tbuckley/cabot-search huggingface dataset:
479. Development and Characterization of a New Noncytopathic Vector Derived from Semliki Forest Virus
Authors: Erkuden Casales, Juan R. Rodriguez-Madoz, Nerea Razquin, Yolanda Cuevas, Jesus Prieto, Cristian Smerdou
Journal: Molecular Therapy (2006)

Alphavirus vectors can express high levels of recombinant proteins in many different cell types. However, this expression is transient, due to the cytopathic nature of viral replication. Several noncytopathic mutants have been obtained from Sindbis virus (SIN) and Semliki Forest virus (SFV), which could be used when sustained transgene expression is desired. However, these noncytopathic vectors are generally only able to replicate in a limited number of cell lines, and have a low packaging effciency. In order generate new SFV noncytopathic vectors we have introduced mutations described to turn SIN noncytopathic into conserved positions in SFV. Interestingly, we found that one of the vectors generated in this way, which contained mutation P718T in nsp2, while apparently not able to replicate in most cells, gave rise with a relative high frequency to noncytopathic variants that formed colonies without selection when using LacZ as a reporter gene. We rationalized that these noncytopathic variants were due to second mutations that appeared naturally in this vector. To isolate these noncytopathic variants we inserted the pac gene into the SFV P718T mutant and puromycine resistant cell clones were selected in BHK cells. The noncytopathic replicons were then cloned by RT-PCR. As hypothesized, one noncytopathic replicon was rescued in this way containing in addition to P718T a second mutation in the nuclear localization signal of nsp2. This noncytopathic mutant had a lower level of replication as compared to the wild type replicon, but it was able to express heterologous proteins at similar levels. Further characterization of this double mutant will be discussed in detail.
The rational clinical examination. Does this patient have splenomegaly?
Authors: S. A. Grover
Journal: JAMA (1993)

<h3>THREE PATIENTS</h3> Among the patients you are seeing today are the following three: The first is an elderly woman who complains of easy fatigability, and her conjunctivae and nail beds are pale. You suspect that she is anemic due to gastrointestinal blood loss, but among your differential diagnoses you consider a lymphoproliferative disorder and decide to examine her for splenomegaly. The second is a college student with failing appetite, ability to concentrate, energy, and grades. You think that he is depressed but want to rule out infectious mononucleosis and decide to examine him for splenomegaly. The third is an otherwise healthy, well-controlled, hypertensive male with a normal cardiovascular examination. As he lies on the examining table, stripped to his waist, you wonder whether you should take the time to examine him for splenomegaly. <h3>WHY EXAMINE THE SPLEEN?</h3> We examine the spleen to see whether it is palpable. Most palpable spleens
Hospital Readmission as an Accountability Measure
Authors: R. Neal Axon, Mark V. Williams
Journal: JAMA (2011)

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
The tachykinin NK2 receptor antagonist SR 48968 inhibits citric acid-induced airway hyperresponsiveness in guinea pigs.
Authors: V Girard, J C Yavo, X Emonds-Alt, C Advenier
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Airway hyperresponsiveness is a main feature of asthma, and several lines of evidence suggest that tachykinins might be involved in the pathogenesis of airway hyperresponsiveness in rodents. We conducted a study designed to describe an original model of airway hyperresponsiveness induced by citric acid administered as aerosol to guinea pigs, and to investigate the effects of the nonpeptide neurokinin1 (NK1) and neurokinin2 (NK2)-receptor antagonists, SR 140333 and SR 48968, respectively, on the development of this airway hyperresponsiveness. Animals received thiorphan 1 mg/kg intraperitoneally and 30 min later were exposed to an aerosol of citric acid 0.4 M for 1 h. After 24 h, the animals were anesthetized and ventilated. Airway hyperresponsiveness was evidenced by significant shifts to the left of dose-response curves for intravenous acetylcholine (ACh) without a change in maximum responses to ACh. Exposure to citric acid induced an airway hyperresponsive that was abolished by chronic pretreatment with capsaicin (120 mg/kg, 5 d before citric acid exposure). SR 48968 1 mg/kg intraperitoneally, given once at 30 min before the citric acid exposure, inhibited airway hyperresponsiveness, whereas SR 140333 1 mg/kg or codeine 30 mg/kg given under similar conditions did not. The inhibition of airway hyperresponsiveness by SR 48968 did not result from functional antagonism, since SR 48968 did not affect ACh-induced bronchoconstriction, nor did it result from inhibition of tachykinin, which could have been released under the influence of ACh in hyperresponsive animals, since SR 48968 given after the exposure to aerosolized citric acid failed to inhibit airway hyperresponsiveness. In conclusion, these results show that inhaled citric acid can induce the development of an airway hyperresponsiveness in the guinea pig through a release of tachykinins, and also demonstrate that NK2-receptor stimulation plays a predominant role in the development of airway hyperresponsiveness.
Scientists call for funding to get stem cell research to the market
Authors: J. Wise
Journal: BMJ (2010)

