tbuckley/cabot-search huggingface dataset:
Oral Vaccination With Adeno-associated Virus Vectors Expressing the Neu Oncogene Inhibits the Growth of Murine Breast Cancer
Authors: Jason C Steel, Giovanni Di Pasquale, Charmaine A Ramlogan, Vyomesh Patel, John A Chiorini, John C Morris
Journal: Molecular Therapy (2013)

Recombinant adeno-associated viruses (AAV) have been used for therapeutic gene transfer. These vectors offer a number of advantages including resistance to the effects of pH, a broad cellular tropism, efficient gene transfer, persistence of gene expression, and little toxicity. AAV vectors; however, at high doses can induce humoral and cellular immune responses. While potentially problematic for replacement gene therapy, this effect may be advantageous for antitumor vaccination. We examined the activity of an oral and intramuscular antitumor vaccination using AAV serotypes 5 and 6 expressing a truncated neu oncogene in a neu-positive murine TUBO breast cancer model. Mice receiving a single oral administration of AAV5-neu or AAV6-neu demonstrated improved survival. Oral vaccination significantly improved survivals compared with intramuscular vaccination. Mice vaccinated with AAV6-neu survived longer than those treated with AAV5-neu. Vaccination with AAV5-neu or AAV6-neu induced both humoral and cellular immune responses against the NEU antigen. These responses were more robust in the mice undergoing oral vaccination compared with mice receiving the intramuscular vaccination. Protection from tumor was long lasting with 80% of the animals treated with oral AAV6-neu surviving a re-challenge with TUBO cells at 120 and 320 days post-vaccination. Further evaluation of AAV-based vectors as tumor vaccines is warranted.
False Aneurysms of an Ascending-Aorta-to-Abdominal-Aorta Bypass for Coarctation of the Aorta
Authors: Arno A.W. Roest, Martin N.J.M. Wasser, Michael I.M. Versteegh, Albert de Roos, Ernst E. van der Wall, Willem A. Helbing, Hubert W. Vliegen
Journal: Circulation (2001)
Immunotoxin Therapy for Cancer
Authors: Lee H. Pai
Journal: JAMA (1993)

DESPITE recent advances using conventional approaches (surgery, chemotherapy, and radiotherapy), most human cancers remain incurable. For those patients who have unresectable cancers at the time of diagnosis, the prognosis remains poor. It is clear that new therapeutic approaches are urgently needed. In the past decade, development of the hybridoma technique by Kohler and Milstein<sup>1</sup>and advances in protein chemistry have led to the development of immunotoxins, a new class of cytotoxic agents consisting of a protein toxin coupled to a monoclonal antibody or a growth factor.<sup>2-4</sup>These toxins are made by plants or bacteria and act by arresting protein synthesis; cell death rapidly follows. The plant toxins generally inactivate ribosomes by cleaving a specific sequence in the 60S rRNA. The bacterial toxins,<i>Pseudomonas</i>exotoxin A (PE) or diphtheria toxin (DT), ribosylate adenosine diphosphate residues, ribosylate and thereby inactivate elongation factor 2, which is necessary for protein synthesis. Several
Noninvasive Fetal Sex Determination Using Cell-Free Fetal DNA
Authors: Stephanie A. Devaney, Glenn E. Palomaki, Joan A. Scott, Diana W. Bianchi
Journal: JAMA (2011)

