tbuckley/cabot-search huggingface dataset:
Molecular Biology of Liver Cancer Stem Cells
Authors: Naoki Oishi, Taro Yamashita, Shuichi Kaneko
Journal: Liver Cancer (2014)

Hepatocellular carcinoma (HCC) is one of the most common and lethal cancers worldwide. The concept of cancer stem cells (CSCs) is based primarily on the clinical and experimental observations that indicate the existence of a subpopulation of cells with the capacity to self-renew and differentiate as well as show increased resistance to radiation and chemotherapy. They are considered as the factors responsible for the cases of tumor relapse. Hepatic progenitor cells (HPCs) could form the basis of some hepatocellular carcinomas (HCC) and cholangiocarcinomas. Liver CSCs have been reported in multiple subtypes of HCC and are considered as the master regulators of HCC initiation, tumor metastasis, and progression. HPCs activators such as epithelial cell adhesion molecule (EpCAM), Wnt/β-catenin, transforming growth factor-beta (TGF-β), Notch and Hedgehog signaling systems expedite tumorigenesis or conversely, serve as a powerful cancer-prevention tool. Recent work has also identified Sal-like protein 4 (SALL4) and some epigenetic regulations as important molecules, while several therapeutic drugs that directly control HPCs have been tested both &lt;i&gt;in vivo&lt;/i&gt; and &lt;i&gt;in vitro&lt;/i&gt;. However, liver CSCs clearly have a complex pathogenesis, with the potential for considerable crosstalk and redundancy in signaling pathways. Hence, the targeting of single molecules or pathways may have limited benefit for treatment. In addition to the direct control of liver CSCs, many other factors are needed for CSC maintenance including angiogenesis, vasculogenesis, invasion and migration, hypoxia, immune evasion, multiple drug resistance, and radioresistance. Here, we provide a brief review of molecular signaling in liver CSCs and present insights into new therapeutic strategies for their targeting.
Rapamycin-regulated gene expression signature determines prognosis in breast cancer.
Authors: A Akcakanat, L Zhang, S Tsavachidis, F Meric-Bernstam
Journal: Cancer Research (2009)

Abstract Abstract #3072 Background: Mammalian target of rapamycin (mTOR) is a serine/threonine kinase involved in multiple intracellular signaling pathways promoting tumor growth. mTOR is aberrantly activated in a significant portion of breast cancers and is a promising target for treatment. Rapamycin and its analogues are in clinical trials for breast cancer treatment. Patterns of gene expression (metagenes) may also be used to simulate a biologic process or effects of a drug treatment. In this study, we tested the hypothesis that the gene-expression signature regulated by rapamycin could predict disease outcome for patients with breast cancer.&amp;#x2028; Methods: MDA-MB-468 breast cancer cell line is triple negative and PTEN null. Sensitivity of MDA-MB-468 breast cancer cell line to rapamycin was determined by in vitro growth assays and in vivo tumor studies. Total RNA was extracted from cell lines treated with rapamycin or DMSO for 24 hours and xenografts treated with DMSO or rapamycin for 1 or 22 days. Total RNA was used for expression profiling and hybridized to Affymetrix HG-U133 Plus 2.0 arrays. We used two well-described primary breast cancer datasets of 251 (Miller et al, Proc. Natl. Acad. Sci. USA 2005;102:13550) and 286 (Wang et al, Lancet. 2005;365:671) patients from the public domain and assessed the prognostic capability of rapamycin-regulated gene expression signatures.&amp;#x2028; Results: Colony formation and sulforhodazine B (IC50 &amp;lt; 1 nM) assays, and xenograft animals showed that MDA-MB-468 cells were sensitive to treatment with rapamycin. The comparison of in vitro and in vivo gene expression data identified a 31-gene expression signature that was up- regulated by rapamycin treatment in vitro as well as in vivo (FDR of 0.1). From the 31 genes on HG-U133 Plus 2.0 array, 20 that were included on HG-U133A array were used for analysis. In the Miller dataset, rapamycin metagene index (RMI) did not correlate with tumor size or lymph node status. High (0.75 percentile) RMI was significantly associated with longer survival (P=0.015). On multivariate analysis, RMI (P=0.029), tumor size (P=0.015) and lymph node status (P=0.001) were prognostic. In the Wang dataset, RMI predicted time to disease relapse (P=0.009).&amp;#x2028; Conclusion: Rapamycin-regulated gene expression signature predicts clinical outcome in breast cancer. This supports the central role of mTOR signaling in breast cancer biology and provides further impetus to pursue mTOR-targeted therapies for breast cancer treatment. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3072.
Searching Question: On-line or CD-ROM?
Authors: Mark L. Nelson
Journal: JAMA (1991)

