tbuckley/cabot-search huggingface dataset:
472. Hematopoietic Cell Differentiation from Common Marmoset (Callithrix jacchus) Embryonic Stem Cells by Their Genetic Manipulation Using the Third Generation Lentiviral Vector
Authors: Tomoko Yokoo, Ryo Kurita, Erika Sasaki, Takashi Hiroyama, Yukoh Nakazaki, Kiyoko Izawa, Hajime Ishii, Yoshikuni Tanioka, Kisaburo Hanazawa, Yuan Son Bai, Yasushi Soda, Kenzaburo Tani
Journal: Molecular Therapy (2005)

Since the successful establishment of human embryonic stem (ES) cell lines in 1998, transplantation of differentiated ES cells to specific organ has been expected to complete their defective function as realistic medicine. However, the safety and efficacies of using differentiated human ES cells in vivo cannot be confirmed because of ethical regulation. So the preclinical studies using animal model systems including non-human primates are essential. We have already demonstrated that non-human primates of common marmosets (CM) are suitable for the laboratory animal models for preclinical studies of hematopoietic stem cell therapy. In this study, we investigated the in vitro differentiation of CMES cells to hematopoietic cells and developed the exogenous gene transfer methods suitable for CMES cells in order to study the feasibility of future gene modified ES cell therapy. First, in our in vitro culture condition, we could mainly obtain CFU-M colonies, occasionally CFU-GM and BFU-E colonies, although the frequency of inducing multipotent hematopoietic stem cells from CMES cells was low. To estimate this result as molecular level, we examined the expression patterns for various hematopoietic gene markers by RT-PCR during in vitro differentiation. The results showed that CD34, one of stem cell markers, was firstly detected at culture day14 and other markers, c-kit, and AC133, were also expressed in early phase. However, the expression of CD45 and gata1 could not be detected at least in this condition. These data were quite correspond to the results of CFU assay, suggesting that our culture condition is incomplete for hematopoietic induction although ES cells differentiated into mesodermal cells to some extent. Next we investigated the possibility of hematopoietic stem cell induction by gene transduction. To introduce exogenous DNA into CMES, VSV-G pseudotyped human immunodeficiency virus (lentiviral) vectors containing several kinds of promoters and GFP gene were constructed. When the HIV vector containing GFP gene under EF1a promoter was used, higher efficient transgenes of GFP could be confirmed in both undifferentiated and differentiated CMES cells. Using this vector system, we are now transducing several genes related to hematopoiesis such as tal1, gata1, gata2, bmi1, and hoxB4 genes into CMES cells to induce hematopoietic stem cell differentiation efficiently in vitro and in vivo.
Abstract 2571: The predictive biomarker for the resistance to antifolate
Authors: Takehiro Uemura, Tetsuya Oguri, Hiroaki Ozasa, Osamu Takakuwa, Yuki Tomita, Makoto Nakao, Takeshi Suzuki, Yasuhito Iwashima, Mikinori Miyazaki, Ken Maeno, Shigeki Sato, Ryuzo Ueda
Journal: Cancer Research (2010)