Scientists have called for more government funding for regenerative medicine amid fears that the UK will lose out in the race to get promising research to the market.

Regenerative medicine aims to use adult or embryonic stem cells to replace or regenerate human cells, tissue, or organs and restore normal function. Much of the research is still at an early stage; but its potential applications include Parkinson’s disease, diabetes, age related macular degeneration, and cartilage damage.

The UK established itself as a world leader in stem cell research during the past decade when the Bush administration imposed severe restrictions on the use of embryonic stem cells in the United States. A lack of UK government funding, however, may mean top researchers will be …
Tobacco companies protest about federal court ruling on corrective statements
Authors: O. Dyer
Journal: BMJ (2014)

The excretion and biotransformation of alfentanil (ALF) and sufentanil (SUF), two recent analogues of the synthetic opioid fentanyl, were studied after single iv administration of the tritium-labeled drugs in male rats and dogs. The drugs were almost completely metabolized in the two species, which resulted in a large number of metabolites. The excretion of the metabolites was rapid and exceeded 95% within 4 days, except for that of ALF metabolites in dogs (about 85%). For ALF, excretion of the radioactivity with the urine (73% in rats, about 76% in dogs) exceeded that with the feces. For SUF, excretion of the radioactivity with the urine amounted to 38 and 60% and that with the feces to 62 and 40%, in rats and dogs, respectively. Bile-cannulated rats excreted 68% with the bile within 24 hr after SUF dosing, and about 22% of this biliary radioactivity was subjected to enterohepatic circulation. After an ALF dose, the biliary excretion amounted to 24%, and the enterohepatic circulation was minimal. The main metabolic pathways of the two drugs were the oxidative N-dealkylation at the piperidine nitrogen and at the amide nitrogen, oxidative O-demethylation, aromatic hydroxylation, and the formation of ether glucuronides. N-[4-(Hydroxymethyl)-4-piperidinyl]-N-phenylpropanamide (M6) was the main metabolite of both ALF and SUF in rats. In dogs, the glucuronide of N-(4-hydroxyphenyl)propanamide (M5) was the main metabolite of ALF. After SUF dosing in dogs, N-[4-(methoxymethyl)-4-piperidinyl]-N-phenylpropanamide was more abundant than M5.
Current Observations of Lymphocyte Function: Relation to Clinical Problems.
Authors: William McFarland
Journal: Annals of Internal Medicine (1966)

