tbuckley/cabot-search huggingface dataset:
Murine lymphoid procoagulant activity induced by bacterial lipopolysaccharide and immune complexes is a monocyte prothrombinase
Authors: BS Schwartz, GA Levy, DS Fair, TS Edgington
Journal: The Journal of Experimental Medicine (1982)

Murine lymphoid cells respond rapidly to bacterial lipopolysaccharide or antigen-antibody complexes to initiate or accelerate the blood coagulation pathways. The monocyte or macrophage has been identified as the cellular source, although lymphocyte collaboration is required for the rapid induction of the procoagulant response. This procoagulant activity is identified in the present study as a direct prothrombin activator, i.e., a prothrombinase. Studies with plasmas deficient in single coagulation factors demonstrate that the induced murine procoagulant activity effector molecule does not require factors XII, VIII, VII, X, or V, but does require prothrombin to transform fibrinogen to fibrin. This enzyme(s) produces limited proteolysis of prothrombin to yield thrombin or thrombinlike products that are functionally capable of converting fibrinogen to fibrin. The prothrombinase is undetectable in freshly isolated Murine lymphoid cells respond rapidly to bacterial lipopolysaccharide or antigen-antibody complexes to initiate or accelerate the blood coagulation pathways. The monocyte or macrophage has been identified as the cellular source, although lymphocyte collaboration is required for the rapid induction of the procoagulant response. This procoagulant activity is identified in the present study as a direct prothrombin activator, i.e., a prothrombinase. Studies with plasmas deficient in single coagulation factors demonstrate that the induced murine procoagulant activity effector molecule does not require factors XII, VIII, VII, X, or V, but does require prothrombin to transform fibrinogen to fibrin. This enzyme(s) produces limited proteolysis of prothrombin to yield thrombin or thrombinlike products that are functionally capable of converting fibrinogen to fibrin. The prothrombinase is undetectable in freshly isolated
Hamster health care
Authors: I. Morrison, R. Smith
Journal: BMJ (2000)

Multiple sclerosis (MS) therapies modulate T-cell autoimmunity in the central nervous system (CNS) but may exacerbate latent infections. Fingolimod, a nonselective sphingosine-1-phosphate (S1P) receptor agonist that induces sustained lymphopenia and accumulates in the CNS, represents a new treatment modality for MS. We hypothesized that sustained lymphopenia would not be required for efficacy and that a selective, CNS-penetrant, peripherally short-acting, S1P<sub>1</sub> agonist would show full efficacy in a mouse MS model. Using daily treatment with 10 mg/kg 2-(4-(5-(3,4-diethoxyphenyl)-1,2,4-oxadiazol-3-yl)-2,3-dihydro-1<i>H</i>-inden-1-yl amino)ethanol (CYM-5442) at the onset of clinical signs in myelin oligodendrocyte glycoprotein MOG<sub>35–55</sub>- induced experimental allergic encephalomyelitis (EAE), we assessed clinical scores, CNS cellular infiltration, demyelination, and gliosis for 12 days with CYM-5442, vehicle, or fingolimod. CYM-5442 levels in CNS and plasma were determined at experiment termination, and blood lymphopenia was measured 3 and 24 h after the last injection. Plasma levels of cytokines were assayed at the end of the protocol. Changes in S1P<sub>1</sub>-enhanced green fluorescent protein expression on neurons and astrocytes during active EAE and upon CYM-5442 treatment were quantified with flow cytometry and Western blotting by using native-locus enhanced green fluorescent protein-tagged S1P<sub>1</sub> mice. S1P<sub>1</sub> agonism alone reduced pathological features as did fingolimod (maximally lymphopenic throughout), despite full reversal of lymphopenia within each dosing interval. CYM-5442 levels in CNS but not in plasma were sustained. Neuronal and astrocytic S1P<sub>1</sub> expression in EAE was suppressed by CYM-5442 treatment, relative to vehicle, and levels of key cytokines, such as interleukin 17A, were also significantly reduced in drug-treated mice. S1P<sub>1</sub>-selective agonists that induce reversible lymphopenia while persisting in the CNS may be effective MS treatments.
In vitro studies of plasmid-mediated penicillinase from Streptococcus faecalis suggest a staphylococcal origin.
Authors: B E Murray, B Mederski-Samoraj, S K Foster, J L Brunton, P Harford
Journal: Journal of Clinical Investigation (1986)

