tbuckley/cabot-search huggingface dataset:
Depolymerized chitosans functionalized with bPEI as carriers of nucleic acids and tuftsin-tethered conjugate for macrophage targeting
Authors: Sushil K. Tripathi, Ritu Goyal, Mahendra P. Kashyap, Aditya B. Pant, Wahajul Haq, Pradeep Kumar, Kailash C. Gupta
Journal: Biomaterials (2012)
Genome-wide association studies of atrial fibrillation: past, present, and future
Authors: M. F. Sinner, P. T. Ellinor, T. Meitinger, E. J. Benjamin, S. Kaab
Journal: Cardiovascular Research (2011)

Genome-wide association studies (GWAS) for atrial fibrillation (AF) have identified three distinct genetic loci on chromosomes 1q21, 4q25, and 16q22 that are associated with the arrhythmia. Susceptibility loci also have been identified by GWAS for PR interval duration, a quantitative phenotype related to AF. In this review article, we have sought to summarize the latest findings for population-based genetic studies of AF, to highlight ongoing functional studies, and to explore the future directions of genetic research on AF.
How will patients use acyclovir to treat herpes?
Authors: Mark L. Fuerst
Journal: JAMA (1982)

With the availability of the first topical agent to show any efficacy in herpes genitalis, desperate patients with recurrent herpes infections may practice self-medication—not surprisingly—once they have a prescription for the agent. But some herpes experts believe that widespread long-term use of the drug—which is only indicated for initial herpes infections and for genital and labial herpes in immunocompromised patients—may facilitate the emergence of resistant organisms and limit the agent's future usefulness in life-threatening situations.  Recent Food and Drug Administration approval and marketing of the antiviral agent acyclovir (Zovirax, Burroughs Wellcome Company, Research Triangle Park, NC) will raise the hopes of many US patients afflicted with recurrent venereal herpes, predicts Andre Nahmias, MD, chief of infectious diseases, allergy, and immunology at Emory University, Atlanta. Some people will apply it four to six times a day [treatment of initial infections is six applications per day for seven days], thinking they will
Smart polymers for the controlled delivery of drugs – a concise overview
Authors: Honey Priya James, Rijo John, Anju Alex, K.R. Anoop
Journal: Acta Pharmaceutica Sinica B (2014)

Smart polymers have enormous potential in various applications. In particular, smart polymeric drug delivery systems have been explored as "intelligent" delivery systems able to release, at the appropriate time and site of action, entrapped drugs in response to specific physiological triggers. These polymers exhibit a non-linear response to a small stimulus leading to a macroscopic alteration in their structure/properties. The responses vary widely from swelling/contraction to disintegration. Synthesis of new polymers and crosslinkers with greater biocompatibility and better biodegradability would increase and enhance current applications. The most fascinating features of the smart polymers arise from their versatility and tunable sensitivity. The most significant weakness of all these external stimuli-sensitive polymers is slow response time. The versatility of polymer sources and their combinatorial synthesis make it possible to tune polymer sensitivity to a given stimulus within a narrow range. Development of smart polymer systems may lead to more accurate and programmable drug delivery. In this review, we discuss various mechanisms by which polymer systems are assembled in situ to form implanted devices for sustained release of therapeutic macromolecules, and we highlight various applications in the field of advanced drug delivery.
Impaired Cardiac Energetics in Mice Lacking Muscle-Specific Isoenzymes of Creatine Kinase
Authors: Kurt W. Saupe, Matthias Spindler, Rong Tian, Joanne S. Ingwall
Journal: Circulation Research (1998)

