tbuckley/cabot-search huggingface dataset:
How we manage follicular lymphoma
Authors: W Hiddemann, B D Cheson
Journal: Leukemia (2014)

Major changes have taken place within the last few years in the management of follicular lymphoma (FL) leading to substantial improvement in prognosis and overall survival. For some patients with limited disease stages I and II, radiotherapy may be associated with durable responses; however, it is unclear whether patients are cured and new approaches such as the combination of irradiation with rituximab or even single-agent rituximab need to be explored. Whereas watch and wait is the current standard for stage III and IV disease with low tumour burden, better indices are warranted to potentially select patients for whom early intervention is preferred. For advanced stages with a high tumour burden, immunochemotherapy followed by 2 years of rituximab maintenance is widely accepted as standard therapy, although re-treatment at recurrence may be an alternative option. Highly attractive new therapeutic options have recently arisen from new antibodies, and from new agents targeting oncogenic pathways such as B-cell receptor signalling pathways or inhibition of bcl 2. Furthermore, immunomodulatory drugs may add to the therapeutic armamentarium and may lead to 'chemotherapy-free' therapies in the near future. Hence, the management of FLs has become a moving target and the hope is justified that the long-term perspectives of patients suffering from the disease will be further improved in the near future.
Vasodilator responses of coronary resistance arteries of exercise-trained pigs.
Authors: J M Muller, P R Myers, M H Laughlin
Journal: Circulation (1994)

BACKGROUND The purpose of this study was to test the hypothesis that vasodilator responses of porcine coronary resistance arteries are increased by exercise training. METHODS AND RESULTS Yucatan miniature swine were randomly divided into groups of exercise-trained (ET) and sedentary (SED) control pigs. ET pigs were placed on a progressive treadmill training program lasting 16 to 20 weeks, and SED pigs remained inactive during the same time period. Coronary resistance arteries 64 to 157 microns in diameter were isolated for in vitro evaluation of relaxation responses to the endothelium-independent dilators sodium nitroprusside (1 x 10(-10) to 1 x 10(-4) mol/L) and adenosine (1 x 10(-10) to 1 x 10(-5) mol/L) and to bradykinin (1 x 10(-13) to 3 x 10(-7) mol/L), an endothelium-dependent agent. Relaxation responses to adenosine and sodium nitroprusside were not altered by exercise training. Endothelium-dependent relaxation to bradykinin was enhanced in coronary resistance arteries from ET pigs (IC50: ET, 0.07 +/- 0.02 nmol/L; SED, 1.59 +/- 0.09 nmol/L). To determine whether prostanoids and/or the nitric oxide synthase pathway were involved in the ET-induced changes in bradykinin-induced vasodilation, responses to bradykinin were examined in coronary resistance arteries from both ET and SED pigs in the presence of indomethacin and in the presence of nitro-monomethyl L-arginine (L-NMMA). Both indomethacin and L-NMMA produced significant inhibition of the bradykinin-induced relaxation in vessels from both groups. Despite decreased bradykinin-induced relaxation after indomethacin, bradykinin-induced vasodilation was still enhanced in vessels from the ET group. L-NMMA caused greater inhibition of the bradykinin-induced relaxation in coronary resistance arteries from ET pigs relative to arteries from SED pigs and eliminated the training-induced enhancement of the bradykinin responses. CONCLUSIONS These results suggest that exercise training enhances bradykinin-induced vasodilation through increased endothelium-derived relaxing factor/nitric oxide production by the L-arginine/nitric oxide synthase pathway.
Disseminated perforating granuloma annulare
Authors: T.J. DELANEY, S.C. GOLD, BARBARA LEPPARD
Journal: British Journal of Dermatology (1973)

Journal Article Disseminated perforating granuloma annulare Get access T.J. DELANEY, T.J. DELANEY Department of Dermatology, St George's Hospital, London, S.W.I Search for other works by this author on: Oxford Academic Google Scholar S.C. GOLD, S.C. GOLD Department of Dermatology, St George's Hospital, London, S.W.I Search for other works by this author on: Oxford Academic Google Scholar BARBARA LEPPARD BARBARA LEPPARD Department of Dermatology, St George's Hospital, London, S.W.I Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 89, Issue 5, 1 November 1973, Pages 523–526, https://doi.org/10.1111/j.1365-2133.1973.tb03016.x Published: 01 November 1973 Article history Accepted: 11 April 1973 Published: 01 November 1973
Impaired production of burst promoting activity by blood mononuclear cells from chronic uremic patients
Authors: Yoshifumi Kawano, Yoichi Takaue, Jun Minakuchi, Takanori Abe, Keiko Matsunaga, Atsushi Hirao, Tsutomu Watanabe, Masao Hirose, Tsuneo Ninomiya, Shuh Kawashima, Yasuhiro Kuroda
Journal: American Journal of Hematology (1991)

