tbuckley/cabot-search huggingface dataset:
Effect of aminophylline on brain tissue oxygenation in patients with chronic obstructive lung disease.
Authors: M Nishimura, A Suzuki, A Yoshioka, M Yamamoto, Y Akiyama, K Miyamoto, F Kishi, Y Kawakami
Journal: Thorax (1992)

BACKGROUND: It is known that theophylline reduces cerebral blood flow in humans. To quantitatively assess the possible adverse effect of theophylline on brain tissue oxygen tension (PO2) due to decreased cerebral blood flow, two sets of experiments were conducted in mildly hypoxaemic patients with chronic obstructive lung disease. METHODS: Firstly, internal jugular venous PO2 (PjO2) was measured simultaneously with arterial and mixed venous blood PO2 (PaO2 and PvO2) during right heart catheterisation in 10 subjects (mean PaO2 73 mm Hg; conversion factor: 10 mm Hg = 1.33 kPa)) before and after intravenous infusion of aminophylline (6 mg/kg). The PjO2 and PvO2 were considered to reflect the average tissue PO2 for the brain and for the whole body respectively. Secondly, the relation between PaO2 and PjO2 over a wide range, with the PaCO2 similar to that in the first study, was investigated in a different group of 12 subjects by stepwise changes in inspiratory gas composition. RESULTS: The mean PjO2 decreased by as much as 6 mm Hg 15 minutes after an infusion of aminophylline, whereas PaO2 stayed at the same level and PvO2 showed only a small decrease. The low PjO2 value of 29 (SD 6) mm Hg with aminophylline in the first study was similar to the PjO2 value of 30 (2) mm Hg obtained during severe hypoxia (PaO2 45 mm Hg) in the second study. The coefficient of oxygen delivery for the brain decreased by 29% with aminophylline treatment, but did not change significantly during severe hypoxic challenge. CONCLUSIONS: These data suggest that an infusion of aminophylline lowers brain tissue PO2 appreciably when given to mildly hypoxaemic patients with chronic obstructive lung disease.
Effect of cigarette smoking on the elastic properties of the human Aorta: a non-invasive study
Authors: C. Viachopoulos, C. Stefanadis, C. Sassalos, C. Stratos, K. Toutouzas, E. Tsiamis, L. Diamantopoulos, D. Tsekoura, S. Vaina, P. Toutouzas
Journal: Journal of the American College of Cardiology (1998)
Production of predominantly polymeric IgA by human peripheral blood lymphocytes stimulated in vitro with mitogens.
Authors: W H Kutteh, W J Koopman, M E Conley, M L Egan, J Mestecky
Journal: The Journal of Experimental Medicine (1980)

Human peripheral blood lymphocytes (PBL) were cultured for various time periods (up to 8 d) in the presence of pokeweed mitogen (PWM), lipopolysaccharide, or Epstein-Barr virus. Cell-free supernates were fractionated on a standardized ultrogel AcA 22 column and the proportion of polymeric and monomeric IgA was determined by radioimmunoassay. The results demonstrate that PBL stimulated with these mitogens produce IgM and IgG with molecular characteristics identical to those found in serum, but that the IgA produced is predominantly of the polymeric type. To prove that this IgA represented disulfide bond-linked polymers rather than aggregated monomers, we have demonstrated that the high molecular weight IgA (a) maintains its polymeric form upon treatment with acidic buffers, (b) contains J chain, a glycoprotein associated only with polymeric immunoglobulins, and (c) dissociates to the monomeric form upon reduction of disulfide bonds. After 1 wk in culture, approximately 60% of the PWM-stimulated cells that contained IgA were positive for IgA2, whereas 40% were IgA1 positive as determined by immunofluorescence. Therefore, peripheral blood contains a population of lymphocytes with the potential to display, after appropriate stimulation and differentiation, characteristics similar to IgA cells found in external secretory tissues. The demonstration of the presence of such cells in the peripheral circulation suggests that these cells are precursors of IgA-producing plasma cells with the potential to populate mucosal tissues.
Sustained Response Following Acute Treatment Of Hereditary Angioedema Attacks With Recombinant Human C1 Esterase Inhibitor
Authors: H. Henry Li, Marc A. Riedl, Jonathan A. Bernstein, William R. Lumry, Avner Reshef, Dumitru Moldovan, Henriette Farkas, Gregor Porebski, Marcin Stobiecki, Yun Hardiman, Anurag Relan, Marco Cicardi
Journal: Journal of Allergy and Clinical Immunology (2014)
Linkage between obesity and a marker near the tumor necrosis factor-alpha locus in Pima Indians.
Authors: R A Norman, C Bogardus, E Ravussin
Journal: Journal of Clinical Investigation (1995)

