tbuckley/cabot-search huggingface dataset:
Fatigue and sarcoidosis
Authors: O.P. Sharma
Journal: European Respiratory Journal (1999)

<h3>Abstract</h3> Cellular uptake of vitamin B<sub>12</sub> in humans is mediated by the endocytosis of the B<sub>12</sub> carrier protein transcobalamin (TC) via its cognate cell surface receptor TCblR (or CD320), encoded by the <i>CD320</i> gene(1). Because <i>CD320</i> expression is associated with the cell cycle and upregulated in highly proliferating cells such as cancer cells(2–4), this uptake route is a potential target for cancer therapy(5). We developed and characterized four camelid nanobodies that bind TC or the interface of the TC:TCblR complex with nanomolar affinities. We determined X-ray crystal structures of all four nanobodies in complex with TC:TCblR, which enabled us to map their binding sites. When conjugated to a toxin, three of these nanobodies are capable of inhibiting the growth of HEK293T cells and therefore have the potential to inhibit the growth of human cancer cells. We visualized the cellular binding and endocytic uptake of the most potent nanobody (TCNB4) using fluorescent light microscopy. The co-crystal structures of TC:TCblR with another nanobody (TCNB34) revealed novel features of the interface of TC and the LDLR-A1 domain of TCblR. Our findings rationalize the structural basis for a decrease in affinity of TC-B<sub>12</sub> binding caused by the TCblR-Glu88 deletion mutant.
Abstract 1168: Cathelicidin is a novel mediator of cancer immune surveillance
Authors: Emilie T. Gross, Carlos D. Peinado, Isis G. Perez, Samaneh Keshavarz, Jack D. Bui
Journal: Cancer Research (2014)

Abstract Cathelicidins are evolutionarily conserved anti-microbial peptides that have been identified in several epithelial tissues and a wide variety of immune cells. These peptides display multiple host-defense activities, as well as documented but underexplored antitumor activity. Using the regressor MCA sarcoma system as a model of immune mediated tumor rejection, we observed that deficiency in cathelicidin in cnlp-/- mice impaired the rejection of multiple regressor cell lines. Cnlp-/- mice also developed spontaneous lymphoma with age, thus confirming in a separate model system the requirement for cathelicidin in tumor immune surveillance. To decipher the immune defect that may engender impaired tumor surveillance, macrophages from cnlp-/- versus wild type (wt) mice were examined. Interestingly, cnlp-/- macrophages were defective in polarizing towards an antitumor M1 phenotype and less potent at phagocytosing target tumor cells. Altogether, these preliminary data suggest a crucial role of cathelicidin in limiting tumor formation and progression. Future experiments will define the role of cathelicidin in tumor surveillance mediated by macrophages and potentially other innate cells that also express cathelicidin, such as neutrophils and natural killer cells. Citation Format: Emilie T. Gross, Carlos D. Peinado, Isis G. Perez, Samaneh Keshavarz, Jack D. Bui. Cathelicidin is a novel mediator of cancer immune surveillance. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1168. doi:10.1158/1538-7445.AM2014-1168
Human eosinophils express functional interleukin 2 receptors.
Authors: T H Rand, D S Silberstein, H Kornfeld, P F Weller
Journal: Journal of Clinical Investigation (1991)

