tbuckley/cabot-search huggingface dataset:
Differential effects of the complement peptides, C5a and C5a des Arg on human basophil and lung mast cell histamine release.
Authors: E S Schulman, T J Post, P M Henson, P C Giclas
Journal: Journal of Clinical Investigation (1988)

The ability of purified anaphylatoxins to induce human lung mast cell mediator release was investigated. In eight anti-IgE responsive (histamine release = 22 +/- 5%, mean +/- SEM) mast cell preparations of 1-96% purity, C5a and C5a des Arg (0.55 pg/ml to 55 micrograms/ml), failed to elicit or potentiate histamine release; lung fragments were similarly unresponsive. The related peptide C3a was also inactive. All anaphylatoxins failed to induce mast cell leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) release. LTC4 release was also negligible from basophils where C5a was a potent histamine release stimulus. Supernatants from C5a-challenged mast cells remained fully active on basophils, excluding carboxypeptidase inactivation of C5a as an explanation for the lung mast cell results. In contrast to lung, skin mast cells were C5a-responsive (histamine release = 8 +/- 1%, at 55 micrograms/ml, n = 2). We conclude that C5a, though devoid of activity on the human lung mast cell, is a human basophil and skin mast cell secretagogue. These findings demonstrate significant organ-specific heterogeneity in mast cell responsiveness.
Masquerader: High Mobility Group Box-1 and Cancer
Authors: Jessica E. Ellerman, Charles K. Brown, Michael de Vera, Herbert J. Zeh, Timothy Billiar, Anna Rubartelli, Michael T. Lotze
Journal: Clinical Cancer Research (2007)

Abstract Since its identification a third of a century ago, the high-mobility group box-1 (HMGB1) protein has been linked to varied diverse cellular processes, including release from necrotic cells and secretion by activated macrophages engulfing apoptotic cells. Initially described as solely chromatin-associated, HMGB1 was additionally discovered in the cytoplasm of several types of cultured mammalian cells 6 years later. In addition to its intracellular role, HMGB1 has been identified extracellularly as a putative leaderless cytokine and differentiation factor. In the years since its discovery, HMGB1 has also been implicated in disease states, including Alzheimer's, sepsis, ischemia-reperfusion, arthritis, and cancer. In cancer, overexpression of HMGB1, particularly in conjunction with its receptor for advanced glycation end products, has been associated with the proliferation and metastasis of many tumor types, including breast, colon, melanoma, and others. This review focuses on current knowledge and speculation on the role of HMGB1 in the development of cancer, metastasis, and potential targets for therapy.
Abstract CT102: Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia
Authors: Michel Sadelain, Renier Brentjens, Marco Davila, Isabelle Riviere, Xiuyan Wang, Shirley Bartido, Jae Park, Diana Bouhassira, Kevin Curran, Stephen Chung, Jolanta Stefanski, Oriana Borquez-Ojeda, Sergio Giralt
Journal: Cancer Research (2014)

