tbuckley/cabot-search huggingface dataset:
Inflammation, Cholesterol Levels, and Risk of Mortality Among Patients Receiving Dialysis
Authors: Uffe Ravnskov
Journal: JAMA (2004)

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
Excision of nucleoside analogs from DNA in mitochondria by p53 protein
Authors: Mary Bakhanashvili, Elena Novitsky, Galia Rahav, Yechezkel Sidi
Journal: Cancer Research (2004)

2959   Nucleoside analogs (NAs), used in cancer chemoherapy and in treatment of virus infections, are incorporated into DNA and cause cell death or inhibit viral replicatin. It is well established that long-term therapy can cause mitochondrial toxicity. The toxicity of NA may be related to their effects on the human mitochondrial DNA polymerase γ, the polymerase responsible for mitochondrial DNA replication. Although mitochondrial polymerase γ has 3′→5′ exonuclease activity, the failure of this proofreading activity to efficiently remove chain terminators may play a role in mitochondrial toxicity of nucleoside analogs. It was recently reported that a fraction of induced tumor suppressor protein p53 translocates to the mitochondria of apoptosing tumor cells. The present is based on our previous observation that the wtp53 with its associated 3′→5′ exonuclease activity is able to preferentially remove mismatched nucleotides from DNA and serve as an external proofreader for DNA polymerases. We further investigated the ability of p53 to remove incorporated nucleoside analogs from DNA. Using mitochondrial fraction of H1299 cells (p53-null) and an in vitro DNA primer extension assay, it was shown that various ddNTPs incorporated into the elongating DNA strand by mitochondrial DNA polymerase γ. Once incorporated, NA became a poor substrate for 3′→5′ exonuclease activity of this DNA polymerase. However, the efficient excision of the incorporated nucleoside analogs from chain terminated 3’end of the DNA primer was observed in the presence of either purified wtp53 or cytoplasmic fraction of LCC2 cells (expressing high levels of p53). Inefficient excision was detected with cytoplasmic extracts obtained from either MCF-7 cells (expressing low levels of wtp53) or MDA cells (expressing mutant p53). Furthermore, immunoprecipitation of p53 from cytoplasmic extracts of LCC2 cells markedly reduced the exonuclease activity. Thus, the data demonstrate that wt p53 in mitochondria could play an important role of external proofreader in removing nucleoside analogs from the 3’-end of the DNA, thus reducing the toxicity of the NA’s.
Lesson of the week: Antenatal screening for rubella---infection or immunity?
Authors: Nilesh M Mehta, Roslyn M Thomas
Journal: BMJ (2002)

Rubella vaccination among schoolgirls and susceptible women in the United Kingdom since 1970 has dramatically reduced the number of cases of congenital rubella syndrome and terminations of pregnancies related to rubella infection.1 In 1988 the combined measles, mumps, and rubella vaccine was introduced for children aged 12-15 months. Reported cases of congenital rubella syndrome declined significantly, with only a few notified cases of infection among immigrants and in infants whose mothers acquired the infection while travelling overseas in early pregnancy. Immune status of pregnant women is determined by routine antenatal screening for rubella IgG antibody, so that susceptible women can receive postpartum vaccination.

We report two infants with congenital rubella syndrome whose mothers had recently arrived from abroad. Both mothers had a rash in early pregnancy in their country of origin, which was not elicited when they booked for antenatal care in the United Kingdom.

### Case 1

A 22 year old primiparous Sri Lankan woman had routine antenatal screening tests at 20 weeks' gestation, soon after her arrival in the United Kingdom. The laboratory reported presence of rubella IgG antibody, “consistent with immunity.” The infant was born with severe symmetrical intrauterine growth restriction, purpura, thrombocytopenia, and a patent ductus arteriosus. Cranial ultrasonography showed bilateral periventricular calcification (fig 1). Skeletal radiographs showed linear radiolucencies in the metaphyses of the long bones and lucent areas in the …
Public thinks genetic testing is “a step too far”
Authors: Cherrill Hicks
Journal: BMJ (2001)

Many people believe that genetic medicine “messes with nature,” and most are opposed to genetic testing for specific diseases, says a new report from the Institute for Public Policy Research, an independent charity and think-tank.

