tbuckley/cabot-search huggingface dataset:
Cyclooxygenase-2 Mediates Dialysate-Induced Alterations of the Peritoneal Membrane
Authors: Luiz S. Aroeira, Enrique Lara-Pezzi, Jesu[Combining Acute Accent]s Loureiro, Abelardo Aguilera, Marta Rami[Combining Acute Accent]rez-Huesca, Guadalupe Gonza[Combining Acute Accent]lez-Mateo, M. Luisa Pe[Combining Acute Accent]rez-Lozano, Patricia Albar-Vizcai[Combining Acute Accent]no, M-Auxiliadora Bajo, Gloria del Peso, Jose[Combining Acute Accent] Antonio Sa[Combining Acute Accent]nchez-Tomero, Jose[Combining Acute Accent] Antonio Jime[Combining Acute Accent]nez-Heffernan, Rafael Selgas, Manuel Lo[Combining Acute Accent]pez-Cabrera
Journal: Journal of the American Society of Nephrology (2009)

During peritoneal dialysis (PD), exposure of the peritoneal membrane to nonphysiologic solutions causes inflammation, ultimately leading to altered structure and function. Myofibroblasts, one of the cell types that contribute to dysfunction of the peritoneal membrane, can originate from mesothelial cells (MCs) by epithelial-to-mesenchymal transition (EMT), a process that has been associated with an increased rate of peritoneal transport. Because cyclooxygenase-2 (COX-2) is induced by inflammation, we studied the role of COX-2 in the deterioration of the peritoneal membrane. We observed that nonepithelioid MCs found in peritoneal effluent expressed higher levels of COX-2 than epithelioid MCs. The mass transfer coefficient for creatinine correlated with MC phenotype and with COX-2 levels. Although COX-2 was upregulated during EMT of MCs <i>in vitro</i>, COX-2 inhibition did not prevent EMT. In a mouse model of PD, however, COX-2 inhibition with Celecoxib resulted in reduced fibrosis and in partial recovery of ultrafiltration, outcomes that were associated with a reduction of inflammatory cells. Furthermore, PD fluid with a low content of glucose degradation products did not induce EMT or COX-2; the peritoneal membranes of mice treated with this fluid showed less worsening than mice exposed to standard fluid. In conclusion, upregulation of COX-2 during EMT may mediate peritoneal inflammation, suggesting COX-2 inhibition as a potential strategy to ameliorate peritoneal deterioration in PD patients.
Outcome of Cancer Patients Considered for Intensive Care Unit Admission: A Hospital-Wide Prospective Study
Authors: Guillaume Thiéry, Élie Azoulay, Michael Darmon, Magali Ciroldi, Sandra De Miranda, Vincent Lévy, Fabienne Fieux, Delphine Moreau, Jean Roger Le Gall, Benoît Schlemmer
Journal: Journal of Clinical Oncology (2005)

Purpose To evaluate the outcome of cancer patients considered for admission to the intensive care unit (ICU). Patients and Methods Prospective, one-year hospital-wide study of all cancer and hematology patients, including bone marrow transplantation patients, for whom admission to the ICU was requested. Results Of the 206 patients considered for ICU admission, 105 patients (51%) were admitted. Of the 101 patients who were not admitted, 54 patients (26.2%) were considered too sick to benefit, and 47 patients (22.8%) were considered to be too well to benefit from the ICU. Of these 47 patients, 13 patients were admitted later. Survival rates after 30 and 180 days were significantly associated with admission status (P &lt; .0001). Remission of the malignancy (odds ratio [OR], 3.37; 95% CI, 1.25 to 9.07) was independently associated with ICU admission, whereas poor chronic health status (OR, 0.38; 95% CI, 0.16 to 0.74) and solid tumor (OR, 0.43; 95% CI, 0.24 to 0.78) were associated with ICU refusal. In admitted patients, 30-day and 6-month survival rates were 54.3% and 32.4%, respectively. Of the patients considered too sick to benefit from ICU admission, 26% were alive on day 30 and 16.7% on day 180. Among patients considered too well to benefit, the 30-day survival rate was a worrisome 78.7%. Calibration of the Mortality Probability Model (the only score available at triage) was of limited value for predicting 30-day survival (area under the curve, 0.62). Conclusion Both the excess mortality in too-well patients later admitted to the ICU and the relatively good survival in too-sick patients suggest the need for a broader admission policy.
Personality Correlates of Success in a Methadone Maintenance Program
Authors: DAVID G. LEVINE, DONALD B. LEVIN, IRA H. SLOAN, JOHN N. CHAPPEL
Journal: American Journal of Psychiatry (1972)

