tbuckley/cabot-search huggingface dataset:
Peroxynitrite inhibits leukocyte-endothelial cell interactions and protects against ischemia-reperfusion injury in rats.
Authors: D J Lefer, R Scalia, B Campbell, T Nossuli, R Hayward, M Salamon, J Grayson, A M Lefer
Journal: Journal of Clinical Investigation (1997)

Peroxynitrite (ONOO-) anion, formed by the interaction of superoxide with nitric oxide (NO), has previously been implicated as a cytotoxic agent. However, the effects of this free radical species on neutrophil (PMN)-endothelial cell interactions is largely unknown. We investigated the direct actions of ONOO- on PMN adhesion to endothelial cells in vitro and in vivo, as well as the effects of ONOO- on PMN-mediated myocardial ischemia-reperfusion injury. In vitro, peroxynitrite (100-1,000 nM) inhibited the adhesion of rat PMNs to the endothelium of isolated thrombin- or H2O2-stimulated rat mesenteric artery (P < 0.01 vs. thrombin or H2O2 alone). In vivo, in the rat mesentery, thrombin (0.5 U/ml) or N(G)-nitro-L-arginine-methyl ester (50 microM) significantly increased venular leukocyte rolling and adherence, which were also significantly (P < 0.01) attenuated by ONOO (800 nM) accompanied by reduced P-selectin expression on the endothelial cell surface. Isolated perfused rat hearts were subjected to global ischemia and reperfusion with rat PMNs (10(8) cells), which resulted in profound cardiac depression (i.e., a marked reduction in left ventricular developed pressure and maximal rate of development of left ventricular pressure). Infusion of ONOO- reversed the myocardial contractile dysfunction of ischemic-reperfused rat hearts to near baseline levels, and markedly attenuated the accumulation of PMNs in the postischemic heart. The present study provides strong evidence that nanomolar concentrations of ONOO- both inhibit leukocyte-endothelial cell interactions and exert cytoprotective effects in myocardial ischemia-reperfusion injury. Furthermore, our results suggest that the inhibition of P-selectin expression by peroxynitrite is a key mechanism of the modulatory actions of ONOO- on leukocyte-endothelial cell interactions.
Memoirs of a Pioneer Surgeon
Authors: Lester S. King
Journal: JAMA (1977)

Personal recollections are the foundations of history. An observer declares, "<i>This</i>is what I saw,<i>this</i>is what I did, and<i>this</i>is the way I interpret things." Such primary sources provide the indispensable raw data that the historian critically examines and, with their help, builds up a picture of the past. Dr Middleton's<i>Memoirs</i>comprises such primary source material. He was born in 1866 in southern Utah, a true son of the frontier. Lacking all the advantages of modern life, he wrested an education despite great difficulties and, after getting a medical degree, started as a literal "horse and buggy doctor," to rise to great professional prominence in his state. He described not only his practice but his extensive postgraduate education in this country and abroad and modestly tells of his rise to professional leadership. He retired from practice in 1932 and died in 1938. He wrote the memoirs
Lymphocyte cytosolic protein 1 is a chronic lymphocytic leukemia membrane-associated antigen critical to niche homing
Authors: Jason A. Dubovsky, Danielle L. Chappell, Bonnie K. Harrington, Kitty Agrawal, Leslie A. Andritsos, Joseph M. Flynn, Jeffrey A. Jones, Michael E. Paulaitis, Brad Bolon, Amy J. Johnson, John C. Byrd, Natarajan Muthusamy
Journal: Blood (2013)
Studies in Bullous Diseases
Authors: S. M. Peck, K. E. Osserman, L. B. Weiner, A. Lefkovits, R. S. Osserman
Journal: New England Journal of Medicine (1968)

The indirect immunofluorescent technic has proved of value in differential diagnosis of bullous diseases. Of 24 patients with pemphigus vulgaris studied, serums of 16 demonstrated an intercellular antiepithelial antibody. There was a definite relation between clinical activity and antibody titer. Of nine patients with bullous pemphigoid, serums in six showed antibodies specific for basement zone. Serial antibody titers in both diseases are of clinical value as guides to management of corticoid therapy. Further evidence is needed before etiologic importance can be ascribed to these autoantibodies. One patient had positive intercellular antibodies demonstrable in serum four years before clinical and histologic evidence of pemphigus vulgaris developed. Another whose serum shows intercellular antibodies has yet not demonstrated acantholysis. Therefore, a potential form of pemphigus vulgaris is postulated. Four of 24 patients with pemphigus vulgaris have concurrent myasthenia gravis.
Cancer, Emotions, and Nurses
Authors: SAMUEL C. KLAGSBRUN
Journal: American Journal of Psychiatry (1970)

