tbuckley/cabot-search huggingface dataset:
513. Prevention of Irradiation-Induced Organizing Alveolitis by Inhalation Delivery of Manganese Superoxide Dismutase-Plasmid/ Liposome (MnSOD-PL) Complexes to Mouse Lung
Authors: Matthew Carpenter, Anurag Agarwal, Suhua Nie, Lauren Hricisak, Michael W. Epperly, Joel S. Greenberger
Journal: Molecular Therapy (2004)

Intratracheal injection of MnSOD-PL has been shown to protect the murine lung from irradiation-induced damage. To translate this modality to fractionated radiotherapy in the clinic, an inhalation model for the delivery of MnSOD-PL was developed. To demonstrate that MnSOD-PL can be delivered to the lungs, an ultrasonic nebulizer was used to deliver either 1 mg of alkaline phosphatase-PL (Alk-PL) complex or hemagglutinin epitope-tagged MnSOD (HA-MnSOD) to C57BL/6J mice. Other mice were intratracheally-injected with Alk-PL or HA-MnSOD-PL (500 μg plasmid DNA). All mice were sacrificed 24 hours after MnSOD-PL administration with the lungs assayed for increased MnSOD biochemical activity or DNA expression. An increase was observed in MnSOD biochemical activity from levels of 2.23 ± 0.15 U/mg protein in control mice to 5.0 ± 0.21 U/mg protein in mice that inhaled MnSOD-PL (p= 0.024). Real time PCR (RT-PCR) using primers specific for the human MnSOD gene detected a significant increase in MnSOD mRNA expression in mice that inhaled MnSOD-PL compared to control, C57BL/6J mice. In a second experiment, subgroups of mice inhaled 0, 250, 500, 1000, or 2000 μg of HA-MnSOD plasmid DNA over 5 minutes. MnSOD biochemical activity was significantly increased with maximal activity of 5.0 ± 0.4 U/mg protein at 500 μg plasmid DNA compared to 2.3 ± 0.1 in control, non-treated lungs (p= 0.0241). To demonstrate that inhalation of MnSOD-PL protected against irradiation-induced lung damage, C57BL/6J mice inhaled 1.0 mg of MnSOD-PL over 10 minutes or were intratracheally-injected with 0.5 mg of MnSOD-PL. Twenty-four hours later, control mice as well as MnSOD-PL-treated mice were irradiated to 20 Gy and followed for development of organizing alveolitis. Mice inhaling MnSOD or injected intratracheally with MnSOD-PL had significantly increased survival (p<0.05) compared to control, irradiated mice. These results demonstrate that inhalation of MnSOD-PL is an effective alternate and practical method for preliminary radioprotective gene therapy.
Antitumor efficacy of LBY135, an anti-DR5 monoclonal antibody, alone or in combination with chemotherapy in human colon tumor cell lines and xenografts
Authors: Jing Li, Betty Tang, Jean Cheng, Joseph Eckman, Christine Miller, Jing Yuan, Youzhen Wang, Deborah Knee, Quinn Deveraux, Marc Nasoff, David Stover
Journal: Cancer Research (2007)

4874   TRAIL, and its functional receptors DR4 and DR5, are of particular interest in the development of cancer therapeutics as they preferentially mediate tumor cell apoptosis. A chimeric monoclonal antibody, LBY135 has been developed that specifically binds to DR5 and mimics TRAIL to induce cell death in tumor cells. LBY135 killed 50% of a panel of 40 human colon cancer cell lines with an IC50 of 10 nM or less. The tumor cell cytotoxicity was further enhanced by addition of 5-Flurouracil (5-FU), while 5-FU toxicity against normal cells was not increased by LBY135. The antitumor efficacy in vivo was evaluated in human colorectal tumor xenograft models in mice, as a single agent and in combination with 5-Fu. As a single agent, LBY135 was able to induce >70% regression of established Colo205 tumor xenografts. Neither LBY135 or 5-FU at its maximally tolerated dose induced regression of HCT116 xenografts; however, combinations of LBY135 and 5-FU induced regressions in this model as well. The data support the use of LBY135 in clinical trials of human colon cancer as either single agent or in combination with the 5-FU pro-drug, capecitabine.
Implications of childhood obesity for adult health
Authors: E L. Gibson
Journal: BMJ (2002)