The report, by Liz Kendall, senior research fellow in health policy at the institute, said that genetic medicine is set to become one of the most important developments in health care, with advances in knowledge about the human genome affecting the treatment of common disorders such as diabetes, cancer, and cardiovascular disease.

Genetic research, it pointed out, could lead to the development of more “personalised” drugs designed to fit specific molecular processes involved in causing disease, and other new types of treatment such as gene therapy, in which defective genes are replaced or repaired. Genetic testing for common disorders such as diabetes and cardiovascular disease …
Medical Oncology: Basic Principles and Clinical Management of Cancer.
Authors: Paul Calabresi, Philip S. Schein
Journal: Annals of Internal Medicine (1991)

This is a 1,576 page textbook.It may be a little bit more medical oncology than most people want to read.For medical oncologists, much of the field is fast moving enough that any text is somewhat outdated when it is published.A very broad spectrum of collaborators of very high quality, however, have made most of the material in this book worth reading.For nononcologists, nonspecialists, there is in-depth consideration of most of the aspects of medical oncology and most of the basic concepts that underlie our current
Eighth International Meeting on N-Nitroso Compounds Occurrence, Biological Effects, and Relevance to Human Cancer
Authors: Helmut Bartsch, Ian K. O'Neill
Journal: Cancer Research (1984)

Existence et formation de composes N-nitroso (NN). Progres analytiques et identification de nouveaux CNN. Reparation de l'ADN, produits d'addition aux macromolecules et effets biologiques. Metabolisme et facteurs modifiants. CCN et carcinogenese par le tabac. Liens des CCN et de leurs precurseurs avec les cancers humains
Concept of lymphoid versus myeloid dendritic cell lineages revisited: both CD8α− and CD8α+dendritic cells are generated from CD4lowlymphoid-committed precursors
Authors: Pilar Martı́n, Gloria Martı́nez del Hoyo, Fabienne Anjuère, Sara Ruiz Ruiz, Cristina Fernández Arias, Alvaro Rodrı́guez Marı́n, Carlos Ardavı́n
Journal: Blood (2000)
Parameters associated with severe pain during photodynamic therapy: results of a large Scottish series
Authors: A.J. Waters, S.H. Ibbotson
Journal: British Journal of Dermatology (2011)

Journal Article Parameters associated with severe pain during photodynamic therapy: results of a large Scottish series Get access A.J. Waters, A.J. Waters Photobiology Unit, Ninewells Hospital and Medical School, Dundee DD1 9SY, U.K. E‐mail: a.waters@nhs.net Search for other works by this author on: Oxford Academic Google Scholar S.H. Ibbotson S.H. Ibbotson Photobiology Unit, Ninewells Hospital and Medical School, Dundee DD1 9SY, U.K. E‐mail: a.waters@nhs.net Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 165, Issue 3, 1 September 2011, Pages 696–698, https://doi.org/10.1111/j.1365-2133.2011.10429.x Published: 01 September 2011
Phospholipase A2 inhibits cisplatin-induced acute kidney injury by modulating regulatory T cells by the CD206 mannose receptor
Authors: Hyunseong Kim, Hyojung Lee, Gihyun Lee, Hyunil Jang, Sung-Su Kim, Heera Yoon, Geun-Hyung Kang, Deok-Sang Hwang, Sun Kwang Kim, Hwan-Suck Chung, Hyunsu Bae
Journal: Kidney International (2015)
Expanding Long-term Care Options for Persons With Serious Mental Illness—Reply
Authors: Dominic A. Sisti, Andrea G. Segal, Ezekiel J. Emanuel
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
Predictors of Low Cardiac Output Syndrome After Isolated Aortic Valve Surgery
Authors: Manjula D. Maganti, Vivek Rao, Michael A. Borger, Joan Ivanov, Tirone E. David
Journal: Circulation (2005)