Abstract Currently, several folate-based antimetabolites are used for cancer treatment. Pemetrexed (MTA) is new generation antifolate which inhibits multiple folate-requiring enzymes, mainly thymidylate synthase (TS). We cultured small lung cell cancer cell line, PC-6 in the presence of MTA and established two MTA resistant cell lines, PC-6/MTA-1.6 and PC-6/MTA-4.0, which grew vigorously in medium containing 1.6uM and 4.0uM, respectively. These cell lines showed cross resistance to methotrexate (MTX), but not to other cytotoxic agents including etoposide, vinorelbine and cisplatin. Among many ATP-binding cassette (ABC) transporters, only ABCC11/MRP8 (ABCC11) gene expression was markedly increased in PC-6/MTA-1.6 cells. In contrast, TS gene expression was markedly increased in PC-6/MTA-4.0 cells. ABCC11 gene expression was not increased in PC-6/MTA-4.0 cells. There were no changes in reduced folate carrier and folylpoly-gamma-glutamate synthetase expression level in MTA resistant cells. To determine if the higher expression of the ABCC11 in the PC-6/MTA-1.6 cells resulted in a greater efflux of drugs, we assayed the intracellular accumulation of MTX, which is known to be a substrate for ABCC11 in the PC-6 and PC-6/MTA-1.6 cells and found that MTX accumulation in PC-6/MTA-1.6 cells was lower than PC-6 cells. We found that decrease of ABCC11 expression by ABCC11 siRNA enhanced MTA and MTX cytotoxicity in PC-6/MTA-1.6 cells. Decreasing the expression of TS by small interfering RNA (siRNA) also enhanced MTA and MTX cytotoxicity in PC-6/MTA-4.0 cells. These results give a concept that resistance for antifolate is advanced as TS gene expression is increased, while ABCC11 may work in early phase of resistance when TS expression is not enough induced. TS and ABCC11 may be useful as predictive biomarkers for the resistance to antifolate. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2571.
Bioethicists' Statement on the U.S. Supreme Court's<i>Cruzan</i>Decision
Authors: George J. Annas, Bob Arnold, Mila Aroskar, Peggy Battin, Dianne Bartels, Tom Beauchamp, Daniel Brock, Allen Buchanan, Arthur Caplan, Cynthia Cohen, Ronald Cranford, Rebecca Dresser, Nancy Dubler, Ruth Faden, Norman Fost, Joel Frader, Leslie Francis, Michael Grodin, Chris Hackler, Bruce Jennings, Marc Lappe, Ruth Macklin, David Mayo, Alan Meisel, Steven Miles, Haavi Morreim, Lawrence J. Nelson, Lisa Parker, Robert Pearlman, Donnie Self, Robyn Shapiro, James Walters, Stephen Wear, Robert Weir, Daniel Wikler, Stuart Youngner
Journal: New England Journal of Medicine (1990)

On June 25, 1990, the U.S. Supreme Court issued its long-awaited decision in the case of Nancy Cruzan, the first "right to die" case to come before it. The purpose of this statement is to clarify the meaning of that case in order to prevent misinterpretation that might lead to serious adverse consequences for hopelessly ill patients, their families, and health care professionals.First, the Supreme Court affirmed the right of competent patients to refuse life-sustaining treatment.Second, the Court did not treat the forgoing of artificial nutrition and hydration differently from the forgoing of other forms of medical treatment. . . .
Hemoglobin queens: α34 (B15) Leu‐Arg structural and functional properties and its association with Hb E
Authors: W. F. Moo‐Penn, D. L. Jue, M. H. Johnson, J. E. McGuffey, H. Simpkins, J. Katz
Journal: American Journal of Hematology (1982)

Abstract Hemoglobin Queens: α34 (B15) Leu‐Arg was found in association with Hb E in a Vietnamese boy. The observed microcytosis and hypochromia were due to Hb E, which also occurred in other members of this family. The functional properties of Hb Queens in the absence and presence of allosteric effectors were normal. The abnormal hemoglobins appear to be unrelated to the hyperbilirubinemia that was observed at birth.
734 Peginterferon alpha-2a (PEGASYS) plus ribavirin (COPEGUS) for 16 or 24 weeks in patients with HCV genotype 2 OR 3. Final results of the accelerate trial
Authors: M.L. Shiffman, S. Pappas, L. Nyberg, S. Greenbloom, A. Gibas, B. Bacons, J. Rasenack, F. Suter, M. Diago, A. Lin, A. Soman, S. Zeuzem
Journal: Journal of Hepatology (2006)
ABC of sexually transmitted diseases: molluscum contagiosum
Authors: M. Adler
Journal: BMJ (1984)

<h3>Abstract</h3> <h3>Summary</h3> We present ATAV, an analysis platform for large-scale whole-exome and whole-genome sequencing projects. ATAV stores variant and coverage data for all samples in a centralized database, which is then efficiently queried by ATAV to support diagnostic analyses for trios and singletons, as well as rare-variant collapsing analyses for finding disease associations in complex diseases. Runtime logs ensure full reproducibility and the modularized ATAV framework makes it extensible to continuous development of new functions. In recent years ATAV has not only been helpful for identifying disease-causing variants for a range of diseases, but has also enabled the discovery of novel genes by rare-variant collapsing on datasets containing more than 20,000 samples. Analyses to date have been performed on more than 110,000 sequenced individuals demonstrating that the framework is robust to large-scale studies. <h3>Availability and implementation</h3> ATAV is open source, cross-platform compatible, and is available under the MIT license at https://github.com/igm-team/atav
Gp budget holding in new zealand: lessons for Britain and elsewhere?
Authors: L Malcolm
Journal: BMJ (1997)