Editor—We are concerned that Abbasi's website of the week review on the article by Wright et al may have left both health professionals and the public with the erroneous impression that obesity in (peripubescent) childhood does not predict obesity in later life and is not a cause for concern.1,2

The data of Wright et al show that body mass index in childhood and at age 50 is strongly associated—for example, among children in the top quarter of weight at 9 years, 73% (59/81) become overweight or obese adults at age 50, whereas of those who are in the top quarter at 13, 82% (64/78) are overweight or obese at age 50. This is a highly significant association, and it is not true that thin children are just as likely to be fat adults. It is also important to remember that the childhood of this sample fell into a postwar environment where undernutrition and other stressors led to impaired growth, and adult obesity was not a public health issue. The environment has changed radically, to the extent that the prevalence of adult obesity in England has trebled in the past two decades, and so any associations in Wright et al's sample are all the more surprising.3

The prevalence of obesity in children is increasing, and it carries its own health risks irrespective of later adult morbidity.4,5 Would health professionals in 40 years' time thank us for ignoring the public health implications of childhood obesity now? We think not.
Abstract 19342: Bilateral Phlegmasia Cerulea Dolens: More Than Meets the IVC
Authors: Thomas Metkus, Steven Yevich, Zahra Maleki
Journal: Circulation (2014)

A 40 year-old woman presented with edema, discoloration and severe pain of the lower extremities. Four weeks prior, she noted chest pain with pain and swelling of the right arm and both legs. Imaging demonstrated sub-segmental pulmonary embolism (PE) with bilateral deep venous thrombi (DVT) of the legs and thrombus of the right brachial vein. She was treated with warfarin however despite anticoagulation, had progressive dyspnea. Repeat imaging demonstrated new PE and progression of bilateral DVT. Anticoagulation was transitioned to argatroban, and an IVC [[Unable to Display Character: &amp;#64257;]]lter was placed. Subsequently, she had worsened edema and discoloration of the lower extremities, weakness, and severe pain. On physical examination, the lower extremities were cold and deeply violaceous with 2/5 strength at the bilateral hips and 0/5 strength below. Pulses were absent. Ultrasound examination demonstrated complete thrombosis of the lower extremity venous system to the level of the IVC. The clinical triad of limb swelling, ischemic pain, and blue color change suggested bilateral phlegmasia cerulea dolens (PCD). She was referred emergently for catheter based thrombolysis, however despite restoration of venous patency, she had progressive lower limb ischemia. She underwent bilateral above-the-knee amputation on hospital day 4. Given her profound thrombotic state, she underwent evaluation for inherited and acquired thrombophilia. To evaluate for malignancy, whole-body PET/CT was performed demonstrating FDG avidity of the gallbladder, multiple liver lesions, and adenopathy at the porta hepatis concerning for metastatic gallbladder carcinoma. Fine-needle biopsy of a liver lesion demonstrated poorly differentiated adenocarcinoma. Given poor prognosis, the patient elected not to pursue further therapy and passed away at home. This patient presented with bilateral PCD as a [[Unable to Display Character: &amp;#64257;]]rst manifestation of metastatic gallbladder carcinoma. PCD is a rare cause of limb ischemia characterized by the clinical triad of limb swelling, ischemic pain, and blue color change. Early attention to restoring venous patency is critical to avoid life and limb loss, and thrombophilia evaluation including evaluation for malignancy should be included in the diagnostic evaluation.
Hopes for HIV Eradication Dim as Stopping HAART Allows Resurgence
Authors: J Stephenson
Journal: JAMA (1999)

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
Abstract 1817: Enalapril Does Not Improve Growth or Ventricular Function in Infants With Single Ventricle: A Multicenter Clinical Trial
Authors: Daphne T Hsu, Victor Zak, Lynn Mahony, Lynn A Sleeper, Andrew M Atz, Jami C Levine, Piers C Barker, Chitra Ravishankar, Brian W McCrindle, Richard V Williams, Karen Altmann, Nancy S Ghanayem, Renee Margossian, Wendy K Chung, William L Border, Gail D Pearson, Mario P Stylianou, Seema Mital
Journal: Circulation (2009)

Systemic ventricular dysfunction and growth failure are common in infants with single ventricle physiology (ISV). We hypothesized that angiotensin converting enzyme inhibitor therapy would improve ...
921. Steps toward Cardiomyopathy Gene Therapy: In Vivo Expression of Human VLCAD
Authors: J. Lawrence Merritt, Jerry Vockley, Dietrich Matern, Miao He, David B. Schowalter
Journal: Molecular Therapy (2005)