The author describes a psychiatric consultation program in a cancer research unit. First the nurses were helped to handle their feelings in regard to terminally ill patients. Later an experiment in self-care by the patients was undertaken; it improved the patients' morale by permitting them to see themselves as continuing to be productive human beings. The resulting changed ward culture represents, in the author's opinion, a workable approach to the problem of patient management on a cancer unit.
Theories of Ethics and Medical Practice
Authors: Chauncey D. Leake
Journal: JAMA (1969)

There is much popular and professional confusion over ethics. It is important at once to realize that "ethics" is not a single agreed-upon system of moral conduct, but rather that there are many ethics and many theories of how it is best to behave. In medical practice, the confusion is heightened by the frequent tendency to think of etiquette as ethics. <h3>Social and Professional Control of Medicine</h3> Current technical advance in biomedical endeavor, such as organ transplantation and fertility control, has brought a bewildering shift in our understanding of moral problems associated with medical practice. No longer are there solid and immutable absolutes for our comfort. We are increasingly facing the necessity of making wise judgments promptly on the spot, on the basis of as many of the factors in the immediate situation as we can recognize and with as full an understanding as possible of the consequences of our
A Phase I Trial of the HIV Protease Inhibitor Nelfinavir with Concurrent Chemoradiotherapy for Unresectable Stage IIIA/IIIB Non-small Cell Lung Cancer: A Report of Toxicities and Clinical Response
Authors: Ramesh Rengan, Rosemarie Mick, Daniel Pryma, Mark A. Rosen, Lilie L. Lin, Amit M. Maity, Tracey L. Evans, James P. Stevenson, Corey J. Langer, John Kucharczuk, Joseph Friedberg, Susan Prendergast, Tiffany Sharkoski, Stephen M. Hahn
Journal: Journal of Thoracic Oncology (2012)
Effect of sialidase on the viability of erythrocytes in circulation
Authors: David Aminoff, William C. Bell, Iia Fulton, Nancy Ingebrigtsen
Journal: American Journal of Hematology (1976)

Abstract Sialic acid has been detected on the erythrocyte surface of a number of different species of animals. The objective of this investigation was to determine the physiological significance of these sialyl residues to the viability of erythrocytes in circulation. Methods have been described for the determination of total sialic acid on red blood cells and the conditions under which it may be released with sialidase. Chicken, dog, goat, and rabbit were chosen for these studies because of the differences in the amount (3 × 10 6 ‐72 × 10 6 residues per erythrocyte), and type (N‐acetyl‐ or N‐glycolyl‐neuraminic acids) of sialic acid found on the surface of their erythrocytes. Radioactive tagging with Na 2 51 CrO 4 was used to monitor the effect of sialidase on the viability of erythrocytes upon autologous transfusion. By the two criteria used to assess the viability of erythrocytes — the percentage of erythrocytes surviving 24 hr after the autologous transfusion, and the half‐life of those red blood cells in circulation that survive the first 24 hr — it is apparent that the presence of sialic acid on the cell surface is crucial for the survival of nonnucleated mammalian erythrocytes. The loss of viability of dog erythrocytes can be elicited by the removal of approximately 10% of the total sialic acid. In marked contrast to the behavior of mammalian erythrocytes, sialidase‐treated chicken erythrocytes appear to retain their viability in circulation.
Engineered recombinant ovomucoid third domain can desensitize Balb/c mice of egg allergy
Authors: P. Rupa, Y. Mine
Journal: Allergy (2006)

The purpose of this study was to determine the in vivo desensitization efficacy of a hypoallergenic variant of egg white ovomucoid third domain (DIII) in Balb/c mice model. We mapped the immunodominant B-cell epitopes of ovomucoid in Balb/c mice. A hypoallergenic ovomucoid third domain (GMFA) mutant isoform having ablated allergenicity against egg allergic patient's sera was used to desensitize DIII-sensitized Balb/c mice by intraperitoneal injections. Ovomucoid DIII generated high levels of plasma histamine and specific immunoglobulin (Ig)E levels, and increased Th2 type cytokine (IL-4). On the other hand, the allergic response of mice desensitized with the GMFA was found to be significantly inhibited and abrogated by prevention of anaphylaxis reactions, low histamine levels and increased Th1-type cytokine (INF-gamma). It was found that significantly higher levels of IL-10 and IL-12 were secreted in the desensitized group. Desensitization with the GMFA antigen also suppressed synthesis of DIII specific-IgE levels and enhanced specific IgG2a and IgG levels compared with the group treated with the DIII antigen. The present results indicated that hyposensitization with the GMFA can desensitize or down-regulate the allergic response in Balb/c mice and this hypoallergenic variant of ovomucoid DIII can shift an ongoing allergen-specific Th2 response towards a Th1 skewed response.
Positive illusions and positive collusions: How social life abets self-enhancing beliefs
Authors: Jonathon D. Brown
Journal: Behavioral and Brain Sciences (2009)

