tbuckley/cabot-search huggingface dataset:
S55 The Aminopeptidase CD13 Regulates Homotypic Aggregation of Neutrophils
Authors: CA Fiddler, G Murphy, AS Cowburn, H Parfrey, ER Chilvers
Journal: Thorax (2012)

Neutrophils are critical effector cells of the innate immune response and are recruited to sites of tissue injury in response to locally generated chemoattractants. Neutrophil recruitment is a highly regulated process involving complex interactions with the vascular endothelium and underlying tissue stroma. In addition to adhering to the endothelium, neutrophils can also self-associate, (a process known as homotypic aggregation - HA), which has been proposed to play a key role in disease states such as sepsis. Aminopepetidase N or CD13 is a widely expressed membrane-bound metallopeptidase involved in the migration and invasion of cancer and endothelial cells. Neutrophils express CD13 on their cell surface, which is upregulated by TNF-α, IL-8 and fMLP We have shown that inhibition of aminopeptidase activity enhances the efficacy of TNF-α-induced neutrophil apoptosis (Cowburn et al. J Biol Chem 2006; 281:12458). Cross-linking anti-CD13 monoclonal antibodies (mAb) have been shown to induce HA of monocytic cells through PI3K activation (Mina-Osorio et al. J Leuk Biol 2006; 79:719). We hypothesised that CD13 may be involved in neutrophil migration and HA. Using plasma-Percoll purified human neutrophils and a modified Boyden filtre assay we showed that IL-8 mediated neutrophil chemotaxis was not affected by either the CD13 mAb WM-15 or the aminopeptidase enzymatic inhibitor bestatin. In contrast, IL-8-mediated neutrophil migration through type 1 collagen gels was significantly impaired by WM-15 and MY7 mAbs, which both inhibit enzymatic activity and induce clustering of CD13. The non-clustering CD13 antibody WM-47 and bestatin had no effect. WM-15 and MY7 also promoted neutrophil aggregation as assessed by light microscopy. Phase-contrast video-microscopy demonstrated that in WM-15 treated neutrophils, where HA was evident, the percentage of cells entering collagen 1 gels in response to IL-8 was significantly reduced (26.9% vs 71.8% in non-HA cells). WM-15 does not prime neutrophils, as assessed by superoxide production and shape change, and the cell surface expression of CD11b, CD18 and CD66b were not altered. These data suggest a novel role for CD13 in the homotypic aggregation of neutrophils, which reduces chemoattractant-induced migration through collagen 1 matrix and may predispose to neutrophil micro-aggregation within the circulation.
Doctors at church operated hospitals in Germany demand better pay and conditions
Authors: Ned Stafford
Journal: BMJ (2007)

Tensions between church operated hospitals and the nation’s largest medical trade union are growing in Germany after the Catholic church failed last week to agree a new contract with its 480 000 health and social workers.

Germany’s largest medical trade union, the Marburger Bund, wants better pay and working conditions for doctors in Catholic and Evangelical hospitals, demanding that church hospitals adopt a wage agreement already approved last year by university and public hospitals.

About 300 doctors demonstrated earlier this month in Bad Honnef, the town where contract negotiations were being held in the labour rights commission of Caritas, the Catholic church’s organisation that oversees 500 of Germany’s 2100 hospitals. …
Observations on the effects of aerosolized albuterol in acute asthma.
Authors: L Strauss, R Hejal, G Galan, L Dixon, E R McFadden
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

To determine the dose of albuterol required to terminate acute episodes of asthma, 92 acutely ill subjects received three doses of 2.5 mg each by nebulization every 20 min. Peak expiratory flow rates (PEFR) and signs and symptoms were serially monitored. A dose-response increase in pulmonary function was found, but only 66% of the subjects improved sufficiently to be sent home. Of these, 56% required < or = 5.0 mg of drug to reach the discharge threshold, whereas the remainder needed 7.5 mg. In 34% of participants, albuterol was ineffectual. These individuals were characterized by more severe obstruction at presentation, and after three doses of medication their PEFR still did not exceed 40% of the expected value. Further treatment in the emergency department (ED) or hospital was not immediately helpful, and these patients ultimately required 3.8 +/- 0.4 d of inpatient care to become asymptomatic. There were no discernible differences between responders and nonresponders in the type or quantity of medications used. However, the nonresponders had more severe disease as measured by recurrent hospitalizations and ED visits. This study demonstrates that, in emergency situations, albuterol does not relieve acute airway obstruction in all asthmatic individuals with equal efficacy. Two-thirds of patients are sensitive, and in these patients 5 to 7.5 mg of albuterol provides optimal treatment. In the remainder, albuterol, even in high doses, has little effect for days.
Mental models: The revised theory brings new problems
Authors: David Hardman
Journal: Behavioral and Brain Sciences (1996)

