tbuckley/cabot-search huggingface dataset:
Intranasal Delivery of HMGB1 siRNA Confers Target Gene Knockdown and Robust Neuroprotection in the Postischemic Brain
Authors: Il-Doo Kim, Joo-Hyun Shin, Seung-Woo Kim, Sunghyun Choi, Junseong Ahn, Pyung-Lim Han, Jong-Sang Park, Ja-Kyeong Lee
Journal: Molecular Therapy (2012)

Noninvasive intranasal drug administration has been noted to allow direct delivery of drugs to the brain. In the present study, the therapeutic efficacy of intranasal small interfering RNA (siRNA) delivery was investigated in the postischemic rat brain. Fluorescein isothiocyanate (FITC)-labeled control siRNA was delivered intranasally in normal adult rats using e-PAM-R, a biodegradable PAMAM dendrimer, as gene carrier. Florescence-tagged siRNA was found in the cytoplasm and processes of neurons and of glial cells in many brain regions, including the hypothalamus, amygdala, cerebral cortex, and striatum, in 1 hour after infusion, and the FITC-fluorescence was continuously detected for at least 12 hours. When siRNA for high mobility group box 1 (HMGB1), which functions as an endogenous danger molecule and aggravates inflammation, was delivered intranasally, the target gene was significantly depleted in many brain regions, including the prefrontal cortex and striatum. More importantly, intranasal delivery of HMGB1 siRNA markedly suppressed infarct volume in the postischemic rat brain (maximal reduction to 42.8 ± 5.6% at 48 hours after 60 minutes middle cerebral artery occlusion (MCAO)) and this protective effect was manifested by recoveries from neurological and behavioral deficits. These results indicate that the intranasal delivery of HMGB1 siRNA offers an efficient means of gene knockdown-mediated therapy in the ischemic brain. Noninvasive intranasal drug administration has been noted to allow direct delivery of drugs to the brain. In the present study, the therapeutic efficacy of intranasal small interfering RNA (siRNA) delivery was investigated in the postischemic rat brain. Fluorescein isothiocyanate (FITC)-labeled control siRNA was delivered intranasally in normal adult rats using e-PAM-R, a biodegradable PAMAM dendrimer, as gene carrier. Florescence-tagged siRNA was found in the cytoplasm and processes of neurons and of glial cells in many brain regions, including the hypothalamus, amygdala, cerebral cortex, and striatum, in 1 hour after infusion, and the FITC-fluorescence was continuously detected for at least 12 hours. When siRNA for high mobility group box 1 (HMGB1), which functions as an endogenous danger molecule and aggravates inflammation, was delivered intranasally, the target gene was significantly depleted in many brain regions, including the prefrontal cortex and striatum. More importantly, intranasal delivery of HMGB1 siRNA markedly suppressed infarct volume in the postischemic rat brain (maximal reduction to 42.8 ± 5.6% at 48 hours after 60 minutes middle cerebral artery occlusion (MCAO)) and this protective effect was manifested by recoveries from neurological and behavioral deficits. These results indicate that the intranasal delivery of HMGB1 siRNA offers an efficient means of gene knockdown-mediated therapy in the ischemic brain.
Special Olympics Bharat: the Indian perspective on disability sport
Authors: Denzil Keelor
Journal: British Journal of Sports Medicine (2010)

Special Olympics International is a worldwide non-profit organisation for benefiting the intellectually disabled through the medium of sports. Special Olympics Bharat is the national accredited programme of Special Olympics International, meeting its high accreditation standards. Special Olympics Bharat is the National Sports Federation (NGO) in India recognised by the Ministry of Youth Affairs and Sports, Government of India, as the sports federation for the intellectually disabled. In India, the programme has so far drawn over 23 000 coaches to work with over 550 000 athletes across 32 State Programmes. India being designated a Priority Nation by Special Olympics International, the goal is to extend the Special Olympics programme throughout the country and reach over 1 000 000 people with intellectual disability by end 2012. The presentation will include issues, challenges and endeavours in establishing and operating this predominantly volunteer driven programme across the country. The presenter will also highlight international linkages and its impact on the programme. In addition speak about what the future is looking like.
Managing HIV disease after Delta
Authors: A. J Pinching
Journal: BMJ (1996)

