tbuckley/cabot-search huggingface dataset:
NCRs and DNAM-1 mediate NK cell recognition and lysis of human and mouse melanoma cell lines in vitro and in vivo
Authors: Tadepally Lakshmikanth, Shannon Burke, Talib Hassan Ali, Silvia Kimpfler, Francesco Ursini, Loredana Ruggeri, Marusca Capanni, Viktor Umansky, Annette Paschen, Antje Sucker, Daniela Pende, Veronika Groh, Roberto Biassoni, Petter Höglund, Masashi Kato, Kazuko Shibuya, Dirk Schadendorf, Andrea Anichini, Soldano Ferrone, Andrea Velardi, Klas Kärre, Akira Shibuya, Ennio Carbone, Francesco Colucci
Journal: Journal of Clinical Investigation (2009)

NK cells use a variety of receptors to detect abnormal cells, including tumors and their metastases. However, in the case of melanoma, it remains to be determined what specific molecular interactions are involved and whether NK cells control metastatic progression and/or the route of dissemination. Here we show that human melanoma cell lines derived from LN metastases express ligands for natural cytotoxicity receptors (NCRs) and DNAX accessory molecule-1 (DNAM-1), two emerging NK cell receptors key for cancer cell recognition, but not NK group 2 member D (NKG2D). Compared with cell lines derived from metastases taken from other anatomical sites, LN metastases were more susceptible to NK cell lysis and preferentially targeted by adoptively transferred NK cells in a xenogeneic model of cell therapy. In mice, DNAM-1 and NCR ligands were also found on spontaneous melanomas and melanoma cell lines. Interference with DNAM-1 and NCRs by antibody blockade or genetic disruption reduced killing of melanoma cells. Taken together, these results show that DNAM-1 and NCRs are critical for NK cell-mediated innate immunity to melanoma cells and provide a background to design NK cell-based immunotherapeutic strategies against melanoma and possibly other tumors.
High-molecular weight kininogen. A secreted platelet protein.
Authors: A H Schmaier, A Zuckerberg, C Silverman, J Kuchibhotla, G P Tuszynski, R W Colman
Journal: Journal of Clinical Investigation (1983)

Human platelets were studied immunochemically to determine if they contain high-molecular weight kininogen. On crossed immunoelectrophoresis with total kininogen antisera (antisera that recognizes both high- and low-molecular weight kininogen) extracts of platelets contained total kininogen antigen. Platelet total kininogen antigen showed complete antigenic identity with plasma total kininogen and displayed the same electrophoretic migration as plasma total kininogen. Using antisera monospecific to high molecular weight kininogen, a competitive enzyme-linked immunosorbent assay (CELISA) was developed to directly measure platelet high-molecular weight kininogen. By CELISA, 27-101 ng of high molecular weight kininogen antigen per 10(8) platelets was quantitated in detergent-soluble lysates of washed human platelets from nine normal donors with a mean level of 60 ng +/- 24/10(8) platelets. Plasma high-molecular weight kininogen, either in the platelet suspending medium or on the surface of the platelets, could only account for 5% of antigen measured in the solubilized platelets. On the CELISA, platelet high-molecular weight kininogen was immunochemically identical to plasma and purified high-molecular weight kininogen. Platelet high-molecular weight kininogen was secreted from platelets after exposure to ionophore A23187 (3-15 microM), collagen (5-150 micrograms/ml), and thrombin (1.6 U/ml). Secreted platelet high-molecular weight kininogen did not become a part of the platelet Triton-insoluble cytoskeleton. On cross immunoelectrophoresis secreted platelet total kininogen antigen had a similar electrophoretic migration to plasma total kininogen. Thus, human platelets contain high-molecular weight kininogen that can be secreted from platelets and that may participate in plasma coagulation reactions.
Local attractor dynamics will introduce further information to synchronous neuronal fields
Authors: J. J. Wright
Journal: Behavioral and Brain Sciences (1997)

Simulations and analytic considerations show that synchronisation occurs in delay neural networks at the surrounds of externally driven sites. In the synchronous fields, network transmission has a static transfer function and H(X|R,C) is minimal. But when autonomous local states with attractor dynamics develop in the network, H(X|R,C) is not minimized. Physiological realism may therefore require some modifications in application of coherent infomax.
Low molecular weight IgM and CD5 B lymphocytes in rheumatoid arthritis.
Authors: H Xu, R Geddes, P J Roberts-Thomson
Journal: Annals of the Rheumatic Diseases (1994)

