tbuckley/cabot-search huggingface dataset:
776. A Novel Dual Functioning Non-Viral Vector - Delivering Genes While Targeting Nuclear Receptor Signaling
Authors: Feng Liu, Christine Conwell, Lisa Scollenbergen, Leaf Huang
Journal: Molecular Therapy (2005)

Non-viral vectors, for example cationic liposomes, have been widely used for in vivo and in vitro gene delivery. These vectors carry DNA through charge interactions into cells. The DNA, upon trafficking into a cell, will release in the cytoplasm and cross the nuclear membrane to gain access to the cellular transcriptional machinery. Currently, most efforts to design a new viral vector focus on only efficiently delivering DNA into cells, which lack an important function regulating nuclei transcription. Recent advances in molecular biology have greatly accelerated knowledge relating to the significance of nuclei transcriptional regulations. Therefore, a new generation of non-viral vectors should exhibit dual functions, which deliver not only xenogenic transgenes but also some candidate ligands targeting nuclear receptor signaling. Accordingly, the ligands delivered can trigger the nuclear receptor signaling that activates the transgene expression, or inactivates a target gene by co-delivery of inhibitors. In this study, we developed a dual function-vector by encapsulating CDCA (chenodexyxholic acid) as a ligand to target the nuclear receptor, farnesoid X receptor (FXR). FXR has been shown to be an essential regulator of bile acid and lipid metabolism. When CDCA binds to FXR, FXR forms a homodimer with the liver X receptor (LXR). Binding of the homodimer to FXR response element (FXRRE) trances chemical signals into transcriptional machinery of target genes which involve in various physiological processes.
273 SHORT TERM SAFETY, TOLERABILITY, PHARMACOKINETICS AND PRELIMINARY ACTIVITY OF GS-9450, A SELECTIVE CASPASE INHIBITOR, IN PATIENTS WITH CHRONIC HCV INFECTION
Authors: M.P. Manns, E. Lawitz, A.I.M. Hoepelman, H.J. Choi, J.Y. Lee, M. Cornpropst, W. Liang, B. King, K.R. Hirsch, D. Oldach, F.S. Rousseau
Journal: Journal of Hepatology (2010)
Antidiuresis and Other Renal Responses to Piperoxan in Pheochromocytoma
Authors: A. C. CORCORAN, HARRIET P. DUSTAN, IRVINE H. PAGE
Journal: Circulation (1956)

The clinical recognition of pheochromocytoma as a cause of hypertension is still a difficult problem for which the many tests that have been devised are at times inadequate. In this article an antidiuretic response to piperoxan in patients with pheochromocytoma is described. In view of the diuretic response of patients without pheochromocytoma, measurement of urinary flow after injection of piperoxan is suggested as a possible simple, confirmatory guide in diagnosis.
Caudal View Aid in Testicular Scanning
Authors: ARNOLD J. KRUBSACK, RASHI AKHTAR
Journal: Clinical Nuclear Medicine (1987)

A false-positive scan for testicular torsion can be obtained in a scrotal scan when either a hernia or hydrocele overlies the testicle. The case of a patient in whom a false-positive scan was avoided by the use of a caudal view is reported.
ADVANTAGES OF A NATIONAL DEPARTMENT OF HEALTH
Authors: J. H. Wolfe
Journal: JAMA (1918)

To the Editor:  —I believeThe Journalhas always favored a national health department or some arrangement by which the national government would have more power to enforce regulations tending to the prevention of disease and handling health problems for the good of the public in general. Conservation of life is more essential than conservation of labor, food, etc. I believe that if you could in some way bring more prominently to the people's mind the fact that during the first year of the war, barring battle fatalities, the death rate in the Army and Navy from disease was only one third as great as that in civil life of men of the same age before the war began, the public would favor such a department. I believe that if the recent epidemic of influenza had been handled by the government in all parts of the United States as it
Direct Observation of Induced Intravascular Thromboembolic Phenomena in the Living Extracorporeal Eye.
Authors: Arthur J. Seaman
Journal: Annals of Internal Medicine (1966)

