tbuckley/cabot-search huggingface dataset:
Treatment Milestones in Chronic Myelogenous Leukemia: Stay the Course or Change Therapy?
Authors: Jerald P. Radich
Journal: Journal of the National Comprehensive Cancer Network (2015)

The success of various generations of tyrosine kinase inhibitors in chronic myelogenous leukemia (CML) is well-known, with many patients experiencing long-term benefits from treatment. However, not every patient with CML can tolerate this therapy, shows response to initial treatment, or avoids disease progression or drug resistance. During his presentation at the NCCN 20th Annual Conference, Jerald Radich, MD, shared his thoughts and some supportive data on the critical role of monitoring response at 3 months, the often-neglected yet key issue of patient adherence to therapy, the recommended timing for mutational analysis, and the pressing need to prevent patients from going from chronic-phase disease into accelerated phase/blast crisis.
Recognition of an immunoglobulin VH epitope by influenza virus-specific class I major histocompatibility complex-restricted cytolytic T lymphocytes.
Authors: W Cao, B A Myers-Powell, T J Braciale
Journal: The Journal of Experimental Medicine (1994)

There are two immunogenic sites on the type A influenza A/Japan/57 (H2N2) hemagglutinin (HA) that can be recognized by class I major histocompatibility complex (MHC), H-2Kd-restricted cytolytic T lymphocytes (CTLs). One of these sites encompasses two distinct partially overlapping epitopes, which span HA residues 204-212 and 210-219. During the analysis of the fine specificity of CTL clones directed to the HA 210-219 epitope, we found that one clone 40-2 also recognized the myeloma cell line P3x63-Ag8. P3x63-Ag8 is derived from the MOPC 21 myeloma and expresses an immunoglobulin (Ig) heavy chain variable region (VH) gene which is a member of the murine 7183 VH gene family. Recognition was specific for the endogenously processed MOPC 21 heavy chain in association with the Kd molecules, since the SP2/0 derivative of P3x63-Ag8, which does not make a functional Ig H chain, is not recognized. The VH epitope recognized by clone 40-2 could be mapped to a 10 amino acid peptide spanning MOPC 21 VH residues 49-58. Cross-reactivity for the VH gene product was also demonstrable in some heterogeneous populations of CTL generated in response to influenza virus infection. These results represent the first demonstration of cross-reactivity for an endogenously processed product of a self-Ig by the CTL directed to a foreign antigen and raise the possibility that the Ig VH expression may regulate the CD8+ T cell response to foreign antigens.
Duration of Red-Cell Storage and Complications after Cardiac Surgery
Authors: Colleen Gorman Koch, Liang Li, Daniel I. Sessler, Priscilla Figueroa, Gerald A. Hoeltge, Tomislav Mihaljevic, Eugene H. Blackstone
Journal: New England Journal of Medicine (2008)

Stored red cells undergo progressive structural and functional changes over time. We tested the hypothesis that serious complications and mortality after cardiac surgery are increased when transfused red cells are stored for more than 2 weeks.We examined data from patients given red-cell transfusions during coronary-artery bypass grafting, heart-valve surgery, or both between June 30, 1998, and January 30, 2006. A total of 2872 patients received 8802 units of blood that had been stored for 14 days or less ("newer blood"), and 3130 patients received 10,782 units of blood that had been stored for more than 14 days ("older blood"). Multivariable logistic regression with propensity-score methods was used to examine the effect of the duration of storage on outcomes. Survival was estimated by the Kaplan-Meier method and Blackstone's decomposition method.The median duration of storage was 11 days for newer blood and 20 days for older blood. Patients who were given older units had higher rates of in-hospital mortality (2.8% vs. 1.7%, P=0.004), intubation beyond 72 hours (9.7% vs. 5.6%, P<0.001), renal failure (2.7% vs. 1.6%, P=0.003), and sepsis or septicemia (4.0% vs. 2.8%, P=0.01). A composite of complications was more common in patients given older blood (25.9% vs. 22.4%, P=0.001). Similarly, older blood was associated with an increase in the risk-adjusted rate of the composite outcome (P=0.03). At 1 year, mortality was significantly less in patients given newer blood (7.4% vs. 11.0%, P<0.001).In patients undergoing cardiac surgery, transfusion of red cells that had been stored for more than 2 weeks was associated with a significantly increased risk of postoperative complications as well as reduced short-term and long-term survival.
Effect of aminophenols (5-ASA and 4-ASA) on colonic interleukin-1 generation.
Authors: D Rachmilewitz, F Karmeli, L W Schwartz, P L Simon
Journal: Gut (1992)