Noninvasive prenatal determination of fetal sex using cell-free fetal DNA provides an alternative to invasive techniques for some heritable disorders. In some countries this testing has transitioned to clinical care, despite the absence of a formal assessment of performance.To document overall test performance of noninvasive fetal sex determination using cell-free fetal DNA and to identify variables that affect performance.Systematic review and meta-analysis with search of PubMed (January 1, 1997-April 17, 2011) to identify English-language human studies reporting primary data. References from review articles were also searched.Abstracts were read independently to identify studies reporting primary data suitable for analysis. Covariates included publication year, sample type, DNA amplification methodology, Y chromosome sequence, and gestational age. Data were independently extracted by 2 reviewers.From 57 selected studies, 80 data sets (representing 3524 male-bearing pregnancies and 3017 female-bearing pregnancies) were analyzed. Overall performance of the test to detect Y chromosome sequences had the following characteristics: sensitivity, 95.4% (95% confidence interval [CI], 94.7%-96.1%) and specificity, 98.6% (95% CI, 98.1%-99.0%); diagnostic odds ratio (OR), 885; positive predictive value, 98.8%; negative predictive value, 94.8%; area under curve (AUC), 0.993 (95% CI, 0.989-0.995), with significant interstudy heterogeneity. DNA methodology and gestational age had the largest effects on test performance. Methodology test characteristics were AUC, 0.988 (95% CI, 0.979-0.993) for polymerase chain reaction (PCR) and AUC, 0.996 (95% CI, 0.993-0.998) for real-time quantitative PCR (RTQ-PCR) (P = .02). Gestational age test characteristics were AUC, 0.989 (95% CI, 0.965-0.998) (<7 weeks); AUC, 0.994 (95% CI, 0.987-0.997) (7-12 weeks); AUC, 0.992 (95% CI, 0.983-0.996) (13-20 weeks); and AUC, 0.998 (95% CI, 0.990-0.999) (>20 weeks) (P = .02 for comparison of diagnostic ORs across age ranges). RTQ-PCR (sensitivity, 96.0%; specificity, 99.0%) outperformed conventional PCR (sensitivity, 94.0%; specificity, 97.3%). Testing after 20 weeks (sensitivity, 99.0%; specificity, 99.6%) outperformed testing prior to 7 weeks (sensitivity, 74.5%; specificity, 99.1%), testing at 7 through 12 weeks (sensitivity, 94.8%; specificity, 98.9%), and 13 through 20 weeks (sensitivity, 95.5%; specificity, 99.1%).Despite interstudy variability, performance was high using maternal blood. Sensitivity and specificity for detection of Y chromosome sequences was greatest using RTQ-PCR after 20 weeks' gestation. Tests using urine and tests performed before 7 weeks' gestation were unreliable.
Mcl-1 and Bcl-xL cooperatively maintain integrity of hepatocytes in developing and adult murine liver
Authors: Hayato Hikita, Tetsuo Takehara, Satoshi Shimizu, Takahiro Kodama, Wei Li, Takuya Miyagi, Atsushi Hosui, Hisashi Ishida, Kazuyoshi Ohkawa, Tatsuya Kanto, Naoki Hiramatsu, Xiao-Ming Yin, Lothar Hennighausen, Tomohide Tatsumi, Norio Hayashi
Journal: Hepatology (2009)

Anti-apoptotic members of the Bcl-2 family, including Bcl-2, Bcl-xL, Mcl-1, Bcl-w and Bfl-1, inhibit the mitochondrial pathway of apoptosis. Bcl-xL and Mcl-1 are constitutively expressed in the liver. Although previous research established Bcl-xL as a critical apoptosis antagonist in differentiated hepatocytes, the significance of Mcl-1 in the liver, especially in conjunction with Bcl-xL, has not been clear. To examine this question, we generated hepatocyte-specific Mcl-1–deficient mice by crossing mcl-1 flox / flox mice and AlbCre mice and further crossed them with bcl-x flox / flox mice, giving Mcl-1/Bcl-xL–deficient mice. The mcl-1 flox / flox AlbCre mice showed spontaneous apoptosis of hepatocytes after birth, as evidenced by elevated levels of serum alanine aminotransferase (ALT) and caspase-3/7 activity and an increased number of terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate nick-end labeling (TUNEL)-positive cells in the liver; these phenotypes were very close to those previously found in hepatocyte-specific Bcl-xL–deficient mice. Although mcl-1 flox /+ AlbCre mice did not display apoptosis, their susceptibility to Fas-mediated liver injury significantly increased. Further crossing of Mcl-1 mice with Bcl-xL mice showed that bcl-x flox /+ mcl-1 flox /+ AlbCre mice also showed spontaneous hepatocyte apoptosis similar to Bcl-xL–deficient or Mcl-1–deficient mice. In contrast, bcl-x flox / flox mcl-1 flox /+ AlbCre , bcl-x flox /+ mcl-1 flox / flox AlbCre, and bcl-x flox / flox mcl-1 flox / flox AlbCre mice displayed a decreased number of hepatocytes and a reduced volume of the liver on day 18.5 of embryogenesis and rapidly died within 1 day after birth, developing hepatic failure evidenced by increased levels of blood ammonia and bilirubin. Conclusion: Mcl-1 is critical for blocking apoptosis in adult liver and, in the absence of Bcl-xL, is essential for normal liver development. Mcl-1 and Bcl-xL are two major anti-apoptotic Bcl-2 family proteins expressed in the liver and cooperatively control hepatic integrity during liver development and in adult liver homeostasis in a gene dose-dependent manner. (Hepatology 2009.)
Altered expression of CD45 isoforms in differentiation of acute myeloid leukemia
Authors: Hayato Miyachi, Yumiko Tanaka, Kazumi Gondo, Tsutomu Kawada, Shunichi Kato, Tamotsu Sasao, Tomomitsu Hotta, Shuichi Oshima, Yasuhiko Ando
Journal: American Journal of Hematology (1999)

