tbuckley/cabot-search huggingface dataset:
Mycophenolate Mofetil in the Treatment of Neuromyelitis Optica Spectrum Disorder
Authors: So-Young Huh, Su-Hyun Kim, Jae-Won Hyun, Ae-Ran Joung, Min Su Park, Byung-Jo Kim, Ho Jin Kim
Journal: JAMA Neurology (2014)

<h3>Importance</h3> Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disorder of the central nervous system. Recently, various immunosuppressant medications were introduced as therapeutic options for preventing relapse of NMOSD. However, our understanding of the effectiveness of mycophenolate mofetil (MMF) in treating patients with NMOSD is based on only a small number of studies. <h3>Objective</h3> To evaluate the efficacy and safety of MMF treatment in patients with NMOSD. <h3>Design, Setting, and Participants</h3> A 3-center retrospective review of our experiences, examining results from 59 patients with NMOSD (24 with neuromyelitis optica and 35 with a limited form of the disease) who were treated with MMF (1000-2000 mg/d). <h3>Main Outcomes and Measures</h3> Patients' annualized relapse rate, disability as measured by the Expanded Disability Status Scale, and experience of adverse effects due to MMF were assessed. <h3>Results</h3> Of the 59 patients, 1 with NMOSD who had to discontinue MMF use in the first month due to a rash was excluded. The remaining 58 patients were included in the drug-efficacy analysis. The median post-MMF annualized relapse rate was significantly lower than the pre-MMF annualized relapse rate (0.0 vs 1.5;<i>P</i> &lt; .001). The Expanded Disability Status Scale scores also significantly decreased after MMF treatment (3.0 vs 2.5;<i>P</i> = .005). Thirty-five patients (60%) were relapse free, and Expanded Disability Status Scale scores were stabilized or improved in 53 patients (91%). Fourteen patients discontinued MMF treatment owing to ongoing relapse (10 patients), rash (1 patient), pregnancy (1 patient), and financial problems (2 patients), but MMF was generally well tolerated. <h3>Conclusions and Relevance</h3> In this observational study, MMF treatment induced reduction of relapse frequency, stabilized or improved disability, and was well tolerated in patients with NMOSD.
1135. Results of a Phase I/II Clinical Trial with OncoVEXGM-CSF, a Second Generation Oncolytic Herpes Simplex Virus
Authors: J. C. Hu, R. S. Coffin, C. J. Davis, N. J. Graham, N. Groves, P. J. Guest, K. J. Harrington, N.D. James, C. A. Love, I. McNeish, L. C. Medley, A. Michael, C. M. Nutting, H. S. Pandha, C. A. Shorrock, J. Simpson, J. Steiner, N. M. Steven, R. C. Coombes
Journal: Molecular Therapy (2005)

OncoVEXGM-CSF is a second generation oncolytic HSV expressing GM-CSF. Deletion of ICP34.5 provides tumour selectivity, a modification extensively studied elsewhere. Compared to previous oncolytic HSV, oncolytic potency is increased using a clinical virus strain with greater lytic capabilities than previous laboratory strains, and by expressing US11 as an IE rather than an L gene. Immune stimulation is improved by deleting ICP47, which blocks antigen presentation, and expression of GM-CSF. Following intra-tumoral injection, OncoVEXGM-CSF is, therefore, intended to stimulate a GM-CSF-enhanced immune response to tumour antigens released by oncolysis. This aims to treat metastatic disease and reduce tumor recurrence.
Anuria and Hydronephrosis Following Ureteral Catheterization
Authors: Benedict R. Harrow
Journal: JAMA (1962)

RARELY has bilateral ureteral catheterization with or without retrograde pyelography caused complete obstruction of both ureters. Two papers in the past have reported anuria due to ureteral obstruction following catherization of normal ureters, with a total of only 4 cases being outlined. Recently, we encountered such an incidence. Report of a Case A 50-year-old man experienced right renal colic and intermittent gross hematuria for 6 weeks. An intravenous urogram on April 15, 1961, revealed prompt function with normal calyces, pelves, and ureters bilaterally with no hydronephrosis or hydro-ureters. A small 3 by 4 mm. stone was discovered in the lower right ureter. At Mercy Hospital the right ureteral stone was easily extracted on the first pass with a wire-like stone basket on the morning of April 25, 1961. At the same time a No. 5 French catheter was passed without difficulty to the left renal pelvis, and x-rays were taken
Abstract 4011: CYP3A4 over-expression promotes ER-positive breast cancer cell growth, in part, through Stat3 activation
Authors: Zhijun Guo, Ranjana Mitra, David A. Potter
Journal: Cancer Research (2010)