A strain of Streptococcus faecalis with plasmid-mediated penicillinase production was studied further. Partially purified penicillinase from the S. faecalis strain hydrolyzed penicillin, ampicillin, and ureido-penicillins but not penicillinase-resistant semisynthetic penicillins, cephalosporins, or imipenem; hydrolysis was inhibited by clavulanic acid. Hydrolysis of a given antibiotic correlated with a marked increase in the minimal inhibitory concentration (MIC) of that drug when a high inoculum was used. As with most enterococci, the MICs of cephalosporins and penicillinase-resistant semisynthetic penicillins were too high for clinical usefulness, although these agents did not show an inoculum effect. Based upon hybridization under stringent conditions of plasmid DNA from the S. faecalis strain to cloned penicillinase genes from Staphylococcus aureus, it appears that these resistance determinants are highly homologous and suggests that this enzyme was introduced into streptococci from staphylococci.
Bacteremia Caused by a Previously Unidentified Species of Rapidly Growing Mycobacterium Successfully Treated with Vancomycin
Authors: LEENA JADEJA
Journal: Annals of Internal Medicine (1983)

Bacteremia caused by rapidly growing mycobacteria are usually due to Mycobacterium fortuitum or M. chelonei. Other rapidly growing mycobacteria generally are considered to be nonpathogenic. We report the case of a patient with bacteremia due to an unidentified, rapidly growing, scotochromogenic mycobacteria that was detected by a radiometric blood culture system. Results of in-vitro susceptibility testing indicated that the organism was susceptible to vancomycin and other antimicrobial agents, and the patient was successfully treated with vancomycin. We believe that this is the first report of successful use of vancomycin therapy for a mycobacterial infection.
Actin grips: Circular actin-rich cytoskeletal structures that mediate the wrapping of polymeric microfibers by endothelial cells
Authors: Desiree Jones, DoYoung Park, Mirela Anghelina, Thierry Pécot, Raghu Machiraju, Ruipeng Xue, John J. Lannutti, Jessica Thomas, Sara L. Cole, Leni Moldovan, Nicanor I. Moldovan
Journal: Biomaterials (2015)
Substance Abuse Terminology
Authors: Sanford M. Reder
Journal: JAMA (1988)

<h3>To the Editor.—</h3> I applaud the effort that has gone into the process of trying to arrive at a consensus on the definition of terms in the field of chemical dependency.<sup>1</sup>In many respects the project has been successful. However, there remains confusion about the definitions of<i>addiction</i>and<i>dependence</i>. For all practical purposes these terms are used interchangeably, and they include the three components that (by modern and current usage) define chemical dependence: compulsive use, loss of control, and continued use despite adverse consequences. Why then, in this nomenclature, does addiction include "compulsive use" and "continued use despite... harm," but dependence simply "implies" "loss of control?" Further confusion arises when (psychoactive substance) dependence is used in<i>DSM-III</i>(revised) as a diagnostic entity that includes all three components noted. Would it not make sense to use these terms interchangeably (and consistently) rather than persist in trying to define them
FATAL APLASTIC ANEMIA FOLLOWING CHLORAMPHENICOL (CHLOROMYCETIN®) ADMINISTRATION
Authors: R. K. Smiley
Journal: JAMA (1952)

Reports of serious toxic effects following administration of chloramphenicol have been few. After the chemical structure of this antibiotic became established, the presence of a nitrobenzene radical caused some apprehension in regard to potential toxicity.<sup>1</sup>The early toxicity studies on animals<sup>2</sup>and man<sup>3</sup>led to the conclusion that chloramphenicol is of low toxicity. Later hematological observations on animals following administration of chloramphenicol by various routes were believed to reveal no deleterious effects that could be ascribed to the drug. Smith and co-workers<sup>4</sup>found that anemia developed following intramuscular administration of chloramphenicol to dogs in a dosage of 0.05 to 0.1 gm. per kilogram of body weight. No change occurred in the total or differential white blood cell count. Anemia did not follow oral administration. Gruhzit and associates,<sup>5</sup>using dogs, administered chloramphenicol by different routes for as long as four months in a dosage of 0.1 to
Brief Communication: Management of Implantable Cardioverter-Defibrillators in Hospice: A Nationwide Survey
Authors: Nathan Goldstein
Journal: Annals of Internal Medicine (2010)