Specific expression of different CD45 isoforms can be seen in various stages of differentiation of normal nucleated hematopoietic cells. Association of membrane expression of CD45 isoforms and differential levels of leukemia cells was studied in 91 cases with de novo acute myeloid leukemia (AML). Membrane expression of CD45RA and CD45RO was analyzed by flow cytometry and their expression patterns were compared with AML subtypes classified according to the French–American–British (FAB) classification. CD45RA was essentially expressed in all of the FAB myelocytic subtypes (M0–M3). Its expression in percentage was lower in the most differentiated subtype of AML (M3) when compared with other myelocytic subtypes. CD45RO expression was rarely observed in cases with myelocytic subtypes (1/56 cases of M0, M1, M2, and M3) except for the minimally differentiated myelocytic subtype (M0) or those with potential for differentiation to T-cell lineage where three of 12 cases showed CD45RO expression. When leukemia cells of an M3 case were differentiated to mature granulocytes by treatment of all-trans-retinoic acid, they showed increasing expression of CD45RO. In subtypes with a monocytic component (M4 and M5), both of CD45RA and CD45RO expression were observed and mutually exclusive. When 10 cases of M5 were subdivided by the differential level into undifferentiated (M5a) and differentiated monocytic leukemia (M5b), expression of CD45RA and CD45RO was strictly restricted to cases with M5a and M5b, respectively. These results suggest that CD45 isoform expression in AML characterizes differential levels both in myelocytic and monocytic lineages and specifically disturbed in each subtype. The assessment of CD45 isoform expression appears to provide an insight on biological characteristics and a useful supplementary test for differential diagnosis of AML subtypes. Am. J. Hematol. 62:159–164, 1999. © 1999 Wiley-Liss, Inc.
An Address on the Eye Complications of the Acute Specific Fevers: Delivered before the Thames Valley Branch of the British Medical Association on March 8th, 1899
Authors: P. Flemming
Journal: BMJ (1899)

EYE troubles frequently arise in the course of the acute specific fevers or remain as sequelie of them.I propose to .considersome of these to-day, and in doing so I shall limit the term "acute specific fevers " to the various fevers that .arecommonlymet with in general practice in this country, and shall nlot include any account of syphilis, tuberculosis, septicemia, etc.ETIOLOGY AND PATHOLOGY.'And in the first place let us bee how the eye may be affected -that is, what are the possible channels by which the virus -may reach the eye.The simplest way is, of course, by direct inoculation.This may be accidental, as when a variolous or vaccine pustule is scratched by the finger, and the latter inadvertently then applied to the eyb.Or it may be, as in facial erysipelas, by direct microbic invasion, the cocci advancing in the lymphatics of the skin, and so ultimately reaching the lids and conjunctiva; but this is not a very common occurrence.More commonly (as in measles) the ~conjunctiva becomes inflamed as part of the general catarrhal condition, or, as in diphtheria, the inflammation may spread by continuity from the nose to the conjunctiva by the nasal .duct.Such modes of infection are easily understood, but -complications of deep structures such as the optic nerve, the -orbital tissue, and even the central nervous system are frequently observed, and it is important to investigate their -mode of origin.According to current pathological doctrines, such conditions are .broughtabout by the absorption of "toxins," the products of the specific organisms, the toxins ipicking out particular structures and acting on them.Such a .selectiveaction is seen in the action of certain drugs : thus arsenic produces conjunctivitis, and tobacco (nicotine) acts on 'the optic nerve, producing definite structural change, and belladonna, taken internally, acts on the pupil and ciliary mntisele.But in addition to this explanation, another is to be
Typing of mycobacteria using spoligotyping
Authors: A C HAYWARD, J M WATSON
Journal: Thorax (1998)

The potential use of spoligotyping—a polymerase chain reaction based typing system for differentiation of strains of Mycobacterium tuberculosis —for studying the epidemiology of tuberculosis in developing countries which do not routinely perform mycobacterial culture is described in this issue of Thorax by Heyderman et al in a study from Zimbabwe.1 How does this newer method compare with the now more established molecular typing methods for tuberculosis?

