tbuckley/cabot-search huggingface dataset:
Abstract 628: Pan-Bcl-2 inhibitor, GX15-070 (Obatoclax), decreases human T regulatory lymphocytes while preserving effector T Lymphocytes: A rationale for its use in combination immunotherapy
Authors: Peter S. Kim, Caroline Jochems, Italia Grenga, Renee N. Donahue, Kwong Y. Tsang, James L. Gulley, Jeffrey Schlom, Benedetto Farsaci
Journal: Cancer Research (2014)

Abstract Bcl-2 inhibitors are currently being evaluated in clinical studies for treatment of patients with solid tumors and hematopoietic malignancies. In this study we explored the potential for combining the pan-Bcl-2 inhibitor GX15-070 (GX15; obatoclax) with immunotherapeutic modalities. We evaluated the in vitro effects of GX15 on human T-cell subsets obtained from PBMCs in terms of activation, memory, and suppressive function. Our results indicated that in healthy-donor PBMCs, mature-activated T cells were more resistant to GX15 than early-activated T cells, and that GX15 preserved memory but not non-memory T-cell populations. Furthermore, GX15 increased the apoptosis of regulatory T cells (Tregs), profoundly down-regulated FOXP3 and CTLA-4 in a dose-dependent manner, and decreased their suppressive function. Treating PBMCs obtained from ovarian cancer patients with GX15 also resulted in increased CD8+:Treg and CD4+:Treg ratios. These results support preclinical studies in which mice vaccinated before treatment with GX15 showed the greatest reduction in metastatic lung tumors as a result of increased apoptotic resistance of mature CD8+ T cells and decreased Treg function brought about by GX15. Taken together, these findings suggest that when a Bcl-2 inhibitor is combined with active immunotherapy in humans, such as the use of a vaccine or immune checkpoint inhibitor, immunotherapy should precede administration of the Bcl-2 inhibitor to allow T cells to become mature, and thus resistant to the cytotoxic effects of the Bcl-2 inhibitor. Citation Format: Peter S. Kim, Caroline Jochems, Italia Grenga, Renee N. Donahue, Kwong Y. Tsang, James L. Gulley, Jeffrey Schlom, Benedetto Farsaci. Pan-Bcl-2 inhibitor, GX15-070 (Obatoclax), decreases human T regulatory lymphocytes while preserving effector T Lymphocytes: A rationale for its use in combination immunotherapy. [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 628. doi:10.1158/1538-7445.AM2014-628
Government orders inquiry into removal of children's organs
Authors: C. Dyer
Journal: BMJ (1999)

Every NHS trust in Britain is being asked to say whether it took organs from dead children without their parents' consent, in the aftermath of an outcry over disclosures that staff at Alder Hey Hospital in Liverpool removed and stored more than 2000 hearts and 800 other organs.

Health secretary Alan Milburn last week announced an external inquiry into the removal and retention of organs at the hospital, the largest children's hospital in Europe.

Alder Hey …
LUNG ABSCESS COMPLICATING A HEALED OPEN TUBERCULOUS CAVITY
Authors: L BRESLAW
Journal: Annals of Internal Medicine (1958)

