tbuckley/cabot-search huggingface dataset:
Use of High-Cost Operative Procedures by Medicare Beneficiaries Enrolled in For-Profit and Not-for-Profit Health Plans
Authors: Eric C. Schneider, Alan M. Zaslavsky, Arnold M. Epstein
Journal: New England Journal of Medicine (2004)

It is widely believed that for-profit health plans are more likely than not-for-profit health plans to respond to financial incentives by restricting access to care, especially access to high-cost procedures. Until recently, data to address this question have been limited.We tested the hypothesis that the rates of use of 12 common high-cost procedures would be lower in for-profit health plans than in not-for-profit plans. Using standardized Medicare HEDIS data on 3,726,065 Medicare beneficiaries 65 years of age or older who were enrolled in 254 health plans during 1997, we compared for-profit and not-for-profit plans with respect to rates of cardiac catheterization, coronary-artery bypass grafting, percutaneous transluminal coronary angioplasty, carotid endarterectomy, reduction of femur fracture, total hip replacement, total knee replacement, partial colectomy, open cholecystectomy, closed cholecystectomy, hysterectomy, and prostatectomy. We adjusted the comparisons for sociodemographic case mix and for characteristics of the health plans other than their tax status, including the plans' location.The rates of carotid endarterectomy, cardiac catheterization, coronary-artery bypass grafting, and percutaneous transluminal coronary angioplasty were higher in for-profit health plans than they were in not-for-profit health plans; the rates of use of other common costly operative procedures were similar in the two types of plan. After adjustment for enrollee case mix and other characteristics of the plans, the for-profit plans had significantly higher rates than the not-for-profit plans for 2 of the 12 procedures we studied and had lower rates for none. The geographic locations of the health plans did not explain these findings.Contrary to our expectations about the likely effects of financial incentives, the rates of use of high-cost operative procedures were not lower among beneficiaries enrolled in for-profit health plans than among those enrolled in not-for-profit health plans.
Novel responses of human skin to intradermal recombinant granulocyte/macrophage-colony-stimulating factor: Langerhans cell recruitment, keratinocyte growth, and enhanced wound healing.
Authors: G Kaplan, G Walsh, L S Guido, P Meyn, R A Burkhardt, R M Abalos, J Barker, P A Frindt, T T Fajardo, R Celona
Journal: The Journal of Experimental Medicine (1992)

Recombinant granulocyte/macrophage-colony-stimulating factor (rGM-CSF), prepared from Chinese hamster ovary (CHO) cells and Escherichia coli, was administered to 35 patients with the borderline and polar lepromatous forms of leprosy by the intradermal and subcutaneous routes at doses of 7.5-45.0 micrograms/d for 10 d. With each of these doses and routes, increases in the number of circulating eosinophils were noted. After the intradermal injection, the local skin sites demonstrated zones of roughening and micronodularity that appeared within 24-48 h and persisted for more than 6 d. Reinjection of sites led to enhanced areas of epidermal reaction. GM-CSF prepared from CHO cells was a more potent inducer of this effect. GM-CSF given by the subcutaneous route, at higher doses, failed to initiate these changes. At the microscopic level, the epidermis became thickened (+75%) with increased numbers and layers of enlarged keratinocytes. These contained increased numbers of ribosomes and prominent nucleoli, and were imbedded in a looser meshwork of the zona Pellucida. The modified keratinocytes remained MHC class II antigen negative throughout the course of the response. A major change in the dermis was the progressive accumulation of CD1+, Birbeck granule-positive cells. These Langerhans were recognizable at 48 h after intradermal injection and reached maximum numbers by 4 d. During this period the number of epidermal Langerhans cells remained relatively constant. No increment in dermal Langerhans cells occurred when GLM-CSF was injected by the subcutaneous route. No appreciable increase in the numbers of T cells and monocytes was noted, and granulocytes and eosinophils were largely present within the dermal microvasculature. 4-mm punch biopsies taken from injected sites and adjacent controls were compared in terms of the rapidity of wound healing. 22 of 26 sites demonstrated more rapid filling and hemostasis, whereas four were equivalent to controls. We conclude that rGM-CSF, when introduced into the skin, leads to enhanced keratinocyte growth, the selective recruitment of Langerhans cells into the dermis, and enhanced wound healing of the prepared site. There was no evidence of an enhanced cell-mediated response to Mycobacterium leprae, and bacillary numbers remained unchanged.
MicroRNA-125a-5p partly regulates the inflammatory response, lipid uptake, and ORP9 expression in oxLDL-stimulated monocyte/macrophages
Authors: Ting Chen, Zhouqing Huang, Liansheng Wang, Yue Wang, Feizhen Wu, Shu Meng, Changqian Wang
Journal: Cardiovascular Research (2009)

