tbuckley/cabot-search huggingface dataset:
176. Target-Site Preferences of Sleeping Beauty Transposons in an Intron of the B-raf Oncogene
Authors: Jason B. Bell, Christopher S. Hackett, Aron M. Geurts, Corey M. Carlson, Lara S. Collier, Geyi Liu, David A. Largaespada, Perry B. Hackett
Journal: Molecular Therapy (2005)

The Sleeping Beauty (SB) transposon is a Tc1/mariner family transposon that is being examined for its efficacy as a non-viral, integrating vector for human gene therapy. Integration of SB transposons, into TA dinucleotide base pairs, with respect to genes (exons and introns) and intergenic regions appears fairly random at the genomic level, but not on a micro-scale, with a previously reported consensus sequence around the TA-integration sites [Vigdal et al. (2002) J. Mol. Biol. 323: 441|[ndash]|452; Carlson et al. (2003) Genetics 165: 243|[ndash]|256]. In an earlier study [Liu et al. (2005) J. Mol. Biol. 346: 161|[ndash]|173], we analyzed target-site preferences of SB transposons using an intra-plasmid transposition assay. We found that preferential sites had a unique deformation pattern that was characterized by an off-center angling, non-uniform twisting of the DNA helix and an increase in the distance between the central base pairs at preferred target sites. Particular deformations of the double helix could be predicted by the Vstep algorithm, which distinguished three categories of TA sites that varied by about 16-fold in their acceptance of SB transposons: preferred, intermediate-preferred, and non-preferred. Here we report our results of integrations into TA sites in the ninth intron of the mouse B-raf gene. Transpositions occurred as a result of remobilization, by SB10 transposase, of chromosomally-resident |[ldquo]|insertionally oncogenic|[rdquo]| transposons in somatic tissues of transgenic mice. This resulted in oncogenic selection of 25 gain-of-function insertions into B-raf in p19Arf|[minus]|/|[minus]| mice [Collier and Carlson et al., submitted]. There are 349 potential TA-integration sites in the 4069-bp intron, of which 22 were targets for 25 unique insertions. The Vstep algorithm predicted preferential patterns for 44 of the 349 possible sites, of which 7 were hit and three were hit twice (a 23% hit rate). There were 107 predicted intermediate-preferred sites of which 11 were targets (10% hit rate), and 198 non-preferred sites of which 4 were hit (a 2% hit rate). These data strongly suggest about an 11-fold preference for integration at certain TA dinucleotide base pairs in chromatin, which can be predicted by the Vstep algorithm. This data suggests that a V-step algorithm can predict preferential insertion sites for transposon vectors during non-viral, SB-mediated gene transfer protocols.
Three Years Experience with Endoscopic Variceal Ligation for Treatment of Bleeding Varices
Authors: J. S. Goff, R. M. Reveille, G. V. Stiegmann
Journal: Endoscopy (1992)

Endoscopic variceal ligation (EVL) was developed as an alternative to endoscopic variceal sclerosis (ES) because of the high complication rate seen with ES. The new technique involves placement of small elastic bands around the variceal channels in the distal esophagus. The first 146 consecutive patients treated with EVL during the period from August, 1986 to July, 1989 are reported. Portal hypertension was caused by alcoholic liver disease in 93 of these patients. The average age of the patients was 53 years and 66% were males. All of the patients had recently bled from esophageal varices. At the time of treatment, 23% of the patients were actively bleeding. They were all treated acutely with EVL and had repeated treatments with the long-term goal of variceal eradication. The overall survival was 73%. Varices were eradicated or reduced to grade one in 78% of the 125 patients who were followed for more than 30 days. Variceal eradication required a mean of 5.5 sessions. Recurrent bleeding occurred in 44% of the total patient population. There were no major complications from EVL. It is concluded from this non-randomized experience that EVL is an effective treatment for bleeding esophageal varices and that it appears to be as effective as sclerotherapy with fewer complications.
Generation and immune-characterization of single chain fragment variable (scFv) antibody recognize breast cancer cells line (MCF-7)
Authors: Ilham Mahgoub, Ahmed K Bolad, Mohamed Mergani
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Phage display technologies were used to produce single-chain antibodies (scFv) against breast cancer cell line (MCF-7). The mouse B cell hybridoma line C3A8 was the starting material, which generates a monoclonal antibody against breast cancer cells (MCF-7). The best candidate
Does it matter who requests necropsies? Prospective study of effect of clinical audit on rate of requests
Authors: I. S Kamal, D. R Forsyth, J. R Jones
Journal: BMJ (1997)