Because T cell-derived cytokines may affect the functioning of eosinophils, we have investigated the capacity of human eosinophils to respond to IL-2. IL-2 was a potent chemoattractant with ED50 of 10(-12) M with eosinophils from all normal and eosinophilic donors tested. The monoclonal antibodies anti-Tac and TU27 against p55 (Tac/CD25) and p75 receptor subunits, respectively, each inhibited IL-2-dependent eosinophil migration. The molar potency of IL-2 and the inhibitory activity of each of the above antibodies suggest that high affinity heterodimeric IL-2 receptor complexes mediated the migration responses of eosinophils to IL-2. Binding of monoclonal antibody against p75 was not detectable by flow cytometry, and high affinity binding sites for 125I-IL-2 were below the limits of quantitation on eosinophils from individuals with eosinophilia. Expression of p55 (Tac/CD25) by eosinophils, without requirement for in vitro activation, was demonstrable by flow cytometry, radioimmunoprecipitation, and Northern blotting for mRNA. Surface expression of p55 on eosinophils from normal or eosinophilic individuals increased during culture for 24-48 h with a biologic activity purified from stimulated U937 cells and to a lesser extent with granulocyte-macrophage CSF or lymphocyte chemoattractant factor but not with nine other cytokines. These studies indicate that blood eosinophils respond to IL-2 and identify one mechanism whereby activation of T lymphocytes may influence the function of eosinophils.
Is there a role for inhaled nitric oxide as a rescue therapy in respiratory failure associated with hematologic malignancies?
Authors: Mark T. Keegan, Eric Nygren, Bekele Afessa, William J. Hogan, Barry A. Harrison
Journal: American Journal of Hematology (2006)

Abstract Inhaled nitric oxide has been demonstrated to improve oxygenation in critically ill patients requiring mechanical ventilation. We therefore performed a retrospective review to determine the outcome of patients with hematological malignancies and acute respiratory failure who received inhaled nitric oxide (INO) in a multidisciplinary intensive care unit of a single tertiary referral medical center. Thirteen patients with hematological malignancies who required endotracheal intubation and mechanical ventilation and received INO for acute respiratory failure between January 1998 and December 2002 were identified. Mean ± standard deviation (SD) age was 47.6 (±13.2) years. The mean ± SD Acute Physiology and Chronic Health Evaluation (APACHE) III score on the day of ICU admission was 94.1 ± 33.7 with a mean (SD) predicted probability of ICU death of 42.4% (±28.6). Mean APACHE III score on the day of initiating INO was 107.6 (±34.4) with a predicted mortality in the intensive care unit of 72.7% (±23.3). Mean PaO 2 to FiO 2 (PF) ratios (±SD) prior to, and immediately after, the initiation of INO were 62.6 (±28.2) and 111 (±65.1), respectively ( P &lt; 0.001). The median duration of INO therapy was 41.8 h (interquartile range, 6.3–98.2). Patients with hematological malignancies and acute respiratory failure to whom INO was administered had clinical deterioration since ICU admission. Despite a marked initial improvement in arterial oxygen tension, all patients ultimately died in the intensive care unit, 8 of them within 48 h of initiating INO. Therefore, despite initial improvement in oxygenation, we did not observe any survival benefit to INO in this setting. Am. J. Hematol., 2006. © 2006 Wiley‐Liss, Inc.
Treatment Is Lacking for Many US Adults With Mental Illness or Substance Abuse
Authors: Bridget M. Kuehn
Journal: JAMA (2011)

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
MicroRNAs of the miR-17∼92 family are critical regulators of TFH differentiation
Authors: Seung Goo Kang, Wen-Hsien Liu, Peiwen Lu, Hyun Yong Jin, Hyung W Lim, Jovan Shepherd, Daniel Fremgen, Eric Verdin, Michael B A Oldstone, Hai Qi, John R Teijaro, Changchun Xiao
Journal: Nature Immunology (2013)
CD4(+) T-lymphocytes mediate ischemia/reperfusion-induced inflammatory responses in mouse liver.
Authors: R M Zwacka, Y Zhang, J Halldorson, H Schlossberg, L Dudus, J F Engelhardt
Journal: Journal of Clinical Investigation (1997)

