tbuckley/cabot-search huggingface dataset:
Abstract LB-386: Targeting of induced cancer stem cells with iniparib in combination with carboplatin and gemcitabine
Authors: Valeria Ossovskaya, Erica Canino, Gnanaratnam Giritharan, Kyung-Ah Kim, Dusko Ilic, Ana Krtolica
Journal: Cancer Research (2011)

Abstract BACKGROUND: Mounting evidence exists that human breast cancers include a stem-like cell population with self-renewing, tumorigenic properties. This population of cells, known as cancer stem cells (CSCs) or tumor-initiating cells, shares phenotypic characteristics with embryonic stem cells (ESCs), including activation of certain developmental pathways, and is resistant to many anticancer therapies. Distinguishing features of stem cells include active DNA repair and resistance to apoptosis, which enable their survival in the presence of conventional cytotoxic and cytostatic therapies that target actively proliferating cells. Identification of pharmaceuticals that preferentially target CSCs represents a novel strategy in modern drug discovery and development. We investigated whether treatment with iniparib (BSI-201) can potentiate the anti-proliferative effects of gemcitabine and carboplatin in CSCs. METHODS: A multi-stage stem cell carcinogenesis model that mirrors the natural progression of carcinogenesis was previously developed using in vitro and in vivo selection of mutated ESCs, which exhibit specific tumor-initiating and cancer stem cell-associated behaviors (SLL Sciences). These induced CSCs (iCSCs) were treated with iniparib (3.7, 11, 33, or 100 μM), gemcitabine (1.5 nM), carboplatin (10 μM), or gemcitabine + carboplatin for 72 hours, and effects on iCSC proliferation were evaluated using an ELISA-based bromodeoxyuridine (BrdU) assay and an ATP-based detection assay for measuring cellular metabolism. Effects of iniparib and/or gemcitabine on DNA damage were evaluated by immunofluorescence staining of iCSC using antibodies against γH2AX (a marker of double strand DNA breaks) at 24 hours after treatment. RESULTS: Treatment with iniparib alone resulted in a dose-dependent decrease in cellular proliferation and metabolism, with the IC50 established at 60 μM. Iniparib (60 μM), gemcitabine (1.5 nM), and carboplatin (10 μM) each induced &amp;gt;50% reduction in iCSC proliferation; addition of iniparib to gemcitabine resulted in an 80% reduction in BrdU incorporation compared with gemcitabine alone (P = 0.027). To assess iniparib-associated DNA damage, γH2AX foci were quantified in &amp;gt; 300 cells for each treatment combination. Cells treated with iniparib, gemcitabine, or iniparib + gemcitabine demonstrated 3.7-, 6.8-, and 8.8-fold increases in γH2AX foci, respectively, compared with untreated control (P &amp;lt; 0.005). CONCLUSIONS: These findings demonstrate that iniparib increases the effects of gemcitabine in terms of antiproliferative activity and DNA damage in this CSC model. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-386. doi:10.1158/1538-7445.AM2011-LB-386
100 years of Rous sarcoma virus
Authors: Robin A. Weiss, Peter K. Vogt
Journal: The Journal of Experimental Medicine (2011)

The discovery of Rous sarcoma virus, which was reported by Peyton Rous in the Journal of Experimental Medicine 100 years ago, opened the field of tumor virology. It showed that some cancers have infectious etiology, led to the discovery of oncogenes, and laid the foundation for the molecular mechanisms of carcinogenesis. Rous spent his entire research career at The Rockefeller Institute, and he was the JEM’s longest serving editor. Here, we comment briefly on the life of this remarkable scientist and on the importance of his discoveries.
Prognosis of Pleural Effusion
Authors: P. L. Deshmukh
Journal: BMJ (1947)

Many Russians in my care during the war, even those who had been wounded before capture, awaited their return home with extreme terror.Why ?I agree that social security, whatever it may mean, has tended to reduce effort for the reasons advanced by Dr. Crichton-Miller.Many economists suggest that the economic basis for this social security is crumbling, so we may soon see the next phase developing.-Iam, etc.,
Leukemia mortality by cell type in petroleum workers with potential exposure to benzene.
Authors: G K Raabe, O Wong
Journal: Environmental Health Perspectives (1996)

