tbuckley/cabot-search huggingface dataset:
Intercellular Trafficking of Adenovirus-Delivered HSV VP22 from the Retinal Pigment Epithelium to the Photoreceptors—Implications for Gene Therapy
Authors: Siobhan M. Cashman, Sonia L. Sadowski, David J. Morris, Jeanne Frederick, Rajendra Kumar-Singh
Journal: Molecular Therapy (2002)

Adenovirus (Ad)-mediated gene transfer is a promising technology for therapy of a wide variety of genetic disorders of the retina. The tropism of Ad vectors limits their utility to cells that express the coxsackie-adenovirus receptor. Upon ocular delivery, Ad vectors primarily infect the retinal pigment epithelium (RPE) and the Müller cells of the retina. However, the most frequent blinding diseases such as retinitis pigmentosa and age-related macular degeneration are associated with the expression of mutant proteins in the photoreceptors. In this study we demonstrate that adenovirus-delivered heterologous proteins fused to the herpes simplex virus tegument protein VP22 can translocate from infected cells to uninfected cells in culture and in vivo. We tested three different ocular cell lines, specifically Y79, RPE-J, and Chang C. We show that there is a 3.25-fold increase in the number of Y79 cells that take up GFP mediated by the intercellular trafficking properties of VP22. Our data are based on FACS analysis of living cells and there was no need for cell fixation for the effect to be observed. When adenovirus expressing a VP22-GFP fusion was injected into the subretinal space of adult mice, the VP22-GFP fusion peptides translocated from the RPE to all of the other layers of the retina, including the outer nuclear layer, which contains the photoreceptor cell bodies. Our study has significant implications for a wide variety of diseases of the retina and other organ systems.
Determining Origins and Causes of Childhood Obesity via Mendelian Randomization Analysis
Authors: Eric L Ding, Frank B Hu
Journal: PLoS Medicine (2008)

Childhood obesity has become a serious public health problem worldwide. The United States Centers for Disease Control and Prevention estimates that one in three children and adolescents are currently overweight/obese [1]. The adverse complications of childhood obesity on physical health and psychosocial development are tremendous [2]. Moreover, pediatric obesity may substantially increase future burden of cardiovascular disease and other morbidities in adulthood [3,4].
THE COST BENEFIT OF PRENATAL ULTRASOUND DETECTION OF CONGENITAL HEART DISEASE AND UTILITY OF INCREASED PRENATAL SONOGRAPHER TRAINING
Authors: Anusha Jegatheeswaran, Carol Oliveira, Constantine Batsos, Anita J. Moon-Grady, Norman H. Silverman, Lisa K. Hornberger, Peter Coyte, Mark K. Friedberg
Journal: Journal of the American College of Cardiology (2011)
Lifetime Risk and Years Lived Free of Total Cardiovascular Disease
Authors: John T. Wilkins, Hongyan Ning, Jarett Berry, Lihui Zhao, Alan R. Dyer, Donald M. Lloyd-Jones
Journal: JAMA (2012)

