tbuckley/cabot-search huggingface dataset:
443. Tissue Specific Expression of Short Hairpin RNAs for the Treatment of HCV Using Liver Specific RNA Pol II Expression Cassettes
Authors: David A. Suhy, Alexander A. Kolykhalov, Linda B. Couto, Luz Maria Garcia, A. Rosanna Schroeder, Amy E. Parker, Gabriel Haniff, Sara M. Cunningham, Mark A. Kay, Peter W. Roelvink
Journal: Molecular Therapy (2005)

Infection with the Hepatitis C virus (HCV) represents a major world-wide health problem. HCV is a liver-tropic RNA virus, and RNAi based treatments have been proposed as a new therapeutic modality. We are developing short-hairpin RNAs to elicit an RNAi response against the HCV genome. Robust expression of shRNAs from ubiquitous Pol III promoters has been demonstrated by various groups and authors. However, the potential for off-target effects makes it desirable to limit expression of shRNAs to the tissue of interest. Toward this goal we have evaluated liver-specific Pol II promoters for the expression of shRNAs. Most, if not all, transcripts generated by RNA pol II polymerase are capped. The 3' ends of these transcripts are usually polyadenylated. The presence of the Cap and/or the polyA tail may negatively affect the activity of Dicer leading to inactive, or low level active shRNAs. Several HCV specific shRNAs were cloned at variable distances downstream of a liver-specific promoter, such that transcription initiation occurred between 1 and 8 nucleotides from the start of the hairpin sequence. Termination of transcription was accomplished using either synthetic poly A sequences (based on the rabbit beta globin terminator, SPA), the U1 box terminator, or the minimal polyA cassette (as described by Xia et al (2002) Nat Biotech 20: 1006-1010). These constructs were evaluated in Huh7 cells by co-transfection with an HCV-luciferase fusion reporter. Transcription of the shRNA from the +2, +3, or +4 position resulted in 60-70 % inhibition of luciferase activity, similar to what has been observed using Pol III promoters. The level of silencing was similar regardless of the terminator used. These analyses have defined the optimal configuration for liver specific expression of anti-HCV short hairpin RNA transcripts. Use of these constructs should limit potential off target effects, without sacrificing high level hepatic expression. In vivo evaluation of these constructs is underway, with the ultimate goal of delivering these potential liver-specific HCV therapeutics to the liver with either viral or non-viral delivery vectors.
Medicine: a partnership of trust and faith
Authors: R. R. F. Address
Journal: BMJ (2014)

<h3>Abstract</h3> Multidrug resistance (MDR) represents the major cause of unsatisfaction in the application of chemotherapy for cancer treatment. So far, an <i>in vivo</i> robust high-throughput screening system for anti-tumor drug MDR is still lacking and the molecular mechanisms for MDR still remain elusive. Given a myriad of merits of zebrafish relative to other animal models, we aimed to establish MDR system in zebrafish stably expressing ATP-binding cassette (ATP-cassette) superfamily transporters and study the potential regulatory mechanism. We first constructed a <i>Tg(abcb4:EGFP)</i> transgenic zebrafish stably expressing both Abcb4 and EGFP using Tol2-mediated approach. The expression level of Abcb4 and EGFP was significantly induced when <i>Tg(abcb4:EGFP)</i> transgenic zebrafish embryos were exposed to doxorubicin (DOX) or vincristine (VCR), accompany with a marked decrease in rhodamine B (RhB) accumulation in embryos, which indicates a remarkable increase in drug efflux upon the exposure to DOX or VCR. Mechanistically, AKT and ERK signaling were activated when treated with DOX or VCR. With the application of AKT and ERK inhibitors, the drug resistance phenomena could be reversed with differential responsive effects. Of note, downstream NF-κB played a central role in the regulation of Abcb4-mediated drug resistance. Taken together, the engineered <i>Tg(abcb4:EGFP)</i> transgenic zebrafish model provides a new platform for drug resistance screening <i>in vivo</i>, which could facilitate and accelerate the process of drug development.
Serum and sputum alpha 2 macroglobulin in patients with chronic obstructive airways disease.
Authors: D Burnett, R A Stockley
Journal: Thorax (1981)

