tbuckley/cabot-search huggingface dataset:
626. Ultrasound-Triggered/Enhanced Delivery of Oligonucleotides into Aorta
Authors: Shao-LIng Huang, David D. McPherson, Robert C. MacDonald
Journal: Molecular Therapy (2005)

Synthesized oligonucleotides (ODNs) are used in anti-sense and anti-gene technology to control gene expression. As tissues and cells do not easily take up ODNs, the development of inexpensive and effective approaches to transiently decrease gene expression in vivo would be useful clinically. These data demonstrate that ultrasound can release ODNs from acoustically-active cationic liposomes and increase the delivery of ODNs into cultured rat aorta tissue. Cationic liposomes were made using the component lipids 1, 2-Myristoyl-sn-glycero-3-ethylphosphocholine(EDMPC), phosphotidylcholine and cholesterol (CH). Liposomes were made acoustically-active by sonication in water, addition of mannitol, freezing, lyophilization, and rehydration. Acoustically-active lipoplexes were made by mixing ODNs with acoustically-active liposomes in a ratio of 1:2. Ultrasound triggered-ODN release was measured as follows: acoustically-active liposomes/FITC-ODNs complex were incorporated with cultured cells, ultrasound (1 MHz, 2W/cm2,10% duty cycle for 10 seconds) was applied after washing out all free ODNs and unattached lipoplexes. The release of ODNs into solution was measured before and after the ultrasound application. ODN release was calculated by subtracting the fluorescence of the background media from the cellular fluorescence. One application of ultrasound caused a 45% release of attached FITC-ODNs from cationic liposomes. Nuclear localization of FITC-ODNs can be seen immediately after ultrasound application in about 3% of the cells. This delivery method was also tested on arterial tissue using freshly-removed rat aorta. Acoustically-active lipoplexes were injected into the endothelium of the aorta in a perfusion system with 20 cm H2O pressure. Ultrasound (1 MHz, 2W/cm2,100% duty cycle) was applied to the aorta for 60 seconds. Aortas were then washed and frozen-sectioned. The distribution of FITC-ODNs was assessed by fluorescent microscopy. Ultrasound enhanced the transport of ODNs through endothelium and the FITC-ODNs was seen extending into the arterial media. These results suggest that ultrasound can both increase the release of nucleic acid from acoustically-active liposome complexes as well as increase the penetration of oligonucleotides into a complex tissue such as arterial muscle. These data indicate that therapeutic transfer using these methods is possible. (See Figure)
Effect of stress on the paracellular barrier in the rat ileum
Authors: E Mazzon
Journal: Gut (2002)

Restraint stress induces permeability changes in the rat small intestine but little is known of the ultrastructural events leading to defects of the paracellular sealing or of the short term evolution of these alterations.In the present study, we performed transmission electron microscopy in the terminal ileum perfused with lanthanum after two hours of immobilisation stress and in non-stressed control rats. Moreover, immunohistochemistry of the tight junction (TJ) associated proteins, occludin and zonula occludens 1 (ZO-1), was carried out together with western blot analysis of the transmembrane protein occludin. TJ morphology was also assessed after a 22 hour recovery period.Immobilisation stress induced a significant increase in epithelial permeability to the lanthanum tracer (p<0.005) which recovered completely after 22 hours. Compared with unstressed controls, in stressed rats no differences were found on freeze fracture analysis. The TJ related immunofluorescence signals of occludin and of ZO-1 were irregularly distributed in stressed rats after two hours but returned to a normal pattern at 24 hours although with minor intensity. No quantitative alterations in occludin were detectable in stressed rats by immunoblot whereas a perinuclear concentration of occludin was observed by immunolocalisation.Immobilisation stress induced an increase in TJ permeability in the rat terminal ileum. These changes were mainly due to modifications and redistribution of the TJ transmembrane protein occludin and of the plaque protein ZO-1 whereas protein synthesis, at least that of occludin, was not affected by stress.
Charcot Arthropathy Secondary to Amyloid Neuropathy
Authors: Steven J. Peitzman
Journal: JAMA (1976)

