tbuckley/cabot-search huggingface dataset:
Abstract LB-305: Identification of p21 as a novel substrate of LATS2 in lung cancer
Authors: Benjamin Yeung
Journal: Cancer Research (2014)

Abstract LATS2 is a serine/threonine kinase and tumor suppressor gene found to be downregulated and mutated in lung cancer. Although LATS2 has been shown to regulate many cancer-related functions such as maintenance of genomic stability, cell proliferation and apoptosis, its roles in lung tumorigenesis are largely unknown. In addition, the downstream cellular genes mediating LATS2 tumor suppressing function in lung cancer remains elusive. Since LATS2 kinase activity is essential for its function, therefore, identification and characterization of LATS2 substrates is critical in understanding the role it plays in lung tumorigenesis and is the focus of this study. To elucidate LATS2 function in lung cancer, we stably overexpressed LATS2 in a variety of lung cancer cell lines using a doxycycline-inducible lentivirus system. We have found that LATS2 strongly suppresses cell proliferation in all of cell lines tested. Further functional screening for LATS2 kinase substrates identified p21CIP1 to be a potential LATS2 substrate mediating LATS2 tumor suppressing function. p21 and LATS2 were found to bind each other as revealed by GST-pulldown and co-immunoprecipitation assays. Importantly, we found that LATS2 specifically phosphorylates p21 at S146, and that this site is critical for suppressing cell proliferation in lung cancer cells. These findings describe a novel LATS2 signalling pathway and improve our understanding of the role of LATS2 in lung tumorigenesis. Citation Format: Benjamin Yeung. Identification of p21 as a novel substrate of LATS2 in lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-305. doi:10.1158/1538-7445.AM2014-LB-305
ABC of palliative care: Mouth care, skin care, and lymphoedema
Authors: C. Regnard, S. Allport, L. Stephenson
Journal: BMJ (1997)

Patients' oral problems can be kept to a minimum by good hydration, brushing the teeth with a fluoride toothpaste twice daily, and daily observation of the oral mucosa. Oral problems can reduce intake of fluid and food because of pain, altered taste, or disorders of swallowing. The first step is to manage the local problems. #### Risk factors for oral problems ### Infection #### Key questions for mouth care Candidiasis usually presents as adherent white plaques but can also present as erythema or angular cheilitis. Nystatin suspension is the usual treatment, but in advanced disease ketoconazole 200 mg once daily for 5 days is cost effective and more convenient for patients (hepatic toxicity has not been reported for 5 day courses). Fluconazole 150 mg as a single dose is equally effective but is more expensive. Recurrent candidiasis in patients with AIDS requires prophylactic treatment with fluconazole 50 mg daily. Oral candidiasis Oral hygiene is important, especially daily cleaning of dentures. Aphthous ulcers are common and can be helped by topical corticosteroids or tetracycline mouthwash. Severe viral infection (herpes simplex or zoster) will need aciclovir 200 mg every 4 hours for 5 days. Malignant ulcers are often associated with anaerobic bacteria that produce a foul odour; this responds to metronidazole, either as 400–500 mg taken orally or rectally every 12 hours or as a topically applied gel. ### Dirty mouth #### Local measures for oral problems ##### Infected mouth ##### Dirty mouth ##### Dry mouth
A Pivotal Medical-Device Case
Authors: Gregory D. Curfman, Stephen Morrissey, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2008)

This spring the Supreme Court of the United States will decide whether premarketing approval of a medical device by the Food and Drug Administration (FDA) immunizes the manufacturer against product-liability litigation in state courts. This decision, we believe, is a matter of particular importance to patients and the medical community.On December 4, 2007, the Supreme Court heard oral arguments in Riegel v. Medtronic.1 In May 1996, Charles Riegel underwent coronary angioplasty in Albany, New York. During the procedure, the balloon ruptured, and advanced cardiac life support and emergency coronary bypass surgery were needed. Mr. Riegel and his wife . . .
Differences in Heart Rate Variability Associated with Long-Term Exposure to NO <sub>2</sub>
Authors: Denise Felber Dietrich, Armin Gemperli, Jean-Michel Gaspoz, Christian Schindler, L.-J. Sally Liu, Diane R. Gold, Joel Schwartz, Thierry Rochat, Jean-Claude Barthélémy, Marco Pons, Frédéric Roche, Nicole M. Probst Hensch, Pierre-Olivier Bridevaux, Margaret W. Gerbase, Urs Neu, Ursula Ackermann-Liebrich
Journal: Environmental Health Perspectives (2008)

