tbuckley/cabot-search huggingface dataset:
Inhibition of platelet function by recombinant soluble ecto-ADPase/CD39.
Authors: R B Gayle, C R Maliszewski, S D Gimpel, M A Schoenborn, R G Caspary, C Richards, K Brasel, V Price, J H Drosopoulos, N Islam, T N Alyonycheva, M J Broekman, A J Marcus
Journal: Journal of Clinical Investigation (1998)

Excessive platelet accumulation and recruitment, leading to vessel occlusion at sites of vascular injury, present major therapeutic challenges in cardiovascular medicine. Endothelial cell CD39, an ecto-enzyme with ADPase and ATPase activities, rapidly metabolizes ATP and ADP released from activated platelets, thereby abolishing recruitment. Therefore, a soluble form of CD39, retaining nucleotidase activities, would constitute a novel antithrombotic agent. We designed a recombinant, soluble form of human CD39, and isolated it from conditioned media from transiently transfected COS-1 cells and from stably transfected Chinese hamster ovary (CHO) cells. Conditioned medium from CHO cells grown under serum-free conditions was subjected to anti-CD39 immunoaffinity column chromatography, yielding a single approximately 66-kD protein with ATPase and ADPase activities. Purified soluble CD39 blocked ADP-induced platelet aggregation in vitro, and inhibited collagen-induced platelet reactivity. Kinetic analyses indicated that, while soluble CD39 had a Km for ADP of 5.9 microM and for ATP of 2.1 microM, the specificity constant kcat/Km was the same for both substrates. Intravenously administered soluble CD39 remained active in mice for an extended period of time, with an elimination phase half-life of almost 2 d. The data indicate that soluble CD39 is a potential therapeutic agent for inhibition of platelet-mediated thrombotic diatheses.
Health Care Access and Birth Outcome
Authors: Bruce Ferguson
Journal: JAMA (1993)

<h3>To the Editor.</h3> —A recent article by Haas et al<sup>1</sup>reported that expansion of Medicaid coverage to uninsured low-income pregnant women with incomes up to 185% of federal poverty level "was not associated with improvements in access to prenatal care or birth outcomes." This is not surprising; Schlesinger and Dronebusch said that "requiring the states to expand Medicaid eligibility... is likely to yield small improvements in access, [and] may well create counterproductive side effects. While financial barriers undoubtedly are important, we believe that the relative importance of other attitudes, motivations, and constraints on women's behavior during pregnancy has not been adequately assessed... Ambivalent feelings about pregnancy [have] had a large effect on access to care."<sup>2</sup>Although some possible causes of the Massachusetts results were mentioned by Haas et al, ambivalent feelings about pregnancy or even "unwanted" pregnancy were not mentioned, although the high prevalence of ambivalent feelings about
Bendable Genes of Warm-blooded Vertebrates
Authors: Alexander E. Vinogradov
Journal: Molecular Biology and Evolution (2001)

It is shown that in the genomes of warm-blooded vertebrates the elevation of genic GC-content is associated with an increase in the bendability of the DNA helix, which is both absolute and relative as compared with random sequences. This trend takes place both in exons and introns, being more pronounced in the latter. At the same time, the free energy of melting (delta G) of exons and introns increases only absolutely with elevation of GC-content, whereas it decreases as compared with random sequences (again, this trend is stronger in the introns). In genes of cold-blooded animals, plants, and unicellular organisms, these regularities are weaker and often not consistent. Generally, there is a negative correlation between bendability and melting energy at any fixed GC-content value. This effect is stronger in the introns. These findings suggest that GC-enrichment of genes in the homeotherm vertebrates can be caused by selection for increased bendability of DNA.
Abstract 3209: Metformin suppresses the growth and modulates the metabolic profiles of pancreatic cancer cells under hypoxia in an IKKα-dependent manner
Authors: Nia Emami-Shahri, Eleni Maniati, Maud Bossard, Thorsten Hagemann
Journal: Cancer Research (2012)