The effect of 5-ASA and 4-ASA, drugs used for the treatment of inflammatory bowel disease, on modulation of experimental colitis and on colonic generation of interleukin-1 was evaluated. Three weeks of treatment with 5-ASA or 4-ASA (50 micrograms/kg) and one week of treatment with 5-ASA significantly decreased colonic interleukin-1 generation and the extent and severity of inflammation in a rat model of colitis induced by trinitrobenzene sulphonic acid. Colonic biopsies were obtained from patients with active ulcerative colitis and organ cultured 24 hours in the absence or presence of the following drugs: sulphasalazine, sulphapyridine, 5-ASA and 4-ASA (25-100 micrograms/ml). Interleukin-1 content in tissue cultured in the presence of 5-ASA (100 micrograms/ml) was two-thirds of its content in tissue cultured in drug free medium and its release into the medium was decreased by 50%. Sulphasalazine 50 micrograms/ml significantly decreased by 33% the tissue content but did not affect interleukin-1 release and a higher dose was not more effective. Sulphapyridine and 4-ASA in doses up to 100 micrograms/ml did not affect either interleukin-1 colonic content or its release into the culture medium. We conclude that pharmacological suppression of colonic interleukin-1 generation may be one, although not the sole mechanism to explain the therapeutic efficacy of 5-ASA in the treatment of inflammatory bowel disease.
Association of stem cell factor expression in nasal polyp epithelial cells with aspirin sensitivity and asthma
Authors: M. L. Kowalski, A. Lewandowska‐Polak, J. Woźniak, A. Ptasińska, A. Jankowski, M. Wągrowska‐Danilewicz, M. Danilewicz, R. Pawliczak
Journal: Allergy (2005)

Mast cells constitute a significant proportion of cells infiltrating nasal polyp tissue, and epithelial cells may release stem cell factor (SCF), a cytokine with chemotactic and survival activity for mast cells. We aimed to assess the expression of SCF in human nasal polyp epithelial cells (NPECs) as related to patients’ clinical phenotypes. Nasal polyp tissues were obtained from 29 patients [including nine with aspirin (ASA)‐hypersensitivity and 12 with bronchial asthma] undergoing polypectomy for nasal obstruction. Epithelial cells were obtained following 6‐week culture of nasal polyps explants. The SCF released into the culture supernatant was assessed by enzyme‐linked immunosorbent assay (ELISA) and total SCF mRNA in the polyp tissue was determined by semiquantitative reverse transcriptase polymerase chain reaction (RT‐PCR). For the whole group of patients, the number of polypectomies correlated with expression of SCF mRNA ( r = 0.62; P &lt; 0.005), SCF protein in the NPECs supernatants ( r = 0.39; P &lt; 0.05) and with density of mast cells in epithelial layer ( r = 0.37; P &lt; 0.05) and stromal layer ( r = 0.5; P &lt; 0.01) of nasal polyps. The SCF/ β ‐actin mRNA ratios were significantly higher in ASA‐hypersensitive (AH) asthmatics (median 0.97, range: 0.8–1.5) when compared with ASA‐tolerant (AT) patients (median 0.5, range: 0.1–0.7; P &lt; 0.001). The SCF protein concentration in NPEC supernatants was also significantly higher in AH asthmatics (median 1.10 pg/ μ g DNA, range: 0.4–1.9) when compared with AT patients (median 0.1 pg/ μ g DNA, range: 0.02–1.2; P &lt; 0.001). In the subpopulation of ASA‐sensitive asthmatics the number of poypectomies correlated also with the density of mast cells and eosinophils in the polyp tissue.
Quinidine delays IK activation in guinea pig ventricular myocytes.
Authors: D M Roden, P B Bennett, D J Snyders, J R Balser, L M Hondeghem
Journal: Circulation Research (1988)