Objective: To investigate the epidemiology of gonorrhoea in an urban area in the United Kingdom.Design: Analysis of all cases of gonorrhoea with regard to age, sex, ethnic group, and socioeconomic group with 1991 census data as a denominator.Setting: Leeds, a comparatively large urban area (population around 700 000) in the United Kingdom.Subjects: All residents of Leeds with culture proved cases of gonorrhoea during 1989-93.Main outcome measure: Relative risk of gonorrhoea.Results: Sex, age, race, and socioeconomic group and area of residence were all independently predictive of risk of infection.Young black men aged 20-29 were at highest risk, with incidences of 3-4% per year.Black subjects were 10 times more likely than white subjects to acquire infection, and subjects from the most deprived socioeconomic areas were more than four times more likely than those from the most affluent areas to acquire infection.Conclusions: Different ethnic and socioeconomic groups vary in their risk of infection with gonorrhoea within an urban area.Targeted interventions and screening to reduce the incidence of sexually transmitted disease are now priorities.
Immediate and Long-Term Safety of Recombinant Adeno-associated Virus Injection into the Nonhuman Primate Muscle
Authors: David Favre, Nathalie Provost, Véronique Blouin, Gilles Blancho, Yan Chérel, Anna Salvetti, Philippe Moullier
Journal: Molecular Therapy (2001)

Previous studies on distribution and toxicity of viral vectors administered in monkeys indicated that the nonhuman primate model has a reasonable predictive value for clinical applications. In this study, eight macaques were injected intramuscularly with recombinant adeno-associated virus (rAAV) at doses similar to those administered to hemophilia B patients, and followed to analyze the dissemination and shedding in biological samples and long-term persistence in distant organs. Following rAAV delivery, we found vector genome in various biological fluids for up to 6 days and infectious particles exclusively in the serum during the first 48–72 hours. rAAV sequences were detected in peripheral blood mononuclear cells (PBMC) for up to 10 months. At necropsy, 8 to 18 months after rAAV delivery, rAAV sequences were found in lymph nodes and livers but never in the gonads. Tissue examination, of liver in particular, showed no abnormalities. We concluded that during our experimental time frame, rAAV-mediated gene transfer into skeletal muscle of macaques seemed to be safe with respect to the recipient and the environment. However, it was associated with a transient viremia and the persistence of rAAV sequences in PBMC, lymph nodes, and liver, the long-term consequences of which remain unknown.
Acute Ulcerative Colitis
Authors: Fred M. Sulzberger
Journal: New England Journal of Medicine (1945)

ONE of the still unsolved problems in medicine is a condition described in the medical literature as "chronic ulcerative colitis." As yet no completely successful treatment has been evolved, and many confusing reports on the efficacy of various therapeutic measures are still to be found. Most authors agree concerning the symptomatology and consider that the disease is essentially chronic in nature, with acute exacerbations as a characteristic feature. The majority of writers also agree that a chronic ulcerative colitis may be caused by several different agents. In one form of the disease, for which no specific cause has as yet . . .
Management of Breast Cancer: Radical Mastectomy
Authors: Thomas J. Anglem
Journal: JAMA (1974)

ONE of the oddities occasionally encountered in science or medicine is the emergence, and for a time the spread, of an idea in spite of a great preponderance of evidence to the contrary. Usually when this occurs it can be accounted for by the prestige or reputation of one or more of its sponsors and the inherent desirability of the goal toward which the idea is directed, quite apart from its practicability. A classic example of this phenomenon in recent history was the socalled Lysenko Affair<sup>1-3</sup>in which the Russian antimendelian agronomistbiologist T. D. Lysenko claimed to have discovered a method of preconditioning wheat grain whereby it could be planted in the summer and harvested in the winter, and planted in the winter and harvested in the summer. He declared that all plant and human life could be controlled by environment. Jovarsky<sup>1</sup>says, Between 1933 and 1935 he
The Syndrome of the Wrist Cutter
Authors: HAROLD GRAFF, RICHARD MALLIN
Journal: American Journal of Psychiatry (1967)