Abstract Nuclear factor-βB; (NF-κB) controls a range of genes involved in inflammation, cell survival, growth and apoptosis. The dysregulated NF-κB pathway has been found to be involved in carcinogenesis and cancer progression. An IKKα-deleted mouse pancreatic cancer cell line was generated using a lentiviral construct with an shRNA. We investigated the effects of metformin, an anti-diabetic drug, on the cell proliferation and metabolism of these cells, under normoxic and hypoxic conditions. A high dose (5 mM) of metformin under normoxic conditions suppressed the growth of both wild-type and IKKα knockdown cell types; however, under hypoxic conditions IKKα knockdown cells were more sensitive to treatment than their wild-type counterpart (p &amp;lt; 0.001). Metabolic assays revealed that metformin treatment under normoxic conditions decreased the oxidative phosphorylation (OXPHOS) whilst increasing the lactate production of both cell types to similar levels. Under hypoxia, metformin treatment of both cancer cells resulted in decreased OXPHOS, with a more profound effect on the IKKα knockdown cells, and a significant decrease in lactate production in the IKKα knockdown cells only (p &amp;lt; 0.001). We believe our findings have implications for understanding the molecular mechanisms of metformin as a therapeutic agent in cancer treatment. 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 3209. doi:1538-7445.AM2012-3209
1102-48 Inhibitory effect of E5555, an orally active thrombin receptor antagonist, on intimal hyperplasia following balloon injury
Authors: Toshiyuki Matsuoka, Motoji Kogushi, Tsutomu Kawata, Akifumi Kimura, Ken-ichi Chiba, Takashi Musha, Hiroko Kobayashi, Tetsuya Kawahara, Shuichi Suzuki, Akiharu Kajiwara, Ieharu Hishinuma
Journal: Journal of the American College of Cardiology (2004)
A CONTROLLED COMPARISON OF AMITRIPTYLINE AND ELECTROCONVULSIVE THERAPY IN THE TREATMENT OF DEPRESSION
Authors: IAN M. McDONALD, MARJORIE PERKINS, GORDON MARJERRISON, MYROLAU PODILSKY
Journal: American Journal of Psychiatry (1966)

The purpose of this study was to compare the effects of amitriptyline and ECT in the treatment of depression. Thirty patients were assigned randomly to 4 treatment groups: amitriptyline, ECT, placebo and simulated ECT. Global improvement ratings, the Depression Rating Scale, the Ward Observation Inventory, the M.M.P.I., the Wechsler-Bellevue Intelligence Scale and the Bender-Gestalt test were used in evaluating the response to treatment. Amitriptyline and ECT were both more effective than control procedures. There was no appreciable difference after one month of treatment between the therapeutic effects of amitriptyline and ECT.
NT-12 * IMPACT OF HUMANIZED CHONDROITINASE ABC ON OV THERAPY FOR INTRACRANIAL TUMORS
Authors: A. Jaime-Ramirez, C. Bolyard, W. Meisen, N. Dmitrieva, Y. Banasavadi-Siddegowda, B. Kaur
Journal: Neuro-Oncology (2014)

Breast cancer is a leading cause of cancer death and source of brain metastases (BM) among women in the US. With a dismal two year survival of 2%, novel treatment modalities are essential. Chondroitin sulfate proteoglycan (CSPG) expression has been directly associated with metastatic potential in breast cancer. The Chondroitinase ABC (Chase) enzyme is able to digest CSPGs, thereby disrupting critical extracellular matrix interactions. We recently generated an oncolytic virus expressing Chase which resulted in some efficacy in mice bearing intracranial gliomas. Here, we developed a second generation Chase mutant (ChaseM) vector, which results in optimal enzymatic expression and function in mammalian cells. ChaseM decreases neurosphere formation in vitro, akin to the phenotype observed with pharmacologic blockade of CSPG assembly. In nude mice bearing glioma xenografts, OV-ChaseM led to a significant increase in median survival over control virus treated animals (p = 0.005). CSPGs in the CNS are formed as an integral part of the glial scar and implicated in the sequestration of inflammation at the site of insult. Thus, we hypothesize that the dissolution of CSPGs by OV-ChaseM will facilitate the influx of immune cells into the tumor stroma, alleviate microglia suppression and elevate T-cell responses following viral therapy, resulting in long term responses. We generated a syngeneic model of BM to test the ability of OV-ChaseM to facilitate these effects. Intracranial implantation of DB7 breast cancer cells results in 100% tumor development and pathology akin to human BM disease. In this model, a single dose of OV-ChaseM resulted in a significant survival advantage compared to controls (p = 0.02). Ongoing studies are evaluating the contribution of host anti-tumor immune activation towards this survival efficacy. With this data, we aim to broaden the scope of treatment for brain cancer patients and provide therapeutic evidence for regiments to be implemented in the clinic.
Crucial role for autophagy in degranulation of mast cells
Authors: Hiroko Ushio, Takashi Ueno, Yuko Kojima, Masaaki Komatsu, Satoshi Tanaka, Akitsugu Yamamoto, Yoshinobu Ichimura, Junji Ezaki, Keigo Nishida, Sachiko Komazawa-Sakon, François Niyonsaba, Tetsuro Ishii, Toru Yanagawa, Eiki Kominami, Hideoki Ogawa, Ko Okumura, Hiroyasu Nakano
Journal: Journal of Allergy and Clinical Immunology (2011)
The First Use of Penicillin in the United States
Authors: Andres G. Ortiz
Journal: Annals of Internal Medicine (2009)