OBJECTIVES--To evaluate the role of low molecular weight (LMW) IgM and CD5 B cells in rheumatoid arthritis (RA) and to explore the possibility that LMW IgM is derived selectively from this subset of B cells. METHODS--LMW IgM in sera and culture supernatants was detected by a sensitive immunoblot technique with an enhanced chemiluminescence detection system. CD5 B cells were determined by FACScan cytometry. In vitro studies were established in culture plates containing pokeweed mitogen with or without 2-mercaptoethanol (2-ME). Supernatants were obtained from CD5 positive hybridomas and CD5 negative hybridomas. Other immunological indices were measured by laser nephelometry. RESULTS--Circulating LMW IgM was detected in all rheumatoid patients with significantly higher levels being observed in sero-positive patients. LMW IgM correlated significantly with total IgM and RF. Peripheral blood mononuclear cells (PBMC) from the majority of the patients with RA secreted LMW IgM in vitro as did mononuclear cells from a synovial fluid sample. The addition of low concentrations of 2-ME to the culture medium enhanced the proportions of secreted monomeric IgM. In contrast, PBMC from healthy subjects secreted only trace quantities of LMW IgM. In RA no significant correlations were observed between CD5 B cells and LMW IgM and RF. LMW IgM could be detected in the supernatants from both CD5+ and CD5- B cell lines. Finally, CD5 B cells were not significantly elevated in RA and levels remained constant over time. CONCLUSION--LMW IgM exists in high concentrations in RA sera and synovial fluid. Serum level correlates with RF and IgM. In vitro studies have suggested that the occurrence of LMW IgM may be due to an intrinsic defect(s) in the assembly of the IgM pentameric molecule. LMW IgM is unlikely to be derived solely from CD5 B cells.
Assessment of Reactivity to Tumor Extracts by Leukocyte Adherence Inhibition and Dermal Testing2
Authors: Denis R. Burger, Arthur A. Vandenbark, Patricia Finke, Arthur Malley, Maureen Frikke, John Black, Karen Acott, Don Begley, R. Mark Vetto
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Assessment of Reactivity to Tumor Extracts by Leukocyte Adherence Inhibition and Dermal Testing Get access Denis R. Burger, Denis R. Burger Search for other works by this author on: Oxford Academic PubMed Google Scholar Arthur A. Vandenbark, Arthur A. Vandenbark Search for other works by this author on: Oxford Academic PubMed Google Scholar Patricia Finke, Patricia Finke Search for other works by this author on: Oxford Academic PubMed Google Scholar Arthur Malley, Arthur Malley Search for other works by this author on: Oxford Academic PubMed Google Scholar Maureen Frikke, Maureen Frikke Search for other works by this author on: Oxford Academic PubMed Google Scholar John Black, John Black Search for other works by this author on: Oxford Academic PubMed Google Scholar Karen Acott, Karen Acott Search for other works by this author on: Oxford Academic PubMed Google Scholar Don Begley, Don Begley Search for other works by this author on: Oxford Academic PubMed Google Scholar R. Mark Vetto R. Mark Vetto Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 59, Issue 2, August 1977, Pages 317–323, https://doi.org/10.1093/jnci/59.2.317 Published: 01 August 1977 Article history Received: 22 November 1976 Accepted: 25 February 1977 Published: 01 August 1977
Cardiovascular Risks from Fine Particulate Air Pollution
Authors: Douglas W. Dockery, Peter H. Stone
Journal: New England Journal of Medicine (2007)

More than a decade ago, prospective epidemiologic studies showed that mortality was increased among people living in communities with elevated concentrations of fine particulate air pollution.1,2 Subsequent research has shown that particulate air pollution is statistically and mechanistically linked to increased cardiovascular disease.3 New data are beginning to shed light on which persons are at heightened risk.In this issue of the Journal, Miller et al.4 report on data from the Women's Health Initiative (WHI) observational study, which greatly expands our understanding of how fine particulate pollution affects health. Earlier long-term prospective cohort studies showed an association between levels . . .
Endobronchial lipoma mimicking bronchial carcinoid tumour
Authors: Yvonne Nussbaumer-Ochsner, Frank Rassouli, Frank Uhlmann, Robert Thurnheer
Journal: Thorax (2015)