Abstract The ability of blood mononuclear cells (MNC) to produce burst promoting activity (BPA) was evaluated in 31 patients with chronic renal failure. The BPA of cells from uremic patients, with or without hemodialysis, was consistently lower than that of 17 normal donors (mean 64%, P &lt; 0.01). Coculture of MNC with recombinant erythropoietin (rEpo) in vitro did not increase BPA production. Five of 31 patients received in vivo treatment with rEpo (1,500 units × 3/week) and showed therapeutic benefit, but in all patients the BPA production remained low. On the other hand, in four patients who were on a hemodialysis protocol and subsequently underwent renal transplantation, impaired BPA production was resolved quickly, and at the same time the number of circulating BFU‐E and the hemoglobin level increased toward normal ranges. Furthermore, such impaired BPA production was not observed in patients receiving continuous ambulatory peritoneal dialysis. These observations suggest that decreased production of BPA may play a role in the development of anemia associated with chronic uremic patients, and the correction of BPA production by the improvement of hemodialysis procedure may result in more effective therapy with rEpo for those patients.
Cost and Price of Comparable Branded and Generic Pharmaceuticals
Authors: Thomas A. Dodd
Journal: JAMA (1987)

To the Editor.—  The recent article entitled Cost and Price of Comparable Branded and Generic Pharmaceuticals 1 was a timely and extensive study of the questions surrounding much of the controversy regarding the role of the physician in cost-effective prescribing. The primary question addressed was Are generic drugs less expensive than comparable brand name drugs? The answer was yes for pharmacies and sometimes for consumers. The reported result is of concern to all of us who are concerned about the cost of medical care and medicines to our patients. In general, the public and physicians have been hoodwinked by the pharmacists, who have convinced state legislators to trust them. Senior citizen-backed groups, third-party payers, and generic-medication manufacturers encourage substitution on the grounds of savings passed on to the consumer. According to Bloom et al, this is a promise that is not always kept.  The physician's office is given a daily
Should the lung be rested or recruited? The Charybdis and Scylla of ventilator management.
Authors: D Dreyfuss, G Saumon
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

"Should the lung be rested or recruited? The Charybdis and Scylla of ventilator management.." American journal of respiratory and critical care medicine, 149(5), pp. 1066–1067
Sjogren's syndrome and fibrosing alveolitis complicated by pulmonary lymphoma.
Authors: R A Asherson, F Muncey, H Pambakian, J Brostoff, G R Hughes
Journal: Annals of the Rheumatic Diseases (1987)