Background: Communication about the deactivation of implantable cardioverter-defibrillators (ICDs) in patients near the end of life is rare. Objective: To determine whether hospices are admitting patients with ICDs, whether such patients are receiving shocks, and how hospices manage ICDs. Design: Cross-sectional survey. Setting: Randomly selected hospice facilities. Participants: 900 hospices, 414 of which responded fully. Measurements: Frequency of admission of patients with ICDs, frequency with which patients received shocks, existence of ICD deactivation policies, and frequency of deactivation. Results: 97% of hospices admitted patients with ICDs, and 58% reported that in the past year, a patient had been shocked. Only 10% of hospices had a policy that addressed deactivation. On average, 42% (95% CI, 37% to 48%) of patients with ICDs had the shocking function deactivated. Limitation: The study relied on the knowledge of hospice administrators. Conclusion: Hospices are admitting patients with ICDs, and patients are being shocked at the end of life. Ensuring that hospices have policies in place to address deactivation may improve the care for patients with these devices. The authors provide a sample deactivation policy. Primary Funding Source: National Institute of Aging and National Institute of Nursing Research.
Abstract 2219: Identification of oncogenes in mutant Rpa1 associated tumorigenesis
Authors: Bin Huang, Weijia Zhang, Winfried Edelmann, Yuxun Wang
Journal: Cancer Research (2010)

Abstract Genetic instability is a hallmark of human cancers. However, the precise molecular mechanism and its role in cancer remain elusive. We have demonstrated that a missense mutation in Rpa1 causes defective DNA repair, genetic instability and predisposes mice to cancer, thereby providing one of the first evidence showing a replication associated protein is essential in maintaining genome stability and suppressing tumorigenesis. In humans, loss of the chromosomal locus containing RPA1 and genetic polymorphisms in RPA1 have been found in a wide range of cancers. Hence, a better understanding about the role of Rpa1 mutation in genetic instability and cancer should have critical clinical implications. The studies from our lab and others established the association between mutant Rpa1 and tumors. However, it remains unknown which target is most related to cancer development associated with mutant Rpa1. To search for the candidate target genes, we applied whole genome array comparative genomic hybridization (aCGH) in the tumors developed in Rpa1 mutant mice. This genome-wide chromosome copy number analysis uncovered multiple chromosomal aberrations involving multiple genetic loci along the chromosomes in Rpa1 mutant tumor cells. Moreover, chromosomal profiling analysis revealed unique pattern of chromosomal changes in Rpa1 mutant lymphomas, which is distinct from lymphomas developed in other knockout mouse models carrying mutations in different tumor suppressors. Furthermore, we analyzed all the currently known tumor related genes and found 10 oncogenes to be involved in the chromosomal gains in Rpa1 mutant tumors including c-Myc on chromosome 15 which appears to be the most recurrent. We confirmed overexpression of c-Myc in Rpa1 mutant tumors while the other candidate oncogenes showed variable expression among different tumors. These results strongly suggest an important role of c-Myc in mutant Rpa1 mediated tumorigenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2219.
Effect of Sustained Isometric Handgrip Exercise on Left Ventricular Performance
Authors: RICHARD H. HELFANT, MARIA A. DEVILLA, STEVEN G. MEISTER
Journal: Circulation (1971)

Sustained isometric handgrip exercise was studied in 28 patients, 19 with and nine without catheterization evidence of heart disease. Significant increases occurred in left ventricular systolic and left ventricular end-diastolic pressures (LVEDP), heart rate, cardiac output, and cardiac index, with decreases in stroke volume and stroke index. When control and abnormal groups were compared, no differences could be demonstrated in systolic pressure or heart rate increases. However, the LVEDP increase in the abnormal subjects (9.7 ± 1.7) was significantly ( P &lt; 0.01) higher than in the controls (2.1 ± 0.7). In addition, cardiac index rose significantly ( P &lt; 0.025) in the controls (0.8 ± 0.2), but not ( P &lt; 0.1) in the abnormal subjects (0.2 ± 0.1). Conversely, there was a significant fall in stroke index in the abnormal ( P &lt; 0.005) but not in the control ( P &lt; 0.4) group. When work or stroke-work index-LVEDP relations were compared, the controls uniformly exhibited steep curves, whereas abnormal patients demonstrated curves that were either less steep or flat. ΔWork/ΔLVEDP ratio was [See Equation in PDF File]1.0 in the controls, with one exception, and [See Equation in PDF File]0.77 in the abnormal subjects, with one exception. The test was performed in less than 4 min and no adverse effects were observed. By virtue of its ease, simplicity, safety, and ability to distinguish normal and abnormal ventricular performance, sustained handgrip is a valuable new stress test.
346. Gene Correction of X-Linked SCID Using Engineered Zinc Finger Nucleases and Integration Defective Lentiviral Delivery
Authors: Angelo Lombardo, Christian Beausejour, Fyodor D. Urnov, Jeffrey C. Miller, Michael C. Holmes, Philip D. Gregory, Luigi Naldini
Journal: Molecular Therapy (2005)