Serum alpha 2 macroglobulin concentrations were measured in patients with chronic obstructive airways disease and an age-matched group of control subjects. The mean serum level of alpha 2 macroglobulin was significantly lower in bronchitic subjects with acute chest infections than the mean value of the controls. No significant differences were observed between serum alpha 2 macroglobulin values in controls, subjects with "emphysema", and bronchitic patients who did not have chest infections. Sputum alpha 2 macroglobulin concentrations were compared in sputum samples from bronchitic patients with and without acute chest infections. The protein was detected (greater than 0.2 mg/l) in 94% of sputum samples from infected subjects but only 60% of non-infected sputum samples. Concentrations of alpha 2 macroglobulin in infected samples were significantly higher than the non-infected samples. Sputum/serum concentration ratios of alpha 2 macroglobulin were also significantly higher in infected samples but this difference was eliminated by "correcting" the values with the albumin sputum/serum ratios of the same samples. The results suggest that alpha 2 macroglobulin concentrations are higher in bronchial secretions during chest infection because of increased transudation from the blood rather than the presence of significant local secretion.
From Mindless to Mindful Practice — Cognitive Bias and Clinical Decision Making
Authors: Pat Croskerry
Journal: New England Journal of Medicine (2013)

Interview with Dr. Pat Croskerry on widespread cognitive biases and ways of counteracting them for accurate diagnosis. (17:18)Download Much diagnostic error is caused by cognitive bias. More than 100 biases affecting clinical decision making have been described, and many medical disciplines acknowledge their pervasive influence on our thinking. Training in critical thinking may ameliorate the problem.
Electrodermal Activity in Low and High Alexithymia Neurotic Patients
Authors: Andreas D. Rabavilas
Journal: Psychotherapy and Psychosomatics (1987)

This study explores the relations between alexithymia and level of arousal in patients suffering from anxiety states. Among 105 patients investigated, two groups were finally identified by means of the Schalling-Sifneos Personality Scale; a group of patients with 'low' and a group with 'high' alexithymia. These groups underwent a psychophysiological assessment concerning electrodermal activity measures recorded during resting and stimulation periods. The results suggested that high alexithymia patients demonstrated significantly higher levels of electrodermal arousal and slower recovery time in novel situations as compared with low alexithymia patients. These findings support the view that an exacerbated degree of arousal may be an important factor with respect to the development of alexithymia, even in a nonpsychosomatic population.
An 81-Year-Old Woman With Temporal Arteritis
Authors: Robert H Shmerling
Journal: JAMA (2006)

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
Psychiatric aspects of pernicious anaemia: a prospective controlled investigation.
Authors: R. Shulman
Journal: BMJ (1967)

Subarachnoid Haemorrhage-Storey Banum recent memory and higher intellectual abilities, but compatible with no loss of employment status except in professional, executive, and similar occupations.Moderate impairment falls be- tween the two above, and is usually associated with a drop in employment status.Physical Disability.-This excludes purely ocular disabilities, and refers mainly to the consequences of weakness or other disturbances of the limbs.Those with C.N.S. signs are not in- cluded unless there is frank disability-which depends mainly on the severity of the signs and the nature of the patient's work. SummarSome results of a psychiatric study of 261 cases of sub- arachnoid haemorrhage are presented, dealing especially with comparisons between operative and conservative treatment of 209 patients with single aneurysms of the posterior communi- cating (P.C.), middle cerebral (M.C.), and anterior communi- cating (A.C.) arteries.The background and trial organization are briefly described.Psychiatric morbidity is high.Of those with aneurysms in the trial comparisons 45% were regarded as unimpaired or nearly so; 24% were mildly, 18% moderately, 10% severely, and 3% very severely affected.Patients with no demonstrable aneurysms (30) had lower morbidity rates.Most of the psychiatric and psychological morbidity is due to brain damage, but anxiety and depressive states also occur in the absence of such damage, and may be very severe.Patients with M.C. aneurysms have a significantly higher morbidity with surgical than with conservative treatment, especially women with left-sided lesions.Possible reasons for this are mentioned.Patients with aneurysms at other sites do slightly but not significantly better with surgery.A group of 13 patients with apparently improved person- alities is described.This improvement is regarded as a leuco- tomy effect.The incidence of epilepsy is 10% overall in patients with single aneurysms.No case of epilepsy occurred in those with A.C. aneurysms or with no demonstrable aneurysm.The rate was 24% in those with M.C. and 7% in those with P.C. aneurysms.There was no difference between operative and conservative treatment in this respect.Several tables have had to be omitted to save space.Details will be sent on request.
Treating Cancer by Targeting the Immune System
Authors: Patrick Hwu
Journal: New England Journal of Medicine (2010)