Estimates of lifetime risk for total cardiovascular disease (CVD) may provide projections of the future population burden of CVD and may assist in clinician-patient risk communication. To date, no lifetime risk estimates of total CVD have been reported.To calculate lifetime risk estimates of total CVD by index age (45, 55, 65, 75 years) and risk factor strata and to estimate years lived free of CVD across risk factor strata.Pooled survival analysis of as many as 905,115 person-years of data from 1964 through 2008 from 5 National Heart, Lung, and Blood Institute-funded community-based cohorts: Framingham Heart Study, Framingham Offspring Study, Atherosclerosis Risk in Communities Study, Chicago Heart Association Detection Project in Industry Study, and Cardiovascular Health Study. All participants were free of CVD at baseline with risk factor data (blood pressure [BP], total cholesterol [TC], diabetes, and smoking status) and total CVD outcome data.Any total CVD event (including fatal and nonfatal coronary heart disease, all forms of stroke, congestive heart failure, and other CVD deaths).At an index age of 45 years, overall lifetime risk for total CVD was 60.3% (95% CI, 59.3%-61.2%) for men and 55.6% (95% CI, 54.5%-56.7%) for women. Men had higher lifetime risk estimates than women across all index ages. At index ages 55 and 65 years, men and women with at least 1 elevated risk factor (BP, 140-149/90-99 mm Hg; or TC, 200-239 mg/dL; but no diabetes or smoking), 1 major risk factor, or at least 2 major risk factors (BP, ≥160/100 mm Hg or receiving treatment; TC, ≥240 mg/dL or receiving treatment; diabetes mellitus; or current smoking) had lifetime risk estimates to age 95 years that exceeded 50%. Despite an optimal risk factor profile (BP, <120/80 mm Hg; TC, <180 mg/dL; and no smoking or diabetes), men and women at the index age of 55 years had lifetime risks (through 85 years of age) for total CVD of greater than 40% and 30%, respectively. Compared with participants with at least 2 major risk factors, those with an optimal risk factor profile lived up to 14 years longer free of total CVD.Lifetime risk estimates for total CVD were high (>30%) for all individuals, even those with optimal risk factors in middle age. However, maintenance of optimal risk factor levels in middle age was associated with substantially longer morbidity-free survival.
Kappa light chains in spinal fluid for diagnosing multiple sclerosis
Authors: S. J. Khoury
Journal: JAMA (1994)

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
The Emergency Department as a Pathway to Admission for Poor and High-Cost Patients
Authors: Robert S. Stern
Journal: JAMA (1991)

<h3>Background.</h3> —To determine the importance of the emergency department as the means of access to the hospital for the poor and the fiscal implications of providing these services, we examined the relationship between patients' socioeconomic status and admission via the emergency department. We also determined the association between entering the hospital via the emergency department and hospital resource use. <h3>Methods.</h3> —We conducted a study of 20 089 patients admitted to five Massachusetts hospitals (three community, two tertiary care) during a 6-month period. We determined the proportions of patients within various socioeconomic and disease groupings who entered through the emergency department. We compared length of stay and charges for patients admitted through the emergency department with those for patients admitted through other routes. <h3>Results.</h3> —Overall, 51% of patients entered via the emergency department. Elderly patients (age &gt;65 years; odds ratio, 1.87) and patients with lower socioeconomic status as measured by income, occupation, and education (odds ratios, 2.38, 1.47, and 1.69, respectively) were more likely to enter the hospital via the emergency department than other patients. After adjustment for diagnosis related group, severity as measured by DRGSCALE, and socioeconomic status as measured by income, and excluding outliers, patients admitted via the emergency department stayed 27% longer and incurred 13% higher charges than other patients (<i>P</i>&lt;.001). <h3>Conclusions.</h3> —Our data indicate that patients with lower socioeconomic status are more likely than other patients to use the emergency department as their means of access to the hospital and that patients admitted via the emergency department use far more resources than patients in the same diagnosis related group admitted by other means. Hospitals that make emergency department services more available may be more likely to hospitalize socioeconomically disadvantaged patients and may be at a substantial financial disadvantage under per-case reimbursement systems such as Medicare. (<i>JAMA</i>. 1991;266:2238-2243)
Toxoplasmosis Testing During Pregnancy
Authors: J. K. Frenkel
Journal: JAMA (1991)

<h3>To the Editor.—</h3> Drs Jack and Culpepper<sup>1</sup>propose preconception tests for toxoplasmosis and counseling of those nonimmune to prevent infection during pregnancy. However, studies in Massachusetts and calculations of regional and national toxoplasma exposure in the United States indicated that 85% of women in the pregnancy age range have no antibody and can be considered nonimmune and at risk to transmit the infection.<sup>2</sup>It is hardly worthwhile to attempt to exclude the 15% of immune women from educational efforts or counseling by means of costly serological tests. All pregnant women should be asked to wash hands before eating and after coming into contact with cats, soil, and meat. In addition, they should be instructed to cook meat adequately.<sup>3</sup>Serological tests in a clinical setting, where case rates are between one in 10 and one in 100, are very useful and yield reasonably predictive values. However, even with
Stirrups or no stirrups for routine speculum examinations?: Patient's perspective
Authors: Rosemary Slosek
Journal: BMJ (2006)