Abstract Chimeric antigen receptors (CARs) are artificial receptors for antigen that redirect antigen specificity, activate T cells and further enhance T cell function through their costimulatory component. Three groups, including our own, have reported objective tumor responses when infusing autologous T cells genetically modified with CD19-targeted CARs into patients with chronic lymphocytic leukemia (CLL), other indolent non-Hodgkin lymphomas (NHL) and, most dramatically in patients with relapsed or refractory B cell acute lymphoblastic leukemia (B-ALL). Here we report on 16 patients with relapsed or refractory B-ALL that we treated with autologous T cells expressing the 19-28z CAR specific to the CD19 antigen. The overall complete response rate was 88%, as assessed by morphological criteria and IgH deep sequencing. This allowed us to transition a majority of these patients to a standard of care allogeneic hematopoietic stem cell transplant (allo-SCT). This therapy was as effective in high-risk patients with Ph+ disease as in those with relapsed disease following prior allo-SCT. Through systematic analysis of clinical data and serum cytokine levels over the first 21 days following T cell infusion, we have defined diagnostic criteria for a severe cytokine release syndrome (sCRS), with the goal of better identifying the subset of patients who will likely require therapeutic intervention with corticosteroids or interleukin-6 receptor blockade to curb the CRS. Additionally, we found that serum C-reactive protein (CRP), a readily available laboratory study, can serve as a reliable indicator for the severity of the CRS and a road map for patient management at centers now contemplating the use of CAR T cell therapy. Based on these remarkably robust clinical results and the toxicity management algorithm we present here, we will soon open a multi-center Phase II clinical trial to further evaluate the efficacy of 19-28z CAR T cells and prospectively validate our proposed CRS monitoring and intervention guidelines in patients who are treated with CAR therapy. Citation Format: Michel Sadelain, Renier Brentjens, Marco Davila, Isabelle Riviere, Xiuyan Wang, Shirley Bartido, Jae Park, Diana Bouhassira, Kevin Curran, Stephen Chung, Jolanta Stefanski, Oriana Borquez-Ojeda, Sergio Giralt. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT102. doi:10.1158/1538-7445.AM2014-CT102
Expression of hsp 27, hsp 60, hsc 70, and hsp 70 stress response genes in cultured human urothelial cells (UROtsa) exposed to lethal and sublethal concentrations of sodium arsenite.
Authors: Michael R Rossi, Seema Somji, Scott H Garrett, Mary Ann Sens, Joginder Nath, Donald A Sens
Journal: Environmental Health Perspectives (2002)

The stress response is one mechanism that the bladder urothelium could potentially employ to protect itself from cellular damage after exposure to arsenic and, in so doing, influence the shape of the dose-response curve at low concentrations of exposure to this environmental pollutant. In the present study, we used the cultured human urothelial cell line UROtsa, a model of human urothelium, to determine the expression of heat shock proteins hsp 27, hsp 60, hsc 70, and hsp 70 after acute and extended exposure of the cells to lethal and sublethal levels of sodium arsenite (NaAsO2). Acute exposure was modeled by exposing confluent cultures of UROtsa cells to 100 micro M NaAsO2 for 4 hr followed by a 48-hr recovery period. Extended exposure was modeled by exposing confluent UROtsa cells to 1, 4, and 8 micro M NaAsO2 for 16 days, with the highest concentration producing cell death by 4 days of exposure. The expression of hsp 27, hsp 60, hsc 70, and hsp 70 mRNA and protein was determined by reverse-transcription polymerase chain reaction and Western analysis. Cell viability was determined by the MTT [(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. The results demonstrated that the expression of hsp 27, hsp 60, and hsc 70 mRNA and protein were not consistently increased by either acute or extended exposure to NaAsO2. In contrast, hsp 70 expression was induced by NaAsO2 after both acute and extended exposure. The degree and duration of the induction of the hsp 70 protein in the extended time course of exposure to NaAsO2 correlated directly with UROtsa cell cytotoxicity. The substantial level of basal expression of hsp 27, hsp 60, and hsc 70 shown previously in human bladder urothelium, coupled with the inducible expression of hsp 70, could provide the human urothelium with a mechanism to withstand and recover from a low level of arsenite exposure.
Protecting the Next Generation — Eliminating Perinatal HIV-1 Infection
Authors: Lynne M. Mofenson
Journal: New England Journal of Medicine (2010)

More than 90% of the 430,000 human immunodeficiency virus type 1 (HIV-1) infections in children each year occur in sub-Saharan Africa, where HIV-1 acquisition through breast milk accounts for more than 40% of infections. However, in Africa, breast-feeding is a cornerstone of child survival. Two randomized trials reported in this issue of the Journal 1,2 show that antiretroviral regimens in breast-feeding infants or lactating mothers significantly decrease postnatal acquisition of HIV-1. It should be possible to eliminate new perinatal HIV-1 infections globally with the use of antiretroviral therapy when needed for maternal health and, when treatment is not otherwise required . . .
The Fire-Safe Cigarette
Authors: Jeffrey R. Botkin
Journal: JAMA (1988)