Abstract Cytochrome P450 3A4 (CYP3A4) is an important monooxygenase that metabolizes a wide range of xenobitics including many drugs and environmental chemicals, as well as endogenous substances such as steroids. Expression of CYP3A4 has been observed in breast tumors, but its studies in breast cancer cells have mainly focused on carcinogen bioactivation, hormone metabolism and chemotherapy resistance. Whether CYP3A4 has a direct effect on breast cancer progression is unknown. To address these questions, we performed RNAi knock down studies, demonstrating roles for CYP3A4 in proliferation, motility, and clonogenicity of the MCF7 line. CYP3A4 knock down also inhibited phosphorylation of key regulatory proteins such as c-Src and STAT3, implicating its importance in breast cancer progression. To further study the effect and mechanisms of CYP3A4 in breast cancer progression, stable CYP3A4 over-expressing MCF7 cell lines were isolated and characterized. CYP3A4 over-expressing clones exhibited a higher proliferation rate than the vector control clone, consistent with the flow cytometry cell cycle analysis in which CYP3A4 over-expressing clones exhibited a markedly higher S phase component. Apoptosis was not increased due to CYP3A4 over-expression. The CYP3A4 over-expressing clones adhere poorly to plastic and require poly-D-lysine coated tissue culture plate to grow robustly. Adhesion to fibronectin was also reduced as the result of over-expression. In immunofluorescence microscopic study, the highest CYP3A4 over-expressing clone displayed disorganized focal adhesions, potentially explaining the poor adhesion. Consistent with the knock down study, CYP3A4 over-expressing clones exhibited elevated phosphorylation of both c-Src and Stat3 that could be responsible for the observed promotion of proliferation. These results support the model that CYP3A4 is an important signaling protein, linked to the c-Src/Stat3 pathway that influences breast cancer progression. 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 4011.
Patient privacy and confidentiality
Authors: J. Chalmers
Journal: BMJ (2003)

The NHS is engaged in a debate about what can and cannot be done legitimately with patients' data. On one hand, anxieties exist about who should have access to the data and for what purposes; on the other hand, requirements for more accountability, performance assessment, effective health protection, and efficient administration are increasing the need for more and better information. How is this being addressed, and how can it be resolved?

Health services have belatedly realised that they have work to do in order to comply with modern legislation about data protection and recent professional guidance.1 In England and Wales a new Health and Social Care Act has been passed, leading to the establishment of the Patient Information Advisory Group, and the NHS Information Authority has just completed a public consultation on the privacy of patients. 2 3 In Scotland the Confidentiality and Security Advisory Group for Scotland has, after 18 months' deliberation, recommended major changes in practice, although these do not include new legislation for Scotland.4 Other countries are also wrestling with similar issues and there …
Next-generation RNA Sequencing of Archival Formalin-fixed Paraffin-embedded Urothelial Bladder Cancer
Authors: Yu Liu, Aidan P Noon, Eduardo Aguiar Cabeza, Jess Shen, Cynthia Kuk, Christine Ilczynski, Ruoyu Ni, Balram Sukhu, Kin Chan, Nuno L Barbosa-Morais, Thomas Hermanns, Benjamin J Blencowe, Azar Azad, Theodorus H van der Kwast, James W F Catto, Alexandre R Zlotta, Jeffrey L Wrana
Journal: European Urology (2014)
The extent of liver steatosis in chronic hepatitis C virus infection is mirrored by caspase activity in serum
Authors: Nicole Seidel, Xandra Volkmann, Florian Länger, Peer Flemming, Michael P. Manns, Klaus Schulze-Osthoff, Heike Bantel
Journal: Hepatology (2005)

