tbuckley/cabot-search huggingface dataset:
Human Helminthology: A Manual for Clinicians, Sanitarians and Medical Zoölogists.
Journal: JAMA (1929)

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
Expression of Extracellular Matrix Proteins Accompanies Lesion Growth in a Model of Intimal Reinjury
Authors: Hiroyuki Koyama, Michael A. Reidy
Journal: Circulation Research (1998)

Abstract —Reinjury of rat arterial lesions induces an increase in lesion size that is not associated with an increase in cell number. In this study, matrix volume was examined after reinjury to preexisting lesions, and the kinetics of matrix gene expression and activity of proteolytic enzymes in the lesion were evaluated. Volume densitometry in intima showed a significant increase in matrix volume 28 days after the reinjury, although no change was observed at 14 days. Three common vascular matrix molecules, α 1 (I)procollagen, tropoelastin, and fibronectin, were expressed highly at 7 days after the reinjury. Expression of tropoelastin remained upregulated for the entire 28 days after the reinjury, whereas α 1 (I)procollagen and fibronectin returned to the control level by 28 days. Protease activity was also increased after reinjury. Within days, a marked increase in urokinase plasminogen activator activity was observed in intima, and this activity decreased to control level by 14 days. The activity of tissue plasminogen activator did not change. The 95-kDa gelatinolytic activity was increased 1 to 2 days after the reinjury, but no change in other gelatinolytic activities was observed. These findings demonstrate that the accumulation of extracellular matrix is important in the increase in lesion size after reinjury and that a balance of matrix synthesis and degradation may explain why no change in matrix volume was detected until 28 days after the reinjury.
Recombinant human interleukin 11 and bacterial infection in patients with haemological malignant disease undergoing chemotherapy: a double-blind placebo-controlled randomised trial
Authors: Michael Ellis, Ferdinand Zwaan, Ulla Hedström, Christopher Poynton, Jörgen Kristensen, Pauline Jumaa, Julie Wassell, Basel al-Ramadi
Journal: The Lancet (2003)
Destruction of tumor vasculature and abated tumor growth upon VEGF blockade is driven by proapoptotic protein Bim in endothelial cells
Authors: Edwina Naik, Lorraine A. O'Reilly, Marie-Liesse Asselin-Labat, Delphine Merino, Ann Lin, Michele Cook, Leigh Coultas, Philippe Bouillet, Jerry M. Adams, Andreas Strasser
Journal: The Journal of Experimental Medicine (2011)

For malignant growth, solid cancers must stimulate the formation of new blood vessels by producing vascular endothelial growth factor (VEGF-A), which is required for the survival of tumor-associated vessels. Novel anticancer agents that block VEGF-A signaling trigger endothelial cell (EC) apoptosis and vascular regression preferentially within tumors, but how the ECs die is not understood. In this study, we demonstrate that VEGF-A deprivation, provoked either by drug-induced tumor shrinkage or direct VEGF-A blockade, up-regulates the proapoptotic BH3 (Bcl-2 homology 3)-only Bcl-2 family member Bim in ECs. Importantly, the tumor growth inhibitory activity of a VEGF-A antagonist required Bim-induced apoptosis of ECs. These findings thus reveal the mechanism by which VEGF-A blockade induces EC apoptosis and impairs tumor growth. They also indicate that drugs mimicking BH3-only proteins may be exploited to kill tumor cells not only directly but also indirectly by ablating the tumor vasculature.
Antecedent long term ethanol consumption in combination with different diets alters the severity of experimental acute pancreatitis in rats.
Authors: O J Ramo
Journal: Gut (1987)

The effect of fat rich (F), protein rich (P) and carbohydrate rich (C) diets and chronic ethanol consumption on experimental acute pancreatitis was studied in rats. One hundred and ninety two animals with induced acute pancreatitis were divided into eight groups fed either a mixture of water and 15% ethanol (v/v), or tap water combined with standard or special diets according to their group, for 12 weeks. The other control 192 rats were divided into equal groups. Bile induced experimental acute pancreatitis caused the highest mortality (37.5%) in the animals receiving F diet and ethanol. In this group significant haemoconcentration, peritoneal exudate formation and the most extensive fat necrosis were also observed. The carbohydrate rich diet with or without ethanol did not have any significant effect on the severity of acute pancreatitis. Diet and ethanol may alter the metabolism of the pancreas and cause derangements at the systemic level. These derangements might cause the increased susceptibility to acute pancreatitis. These changes in the metabolism may be fatal because of the increased toxicity of the peritoneal exudate secreted during the inflammation.
Interferon alfa down-regulates collagen gene transcription and suppresses experimental hepatic fibrosis in mice
Authors: Y Inagaki
Journal: Hepatology (2003)