Many hospitals are experiencing an influx of patients who have made several suicide attempts through wrist slashing. A study was undertaken to learn the possible causes of such behavior. It suggested that the wrist slashers have a common behavior pattern stemming from early maternal deprivation and imbedded in inability to give and receive meaningful verbal communications. Therapy is directed at fostering more mature methods of giving and receiving love.
Is it better to be smart or stupid?
Authors: Kamran Abbasi
Journal: BMJ (2004)

At a meeting last week I was reminded of a quote by Victor Hugo: “A stand can be made against invasion by an army; no stand can be made against invasion of an idea.” We'd like to think your cluttered heads permit invasion by a few ideas from each week's BMJ about how to make decisions on patient management or policy making, things that are useful in day to day practice. One of the criticisms we often hear is that this focus misses some of the more innovative and interesting work done to test early ideas and …
Autoantibody secreting cells and long-lived plasma cells are enriched within inflamed kidneys of NZB/NZW F1 lupus mice and sensitive to bortezomib treatment
Authors: C. Starke, S. Frey, U. Wellmann, V. Urbonaviciute, G. Schett, T. Winkler, R. E. Voll
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Autoantibodies to double stranded (ds)DNA represent an important marker for serological diagnosis of systemic lupus erythematosus (SLE) and may critically contribute to the pathogenesis of lupus nephritis. A long-term production of (auto-) antibodies is maintained by long-lived plasma cells. However, the anatomical sites of these cells are not yet fully identified. In contrast to short-lived plasma cells, long-lived plasma cells are extremely resistant to therapy and may often sustain refractory disease courses. Therefore, the development of novel therapeutic strategies to specifically target long-lived plasma cells is of particular importance. <h3>Objectives</h3> Using the New Zealand black × New Zealand white (NZB/NZW) F1 mouse model of SLE the authors characterised antigen-producing cells in nephritic kidneys in respect to antigen-specificity, longevity and susceptibility to the proteasome inhibition by bortezomib (Bz). <h3>Material and methods</h3> For discrimination between short- and long-lived plasma cells, female NZB/NZW F1 mice which already showed proteinuria and have developed high titres of anti-dsDNA antibodies were fed with 5-bromo-29-deoxy-uridine (BrdU). Short- and long-lived plasma cells within inflamed kidneys were quantified by flow cytometry. The existence of plasma cells in the kidneys was confirmed by histological analyses. Anti-dsDNA and anti-nucleolin producing cells were detected by ELISPOT assay. Diseased lupus mice were treated short-term with Bz (1 mg/kg, twice in a 12 h interval intravenously). <h3>Results</h3> The authors found the CD138/intracellular κ/λ-L chain<sup>+</sup> plasma cells in renal tissue of NZB/NZW F1 mice which often formed small clusters and correlated with disease activity. Using in vivo BrdU-labelling the authors identified not only short-lived but also substantial amounts of long-lived plasma cells within nephritic kidneys. Bz treatment remarkably reduced both plasma cell compartments and T lymphocytes in inflamed kidneys. In addition, the numbers of detected cells secreting autoantibodies to dsDNA and nucleolin were significantly decreased after treatment with Bz. Moreover, the frequency of autoreactive cells in the inflamed kidneys was higher than in the spleen and bone marrow. <h3>Conclusion</h3> Pathogenic short- and long-lived plasma cells are present in the nephritic kidneys of NZB/NZW F1 lupus mice and can be efficiently depleted by treatment with Bz. Hence, the elimination of autoreactive plasma cells from the inflamed kidneys may represent a new treatment strategy for lupus nephritis which may critically contribute to the amelioration of lupus nephritis.
Effect of ketanserin, a new blocking agent of the 5‐HT<sub>2</sub> receptor, on airway responsiveness in asthma
Authors: M. Cazzola, G. Assogna, G. Lucchetti, G. Cicchitto, G. D'Amato
Journal: Allergy (1990)

Most of the antihypertensive drugs have a liability for adverse effects in asthma. Since there are few available data on the effect of ketanserin, a new antihypertensive drug which is a type‐2 serotonin receptor antagonist, on human respiratory function, we have tested whether this drug can modify bronchial hyperresponsiveness to methacholine in asthmatic patients. The protective effect of intravenous ketanserin (0.14 mg/kg) was small, but significant.
A Four-Year Appraisal of Thioridazine
Authors: YVAN LEGER
Journal: American Journal of Psychiatry (1966)