The recent election in New Zealand resulted in the new coalition government rejecting key aspects of the National government's controversial, Treasury led health reforms implemented in 1993.1 2 Based on the largely successful economic and state sector reforms of the 1980s, the health reforms had two key goals: improved efficiencies and better access, especially to elective surgery.3 Superficial assessment of the hospital sector had led to expectations that savings of 20-30% could be achieved through competitive and commercial incentives.3 Yet actual expenditure has increased by this amount, and waiting lists have grown by 50% since 1993.1 4 The new government favours collaboration over competition, and its health policy is to abolish the market oriented CHEs (Crown health enterprises) and replace them with regional hospital and community service units, which will be required to improve the health of their communities.2 The four regional purchasers that have a contract with providers are to be replaced with a central funding authority. The funder-provider split remains, but “purchasing” has been rejected as being too commercial. The government now seems to recognise that health is primarily a social service, not a business. The bottom line is not profit; it is better health outcomes.

The new government has recognised that collaboration may be much more effective than competition as an incentive in health care.5 6 Nowhere has this collaboration been more clearly demonstrated than in primary care through the formation of independent practice associations.7 The concept of independent practice associations, and their moves towards managed and integrated care, was borrowed from the United States. In practice, however, these associations have been much closer to British fundholding.7 8

Initial opposition to independent practice associations from the medical profession …
Hyperoxic lung injury reduces exogenous surfactant clearance in vivo.
Authors: W E Novotny, B B Hudak, S Matalon, B A Holm
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

We studied the rate of clearance of treatment doses of radiolabeled calf lung surfactant extract, which was instilled into the lungs of young adult rabbits exposed to air (control) or 100% oxygen for 64 h. More than 75% of the instilled surfactant remained lung-associated at all time points up to 24 h post-instillation in both groups; however, significantly more of the labeled phosphatidylcholine (PC) remained in the alveolar wash of oxygen-exposed rabbits (44 +/- 9% in 100% O2 versus 27 +/- 5% in controls at 6 h and 27 +/- 2% in 100% O2 versus 6 +/- 1% in control rabbits at 24 h, p < 0.05). Less of the labeled PC could be found in type II pneumocytes isolated from the oxygen exposed animals than in control animals, both at 6 h (24 +/- 2 cpm/10(6) cells in O2 versus 38 +/- 7 cpm/10(6) cells in control) and 24 h (42 +/- 5 cpm/10(6) cells in O2 versus 70 +/- 12 cpm/10(6) cells in control) post-instillation. Type II cells from animals exposed to 100% oxygen also demonstrated significantly lower PC synthesis rates than cells from lungs of control animals. Interestingly, clearance of exogenous surfactant in rabbits exposed to 100% oxygen for 48 h, an exposure that does not cause significant type II pneumocyte dysfunction, was not different from control. We concluded that injury to type II pneumocytes may result in decreased clearance of instilled surfactant from the alveolar space and may be important in determining dosing regimens for the use of surfactant therapy in adult respiratory distress syndrome.
Abstract 166: A novel therapeutic approach for triple negative breast cancer
Authors: Thiyagarajan Boopalan, Arunkumar Arumugam, Suman Suman, Trinath P. Das, Chendil Damodaran, Rajkumar Lakshmanaswamy
Journal: Cancer Research (2012)

