tbuckley/cabot-search huggingface dataset:
A1.08 CD141<sup>+</sup>CLEC9A<sup>+</sup>dendritic cells are enriched in an active state in the inflamedsynovium and contribute to synovial inflammation in rheumatoid arthritis
Authors: M Canavan, M O’Rourke, C Orr, S Basdeo, J Fletcher, DJ Veale, U Fearon
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Introduction</h3> Dendritic cells (DC) are a heterogeneous population of professional antigen presenting cells. Currently their classification within blood and skin has been well characterised however their identification within other tissues, in particular in the context of autoimmunity is limited. This work aims to identify DC within the inflamed synovium and elucidate how DC are altered by the microenvironment within the joint. <h3>Methods</h3> DC immunophenotyping was assessed in whole blood (WB), synovial fluid (SF) and synovial tissue (ST) using 9 colour flow cytometry. CD141<sup>+</sup> DC were isolated from SF, cultured overnight +/- TLR3 ligands and stained with a panel of antibodies. Monocyte derived DC were cultured in the presence of explant conditioned media (ECM) or SF. MoDC treated with SF were also cocultured with CD4<sup>+</sup> T cells for 5 days, after which T cell proliferation and intracellular cytokines were examined. <h3>Results</h3> RA patients have a significant decrease (p &lt; 0.05) in mDC in WB compared to HC. CD11c<sup>+</sup> HLADR<sup>+</sup> myeloid cells are increased in the ST compared to WB, express higher levels of CD80/CD40 and express CD64, CD14 and CD16. These cells may represent a myeloid subset of cells unique to inflammatory tissues. DC in SF are more mature than PB DC (increased CD80/CD40; p &lt; 0.05). SF is enriched in CD141<sup>+</sup>CLEC9A<sup>+</sup>DC compared to PB (p &lt; 0.005). These cells are rare in WB and previously unidentified in SF. SF CD141<sup>+</sup> DC express TREM1 while blood CD141<sup>+</sup> DC do not. SF CD141<sup>+</sup> DC express higher levels of CD80/CD86 and CD40 compared to blood CD141<sup>+</sup> DC. To examine the effect of the synovial microenvironment on DC, MoDC were cultured in the presence of ECM or SF. Both induced a significant increase in the expression of CD80 (p &lt; 0.05 and p &lt; 0.0001). Finally DC treated with SF and subsequently cocultured with CD4<sup>+</sup> T cells have enhanced IFNγ production and T cell proliferation. <h3>Conclusion</h3> Unique DC subsets are found in both ST and SF within the joint. These cells display a more activated phenotype than DC in circulation and &nbsp;the inflammatory nature of the joint contributes to this activation. These uniquely activated DC induce T cell proliferation and cytokine production.
IB-01 * GLIOMA-DERIVED GALECTIN-1 IS A POTENT SUPPRESSOR OF NK IMMUNOSURVEILLANCE
Authors: G. Baker, P. Chockley, V. Yadav, R. Doherty, M. Ritt, S. Sivaramakrishnan, M. Castro, P. Lowenstein
Journal: Neuro-Oncology (2014)

Natural killer (NK) cells safeguard against early tumor formation by destroying transformed target cells in a process referred to as NK immunosurveillance. However, the mechanisms used by malignant brain tumors to subvert this innate immune function remain unclear. We show that shRNA-mediated knockdown of the β-galactoside-binding lectin, galectin-1 (gal-1), in malignant glioma cells leads to the failure to form lethal intracranial tumors in RAG1-/- mice, a mouse strain devoid of adaptive immunity. However, gal-1 deficient glioma growth is fully restored on implantation into the brain of severely immunocompromised NOD-scid IL2Rg null mice, which lack both adaptive and innate immune function, thus implicating the innate immune response in the early rejection of gal-1 deficient glioma. Immunodepletion of NK cells in RAG1-/- or C57BL/6J mice using anti-asialo GM1 or anti-NK1.1 antibodies permit the growth of large gal-1 deficient gliomas. Antigen-specific IFN-γ ELISpot assays using splenocytes from immunocompetent C57BL/6J mice indicate that gal-1 deficient glioma is cleared prior to the onset of an adaptive anti-tumor immune response. Flow cytometric analysis of brain tumor-infiltrating immune cells reveal that gal-1 deficient gliomas contain significantly more granzyme B+ NK cells compared to gal-1 expressing gliomas. In-vitro experiments further show that gal-1 deficient glioma cells are over three times more sensitive to NK-mediated tumor lysis. We conclude that glioma-derived gal-1 is a powerful inhibitor of NK-mediated cytotoxicity in-vivo, and predict that its suppression will be of therapeutic value in the treatment of human malignant brain tumors by dramatically heightening anti-tumor NK immunosurveillance.
Dissecting Temporal Profiles of Neuronal and Axonal Damage After Mild Traumatic Brain Injury
Authors: Tanya Bogoslovsky, Ramon Diaz-Arrastia
Journal: JAMA Neurology (2016)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Neurology journal
Abstract 3316: The stem cell marker nestin inhibits growth and invasion of malignant melanoma
Authors: Michiko Akiyama, Yoko Matsuda, Masahito Hagio, Kiyoko Kawahara, Taeko Suzuki, Toshiyuki Ishiwata, Seiji Kawana, Zenya Naito
Journal: Cancer Research (2012)