Fires caused by cigarettes through the ignition of upholstered furniture and mattresses are a serious public health problem, accounting for more than 1500 deaths and 7000 serious injuries per year in the United States. Fire-resistant fabrics and stuffings, public education, and smoke detectors have had a limited impact on this problem. The federal government recently has completed a three-year study of possible modifications in cigarette design. The study has demonstrated the technical feasibility of product design changes that would substantially reduce the propensity of cigarettes to ignite fires. Legislation currently is pending in Congress and in three state legislatures to mandate a cigarette fire safety standard. This legislation deserves strong support by the medical profession. (<i>JAMA</i>1988;260:226-229)
4 HCV SPRINT-1 FINAL RESULTS: SVR 24 FROM A PHASE 2 STUDY OF BOCEPREVIR PLUS PEGINTRON™ (PEGINTERFERON ALFA-2B)/RIBAVIRIN IN TREATMENT- NAIVE SUBJECTS WITH GENOTYPE-1 CHRONIC HEPATITIS C
Authors: P. Kwo, E. Lawitz, J. McCone, E. Schiff, J. Vierling, D. Pound, M. Davis, J. Galati, S. Gordon, N. Ravendhran, L. Rossaro, F. Anderson, I. Jacobson, R. Rubin, K. Koury, C. Brass, E. Chaudhri, J. Albrecht
Journal: Journal of Hepatology (2009)
Salicylate-Induced Pulmonary Edema
Authors: JOHN E. HEFFNER
Journal: Annals of Internal Medicine (1981)

To assess the course and prognosis of salicylate-induced pulmonary edema, we reviewed the records of 36 consecutive patients admitted with serum salicylate levels greater than 30 mg/dL. Pulmonary edema developed in eight patients, and pulmonary infiltrates were never seen in 28 patients. Several features distinguished the two patient groups. Persons with pulmonary edema were older, ingested salicylates chronically, and had a history of smoking. They also were more likely to present with neurologic abnormalities, proteinuria, and serum salicylate levels greater than 40 mg/dL. The severity of pulmonary edema ranged from moderate (no assisted ventilation) to severe (characteristics of adult respiratory distress syndrome requiring assisted ventilation with positive end-expiratory pressure). Pulmonary edema resolved concomitant with a decline in serum salicylate levels. We concluded that certain patients are at increased risk for salicylate pulmonary edema, which responds to measures that lower serum salicylate levels.
Getting guns out of homes
Authors: S. Chapman
Journal: BMJ (1996)

Gun killing sprees, particularly those where people unknown to the gunman are killed in public places, have recently been the catalysts for radical gun law reform in four nations. In 1989 Patrick Purdy returned to his primary school in Stockton, California, shot five children, and injured another 30 before killing himself. The resultant outrage led to the eventual banning of newly manufactured and imported assault rifles in the United States in September 1994.1 Later that year, the murder of 14 women at Montreal's l'Ecole Polytechnique also set in train what eventually became gun control Bill C-68, proclaimed in the Canadian parliament on 6 December 1995. Among various provisions, the bill required the registration of all firearms—a provision always virulently opposed by gun lobbies throughout the world.

The grotesque world record for a mass gun killing in recent peacetime occurred at Tasmania's Port Arthur tourist site on 28 April this year, when Martin Bryant killed 35 people and wounded 18. Within two weeks of …
Physiologic and Pathologic Tremors
Authors: JOSEPH JANKOVIC
Journal: Annals of Internal Medicine (1980)

Tremor, the commonest of the involuntary movement disorders, is characterized by rhythmical oscillatory movement that occurs at rest or during activity; all tremors cease during sleep. Physiologic tremor is present in normal persons and is asymptomatic. Tremor is considered pathologic when it impairs a patient's function. Clinically, the pathologic tremors may be classified as accentuated physiologic, parkinsonian, essential, and cerebellar. We review here the basic mechanisms and clinical features of various tremors and emphasize recent advances in pathophysiology and management.
THE RATIONAL TREATMENT OF URETHRITIS.
Authors: NOAH E. ARONSTAM
Journal: JAMA (1906)

