tbuckley/cabot-search huggingface dataset:
From the Ground Up: A Look at the Role of Foundations in Health
Authors: Linda Gundersen
Journal: Annals of Internal Medicine (2000)

Currents16 May 2000From the Ground Up: A Look at the Role of Foundations in HealthLinda GundersenLinda GundersenSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-132-10-200005160-00102 SectionsAboutFull Text ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail In the United States, wealthy philanthropists, including Robert Wood Johnson and John A. Hartford, have historically formed foundations to structure their charitable giving. In 1995, foundations donated an estimated $1.9 billion to health-related causes (Renz L, Lawrence S. Health policy grantmaking: a report on foundation trends. New York: The Foundation Center; 1999). In 1998, all U.S. foundations donated a staggering $19.5 billion to various causes. That same year, 17% of grant dollars went to the health sector (Renz L, Lawrence S, Kendzior J. Foundation giving: yearbook of facts and figures on private, corporate, and community foundations. New York: The Foundation ... Author, Article, and Disclosure InformationAuthors: Linda Gundersen PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHealth Care in America: Lost Opportunities Amid Plenty 16 May 2000Volume 132, Issue 10 Page: 849 Keywords Children Congenital disorders Elderly Geriatrics Health care Health care policy Health insurance Poliomyelitis Prevention, policy, and public health Research funding ePublished: 15 August 2000 Issue Published: 16 May 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.Loading ...
Myocardial Nucleotide Synthesis from Purine Bases and Nucleosides
Authors: DONALD H. NAMM
Journal: Circulation Research (1973)

14 C-Labeled adenosine, inosine, hypoxanthine, and adenine were extracted by the isolated rat heart in amounts proportional to their concentration in the perfusion medium between 0.05 and 5 µM. With each of the precursor materials, nearly all of the radioactivity retained by the heart was identified as acid-soluble nucleotide. Nucleotide formation from the four isotopic precursors occurred at similar rates when the concentration of the precursors was below 1 µM. Above this concentration, the heart appeared to utilize adenosine for nucleotide synthesis at rates three to five times those for the other purines. Several experimental approaches were employed to determine the predominant enzymatic routes in the rat heart for the conversion of the nucleosides adenosine and inosine to nucleotides. The results indicated that adenosine was directly phosphorylated to 5'-adenosine monophosphate by a nucleoside kinase. Inosine appeared to proceed to the nucleotide, at least partially, through an initial conversion to hypoxanthine.
Antioxidant Supplements May Lessen Benefit of Radiation and Chemotherapy
Authors: L. Savage
Journal: JNCI Journal of the National Cancer Institute (2008)

Antioxidant Supplements May Lessen Benefi t of Radiation and ChemotherapyCancer patients should avoid the routine use of antioxidant supplements during radiation and chemotherapy because the supplements may reduce the anticancer benefi ts of therapy, researchers concluded in a commentary published online May 27 in the Journal of the National Cancer Institute .Radiation and many chemotherapy agents work to kill cells by inducing free radicals that damage DNA and proteins.Therefore, there is a possibility that taking antioxidant supplements, such as vitamin E or ␤ -carotene, may interfere with the therapies and reduce their anticancer activity.On the other hand, some investigators hypothesize that antioxidant supplementation may protect healthy tissues and reduce the side effects of treatment.Despite two decades of research into this question, no clear answer has appeared.To evaluate the potential harms or benefi ts of antioxidant supplementation, Brian D. Lawenda, M.D., of the Naval Medical Center San Diego and colleagues reviewed all of the randomized trials they could identify that tested the effect of antioxidant supplements on radiation therapy or chemotherapy.In the case of radiotherapy, they identifi ed nine studies that addressed the question, including two meta-analyses.However, only three studies were randomized controlled trials designed to look at the clinical effect of antioxidant therapy on radiation.In the largest of the randomized trials, antioxidant supplementation was associated with a reduction in overall survival.One antioxidant agent, amifostine, which is already approved by the U.S. Food and Drug Administration to increase radioresistance in healthy salivary gland tissues, may protect normal tissues without increasing tumor radioresistance.Lawenda and colleagues caution that the question needs to be studied further before a solid conclusion can be made.The authors identifi ed 16 randomized controlled trials that examined the impact of antioxidant supplementation on chemotherapy.Six of the trials were placebo-controlled.Of the studies that included information on response rates, none reported a decrease in response in the antioxidant arm of the trial compared with the control arm.However, Lawenda and colleagues caution that none of the trials was large enough to reliably detect such differences."Despite some intriguing studies that have suggested the benefi t of adjunctive antioxidant treatments in cancer patients, the totality of the available evidence is equivocal at best and leaves us with serious concerns about the potential for harm," the authors write.
Safety of Bevacizumab in Patients With Non–Small-Cell Lung Cancer and Brain Metastases
Authors: Mark A. Socinski, Corey J. Langer, Jane E. Huang, Margaret M. Kolb, Peter Compton, Lisa Wang, Wallace Akerley
Journal: Journal of Clinical Oncology (2009)