Because tumor necrosis factor-alpha (TNF-alpha) expression is increased in adipose tissue of both rodent models of obesity and obese humans, it has been considered as a candidate gene for obesity. Pima Indians were scored for genotypes at three polymorphic dinucleotide repeat loci (markers) near the gene TNF-alpha at 6p21.3. In a sib-pair linkage analysis, percent body fat, as measured by hydrostatic weighing, was linked (304 sib-pairs, P = 0.002) to the marker closest (10 kb) to TNF-alpha. The same marker was associated (P = 0.01) by analysis of variance with BMI. To search for possible DNA variants in TNF-alpha that contribute to obesity, single stranded conformational polymorphism analysis was performed from 20 obese and 20 lean subjects. Primer pairs were designed for the entire TNF-alpha protein coding region and part of the promoter. Only a single polymorphism located in the promoter region was detected. No association could be demonstrated between alleles at this polymorphism and percent body fat. We conclude that the linkage of TNF-alpha to obesity might be due to a sequence variant undetected in TNF-alpha or due to a variant in some other closely linked gene.
Upturned on Virginia Route 311
Authors: Molly O’Dell
Journal: JAMA (2009)

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
Differential Activity of IL-12 and IL-23 in Mucosal and Systemic Innate Immune Pathology
Authors: Holm H. Uhlig, Brent S. McKenzie, Sophie Hue, Claire Thompson, Barbara Joyce-Shaikh, Renata Stepankova, Nicolas Robinson, Sofia Buonocore, Helena Tlaskalova-Hogenova, Daniel J. Cua, Fiona Powrie
Journal: Immunity (2006)
Transcript copy number estimation using a mouse whole-genome oligonucleotide microarray.
Authors: Mark G Carter, Alexei A Sharov, Vincent VanBuren, Dawood B Dudekula, Condie E Carmack, Charlie Nelson, Minoru SH Ko
Journal: Genome biology (2005)

Abstract The ability to quantitatively measure the expression of all genes in a given tissue or cell with a single assay is an exciting promise of gene-expression profiling technology. An in situ -synthesized 60-mer oligonucleotide microarray designed to detect transcripts from all mouse genes was validated, as well as a set of exogenous RNA controls derived from the yeast genome (made freely available without restriction), which allow quantitative estimation of absolute endogenous transcript abundance.
High Frequency of <i>PIK3R1</i> and <i>PIK3R2</i> Mutations in Endometrial Cancer Elucidates a Novel Mechanism for Regulation of PTEN Protein Stability
Authors: Lydia W.T. Cheung, Bryan T. Hennessy, Jie Li, Shuangxing Yu, Andrea P. Myers, Bojana Djordjevic, Yiling Lu, Katherine Stemke-Hale, Mary D. Dyer, Fan Zhang, Zhenlin Ju, Lewis C. Cantley, Steven E. Scherer, Han Liang, Karen H. Lu, Russell R. Broaddus, Gordon B. Mills
Journal: Cancer Discovery (2011)

