tbuckley/cabot-search huggingface dataset:
New HIV Drugs Cast in Supporting Roles
Authors: Rebecca Voelker
Journal: JAMA (1996)

THEY MAY NOT pack the punch of protease inhibitors, but non-nucleoside reverse transcriptase inhibitors appear to have a promising future as a niche drug in the treatment and prevention of HIV infection. During the XI International Conference on AIDS in Vancouver, British Columbia, researchers said the drugs will be useful in a variety of scenarios, from playing a role in combination therapy to serving as a potential "morning after" pill to prevent infection following unprotected sex. "There is something special about these drugs," said Joep Lange, MD, professor of internal medicine at the Academic Medical Centre, University of Amsterdam, The Netherlands. <h3>Direct Inhibition</h3> The non-nucleoside drugs are similar to nucleoside analogs like AZT (zidovudine) in that they change the function of reverse transcriptase (RT), an enzyme that HIV needs to replicate. However, the non-nucleoside drugs do not have to be activated by cellular enzymes. And while inhibitory mechanisms of nucleoside
Widespread Distribution of Extensive Chromosomal Fragmentation in Ciliates
Authors: Jennifer L. Riley, Laura A. Katz
Journal: Molecular Biology and Evolution (2001)

Ciliates are a diverse group of eukaryotes characterized by their division of nuclear function into a "germ line" micronucleus and a "somatic" macronucleus. After conjugation, chromosomes in the transcriptionally active macronucleus develop by fragmentation, elimination, and amplification of germ line chromosomes. Extensive chromosomal processing that generates a macronucleus with gene-sized fragments has thus far been well documented in members of only one class of ciliates, the Spirotrichea. Here we establish the broad distribution of extensive fragmentation among members of the class Phyllopharyngea and the genera Metopus (order Armophorida) and Nyctotherus (order Clevelandellida). Moreover, analyses of small-subunit rDNA genealogies indicate that gene-sized chromosomes occur in members of the three separate clades: (1) the class Spirotrichea, (2) the class Phyllopharyngea, and (3) the two orders Clevelandellida and Armophorida. Together, these data indicate that the generation of gene-sized chromosomes is widespread and demonstrate multiple origins of extensive fragmentation within ciliates.
A73: A Comparison of Serologic Profiles of Children With Sjögren Syndrome Based on the Presence or Absence of Parotitis
Authors: Jay Mehta, Naoto Yokogawa, Scott Lieberman
Journal: Arthritis & Rheumatology (2014)