Case Reports1 June 1958LUNG ABSCESS COMPLICATING A HEALED OPEN TUBERCULOUS CAVITYLEONARD BRESLAW, M.D.LEONARD BRESLAW, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-48-6-1373 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThis case is being presented to call attention to the unusual response of a healed open tuberculous cavity complicated by a coincident lung abscess. The unusual character of healed tuberculous lesions has been widely described in current literature. As a result of therapy with the new chemotherapeutic agents, lesions that formerly terminated fatally are now being healed or arrested. As more patients are released from sanatorium care and are exposed to the bacterial vicissitudes of the general population, complications such as this may become more prevalent.CASE REPORTA 33 year old Negro male, in October, 1951, while working in...Bibliography1. Auerbach O: Pulmonary tuberculosis after prolonged use of chemotherapy, Am. Rev. Tuberc. 71: 165 (Feb.) 1955. MedlineGoogle Scholar2. Amberson JB: Evolution of tuberculosis and its behavior under treatment, Bull. Johns Hopkins Hosp. 94: 337-347 (June) 1954. MedlineGoogle Scholar3. HobbyAuerbachLennertSmallComer GLOTFMJJV: Late emergence of M. tuberculosis in liquid cultures of pulmonary lesions resected from humans, Am. Rev. Tuberc. 70: 191-218 (Aug.) 1954. MedlineGoogle Scholar4. AuerbachHobbySmallLennertComer OGLMJTFJV: Clinicopathologic significance of demonstration of viable tubercle bacilli on resected lesions, J. Thoracic Surg. 29: 109-135 (Feb.) 1955. CrossrefGoogle Scholar5. Medlar EM: Pathogenesis of minimal pulmonary tuberculosis, Am. Rev. Tuberc. 58: 583, 1948. MedlineGoogle Scholar6. Muschenheim CA: Schema of treatment in tuberculosis, Am. Rev. Tuberc. 71: 386, 1955. Google Scholar7. SzeSamadiConant KCAJS: Pulmonary resection for tuberculosis, Am. Rev. Tuberc. 71: 349, 1955. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Hollywood, California*Received for publication November 21, 1956.Requests for reprints should be addressed to Leonard Breslaw, M.D., 1845 North Edgemont, Hollywood 27, California. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 June 1958Volume 48, Issue 6Page: 1373-1383KeywordsAbscessesChemotherapeutic agentsLesionsLungsPneumoniaTuberculosis ePublished: 1 December 2008 Issue Published: 1 June 1958 PDF downloadLoading ...
560. Induction of Prion Protein-Specific Antibody Responses Using PrP-Retroparticles
Authors: Daphne Nikles, Patricia Bach, Klaus Boller, Christoph A. Merten, Fabio Montrasio, Ulrich Kalinke, Klaus Cichutek, Christian J. Buchholz
Journal: Molecular Therapy (2004)

Passive immunization with antibodies directed against the cellular form of the prion protein can protect against prion disease. However, so far active immunization with recombinant prion protein failed to induce in vivo protective prion protein (PrP)-specific antibody responses.
Abstract 2479: Nuclear promyelocytic leukemia bodies tether to early endosomes during mitosis
Authors: Vuk Palibrk, Emma Lång, Anna Lång, Alexander Rowe, Stig Ove Bøe
Journal: Cancer Research (2014)

Abstract During mitosis, the nuclear envelope breaks down, leading to potential interactions between cytoplasmic and nuclear components. PML bodies are nuclear structures with tumor suppressor functions. However, the protein responsible for generating these bodies, the promyelocytic leukemia protein (PML), has been shown to support both nuclear and cytoplasmic activities. Here we demonstrate that PML bodies form stable interactions with the cytoplasmic transport vesicles early endosomes immediately following entry into mitosis. The two compartments remain stably associated throughout the mitotic phase and dissociate in the cytoplasm of newly divided daughter cells. We also show that PML promotes ligand-induced endosome-mediated degradation of the epidermal growth factor receptor, and that a minor subset of PML bodies become anchored to the mitotic spindle during cell division. The study demonstrates a stable mitosis-specific interaction between a cytoplasmic and a nuclear compartment. The implications of these findings will be discussed in relation to PMLs role in tumor suppression and as a target for cancer therapy. Citation Format: Vuk Palibrk, Emma Lång, Anna Lång, Alexander Rowe, Stig Ove Bøe. Nuclear promyelocytic leukemia bodies tether to early endosomes during mitosis. [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 2479. doi:10.1158/1538-7445.AM2014-2479
Abstract 4017: Dynamic biochemical tissue analysis detects functional selectin ligands expressed on breast, colorectal, liver, lung, ovarian, pancreatic, prostate, and stomach cancer tissues
Authors: Eric Martin, Ramiro Malgor, Douglas Goetz, Monica Burdick
Journal: Cancer Research (2014)