Managing HIV disease after Delta Questions remain about how to manage patients already on nucleoside monotherapy It is not often that the results of clinical trials change clinical practice almost overnight.But that is what has happened with two clinical trials (Delta and ACTG175) of combination nucleoside analogue antiretroviral treatment for patients infected with HIV.The previously standard monotherapy had evident limitations in the extent and durability of response.The need for and expectations of better treatments was high, fuelling but also distorting the investigation of improved approaches.What are the practical implications of these studies?Delta (conducted by a European/Australian group co- ordinated by Britain's Medical Research Council and the Agence National de Recherches sur le SIDA in France) and ACTG175 (conducted in the United States by the AIDS Clinical Trials Group of the National Institutes of Health) have recently released their main findings.They were large randomised double blind placebo controlled trials of zidovudine (AZT) monotherapy versus combinations of zidovudine and didanosine (ddI) or zidovudine and zalcitabine (ddC) with an additional limb of didanosine monotherapy in ACTG1 75.Both used clinical end points, and ACTG175 also used changes in CD4 cell count.Both recruited patients who had not previously been exposed to nucleosides (Delta 2124 patients, ACTG175 1067 patients) and symptomatic patients who had previously received nucleosides (Delta 1083 patients including patients with AIDS, CD4 count 50-350; ACTG175 1400 patients excluding patients with AIDS, CD4 count 200-500.)They showed that, for patients who had never received nucleosides, combinations of zidovudine and didanosine, or zidovudine and zalcitabine, were significantly more effective than zidovudine alone in delaying disease progression.However, patients already exposed to nucleosides gained no benefit from combination therapy (though recently
Polymorphisms in the Vitamin D Receptor and Risk of Ovarian Cancer in Four Studies
Authors: Shelley S. Tworoger, Margaret A. Gate, I-Min Lee, Julie E. Buring, Linda Titus-Ernstoff, Daniel Cramer, Susan E. Hankinson
Journal: Cancer Research (2009)

Abstract Prior studies have suggested that vitamin D may reduce ovarian cancer risk. Thus, we examined whether three single nucleotide polymorphisms (SNP) in the vitamin D receptor (VDR) gene (Fok1, Bsm1, Cdx2) were associated with risk of epithelial ovarian cancer in a retrospective case-control study (New England Case-Control study, NECC) and a nested case-control study of three prospective cohort studies: the Nurses' Health Study (NHS), NHSII, and the Women's Health Study. Data from the cohort studies were combined and analyzed using conditional logistic regression and pooled with the results from the NECC, which were analyzed using unconditional logistic regression, using a random effects model. We obtained genotype data for 1,473 cases and 2,006 controls. We observed a significant positive association between the number of Fok1 f alleles and ovarian cancer risk in the pooled analysis (Ptrend = 0.03). The odds ratio (OR) for the ff versus FF genotype was 1.26 [95% confidence interval (CI) = 1.01–1.57]. Neither the Bsm1 (Ptrend = 0.96) or Cdx2 (Ptrend = 0.13) SNPs were significantly associated with ovarian cancer risk. Among the prospective studies, the risk of ovarian cancer by plasma vitamin D levels did not clearly vary by any of the genotypes. For example, among women with the Fok1 FF genotype, the OR comparing plasma 25-hydroxyvitamin D ≥32 ng/mL versus &amp;lt;32 ng/mL was 0.66 (95% CI, 0.34–1.28), and among women with the Ff or ff genotype the OR was 0.71 (95% CI, 0.43–1.18). Our results of an association with the Fok1 VDR polymorphism further support a role of the vitamin D pathway in ovarian carcinogenesis. [Cancer Res 2009;69(5):1885–91]
Shelter and indoor air in the twenty-first century--radon, smoking, and lung cancer risks.
Authors: J I Fabrikant
Journal: Environmental Health Perspectives (1990)