Abstract— Our purpose was to determine whether hearts from mice bioengineered to lack either the M isoform of creatine kinase (MCK −/− mice) or both the M and mitochondrial isoforms (M/MtCK −/− mice) have deficits in cardiac contractile function and energetics, which have previously been reported in skeletal muscle from these mice. The phenotype of hearts with deleted creatine kinase (CK) genes is of clinical interest, since heart failure is associated with decreased total CK activity and changes in the relative amounts of the CK isoforms in the heart. We measured isovolumic contractile performance in isolated perfused hearts from wild-type, MCK −/− , and M/MtCK −/− mice simultaneously with cardiac energetics ( 31 P-nuclear magnetic resonance spectroscopy) at baseline, during increased cardiac work, and during recovery. Hearts from wild-type, MCK −/− , and M/MtCK −/− mice had comparable baseline function and responded to 10 minutes of increased heart rate and perfusate Ca 2+ with similar increases in rate-pressure product (48±5%, 42±6%, and 51±6%, respectively). Despite a similar contractile response, M/MtCK −/− hearts increased [ADP] by 95%, whereas wild-type and MCK −/− hearts maintained [ADP] at baseline levels. The free energy released from ATP hydrolysis decreased by 3.6 kJ/mol in M/MtCK −/− hearts during increased cardiac work but only slightly in wild-type (1.7 kJ/mol) and MCK −/− (1.5 kJ/mol) hearts. In contrast to what has been reported in skeletal muscle, M/MtCK −/− hearts were able to hydrolyze and resynthesize phosphocreatine. Taken together, our results demonstrate that when CK activity is lowered below a certain level, increases in cardiac work become more “energetically costly” in terms of high-energy phosphate use, accumulation of ADP, and decreases in free energy released from ATP hydrolysis, but not in terms of myocardial oxygen consumption.
Becoming Evil: How Ordinary People Commit Genocide and Mass Killing
Authors: Tony Miksanek
Journal: JAMA (2008)

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
Effects of sublingual nifedipine on hemodynamics and systolic and diastolic function in patients with hypertrophic cardiomyopathy.
Authors: S Betocchi, R O Cannon, R M Watson, R O Bonow, H G Ostrow, S E Epstein, D R Rosing
Journal: Circulation (1985)

The hemodynamic effects of sublingual nifedipine were examined in 36 patients with hypertrophic cardiomyopathy. Twenty-one patients were initially given 20 mg and 15 patients were given 10 mg of the drug; 30 min after this first dose 26 patients received 10 mg and one patient 20 mg as a second dose. Hemodynamic findings in patients who received different doses of the drug were similar. Peak effects included an increase in heart rate from 79 +/- 12 to 91 +/- 14 (mean +/- 1 SD) beats/min (p less than .01), and a decrease in mean blood pressure from 89 +/- 12 to 77 +/- 10 mm Hg (p less than .01). Cardiac index increased after nifedipine (2.8 +/- 0.6 to 3.3 +/- 0.8 liters/min/m2; p less than .01); stroke volume index, however, did not change (36 +/- 7 to 36 +/- 8 ml/beat/m2; NS). Peripheral vascular resistance index fell significantly from 822 +/- 261 to 610 +/- 197 dynes X sec X cm-5 (p less than .01). Overall, left ventricular outflow tract gradient (LVOTG) did not change in patients with significant (greater than or equal to 30 mm Hg) basal LVOTG (75 +/- 22 to 83 +/- 22 mm Hg; NS), but it increased significantly in those six patients in whom peripheral vascular resistance fell by 25% or more (73 +/- 28 to 99 +/- 22 mm Hg; p less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract 4921: Selective promoter methylation of the cell differentiation marker, intestinal alkaline phosphatase (iALP), in microsatellite unstable colon cancer
Authors: Joongho Shin, Azadeh Azarbayejani, Victoria Lai, Naseem Ahmed, Richard Hodin, Madhu Malo, Diego Arango, Thomas Weber, John M. Mariadason
Journal: Cancer Research (2010)