Workers in the petroleum industry are potentially exposed to a variety of petrochemicals, including benzene or benzene-containing liquids. Although a large number of studies of petroleum workers have been conducted to examine leukemia and other cancer risks, few existing studies have investigated cell-type-specific leukemias. One of the major reasons for the lack of cell-type-specific analysis was the small number of deaths by cell type in individual studies. In the present investigation, all cohort studies of petroleum workers in the United States and the United Kingdom were combined into a single database for cell-type-specific leukemia analysis. The majority of these workers were petroleum refinery employees, but production, pipeline, and distribution workers in the petroleum industry were also included. The combined cohort consisted of more than 208,000 petroleum workers, who contributed more than 4.6 million person-years of observation. Based on a meta-analysis of the combined data, cell-type-specific leukemia risks were expressed in terms of standardized mortality ratios (meta-SMRs). The meta-SMR for acute myeloid leukemia was 0.96. The lack of an increase of acute myeloid leukemia was attributed to the low levels of benzene exposure in the petroleum industry, particularly in comparison to benzene exposure levels in some previous studies of workers in other industries, who had been found to experience an increased risk of acute myeloid leukemia. Similarly, no increase in chronic myeloid, acute lymphocytic, or chronic lymphocytic leukemias was found in petroleum workers (meta-SMRs of 0.89, 1.16, and 0.84, respectively). Stratified meta-analyses restricted to refinery studies or to studies with at least 15 years of follow-up yielded similar results. The findings of the present investigation are consistent with those from several recent case-control studies of cell-type-specific leukemia. Patterns and levels of benzene exposure in the petroleum industry are reviewed. The results of the present epidemiologic investigation are discussed in conjunction with recent advances in leukemogenesis from other scientific disciplines.
Cumulative Lead Dose and Cognitive Function in Adults: A Review of Studies That Measured Both Blood Lead and Bone Lead
Authors: Regina A. Shih, Howard Hu, Marc G. Weisskopf, Brian S. Schwartz
Journal: Environmental Health Perspectives (2006)

We review empirical evidence for the relations of recent and cumulative lead dose with cognitive function in adults.A systematic search of electronic databases resulted in 21 environmental and occupational studies from 1996 to 2006 that examined and compared associations of recent (in blood) and cumulative (in bone) lead doses with neurobehavioral outcomes.Data were abstracted after consideration of exclusion criteria and quality assessment, and then compiled into summary tables.At exposure levels encountered after environmental exposure, associations with bio-markers of cumulative dose (mainly lead in tibia) were stronger and more consistent than associations with blood lead levels. Similarly, in studies of former workers with past occupational lead exposure, associations were also stronger and more consistent with cumulative dose than with recent dose (in blood). In contrast, studies of currently exposed workers generally found associations that were more apparent with blood lead levels; we speculate that the acute effects of high, recent dose may mask the chronic effects of cumulative dose. There is moderate evidence for an association between psychiatric symptoms and lead dose but only at high levels of current occupational lead exposure or with cumulative dose in environmentally exposed adults.
Anti-idiotype antibodies may do what vaccines don't
Authors: Kathryn Simmons
Journal: JAMA (1986)

A new type of vaccine that may prove useful for protecting humans against a variety of diseases is being developed in experimental animals and reportedly has produced immunity against numerous viruses, bacteria, and parasites. Reports say that, with this vaccine (and unlike conventional vaccines), no pathogenic antigen is needed to stimulate the host's immunity. Instead, this approach enlists "anti-idiotype antibodies." An idiotype—the site where an antigen binds to an antibody—can itself act as an antigen to stimulate antibody production. Antibodies that are stimulated by idiotypes are called anti-idiotype antibodies. If the idiotype could be represented by a domino with, say, four dots, the antigen might be a four-two combination and the anti-idiotype antibody might be a four-three. Both will hook up with the idiotype even though they are different "molecules." It is debatable how far in the future this technique will be tried in humans. Some researchers suggest it will
Sites of dermatitis in a patch test population: hand dermatitis is associated with polysensitization
Authors: B.C. Carlsen, K.E. Andersen, T. Menné, J.D. Johansen
Journal: British Journal of Dermatology (2009)