Heart rate variability (HRV), a measure of cardiac autonomic tone, has been associated with cardiovascular morbidity and mortality. Short-term studies have shown that subjects exposed to higher traffic-associated air pollutant levels have lower HRV.Our objective was to investigate the effect of long-term exposure to nitrogen dioxide on HRV in the Swiss cohort Study on Air Pollution and Lung Diseases in Adults (SAPALDIA).We recorded 24-hr electrocardiograms in randomly selected SAPALDIA participants >or= 50 years of age. Other examinations included an interview investigating health status and measurements of blood pressure, body height, and weight. Annual exposure to NO2 at the address of residence was predicted by hybrid models (i.e., a combination of dispersion predictions, land-use, and meteorologic parameters). We estimated the association between NO2 and HRV in multivariable linear regression models. Complete data for analyses were available for 1,408 subjects.For women, but not for men, each 10-microg/m3 increment in 1-year averaged NO2 level was associated with a decrement of 3% (95% CI, -4 to -1) for the standard deviation of all normal-to-normal RR intervals (SDNN), -6% (95% CI, -11 to -1) for nighttime low frequency (LF), and -5% (95% CI, -9 to 0) for nighttime LF/high-frequency (HF) ratio. We saw no significant effect for 24-hr total power (TP), HF, LF, or LF/HF or for nighttime SDNN, TP, or HF. In subjects with self-reported cardiovascular problems, SDNN decreased by 4% (95% CI, -8 to -1) per 10-microg/m3 increase in NO2.There is some evidence that long-term exposure to NO2 is associated with cardiac autonomic dysfunction in elderly women and in subjects with cardiovascular disease.
UK strategy to cut antibiotic use outlined
Authors: A. Brooks
Journal: BMJ (1998)

Patients should not be prescribed antibiotics for simple coughs and colds or for viral sore throats, recommends a report published last week by the UK Standing Medical Advisory Committee.

The report also advises that women with uncomplicated cystitis should be given only a three day course of treatment and that telephone prescription of anti-biotics should occur only in …
Survey of 3,000 Unwanted Pregnancies
Authors: J. Lambert
Journal: BMJ (1971)

A survey of 3,000 unwanted pregnancies disclosed two main populations differing in age, marital status, and contraceptive practice. Failure to use contraception accounted for two-thirds of the pregnancies. More than half of the patients were married women or single women in stable relationships, but many single women faced their predicament alone, without help from partner or parent.Some evidence is given of valid needs which could not be met by existing N.H.S. facilities.
Scatter factor/hepatocyte growth factor in brain tumor growth and angiogenesis
Authors: Roger Abounader, John Laterra
Journal: Neuro-Oncology (2005)

The multifunctional growth factor scatter factor/hepatocyte growth factor (SF/HGF) and its receptor tyrosine kinase c-Met have emerged as key determinants of brain tumor growth and angiogenesis. SF/HGF and c-Met are expressed in brain tumors, the expression levels frequently correlating with tumor grade, tumor blood vessel density, and poor prognosis. Overexpression of SF/HGF and/or c-Met in brain tumor cells enhances their tumorigenicity, tumor growth, and tumor-associated angiogenesis. Conversely, inhibition of SF/HGF and c-Met in experimental tumor xenografts leads to inhibition of tumor growth and tumor angiogenesis. SF/HGF is expressed and secreted mainly by tumor cells and acts on c-Met receptors that are expressed in tumor cells and vascular endothelial cells. Activation of c-Met leads to induction of proliferation, migration, and invasion and to inhibition of apoptosis in tumor cells as well as in tumor vascular endothelial cells. Activation of tumor endothelial c-Met also induces extracellular matrix degradation, tubule formation, and angiogenesis in vivo. SF/HGF induces brain tumor angiogenesis directly through only partly known mechanisms and indirectly by regulating other angiogenic pathways such as VEGF. Different approaches to inhibiting SF/HGF and c-Met have been recently developed. These include receptor antagonism with SF/HGF fragments such as NK4, SF/HGF, and c-Met expression inhibition with U1snRNA/ribozymes; competitive ligand binding with soluble Met receptors; neutralizing antibodies to SF/HGF; and small molecular tyrosine kinase inhibitors. Use of these inhibitors in experimental tumor models leads to inhibition of tumor growth and angiogenesis. In this review, we summarize current knowledge of how the SF/HGF:c-Met pathway contributes to brain tumor malignancy with a focus on glioma angiogenesis.
Antithyroid effects of lithium
Authors: S. C. Berens, R. S. Bernstein, J. Robbins, J. Wolff
Journal: Journal of Clinical Investigation (1970)