Abstract Tumorigenesis is characterized by excessive cell growth, resistance to apoptosis and aberrant cellular differentiation. In particular, MSI colorectal cancer is frequently characterized by poorly differentiated histology. Histone Deacetylase inhibitors (HDACi) are a novel class of cancer therapeutics that induce growth arrest, apoptosis and differentiation of a variety of tumour types, including colon cancer cells. Differentiation inducing agents have been used effectively to treat hematopoietic malignancies, prompting us to examine the effects of HDACi treatment on differentiation of colon cancer cells, and to compare the effects induced in MSS and MSI colon cancers. Remarkably, while HDACi treatment robustly and consistently induced differentiation induction as measured by alkaline phosphatise activity and iALP gene expression in multiple MSS colon cancer cell lines, approximately 70% of MSI colon cancer cell lines were highly resistant to HDACi-induced ALP induction. Examination of the coding sequence of the iALP gene failed to identify any significant repeat elements suggesting mutation is unlikely to be responsible for lack of iALP induction. Furthermore, transient transfection of an iALP promoter reporter construct demonstrated robust induction in response to butyrate treatment in both MSS and MSI lines, suggesting loss of a key regulatory factor in MSI cell lines is not likely to be responsible. Conversely, examination of iALP promoter methylation by bisulphite conversion and direct sequencing demonstrated multiple CpG sites, including a Sp1/Sp3 binding site, to be methylated in 4 of 5 MSI lines examined, while no methylation was observed in MSS lines. These findings were confirmed using the sequenom assay. ALP promoter methylation was independent of CIMP status. The importance of Sp1/Sp3 in butyrate-induced iALP induction was demonstrated by the ability of the Sp1/Sp3 inhibitor, mithramycin, to attenuate butyrate-induced ALP activity. Finally, consistent with methylation being a key determinant of iALP expression in MSI lines, azacytidine treatment was able to re-induce iALP expression, and butyrate-induction of ALP expression was markedly enhanced in isogenic HCT116 cells lacking the DNA methyltransferases Dnmt1 and Dnmt3b (DKO), compared to parental cells. These findings demonstrate selective promoter methylation of iALP in MSI colon cancer cell lines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4921.
Evaluation of methods for the quantification of experimental myocardial infarction.
Authors: A J Roberts, P R Cipriano, D R Alonso, J G Jacbostein, J R Combes, W A Gay
Journal: Circulation (1978)

Several invasive and noninvasive techniques used in determining the size of experimental myocardial infarction were evaluated after acute ligation of the left anterior descending (LAD) coronary artery in ten dogs. Systemic blood pressure, left ventricular end-diastolic pressure (LVEDP), and heart rate did not change significantly for up to 24 hours after coronary occlusion. Left ventricular wall motion abnormalities were detected by left ventriculography in the distribution of the LAD but these changes did not correlate well with the infarct weight determined at autopsy. On the other hand, the number of epicardial sites with ST-segment elevation of greater than or equal to 2 mm (mean 15.1 sites +/- 0.6 SEM) and the infarct area as measured by 99mTc-glucoheptonate (TcGH) myocardial imaging (15.7 sq cm +/- 0.6) did correlate strongly with the infarct weight (16.8 g +/- 0.7) determined by the nitroblue tetrazolium (NBT) technique (r = 0.91). TcGH myocardial scintigraphy and epicardial ST-segment mapping allowed early and accurate quantification of experimental myocardial infarcts ranging from less than 1 g to 28 g.
Intracellular and nuclear binding of [3H]dihydrotestosterone in cultured genital skin fibroblasts of patients with severe hypospadias.
Authors: H U Schweikert, M Schlüter, G Romalo
Journal: Journal of Clinical Investigation (1989)