Abstract Triple negative breast cancers (TNBCs) are defined as tumors that lack expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (EGFR2). TNBCs account for 15-20% of all breast tumors. These breast tumors are usually aggressive and have a specific molecular profile. Unfortunately, treatment options for TNBCs are limited, leading to a poor prognosis and high mortality rates. Thus, novel therapeutic approaches are needed to treat TNBCs. To date, several molecular targets have been identified (e.g., PARP, EGFR, mTOR, Akt, and BRAC-1). Moreover, many pre-clinical and clinical trials are underway to determine the efficacy of specific inhibitors against these molecular targets, used either alone or in combination with chemotherapeutic agents. So far, these trials have failed to produce significant promising results. Hence, our goal is to identify novel therapeutic agents that specifically target breast tumor cells, especially TNBCs, without causing toxicity to normal cells. Our studies identified nimbolide as a novel therapeutic agent. Nimbolide is a major bioactive compound derived from the Azadirachta indica (Neem) leaves, which is well-known medicinal plant having a wide spectrum of biological activities. In our studies, nimbolide targeted TNBC cells without causing toxicity to normal primary breast epithelial cells. We also explored the molecular mechanism underlying the anti-cancer effect of nimbolide on TNBC cells and found that nimbolide, simultaneously inhibited phosphorylation of Akt mediates pro-survival signaling. In addition, downstream signaling by mTOR and NF-kappa-B was down regulated by nimbolide which resulted in the induction of pJNK and pc-Jun mediated pro-apoptotic signaling and apoptosis in TNBC cells. These changes in the pro and anti-apoptotic molecular circuits also inhibited migration and invasion properties of TNBC cells. Altogether, our results strongly suggest that nimbolide could be a potent compound for the prevention and/or treatment of TNBC. Our ongoing in vivo studies may reveal the in vivo efficacy of nimbolide and toxicity to other organs or cells if any. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 166. doi:1538-7445.AM2012-166
Flavopiridol causes early mitochondrial damage in chronic lymphocytic leukemia cells with impaired oxygen consumption and mobilization of intracellular calcium
Authors: Syed-Rehan A. Hussain, David M. Lucas, Amy J. Johnson, Thomas S. Lin, Alan P. Bakaletz, Vinh X. Dang, Serge Viatchenko-Karpinski, Amy S. Ruppert, John C. Byrd, Periannan Kuppusamy, Elliott D. Crouser, Michael R. Grever
Journal: Blood (2008)
Controversy over Sclerotherapy for Malignant Pleural Effusions
Authors: Daniel J. Wallace
Journal: Annals of Internal Medicine (1994)

Letters15 July 1994Controversy over Sclerotherapy for Malignant Pleural EffusionsDaniel J. Wallace, MDDaniel J. Wallace, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-121-2-199407150-00020 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:The comprehensive review by Walker-Renard and colleagues [1] of chemical pleurodesis for malignant pleural effusions claimed to have selected all articles since 1966 involving 1168 patients treated with 13 different agents.Inexplicably, one of the most important agents, quinacrine, was omitted. Far more commonly used than most of the chemicals discussed, quinacrine is an extremely effective agent. For example, within the last year it was shown to be superior to bleomycin in a randomized study [2]. Two other relevant studies are cited here that allow the reader to access the 20 to 30 articles on the subject, ...References1. Walker-Renard PB, Vaughan LM, Sahn SA. Chemical pleurodesis for malignant pleural effusions. Ann Intern Med. 1994; 120:56-64. Google Scholar2. Koldsland S, Svennevig JL, Lehne G, Johnson E. Chemical pleurodesis in malignant pleural effusions: a randomised prospective study of mepacrine versus bleomycin. Thorax. 1993; 48:790-3. Google Scholar3. Janzig HM, Derom A, Derom E. Intrapleural quinacrine instillation for recurrent pneumothorax or persistent air leak. Ann Thorac Surg. 1993; 55:369-71. Google Scholar4. Argenius V, Chmielewska J, Widstrom O, Blomback M. Pleural fibrinolytic activity is decreased in inflammation as demonstrated in quinacrine pleurodesis treatment of malignant pleural effusion. Am Rev Respir Dis. 1989; 140:1381-5. Google Scholar5. Wallace DJ. The use of quinacrine (Atabrine) in rheumatic diseases: a reexamination. Semin Arthritis Rheum. 1989; 18:282-97. Google Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 15 July 1994Volume 121, Issue 2Page: 150-151KeywordsAntimalarialsPharmacistsPleural effusion ePublished: 15 August 2000 Issue Published: 15 July 1994 Copyright & PermissionsCopyright © 1994 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Gastroptosia Not Gastroptosis. Perityphlitis Not Appendicitis.
Authors: William J. Robinson
Journal: JAMA (1902)

New York City, Aug. 16, 1902. <h3>To the Editor:</h3> —We physicians are frequently charged by intelligent laymen with a love for hair-splitting, with fighting over unimportant trifles, with wasting our energies on speculative theories, etc., while neglecting the most important part, the welfare of the patient. Dr. Rose's letter in to-day's issue ofThe Journalshows conclusively that those charges are not without foundation. To judge by the intense earnestness of his tone and by the severity of his remonstance to the journals which have been so sacrilegious as to print gastroptosis and nephroptosis instead of gastroptosia and nephroptosia, one would think that it was a matter of life and death, that it was an important question in therapeutics, the proper discussion of which involved the weal or. woe of thousands of suffering patients. Oh, those hair-splitting purists! In spite of repeated admonitions, they seem to forget (or do not
Personalized Management of Hyperglycemia in Type 2 Diabetes
Authors: Itamar Raz, Matthew C. Riddle, Julio Rosenstock, John B. Buse, Silvio E. Inzucchi, Philip D. Home, Stefano Del Prato, Ele Ferrannini, Juliana C.N. Chan, Lawrence A. Leiter, Derek LeRoith, Ralph DeFronzo, William T. Cefalu
Journal: Diabetes Care (2013)