Abstract Hepatic steatosis is a frequent histological alteration in chronic hepatitis C virus (HCV) infection that sensitizes the liver to cell injury, inflammation, and fibrosis via unclear mechanisms. Although apoptosis has been implicated in various liver diseases, its importance in HCV-associated steatosis is largely unknown. In this study, we investigated the role of caspases, the key regulators of apoptosis, and employed two novel caspase assays, an immunological and a luminometric enzyme test, to detect hepatic caspase activation in sera from HCV patients with different grades of steatosis. Our data show that increased caspase activation can be found not only in liver biopsies, but also in sera from HCV patients with liver steatosis. Patients with steatosis exhibited significantly higher serum levels of caspase activity compared with normal healthy individuals. Moreover, the extent of steatosis closely correlated with serum caspase activity, whereas in particular in cases of low or moderate steatosis, no correlation was found with aminotransferase levels. In conclusion , apoptotic caspase activation is considerably elevated in HCV-associated steatosis. More importantly, our data imply that measurement of caspase activation might be a sensitive serum biomarker to detect liver steatosis in patients with chronic HCV infection and other liver diseases. (Hepatology 2005.)
Molecular identification of the role of voltage-gated K+ channels, Kv1.5 and Kv2.1, in hypoxic pulmonary vasoconstriction and control of resting membrane potential in rat pulmonary artery myocytes.
Authors: S L Archer, E Souil, A T Dinh-Xuan, B Schremmer, J C Mercier, A El Yaagoubi, L Nguyen-Huu, H L Reeve, V Hampl
Journal: Journal of Clinical Investigation (1998)

Hypoxia initiates pulmonary vasoconstriction (HPV) by inhibiting one or more voltage-gated potassium channels (Kv) in the pulmonary artery smooth muscle cells (PASMCs) of resistance arteries. The resulting membrane depolarization increases opening of voltage-gated calcium channels, raising cytosolic Ca2+ and initiating HPV. There are presently nine families of Kv channels known and pharmacological inhibitors lack the specificity to distinguish those involved in control of resting membrane potential (Em) or HPV. However, the Kv channels involved in Em and HPV have characteristic electrophysiological and pharmacological properties which suggest their molecular identity. They are slowly inactivating, delayed rectifier currents, inhibited by 4-aminopyridine (4-AP) but insensitive to charybdotoxin. Candidate Kv channels with these traits (Kv1.5 and Kv2.1) were studied. Antibodies were used to immunolocalize and functionally characterize the contribution of Kv1. 5 and Kv2.1 to PASMC electrophysiology and vascular tone. Immunoblotting confirmed the presence of Kv1.1, 1.2, 1.3, 1.5, 1.6, and 2.1, but not Kv1.4, in PASMCs. Intracellular administration of anti-Kv2.1 inhibited whole cell K+ current (IK) and depolarized Em. Anti-Kv2.1 also elevated resting tension and diminished 4-AP-induced vasoconstriction in membrane-permeabilized pulmonary artery rings. Anti-Kv1.5 inhibited IK and selectively reduced the rise in [Ca2+]i and constriction caused by hypoxia and 4-AP. However, anti-Kv1.5 neither caused depolarization nor elevated basal pulmonary artery tone. This study demonstrates that antibodies can be used to dissect the whole cell K+ currents in mammalian cells. We conclude that Kv2. 1 is an important determinant of resting Em in PASMCs from resistance arteries. Both Kv2.1 and Kv1.5 contribute to the initiation of HPV.
Hepatocyte-specific mutation of both NF-κB RelA and STAT3 abrogates the acute phase response in mice
Authors: Lee J. Quinton, Matthew T. Blahna, Matthew R. Jones, Eri Allen, Joseph D. Ferrari, Kristie L. Hilliard, Xiaoling Zhang, Vishakha Sabharwal, Hana Algül, Shizuo Akira, Roland M. Schmid, Stephen I. Pelton, Avrum Spira, Joseph P. Mizgerd
Journal: Journal of Clinical Investigation (2012)

The acute phase response is an evolutionarily conserved reaction in which physiological stress triggers the liver to remodel the blood proteome. Although thought to be involved in immune defense, the net biological effect of the acute phase response remains unknown. As the acute phase response is stimulated by diverse cytokines that activate either NF-κB or STAT3, we hypothesized that it could be eliminated by hepatocyte-specific interruption of both transcription factors. Here, we report that the elimination in mice of both NF-κB p65 (RelA) and STAT3, but neither alone, abrogated all acute phase responses measured. The failure to respond was consistent across multiple different infectious, inflammatory, and noxious stimuli, including pneumococcal pneumonia. When the effects of infection were analyzed in detail, pneumococcal pneumonia was found to alter the expression of over a thousand transcripts in the liver. This outcome was inhibited by the combined loss of RelA and STAT3. Moreover, this interruption of the acute phase response increased mortality and exacerbated bacterial dissemination during pneumonia, possibly as a result of acute humoral enhancement of macrophage opsonophagocytosis, which was impaired in the mutant mice. Thus, we conclude that RelA and STAT3 are essential for stress-induced transcriptional remodeling in the liver and the subsequent activation of the acute phase response, whose functional role includes compartmentalization of local infection.
Blood-pressure screening and supervision in general practice.
Authors: J H Barber, D G Beevers, R Fife, V M Hawthorne, H M McKenzie, R G Sinclair, R J Simpson, G M Stewart, D I Williams
Journal: BMJ (1979)