Abstract BACKGROUND: Nestin, a class VI intermediate filament protein, was first described as a neural stem cell/progenitor cell marker. Nestin was detected in various neoplasms, and its expression level has relevance to the poor prognosis in some tumors, including malignant melanomas. Recently, nestin was reported as one of the cancer stem cell markers in melanomas. Furthermore, nestin is expressed in circulating tumor cells of melanoma patients, and its expression was found to be correlated with the prognosis. These reports indicate that nestin plays important roles in melanomas, and has the possibility of becoming a therapeutic target in melanomas. In the present study, we used a silencing strategy of nestin to clarify the effectiveness of nestin-targeting therapy in malignant melanomas. METHODS: We constructed a plasmid vector of short hairpin RNA (shRNA) tageting nestin and scramble vector as a negative control. Human malignant melanoma cells, A375 cells, were stably transfected with these vectors. Using nestin-shRNA-transfected cells, scramble vector-transfected cells, and wild-type cells, we analyzed cell growth, sphere formation, and invasion in vitro. Activation of the AKT/MAPK pathway was analyzed using a phosphorylated protein array. To determine the effect of nestin-knockdown in vivo, we performed tail vein injection of transfected and wild-type A375 cells into nude mice, and analyzed the metastatic tumor formation in 5 weeks. RESULTS: Nestin shRNA transfection suppressed cell growth, invasion, and sphere formation of A375 cells in vitro. In the protein array, the suppression of nestin decreased the phosphorylation of AKT and p53. The incidence of liver metastasis in nude mice was 100% in wild-type cell-injected mice, 75% in scramble vector-transfected cell-injected mice, and 16.7% in nestin-shRNA-transfected cell-injected mice. CONCLUSION: These findings suggest that nestin regulates cell growth, stemness, invasion, and metastasis of melanomas, in part, by alterling the phosphorylation of the MAPK/AKT pathway. Nestin may be a candidate therapeutic target in malignant melanomas. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3316. doi:1538-7445.AM2012-3316
BI-24 * COLLAGEN PLAYS A ROLE IN GLIOBLASTOMA TUMOR INVASION AND PATIENT SURVIVAL
Authors: K. B. Pointer, K. W. Eliceiri, P. A. Clark, J. S. Kuo
Journal: Neuro-Oncology (2014)

BACKGROUND: Glioblastoma (GBM) is the most malignant brain cancer. Collagen is minimally expressed in normal brain parenchyma; however, previous reports show upregulated collagen gene expression in GBM. We perform the first direct GBM collagen visualization, identify clinically relevant collagen signatures in focal and invasive GBMs and link them to differential patient survival. METHODS: Customized second harmonic generation (SHG) multiphoton workstation with excitation wavelength tuned to 890nm and a 445± 25nm bandpass emission filter was used to detect collagen in a clinically-annotated human GBM tissue microarray (TMA) for 111 patients. Human GBM cancer stem cell lines that form focal or invasive xenografts were implanted into mice brains. Symptomatic mice with verified xenografts were euthanized, brains excised, and stained with picrosirius red. Quantitative characterization of collagen fibers in xenografts and TMA images was performed with custom software. RESULTS: Collagen was directly visualized in GBMs with SHG and picrosirius red. In focal GBM xenografts, collagen was observed at tumor-brain boundaries, appearing to encapsulate the tumors. For invasive GBM xenografts, collagen was intercalated with tumor cells. Quantitative collagen analysis showed significant differences for mean angle between fibers for focal (60.3856 ± 2.2113) and invasive (70.2529 ± 1.6211) GBM xenografts. GBM TMA specimens were segregated into two collagen groups: fibrillar and immature. Patients with fibrillar GBM collagen had a statistically significantly better median survival (69.6 weeks) compared to immature GBM collagen patients (30.4 weeks). The mean angle between fibers was significantly different for GBMs with fibrillar (84.37 ± 7.298) versus immature (113.2 ± 11.60) collagen. CONCLUSIONS: We demonstrate that collagen can be directly visualized in GBMs, and is different in focal vs. invasive tumors. Our data suggest collagen is a potential survival marker: patients with fibrillar collagen have improved survival. Therefore, we hypothesize that collagen may influence tumor cell invasion by acting as a barrier, and collagen disruption may promote tumor invasion.
Ruptured Liver Metastasis With Active Hemorrhage Has the Classic Appearance of a Giant Cavernous Hemangioma on 99mTc-Labeled RBC Scintigraphy
Authors: Robert M. Wolfson, Jonathan Romsa
Journal: Clinical Nuclear Medicine (2012)