The new notation for mental-models theory proposed by Johnson-Laird and Byrne (1991; 1993) makes predictions that are inconsistent with those made previously by those authors. Notably, two frequently observed reasoning fallacies are not predicted by the theory. Moreover, the assumption made in the domain of syllogistic reasoning, that arbitrary numbers of individuals are used to represent premises, is also shown to cause problems for the prediction of problem difficulty.
Kinetics of the development and recovery of the lung from IgE-mediated inflammation: dissociation of pulmonary eosinophilia, lung injury, and eosinophil-active cytokines.
Authors: J R Shaver, J G Zangrilli, S K Cho, R A Cirelli, M Pollice, A T Hastie, J E Fish, S P Peters
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Events occurring up to 16 d after antigen challenge were characterized using a novel protocol employing four bronchoscopies, two segmental antigen challenge (SAC) procedures (on Days 1 and 2), and six bronchoalveolar lavages (BALs) (on Days 1, 2, 9, and 16) in three groups: ragweed allergic asthmatics with dual phase airway reactions (AA-D), allergic asthmatics with a single early airway reaction (AA-S), and nonallergic nonasthmatic control subjects. In AA-D subjects, SAC produced a marked eosinophilic inflammatory response at 24 h associated with eosinophil degranulation (eosinophil cationic protein [ECP] in BAL fluid) and lung injury, which largely resolved by Day 16. When the second antigen-challenged segment (SAC performed on Day 2) was lavaged 7 d after challenge (Day 9), a persistent pulmonary eosinophilia was noted accompanied by minimal elevations in ECP and albumin. Eosinophil-active cytokines showed unique patterns: interleukin-5 (IL-5) increased in the antigen segment on Day 2 then returned to baseline after 7 d; granulocyte-macrophage colony-stimulating factor (GM-CSF) peaked at Day 2 but was persistently elevated throughout Day 16 in antigen segments, and increased in control segments at late time points; IL-3 levels were constant and similar in antigen and control segments. Changes were specific to AA-D subjects in comparison with control subjects. Elements of the IgE-mediated pulmonary inflammatory response differ markedly in their development and resolution.
Recovery of the human immunodeficiency virus from fibreoptic bronchoscopes.
Authors: P J Hanson, D Gor, J R Clarke, M V Chadwick, B Gazzard, D J Jeffries, H Gaya, J V Collins
Journal: Thorax (1991)

Ten bronchoscopes that had been used on patients with the acquired immunodeficiency syndrome were sampled to determine the nature and extent of microbial contamination. Samples were taken by irrigating the suction biopsy channel with modified viral transport medium and by swabbing the insertion tube. Sampling was repeated after they had been cleaned in detergent and after two minutes9 disinfection in 2% alkaline glutaraldehyde. Before being cleaned the seven bronchoscopes tested by polymerase chain reaction were contaminated with the human immunodeficiency virus, though infectivity and antigen assays gave negative results. Other organisms identified were hepatitis B virus (1), commensal bacteria (9), and Pneumocystis carinii (4). Mean bacterial contamination was 2.27 log colony forming organisms per millilitre. Cleaning the bronchoscope before disinfection removed all detectable contaminants with a reduction in bacterial growth of up to 8 log colony forming units/ml.
THE OXYGEN CONTENT OF THE BLOOD IN RABBITS INFECTED WITH PNEUMOCOCCUS
Authors: Francis W. Peabody
Journal: The Journal of Experimental Medicine (1913)