<h3>Tb the Editor.</h3> —I was surprised to read that a discussion of MEDLINE database searching<sup>1</sup>excluded CD-ROM products and technology. Each of the features presented as desirable or attractive by Dr Hogan has been available on CD-ROM or on the locally based MEDLINE systems for at least the last 4 years. Not only do on-line services have a clearly outdated interface (such as single-line display or the inability to search abstracts), but CD-ROM products deliver far more than has ever been expected of on-line database searching and retrieval in the past. Likewise, it was a disservice to your readers for Hogan to imply that a professional searcher or medical librarian is not capable of getting what's needed when searching a medical database. To begin searching on-line, one is required to have a fairly sophisticated understanding of tree structures, indexing, and MESH syntax. Without MESH vocabulary assistance, most on-line searchers
Enhanced erythropoiesis in Hfe-KO mice indicates a role for Hfe in the modulation of erythroid iron homeostasis
Authors: Pedro Ramos, Ella Guy, Nan Chen, Catia C. Proenca, Sara Gardenghi, Carla Casu, Antonia Follenzi, Nico Van Rooijen, Robert W. Grady, Maria de Sousa, Stefano Rivella
Journal: Blood (2010)
Mechanisms Underlying Caloric Restriction and Lifespan Regulation
Authors: Zoltan Ungvari, Cristina Parrado-Fernandez, Anna Csiszar, Rafael de Cabo
Journal: Circulation Research (2008)

This review focuses on the emerging evidence that attenuation of the production of reactive oxygen species and inhibition of inflammatory pathways play a central role in the antiaging cardiovascular effects of caloric restriction. Particular emphasis is placed on the potential role of the plasma membrane redox system in caloric restriction–induced pathways responsible for sensing oxidative stress and increasing cellular oxidative stress resistance. We propose that caloric restriction increases bioavailability of NO, decreases vascular reactive oxygen species generation, activates the Nrf2/antioxidant response element pathway, inducing reactive oxygen species detoxification systems, exerts antiinflammatory effects, and, thereby, suppresses initiation/progression of vascular disease that accompany aging.
A Chimpanzee-Origin Adenovirus Vector Expressing the Rabies Virus Glycoprotein as an Oral Vaccine against Inhalation Infection with Rabies Virus
Authors: Dongming Zhou, Ann Cun, Yan Li, Zhiquan Xiang, Hildegund C.J. Ertl
Journal: Molecular Therapy (2006)

Rabies has the highest fatality rate of all human viral infections and the virus could potentially be disseminated through aerosols. Currently licensed vaccines to rabies virus are highly effective but it is unknown if they would provide reliable protection to rabies virus transmitted through inhalation, which allows rapid access to the central nervous system upon entering olfactory nerve endings. Here we describe preclinical data with a novel vaccine to rabies virus based on a recombinant replication-defective chimpanzee-origin adenovirus vector expressing the glycoprotein of the Evelyn Rokitniki Abelseth strain of rabies virus. This vaccine, termed AdC68rab.gp, induces sustained central and mucosal antibody responses to rabies virus after oral application and provides complete protection against rabies virus acquired through inhalation even if given at a moderate dose.
Evaluation of the forced oscillation technique for the determination of resistance to breathing
Authors: Aron B. Fisher, Arthur B. DuBois, Richard W. Hyde
Journal: Journal of Clinical Investigation (1968)