Lithium has been reported to be goitrogenic when used for the treatment of manic-depressive psychosis. To investigate the effects of lithium on iodine metabolism, male Sprague-Dawley rats were placed on a low iodine (LID) or normal iodine diet (NID) containing enough Li(2)CO(3) to give serum lithium levels of 0.23-0.86 mEq/liter (human therapeutic range is 0.6-1.6 mEq/liter). The following effects were noted with lithium treatment: (a) thyroid weight increased concomitant with a slowing of thyroidal iodine release; (b) the ability to concentrate iodide was increased only after goiters were established; (c) on the LID, (131)I uptake was elevated throughout all phases of treatment, even when the release rate was normal; (d) iodine organification was unaffected but the proportion of (131)I present as iodothyronines was decreased; (e) the thyroidal (127)I content was increased; (f) despite these changes, the serum PBI remained normal as did the thyroxine turnover rate; and (g) thyrotropin (TSH) levels in serum were the same as controls except for a slight elevation early in the course of treatment; TSH levels did not correlate with goitrogenesis. When LiCl was injected in large doses into intact rats (giving serum lithium levels of 3.08-3.89 mEq/liter), the iodide concentrating mechanism, (131)I uptake, and (131)I release rates were depressed. Similar experiments in hypophysectomized rats receiving TSH demonstrated these to be local antithyroid effects not mediated through the pituitary. The discrepancy between acute and chronic responses to lithium, and the dissociation between the inhibition of iodine release and stimulatory effects is discussed.
Trisomy and D/G Translocation Mongolism in Brothers
Authors: Theodore H. Ingalls, Thomas A. Henry
Journal: New England Journal of Medicine (1968)

The unique occurrence of D/G translocation in 1 and trisomy in the second of 2 brothers with Down's syndrome is reported. Blood samples from 7 other members of the family showed normal chromosomal patterns. Karyotypes on aneuploid cells revealed no minor mosaic patterns. The chromosomal patterns observed, as well as analysis of the family history, suggest that ecologic as well as genetic determinants have to be considered in speculating on the pathogenesis of Down's syndrome.
THE COLOUR CHANGES SEEN IN SKIN AND MUSCLE IN GAS GANGRENE
Authors: C. Wallace
Journal: BMJ (1917)

T Enmsg 72 Blood Pressure during Operations on the TWtoun?dedAbdomen.During tlhe course of an ether vapour anaestlhetic the blood pressure shows a tendency to rise, but if there is muchll niaipulation of gut and mesentery, it will gradutally fall.The process imay be continued for hours witlhout the pressure falling to a dangerous level.E.-?posure of gut A4naeshetic (int-aveno7ns ether eases.
Ventilation of Schoolrooms
Authors: F. H. Hartshorne
Journal: BMJ (1860)

<h3>Abstract</h3> The repetitive nature and complexity of multiple medically important genes make them intractable to accurate analysis, despite the maturity of short-read sequencing, resulting in a gap in clinical applications of genome sequencing. The Genome in a Bottle Consortium has provided benchmark variant sets, but these excluded some medically relevant genes due to their repetitiveness or polymorphic complexity. In this study, we characterize 273 of these 395 challenging autosomal genes that have multiple implications for medical sequencing. This extended, curated benchmark reports over 17,000 SNVs, 3,600 INDELs, and 200 SVs each for GRCh37 and GRCh38. We show that false duplications in either GRCh37 or GRCh38 result in reference-specific, missed variants for short- and long-read technologies in medically important genes including <i>CBS</i>, <i>CRYAA</i>, and <i>KCNE1</i>. Our proposed solution improves variant recall in these genes from 8% to 100%. This benchmark will significantly improve the comprehensive characterization of these medically relevant genes and guide new method development.
Bosentan Improves Exercise Capacity in Adolescents and Adults After Fontan Operation
Authors: Anders Hebert, Ulla R. Mikkelsen, Ulf Thilen, Lars Idorn, Annette S. Jensen, Edit Nagy, Katarina Hanseus, Keld E. Sørensen, Lars Søndergaard
Journal: Circulation (2014)