The most commonly used typing system for tuberculosis is IS6110 based restriction fragment length polymorphism (RFLP).2Extensive experience with IS6110 based RFLP typing has shown that there is a high degree of heterogeneity in typing patterns. This means that the technique is highly discriminatory so that it is unlikely that two organisms will share indistinguishable typing patterns by chance.3-6 This property has allowed RFLP typing to be used in a variety of ways. For example, typing can be used to confirm outbreaks of tuberculosis7 8 or incidents of suspected laboratory cross contamination,9 10 and the technique has been used to investigate the relative importance of reactivation versus reinfection in patients with a second episode of tuberculosis.11 12 Studies which type all available isolates from a defined geographical area over a specified time period can help to estimate the importance of recent transmission and to identify risk factors for the spread of tuberculosis.4-6 

There are a number of difficulties with standard IS6110 typing—for example, the technique is less discriminatory in isolates with low copy numbers of IS6110 (secondary typing using techniques based on different genetic markers such as direct repeat (DR) typing or polymorphic GC rich repetitive …
Why markets don't work in healthcare
Authors: F. Godlee
Journal: BMJ (2012)

Like any commercial company, the BMJ Group uses management consultants to help develop strategy and implement change. By and large we have found them a good investment. The NHS and the Department of Health use them too, spending a reported £30m in England on these services between 2006 and 2010. Should we care about how such a tiny proportion of the NHS’s £100bn annual budget is spent? Perhaps we needn’t worry too much about the money, which can be accounted for, but should worry about the nature and extent of the influence, which is harder to keep tabs on. With their ethos and skills deeply embedded in the private sector, are consultants inevitably …
Evaluation and Percutaneous Management of Atherosclerotic Peripheral Vascular Disease
Authors: David M. Widlus
Journal: JAMA (1989)

ATHEROSCLEROTIC peripheral vascular disease (PVD) of the lower extremities deprives a person of the ability to exercise to their satisfaction, later of the ability to perform the activities of their daily life, and finally of their legs themselves. Peripheral vascular disease has long been managed by the vascular surgeon utilizing endarterectomy and peripheral arterial bypass.<sup>1-4</sup>These surgical techniques have been shown to be effective in relieving symptoms and to be durable with the passage of time. Postoperative morbidity, rising health care costs, and refinement of percutaneous catheter technology have led to the development and use of nonsurgical modalities for the management of PVD.<sup>5</sup>Patient acceptance of nonsurgical, percutaneous procedures such as percutaneous transluminal balloon angioplasty (PTA) is high.<sup>6</sup>Increased utilization of these procedures has led to improved techniques and adjuncts to therapy, as well as more critical review of long-term results. This article will review the evaluation
In treating the pathological gambler, MDs must overcome the attitude, 'why bother?'
Authors: D. L. Breo
Journal: JAMA (1989)

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
Protection against Methacholine Bronchoconstriction to Assess Relative Potency of Inhaled β<sub>2</sub>-Agonist
Authors: KRISHNAN N. PARAMESWARAN, MARK D. INMAN, BRUCE P. EKHOLM, MARILYN M. MORRIS, EDIE SUMMERS, PAUL M. O'BYRNE, FREDERICK E. HARGREAVE
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

The purposes of this study were to estimate the relative dose potency (RP) of two formulations of salbutamol pressurized metered-dose inhalers (Proventil-HFA and Ventolin-CFC MDIs) to protect against methacholine bronchoconstriction, to validate this method and provide recommendations. The protective effects of 100-, 200-, and 400- μ g doses of Proventil-HFA were compared with the same doses of Ventolin-CFC in 18 adult asthmatics (mean FEV1, 92% predicted; mean baseline PC20 methacholine, 1.8 mg/ml), in a dose-level blind, balanced, eight-period, crossover, placebo-controlled study. The log-transformed PC20 values after each dose of the drugs were compared by repeated-measures analysis of variance (ANOVA). A significant dose-effect was present (p < 0.0001). Using the Finney assay, the RP of Proventil-HFA compared with Ventolin-CFC was 1.08 (90% CI, 0.81–1.46) (80% power). This was also estimated using a nonlinear Emax model to validate the Finney method. The most precise estimate of RP was obtained with the comparison between 100- and 200- μ g doses (RP, 1.00; 90% CI, 0.77–1.31). There were no adverse events resulting from the drugs or methacholine. We conclude that Proventil-HFA salbutamol is bioequivalent to Ventolin-CFC salbutamol. Bronchoprotection to methacholine is a valid method of demonstrating bioequivalence. By this method, 100- and 200- μ g doses of salbutamol inhalations from an MDI will suffice.
The Confirmation and Maintenance of Smallpox Eradication
Authors: Joel G. Breman, Isao Arita
Journal: New England Journal of Medicine (1980)