X-linked severe combined immunodeficiency (X-SCID) is a fatal monogenic disorder caused by mutations in the IL2R|[gamma]| gene. Recently, the disease was successfully treated by retroviral vector (RV) mediated gene replacement in hematopoietic stem cells (HSC). A crucial factor for the success of this approach was the selective growth advantage of gene modified cells in vivo, which allowed full lymphoid repopulation from a small number of transduced HSC. Unfortunately, leukemia developed in a fraction of treated patients, and its origin was linked to RV insertional mutagenesis. Thus, although stable genetic modification is required for HSC gene therapy, the widespread non-random distribution of retroviral integration poses a challenge for the safe use of RV in HSC. An alternative approach to gene replacement is the correction of the endogenous gene using engineered zinc finger protein-based nucleases (ZFNs) to specifically target a DNA double stranded break at the site of mutation. One mechanism the cell uses to repair these breaks is homologous recombination (HR), and specific nucleotide substitution can be made in the genome by delivering an extrachromosomal donor molecule to serve as the repair template during HR. By the combined delivery of the cognate ZFNs and template DNA, mutations may be corrected and normal gene function restored. Although this only occurs in a fraction of treated cells, selection of the corrected cells may allow successful exploitation of this new technology for gene therapy. Moreover, because gene correction stably restores both gene function and its normal regulation, it overcomes the limitations of integrative gene replacement and eliminates its possible adverse effects. However, for gene therapy applications, both ZFNs and donor DNA must be delivered into HSCs with high efficiency and without perturbing their function, a major challenge for current non-viral gene transfer technologies.
Chains of transmission and control of Ebola virus disease in Conakry, Guinea, in 2014: an observational study
Authors: Ousmane Faye, Pierre-Yves Boëlle, Emmanuel Heleze, Oumar Faye, Cheikh Loucoubar, N'Faly Magassouba, Barré Soropogui, Sakoba Keita, Tata Gakou, El Hadji Ibrahima Bah, Lamine Koivogui, Amadou Alpha Sall, Simon Cauchemez
Journal: The Lancet Infectious Diseases (2015)
Once-Daily Pefloxacin + Teicoplanin vs Netilmicin + Teicoplanin in Empirical Therapy for Fever and Neutropenia
Authors: M. Studená, E. Hlavácová, L. Helpianska, S. Spanik, J. Lacka, E. Kukucková, T. Kollár, T. Sálek, J. Sufliarsky, J. Trupl, V. Krcméry
Journal: Drugs (1995)
MBK Neuropathy Among Spray Painters
Authors: Joseph S. Mallov
Journal: JAMA (1976)

It has been suggested that the solvent methyl<i>N</i>-butyl ketone (MBK) may cause peripheral neuropathy in humans. An Investigation was undertaken after two cases of peripheral neuropathy among spray painters at one work site were reported to the National Institute for Occupational Safety and Health. Twenty-six painters were interviewed and examined. Two were found to have definite peripheral neuropathy and one had a probable case. Although one of these men had been exposed to lead in the past, there are strong reasons to believe that MBK was responsible for his neuropathy. There was nothing to suggest excessive lead absorption in the other two men. (<i>JAMA</i>235:1455-1457, 1976)
Regulation of the mature human T cell receptor gamma repertoire by biased V-J gene rearrangement.
Authors: H Kohsaka, P P Chen, A Taniguchi, W E Ollier, D A Carson
Journal: Journal of Clinical Investigation (1993)