The equilibrium between the production and degradation of collagen is rigorously controlled by a number of growth factors and cytokines. Interferon alfa (IFN-alpha) is now widely used for the treatment of chronic hepatitis C, which can improve serum levels of fibrotic markers and the degree of hepatic fibrosis, not only in patients who responded to therapy but also in those in whom it is ineffective. These findings may suggest that IFN-alpha possesses direct antifibrotic effects in addition to its antiviral activity. However, in contrast to IFN-gamma, which has been shown to suppress collagen gene transcription, little is known about the mechanisms responsible for the antifibrotic effects of IFN-alpha. Here, we report that IFN-alpha, when administered into transgenic mice harboring the alpha2(I) collagen gene (COL1A2) promoter sequence, significantly repressed promoter activation and prevented the progression of hepatic fibrosis induced by carbon tetrachloride injection. Transient transfection assays indicated that IFN-alpha decreased the steady-state levels of COL1A2 messenger RNA (mRNA) and inhibited basal and TGF-beta/Smad3-stimulated COL1A2 transcription in activated hepatic stellate cells (HSC). These inhibitory effects of IFN-alpha on COL1A2 transcription were exerted through the interaction between phosphorylated Stat1 and p300. Blocking of the IFN-alpha signal by overexpressing the intracellular domain-deleted IFN receptor increased basal COL1A2 transcription and abolished the inhibitory effects of IFN-alpha. In conclusion, our results indicate that IFN-alpha antagonizes the TGF-beta/Smad3-stimulated COL1A2 transcription in vitro and suppresses COL1A2 promoter activation in vivo, providing a molecular basis for antifibrotic effects of IFN-alpha.
Novel approaches to the treatment of<i>Pseudomonas aeruginosa</i>infections in cystic fibrosis
Authors: Matthew N. Hurley, Miguel Cámara, Alan R. Smyth
Journal: European Respiratory Journal (2012)

Pseudomonas aeruginosa chronically infects patients with cystic fibrosis and is associated with greater morbidity. There has been limited progress on the clinical development of new antibiotics with novel modes of action. This review addresses some of the latest research developments on the exploitation of candidate adjuvant therapeutic agents that may act alongside conventional antibiotics as an alternative therapeutic strategy. After considering key mechanisms this opportunistic pathogen employs to control virulence, the progress of various strategies including the inhibition of quorum sensing, efflux pumps and lectins, and the use of iron chelators, bacteriophages, immunisation and immunotherapy is reviewed. Both therapeutic approaches in early development and clinical phase are discussed.
Whole genome sequencing of a single Bos taurus animal for single nucleotide polymorphism discovery
Authors: Sebastian H Eck, Anna Benet-Pagès, Krzysztof Flisikowski, Thomas Meitinger, Ruedi Fries, Tim M Strom
Journal: Genome biology (2009)

Abstract Background The majority of the 2 million bovine single nucleotide polymorphisms (SNPs) currently available in dbSNP have been identified in a single breed, Hereford cattle, during the bovine genome project. In an attempt to evaluate the variance of a second breed, we have produced a whole genome sequence at low coverage of a single Fleckvieh bull. Results We generated 24 gigabases of sequence, mainly using 36-bp paired-end reads, resulting in an average 7.4-fold sequence depth. This coverage was sufficient to identify 2.44 million SNPs, 82% of which were previously unknown, and 115,000 small indels. A comparison with the genotypes of the same animal, generated on a 50 k oligonucleotide chip, revealed a detection rate of 74% and 30% for homozygous and heterozygous SNPs, respectively. The false positive rate, as determined by comparison with genotypes determined for 196 randomly selected SNPs, was approximately 1.1%. We further determined the allele frequencies of the 196 SNPs in 48 Fleckvieh and 48 Braunvieh bulls. 95% of the SNPs were polymorphic with an average minor allele frequency of 24.5% and with 83% of the SNPs having a minor allele frequency larger than 5%. Conclusions This work provides the first single cattle genome by next-generation sequencing. The chosen approach - low to medium coverage re-sequencing - added more than 2 million novel SNPs to the currently publicly available SNP resource, providing a valuable resource for the construction of high density oligonucleotide arrays in the context of genome-wide association studies.
The PPARα/p16 <sup>INK4a</sup> Pathway Inhibits Vascular Smooth Muscle Cell Proliferation by Repressing Cell Cycle–Dependent Telomerase Activation
Authors: Florence Gizard, Takashi Nomiyama, Yue Zhao, Hannes M. Findeisen, Elizabeth B. Heywood, Karrie L. Jones, Bart Staels, Dennis Bruemmer
Journal: Circulation Research (2008)