In December 1979, an independent scientific commission certified global eradication of smallpox. This conclusion was accepted at the 33d World Health Assembly of the World Health Organization (WHO) in May 1980. After WHO's intensified eradication program began in 1967, special certification procedures were used in 35 countries where the disease had been endemic and in 44 others at special risk. Six laboratories are known to retain variola virus; efforts have been made to ensure strict containment of these strains. There is no evidence that smallpox will recur as an endemic disease. Nevertheless, WHO will promote surveillance of smallpox-like disease and selected laboratory research on certain orthopoxviruses. These efforts will maintain confidence that smallpox has been eradicated and confirm that there are no animal reservoirs of variola virus. A more complete understanding of the orthopoxviruses, including monkeypox virus, should also be obtained.
Challenges for Junior Faculty: Mentoring and Family
Authors: Janet M. Williams
Journal: JAMA (1996)

<h3>To the Editor.</h3> —We would like to commend Dr Fried and her colleagues<sup>1</sup>on their work in developing an institutional strategy to enhance the growth of women in academic medicine. The intervention was thought to have benefited both men and women in academics as well as increased the retention of women in academic medicine. However, the intervention was designed and implemented in a large university-affiliated department of medicine involving 188 full-time, tenure-track faculty. Whether such an intervention would be effective in smaller or newly established academic settings is questionable for a variety of reasons. First, small or newly established academic departments with fewer faculty members, of whom a minority are in the tenure track, often lack both senior faculty with strong leadership skills and role models to guide the development of more junior faculty. Second, the lack of experienced researchers in such settings where a research track record has
Two novel mast cell phenotypic markers, monoclonal antibodies Ki-MC1 and Ki-M1P, identify distinct mast cell subtypes
Authors: K. HAMANN, N. HAAS, J. GRABBE, P. WELKER, B.M. CZARNETZKI
Journal: British Journal of Dermatology (1995)

In order to identify more specific or selective mast cell markers, the reactivity of two monoclonal antibodies, Ki-MC1 and Ki-M1P, was studied by immunohistochemistry in two human cell lines (mast cell line HMC-1, basophilic cell line KU812), in mast cells cultured from blood precursors, in adherent mononuclear cells from peripheral blood, and in mast cells of tissue sections from 13 urticaria pigmentosa lesions, five mastocytomas and five normal skin specimens. Toluidine blue staining, fluorescence staining with FITC-conjugated avidin, and immunohistochemical staining (APAAP) with other mast cell reactive monoclonal antibodies, was performed for comparison. Double staining with the APAAP method, using the Ki-antibodies and toluidine blue, was also carried out. Both Ki-antibodies showed reactivity for skin mast cells, but with a different staining pattern. In addition, the Ki-MC1 antibody did not react with the cell lines, and reacted only with a few peripheral blood mononuclear cells and cultured mast cells. In contrast, the Ki-M1P antibody reacted with almost all cultured mast cells and blood mononuclear cells, but stained only about one-half of lesional and one-fifth of normal skin mast cells. Ki-M1P also reacted with many toluidine blue-negative dermal cells, particularly in urticaria pigmentosa. Ki-MC1 antibody can thus be considered as a useful additional marker for normal skin mast cells. In contrast, the Ki-M1P antibody primarily identifies immature mast cells and monocytes/macrophages, suggesting that these cell types probably originate from the same bone marrow precursor.
The Circulating Level of FABP3 Is an Indirect Biomarker of MicroRNA-1
Authors: Francesca Varrone, Barbara Gargano, Pierluigi Carullo, Dario Di Silvestre, Antonella De Palma, Ludovica Grasso, Carolina Di Somma, Pierluigi Mauri, Louise Benazzi, Anna Franzone, Gloria Saccani Jotti, Marie-Louise Bang, Giovanni Esposito, Annamaria Colao, Gianluigi Condorelli, Daniele Catalucci
Journal: Journal of the American College of Cardiology (2012)