Thirty black, male heroin addicts who had been treated in a methadone maintenance clinic were interviewed to assess psychiatric diagnosis and disability and to rate manifestations of anxiety, depression and paranoia, object relatedness, and compliance. These findings were evaluated in light of each subject's success in treatment. Success correlated strongly with a high score in compliance. Successful subjects also scored high in anxiety; failures scored high in depression. The authors discuss treatment implications.
Preclinical Investigation of PEGylated Tumor Necrosis Factor α in Dogs with Spontaneous Tumors: Phase I Evaluation
Authors: Douglas H. Thamm, Ilene D. Kurzman, Mike A. Clark, E.J. Ehrhart, Susan L. Kraft, Daniel L. Gustafson, David M. Vail
Journal: Clinical Cancer Research (2010)

Tumor necrosis factor-alpha (TNF) is a cytokine with potent antitumor activity; however, toxicity and short half-life have limited its utility. Polyethylene glycol (PEG) conjugation of biotherapeutics can decrease immunogenicity while improving bioactivity and half-life. PEGylation of TNF (PEG-TNF) significantly improved half-life and toxicity in mice, resulting in enhanced antitumor activity. This study characterized toxicity, biological effect, and antitumor activity of PEG-TNF in pet dogs with spontaneous cancer.A phase I clinical trial enrolled dogs with measurable tumors in which standard therapy had failed or been declined. Physiologic, hematologic, and biochemical parameters were evaluated and tumor biopsies obtained serially. A subset of patients underwent serial dynamic contrast-enhanced magnetic resonance imaging.Fifteen dogs were enrolled at doses from 20.0 to 30.0 microg/kg. Dose-limiting toxicity at 30.0 microg/kg consisted of vascular leak in one and hypotension/coagulopathy in one, establishing 26.7 microg/kg as the maximum tolerated dose. Mean elimination half-life was 15.3 +/- 4.9 hours. Biological activity (transient fever and leukopenia, increased tumor inflammation, and necrosis) was observed at all dosages. A significant increase in tumor blood flow was observed with dynamic contrast-enhanced magnetic resonance imaging. Minor/transient antitumor responses were observed in dogs with melanoma, squamous cell carcinoma, and mammary carcinoma, and a partial response was observed in a dog with angiosarcoma.Using a clinically relevant, spontaneous large animal model of neoplasia, we have shown that biologically effective doses of PEG-TNF can be administered safely, and that PEG-TNF administration is associated with encouraging biological activity. These results justify the clinical evaluation of PEG-TNF in human cancer.
Induced Epithelial Hyperplasia in Organ Cultures of Mouse Mammary Tissues. Effects of the Milk Agent2
Authors: Etienne Y. Lasfargues, Margaret R. Murray, Dan H. Moore
Journal: JNCI Journal of the National Cancer Institute (1965)