Since April 1975 all men aged 35-69 years registered with four general practices in west central Scotland have had their blood pressure checked whenever they visit the surgery. Although the practice locations range from rural to city centre and observers comprise receptionists, nurses, and doctors, a standard procedure has been adopted for the examination, recording, follow-up, and management of high blood pressure. The results confirm that raised blood pressure is common and often goes undetected. Even when hypertension is known, casual blood pressure readings often exceed accepted normal levels. The findings also show that a population may be routinely examined through normal contact with the family doctor, and that this can provide a convenient, acceptable, and effective means of detecting and reducing raised blood pressure.
Characterization of the adhesion of the human monocytic cell line U937 to cultured endothelial cells.
Authors: P E DiCorleto, C A de la Motte
Journal: Journal of Clinical Investigation (1985)

Adhesion of blood-borne monocytes to the vascular endothelium is the first step in the infiltration of this leukocyte into the vessel wall or the interstitial space during inflammation. A significant role for the monocyte in both wound healing and atherogenesis is now well accepted. The molecular interactions involved in monocyte attachment to the endothelium are unknown. To study this phenomenon we have developed an in vitro system that uses the human monocytic tumor cell line U937 as a model for the blood-borne monocyte. 51Cr-labeled U937 cells were found to adhere with high affinity to cultured endothelial cells (ECs) from several sources. Much less binding was observed to either smooth muscle cells or fibroblasts from several species. Conditioned medium and cocultivation experiments ruled out the possibility that target cells could affect U937 cell binding by secretion of factors. Binding of U937 cells to porcine aortic ECs reached equilibrium after 30 min at 37 degrees C and 90 min at 4 degrees C with similar extent of binding at the two temperatures. Binding of U937 to the endothelium reached saturation at 9-12 U937 per porcine aortic EC (semi-confluent) with half-maximal binding at 1.5 X 10(6) U937 cells/ml. Bound cells dissociated with a half-life of 20 h at 37 degrees C. Adhesion of U937 cells was blocked by prior incubation of ECs with normal monocytes but not with platelets, lymphocytes, or neutrophils. Trypsin treatment or detergent solubilization of ECs inhibited U937 cell binding. A striking effect of EC density on monocytic cell adhesion was observed with bovine, rat, and porcine ECs. Confluent cultures of these cells exhibited negligible binding of U937, but when plated sparsely, the same cells were excellent targets for U937 cell adhesion. In addition, when confluent cultures of bovine aortic ECs were "wounded" with a cotton swab and then allowed to recover for 24 h at 37 degrees C, U937 cells were found to adhere most readily to the ECs migrating into the wound and neighboring the wound but not to ECs in the confluent monolayer away from the wound edge. These latter results may have implications for the focal adhesion of monocytes to the vessel wall in vivo.
Pregnancy Loss and Later Risk of Atherosclerotic Disease
Authors: Mattis Flyvholm Ranthe, Elisabeth A. Wreford Andersen, Jan Wohlfahrt, Henning Bundgaard, Mads Melbye, Heather A. Boyd
Journal: Circulation (2013)