Neuropathic (Charcot) ankle joints developed in a 50-year-old patient with end-stage renal disease from primary, nonfamilial amyloidosis. Sensory neuropathy in the legs had been noted three years before the onset of uremia and had progressed. Sural nerve, but not synovial biopsy specimen, showed amyloid in and around arteriolar walls by light and electron microscopy. Since Charcot joints are only rarely associated with amyloid neuropathy, it is possible that uremic neuritis, or prolonged survival by dialysis, contributed to progression of the neuropathy, allowing subsequent joint degeneration. (<i>JAMA</i>235:1345-1347, 1976)
Education of the Health Team
Authors: Luther Christman
Journal: JAMA (1970)

The rapid changes that are occurring in the social scene are acting as catalysts to bring about an extensive reformulation of the modus operandi of the relationships between the health professions. An affluent society, an educated public, the unprecedented pile-up of technology, and the rapid expansion of scientific knowledge are the ingredients of ferment. All of these social events, in some form or other, are becoming interlaced with the so-called activist movement at numerous levels of society in many different kinds of settings. This interaction is causing so much turbulence that the old, settled way by which the members of the health professions have worked with one another no longer seems functional. In all likelihood, the pace of change in all of the above variables will accelerate. Given this set of conditions, it appears wise and prudent to begin now to plan together to develop educational patterns and work arrangements.
Physicochemical and physiological properties of cholylsarcosine. A potential replacement detergent for bile acid deficiency states in the small intestine.
Authors: J Lillienau, C D Schteingart, A F Hofmann
Journal: Journal of Clinical Investigation (1992)

The properties of cholylsarcosine (the synthetic N-acyl conjugate of cholic acid with sarcosine [N-methylglycine]) were examined to determine its suitability as a bile acid replacement agent for conditions of bile acid deficiency in the small intestine, which causes fat malabsorption. Previous studies in rodents had shown that the compound was well transported by the liver and ileum and underwent neither deconjugation nor dehydroxylation during enterohepatic cycling. By 1H-nuclear magnetic resonance, cholylsarcosine was found to exist in dilute aqueous solution as an almost equimolar mixture of two geometric isomers--cis and trans (around the amide bond)--in contrast to cholylglycine, which was present entirely in the trans form. The critical micellization concentration was 11 mmol/liter, similar to that of cholylglycine (10 mmol/liter). By nonaqueous titrimetry, the pKa' of cholylsarcosine was 3.7, only slightly lower than that of cholylglycine (3.9). Cholylsarcosine was poorly soluble below pH 3.7, but highly soluble above pH 4. In vitro, cholylsarcosine behaved as cholylglycine with respect to promoting lipolysis by lipase/colipase. There was little difference between cholylsarcosine and cholylglycine in their solubilization of an equimolar mixture of oleic acid, oleate, and monoolein (designed to simulate digestive products of triglyceride) or in their solubilization of monooleyl-glycerol alone. When a [3H]triolein emulsion with either cholylsarcosine or cholyltaurine was infused intraduodenally in biliary fistula rats, recovery of 3H in lymph was 52 +/- 10% (mean +/- SD) for cholylsarcosine and 52 +/- 11% for cholyltaurine. When perfused into the colon of the anesthetized rabbit, cholylsarcosine (5 mmol/liter) did not influence water absorption or permeability to erythritol, in contrast to chenodeoxycholate, which induced vigorous water secretion and caused erythritol loss. We conclude that cholylsarcosine possesses the physicochemical and physiological properties required for a suitable bile acid replacement in deficiency states.
CD40 Is a Cellular Receptor Mediating Mycobacterial Heat Shock Protein 70 Stimulation of CC-Chemokines
Authors: Yufei Wang, Charles G. Kelly, Jaana T. Karttunen, Trevor Whittall, Paul J. Lehner, Lidia Duncan, Paul MacAry, Justine S. Younson, Mahavir Singh, Wulf Oehlmann, Genhong Cheng, Lesley Bergmeier, Thomas Lehner
Journal: Immunity (2001)
Industry and Bioethics: What Price the Relationship?
Authors: Mark Boyd, Wendy Rogers
Journal: PLoS Medicine (2006)

We read with interest the article by Mackie et al. entitled “Lessons on Ethical Decision Making from the Bioscience Industry” [ 1]. The authors recognise some study limitations, including the possibility of social desirability bias, but fail to address other limitations that in our view seriously weaken the paper. 