Total respiratory resistance (RT) was measured by the application of a sine wave of airflow to the mouth at the resonant frequency of the respiratory system. The mean respiratory resistance of 42 normal subjects, measured at a mean functional residual capacity of 3.3 liters, was 2.3, SD ± 0.5, cm H2O/liter per sec, and the resonant frequency was between 5 and 8 cycle/sec. The airway resistance measured in these same subjects with the body plethysmograph at a mean panting thoracic gas volume of 3.5 liters was 1.3, SD ± 0.3, cm H2O/liter per sec. Total respiratory resistance was found to vary inversely with lung volume (V) measured plethysmographically; prediction formulae for normal subjects based on this relationship are: RT (mean) = 7.1/V, RT (range) = 4.0/V to 11.6/V where V is in liters and RT is in cm H2O/liter per sec. When these criteria were applied to subjects with thoracic disease the following results were obtained: 17 subjects with obstructive lung disease all had elevated total respiratory resistance; 9 subjects with diffuse lung disease without airway obstruction all had normal respiratory resistance; all but 1 of 5 obese subjects and all but 2 of a heterogeneous group of 9 subjects without airway obstruction had normal respiratory resistance. Failure to take lung volume into account resulted in a considerable decrease in the ability to discriminate between obstructive and nonobstructive lung disease on the basis of the forced oscillation test. The resonant frequency of the respiratory system of patients with obesity or nonobstructive lung disease was similar to that obtained in the normal group; accurate evaluation of resonant frequency in subjects with obstructive lung disease was frequently not possible. The combined resistances of lung, thoracic wall and abdominal tissues were found to account for less than 43% of the total respiratory resistance in normal subjects and were only slightly increased by the presence of obesity, restrictive diseases of the thoracic wall, and hyperinflation of the thorax. The forced oscillation method is potentially of value in the study of resistance to breathing of patients who cannot undergo body plethysmography, such as acutely ill, anesthetized, or unconscious subjects. Accurate evaluation of RT requires an independent measure of lung volume as well as careful attention during measurements to the airflow rate, phase of respiration, and the adequacy of cheek compression and laryngeal relaxation.
Serum Aluminum Levels and Erythrocyte Dihydropteridine Reductase Activity in Patients on Hemodialysis
Authors: Paul Altmann, Farah Al-Salihi, Keith Butter, Paul Cutler, John Blair, Robert Leeming, John Cunningham, Frank Marsh
Journal: New England Journal of Medicine (1987)

Aluminum intoxication due to aluminum-containing antacids or dialysate can cause encephalopathy in patients undergoing hemodialysis, but the biochemical mechanism has not been defined. The enzyme dihydropteridine reductase (DHPR) is essential for the maintenance of normal brain concentrations of tetrahydrobiopterin, which is itself required for the synthesis of specific neurotransmitters. This enzyme is also present in erythrocytes. We measured erythrocyte DHPR activity and concentrations of the biopterin derivatives of its substrate and of aluminum in 38 patients on hemodialysis who had no clinical evidence of encephalopathy. Serum aluminum levels ranged from 15 to 190 micrograms per liter (mean, 67.6 +/- 7.7) as compared with 4.9 +/- 0.99 micrograms per liter in normal subjects. DHPR activity was inversely related to the serum aluminum concentration (r = -0.61, P less than 0.001) and was less than the activity predicted from the hemoglobin concentration in these patients. Serum concentrations of biopterin derivatives were markedly elevated. Eighteen patients were given the aluminum-chelating agent deferoxamine in a single dose, after which DHPR activity doubled. These studies suggest that aluminum inhibits DHPR activity in erythrocytes and that aluminum chelation reverses this effect. Although we did not directly measure DHPR activity in the brains of dialysis patients without encephalopathy, we propose that the reduction in activity in erythrocytes may reflect a similar reduction in the brain. Our findings could help to explain the encephalopathy associated with aluminum intoxication.
Breast cancer hotline to resume operation
Authors: Gail McBride
Journal: JAMA (1981)

For women with breast cancer who are confused about their treatment options, there is help on an authoritative lay level. Rose Kushner, a former breast cancer patient and a lay member of the President's National Cancer Advisory Board, will resume her telephone hotline for breast cancer patients on March 15. The new phone number of Kushner's Breast Cancer Advisory Service is not yet known, but the new offices of the service will be located at 7910 Woodmont Ave, Bethesda, MD 20014, very close to the National Cancer Institute (NCI). The one woman-plus-volunteers service has been in existence for more than four years and has handled 12,000 or so written and telephone inquiries during that time. But it has been located in Kushner's home and, partly because Kushner finds it difficult to refuse to help a worried woman in search of information, it got to be too disruptive for her and
Independent Roles of Apical Membrane Antigen 1 and Rhoptry Neck Proteins during Host Cell Invasion by Apicomplexa
Authors: Donatella Giovannini, Stephan Späth, Céline Lacroix, Audrey Perazzi, Daniel Bargieri, Vanessa Lagal, Camille Lebugle, Audrey Combe, Sabine Thiberge, Patricia Baldacci, Isabelle Tardieux, Robert Ménard
Journal: Cell Host & Microbe (2011)
Studies on the relationship between the level of specific IgE antibodies and the clinical expression of allergy: I. Definition of levels distinguishing patients with symptomatic from patients with asymptomatic allergy to common aeroallergens
Authors: Elide A. Pastorello, Cristoforo Incorvaia, Claudio Ortolani, Sergio Bonini, Giorgio W. Canonica, Sergio Romagnani, Alfredo Tursi, Carlo Zanussi
Journal: Journal of Allergy and Clinical Immunology (1995)
Factors influencing the ejection fraction and the mean rate of circumferential fibre shortening during atrial fibrillation in man
Authors: J. S. KARLINER, J. H. GAULT, R. J. BOUCHARD, J. HOLZER
Journal: Cardiovascular Research (1974)