Abstract Accumulating evidence suggests that selectin/selectin ligand interactions are involved in mediating the adhesion of bloodborne circulating tumor cells at distant sites during the later stages of cancer metastasis. Presently, immunostaining is the standard method for detecting selectin ligands expressed on tissue, but this approach cannot ascertain if the selectin ligands are functional. That is, detection of purported selectin ligands by static (no-force) immunostaining under equilibrium conditions does not necessitate that the reactive antigens are able to mediate cell adhesion with hemodynamic flow (force) under non-equilibrium conditions. The relevance of functional selectin ligands as a biomarker is presently unclear because of the lack of adequate detection methods. Recently, we developed a method to detect functional selectin ligands in situ by perfusing selectin-coated microspheres (probes) over cancer tissues in a microfluidic device. This method of tissue interrogation is termed dynamic biochemical tissue analysis (DBTA). Preliminary analysis of signet ring cell colon carcinoma tissue revealed the highest amount of specific probe adhesion relative to negative control probes occurred with a murine E-selectin probe, rather than human E-, P-, or L-selectin probes. Therefore, to investigate the relevance of functional selectin ligand expression on cancer tissue as a biomarker, 196 cases of various solid tumors at primary and metastatic sites were investigated with DBTA using murine E-selectin. Probe adhesion occurred on multiple cases of breast, colon, liver, lung, ovarian, pancreatic, prostate, and stomach cancers, demonstrating the presence of functional selectin ligands. In addition, probe adhesion occurred on multiple cases of breast, colon, liver, lung, ovarian, pancreatic, rectal, and stomach cancer tissues sampled from metastatic sites. Overall, probe adhesion levels for the tissues investigated ranged from 10 specifically adherent probes/mm2 on lung adenosquamous carcinoma to 1170 specifically adherent probes/mm2 on ovarian endometrioid adenocarcinoma, indicating broad levels of functional selectin ligand expression. In summary, DBTA detects functional selectin ligands expressed on tissue from multiple cancer types at both the primary and metastatic sites, data that may provide valuable diagnostic and prognostic information for malignant tumors. Citation Format: Eric Martin, Ramiro Malgor, Douglas Goetz, Monica Burdick. Dynamic biochemical tissue analysis detects functional selectin ligands expressed on breast, colorectal, liver, lung, ovarian, pancreatic, prostate, and stomach cancer tissues. [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 4017. doi:10.1158/1538-7445.AM2014-4017
Functional characterization of CD4+CD25+ regulatory T cells differentiated in vitro from bone marrow-derived haematopoietic cells of psoriasis patients with a family history of the disorder
Authors: K. Zhang, X. Li, G. Yin, Y. Liu, X. Niu, R. Hou
Journal: British Journal of Dermatology (2007)

In psoriasis CD4+CD25+ regulatory T cells are functionally deficient. The imbalance between regulatory and effector T-cell functions is important for inducing psoriasis. It is reasonable to speculate that the dysfunctional activity of CD4+CD25+ regulatory cells may originate partly from the abnormal haematopoietic cells determined mainly by genetic background.To test the hypothesis that haematopoietic stem cells are responsible for dysfunctional CD4+CD25+ regulatory cells in psoriasis.Bone marrow-derived CD34+ haematopoietic cells from patients with psoriasis (with a family history of psoriasis) and from normal controls were differentiated into T cells in vitro. CD4+CD25+ T cells were isolated by an immunomagnetic bead method, and proliferation activity and capacity for cytokine secretion were determined. Furthermore, the ability of CD4+CD25+ T cells to suppress the proliferative responses of allogeneous peripheral blood CD4+CD25- effector T cells was assessed in vitro.The differentiated CD4+CD25+ T cells of psoriatic origin showed similar characteristics to those of normal volunteers, including proliferation activity and secretion profile of the cytokines interleukin (IL)-2, IL-4, IL-8, IL-10 and interferon (IFN)-gamma. However, proliferation and secretion levels of the cytokines IL-2 and IL-10 for CD4+CD25+ cells of psoriatic CD34+ cell origin were significantly lower than those of normal controls in response to streptococcal superantigen (Strep-A). In particular, CD4+CD25+ T cells differentiated from psoriatic CD34+ cells were functionally insufficient to restrain effector T-cell proliferation.CD4+CD25+ T cells differentiated in vitro from haematopoietic cells of patients with psoriasis are impaired in regulatory function. The dysfunction of psoriatic CD4+CD25+ T cells may be due to inherent genetic programming passed down from bone marrow-derived haematopoietic cells.
Official Call to the Officers and Members of the American Medical Association to Attend the Interim Meeting of the House of Delegates in Las Vegas, Dec 7 Through 10, 1986
Authors: John J. Coury
Journal: JAMA (1986)