Androgens stimulate the development and growth of the male external genitalia. Because hypospadias is the most common congenital defect of the male urethra and because in most cases the cause of this malformation is unknown, we examined the hypothesis that the etiology of the severe forms of this disorder, which is frequently associated with other genital anomalies, might be explained by receptor abnormalities. Intracellular and nuclear binding of androgens were determined in cultured genital skin fibroblasts from 10 males who underwent circumcision for phimosis (controls A), 2 patients with 5 alpha-reductase deficiency (controls B), and 11 patients with severe forms of hypospadias of unknown etiology. Genital skin fibroblast monolayers were incubated for 60 min at 37 degrees C with varying concentrations of [3H]-dihydrotestosterone ([3H]DHT), and specific binding in whole cells and nuclei was measured. Maximum binding (Bmax) in the whole cell assay averaged 0.88 +/- 0.15 fmol . microgram DNA-1 (mean +/- SD) in the control group (controls A, 0.89 +/- 0.16 fmol . microgram DNA-1; controls B, 0.85 fmol . microgram DNA-1) and 0.7 +/- 0.25 fmol . microgram DNA-1 in the patients with hypospadias. In the latter group, Bmax in six patients was below the minimum values determined in the controls. Maximum specific nuclear binding in the control groups averaged 43% (range, 30-55%) of the corresponding intracellular binding. In contrast, nuclear binding in strains from patients with hypospadias was lower (range, 0-12% of whole cell Bmax). In particular, no high affinity saturable nuclear [3H]DHT binding could be measured in 6 of the 11 patients. We interpret these data to suggest that defective intracellular and/or nuclear binding might be the cause of defective genital development in some patients with severe hypospadias.
The RhoA/Rho kinase pathway in the myocardium
Authors: S PETERS, M MICHEL
Journal: Cardiovascular Research (2007)

The small GTPase RhoA and its downstream target Rho kinase (Rho-associated coiled-coil protein kinase or ROCK) are involved in cell contraction and a variety of other cellular processes via modulation of actin cytoskeletal assembly.Several studies, including investigations in humans, have clearly shown an important pathophysiological role of this pathway in the cardiovascular system and in disease states such as hypertension, heart failure, stroke, and diabetes [1].The RhoA/ROCK pathway is best described in smooth muscle cells, where it mediates calcium sensitization and thereby enhances and sustains contraction.However, the role of the RhoA/ROCK pathway in the myocardium is less well understood.Most studies on RhoA/ROCK in the heart address its involvement in cardiac hypertrophy and remodelling, and chronic inhibition of the pathway may prevent these long-term effects.In the current issue of Cardiovascular Research Lin et al. [2] describe a possible role of the RhoA/ROCK pathway in the contractile function of diabetic rat heart.These authors report that the decreased contractile function of hearts of diabetic animals was associated with an increased expression and activity of RhoA and ROCK.Interestingly, acute inhibition of ROCK improved cardiac performance in vivo and in vitro.These findings show an involvement of the RhoA/ ROCK pathway in diabetic cardiomyopathy and that this system is also involved in myocardial contraction.
Mineral density of bone in the forearm in premenopausal women with fractured wrists.
Authors: M. Horowitz, J. M. Wishart, M. Bochner, A. G. Need, B. E. Chatterton, B. E. Nordin
Journal: BMJ (1988)

The baby's delivery and that of the placenta was spontaneous and complete without any help.The baby cried immediately, and his Apgar score was 10 at one and five minutes; he weighed 3000 g.During examination, however, his scrotum was found to be almost completely severed except for an anterior tag, and he was bleeding profusely.It was soon realised that the two pearly structures had been the baby's testicles, and the scrotum had been severed with the episiotomy.General surgeons were urgently called for, but nothing could be done except to stop the bleeding and stitch back the scrotum.Histological examination of the spherical structures confirmed that they were testicles.
Status epilepticus. The role of intravenous phenytoin
Authors: James C. Cloyd, Robert J. Gumnit, L. William McLain
Journal: JAMA (1980)