There is currently great interest in the targeted therapy of cancer. Antibodies that target specific antigens on the surface of cancer cells — such as rituximab, which binds to CD20 on lymphoid tumors, and trastuzumab, which blocks HER2 on breast-cancer cells — were early successes. However, a novel method of using antibodies to stimulate an antitumor response was pioneered in the mid-1990s by James Allison and colleagues.1 Because the body's immune response, if left unchecked, can result in autoimmunity, we have evolved a number of immune "checkpoints" that work as braking mechanisms to counterbalance immune activation. Studies in animals have . . .
Evaluation of coal tar fractions for use in psoriasiform diseases using the mouse tail test
Authors: ROSANNE WRENCH, ADAM Z. BRITTEN
Journal: British Journal of Dermatology (2006)

Mouse tail scale epidermis was used as a model to evaluate anti-parakeratotic activity of tar oil acids (phenols) boiling between 175 and 400 degrees C. Lower boiling phenols seemed to cause more irritation, whereas high boiling phenols caused granular layer induction in formerly parakeratotic skin.
Autologous Transplantation of Muscle Precursor Cells Modified with a Lentivirus for Muscular Dystrophy: Human Cells and Primate Models
Authors: Simon P Quenneville, Pierre Chapdelaine, Daniel Skuk, Matin Paradis, Marlyne Goulet, Joël Rousseau, Xiao Xiao, Luis Garcia, Jacques P Tremblay
Journal: Molecular Therapy (2007)

Duchenne muscular dystrophy (DMD) is characterized by the absence of dystrophin. We tested the ability of lentiviral vectors to deliver a transgene into myogenic cells before their transplantation. Enhanced green fluorescent protein (eGFP) transgene was efficiently transferred into cells and eGFP-positive fibers were generated following transplantation. An eGFP-micro-dystrophin transgene under the control of a cytomegalovirus promoter was then transferred with the same viral vector but caused some toxicity to the mono-nucleated cells. We then used instead a muscle creatine kinase promoter. Dystrophin expression was observed in the muscle fibers after the transplantation of such genetically modified cells into mdx and severe combined immunodeficient mice. Micro-dystrophin expression was also observed in monkey muscles a month after allogenic or autologous transplantation of genetically modified myoblasts. Therapeutic exon skipping was induced by infecting myoblasts of a DMD patient, deleted for dystrophin exons 49 and 50, with a lentivirus expressing a U7 small nuclear RNA containing antisense sequences against exon 51. The modification led to correct exon skipping and to the expression of a quasi-dystrophin in vitro and in vivo. These results demonstrate the feasibility of lentiviral-based ex vivo gene therapy for DMD.
Edema in the Ectopic ACTH Syndrome
Authors: ALAN WASSERSTEIN
Journal: Annals of Internal Medicine (1982)