A major action of the antiarrhythmic agent quinidine is prolongation of cardiac repolarization. In these experiments, the time-dependent effects of quinidine on the delayed rectifier potassium current, IK, a current contributing to cardiac repolarization, were investigated in acutely disaggregated guinea pig ventricular myocytes using the whole-cell recording configuration of the patch-clamp method. The effect of quinidine on IK was dependent on the duration of depolarization. After long (2,000 msec) pulses, IK was reduced by 30 +/- 27% (SD; n = 8, paired) by 10 microM quinidine; in contrast, after short (100 msec) pulses, the drug decreased IK 65 +/- 35% (p less than 0.05). This effect was found both in paired experiments as well as when quinidine-pretreated cells were compared to non-pretreated cells. Quinidine significantly delayed IK activation (9 +/- 20 msec at baseline vs. 44 +/- 25 msec in drug, p less than 0.05), but did not alter the subsequent time course of activation (time constant 659 +/- 118 msec). These findings are consistent with the hypothesis that quinidine promotes occupancy of a channel state from which opening does not occur.
Immunohistochemical findings in a patient with penicillamine pemphigus
Authors: M. C. J. M. JONG, H. M. G. DOEGLAS, J. W. E. DIJKSTRA
Journal: British Journal of Dermatology (1980)

This report describes the immunofluorescence (IF) findings in sequential skin biopsies and serum obtained during a follow‐up study of a patient who developed pemphigus lesions after D‐penicillamine treatment of arthritis. The distribution in the skin of IgG, IgM and C3 varied with the date, type and site of the biopsy sample. Thus IF patterns showed features of (a) pemphigus vulgaris, (b) pemphigus foliaceus and (c) pemphigus erythematosus. Indirect IF examination indicated the presence of circulating intercellular epithelial antibody of both the IgG and IgM class.
Some Points CONCERNING THE DUODENUM AND THE APPENDIX IN INTESTINAL STASIS
Authors: A. C. Jordan
Journal: BMJ (1912)

THE symptoms and signs of intestinal stasis arl3 very definite and frequently very severe,' 1112 iyet one of the most striking points in connexion with intestinal stasis concerns the position of those medical men who are not familiar wi:hl the phenomena of the disease when they are brought in 1l-luir practice face to face with a well-marked case.They are quite unable to make a diagnosis, and they are * Founded on a demonstration to the Hunterian Society.-
Very late activation antigens (VLA) are human leukocyte-neuronal crossreactive cell surface antigens.
Authors: K D Pischel, H G Bluestein, V L Woods
Journal: The Journal of Experimental Medicine (1986)

The antigenic relationship between human neuronal and lymphocyte cell surface antigens has been analyzed using heteroantisera raised against human peripheral blood mononuclear cells (PBMC). The specificities of the crossreactive antigens were examined by immunoprecipitation of 125I-labeled SK-N-SH cultured neuronal cells using rabbit anti-PBMC (RAPBMC) sera and compared to known specificities using mAb. The predominant reactivity of each rabbit antiserum tested against SK-N-SH cells was with three molecules of 130,000, 160,000, and 180,000 Mr. These three chains comigrated with three molecules precipitated with the very late activation antigen (VLA)-specific mAb A-1A5. Sequential precipitations with mAb A-1A5 established that the three RAPBMC-precipitated bands were members of the VLA complex. This was confirmed by two-dimensional PAGE of the RAPBMC and A-1A5 immunoprecipitates, which were indistinguishable from one another. The two-dimensional pattern was more complex than was anticipated from the heterodimeric model of VLA chain association, and suggests an additional 130,000 Mr component of VLA. The three chains of the VLA complex precipitated by RAPBMC or mAb A-1A5 from SK-N-SH neurons closely resembled the VLA pattern present on activated T cells, including the 180,000 Mr activation-specific alpha 1 chain recognized by mAb TS2/7. Normal brain cell membranes also contain VLA molecules that are precipitated by RAPBMC and mAb A-1A5. Thus the VLA complex provides potentially important shared immunogens on human neurons and T cells.
Tuberculosis Among Foreign-Born Persons in the United States, 1993-1998
Authors: Elizabeth A. Talbot
Journal: JAMA (2000)