The Fontan procedure has improved survival in children with functionally univentricular hearts. With time, however, complications such as reduced exercise capacity are seen more frequently. Exercise intolerance is multifactorial, but pulmonary vascular resistance probably plays a crucial role. Elevated pulmonary vascular resistance has been associated with raised levels of endothelin-1, which are common both before and after Fontan operations. Treatment with endothelin-1 receptor antagonists could theoretically improve cardiopulmonary hemodynamics and exercise capacity. The aim of this study was therefore to examine the efficacy and safety of bosentan in Fontan patients.Seventy-five adolescents and adults were randomized 1:1 to 14 weeks of treatment with bosentan or placebo. Cardiopulmonary exercise test, functional class, blood samples, and quality-of-life questionnaires were evaluated at baseline and at the end of treatment. Sixty-nine patients (92%) completed the study. Peak oxygen consumption increased 2.0 mL·kg(-1)·min(-1) (from 28.7 to 30.7 mL·kg(-1)·min(-1)) in the bosentan group compared with 0.6 mL·kg(-1)·min(-1) (from 28.4 to 29.0 mL·kg(-1)·min(-1)) in the placebo group (P=0.02). Cardiopulmonary exercise test time increased by 0.48 minute (from 6.79 to 7.27 minutes) versus 0.08 minute (from 6.94 to 7.02 minutes; P=0.04). Nine bosentan-treated patients improved 1 functional class, whereas none improved in the placebo group (P=0.0085). Side effects were mild and occurred equally in both groups. No serious adverse effects were seen, and no patients had liver enzyme levels above the 3-fold upper limit.Bosentan improves exercise capacity, exercise time, and functional class in Fontan patients without serious adverse events or hepatotoxicity.http://www.clinicaltrials.gov. Unique identifier: NCT01292551.
BASAL METABOLISM IN THE SAME PERSON AFTER AN INTERVAL OF FIFTY YEARS
Authors: Adolf Magnus-Levy
Journal: JAMA (1942)

My basal metabolism was first examined in Zuntz's laboratory in 1891 at the age of 26 years. When I was 76 I had the opportunity of having it reexamined by Dr. Walter A. Boothby when I was at the Mayo Clinic in 1941 to give a lecture. During the interval, no measurements were made. Although the figures reveal nothing new, it might be of interest to publish them since they are unique. The decline of basal metabolism with advancing age, established by Falk and Magnus-Levy,<sup>1</sup>has been subsequently confirmed by a number of workers. Du Bois<sup>2</sup>quotes values of 39.5 calories per square meter per hour at 20 to 30 years and 35.5 calories per square meter per hour at 70 to 76 years, a decrease of 10 per cent. My record is given in table 1. The values for surface area are based on Du Bois's formula.
THE EFFICACY, SAFETY, AND NET CLINICAL BENEFIT OF CANGRELOR IN WOMEN UNDERGOING ELECTIVE OR URGENT PCI: INSIGHTS FROM THE CHAMPION-PHOENIX TRIAL
Authors: Michelle L. O’Donoghue, Deepak L. Bhatt, Gregg Stone, Philippe Steg, C. Michael Gibson, Christian Hamm, Matthew Price, Jayne Prats, Tiepu Liu, Efthymios Deliargyris, Kenneth Mahaffey, Harvey White, Robert Harrington
Journal: Journal of the American College of Cardiology (2015)
Novel Artificial Neural Network for Early Detection of Prostate Cancer
Authors: Bob Djavan, Mesut Remzi, Alexandre Zlotta, Christian Seitz, Peter Snow, Michael Marberger
Journal: Journal of Clinical Oncology (2002)