Letters20 January 2009The First Use of Penicillin in the United StatesAndres G. Ortiz, MDAndres G. Ortiz, MDFrom Hospital de Lidice, Caracas 1070, Venezuela.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-150-2-200901200-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:After reading the article by Grossman (1), I became interested in learning about the first use of penicillin in my country. After searching the Internet, I found that the first reported use of penicillin in Venezuela was published in Gaceta Médica de Caracas in 1944. This journal, established in 1893 by Dr. Luis Razetti, was the first of its kind in Venezuela and the third of its kind in Latin America, after Gaceta Médica de México, established in 1864, and the Revista Médica de Chile, established in 1872. The article that I found was a preliminary report ...Reference1. Grossman CM. The first use of penicillin in the United States. Ann Intern Med. 2008;149:135-6. [PMID: 18626052] LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: From Hospital de Lidice, Caracas 1070, Venezuela.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe First Use of Penicillin in the United States Charles M. Grossman The First Use of Penicillin in the United States Jesse J. Waggoner The First Use of Penicillin in the United States Eric A. Jackson The First Use of Penicillin in the United States Charles M. Grossman Metrics Cited byThe First Use of Penicillin in the United StatesCharles M. Grossman, MD 20 January 2009Volume 150, Issue 2Page: 145KeywordsConflicts of interestInternetPenicillin ePublished: 20 January 2009 Issue Published: 20 January 2009 Copyright & PermissionsCopyright © 2009 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Magnetoliposomes Loaded with Poly-Unsaturated Fatty Acids as Novel Theranostic Anti-Inflammatory Formulations
Authors: Daniel Calle, Viviana Negri, Paloma Ballesteros, Sebastián Cerdán
Journal: Theranostics (2015)

We describe the preparation, physico-chemical characterization and anti-inflammatory properties of liposomes containing the superparamagnetic nanoparticle Nanotex, the fluorescent dye Rhodamine-100 and omega-3 polyunsaturated fatty acid ethyl ester (ω-3 PUFA-EE), as theranostic anti-inflammatory agents.Liposomes were prepared after drying chloroform suspensions of egg phosphatidylcholine, hydration of the lipid film with aqueous phases containing or not Nanotex, Rhodamine-100 dye or ω-3 PUFA-EE, and eleven extrusion steps through nanometric membrane filters.This resulted in uniform preparations of liposomes of approximately 200 nm diameter.Extraliposomal contents were removed from the preparation by gel filtration chromatography.High Resolution Magic Angle Spinning 1 H NMR Spectroscopy of the liposomal preparations containing ω-3 PUFA-EE revealed well resolved 1 H resonances from highly mobile ω-3 PUFA-EE, suggesting the formation of very small (ca. 10 nm) ω-3 PUFA-EE nanogoticules, tumbling fast in the NMR timescale.Chloroform extraction of the liposomal preparations revealed additionally the incorporation of ω-3 PUFA-EE within the membrane domain.Water diffusion weighted spectra, indicated that the goticules of ω-3 PUFA-EE or its insertion in the membrane did not affect the average translational diffusion coefficient of water, suggesting an intraliposomal localization, that was confirmed by ultrafiltration.The therapeutic efficacy of these preparations was tested in two different models of inflammatory disease as inflammatory colitis or the inflammatory component associated to glioma development.Results indicate that the magnetoliposomes loaded with ω-3 PUFA-EE allowed MRI visualization in vivo and improved the outcome of inflammatory disease in both animal models, decreasing significantly colonic inflammation and delaying, or even reversing, glioma development.Together, our results indicate that magnetoliposomes loaded with ω-3 PUFA-EE may become useful anti-inflammatory agents for image guided drug delivery.
Overexpression of cholesterol 7α-hydroxylase promotes hepatic bile acid synthesis and secretion and maintains cholesterol homeostasis
Authors: Tiangang Li, Michelle Matozel, Shannon Boehme, Bo Kong, Lisa-Mari Nilsson, Grace Guo, Ewa Ellis, John Y. L. Chiang
Journal: Hepatology (2010)