Journal Article Factors influencing the ejection fraction and the mean rate of circumferential fibre shortening during atrial fibrillation in man Get access JOEL S. KARLINER, JOEL S. KARLINER 2 From the Cardiovascular Division, University of California at San Diego, La Jolla, California 92037, USA 2Reprint requests to Dr Joel S. Karliner, University Hospital of San Diego County, 225 West Dickinson Street, San Diego, California 92103, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar JAMES H. GAULT, JAMES H. GAULT From the Cardiovascular Division, University of California at San Diego, La Jolla, California 92037, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar RICHARD J. BOUCHARD, RICHARD J. BOUCHARD From the Cardiovascular Division, University of California at San Diego, La Jolla, California 92037, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar JOHN HOLZER JOHN HOLZER From the Cardiovascular Division, University of California at San Diego, La Jolla, California 92037, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 8, Issue 1, January 1974, Pages 18–25, https://doi.org/10.1093/cvr/8.1.18 Published: 01 January 1974
Targeting connexin 43 protects against the progression of experimental chronic kidney disease in mice
Authors: Ahmed Abed, Julie Toubas, Panagiotis Kavvadas, Florence Authier, Dominique Cathelin, Carlo Alfieri, Jean-Jacques Boffa, Jean-Claude Dussaule, Christos Chatziantoniou, Christos E. Chadjichristos
Journal: Kidney International (2014)
A CASE OF PAPULAR SYPHILIDE OF THE CONJUNCTIVA.
Authors: W. FRANKLIN COLEMAN
Journal: JAMA (1895)

As several of my confrères have never seen a secondary syphilitic lesion of the conjunctiva, and since, until recently, no case has come under my own observation, the disease seems sufficiently rare to demand that every instance of it be put on record. Before reporting our own case, we will take a glance at the literature of the subject, to illustrate the infrequency and the nature of syphilitic disease of the conjunctiva (especially secondary lesions) and will refer chiefly to Bull's excellent resumé in 1878, and to writings indicated under the head of "Diseases of the Conjunctiva" in the "Index Medicus" from its first issue (1879) to date. The following is taken from a paper by Charles Stedman Bull, M.D., in<i>American Journal Medical Sciences</i>, October, 1878: "Syphilitic lesions of the conjunctiva, existing independently, and not connected with lesions of the eyelid on the one hand, or the eyeball on
Short hairpin RNA-directed cytosine (CpG) methylation of the RASSF1A gene promoter in HeLa cells
Authors: Daniela Castanotto, Stella Tommasi, Mingjie Li, Haitang Li, Stephanie Yanow, Gerd P. Pfeifer, John J. Rossi
Journal: Molecular Therapy (2005)

Methylation of cytosines in CpG motifs is an important mechanism for epigenetic regulation of gene expression in mammalian cells. The initiating event(s) for de novo methylation in mammalian cells, particularly in cancer, is unknown. In plants, short RNAs homologous to DNA sequences are known to initiate de novo methylation. To investigate whether short hairpin RNAs (shRNAs) may also serve as initiators for de novo methylation in human cells we have expressed short hairpin RNAs complementary to the CpG island including the promoter and early transcribed regions of the human RASSF1A gene. RASSF1A encodes a putative tumor suppressor that is hypermethylated in a variety of human cancers, whereas in some human cell lines, such as HeLa, RASSF1A is unmethylated and transcriptionally active. We demonstrate that shRNAs complementary to the RASSF1A promoter or early transcribed regions can direct low levels of de novo DNA methylation and partial gene silencing in HeLa cells. In contrast, an shRNA harboring four central mismatches with the target cannot direct such methylation. The results presented suggest provocative potential mechanisms for transcriptional gene silencing via DNA methylation in cancer cells.
Existence of exine-free airborne allergen particles of Japanese cedar (Cryptomeria japonica) pollen
Authors: Y. Takahashi, M. Sakaguchi, S. Inouye, H. Miyazawa, K. Imaoka, S. Katagiri
Journal: Allergy (1991)