ContextImmigration is a major force sustaining the incidence of tuberculosis (TB) in the United States.ObjectiveTo describe trends and characteristics of foreign-born persons with TB and the implications for TB program planning and policy development.Design, Setting, and SubjectsDescriptive analysis of US TB surveillance data from case reports submitted from 1993 to 1998.Main Outcome MeasureDemographic and clinical characteristics of foreign-born persons with TB.ResultsThe number of TB cases among foreign-born persons increased 2.6%, from 7402 in 1993 to 7591 in 1998, and the proportion of US cases that were foreign-born increased from 29.8% to 41.6%. During 1993-1998, the TB case rate was 32.9 per 100,000 population in foreign-born persons compared with 5.8 per 100,000 in US-born persons. Six states reported 73.4% of foreign-born cases (California, New York, Texas, Florida, New Jersey, and Illinois). Approximately two thirds of these cases were originally from Mexico, the Philippines, Vietnam, India, China, Haiti, and South Korea. Among those for whom date of US entry was known, 51.5% arrived 5 years or less prior to the diagnosis of TB. Most were male and aged 25 to 44 years. During 1993-1996, the proportion receiving some portion of treatment under directly observed therapy increased from 27.3% to 59.1% and approximately 70% completed therapy in 12 months. The rate of primary resistance to isoniazid was 11.6% and to both isoniazid and rifampin was 1.7%.ConclusionsAs the United States moves toward the goal of TB elimination, success will depend increasingly on reducing the impact of TB in foreign-born persons. Continued efforts to tailor local TB control strategies to the foreign-born community and commitment to the global TB battle are essential.
Estrogen’s bone-protective effects may involve differential IL-1 receptor regulation in human osteoclast-like cells
Authors: Teresa Sunyer, Jennifer Lewis, Patricia Collin-Osdoby, Philip Osdoby
Journal: Journal of Clinical Investigation (1999)

Declining estrogen levels during the first postmenopausal decade lead to rapid bone loss and increased fracture risk that can be reversed by estrogen replacement therapy. The bone-protective effects of estrogen may involve suppression of inflammatory cytokines that promote osteoclastogenesis and bone resorption, such as IL-1, TNF-α, and IL-6. We investigated whether estrogen modulates IL-1 actions on human osteoclasts (OCs) and other bone cell types. Isolated human OCs and primary bone marrow–derived OC-like cells expressed both the signaling (IL-1RI) and decoy (IL-1RII) IL-1 receptors, whereas only IL-1RI was detected in osteoblasts. IL-1RII/IL-1RI mRNA ratios and release of soluble IL-1RII (sIL-1RII) were lower in OC-like cells derived from women in the late postmenopausal period compared with younger women, but were unrelated to male donor age, suggesting that estrogen might play a role in regulating IL-1 receptor levels in vivo. Estrogen directly reduced in vitro OC-like cell IL-1RI mRNA levels while increasing IL-1RII mRNA levels and sIL-1RII release. These estrogenic events were associated with inhibited IL-1–mediated cytokine (IL-8) mRNA induction and cell survival, i.e., increased apoptosis. In contrast, estrogen did not alter IL-1R levels or IL-1 responsiveness in primary human osteoblasts or bone marrow stromal cells. We conclude that one novel mechanism by which estrogen exerts bone-protective effects may include a selective modulation of IL-1R isoform levels in OC or OC-like cells, thereby reducing their IL-1 responsiveness and cell survival. Conversely, this restraint on IL-1 actions may be lost as estrogen levels decline in aging women, contributing to an enhanced OC-mediated postmenopausal bone loss.
Randomized Controlled Trial of Annual Zoledronic Acid to Prevent Gonadotropin-Releasing Hormone Agonist–Induced Bone Loss in Men With Prostate Cancer
Authors: M. Dror Michaelson, Donald S. Kaufman, Hang Lee, Francis J. McGovern, Philip W. Kantoff, Mary Anne Fallon, Joel S. Finkelstein, Matthew R. Smith
Journal: Journal of Clinical Oncology (2007)