The case of a middle aged woman who presented with fibrosing alveolitis, in her mid-forties, followed by a sicca syndrome and who subsequently developed a pulmonary lymphoma (B cell) while receiving azathioprine therapy is recorded. Of interest was the absence of polyclonal B cell activation, e.g., production of rheumatoid factor, hypergammaglobulinaemia, high titre antinuclear antibodies or antibodies to extractable nuclear antigens (ENA) during most of her illness. Persistently raised IgM levels and low IgA levels were demonstrated. The relevance of azathioprine to development of the lymphoma is discussed.
The expression of splice forms for the rheumatoid arthritis risk associated gene PTPN22 is significantly different for patients compared to controls
Authors: Marcus Ronninger, Yongjing Guo, Klementy Shchetynsky, Andrew Hill, Mohsen Khademi, Tomas Olsson, Padmalatha S Reddy, Maria Seddighzadeh, James D Clark, Lih-Ling Lin, Margot O'Toole, Leonid Padyukov
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Several genetic risk factors have been revealed for rheumatoid arthritis (RA) whereof <i>HLA-DRB1</i> shared epitope alleles and <i>PTPN22</i> remains the two most undisputed for the disease. Hypotheses for how these associations confer their risk exist but the etiology is still not completely explained. The <i>PTPN22</i> risk allele is associated with a gain of function of the protein product. However, the <i>PTPN22</i> gene has alternatively spliced transcripts where at least two of the splice forms have confirmed different <i>PTPN22</i> (LYP) proteins, which may influence the proteins pathways. <h3>Objectives</h3> Our hypothesis was that <i>PTPN22</i> splice forms may have a different expression pattern in patients compared to controls. Such an effect could enhance other effects from the associated risk alleles. <h3>Material and methods</h3> The authors have investigated the expression of <i>PTPN22</i> splice forms in peripheral blood cells and used genotypic and phenotypic data for analysis of RA patients and controls of Caucasian origin. <h3>Results</h3> <i>PTPN22</i> was found to be different in individuals with RA compared to controls. On average, the shorter splice form was reduced (0.8-fold, p=0.08) and the longer was increased (1.2-fold, p=0.006) for patients. This effect was further enhanced if the ratio of the transcripts for each individual was compared (1.4-fold, p=6 × 10<sup>−9</sup>). This finding was replicated in two independent cohorts of the total size of 165 individuals. <h3>Conclusions</h3> The authors found important differences in expression of <i>PTPN22</i> splice forms between healthy individuals and RA patients, which may increase a gain of function that influence development of the disease. The balance between splice forms may also be of importance during immune response due to great structural differences in the encoded PTPN22 proteins.
TIE2-expressing macrophages limit the therapeutic efficacy of the vascular-disrupting agent combretastatin A4 phosphate in mice
Authors: Abigail F. Welford, Daniela Biziato, Seth B. Coffelt, Silvia Nucera, Matthew Fisher, Ferdinando Pucci, Clelia Di Serio, Luigi Naldini, Michele De Palma, Gillian M. Tozer, Claire E. Lewis
Journal: Journal of Clinical Investigation (2011)

Vascular-disrupting agents (VDAs) such as combretastatin A4 phosphate (CA4P) selectively disrupt blood vessels in tumors and induce tumor necrosis. However, tumors rapidly repopulate after treatment with such compounds. Here, we show that CA4P-induced vessel narrowing, hypoxia, and hemorrhagic necrosis in murine mammary tumors were accompanied by elevated tumor levels of the chemokine CXCL12 and infiltration by proangiogenic TIE2-expressing macrophages (TEMs). Inhibiting TEM recruitment to CA4P-treated tumors either by interfering pharmacologically with the CXCL12/CXCR4 axis or by genetically depleting TEMs in tumor-bearing mice markedly increased the efficacy of CA4P treatment. These data suggest that TEMs limit VDA-induced tumor injury and represent a potential target for improving the clinical efficacy of VDA-based therapies.
Factors associated with sun protection compliance: results from a nationwide cross-sectional evaluation of 2215 patients from a dermatological consultation
Authors: U. Sattler, S. Thellier, V. Sibaud, C. Taïeb, S. Mery, C. Paul, N. Meyer
Journal: British Journal of Dermatology (2014)

Journal Article Factors associated with sun protection compliance: results from a nationwide cross‐sectional evaluation of 2215 patients from a dermatological consultation Get access U. Sattler, U. Sattler Laboratoires Dermatologiques Avène Pierre Fabre Dermo‐Cosmétique Lavaur France Search for other works by this author on: Oxford Academic Google Scholar S. Thellier, S. Thellier Department of Dermatology Paul Sabatier University and Larrey Hospital Toulouse France Search for other works by this author on: Oxford Academic Google Scholar V. Sibaud, V. Sibaud Laboratoires Dermatologiques Avène Pierre Fabre Dermo‐Cosmétique Lavaur France Search for other works by this author on: Oxford Academic Google Scholar C. Taïeb, C. Taïeb Public Health and Quality of Life Pierre Fabre SA Paris France Search for other works by this author on: Oxford Academic Google Scholar S. Mery, S. Mery Laboratoires Dermatologiques Avène Pierre Fabre Dermo‐Cosmétique Lavaur France Search for other works by this author on: Oxford Academic Google Scholar C. Paul, C. Paul Department of Dermatology Paul Sabatier University and Larrey Hospital Toulouse France Search for other works by this author on: Oxford Academic Google Scholar N. Meyer N. Meyer Department of Dermatology Paul Sabatier University and Larrey Hospital Toulouse FranceInserm UMR 1037‐CRCT 'Rho GTPases and Cancer' Toulouse France Correspondence Nicolas Meyer. E‐mail: meyer.n@chu-toulouse.fr Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 170, Issue 6, 1 June 2014, Pages 1327–1335, https://doi.org/10.1111/bjd.12966 Published: 01 June 2014
Genetic Analysis of Chromosome Pairing, Recombination, and Cell Cycle Control during First Meiotic Prophase in Mammals
Authors: P. E. Cohen, S. E. Pollack, J. W. Pollard
Journal: Endocrine Reviews (2006)