Background/Purpose: Sjögren syndrome is a complex autoimmune disease that affects lacrimal and salivary glands along with the potential to cause damage to other organs. Diagnosis of childhood Sjögren syndrome is currently based on expert opinion due to the lack of child‐specific diagnostic criteria. Children do not typically present with the sicca symptoms characteristic of adult Sjögren syndrome. While they most commonly present with recurrent parotitis, some children present with other organ involvement in the absence of parotitis. The latter may be severe requiring more extensive immunomodulatory therapy. The goal of this study was to compare serologic profiles of cohorts of children with Sjögren syndrome presenting with or without parotitis to determine if separate serology‐based diagnostic criteria are needed for these two groups. Methods: We retrospectively reviewed childhood Sjögren syndrome cases from a single center as well as those in the published English literature with individual patient data. We collected available data on sicca symptoms, serologies (ANA, anti‐SSA/B, RF), lacrimal and salivary gland function, imaging, and histopathology. For analyses of individual components, cases were excluded if specific data was not explicitly reported, so denominators may vary. Results: We identified 26 cases of childhood Sjögren syndrome diagnosed and followed at The Children's Hospital of Philadelphia and 67 cases in the literature that contained information on individual children. Parotitis status was reported for 82 cases and was a main feature of presentation in 59 (72%) cases. 28 of 51 (55%) children with parotitis and 13 of 22 (59%) children without parotitis presented with sicca symptoms. 53 of 58 (91%) children with parotitis and 21 of 23 (91%) children without parotitis were ANA positive. 49 of 58 (84%) children with parotitis and 20 of 23 (87%) children without parotitis were anti‐SSA/B positive. 42 of 51 (82%) children with parotitis and 7 of 13 (54%) children without parotitis were RF positive. 56 of 58 (97%) children with parotitis and 22 of 23 (96%) children without parotitis were positive for either ANA or anti‐SSA/B. Conclusion: A large majority (96%) of children with Sjögren syndrome have positive ANA and/or anti‐SSA/B, and the serologic profiles do not significantly differ based on the presence or absence of parotitis. Thus, testing for ANA and anti‐SSA/B is warranted in the diagnostic workup of any child suspected of having Sjögren syndrome, especially in patients who do not present with parotitis. Given the selection bias inherent in this approach, development of childhood Sjögren syndrome‐specific diagnostic criteria are needed for future prospective studies to better characterize the prognosis and optimal therapies for this potentially devastating disease.
A PDGFRB-positive acute myeloid malignancy with a new t(5;12)(q33;p13.3) involving the ERC1 gene
Authors: P Gorello, R La Starza, L Brandimarte, S M Trisolini, V Pierini, B Crescenzi, M Z Limongi, M Nanni, E Belloni, C Tapinassi, E Gerbino, M F Martelli, R Foà, G Meloni, P G Pelicci, C Mecucci
Journal: Leukemia (2007)
R222Q SCN5A Mutation Is Associated With Reversible Ventricular Ectopy and Dilated Cardiomyopathy
Authors: Stefan A. Mann, Maria L. Castro, Monique Ohanian, Guanglan Guo, Poonam Zodgekar, Angela Sheu, Kathryn Stockhammer, Tina Thompson, David Playford, Rajesh Subbiah, Dennis Kuchar, Anu Aggarwal, Jamie I. Vandenberg, Diane Fatkin
Journal: Journal of the American College of Cardiology (2012)
New insights into the molecular basis of atrial fibrillation: mechanistic and therapeutic implications
Authors: D. Dobrev, S. Nattel
Journal: Cardiovascular Research (2011)

This editorial refers to a collection of nine reviews and nine original articles that are part of this special issue on atrial fibrillation, guest edited by Dobromir Dobrev and Stanley Nattel. 

Atrial fibrillation (AF), the most common sustained arrhythmia, is associated with substantial cardiovascular morbidity and mortality, with stroke being the most critical complication.1 Present drugs used for AF therapy have major limitations, including incomplete efficacy and risks of life-threatening proarrhythmic events and bleeding complications.1,2 Non-pharmacological ablation procedures are efficient and relatively safe, but the very large size of the patient population allows ablation treatment of only a small number of patients. Therefore, drug therapy remains the mainstay of AF treatment. Maintenance of sinus rhythm (rhythm control) appears preferable, but studies to date have failed to demonstrate tangible advantages of rhythm control. The failure to show benefits in mortality and stroke incidence motivates attempts to identify new therapeutic targets relating to basic mechanisms underlying arrhythmia susceptibility. A better mechanistic understanding of the molecular basis of AF may allow for the development of safer and more effective treatment approaches.

The mechanisms underlying AF susceptibility are multiple and incompletely understood. The two major determinants of AF maintenance are reentry and ectopic impulse formation (ectopic activity).3 Reentry induction requires an appropriate arrhythmogenic substrate and a trigger that initiates reentry within the substrate. The likelihood of reentry is determined by the tissue properties of conduction and refractoriness, with slow conduction and short refractoriness making persistence of reentry more likely. Ectopic activity is governed by factors controlling the occurrence of afterdepolarizations, primarily Ca2+ handling abnormalities that can cause early and delayed afterdepolarizations. The changes in atrial structure and function that result from heart disease, and indeed AF itself, constitute atrial remodelling and are key elements of the …
Blood-group Studies in Friedreich's Ataxia
Authors: E. D. U. Powell
Journal: BMJ (1961)