Firstly, there is no discussion regarding an understanding of the use of the term “ethics” by the authors and bioscience companies. There appears to be an assumption that “ethics” is a straightforward term whose meaning would be agreed by all those engaged in the field. However, the requirements of business ethics, for example, may differ significantly from the requirements of healthcare ethics. When one considers issues such as priority-setting, environmental concerns, sales and marketing, and the like, it is not clear that the ethical imperatives of the bioscience and healthcare industries substantially overlap. This study engages with what might be defined as procedural issues, but ignores substantive philosophical issues. The latter may have been beyond the scope of the paper, but if this were the case, it should have been acknowledged.

Secondly, there is no comment upon the authors' industry links. These are disclosed in their listing of their competing interests and include receipt of industry funding, direct links with companies subject to study, and funding awarded by some of the involved companies after the study. However, there is no discussion of the potential for these links to interfere with study conduct and interpretation. The authors do acknowledge the debate regarding bioethics and links with industry, but such acknowledgements cannot realistically compensate for the conflict of interest faced in the conduct of this particular study. Despite the growing literature on these links, there is no comprehensive analysis of industry-associated bioethics research [ 2, 3]. We cannot therefore confidently claim that there is an observable industry bias in such research. There is, however, overwhelming evidence that bias favourable toward funders occurs in medical research and healthcare prescribing [ 4–6]. It would therefore seem naive to believe that bioethicists are in some way immune from factors that demonstrably lead to bias in other disciplines. 

In addition to these omissions, the accompanying Perspectives commentary [ 7] neglects to discuss the implications of the conflicts of interest for the design, conduct, conclusions, and interpretation of the study. There was an allusion to these conflicts, but in this context we would have expected a review to be far more explicit regarding the potentially crucial importance of such conflicts. 

Ethicists are wooed by industry precisely because their views and opinions carry weight. This currency will soon become valueless unless researchers, authors, reviewers, and journal editors take a strong stand for intellectual honesty and self-critique in the presence of conflicts of interest.
Integrating Hospitals into Community Emergency Preparedness Planning
Authors: Barbara I. Braun, Nicole V. Wineman, Nicole L. Finn, Joseph A. Barbera, Stephen P. Schmaltz, Jerod M. Loeb
Journal: Annals of Internal Medicine (2006)

Background: Strong community linkages are essential to a health care organization's overall preparedness for emergencies. Objective: To assess community emergency preparedness linkages among hospitals, public health officials, and first responders and to investigate the influence of community hazards, previous preparation for an event requiring national security oversight, and experience responding to actual disasters. Design: With expert advice from an advisory panel, a mailed questionnaire was used to assess linkage issues related to training and drills, equipment, surveillance, laboratory testing, surge capacity, incident management, and communication. Setting: A simple random sample of 1750 U.S. medical–surgical hospitals. Participants: Of 678 hospital representatives that agreed to participate, 575 (33%) completed the questionnaire in early 2004. Respondents were hospital personnel responsible for environmental safety, emergency management, infection control, administration, emergency services, and security. Measurements: Prevalence and breadth of participation in community-wide planning; examination of 17 basic elements in a weighted analysis. Results: In a weighted analysis, most hospitals (88.2% [95% CI, 84.1% to 92.3%]) engaged in community-wide drills and exercises, and most (82.2% [CI, 77.8% to 86.5%]) conducted a collaborative threat and vulnerability analysis with community responders. Of all respondents, 57.3% (CI, 52.1% to 62.5%) reported that their community plans addressed the hospital's need for additional supplies and equipment, and 73.0% (CI, 68.1% to 77.9%) reported that decontamination capacity needs were addressed. Fewer reported a direct link to the Health Alert Network (54.4% [CI, 49.3% to 59.5%]) and around-the-clock access to a live voice from a public health department (40.0% [CI, 35.0% to 45.0%]). Performance on many of 17 basic elements was better in large and urban hospitals and was associated with a high number of perceived hazards, previous national security event preparation, and experience in actual response. Limitations: Responses reflect hospitals' self-perception of linkages. The quality of linkages and the extent of possible biases favoring positive responses were not assessed. Conclusions: In this baseline assessment, most hospitals reported substantial integration. However, results suggest that relationships between hospitals, public health departments, and other critical response entities are not adequately robust. Suggestions for enhancing linkages are discussed.
SIMILARITIES IN THE LIGHT CHAINS OF ANTI-γ-GLOBULINS SHOWING CROSS-IDIOTYPIC SPECIFICITIES
Authors: H. G. Kunkel, R. J. Winchester, F. G. Joslin, J. D. Capra
Journal: The Journal of Experimental Medicine (1974)