Recognition that radon and its daughter products may accumulate to high levels in homes and in the workplace has led to concern about the potential lung cancer risk resulting from indoor domestic exposure. While such risks can be estimated with current dosimetric and epidemiological models for excess relative risks, it must be recognized that these models are based on data from occupational exposure and from underground miners' mortality experience. Several assumptions are required to apply risk estimates from an occupational setting to the indoor domestic environment. Analyses of the relevant data do not lead to a conclusive description of the interaction between radon daughters and cigarette smoking for the induction of lung cancer. The evidence compels the conclusion that indoor radon daughter exposure in homes represents a potential life-threatening public health hazard, particularly in males, and in cigarette smokers. Resolution of complex societal interactions will require public policy decisions involving the governmental, scientific, financial, and industrial sectors. These decisions impact the home, the workplace, and the marketplace, and they extend beyond the constraints of science. Risk identification, assessment, and management require scientific and engineering approaches to guide policy decisions to protect the public health. Mitigation and control procedures are only beginning to receive attention. Full acceptance for protection against what could prove to be a significant public health hazard in the twenty-first century will certainly involve policy decisions, not by scientists, but rather by men and women of government and law.
Biotechnology to Protect Army
Authors: Mike Mitka
Journal: JAMA (2001)

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
A Biochemical and Morphological Study of Protein Synthesis in Normal Rat Myocardium
Authors: B. D. McCallister, A. L. Brown
Journal: Cardiovascular Research (1969)

The incorporation of tritiated leucine into normal rat myocardium was studied quantitatively by fine-structure autoradiography and protein fractionation techniques. Within the limits of this study it appears that at 15 min and at 1 hr myofibrillar proteins are synthesized at essentially the same rate as mitochondrial proteins.
Accuracy of Offspring Reports of Parental Cardiovascular Disease History: The Framingham Offspring Study
Authors: Joanne M. Murabito, Byung-Ho Nam, Ralph B. D'Agostino, Donald M. Lloyd-Jones, Christopher J. O'Donnell, Peter W.F. Wilson
Journal: Annals of Internal Medicine (2004)

Background: Family history is used to infer the risk for heart disease; however, little is known about the accuracy of family history reports. Objective: To examine the accuracy of offspring reports of parental cardiovascular disease. Design: Validation study. Setting: Framingham Heart Study. Participants: Offspring participants of the multigenerational Framingham Heart Study with both parents in the original cohort. Measurements: 791 men and 837 women (mean age, 57 years) completed a family history questionnaire from 1995 to 1998. Offspring reports were compared with confirmed medical evidence of parental status, and positive and negative predictive values and likelihood ratios were calculated. Results: Positive reports of high blood pressure, diabetes, and high cholesterol levels in fathers were accurate: Positive predictive values were 83% (95% CI, 80% to 86%), 76% (CI, 70% to 82%), and 78% (CI, 73% to 83%), respectively. Corresponding positive predictive values for reports in mothers were 91% (CI, 89% to 93%), 79% (CI, 73% to 85%), and 88% (CI, 84% to 92%), respectively. Positive predictive values for reports of paternal heart attack occurring before 55 years of age and for stroke occurring before 65 years of age were 28% (CI, 22% to 34%) and 43% (CI, 33% to 53%), respectively, whereas the positive likelihood ratios were 8.6 (CI, 6.8 to 10.9) and 11.2 (CI, 9.2 to 13.6), respectively. Negative predictive values for parental history reports were greater than 90%, except for high blood pressure and high cholesterol level (negative predictive values, 33% to 55%, and negative likelihood ratios, 0.47 to 0.88). Limitations: This study does not determine whether more accurate measures of family history would meaningfully improve estimation of cardiovascular risk. Conclusions: Negative parental history reports were reliable, except for hypertension and high cholesterol levels. Although reports of parental premature heart attack and stroke had high likelihood ratios, their predictive values were low because the prevalence of these conditions was low in parents. If patients were more aware of their parents' medical illnesses, they might be able to estimate their risk for disease more accurately and perhaps motivate themselves to follow a healthy lifestye.
Persistent activation of coagulation mechanism in unstable angina and myocardial infarction.
Authors: P A Merlini, K A Bauer, L Oltrona, D Ardissino, M Cattaneo, C Belli, P M Mannucci, R D Rosenberg
Journal: Circulation (1994)