He has felt " dazed " after hard blows on the head.E.E.G. recordings taken at rest showed sporadic bursts of disordered activity in both " unipolar " and bipolar records (Fig. 1).Case 2.-This man, aged 27, had boxed for the last five years.He did not complain of headaches or loss of memory, but had had one knock-out and was unconscious for eight hours (two years before the E.E.G. recording was made).His E.E.G. showed spontaneous bursts of disordered activity (Fig. 2).Case 3.-This man, aged 21, had boxed from 1952 to 1956; he then stopped until 1960.He gave a history of having been struck by a stone on the head in 1954 and was unconscious for about two hours on that occasion.He complained of frequent attacks of headaches and was referred to us for an E.E.G. in May, 1960.The E.E.G. was reported as being within the limits of normal variation (Fig. 3).In August, 1960, he was sent for an E.E.G. as he was unconscious for about 20 minutes after a blow on the chin during a university boxing meet.This E.E.G. was taken three days after the "knock-out."The recording showed spontaneous bursts of disordered activity (Fig. 4).~~~~....... |~| FI. 3.-Case 3.No abnormal E.E.G. changes before the knock- out.(Record taken in May, 1960.)Fia.4.-Case 3. Spontaneous bursts of disordered activity occurnng in several leads.(Record taken in August, 1960.)Discuson The variations found in our control group of cases (8%) is well within the expected figures.The presence of disordered activity among 60% of the boxers is statistically very significant.Further, it is noticed that, although only 34% of the boxers gave a history of knock-outs, 60% showed disordered activity.Our findings therefore show that E.E.G. recordings of boxers taken under identical conditions (at rest) show a significant change in the wave form in a large percentage of cases.We are grateful to the boxers for their help and also to the Rockefeller Foundation, New York, for the valuable apparatus with which we carried out this investigation.
BI-07 * HYPERPOLARIZED [1-13C] GLUTAMATE: A METABOLIC IMAGING BIOMARKER OF IDH1 MUTATIONAL STATUS IN GLIOMA
Authors: M. Chaumeil, P. Larson, S. Woods, L. Cai, P. Eriksson, A. Robinson, J. Lupo, D. Vigneron, S. Nelson, R. Pieper, J. Phillips, S. Ronen
Journal: Neuro-Oncology (2014)

Mutations of the isocitrate dehydrogenase 1 (IDH1) gene are among the most prevalent in low-grade glioma and secondary glioblastoma, represent an early pathogenic event and are being considered a promising therapeutic target. Consequently, non-invasive imaging methods are needed to monitor IDH1 status. Amongst these, we previously demonstrated the use of 13C MR spectroscopic imaging of hyperpolarized [1-13C] α-ketoglutarate (α-KG) to non-invasively assess IDH1 status through the detection of the conversion of hyperpolarized α-ketoglutarate to 2-hydroxyglutarate (2-HG) catalyzed by mutant IDH1. Importantly, in addition to its oncogenic role, IDH1 mutation is also associated with global modulations in metabolism. Interestingly, a study recently uncovered a relationship between presence of IDH1 mutation and decreased activity of the branched chained amino acid transaminase 1 (BCAT1) enzyme, which transaminates amino acids while converting α-KG to glutamate. Given this new study, we decided to expand on our previous findings and investigated the potential of hyperpolarized α-KG as an imaging probe to monitor BCAT1-driven α-KG-to-glutamate conversion and its modulation in the presence of IDH1 mutation. We investigated two isogenic glioblastoma lines that differed only in their IDH1 status, and performed experiments in live cells and in vivo in rat orthotopic tumors. Following injection of hyperpolarized α-KG, hyperpolarized glutamate production was detected both in cells and in vivo, and the level of hyperpolarized glutamate was significantly lower in mutant IDH1 cells and tumors compared to their IDH1-wild-type counterparts. Importantly however, the observed drop in hyperpolarized glutamate was likely mediated not only by a drop in BCAT1 activity, but also by reductions in aspartate transaminase and glutamate dehydrogenase activities, suggesting additional metabolic reprogramming at least in our model. Hyperpolarized glutamate could thus inform on multiple mutant IDH1-associated metabolic events and serve as a secondary metabolic biomarker of IDH1 mutational status in gliomas, together with 2-HG.
Long-term results of noncultured epidermal cellular grafting in vitiligo, halo naevi, piebaldism and naevus depigmentosus
Authors: N. Van Geel, E. Wallaeys, B.K. Goh, M. De Mil, J. Lambert
Journal: British Journal of Dermatology (2010)

