tbuckley/cabot-search huggingface dataset:
Focal Gains of <i>VEGFA</i> and Molecular Classification of Hepatocellular Carcinoma
Authors: Derek Y. Chiang, Augusto Villanueva, Yujin Hoshida, Judit Peix, Philippa Newell, Beatriz Minguez, Amanda C. LeBlanc, Diana J. Donovan, Swan N. Thung, Manel Solé, Victoria Tovar, Clara Alsinet, Alex H. Ramos, Jordi Barretina, Sasan Roayaie, Myron Schwartz, Samuel Waxman, Jordi Bruix, Vincenzo Mazzaferro, Azra H. Ligon, Vesna Najfeld, Scott L. Friedman, William R. Sellers, Matthew Meyerson, Josep M. Llovet
Journal: Cancer Research (2008)

Abstract Hepatocellular carcinomas represent the third leading cause of cancer-related deaths worldwide. The vast majority of cases arise in the context of chronic liver injury due to hepatitis B virus or hepatitis C virus infection. To identify genetic mechanisms of hepatocarcinogenesis, we characterized copy number alterations and gene expression profiles from the same set of tumors associated with hepatitis C virus. Most tumors harbored 1q gain, 8q gain, or 8p loss, with occasional alterations in 13 additional chromosome arms. In addition to amplifications at 11q13 in 6 of 103 tumors, 4 tumors harbored focal gains at 6p21 incorporating vascular endothelial growth factor A (VEGFA). Fluorescence in situ hybridization on an independent validation set of 210 tumors found 6p21 high-level gains in 14 tumors, as well as 2 tumors with 6p21 amplifications. Strikingly, this locus overlapped with copy gains in 4 of 371 lung adenocarcinomas. Overexpression of VEGFA via 6p21 gain in hepatocellular carcinomas suggested a novel, non–cell-autonomous mechanism of oncogene activation. Hierarchical clustering of gene expression among 91 of these tumors identified five classes, including “CTNNB1”, “proliferation”, “IFN-related”, a novel class defined by polysomy of chromosome 7, and an unannotated class. These class labels were further supported by molecular data; mutations in CTNNB1 were enriched in the “CTNNB1” class, whereas insulin-like growth factor I receptor and RPS6 phosphorylation were enriched in the “proliferation” class. The enrichment of signaling pathway alterations in gene expression classes provides insights on hepatocellular carcinoma pathogenesis. Furthermore, the prevalence of VEGFA high-level gains in multiple tumor types suggests indications for clinical trials of antiangiogenic therapies. [Cancer Res 2008;68(16):6779–88]
Effects of Stress Hyperglycemia on Acute Myocardial Infarction
Authors: Raffaele Marfella, Mario Siniscalchi, Katherine Esposito, Ausilia Sellitto, Umberto de Fanis, Ciro Romano, Michele Portoghese, Silvio Siciliano, Francesco Nappo, Ferdinando Carlo Sasso, Nicola Mininni, Federico Cacciapuoti, Giacomo Lucivero, Riccardo Giunta, Mario Verza, Dario Giugliano
Journal: Diabetes Care (2003)

Stress hyperglycemia has been associated with increased mortality in patients with myocardial infarction (MI). We examined the association between plasma glucose levels, circulating inflammatory markers, T-cell activation, and functional cardiac outcome in patients with first MI.Echocardiographic parameters, circulating levels of interleukin-18 (IL-18), C-reactive protein (CPR), and the percent of CD16-CD56, CD4/CD8, CD152, and HLA-DR expression were investigated in 108 patients with acute MI on admission to the emergency ward.Our review found that 31 new hyperglycemic patients (glycemia >or=7 mmol/l) had higher infarct segment length (P < 0.05) and myocardial performance index (P < 0.02) and reduced transmitral Doppler flow (P < 0.05), pulmonary flow analysis (P < 0.02), and ejection fraction (P < 0.05) compared with 36 hyperglycemic diabetic patients and 41 normoglycemic patients. Plasma IL-18 and CRP were higher in the hyperglycemic than in the normoglycemic patients (P < 0.005), with the highest values in patients with new hyperglycemia (P < 0.05). Hyperglycemic patients had a higher percent of CD16+/CD56+ cells and CD4/CD8 ratio (P < 0.01), whereas they had lower CD152 expression (which has a negative regulatory function in T-cell activation) compared with normoglycemic patients (P < 0.001).During MI, hyperglycemia is associated with increased levels of inflammatory markers, enhanced expression of cytotoxic T-cells, and reduced expression of T-cells, which are implicated in limiting the immune process. An increased inflammatory immune process seems a likely mechanism linking acute hyperglycemia to poor cardiac outcome in MI patients.
Pharmacology and biochemistry of noradrenergic receptors
Authors: S. Z. LANGER, C. PIMOULE
Journal: British Journal of Dermatology (1982)