Abstract Most people hold overly (though not excessively) positive self-views of themselves, their ability to shape environmental events, and their future. These positive illusions are generally (though not always) beneficial, promoting achievement, psychological adjustment, and physical well-being. Social processes conspire to produce these illusions, suggesting that affiliation patterns may have evolved to nurture and sustain them.
Increased Protein Kinase C Activity and Expression of Ca <sup>2+</sup> -Sensitive Isoforms in the Failing Human Heart
Authors: Nancy Bowling, Richard A. Walsh, Guojie Song, Thomas Estridge, George E. Sandusky, Rebecca L. Fouts, Karen Mintze, Todd Pickard, Robert Roden, Michael R. Bristow, Hani N. Sabbah, Jacques L. Mizrahi, Gianni Gromo, George L. King, Chris J. Vlahos
Journal: Circulation (1999)

Background —Increased expression of Ca 2+ -sensitive protein kinase C (PKC) isoforms may be important markers of heart failure. Our aim was to determine the relative expression of PKC-β1, -β2, and -α in failed and nonfailed myocardium. Methods and Results —Explanted hearts of patients in whom dilated cardiomyopathy or ischemic cardiomyopathy was diagnosed were examined for PKC isoform content by Western blot, immunohistochemistry, enzymatic activity, and in situ hybridization and compared with nonfailed left ventricle. Quantitative immunoblotting revealed significant increases of &gt;40% in PKC-β1 ( P &lt;0.05) and -β2 ( P &lt;0.04) membrane expression in failed hearts compared with nonfailed; PKC-α expression was significantly elevated by 70% in membrane fractions ( P &lt;0.03). PKC-ε expression was not significantly changed. In failed left ventricle, PKC-β1 and -β2 immunostaining was intense throughout myocytes, compared with slight, scattered staining in nonfailed myocytes. PKC-α immunostaining was also more evident in cardiomyocytes from failed hearts with staining primarily localized to intercalated disks. In situ hybridization revealed increased PKC-β1 and -β2 mRNA expression in cardiomyocytes of failed heart tissue. PKC activity was significantly increased in membrane fractions from failed hearts compared with nonfailed (1021±189 versus 261±89 pmol · mg −1 · min −1 , P &lt;0.01). LY333531, a selective PKC-β inhibitor, significantly decreased PKC activity in membrane fractions from failed hearts by 209 pmol · min −1 · mg −1 (versus 42.5 pmol · min −1 · mg −1 in nonfailed, P &lt;0.04), indicating a greater contribution of PKC-β to total PKC activity in failed hearts. Conclusions —In failed human heart, PKC-β1 and -β2 expression and contribution to total PKC activity are significantly increased. This may signal a role for Ca 2+ -sensitive PKC isoforms in cardiac mechanisms involved in heart failure.
Antiproliferation effects of oridonin on HPB-ALL cells and its mechanisms of action
Authors: Jia-Jun Liu, Ren-Wei Huang, Dong-Jun Lin, Xiang-Yuan Wu, Jun Peng, Xiang-Lin Pan, Qu Lin, Ming Hou, Mao-Hong Zhang, Feng Chen
Journal: American Journal of Hematology (2006)