BACKGROUND The blood coagulation system is activated in the acute phase of unstable angina and acute myocardial infarction. However, it remains unclear whether augmented function of the hemostatic mechanism serves only as a marker of the acute thrombotic episode or whether a hypercoagulable state persists for a prolonged period after clinical stabilization. METHODS AND RESULTS We prospectively measured the plasma concentrations of prothrombin fragment 1 + 2 (F1 + 2) and fibrinopeptide A (FPA) in consecutive patients presenting with unstable angina (n = 81) or acute myocardial infarction (n = 32), respectively. At 6 months, plasma determinations were repeated in patients experiencing an uneventful clinical course (unstable angina, n = 57; myocardial infarction, n = 23). We quantitated the plasma levels of F1 + 2 and FPA in control patients with stable angina (n = 37) or healthy individuals (n = 32) who were matched for age and sex. The median plasma concentrations of F1 + 2 and FPA are significantly higher in patients presenting with unstable angina (F1 + 2, 1.08 nmol/L; FPA, 2.4 nmol/L) or acute myocardial infarction (F1 + 2, 1.27 nmol/L; FPA, 3.55 nmol/L) compared with patients with stable angina (F1 + 2, 0.74 nmol/L; FPA, 1.3 nmol/L; P &lt; .0001) or healthy individuals (F1 + 2, 0.71 nmol/L; FPA, 0.80 nmol/L; P &lt; .0001). At 6 months, the median plasma levels of F1 + 2 in patients exhibiting an uneventful clinical course did not differ from values obtained at admission (unstable angina, 1.26 versus 1.07 nmol/L, P = NS; myocardial infarction, 1.22 versus 1.29 nmol/L, P = NS), whereas the median plasma levels of FPA in the same two subpopulations were significantly reduced (unstable angina, 1.1 versus 2.9 nmol/L, P = .0003; myocardial infarction, 1.1 versus 3.0 nmol/L; P = .0028). CONCLUSIONS During the acute phase of unstable angina and myocardial infarction, patients exhibit increased coagulation system activity. Over the next 6 months, patients with unstable angina or myocardial infarction experiencing an uneventful clinical course manifest a persistent hypercoagulable state with minimal generation of fibrin.
Inhibition of Angiogenesis by Interleukin 4
Authors: Olga V. Volpert, Tim Fong, Alisa E. Koch, Jeffrey D. Peterson, Carl Waltenbaugh, Robert I. Tepper, Noël P. Bouck
Journal: The Journal of Experimental Medicine (1998)

Interleukin (IL)-4, a crucial modulator of the immune system and an active antitumor agent, is also a potent inhibitor of angiogenesis. When incorporated at concentrations of 10 ng/ml or more into pellets implanted into the rat cornea or when delivered systemically to the mouse by intraperitoneal injection, IL-4 blocked the induction of corneal neovascularization by basic fibroblast growth factor. IL-4 as well as IL-13 inhibited the migration of cultured bovine or human microvascular cells, showing unusual dose–response curves that were sharply stimulatory at a concentration of 0.01 ng/ml but inhibitory over a wide range of higher concentrations. Recombinant cytokine from mouse and from human worked equally well in vitro on bovine and human endothelial cells and in vivo in the rat, showing no species specificity. IL-4 was secreted at inhibitory levels by activated murine T helper (TH0) cells and by a line of carcinoma cells whose tumorigenicity is known to be inhibited by IL-4. Its ability to cause media conditioned by these cells to be antiangiogenic suggested that the antiangiogenic activity of IL-4 may play a role in normal physiology and contribute significantly to its demonstrated antitumor activity.
Inhibition of red cell membrane lipid peroxidation by sulphasalazine and 5-aminosalicylic acid.
Authors: S M Greenfield, N A Punchard, R P Thompson
Journal: Gut (1991)

The effects of sulphasalazine, 5-aminosalicylic acid (5-ASA), and sulphapyridine on peroxidation of red cell membrane lipids, measured as malondialdehyde production, were assessed. Sulphasalazine and 5-ASA, at concentrations of 10(-5)-10(-3) M significantly inhibit lipid peroxidation, suggesting an antioxidant action that may explain the efficacy of these drugs in treating inflammatory bowel disease. Sulphapyridine, which is not effective in inflammatory bowel disease inhibited malondialdehyde production at a concentration of 10(-3) M only.
Protection of canine cardiac mitochondrial function by verapamil-cardioplegia during ischemic arrest.
Authors: S B Yoon, J B McMillin-Wood, L H Michael, R M Lewis, M L Entman
Journal: Circulation Research (1985)