A marked homogeneity of the light chains was observed in an analysis of 17 IgM proteins with anti-gamma-globulin activity. The V region subgroups of the light chains were determined by both sequence and antigenic analysis. The latter procedure permitted large scale screening for comparisons with control proteins. The two methods showed general agreement in the determination of Kappa III proteins; all proteins positive by antigenic analysis were also positive by sequence but exceptions were noted in the opposite direction. The anti-gamma-globulins showed by antigenic analysis a 92% incidence of VK III light chains as compared to an incidence of 27% among 81 control proteins without this activity. A similar selection was observed for an antigen (VK III b) which subdivided the kappa III proteins. The major Wa group of anti-gamma-globulins which had been delineated previously on the basis of cross-idiotypic specificity was primarily responsible for the special light-chain selection. All the proteins of this group contain VK III light chains and all were of the VK III b type. Current evidence indicates that additional light-chain similarities were involved in the cross-idiotypic specificity of the Wa group. It thus appears that for the anti-gamma-globulins various levels of selection of light chains are manifest ranging from a preponderance of kappa type, of kappa III subgroup, of kappa III b sub-subgroup and perhaps of still further subdivisions to account for the cross-idiotypic specificity.
HEAT LABILE OPSONINS TO PNEUMOCOCCUS
Authors: Hyun S. Shin, Mary Ruth Smith, W. Barry Wood
Journal: The Journal of Experimental Medicine (1969)

When encapsulated type 25 pneumococci (Pn25) were opsonized with normal guinea pig serum, they consumed much more C3 than other complement (C) components. Fixation of C3 to the organisms was demonstrated by radio-labeling techniques, and its capsular localization was established by the use of monospecific anti-C3 antibody. Treatment of the serum with an appropriate dose of a purified cobra venom factor (VF) destroyed C3 and all of the opsonic activity, without appreciably affecting the other C components. Addition of purified C3 completely restored the opsonic activity of the VF-treated serum, indicating a requirement for C3. Since purified C3 alone had no opsonic activity, it was concluded that the C3 molecules had to be cleaved (to C3b) to function as opsonins. Experiments with C5-deficient mice revealed that C5 also plays a definite, but quantitatively less impressive, role in antipneumococcal defense.
DNA adducts in target and nontarget tissues of 3,2'-dimethyl-4-aminobiphenyl in rats.
Authors: T Shirai, M Tada, M Kojima, R Hasegawa, T Masui, N Ito
Journal: Environmental Health Perspectives (1994)

3,2'-Dimethyl-4-aminobiphenyl (DMAB) is a potent carcinogenic aromatic amine which demonstrates multiorgan tropism in rats. Using polyclonal antibodies against DMAB-DNA adducts, an immunohistochemical procedure as well as an ELISA were applied to investigate the relationship between DMAB-DNA adduct formation and tumorigenicity. Dose-related nuclear staining was observed 24 hr after application of the carcinogen but specificity in terms of sites of tumor development was lacking. No observable decrease in staining intensity was evident in most organs by 168 hr after administration of DMAB. Specific DNA lesions which could be responsible for carcinogenesis were not detected by the 32P-postlabeling method. The tumorigenic response of the ventral prostate in five strains of rats was roughly paralleled by DMAB-DNA adduct levels generated in the tissue. Strong enhancement of bladder tumor development by combined administration of the antioxidants, butylated hydroxyanisole, or butylated hydroxytoluene, with DMAB, was well correlated with an increase in DNA adducts. Our findings so far suggest that DNA adduct formation itself does not determine the carcinogenic organotropism of DMAB. Other factors (including cell proliferation and promotion by exogenous agents) may play important additional roles. For individual target organs or tissues, however, there seems to be a correlation between adduct levels and carcinogenic potential.
Persistent vitiligo induced by diphencyprone
Authors: P. Duhra, I.S. Foulds
Journal: British Journal of Dermatology (1990)