The rational treatment of this affection depends on the etiologic factors that are responsible for its causation. The non-specific forms demand an entirely different regimen than the specific variety. We must endeavor in all cases to eliminate the cause so far as possible. To dwell at length on the treatment of the various types of the malady under discussion would require more time and space than has been allotted to me. Suffice to state, however, that urethritis dependent on certain dyscrasiæ and diatheses must receive their adequate consideration before we can expect favorable results. To treat any given case of urethritis merely with a hand injection and the internal exhibition of some nondescript "urinary antiseptic," without having recourse to physical, urinary and microscopic examination, if necessary, is just as absurd as to treat the symptoms of a febrile disorder, without taking cognizance of the specific elements which may have precipitated
A Randomized Phase II Trial of Single-Agent Gemcitabine, Vinorelbine, or Docetaxel in Patients with Advanced Non-small Cell Lung Cancer Who Have Poor Performance Status and/or Are Elderly
Authors: Swan Swan Leong, Chee Keong Toh, Wan Teck Lim, Xu Lin, Say Beng Tan, Donald Poon, Miah Hiang Tay, Kian Fong Foo, Juliana Ho, Eng Huat Tan
Journal: Journal of Thoracic Oncology (2007)
Studies of the Metabolism and Distribution of Fibrinogen in Patients with Hemophilia A*
Authors: Y. Takeda, Alan Y. Chen
Journal: Journal of Clinical Investigation (1967)

Using autologous (131)I-fibrinogen, we made studies of the metabolism and distribution of fibrinogen in 10 patients with hemophilia A. In two patients simultaneous studies of autologous (131)I-fibrinogen and homologous (125)I-fibrinogen prepared from healthy donors' plasma were carried out. The average value for the plasma volume was 42.1 +/- 8.8 ml/kg; for the plasma fibrinogen concentration, 349 +/- 90 mg/100 ml; for the intravascular fibrinogen, 144 +/- 32 mg/kg; for the interstitial fibrinogen, 30 +/- 11 mg/kg; for the slower half-life of (131)I-fibrinogen, 2.34 +/- 0.17 days; for the transcapillary transfer rate of fibrinogen, 109 +/- 37 mg/kg per day; and for the catabolic and synthetic rates of fibrinogen, 51.7 +/- 13.1 mg/kg per day. Comparison of these results with those of the previous study in healthy male subjects showed that in patients with hemophilia A the catabolic and synthetic rates of fibrinogen are markedly increased, whereas the plasma fibrinogen concentration, intravascular and interstitial fibrinogen, and the transcapillary transfer rate of fibrinogen are not significantly different. The simultaneous studies of autologous (131)I-fibrinogen and normal homologous (125)I-fibrinogen in two subjects revealed that the two preparations behaved very similarly. Based on these findings, we concluded that our present findings are not due to the qualitative difference between the hemophilia A and normal fibrinogens, but that they are due to the difference in the host condition with respect to the fibrinogen metabolism, which is either an increased rate of direct breakdown of fibrinogen or an increased rate of fibrinogen breakdown after fibrin formation, or both.
Dealing with sickness and incompetence: success and failure.
Authors: R. Smith
Journal: BMJ (1989)

BrMedJ 1989;298:1695-8 The General Medical Council's mechanism for dealing with sick doctors  widely perceived as one of its triumphs whereas its inability to tackle incompetence  one of its failures. The present president said on his appointment in November 1988 that the health committee is one of the successes of the GMC and working well. Our 'cure' rate  about a third.1 And Jean Robinson, a lay member of the council and one of its sternest critics, says that the health committee seems to work effectively and humanely.2 If the machinery has a deficiency it lies not in its effectiveness in dealing with doctors it encounters but rather in its failure to make contact with many of the sick doctors who are putting themselves and their patients at risk. Another defect may be that the council has no power over sick medical students despite evidence that sick doctors' problems commonly began when they were students.3 The number of incompetent doctors  unknown, but the president of the GMC suggested to me that it may be of the order of 10-15% of independently practising doctors?that is, consultants or principals in general practice. Prevalences of 5% were bandied around at a closed meeting held a few years ago that included members of the defence societies. A Canadian study found   in the medical records or care of 8% of a random sample of 255 family practitioners and three of a sample of 136 specialists.4 A later study found that 15% of 649 family practitioners and 2% of 255 specialists from 11 disciplines had serious deficiencies (RG McAuley, congress on continu ing medical education, Los Angeles, 1988). The prevalence clearly depends critically on how incom? petence  defined and measured, but few doctors dispute in private that incompetence  an important problem. At the moment the GMC can deal with incompetent doctors only through its disciplinary machinery, and the key question  whether there should be some other mechanism?as there  for sick doctors.
LIVING ON BREAD.
Authors: ALEXANDER HAIG
Journal: JAMA (1902)