Meiosis is a double-division process that is preceded by only one DNA replication event to produce haploid gametes. The defining event in meiosis is prophase I, during which chromosome pairs locate each other, become physically connected, and exchange genetic information. Although many aspects of this process have been elucidated in lower organisms, there has been scant information available until now about the process in mammals. Recent advances in genetic analysis, especially in mice and humans, have revealed many genes that play essential roles in meiosis in mammals. These include cell cycle-regulatory proteins that couple the exit from the premeiotic DNA synthesis to the progression through prophase I, the chromosome structural proteins involved in synapsis, and the repair and recombination proteins that process the recombination events. Failure to adequately repair the DNA damage caused by recombination triggers meiotic checkpoints that result in ablation of the germ cells by apoptosis. These analyses have revealed surprising sexual dimorphism in the requirements of different gene products and a much less stringent checkpoint regulation in females. This may provide an explanation for the 10-fold increase in meiotic errors in females compared with males. This review provides a comprehensive analysis of the use of genetic manipulation, particularly in mice, but also of the analysis of mutations in humans, to elucidate the mechanisms that are required for traverse through prophase I.
The Relation between Retinal and Cerebral Vascular Reactivity in Normal and Arteriosclerotic Subjects
Authors: J. B. HICKAM, J. F. SCHIEVE, W. P. WILSON
Journal: Circulation (1953)

It has been found that retinal arterial reactivity to oxygen is diminished in persons with retinal arteriosclerosis, and that cerebral blood flow and the increment in cerebral flow upon inhalation of carbon dioxide are diminished in persons with cerebral arteriosclerosis. The present study demonstrates that there is a significant positive correlation between retinal arterial reactivity on the one hand, and cerebral blood flow and reactivity, on the other. This finding is taken to mean that arteriosclerosis severe enough to affect measurements of this sort is apt to involve retinal and cerebral vessels together.
Computer-Based Instruction and Diagnosis of Acid-Base Disorders
Authors: Martin Goldberg
Journal: JAMA (1973)

A computer-based approach for instruction and diagnosis of clinical acidbase disorders has been developed. Its significant features are the following: (1) consideration of a differential diagnosis list (rather than a single diagnosis) for any given blood pH plus either carbon dioxide content, bicarbonate level, or partial pressure of carbon dioxide; (2) use of ancillary clinical and laboratory information about the patient to arrive at the most likely diagnosis from the differential diagnosis list; (3) adaptability to users of widely differing clinical expertise and educational backgrounds; and (4) provision for tabulating the relative frequencies of acid-base disorders presented to the computer. The computer's differential diagnosis is based on an acid-base map. A sample case illustrates the logical process involved. This program demonstrates that the computer can mimic the clinical consultant in its approach to diagnosis and in its ability to teach.
Transplantation for Idiopathic Pulmonary Arterial Hypertension
Authors: Justin M. Schaffer, Steve K. Singh, David L. Joyce, Bruce A. Reitz, Robert C. Robbins, Roham T. Zamanian, Hari R. Mallidi
Journal: Circulation (2013)

