tbuckley/cabot-search huggingface dataset:
Bronchoscopic surfactant administration in patients with severe adult respiratory distress syndrome and sepsis.
Authors: D Walmrath, A Günther, H A Ghofrani, R Schermuly, T Schneider, F Grimminger, W Seeger
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

The present study was performed on 10 patients with severe adult respiratory distress syndrome (ARDS), all suffering from sepsis (mean lung injury score [LIS] (1): 3.25 +/- 0.1; duration of mechanical ventilation upon study entry: 3.1 +/- 0.6 d). Ex vivo analysis of the alveolar surfactant system, obtained by bronchoalveolar lavage (BAL), showed severe impairment of surfactant function. Three hundred milligrams of natural surfactant/kg body weight (Alveofact) was delivered bronchoscopically in separate doses to each segment of both lungs. This caused an immediate increase in PaO2/FlO2 from 85 +/- 7 mm Hg to 200 +/- 20 mm Hg (p < 0.001), mainly due to a decrease in shunt flow (42 +/- 4 to 20 +/- 2% [p < 0.001]). Reanalysis of the alveolar surfactant showed that its function was significantly improved. In five patients the increase in arterial oxygenation was partially lost within the next few hours, and a second dose of 200 mg/kg surfactant was applied 18 to 24 h later, again increasing PaO2/FlO2 values. Eight patients survived the subsequent 14-d observation period with progressive improvement of gas exchange, and five patients were definitely weaned from the respirator. All fatalities were due to non-respiratory causes. We conclude that the bronchoscopic application of a high dose of surfactant aimed at overcoming inhibitory factors in the alveolar space of these patients, may offer a feasible and safe approach to improving gas exchange in severe ARDS.
Abstract 1087: The role of fibroblast growth factor 9 in the recurrence after radical prostatectomy
Authors: Jun Teishima, Tetsutaro Hayashi, Koichi Shoji, Akio Matsubara
Journal: Cancer Research (2011)

Abstract Introduction and Objectives: The aim of this study was to investigate the role of fibroblast growth factor 9 (FGF9) in the recurrence after radical prostatectomy. Methods: Immunohistochemical staining using anti-FGF9 antibody was performed for tissues derived from radical prostatectomy in 133 male patients. Cell viability, apoptosis and invasion of LNCaP and androgen-independent LNCaP (AI-LNCaP) cells were assessed with the MTT assay, Apopercentage apoptosis assay and Matrigel invasion assay, respectively, in the presence or absence of treatment with recombinant FGF9 or anti-FGF9 neutralizing antibody. Results: In immunohistochemical staining, FGF9-positive cells were detected in 20 samples. In cases with a Gleason score of 8 or higher, the incidence of cases with FGF9-positive cells was 34.2%, which was significantly higher than that for those with Gleason scores of 7 or lower (7.3%, p=0.0003), respectively. The 3-year biochemical relapse-free survival rate in cases with FGF9-positive cells was 17.5%, which was significantly lower than that in cases in which FGF9-positive cells were not detectable (76.6%, p&amp;lt;0.0001). In androgen-depleted medium, the cell viability of LNCaP was significantly lower than that of AI-LNCaP, and was enhanced to the same level by treatment with recombinant FGF9. Invasion was significantly enhanced and apoptosis by androgen deprivation was significantly suppressed by treatment of LNCaP cells with recombinant FGF9. Furthermore, these effects were significantly suppressed by treatment with anti-FGF9 neutralizing antibody. Conclusions: These results indicate that FGF9 contributes to postoperative recurrence of prostate cancer through stimulation of cell proliferation and invasion, and induction of an anti-apoptotic effect. 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 1087. doi:10.1158/1538-7445.AM2011-1087
Dipeptidylpeptidase 4 negatively regulates colony-stimulating factor activity and stress hematopoiesis
Authors: Hal E Broxmeyer, Jonathan Hoggatt, Heather A O'Leary, Charlie Mantel, Brahmananda R Chitteti, Scott Cooper, Steven Messina-Graham, Giao Hangoc, Sherif Farag, Sara L Rohrabaugh, Xuan Ou, Jennifer Speth, Louis M Pelus, Edward F Srour, Timothy B Campbell
Journal: Nature Medicine (2012)
Interferon Regulatory Factor 1 Marks Activated Genes and Can Induce Target Gene Expression in Systemic Lupus Erythematosus
Authors: Zhe Zhang, Lihua Shi, Li Song, Elshaddai Ephrem, Michelle Petri, Kathleen E. Sullivan
Journal: Arthritis & Rheumatology (2014)