There are several forms of the uric acid free diet as I have elsewhere mentioned,<sup>1</sup>such as:<sup>1</sup>, that which consists of milk, cheese, potatoes and fruit, and contains no bread; 2, that which contains these things with more or less bread and breadstuffs, and 3, the form with which I am concerned to-day, in which bread and breadstuffs form the chief sources of nourishment and a small quantity of fruit and vegetables are taken merely as sauces for the bread. For the sake of comparison I shall give the approximate quantities required in each of these diets for a man of 140 pounds weight, who is supposed to be young and leading an active life, and therefore requiring a rather full diet, one that will yield 3.3 grs. of urea per pound of body weight per day. The milk, cheese, potato and fruit diet for this man would be
Sjögren's Syndrome (Sicca Syndrome): Current Issues
Authors: HARALAMPOS M. MOUTSOPOULOS
Journal: Annals of Internal Medicine (1980)

This paper outlines the clinical, serologic, and immunogenetic differences and similarities of Sjögren's syndrome alone (primary) and Sjögren's syndrome associated with rheumatoid arthritis and systemic lupus erythematosus (secondary). The immunoregulation in Sjögren's syndrome is discussed and the incidence of immune complex-like material, its nature, pathophysiology, and clearance by the Fc recptor of the reticuloendothelial system presented.
The Burlington Randomized Trial of the Nurse Practitioner
Authors: Walter O. Spitzer, David L. Sackett, John C. Sibley, Robin S. Roberts, Michael Gent, Dorothy J. Kergin, Brenda C. Hackett, Anthony Olynich, W. I. Hay, G. Lefroy, G. Sweeny, I. Vandervlist, H.S. Nielsen, E. V. MacKrell, N. Prowse, A. Brame, E. Fedor, K. Wright
Journal: New England Journal of Medicine (1974)

Abstract From July, 1971, to July, 1972, in a large suburban Ontario practice of two family physicians, a randomized controlled trial was conducted to assess the effects of substituting nurse practitioners for physicians in primary-care practice. Before and after the trial, the health status of patients who received conventional care from family physicians was compared with the status of those who received care mainly from nurse practitioners. Both groups of patients had a similar mortality experience, and no differences were found in physical functional capacity, social function or emotional function. The quality of care rendered to the two groups seemed similar, as assessed by a quantitative "indicator-condition" approach. Satisfaction was high among both patients and professional personnel. Although cost effective from society's point of view, the new method of primary care was not financially profitable to doctors because of current restrictions on reimbursement for the nurse-practitioner services. (N Engl J Med 290:251–256, 1974)
METHODS FOR THE PURE CULTURE OF CERTAIN PROTOZOA
Authors: R.W. Glaser, N. A. Coria
Journal: The Journal of Experimental Medicine (1930)

Some media are described which inhibit bacterial growth, but are favorable to protozoan development. A purification technique, which takes advantage of geotropic responses, was devised and used successfully with 7 species of protozoa, including flagellates and ciliates. The method was also used with a Spirillum. For one flagellate which could not be purified in this manner, a procedure involving chemical sterilization was employed. Paramecium caudatum was purified, but failed to develop subsequently in the absence of living microorganisms. Four of the protozoa which were purified ingest other microorganisms normally. The work shows that purified protozoa grow well under proper conditions, and then they can be studied culturally and biologically, like bacteria.
An Affair of the Heart
Authors: Howard Bird
Journal: New England Journal of Medicine (1992)

A title like that tells where you are going — a relationship as old as Adam and Eve. What gives away the meaning? It's the word heart, that all-purpose metaphor for love and emotion.Hearts have astonishing lives of their own. Hearts are faint and hearts are stout; hearts are open, hearts are closed; hearts are clean and hearts are mean; warm and cold, and faint and bold; hearts are light and hearts are heavy, some as heavy as a stone.They beat as one — two hearts in waltz time. Other hearts are lonely hunters. Hearts are whole . . .