In rabbits with a severe pneumococcus bacteremia, the oxygen-combining power of the blood falls progressively up to the time of death. Coincident with this there is an even more marked fall in the oxygen content of the arterial blood. The changes in the blood in infected animals are analogous to those seen when the pneumococcus is grown on blood in vitro. They are due to the conversion of hemoglobin into methemoglobin.
THE NATURE, INCIDENCE AND TREATMENT OF ENDAMEBIASIS
Authors: PHILIP W. BROWN
Journal: JAMA (1926)

For the last twenty-five years, the wide distribution of the endameba throughout the temperate zone has provoked much discussion. One of the most significant reports is that by Kofoid and others,<sup>1</sup>who examined the stools of 1,500 soldiers. They found<i>Endameba histolytica</i>present in 3 per cent, of the home service men and in 10.8 per cent, of the overseas men. It is unlikely that the incidence of this ameba is greater in Europe, but the impaired sanitary conditions of actual warfare permitted the 3 per cent, to increase to 10.8 per cent. I have reviewed the last five years' work in the Mayo Clinic, from 1920 to 1924, inclusive. In this period the endameba was identified in 533 cases; however, less than 5 per cent. of all patients are subjected to stool tests. <h3>INCIDENCE AND GENERAL CONSIDERATIONS OF THE ENDAMEBA</h3> As may be seen by the map, most
THE INCUBATION PERIOD IN EPIDEMIC POLIOMYELITIS
Authors: ALBERT E. CASEY
Journal: JAMA (1942)

Recent reviews of work on poliomyelitis<sup>1</sup>contain no data pertinent to the incubation period of this disease in man. Many persons following Wickmann's<sup>2</sup>lead attempted to estimate the incubation period from the occurrence of multiple cases in given families. Aycock and Eaton,<sup>3</sup>in studies of multiple cases in more than 500 families, demonstrated that simultaneous infection is the rule in familial poliomyelitis and that the shorter intervals are probably due to a variation in the incubation period in simultaneously infected persons. Since the method of transmission of the disease has not been proved for man,<sup>4</sup>the only feasible method of estimating the incubation period directly is to collect a series of instances in which the initial victim in a neighborhood either visited or was visited by a patient with acute poliomyelitis from some other neighborhood. In an extensive outbreak in Walker County, Ala., in the summer
FDA and Pharma Seek Better Ways to Assess Drug Safety, Efficacy in Clinical Trials
Authors: Mike Mitka
Journal: JAMA (2012)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Pharmacokinetics of drugs in patients with the nephrotic syndrome.
Authors: R Gugler, D W Shoeman, D H Huffman, J B Cohlmia, D L Azarnoff
Journal: Journal of Clinical Investigation (1975)

Since the binding of drugs to plasma proteins can significantly after the intensity of pharmacological and toxicological effects of drugs, we studied the pharmacokinetics of three drugs in patients with hypoalbuminemia secondary to the nephrotic syndrome, but with relatively normal renal function. No significant differences were seen in the pharmacokinetic parameters observed for antipyrine, a drug which is less than 10% bound to plasms proteins. The percentage of unbound diphenylhydantoin, a highly plasms protein-bound drug, was found in patients with the nephrotic syndrome to be twice that of healthy individuals (19,2 vs. 10.1%, P smaller than 0.001). However, there was also a lower steady-state plasma concentration of diphenylhydantoin (2.9 plus or minus 0.6 vs. 6.8 plus or minus 0.6 mug/ml, P smaller than 0.001) secondary to an increase in the plasms clearance (0.048 plus or minus 0.019 vs. 0.022 plus or minus 0.006 liter/kg.h, P smaller than 0.001) in the nephrotic patients. The net effect is no difference in the absolute concentration of unbound diphenylhydantoin in healthy individuals (0.69 plus or minus 0.05 mug/ml) and patients with the nephrotic syndrome (0.59 plus or minus 0.06 mug/ml). Qualitatively, similar differences were observed with clofibrate. The dose of these drugs need not be routinely reduced in patients with the nephrotic syndrome as long as they have reasonably normal renal function (creatinine clearance greater than 50 ml/min). With all highly bound acidic drugs, knowledge of the concentration of unbound drug is essential to the proper interpretation of total blood levels and subsequent treatment of the patient.
Insulin-Specific IgG and IgE Antibody Response in Type I Diabetic Subjects Exclusively Treated with Human Insulin (recombinant DNA)
Authors: H G Velcovsky, K F Federlin
Journal: Diabetes Care (1982)