Editor-The report from the chief medical officer for England has implications for all UK doctors and needs to be considered very carefully. 1Its aim is a system of medical regulation that puts patients' safety first through the early detection, and where possible, remediation, of poor performance.If the report contributes to that aim, and commands public and professional support, it should be welcomed by everyone involved in health care.The Merrison report was the collective effort of Sir William Merrison and the other 14 members of his committee of inquiry, who took both oral and written evidence. 2A different process has been followed in this case.The government, sensibly, has therefore decided on a period of consultation during which the recommendations can be properly debated, tested, and costed.We have already said that we believe that the recommendations to divorce oversight of medical education from the other regulatory functions of standards, registration, and fitness to practise are not in patients' best interests.We will now be consulting widely with our partners before we submit our considered response.It may be another 30 years before there is another opportunity such as this.We must seize it so that future generations of patients can say that we did not fail them.
The Use of the Forceps in the First Stage of Labour
Authors: J. G. Swayne
Journal: BMJ (1877)

THE first stage of labour must be perfectly finished before we think of applying the forceps."This is Denman s fourth aphorism, and is a rule of practice which has held almost undisputed sway for nearly a hundred years.In the present day, however, the motto of the ac- coucheur may be said to be " Nullius addictus jurare in verba magistri".No truth is considered to be so firmly established that it is taken for granted and allowed to pass without question.The modern accoucheur does not feel bound to swear by a particular rule of practice because it was that of his " old master" at London, Edinburgh, or Dublin, as the case may be, but reserves his judgment until he has had frequent opportunities of testing it for himself by his own experience.This is the case very much with the use of the forceps.In no branch of obstetrics have we departed so much from the precepts and practice of our fore- fathers as in this.The forceps is now used with much greater free- dom than it was formerly, and, as experience has abundantly proved, with the best effects.
Liver disease in ulcerative colitis: an epidemiological and follow up study in the county of Stockholm.
Authors: U Broome, H Glaumann, G Hellers, B Nilsson, J Sorstad, R Hultcrantz
Journal: Gut (1994)

In an epidemiological study of the incidence of ulcerative colitis (UC) in the county of Stockholm between 1955 and 1979, 1274 patients with UC were discovered. Almost all these patients had regularly been investigated with liver function tests; 142 (11%) of them showed signs of hepatobiliary disease. A follow up study on all 142 patients with abnormal liver function and UC was made between 1989 and 1991 to evaluate the cause of the liver abnormality and to find out if the liver disease had affected the survival rates. At follow up, eight patients were reclassified as having Crohn9s disease, 60 had developed normal liver function as judged from test results, while the remaining 74 still had signs of hepatobiliary disease. The most common explanation for a transient abnormality in liver function was active colitis. The temporary signs of liver injury were not associated with changes in survival rates for these patients. Infections, especially those because of hepatitis B and C virus transmitted by blood transfusions accounted for the abnormalities in liver function in 21 patients, nine of which had a chronic, but non-fatal course. Twenty nine (2.3%) of the patients developed primary sclerosing cholangitis (PSC), and 12 of them died during the study period four because of cholangiocarcinoma and eight because of hepatic failure; one patient had a transplant. The estimated median time of survival from the first presentation of evidence of a liver function, compatible with the diagnosis of PSC, to death or liver transplantation was 21 years. A comparison of survival rates in patients with UC and patients with UC and concurrent PSC showed, a significant reduction in survival in the PSC group (p&lt;0.0001). The number of patients with UC who developed PSC remained constant during the study period. Thus, although evidence of abnormal liver function is a common finding in UC, a spontaneous return to normal levels is common. In this study, which did not have a selection bias, the median time of survival among PSC patients was far longer than previously described although development of PSC among patients with UC does significantly reduce the estimated median time of survival.
The Effect of Hyperventilation on the Normal Adult Electrocardiogram
Authors: R. H. WASSERBURGER, K. L. SIEBECKER, W. C. LEWIS, C. Janet Lloyd
Journal: Circulation (1956)