Journal Article Pharmacology and biochemistry of noradrenergic receptors Get access S. Z. LANGER, S. Z. LANGER Department of Biology, Laboratoires d'Etudes et de Recherches‐Synthélabo, 58, rue de la Glacière, 75013 Paris, France Search for other works by this author on: Oxford Academic Google Scholar C. PIMOULE C. PIMOULE Department of Biology, Laboratoires d'Etudes et de Recherches‐Synthélabo, 58, rue de la Glacière, 75013 Paris, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 107, Issue s23, 1 November 1982, Pages 147–153, https://doi.org/10.1111/j.1365-2133.1982.tb01048.x Published: 01 November 1982
Abstract P5-08-09: Synergistic cytotoxicity of digoxin and 5-fluorouracil in doxorubicin-resistant breast cancer cell lines
Authors: J Niu, Y Zhang, Y Qiu, S Clark, MB Maddona, F Chu
Journal: Cancer Research (2013)

Abstract BACKGROUND: Metastatic breast cancer is the leading cause of cancer death for women in the US. Cytotoxic chemotherapy remains one of the most important systemic treatment options for breast cancer patients. To enhance the tumor response to chemotherapy, attention has been focused on agents that reverse multidrug resistance (MDR) and increase the sensitivity of tumor cells to chemical drugs. Although many reversal drugs have been identified in vitro, their clinical application has been limited due to their own toxicity. It was reported that 5 years after mastectomy, the recurrence rate of breast cancer among patients on cardiac glycoside therapy, namely digoxin or digitoxin, was almost 10 times lower as compared with those who were not on cardiac glycoside therapy. Digoxin has also been shown to inhibit hypoxia-inducible factors (HIF) and block lung metastasis in a breast cancer model. Interestingly, digoxin was demonstrated to stimulate cell death in various cell lines including breast cancer. Therefore the aim of this study was to examine the reversal effect of combined digoxin and 5-fluorouracil (5-FU) on MDR resistance in human breast cell lines MCF-7 and MDA-MB-231 in vitro, as well as its mechanism of action. METHODS: Wild-type and doxorubicin-resistant ER-positive (MCF-7 and MCF-7/DoxR) and triple negative (MDA-MB-231 and MDA-231/DoxR) breast cancer lines were used for this study. We have previously shown that both doxorubicin-resistant cell lines are also cross-resistant to 5-FU. Cell viability of both resistant cancer cell lines to 5-FU, digoxin, and both 5-FU with digoxin were compared to control at 96 hours of incubation both in normoxia and hypoxia using MTT assay. Western blot was used to quantify the level of HIF-1α and p-glycoprotein (P-gP). RESULTS: In both doxorubicin-resistant cell lines, sub-IC50 concentration of digoxin together with 5-FU significantly decreased the cell viabilities at 96 hours compared to single agent digoxin and 5-FU. Under both normoxic and hypoxic conditions, the same synergistic cytotoxic effects were demonstrated. Western blot revealed that HIF-1α and P-gP were decreased in both doxorubicin-resistant breast cancer cells treated with the digoxin and 5-FU combination compared to single agent digoxin or 5-FU. CONCLUSION: The combination of digoxin and 5-FU demonstrates a synergistic cytotoxic effect in doxorubicin-resistant breast cancer cell lines that is maintained under hypoxic conditions. This is, at least in part, via the inhibitory effects on both HIF-1α and P-gP. The combination of digoxin and 5-FU could be an effective clinical treatment strategy to overcome MDR in breast cancer. A phase II clinical trial is ongoing to test this hypothesis in patients with doxorubicin-resistant metastatic breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-08-09.
Between-visit variability of small airway obstruction markers in patients with asthma
Authors: Sherif Gonem, Steven Corkill, Amisha Singapuri, Per Gustafsson, Rino Costanza, Christopher E. Brightling, Salman Siddiqui
Journal: European Respiratory Journal (2014)

To the Editor: 

Clinical trials in patients with airway diseases often use forced expiratory volume in 1 s (FEV1) as the sole physiological outcome measure. However, FEV1 is thought to be insensitive to obstruction of the smaller airways, which may be particularly relevant in asthma [1]. Putative markers of small airway obstruction include measures of airway resistance using impulse oscillometry (IOS) [2] and indices of ventilation heterogeneity derived from multiple-breath inert gas washout (MBW) [3]. We recently showed that increased airway resistance at 5 Hz ( R 5) and 20 Hz ( R 20) is associated with worse asthma control and more frequent exacerbations [4], and Farah et al. [5] demonstrated that MBW parameters may be responsive to asthma therapy.