Pregnancy losses and atherosclerotic disease may be etiologically linked through underlying pathology. We examined whether miscarriage and stillbirth increase later risk of myocardial infarction, cerebral infarction, and renovascular hypertension.Among women pregnant at least once between 1977 and 2008, we identified a cohort of women with miscarriages, stillbirths, or live singleton births. These women were followed from the end of pregnancy for incident myocardial infarction, cerebral infarction, and renovascular hypertension. Using Poisson regression, we estimated incidence rate ratios for each of the outcomes by history of miscarriage and stillbirth. Among 1,031,279 women followed for >15,928,900 person-years, we identified 27 98 myocardial infarctions, 40 53 cerebral infarctions, and 1269 instances of renovascular hypertension. Women with stillbirths had 2.69 (95% confidence interval, 2.06-3.50), 1.74 (1.32-2.28), and 2.42 (1.59-3.69) times the rates of myocardial infarction, cerebral infarction, and renovascular hypertension, respectively, as women with no stillbirths. Compared with women with no miscarriages, women with miscarriages had 1.13 (1.03-1.24), 1.16 (1.07-1.25), and 1.20 (1.05-1.38) times the rates of these same outcomes, respectively; these associations were dose dependent, with each additional miscarriage increasing the rates of myocardial and cerebral infarction and renovascular hypertension by 9% (3% to 16%), 13% (7% to 19%), and 19% (9% to 30%), respectively. Associations were strongest in younger women (<35 years).Pregnancy losses were associated with subsequent risks of myocardial infarction, cerebral infarction, and renovascular hypertension, consistent with either shared etiology or the initiation of pathological processes by a pregnancy loss leading to atherosclerosis.
Anti-CD22 and anti-CD79B antibody drug conjugates are active in different molecular diffuse large B-cell lymphoma subtypes
Authors: M Pfeifer, B Zheng, T Erdmann, H Koeppen, R McCord, M Grau, A Staiger, A Chai, T Sandmann, H Madle, B Dörken, Y-W Chu, A I Chen, D Lebovic, G A Salles, M S Czuczman, M C Palanca-Wessels, O W Press, R Advani, F Morschhauser, B D Cheson, P Lenz, G Ott, A G Polson, K E Mundt, G Lenz
Journal: Leukemia (2015)
A Study of the Mechanism of the Toluidine Blue Dye Test
Authors: P. Herlin, J. Marnay, J.H. Jacob, J.M. Ollivier, A.M. Mandard
Journal: Endoscopy (1983)

Toluidine blue is commonly used by endoscopists as a screening test for squamous cell carcinoma. Little information is available on the mechanism of vital staining as it is not preserved by conventional fixation. By using a simple method to stabilize toluidine blue, the authors were able to study the action of the dye under the light and electron microscope. The findings are reported.
Survivors Speak Up For Their Rights
Authors: J. Burklow
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Survivors Speak Up For Their Rights Get access John Burklow John Burklow Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 24, 19 December 1990, Pages 1878–1879, https://doi.org/10.1093/jnci/82.24.1878 Published: 19 December 1990
A quarter of patients with neurotic disorders dont seek help
Authors: R. Dobson
Journal: BMJ (2003)

One in four people with neurotic disorders avoid seeking profession help. Of a study sample of nearly 1400 people, a quarter said they had not been to see a doctor at some time in the past year, in spite of the fact that either they or their family felt they should have.

“The attitudes detected in our subjects with neurotic disorders help to explain why people do not always seek effective help for their mental disorders, and are indicators of a worrying public education gap that will be hard …
Human T-cell heterogeneity as delineated with a specific human thymus lymphocyte antiserum. In vitro effects on mitogen response mixed leukocyte culture, cell-mediated lymphocytotoxicity, and lymphokine production.
Authors: J N Woody, A Ahmed, R C Knudsen, D M Strong, K W Sell
Journal: Journal of Clinical Investigation (1975)

Human peripheral blood lymphocytes (PBL) were evaluated by their responses to phytohemmagglutinin (PHA-P), concanavallin A (con-A), and pokeweed mitogen (PWM), both before and after treatment with an antiserum against human thymic lymphocyte antigens (HTLA) that had been made T-cell-specific by multiple absorptions with immunoglobulin EAC-positive lymphoblast cell lines (B cells). Cells treated with HTLA were examined for their ability to react in a mixed lymphocyte culture (MLC) and to form killer cells in a cell-mediated lymphocytotoxicity (CML) system. Sensitized cells were also examined for their ability to respond to purified protein derivative (PPD) by blastogenesis, migration inhibitory factor release (MIP), and lymphotoxin (LT) production, both before and after treatment with HTLA and complement. The HTLA was in itself highly stimulatory to PBL. However, with the addition of complement and subsequent cell destruction, a marked decrease in its stimulatory response was noted. PBL treated with HTLA and complement exhibited marked inhibition of responsiveness to con-A with little decrease in PHA-P -OR PWM stimulation except at very high concentration of HTLA. MLC reaction was inhibited only when responder cells were treated with HTLA + C'. Treatment of stimulator cells with HTLA + C' did not significantly alter the MLC response. The HTLA + C'-treated cells failed to form killer cells in the CML reaction and inhibited PPD-induced blasto-genesis from PPD-sensitized individuals; however, treatment of sensitized cells with HTLA + C' had little effects on the release of MIF and LT. It is suggested that subpopulations of T-cells carry surface antigens that bind with this specific antisera, and that the con-A-responsive cells, the responder cells in the MLC, and killer T-cells comprise a separate subset from cells responding to PHA-P or PWM, OR THE MIF-and LT-producing cells.