The effect of brief hyperventilation on the precordial T waves of 350 normal adults is described. Evidence is presented that brief hyperventilation initiates a vagal reflex which results in the T-wave inversion. Supportive data are also given to exclude respiratory alkalosis as a possible mechanism. Caution is advised in interpreting isolated T-wave inversions as indicative of organic heart disease. It is proposed that isolated T-wave inversion be deleted as a criterion for a "positive" exercise test.
Noninvasive evaluation of pulmonary hypertension by a pulsed Doppler technique.
Authors: A Kitabatake, M Inoue, M Asao, T Masuyama, J Tanouchi, T Morita, M Mishima, M Uematsu, T Shimazu, M Hori, H Abe
Journal: Circulation (1983)

We used a pulsed Doppler technique to examine the flow velocity pattern in the right ventricular outflow tract in 33 adults. In the patients with normal pulmonary artery pressure (mean pressure less than 20 mm Hg, 16 patients), ejection flow reached a peak level at midsystole (137 +/- 24 msec, mean +/- SD), producing a domelike contour of the flow velocity pattern during systole. In contrast, the flow velocity pattern in patients with pulmonary hypertension (mean pressure greater than or equal to 20 mm Hg, 17 patients) was demonstrated to accelerate rapidly and to reach a peak level sooner (97 +/- 20 msec, p less than .01); in 10 of the pulmonary hypertensive patients a secondary slower rise in flow velocity was observed during a deceleration, resulting in the midsystolic notching. The time to peak flow (acceleration time, AcT) and right ventricular ejection time (RVET) were measured from the flow velocity pattern. Either AcT or AcT/RVET decreased with increase in mean pulmonary artery pressure, and a very high correlation (r = -.90) was found between AcT/RVET and log10 (mean pulmonary artery pressure). The use of this technique permitted the noninvasive estimation of the pulmonary artery pressure.
Abstract 626: Therapeutic effect of HGF inhibitors against HGF-induced EGFR-TKI resistance in lung cancer harboring <i>EGFR</i> mutations
Authors: Seiji Yano, Wei Wang, Qi Li, Ivan S. Donev, Shinji Takeuchi, Tadaaki Yamada, Kunio Matsumoto, Yasuhiko Nishioka, Saburo Sone
Journal: Cancer Research (2010)

Abstract Introduction: Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR)-activating mutations (EGFRmu) responds favorably to the EGFR tyrosine kinase inhibitors (EGFR-TKIs), gefitinib or erlotinib. However, the responders invariably acquire resistance to EGFR-TKIs. Two mechanisms, second-site point mutation that substitutes methionine for threonine at position 790 (T790M) in EGFR and amplification of MET proto-oncogene, which contribute to acquired resistance to EGFR-TKIs have been reported. As the third mechanism, we recently demonstrated that hepatocyte growth factor (HGF), specific ligand for MET, induced resistance to EGFR-TKIs. The purpose of this study was to examine whether inhibitor of HGF could overcome resistance to EGFR-TKIs induced by HGF in NSCLC cells with EGFRmu. Results: HGF induced the resistance to gefitinib and erlotinib in lung cancer cells (PC-9 and HCC827) with EGFRmu, by restoring Akt phosphorylation through MET but not EGFR or ErbB3. These NSCLC cells also became resistant to EGFR-TKIs when co-cultured in vitro with HGF-producing fibroblasts and co-injected into SCID mice. Importantly, combined use of gefitinib plus anti-HGF antibody or the HGF antagonist, NK4 successfully overcame the fibroblast-induced EGFR-TKI resistance both in vitro and in vivo. Conclusions: These findings indicate that HGF inhibitor, such as anti-HGF antibody and NK4, may be useful for controlling HGF-induced EGFR-TKI resistance in NSCLC harboring EGFRmu in humans. 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 626.
Thromboxane A2 and prostaglandin endoperoxide receptors in platelets and vascular smooth muscle.
Authors: D L Saussy, D E Mais, D R Knapp, P V Halushka
Journal: Circulation (1985)