Several surgical techniques are available for the treatment of stable leucoderma. The use of noncultured epidermal cellular grafting was introduced in 1992. Data on long-term follow-up regarding stability of the repigmented area, time to achieve the final repigmentation, colour matching, reaction to sun exposure and patient satisfaction with treatment have been reported only a few times previously.To evaluate the long-term results of the noncultured epidermal cellular grafting technique in patients with different types of leucoderma, including segmental vitiligo (n = 33), generalized vitiligo (n = 33), mixed vitiligo (n = 6), halo naevi (n = 11), piebaldism (n = 3) and naevus depigmentosus (n = 1).Patients were evaluated by examination and questionnaire in a retrospective setting after transplantation by autologous noncultured cellular grafting. Percentage of repigmentation was evaluated in 82 patients using a digital imaging analysis system (mean follow-up 15 months). Long-term results were evaluated by 54 patients using a questionnaire up to 7·7 years after treatment (mean 4 years).More than 75% repigmentation was achieved in 71% of patients. Best results were obtained in segmental vitiligo, halo naevi and piebaldism, whereas results in generalized or mixed vitiligo were inferior. According to the patients, final repigmentation was achieved after a mean of 10 months post-treatment. In 80% some colour mismatch (hyperpigmentation and hypopigmentation) was reported between the treated area and the surrounding skin, although this was not disturbing for the majority. This colour mismatch was reported significantly less after sun exposure (P = 0·012). During follow-up 7% of patients, all with generalized vitiligo, observed some loss of the achieved repigmentation.Autologous epidermal cellular grafting achieved a high percentage of repigmentation, which was maintained during follow-up in the majority of patients. Although it improved quality of life, a perfect colour match was seldom obtained.
Go Like Water, Come Back Like Water
Authors: Stephen Thomas Harvey
Journal: JAMA (2013)

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
G.M.C. and Indian Doctors
Authors: R. Burkitt
Journal: BMJ (1975)

The current prospective cohort study assessed the diagnostic yield of chest radiography (CXR) in primary-care patients suspected of pneumonia. In total, 192 patients with a clinical suspicion of pneumonia aged ≥18 yrs were referred by their general practitioner (GP) for CXR to one of the three participating hospitals in the Netherlands. All GPs were asked to complete a standardised form before and after CXR. Pneumonia was diagnosed by GPs in 35 (18%) patients, of whom 27 (14%) patients had a positive CXR, and eight (4%) patients a negative CXR, but with an assumed high probability of pneumonia by the GP. CXR clearly influenced the diagnosis of pneumonia by the GP in 53% of the patients. CXR ruled out pneumonia in 47% and the probability of pneumonia substantially increased in 6% of the patients. Patient management changed after CXR in 69% of the patients, mainly caused by a reduction in medication prescription (from 43 to 17%) and more frequent reassurance of the patient (from 8 to 35%). In conclusion, pneumonia was frequently over diagnosed clinically by general practitioners. Chest radiography is a valuable diagnostic tool to substantially reduce the number of patients misdiagnosed and is particularly important for the exclusion of pneumonia in general practice.
Increased serum PAD4 and RF in lung cancer is not associated with anti CCP antibody production
Authors: Z. Baka, P. Barta, G. Losonczy, T. Krenacs, J. Papay, E. Szarka, G. Sarmay, A. Magyar, E. Buzas, A. Falus, G. Nagy
Journal: Annals of the Rheumatic Diseases (2011)