s1 May 1966Direct Observation of Induced Intravascular Thromboembolic Phenomena in the Living Extracorporeal Eye.Arthur J. Seaman, M.D., F.A.C.P., C. Lawrence Lutcher, M.D., Charlotte Mofft, Bonita HueberArthur J. Seaman, M.D., F.A.C.P.Search for more papers by this author, C. Lawrence Lutcher, M.D.Search for more papers by this author, Charlotte MofftSearch for more papers by this author, Bonita HueberSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-64-5-1163_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA new experimental technique, the living extracorporeal eye (Seaman and associates: Clin. Res. 13: 138, 1965 (Abstract); Scand. J. Clin. Lab. Invest. Supplement 84, 17: 101, 1965) is used to study blood flow and thromboembolic phenomena. Bovine eyes are enucleated immediately after slaughter. The ciliary artery is catheterized. The retinal circulation is cleared with modified Krebs' solution. Perfusion with compatible oxygenated human or bovine blood is commenced and recorded with still and cinephotography.Upon addition of adenosine diphosphate to the heparinized arterial inflow, grossly visible platelet aggregates appear. These visible emboli impede flow and may adhere to the intima. They... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Portland, Oregon PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1966Volume 64, Issue 5Page: 1163-1163KeywordsAdenosine diphosphateArteriesBloodBlood flowPlatelets Issue Published: 1 May 1966 PDF DownloadLoading ...
Basic Clinical Parasitology
Authors: J. Walter Beck
Journal: JAMA (1964)

The second edition of<i>Basic Clinical Parasitology</i>reflects to a marked degree the touch of the senior author, who has apparently taken over the editing of Belding's text. The first edition was an abridged version of the well-known<i>Textbook of Clinical Parasitology</i>by Belding. Whereas it was a superb literary accomplishment, a feeling remained that the transition from the author's larger text to a "basic" book was not fully accomplished. Perhaps this is best achieved by another, for Brown has succeeded in making this transition rather well. Condensation by approximately 150 pages has resulted in an improved text, though such omissions as that of the formalin-ether concentration technique, for example, seem in error. Many line drawings have been simplified and life cycles made more readily understandable. The use of more photographs of clinical material has enhanced the value and interest for medical students and for physicians not likely to come
THE EFFECT OF NUCLEIC ACIDS AND OF CARBOHYDRATES ON THE FORMATION OF STREPTOLYSIN
Authors: Alan W. Bernheimer, Marcelle Rodbart
Journal: The Journal of Experimental Medicine (1948)

1. Ribonucleic acid of yeast causes the formation of a potent hemolysin in broth cultures of Streptococcus pyogenes. 2. The hemolysin whose formation is induced by yeast ribonucleic acid appears to be identical with streptolysin S. 3. Desoxyribonucleic acid, products of acid or alkaline hydrolysis of ribonucleic acid, or many other substances tested, fail to produce a similar effect. 4. Digestion by ribonuclease increases markedly the streptolysin-inducing activity of certain preparations of ribonucleic acid. 5. A fraction (AF) of yeast nucleic acid has been isolated which possesses approximately 100 times the streptolysin-inducing capacity of the starting material. Some of the properties which distinguish AF, a polynucleotide, from ordinary yeast nucleic acid are described. AF is associated with the ribonuclease-resistant fraction of yeast nucleic acid. 6. Ribonucleic acid prepared from streptococci, wheat germ, and mammalian liver, and subsequently treated with ribonuclease, is about as active in causing streptolysin formation as ribonuclease-treated yeast nucleic acid. 7. Ribonucleic acid of tobacco mosaic virus, tested under comparable conditions, was found to be inactive. 8. Ribonucleic acid prepared from streptococci, wheat germ, and tobacco mosaic virus resembles yeast nucleic acid in possessing a ribonuclease-resistant fraction. 9. In addition to AF, a factor (or factors), present in meat infusion and in peptone, was found to be required for the formation of streptolysin. 10. The factor can be partially replaced by any one of several carbohydrates, the most active being maltose, glucosamine, and trehalose, in that order. 11. When appropriate concentrations of AF, maltose, and glucose are used, the nucleic acid-induced streptolysin can be produced in a medium whose chemical composition is essentially defined.
Abstract 2055: Influence of intermittent hypoxia on differentiation in neuroblastoma
Authors: Vasantha Kumar Bhaskara, Indra Mohanam, Jasti S. Rao, Sanjeeva Mohanam
Journal: Cancer Research (2011)