s1 May 1966Current Observations of Lymphocyte Function: Relation to Clinical Problems.William McFarland, M.D., F.A.C.P., Dorothy H. Heilman, M.D., John F. Moorhead, M.D.William McFarland, M.D., F.A.C.P.Search for more papers by this author, Dorothy H. Heilman, M.D.Search for more papers by this author, John F. Moorhead, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-64-5-1166_3 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAs a result of recent progress in understanding of mechanisms of immunologic reactions including homograft rejection, the lymphocyte, a cell whose functions were little known a decade ago, has been assigned a major role. Particularly noteworthy from an investigative standpoint is the fact that the lymphocyte is capable of reacting not only in vivo but also in vitro to specific antigens and homologous cells, thus providing a model that promises to contribute significantly to knowledge at both the basic and clinical levels.Time-lapse cinephotomicrographic studies of viable lymphocytes demonstrate a functional appendage on the lymphocyte, termed the "uropod," by which... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Washington, D. C. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1966Volume 64, Issue 5Page: 1166-1167KeywordsAntigensHomograftsLymphocytes Issue Published: 1 May 1966 PDF downloadLoading ...
LATERAL VIEWS OF THE HEART AND AORTA
Authors: SAMUEL BROWN
Journal: JAMA (1927)

Clinicians differ regarding the value of percussion of the heart borders. Many feel that accurate determination of the borders is well nigh impossible, especially in the obese and in women, while others maintain that a high degree of accuracy may be obtained by percussion. However, difficulties are recognized when percussion for the heart borders is attempted in persons with greatly enlarged hearts and those having pulmonary emphysema. With the advent of the roentgen ray, much accurate information has been obtained in determining the borders of the heart. One is now able to learn the position of the heart in relation to the transverse diameter of the thorax. It is also possible, by means of the orthodiagram or teleroentgenogram, to determine to a high degree of accuracy the absolute size of the heart. However, the front view of the heart and aorta fails to give us the position of the heart
Multiple primary melanoma: risk factors and prognostic implications
Authors: A D Burden, J P Vestey, J M Sirel, T C Aitchison, J A A Hunter, R M MacKie
Journal: BMJ (1994)

Patients who have had one cutaneous melanoma are at increased risk of developing a second primary melanoma. Previous studies may have overestimated this risk as they have been of patients from specialist referral centres and so are subject to selection bias.*RF 1-4* We report the risk of and mortality from multiple primary melanoma in a well defined, geographically based group of British patients with primary melanoma.



Comparative survival curves in 38 matched patients with single and multiple primary melanomas



The Scottish Melanoma Group maintains a well validated database of all cases of melanoma diagnosed in Scotland.5 We studied 3818 patients (from a population of 3 907 300) who had been registered with the group as having primary melanoma between 1979 and 1991.

Forty five patients developed more than one histologically confirmed invasive primary …
Simple Quantitative Vectorcardiographic Criteria for the Diagnosis of Right Ventricular Hypertrophy
Authors: TE-CHUAN CHOU, MANUEL P. MASANGKAY, RAYMOND YOUNG, GENE F. CONWAY, ROBERT A. HELM
Journal: Circulation (1973)

The vectorcardiogram is a useful supplement to the conventional electrocardiogram in the recognition of right ventricular hypertrophy. Many quantitative criteria have been proposed. However they are often too complicated for routine clinical application. Based on the distribution of the QRS loop area in the various quadrants in the vectorcardiogram in 198 normal subjects, three simple criteria for diagnosis of right ventricular hypertrophy are derived: 1) the anterior and rightward QRS loop area in the transverse plane is greater than 70% of the total; 2) the QRS loop area in the right posterior quadrant of the transverse plane is greater than 20% of the total; 3) the QRS loop area in the right inferior quadrant in the frontal plane is greater than 20% of the total. Vectorcardiogram recordings in 97 patients with atrial septal defect, mitral stenosis, and chronic obstructive lung disease with pulmonary hypertension met one or more of the criteria in 80 (83%). The conventional electrocardiogram of these patients was suggestive of right ventricular hypertrophy in 64 (66%). It is concluded that the proposed vectorcardiographic criteria provide a sensitive means for the diagnosis of right ventricular hypertrophy. Their specificity however was not tested.
John Alexander Tulloch
Authors: D. Dorward, M. Dorward
Journal: BMJ (2009)

John Alexander Tulloch, formerly a consultant physician at Stracathro Hospital, Angus, has died after a long illness.

Born and brought up in Forres, John was dux of the academy there. He graduated from Edinburgh University in 1943, doing so six months early to join the war effort as a medical officer with a commando unit.