Cardiomyopathy (CM) is an important cause of morbidity and mortality in children. Deficiency of very-long-chain acyl-CoA dehydrogenase (VLCAD), one of four nuclear encoded mitochondrial enzymes that catalyze the initial step in the beta-oxidation of straight-chain fatty acids, often presents with CM and/or sudden death. How VLCAD deficiency causes CM is unclear, but appears to be related to the accumulation of toxic long-chain acyl-carnitine species rather than a block in energy metabolism. While dietary therapy for VLCAD deficiency has been beneficial to some, many people do not respond, and intercurrent illness with diminished oral intake, exercise, or fasting all increase demand for fatty acid metabolism and can trigger catastrophic events even in those on diet therapy. While VLCAD deficiency is a rare metabolic deficiency, the development of a safe and durable gene therapy for VLCAD deficiency would be the first curative gene therapy for CM.
Hair-Shaft Abnormality in a 7-Year-Old Girl—Quiz Case
Authors: Lena Lünnemann, Annika Vogt, Ulrike Blume-Peytavi, Natalie Garcia Bartels
Journal: JAMA Dermatology (2013)

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Renal effects of adenosine 3′,5′-cyclic monophosphate and dibutyryl adenosine 3′,5′-cyclic monophosphate
Authors: John R. Gill, Alfred G. T. Casper
Journal: Journal of Clinical Investigation (1971)

Stable water diuresis was produced in anesthetized, hydrocortisone-treated hypophysectomized dogs by infusion of 2.5% dextrose. Infusion of adenosine 3',5'-cyclic monophosphate (cyclic AMP) in the left renal artery decreased ipsilaterally glomerular filtration rate (GFR), cortical and non-cortical renal plasma flow, and tended to increase urine flow (V) and free-water clearance (C(H2O)) despite a decrease in mean arterial pressure. Infusion of dibutyryl adenosine 3',5'-cyclic monophosphate (dibutyryl cyclic AMP) in the left renal artery increased V and C(H2O) significantly (P<0.01) bilaterally with essentially no change in GFR, in total renal plasma flow or its cortical and non-cortical components. For each kidney the magnitude of the change in V was similar to the magnitude of the change in C(H2O) and the change in sodium excretion was trivial. Cyclic AMP probably produced its effects on renal hemodynamics and mean arterial pressure wholly or in part through the action of metabolites such as 5'-AMP and adenosine on the renal and systemic vasculature. The absence of an effect of dibutyryl cyclic AMP on renal hemodynamics and its bilateral effect may be explained by the resistance of this nucleotide derivative to metabolism. Dibutyryl cyclic AMP appears to decrease by direct cellular effect(s) proximal tubular sodium reabsorption but does not prevent virtually complete reabsorption of the increased load of sodium in the distal nephron. This effect on the kidney is qualitatively and quantitatively similar to the effect of renal arterial infusion of isoproterenol. The results suggest that synthesis of cyclic AMP in proximal renal tubule cells in response to stimulation of beta adrenergic or other receptors can mediate a decrease in the proximal tubular reabsorption of sodium.
Using biomedical informatics to see the forest AND the trees for molecular diagnostics in cancer therapeutic development
Authors: Kenneth H. Buetow
Journal: Clinical Cancer Research (2010)

Abstract Cancer research in general—and molecular diagnostic development in particular—are leveraging the diverse collection of publicly-accessible molecular information that underpins disease. The ability to access and integrate this information will be crucial to the development of molecular diagnostics. Use of this data requires overcoming the silos and data disconnects common throughout biomedicine and new models for interpreting this massive amount of information. The National Cancer Institute has developed the caBIG® initiative (Cancer Biomedical Informatics Grid) to integrate the diverse multidimensional data. An active area of research is developing biologic process models for integrating and interpreting this massive volume of data. The Cancer Genome Atlas (TCGA) is an example of the challenges faced in transforming data to information. Large volumes of diverse, multidimensional data including various genomic characterizations and clinical information must be synthesized. Through the caBIG® generated Cancer Molecular Analysis portal (http://cma.nci.nih.gov), it is possible to see integrated views of the TCGA data from different research perspectives including genomic and clinical views. Tools leveraging this data can be used to display and analyze the data in biologic networks. As more TCGA data and additional molecular data are shared through the portal it will become increasingly possible to obtain a comprehensive view of the molecular basis of cancer and drive development of molecular diagnostics.
THE AMBULATORY TREATMENT OF PATIENTS HOSPITALIZED WITH PULMONARY TUBERCULOSIS
Authors: James A. Wier, Robert L. Taylor, Richard S. Fraser
Journal: Annals of Internal Medicine (1957)