Peroxisome proliferator-activated receptor (PPAR)alpha, the molecular target for fibrates used to treat dyslipidemia, exerts pleiotropic effects on vascular cells. In vascular smooth muscle cells (VSMCs), we have previously demonstrated that PPARalpha activation suppresses G(1)-->S cell cycle progression by targeting the cyclin-dependent kinase inhibitor p16(INK4a) (p16). In the present study, we demonstrate that this inhibition of VSMC proliferation by PPARalpha is mediated through a p16-dependent suppression of telomerase activity, which has been implicated in key cellular functions including proliferation. PPARalpha activation inhibited mitogen-induced telomerase activity by repressing the catalytic subunit telomerase reverse transcriptase (TERT) through negative cross-talk with an E2F-1-dependent trans-activation of the TERT promoter. This trans-repression involved the recruitment of the retinoblastoma (RB) family proteins p107 and p130 to the TERT promoter resulting in impaired E2F-1 binding, an effect that was dependent on p16. The inhibition of cell proliferation by PPARalpha activation was lost in VSMCs following TERT overexpression or knockdown, pointing to a key role of telomerase as a target for the antiproliferative effects of PPARalpha. Finally, we demonstrate that PPARalpha agonists suppress telomerase activation during the proliferative response following vascular injury, indicating that these findings are applicable in vivo. In concert, these results demonstrate that the antiproliferative effects of PPARalpha in VSMCs depend on the suppression of telomerase activity by targeting the p16/RB/E2F transcriptional cascade.
FROZEN AND DRIED PLASMA FOR CIVIL AND MILITARY USE
Authors: MAX M. STRUMIA
Journal: JAMA (1941)

Recent experimental and clinical observations have definitely established the value of plasma as a substitute for whole blood in many clinical conditions.<sup>1</sup>The use of plasma in place of whole blood is suggested by two independent lines of thought. The first is a critical appraisal of the clinical indications for blood transfusion based on the physiologic action of each one of its components; the second is a matter of technical convenience concerned mostly with the problems of preservation and administration. We will consider these two elements separately and briefly. <h3>CLINICAL CONSIDERATIONS</h3> The accompanying table lists what we consider at present the indications for the use of plasma in place of whole blood as well as the conditions in which the use of whole blood is recommended. From the clinical standpoint it is also most essential to bear in mind that plasma properly prepared offers the following advantages: There
Implementation of Guidelines Improves the Standard of Care
Authors: Karim Kalla, Günter Christ, Ronald Karnik, Reinhard Malzer, Georg Norman, Herbert Prachar, Wolfgang Schreiber, Gerhard Unger, Helmut D. Glogar, Alfred Kaff, Anton N. Laggner, Gerald Maurer, Johannes Mlczoch, Joerg Slany, Heinrich S. Weber, Kurt Huber
Journal: Circulation (2006)