A four-year survey of the use of thioridazine is reported. A high success rate was obtained in a variety of mental disorders encountered in 1,225 psychiatric patients, both hospitalized and outpatient. The results obtained in the largest group, the schizophrenics, were especially striking. The capacity of thioridazine to suppress the symptoms of schizophrenia was reflected in the prototype of a calm, obedient, well-behaved, and manageable patient. In mental defectives, with and without epilepsy, thioridazine proved to be effective in behavioral problems. Freedom from excessive sedation or obtunding effect made it especially valuable in remotivating outpatients and facilitating their adaptation to the outside world. Results obtained with thioridazine show it to be highly effective, well tolerated, and consistent in its therapeutic action.
Case 28-1979
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, Timothy E. Guiney, John T. Fallon
Journal: New England Journal of Medicine (1979)

Presentation of CaseAn 80-year-old woman was admitted to the hospital because of dyspnea.She was well until three years earlier, when she began to have episodes of diplopia, dizziness and faintness when stooping or working in a hot environment. On one occasion she fainted; a physician found a heart murmur. Two years before admission these episodes ceased. Twenty-one months before entry she began to have gradually increasing exertional dyspnea, followed by paroxysmal nocturnal dyspnea and edema. One month later she entered another hospital, where a diagnosis of aortic stenosis with congestive heart failure was made. Digoxin and hydrochlorothiazide were . . .
Measles Virus and Its Biology
Authors: Sidney Kibrick
Journal: JAMA (1978)

The current explosion of information regarding the various animal viruses has made it difficult for those with general interests in the field to keep abreast of recent developments. This monograph,<i>Measles Virus and Its Biology</i>, is the first offering in a new series entitled<i>Experimental Virology</i>, which is directed at providing a solution for this problem. The monographs in this series are not intended to be encyclopedic but rather to present concise, selective, updated reviews on viruses of topical interest. The proposed readership includes virologists, teachers of virology, clinical researchers, medical and graduate students, and those in allied fields whose research might benefit from such information. This volume reviews and updates current knowledge about measles and attempts to relate these data to various unresolved aspects of this agent and its complication. Emphasis is placed on the interactions between the virus and its host cells at a cellular level and on
Phase 1b study of lenalidomide in combination with rituximab-CHOP (R2-CHOP) in patients with B-cell lymphoma
Authors: H Tilly, F Morschhauser, G Salles, R-O Casasnovas, P Feugier, T J Molina, F Jardin, L Terriou, C Haioun, B Coiffier
Journal: Leukemia (2012)
PARATHORMONE LEVELS ARE INDEPENDENTLY ASSOCIATED WITH THE PRESENCE OF LEFT VENTRICULAR HYPERTROPHY IN PATIENTS WITH CORONARY ARTERY DISEASE
Authors: Alvaro Aceña, Maria Gonzalez-Casaus, Luis Blanco-Colio, Jose Luis Martin Ventura, Ana Maria Pello, Rocío Carda, Julia Anna Palfy, Orejas Miguel, Rosa Rabago, Emilio Gonzalez-Parra, Oscar Lorenzo, Jeronimo Farre, Jesus Egido, José Tunon
Journal: Journal of the American College of Cardiology (2014)
Role of Bruton’s tyrosine kinase (BTK) in growth and metastasis of INA6 myeloma cells
Authors: R Bam, S U Venkateshaiah, S Khan, W Ling, S S Randal, X Li, Q Zhang, F van Rhee, B Barlogie, J Epstein, S Yaccoby
Journal: Blood Cancer Journal (2014)