Purpose Patients with non–small-cell lung cancer (NSCLC) and brain metastases have previously been excluded from trials of bevacizumab because of suspected risk of CNS hemorrhage. This phase II trial, AVF3752g (PASSPORT), specifically addressed bevacizumab safety (incidence of grade ≥ 2 CNS hemorrhage) in patients with NSCLC and previously treated brain metastases. Patients and Methods This open-label multicenter trial for first- and second-line treatment of nonsquamous NSCLC enrolled patients with treated brain metastases. First-line patients received bevacizumab (15 mg/kg) every 3 weeks with platinum-based doublet therapy or erlotinib (at physician's decision), and second-line patients received bevacizumab with single-agent chemotherapy or erlotinib, until disease progression or death. Results Of the 115 enrolled patients, 66 of 76 first-line patients received carboplatin-based chemotherapy; 22 of 39 second-line patients received pemetrexed, and nine of 39 received erlotinib. As of the June 23, 2008 data cut, among 106 safety-evaluable patients, median on-study duration was 6.3 months (range, 0 to 22 months), with a median of five bevacizumab cycles (range, one to 17), and no reported episodes of grade ≥ 2 CNS hemorrhage (95% CI, 0.0% to 3.3%). Of the bevacizumab-targeted adverse events reported, two were grade 5. Both were pulmonary hemorrhages, one occurring during treatment and the other occurring 6 weeks after the data cut; there was also one grade 4, nonpulmonary/non-CNS hemorrhage. Twenty-six patients (24.5%) discontinued study treatment as a result of an adverse event, and 37 (34.9%) discontinued because of disease progression. Conclusion Addition of bevacizumab to various chemotherapy agents or erlotinib in patients with NSCLC and treated brain metastases seems to be safe and is associated with a low incidence of CNS hemorrhage.
Interferon-gamma and tumor necrosis factor synergize to induce nitric oxide production and inhibit mitochondrial respiration in vascular smooth muscle cells.
Authors: Y Geng, G K Hansson, E Holme
Journal: Circulation Research (1992)

Nitric oxide (NO) is an important signal substance in cell-cell communication and can induce relaxation of blood vessels by activating guanylate cyclase in smooth muscle cells (SMCs). NO is synthesized from L-arginine by the enzyme NO synthase, which is present in endothelial cells. It was recently shown that SMCs may themselves produce NO or an NO-related compound. We have studied NO production and its effects on energy metabolism in cultured rat aortic smooth muscle cells. It was observed that the cytokines, interferon-gamma and tumor necrosis factor-alpha, synergistically induced an arginine-dependent production of NO in these cells. This was associated with an inhibition of complex I (NADH: ubiquinone oxidoreductase) and complex II (succinate: ubiquinone oxidoreductase) activities of the mitochondrial respiratory chain, suggesting that NO blocks mitochondrial respiration in these cells. Lactate accumulated in the media of the cells, implying an increased anaerobic glycolysis, but there was no reduction of viability. An NO-dependent inhibition of mitochondrial respiration and a switch to anaerobic glycolysis would reduce energy production of the SMCs. This would in turn reduce the contractile capacity of the cell and might represent another NO-dependent vasodilatory mechanism. It could be of particular importance in inflammation, since cytokines released by inflammatory cells may induce autocrine NO production in SMCs.
ORAL HEALTH AND IMPACT ON PERFORMANCE OF ATHLETES PARTICIPATING IN THE LONDON 2012 OLYMPIC GAMES
Authors: I Needleman, P Ashley, A Petrie, F Fortune, W Turner, J Jones, J Niggli, L Engebretsen, R Budgett, N Donos, T Clough, S Porter
Journal: British Journal of Sports Medicine (2014)