Letters and Corrections1 June 1982Edema in the Ectopic ACTH SyndromeALAN WASSERSTEIN, M.D.ALAN WASSERSTEIN, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-96-6-785_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: Peripheral edema may be a prominent feature of the ectopic adrenocorticotropic hormone (ACTH) syndrome, and has been attributed to mineralocorticoid excess (1,2). However, in other cases of mineralocorticoid excess, such as primary aldosteronism, escape from the salt-retaining effects of mineralocorticoids prevents the formation of edema. Escape from these effects has also been shown after constant daily exogenous ACTH infusion (3). The mechanism of the failure of sodium escape in the ectopic ACTH syndrome is uncertain. Conceivably, some factors associated with underlying malignancy, such as protein-calorie malnutrition or profound potassium depletion, could favor salt retention and prevent escape....References1. LIDDLE G. The adrenals. In: WILLIAMS RH, ed. Textbook of Endocrinology. Philadelphia: WB Saunders; 1981:269. Google Scholar2. SHERWOOD L. Endocrine manifestations of non-endocrine diseases, In: ISSELBACHER KJ, ADAMS RD, BRAUNWALD E, PETERSDORF RG, WILSON JD, eds. Harrison's Principles of Internal Medicine. New York: McGraw-Hill; 1980:1816-7. Google Scholar3. BIGLIERISCHAMBELANSLATON EMP. Effects of adrenocorticotropin on desoxycorticosterone, corticosterone and aldosterone excretion. J Clin Endocrinol Metab. 1969;29:1090-101. CrossrefMedlineGoogle Scholar4. COHEN J. Disorders of hydrogen ion metabolism. In: EARLEY LE, GOTTSCHALK CW, eds. Strauss and Welt's Diseases of the Kidney. Boston: Little, Brown & Co.; 1979:1571. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Hospital of the University of Pennsylvania Philadelphia, PA 19104 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByUnusual presentation and course of cushing's syndrome due to ectopic ACTH secretion by a bronchial carcinomaEndocrine and Metabolic Function in Patients with Neoplastic Disease 1 June 1982Volume 96, Issue 6_Part_1Page: 785-786KeywordsAdrenocorticotropic hormoneEdemaMalnutritionMineralocorticoidsPotassiumProteinsSaltsSodium Issue Published: 1 June 1982 PDF DownloadLoading ...
Immediate Uptake of Radioactive Iodine as a Test of Thyroid Function
Authors: H. E. A. Farran
Journal: BMJ (1958)

JOURNALwas produced by D-thyroxine but not by L-thyroxine might suggest that D-thyroxine has a qualitatively different effect from that of L-thyroxine on the anterior pituitary.This seems highly improbable, and further work with both isomers is necessary to resolve the dilemma.The expectation that cases of thyrotoxicosis might be found in which it would be possible to reduce the metabolism to normal by means of D-thyroxine has apparently been fulfilled in two of six patients treated for three months.This is not so surprising, for Means (1948) has reported a clinical improvement in cases of Graves's disease treated with desiccated thyroid, and Werner et al. (1952) quote a single case personally communicated to them by Greer.Moreover, these authors noted that in several of their patients treatment with thyroid was accompanied by a fall in the level of P.B.I.They advanced three possible causes for this finding-the effects of non-hormonal iodine in the desiccated thyroid, of repeated doses of "31I, or of rest in bed.None of these explanations is applicable in our patients.Moreover, the danger to the patient of using thyroid or L-thyroxine is absent when the relatively non- calorigenic D-thyroxine is used.AIthough the output of T.S.H. was inhibited, at least tem- porarily, in almost every case in our series, in no instance was any change seen in the degree of exophthalmos.This observation cannot be explained by the hypothesis that exophthalmos, originally produced by an excess of T.S.H., has become irreversible, for it is a common observation that exophthalmos may decrease or even disappear spon- taneously.The doses of D-thyroxine used, smaller than in the hypothyroid patients, were large enough to depress the uptake of radio-iodine for periods up to 10 months, but not large enough to increase metabolism.Our results give sup- port to those who have long doubted the classical hypo- thesis that exophthalmos is due to an excessive production of T.S.H. by the pituitary. SummaryThe metabolic effects of D-thyroxine are very slight when compared with those of L-thyroxine, the latter being at least ten times as potent.On the other hand, doses of D-thyroxine too small to effect metabolism directly are capable in most cases, even of thyrotoxi- cosis, of suppressing the uptake of radio-iodine and, by inference, the production of T.S.H. Suppression of the production of T.S.H. appeared to induce a remission of Graves's disease in two of six patients, but the exoph- thalmos was not improved.We are grateful to other members of the staff of the department of endocrinology of New End Hospital for allowing access to their patients, and to Dr. A. W. G. Goolden for much helpful advice.Glaxo Laboratories Ltd.
Liver transplantation in babies
Authors: R. Hopkinson
Journal: BMJ (1993)

A survey conducted in England and Wales by the Office of Population Censuses and Surveys in 1980 showed that out of 1303 drinkers interviewed, 64 reported problems related to alcohol.Two thirds of these drinkers admitted to drinking less than 50 units a week, and only one third admitted to consumption above that.There are many similar examples from international surveys.We believe that there are no grounds for revising the guidelines on sensible drinking and that they provide an invaluable marker in assessing the clinical importance of a patient's drinking habits.
Prognostic Factors for Breast Cancer with 10 or More Lymph Nodes Metastasis.
Authors: S. Choi, H. Park, J. Lee, S. Park, B. Park
Journal: Cancer Research (2009)