A 68-year-old smoker on aspirin/clopidogrel due to recent percutaneous coronary intervention (PCI) / stenting presented with intermittent haemoptysis. Bronchoscopy revealed an endoluminal tumour in a right-lower-lobe segment (figure 1). No biopsy was taken due to bleeding risk. Aspirate analysis showed sparse cells with granular cytoplasm, and a presumptive diagnosis of bronchial carcinoid was …
An RNA Profile Identifies Two Subsets of Multiple Sclerosis Patients Differing in Disease Activity
Authors: Linda Ottoboni, Brendan T. Keenan, Pablo Tamayo, Manik Kuchroo, Jill P. Mesirov, Guy J. Buckle, Samia J. Khoury, David A. Hafler, Howard L. Weiner, Philip L. De Jager
Journal: Science Translational Medicine (2012)

The multiple sclerosis (MS) patient population is highly heterogeneous in terms of disease course and treatment response. We used a transcriptional profile generated from peripheral blood mononuclear cells to define the structure of an MS patient population. Two subsets of MS subjects (MS(A) and MS(B)) were found among 141 untreated subjects. We replicated this structure in two additional groups of MS subjects treated with one of the two first-line disease-modifying treatments in MS: glatiramer acetate (GA) (n = 94) and interferon-β (IFN-β) (n = 128). One of the two subsets of subjects (MS(A)) was distinguished by higher expression of molecules involved in lymphocyte signaling pathways. Further, subjects in this MS(A) subset were more likely to have a new inflammatory event while on treatment with either GA or IFN-β (P = 0.0077). We thus report a transcriptional signature that differentiates subjects with MS into two classes with different levels of disease activity.
Increased asthma medication use in association with ambient fine and ultrafine particles
Authors: S. von Klot, G. Wölke, T. Tuch, J. Heinrich, D.W. Dockery, J. Schwartz, W.G. Kreyling, H.E. Wichmann, A. Peters
Journal: European Respiratory Journal (2002)

The association between particulate air pollution and asthma medication use and symptoms was assessed in a panel study of 53 adult asthmatics in Erfurt, Germany in winter 1996/1997. Number concentrations of ultrafine particles, 0.01–0.1 µm in diameter (NC 0.01–0.1 ), mean 17,300·cm −3 , and mass concentrations of fine particles 0.01–2.5 µm in diameter (MC 0.01–2.5 ), mean 30.3 µg·m −3 , were measured concurrently. They were not highly correlated (r=0.45). The associations between ambient particle concentrations and the prevalence of inhaled β 2 -agonist, corticosteroid use and asthma symptoms, were analysed separately with logistic regression models, adjusting for trend, temperature, weekend, holidays, and first order autocorrelation of the error. Cumulative exposures over 14 days of ultrafine and fine particles were associated with corticosteroid use. β 2 -agonist use was associated with 5-day mean NC 0.01–0.1 and MC 0.01–2.5 . The prevalence of asthma symptoms was associated with ambient particle concentrations. The results suggest that reported asthma medication use and symptoms increase in association with particulate air pollution and gaseous pollutants such as nitrogen dioxide.
La Psiquiatría del Médico práctico.
Authors: Antonio Fernandez-Victorio Cociña
Journal: JAMA (1922)

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
Herniation of the Heart After Intrapericardial Pneumonectomy for Bronchial Carcinoma
Authors: V. N. Sharma, M. Bates, R. L. Hurt
Journal: Thorax (1959)