The success of orthotopic liver transplantation is dependent on multiple factors including MHC tissue compatibility and ischemic/reperfusion injury. Ischemic/reperfusion (I/R) injury in the liver occurs in a biphasic pattern consisting of both acute phase (oxygen free radical mediated) and subacute phase (neutrophil-mediated) damage. Although numerous studies have given insights into the process of neutrophil recruitment after I/R injury to the liver, the exact mechanism that initiates this subacute response remains undefined. Using a T cell-deficient mouse model, we present data that suggests that T-lymphocytes are key mediators of subacute neutrophil inflammatory responses in the liver after ischemia and reperfusion. To this end, using a partial lobar liver ischemia model, we compared the extent of reperfusion injury between immune competent BALB/c and athymic nu/nu mice. Studies evaluating the extent of liver damage as measured by serum transaminases (GPT) demonstrate similar acute (3-6 h) post-I/R responses in these two mouse models. In contrast, the subacute phase (16-20 h) of liver injury, as measured by both serum GPT levels and percent hepatocellular necrosis, was dramatically reduced in T cell-deficient mice as compared with those with an intact immune system. This reduction in liver injury seen in nu/nu mice was associated with a 10-fold reduction in hepatic neutrophil infiltration. Adoptive transfer of T cell-enriched splenocytes from immune competent mice was capable of reconstituting the neutrophil-mediated subacute inflammatory response within T cell-deficient nu/nu mice. Furthermore, in vivo antibody depletion of CD4(+) T-lymphocytes in immune competent mice resulted in a reduction of subacute phase injury and inflammation as measured by serum GPT levels and neutrophil infiltration. In contrast, depletion of CD8(+) T-lymphocytes had no effect on these indexes of subacute inflammation. Kinetic analysis of T cell infiltration in the livers of BALB/c mice demonstrated a fivefold increase in the number of hepatic CD4(+) T-lymphocytes within the first hour of reperfusion with no significant change in the number of CD8(+) T-lymphocytes. In summary, these results implicate CD4(+) T-lymphocytes as key regulators in initiating I/R-induced inflammatory responses in the liver. Such findings have implications for therapy directed at the early events in this inflammatory cascade that may prove useful in liver transplantation.
Abstract 4925: Promoter methylation of <i>RASSF1A</i> Tumor Suppressor Gene Modulates the Effect of Microtubule-Targeting Agent, docetaxl, in Breast Cancer
Authors: Gil Eun-Young, Uk Hyun Jo, Hae Yun Jung, Ok Hee Woo, Jae Hong Seo, Aeree Kim, Eun-Sook Lee, Kyu-Ran Cho, Yeul Hong Kim, Jun Suk Kim, In Sun Kim, Kyong Hwa Park
Journal: Cancer Research (2010)

Abstract RASSF1A has been previously demonstrated to be inactivated by CpG island methylation in breast cancer cell lines and primary tumor tissues. There have been evidences suggesting that methylation of this gene have a significant impact on biological characteristics of breast tumors and have a relationship with prognosis in breast cancer. The tumor suppressive effect of RASSF1A has been reported to be mediated by its 2 important roles in other cells; induction of cell cycle arrest and apoptosis. Therefore, it is possible that expression status of RASSF1A by promoter methylation may alter patient's sensitivity to chemotherapeutic agents affecting cell cycle. However, there is few data regarding the relationship between the methylation status of RASSF1A gene and clinical response to chemotherapeutic agents in breast cancer patients. In this current study, we show that RASSF1A gene expression was suppressed in the human breast cancer cell lines (MCF-7, MDA-MB-231, and ZR75-1) by the mechanism of promoter methylation using methylation -specific PCR. It was confirmed by the results that treatment with the DNA demethylating agent, 5-aza-2′-deoxycytidine, reactivated the expression of RASSF1A at the level of mRNA and protein. Re-expression of RASSF1A gene in breast cancer cell lines could decrease the cell growth and proliferation by both decreasing cyclin D1 expression and inducing cyclin A and B1 accumulation, then resulting in cell cycle arrest at G2/M phase. In addition, re-introduction of RASSF1A further increased docetaxel-induced cell death in breast cancer cells. We next questioned whether the methylation status of RASSF1A gene is associated with clinical response to taxane-based chemotherapy in breast cancer patients. Fresh frozen primary breast cancer tissues were ananlyzed for methylation status of RASSF1A gene using MS-PCR. Thirty three out of 39 patients (84.6%) showed RASSF1A methylation and 6 had un-methylated gene. Patients who had unmethylated or partially methylated RASSF1A gene showed some mRNA in RT-PCR analysis. And, the clinical response to taxane-based chemotherapy was significantly better in the un-, or partially-methylated patient group (100% vs 62.5%). These results suggest that hypermethylation of the CpG island promoter of RASSF1A may play an important role in breast cancer pathogenesis and is a modulating factor for docetaxel activity in breast cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4925.
Setting Standards for the Use of DNA-Typing Results in the Courtroom — The State of the Art
Authors: George J. Annas
Journal: New England Journal of Medicine (1992)