Journal Article Induced Epithelial Hyperplasia in Organ Cultures of Mouse Mammary Tissues. Effects of the Milk Agent Get access Etienne Y. Lasfargues, Etienne Y. Lasfargues Department of Microbiology and Anatomy, College of Physicians and Surgeons, Columbia University, and The Rockefeller Institute, New York, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar Margaret R. Murray, Margaret R. Murray Department of Microbiology and Anatomy, College of Physicians and Surgeons, Columbia University, and The Rockefeller Institute, New York, New York Search for other works by this author on: Oxford Academic PubMed Google Scholar Dan H. Moore Dan H. Moore Department of Microbiology and Anatomy, College of Physicians and Surgeons, Columbia University, and The Rockefeller Institute, New York, New York 3We express our thanks to Dr. George Miroff who kindly supplied the samples of A and Ax milks, and gratefully acknowledge the valuable technical assistance and photographic services of Mr. J. Segarra and Mr. E. Grave. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 34, Issue 1, January 1965, Pages 141–152, https://doi.org/10.1093/jnci/34.1.141 Published: 01 January 1965 Article history Received: 02 July 1964 Published: 01 January 1965
Sequential acetaldehyde production, lipid peroxidation, and fibrogenesis in micropig model of alcohol-induced liver disease
Authors: Onni Nlemelä, Seppo Parkkila, Seppo Ylä-herttuala, Jesus Villanueva, Boris Ruebner, Charles H. Halsted
Journal: Hepatology (1995)

The pathogenesis of alcohol-induced liver disease involves the adverse effects of ethanol metabolites and oxidative tissue injury. Previous studies indicated that covalent protein adducts with reactive aldehydes may be formed in alcohol consumers. To study the role of such protein adducts in the development of liver injury, we examined the sequential appearances of adducts of the ethanol metabolite acetaldehyde (AA) and of two products of lipid peroxidation, malondialdehyde (MDA) and 4-hydroxynonenol (HNE), in ethanol-fed micropigs. Immunohistochemical stainings using specific antibodies that recognize epitopes of each adduct were performed from liver biopsy specimens obtained at 1, 5, and 12 months from micropigs fed either control diet (n = 5) or ethanol-containing diets (n = 5). After 1 month on the ethanol diet, AA and MDA adducts were observed primarily in the perivenous regions co-localizing with each other and coinciding with increased concentrations of serum aminotransferase markers of liver injury. HNE adducts were usually less intense and more diffuse, and were also seen in some biopsy specimens from control animals. Although the most intense staining reactions at 5 months remained in zone 3, a more widespread distribution was usually seen together with increased evidence of steatonecrosis and focal inflammation. In terminal biopsies at 12 months, perivenous fibrosis was present in three of five biopsy specimens. More extensive pericentral and intralobular fibrosis was noted in one micropig fed ethanol for 21 months. These studies demonstrate that covalent adducts of proteins with reactive aldehydes are formed in early phases of alcohol-induced liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Hemophiliacs With HIV Antibody Are Actively Infected
Authors: J. Brooks Jackson
Journal: JAMA (1988)

Cultures of peripheral blood mononuclear cells for human immunodeficiency virus type 1 (HIV-1) and assays for the p24 antigen were performed for a group of 75 unselected hemophiliacs to determine whether patients positive for HIV-1 antibody are actively infected rather than immunized by viral proteins in non— heat-treated factor VIII or IX concentrates. Fifty-six (75%) of the 75 hemophiliacs were antibody positive and 55 (98%) of the 56 with antibodies also had positive cultures. The one culture-negative individual had detectable HIV-1 proviral DNA sequences in three separate samples of peripheral blood mononuclear cell DNA, as detected by a polymerase chain reaction assay. Detection of serum p24 antigen and the time to development of a positive culture were significantly more frequent and shorter, respectively, in symptomatic vs asymptomatic patients. None of the 19 hemophiliacs negative for HIV-1 antibody had positive cultures, detectable p24 serum antigen, or symptoms of HIV-1 infection. Moreover, latent HIV-1 infection was not detected in 16 female sexual partners of hemophiliacs positive for HIV-1 antibody using Western blot testing, assays for p24 antigen, HIV-1 cultures, and polymerase chain reaction assays, despite repeated unprotected sexual exposure. We conclude that antibody-positive hemophiliacs have been actively infected by HIV-1 and that a long period of latent HIV-1 infection prior to overt seroconversion is unlikely. (<i>JAMA</i>1988;260:2236-2239)
Insulin-like growth factor-1 contributes to the pulmonary artery smooth muscle cell proliferation in pulmonary arterial hypertension
Authors: Laurence Dewachter, Céline Dewachter, Asmae Belhaj, Sophie Lalande, Benoit Rondelet, Myriam Remmelink, Jean-Luc Vachiéry, Robert Naeije
Journal: European Respiratory Journal (2014)