Although IgM serves as a first barrier to Ag spreading, the cellular and molecular mechanisms following B lymphocyte activation that lead to IgM secretion are not fully understood. By virtue of their anatomical location, marginal zone (MZ) B cells rapidly generate Ag-specific IgM in response to blood-borne pathogens and play an important role in the protection against these potentially harmful Ags. In this study, we have explored the contribution of TLR agonists to MZ B cell activation and mobilization as well as their ability to promote primary IgM responses in a mouse model. We demonstrate that diverse TLR agonists stimulate MZ B cells to become activated and leave the MZ through pathways that are differentially dependent on MyD88 and IFN-αβ receptor signaling. Furthermore, in vivo stimulation of MZ B cells with TLR agonists led to a reduction in the expression of the sphingosine-1-phosphate (S1P) receptors expressed by MZ B cells and/or increased CD69 cell surface levels. Importantly, as adjuvants for a T cell-dependent protein Ag, TLR agonists were found to accelerate the kinetics but not magnitude of the Ag-specific IgM response. Together, these data demonstrate that in vivo TLR agonist treatment enhances the early production of Ag-specific IgM and activates MZ B cells to promote their relocation.
Ischaemia-induced mucus barrier loss and bacterial penetration are rapidly counteracted by increased goblet cell secretory activity in human and rat colon
Authors: Joep Grootjans, Inca H R Hundscheid, Kaatje Lenaerts, Bas Boonen, Ingrid B Renes, Fons K Verheyen, Cornelis H Dejong, Maarten F von Meyenfeldt, Geerard L Beets, Wim A Buurman
Journal: Gut (2012)

<h3>Objective</h3> Colonic ischaemia is frequently observed in clinical practice. This study provides a novel insight into the pathophysiology of colon ischaemia/reperfusion (IR) using a newly developed human and rat experimental model. <h3>Design</h3> In 10 patients a small part of colon that had to be removed for surgical reasons was isolated and exposed to 60 min of ischaemia (60I) with/without different periods of reperfusion (30R and 60R). Tissue not exposed to IR served as control. In rats, colon was exposed to 60I, 60I/30R, 60I/120R or 60I/240R (n=7 per group). The tissue was snap-frozen or fixed in glutaraldehyde, formalin or methacarn fixative. Mucins were stained with Periodic Acid Schiff/Alcian Blue (PAS/AB) and MUC2/Dolichos biflorus agglutinin (DBA). Bacteria were studied using electron microscopy (EM) and fluorescent in situ hybridisation (FISH). Neutrophils were studied using myeloperoxidase staining. qPCR was performed for MUC2, interleukin (IL)-6, IL-1β and tumour necrosis factor α. <h3>Results</h3> In rats, PAS/AB and MUC2/DBA staining revealed mucus layer detachment at ischaemia which was accompanied by bacterial penetration (in EM and FISH). Human and rat studies showed that, simultaneously, goblet cell secretory activity increased. This was associated with expulsion of bacteria from the crypts and restoration of the mucus layer at 240 min of reperfusion. Inflammation was limited to minor influx of neutrophils and increased expression of proinflammatory cytokines during reperfusion. <h3>Conclusions</h3> Colonic ischaemia leads to disruption of the mucus layer facilitating bacterial penetration. This is rapidly counteracted by increased secretory activity of goblet cells, leading to expulsion of bacteria from the crypts as well as restoration of the mucus barrier.
Genetic Aspects of Pancreatitis
Authors: David C. Whitcomb
Journal: Annual Review of Medicine (2010)

Acute pancreatitis and chronic pancreatitis are complex inflammatory disorders of the pancreas with unpredictable severity, complications, and clinical courses. Growing evidence for genetic risk and modifying factors, plus strong evidence that only a minority of patients with these disorders are heavy alcohol drinkers, has revolutionized our concept of these diseases. Once considered a self-inflicted injury, pancreatitis is now recognized as a complex inflammatory condition like inflammatory bowel disease. Genetic linkage and candidate gene studies have identified six pancreas-targeting factors that are associated with changes in susceptibility to acute and/or chronic pancreatitis, including cationic trypsinogen (PRSS1), anionic trypsinogen (PRSS2), serine protease inhibitor Kazal 1 (SPINK1), cystic fibrosis transmembrane conductance regulator (CFTR), chymotrypsinogen C (CTRC) and calcium-sensing receptor (CASR). Patients with mutations in these genes are at increased risk of pancreatitis caused by a variety of stresses including hyperlipidemia and hypercalcemia. Multiple studies are reporting new polymorphisms, as well as complex gene × gene and gene × environmental interactions.
Responses of Dog's Pad Vessels to Epinephrine Following Sympathectomy or Denervation
Authors: THEODORE COOPER, VALLEE L. WILLMAN, ALRICK B. HERTZMAN
Journal: Circulation Research (1959)