Interferon regulatory factor 1 (IRF-1) mediates both induction of interferons (IFNs) and responses to type I IFNs. It has been implicated as a critical mediator of inflammation in murine lupus models. In a previous study of chromatin modifications in monocytes from patients with systemic lupus erythematosus (SLE), IRF-1 was implicated as being associated with increased histone acetylation in this disease. The present study was undertaken to directly investigate IRF-1 binding sites on chromatin.Cells from 9 female SLE patients and 7 female controls were examined. Monocytes were purified from peripheral blood and subjected to library preparation using a validated antibody to IRF-1. IRF-1 binding sites on chromatin were identified by chromatin immunoprecipitation followed by sequencing. The effect of IRF-1 on target gene expression was confirmed using an overexpression system in cell lines, and coimmunoprecipitation was used to identify protein interactions.IRF-1 binding around transcribed regions was increased in SLE patient monocytes, but histone modifications at potential IRF-1 binding sites without detectable IRF-1 binding were increased as well. Overexpression of IRF-1 was sufficient to drive transcription of target genes. IRF-1 overexpression was also able to alter histone modifications at a focus set of target genes, and treatment with an IRF-1 inhibitor reduced both expression and histone modifications at target genes. IRF-1 was found to interact with a select set of histone-modifying enzymes and other transcription factors.IRF-1 is an important signaling protein in the interferon pathway. It not only activates gene expression as a transcription factor, but may perpetuate disease by leading to a dysregulated epigenome.
Medical Management of Vulnerable and Underserved Patients: Principles, Practice, and Populations
Authors: Jessica Gregg
Journal: JAMA (2007)

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
The Skin Cancer Chemotherapeutic Agent Ingenol-3-Angelate (PEP005) Is a Substrate for the Epidermal Multidrug Transporter (ABCB1) and Targets Tumor Vasculature
Authors: Luowei Li, Suneet Shukla, Andrew Lee, Susan H. Garfield, David J. Maloney, Suresh V. Ambudkar, Stuart H. Yuspa
Journal: Cancer Research (2010)

Ingenol-3-angelate (Ing3A), extracted from Euphorbia peplus, is currently in clinical trials for eradicating basal cell carcinoma, actinic keratosis, and squamous cell carcinoma (SCC) in situ by topical application. Although structurally related to phorbol esters and a protein kinase C activator, topical Ing3A, but not phorbol 12-myristate 13-acetate (PMA), inhibited the growth of subcutaneous tumors derived from PAM212 (mouse SCC) and B16 (mouse melanoma). Ing3A and PMA both induced acute neutrophilic inflammation on mouse skin, but only Ing3A caused subcutaneous hemorrhage and vascular damage. Both Ing3A and PMA activated extracellular signal-regulated kinase 1/2 (ERK1/2) in epidermis, but Ing3A also activated ERK1/2 in skin dermal fibroblasts and endothelial cells. Pretreatment with topical cyclosporin A (CsA), verapamil, or XR9576, modulators of P-glycoprotein (P-gp), prevented Ing3A-induced hemorrhage but not neutrophil infiltration. CsA also impaired the anticancer activity of Ing3A, whereas the anti-inflammatory dexamethasone did not. Ing3A, but not PMA, blocked photoaffinity labeling of human P-gp with [(125)I]iodoaryazidoprazosin and inhibited P-gp-mediated drug resistance to HCT-15 cells. The intracellular levels of Ing3A were significantly lower in P-gp-expressing cells, and treatment with XR9576 increased the levels to those of cells that do not express P-gp, showing that Ing3A binds to and is transported by P-gp. Taken together, our results suggest that P-gp-mediated absorptive transport, dermal penetration, and vascular damage contribute to the anticancer activity of Ing3A in vivo.
Selective Renal Artery Embolization
Authors: Robert W. Rand
Journal: JAMA (1977)