Sites of dermatitis in larger series of contact allergic patients are rarely reported. Increased risk of polysensitization has been linked only to stasis dermatitis and leg ulcers. However, a large proportion of polysensitized individuals may have dermatitis in other skin areas.To examine the site of dermatitis at time of first appearance in contact allergic individuals with special focus on the distribution of dermatitis in polysensitized individuals and to examine if widespread dermatitis is more frequent in polysensitized than in single/double-sensitized patients.A matched case-control study was carried out including 394 polysensitized and 726 single/double-sensitized patients who responded to a postal questionnaire. All subjects were recruited from a hospital patch test population.The hands were the most frequent and the anogenital region was the least frequent skin area affected with dermatitis. Dermatitis on the hands/wrists [odds ratio (OR) 1.58], in the armpits (OR 1.56) and on the back (OR 1.91) was positively associated with polysensitization. The hands were the only skin area with dermatitis which maintained the association to polysensitization in two subpopulations consisting of, respectively, individuals with and without atopic eczema. Dermatitis on the scalp was negatively associated with polysensitization (OR 0.66) primarily for individuals without atopic eczema. The dermatitis did not seem to be more widespread in polysensitized compared with single/double-sensitized patients.Special awareness in patients with hand dermatitis seems justified either to prevent development of multiple contact allergies or to document polysensitization as an aetiological factor.
How Good Is “Good Enough”?
Authors: Thoralf M. Sundt
Journal: JAMA Surgery (2013)

The safety and durability of endoscopic vein graft harvest in coronary artery bypass graft (CABG) surgery has recently been called into question.To compare the long-term outcomes of endoscopic vs open vein-graft harvesting for Medicare patients undergoing CABG surgery in the United States.An observational study of 235 394 Medicare patients undergoing isolated CABG surgery between 2003 and 2008 at 934 surgical centers participating in the Society of Thoracic Surgeons (STS) national database. The STS records were linked to Medicare files to allow longitudinal assessment (median 3-year follow-up) through December 31, 2008.All-cause mortality. Secondary outcome measures included wound complications and the composite of death, myocardial infarction, and revascularization.Based on Medicare Part B coding, 52% of patients received endoscopic vein-graft harvesting during CABG surgery. After propensity score adjustment for clinical characteristics, there were no significant differences between long-term mortality rates (13.2% [12 429 events] vs 13.4% [13 096 events]) and the composite of death, myocardial infarction, and revascularization (19.5% [18 419 events] vs 19.7% [19 232 events]). Time-to-event analysis for those patients receiving endoscopic vs open vein-graft harvesting revealed adjusted hazard ratios (HRs) of 1.00 (95% CI, 0.97-1.04) for mortality and 1.00 (95% CI, 0.98-1.05) for the composite outcome. Endoscopic vein-graft harvesting was associated with lower harvest site wound complications relative to open vein-graft harvesting (3.0% [3654/122 899 events] vs 3.6% [4047/112 495 events]; adjusted HR, 0.83; 95% CI, 0.77-0.89; P < .001).Among patients undergoing CABG surgery, the use of endoscopic vein-graft harvesting compared with open vein-graft harvesting was not associated with increased mortality.
Trypsinogen activation peptides (TAP) concentrations in the peritoneal fluid of patients with acute pancreatitis and their relation to the presence of histologically confirmed pancreatic necrosis.
Authors: D I Heath, C Wilson, A M Gudgeon, A Jehanli, A Shenkin, C W Imrie
Journal: Gut (1994)