In order to conduct clinical trials using these alternative outcome measures, it is necessary to be assured of their repeatability and stability over time. Moreover, an estimate of between-visit variability in the stable state is required so that sample size calculations can be performed. We therefore aimed to determine the between-visit variability of a range of IOS and MBW indices in a group of patients with asthma in the stable state. We investigated between-visit variability over two time intervals, namely 2 weeks and 3 months, in order to encompass the typical lengths of treatment period that are used in clinical trials.

We recruited 18 adults (age >18 years) with moderate-to-severe asthma (Global Initiative for Asthma treatment steps 3–5 [6]), diagnosed by a specialist asthma physician in a secondary care setting, according to British Thoracic Society guidelines [ …
Two American hospitals in dilemma over brain death
Authors: F B Charatan
Journal: BMJ (1994)

Baby K, a 16 month anencephalic girl, will stay on a ventilator at Fairfax Hospital, Virginia, after the federal appeal court decided that doctors must continue to treat her. Two out of three judges ruled that the 1986 Emergency Medical Treatment and Active Labor Act applied in the case of Baby K. The law, enacted to prevent hospitals from dumping indigent patients, was interpreted by the judges to mean that hospitals must give emergency treatment to all patients who need it, even when doctors think that treatment is inappropriate. The judges said that Baby K needed emergency treatment for apnoea. The federal law pre-empts Virginian state law, which exempts doctors from having to provide …
Ventricular tachycardia associated with infusion of rituximab in mantle cell lymphoma
Authors: Yukihiro Arai, Jiro Tadokoro, Kinuko Mitani
Journal: American Journal of Hematology (2005)

To the Editor: The association of hematologic malignancies in Klinefelter syndrome, in which the chromosomal abnormality of XXY is observed, has rarely been reported in acute myeloblastic leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, myelodysplastic syndrome, or malignant lymphoma [1].It is not yet known how this chromosomal abnormality affects hematopoiesis.We encountered a case of severe thrombocytopenia associated with idiopathic thrombocytopenic purpura and cerebral hemorrhage, which responded to cyclosporine administration.A 27-year-old male complained of severe headache and was admitted to the neurosurgery department for cerebral hemorrhage.CBC demonstrated RBC 434Â10 4 /ml, Hb 13.4 g/dL, Hct 38%, platelets 1.1Â10 4 /mL, and WBC 18,600/ mL with normal differentials.Bone marrow aspiration smear demonstrated normocellular marrow, M/E 2.93, megakaryocytes were sufficiently present, and there were no leukemic or dysplastic cells of any hematopoietic lineage.Platelet-associated antigen was 1,232 ng/10 7 cells (normal value, 9-25 ng/10 7 ).The patient was diagnosed with idiopathic thrombocytopenic purpura.He underwent surgery to evacuate hematoma after the platelet count was increased by platelet transfusion and high-dose immunoglobulin administration.Postoperatively, he was referred to hematology and initially treated with corticosteroid administration starting at 60 mg/day and then tapered over 3 months.However, the platelet count did not increase at all.Subsequently, cyclosporine (200 mg/day) was administered, and the platelet count increased after a month to 10Â10 4 /ml.During this treatment, chromosomal analysis of bone marrow cells was demonstrated to be 47, XXY, and that of the peripheral blood showed the same phenotype.This patient was diagnosed with idiopathic thrombocytopenia purpura, because only thrombocytopenia was observed and there were no dysplastic cells or additional chromosome abnormalities.There are no reports of thrombocytopenia due to idiopathic thrombocytopenic purpura associated with Klinefelter syndrome.Thrombocytopenia in our patient may have been pre-senting an isolated thrombocytopenia due to refractory cytopenia of myelodysplastic syndrome [2], because immune pathogenesis and preleukemic state are considered in myelodysplastic syndrome, and our patient responded to cyclosporine administration.Careful follow-up of this patient is necessary.
CCR5-binding chemokines modulate CXCL12 (SDF-1)–induced responses of progenitor B cells in human bone marrow through heterologous desensitization of the CXCR4 chemokine receptor
Authors: Marek Honczarenko, Yi Le, Aleksandra M. Glodek, Marcin Majka, James J. Campbell, Mariusz Z. Ratajczak, Leslie E. Silberstein
Journal: Blood (2002)
The Patient Self-Determination Act
Authors: Margot L. White
Journal: JAMA (1991)