Abstract We demonstrate that phosphatidylinositol 3-kinase (PI3K) pathway aberrations occur in &amp;gt;80% of endometrioid endometrial cancers, with coordinate mutations of multiple PI3K pathway members being more common than predicted by chance. PIK3R1 (p85α) mutations occur at a higher rate in endometrial cancer than in any other tumor lineage, and PIK3R2 (p85β), not previously demonstrated to be a cancer gene, is also frequently mutated. The dominant activation event in the PI3K pathway appears to be PTEN protein loss. However, in tumors with retained PTEN protein, PI3K pathway mutations phenocopy PTEN loss, resulting in pathway activation. KRAS mutations are common in endometrioid tumors activating independent events from PI3K pathway aberrations. Multiple PIK3R1 and PIK3R2 mutations demonstrate gain of function, including disruption of a novel mechanism of pathway regulation wherein p85α dimers bind and stabilize PTEN. Taken together, the PI3K pathway represents a critical driver of endometrial cancer pathogenesis and a novel therapeutic target. Significance: Our data indicate that the PI3K pathway is targeted in the vast majority of endometrioid endometrial cancers leading to PI3K pathway activation. Frequent oncogenic mutations in PIK3R1 and PIK3R2 provide evidence for their role in endometrial cancer pathophysiology with patient-specific mutations revealing a novel mechanism by which p85α regulates the PI3K pathway through stabilizing PTEN. Cancer Discovery; 1(2); 170–85. ©2011 AACR. Read the Commentary on this article by Herrero-Gonzalez and Di Cristofano, p. 106 This article is highlighted in the In This Issue feature, p. 91
Growth of B-lymphocytes clones in semisolid culture is mitogen dependent.
Authors: P W Kincade, P Ralph, M A Moore
Journal: The Journal of Experimental Medicine (1976)

A substance which was mitogenic for murine B lymphocytes in the presence of 2-mercaptoethanol was isolated from agar. Stimulating activity of this material was stable to proteolysis or protein denaturants but was destroyed by periodate treatment. Agar-derived mitogen stimulation was distinct from that obtained with dextran sulfate or lipopolysaccharide and may define different populations of B lymphocytes.
`Lactate Washout' Following Circulatory Arrest
Authors: Jeffrey A. Leavy
Journal: JAMA (1988)

The measurement of arterial blood lactate concentration for the purpose of estimating the severity and prognosis of acute perfusion failure is suspect because of theoretical errors due to systemic "lactate washout" immediately following restoration of perfusion. If arterial lactate concentrations continue to increase following resuscitation, the assumption that increasing lactate concentrations indicate progression of anaerobiosis due to perfusion failure would be invalidated. Lactate washout was therefore investigated in a porcine model of cardiac arrest due to electromechanical dissociation. Cardiopulmonary resuscitation was initiated and maintained for intervals of 30 minutes or until spontaneous circulation was restored. In 25 trials on 14 successfully resuscitated animals, the arterial blood lactate concentration decreased within four minutes after resuscitation from cardiac arrest. In 24 animals in whom resuscitation efforts failed, arterial lactate concentrations increased throughout the observation period. Lactate washout occurred during an interval of only 2.6 ±0.3 minutes (mean ± SEM). These results indicate that lactate measurements are not invalidated because of a washout phenomenon under the extreme conditions of cardiac arrest. (<i>JAMA</i>1988;260:662-664)
HOXB13 Mediates Tamoxifen Resistance and Invasiveness in Human Breast Cancer by Suppressing ERα and Inducing IL-6 Expression
Authors: Nilay Shah, Kideok Jin, Leigh-Ann Cruz, Sunju Park, Helen Sadik, Soonweng Cho, Chirayu Pankaj Goswami, Harikrishna Nakshatri, Rajnish Gupta, Howard Y. Chang, Zhe Zhang, Ashley Cimino-Mathews, Leslie Cope, Christopher Umbricht, Saraswati Sukumar
Journal: Cancer Research (2013)