DNA typing, sometimes called DNA fingerprinting or profiling, has been the focus of heated exchanges in courtrooms, the popular press, and scientific journals. It is a powerful law-enforcement weapon, especially in cases of rape, because it has the potential to exonerate a suspect or to place him at the scene of a crime. On the other hand, it is of no use in rape cases like those in which William Kennedy Smith and Mike Tyson were accused, in which coitus is conceded to have occurred and the only real issue is consent. When should judges permit evidence from DNA typing . . .
Diverted by the Chief Complaint
Authors: S G Pauker, R I Kopelman, R M Lechan
Journal: New England Journal of Medicine (1995)

A 59-year-old building contractor reported facial flushing while working at a physician's home. His blood pressure was 185/120 mm Hg.Facial flushing is fairly nonspecific, although the carcinoid syndrome comes to mind. The blood pressure of 185/120 mm Hg is more impressive. Were previous values this high?The patient did not have a history of sustained hypertension, but on two occasions during the previous six months he had been told that his blood pressure was moderately elevated. During this same period, he had had episodes of feeling flushed, which occurred, on average, once a week and lasted . . .
Repeatability of peak nasal inspiratory flow measurements and utility for assessing the severity of rhinitis
Authors: R. Starling‐Schwanz, H. L. Peake, C. M. Salome, B. G. Toelle, K. W. Ng, G. B. Marks, M. L. Lean, S. J. Rimmer
Journal: Allergy (2005)

Background: The measurement of peak nasal inspiratory flow (PNIF) provides a simple, cheap, fast and readily available tool for determining the extent of nasal airway patency. However, there are questions regarding its repeatability when used to assess the degree of nasal obstruction in large populations. Therefore, this study aimed to evaluate the repeatability of PNIF measurements and to assess their association with the signs and symptoms of rhinitis. Methods: The PNIF, rhinitis symptoms, judged by Meltzer questionnaire and rhinitis signs, as determined by anterior rhinoscopy, were assessed in 283 adults representative of the general population. One training and two test PNIF measurements were recorded during the same session. Results: The PNIF was highly reproducible (ICC = 0.92; 95% limits of agreement: ±36 l/min). The PNIF was strongly correlated with rhinitis signs, measured by anterior rhinoscopy ( r s = −0.38, P &lt; 0.0001) but was not correlated with rhinitis symptoms, measured by questionnaire ( r s = −0.11, P = 0.057). Differences in PNIF for subjects categorized as asymptomatic, mild or moderate/severe on the basis of rhinitis signs, were highly significant ( P &lt; 0.0001), but less significant on the basis of rhinitis symptoms ( P = 0.04). A PNIF cut‐off of 115 l/min had moderately high specificity (72%) and sensitivity (65%) and a high negative predictive value (90%) for moderate/severe signs of rhinitis. Conclusion: In a large general population‐based sample of young adults, PNIF was highly reproducible and closely related to the signs of rhinitis, as determined by clinical examination. The PNIF provides information that is qualitatively different to that provided by symptom scores and may be useful to measure the extent of nasal obstruction.
MicroRNA-125b protects against myocardial ischaemia/reperfusion injury via targeting p53-mediated apoptotic signalling and TRAF6
Authors: Xiaohui Wang, Tuanzhu Ha, Jianghuan Zou, Danyang Ren, Li Liu, Xia Zhang, John Kalbfleisch, Xiang Gao, David Williams, Chuanfu Li
Journal: Cardiovascular Research (2014)