PURPOSE: Two artificial neural networks (ANN) for the early detection of prostate cancer in men with total prostate-specific antigen (PSA) levels from 2.5 to 4 ng/mL and from 4 to 10 ng/mL were prospectively developed. The predictive accuracy of the ANN was compared with that obtained by use of conventional statistical analysis of standard PSA parameters. PATIENTS AND METHODS: Consecutive men with a serum total PSA level between 4 and 10 ng/mL (n = 974) and between 2.5 and 4 ng/mL (n = 272) were analyzed. A separate ANN model was developed for each group of patients. Analyses were performed to determine the presence of prostate cancer. RESULTS: The area under the receiver operator characteristic (ROC) curve (AUC) was 87.6% and 91.3% for the 2.5 to 4 ng/mL and 4 to 10 ng/mL ANN models, respectively. For the latter model, the AUC generated by the ANN was significantly higher than that produced by the single variables of total PSA, percentage of free PSA, PSA density of the transition zone (TZ), and TZ volume (P &lt; .01), but not significantly higher compared with multivariate analysis. For the 2.5 to 4 ng/mL model, the AUC of the ANN ROC curve was significantly higher than the AUCs for percentage of free PSA (P = .0239), PSA-TZ (P = .0204), and PSA density and total prostate volume (P &lt; .01 for both). CONCLUSION: The predictive accuracy of the ANN was superior to that of conventional PSA parameters. ANN models might change the way patients referred for early prostate cancer detection are counseled regarding the need for prostate biopsy.
A piece of my mind. The generic H &amp; P
Authors: F. L. Brancati
Journal: JAMA (1989)

8 AM—the end of another long call night and time for attending rounds. Your team awaits you. "Gee, you look terrible. How many did you get last night?" "Seven. Actually, eight if you count that ICU transfer. Not too bad." Not too bad for an intern like you, but a killer call night for a lesser house officer. You know it and they know it—you're Chief Resident material. You reach into your pocket for that stack of index cards, your notes from last night. Instead, you discover a Hemoccult card, some Kleenex, and a gum wrapper. No note cards. Your cheeks flush. Beads of sweat collect on your upper lip. You feel your esophagus twist like a rubber band in a model airplane. You spent most of last night learning the intricacies of your patients' lives and illnesses, but right now your mind's a blank. How can you honestly present
Multiple Blood Pressure Medications and Mortality Among Elderly Individuals
Authors: Wilbert S. Aronow
Journal: JAMA (2015)

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
High pressure paint gun injuries.
Authors: C M Booth
Journal: BMJ (1977)

Despite their use for the past 20 years the dangers of injuries from high pressure paint guns are not widely known. Two cases treated incorrectly through ignorance in our casualty department resulted in amputation of digits. Paint solvents are far moe damaging than paint of grease injection. All cases should be treated urgently by an experienced surgeon as fairly extensive surgery may be needed.
Neural progenitor cells labeling with microbubble contrast agent for ultrasound imaging in vivo
Authors: Wenjin Cui, Sidhartha Tavri, Michael J. Benchimol, Malak Itani, Emilia S. Olson, Hong Zhang, Marika Decyk, Rosemarie G. Ramirez, Christopher V. Barback, Yuko Kono, Robert F. Mattrey
Journal: Biomaterials (2013)
Molecular basis of inherited antithrombin deficiency in Portuguese families: Identification of genetic alterations and screening for additional thrombotic risk factors
Authors: Dezsö David, Sofia Ribeiro, Lénia Ferrão, Teresa Gago, Francisco Crespo
Journal: American Journal of Hematology (2004)

Abstract Antithrombin (AT), the most important coagulation serine proteases inhibitor, plays an important role in maintaining the hemostatic balance. Inherited AT deficiency, mainly characterized by predisposition to recurrent venous thromboembolism, is transmitted in an autosomal dominant manner. In this study, we analyzed the underlying genetic alterations in 12 unrelated Portuguese thrombophilic families with AT deficiency. At the same time, the modulating effect of the FV Leiden mutation, PT 20210A, PAI‐1 4G, and MTHFR 677T allelic variants, on the thrombotic risk of AT deficient patients was also evaluated. Three novel frameshift alterations, a 4‐bp deletion in exon 4 and two 1‐bp insertions in exon 6, were identified in six unrelated type I AT deficient families. A novel missense mutation in exon 3a, which changes the highly conserved F147 residue, and a novel splice site mutation in the invariant acceptor AG dinucleotide of intron 2 were also identified in unrelated type I AT deficient families. In addition to these, two previously reported missense mutations changing the AT reactive site bond (R393–S394) and leading to type II‐RS deficiency, and a previously reported cryptic splice site mutation (IVS4–14G→A), were also identified. In these families, increased thrombotic risk associated with co‐inheritance of the FV Leiden mutation and of the PAI‐1 4G variant was also observed. In conclusion, we present the first data regarding the underlying genetic alterations in Portuguese thrombophilic families with AT deficiency, and confirm that the FV Leiden mutation and probably the PAI‐1 4G variant represent additional thrombotic risk factors in these families. Am. J. Hematol. 76:163–171, 2004. © 2004 Wiley‐Liss, Inc.