Abstract Neuroblastomas are the most common extracranial solid tumors in children. Neuroblastomas derive from neural crest stem cells blocked at different stages of the sympathetic nervous system development. Neuroblastomas display a variety of histological features that range from undifferentiated tumors in patients with poor outcome to those containing differentiated cell types which show a better prognosis. Hypoxia has been linked to tumor progression and increased malignancy. Like the most common malignant solid tumors, neuroblastomas contain zones of chronic or acute hypoxia reflecting poor oxygenation. Transient hypoxia and subsequent reoxygenation are common phenomena in solid tumors that greatly influence the outcome of therapies. Differentiation is a key feature in pathologic classification and prognosis of neuroblastomas. The present study focuses on how intermittent hypoxia (IH) modulates the differentiation of neuroblastoma cells. IH-conditioned cells were derived by exposing tumor cells to 10 repeated cycles of hypoxia followed by reoxygenation. We found IH-induced changes in the expression of dedifferentiation markers and genes associated with neural crest-like phenotype in human neuroblastoma cells. The protein levels of HIF-1α, HIF-2α, tyrosine hydroxylase and c-kit were found upregulated in IH-conditioned human neuroblastoma cells as determined by western blotting. Similarly the expression of genes of neuronal crest phenotypic markers Oct-4, Notch-1and angiogenic molecule VEGF was found increased in IH-conditioned neuroblastoma cells. Expression of the cancer stem cell marker CD133 was also found increased in IH-conditioned neuroblastoma cells as evaluated by immunoflorescence analysis. Parallel studies were also performed in neuroblastoma cells exposed to hypoxia for 24h. It has been observed that IH-conditioned neuroblastoma cells exhibit increased expression of the proteins of dedifferentiation markers and genes associated with neural crest-like phenotype compared with neuroblastoma cells exposed to hypoxia for 24h. We cultured neuroblastoma cells, exposed the cells to defined doses of retinoic acid and studied neurite extension. A decrease in the levels of HIF-1α, and neuronal differentiation marker NF-M protein was observed in hypoxic neuroblastoma cells treated with retinoic acid. IH-conditioned neuroblastoma cells showed significantly less neurite extensions when compared with parental cells indicating that IH may suppress the differentiation of neuroblastoma cells. Taken together, our data suggest that IH inhibits differentiation and facilitates stem cell-like characteristics in human neuroblastoma cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2055. doi:10.1158/1538-7445.AM2011-2055
Tc-99m Leukocyte Scintigraphy in Infective Endocarditis
Authors: BRUCE K. ADAMS
Journal: Clinical Nuclear Medicine (1995)

A 56-year-old man with Staphylococcal aureus septicemia and clinically suspected infective endocarditis was imaged using Tc-99m HMPAO leukocytes. Although abnormal uptake was seen at 3 hours after injection, 24-hour images demonstrated marked concentration of radiolabeled leukocytes in a myocardial abscess and large posterior parietal infarct. In addition, multiple splenic infarcts were shown. The Tc-99m labeled leukocyte scan proved to be an excellent whole body screening procedure for diagnosing sites of infection and infarction in this patient.
Loss of orphan receptor small heterodimer partner sensitizes mice to liver injury from obstructive cholestasis
Authors: Young Joo Park, Mohammed Qatanani, Steven S. Chua, Jennifer L. LaRey, Stacy A. Johnson, Mitsuhiro Watanabe, David D. Moore, Yoon Kwang Lee
Journal: Hepatology (2008)