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
AIR TRANSPORTATION OF CARDIAC AND PULMONARY PATIENTS
Authors: Vincent M. Downey, Benjamin A. Strickland
Journal: Annals of Internal Medicine (1952)

Article1 February 1952AIR TRANSPORTATION OF CARDIAC AND PULMONARY PATIENTSVINCENT M. DOWNEY, BENJAMIN A. STRICKLAND JR.VINCENT M. DOWNEYSearch for more papers by this author, BENJAMIN A. STRICKLAND JR.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-36-2-525 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAir transportation of patients has become commonplace. In quickly transporting the sick and wounded from distant areas of military operations, such as Korea, to well-equipped and well-staffed medical facilities which provide thorough, definitive treatment, the airplane is of the greatest value and has been acclaimed by many as one of the really great advances in military medicine.This paper presents the findings of an investigation carried out by the United States Air Force Medical Service in the worldwide air evacuation system which has been in operation since 1942. An analysis has been made of 1,777 flights of patients with cardiac...Bibliography1. TillischStotlerLovelace JHJFWR: Study of the effects of airplane transportation of 200 patients, J. Aviation Med. 14: 162-169, 1943. Google Scholar2. StricklandRafferty BAJA: Effects of air transportation on clinical conditions, an analysis of 16,020 cases reported in 1949, J. A. M. A. 145: 129-133 (Jan. 20) 1951. CrossrefMedlineGoogle Scholar3. LevyBarachBruenn RLALHS: Effects of induced oxygen want in patients with cardiac pain, Am. Heart J. 15: 187, 1938. CrossrefGoogle Scholar4. White MS: The effects of anoxia of high altitude flights on the electrocardiogram, J. Aviation Med. 10: 176, 1940. Google Scholar5. May SH: Air travel and the cardiac patient, Am. Heart J. 40: 363-368 (Sept.) 1950. CrossrefMedlineGoogle Scholar6. Graybiel A: A consideration of the effects of oxygen lack on the cardiovascular system from the viewpoint of aviation with an analysis of deaths occurring aloft on commercial aircraft, J. Aviation Med. 12: 191, 1941. Google Scholar7. Friedberg CK: Diseases of the heart, 1949, W. B. Saunders Co., Philadelphia, p. 392. Google Scholar8. Dowd KE: Report of death of passenger under treatment by pneumothorax, J. Aviation Med. 16: 346-349 (Oct.) 1945. MedlineGoogle Scholar9. RoperWaring WHJJ: Air evacuation of tuberculous military patients, Am. Rev. Tuberc. 61: 678 (May) 1950. MedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Presented at the Thirty-second Annual Session of the American College of Physicians, St. Louis, Mo., April 10, 1951. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byMedical Criteria for Passenger FlyingTherapie 1 February 1952Volume 36, Issue 2_Part_2Page: 525-535KeywordsArmed forcesMedical servicesMilitary medicine ePublished: 1 December 2008 Issue Published: 1 February 1952 PDF downloadLoading ...
Galectin-3 in Heart Failure With Preserved Ejection Fraction
Authors: Omar F. AbouEzzeddine, Phillip Haines, Susanna Stevens, Jose Nativi-Nicolau, G. Michael Felker, Barry A. Borlaug, Horng H. Chen, Russell P. Tracy, Eugene Braunwald, Margaret M. Redfield
Journal: JACC Heart Failure (2015)
The Blood of Strangers: True Stories from the Emergency Room
Authors: Giles Kent
Journal: BMJ (2001)

Frank Huyler Fourth Estate, £10, pp 188 ISBN 1 84115 445 8

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Frank Huyler is an emergency room physician in “it's all a bit quirky” Alberquerque, New Mexico. He describes the characters of a vast spectrum of patients and doctors: a surgeon who unexpectedly commits suicide; a neurosurgeon who speaks in tongues; a man who was chased across the desert by a heat seeking missile; and a strong believer in God who refuses life saving treatment. …

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Abstract 16907: Modification of Hemeoxygenase-1 Expression Enhances the Therapeutic Potency of CD34+ Cells in Ischemic Tissue Repair
Authors: Jörn Tongers, Kentaro Jujo, Jerome G Roncalli, Marie-Ange Renault, Christine E Kamide, Ekaterina Klyachko, Tina Thorne, Johann Bauersachs, David L Amrani, Delara Motlagh, Douglas W Losordo
Journal: Circulation (2011)