The treatment of status epilepticus can be improved by using recent developments in the pharmacokinetics and method of intravenous (IV) administration of phenytoin sodium. While diazepam, administered IV, remains the drug of choice for the short-term control of seizures associated with compromised respiratory exchange, phenytoin is effective in preventing recurrence of such seizures and in treating most other forms of status epilepticus. A loading dose of 18 mg/kg given by IV infusion in either 0.45% or 0.9% sodium chloride at a rate no greater than 50 mg/min results in therapeutic serum levels for up to 24 hours in most patients. Maintenance therapy with phenytoin should start at 4 to 7 mg/kg/day and be adjusted to both clinical response and serum levels. (<i>JAMA</i>244:1479-1481, 1980)
Intermittent high permeability hemofiltration in septic patients with acute renal failure
Authors: Stanislao Morgera, Jens Rocktäschel, Michael Haase, Christian Lehmann, Christian von Heymann, Sabine Ziemer, Friedrich Priem, Berthold Hocher, Hermann Göhl, Wolfgang J. Kox, Hans-W. Buder, Hans-H. Neumayer
Journal: Intensive Care Medicine (2003)
Molecular Imaging of Activated von Willebrand Factor to Detect High-Risk Atherosclerotic Phenotype
Authors: Owen J.T. McCarty, Robert B. Conley, Weihui Shentu, Garth W. Tormoen, Daogang Zha, Aris Xie, Yue Qi, Yan Zhao, Chad Carr, Todd Belcik, Douglas R. Keene, Philip G. de Groot, Jonathan R. Lindner
Journal: JACC. Cardiovascular imaging (2010)
Increase in Serum Amyloid A Evoked by Dietary Cholesterol Is Associated With Increased Atherosclerosis in Mice
Authors: Katherine E. Lewis, Elizabeth A. Kirk, Thomas O. McDonald, Shari Wang, Thomas N. Wight, Kevin D. O’Brien, Alan Chait
Journal: Circulation (2004)

Elevated serum amyloid A (SAA) levels are associated with increased cardiovascular risk. SAA levels can be increased by dietary fat and cholesterol. Moreover, SAA can cause lipoproteins to bind extracellular vascular proteoglycans, a process that is critical in atherogenesis. Therefore, we hypothesized that diet-induced increases in SAA would increase atherosclerosis independent of their effect on plasma cholesterol levels.Female LDL-receptor-null (LDLR-/-) mice were fed high-saturated fat diets (21%, wt/wt), with or without added cholesterol (0.15%, wt/wt), for 10 weeks. Compared with chow-fed controls, the high-fat diets increased plasma SAA levels. Addition of cholesterol further increased SAA levels 2-fold (P<0.05) without further increasing plasma cholesterol levels. Addition of dietary cholesterol also increased atherosclerosis (P<0.05). Four lines of evidence suggest that SAA actually might cause atherosclerosis: (1) SAA levels when mice were euthanized correlated with the extent of atherosclerosis (r=0.49; P<0.02); (2) SAA levels after 5 weeks of diet correlated with the extent of atherosclerosis at 10 weeks (r=0.66; P<0.01); (3) binding of HDL from these animals to proteoglycans in vitro was related to the HDL-SAA content (r=0.65; P<0.01); and (4) immunoreactive SAA was present in lesion areas enriched with both proteoglycans and apolipoprotein A-I, the major HDL apolipoprotein.Addition of cholesterol to a high-fat diet increased plasma SAA levels and atherosclerosis independent of an adverse effect on plasma lipoproteins, consistent with the hypothesis that SAA may promote atherosclerosis directly by mediating retention of SAA-enriched HDL to vascular proteoglycans.
Pan-histone deacetylase inhibitor panobinostat depletes CXCR4 levels and signaling and exerts synergistic antimyeloid activity in combination with CXCR4 antagonists
Authors: Aditya Mandawat, Warren Fiskus, Kathleen M. Buckley, Kelly Robbins, Rekha Rao, Ramesh Balusu, Jean-Marc Navenot, Zi-Xuan Wang, Celalettin Ustun, Daniel G. Chong, Peter Atadja, Nobutaka Fujii, Stephen C. Peiper, Kapil Bhalla
Journal: Blood (2010)
Long-Term Results of Rabbit Antithymocyte Globulin and Basiliximab Induction
Authors: Daniel C. Brennan, Mark A. Schnitzler
Journal: New England Journal of Medicine (2008)

To the Editor: In our recently reported prospective, randomized, international clinical trial comparing rabbit antithymocyte globulin and basiliximab in renal transplantation (ClinicalTrials.gov number, NCT00235300),1 we observed that induction treatment with rabbit antithymocyte globulin was as safe as and more effective than basiliximab at 1 year in preventing acute rejection in patients who had received kidney transplants from deceased donors and who were at increased risk for acute rejection or delayed graft function. Whether the apparent benefits of rabbit antithymocyte globulin over basiliximab persist is unknown. The duration of follow-up in a clinical study is limited by whether patients are willing . . .