The inflammatory responses of monocytes/macrophages and the stimulation of lipid uptake into these cells by oxidized low density lipoprotein (oxLDL) are critical to the initiation and development of atherosclerosis. Increasing evidence has demonstrated that many microRNAs play important roles in the cell proliferation, apoptosis, and differentiation that accompany inflammatory responses. However, whether microRNAs are associated with monocyte/macrophage inflammatory responses or oxLDL stimulation is not yet known. The aim of the present study is to investigate microRNAs in monocytes/macrophages and their potential role in oxLDL-stimulation of lipid uptake and other atherosclerotic responses. Microarrays were used to analyse the global expression of microRNAs in oxLDL-stimulated human primary peripheral blood monocytes. Expression profiles of the microRNAs were verified using TaqMan real-time PCR. Five microRNAs (microRNA-125a-5p, microRNA-9, microRNA-146a, microRNA-146b-5p, and microRNA-155) were aberrantly expressed after oxLDL treatment of human primary monocytes. Bioinformatics analysis suggested that microRNA-125a-5p is related to a protein similar to ORP9 (oxysterol binding protein-like 9) and this was confirmed by a luciferase reporter assay. MicroRNA-125a-5p was found to mediate lipid uptake and to decrease the secretion of some inflammatory cytokines (interleukin-2, interleukin-6, tumour necrosis factor-α, transforming growth factor-beta) in oxLDL-stimulated monocyte-derived macrophages. MicroRNA-125a-5p may partly provide post-transcriptional regulation of the proinflammatory response, lipid uptake, and expression of ORP9 in oxLDL-stimulated monocyte/macrophages.
Tasquinimod (ABR-215050), a quinoline-3-carboxamide anti-angiogenic agent, modulates the expression of thrombospondin-1 in human prostate tumors
Authors: Anders Olsson, Anders Björk, Johan Vallon-Christersson, John T Isaacs, Tomas Leanderson
Journal: Molecular Cancer (2010)

The orally active quinoline-3-carboxamide tasquinimod [ABR-215050; CAS number 254964-60-8), which currently is in a phase II-clinical trial in patients against metastatic prostate cancer, exhibits anti-tumor activity via inhibition of tumor angiogenesis in human and rodent tumors. To further explore the mode of action of tasquinimod, in vitro and in vivo experiments with gene microarray analysis were performed using LNCaP prostate tumor cells. The array data were validated by real-time semiquantitative reversed transcriptase polymerase chain reaction (sqRT-PCR) and protein expression techniques.One of the most significant differentially expressed genes both in vitro and in vivo after exposure to tasquinimod, was thrombospondin-1 (TSP1). The up-regulation of TSP1 mRNA in LNCaP tumor cells both in vitro and in vivo correlated with an increased expression and extra cellular secretion of TSP1 protein. When nude mice bearing CWR-22RH human prostate tumors were treated with oral tasquinimod, there was a profound growth inhibition, associated with an up-regulation of TSP1 and a down- regulation of HIF-1 alpha protein, androgen receptor protein (AR) and glucose transporter-1 protein within the tumor tissue. Changes in TSP1 expression were paralleled by an anti-angiogenic response, as documented by decreased or unchanged tumor tissue levels of VEGF (a HIF-1 alpha down stream target) in the tumors from tasquinimod treated mice.We conclude that tasquinimod-induced up-regulation of TSP1 is part of a mechanism involving down-regulation of HIF1alpha and VEGF, which in turn leads to reduced angiogenesis via inhibition of the "angiogenic switch", that could explain tasquinimods therapeutic potential.
Prevalence of Birt–Hogg–Dubé syndrome in patients with apparently primary spontaneous pneumothorax
Authors: Paul C. Johannesma, Rinze Reinhard, Yael Kon, Jincey D. Sriram, Hans J. Smit, R. Jeroen A. van Moorselaar, Fred H. Menko, Pieter E. Postmus
Journal: European Respiratory Journal (2014)