Journal Article Persistent vitiligo induced by diphencyprone Get access P. Duhra, P. Duhra The Skin Hospital, George Road, Edgbaston, Birmingham B15 1PR, U. K. Search for other works by this author on: Oxford Academic Google Scholar I.S. Foulds I.S. Foulds The Skin Hospital, George Road, Edgbaston, Birmingham B15 1PR, U. K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 123, Issue 3, 1 September 1990, Pages 415–416, https://doi.org/10.1111/j.1365-2133.1990.tb06306.x Published: 01 September 1990
Steroids in Alcoholic Hepatitis
Authors: J. J. ROBBINS
Journal: Annals of Internal Medicine (1971)

Letters, Comments, and Corrections1 August 1971Steroids in Alcoholic HepatitisJ. J. ROBBINS, M.D.J. J. ROBBINS, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-75-2-318 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: I was very much interested in the article by Helman and colleagues in the March 1971 issue of the ANNALS, attesting to the value of prednisolone in treatment of hepatic coma. I had been hesitant to credit steroid therapy for the recovery of my last half dozen or more patients from severe hepatic coma. Their controlled study was therefore gratifying in confirming my impressions.The editorial, "Alcoholic Hepatitis," by Reynolds and Edmondson in the same issue, however, quotes studies with conflicting results.What may appear to be an inconsequential detail is that in the series in which...References1. COPPAGEISLANDCOONER WDA: The metabolism of aldosterone in normal subjects and in patients with hepatic cirrhosis. J Clin Invest 41:1672-1680, 1962 CrossrefMedlineGoogle Scholar2. PETERSON R: Metabolism of adrenocorticosteroids in man. Ann NY Acad Sci 82:846-853, 1959 CrossrefMedlineGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: 1634 B St. Hayward, Calif. 945411 PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 August 1971Volume 75, Issue 2Page: 318-318KeywordsAlcoholicsComaHepatitisSteroid therapySteroids Issue Published: 1 August 1971 PDF downloadLoading ...
Abstract 675: Jarid2 is a novel target for lung cancer therapy.
Authors: Young K. Hong, Mary Zhang, Scott Atay, Manish Raiji, Trevor Upham, Julie A. Hong, Mahadev Rao, David S. Schrump
Journal: Cancer Research (2013)

Abstract Increasing evidence indicates that aberrant expression/activity of polycomb repressive-complex-2 (PRC-2) contributes to the pathogenesis of a variety of human malignancies including lung cancers. In recent studies we have demonstrated that depletion of EZH2- a core component of PRC-2, either by biochemical or pharmacologic techniques inhibits the malignant phenotype of lung cancer cells, indicating that PRC-2 is a target for epigenetic therapy of lung cancer. In the present study, we sought to further examine the potential efficacy of targeting PRC-2 in lung cancers via depletion of Jarid2, which modulates gene expression in stem cells in part via targeting PRC-2 to DNA. Quantitative RT-PCR and immunoblot experiments demonstrated over-expression of Jarid2 in cultured lung cancer cells and primary lung cancers relative to normal respiratory epithelia or histologically normal lung tissues. In subsequent experiments, shRNA techniques were used to inhibit Jarid2 expression in lung cancer cells. Quantitative RT-PCR and immunoblot experiments demonstrated that knock-down of Jarid2 had relatively modest effects on global H3K27Me3 levels in lung cancer cells. These finding were in contrast to knock-down of EZH2, which markedly inhibited H3K27 trimethylation in these cancer cells. Interestingly, knock-down of Jarid2 inhibited in vitro proliferation of lung cancer cells by approximately 70% relative to respective controls, and significantly diminished growth of subcutaneous lung cancer xenografts in athymic nude mice. The anti-proliferative effects of Jarid2 knock-down were relatively comparable to those observed following depletion of EZH2 in lung cancer cells. Jarid2 knock- down only modestly enhanced cytotoxicity mediated by DZNep in lung cancer cells. Microarray experiments are currently in progress to compare gene expression profiles in lung cancer cells mediated by Jarid2 knock-down relative to EZH2 depletion or DZNep treatment, and to delineate the mechanisms by which Jarid2 enhances the malignant phenotype of lung cancer cells. Collectively, these preliminary findings warrant further analysis of Jarid2 expression during pulmonary carcinogenesis, and suggest that Jarid2 may be a novel target for lung cancer therapy. Citation Format: Young K. Hong, Mary Zhang, Scott Atay, Manish Raiji, Trevor Upham, Julie A. Hong, Mahadev Rao, David S. Schrump. Jarid2 is a novel target for lung cancer therapy. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 675. doi:10.1158/1538-7445.AM2013-675