Background— The purpose of this study was to determine whether implementation of recent guidelines improves in-hospital mortality from acute ST-elevation myocardial infarction (STEMI) in a metropolitan area. Methods and Results— We organized a network that consisted of the Viennese Ambulance Systems, which is responsible for diagnosis and triage of patients with acute STEMI, and 5 high-volume interventional cardiology departments to expand the performance of primary percutaneous catheter intervention (PPCI) and to use the fastest available reperfusion strategy in STEMI of short duration (2 to 3 hours from onset of symptoms), either PPCI or thrombolytic therapy (TT; prehospital or in-hospital), respectively. Implementation of guidelines resulted in increased numbers of patients receiving 1 of the 2 reperfusion strategies (from 66% to 86.6%). Accordingly, the proportion of patients not receiving reperfusion therapy dropped from 34% to 13.4%, respectively. PPCI usage increased from 16% to almost 60%, whereas the use of TT decreased from 50.5% to 26.7% in the participating centers. As a consequence, in-hospital mortality decreased from 16% before establishment of the network to 9.5%, including patients not receiving reperfusion therapy. Whereas PPCI and TT demonstrated comparable in-hospital mortality rates when initiated within 2 to 3 hours from onset of symptoms, PPCI was more effective in acute STEMI of &gt;3 but &lt;12 hours’ duration. Conclusions— Implementation of recent guidelines for the treatment of acute STEMI by the organization of a cooperating network within a large metropolitan area was associated with a significant improvement in clinical outcomes.
Matched T cell repertoire analysis of peripheral blood and tumor-infiltrating lymphocytes (TILs) in early stage breast cancer (ESBC) patients (pts) treated with pre-operative cryoablation (cryo) and/or Ipilimumab (Ipi)
Authors: David B Page, Heather McArthur, Zhiwan Dong, Phillip Wong, Ryan Emerson, Zhenyu Mu, Chunjun Zhao, Christopher Comstock, Elizabeth Morris, Elizabeth Comen, Alan Kotin, Janice Sung, Edi Brogi, Monica Morrow, Stephen Solomon, Virgilio Sacchini, Majid Maybody, Deirdre Neville, Adi Diab, Padmanee Sharma, Harlan Robins, Sujata Patil, Jedd D Wolchok, Clifford Hudis, Larry Norton, James Allison, Jianda Yuan
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Cryo plus anti-CTLA-4 therapy induces antigen-specific clonal T cell expansion, enhanced survival, and long-term anti-tumor immunity in mice [[1][1]]. We recently demonstrated that pre-operative cryo and/or anti-CTLA-4 therapy with Ipi is well tolerated and clinically feasible in
Immunogenicity of 1967 Polyvalent and 1968 Hong Kong Influenza Vaccines
Authors: William J. Mogabgab
Journal: JAMA (1970)

Influenza A2 vaccine containing 300 chick-cell agglutination (CCA) units per dose of the Hong Kong variant provided a high degree of protection during an outbreak of respiratory illnesses in military personnel in December 1968 and January 1969. This inactivated chicken embryo-propagated virus vaccine stimulated hemagglutination-inhibition antibody responses that were equivalent to natural infection. Polyvalent vaccine, 1967 formula, was not without some contribution in preventing disease in those who did not receive Hong Kong influenza vaccine. Influenza A2 comprised 56% of all respiratory illnesses during the outbreak. Virus was isolated in rhesus monkey kidney cultures from pharyngeal washings of a third of the individuals with serologic evidence of infection by influenza A2.
Impact of Epidermal Growth Factor Receptor and <i>KRAS</i> Mutations on Clinical Outcomes in Previously Untreated Non–Small Cell Lung Cancer Patients: Results of an Online Tumor Registry of Clinical Trials
Authors: David M. Jackman, Vincent A. Miller, Leigh-Anne Cioffredi, Beow Y. Yeap, Pasi A. Jänne, Gregory J. Riely, Marielle Gallegos Ruiz, Giuseppe Giaccone, Lecia V. Sequist, Bruce E. Johnson
Journal: Clinical Cancer Research (2009)

Abstract Purpose: The impact of epidermal growth factor receptor (EGFR) and KRAS genotypes on outcomes with erlotinib or gefitinib therapy continues to be debated. This study combines patient data from five trials in predominantly Western populations to assess the impact of EGFR and KRAS mutations on first-line therapy with an EGFR–tyrosine kinase inhibitor (TKI) and compare clinical versus molecular predictors of sensitivity. Experimental Design: Chemotherapy-naïve patients with advanced non–small cell lung cancer and known EGFR mutation status treated with erlotinib or gefitinib monotherapy as part of a clinical trial were eligible for inclusion. Patients received daily erlotinib (150 mg) or gefitinib (250 mg) until disease progression or unacceptable toxicity. Data were collected in a password-protected web database. Clinical outcomes were analyzed to look for differences based on EGFR and KRAS genotypes, as well as clinical characteristics. Results: Patients (223) from five clinical trials were included. Sensitizing EGFR mutations were associated with a 67% response rate, time to progression (TTP) of 11.8 months, and overall survival of 23.9 months. Exon 19 deletions were associated with longer median TTP and overall survival compared with L858R mutations. Wild-type EGFR was associated with poorer outcomes (response rate, 3%; TTP, 3.2 months) irrespective of KRAS status. No difference in outcome was seen between patients harboring KRAS transition versus transversion mutations. EGFR genotype was more effective than clinical characteristics at selecting appropriate patients for consideration of first-line therapy with an EGFR-TKI. Conclusion: EGFR mutation status is associated with sensitivity to treatment with an EGFR-TKI in patients with advanced non–small cell lung cancer. Patients harboring sensitizing EGFR mutations should be considered for first-line erlotinib or gefitinib. (Clin Cancer Res 2009;15(16):5267–73)
Sorting out the cytokines of asthma.
Authors: J M Drazen, J P Arm, K F Austen
Journal: The Journal of Experimental Medicine (1996)