Pneumothorax is classified "spontaneous pneumothorax" if there is no external force causing it and is classified as "primary spontaneous pneumothorax" (PSP) if there is no underlying lung disease. According to the guidelines of the British Thoracic Society (BTS), "no underlying lung disease" is based on history, physical examination and chest radiography [1]. Birt–Hogg–Dubé syndrome is probably the cause of pneumothorax in 5–10% of primary spontaneous pneumothorax patients <http://ow.ly/FiIGS> The additional participating principal investigators of the Amsterdam BHD working group were Marianne A. Jonker (Dept of Epidemiology and Biostatistics, VU University Medical Center, Amsterdam the Netherlands), Arjan C. Houweling (Dept of Clinical Genetics, VU University Medical Center), Quinten Waisfisz (Dept of Clinical Genetics, VU University Medical Center), Johannes J.P. Gille (Dept of Clinical Genetics, VU University Medical Center), Erik Thunnissen (Dept of Pathology, VU University Medical Center), JanHein T.M. van Waesberghe (Dept of Radiology, VU University Medical Center) and Theo M. Starink (Dept of Dermatology, VU University Medical Center). We are grateful to all included pneumothorax patients who participated in this study.
Association of <i>ATP1A1</i> and <i>Dear</i> Single-Nucleotide Polymorphism Haplotypes With Essential Hypertension
Authors: Nicola Glorioso, Victoria L.M. Herrera, Pia Bagamasbad, Fabiana Filigheddu, Chiara Troffa, Giuseppe Argiolas, Emanuela Bulla, Julius L. Decano, Nelson Ruiz-Opazo
Journal: Circulation Research (2007)

Essential hypertension remains a major risk factor for cardiovascular and cerebrovascular diseases. As a complex multifactorial disease, elucidation of susceptibility loci remains elusive. ATP1A1 and Dear are candidate genes for 2 closely linked rat chromosome-2 blood pressure quantitative trait loci. Because corresponding human syntenic regions are on different chromosomes, investigation of ATP1A1 (chromosome [chr]-1p21) and Dear (chr-4q31.3) facilitates genetic analyses of each blood pressure quantitative trait locus in human hypertension. Here we report the association of human ATP1A1 (P<0.000005) and Dear (P<0.03) with hypertension in a relatively isolated, case/control hypertension cohort from northern Sardinia by single-nucleotide polymorphism haplotype analysis. Sex-specific haplotype analyses detected stronger association of both loci with hypertension in males than in females. Haplotype trend-regression analyses support ATP1A1 and Dear as independent susceptibility loci and reveal haplotype-specific association with hypertension and normotension, thus delineating haplotype-specific subsets of hypertension. Although investigation in other cohorts needs to be performed to determine genetic effects in other populations, haplotype subtyping already allows systematic stratification of susceptibility and, hence, clinical heterogeneity, a prerequisite for unraveling the polygenic etiology and polygene-environment interactions in essential hypertension. As hypertension susceptibility genes, coexpression of ATP1A1 and Dear in both renal tubular cells and vascular endothelium suggest a cellular pathogenic scaffold for polygenic mechanisms of hypertension, as well as the hypothesis that ATP1A1 and/or Dear could contribute to the known renal and vascular endothelial dysfunction associated with essential (polygenic) hypertension.
Advances in neoplastic disease of the liver and biliary tract.
Authors: P J Johnson, M L Wilkinson, J Karani
Journal: Gut (1991)

The last 25 years have seen an explosion of interest in hepatic and biliary neoplasia reflecting not only the worldwide importance of these tumours, but also the fact that recent advances in serological and radiological diagnosis and the new techniques ofmolecular biology have all had a major impact.It seems hard to believe that in 1965, none of the hepatitis viruses had been identified and although 'Australian antigen' had just been described its significance was yet to be realised.Computerised tomography, ultrasono- graphy and ERCP were all unheard of.The idea of useful tumour markers was still the stuff of oncologists' dreams, alphafetoprotein having only been recognised in animal studies in the year the first liver transplant programme was started (1964).This review aims to summarise progress over the period in question and high- light some of the contributions and current areas of interest of the Institute over this period.
Outcomes following non-invasive ventilation for hypercapnic exacerbations of chronic obstructive pulmonary disease
Authors: I. Murray, E. Paterson, G. Thain, G. P. Currie
Journal: Thorax (2010)