Background Oral health is important both for wellbeing and successful elite sporting performance. Reports from Olympic Games have found significant treatment needs; however, few studies have examined oral health directly. Objective The aim of this study was to evaluate oral health, the determinants of oral health and the effect of oral health on wellbeing, training and performance of athletes participating in the London 2012 Games. Design Cross-sectional study. Setting Dental clinic within the London 2012 Polyclinic. Participants Participating athletes able to understand the consent process. 302 athletes from 25 sports were recruited with data available for 278. Interventions Following informed consent, a standardised history, comprehensive oral health clinical examination and questionnaire were conducted. Main outcome measures Oral health status, determinants of oral health, impact of oral health on wellbeing, training and performance. Results The majority of athletes were from Africa, the Americas and Europe. Overall, the results demonstrated high levels of poor oral health including dental caries (55% of athletes), dental erosion (45% athletes) and periodontal disease (gingivitis 76% athletes, periodontitis 15% athletes). More than 40% of athletes were ‘bothered’ by their oral health with 28% reporting an impact on quality of life and 18% on training and performance. Nearly half of participants had not attended for a dental examination or hygiene care in the previous year. Conclusions The oral health of athletes attending the dental clinic of the London 2012 Games was poor with a resulting substantial negative impact on wellbeing, training and performance. As oral health is an important element of overall health and wellbeing, health promotion and disease prevention interventions are urgently required to optimise athletic performance.
Bevacizumab in Combination with Irinotecanand Capecitabine as First-Line Treatment for MCRC – Efficacy and Safety
Authors: Jungic Sasa, Kecman Malcic Gordana, Rakita Ivanka, Jovanovic Dusan, Gajanin Radoslav, Maric Zdravko, Tubic Biljana, Gojkovic Zdenka
Journal: Annals of Oncology (2014)
Retinoic acid prevents experimental Cushing syndrome
Authors: Marcelo Páez-Pereda, Damian Kovalovsky, Ursula Hopfner, Marily Theodoropoulou, Uberto Pagotto, Eberhard Uhl, Marco Losa, Johanna Stalla, Yvonne Grübler, Cristina Missale, Eduardo Arzt, Günter K. Stalla
Journal: Journal of Clinical Investigation (2001)

Cushing syndrome is caused by an excess of adrenocorticotropic hormone (ACTH) production by neuroendocrine tumors, which subsequently results in chronic glucocorticoid excess. We found that retinoic acid inhibits the transcriptional activity of AP-1 and the orphan receptors Nur77 and Nurr1 in ACTH-secreting tumor cells. Retinoic acid treatment resulted in reduced pro-opiomelanocortin transcription and ACTH production. ACTH inhibition was also observed in human pituitary ACTH-secreting tumor cells and a small-cell lung cancer cell line, but not in normal cells. This correlated with the expression of the orphan receptor COUP-TFI, which was found in normal corticotrophs but not in pituitary Cushing tumors. COUP-TFI expression in ACTH-secreting tumor cells blocked retinoic acid action. Retinoic acid also inhibited cell proliferation and, after prolonged treatment, increased caspase-3 activity and induced cell death in ACTH-secreting cells. In adrenal cortex cells, retinoic acid inhibited corticosterone production and cell proliferation. The antiproliferative action and the inhibition of ACTH and corticosterone produced by retinoic acid were confirmed in vivo in experimental ACTH-secreting tumors in nude mice. Thus, we conclude that the effects of retinoic acid combine in vivo to reverse the endocrine alterations and symptoms observed in experimental Cushing syndrome.
Metabolic Evaluation of Nephrolithiasis in Patients With Medullary Sponge Kidney
Authors: Michael O'Neill
Journal: JAMA (1981)

Seventeen patients with documented medullary sponge kidney and nephrolithiasis underwent metabolic evaluation. These patients constituted 3.6% of our stone-forming population. Fifteen (88%) of 17 were hypercalciuric. The most common abnormality was absorptive hypercalciuria, occurring in 59%. Only three patients (18%) had renal hypercalciuria. None of the patients had primary hyperparathyroidism. Hyperuricosuria occurred together with hypercalciuria in five patients. In two patients, the precise cause of hypercalciuria could not be determined, and in another two patients, no metabolic abnormality could be detected. Thus, the patients with medullary sponge kidney and renal stones had the same spectrum of metabolic abnormalities as the overall population of stone formers. While these patients may theoretically have a greater anatomic propensity to form stones because of their anatomic abnormality, they should be evaluated and treated appropriately for any metabolic defect. (<i>JAMA</i>1981;245:1233-1236)
Accumulation of apolipoprotein E-rich high density lipoproteins in hyperalphalipoproteinemic human subjects with plasma cholesteryl ester transfer protein deficiency.
Authors: S Yamashita, D L Sprecher, N Sakai, Y Matsuzawa, S Tarui, D Y Hui
Journal: Journal of Clinical Investigation (1990)