Asthma is a complex disorder characterized by intermittent, reversible airway obstruction, and by airway hyperresponsiveness and inflammation. Although its cause(s) remain unknown, we now recognize that asthma is a syndrome whose common pathologic expression is inflammation of the airways. The airways of patients with even mild asthma are inflamed, and some data suggest that the severity of the asthma parallels the degree of inflammation (1-3). The airway inflammation of asthma is unique in that the airway wall is infiltrated by T lymphocytes bearing the T helper type 2 phenotype (4) and by eosinophils and mast ceils (2, 5, 6). Each of these cells is thought to contribute to the physiologic changes that characterize asthma (Fig. 1). The TH2 lymphocytes produce a limited panel ofcytokines including IL-3, IL-4, IL-5, and GM-CSF. Although the primary signals resulting in the infiltration of the asthmatic airways by this lymphocyte subset have not yet been identified, a number of models have been proposed based on the concept that the inflammtory process is triggered by the presentation of a restricted panel of antigens in the presence of appropriate cytokines. The net effect of antigen presentation in this microenvironment is to promote the synthesis of IgE through the actions of IL-4 on Ig isotype switching (7) and to enhance the differentiation, migration, and pathobiologic capacity of eosinophils through the actions of GMCSF, IL-3, and IL-5 (8, 9). The IgE produced in asthmatic airways binds to Fc~RI on mast cells, priming them for activation by antigen. Mast cells arise from bone marrow precursors, enter the circulation as non-metachromatically staining, agranular, CD34 +, c-kit +, and F%I<I + mononuclear leukocytes (10), and localize to mucosal and submucosal sites such as the bronchi. Once localized, these lineage-committed immature mast cells undergo tissue-specific differentiation along with maturation and expansion. Their development and movement involves growth factors and cytokines derived from both structural and hematopoietic cells in their microenvironment. The mast cells that further migrate into the luminal space, and which can be recovered by bronchoalveolar lavage, are primed for an augmented activation response (11). Mast cells also elaborate IL-4 (12, 13), which favors conversion ofT cells to the TH 2 phenotype, and IL-5 (14), which contributes to eosinophilopoiesis and to the priming of eosinophils for augmented responses. Once recruited from the circulation, mature eosinophils, in the presence ofasthmatic cytokines, convert to an autoaggressive phenotype (15, 16), termed hy
Reproducibility of Proximal Isovelocity Surface Area, Vena Contracta, and Regurgitant Jet Area for Assessment of Mitral Regurgitation Severity
Authors: Simon Biner, Asim Rafique, Farhad Rafii, Kirsten Tolstrup, Omid Noorani, Takahiro Shiota, Swaminatha Gurudevan, Robert J. Siegel
Journal: JACC. Cardiovascular imaging (2010)
Mallory-Weiss Syndrome
Authors: H. David Watts
Journal: JAMA (1974)

A review of seven years' experience with upper gastrointestinal bleeding at a large metropolitan hospital showed 36 cases of the Mallory-Weiss lesion (4.5% of all cases of upper gastrointestinal hemorrhage during this period). Diagnosis was established with endoscopy or surgery. Nineteen percent of patients with the Mallory-Weiss syndrome required surgery, and only 61% required transfusion. These data suggest that the Mallory-Weiss syndrome has a wider and more benign clinical spectrum than has been reported previously. (<i>JAMA</i>230:1674-1675, 1974)