Hemodynamic and mitochondrial function recover following 60 minutes of ischemic arrest and reperfusion in hearts pretreated with verapamil. The present study was carried out to determine whether verapamil prevents the onset of mitochondrial oxidative impairment after 60 minutes of ischemic arrest without reperfusion. Two preparations of mitochondria isolated following Polytron homogenization and subsequent treatment of the myofibrillar pellet with Nagarse were examined for phosphorylating respiration. The Polytron mitochondria were more sensitive to ischemic arrest than were the Nagarse mitochondria with either glutamate-malate (57% vs. 22% inhibition), succinate (+ rotenone) (41% vs. 14% inhibition), or palmitoylcarnitine (57% vs. 27% inhibition) as respiratory substrates. Verapamil pretreatment significantly increased oxidation of all substrates by the subsequently isolated Polytron mitochondria, but only succinate-supported respiration returned to control levels. In contrast, the small amount of respiratory inhibition exhibited by the Nagarse mitochondria after ischemic arrest was insensitive to verapamil pretreatment. We conclude that the Polytron preparation of mitochondria is more susceptible to ischemia than the Nagarse mitochondria, and this susceptibility correlates with a striking sensitivity to verapamil protection. In general, oxidation of NADH-linked substrates, including palmitoylcarnitine, is more affected by ischemic arrest than succinate, and only oxidation of the latter substrate is totally protected by verapamil. The beneficial action of verapamil on mitochondrial function occurs prior to reperfusion. The data suggest that alterations in calcium homeostasis occur during the ischemic period, as well as in the subsequent reperfusion period.
Aortic smooth muscle cell phenotypic modulation and fibrillar collagen deposition in angiotensin II-dependent hypertension
Authors: G Rossi
Journal: Cardiovascular Research (2002)

Background: We investigated the effect of nifedipine, AT-1 and ET-1 receptor blockade on arterial smooth muscle cell phenotypes and collagen deposition in TGRen2 transgenic rat (TGR). Methods: Four-week-old TGR were blood pressure (BP)-matched and allocated to receive a placebo (n = 8), the calcium antagonist nifedipine (n = 6), the AT-1 specific receptor antagonist irbesartan (n = 6), the ETA/ETB antagonist bosentan (n = 6) or the ETA-selective antagonist BMS-182874 (n = 5). Sprague–Dawley normotensive rats served as controls (n = 6). After 4 weeks of treatment animals were euthanized and the left ventricle (LV) and the structural changes in intracardiac arterioles and aorta were assessed histomorphometrically. Smooth muscle cell phenotypes and fibrillar collagen content of the aortic wall were evaluated by immunostaining, using differentiation markers—specific antibodies and Syrius red staining, respectively. The changes in ETA and ETB receptor density were also assessed with quantitative autoradiography. Results: Compared to placebo, only irbesartan lowered BP (P<0.001) and prevented LV and small resistance artery hypertrophy. The aorta of placebo-treated TGR showed an increase in foetal-type smooth muscle cell content and fibrillar collagen staining, compared to controls. These changes were blunted by irbesartan, which increased ETA receptors in the arterial wall, enhanced by BMS-182874 and unaffected by bosentan. Nifedipine also blunted both the VSMC and collagen changes despite having no effect on BP and ETA receptors. Conclusions: In TGRen2, vascular hypertrophy entails both smooth muscle cell phenotypic modulation and collagen deposition. These alterations do not follow closely the BP changes and seem to imply the dihydropyridine-sensitive calcium channels.
THE ROLE OF RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS AND ITS LIGAND HIGH MOBILITY GROUP BOX 1 IN AUTOIMMUNE MYOCARDITIS
Authors: Anna Bangert, Martin Andrassy, Christian Volz, Anna-Maria Mueller, Felix Lasitschka, Renate Oettl, Vesna Vukovic, Angelika Bierhaus, Hugo. Katus, Ziya Kaya
Journal: Journal of the American College of Cardiology (2014)
52 A randomized trial of telbivudine (LDT) vs. adefovir for HBeAg-positive chronic hepatitis B: Results of the primary week 24 analysis
Authors: H.L.Y. Chan, C.L. Lai, M. Cho, J. Heathcote, Y.-M. Moon, Y.-C. Chao, R. Myers, G. Minuk, P. Marcellin, L. Jeffers, W. Sievert, R. Kaiser, G. Chao, N. Brown
Journal: Journal of Hepatology (2006)