Gonadotropin-releasing hormone (GnRH) agonists decrease bone mineral density (BMD) and increase fracture risk in men with prostate cancer. Annual zoledronic acid increases BMD in postmenopausal women, but its efficacy in hypogonadal men is not known.In a 12-month study, 40 men with nonmetastatic prostate cancer who were receiving a GnRH agonist and had T scores more than -2.5 were randomly assigned to zoledronic acid (4 mg intravenously on day 1 only) or placebo. BMD of the posteroanterior lumbar spine and proximal femur were measured by dual-energy x-ray absorptiometry.Mean (+/- SE) BMD of the posteroanterior lumbar spine decreased by 3.1% +/- 1.0% in men assigned to placebo and increased by 4.0% +/- 1.0% in men assigned to zoledronic acid (P < .001). BMD of the total hip decreased by 1.9% +/- 0.7% in men assigned to placebo and increased by 0.7% +/- 0.5% in men assigned to zoledronic acid (P = .004). Similar between-group differences were observed for the femoral neck and trochanter. Serum N-telopeptide, a marker of osteoclast activity, decreased significantly after zoledronic acid treatment.In men receiving a GnRH agonist, a single treatment with zoledronic acid significantly increased BMD and durably suppressed serum N-telopeptide levels for 12 months. Annual zoledronic acid may be a convenient and effective strategy to prevent bone loss in hypogonadal men.
An Official American Thoracic Society Research Statement: Noninfectious Lung Injury after Hematopoietic Stem Cell Transplantation: Idiopathic Pneumonia Syndrome
Authors: Angela Panoskaltsis-Mortari, Matthias Griese, David K. Madtes, John A. Belperio, Imad Y. Haddad, Rodney J. Folz, Kenneth R. Cooke
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Section:ChooseTop of pageAbstract <<CONTENTSINTRODUCTIONMETHODSRESULTSIDIOPATHIC PNEUMONIA SYND...THE PATHOGENESIS OF IPS A...THE ROLE OF SOLUBLE MEDIA...THE ROLE OF CELLULAR EFFE...MECHANISMS OF LEUKOCYTE R...TARGETS OF INFLAMMATION A...PRECLINICAL INTERVENTIONS...THE DIAGNOSTIC AND THERAP...CONCLUSIONS AND FUTURE DI...ReferencesCITING ARTICLES
Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study
Authors: Max S Topp, Nicola Gökbuget, Anthony S Stein, Gerhard Zugmaier, Susan O'Brien, Ralf C Bargou, Hervé Dombret, Adele K Fielding, Leonard Heffner, Richard A Larson, Svenja Neumann, Robin Foà, Mark Litzow, Josep-Maria Ribera, Alessandro Rambaldi, Gary Schiller, Monika Brüggemann, Heinz A Horst, Chris Holland, Catherine Jia, Tapan Maniar, Birgit Huber, Dirk Nagorsen, Stephen J Forman, Hagop M Kantarjian
Journal: The Lancet Oncology (2014)
TOXIC EPIDERMAL NECROLYSIS PRODUCED BY AN EXTRACELLULAR PRODUCT OF STAPHYLOCOCCUS AUREUS
Authors: J. P. ARBUTHNOTT, JANET KENT, A. LYELL, C. G. GEMMELL
Journal: British Journal of Dermatology (1971)