<h3>To the Editor.—</h3> I was pleased to see the article on selective renal artery embolization in the treatment of metastatic sarcoma with hematuria by Drs Mariasoosai, Wilson, and Gonick (237:363, 1977). The authors point out that A. F. Lalli<sup>1</sup>and associates were the first to produce infarction of the kidney and lung in dogs using modified dextran. They further cite the treatment of renal adenocarcinoma by embolic occlusion of renal circulation as reported in 1973.<sup>2</sup> However, they neglect to cite the work of Turner and co-workers,<sup>3</sup>which appeared in 1975 regarding this same general technique for the treatment of renal carcinoma and other types of tumors. The authors say that nephrectomy and anesthesia were avoided by the use of the embolization technique. However, the absorbable gelatin they used will not affect the entire vascular tree of that tumor because it will not penetrate to the level of
Whose Death Is It, Anyway
Authors: Jeffrey E. Salon
Journal: Annals of Internal Medicine (1997)

Letters1 April 1997Whose Death Is It, AnywayJeffrey E. Salon, MDJeffrey E. Salon, MDColumbus, OH 43213Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-126-7-199704010-00019 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The article by Gilligan and Raffin [1] and the essay by Hansot [2] highlight a troubling but unfortunately too-frequent occurrence in hospitals today. Gilligan and Raffin express the politically correct position that the physicians caring for Ms. Hansot were motivated by their “preoccupation with the preservation of life.” References to the intensive care unit as a place where the patient may be intubated and sedated and “in which the physician–patient relationship may be reduced to a daily 2-minute physical examination” do not support this viewpoint. Rounds this brief cannot represent a desire to preserve life but rather ...References1. Gilligan T, Raffin TA. Whose death is it, anyway? Ann Intern Med. 1996; 125:137-41. Google Scholar2. Hansot E. A letter from a patient's daughter. Ann Intern Med. 1996; 125:149-51. Google Scholar3. Weil MH, Shoemaker WC, Rackow EC. Competent and continuing care of the critically ill. Crit Care Med. 1988; 16:298. Google Scholar Author, Article, and Disclosure InformationAuthors: Jeffrey E. Salon, MDAffiliations: Columbus, OH 43213 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1997Volume 126, Issue 7Page: 585KeywordsCaregiversChartsCritical careFearIntensive care unitsNursesResearch laboratories ePublished: 15 August 2000 Issue Published: 1 April 1997 Copyright & PermissionsCopyright © 1997 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
GE-03 * GENOMIC CHARACTERIZATION OF SURVIVAL OUTLIERS IN GLIOBLASTOMA MULTIFORME
Authors: M. Berens, B. Armstrong, S. Peng, J. Ross, B. Salhia, S. Byron, S. Virk, H. Dhruv, N. Tran, A. Sloan, Q. Ostrom, J. Barnholtz-Sloan
Journal: Neuro-Oncology (2014)

Despite the general poor prognosis for patients with GBM, a proportion survives well beyond the median survival of 12-14 months following diagnosis. To elucidate molecular features associated with disproportionately protracted survival, we conducted deep genomic comparative analysis of a cohort of patients receiving standard therapy (surgery plus concurrent radiation and temozolomide) wherein "GBM outliers" were identified: patients who responded (long-term survivor, LTS) versus those who failed rapidly (short-term survivor, STS). The datasets enabled interrogation for signatures indicative of tumor vulnerability. Whole genomic, epigenetic and transcriptomic analyses of 18 patients, including 8 LTS with an average 30 months overall survival (OS) and 10 STS with an average of 7 months OS were performed to capture single nucleotide variants (SNVs), indels, translocations, intra-chromosomal rearrangements, copy number variants, along with DNA methylation and mRNA expression. LTS and STS cases showed equal proportion of 7p11.2 (EGFR) amplification and 9p21.3 (CDKN2A) deletion. However, LTS GBM showed frequent chromosomal gains in 4q12 (PDGFRA and KIT) and 12q14.1 (CDK4) and deletion in 19q13.33 (BAX, BCAT2 and CD33), whereas, STS GBM showed frequent deletion in 9p11.2 (FOXD4L2 and AQP7P3) and 22q11.21 (HIC2). In addition, LTS GBM showed a 2-fold increased chromosomal instability as compared to STS GBM. By gene expression analysis, supervised clustering using the CIN70 chromosomal instability signature showed a decreased expression of these markers in LTS GBM, corroborating the genomic analysis. Finally, integrating DNA methylation data with gene expression revealed in STS GBM hypermethylation and downregulation of EPHA3, MEG, and PPP1R9A, linked to defective cell migration and adhesion. In contrast, LTS GBM showed hypomethylation and an increased gene expression of KIT. We posit that genomic instability predicts vulnerability of GBM to standard therapy and coupled with genetic and epigenetic signatures may identify patients where front-line entry into alternative, targeted regimens would be a preferred, more-efficacious management.
Control of Surgical Incontinence by Means of the Portsmouth Valved Catheter
Authors: J. J. Foley
Journal: BMJ (1959)