He served in Holland and Germany and was …
Residency Training at a Crossroads
Authors: Badri Giri
Journal: Annals of Internal Medicine (2011)

Letters7 June 2011Residency Training at a CrossroadsBadri Giri, MDBadri Giri, MDFrom Carolinas Hospital System, Florence, SC 29501.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-154-11-201106070-00016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:It is interesting to see changes mandated by the Accreditation Council for Graduate Medical Education (ACGME) every 4 to 5 years, such as those discussed in Volpp and colleagues' article (1). I was surprised that the most recent change applied only to interns. Is the ACGME aware that there are second- and third-year residents who work 24-hour shifts? Won't their fatigue level and sleep deprivation affect patient care?The interesting point is that there is no uniformity in work and teaching environment among all residency programs. I strongly believe that this needs to be reviewed. The ACGME ...Reference1. Volpp KG, Friedman W, Romano PS, Rosen A, Silber JH. Residency training at a crossroads: duty-hour standards 2010. Ann Intern Med. 2010;153:826-8. [PMID: 20956679] LinkGoogle Scholar Author, Article, and Disclosure InformationAuthors: Badri Giri, MDAffiliations: From Carolinas Hospital System, Florence, SC 29501.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoResidency Training at a Crossroads: Duty-Hour Standards 2010 Kevin G. Volpp , William Friedman , Patrick S. Romano , Amy Rosen , and Jeffrey H. Silber Residency Training at a Crossroads Rajasree Pai Ramachandra Pai Metrics 7 June 2011Volume 154, Issue 11Page: 779KeywordsConflicts of interestFatigueForecastingGraduate medical educationPatientsResidencySleep deprivation ePublished: 7 June 2011 Issue Published: 7 June 2011 Copyright & PermissionsCopyright © 2011 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Incidence of adverse reactions to cyclosporine after liver transplantation is predicted by the first blood level
Authors: Daniel Azoulay, Antoinette Lemoine, Ashley Dennison, Jean Michel Gries, Isabelle Dolizy, Denis Castaing, Philippe Beaune, Henri Bismuth
Journal: Hepatology (1993)

Despite the availability of whole-blood cyclosporine assays, the different responses of individual patients to its administration after transplantation continue to pose clinical problems, particularly with respect to toxicity. Fifty-seven recipients of first orthotopic liver transplants were studied between January 1992 and July 1992. Initial immunosuppression was carried out with azathioprine, methylprednisolone and cyclosporine, at a dose of 1 mg/kg/day adjusted to achieve blood levels between 400 and 600 ng/ml. Cyclosporine levels were measured 12 hr after the start of intravenous administration and correlated with the occurrence of toxic complications. Twelve patients experienced toxic complications in the first 7 days after orthotopic liver transplantation. These were neurological in six patients (of whom four also had kidney failure) and renal complications in the other six patients. All complications were reversed by reducing or stopping administration of cyclosporine. We noted excellent correlation between the occurrence of complications and cyclosporine whole-blood levels (p < 0.0001) despite the fact that levels did not exceed the therapeutic range. However, no correlation was observed between toxicity and cumulative dosage. In this study we were able to demonstrate that a standardized dose of cyclosporine does not prevent the occurrence of toxic side effects even when cyclosporine whole-blood levels are subsequently maintained in the therapeutic range. This highlights the importance of the first dose of cyclosporine and consequent early postoperative blood levels and indicates that these problems are unlikely to be overcome until a method of predicting individual requirements can be established in clinical practice. (HEPATOLOGY 1993;18:1123–1126.)
OX40 Agonist Therapy Enhances CD8 Infiltration and Decreases Immune Suppression in the Tumor
Authors: Michael J. Gough, Carl E. Ruby, William L. Redmond, Birat Dhungel, Alexis Brown, Andrew D. Weinberg
Journal: Cancer Research (2008)