A 55-year-old woman with abdominal pain, trace hematochezia, and anemia underwent 99mTc-labeled RBC scintigraphy to assess for gastrointestinal bleeding. The patient had a remote history of malignant melanoma and had been in a motor vehicle collision 3 weeks prior. The scintigraphic findings were compatible with a giant cavernous hemangioma in the liver. A subsequent contrast-enhanced abdominal CT scan demonstrated venous extravasation into a ruptured liver metastasis.
Millions of Americans would drop insurance if exchange subsidies didn't exist, studies find
Authors: M. McCarthy
Journal: BMJ (2015)

Between eight and 10 million people would be likely to drop their health insurance if the US Supreme Court ruled in favor of a lawsuit challenging the legality of subsidies for insurance purchased on the federally run health insurance exchanges created by the Affordable Care Act, two studies have found.

A study by the RAND Corporation released estimates that a ruling leading to the elimination of the subsidies would cause 9.6 million people to go without insurance, as the number of people insured through the exchanges would drop from 13.7 million to 4.1 million.1

In addition, because many of those leaving the insurance pool would be younger, healthier people with lower health costs, premiums would rise for everyone who purchased cover on the individual insurance …
WARFARIN AND THE RISK OF STROKE AND BLEEDING IN ATRIAL FIBRILLATION PATIENTS UNDERGOING DIALYSIS
Authors: Meytal Avgil Tsadok, Cynthia Jackevicius, Mark Eisenberg, Mitesh Shah, Vidal Essebag, Elham Rahme, Karin Humphries, Jack Tu, Louise Pilote
Journal: Journal of the American College of Cardiology (2013)
Asymmetric Limb Uptake on Ga-67 Citrate Scintigraphy
Authors: MELTEM CAGLAR, SENIHA NALDOKEN
Journal: Clinical Nuclear Medicine (2001)

From Departments of Nuclear Medicine, Hacettepe University Medical Faculty* and Numune Hospital,† Ankara, Turkey Received for publication June 12, 2000. Accepted December 8, 2000. Reprint requests: Meltem Caglar, Hacettepe University Medical Faculty, Department of Nuclear Medicine, Sihhiye Ankara 06100, Turkey. E-mail: [email protected]
Human Immunodeficiency Virus Nephropathy and Intraglomerular Cryptococcus Neoformans
Authors: A Veatch, S H Dikman
Journal: New England Journal of Medicine (1998)

Figure 1. A 24-year-old man with the acquired immunodeficiency syndrome presented in May 1997 with proteinuria and renal insufficiency. The most recent assessment of viral burden revealed a human immunodeficiency virus (HIV) type 1 RNA level of 62,000 copies per milliliter. In September 1996, Cryptococcus neoformans infection had been diagnosed on the basis of blood and cerebrospinal fluid cultures (cerebrospinal fluid findings: glucose, 55 mg per deciliter [3.1 mmol per liter]; protein, 17 mg per deciliter; 6 red cells; and 0 white cells). The patient received a cumulative dose of 4.5 g of intravenous amphotericin B but declined maintenance therapy. . . .
Tc-99m MDP Uptake in Primary Breast Lymphoma
Authors: MANISH GOYAL, DAN BANG
Journal: Clinical Nuclear Medicine (1998)