Oridonin, an ent-kaurane diterpenoid derived from the herbal Rabdosia rubescens, has been recently reported to have antitumor effects on a large variety of cancer cells. The present study was undertaken to investigate the in vitro antiproliferation and apoptosis inducing effects of oridonin on HPB-ALL cell lines and its mechanisms of action. HPB-ALL cells in culture medium in vitro were treated with different concentrations of oridonin (16–56 μmol/L). MTT assay was used to detect the cell growth inhibitory rate, and the cell viability was assessed by the trypan blue dye-exclusion method. Cell apoptosis and the mitochondrial membrane potential (Δψm) were investigated by flow cytometry (FCM), Hoechst 33258 staining, and DNA fragmentation analysis. The expression of caspase-3 and different apoptosis modulators, including Fas and Bcl-2 family members, was analyzed by Western blotting. The results revealed that oridonin could significantly inhibit the growth of HPB-ALL cells and cause apoptosis, and the suppression was both time- and dose-dependent. After treatment with oridonin for 48 hr, the percentage of disruption of Δψm gradually increased in a dose-dependent manner along with marked changes of cell apoptosis, and necrotic cells increased remarkably after the cells were treated with oridonin for 72 hr; Western blotting showed cleavage of the caspase-3 zymogen protein (32 kDa) with the appearance of its 20-kDa subunit when apoptosis occurred; expression of Bcl-2 and Bcl-XL was downregulated remarkably while expression of Bax and Bid was upregulated concurrently after the cells were treated with oridonin for 24 hr. Of note, the expressions of Fas and other Bcl-2 family members including Bak and Bad remained constant before and after apoptosis occurred. We therefore conclude that oridonin has significant antiproliferation effects on HPB-ALL cells by induction of apoptosis as well as directly causing cell necrosis and that oridonin-induced apoptosis on HPB-ALL cells is mainly related to the disruption of Δψm and activation of caspase-3 as well as downregulation of anti-apoptotic protein Bcl-2, Bcl-XL, and upregulation of pro-apoptotic proteins Bax and Bid. The results indicate that oridonin may serve as a potential antileukemia reagent. Am. J. Hematol. 81:86–94, 2006. © 2006 Wiley-Liss, Inc.
A NOTE ON SYPHILIS AND CANCER, ETC., AND ON SOME PROTOZOA
Authors: J. J. Clarke
Journal: BMJ (1906)

I96infection by the Diplococcus pneumoniae rather than by other forms of organism.As might be expected, the treatment by antistreptococcic serum was without any appreciable result on the course of the illness.Though the temperature fell slightly after the injections, tlle pulse and respirations were not affected.The identification of the Diplococcus pneumoniae was only completed by the result of the inoculation experiments, and so came too late to modify the vigorous antistreptococcic treatment pursued.
If I had . . . gangrene of the toes.
Authors: M L Obeid
Journal: BMJ (1978)

Antitumor evaluation in tumor-bearing mouse is time- and energy-consuming. We aimed to investigate whether in vivo antitumor efficacy could be predicted on the basis of in vitro pharmacodynamics using deoxypodophyllotoxin (DPT), an antitumor candidate in development, as a model compound. Proliferation kinetics of monolayer-cultivated NCI-H460 cells under various DPT concentrations were quantitatively investigated and expressed as calibration curves. Koch two-phase natural growth model combined with sigmoid <i>E<sub>max</sub></i> model, i.e., dM/dt = 2<i>λ</i><sub>0</sub><i>λ</i><sub>1</sub>M/(<i>λ</i><sub>1</sub> + 2<i>λ</i><sub>0</sub>M) − <i>E<sub>max</sub></i>C<i><sup>γ</sup></i>/(EC<sub>50</sub><i><sup>γ</sup></i> + C<i><sup>γ</sup></i>)·M, was introduced to describe cell proliferation (M) against time under DPT treatment (C). Estimated in vitro pharmacodynamic parameters were: EC<sub>50</sub>, 8.97 nM; <i>E<sub>max</sub></i>, 0.820 day<sup>−1</sup>, and <i>γ</i>, 7.13. A physiologically based pharmacokinetic model including tumor compartment was introduced to predict DPT disposition in plasma, tumor tissue, and main normal tissues of NCI-H460 tumor-bearing mice following a single dose. The in vivo pharmacodynamic model and parameters were assumed the same as the in vitro ones, and linked with simulated tumor pharmacokinetic profiles by a physiologically based pharmacokinetic (PBPK) model to build a PBPK-pharmacodynamic (PBPK-PD) model. After natural growth parameters (<i>λ</i><sub>0</sub> and <i>λ</i><sub>1</sub>) were estimated, the objective in this study was to predict with the PBPK-PD model the tumor growth in NCI-H460 tumor-bearing mice during multidose DPT treatment, a use of the model similar to what others have reported. In our work, the model was successfully applied to predict tumor growth in SGC-7901 tumor-bearing mice. The resulting data indicated that in vivo antitumor efficacy might be predicted on the basis of in vitro cytotoxic assays via a PBPK-PD model approach. We demonstrated that the approach is reasonable and applicable and may facilitate and accelerate anticancer candidate screening and dose regimen design in the drug discovery process.
Immunohistochemical analysis of the skin in junctional epidermolysis bullosa using laminin 5 chain specific antibodies is of limited value in predicting the underlying gene mutation
Authors: J.R. MCMILLAN, J.A. MCGRATH, L. PULKKINEN, A. KON, R.E. BURGESON, J-P. ORTONNE, G. MENEGUZZI, J. UITTO, R.A.J. EADY
Journal: British Journal of Dermatology (1997)