Pulmonary arterial hypertension (PAH) is a fatal disease characterised by increased pulmonary vascular resistance and abnormal pulmonary arteriolar remodelling, mainly due to pulmonary artery smooth muscle cell (PA-SMC) hyperplasia. Insulin-like growth factor-1 (IGF-1), a mitogen for vascular SMCs, has been implicated in the pathogenesis of atherosclerosis. Moreover, low circulating IGF-1 levels are associated with an increased risk for cardiovascular diseases.

We, therefore, hypothesized that the IGF-1 signaling could play a role in PAH pathogenesis.

Relative gene expressions of IGF-1 and IGF-1 receptor were evaluated in total lung homogenates and in cultured PA-SMCs from PAH patients (n=6) and controls (n=10). PA-SMCs treated with IGF-1 (10 and 100ng/mL) were assessed for cell proliferation (by MTT assay and cell counting) and apoptosis (by Bax/Bcl-2 evaluation). Seric IGF-1 levels were evaluated by ELISA in sera from PAH patients (n=25) and controls (n=26).

Expression of IGF-1 was 5-fold increased in total lung homogenates from PAH patients compared to controls, while pulmonary IGF-1 receptor expression did not change. In PA-SMCs from PAH patients, the expressions of IGF-1 and IGF-1 receptor were increased. Treatment with IGF-1 dose-dependently induced proliferation and decreased Bax/Bcl-2 ratio in PA-SMCs. These effects were stronger in PA-SMCs from PAH patients compared to controls. After adjustment for age and body mas index, seric IGF-1 level was higher in PAH patients compared to controls.

In PAH patient, the paracrine IGF-1 signalling is exacerbated in the lungs, probably contributing to PA-SMC hyperplasia, while circulating IGF-1 is reduced.
THE EFFECT OF TRACHOMA VIRUS VACCINE ON THE COURSE OF EXPERIMENTAL TRACHOMA INFECTION IN BLIND HUMAN VOLUNTEERS
Authors: J. Thomas Grayston, San-Pin Wang, Yen-Fei Yang, Robert L. Woolridge
Journal: The Journal of Experimental Medicine (1962)

The TRIC-Taiwan-1-1958 strain of elementary body virus isolated from a trachoma patient on Taiwan has been proven capable of reproducing trachoma by experimental inoculation of six human volunteers. Virus material derived from the seventh passage in embryonated hen eggs caused the clinical picture of trachoma in every inoculation, even at the dilution of 10(-4) of infected yolk sacs (approximately 1 EID(50)). There was a similar clinical picture with each inoculation beginning with an acute follicular conjunctivitis which progressed for 4 months and then persisted with chronic changes until 9 months when treatment was begun. The illness was generally more acute than would be expected in natural trachoma. That trachoma was reproduced was shown by the involvement of the cornea with epithelial keratitis and pannus, and by the occurrence of gelatinous follicles and eventual cicatrization of the conjunctiva. These clinical findings were supported by repeated demonstrations of typical inclusion bodies of Halberstaedter-Prowazek from conjunctival and even corneal cells, by repeated reisolation of elementary body virus in egg yolk sacs, and by the development of complement-fixing antibody with a "specific" trachoma antigen in each volunteer. Control inoculations with adenovirus type 4 and normal yolk sac showed different clinical and laboratory findings. Experimental trachoma vaccine was given to three of the volunteers to study its effect on the course of illness. An antibody response to the vaccine was demonstrated and there was a modification of disease in the volunteers receiving vaccine. While the three volunteers who received placebo each developed cross-infection of their uninoculated eye and had an acute reactivation of the bilateral disease after 1 to 2 months of antibiotic eye ointment therapy, the vaccinated volunteers remained free of infection in uninoculated eyes and showed no relapse after ointment therapy. Treatment with sulfamethoxypyridazine, a sulfa drug with prolonged action, proved to be an effective and relatively simple method of therapy for experimental trachoma.
In Vitro Studies of Poison Oak Immunity
Authors: Vera S. Byers, Neal Castagnoli, William L. Epstein
Journal: Journal of Clinical Investigation (1979)