Many carefully crafted studies with different end points have shown significant benefits with non-invasive ventilation (NIV) over and above conventional medical treatment alone in the management of hypercapnic exacerbations of chronic obstructive pulmonary disease (COPD).1 However, most data have evaluated highly selected patients within stringent realms of randomised controlled trials. Since strict criteria need to be fulfilled before clinical trial entry (often excluding elderly patients and those with major co-morbidities, electrolyte disturbance and severe exacerbations), outcomes may not be reflective of everyday practice. We wished to highlight demographics, physiological variables, outcomes and 1-year survival in a large cohort of patients receiving ward-based NIV for hypercapnic exacerbations …
β‐thalassemia alleles and unstable hemoglobin types among russian pediatric patients
Authors: M. A.çürük, T. P. Molchanova, Yu. V. Postnikov, D. D. Pobedimskaya, R. Liang, E. Baysal, S. Kolodey, N. S. Smetanina, Yu. N. Tokarev, A. G. Rumyantsev, T. H. J. Huisman
Journal: American Journal of Hematology (1994)

Abstract A recently initiated collaboration between Russian and American institutions has resulted in the characterization of several known or new β‐thalassemia alleles and unstable hemoglobin types. Nine known β‐thalassemia alleles were present which have also been found in Mediterranean, East Asian, and Black populations; the possibility of independent mutations for some of the rare alleles should be considered. Hb Durham‐N.C./Brescia with a codon 114 (CTG → CCG; Leu → Pro) change was present in six members of two families. This condition and two new variants have the characteristics of a dominant type of β‐thalassemia heterozygosity with moderate anemia, Heinz body formation, splenomegaly, etc. One new β‐thalassemia allele is a frame‐shift at codon 124 (‐A), while another is characterized by the introduction of an extra proline residue (codon: CCA) between residues Thr (β123) and Val (β126) to give the sequence ‐Thr‐Pro‐Pro‐Pro‐Val‐. © 1994 Wiley‐Liss, Inc.
Up-regulation of type I procollagen C-proteinase enhancer protein messenger RNA in rats with CCl4-induced liver fibrosis
Authors: I Ogata, A S Auster, A Matsui, P Greenwel, A Geerts, T D'Amico, K Fujiwara, E Kessler, M Rojkind
Journal: Hepatology (1997)

Using a polyclonal antibody raised against a liver stellate cell (LSC) line derived from a rat CCl 4 -cirrhotic liver, we isolated 14 clones from a complementary DNA library prepared with total RNA extracted from the same cell line, with nucleotide sequences homologous to that of the type I procollagen C-proteinase enhancer protein (PCPE) gene. The longest PCPE insert of 1,530 base pairs contained an open reading frame coding for 468 amino acids. PCPE cDNA recognized by Northern blot a 1.7-kilobase messenger RNA (mRNA) in total RNA extracted from freshly isolated and early passaged LSC, LSC lines derived from normal (NFSC) and cirrhotic (CFSC) rat livers, and various LSC clones derived from CFSC. The expression of PCPE mRNA was increased threefold in CFSC compared with NFSC. PCPE mRNA was not detected in total rat liver, freshly isolated hepatocytes, or endothelial or Kupffer cells. However, the expression of PCPE mRNA was induced in fibrotic livers of rats treated with CCl 4 . PCPE mRNA expression in LSC was up-regulated by transforming growth factor β1 (TGF-β1) and down-regulated by tumor necrosis factor α (TNF-α), similar to the changes in α1 (1) procollagen mRNA induced by these cytokines. PCPE was not detectable in liver biomatrix proteins obtained from normal liver. However, PCPE was increased in liver biomatrix proteins from cirrhotic livers and was proportional to the amount of collagen. These data suggest that PCPE may play an important role in the processing of type I collagen during liver fibrogenesis, and that TGF-β1 and TNF-α regulate its expression.
Detection of new genotypes of Orientia tsutsugamushi infecting humans in Thailand
Authors: P.-E. Fournier, S. Siritantikorn, J.-M. Rolain, Y. Suputtamongkol, S. Hoontrakul, S. Charoenwat, K. Losuwanaluk, P. Parola, D. Raoult
Journal: Clinical Microbiology and Infection (2008)
Protein-based human iPS cells efficiently generate functional dopamine neurons and can treat a rat model of Parkinson disease
Authors: Yong-Hee Rhee, Ji-Yun Ko, Mi-Yoon Chang, Sang-Hoon Yi, Dohoon Kim, Chun-Hyung Kim, Jae-Won Shim, A-Young Jo, Byung-Woo Kim, Hyunsu Lee, Suk-Ho Lee, Wonhee Suh, Chang-Hwan Park, Hyun-Chul Koh, Yong-Sung Lee, Robert Lanza, Kwang-Soo Kim, Sang-Hun Lee
Journal: Journal of Clinical Investigation (2011)