Background— Low cardiac output syndrome (LCOS), defined as the need for postoperative intraaortic balloon pump or inotropic support for &gt;30 minutes in the intensive care unit, remains a relatively common complication of aortic valve (AV) surgery. The aim of this study is to identify the preoperative predictors of LCOS in patients undergoing isolated AV surgery. Methods and Results— We conducted a retrospective review of data prospectively entered into an institutional database. Between 1990 and 2003, 2255 patients underwent isolated AV surgery with no other concomitant cardiac surgery. The independent predictors of LCOS and operative mortality (OM) were determined by stepwise logistic regression analysis. The overall prevalence of LCOS was 3.9%. The independent predictors of LCOS were (odds ratio in parentheses) renal failure (5.0), earlier year of operation (4.4), left ventricular ejection fraction &lt;40% (3.6), shock (3.2), female gender (2.8), and increasing age (1.02). Overall OM was 2.9%. The OM was higher in patients who experienced LCOS (38% versus 1.5%; P &lt;0.001). The independent predictors of mortality were (odds ratio in parentheses) preoperative renal failure (8.3), urgency of surgery (3.4), previous stroke (2.9), congestive heart failure (2.6), previous cardiac surgery (2.3), hypertension (1.7), and small AV size (1.3). Conclusions— Low-output syndrome is associated with significantly increased morbidity and mortality. Novel strategies to preserve renal function, optimization of preexisting heart failure symptoms, and avoidance of prosthesis-patient mismatch may reduce the incidence of LCOS and lead to improved results after AV surgery.
Randomized Double-Blind Comparison of Sirolimus-Eluting Stent Versus Bare-Metal Stent Implantation in Diseased Saphenous Vein Grafts
Authors: Paul Vermeersch, Pierfrancesco Agostoni, Stefan Verheye, Paul Van den Heuvel, Carl Convens, Nico Bruining, Frank Van den Branden, Glenn Van Langenhove
Journal: Journal of the American College of Cardiology (2006)
International Plans to Deter Antibiotic Resistance Need Improvement
Authors: M. J. Friedrich
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
Comparative pharmacokinetics in mice of the novel camptothecin analog DB-67 administered in diluted cremophor/ethanol or a supersaturated solution stabilized by a chemically-modified cyclodextrin.
Authors: Markos Leggas, Jamie Horn, Sherri Jordan, Michael J. Roberts, Bradley D. Anderson
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5538 