Studies were performed to ascertain the effect of urushiol analogues on the in vitro lymphocyte blastogenesis elicited by urushiol in peripheral blood lymphocytes taken from individuals sensitized to poison oak or ivy. Urushiol is a mixture of alkylcatechols composed of a catechol ring coupled to mono-, di-, or tri-unsaturated C-15 or C-17 carbon side chains. Each of these two moieties, catechol ring and side chain, was tested for its role in eliciting reactivity. Analogues tested represented the catechol ring (3-methylcatechol), the mono- or di-unsaturated side chain (oleic or linoleic acid), and the saturated side chain coupled to a catechol ring (pentadecylcatechol), a blocked catechol ring (heptadecylveratrole), or a resorcinol (pentadecylresorcinol). Urushiol with a blocked catechol ring (urushiol dimethyl ether) was also included. Of these, only pentadecylcatechol evoked reactivity in sensitized lymphocytes, and this reactivity was only a fraction of that evoked by urushiol. This suggested that the system has some requirement for the side chain, and that the catechol ring is critical for reactivity. This was further investigated by testing the ability of some of these analogues to inhibit urushiol-specific blastogenesis. No inhibition was noted with compounds bearing the saturated side chain with modified ring structures (pentadecylresorcinol and heptadecylveratrole). However, both 3-methylcatechol and pentadecylcatechol (at equimolar concentrations) blocked reactivity. The results of our experiments suggested that although both the side chain and the catechol ring are required for reactivity, the latter is most critical. Unsaturation in the side chain is important for maximal reactivity because the saturated catechols were only partially as active as the urushiol oil. There may be a greater dose requirement for the catechol ring than for the side chain.
Treatment Completion and Costs of a Randomized Trial of Rifampin for 4 Months versus Isoniazid for 9 Months
Authors: Dick Menzies, Marie-Josée Dion, Barry Rabinovitch, Sharyn Mannix, Paul Brassard, Kevin Schwartzman
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

There is little published information regarding treatment completion, safety, and efficacy of rifampin administered daily for 4 months—a recommended alternative to 9 months of isoniazid for therapy of latent tuberculosis infection. In an open-label randomized trial at a university-affiliated respiratory hospital, consenting patients whose treating physician had recommended therapy for latent tuberculosis infection were randomized to daily self-administered rifampin for 4 months or daily self-administered isoniazid for 9 months. Of 58 patients randomized to rifampin, 53 (91%) took 80% of doses, and 50 (86%) took more than 90% of doses within 20 weeks compared with 44 (76%) and 36 (62%) who took 80 and 90%, respectively, of doses of isoniazid within 43 weeks (relative risks: 80% of doses, 1.2 [95% confidence interval: 1.02, 1.4]; 90% of doses, 1.4 [1.1, 1.7]). Adverse events resulted in permanent discontinuation of therapy for two (3%) patients taking rifampin, and for eight (14%) patients taking isoniazid. Three patients developed drug-induced hepatitis—all were taking isoniazid. Total costs of therapy were significantly higher for isoniazid. In conclusion, completion of therapy was significantly better with 4 months of rifampin and major side effects were somewhat lower. Further studies are needed to assess the safety and efficacy of the 4-month rifampin regimen.
Effects of the Diuretic Agent Indapamide on Na <sup>+</sup> , Transient Outward, and Delayed Rectifier Currents in Canine Atrial Myocytes
Authors: Yanjie Lu, Lixia Yue, Zhiguo Wang, Stanley Nattel
Journal: Circulation Research (1998)