Parkinson disease (PD) involves the selective loss of midbrain dopamine (mDA) neurons and is a possible target disease for stem cell-based therapy. Human induced pluripotent stem cells (hiPSCs) are a potentially unlimited source of patient-specific cells for transplantation. However, it is critical to evaluate the safety of hiPSCs generated by different reprogramming methods. Here, we compared multiple hiPSC lines derived by virus- and protein-based reprogramming to human ES cells (hESCs). Neuronal precursor cells (NPCs) and dopamine (DA) neurons delivered from lentivirus-based hiPSCs exhibited residual expression of exogenous reprogramming genes, but those cells derived from retrovirus- and protein-based hiPSCs did not. Furthermore, NPCs derived from virus-based hiPSCs exhibited early senescence and apoptotic cell death during passaging, which was preceded by abrupt induction of p53. In contrast, NPCs derived from hESCs and protein-based hiPSCs were highly expandable without senescence. DA neurons derived from protein-based hiPSCs exhibited gene expression, physiological, and electrophysiological properties similar to those of mDA neurons. Transplantation of these cells into rats with striatal lesions, a model of PD, significantly rescued motor deficits. These data support the clinical potential of protein-based hiPSCs for personalized cell therapy of PD.
Early onset of pulmonary vascular obstruction in patients with aortopulmonary transposition and intact ventricular septum.
Authors: J B Lakier, P Stanger, M A Heymann, J I HoffmaN, A M Rudolph
Journal: Circulation (1975)

Of 29 patients with aortopulmonary transposition with intact ventricular septum who underwent cardiac catheterization as neonates, five subsequently developed increased pulmonary vascular resistance at an early age (7 months to 2 1 2 years). The resistance was high in two patients (11.0 and 12.9 units (U)/m-2), moderate in one (5.5 U/m-2) and mild in two (3.6 and 4.6 U/m-2). The two patients with the highest resistances died as a result of the pulmonary vascular obstruction and it was probably a contributing factor in the death of a third patient. The finding of pulmonary vascular obstruction at an early age in five of 29 patients with transposition of the great arteries with intact septa is noteworthy. It assumes even greater significance as the measurement methods tend to underestimate pulmonary vascular resistance. The possible errors in assessing pulmnary vascular resistance and factors possibly contributing to early development of pulmonary vascular obstruction are discussed.
Targeting the Proteolytic Arsenal of Neutrophils
Authors: Prediman K. Shah
Journal: Circulation (1999)

f patients who undergo cardiopulmonary bypass (CPB), a procedure essential to most cardiac operations, Ϸ1% to 2% develop a syndrome of pulmonary dysfunction called the postpump syndrome, which is analogous to the adult respiratory distress syndrome (ARDS) that develops as a complication of trauma, sepsis, inhalation injury, aspiration pneumonia, pancreatitis, and other disease states. 1,2This syndrome is characterized by evidence of pulmonary microvascular endothelial damage, increased microvascular permeability, increased lung water accumulation, increased intrapulmonary shunting, hypoxia, respiratory failure, and a variable severity of clinical expression.Despite many technical and therapeutic advances, the overall mortality associated with this syndrome continues to be high, ranging from Ϸ40% to Ն60%. 1,2The precise mechanisms responsible for microvascular damage and tissue destruction in postpump syndrome and ARDS are incompletely understood.An important role for inflammatory cells, specifically neutrophil sequestration and activation, is suggested by a number of experimental and clinical observations. 3-7It has been suggested that CPB primes the neutrophils, causing their sequestration in the pulmonary microvasculature, with subsequent activation resulting in the release of tissuedestructive mediators.Several cytokines, such as interleukin-1, interleukin-6, interleukin-8, tumor necrosis factor-␣, and leukemia inhibitory factor, have been implicated in neutrophil recruitment or activation in ARDS. 6,8 -146][7]15,16 Experimental observations suggest that neutrophil elastase may serve as an activator of gelatinase B (matrix metalloproteinase [MMP]-9). 17Both elastase and metalloproteinases, when activated, can induce breakdown of extracellular matrix components such as elastin and basement membrane collagen type IV, resulting in microvascular endothelial damage and increased permeability. 15Furthermore, it has also been postulated that increased