DB-67 (7- t -butyldimethylsilyl-10-hydroxycamptothecin) is a third generation camptothecin analog engineered to be blood stable and highly potent. After evaluation through the Rapid Access to Intervention Development (RAID) program at the National Cancer Institute (NCI), it will be tested in patients with solid tumors. Presently, the drug is formulated in 50% cremophor EL/ethanol for dilution prior to injection, but this vehicle is known to cause hypersensitivity in patients. Here we compared the DB-67 pharmacokinetics (PK) in mice after oral (PO) or intravenous (IV) administration of a cremophor/ethanol solution and a supersaturated solution containing a chemically-modified cyclodextrin (SBE-CD (Captisol®)) as a potential alternative. DB-67 (1mg/kg) was administered PO or IV as a bolus tail vein injection to mice. Blood was collected via cardiac puncture at 5 and 30 min and at 1, 3, and 6 hours after PO administration. Similarly, samples were collected at 5 and 15 min and at 1, 3, 6, and 8 hours after IV administration. Samples were centrifuged and plasma was extracted with 4 volumes of cold methanol. Extracts were vortexed, centrifuged, and supernatants were analyzed by HPLC. The assay employed a reversed-phase column and a mobile phase consisting of 0.15 M ammonium acetate/10 mM tetrabutylammonium dihydrogen phosphate (pH 6.5): acetonitrile (65:35, v/v) with fluorescence detection to monitor the carboxylate and lactone forms of DB-67. The HPLC method allowed the simultaneous determination of both DB-67 carboxylate and lactone. Validation demonstrated selectivity and specificity for the carboxylate and lactone, with linearity between 5–300 ng/mL for both analytes (accuracy ± 9 % of theory and coefficient of variation ≤5.7 %). Carboxylate to lactone conversion was <4% using this method. Pharmacokinetic parameters were estimated using compartmental modeling. As expected for this blood stable camptothecin, the lactone was the predominant species in blood during the 6 or 8 hour periods of sampling. Drug disposition was identical with either formulation after either PO or IV administration. The oral bioavailability estimated from the ratios of AUCs for the PO and IV doses was ∼33%. We have established an accurate and precise HPLC assay for the quantitation of DB-67 and have demonstrated its utility in pharmacokinetic studies. DB-67 disposition is similar in cremophor/ethanol and SBE-CD formulations. Thus, a supersaturated solution stabilized by a chemically-modified cyclodextrin may be a useful alternative formulation to avoid the adverse reactions to cremophor/ethanol observed in the clinic. Interestingly, the oral bioavailability of DB-67 in mice is similar to reported oral bioavailabilities for other commercially available analogs.
Immortalized keratinocytes derived from patients with epidermolytic ichthyosis reproduce the disease phenotype: a useful<i>in vitro</i>model for testing new treatments
Authors: J.C. Chamcheu, I. Pihl-Lundin, C.E. Mouyobo, T. Gester, M. Virtanen, A. Moustakas, H. Navsaria, A. Vahlquist, H. Törmä
Journal: British Journal of Dermatology (2010)

Epidermolytic ichthyosis (EI) is a skin fragility disorder caused by mutations in genes encoding suprabasal keratins 1 and 10. While the aetiology of EI is known, model systems are needed for pathophysiological studies and development of novel therapies.To generate immortalized keratinocyte lines from patients with EI for studies of EI cell pathology and the effects of chemical chaperones as putative therapies.We derived keratinocytes from three patients with EI and one healthy control and established immortalized keratinocytes using human papillomavirus 16-E6/E7. Growth and differentiation characteristics, ability to regenerate organotypic epidermis, keratin expression, formation of cytoskeletal aggregates, and responses to heat shock and chemical chaperones were assessed.The cell lines EH11 (K1_p.Val176_Lys197del), EH21 (K10_p.156Arg>Gly), EH31 (K10_p.Leu161_Asp162del) and NKc21 (wild-type) currently exceed 160 population doublings and differentiate when exposed to calcium. At resting state, keratin aggregates were detected in 9% of calcium-differentiated EH31 cells, but not in any other cell line. Heat stress further increased this proportion to 30% and also induced aggregates in 3% of EH11 cultures. Treatment with trimethylamine N-oxide and 4-phenylbutyrate (4-PBA) reduced the fraction of aggregate-containing cells and affected the mRNA expression of keratins 1 and 10 while 4-PBA also modified heat shock protein 70 (HSP70) expression. Furthermore, in situ proximity ligation assay suggested a colocalization between HSP70 and keratins 1 and 10. Reconstituted epidermis from EI cells cornified but EH21 and EH31 cells produced suprabasal cytolysis, closely resembling the in vivo phenotype.These immortalized cell lines represent a useful model for studying EI biology and novel therapies.
NEUROCIRCULATORY ASTHENIA: REPORT OF A CASE TREATED BY ADRENAL DENERVATION
Authors: John P. Anderson
Journal: Annals of Internal Medicine (1936)