The Patient Self-Determination Act (hereafter, the Act), which takes effect on December 1,1991, creates no new rights for patients or for citizens generally. The law requires Medicare/Medicaid-receiving health care providers to inform patients of their existing rights under state law to refuse treatment and prepare advance directives. By doing so, it merely affirms principles that have their roots in both common law and constitutional law dating back to the late 19th century. ("[N]o right is held more sacred, or is more carefully guarded, by the common law, than the right of every individual to the possession and control of his person, free from all restraint or interference of others, unless by clear and unquestionable authority of law."<sup>1</sup>) Legal and ethical principles that govern decision making about medical treatment, familiar to most clinicians as the doctrine of informed consent, have played a significant role in clinical decision making for decades
X-Linked Pseudohypertrophic Muscular Dystrophy with a Late Onset and Slow Progression
Authors: C. Charlton Mabry, Irene E. Roeckel, Richard L. Munich, Denver Robertson
Journal: New England Journal of Medicine (1965)

PROGRESSIVE muscular dystrophy was recognized over a century ago, and Gowers noted its familial occurrence soon afterward. The disease, which is similar in affected members of a family, may vary in mode of inheritance and clinical characteristics from kindred to kindred. The most common form, described by Duchenne in 1868, is transmitted as an X-linked recessive characteristic. Typically, these affected males show weakness in their pelvifemoral muscles before the age of six, experience rapid progression of their muscle weakness, acquire pseudohypertrophy of the calves, are chair bound by twelve years and are dead by twenty years of age. In the . . .
Characterization of Bile Acid Absorption across the Unstirred Water Layer and Brush Border of the Rat Jejunum
Authors: Frederick A. Wilson, John M. Dietschy
Journal: Journal of Clinical Investigation (1972)

We have examined the rate-limiting steps involved in bile acid absorption across the unstirred water layer and lipid cell membrane of the jejunal mucosa. Uptake of the polar bile acid taurocholate is limited solely by the cell membrane since this compound permeates the unstirred water layer more rapidly than the lipid cell membrane and stirring does not enhance uptake. With less polar bile acids which permeate the cell membrane relatively more rapidly, however, the unstirred water layer does exert resistance to mucosal uptake of these compounds. That the unstirred water layer is even more rate limiting to uptake from micellar solutions is indicated by the facts that the rate of bile acid absorption from such solutions is lower than from corresponding monomer solutions, stirring markedly enhances uptake from micellar solutions while increases in viscosity of the incubation media depress uptake and expansion of the micelle size further depresses absorption rates. We also have examined the important question of whether the micelle crosses the brush border intact once it reaches the aqueous-lipid interface. The observations that the calculated permeation rate of the micelle should be extremely low, the rate of mucosal cell uptake plateaus at a constant value when the critical micelle concentration is reached at the aqueous-lipid interface, and the different components of a mixed micelle are taken up at different rates indicate that uptake of the intact micelle does not occur; rather, bile acid absorption must be explained in terms of monomers in equilibrium with the micelle. Finally, after correction of the permeability coefficients of the various bile acids for the unstirred layer resistance the incremental partial molar free energy of solution of the hydroxyl group in the brush border membrane was calculated to equal −6126 cal·mole−1 indicating that passive diffusion of these compounds occurs through a very polar region of the cell membrane.
RENAL CIRCULATORY DYNAMICS AND URINARY PROTEIN EXCRETION DURING INFUSIONS OF l-NOREPINEPHRINE AND l-EPINEPHRINE IN PATIENTS WITH RENAL DISEASE 12
Authors: Willoughby Lathem
Journal: Journal of Clinical Investigation (1956)