Abstract We reported previously that mice overexpressing cytochrome P450 7a1 (Cyp7a1; Cyp7a1-tg mice) are protected against high fat diet–induced hypercholesterolemia, obesity, and insulin resistance. Here, we investigated the underlying mechanism of bile acid signaling in maintaining cholesterol homeostasis in Cyp7a1-tg mice. Cyp7a1-tg mice had two-fold higher Cyp7a1 activity and bile acid pool than did wild-type mice. Gallbladder bile acid composition changed from predominantly cholic acid (57%) in wild-type to chenodeoxycholic acid (54%) in Cyp7a1-tg mice. Cyp7a1-tg mice had higher biliary and fecal cholesterol and bile acid secretion rates than did wild-type mice. Surprisingly, hepatic de novo cholesterol synthesis was markedly induced in Cyp7a1-tg mice but intestine fractional cholesterol absorption in Cyp7a1-tg mice remained the same as wild-type mice despite the presence of increased intestine bile acids. Interestingly, hepatic but not intestinal expression of several cholesterol (adenosine triphosphate–binding cassette G5/G8 [ABCG5/G8], scavenger receptor class B, member 1) and bile acid (ABCB11) transporters were significantly induced in Cyp7a1-tg mice. Treatment of mouse or human hepatocytes with a farnesoid X receptor (FXR) agonist GW4064 or bile acids induced hepatic Abcg5/g8 expression. A functional FXR binding site was identified in the Abcg5 gene promoter. Study of tissue-specific Fxr knockout mice demonstrated that loss of the Fxr , gene in the liver attenuated bile acid induction of hepatic Abcg5/g8 and gallbladder cholesterol content, suggesting a role of FXR in the regulation of cholesterol transport. Conclusion: This study revealed a new mechanism by which increased Cyp7a1 activity expands the hydrophobic bile acid pool, stimulating hepatic cholesterol synthesis and biliary cholesterol secretion without increasing intestinal cholesterol absorption. This study demonstrated that Cyp7a1 plays a critical role in maintaining cholesterol homeostasis and underscores the importance of bile acid signaling in regulating overall cholesterol homeostasis. (Hepatology 2011)
Drug-induced anogenital cicatricial pemphigoid
Authors: TH. VAN JOOST, W. R. FABER, H. R. MANUEL
Journal: British Journal of Dermatology (1980)

A case of cicatricial pemphigoid (CP) with a rare primary localization on the mucosal surfaces of the anus and the vulva and on perianal skin, associated with long-term therapy with clonidine, is described. Direct immunofluorescence investigation of lesional skin suggests possible complement mediated tissue injury in between basement membrane and epidermal basal cells. The possibility is discussed that drug induced metabolic disturbance (cyclic AMP-system) at a local level at the site of the basal cells might lead to the formation of immunogens and be one of the initiating factors in subepidermal bullous immune dermatoses. It is concluded that in cases of cicatricial pemphigoid the use of drugs must be considered as one of the aetiological possibilities.
Niemann-Pick Disease Type C
Authors: Raphael Schiffmann
Journal: JAMA (1996)

<h3>SELECTED CASES</h3><h3>Patient 1</h3> A full-term girl was born after normal pregnancy and delivery. Starting in the first few days of life, she developed prolonged neonatal jaundice with hepatosplenomegaly. Total bilirubin level was 92 μmol/L (5.4 mg/dL) at 10 weeks of age. The direct fraction was 52 μmol/L (2.9 mg/dL). By 10 months of age, the jaundice resolved. Because of persistent organomegaly, a liver biopsy was performed that showed cirrhosis with clusters of foam cells containing periodic acid—Schiff—positive material. Electron microscopy revealed amorphous laminated lysosomal inclusions in hepatocytes and in Kupffer cells. Subsequently, her spleen remained moderately enlarged and her liver was mildly enlarged with normal function. By 2 years of age, she was noted to have paresis of voluntary upgaze saccades (vertical supranuclear gaze palsy) and dystonic posture of both feet. When examined at 3 years of age at the National Institutes of Health, she had normal head circumference
Speech as an opportunistic vehicle of thinking
Authors: Csaba Pléh
Journal: Behavioral and Brain Sciences (2002)

