few patients and controls. Conclusions The wheat protein antigens, especially the p62–75 peptide, might be of interest in a subgroup of patients with psoriasis.