Bovine and porcine insulins elicit specific antibody response in diabetic subjects after a few months of treatment. In seven type I diabetic individuals who were exclusively treated with human insulin (recombinant DNA) each month, sera were examined for the development of insulin-specific IgG and IgE antibodies. In all patients (except one), IgG antibodies occurred after 2 mo and tended to further increase in concentration after 5–6 mo. IgE antibodies could be detected after 1 mo with a further increase after 2–3 mo and a marked decline thereafter. No patient exhibited allergic symptoms. The results indicate that physicochemical properties of insulin preparations used for treatment and the route of administration are of more importance for immunogenicity than species differences of insulin.
Effects of thymocytes on marrow cells from normal and Busulfan‐treated mice
Authors: Solomon S. Adler
Journal: American Journal of Hematology (1984)

Abstract To study the effects of thymocytes on hemopoiesis, we 1) cocultured marrow cells with and without thymocytes in an erythroid burst (BFU‐E) culture system, 2) injected marrow cells with and without thymocytes into supralethally irradiated mice to assay CFU‐S, and 3) assessed the survival of supralethally irradiated mice transplanted with marrow cells with or without thymocytes. The marrow cells used were either from mice given six injections of busulfan and then permitted to rest for 2, 5, or 10 weeks or from mice treated similarly with the busulfan vehicle alone. Thymocytes did not alter spleen surface colony counts or survivorship in any of the test groups. Thymocytes did effect an increase in BFU‐E cultured from marrow obtained from the vehicle‐treated mice but not from marrow of busulfan‐treated mice. Thus, in addition to decreasing the population of hemopoietic precursors in the marrow, busulfan alters the nature of the remaining early erythroid precursor cell population rendering it unresponsive to thymocytes in vitro.
AGGLUTININ RESPONSE AFTER ARMY TRIPLE TYPHOID VACCINATION
Authors: ERIC A. FENNEL
Journal: JAMA (1918)

The efficiency of typhoid vaccination in the United States Army, as developed by Colonel Russell, is now a matter of history. That typhoid inoculation results in the production of an effective immunity over a considerable period of time has long since been proved, both experimentally and clinically. On the one hand, agglutinin and bactericidal experiments, and on the other, the vital statistics of the Army since the typhoid inoculation became an order, are quite conclusive. The history of paratyphoid and the mixed inoculations is now being made. There is little reason to doubt that they will be as successful as the typhoid inoculations. To determine to what extent specific agglutinins for the three types of organisms used by the Army were produced by the men inoculated, at the suggestion of Lieutenant-Colonel Whitmore, the series of cases here summarized were studied. The series included men who had had no typhoid or
Etiology and prognostic significance of severe uremic pruritus in chronic hemodialysis patients
Authors: I. Narita, B. Alchi, K. Omori, F. Sato, J. Ajiro, D. Saga, D. Kondo, M. Skatsume, S. Maruyama, J.J. Kazama, K. Akazawa, F. Gejyo
Journal: Kidney International (2006)
Nasal mast cells in perennial allergic rhinitics exhibit increased expression of the Fc epsilonRI, CD40L, IL-4, and IL-13, and can induce IgE synthesis in B cells.
Authors: R Pawankar, M Okuda, H Yssel, K Okumura, C Ra
Journal: Journal of Clinical Investigation (1997)