Various conditions, including carcinoma of the breast and inflammatory mastitis, may show increased and often asymmetric activity in the breast on bone scans. The authors present a previously unpublished cause of diffuse uptake of Tc-99m MDP in the breast in a patient with primary malignant breast lymphoma. There was no history of surgical intervention, chemotherapy, or radiation to the breast. Although an infrequent cause of breast mass or enlargement, lymphoma should be considered in patients with increased, asymmetric breast uptake seen on bone scans.
Serosal lacerations during colonoscopy - a rare complication
Authors: N. Alcaide, P. Diez-Redondo, M. Herranz-Bachiller, P. Simón, R. Velasco-Lopez, M. Perez-Miranda
Journal: Endoscopy (2012)

A 47-year-old man underwent colonoscopy due to chronic diarrhea. A polypectomy of three polyps of less than 7 mm in the sigmoid was performed without complications. Shortly after the procedure, the patient complained of pain in the right iliac fossa, which was increasing in intensity. Examination of the patient revealed peritoneal irritation, leukocytosis, and elevation of C-reactive protein. Due to a suspicion of perforation, an abdominal computed tomography (CT) scan was performed, which showed pneumoperitoneum. At laparoscopy, multiple serosal lacerations were observed in the cecum and ascending colon ([Fig. 1]), and hematomas in the transverse colon, with ap-parent intact colonic mucosa. Washing of the peritoneal cavity was performed, and drains were placed. The patient's postoperative course was uneventful, and he was discharged 6 days after admission.
Hematopoietic Growth Factors Allowing Aggressive Treatment
Authors: J. Ismach
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Hematopoietic Growth Factors Allowing Aggressive Treatment Get access Judy Ismach Judy Ismach Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 23, 4 December 1991, Pages 1710–1711, https://doi.org/10.1093/jnci/83.23.1710 Published: 04 December 1991
1378 EFFECT OF ABCC2 HAPLOTYPES ON INDIOSYNCRATIC DRUG-INDUCED LIVER INJURY (DILI) SUSCEPTIBILITY
Authors: E. Ulzurrun, P. Saenz-Lopez, C. Stephens, F. Ruiz-Cabello, Y. Borraz, M. Robles, M.R. Cabello, G. Pelaez, M. Romero- Gomez, H. Hallal, J.M. Moreno-Planas, R. Planas, C. Guarner, A. Castiella, M.I. Lucena, R.J. Andrade
Journal: Journal of Hepatology (2012)
S11 Pirfenidone Post-authorisation Safety Registry (passport)-interim Analysis Of Ipf Treatment
Authors: T. Maher, V. Cottin, M. Skoeld, S. Tomassetti, A. Azuma, C. Giot, D. Yocum, S. Hamza, D. Koschel
Journal: Thorax (2014)