This study measured the volume and colour, as well as concentrations of trypsinogen activation peptides (TAP) in the peritoneal fluid of 22 patients with acute pancreatitis and related these findings to the presence of pancreatic necrosis. Nine patients had a severe attack with histologically confirmed pancreatic necrosis, seven a severe attack without confirmed necrosis, and six a mild attack, also without confirmed necrosis. A free fluid volume > 20 ml or free fluid colour > grade 5 on the Leeds chart, or both detected histologically confirmed pancreatic necrosis with a sensitivity of 100% and specificity of 31%. A total peritoneal fluid TAP concentration of > or = nmol detected histologically confirmed pancreatic necrosis with a sensitivity of 89% and specificity of 85%, figures comparable with contrast enhanced computed tomography. These findings suggest that the measurement of peritoneal fluid TAP concentrations can detect effectively histologically confirmed pancreatic necrosis and that such measurements may prove useful in the selection of patients for surgery.
Receptor for Activated C-Kinase 1, a Novel Interaction Partner of Type II Bone Morphogenetic Protein Receptor, Regulates Smooth Muscle Cell Proliferation in Pulmonary Arterial Hypertension
Authors: Anna Zakrzewicz, Matthias Hecker, Leigh M. Marsh, Grazyna Kwapiszewska, Bozena Nejman, Lu Long, Werner Seeger, Ralph T. Schermuly, Nicholas W. Morrell, Rory E. Morty, Oliver Eickelberg
Journal: Circulation (2007)

Background— Pulmonary arterial hypertension (PAH) is characterized by selective elevation of pulmonary arterial pressure. The pathological hallmark of PAH is the narrowing of pulmonary arterioles secondary to endothelial cell dysfunction and smooth muscle cell proliferation. Heterozygous mutations in BMPR2 , encoding the type II bone morphogenetic protein receptor (BMPRII), were identified in PAH, suggesting that alterations to BMPRII function are involved in disease onset and/or progression. Methods and Results— We identified the receptor for activated C-kinase (RACK1) as a novel interaction partner of BMPRII by yeast 2-hybrid analyses using the kinase domain of BMPRII as a bait. Glutathione-S-transferase pull-down and coimmunoprecipitation confirmed the interaction of RACK1 with BMPRII in vitro and in vivo. RACK1–BMPRII interaction was reduced when kinase domain mutations occurring in patients with PAH were introduced to BMPRII. Immunohistochemistry of lung sections from PAH and control patients and immunofluorescence analysis of primary pulmonary arterial smooth muscle cells demonstrated colocalization of BMPRII and RACK1 in vivo. Quantitative reverse-transcription polymerase chain reaction and Western blot analysis showed significant downregulation of RACK1 expression in the rat model of monocrotaline-induced PAH but not in pulmonary arterial smooth muscle cells from PAH patients. Abrogation of RACK1 expression in pulmonary arterial smooth muscle cells led to decreased Smad1 phosphorylation and increased proliferation, whereas overexpression of RACK1 led to increased Smad1 phosphorylation and decreased proliferation. Conclusions— RACK1, a novel interaction partner of BMPRII, constitutes a new negative regulator of pulmonary arterial smooth muscle cell proliferation, suggesting a potential role for RACK1 in the pathogenesis of PAH.
THE NEW UNITED STATES PHARMACOPEIA.
Authors: JOSEPH P. REMINGTON
Journal: JAMA (1903)

The numerous inquiries from all parts of the United States with regard to the appearance of the new Pharmacopeia would seem to require at this time a communication as to the progress of the revision, and the writer takes this opportunity of stating that the work is progressing favorably. On account of the death of the distinguished chairman of the Committee of Revision, Dr. Charles Rice, May 13, 1901, revision was necessarily retarded; nevertheless, the subcommittees to whom the details had been assigned have performed a large amount of work. The twenty-six members from all sections of our country, composing the Committee of Revision, were selected by the United States Pharma-copeial Convention in May, 1900, to complete the work of revision, because of their fitness for their work, and necessarily the majority are specialists in the various departments of therapeutics, pharmacognosy, chemistry, botany, analytical chemistry and various other departments
Risks of Anticoagulant Therapy in Pregnant Women with Artificial Heart Valves
Authors: Ignacio Iturbe-Alessio, María del Carmen Fonseca, Osvaldo Mutchinik, Miguel Angel Santos, Alejandro Zajarías, Eduardo Salazar
Journal: New England Journal of Medicine (1986)