The present study examined the role of microRNA-125b (miR-125b) in myocardial ischaemia/reperfusion (I/R) injury. We constructed lentivirus-expressing miR-125b (LmiR-125b) and developed transgenic mice with overexpression of miR-125b. LmiR-125b was transfected into mouse hearts through the right common carotid artery. Lentivirus vector (LmiR-Con) served as vector control. Untreated mice served as I/R control. Sham operation served as sham control. Seven days after transfection, the hearts were subjected to ischaemia (45 min) followed by reperfusion (4 h). Myocardial infarct size was analysed by 2,3,5-triphenyltetrazolium chloride staining. In separate experiments, hearts were subjected to ischaemia (45 min) followed by reperfusion for up to 7 days. Cardiac function was measured by echocardiography before, as well as 3 and 7 days after myocardial I/R. Increased expression of miR-125b significantly decreased I/R-induced myocardial infarct size by 60% and prevented I/R-induced decreases in ejection fraction (EF%) and fractional shortening (%FS). Transgenic mice with overexpression of miR-125b also showed the protection against myocardial I/R injury. Increased expression of miR-125b attenuated I/R-induced myocardial apoptosis and caspase-3/7 and -8 activities. Western blot showed that increased expression of miR-125b suppresses p53 and Bak1 expression in the myocardium. In addition, transfection of LmiR-125b decreased the levels of TNF receptor-associated factor 6 (TRAF6) and prevented I/R-induced NF-κB activation. miR-125 protects the myocardium from I/R injury by preventing p53-mediated apoptotic signalling and suppressing TRAF6-mediated NF-κB activation.
Effect of secretin and jejunal acidification on gastric and pancreatic secretion in man
Authors: S. J. Konturek
Journal: Gut (1970)

The inhibitory effect of intravenous secretin and intrajejunal acid infusion on basal and pentagastrin-induced gastric acid secretion as well as the stimulatory influence of both infusions on pancreatic flow rate and bicarbonate output were compared in two groups of healthy subjects. Secretin strongly inhibited basal acid output and slightly decreased pentagastrin induced gastric secretion. Intrajejunal acid infusion did not affect the gastric secretion but resulted in an increase in pancreatic volume flow and bicarbonate output reaching about 40% of the pancreatic response to secretin<sup>1</sup> infused intravenously in a dose of 2 units per kilogram per hour. It is concluded that this provides evidence that secretin is a strong inhibitor of spontaneous gastric acid secretion and that acid in the jejunum causes the release of secretin in man.
Differential IL-21 signaling in APCs leads to disparate Th17 differentiation in diabetes-susceptible NOD and diabetes-resistant NOD.Idd3 mice
Authors: Sue M. Liu, David H. Lee, Jenna M. Sullivan, Denise Chung, Anneli Jäger, Bennett O.V. Shum, Nora E. Sarvetnick, Ana C. Anderson, Vijay K. Kuchroo
Journal: Journal of Clinical Investigation (2011)

Type 1 diabetes (T1D) is an autoimmune disease that shows familial aggregation in humans and likely has genetic determinants. Disease linkage studies have revealed many susceptibility loci for T1D in mice and humans. The mouse T1D susceptibility locus insulin-dependent diabetes susceptibility 3 (Idd3), which has a homologous genetic interval in humans, encodes cytokine genes Il2 and Il21 and regulates diabetes and other autoimmune diseases; however, the cellular and molecular mechanisms of this regulation are still being elucidated. Here we show that T cells from NOD mice produce more Il21 and less Il2 and exhibit enhanced Th17 cell generation compared with T cells from NOD.Idd3 congenic mice, which carry the protective Idd3 allele from a diabetes-resistant mouse strain. Further, APCs from NOD and NOD.Idd3 mice played a central role in this differential Th17 cell development, and IL-21 signaling in APCs was pivotal to this process. Specifically, NOD-derived APCs showed increased production of pro-Th17 mediators and dysregulation of the retinoic acid (RA) signaling pathway compared with APCs from NOD.Idd3 and NOD.Il21r-deficient mice. These data suggest that the protective effect of the Idd3 locus is due, in part, to differential RA signaling in APCs and that IL-21 likely plays a role in this process. Thus, we believe APCs provide a new candidate for therapeutic intervention in autoimmune diseases.