The orphan nuclear hormone receptor small heterodimer partner (SHP) regulates the expression of several genes involved in bile acid homeostasis in the liver. Because bile acid toxicity is a major source of liver injury in cholestatic disease, we explored the role of SHP in liver damage induced by common bile duct ligation (BDL). Shp −/− mice show increased sensitivity in this model of acute obstructive cholestasis, with greater numbers of bile infarcts and higher mortality than wild-type C57BL/6 mice. This increased sensitivity could not be accounted for by differences in expression of bile acid homeostatic genes 2 or 5 days after BDL. Instead, higher basal expression of such genes, including the key biosynthetic enzyme cholesterol 7α hydroxylase (Cyp7A1) and the bile salt export pump, is associated with both an increase in bile flow prior to BDL and an increase in acute liver damage at only 1.5 hours after BDL in Shp −/− mice, as shown by bile infarcts. At 3 hours, Cyp7A1 expression still remained elevated in Shp −/− with respect to wild-type mice, and the hepatic and serum bile acid levels and total hepatobiliary bile acid pool were significantly increased. The increased sensitivity of mice lacking SHP contrasts with the decreased sensitivity of mice lacking the farnesoid X receptor (FXR; nuclear receptor subfamily 1, group H, member 4) to BDL, which has been associated with decreased intraductal pressure and fewer bile infarcts. Conclusion: We propose that differences in acute responses to BDL, particularly the early formation of bile infarcts, are a primary determinant of the differences in longer term sensitivity of the Fxr −/− and Shp −/− mice to acute obstructive cholestasis.
Increased Carotid Atherosclerosis in Andropausal Middle-Aged Men
Authors: Juuso Mäkinen, Mikko J. Järvisalo, Pasi Pöllänen, Antti Perheentupa, Kerttu Irjala, Markku Koskenvuo, Juha Mäkinen, Ilpo Huhtaniemi, Olli T. Raitakari
Journal: Journal of the American College of Cardiology (2005)
Data on take home naloxone are unclear but not condemnatory
Authors: D. Bigg
Journal: BMJ (2002)

EDITOR—In Chicago we have been teaching active opiate injectors how to manage overdoses for some time, providing naloxone to appropriate people, as has been discussed in these letters columns.1 This programme now uses two physician volunteers who fill in the legally required prescription.

To date, we have reached over 550 people with this intervention and have received reports of 52 uses of naloxone in physically …
Molecular Determinants for Recognition of Divergent SAMHD1 Proteins by the Lentiviral Accessory Protein Vpx
Authors: David Schwefel, Virginie C. Boucherit, Evangelos Christodoulou, Philip A. Walker, Jonathan P. Stoye, Kate N. Bishop, Ian A. Taylor
Journal: Cell Host & Microbe (2015)

The SAMHD1 triphosphohydrolase inhibits HIV-1 infection of myeloid and resting T cells by depleting dNTPs. To overcome SAMHD1, HIV-2 and some SIVs encode either of two lineages of the accessory protein Vpx that bind the SAMHD1 N or C terminus and redirect the host cullin-4 ubiquitin ligase to target SAMHD1 for proteasomal degradation. We present the ternary complex of Vpx from SIV that infects mandrills (SIVmnd-2) with the cullin-4 substrate receptor, DCAF1, and N-terminal and SAM domains from mandrill SAMHD1. The structure reveals details of Vpx lineage-specific targeting of SAMHD1 N-terminal "degron" sequences. Comparison with Vpx from SIV that infects sooty mangabeys (SIVsmm) complexed with SAMHD1-DCAF1 identifies molecular determinants directing Vpx lineages to N- or C-terminal SAMHD1 sequences. Inspection of the Vpx-DCAF1 interface also reveals conservation of Vpx with the evolutionally related HIV-1/SIV accessory protein Vpr. These data suggest a unified model for how Vpx and Vpr exploit DCAF1 to promote viral replication.
Captopril and Impaired Renal Function
Authors: Vittorio E. Andreucci, Giuseppe Conte, Antonio Dal Canton
Journal: Annals of Internal Medicine (1986)