9,11-Dimethylmethano-11,12-methano-16-(3-iodo-4-hydroxyphenyl)-13, 14-dihydro-13-aza-15 alpha beta-omega-tetranor-TXA2 (I-PTA-OH), a recently synthesized thromboxane (TX) A2/prostaglandin (PG) H2 receptor antagonist, was shown to be a competitive antagonist of human platelet aggregation induced by the stable endoperoxide analog U46619. This antagonism was due to competitive blockade of the platelet TXA2/PGH2 receptor since I-PTA-OH did not antagonize the first phase of ADP-induced aggregation which is TXA2/PGH2 independent, nor did it inhibit TXA2 synthesis. In addition, analysis of dose-response curves to U46619 (0.1 to 40 microM) in the presence of increasing concentrations of I-PTA-OH (0.5 to 10 microM) showed that I-PTA-OH produced a parallel rightward shift of the dose-response curve. Further analysis of the data in the form of a Schild plot yielded a straight line with a slope (m = 1.03) not significantly different from -1. These results are consistent with the notion that I-PTA-OH acts as a competitive antagonist of the TXA2/PGH2 receptor.
Cisplatin Combined With Carboplatin: A New Way of Intensification of Platinum Dose in the Treatment of Advanced Ovarian Cancer
Authors: M. J. Piccart, J. M. Nogaret, L. Marcelis, H. Longree, F. Ries, J. P. Kains, P. Gobert, A. M. Domange, J. P. Sculier, C. Gompel
Journal: JNCI Journal of the National Cancer Institute (1990)

We performed a phase I-II trial of escalating doses of cisplatin (CDDP: 50-100 mg/m2 per course) plus carboplatin (CBDCA: 300-400 mg/m2 per course) as a potential way in which to maximize platinum doses without causing excessive toxic effects in patients with advanced ovarian cancer. Thirty-three patients with nonoptimally debulked disease of FIGO (International Federation of Gynecology and Obstetrics) stages IIc-IV [median age: 60 yr; median WHO (World Health Organization) performance status: 2; no prior chemotherapy] received a median of six courses of therapy. CBDCA was infused on day 1 and CDDP on day 2 with an aggressive 48-hour hydration regimen. Myelosuppression was dose-limiting: at the highest dose levels, WHO grade 4 neutropenia and thrombocytopenia led to dose reduction and/or treatment delay in 45% of the patients. Nonhematologic toxic effects included acute nausea and vomiting (97% of the patients), mild alopecia (45%), ototoxic effects (39%), neurotoxic effects (21%), and renal toxic effects (serum creatinine greater than 1.5 mg/dL: 12.5%). The pathologic complete response rate was 22%. We conclude that CBDCA and CDDP can be given safely in combination at reasonably high doses (CBDCA at 300 mg/m2 per course and CDDP at 100 mg/m2 per course) over a 6-month period, provided a close hematologic follow-up is conducted. Randomized clinical trials are needed to define whether this regimen is any better than standard combination chemotherapy.
Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumor cells in mice.
Authors: Y Zhang, Y Deng, T Luther, M Müller, R Ziegler, R Waldherr, D M Stern, P P Nawroth
Journal: Journal of Clinical Investigation (1994)

Meth-A sarcoma cells were stable transfected to overexpress (sense construct) or underexpress (antisense construct) tissue factor. In vitro, there was no difference in plating efficiency or growth between these cell lines. In vivo, tumor cells transfected to overexpress tissue factor grew more rapidly, and established larger and more vascularized tumors than control transfectants. Antisense transfectants grew the slowest and were the least vascularized. Anticoagulation of mice with warfarin did not alter the difference between these tumor lines. Tumor cells over-expressing tissue factor released more (compared with control transfectants) mitogenic activity for endothelial cells in parallel with enhanced transcription of vascular permeability factor/vascular endothelial cell growth factor (VEGF/VPF), and diminished transcription of thrombospondin (TSP2), a molecule with anti-angiogenic properties. Antisense tissue factor transfectants, while releasing the lowest amount of mitogenic activity, had increased thrombospondin and decreased VEGF/VPF transcription compared with control transfectants or wild-type cells. Experiments with these sense, antisense, truncated sense, or vector tumor lines gave comparable results in complete medium, serum free medium or in the presence of hirudin, indicating that the activation of the coagulation mechanism was not likely to be responsible for changes in tumor cell properties. These results suggest that tissue factor regulates angiogenic properties of tumor cells by altering the production of growth regulatory molecules of endothelium by a mechanism distinct from tissue factor activation of the coagulation mechanism.