HYPERCALCAEMIAThe electrocardiographic changes are not those usually associated with hypercalcaemia.The pattern does, however, closely resemble that found in some patients suffering from vitamin-D poisoning.Such electrocardiographic changes may possibly result from lesions of the myocardium or coronary arteries.The possibility exists that residual coronary artery damage from idiopathic hypercalcaemia in early childhood may persist into later life.I am indebted to Professor Stanley Graham for permission to study patients who were under his care and for his
Arsenic-Transformed Malignant Prostate Epithelia Can Convert Noncontiguous Normal Stem Cells into an Oncogenic Phenotype
Authors: Yuanyuan Xu, Erik J. Tokar, Yang Sun, Michael P. Waalkes
Journal: Environmental Health Perspectives (2012)

Cancer stem cells (CSCs) are likely critical to carcinogenesis, and, like normal stem cells (NSCs), are affected by microenvironmental factors. Malignant cells release extracellular factors, modifying tumor behavior. Inorganic arsenic, a human carcinogen, is associated with an overproduction of CSCs in various model systems of carcinogenesis.We aimed to determine if NSCs are influenced by nearby arsenic-transformed malignant epithelial cells (MECs) as a possible factor in arsenic-associated CSC overabundance.Transwell noncontact co-culture allowed the study of the effects of non-contiguous, arsenic-transformed prostate MECs on the isogenic human prostate NSC line, WPE-stem. Cancer phenotype was assessed by evaluating secreted matrix metalloproteinases (MMPs), invasiveness, colony formation, and spheroid formation. Gene expression was assessed at the protein (Western blot) or mRNA (real-time reverse transcription-polymerase chain reaction) levels.Noncontact co-culture of MECs and NSCs rapidly (≤ 3 weeks) caused hypersecretion of MMPs and marked suppression of the tumor suppressor gene PTEN in NSCs. NSCs co-cultured with MECs also showed increased invasiveness and clonogenicity and formed more free-floating spheroids and highly branched ductal-like structures in Matrigel, all typical for CSCs. MEC co-culture caused dysregulated self-renewal and differentiation-related gene expression patterns and epithelial-to-mesenchymal transition in NSCs consistent with an acquired cancer phenotype. Interleukin-6 (IL-6), a cytokine involved in tumor microenvironment control, was hypersecreted by MECs, and IL-6 exposure of NSCs resulted in the duplication of several responses in NSCs of conversion to CSCs via MEC co-culture (e.g., MMP hypersecretion, decreased PTEN).Arsenic-transformed MECs recruit nearby NSCs into a cancer phenotype, thereby potentially increasing CSC number. This may be a factor in arsenic-induced CSC overabundance seen in multiple model systems.
NOTES ON THE ETIOLOGY OF DYSENTERY
Authors: C. J. Martin, F. E. Williams
Journal: BMJ (1917)