Abstract Background: Although the proportion of early breast cancer has been increased, advanced breast cancers of N3 stage still compose about 10% of all breast cancers. The purpose of this study was to investigate factors associated with prognosis of breast cancers with extensive nodal metastasis.Patients and method: Of 3912 invasive breast cancer patients who underwent surgery between April 1986 and May 2006 at Severance Hospital, patients who had 10 or more metastatic lymph nodes without distant metastasis were 304 (7.8%). With 55 months of median follow-up period, their clinicopathologic characteristics, follow-up of survival and the factors associated with disease free survival (DFS) and overall survival (OS) were analyzed.Result: Median age was 46.5 years and median number of positive lymph node was 16 with metastases to supraclavicular lymph nodes in 14 patients (4.6%). Median 5-year DFS rate were 42.4% and OS rate was 47.5%. In the Kaplan-Meier survival analysis, age less than 35 years (19.4% vs. 45.9%; p=0.001), the history of NAC (13.1% vs. 48.8%; p&amp;lt;0.001), T4 stage (15.8% vs. 45.8%, excluding T4d; p&amp;lt;0.001), 20 or more positive lymph nodes (27.0% vs. 50.2%; p&amp;lt;0.001), lymphovascular invasion (20.2% vs. 48.4%; p=0.003), and negative progesterone receptor (32.8% vs. 49.3%; p=0.003) were significantly associated to poor 5-year DFS. For 5-year OS, age less than 35 years (43.8% vs. 59.7%; p=0.033), the history of NAC (28.0% VS. 63.8%; p&amp;lt;0.001), T4 stage (21.1% vs. 61.0%, excluding T4d; p=0.001), 20 or more positive lymph nodes (48.9% vs. 63.8%; p&amp;lt;0.001), and negative progesterone receptor (49.0% vs. 64.2%; p=0.013) were statistically significant. On the multivariate analysis, significant factors associated with poor DFS and OS were 20 or more metastatic lymph nodes (relative risk [RR] =1.598 and p=0.024 for DFS; RR=1.956 and p&amp;lt;0.001 for OS), the history of neoadjuvant chemotherapy (RR=3.163 and p&amp;lt;0.001 for DFS; RR=2.900 and p&amp;lt;0.001 for OS). The contribution of lymphovascular invasion was significant only to DFS on the multivariate analysis.Conclusion: The patients with the same N3 stage show various prognosis. Clinical trial using new therapeutic agents should be applied in advanced breast cancers with high risk, which are predicted to be refractory to conventional adjuvant therapy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4064.
Elimination of Sewing Ring-Metal Seat Interface in Mitral Valve Prostheses
Authors: ARTHUR C. BEALL, ROBERT D. BLOODWELL, DOMINGO LIOTTA, DENTON A. COOLEY, MICHAEL E. DE BAKEY
Journal: Circulation (1968)

In an effort to decrease the incidence of thromboembolic phenomena associated with prosthetic replacement of the mitral valve and to eliminate problems associated with swelling of moving parts employed in cardiac valve prostheses, a new mitral Teflon disc valve made of titanium was designed. The cage legs are covered with Teflon to reduce wear, and the entire sewing ring and base are covered with Dacron velour to encourage rapid tissue encapsulation. After accelerated fatigue testing and animal investigations, preliminary results in a clinical series of 73 patients appear most encouraging. Further time must pass, however, before statistically valid conclusions can be reached.
Intramural diverticulosis of the oesophagus.
Authors: R D Montgomery, K Mendl, S F Stephenson
Journal: Thorax (1975)

Four cases of intramural diverticulosis of the oesophagus are described, and the findings are reviewed in 12 previously reported cases. Evidence is presented that this condition is a true pulsion diverticulosis due to deranged motor activity and raised intraluminal pressure. It may occur in cases of diffuse oesophageal spasm, or it may follow inflammation, stricture or surgery. The course is benign, complications being those of the underlying disorder.