ExcerptFor the last several years there has been a widespread tendency to liberalize bed-rest requirements in the treatment of patients with pulmonary tuberculosis, increasing ambulation of patients being allowed; indeed, in some treatment centers, nearly complete ambulatory treatment has become the accepted practice. However, there has been no properly controlled study which would compare the results of treatment in patients permitted early ambulation with those in patients on standard bed-rest programs. It is the purpose of this paper to report the results of a study evaluating the need for bed-rest in the treatment of tuberculosis.Actually, the use of ambulation,...
Dendritic cells directly trigger NK cell functions: Cross-talk relevant in innate anti-tumor immune responses in vivo
Authors: Nadine C. Fernandez, Anne Lozier, Caroline Flament, Paola Ricciardi-Castagnoli, Dominique Bellet, Mark Suter, Michel Perricaudet, Thomas Tursz, Eugene Maraskovsky, Laurence Zitvogel
Journal: Nature Medicine (1999)
Abstract 11888: MyD88 Expressed by Myeloid Cells is Essential for Angiotensin II-Induced Vascular Dysfunction, Inflammation and Arterial Hypertension
Authors: Sabine Kossmann, Tanja Schönfelder, Stefanie Finger, Melanie Brähler, Daniel Minwegen, Maike Knorr, Andreas Daiber, Markus Radsak, Thomas Münzel, Philip Wenzel
Journal: Circulation (2014)

Background: Angiotensin II (ATII) causes hypertension and promotes infiltration of inflammatory cells into the vessel wall. Vascular superoxide formation and shear stress mediated inflammatory remodeling of conduit arteries was shown to be myeloid differentiation factor 88 (MyD88) dependent, but the exact mechanism are unknown. Objective: The goal of this study was to determine the mechanism, how MyD88 contributes to the development of ATII-induced vascular dysfunction and arterial hypertension. Methods and Results: MyD88 deficiency profoundly attenuated ATII-induced (1 mg/kg/d for 7 days) blood pressure increase (measured by radio telemetry) and vascular dysfunction (assessed by aortic ring relaxation studies). Additionally vascular superoxide levels as well as mRNA expression levels of VCAM-1, iNOS, Nox2 were decreased in ATII-infused MyD88 -/- mice compared to WT controls. Aortic flow cytometric analysis revealed that ATII-induced infiltration with CD11b + Ly6C high inflammatory monocytes was significantly dampened in MyD88 -/- mice. ATII led to an increased expression of inflammatory monocyte markers in blood and aorta, which was blocked in MyD88 -/- mice, indicating a role of MyD88 for myeloid cell differentiation. Additionally less IFN-gamma + NK cells were detected in the vessel wall of ATII-treated MyD88 -/- mice and aortic lysates showed reduced mRNA levels of several proinflammatory cytokines like IL-12 and IL-1beta. Bone marrow transfer experiments further revealed a protective effect of MyD88 deficiency in inflammatory cells represented by a reduction of vascular dysfunction and inflammation. Conclusion: We provide first evidence that MyD88 expressed by bone marrow-derived cells plays an essential role in ATII-induced vascular dysfunction and arterial hypertension. Our data indicate that MyD88 is important for cytokine production and might be required for ATII-induced differentiation of monocytes into an inflammatory phenotype.
Abstract 11525: Physical Activity and Incident Heart Failure in Community Dwelling Older Adults with and without Metabolic Syndrome
Authors: Siddharth Singh, Yan Zhang, Ravi Desai, Xuemei Sui, Gregg Fonarow, Inmaculada Aban, Steven Blair, Gilbert Perry, Vera Bittner, Prakash Deedwania, Ali Ahmed
Journal: Circulation (2011)

Background: Physical activity (PA) has previously been shown to be associated with lower risk of incident heart failure (HF). Its effects may be more pronounced in metabolic syndrome (MetS) subject...
Abstract 11256: Handheld Echocardiography Improves Detection of Rheumatic Heart Disease in Ugandan Schoolchildren Compared to Auscultation
Authors: Justin Godown, Jimmy C Lu, Andrea Beaton, Craig Sable, Grace Mirembe, Richard Sanya, Twalib Aliku, Sunkyung Yu, Gregory J Ensing
Journal: Circulation (2014)