The potency of cell-based therapy in ischemic tissue repair is limited by low viability and retention of transplanted cells. The hemeoxygenase system catabolizes heme cleavage and has been shown to exert cytoprotection via its anti-oxidative, -apoptotic, -inflammatory properties. HO-1, inducible in various pathologic states, has been shown to influence progenitor cell biology. We hypothesized that HO-1 over-expression enhances the therapeutic potency of CD34+ cells for ischemic tissue repair. CD34+ from healthy donors were enriched from the peripheral blood mononuclear cell fraction of healthy donors after G-CSF mobilization (Isolex 300i). Adenoviral transduction of HO-1/GFP or GFP led to a substantial increase of HO-1 expression (HO-1/18s RNA expression: 62-fold increase, protein expression: 20-fold increase; n=3). After allowing 48 hrs for target gene expression, CD34+ cells were FACS-sorted for GFP followed by overnight recovery in-vitro. A low-therapeutic dose (10^5 cells/kg) of HO-1+/GFP+ (HO-1) or GFP+ (GFP) CD34+ cells was locally injected into the border zone after complete ligation of the left coronary artery in 8-week-old, male nude mice (saline control: 2x 15 μl). At day 28, LV ejection fraction of mice treated with HO-1 over-expressing CD34+ cells was significantly improved (fractional shortening: saline 19±2%, HO-1 30±1%, GFP 24±1%; n=6-8/group, P&lt;0.01). This functional improvement can be explained by a preservation of the border-zone: the number of lectin+ capillaries was increased (lectin staining: saline 73±5/hpf, HO-1 99±4/hpf, GFP 79±7/hpf; n=7-8/group, P&lt;0.01) with the use of HO-1 modified CD34+ cells while lectin+/alpha-smooth-muscle actin+ structures indicative for resistance vessels remained unchanged (P=ns). Apoptosis of resident myocardial cells was attenuated (TUNEL staining: saline 69±5/hpf, HO-1 31±3, GFP 54±9, P&lt;0.05). As a result, the infarct size in mice treated with HO-1 modified cells was reduced (Masson-trichrome staining: saline 39±1%, HO-1 36±2%, GFP 42±1%; n=6-8/group, P&lt;0.05). Ongoing studies are addressing the underlying mechanism(s) on cellular basis as well as the clinical relevance. Conclusion: HO-1 gene modification enhances the therapeutic potency of CD34+ in ischemic tissue repair.
Analysis of the high affinity IgE receptor genes reveals epistatic effects of <i>FCER1A</i> variants on eczema risk
Authors: J. M. Mahachie John, H. Baurecht, E. Rodríguez, A. Naumann, S. Wagenpfeil, N. Klopp, M. Mempel, N. Novak, T. Bieber, H.‐E. Wichmann, J. Ring, T. Illig, T. Cattaert, K. Van Steen, S. Weidinger
Journal: Allergy (2009)

High levels of total and allergen-specific IgE levels are a key feature in allergic diseases. The high-affinity receptor for IgE, which is composed of one alpha (FCER1A), one beta (FCER1B), and two gamma (FCER1G) subunits, represents the central receptor of IgE-induced reactions. In a genome-wide association scan, we recently identified associations between functional FCER1A variants and total serum IgE levels. Previous studies had reported linkage and association of FCER1B variants with IgE and atopic traits. The FCER1G gene has not yet been investigated with regard to atopy. Filaggrin (FLG) is the strongest known risk gene for eczema, in particular the allergic subtype of eczema.We investigated the association of FCER1A, FCER1B, and FCER1G variants with IgE in a large population-based cohort (n = 4261) and tested for epistatic effects using the model-based multifactor dimensionality reduction (MB-MDR) method. In addition, we investigated a potential interaction between FLG and FCER1A variants in a large collection of eczema cases (n = 1018) and population controls.Three strongly correlated FCER1A polymorphisms were significantly associated with total and specific IgE levels as well as allergic sensitization. No associations were seen for FCER1B and FCER1G. After adjustment for FLG effects, a significant epistatic effect of the FCER1A variants rs10489854 and rs2511211 on eczema risk was detected.These results suggest that FCER1A variants by themselves and in combination influence IgE levels and act synergistically to influence eczema risk.