In an attempt to identify the best treatment for pregnant women with cardiac-valve prostheses who are receiving oral anticoagulants, we studied 72 pregnancies prospectively. In 23 pregnancies (Group I), the coumarin derivative acenocoumarol was discontinued and the patients received 5,000 U of subcutaneous heparin every 12 hours from the 6th to the 12th week of gestation, in 12 pregnancies (Group II), heparin was not substituted for the coumarin derivative until after the 7th week, and in 37 pregnancies, detected after the first trimester (Group III), the coumarin derivative was given throughout gestation. In most patients heparin was again substituted for the oral anticoagulant after the 38th week. Three mothers had thrombosis of a tilting-disk mitral prosthesis (two cases were fatal) during heparin treatment. No differences were found in the rates of spontaneous abortion in the three groups. Coumarin embryopathy occurred in 25 percent and 29.6 percent of the pregnancies in Groups II and III, respectively. We conclude that in the second and third trimesters of pregnancy, coumarin derivatives provide effective protection against thromboembolism while causing few fetopathic effects, but that these agents are contraindicated from the 6th to the 12th weeks of gestation. Low-dose heparin does not protect against prosthetic-valve thrombosis, and the possibility that a larger dose might be more effective requires further exploration.
Differences in World Responses to Natural Disasters and Complex Emergencies
Authors: Paul B. Spiegel
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
Unrefined Antihistamine Lode
Authors: F. J. Ingelfinger
Journal: New England Journal of Medicine (1974)

A few months ago, an "Old Histamine Prospector" got all excited when he saw gold in them thar antihistamine hills. Indeed, he had maps showing where a rich lode of a new type of histamine antagonists might be found — agents that could inhibit gastric secretion by blocking a second type of histamine receptor symbolized by "H2".1 Equally jubilant on hearing of the discovery were many doctors and patients, the former weary of treating duodenal ulcers with dietary and antacid regimens, and the latter even more weary of observing them. But their ardor has been chilled by the . . .
miR-31 Dysregulation in Cystic Fibrosis Airways Contributes to Increased Pulmonary Cathepsin S Production
Authors: Sinéad Weldon, Paul McNally, Danny F. McAuley, Irene K. Oglesby, Christine L. Wohlford-Lenane, Jennifer A. Bartlett, Christopher J. Scott, Noel G. McElvaney, Catherine M. Greene, Paul B. McCray, Clifford C. Taggart
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Cathepsin S (CTSS) activity is increased in bronchoalveolar lavage (BAL) fluid from patients with cystic fibrosis (CF). This activity contributes to lung inflammation via degradation of antimicrobial proteins, such as lactoferrin and members of the β-defensin family.In this study, we investigated the hypothesis that airway epithelial cells are a source of CTSS, and mechanisms underlying CTSS expression in the CF lung.Protease activity was determined using fluorogenic activity assays. Protein and mRNA expression were analyzed by ELISA, Western blotting, and reverse-transcriptase polymerase chain reaction.In contrast to neutrophil elastase, CTSS activity was detectable in 100% of CF BAL fluid samples from patients without Pseudomonas aeruginosa infection. In this study, we identified epithelial cells as a source of pulmonary CTSS activity with the demonstration that CF airway epithelial cells express and secrete significantly more CTSS than non-CF control cells in the absence of proinflammatory stimulation. Furthermore, levels of the transcription factor IRF-1 correlated with increased levels of its target gene CTSS. We discovered that miR-31, which is decreased in the CF airways, regulates IRF-1 in CF epithelial cells. Treating CF bronchial epithelial cells with a miR-31 mimic decreased IRF-1 protein levels with concomitant knockdown of CTSS expression and secretion.The miR-31/IRF-1/CTSS pathway may play a functional role in the pathogenesis of CF lung disease and may open up new avenues for exploration in the search for an effective therapeutic target.