Background:  Rheumatic heart disease (RHD) remains a major public health concern in developing countries and routine screening has the potential to improve outcomes. Standard portable echocardiography (SPE) is far more sensitive than auscultation for the detection of RHD, but remains cost-prohibitive in resource-limited settings. With its lower cost, handheld echocardiography (HHE) has the potential to fill this void. The purpose of this study was to assess the incremental value of HHE over auscultation to identify RHD, as compared to SPE.   Methods:  Over 1 week, children at 5 schools in Gulu, Uganda underwent focused SPE (parasternal and apical views). Any child with mitral or aortic regurgitation or stenosis, plus a randomly selected group of children with normal SPE findings underwent HHE by echocardiographers and auscultation by a local physician. SPE and HHE studies were interpreted blindly using the 2012 World Heart Federation criteria by 6 experienced cardiologists. A second reader confirmed any study with borderline or definite RHD, with discrepancies resolved by a third reader. Sensitivity and specificity of HHE and auscultation for the detection of any RHD, definite RHD, and pathologic mitral or aortic regurgitation were calculated using SPE as the gold standard.   Results:  Of 4,773 children who underwent screening with SPE, a subgroup of 1,317 children (46 % male, 10.8 ± 2.6 years of age) underwent HHE and auscultation. Auscultation had uniformly poor sensitivity to detect RHD or valve disease. Sensitivity was significantly improved using HHE compared to auscultation for the detection of definite RHD (97.8% vs 22.2%), borderline or definite RHD (78.4% vs 16.4%), and pathologic aortic insufficiency (81.8% vs 13.6%) (Table).   Conclusions:  Auscultation is a poor screening test for the detection of RHD. HHE significantly improves detection of RHD and may be a useful adjunct to or replacement of auscultation in resource-limited settings.
Predictors of violence in civilly committed acute psychiatric patients
Authors: D E McNiel, R L Binder, T K Greenfield
Journal: American Journal of Psychiatry (1988)

The authors investigated the relationship between community violence and violence in the hospital for patients hospitalized through emergency civil commitment. The medical charts of 238 patients involuntarily admitted to a university-based acute inpatient unit were reviewed for evidence of violence during the 2 weeks before commitment and the first 72 hours of hospitalization. Patients who were violent in the community were more likely to be violent in the hospital. A discriminant function analysis was used to identify the combination of information concerning community violence and patient background characteristics that most efficiently predicted which patients were violent during emergency commitment.
Hormonal Chaos: The Scientific and Social Origin of the Environmental Endocrine Hypothesis
Authors: Donald Campbell
Journal: BMJ (2000)

Sheldon Krimsky    ![][1] 

Johns Hopkins University Press, £23, pp 256

ISBN 0 8018 6279 5

Rating: ![Graphic][2] 

For at least half of the 20th century, the public perception of chemical hazards has been influenced largely by the fear of cancer. The Western world's obsession with “the dread disease” has been the window through which research into toxic chemicals has been viewed. The finding that chemicals cause genetic mutations in somatic cells, along with the concept that mutations are associated with the development of cancer cells, …

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Incorporation of I-14C-acetate into epidermal lipids.
Authors: V.J.W. LONG
Journal: British Journal of Dermatology (1977)

Suspensions of pig epidermal cells were prepared by trypsinisation of epidermis and incubated with I-14C-acetate in Eagle's minimum essential medium containing 10% serum. The incorporation of radioactivity into the total lipids of the cells increased with time despite the decrease in the proportion of viable cells which occurred during the period of incubation. The pattern of incorporation into the phospholipids and glycolipids showed similar changes with time to those observed previously with rat epidermal cell suspensions. Pig epidermal slices were incubated with I-14C-acetate in Eagle's minimum essential medium in the presence and absence of 10% serum. The proportion of radioactivity incorporated into the polar lipids was much greater in the epidermal slices than in the suspensions of epidermal cells. The pattern of incorporation in the phospholipids and glycolipids of epidermal slices differed from that found with epidermal cell suspensions and the pattern did not alter so markedly with the time of incubation. However, in each case reproducible patterns of incorporation were obtained under controlled conditions. The method of analysis can therefore be used to study lipid changes in small biopsies of normal and pathological skin.