Abstract Bruton’s tyrosine kinase (BTK) and the chemokine receptor CXCR4 are linked in various hematologic malignancies. The aim of the study was to understand the role of BTK in myeloma cell growth and metastasis using the stably BTK knockdown luciferase-expressing INA6 myeloma line. BTK knockdown had reduced adhesion to stroma and migration of myeloma cells toward stromal cell-derived factor-1. BTK knockdown had no effect on short-term in vitro growth of myeloma cells, although clonogenicity was inhibited and myeloma cell growth was promoted in coculture with osteoclasts. In severe combined immunodeficient-rab mice with contralaterally implanted pieces of bones, BTK knockdown in myeloma cells promoted their proliferation and growth in the primary bone but suppressed metastasis to the contralateral bone. BTK knockdown myeloma cells had altered the expression of genes associated with adhesion and proliferation and increased mammalian target of rapamycin signaling. In 176 paired clinical samples, BTK and CXCR4 expression was lower in myeloma cells purified from a focal lesion than from a random site. BTK expression in random-site samples was correlated with proportions of myeloma cells expressing cell surface CXCR4. Our findings highlight intratumoral heterogeneity of myeloma cells in the bone marrow microenvironment and suggest that BTK is involved in determining proliferative, quiescent or metastatic phenotypes of myeloma cells.
Restoration of liver insulin signaling in Insr knockout mice fails to normalize hepatic insulin action
Authors: Haruka Okamoto, Silvana Obici, Domenico Accili, Luciano Rossetti
Journal: Journal of Clinical Investigation (2005)

Partial restoration of insulin receptor Insr expression in brain, liver, and pancreatic beta cells is sufficient for rescuing Insr knockout mice from neonatal death, preventing diabetes ketoacidosis, and normalizing life span and reproductive function. However, the transgenically rescued mice (referred to as L1) have marked hyperinsulinemia, and approximately 30% develop late-onset type 2 diabetes. Analyses of protein expression indicated that L1 mice had modestly reduced Insr content but normal insulin-stimulated Akt phosphorylation in the liver. Conversely, L1 mice had a near complete ablation of Insr protein product in the arcuate and paraventricular nuclei of the hypothalamus, which was associated with a failure to undergo insulin-dependent Akt phosphorylation in the hypothalamus. To test whether reconstitution of insulin signaling in the liver is sufficient for restoring in vivo hepatic insulin action, we performed euglycemic hyperinsulinemic clamp studies in conscious L1 and WT mice. During the clamp, L1 mice required an approximately 50% lower rate of glucose infusion than did WT controls, while the rate of glucose disappearance was not significantly altered. Conversely, the rate of glucose production was increased approximately 2-fold in L1 mice. Thus, restoration of hepatic insulin signaling in Insr knockout mice fails to normalize the in vivo response to insulin.
Elevated Lipoprotein(a) and Premature Coronary Heart Disease-Reply
Authors: Andrew G. Bostom
Journal: JAMA (1997)

<h3>In Reply.</h3> —Drs Maher and Brown emphasize several explanations for why we failed to detect a positive interaction between LDL cholesterol levels and elevated plasma Lp(a) levels, resulting in a heightened risk for incident premature CHD: low mean LDL cholesterol levels, low sensitivity of sinking pre-β lipoprotein band on electrophoresis, and the impact of LDL cholesterol-lowering therapeutic measures in the cohort. In fact, the mean LDL cholesterol levels are irrelevant—we sought evidence of interaction only in those individuals who had both elevated LDL cholesterol (ie, ≥4.1 mmol/L [160 mg/dL]) and elevated plasma Lp(a) levels. We agree that the sensitivity of sinking pre-β lipoprotein band is limited. However, our study was based on 129 incident CHD events vs only 16 incident CHD events in the study by Maher and colleagues.<sup>1</sup>Accordingly, we must have had at least as much power to detect a positive interaction equivalent in magnitude to the one reported
NICE recommends widening choice of biological drugs for patients with rheumatoid arthritis
Authors: S. Mayor
Journal: BMJ (2010)

Patients with rheumatoid arthritis can be offered treatment with rituximab, a drug that depletes B cells, or with the tumour necrosis factor (TNF) inhibitors adalimumab, etanercept, infliximab, or abatacept, after previous treatment (including at least one TNF inhibitor) has failed, says final draft guidance published by the UK National Institute for Health and Clinical Excellence (NICE). This overturns previous guidance limiting patients to only one course of TNF inhibitor.

Disease modifying anti-rheumatic drugs may be classified as conventional (such as methotrexate or sulfasalazine) or biological, which includes the TNF inhibitors and rituximab.

The latest guidance recommends rituximab, in combination with methotrexate, as an option for adults with severe, active rheumatoid arthritis who have had an inadequate response to or who are intolerant of other disease modifying drugs, including …