<h3>Introduction</h3> Pirfenidone (Esbriet<sup>®</sup>) is approved for mild/moderate idiopathic pulmonary fibrosis (IPF). PASSPORT is a post-authorisation safety registry required by the European Medicine Agency. <h3>Objective</h3> To present interim data from PASSPORT. <h3>Method</h3> Up to 140 EU sites will enrol 1000 patients. Safety data are recorded at routine clinic visits for 2 years. Adverse drug reactions (ADR: a noxious, unintended drug response at therapeutic doses) and serious ADRs (SADR: ADRs that are life-threatening; cause death, disability, congenital anomaly; require hospitalisation or an intervention to prevent permanent impairment) are collected. <h3>Results</h3> Data from 530 patients enrolled by 68 sites in 7 countries are included. Age was 69 ± 8.8 years (mean ± SD); IPF diagnosis duration was 1.8 ± 3.51 years; 81% were men. Median time in study was 5.5 months; total exposure was 284 person-years. Of 311 patients with ADRs, 85 discontinued due to ADR and 41 discontinued for other reasons. Approximately 1/3 of patients with ADRs had their dose adjusted. For patients who experienced an ADR: 55% of patients without a dose adjustment were able to continue treatment, while 69% of those with a dose adjustment were able to continue treatment. 20% discontinued due to the ADR after having a dose adjustment, but 31% discontinued due to the ADR without a dose adjustment. When ADRs were managed by dose adjustment, dose adjustment was associated with continuing treatment. <h3>Conclusion</h3> PASSPORT ADRs are comparable to those in clinical trials of pirfenidone in IPF. No new safety issues emerged. Dose adjustment may influence long-term tolerability of pirfenidone.
CD3ζ-chain expression is regulated by tumor necrosis factor via Src-like adaptor protein dependent proteosomal degradation in human T lymphocytes
Authors: Barbara Érsek, Viktor Molnár, Andrea Balogh, János Matkó, Andrew P Cope, Edit I Buzás, András Falus, György Nagy
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background and objectives</h3> decreased expression of the T cell receptor (TCR) ζ-chain has been reported in several autoimmune, inflammatory and malignant diseases, suggesting that ζ-chain downregulation is common at sites of chronic inflammation. While ζ-chain is critically important in T lymphocyte activation, the mechanism of the decreased ζ-chain expression is not known. Src-like adaptor protein (SLAP) is a master regulator of T cell activation; previous data indicated that SLAP regulates immunoreceptor signaling. The authors have examined the mechanism and the functional consequences of CD3 ζ-chain downregulation. <h3>Materials and methods</h3> CD3ζ and SLAP protein levels of Jurkat cells and primary human T lymphocytes were measured by Western blot. Jurkat cells were transiently transfected with siRNAs to silence SLAP, knockdown efficiency of the siRNAs was measured by real-time RT-PCR and by Western blot. For confocal microscopy experiments cells were transfected with eGFP-SLAP expression-ready, full-length cDNA vector or control eGFP vector. The colocalisation between CD3ζ and SLAP were determined by laser confocal microscopy. CD3ζ mRNA was measured by quantitative real-time RT-PCR, IL-2 level was measured by ELISA method. <h3>Results</h3> TNF treatment of human T lymphocytes (15–40 ng/ml) selectively downregulates CD3 ζ-chain expression in a dose dependent manner (p&lt;0.001), and decreases the activation induced IL-2 synthesis (p&lt;0.01). Although blocking of the lysosomal compartment fails to restore the TNF-induced CD3 ζ-chain downregulation, the inhibition of the proteasome prevented the effect of TNF. Both SLAP expression and the colocalisation of SLAP with CD3 ζ-chain was enhanced by TNF treatment (p&lt;0.05; p&lt;0.009 respectively), while TNF induced ζ-chain downregulation was inhibited by silencing SLAP with siRNA (p&lt;0.01). <h3>Conclusions</h3> Our present data suggest that TNF modulates T cell activation during inflammatory processes, by regulating the amount of CD3 ζ-chain expression via SLAP dependent mechanism. These data indicate that SLAP dependent regulation of CD3 ζ-chain provides fine control of TCR signaling.
Peer led programme for asthma education in adolescents
Authors: T. J Peters, A. Graham, C. Salisbury, L. Moore, M. Underwood, S. Eldridge, P. G Gibson, S. Shah, D. Sindhusake, H. Wang, J. K Peat, R. L Henry
Journal: BMJ (2001)

Editor—We have concerns about the design and analysis of Shah et al's cluster randomised trial of a peer led education programme for asthma.1 Neither the printed nor the (longer) electronic version mentioned how clustering was accounted for in the trial design. The sample size was not justified—neither the number of clusters (six) nor numbers of children in them. This may seem unimportant since confidence intervals were provided for the comparisons between arms, but the omission is crucial.

The authors did not specify the magnitude of differences considered in advance as clinically important. The small intracluster correlations observed could just be fortuitous. With so few clusters, any estimate of between-cluster variance (and hence intracluster correlation) will be extremely imprecise. Without proper details of trial design, the danger of publication bias remains, where a study with low power is more likely to be published when significance is attained. The widths of the comparative confidence intervals are not reassuring here.

It is unlikely that a fully considered trial design would include only six clusters, with apparently no attention being paid to stratification, given the sex and year imbalances.2 Important information was also omitted regarding the analysis plan, with between-arm comparisons in table 2 for quality of life as a total score and three subdomains. Only the electronic version states that the total score was the primary outcome.

More fundamentally, comparisons for each of the four outcomes were presented first for all children and then for four subgroups (males and females in years 7 and 10). Separate tests for subgroups rather than formal interaction tests are highly prone to false positive results. There was no indication that these subgroup analyses were established in advance, nor specifically whether others were conducted. The analysis section of the electronic version refers to sex and year as potential confounders, not effect modifiers.

If the principle of “electronic long, paper short” publishing is to be successful, it is important that short versions do not omit crucial methodological information. It cannot be assumed that all readers have access to electronic versions, and Plummer has commented on the paper (in his rapid response) without apparently checking the long version.3

We appreciate that the exclusion of cluster adjusted results was justified here on grounds of space,4 but we contend that issues of design and analysis are vital in cluster randomised trials and should have been mentioned in the short version.