That hemodynamic adjustments within the kidney may modify the rate of transport of protein molecules across glomerular capillary membranes has been suggested by a variety of experimental studies. The mechanisms which alter protein transport under these conditions are not clear, but since proteins apparently traverse capillary walls by diffusion as well as filtration (2), differing mechanisms may play a role depending on the nature and circumstances of the associated vascular adjustments. Thus filtration may be modified under conditions which alter intraglomerular hydrostatic pressure (3-5) and diffusion under circumstances which influence the rate of formation of glomerular filtrate (2). It has been suggested that protein transport and urinary protein excretion may be altered by renal circulatory adjustments which modify the area available for transport within the kidney (6) or which influence the integrity of the capillary wall (7-9). Moreover, it has recently been suggested that protein transport may also be conditioned by the velocity of blood flow through the glomerulus (10). In the present study an examination of these factors was undertaken in patients with renal disease and proteinuria. The urinary excretion and renal clearance of plasma proteins were determined under circumstances in which intrarenal circulatory adjustments were induced by the administration of the adrenal medullary hormones, l-norepinephrine and l-epinephrine.
"Premature" Children at Primary Schools
Authors: J. W. B. Douglas
Journal: BMJ (1960)

A controlled study of a representative group of 706 legitimate single-born premature infants was conducted and the progress of premature children attending normal primary schools is described.  Information was lacking on the home conditions of 31 of these children but each of the remaining 675 was matched with a child (the control) who was born during the Maternity Survey of 1946 (Great Britain) survey week (the 1st week of March 1946).  The tests used for this inquiry were designed by the National Foundation for Educational Research in England and Wales.  4 tests were given the children at age 8 and another 4 at age 11 years 3 months.  The preliminary findings were that premature children: 1) made consistently lower scores than their matched controls in 8 tests of mental ability and school achievement;  2) were the subject of more adverse comment than their controls by their teachers regarding their attitude towards work ability to concentrate and discipline in class;  and 3) were less than 1/2 as likely as their controls to gain grammarschool places in the 11+ examination.  The differences are basically explained by the fact that premature birth is associated at each social level with low standards of maternal care and lack of educational interest as well as with poor living conditions.
Hormone releasing intrauterine system should be used more widely in primary care for menorrhagia, study concludes
Authors: Z. Kmietowicz
Journal: BMJ (2013)

Women with menorrhagia reported more improvement in bleeding and quality of life with the levonorgestrel releasing intrauterine system than with other treatments available in primary care, a two year study in England has found.1

Women fitted with the levonorgestrel releasing intrauterine system (also known as LNG-IUS or Mirena) were also more likely to stick with treatment, found the study, called the Effectiveness and Cost-Effectiveness of Levonorgestrel-Containing Intrauterine System in Primary Care against Standard Treatment for Menorrhagia (ECLIPSE) study.

Researchers from the Universities of Birmingham and Nottingham randomised 571 …
Private Insurers Resist Covering Investigational Therapy
Authors: Hugh McIntosh
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Private Insurers Resist Covering Investigational Therapy Get access Hugh McIntosh Hugh McIntosh Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 12, 20 June 1990, Pages 996–998, https://doi.org/10.1093/jnci/82.12.996 Published: 20 June 1990
A QUANTITATIVE THEORY OF THE PRECIPITIN REACTION
Authors: Elvin A. Kabat, Michael Heidelberger
Journal: The Journal of Experimental Medicine (1937)

1. The reaction between crystalline horse serum albumin and homologous antibody in rabbit sera is quantitatively accounted for by expressions similar to those derived from the law of mass action for other immune precipitating systems. 2. The reaction of an azo dye prepared from crystalline serum albumin by coupling with diazotized R-salt-azo benzidine was also studied with homologous antibody and anti-serum albumin. 3. Quantitative data obtained on cross reactions with the two antigens differ markedly from data on the corresponding reactions in the egg albumin system and indicate that tyrosine and perhaps histidine, while important in determining the serological specificity of egg albumin, have little connection with the specificity of serum albumin. 4. Calculations are made of the equivalent composition of the specific precipitate at various reference points in the reaction range.
NOGG guideline should be implemented
Authors: J. H Tobias, A. Bajkowski, P. Holmes, A. Nunn, D. Moran, J. Stenmark, C. Marx, J. Wass, R. Jones
Journal: BMJ (2008)

During the protracted development of guidance on osteoporosis from the National Institute for Health and Clinical Excellence (NICE),1 the appraisal committee has disregarded input from public and professional bodies alike. When the guidance is at odds with clinical judgment and patients’ best interests, requiring that patients identified at …