Case Reports1 March 1936NEUROCIRCULATORY ASTHENIA: REPORT OF A CASE TREATED BY ADRENAL DENERVATIONJOHN P. ANDERSON, M.D., F.A.C.P.JOHN P. ANDERSON, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-9-9-1255 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe term, neurocirculatory asthenia, is used to represent a syndrome characterized by a sense of fatigue, palpitation, precordial pain, and a tendency to giddiness. The symptom complex it presents is almost as definite as that of angina. It has been called by various other names, for example, irritable heart, effort syndrome, and disordered action of the heart, but none is quite so descriptive as neurocirculatory asthenia.Persons afflicted with this condition are usually thin and asthenic in stature and appearance. They have quick, nervous temperaments and are intelligent. They have a marked degree of initiative but usually lack the physical... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Cleveland, Ohio*Received for publication January 2, 1935. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 March 1936Volume 9, Issue 9Page: 1255-1258KeywordsAnginaDenervationFatigueHeart ePublished: 1 December 2008 Issue Published: 1 March 1936 PDF downloadLoading ...
Abstract 16882: Over Expression of <i>Scn5a</i> in Mouse Heart Mimics Human Syndrome of Enhanced Atrioventricular Nodal Conduction
Authors: Gongxin Liu, Luiz Belardinelli, Sridharan Rajamani, Carol Ann Remme, Bastiaan J.D. Boukens
Journal: Circulation (2014)

Introduction: The mechanism of enhanced atrioventricular nodal conduction (EAVNC), including Lown-Ganong-Levine (LGL) syndrome, is not well described. Transgenic mice with the over-expression SCN5A results in a shorter P-R interval; hence, we tested the hypothesis that overexpression of SCN5A may provide an animal model mimicking EAVNC. Methods: Electrocardiogram (ECG), atrial, His-bundle and ventricular electrograms were recorded from wild type (WT) and transgenic mice over-expressing SCN5A (TG). Peak Na + current (I Na ) and Nav1.5 expression were measured using patch-clamp technique and immunohistochemistry method, respectively. Results: P-R interval in TG was much shorter than in WT mice (13.6±1.20 vs. 40.2±0.59 ms, n=20 and 35). In TG isolated hearts the A-V conduction during right atrial pacing remains shorter than that of WT isolated hearts (14.4±0.81 vs. 39.5±0.62 ms, n=28 each). His-bundle electrogram (HBE) revealed a short A-H and H-V intervals in TG, compared to WT mice (Figure 1A-D). In addition, TG mice had a short Wenckebach cycle length (CL) and atrioventricular effective refractory period (AVERP). Peak I Na was 2-fold greater in TG compared to WT ventricular myocytes (198.2±16.22 vs. 89.6±5.35 pA/pF, n=12). Flecainide (6 μM, n=6) led to prolongation of A-V conduction time in TG to a value close to that of WT hearts. Nifedipine (1 μM, n=) prolonged A-H interval in WT but not in TG hearts. Immunohistochemistry studies revealed increased Nav1.5 labeling in TG atrial and ventricular tissue, and Nav1.5 expression in A-V junction and A-V ring regions of TG compared to WT hearts. Conclusion: SCN5A over expression in TG mice enhanced the A-V conduction mimicking EAVNC. Thus, higher level of sodium channel expression in the A-V nodal region may be an electrophysiological substrate responsible for the syndrome of EAVNC. Figure 1
294. Herpes Simplex Virus Mediated Oncolysis Is an Effective Intratumoral Therapy in High-Risk Neuroblastoma Tumor Models
Authors: Nehal S. Parikh, Mark A. Currier, Lisa C. Adams, Margaret H. Collins, Timothy P. Cripe
Journal: Molecular Therapy (2004)

Background: High risk neuroblastoma is incurable using current treatment regimens in the majority of patients. Oncolytic virotherapy offers a novel approach to treating cancer. In vitro and in vivo studies in adult tumor models have shown efficacy with the use of cancer selective, attenuated, replication-competent Herpes Simplex Virus (HSV)-derived vectors. Such viruses are currently in clinical trials for several adult cancers.