Abstract Acquisition of full T-cell effector function and memory differentiation requires appropriate costimulatory signals, including ligation of the costimulatory molecule OX40 (TNFRSF4, CD134). Tumors often grow despite the presence of tumor-specific T cells and establish an environment with weak costimulation and immune suppression. Administration of OX40 agonists has been shown to significantly increase the survival of tumor-bearing mice and was dependent on the presence of both CD4 and CD8 T cells during tumor-specific priming. To understand how OX40 agonists work in mice with established tumors, we developed a model to study changes in immune cell populations within the tumor environment. We show here that systemic administration of OX40 agonist antibodies increased the proportion of CD8 T cells at the tumor site in three different tumor models. The function of the CD8 T cells at the tumor site was also increased by administration of OX40 agonist antibody, and we observed an increase in the proportion of antigen-specific CD8 T cells within the tumor. Despite decreases in the proportion of T regulatory cells at the tumor site, T regulatory cell function in the spleen was unaffected by OX40 agonist antibody therapy. Interestingly, administration of OX40 agonist antibody caused significant changes in the tumor stroma, including decreased macrophages, myeloid-derived suppressor cells, and decreased expression of transforming growth factor-β. Thus, therapies targeting OX40 dramatically changed the tumor environment by enhancing the infiltration and function of CD8 T cells combined with diminished suppressive influences within the tumor. [Cancer Res 2008;68(13):5206–15]
Characteristics of the Ventricular Insertion Sites of Accessory Pathways With Anterograde Decremental Conduction Properties
Authors: Michel Haı̈ssaguerre, Bruno Cauchemez, Frank Marcus, Philippe Le Métayer, Philippe Lauribe, Franck Poquet, Laurent Gencel, Jacques Clémenty
Journal: Circulation (1995)

Background Accessory pathways (APs) with anterograde decremental conduction properties referred to as Mahaim fibers have recently been recognized as originating from the right lateral atrium. Little information is available about their distal insertion. The purpose of this study was to determine the different kinds of APs involved and the characteristics of their distal insertion site. Methods and Results Twenty-one patients (mean age, 28±13 years) with reciprocating tachycardia or atrial fibrillation were studied. Right-sided atrial and/or ventricular endocardial mapping during tachycardia identified different types of APs. (1) Seventeen patients had long APs originating from the right lateral atrium and coursing several centimeters to the right ventricle. In 10 patients, the AP terminated in or close to the right bundle-branch system (atriofascicular AP) and in 7, the AP terminated in the anterior right ventricle (atrioventricular AP). Patients with atriofascicular APs had narrower QRS complexes (133±10 versus 165±26 milliseconds, P =.02) and narrower initial r wave in leads V 2 through V 4 during maximal preexcitation than patients with atrioventricular APs. In addition, they had earlier His-bundle and right bundle-branch retrograde activation, ie, shorter V-His (16±5 versus 37±9 milliseconds, P &lt;.01) and V–right bundle intervals (3±5 versus 25±6 milliseconds, P &lt;.01). In 6 patients, minimal preexcitation not readily apparent was present in sinus rhythm despite the appearance of a narrow QRS complex. A wide distal insertion site of 0.5 to 2 cm in diameter consistent with arborization of the AP was found in 10 patients. The distal application of radiofrequency current produced a change in the preexcitation pattern in 4 patients and ablated the AP in 2 patients. In the other patients, radiofrequency current was applied more proximally and successfully ablated the AP bundle (n=9) or AP proximal insertion (n=6). No recurrence was observed during a follow-up period of 12±10 months. (2) Four patients had short paratricuspid atrioventricular APs; in one, the decremental conduction property was acquired as demonstrated by two electrophysiological studies performed 7 years apart. Radiofrequency ablation was successfully accomplished in all 4 patients at the tricuspid annulus. Conclusions Different types of APs account for tachycardias previously called Mahaim fibers. Long and short atrioventricular APs are observed in 81% and 19%, respectively. Long APs often have a distal arborization and may have either a fascicular or ventricular insertion. Radiofrequency current is more efficient when applied to the AP bundle or AP proximal insertion rather than to the distal insertion in patients with long APs.