Cross-linking of allergen specific IgE bound to the high affinity IgE receptor (FC epsilonRI) on the surface of mast cells with multivalent allergens results in the release of both pre-formed and newly generated mediators, and in the manifestation of allergic symptoms. The expression of Fc epsilonRI, and the synthesis of IgE are therefore critical for the development of allergic diseases. In this study, we report that nasal mast cells (NMC) from patients with perennial allergic rhinitis (PAR) expressed significantly greater levels of the Fc epsilonRI, CD40L, IL-4, and IL-13 as compared to NMC from patients with chronic infective rhinitis (CIR). The level of Fc epsilonRI expression in NMC of PAR patients strongly correlated with the levels of serum total (r = 0.8, P < 0.003) and specific IgE (r = 0.89, P < 0.0004) antibodies. In addition, stimulation of NMC with IL-4, upregulated the Fc epsilonRIalpha chain expression both at the protein and mRNA levels, as detected by flow cytometry and reverse transcriptase-polymerase chain reaction. Furthermore, NMC from PAR, but not CIR, patients induced IgE synthesis by purified B cells in the presence of Der fII (mite antigen). These results suggest novel and critical roles for mast cells in promoting the allergic reaction through the increased expression of Fc epsilonRI and by enhancing and amplifying the IgE production, within the local microenvironment.
Abstract B54: Coordinate RB/PTEN tumor suppressor loss: Drives aggressive invasive behavior and is strongly associated with the progression of ductal carcinoma to invasive breast cancer
Authors: Agnieszka Witkiewcz, Thomas Pajak, Gordon Schwartz, Erik Knudsen
Journal: Cancer Research (2013)

Abstract Background: A subset of patients with ductal carcinoma in situ (DCIS) treated by surgery will progress to invasive breast cancer. However, there is a limited understanding of the pathways driving such invasive progression and no accepted markers to differentiate lesions at high risk from those at lower risk of developing invasive disease. Methods: The association of two tumor suppressor genes, retinoblastoma (RB) and phosphatase and tensin homolog (PTEN), with risk of any ipsilateral breast event (IBE) or progression to invasive breast cancer (IBC) was analyzed using data from 236 DCIS patients treated with breast conserving surgery with long-term follow up. RB and PTEN expression was assessed with immunohistochemistry. The functional effects of RB and/or PTEN loss were evaluated in preclinical models. Results: Modeling of RB and PTEN loss as observed in DCIS, revealed that the tumor suppressors coordinate complementary processes with respect to proliferation, motility, and invasiveness. Correspondingly, pharmaceutical interventions that mimic activation of RB or PTEN limit the invasive properties of such models. Gene expression profiling demonstrated unique transcriptional programs regulated by each tumor suppressor that are associated with epithelial mesenchymal transition and invasive disease progression. Loss of RB immunoreactivity in DCIS was strongly associated with risk of IBE occurrence (HR=2.64, 95% CI = 1.64 to 4.25) and IBC recurrence (HR=4.66, 95% CI = 2.19 to 9.93). The prognostic power of RB loss alone remained statistically significant in multivariable analyses, although PTEN loss alone did not. However, patients with DCIS lesions that were both RB and PTEN deficient were at higher risk for IBE (HR=3.39, 95% CI = 1.92 to 5.99) and IBC recurrence (HR=6.1, 95% CI = 2.5 to 14.76). Conclusions: These studies indicate that RB and PTEN have independent functions that modulate the invasive potetntial of breast cancer, and together have prognostic utility that could be used to improve the management of DCIS. Citation Format: Agnieszka Witkiewcz, Thomas Pajak, Gordon Schwartz, Erik Knudsen. Coordinate RB/PTEN tumor suppressor loss: Drives aggressive invasive behavior and is strongly associated with the progression of ductal carcinoma to invasive breast cancer. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B54.
The Antivivisection Bill and the Senate.
Authors: S. M. Cullom
Journal: JAMA (1896)

The following informal and unofficial correspondence is self-explanatory: Chicago, May 14, 1896. TheHon. S. M. Cullom, U. S. Senate. <h3>Dear Mr. Senator:</h3> —The views of theAmerican Medical Association, and of the profession generally, are so opposed to the bill now pending in the Senate for the restriction of vivisection that I venture to ask your powerful aid in defeating the measure, which I understand has in the Senate no less adroit an advocate than Senator Gallinger. Nearly every notable advance in the science of physiology,<i>i</i>.<i>e</i>., knowledge of the functions of the organs of the body, and the most valuable facts in connection with animal chemistry, and the effects of medicines, have been made and recorded in consequence of experimentation upon the lower animals, and we therefore look with alarm upon a bill which if it become a law, will relegate science in this country to a