SUMMARY.— A typical phage group 2 staphylococcal isolate from a case of toxic epidermal necrolysis of Ritter's type produces a diffusible macromolecular thermolabile product which rapidly induces epidermal necrolysis in new‐born mice. The susceptibility to this necrolytic factor decreases markedly with age. The factor responsible has been partly purified.
Role of fear in overdiagnosis and overtreatment--an essay by Iona Heath
Authors: I. Heath
Journal: BMJ (2014)

Iona Heath argues that doctors and patients need to face up to their fears of uncertainty and death if we are to control overmedicalisation

In the preface to her influential essay Illness as Metaphor , Susan Sontag wrote:

> Illness is the night side of life, a more onerous citizenship. Everyone who is born holds dual citizenship, in the kingdom of the well and in the kingdom of the sick. Although we all prefer to use the good passport, sooner or later each of us is obliged, at least for a spell, to identify ourselves as citizens of that other place.1

Today the kingdom of the well is being rapidly absorbed into the kingdom of the sick, as clinicians and health services busy themselves in ushering people across this important border in ever increasing numbers. Sontag clearly recognises the discomforts of the kingdom of the sick and the extent to which an imposed citizenship there corrodes the joys of life. Yet her essay was first published in 1978, long before the erosion of the kingdom of the well had begun in earnest. With the rise of neoliberal economics, health became a commodity like any other. The exploitation of sickness, and fears of sickness, for the pursuit of profit increased hugely over the subsequent decades, underpinned by the rapid commercialisation of healthcare.

Now, more than three decades later, fewer and fewer of us find ourselves still holding Sontag’s good passport and ever more are corralled into the kingdom of the sick earlier than ever, and residency there becomes longer and longer. All this is legitimised by being described as an epidemic of chronic illness, although many of those affected have no symptoms whatsoever. The motivation for the invasion is provided by a toxic combination of good intentions, wishful thinking, and vested …
Calcium, its role in isoproterenol-stimulated atrial natriuretic peptide secretion by superfused rat atria.
Authors: R J Schiebinger
Journal: Circulation Research (1989)

The beta-adrenergic agonist isoproterenol stimulates immunoreactive atrial natriuretic peptide (IR-ANP) secretion by superfused rat atria in vitro. beta-Adrenergic agonists alter the cellular handling of calcium, which culminates in a rise in the systolic calcium concentration. This is achieved by increasing calcium influx through voltage-dependent calcium channels and by increasing the storage pool of calcium in the sarcoplasmic reticulum (SR). We therefore asked the question whether isoproterenol-stimulated IR-ANP secretion was dependent on the protein kinase A-induced rise in systolic calcium or was due to a direct effect of protein kinase A activation. Isolated rat left atria paced at 3 Hz were superfused in vitro. IR-ANP secretion was determined by radioimmunoassay of timed collections of the superfusate. Superfusion with 0.1 microM isoproterenol or 0.5 mM dibutyryl cyclic AMP increased IR-ANP secretion twofold. Stimulated IR-ANP secretion was lowered to near baseline by lowering the buffer calcium concentration from 1.8 to 0.2 mM or by adding to the superfusate 10 microM nitrendipine (a calcium-channel blocker) or 1 microM ryanodine (an inhibitor of SR calcium release). Superfusion of nonbeating, electrically quiescent left atria with 0.1 microM isoproterenol failed to stimulate IR-ANP secretion. We conclude: 1) Isoproterenol-stimulated IR-ANP secretion is dependent on calcium influx through voltage-dependent calcium channels and on the release of calcium from the SR. 2) Enhanced calcium influx alone is not adequate to maintain isoproterenol-stimulated IR-ANP secretion. 3) The SR appears to be the primary source of calcium for isoproterenol-stimulated IR-ANP secretion.(ABSTRACT TRUNCATED AT 250 WORDS)