Background Rheumatoid arthritis (RA) is characterised by anticitrullinated protein antibodies (ACPAs), produced against citrullinated proteins. In the pathogenesis of the disease the interaction of environment and genetics have a role as smoking is an important risk factor for the development of ACPA positive RA, especially in shared epitope carriers. However, the link among smoking, citrullination, catalysed by peptidyl arginine deiminases (PADs), and ACPAs has not yet been elucidated. Thus, we searched for a model without polyarthritis where there is increased cell death allowing the formation of autoantibodies. Objectives We proposed that lung cancer might be a good candidate supported by the following considerations: smoking plays a role in its pathogenesis; the disease is often accompanied by paraneoplastic syndrome; smoking increases citrullination in the lung; several malignant tumour tissues are associated with increased citrullination; RA synovium and lung cancer tissue have similarities. Patients and methods Serum PAD4, rheumatoid factor (RF) and ACPA levels were measured in 42 lung cancer patients and 67 non-tumourous pulmonary patients and healthy controls. All parameters were compared according to smoking history. None of the patients had polyarthritis or autoimmune disease. Results Abnormal PAD4 and RF levels were frequently found in smoker lung cancer patients, compared to non-smokers. Two out of 30 smoker lung cancer patients had high anti-CCP levels. Smoking intensity (packyears) was significantly higher among smoker lung cancer patients, compared to healthy smokers, however, did not correlate to the measured serum parameters. Conclusions smoking might influence PAD4 levels and RF production. High serum PAD4 and RF levels together with smoking are not sufficient for the formation of ACPAs and autoimmunity.
Year in review in Intensive Care Medicine 2014: I. Cardiac dysfunction and cardiac arrest, ultrasound, neurocritical care, ICU-acquired weakness, nutrition, acute kidney injury, and miscellaneous
Authors: Giuseppe Citerio, Jan Bakker, Matteo Bassetti, Dominique Benoit, Maurizio Cecconi, J. Randall Curtis, Gordon S. Doig, Margaret Herridge, Samir Jaber, Michael Joannidis, Laurent Papazian, Anders Perner, Mark J. Peters, Pierre Singer, Martin Smith, Marcio Soares, Antoni Torres, Antoine Vieillard-Baron, Jean-François Timsit, Elie Azoulay
Journal: Intensive Care Medicine (2015)

Intensive Care Medicine is changing. New types of pa pers, such as “What’s New in Intensive Care?”, “Understanding the Disease” and “My Paper 20 Years Later”, form a stable proportion of the articles published in the 2014 issues. This diversification has been received with an extraordinary enthusiasm and appreciation by the worldwide readership, as evidenced by the massive number of hits and downloads. In this first of three 2014 “Year in Review” articles, we cover those papers published in Intensive Care Medicine during the past year which focus on cardiac arrest, ultrasonography in critically ill patients, neurocritical care, ICU-acquired weakness, nutrition, acute kidney injury, as well as a number of miscellaneous topics.
Abstract 3779: ARHI-induced autophagy is mediated through activation of FoxO3a and induction of its target genes to promote the formation of autophagic complexes
Authors: Warren S. Liao, Zhen Lu, Fengqin Gao, Maojie Yang, Robert C. Bast
Journal: Cancer Research (2011)

Abstract The role of autophagy in oncogenesis remains ambiguous and the mechanisms that induce autophagy and regulate its outcome in human cancer are poorly understood. ARHI (DIRAS3), a Ras-related tumor suppressor, is downregulated in &amp;gt;60% of ovarian cancers. Re-expression of ARHI in ovarian cancer cells induces autophagy in culture and in xenografts, by blocking Ras activation and inhibiting PI3 kinase activity. ARHI also participates directly in the formation of autophagosomes by upregulating Atg4 and co-localizing with processed LC-3 II. Here we show that inhibition of PI3 kinase/Akt signaling and Ras activation by ARHI is mediated, in part, by down regulation of EGFR expression and EGFR phosphorylation. Inhibition of these signaling pathways reduced phosphorylation of FoxO3a and enhanced nuclear accumulation of FoxO3a transcription factor, resulting in increased transcription of Atg4, MAP-LC-3, and PUMA. Knockdown of FoxO3a by siRNA reduced ARHI- and rapamycin-induced autophagy. Whereas ARHI inhibits Class I PI3K activity, its expression induces Class III PI3K activity and contributes to the enhanced autophagy. Thus, ARHI-induced autophagy is through activation of the transcription factor FoxO3a, which increases the expression of several autophagy-related genes that contribute to the formation of the autophagic complexes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3779. doi:10.1158/1538-7445.AM2011-3779