We investigated whether exine-free pollen allergen particles exist together with the intact pollen grains of Japanese cedar (Cryptomeria japonica) in the air during the pollen season in Yamagata City. First, we separated the allergen particles in an Andersen multi-stage air-sampler according to their aerodynamic diameters. The amount of major allergen (Cry j I) on each stage of the sampler was determined by a sensitive fluorometric sandwich ELISA, and the pollen count of the same samples was done by light microscopy after Carberla staining. Cry j I was found in stages 1 to 6, whereas most of intact and ruptured pollen grains were microscopically observed only in stages 1 and 2. Second, we suctioned the air through a tandem membrane filter system (the first filter, Nuclepore filter with 5 microns-pores; and the second, Millipore filter with 0.3 micron-pores). None of the pollen grains was detectable on the 0.3 micron-pore filter with light microscopy. However, Cry j I was detectable in the aqueous extract from the second filter. From these results, we concluded that pollen-free Cry j I existed in the air of Yamagata City during the pollen season.
A Fragile Balance
Authors: Asaf Bitton, Maria Yialamas, Bruce D. Levy, Joel T. Katz, Joseph Loscalzo
Journal: New England Journal of Medicine (2009)

A 31-year-old man presented to the emergency department with pain in the left shoulder. He had tripped over his backpack shoulder strap earlier in the day and noted immediate severe pain around his left shoulder. Physical examination revealed bony point tenderness over the humeral head and limited range of motion due to pain; crepitus was present. Shoulder radiographs revealed an impacted fracture of the left humerus and evidence of osteopenia.
Interaction of malaria and HIV in Africa
Authors: R. Reithinger, M. R Kamya, C. J. Whitty, G. Dorsey, S. H Vermund
Journal: BMJ (2009)

With the continuing surge in mergers and corporate takeovers in the realm of both public and private equity transactions, parties to these dealings are wise to examine carefully the role of the board of directors. Officers and directors, as well as management, may face a conflict of interest as they implement corporate change-of-control and other significant transactions. To effect a smooth transaction it is critical that precautions are taken to assure the “fairness” of the transaction and the process under state corporate law standards. This article examines the use of an independent, “disinterested” special committee in such a transaction. The committee9 proper function provides protection against potential legal challenges by disgruntled shareholders or competing bidders.
The Use of Drugs in Combination for the Treatment of Cancer
Authors: Vincent T. DeVita, Philip S. Schein
Journal: New England Journal of Medicine (1973)

INTEREST in the use of drugs in combination tor the treatment of cancer is not a new phenomenon. It stems from the inability to obtain entirely satisfactory results when available agents are given singly. Theoretical interest in this area can be traced back more than 10 years with the work of Goldin,1 Potter,2 Elion,3 Skipper,4 and Lepage and Sartorelli.5 6 7 The first major clinical effort began in the late 1950's, with the use of drug combinations in the treatment of neoplasms of the testes and other tumors.8 , 9 The current intensity of the interest in this approach derives from two major sources. . . .
High incidence of a concentration-dependent skin reaction in children treated with phenytoin.
Authors: J T Wilson, B Hojer, G Tomson, A Rane, F Sjoqvist
Journal: BMJ (1978)

A particularly high incidence of rash was seen in children with epilepsy treated with phenytoin. Ten children with untreated epilepsy were therefore included in a prospective study and given either 3 (group 1) or 6 (group 2) mg of phenytoin/kg body weight/day for five days followed by 6 mg/kg body weight/day for both groups. Four of the five children in group 2 compared with only one of the five in group 1 developed a rash seven to 12 days after the start of treatment. Patients with rashes had significantly higher plasma phenytoin concentrations. Whenever the phenytoin concentration was higher than 14 micromol/l on day 5 a rash occurred. These findings indicate that the generalised skin reaction is caused by a high body burden of phenytoin, which results from either a high load of the drug or a low clearance rate.