Carruthers clearly identifies the basic issues involved in language and thought relations and argues for an adaptive central model. Similar conclusions were reached by classical research in the inner speech tradition. Sokolov (1968; 1972) especially emphasized that inner speech appears only when the task is difficult. The use of inner speech is not a necessity to transform representations, but it is called for when transformations become difficult. This might be related to the cognitive reorganizations leading to language as emphasized by Donald (2001).
Influence of early and current environmental exposure factors on sensitization and outcome of asthma in pre‐school children
Authors: E. Melén, M. Wickman, S. Nordvall, M. Van Hage‐Hamsten, A. Lindfors
Journal: Allergy (2001)

Background: Exposure to furred pets in early life has been considered to increase the risk of allergic sensitization and consequent development of asthma later in children. However, recently, it has been suggested that early exposure to pets prevents sensitization. The aim of this study was to evaluate the importance of early exposure to pets and other environmental risk factors in asthmatic children. Methods: This is a follow‐up study after 2 years of a previously investigated group of 193 asthmatic children, aged 1–4 years. The study was completed by 181 children, who were clinically examined; serum IgE antibodies were also measured and a questionnaire was answered. Results: Children with reported exposure to cats during the first 2 years of life were more likely to have developed sensitization to cat by 4 years of age than unexposed children. High levels of cat allergen (Fel d 1≥8 µg/g dust) were associated with an increased risk of sensitization to cat and, in combination with tobacco smoke, also with the development of more severe asthma. Conclusions: In young asthmatic children, early exposure to cat and tobacco smoke increased the risk of allergic sensitization and further development of more severe asthma later in childhood.
Abstract 5048: TAp73a enhances the cellular chemosensitivity to cisplatin in ovarian cancer cells
Authors: Pingde Zhang, Stephanie S. Liu, Hextan YS Ngan
Journal: Cancer Research (2010)

Abstract Ovarian cancer is the most lethal gynecological malignancy. Most ovarian cancer patients relapse and subsequently die due to the development of resistance to chemotherapy. Strategies for overcoming resistance to chemotherapy and improving prognosis of ovarian cancer patients are very critical. P73, one member of the tumor suppressor p53 family, shares highly structural and functional similarity to p53. Established evidence showed that p73 mediated cellular sensitivity to chemotherapeutic agents in some human tumor cells. However, the role of p73 in the regulation of cellular response to DNA damaging agents in ovarian cancer is still poorly understood, and the function of the transcriptionally active isoform TAp73 as a tumor suppressor is still controversial. The aim of the present study was to examine the effect of TAp73a on cellular response to commonly used chemotherapeutic agent cisplatin in ovarian cancer cells. We established TAp73a overexpressed stable clones in two ovarian cancer cell lines: OVCA433 (wild-type p53) and SKOV3 (null p53). We found that TAp73a enhanced chemosensitivity of ovarian cancer cells to cisplatin by inhibiting cell growth and inducing cell cycle arrest and apoptosis in wild-type p53 OVCA433 cells. Additionally, TAp73a up-regulated the p53 expression and its downstream genes: PUMA, NOXA, p53AIP1, and down-regulated the phosphorylation of Akt as assessed by western blotting. The accumulation of p53 protein induced by TAp73a was found at the post-transcriptional level. Co-immunoprecipitation assay demonstrated that TAp73a directly bound to p53 protein, suggesting that such interaction might block the degradation of p53 protein in OVCA433 cells. In p53-null SKOV3 cells, the increase of chemosensitivity induced by TAp73a was also observed, indicating that TAp73a also functioned independent of p53 by up-regulating the cell cycle inhibitor p21 expression. In conclusion, these results suggested that TAp73a might play an important role in the enhancement of cellular sensitivity to chemotherapeutic drug cisplatin in ovarian cancer cells through p53 dependent and independent pathways. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 5048.