This study characterized the plasma lipoproteins of familial hyperalphalipoproteinemic patients with or without deficiency of cholesteryl ester transfer protein (CETP) activity. The subjects with CETP deficiency have increased levels of apolipoprotein (apo) E. The increased concentration of apo E in these subjects was correlated to the appearance of apo E-rich high density lipoproteins (HDL). Sodium dodecyl sulfate-polyacrylamide gel analysis revealed that these lipoproteins contained predominantly the apo E (82%) and little amount of apo A-I (18%). These apo E-rich HDL displayed a much higher affinity than human LDL in binding to LDL receptors on human fibroblasts. Furthermore, 3.5 times fewer apo E-rich HDL than LDL were required to saturate the receptors on fibroblasts. These data indicated that the apo E-rich HDL in CETP-deficient human subjects contained multiple copies of apo E and bound to the LDL receptor through multiple interactions. The apo E-rich HDL, with similar properties as cholesterol-induced apo E HDLc, were not detectable in normal human subjects or in hyperalphalipoproteinemic subjects with normal CETP activity. The apo E-containing HDL in the latter subjects were smaller and contained only small amounts of apo E (14%). The difference in apo E-containing HDL in these subjects suggests a correlation between CETP level and the appearance of apo E-rich HDL.
Effect of biologic therapies targeting tumour necrosis factor-α on cutaneous mesenchymal stem cells in psoriasis
Authors: A. Campanati, M. Orciani, S. Gorbi, F. Regoli, R. Di Primio, A. Offidani
Journal: British Journal of Dermatology (2012)

Psoriasis is a Th1 immune-mediated, inflammatory disease, in which skin lesions appear many years before the related metabolic and cardiovascular comorbidities, according to the theory of the 'psoriatic march'. Inducible nitric oxide synthetase (iNOS), tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF) are directly implicated in determining both skin lesions and systemic involvement in psoriasis. Reactive oxygen species actively promote the secretion of inflammatory Th1 cytokines directly involved in the pathogenesis of psoriasis.Evaluation of VEGF expression and production, nitric oxide (NO) production, iNOS expression, and the antioxidant response of mesenchymal stem cells (MSCs), both before and after 12 weeks of treatment with the TNF-α inhibitors adalimumab or etanercept.Biochemical, morphological and immunohistochemical analyses were performed in MSCs isolated from nonlesional, perilesional and lesional skin of patients with psoriasis, before and after treatment.The treatments were able to reduce the expression and production of VEGF, the expression of iNOS and the production of NO in MSCs of patients with psoriasis. TNF-α inhibitors also reduced the oxidative damage in MSC membrane and proteins, several antioxidant systems responded to treatments with a general inhibition of activities (glutathione S-transferase and catalase) and these effects were also supported by a general decrease of total oxyradical scavenging capacity towards hydroxyl radicals and peroxynitrite.TNF-α inhibitors are able to change the physiopathological pathway of psoriasis, and our results suggest their therapeutic effects already take place at the level of MSCs, which probably represent the cells primarily involved in the 'psoriatic march'.
INTENSIVE POSTURAL REST IN THE TREATMENT OF PULMONARY TUBERCULOSIS
Authors: W. A. GEKLER
Journal: JAMA (1928)