Lung transplantation and heart-lung transplantation represent surgical options for treatment of medically refractory idiopathic pulmonary arterial hypertension. The effect of the lung allocation score on wait-list and transplantation outcomes in patients with idiopathic pulmonary arterial hypertension is poorly described.Adults diagnosed with idiopathic pulmonary arterial hypertension and listed for transplantation in the 80 months before and after the lung allocation score algorithm was implemented (n=1430) were identified in the United Network for Organ Sharing thoracic registry. Patients were stratified by organ listed and pre- and post-lung allocation score era. The cumulative incidences of transplantation and mortality for wait-listed patients in both eras were appraised with competing outcomes analysis. Posttransplantation survival was assessed with the Kaplan-Meier method. These analyses were repeated in propensity-matched subgroups. Cox proportional hazards analysis evaluated the effect of prelisting and pretransplantation characteristics on mortality. We found that patients in the post-lung allocation score era had significantly worse comorbidities; nevertheless, both lung transplantation and heart-lung transplantation candidates in this era enjoyed lower wait-list mortality and a higher incidence of transplantation in unmatched and propensity-matched analyses. On multivariable analysis, heart-lung transplantation and double-lung transplantation were associated with improved survival from the time of wait-listing, as was being listed at a medium- to high-volume institution. Donor/recipient sex matching predicted posttransplantation survival.The incidence of transplantation has increased while wait-list mortality has decreased in patients with idiopathic pulmonary arterial hypertension wait-listed for transplantation in the post-lung allocation score era. Both heart-lung transplantation and double-lung transplantation are predictive of survival in transplantation candidates with idiopathic pulmonary arterial hypertension, as is being listed at a medium- to high-volume institution. Donor/recipient sex matching is associated with better posttransplantation survival.
p66ShcA modulates oxidative stress and survival of endothelial progenitor cells in response to high glucose
Authors: Valeria Di Stefano, Chiara Cencioni, Germana Zaccagnini, Alessandra Magenta, Maurizio C. Capogrossi, Fabio Martelli
Journal: Cardiovascular Research (2009)

A close relationship exists between hyperglycaemia, oxidative stress, and diabetic complications. In fact, high glucose (HG) determines the overproduction of reactive oxygen species (ROS) by the mitochondria. p66ShcA is a gene that regulates the apoptotic responses to oxidative stress. Indeed, p66ShcA knockout (ko) mice display decreased ROS production and increased resistance to ROS-induced cell death in a variety of pathophysiological settings. Reduced endothelial progenitor cell (EPC) number, differentiation, and function are relevant components of the angiogenesis impairment observed in diabetic patients. We examined the role of p66ShcA in the EPC deficit induced by HG. Mouse bone marrow-derived c-kit+ cells differentiate in endothelial-like cells when plated on fibronectin (BM-derived EPCs). We found that cell culture in the presence of HG up-regulated p66ShcA protein expression and that HG exposure markedly decreased the number of BM-derived EPCs. Conversely, p66ShcA ko BM-derived EPCs were not sensitive to HG inhibition. Indeed, the resistance of p66ShcA ko BM-derived EPCs to HG was associated with reduced levels of both apoptosis and oxidative stress. To functionally link the HG response to ROS production, p66ShcA ko BM-derived EPCs were reconstituted either with p66ShcA wild-type (wt) or with a p66ShcA allele (p66ShcA qq) that was devoid of its ROS-generating function. We found that only p66ShcA wt and not the qq mutant rescued p66ShcA ko cell sensitivity to HG. One major feature of oxidative stress is its ability to reduce the bio-availability of nitric oxide (NO) that, in turn, plays a crucial role in endothelial differentiation and function. We found that the p66ShcA deletion prevented the HG-induced increase of nitrotyrosine, and that the resistance to HG of p66ShcA ko BM-derived EPCs was prevented by NO synthase inhibition. With a reciprocal approach, the treatment of p66ShcA wt cells with a NO donor prevented the HG-induced deficit. Finally, using a Matrigel plug angiogenesis assay, we demonstrated that p66ShcA ko prevented diabetic impairment of angiogenesis in vivo. p66ShcA deletion rescues the BM-derived EPCs defect induced by HG, indicating p66ShcA as a potential therapeutic target in diabetic vasculopathy.
Inhibition of aspirin-induced bronchoconstriction by sodium cromoglycate inhalation.
Authors: N A Martelli, G Usandivaras
Journal: Thorax (1977)

Five patients with asthma and severe aspirin hypersensitivity were challenged on separate days with increasing doses of aspirin given by mouth, starting with 5 mg, until a reduction in FEV1 greater than 15% was obtained. Sodium cromoglycate in doses of 20-40 mg inhibited the bronchoconstrictive reaction not only when inhaled before the challenge but also after it, at a time when progressive reduction in FEV1 values was taking place. According to these results, it seems reasonable to postulate sequential mast cell degranulation and liberation of mediators of anaphylaxis as the mechanism through which aspirin induces bronchoconstriction in aspirin-sensitive asthmatics. The differences between bronchial provocation tests and oral challenge with aspirin are stressed.