The anchoring filament protein laminin 5 is composed of three polypeptide chains (alpha 3, beta 3 and gamma 2) each encoded by separate genes (LAMA3, LAMB3 and LAMC2, respectively). Mutations in any of these three genes may give rise to the autosomal recessive blistering skin disease, junctional epidermolysis bullosa. At present, there is no easy way of predicting which of these three genes might harbour the pathogenetic laminin 5 mutations in a case of junctional epidermolysis bullosa. In this study, we assessed whether immunohistochemistry might be helpful in this regard. We performed immunohistochemical labelling of the dermal-epidermal junction using alpha 3, beta 3 and gamma 2 chain-specific antibodies in 11 patients with junctional epidermolysis bullosa, in whom the laminin 5 mutations had been previously delineated. Although, labelling for the laminin 5 chain bearing the mutations was attenuated or undetectable in all cases, a complete absence of labelling or a reduction in the staining intensity for the other two chains was also seen in all cases. The results showed that immunohistochemical labelling of the dermal-epidermal junction using alpha 3, beta 3 and gamma 2 chain-specific antibodies is not a specific indicator for which of the laminin 5 chain genes contains the pathogenetic mutations, and is therefore unreliable in screening for individual laminin 5 gene mutations in cases of junctional epidermolysis bullosa.
Identification of Human Lung and Skin Proteins Conjugated with Hexamethylene Diisocyanate<i>In Vitro</i> and <i>In Vivo</i>
Authors: ADAM V. WISNEWSKI, RANJANA SRIVASTAVA, CHRISTINA HERICK, LAN XU, RANULFO LEMUS, HILARY CAIN, NADINE M. MAGOSKI, MERYL H. KAROL, KIM BOTTOMLY, CARRIE A. REDLICH
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Diiisocyanates are asthma-causing chemicals used in the commercial production of polyurethane. We have previously shown that human lung epithelial cell proteins can become conjugated with hexamethylene diisocyanate (HDI) and may be biologically important in diisocyanate-induced asthma. The objective of this study was to identify specific human lung and skin proteins that become conjugated with diisocyanate after in vitro and in vivo exposure. Following in vitro exposure of human airway epithelial cells (A549), keratin 18, the 78-kD glucose-regulated protein, trans-1,2-dihyrobenzene-1,2-diol dehydrogenase, and actin were identified as prominent diisocyanate-conjugated proteins through use of a combination of immunocytochemical and mass spectrometric techniques. Following in vivo inhalation of an HDI aerosol, keratin 18 was also identified as the predominant diisocyanate-conjugated protein in human endobronchial biopsy samples, whereas albumin was the predominant diisocyanate-conjugated protein in bronchoalveolar lavage fluid. Keratin was also identified as a predominant diisocyanate-conjugated protein in human skin biopsy samples after epicutaneous exposure to liquid-phase HDI, although the major skin diisocyanate-conjugated protein (56-kD) differed from the predominant lung diisocyanate-conjugated keratin (47-kD). The data from this study identify keratin and other proteins as potential "carriers" for diisocyanates in vivo, and suggest that HDI conjugation of these proteins may play a role in the pathogenesis of diisocyanate-induced asthma.
Stereotactic Radiotherapy for Neovascular Age-related Macular Degeneration
Authors: Timothy L. Jackson, Usha Chakravarthy, Peter K. Kaiser, Jason S. Slakter, Ernest Jan, Francesco Bandello, Denis O'Shaughnessy, Michael E. Gertner, Linda Danielson, Darius M. Moshfeghi
Journal: Ophthalmology (2013)
Anaphylaxis from the Product(s) of Ethylene Oxide Gas
Authors: J. POOTHULLIL
Journal: Annals of Internal Medicine (1975)

This report describes a patient who experienced typical systemic allergic reactions associated with hemodialysis and the use of a plastic and rubber connecting tube in an arteriovenous shunt. A buffer solution placed in a connecting tube sterilized with ethylene oxide gas elicited positive reactions to skin tests. The patient had no detectable sensitivity to other substances considered to potentially represent alternative sources of the reactions. Human serum albumin exposed to ethylene oxide gas induced positive reactions in the patient and the release of histamine from his leukocytes. Corresponding tests in two control subjects were negative. Preliminary flushing of his hemodialysis system reduced the severity of reactions, apparently by removal of the sensitizing substance(s). It was concluded that there was sensitization and anaphylaxis from exposure to a product(s) of ethylene oxide gas used in sterilization.