In June 2012, 13 thought leaders convened in a Diabetes Care Editors’ Expert Forum to discuss the concept of personalized medicine in the wake of a recently published American Diabetes Association/European Association for the Study of Diabetes position statement calling for a patient-centered approach to hyperglycemia management in type 2 diabetes. This article, an outgrowth of that forum, offers a clinical translation of the underlying issues that need to be considered for effectively personalizing diabetes care. The medical management of type 2 diabetes has become increasingly complex, and its complications remain a great burden to individual patients and the larger society. The burgeoning armamentarium of pharmacological agents for hyperglycemia management should aid clinicians in providing early treatment to delay or prevent these complications. However, trial evidence is limited for the optimal use of these agents, especially in dual or triple combinations. In the distant future, genotyping and testing for metabolomic markers may help us to better phenotype patients and predict their responses to antihyperglycemic drugs. For now, a personalized (“n of 1”) approach in which drugs are tested in a trial-and-error manner in each patient may be the most practical strategy for achieving therapeutic targets. Patient-centered care and standardized algorithmic management are conflicting approaches, but they can be made more compatible by recognizing instances in which personalized A1C targets are warranted and clinical circumstances that may call for comanagement by primary care and specialty clinicians.
Changes in Insulin Resistance and Cardiovascular Risk During Adolescence
Authors: Antoinette Moran, David R. Jacobs, Julia Steinberger, Lyn M. Steffen, James S. Pankow, Ching-Ping Hong, Alan R. Sinaiko
Journal: Circulation (2008)

Background— Developmental changes in insulin resistance and cardiovascular risk were studied in youths 11 to 19 years of age. Methods and Results— A cohort was randomly selected after blood pressure screening of Minneapolis, Minn, school children. Studies were done 3 times on this cohort and once on their siblings (996 observations on 507 individuals from 363 families). Insulin sensitivity was determined by euglycemic clamp. Body mass index and waist circumference increased similarly in both sexes from ages 11 to 19 years. Body fat decreased in males and increased in females ( P &lt;0.001). Lean body mass increased at a steeper rate in males ( P &lt;0.0001). Insulin resistance was lower in males at 11 years but increased steadily to 19 years ( P =0.003); in contrast, it did not increase in females. Thus, despite being less insulin resistant at 11 years and decreasing in fatness during puberty, males became more insulin resistant than females by 19 years of age. Triglycerides increased in males and high-density lipoprotein cholesterol decreased, whereas the opposite pattern was seen in females, which resulted in higher triglycerides and lower high-density lipoprotein cholesterol in males at 19 years. No gender difference in low-density lipoprotein or total cholesterol was seen. Systolic blood pressure increased in both sexes but at a greater rate in boys ( P =0.03). Conclusions— During the transition from late childhood through adolescence, insulin resistance in males increased in association with increased triglycerides and decreased high-density lipoprotein cholesterol, despite a concurrent reduction in body fatness, whereas the opposite occurred in females. These gender-related developmental changes in insulin resistance, which were independent from changes in fatness, total cholesterol, and low-density lipoprotein cholesterol, are consistent with an early role for insulin resistance in the increased cardiovascular risk found in males.
Physiology and Natural History of Obesity
Authors: Ralph A. Nelson
Journal: JAMA (1973)

Physiologic studies reported here show that obese persons use carbohydrate, fat, and protein normally during rest and exercise and are not unusually efficient in the use of these energy substrates. Obese subjects mobilize fat stores for energy as readily as normals. It is not necessary to overeat to become obese; the decrease of basal calorie requirements with age is such that obesity can develop with advancing age while exercise remains constant, even if food intake is reduced to some extent. Subjects tested were persons of various ages whose intake of food ranged from that of hypophagia to that of hyperphagia and whose body weights varied similarly.