Several years ago Webb<sup>1</sup>and his co-workers called attention to a new method of treating pulmonary tuberculosis; namely, "postural rest." The absence of further reports since that time leads us to believe that this method has not received the recognition it deserves. We offer this brief report in the hope that other workers may learn of its value. The object of postural rest, according to Webb, is to secure practically complete rest of the diseased lung by having the patient lie on the affected side. He showed that after from thirty minutes to an hour in this position the respiratory excursions of the chest wall are greatly diminished. In some cases there is a definite sagging of the heart and mediastinum due to gravity. Often after several months of postural rest there is a marked shrinkage of the diseased lung caused by fibrosis, with decrease in the size of
Effects of Albumin/Furosemide Mixtures on Responses to Furosemide in Hypoalbuminemic Patients
Authors: NAGA CHALASANI, CHRISTOPHER J. GORSKI, JOHN C. HORLANDER, REBECCA CRAVEN, HELENA HOEN, JUAN MAYA, CRAIG D. BRATER
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Hypoalbuminemic patients often have sufficient fluid accumulation to mandate diuretic therapy but are often resistant to diuresis. Studies have suggested that hypoalbuminemia itself impairs delivery of effective amounts of diuretic agent into the urine, the site of action. Therefore, administration of mixtures of albumin and loop diuretics may enhance responses. Thirteen patients with biopsy-proven cirrhosis and ascites (age, 51.2 ± 8.1 yr; Child-Pugh score, 8.5 ± 1.0; serum albumin concentration, 3.0 ± 0.6 g/dl) were studied in this randomized crossover study. Sodium balance was maintained throughout the study with a metabolic diet. All patients received spironolactone, but administration of all other diuretic agents was discontinued. Each patient received all of the following four treatments intravenously: ( 1 ) 40 mg of furosemide, ( 2 ) 25 g of albumin, ( 3 ) 40 mg of furosemide and 25 g of albumin premixed ex vivo , and ( 4 ) 40 mg of furosemide and 25 g of albumin infused simultaneously into different arms. Responses were assessed by measuring urinary sodium excretion and relating the urinary furosemide excretion rate to the sodium excretion rate. Additionally, the pharmacokinetics of furosemide were assessed. Furosemide pharmacokinetics were similar for all treatment arms. Albumin alone had negligible diuretic effects. Neither albumin regimen increased the response to furosemide. Moreover, the relationship between the urinary furosemide excretion rate and the sodium excretion rate was unaffected by albumin. In conclusion, albumin failed to enhance the diuretic effects of furosemide in cirrhotic patients with ascites. Therefore, the coadministration of albumin and furosemide for the treatment of cirrhosis, and likely other hypoalbuminemic conditions, should not be used clinically.
Phospholipid Scramblase 1, an interferon-regulated gene located at 3q23, is regulated by SnoN/SkiL in ovarian cancer cells
Authors: Karthik M. Kodigepalli, Pavana Anur, Paul Spellman, Peter J. Sims, Meera Nanjundan
Journal: Molecular Cancer (2013)

Treatment of advanced stage ovarian cancer continues to be challenging due to acquired drug resistance and lack of early stage biomarkers. Genes identified to be aberrantly expressed at the 3q26.2 locus (i.e. SnoN/SkiL) have been implicated in ovarian cancer pathophysiology. We have previously shown that SnoN expression is increased in advanced stage ovarian cancers and alters cellular response to arsenic trioxide (As2O3).We now demonstrate increased DNA copy number levels (TCGA data) of phospholipid scramblase 1 (PLSCR1, located at 3q23) whose transcript expression in ovarian cell lines is highly correlated with SnoN mRNA. Interestingly, SnoN can modulate PLSCR1 mRNA levels in the absence/presence of interferon (IFN-2α). Both IFN-2α and As2O3 treatment can modulate PLSCR1 mRNA levels in ovarian carcinoma cells. However, SnoN siRNA does not lead to altered PLSCR1 protein implicating other events needed to modulate its protein levels. In addition, we report that PLSCR1 can modulate aspects of the As2O3 cellular response.Our findings warrant further investigation into the role of PLSCR1 in ovarian cancer development and chemoresistance.
TORC-Specific Phosphorylation of Mammalian Target of Rapamycin (mTOR): Phospho-Ser2481 Is a Marker for Intact mTOR Signaling Complex 2
Authors: Jeremy Copp, Gerard Manning, Tony Hunter
Journal: Cancer Research (2009)

The mammalian target of rapamycin (mTOR) serine/threonine kinase is the catalytic component of two evolutionarily conserved signaling complexes. mTOR signaling complex 1 (mTORC1) is a key regulator of growth factor and nutrient signaling. S6 kinase is the best-characterized downstream effector of mTORC1. mTOR signaling complex 2 (mTORC2) has a role in regulating the actin cytoskeleton and activating Akt through S473 phosphorylation. Herein, we show that mTOR is phosphorylated differentially when associated with mTORC1 and mTORC2 and that intact complexes are required for these mTORC-specific mTOR phosphorylations. Specifically, we find that mTORC1 contains mTOR phosphorylated predominantly on S2448, whereas mTORC2 contains mTOR phosphorylated predominantly on S2481. Using S2481 phosphorylation as a marker for mTORC2 sensitivity to rapamycin, we find that mTORC2 formation is in fact rapamycin sensitive in several cancer cell lines in which it had been previously reported that mTORC2 assembly and function were rapamycin insensitive. Thus, phospho-S2481 on mTOR serves as a biomarker for intact mTORC2 and its sensitivity to rapamycin.