Most breast cancers expressing the estrogen receptor α (ERα) are treated successfully with the receptor antagonist tamoxifen (TAM), but many of these tumors recur. Elevated expression of the homeodomain transcription factor HOXB13 correlates with TAM-resistance in ERα-positive (ER+) breast cancer, but little is known regarding the underlying mechanism. Our comprehensive evaluation of HOX gene expression using tiling microarrays, with validation, showed that distant metastases from TAM-resistant patients also displayed high HOXB13 expression, suggesting a role for HOXB13 in tumor dissemination and survival. Here we show that HOXB13 confers TAM resistance by directly downregulating ERα transcription and protein expression. HOXB13 elevation promoted cell proliferation in vitro and growth of tumor xenografts in vivo. Mechanistic investigations showed that HOXB13 transcriptionally upregulated interleukin (IL)-6, activating the mTOR pathway via STAT3 phosphorylation to promote cell proliferation and fibroblast recruitment. Accordingly, mTOR inhibition suppressed fibroblast recruitment and proliferation of HOXB13-expressing ER+ breast cancer cells and tumor xenografts, alone or in combination with TAM. Taken together, our results establish a function for HOXB13 in TAM resistance through direct suppression of ERα and they identify the IL-6 pathways as mediator of disease progression and recurrence.
Risk of Myocardial Infarction and Angina in Patients With Severe Peripheral Vascular Disease
Authors: Elisabetta Rossi, Luigi M. Biasucci, Franco Citterio, Simona Pelliccioni, Claudia Monaco, Francesca Ginnetti, Dominick J. Angiolillo, Gianni Grieco, Giovanna Liuzzo, Attilio Maseri
Journal: Circulation (2002)

Background— Patients undergoing revascularization procedures for peripheral vascular disease (PVD) have a greatly increased risk for coronary artery disease (CAD) that is predicted only partly by clinical data and cardiovascular risk factors. We investigated whether the prognostic assessment in PVD patients could be improved by preoperative measurements of C-reactive protein (CRP). Methods and Results— We assessed clinical and risk factors profiles, Eagle clinical scores, and preoperative CRP serum levels in 51 patients with PVD at Fontaine-Leriche stages II to IV without severe rest ventricular dysfunction or ischemia. During 24 months of follow-up, 17 patients (34%) had fatal (11) or nonfatal (6) myocardial infarction (MI). With univariate logistic regression analysis, only previous history of CAD, Eagle score, and CRP were independently related to MI. At multivariate logistic regression analysis, only CRP values in the upper tertile (&lt;9 mg/L) were significantly associated with MI ( P &lt;0.05) and identified 65% of cases. Conclusions— The high incidence of MI in patients with PVD severe enough to require revascularization is strongly predicted by preprocedural measurements of serum CRP, independent of previous CAD, Eagle score index, and traditional cardiovascular risk factors. These patients may benefit from therapy modulating the inflammatory response.
Induced pluripotent stem cells from human revertant keratinocytes for the treatment of epidermolysis bullosa
Authors: Noriko Umegaki-Arao, Anna M. G. Pasmooij, Munenari Itoh, Jane E. Cerise, Zongyou Guo, Brynn Levy, Antoni Gostyński, Lisa R. Rothman, Marcel F. Jonkman, Angela M. Christiano
Journal: Science Translational Medicine (2014)

Epidermolysis bullosa patient–specific iPSCs were generated from spontaneously corrected revertant keratinocytes for skin reconstitution.
Pentraxin-3 in COPD: innocent bystander or amplifier?
Authors: A. Mantovani
Journal: European Respiratory Journal (2012)

In this issue of the European Respiratory Journal , Van Pottelberge et al. [1] report on the association between interstitial levels of the long pentraxin, PTX3, and chronic obstructive pulmonary disease (COPD). COPD remains a formidable challenge in terms of identifying prognostic markers and innovative therapeutic approaches. COPD is characterised by worsening lung function sustained by an unrestrained nonresolving inflammatory response. There is a need for innovative prognostic markers relevant to disease progression and its complications [2]. In this report, Van Pottelberge et al. [1] found that lower levels of PTX3 in the lung interstitium of COPD patients were associated with airway obstruction as assessed by forced expiratory volume in 1 s (FEV1). The different levels of PTX3 were not a reflection of different amounts of PTX3 mRNA transcripts, as assessed in whole tissue extracts. Sputum levels were uninformative. Unlike C-reactive protein (CRP), PTX3 levels did not increase in COPD, but a correlation between …
Lateral Gene Transfer of Family A DNA Polymerases between Thermophilic Viruses, Aquificae, and Apicomplexa
Authors: Thomas W. Schoenfeld, Senthil K. Murugapiran, Jeremy A. Dodsworth, Sally Floyd, Michael Lodes, David A. Mead, Brian P. Hedlund
Journal: Molecular Biology and Evolution (2013)