Augmented reactivity of the skin vessels of the hind limbs of dogs to doses of l-epinephrine in the physiologic range could not be detected following conventional sympathectomy. Larger doses of epinephrine resulted in exaggerated reactions. Augmented reactivity of these vessels to physiologic doses of epinephrine was detectable if total cholinergic as well as adrenergic denervation of the limb was accomplished.
Propranolol for portal hypertensive gastropathy: Another virtue of β-blockade?
Authors: Santiago J. Muñoz
Journal: Hepatology (1992)

The two main causes of gastrointestinal bleeding in cirrhosis are oesophageal varices and portal hypertensive gastropathy (PHG). Rebleeding from varices can be prevented by beta-blockers, but it is not clear whether these drugs effectively reduce rebleeding from PHG. 54 cirrhotic patients with acute or chronic bleeding from severe PHG took part in a randomised, controlled trial to investigate the efficacy of propranolol in prevention of rebleeding from PHG. 26 patients were randomised to receive propranolol daily at a dose that reduced the resting heart rate by 25% or to 55 bpm (20-160 mg twice daily), throughout mean follow-up of 21 (SD 11) months. 28 untreated controls were followed-up, with the same examinations, for 18 (13) months. The actuarial percentages of patients free of rebleeding from PHG were significantly higher in the propranolol-treated patients than in the untreated controls at 12 months (65% vs 38%; p &lt; 0.05) and at 30 months of follow-up (52% vs 7%; p &lt; 0.05). Propranololtreated patients had fewer episodes of acute bleeding than controls (0 · 010 [0 · 004] vs 0 · 120 [0 · 040] per patient per month). Multivariate analysis showed that absence of propranolol treatment was the only predictive variable for rebleeding. Actuarial survival was slightly higher in the propranolol group than in the controls, but the difference was not significant. Thus, long-term propranolol treatment significantly reduces the frequency of rebleeding from severe PHG, and may improve the prognosis of cirrhotic patients with this disorder.
PTEN Mutation, EGFR Amplification, and Outcome in Patients With Anaplastic Astrocytoma and Glioblastoma Multiforme
Authors: J. S. Smith, I. Tachibana, S. M. Passe, B. K. Huntley, T. J. Borell, N. Iturria, J. R. O'Fallon, P. L. Schaefer, B. W. Scheithauer, C. D. James, J. C. Buckner, R. B. Jenkins
Journal: JNCI Journal of the National Cancer Institute (2001)

Background: Survival of patients with anaplastic astrocytoma is highly variable. Prognostic markers would thus be useful to identify clinical subsets of such patients. Because specific genetic alterations have been associated with glioblastoma, we investigated whether similar genetic alterations could be detected in patients with anaplastic astrocytoma and used to identify those with particularly aggressive disease. Methods: Tissue specimens were collected from 174 patients enrolled in Mayo Clinic Cancer Center and North Central Cancer Treatment Group clinical trials for newly diagnosed gliomas, including 63 with anaplastic astrocytoma and 111 with glioblastoma multiforme. Alterations of the EGFR, PTEN, and p53 genes and of chromosomes 7 and 10 were examined by fluorescence in situ hybridization, semiquantitative polymerase chain reaction, and DNA sequencing. All statistical tests were two-sided. Results: Mutation of PTEN, amplification of EGFR, and loss of the q arm of chromosome 10 were statistically significantly less common in anaplastic astrocytoma than in glioblastoma multiforme (P = .033, P = .001, and P<.001, respectively), and mutation of p53 was statistically significantly more common (P<.001). Univariate survival analyses of patients with anaplastic astrocytoma identified PTEN (P = .002) and p53 (P = .012) mutations as statistically significantly associated with reduced and prolonged survival, respectively. Multivariate Cox analysis of patients with anaplastic astrocytoma showed that PTEN mutation remained a powerful prognostic factor after adjusting for patient age, on-study performance score, and extent of tumor resection (hazard ratio = 4.34; 95% confidence interval = 1.82 to 10.34). Multivariate classification and regression-tree analysis of all 174 patients identified EGFR amplification as an independent predictor of prolonged survival in patients with glioblastoma multiforme who were older than 60 years of age. Conclusion: PTEN mutation and EGFR amplification are important prognostic factors in patients with anaplastic astrocytoma and in older patients with glioblastoma multiforme, respectively.