Letters and Corrections1 February 1986Captopril and Impaired Renal FunctionVITTORIO E. ANDREUCCI, M.D., GIUSEPPE CONTE, M.D., ANTONIO DAL CANTON, M.D.VITTORIO E. ANDREUCCI, M.D.Search for more papers by this author, GIUSEPPE CONTE, M.D.Search for more papers by this author, ANTONIO DAL CANTON, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-104-2-283_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In his report on captopril-induced renal insufficiency (1), Dr. Hricik confirms our results published in 1984 (2) and presented in June 1984 at the Congress of the International Society of Nephrology in Los Angeles.In our opinion, however, the impairment of renal function after administration of 25 mg of captopril during sodium depletion is not due to captopril, but to the combination of a fall in blood pressure and sodium depletion; unfortunately neither renal function nor blood pressure were evaluated immediately before administration of captopril. The decrease in blood pressure was probably not due to captopril (the...References1. HRICIK D. Captopril-induced renal insufficiency and the role of sodium balance. Ann Intern Med. 1985;103:222-3. LinkGoogle Scholar2. ANDREUCCI V. Different forms of ischemic/toxic acute renal failure in humans. In: ANDREUCCI VE, ed. Acute Renal Failure. Boston: Martinus Nijhoff Publishing; 1984:51-118. CrossrefGoogle Scholar3. SWARTZ S, WILLIAMS G, HOLLENBERG N, LEVINE L, DLUHY R, and MOORE T. Captopril-induced changes in prostaglandin production. J Clin Invest. 1980;65:1257-64. CrossrefMedlineGoogle Scholar4. USBERTI M, DI MINNO G, and UNGARO B. Effects of angiotensin II inhibition with Captopril on plasma ADH, prostaglandin synthesis, and renal function in normal man. Am J Physiol. (In press). Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAuthors: VITTORIO E. ANDREUCCI, M.D.; GIUSEPPE CONTE, M.D.; ANTONIO DAL CANTON, M.D.Affiliations: II Facoltà di Medicina e Chirurgia Università delgi Studi di Napoli 80131 Napoli, Italia PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byDrugs and the Kidney 1 February 1986Volume 104, Issue 2Page: 283-283KeywordsBlood pressureFallsNephrologySodium ePublished: 1 December 2008 Issue Published: 1 February 1986 PDF downloadLoading ...
Provision of Health Care for Persons With Developmental Disabilities Living in the Community
Authors: Philip R. Ziring
Journal: JAMA (1988)

Persons with developmental disabilities living in the community have a greater number and variety of health care needs than the average population of the same age and sex. The erroneous assumption that the generic health care system would be able to provide all necessary services to the large number of individuals recently transferred from state residential facilities to the community has proved to be an unexpected disappointment to human service policymakers. In an effort to remedy this situation, a program of health care services was established by the New Jersey Department of Human Services at a community teaching hospital to supplement the existing generic system of medical care. Within four years, the program had rapidly grown to provide care for 729 patients who had come to rely on the center for primary care, specialty medical and dental services, and medical case management. The demographic characteristics of this program are described as well as data on morbidity, service utilization, and special problems encountered when care was provided to this complex and medically underserved population.
Characteristics of the RNA synthesized in vitro by the normal human small lymphocyte and the changes induced by phytohemagglutinin stimulation
Authors: Umberto L. Torelli, Patrick H. Henry, Sherman M. Weissman
Journal: Journal of Clinical Investigation (1968)

These studies demonstrate that the circulating human small lymphocyte synthesizes ribonucleic acid (RNA) of high molecular weight which is not primarily a ribosomal precursor and which is, in part, complementary to human deoxyribonucleic acid (DNA). The stimulation of these lymphocytes by PHA brings a cell population in which few ribosomes are synthesized to a functional condition in which a large amount of these particles are produced. This increase in the synthesis of ribosomal RNA is one of the earliest and most relevant effects of PHA on the RNA metabolism of small lymphocytes.
Timed-Release Aspirin
Authors: Robert John
Journal: JAMA (1974)

To the Editor.—  As medical director of Glenbrook Laboratories, which markets timed-release aspirin, I was somewhat surprised that Dr. James Hoon (229:841, 1974) reported uncontrolled observations, which are, of course, open to interpretation, based on data from only three patients.  In the interest of furthering scientific inquiry, I would like to discuss a previously unpublished study on this subject that is in our files. In a well-controlled crossover study of 18 subjects who each received 250 microcuries of radioactive chromium to determine gastrointestinal blood loss from sustained-release aspirin, the mean blood loss did not reach any level of clinical significance. In real values, the mean average blood loss for the 18 subjects in the control period was 0.51 ml, whereas the mean for regular aspirin was 4.11 ml, and for sustained-release aspirin, 3.09 ml. The difference between the latter two figures is statistically significant, but the losses are clinically insignificant.
Obituary Listing
Authors: R. Santos
Journal: JAMA (1998)

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