Bioinformatics and functional screens identified a group of Family A-type DNA Polymerase (polA) genes encoded by viruses inhabiting circumneutral and alkaline hot springs in Yellowstone National Park and the US Great Basin. The proteins encoded by these viral polA genes (PolAs) shared no significant sequence similarity with any known viral proteins but were remarkably similar to PolAs encoded by two of three families of the bacterial phylum Aquificae and by several apicoplast-targeted PolA-like proteins found in the eukaryotic phylum Apicomplexa, which includes the obligate parasites Plasmodium, Babesia, and Toxoplasma. The viral gene products share signature elements previously associated only with Aquificae and Apicomplexa PolA-like proteins and were similar to proteins encoded by prophage elements of a variety of otherwise unrelated Bacteria, each of which additionally encoded a prototypical bacterial PolA. Unique among known viral DNA polymerases, the viral PolA proteins of this study share with the Apicomplexa proteins large amino-terminal domains with putative helicase/primase elements but low primary sequence similarity. The genomic context and distribution, phylogeny, and biochemistry of these PolA proteins suggest that thermophilic viruses transferred polA genes to the Apicomplexa, likely through secondary endosymbiosis of a virus-infected proto-apicoplast, and to the common ancestor of two of three Aquificae families, where they displaced the orthologous cellular polA gene. On the basis of biochemical activity, gene structure, and sequence similarity, we speculate that the xenologous viral-type polA genes may have functions associated with diversity-generating recombination in both Bacteria and Apicomplexa.
CD1d-restricted Help To B Cells By Human Invariant Natural Killer T Lymphocytes
Authors: Grazia Galli, Sandra Nuti, Simona Tavarini, Luisa Galli-Stampino, Claudia De Lalla, Giulia Casorati, Paolo Dellabona, Sergio Abrignani
Journal: The Journal of Experimental Medicine (2003)

Invariant natural killer T (NKT) cells are a highly conserved subset of T lymphocytes expressing a semi-invariant T cell receptor (TCR), which is restricted to CD1d and specific for the glycosphingolipid antigen α-galactosylceramide. Their ability to secrete a variety of cytokines, which in turn modulate the activation of cells of both innate and acquired immune responses, suggests that invariant NKT cells exert a regulatory role mainly via indirect mechanisms. A relevant question is whether invariant NKT cells can directly help B cells. We document here that human invariant NKT cells are as efficient as conventional CD4+ Th0 lymphocytes in promoting proliferation of autologous memory and naive B lymphocytes in vitro, and in inducing immunoglobulin production. Help to B cells by invariant NKT cells is CD1d-dependent and delivered also in the absence of α-galactosylceramide, suggesting that NKT cells recognize an endogenous ligand presented by CD1d on B cells. The two major subsets of invariant NKT cells, CD4+ and double negative (CD4−CD8−), express comparable levels of CD40 ligand and cytokines, but differ in helper functions. Indeed, both subsets induce similar levels of B cell proliferation, whereas CD4+ NKT cells induce higher levels of immunoglobulin production. These results suggest a direct role for invariant NKT cells in regulating B lymphocyte proliferation and effector functions.
Evasion of COPD in smokers: at what price?
Authors: Manuel G. Cosio, Marina Saetta
Journal: European Respiratory Journal (2011)

Investigations toward the understanding of chronic obstructive pulmonary disease (COPD) have been directed, so far, to the study of mechanisms leading to the disease. We believe that understanding why ∼80% of smokers evade COPD and how this evasion is accomplished might be a fruitful endeavour that could advance knowledge of the development of the disease. Since the inflammatory infiltrate smokers develop seems to be the key element leading to the lung destruction in COPD, the understanding of the possible ways inflammation can be dampened, as well as its consequences, ought to be important. We review here some of the mechanisms by which inflammation is controlled: by the post-translational regulons, by the mechanisms preventing full activation of dendritic cells and by the regulatory T-cells. The potential role of the M2 alveolar macrophage phenotype and the newly described myeloid-derived suppressor cells is mentioned. We also point out that evasion comes at a price, as healthy smokers might be immunosuppressed to some extent and unable to prevent the development of cancer, certainly less so than in severe COPD, where immunity is heightened. Probably, the knowledge of the mechanisms of evasion from COPD could add significantly to the understanding of those leading to the disease.