The relevance of double-strand DNA repair genes has been demonstrated in several tumours. The main aim of this study was to analyse the expression of the heterodimers Ku70 and Ku80, building regulatory subunits of the DNA-dependent protein kinase in 40 oral carcinomas. Ku70 expression was found in 87.5% of grade 1 and grade 3 tumours and in 82.9% of grade 2 carcinomas. Ku80 presence was noted in 87.5% of grade 1 tumours, 82.9% of grade 2 tumours and in all grade 3 tumours. Ku70-positive cells were present in 90.5% of tumours without and in 80% of tumours with lymphatic metastases. A similar relationship was found for Ku80 expression. Additionally, the expression of Ku70 was highly significantly related to smoking habits. Our results demonstrated that defects of DNA double-strand repair genes play an important role in the tumour progression of oral carcinomas.
The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life.
Authors: D J Barker, C Osmond, S J Simmonds, G A Wield
Journal: BMJ (1993)

OBJECTIVE--To determine how fetal growth is related to death from cardiovascular disease in adult life. DESIGN--A follow up study of men born during 1907-24 whose birth weights, head circumferences, and other body measurements were recorded at birth. SETTING--Sheffield, England. SUBJECTS--1586 Men born in the Jessop Hospital. MAIN OUTCOME MEASURE--Death from cardiovascular disease. RESULTS--Standardised mortality ratios for cardiovascular disease fell from 119 in men who weighed 5.5 pounds (2495 g) or less at birth to 74 in men who weighed more than 8.5 pounds (3856 g). The fall was significant for premature cardiovascular deaths up to 65 years of age (chi 2 = 5.0, p = 0.02). Standardised mortality ratios also fell with increasing head circumference (chi 2 = 4.6, p = 0.03) and increasing ponderal index (weight/length3) (chi 2 = 3.8, p = 0.05; for premature deaths chi 2 = 6.0, p = 0.01). They were not related to the duration of gestation. Among men for whom the ratio of placental weight to birth weight was in the highest fifths the standardised mortality ratio was 137. CONCLUSION--These findings show that reduced fetal growth is followed by increased mortality from cardiovascular disease. They suggest that reduction in growth begins early in gestation. They are further evidence that cardiovascular disease originates through programming of the body9s structure, physiology, and metabolism by the environment during fetal life. Maternal nutrition may have an important influence on programming.
p-Benzoquinone, a Reactive Metabolite of Benzene, Prevents the Processing of Pre-Interleukins-1a and -1b to Active Cytokines by Inhibition of the Processing Enzymes, Calpain, and Interleukin-1b Converting Enzyme
Authors: George F. Kalf, John F. Renz, Rodica Niculescu
Journal: Environmental Health Perspectives (1996)

Chronic exposure of humans of benzene affects hematopoietic stem and progenitor cells and leads to aplastic anemia. The stromal macrophage, a target of benzene toxicity, secretes interleukin-1 (IL-1), which induces the stromal fibroblast to synthesize hematopoietic colony-stimulating factors. In a mouse model, benzene causes an acute marrow hypocellularity that can be prevented by the concomitant administration of IL-1 alpha. The ability of benzene to interfere with the production and secretion of IL-1 alpha was tested. Stromal macrophages from benzene-treated mice were capable of the transcription to the IL-1 alpha gene and the translation of the message but showed an inability to process the 34-kDa pre-IL-1 alpha precursor to the 17-kDa biologically active cytokine. Treatment of normal murine stromal macrophages in culture with hydroquinone (HQ) also showed an inhibition in processing of pre-IL-1 alpha. Hydroquinone is oxidized by a peroxidase-mediated reaction in the stromal macrophage to p-benzoquinone, which interacts with the sulfhydryl (SH) groups of proteins and was shown to completely inhibit the activity of calpain, the SH-dependent protease that cleaves pre-IL-1 alpha. In a similar manner, HQ, via peroxidase oxidation to p-benzoquinone, was capable of preventing the IL-1 beta autocrine stimulation of growth of human B1 myeloid tumor cells by preventing the processing of pre-IL-1 beta to mature cytokine. Benzoquinone was also shown to completely inhibit the ability of the SH-dependent IL-1 beta converting enzyme. Thus benzene-induced bone marrow hypocellularity may result from apoptosis of hematopoietic progenitor cells brought about by lack of essential cytokines and deficient IL-1 alpha production subsequent to the inhibition of calpain by p-benzoquinone and the prevention of pre-IL-1 processing.