Abstract —The diuretic agent indapamide has been reported to block the slow component of the delayed rectifier K + current ( I Ks ) without altering the rapid component ( I Kr ) or the inward rectifier current and has been used as a pharmacological probe for I Ks ; however, the effects of indapamide on Na + ( I Na ), L-type Ca 2+ ( I Ca ), and transient outward K + ( I to ) currents have not been determined. We applied tight-seal, whole-cell, patch-clamp techniques to assess the effects of indapamide on I Na , I to , I Ca , and I Ks in canine atrial myocytes. Indapamide inhibited I Na , I to , and I Ks in a concentration-dependent and reversible way, without altering I Ca . Block increased with depolarization, with the 50% blocking concentration (EC 50 ) decreasing from 129±26 μmol/L (at −60 mV) to 79±17 μmol/L (at −10 mV) for I Na , from 174±19 μmol/L (at +10 mV) to 98±7 μmol/L (at +60 mV) for I to , and from 148±28 μmol/L (at +10 mV) to 86±18 μmol/L (at +60 mV) for I Ks . Significant inhibition was seen at concentrations as low as 10 μmol/L for all 3 currents. In addition, indapamide effectively inhibited the ultrarapid delayed rectifier current in a voltage-independent way, with an EC 50 of 138±7 μmol/L at +10 mV. Standard microelectrode experiments showed the effects of indapamide on the action potential to be consistent with the ionic actions seen. We conclude that in addition to its well-recognized I Ks -blocking action, indapamide also inhibits I Na and I to effectively and with similar potency. Thus, indapamide is not a reliable pharmacological probe with which to study the specific effects of I Ks blockade, and I Na and I to block may contribute to the potential profile of cardiac actions of the compound.
Immunoglobulin Secreting Cells in Normal Human Bronchial Lavage Fluids
Authors: E. Clinton Lawrence, R. Michael Blaese, R. Russell Martin, Paul M. Stevens
Journal: Journal of Clinical Investigation (1978)

Immunoglobulin secreting cells were quantitated in the bronchial lavage fluids of 12 normal volunteers and compared with immunoglobulin secreting cells in peripheral blood, by a reverse hemolytic plaque assay. The mean number of cells secreting immunoglobulin (Ig)G in bronchial lavage fluids was 489 per million lymphocytes vs. a mean of 175 IgG secreting cells per million lymphocytes in peripheral blood (P < 0.02). The mean number of IgA secreting cells in bronchial lavage fluids was 633 per million lymphocytes as compared to 100 per million lymphocytes in peripheral blood (P < 0.005). Thus, compared to peripheral blood, cells from the lavage fluids were relatively enriched for both IgG and IgA secreting cells. However, IgA secreting cells were the major class of immunoglobulin secreting cells in bronchial lavage fluids, whereas IgG secreting cells predominated in peripheral blood. The prominence of IgA secreting cells in bronchial lavage fluids was further demonstrated by a mean ratio of IgA/IgG secreting cells in bronchial lavage fluids of 1.26 compared to a ratio in peripheral blood of 0.57 (P < 0.02). Cells secreting IgM were identified in only four of seven bronchial lavage fluid samples studied but in all peripheral blood samples. IgE secreting cells were not present in normal peripheral blood but could be demonstrated in 5 of 11 lavage fluid specimens. Thus, cells actively secreting immunoglobulins can be identified in the lower bronchial-alveolar tree of normal human subjects. Cells secreting IgG, IgA, or IgM may function in local lung defenses against infection; cells secreting IgE may contribute to hypersensitivity reactions in the lung.