To delineate how gene rearrangement influences the expressed human gamma delta T cell repertoire, we generated T cell receptor gamma (TCR gamma) V domain-specific cDNA libraries from the peripheral lymphocytes of eight donors and sequenced a total of 232 TCR gamma gene transcripts. The libraries consisted of both in-frame and out-of-frame rearranged TCR gamma genes. The in-frame TCR gamma gene transcripts were used to determine the diversity of functional T cells, whereas the out-of-frame transcripts, primarily derived from alpha beta T cells, were used to assess the frequencies of TCR V gamma-J gamma rearrangements in progenitor T lymphocytes. The results showed that both sets of transcripts exhibited strikingly restricted V gamma-J gamma combinations. Only 11 of 40 potential V gamma-J gamma rearrangements were common ( > or = 3% of total). The pattern of gene usage in the functional and nonfunctional transcripts was similar and did not differ markedly among donors. The only exception was the predominance of V gamma 9-JP in potentially functional transcripts from seven of eight individuals. These results show that V gamma-J gamma rearrangement is nonrandom and suggest that the diversity of TCR gamma genes in the functional gamma delta T cell repertoire partly depends upon preferentially rearranged V gamma-J gamma gene combinations. However, the expansion of V gamma 9/V gamma 2 T cells in adult peripheral blood can only be explained by antigenic selection of relatively rare V gamma 9-JP recombinants.
British public will rule on fertility advances
Authors: L Dillner
Journal: BMJ (1994)

Members of the Human Fertilisation and Embryology Authority (HFEA), which licenses fertility clinics in Britain, admitted last week to feelings of unease and distaste at the idea of eggs from aborted fetuses being used to treat infertile women. They said that the public would have the largest say in whether such treatments went ahead.

Professor Sir Colin Campbell, chairman of the authority, said that such scientific advances were everyone's concern and that the authority was trying to establish guidelines for treatments that were only two or three years away. By that time eggs and ovarian tissues from both aborted fetuses and cadavers could be used to treat infertile women.

Professor Campbell's remarks were made at the launch of the authority's 12 page consultation document that sets out the pros and cons of potential advances in infertility treatments and calls for comments over the next five months. The HFEA brought the publication of its report forward after the media reported that a 59 year old British woman had given birth …
An unusual presentation of extramedullary plasmacytoma occurring sequentially in the testis, subcutaneous tissue, and heart
Authors: L.A. Fernandez, S. Couban, R. Sy, R. Miller
Journal: American Journal of Hematology (2001)

Abstract Extramedullary plasmacytoma (EMP) is a rare neoplasm of soft tissue that usually arises in the respiratory tract, nasal cavity, sinuses, and nasopharynx. It is even more uncommon for it to arise either in the testis or heart. We report the presentation of a case where plasmacytomas were found sequentially in the testis, subcutaneous tissue, and heart. EMP usually has a good prognosis except when it involves the heart. Our patient survived for only 15 months post autologous hematopoietic stem cell transplantation. Am. J. Hematol. 67:194–196, 2001. © 2001 Wiley‐Liss, Inc.
Coumaphos Exposure and Incident Cancer among Male Participants in the Agricultural Health Study (AHS)
Authors: Carol H. Christensen, Elizabeth A. Platz, Gabriella Andreotti, Aaron Blair, Jane A. Hoppin, Stella Koutros, Charles F. Lynch, Dale P. Sandler, Michael C.R. Alavanja
Journal: Environmental Health Perspectives (2009)

BackgroundCoumaphos is an organophosphate livestock insecticide. Previous research in the Agricultural Health Study (AHS) cohort observed a positive association between coumaphos and prostate cancer in men with a family history of prostate cancer.ObjectivesThis study was performed to determine the association between coumaphos and other major cancer sites and to explore the consistency of the association with prostate cancer early (1993–1999) and later (2000–2005) in AHS follow-up.MethodsThis study included 47,822 male licensed pesticide applicators. Incident cases were ascertained by linkage to state cancer registries, and exposure data were collected by enrollment questionnaire. Poisson regression was used to estimate rate ratio (RR) and 95% confidence interval (CI) of cancer for coumaphos exposure controlling for potentially confounding variables.ResultsApproximately 8% of applicators reported use of coumaphos; 8.5% reported a family history of prostate cancer. Cumulative exposure to coumaphos was not associated with cancer risk overall or with any major cancer site including prostate. In men with a family history of prostate cancer, we observed a positive association between ever use of coumaphos and prostate cancer in both early (RR = 2.07; 95% CI, 1.19–3.62, p-interaction = 0.005) and later (RR = 1.46; 95% CI, 0.89–2.40; p-interaction = 0.11) periods of follow-up. Across all years, this association was statistically significant (RR = 1.65; 95% CI, 1.13–2.38; p-interaction = 0.004).ConclusionCoumaphos was not associated with any cancer evaluated here. In men with a family history of disease, there was evidence of an association between coumaphos and prostate cancer, possibly due to genetic susceptibility; however, other explanations, including chance, are plausible.